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1.
BMC Med ; 19(1): 243, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34641873

RESUMO

BACKGROUND: Plasma cell-free DNA (cfDNA) methylation has shown promising results in the early detection of multiple cancers recently. Here, we conducted a study to investigate the performance of cfDNA methylation in the early detection of esophageal cancer (ESCA). METHODS: Specific methylation markers for ESCA were identified and optimized based on esophageal tumor and paired adjacent tissues (n = 24). Age-matched participants with ESCA (n = 85), benign esophageal diseases (n = 10), and healthy controls (n = 125) were randomized into the training and test sets to develop a classifier to differentiate ESCA from healthy controls and benign esophageal disease. The classifier was further validated in an independent plasma cohort of ESCA patients (n = 83) and healthy controls (n = 98). RESULTS: In total, 921 differentially methylated regions (DMRs) between tumor and adjacent tissues were identified. The early detection classifier based on those DMRs was first developed and tested in plasma samples, discriminating ESCA patients from benign and healthy controls with a sensitivity of 76.2% (60.5-87.9%) and a specificity of 94.1% (85.7-98.4%) in the test set. The performance of the classifier was consistent irrespective of sex, age, and pathological diagnosis (P > 0.05). In the independent plasma validation cohort, similar performance was observed with a sensitivity of 74.7% (64.0-83.6%) and a specificity of 95.9% (89.9-98.9%). Sensitivity for stage 0-II was 58.8% (44.2-72.4%). CONCLUSION: We demonstrated that the cfDNA methylation patterns could distinguish ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Further prospective evaluation of the classifier in the early detection of ESCAs in high-risk individuals is warranted.

2.
mBio ; : e0137221, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34634929

RESUMO

Interleukin6 (IL-6) is a key driver of hyperinflammation in COVID-19, and its level strongly correlates with disease progression. To investigate whether variability in COVID-19 severity partially results from differential IL-6 expression, functional single-nucleotide polymorphisms (SNPs) of IL-6 were determined in Chinese COVID-19 patients with mild or severe illness. An Asian-common IL-6 haplotype defined by promoter SNP rs1800796 and intronic SNPs rs1524107 and rs2066992 correlated with COVID-19 severity. Homozygote carriers of C-T-T variant haplotype were at lower risk of developing severe symptoms (odds ratio, 0.256; 95% confidence interval, 0.088 to 0.739; P = 0.007). This protective haplotype was associated with lower levels of IL-6 and its antisense long noncoding RNA IL-6-AS1 by cis-expression quantitative trait loci analysis. The differences in expression resulted from the disturbance of stimulus-dependent bidirectional transcription of the IL-6/IL-6-AS1 locus by the polymorphisms. The protective rs2066992-T allele disrupted a conserved CTCF-binding locus at the enhancer elements of IL-6-AS1, which transcribed antisense to IL-6 and induces IL-6 expression in inflammatory responses. As a result, carriers of the protective allele had significantly reduced IL-6-AS1 expression and attenuated IL-6 induction in response to acute inflammatory stimuli and viral infection. Intriguingly, this low-producing variant that is endemic to present-day Asia was found in early humans who had inhabited mainland Asia since ∼40,000 years ago but not in other ancient humans, such as Neanderthals and Denisovans. The present study suggests that an individual's IL-6 genotype underlies COVID-19 outcome and may be used to guide IL-6 blockade therapy in Asian patients. IMPORTANCE Overproduction of cytokine interleukin-6 (IL-6) is a hallmark of severe COVID-19 and is believed to play a critical role in exacerbating the excessive inflammatory response. Polymorphisms in IL-6 account for the variability of IL-6 expression and disparities in infectious diseases, but its contribution to the clinical presentation of COVID-19 has not been reported. Here, we investigated IL-6 polymorphisms in severe and mild cases of COVID-19 in a Chinese population. The variant haplotype C-T-T, represented by rs1800796, rs1524107, and rs2066992 at the IL-6 locus, was reduced in patients with severe illness; in contrast, carriers of the wild-type haplotype G-C-G had higher risk of severe illness. Mechanistically, the protective variant haplotype lost CTCF binding at the IL-6 intron and responded poorly to inflammatory stimuli, which may protect the carriers from hyperinflammation in response to acute SARS-CoV-2 infection. These results point out the possibility that IL-6 genotypes underlie the differential viral virulence during the outbreak of COVID-19. The risk loci we identified may serve as a genetic marker to screen high-risk COVID-19 patients.

