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Both seed germination and subsequent seedling establishment are key checkpoints during the life cycle of seed plants, yet flooding stress markedly inhibits both processes, leading to economic losses from agricultural production. Here, we report that melatonin (MT) seed priming treatment enhances the performance of seeds from several crops, including soybean, wheat, maize, and alfalfa, under flooding stress. Transcriptome analysis revealed that MT priming promotes seed germination and seedling establishment associated with changes in abscisic acid (ABA), gibberellin (GA), and reactive oxygen species (ROS) biosynthesis and signaling pathways. Real-time quantitative RT-PCR (qRT-PCR) analysis confirmed that MT priming increases the expression levels of GA biosynthesis genes, ABA catabolism genes, and ROS biosynthesis genes while decreasing the expression of positive ABA regulatory genes. Further, measurements of ABA and GA concentrations are consistent with these trends. Following MT priming, quantification of ROS metabolism-related enzyme activities and the concentrations of H2O2 and superoxide anions (O2 -) after MT priming were consistent with the results of transcriptome analysis and qRT-PCR. Finally, exogenous application of GA, fluridone (an ABA biosynthesis inhibitor), or H2O2 partially rescued the poor germination of non-primed seeds under flooding stress. Collectively, this study uncovers the application and molecular mechanisms underlying MT priming in modulating crop seed vigor under flooding stress.
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Ácido Abscísico , Inundações , Germinação , Giberelinas , Melatonina , Espécies Reativas de Oxigênio , Plântula , Sementes , Melatonina/farmacologia , Melatonina/metabolismo , Germinação/efeitos dos fármacos , Ácido Abscísico/metabolismo , Giberelinas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Plântula/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/genética , Sementes/efeitos dos fármacos , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/genética , Estresse Fisiológico , Produtos Agrícolas/metabolismo , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacosRESUMO
Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-ß, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification.
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Células Estreladas do Fígado , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células Estreladas do Fígado/metabolismo , Animais , Camundongos , Transplante de Células-Tronco Mesenquimais/métodos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/terapia , Doença Hepática Induzida por Substâncias e Drogas/genética , Masculino , Tetracloreto de Carbono/efeitos adversos , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento de Hepatócito/genética , Camundongos Endogâmicos C57BL , Movimento CelularRESUMO
OBJECTIVE: To investigate the association between caesarean scar defects and abnormal uterine bleeding through systematic literature review. METHODS: PubMed, Web of Science, Cochrane Library and Embase databases were searched based on PRISMA 2020 to include studies exploring abnormal uterine bleeding in women with caesarean scar defects. The combined relative risk (RR) of uterine bleeding, combined prevalence of abnormal uterine bleeding and combined RR of intermenstrual uterine bleeding were calculated using a fixed- or random-effects model. RESULTS: Ten studies involving 1,183 women with caesarean scar defects met the inclusion criteria for this study. Compared with women without caesarean scar defects, those with caesarean scar defects had a higher risk of abnormal uterine bleeding (RR: 3.22, 95% CI: 1.83-5.66) and intermenstrual bleeding (RR: 2.93, 95% CI: 1.91-4.50). The prevalence of abnormal uterine bleeding was approximately 0.46 (95% CI: 0.27-0.64), and across populations, women with a previous caesarean section who had undergone imaging specifically for gynaecological disease had a significantly higher prevalence of abnormal uterine bleeding (0.77, 95% CI: 0.65-0.89) than those with at least one caesarean Sect. (0.25, 95% CI: 0.10-0.39). CONCLUSION: A significant association was observed between caesarean scar defects and abnormal uterine bleeding, with the former being a risk factor for the latter. However, previous studies have differed in the definition of caesarean scar defects and abnormal uterine bleeding, and more high-quality studies are needed to further investigate the relevant definitions and study results in the future.
