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Thermally activated delayed fluorescent (TADF) emitters have received great attention in organic light-emitting diodes and laser diodes because of high exciton utilization efficiency and low optical loss caused by triplets. However, the direct observation of lasing emission from nondoped TADF microcrystals has yet to be reported. Here, we demonstrated a three-color (green, yellow, and red) microlaser from three nondoped TADF microcrystals with well-controlled geometries. The temperature-dependent dynamic analyses testify that the regenerated singlets which originated from the reverse intersystem crossing process at room temperature are beneficial for population inversion and reduce triplet-absorption/annihilation optical loses, together resulting in thermally activated lasing actions. Thanks to single-crystalline structures of TADF emitters, the relationship between triplet-harvesting capability and the molecular structure was systematically investigated. The results not only offer rational design of pure TADF gain materials but also provide guidance for the high-performance electrically driven organic solid-state lasers and multicolor laser integration.
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Singlet fission (SF), the conversion of one high-energy singlet to two low-energy triplets, provides the potential to increase the efficiency of photovoltaic devices. In the SF chromophores with C2h symmetry, exemplified by polyenes, singlet-to-triplet conversion generally involves a low-lying 21Ag dark state, which serves as either a multiexciton (ME) intermediate to promote the SF process or a parasitic trap state to shunt excited-state populations via internal conversion. This controversial behavior calls for a deep understanding of dark-state-related photophysics involving the higher-lying singlet state. However, the optical "dark" and "transient" nature of these dark states and strong correlation feature of double exciton species make their characterization and interpretation challenging from both experimental and computational perspectives. In the present work combining transient spectroscopy and multireference electronic structure calculations (XDW-CASPT2), we addressed a new photophysical model, i.e., a high-lying 31Ag dark-state-mediated ultrafast SF process in the benzodipyrrolidone (BDPP) skeleton. Such a 31Ag dark state with distinctive double excitation character, described as the ME state, could be populated from the initial 11Bu bright state on an ultrafast time scale given the quasi-degeneracy and intersection of the two electronic states. Furthermore, the suitable optical band gap and triplet energy, high triplet yield, and excellent photostability render BDPP a promising SF candidate for photovoltaic devices. These results not only enrich the arsenal of SF materials but also shed new insights into the understanding of dark-state-related photophysics, which could promote the development of new SF-active materials.
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Control of excited-state dynamics is key in tuning room-temperature phosphorescence (RTP) and thermally activated delayed fluorescence (TADF) emissions but is challenging for organic luminescent materials (OLMs). We show the regulation of TADF and RTP emissions of a boron difluoride ß-acetylnaphthalene chelate (ßCBF2 ) by controlling the excited-state dynamics via its J- and H-aggregation states. Two crystalline polymorphs emitting green and red light have been controllably obtained. Although both monoclinic, the green and red crystals are dominated by J- and H-aggregation, respectively, owing to different molecular packing arrangements. J-aggregation significantly reduces the energy gap between the lowest singlet and triplet excited states for ultra-fast reverse intersystem crossing (RISC) and enhances the radiative singlet decay, together leading to TADF. The H-aggregation accelerates the ISC and suppresses the radiative singlet decay, helping to stabilize the triplet exciton for RTP.
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Fine particulate matter (PM2.5) airborne pollution increases the risk of chronic respiratory diseases, such as idiopathic pulmonary fibrosis (IPF), which is characterized by non-specific inflammation of the interstitial lung and extensive deposition of collagen fibers. Type 2 alveolar epithelial cells (AEC2s) are alveolar stem cells in the adult lung that contribute to the lung repair process through complex signaling. Our previous studies demonstrated that OGG1, a kind of DNA repair enzyme, have a critical role in protecting cells from oxidative damage and apoptosis induced by PM2.5, but the contribution of OGG1 in proliferation and self-renewal of AEC2s is not known. Here, we constructed OGG1-/-mice to test the effect and mechanism of OGG1 on PM2.5-induced pulmonary fibrosis and injury in vivo. We detected proliferation and self-renewal of OGG1 overexpression or OGG1 knockout AEC2s after PM2.5 injury by flow cytometry and clone formation. We observed that knockout of OGG1 aggravated pulmonary fibrosis, oxidative stress, and AEC2 cell death in PM2.5-injured mice. In addition, OGG1 is required for the proliferation and renewal of AEC2s after PM2.5 injury. Overexpression of OGG1 promotes the proliferation and self-renewal of AEC2s by inhibiting PM2.5-mediated oxidative stress and NF-κB signaling hyperactivation in vitro. Furthermore, NF-κB inhibitors promoted proliferation and self-renewal of OGG1-deficient AEC2s cells after PM2.5 injury, and attenuated PM2.5-induced pulmonary fibrosis and injury in mice. These data establish OGG1 as a regulator of NF-κB signal that serves to regulate AEC2 cell proliferation and self-renewal, and suggest a mechanism that inhibition of the NF-κB signaling pathway may represent a potential therapeutic strategy for IPF patients with low-expression of OGG1.