3.
Opt Express ; 29(16): 25327-25336, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34614865

RESUMO

We proposed an adaptive incremental method for the cumulative strain estimation in phase-sensitive optical coherence elastography. The method firstly counts the amount of phase noise points by mapping a binary noise map. After the noise threshold value is preset, the interframe interval is adaptively adjusted in terms of the phase noise ratio. Finally, the efficient estimation of cumulative strain is implemented by reducing the cumulative number. Since the level of phase noise is related to the different strain rates in accordance with the speckle decorrelation, the proposed method can estimate the large strains with high computation efficiency as well as signal-to-noise ratio (SNR) enhancement in nonlinear change of sample deformations. Real experiments of visualizing polymerization shrinkage with nonlinear change of deformations were performed to prove the superiority of adaptive incremental method in estimating the large strains. The proposed method expands the practicability of the incremental method in more complex scenes.

4.
Appl Opt ; 60(25): 7574-7580, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613223

RESUMO

Three types of alumina surface irradiated by laser are simulated in this study to investigate stray light ablation. Results indicate that temperature fields of triangular and rectangular microstructures exhibit the "head effect," while overall still exhibit Gaussian distributions. For the stress, there is a notable difference between the microstructure surface and the ideal surface. The most stress concentration occurs at the corners on the microstructure surface termed as the "bottom effect." The maximum tensile stress of a triangular microstructure appears below the midline of the slope. The location of the maximum tensile stress on the triangle first shifts down and then up. The inflection point is 0.9 µm in height of the triangle.

5.
Environ Monit Assess ; 193(9): 568, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34386879

RESUMO

The level, source, and risk of toxic elements in traditional agricultural soils are particularly crucial for the sustainable development of agriculture. An important agricultural production base was selected, a total of 251 topsoil samples were collected, eight toxic elements (As, Cd, Cr, Cu, Hg, Ni, Pb, Zn) in soil were analyzed, and environmental and health risk assessments were conducted. Results showed that all concentrations of eight elements in soil samples were lower than the risk screening values with negligible pollution risk. Approximately 83.8% of Hg in soil was originated from atmospheric deposition related to industrial emissions, 53.2% of Cd was derived from direct industrial activities, and the other elements came from soil parent materials or agricultural activities. Accumulation risk of As in agricultural products, potential ecological risk from Cd, and As's ingestion risk and Cr's dermal contact risk should be paid more attention. More stricter monitoring and coping countermeasures and strategies should be established to ensure the sustainable development of agriculture.


Assuntos
Metais Pesados , Poluentes do Solo , Adaptação Psicológica , Agricultura , China , Monitoramento Ambiental , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
6.
World J Surg Oncol ; 19(1): 234, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34364369

RESUMO

BACKGROUND: To avoid the inconvenience of triangulation among various rigid operating instruments in mediastinoscopy-assisted esophagectomy, we invented a new technique: used a flexible endoscope to mobilize thoracic esophagus and dissected mediastinal lymph nodes through the left cervical incision. This technology has not been reported so far. In this study, we introduce our long-term experience and demonstrate this new technique. METHODS: Twenty-nine patients with early esophageal cancer underwent mediastinoscopy-assisted esophagectomy in our hospital from June 2018 to September 2020. Among them, 12 patients used flexible mediastinoscopy, and 17 patients used conventional rigid mediastinoscopy and instruments to observe their therapeutic effect. RESULTS: There were no significant differences between the two groups in gender, average age, body mass index, incidence of adverse reactions, bleeding volume, and postoperative hospital stay. The operation time of flexible mediastinoscopy group was significantly shorter than that of rigid mediastinoscopy group (192.9 ± 13.0 vs 246.8 ± 6.9 min, p < 0.01). The number of lymph nodes removed by flexible endoscopy was significantly more than that of rigid endoscopy (8.5 ± 0.6 vs 6.0 ± 0.3, P < 0.01). Postoperative follow-up was completed for all patients, and the average follow-up time was 11.6 ± 7.2 months. During the follow-up period, no recurrence or death was observed. CONCLUSIONS: Mediastinoscopy-assisted esophagectomy is an effective way to treat early esophageal cancer. The application of flexible mediastinoscopy provides more convenience and better stability. It can facilitate the operation of the surgeon and lymph node dissection, which proved to be a feasible technology.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Neoplasias Esofágicas/cirurgia , Humanos , Excisão de Linfonodo , Mediastinoscopia , Recidiva Local de Neoplasia , Prognóstico , Tecnologia
7.
Med Image Anal ; 74: 102205, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34425317