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Cesárea , Cicatriz , Hemorragia Uterina , Humanos , Feminino , Cicatriz/complicações , Cesárea/efeitos adversos , Cesárea/estatística & dados numéricos , Hemorragia Uterina/etiologia , Hemorragia Uterina/epidemiologia , Fatores de Risco , Adulto , Prevalência , GravidezRESUMO
Inflammatory bowel disease (IBD) is distinguished by persistent immune-mediated inflammation of the gastrointestinal tract. Previous experimental investigations have shown encouraging outcomes for the use of mesenchymal stem cell (MSC)-based therapy in the treatment of IBD. However, as a primary medication for IBD patients, there is limited information regarding the potential interaction between 5-aminosalicylates (5-ASA) and MSCs. In this present study, we employed the dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mouse model to examine the influence of a combination of MSCs and 5-ASA on the development of UC. The mice were subjected to weight measurement, DAI scoring, assessment of calprotectin expression, and collection of colons for histological examination. The findings revealed that both 5-ASA and MSCs have demonstrated efficacy in the treatment of UC. However, it is noteworthy that 5-ASA exhibits a quicker onset of action, while MSCs demonstrate more advantageous and enduring therapeutic effects. Additionally, the combination of 5-ASA and MSC treatment shows a less favorable efficacy compared to the MSCs alone group. Moreover, our study conducted in vitro revealed that 5-ASA could promote MSC migration, but it could also inhibit MSC proliferation, induce apoptosis, overexpress inflammatory factors (IL-2, IL-12P70, and TNF-α), and reduce the expression of PD-L1 and PD-L2. Furthermore, a significant decrease in the viability of MSCs within the colon was observed as a result of 5-ASA induction. These findings collectively indicate that the use of 5-ASA has the potential to interfere with the therapeutic efficacy of MSC transplantation for the treatment of IBD.
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Colite Ulcerativa , Sulfato de Dextrana , Modelos Animais de Doenças , Mesalamina , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Colite Ulcerativa/terapia , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Colite Ulcerativa/induzido quimicamente , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos , Humanos , Camundongos Endogâmicos C57BL , Colo/patologia , Colo/efeitos dos fármacos , Colo/imunologia , Células Cultivadas , Masculino , Proliferação de Células/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêuticoRESUMO
BACKGROUND: Automated Breast Ultrasound (AB US) has shown good application value and prospects in breast disease screening and diagnosis. The aim of the study was to explore the ability of AB US to detect and diagnose mammographically Breast Imaging Reporting and Data System (BI-RADS) category 4 microcalcifications. METHODS: 575 pathologically confirmed mammographically BI-RADS category 4 microcalcifications from January 2017 to June 2021 were included. All patients also completed AB US examinations. Based on the final pathological results, analyzed and summarized the AB US image features, and compared the evaluation results with mammography, to explore the detection and diagnostic ability of AB US for these suspicious microcalcifications. RESULTS: 250 were finally confirmed as malignant and 325 were benign. Mammographic findings including microcalcifications morphology (61/80 with amorphous, coarse heterogeneous and fine pleomorphic, 13/14 with fine-linear or branching), calcification distribution (189/346 with grouped, 40/67 with linear and segmental), associated features (70/96 with asymmetric shadow), higher BI-RADS category with 4B (88/120) and 4 C (73/38) showed higher incidence in malignant lesions, and were the independent factors associated with malignant microcalcifications. 477 (477/575, 83.0%) microcalcifications were detected by AB US, including 223 malignant and 254 benign, with a significantly higher detection rate for malignant lesions (x2 = 12.20, P < 0.001). Logistic regression analysis showed microcalcifications with architectural distortion (odds ratio [OR] = 0.30, P = 0.014), with amorphous, coarse heterogeneous and fine pleomorphic morphology (OR = 3.15, P = 0.037), grouped (OR = 1.90, P = 0.017), liner and segmental distribution (OR = 8.93, P = 0.004) were the independent factors which could affect the detectability of AB US for microcalcifications. In AB US, malignant calcification was more frequent in a mass (104/154) or intraductal (20/32), and with ductal changes (30/41) or architectural distortion (58/68), especially with the both (12/12). BI-RADS category results also showed that AB US had higher sensitivity to malignant calcification than mammography (64.8% vs. 46.8%). CONCLUSIONS: AB US has good detectability for mammographically BI-RADS category 4 microcalcifications, especially for malignant lesions. Malignant calcification is more common in a mass and intraductal in AB US, and tend to associated with architectural distortion or duct changes. Also, AB US has higher sensitivity than mammography to malignant microcalcification, which is expected to become an effective supplementary examination method for breast microcalcifications, especially in dense breasts.