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Poluentes Atmosféricos/toxicidade , Células Epiteliais Alveolares/efeitos dos fármacos , Autorrenovação Celular/genética , DNA Glicosilases/metabolismo , Material Particulado/toxicidade , Fibrose Pulmonar/induzido quimicamente , Células-Tronco/efeitos dos fármacos , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , DNA Glicosilases/genética , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia , Transdução de Sinais , Células-Tronco/metabolismo , Células-Tronco/patologiaRESUMO
The aim of this paper was to investigate the effect of Schizonepetae Herba and Saposhnikoviae Radix(wind medicine) on the expression of AQP4 and AQP8 in colonic mucosa in rats with ulcerative colitis(UC). A total of 35 healthy SD male rats were randomly divided into normal group(gavaged with normal saline), DSS model group, as well as low, middle, and high dose wind medicine groups(Schizonepeta and Saposhnikovia 1â¶1, gavaged at dosages of 6, 12, and 24 g·kg~(-1)·d~(-1)), with 7 in each group. UC rat model was established by free drinking of 3% dextran sulphate sodium(DSS) solution for 10 days. At the end of the 10 th day after the treatment, mice were put to death to collect colonic mucosa. The length of colon was measured; the colonic mucosal injury index(CMDI) and pathological changes of colon were observed. ELISA method was used for measuring the content of serum IL-1, IL-8, and immunohistochemical method was used to measure AQP4, AQP8 protein expressions in colon mucosa. The expressions of AQP4, AQP8 mRNA were measured by Real-time PCR. As compared with the normal group, the length of colon tissue was significantly reduced(P<0.01), CMDI scores and pathological scores were significantly increased(P<0.01), the levels of serum IL-1 and IL-8 were significantly increased(P<0.05) in model group; the immunohistochemical results showed that the protein expressions of AQP4, AQP8 were lower; the color was light yellow or brown; AQP4, AQP8 mRNA expressions in colon mucosa were significantly decreased in model group(P<0.01). CMDI scores, pathological scores, and the levels of serum IL-1, IL-8 in high, middle, low dose wind medicine groups were obvious lower than those in the model group(P<0.01 or P<0.05); the protein expressions of AQP4, AQP8 were higher; the color was chocolate brown or dark brown; the length of colon tissue, and the expressions of AQP4, AQP8 mRNA were obvious higher in wind medicine groups(P<0.01 or P<0.05). Schizonepetae Herba and Saposhnikoviae Radix could significantly improve the symptoms and histopathology of UC model rats and accelerate the intestinal mucosal healing. The mechanism may be related with up-regulating the expression level of AQP4 and AQP8 in colonic mucosa.