RESUMO

With the global outbreak of COVID-19 in early 2020, rapid diagnosis of COVID-19 has become the urgent need to control the spread of the epidemic. In clinical settings, lung infection segmentation from computed tomography (CT) images can provide vital information for the quantification and diagnosis of COVID-19. However, accurate infection segmentation is a challenging task due to (i) the low boundary contrast between infections and the surroundings, (ii) large variations of infection regions, and, most importantly, (iii) the shortage of large-scale annotated data. To address these issues, we propose a novel two-stage cross-domain transfer learning framework for the accurate segmentation of COVID-19 lung infections from CT images. Our framework consists of two major technical innovations, including an effective infection segmentation deep learning model, called nCoVSegNet, and a novel two-stage transfer learning strategy. Specifically, our nCoVSegNet conducts effective infection segmentation by taking advantage of attention-aware feature fusion and large receptive fields, aiming to resolve the issues related to low boundary contrast and large infection variations. To alleviate the shortage of the data, the nCoVSegNet is pre-trained using a two-stage cross-domain transfer learning strategy, which makes full use of the knowledge from natural images (i.e., ImageNet) and medical images (i.e., LIDC-IDRI) to boost the final training on CT images with COVID-19 infections. Extensive experiments demonstrate that our framework achieves superior segmentation accuracy and outperforms the cutting-edge models, both quantitatively and qualitatively.

8.
Theranostics ; 11(16): 7658-7670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335956

RESUMO

SNAI1 is widely regarded as a master driver of epithelial-mesenchymal transition (EMT) and associated with breast cancer progression and metastasis. This pro-malignant role is strongly linked to posttranslational modification, especially phosphorylation, which controls its protein levels and subcellular localization. While multiple kinases are implicated in regulation of SNAI1 stability, the precise mechanism by which SNAI1 is stabilized in tumors remains to be fully elucidated. Methods: A series of in vitro and in vivo experiments were conducted to reveal the regulation of SNAI1 by Serine/Threonine Kinase 39 (STK39) and the role of STK39 in breast cancer metastasis. Results: We identified STK39, a member of Stem 20-like serine/threonine kinase family, as a novel posttranslational regulator that enhances the stability of SNAI1. Inhibition of STK39 via knockdown or use of a specific inhibitor resulted in SNAI1 destabilization. Mechanistically, STK39 interacted with and phosphorylated SNAI1 at T203, which is critical for its nuclear retention. Functionally, STK39 inhibition markedly impaired the EMT phenotype and decreased tumor cell migration, invasion, and metastasis both in vitro and in vivo. These effects were rescued by ectopic SNAI1 expression. In addition, depletion of STK39 dramatically enhanced sensitivity to chemotherapeutic agents. Conclusions: Our study demonstrated that STK39 is a key mediator of SNAI1 stability and is associated with the pro-metastatic cellular process, highlighting the STK39-SNAI1 signaling axis as promising therapeutic targets for treatments of metastatic breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Transcrição da Família Snail/metabolismo , Animais , Neoplasias da Mama/fisiopatologia , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Camundongos , Camundongos SCID , Invasividade Neoplásica/genética , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição/metabolismo
9.
Sci Rep ; 11(1): 14398, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34257323