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Neoplasias da Mama , Calcinose , Ultrassonografia Mamária , Humanos , Calcinose/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Ultrassonografia Mamária/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Adulto , Idoso , Mamografia/métodos , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Stroke is a leading cause of mortality and disability with ischemic stroke being the most common type of stroke. Salvianolic acid C (SalC), a polyphenolic compound found in Salviae Miltiorrhizae Radix et Rhizoma, has demonstrated therapeutic potential in the recovery phase of ischemic stroke. However, its pharmacological effects and underlying mechanisms during the early stages of ischemic stroke remain unclear. This study aimed to examine the potential mechanism of action of SalC during the early phase of ischemic stroke using network pharmacology strategies and RNA sequencing analysis. METHODS: SalC effects on infarct volume, neurological deficits, and histopathological changes were assessed in a mouse model of transient middle cerebral artery occlusion (tMCAO). By integrating RNA sequencing data with a cerebral vascular disease (CVD)-related gene database, a cerebral ischemic disease (CID) network containing dysregulated genes from the tMCAO model was constructed. Network analysis algorithms were applied to evaluate the key nodes within the CID network. In vivo and in vitro validation of crucial targets within the identified pathways was conducted. RESULTS: SalC treatment significantly reduced infarct volume, improved neurological deficits, and reversed pathological changes in the tMCAO mouse model. The integration of RNA sequencing data revealed an 80% gene reversion rate induced by SalC within the CID network. Among the reverted genes, 53.1% exhibited reversion rates exceeding 50%, emphasizing the comprehensive rebalancing effect of SalC within the CID network. Neuroinflammatory-related pathways regulated by SalC, including the toll-like-receptor 4 (TLR4)- triggering receptor expressed on myeloid cells 1 (TREM1)-nuclear factor kappa B (NF-κB) pathway, were identified. Further in vivo and in vitro experiments confirmed that TLR4-TREM1-NF-κB pathway was down-regulated by SalC in microglia, which was essential for its anti-inflammatory effect on ischemic stroke. CONCLUSIONS: SalC attenuated cerebral ischemic injury by inhibiting neuroinflammation mediated by microglia, primarily through the TLR4-TREM1-NF-κB pathway. These findings provide valuable insights into the potential therapeutic benefits of SalC in ischemic stroke.
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Wnt/ß-catenin signaling plays a crucial role in the migration of mesenchymal stem cells (MSCs). However, our study has revealed an intriguing phenomenon where Dickkopf-1 (DKK1), an inhibitor of Wnt/ß-catenin signaling, promotes MSC migration at certain concentrations ranging from 25 to 100 ng/mL while inhibiting Wnt3a-induced MSC migration at a higher concentration (400 ng/mL). Interestingly, DKK1 consistently inhibited Wnt3a-induced phosphorylation of LRP6 at all concentrations. We further identified cytoskeleton-associated protein 4 (CKAP4), another DKK1 receptor, to be localized on the cell membrane of MSCs. Overexpressing the CRD2 deletion mutant of DKK1 (ΔCRD2), which selectively binds to CKAP4, promoted the accumulation of active ß-catenin (ABC), the phosphorylation of AKT (Ser473) and the migration of MSCs, suggesting that DKK1 may activate Wnt/ß-catenin signaling via the CKAP4/PI3K/AKT cascade. We also investigated the effect of the CKAP4 intracellular domain mutant (CKAP4-P/A) that failed to activate the PI3K/AKT pathway and found that CKAP4-P/A suppressed DKK1 (100 ng/mL)-induced AKT activation, ABC accumulation, and MSC migration. Moreover, CKAP4-P/A significantly weakened the inhibitory effects of DKK1 (400 ng/mL) on Wnt3a-induced MSC migration and Wnt/ß-catenin signaling. Based on these findings, we propose that DKK1 may activate the PI3K/AKT pathway via CKAP4 to balance the inhibitory effect on Wnt/ß-catenin signaling and thus regulate Wnt3a-induced migration of MSCs. Our study reveals a previously unrecognized role of DKK1 in regulating MSC migration, highlighting the importance of CKAP4 and PI3K/AKT pathways in this process.