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Apiaceae , Colite Ulcerativa , Animais , Aquaporina 4 , Colo , Mucosa Intestinal , Masculino , Camundongos , Raízes de Plantas , RatosRESUMO
BACKGROUND: Epigenetic regulation of oocyte-specific maternal factors is essential for oocyte and early embryonic development. KPNA7 is an oocyte-specific maternal factor, which controls transportation of nuclear proteins important for early embryonic development. To elucidate the epigenetic mechanisms involved in the controlled expression of KPNA7, both DNA methylation associated transcriptional silencing and microRNA (miRNA)-mediated mRNA degradation of KPNA7 were examined. RESULTS: Comparison of DNA methylation profiles at the proximal promoter of KPNA7 gene between oocyte and 6 different somatic tissues identified 3 oocyte-specific differentially methylated CpG sites. Expression of KPNA7 mRNA was reintroduced in bovine kidney-derived CCL2 cells after treatment with the methylation inhibitor, 5-aza-2'-deoxycytidine (5-Aza-CdR). Analysis of the promoter region of KPNA7 gene in CCL2 cells treated with 5-Aza-CdR showed a lighter methylation rate in all the CpG sites. Bioinformatic analysis predicted 4 miRNA-1296 binding sites in the coding region of KPNA7 mRNA. Ectopic co-expression of miRNA-1296 and KPNA7 in HEK293 cells led to reduced expression of KPNA7 protein. Quantitative real time PCR (RT-qPCR) analysis revealed that miRNA-1296 is expressed in oocytes and early stage embryos, and the expression reaches a peak level in 8-cell stage embryos, coincident with the time of embryonic genome activation and the start of declining of KPNA7 expression. CONCLUSIONS: These results suggest that DNA methylation may account for oocyte-specific expression of KPNA7, and miRNA-1296 targeting the coding region of KPNA7 is a potential mechanism for KPNA7 transcript degradation during the maternal-to-zygotic transition.
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Metilação de DNA , MicroRNAs/genética , Oócitos/crescimento & desenvolvimento , alfa Carioferinas/genética , Animais , Sítios de Ligação , Bovinos , Linhagem Celular , Desenvolvimento Embrionário , Epigênese Genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Células HEK293 , Humanos , Oócitos/química , Especificidade de Órgãos , Regiões Promotoras Genéticas , Estabilidade de RNA , RNA Mensageiro/química , alfa Carioferinas/químicaRESUMO
BACKGROUND: Although perioperative care during heart surgery has improved considerably, the rate of postoperative complications has remained stable. It has not been concluded how to better apply grip strength to clinical, postoperative complications. So our study aimed at researching the best way for using grip value for predicting early postoperative complications. METHODS: A total of 212 patients with mean age 63.8 ± 6.3 who underwent cardiac surgery participated in our study. We analyzed the ROC curve of grip strength, grip/weight and grip recovery with complications, found the best cutoff point. Logistic regression confirmed the association between grip strength grouping and complications. RESULTS: We found that 36 patients had 30-day complications. EuroSCORE were 2.15 ± 1.52 and 2.42 ± 1.58 between normal and complication groups, respectively. The area under the receiver-operating characteristic curve (AUC) of grip recovery take the most area (0.837, p < 0.001), and the cutoff point was 83.92%. In logistic regression, lower grip recovery has higher risk impact on 30-day complications for 25.68 times than normal group, after adjusted surgery-related factors. After regrouped characteristic information by grip recovery cutoff point, we found that percentage of the estimated 6 min walk distance (41.5 vs 48.3, p = 0.028) and hospitalization time (7.2 vs 6.1, p = 0.042) had worse trends in lower recovery group. CONCLUSIONS: Poor grip recovery may be related to higher risk of postoperative complications within 30 days after discharge in middle-aged and older people independent of surgical risk. The results of this study provide a reference for the development of rehabilitation programs in the early postoperative recovery, and may also be a prognostic indicator for postoperative high-risk groups. TRIAL REGISTRATION: Our research was registered on Research Registry website, the registry number was ChiCTR1800018465. Date: 2018/9/20. Status: Successful.