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Movimento Celular , Peptídeos e Proteínas de Sinalização Intercelular , Células-Tronco Mesenquimais , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Via de Sinalização Wnt , Proteína Wnt3A , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células-Tronco Mesenquimais/metabolismo , Movimento Celular/efeitos dos fármacos , Proteína Wnt3A/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Humanos , Animais , beta Catenina/metabolismo , Fosforilação/efeitos dos fármacos , Camundongos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genéticaRESUMO
INTRODUCTION: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates brain states by applying a weak electrical current to the brain cortex. Several studies have shown that anodal stimulation of the ipsilesional primary motor cortex (M1) may promote motor recovery of the affected upper limb in patients with stroke; however, a high-level clinical recommendation cannot be drawn in view of inconsistent findings. A priming brain stimulation protocol has been proposed to induce stable modulatory effects, in which an inhibitory stimulation is applied prior to excitatory stimulation to a brain area. Our recent work showed that priming theta burst magnetic stimulation demonstrated superior effects in improving upper limb motor function and neurophysiological outcomes. However, it remains unknown whether pairing a session of cathodal tDCS with a session of anodal tDCS will also capitalise on its therapeutic effects. METHODS AND ANALYSIS: This will be a two-arm double-blind randomised controlled trial involving 134 patients 1-6 months after stroke onset. Eligible participants will be randomly allocated to receive 10 sessions of priming tDCS+robotic training, or 10 sessions of non-priming tDCS+robotic training for 2 weeks. The primary outcome is the Fugl-Meyer Assessment-upper extremity, and the secondary outcomes are the Wolf Motor Function Test and Modified Barthel Index. The motor-evoked potentials, regional oxyhaemoglobin level and resting-state functional connectivity between the bilateral M1 will be acquired and analysed to investigate the effects of priming tDCS on neuroplasticity. ETHICS AND DISSEMINATION: The study has been approved by the Research Ethics Committee of the Shanghai Yangzhi Rehabilitation Center (reference number: Yangzhi2023-022) and will be conducted in accordance with the Declaration of Helsinki of 1964, as revised in 2013. TRIAL REGISTRATION NUMBER: ChiCTR2300074681.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Recuperação de Função Fisiológica , China , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Extremidade Superior , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Plant cuticular wax forms a hydrophobic structure in the cuticle layer covering epidermis as the first barrier between plants and environments. Ammopiptanthus mongolicus, a leguminous desert shrub, exhibits high tolerances to multiple abiotic stress. The physiological, chemical, and transcriptomic analyses of epidermal permeability, cuticular wax metabolism and related gene expression profiles under osmotic stress in A. mongolicus leaves were performed. Physiological analyses revealed decreased leaf epidermal permeability under osmotic stress. Chemical analyses revealed saturated straight-chain alkanes as major components of leaf cuticular wax, and under osmotic stress, the contents of total wax and multiple alkane components significantly increased. Transcriptome analyses revealed the up-regulation of genes involved in biosynthesis of very-long-chain fatty acids and alkanes and wax transportation under osmotic stress. Weighted gene co-expression network analysis identified 17 modules and 6 hub genes related to wax accumulation, including 5 enzyme genes coding KCS, KCR, WAX2, FAR, and LACS, and an ABCG transporter gene. Our findings indicated that the leaf epidermal permeability of A. mongolicus decreased under osmotic stress to inhibit water loss via regulating the expression of wax-related enzyme and transporter genes, further promoting cuticular wax accumulation. This study provided new evidence for understanding the roles of cuticle lipids in abiotic stress tolerance of desert plants.