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Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Força da Mão , Alta do Paciente , Complicações Pós-Operatórias/etiologia , Fatores Etários , Idoso , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Projetos Piloto , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/fisiopatologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Reduced muscle strength, as measured by handgrip strength (HS), has been associated with an increased risk of cardiovascular disease (CVD). The aim of this study was to examine the association between different HS indexes and CVD risk factors in elderly Chinese individuals. We also determine optimal cutoffs of HS indexes for predicting CVD risk factors. METHODS: Data were obtained from 603 men and 789 women aged ≥60 years (average age 66.8 ± 6.4 y). These study participants were recruited in the suburb area of Tianjin, China. An individual was considered a patient when they exhibited any one of three CVD risk factors: diabetes mellitus, hypertension and dyslipidemia. All participants were interviewed face-to-face. In addition, serum samples were collected from all participants, and all participants underwent measures of anthropometry and HS. RESULTS: The optimal cutoffs were 0.376 of HS/weight in men and 0.726 of HS/body fat mass in women for predicting diabetes mellitus. The adjusted odds ratios (ORs) of at least one CVD risk factor for those with low muscle strength identified by HS/body fat mass were 2.14 (95% confidence interval [CI]: 1.53, 3.44; p < 0.001) in men and 2.32 (95% CI: 1.60, 3.29; p < 0.001) in women. CONCLUSION: HS/body fat mass appear to be the index best associated with CVD risk factors except diabetes mellitus in men. The optimal cutoffs of HS indexes have the potential to identify elderly adults at risk of CVD.
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Adiposidade , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Força da Mão , Hipertensão/epidemiologia , Idoso , Índice de Massa Corporal , Peso Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Vida Independente , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Fatores de Risco , População SuburbanaRESUMO
The aim of this paper was to screen the active targets of Schizonepetae Herba and Saposhnikoviae Radix in the treatment of ulcerative colitis by means of network pharmacology,and to investigate their mechanism of action. The effective components of Schizonepetae Herba and Saposhnikoviae Radix were screened out by traditional Chinese medicine systematic pharmacological( TCMSP)database,with oral bioavilability( OB) ≥30% and drug-like( DL) ≥18% selected as the thresholds. Target PPI network was built between the main components and their corresponding targets. One hundred and eighty-two human genes corresponding to the medicine target sites were obtained from Uniprot database; 3 874 genes corresponding to ulcerative colitis were obtained from Genecard database.A total of 115 intersection genes were screened from disease genes and medicine genes,and the PPI interaction analysis was conducted by using String tool. Disease-target PPI network was drawn by using Cytoscape software,and component-target-disease network was constructed. One hundred and eight nodes and 1 882 connections were found,and then Cytoscape software was used to merge the networks and filter the core network for gene GO function analysis and KEGG pathway enrichment analysis. The mechanism of Schizonepetae Herba and Saposhnikoviae Radix was then verified by animal experiment. Gene GO functional analysis suggested that biological process,molecular functions and cell components were involved,and it was found that ulcerative colitis might be related to transcription factor activity,and cytokine receptor binding,etc. Gene KEGG pathway enrichment analysis showed that the mechanism of ulcerative colitis might be associated with TNF and Toll-like receptors( TLRs) signaling pathway-mediated cytoinflammatory factors interleukin-1( IL-1) and interleukin-6( IL6). The possible mechanism of the effective components of Schizonepetae Herba and Saposhnikoviae Radix in treating ulcerative colitis might be related to intervening the cytokine receptor binding of TNF and TLRs signaling pathways,reducing the transcription of nuclear factor-kappaB( NF-κB),and inhibiting the secretion of intestinal inflammatory factors IL-1 and IL-6.
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Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Mapeamento de Interação de Proteínas , Animais , Apiaceae/química , Bases de Dados Genéticas , Humanos , Interleucinas/metabolismo , Lamiaceae/química , Medicina Tradicional Chinesa , Fitoterapia , Raízes de Plantas/química , Transdução de Sinais , Software , Receptores Toll-Like/metabolismoRESUMO
BACKGROUND: Assessment of the association of muscle strength and muscle mass with osteoporosis (OP) is of special interest as muscles are a potential target for interventions (i.e., strength training). METHODS: A cross-sectional descriptive study encompassing people aged ≥ 60 years (average age: 66.9 ± 6.2 years; men, n = 516; women, n = 652) in the Hangu area of Tianjin, China. The study populations were invited to participate in a comprehensive geriatric assessment. OS was identified by measuring the calcaneal using a quantitative ultrasound and a T score of less than -2.5. Muscle characteristics included grip strength and appendicular skeletal muscle mass (ASM). RESULTS: The prevalence of OS in this study was 61.6% (male 52.1%, female 69.1%). Grip strength was negatively related to OS and after adjusting for all other variables, higher grip strength was found to be associated with a lower OS risk (p = 0.023). ASM/height2 was not associated with OS (p = 0.205). CONCLUSION: Based on our study, muscle strength rather than muscle mass is negatively associated with OS in older people; thus, we should pay more attention to muscle strength training in the early stage of the OS.
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Força da Mão , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/fisiopatologia , Osteoporose/fisiopatologia , Idoso , China , Estudos Transversais , Feminino , Avaliação Geriátrica , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , PrevalênciaRESUMO
Even though stroke is the third, not the first, most common cause of disability-adjusted life years in developed countries, it is one of the most expensive to treat. Part of the expense is due to secondary problems in the post-stroke period including: cognition, memory, attention span, pain, sensation loss, psychological issues, and problems with mobility and balance. Research has identified that exercise has both positive physical and psychosocial effects for post-stroke patients. Therefore, this scientific statement provides an overview on exercise rehabilitation for post-stroke patients.We will use systematic literature reviews, clinical and epidemiology reports, published morbidity and mortality studies, clinical and public health guidelines, patient files, and authoritative statements to support this overview.Evidence clearly supports the use of various kinds of exercise training (e.g., aerobic, strength, flexibility, neuromuscular, and traditional Chinese exercise) for stroke survivors. Aerobic exercise, the main form of cardiac rehabilitation, may play an important role in improving aerobic fitness, cardiovascular fitness, cognitive abilities, walking speed and endurance, balance, quality of life, mobility, and other health outcomes among stroke patients. Strength exercise, included in national stroke guidelines and recommended for general health promotion for stroke survivors, can lead to improvements in functionality, psychosocial aspects, and quality of life for post-stroke patients. Flexibility exercises can relieve muscle spasticity problems, improve motor function, range of motion, and prevent contractures. Stretching exercises can also prevent joint contractures, muscle shortening, decrease spasticity, reduce joint stiffness and improve a post-stroke patient's overall function. Neuromuscular exercises can improve activities of daily living (ADL) through coordination and balance activities. Traditional Chinese exercises are used to improve walking and balance ability as well as increase muscle strength, which is important for post-stroke patients.The present evidence strongly supports the power of exercise for post-stroke patients, which in this study combined aerobic exercises, strength training, flexibility exercises, neuromuscular exercises, and traditional Chinese exercises. This research can encourage post-stroke survivors to consider the importance of exercise in the rehabilitation process.
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Terapia por Exercício/métodos , Exercício Físico/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Atividades Cotidianas , Cognição/fisiologia , Humanos , Força Muscular/fisiologia , Qualidade de Vida , Caminhada/fisiologiaRESUMO
miR-203 act as tumor repressor by inhibiting cell proliferation and is repressed in a variety of human tumors, although the molecular mechanisms responsible have not been elucidated. Here, we reveal that miR-203 is regulated by E2F1, an important transcription factor that can induce cell proliferation by controlling cell cycle progression. We found that miR-203 expression was induced by cisplatin, which also induced E2F1 protein accumulation in esophageal squamous cell carcinoma (ESCC) cell lines. miR-203 expression was elevated upon activation of ectopic E2F1, whereas this induction was abolished when the E2F1 gene was silenced. Moreover, with luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays, we demonstrated that E2F1 transactivates miR-203 by directly binding to the miR-203 gene promoter. In addition, we found that miR-203 inhibited cell proliferation by inducing G1/S cell cycle arrest, but not apoptosis, in ESCC cell lines. Finally, we observed that miR-203 negatively inhibited the expression of CDK6, subsequently decreasing E2F1 expression possibly through Rb phosphorylation. Taken together, our data show that cancer-related miR-203 is a novel transcriptional target of E2F1 and that it regulates cell cycle arrest by participating in a feedback loop with E2F1.