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Perfilação da Expressão Gênica , Folhas de Planta , Pressão Osmótica , Folhas de Planta/química , Água/metabolismo , Alcanos , Regulação da Expressão Gênica de PlantasRESUMO
Carbon fiber composites have great application prospects as a potential electromagnetic (EM) wave-absorbing material, yet it remains extremely challenging to integrate multiple functions of EM wave absorption, mechanical strength, thermal insulation, and flame retardancy. Herein, a novel carbon fiber reinforced C/SiOC aerogel (CF/CS) composite is successfully prepared by sol-gel impregnation combined with an ambient drying process for the first time. The density of the obtained CF/CS composites can be controlled just by changing sol-gel impregnation cycles (original carbon fiber felt (S0), and samples with one (S1) and two (S2) impregnation cycles are 0.249, 0.324, and 0.402 g cm-3, respectively), allowing for efficient tuning of their properties. Remarkably, S2 displays excellent microwave absorption properties, with an optimal reflection loss of -65.45 dB, which is significantly improved than S0 (-10.90 dB). Simultaneously, compared with S0 (0.75 and 0.30 MPa in the x/y and z directions), the mechanical performance of S2 is dramatically improved with a maximum compressive strength of 10.37 and 4.93 MPa in the x/y and z directions, respectively. Moreover, CF/CS composites show superior thermal insulation capability than S0 and obtain good flame-retardant properties. This work provides valuable guidance and inspiration for the development of multifunctional EM wave absorbers.
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Bovine diarrhea is a multi-factorial disease and remains one of the biggest health problems in animal husbandry. The endemic trends of the main pathogens responsible for bovine diarrhea in Inner Mongolia have not been analyzed systematically before. Therefore, the purpose of this study was to estimate the prevalence of bovine diarrhea pathogens found in the scattered households of Inner Mongolia in China. Additionally, we assessed for differences in the prevalence of infection based on age and region, as well as determined local prevalence rates and the rates of mixed infections. Using a two-stage random sampling strategy, 3,050 serum samples were collected from 72 bovine herds in 11 leagues and cities in Inner Mongolia, and the positive rates of BVDV, BRV, BCoV, K99, and Mycobacterium paratuberculosis (M. paratuberculosis) antibodies in the samples were detected by ELISA to determine the epidemic trends and epidemic differences of the five pathogens in Inner Mongolia. The positive rates of antibodies based on serum samples were: BVDV, 18.79% (95% CI [17.44-20.22]); BRV, 12.39% (95% CI [11.27-13.61]); BCoV, 12.82% (95% CI [11.68-14.05]); K99, 13.80% (95% CI [12.62-15.07]); and M. paratuberculosis, 10.79% (95% CI [9.74-11.94]). The prevalence rates of BRV, BCoV and K99 at 0-2 months were significantly different from that at 2-6 months, 6-18 months and adult cattle (P < 0.05). The prevalence of BVDV and M. paratuberculosis was the highest in adult cattle, which was significantly different from that in other age groups (P < 0.05). Furthermore, obvious regional epidemiological differences among the five diseases were observed. There was a mixed infection of BRV+BCoV in each age stage, the highest mixed infection being BVDV+BRV+K99 at 0-2 months of age. Our results showed that the cattle of scattered households in the Inner Mongolia of China were endemicly infected with several important cattle pathogens. Most of the pathogens studied occurred between 0-2 months of age and were mixed infections, which greatly influences the health of the cattle and leads to economic loss. These findings are of practical significance for the future prevention and control of bovine diarrhea in the Inner Mongolia or other regions of China.
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Doença das Mucosas por Vírus da Diarreia Viral Bovina , Coinfecção , Vírus da Diarreia Viral Bovina , Paratuberculose , Bovinos , Animais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/epidemiologia , Estudos Soroepidemiológicos , Anticorpos Antivirais , China/epidemiologia , Diarreia/epidemiologiaRESUMO
Reticulocalbin-1 (RCN1) is expressed aberrantly and at a high level in various tumors, including acute myeloid leukemia (AML), yet its impact on AML remains unclear. In this study, we demonstrate that RCN1 knockdown significantly suppresses the viability of bone marrow mononuclear cells (BMMNCs) from AML patients but does not affect the viability of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSCs) from healthy donors in vitro. Downregulation of RCN1 also reduces the viability of AML cell lines. Further studies showed that the RCN1 knockdown upregulates type I interferon (IFN-1) expression and promotes AML cell pyroptosis through caspase-1 and gasdermin D (GSDMD) signaling. Deletion of the mouse Rcn1 gene inhibits the viability of mouse AML cell lines but not the hematopoiesis of mouse bone marrow. In addition, RCN1 downregulation in human AML cells significantly inhibited tumor growth in the NSG mouse xenograft model. Taken together, our results suggest that RCN1 may be a potential target for AML therapy.
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Leucemia Mieloide Aguda , Piroptose , Humanos , Animais , Camundongos , Regulação para Baixo/genética , Piroptose/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Transdução de SinaisRESUMO
Aims: To summarize and clarify the current research status and indicate possible future directions in the field of autophagy in ischemic stroke, we performed a comprehensive and multidimensional bibliometric analysis of the literature in this field published from 2011 to 2022. Methods: We retrieved articles on the field of autophagy in ischemic stroke published between 2011 and 2022 from Web of Science Core Collection (WOSCC). VOSviewer (version 1.6.19) and CiteSpace (version 6.2.R2 Basic) were used to identify the leading topics as well as generate visual maps of Countries/regions, organizations, authors, journals, and keyword networks in the related field. Results: A total of 568 publications were contained in this research. The journal with the most publications were Front Pharmacol, Mol Neurobiol, and Neuroscience. China was the most productive country with respect to co-authorship, with the Capital Med Univ being the organization with the most. co-authorships. In terms of authorship analysis, eight of the top 10 most contributive authors were from China. The co-occurring author keywords can be divided into three main clusters, including "protective effect of autophagy in ischemic stroke," "autophagy-targeted therapy for ischemic stroke," and "mitochondrial function in cerebral ischemia-reperfusion injury". Conclusion: This bibliometric analysis helps us reveal the current research hotspots in the research field of autophagy in ischemic stroke and guide future research directions. Subsequent trends in this special field are likely to identify and develop novel autophagy-targeted therapy strategies to effectively prevent and treat ischemic stroke.
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Rapid alkalinization factor (RALF) is widespread throughout the plant kingdom and controls many aspects of plant life. Current studies on the regulatory mechanism underlying RALF function mainly focus on Arabidopsis, but little is known about the role of RALF in crop plants. Here, we systematically and comprehensively analyzed the relation between RALF family genes from five important crops and those in the model plant Arabidopsis thaliana. Simultaneously, we summarized the functions of RALFs in controlling growth and developmental behavior using conservative motifs as cues and predicted the regulatory role of RALFs in cereal crops. In conclusion, RALF has considerable application potential in improving crop yields and increasing economic benefits. Using gene editing technology or taking advantage of RALF as a hormone additive are effective way to amplify the role of RALF in crop plants.