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Carcinoma de Células Escamosas/metabolismo , Pontos de Checagem do Ciclo Celular , Proliferação de Células/genética , Fator de Transcrição E2F1/metabolismo , Neoplasias Esofágicas/metabolismo , MicroRNAs/metabolismo , Apoptose/fisiologia , Carcinoma de Células Escamosas/genética , Pontos de Checagem do Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Fator de Transcrição E2F1/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , MicroRNAs/genéticaRESUMO
OBJECTIVE: To determine if transit time for excretion of gadoxetate into major bile ducts and duodenum correlates with clinical models of hepatocellular function. METHODS: This retrospective research was approved by the Institutional Review Board with waiver of informed consent. Search of the radiology database from January 1, 2013 to March 4, 2014 revealed 84 patients with chronic liver disease (65 males, mean age 47 years). Eighteen control subjects with no known liver disease or risk factors were also enrolled for analysis (9 males, mean age 43 years). MRI was performed with hepatobiliary phases at 10, 15, 20, and 25 min after injection of 0.025 mmol/kg of gadoxetate (Primovist, Bayer HealthCare, Shanghai, China). The time of excreted contrast appearing in the biliary tree and in the duodenum was recorded. Linear trend analysis was performed to determine the relationship between excretion time and hepatic function. RESULTS: The patient cohort was stratified by Child-Pugh classification (A, B, and C with n = 53, 27, and 4, respectively). Arrival of gadoxetate in the gall bladder at 10-min hepatobiliary phase was seen in 87% of control group and 45% of Child-Pugh A group (p = 0.02). There was no difference between these groups for later hepatobiliary phases. The arrival of biliary contrast in the right hepatic duct, common bile duct, and gall bladder were significantly earlier in the Child-Pugh A group compared to the Child-Pugh B/C group at all hepatobiliary phases after 10 min (p < 0.05). Linear trend analysis showed that biliary transit times were significantly delayed with worsening liver function (p = 0.01). There was no difference in entry time of gadoxetate into the duodenum between the normal, Child-Pugh A, and Child-Pugh B/C groups. CONCLUSIONS: The transit time for gadoxetate to appear in extrahepatic duct is a reasonable indicator of liver function, and may be included in radiology reports. The appearance in the duodenum, however, may depend on factors other than liver function, such as the physiology of the gallbladder and sphincter of Oddi.
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Meios de Contraste/farmacocinética , Gadolínio DTPA/farmacocinética , Hepatócitos/patologia , Fígado/fisiopatologia , Imageamento por Ressonância Magnética , Adolescente , Adulto , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
Nuclear proteins are required for the initiation of transcription in early embryos before embryonic genome activation. The regulated transport of nuclear proteins is mediated by factors known as importins (karyopherins). Kpna7, a newly discovered member of the importin α family, is critical for early development in mammals. In this study, we characterize rainbow trout Kpna7. The cDNA for rainbow trout Kpna7 encodes a 519 amino acid protein that contains a conserved importin ß binding (IBB) domain and seven armadillo/beta-catenin-like repeat (ARM) motifs. Reverse-transcriptase PCR and Western blot analyses revealed that Kpna7 is specifically expressed in eggs/ovary. Real-time PCR analysis demonstrated that expression of Kpna7 mRNA is high in unfertilized eggs, gradually decreases in early-stage embryos until 3 days post-fertilization, and declines sharply thereafter, reaching a level that is barely detectable in 4-day-old embryos. Using a yeast two-hybrid screening system, we identified two Kpna7-interacting proteins from a rainbow trout egg cDNA library: Stl3 (rhamnose-binding lectin 3) and an uncharacterized protein. Both genes appear to be expressed specifically in eggs/testis. Co-immunoprecipitation assays confirmed the interaction between Kpna7 and Stl3, and co-transfection experiments using EGFP-tagged Stl3 showed that Kpna7 facilitates the nuclear transport of Stl3 through an interaction with the predicted nuclear-localization signal cluster at the carboxy-terminus of Stl3. Our data suggest that Kpna7 may function in early embryonic development as a unique nuclear transporter for egg-specific proteins.