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Inducing tumor-specific T cell responses and regulating suppressive tumor microenvironments have been a challenge for effective tumor therapy. CpG (ODN), the Toll-like receptor 9 agonist, has been widely used as adjuvants of cancer vaccines to induce T cell responses. We developed a novel adjuvant to improve the targeting of lymph nodes. CpG were modified with lipid and glycopolymers by the combination of photo-induced RAFT polymerization and click chemistry, and the novel adjuvant was termed as lipid-glycoadjuvant@AuNPs (LCpG). OVA protein was used as model antigen and melanoma model was established to test the immunotherapy effect of the adjuvant. In tumor model, the antitumor effect and mechanism of LCpG on the response of CTLs were examined by flow cytometry and cell cytotoxicity assay. The effects of LCpG on macrophage polarization and Tregs differentiation in tumor microenvironment were also studied by cell depletion assay and cytokine neutralization assay. We also tested the therapeutic effect of the combination of the adjuvant and anti-PD-1 treatment. LCpG could be rapidly transported to and retained longer in the lymphoid nodes than unmodified CpG. In melanoma model, LCpG controlled both primary tumor and its metastasis, and established long-term memory. In spleen and tumor draining lymphoid nodes, LCpG activated tumor-specific Tc1 responses, with increased CD8+ T-cell proliferation, antigen-specific Tc1 cytokine production and specific-tumor killing capacity. In tumor microenvironments, antigen-specific Tc1 induced by the LCpG promoted CTL infiltration, skewed tumor associated macrophages to M1 phenotype, regulated Treg and induced proinflammatory cytokines production in a CTL-derived IFN-γ-dependent manner. In vivo cell depletion and adoptive transfer experiments confirmed that antitumor activity of LCpG included vaccine was mainly dependent on CTL-derived IFN-γ. The anti-tumor efficacy of LCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. LCpG was a promising adjuvant for vaccine formulation which could augment tumor-specific Tc1 activity, and regulate tumor microenvironments.
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Vacinas Anticâncer , Melanoma , Nanopartículas Metálicas , Animais , Camundongos , Microambiente Tumoral , Interferon gama/metabolismo , Ouro/metabolismo , Ouro/farmacologia , Linfócitos T CD8-Positivos , Adjuvantes Imunológicos , Melanoma/metabolismo , Lipídeos/farmacologia , Camundongos Endogâmicos C57BLRESUMO
RNA editing is a post-transcriptional modification with a cell-specific manner and important biological implications. Although single-cell RNA-seq (scRNA-seq) is an effective method for studying cellular heterogeneity, it is difficult to detect and study RNA editing events from scRNA-seq data because of the low sequencing coverage. To overcome this, we develop a computational method to systematically identify RNA editing sites of cell types from scRNA-seq data. To demonstrate its effectiveness, we apply it to scRNA-seq data of human hematopoietic stem/progenitor cells (HSPCs) with an annotated lineage differentiation relationship according to previous research and study the impacts of RNA editing on hematopoiesis. The dynamic editing patterns reveal the relevance of RNA editing on different HSPCs. For example, four microRNA (miRNA) target sites on 3' UTR of EIF2AK2 are edited across all HSPC populations, which may abolish the miRNA-mediated inhibition of EIF2AK2. Elevated EIF2AK2 may thus activate the integrated stress response (ISR) pathway to initiate global translational attenuation as a protective mechanism to maintain cellular homeostasis during HSPCs' differentiation. Besides, our findings also indicate that RNA editing plays an essential role in the coordination of lineage commitment and self-renewal of hematopoietic stem cells (HSCs). Taken together, we demonstrate the capacity of scRNA-seq data to exploit RNA editing events of cell types, and find that RNA editing may exert multiple modules of regulation in hematopoietic processes.
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MicroRNAs , Análise da Expressão Gênica de Célula Única , Humanos , Análise de Célula Única/métodos , MicroRNAs/genética , Hematopoese/genética , Diferenciação Celular , Análise de Sequência de RNA/métodos , Regiões 3' não Traduzidas , Perfilação da Expressão Gênica/métodosRESUMO
Valuable piperidin-4-one derivatives were synthesized in excellent yields via an α-imino carbene-initiated cascade reaction involving 1,2-aryl/alkyl migration and annulation. The excellent selectivity of alkyl migration was attributed to the neighboring group participation of 2-bromoethyl. Features such as high efficiency, excellent migrating selectivity, broad substrate scope, and convenient one-pot procedure qualified this protocol as an effective tool for piperidine derivative synthesis. The product could be transformed to a bioactive molecule easily. The migration-annulation reaction of α-imino carbene provided a powerful strategy for heterocycle construction.
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PURPOSE: To investigate the efficiency and impact factors of anatomical intelligence for breast (AI-Breast) and hand-held ultrasound (HHUS) in lesion detection. METHODS: A total of 172 outpatient women were randomly selected, underwent AI-Breast ultrasound (Group AI) once and HHUS twice. HHUS was performed by breast imaging radiologists (Group A) and general radiologists (Group B). For the AI-Breast examination, a trained technician performed the whole-breast scan and data acquisition, while other general radiologists performed image interpretation. The examination time and lesion detection rate were recorded. The impact factors for breast lesion detection, including breast cup size, number of lesions, and benign or malignant lesions were analyzed. RESULTS: The detection rates of Group AI, A, and B were 92.8 ± 17.0%, 95.0 ± 13.6%, and 85.0 ± 22.9%, respectively. Comparable lesion detection rates were observed in Group AI and Group A (P > 0.05), but a significantly lower lesion detection rate was observed in Group B compared to the other two (both P < 0.05). Regarding missed diagnosis rates of malignant lesions, comparable performance was observed in Group AI, Group A, and Group B (8% vs. 4% vs. 14%, all P > 0.05). Scan times of Groups AI, A, and B were 262.15 ± 40.4 s, 237.5 ± 110.3 s, 281.2 ± 86.1 s, respectively. The scan time of Group AI was significantly higher than Group A (P < 0.01), but was slightly lower than Group B (P > 0.05). We found a strong linear correlation between scan time and cup size in Group AI (r = 0.745). No impacts of cup size and number of lesions were found on the lesion detection rate in Group AI (P > 0.05). CONCLUSIONS: With the assist of AI-Breast system, the lesion detection rate of AI-Breast ultrasound was comparable to that of a breast imaging radiologist and superior to that of the general radiologist. AI-Breast ultrasound may be used as a potential approach for breast lesions surveillance.
Assuntos
Neoplasias da Mama , Interpretação de Imagem Assistida por Computador , Feminino , Humanos , Sensibilidade e Especificidade , Interpretação de Imagem Assistida por Computador/métodos , Mama/diagnóstico por imagem , Mama/patologia , Ultrassonografia Mamária/métodos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologiaRESUMO
Migration of mesenchymal stem cells (MSCs) to the site of injury is crucial in transplantation therapy. Studies have shown that cell migration is regulated by the cellular microenvironment and accompanied by changes in cellular metabolism. However, limited information is available about the relationship between MSC migration and cellular metabolism. Here, we show that basic fibroblast growth factor (bFGF) promotes the migration of MSCs with high levels of glycolysis and high expression of hexokinase 2 (HK2), a rate-limiting enzyme in glycolysis. The enhancement of glycolysis via the activation of HK2 expression promoted the migration of MSCs, whereas the inhibition of glycolysis, but not of oxidative phosphorylation, inhibited the bFGF-induced migration of these cells. Furthermore, bFGF enhanced glycolysis by increasing HK2 expression, which consequently promoted ß-catenin accumulation, and the inhibition of glycolysis inhibited the bFGF-induced accumulation of ß-catenin. When the accumulation of glycolytic intermediates was altered, phosphoenolpyruvate was found to be directly involved in the regulation of ß-catenin expression and activation, suggesting that bFGF regulates ß-catenin signaling through glycolytic intermediates. Moreover, transplantation with HK2-overexpressing MSCs significantly improved the effect of cell therapy on skull injury in rats. In conclusion, we propose a novel glycolysis-dependent ß-catenin signaling regulatory mechanism and provide an experimental and theoretical basis for the clinical application of MSCs.