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Núcleo Celular/metabolismo , Proteínas de Peixes/metabolismo , Lectinas/metabolismo , Oncorhynchus mykiss/embriologia , Óvulo/metabolismo , alfa Carioferinas/metabolismo , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Western Blotting , DNA Complementar/genética , Feminino , Imunoprecipitação , Masculino , Oncorhynchus mykiss/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testículo/metabolismo , Técnicas do Sistema de Duplo-Híbrido , alfa Carioferinas/genéticaRESUMO
BACKGROUND: The serine/threonine kinase 11 (STK11) gene is the main causal gene in Peutz-Jeghers syndrome (PJS). Abnormal STK11 may increase cancer risk of PJS patients via affecting its target proteins such as P53, AMPK, and PTEN. In this study, we investigated the molecular basis of six Chinese PJS patients. MATERIALS AND METHODS: Blood samples were collected from four Chinese PJS families and two sporadic patients. The entire coding region of the STK11 gene was amplified by polymerase chain reaction and analyzed by direct sequencing. Functions of mutants were assessed by PolyPhen-2, Swiss-Model software, and luciferase reporter assay. RESULTS: Novel mutations (c.842_843insC, c.804_805insG, and c.922T>G) and recurrent mutations (c.526G>A, c.180C>G, and c.1062C>G) were identified. Missense mutation c.922T>G and c.526G>A were predicted as probably damaging by PolyPhen-2, while c.1062C>G was benign. Mutation c.108C>G was a nonsense mutation. The 284Ter mutants of c.842_843insC and c.804_805insG significantly diminished the capacity of P53 activity in 293FT cells. CONCLUSIONS: Our results support that STK11 gene mutations underlie Chinese patients with PJS. Mutation involving partial kinase domain disrupts normal function of STK11. Our results also enlarge the spectrum of STK11 variants in PJS patients.
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Síndrome de Peutz-Jeghers/genética , Proteínas Serina-Treonina Quinases/genética , Quinases Proteína-Quinases Ativadas por AMP , Adolescente , Povo Asiático , China , Análise Mutacional de DNA , Feminino , Variação Genética , Humanos , Masculino , Adulto JovemRESUMO
UNLABELLED: Pachyonychia congenita (PC), a rare autosomal dominant disorder characterized by hypertrophic nail dystrophy, is classified into two main clinical subtypes: PC-1 and PC-2. PC-1 is associated with mutations in the KRT6A or KRT16 genes, whereas PC-2 is linked to KRT6B or KRT17 mutations. Blood samples were collected from three generations of a new Chinese PC-1 family, including three PC patients and five unaffected family members. A novel missense mutation p.Leu128Pro (c.383T>C) was identified in a highly conserved helix motif in domain 1A of K16. The disease haplotype carried the mutation and cosegregated with the affection status. PolyPhen2 and SIFTS analysis rated the substitution as probably damaging; Swiss-Model analysis indicated that the structure of the mutant protein contained an unnormal α-helix. Overexpression of mutant protein in cultured cells led to abnormal cell morphology. CONCLUSION: The wider spectrum of KRT16 mutations suggests that changes in codons 125, 127, and 132 are most commonly responsible for PC-1 and that proline substitution mutations at codons 127 or 128 may produce more severe disease. This study extends the KRT16 mutation spectrum and adds new information on the clinical and genetic diversity of PC.
Assuntos
Povo Asiático/genética , Queratina-16/genética , Ceratodermia Palmar e Plantar Difusa/genética , Mutação de Sentido Incorreto , Paquioníquia Congênita/genética , Papiloma/genética , Adulto , Pré-Escolar , Feminino , Humanos , Masculino , Linhagem , FenótipoRESUMO
This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.
Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa , Metotrexato/administração & dosagem , Sulfassalazina/administração & dosagem , Ocidente , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , China , Esquema de Medicação , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Metotrexato/efeitos adversos , Indução de Remissão , Método Simples-Cego , Sulfassalazina/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Rectal cancer (RC) is a globally prevalent malignant tumor, presenting significant challenges in its management and treatment. Currently, magnetic resonance imaging (MRI) offers superior soft tissue contrast and radiation-free effects for RC patients, making it the most widely used and effective detection method. In early screening, radiologists rely on patients' medical radiology characteristics and their extensive clinical experience for diagnosis. However, diagnostic accuracy may be hindered by factors such as limited expertise, visual fatigue, and image clarity issues, resulting in misdiagnosis or missed diagnosis. Moreover, the distribution of surrounding organs in RC is extensive with some organs having similar shapes to the tumor but unclear boundaries; these complexities greatly impede doctors' ability to diagnose RC accurately. With recent advancements in artificial intelligence, machine learning techniques like deep learning (DL) have demonstrated immense potential and broad prospects in medical image analysis. The emergence of this approach has significantly enhanced research capabilities in medical image classification, detection, and segmentation fields with particular emphasis on medical image segmentation. This review aims to discuss the developmental process of DL segmentation algorithms along with their application progress in lesion segmentation from MRI images of RC to provide theoretical guidance and support for further advancements in this field.
RESUMO
OBJECTIVE: To understand the cognition for insomnia and preference for acupuncture in breast cancer survivors based on the in-depth interview. METHODS: Thirty breast cancer survivors with insomnia symptoms were collected for in-depth interview. The interview questions included three aspects, i.e. sleep expectation, cognition for insomnia (discomfort caused by insomnia, and underlying inducing factors of insomnia) and the preference for acupuncture (treatment methods used in the past, the reasons for not choosing acupuncture, and the tendency of acupuncture treatment). Using Colaizzi content analysis method, the data was analyzed. RESULTS: Regarding sleep expectation, most breast cancer survivors with insomnia symptoms were able to maintain normal activity in daytime. Insomnia symptoms often led to fatigue, and the inducing factors of insomnia referred to the treatment with endocrine therapy, anticipatory anxiety and inadequate sleep hygiene. All of the patients had received pharmacotherapy. The use proportion of non-pharmacological therapies was relatively low, and acupuncture was not chosen due to "not familiar with" and "fear of pain". Concerning to the preference for acupuncture, patients preferred the therapeutic methods of acupuncture with mild pain sensation and gentle stimulation; and the treatment should be more acceptable if delivered 2 or 3 times a week. CONCLUSION: Breast cancer survivors have the expectations for sleep, and are willing to receive the treatment with medication for their sleep disorders. Because of lack of the knowledge for acupuncture effect on insomnia and fear of strong needling sensation, a part of patients are unwilling to be treated with acupuncture therapy, but they are expected to receive the treatment with acupuncture while feeling more comfortable.
Assuntos
Terapia por Acupuntura , Neoplasias da Mama , Sobreviventes de Câncer , Cognição , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Distúrbios do Início e da Manutenção do Sono/etiologia , Distúrbios do Início e da Manutenção do Sono/psicologia , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/complicações , Neoplasias da Mama/psicologia , Pessoa de Meia-Idade , Adulto , Sobreviventes de Câncer/psicologia , Idoso , Sono , Preferência do PacienteRESUMO
OBJECTIVES: To evaluate the outcomes of adjuvant radiotherapy in patients with esophageal cancer (EC) who underwent esophagectomy following neoadjuvant chemoradiotherapy (NCRT). METHODS: The data of EC patients who received adjuvant therapy after NCRT between 2004 to 2019 was retrieved from the SEER database. The patients were split into the adjuvant radiotherapy with or without chemotherapy (RT±CT) and the adjuvant chemotherapy (CT) groups. The process of propensity score matching (PSM) was employed. RESULTS: Following PSM, 157 patients in total were recruited in each treatment group. There were no significant variations in either overall survival (OS) or cancer-specific survival (CSS) between the RT±CT and CT groups (median OS: 28 months versus. 51 months, p=0.063; median CSS: 31 months versus. 52 months, p=0.16). Within the CT group, patients with ypI/II or cI/II tumor stage, positive lymph node ratio (LNR) ≤0.1, and tumor size ≥50 mm (p<0.05) had higher OS compared to the RT±CT groups. Among patients with cT3-4 tumors in N-stage downstaging group, the OS and CSS were significantly greater for those underwent RT±CT as opposed to the CT group (5-year OS:56.6% versus 19.4%, p=0.042; 5-year CSS:67.9% versus. 19.4%, p=0.023). Multivariate Cox regression analysis identified the tumor histology grade as an independent prognostic factor of OS and CSS. CONCLUSION: Radiotherapy-based adjuvant therapy does not significantly improve the prognosis of EC patients after NCRT, although it may provide a survival benefit for patients with cT3-4 tumors in N-stage downstaging.