RESUMO

Inaccurate egocentric distance and speed perception are two main explanations for the high accident rate associated with driving in foggy weather. The effect of foggy weather on speed has been well studied. However, its effect on egocentric distance perception is poorly understood. The paradigm for measuring perceived egocentric distance in previous studies was verbal estimation instead of a nonverbal paradigm. In the current research, a nonverbal paradigm, the visual matching task, was used. Our results from the nonverbal task revealed a robust foggy effect on egocentric distance. Observers overestimated the egocentric distance in foggy weather compared to in clear weather. The higher the concentration of fog, the more serious the overestimation. This effect of fog on egocentric distance was not limited to a certain distance range but was maintained in action space and vista space. Our findings confirm the foggy effect with a nonverbal paradigm and reveal that people may perceive egocentric distance more "accurately" in foggy weather than when it is measured with a verbal estimation task.

10.
Stem Cell Res Ther ; 12(1): 391, 2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256842

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) have to be expanded in vitro to reach a sufficient cell dose for the treatment of various diseases. During the process of expansion, some obstacles remain to be overcome. The purpose of this study was to investigate the effects of storage solutions and heterogeneity on the behavior of MSCs in vitro and in vivo. METHODS: Umbilical cord MSCs (UC-MSCs) of similar sizes within normal ranges were suspended in three different storage solutions, phosphate buffer solution, normal saline, and Dulbecco's modified Eagle medium. Then, the ultrastructure, viability, and safety of these cells were compared. Other two UC-MSC populations of different sizes were categorized based on their mean diameters. The ultrastructure, proliferation, immunosuppression, hepatic differentiation potential, and number of senescent cells were investigated and compared. The survival rates of mice after the infusion of UC-MSCs of different sizes were compared. RESULTS: For UC-MSCs suspended in different storage solutions, the cell apoptosis rates, ultrastructure, and survival rates of mice were similar, and no differences were observed. Cells with a diameter of 19.14 ± 4.89 µm were categorized as the larger UC-MSC population, and cells with a diameter of 15.58 ± 3.81 µm were categorized as the smaller population. The mean diameter of the larger UC-MSC population was significantly larger than that of the smaller UC-MSC population (p < 0.01). Smaller UC-MSCs had more powerful proliferation and immunosuppressive potential and a higher nucleus-cytoplasm ratio than those of large UC-MSCs. The number of cells positive for ß-galactosidase staining was higher in the larger UC-MSC population than in the smaller UC-MSC population. The survival rates of mice receiving 1 × 106 or 2 × 106 smaller UC-MSCs were 100%, both of which were higher than those of mice receiving the same amounts of larger UC-MSCs (p < 0.01). The cause of mouse death was explored and it was found that some larger UC-MSCs accumulated in the pulmonary capillary in dead mice. CONCLUSION: Different storage solutions showed no significant effects on cell behavior, whereas heterogeneity was quite prevalent in MSC populations and might limit cells application. Hence, it is necessary to establish a more precise standardization for culture-expanded MSCs.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Apoptose , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Camundongos , Cordão Umbilical
11.
Br J Psychol ; 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34159589

RESUMO

Reward has a significant impact on behaviour and perception. Most past work in associative reward learning has used perceptually distinct visual cues to associate with different reward values. Thus, it remains unknown to what extent the learned bias towards reward-associated stimuli depends on consciousness of the apparent differences between stimuli. Here, we resolved this issue by using an inter-ocular suppression paradigm with the monetary rewarding and non-rewarding cues identical to each other except for their eye-of-origin information. Thus, the reward coding system cannot rely on consciousness to select the reward-associated cue. Surprisingly, the targets in the rewarded eye broke into awareness faster than those in the non-rewarded eye. We further revealed that producing this effect required both top-down attention and inter-ocular suppression. These findings suggest that the human's reward coding system can produce two different types of reward-based learning. One is independent of consciousness yet fairly consuming attentional resources. The other one results from volitional selection of stimuli of behavioural significance.

12.
Medicine (Baltimore) ; 100(19): e25358, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106587

RESUMO

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH), which ranks only second to viral hepatitis and poses an increasingly serious challenge to global public health and economy. NAFLD has attracted more and more attention, but there is no drugs with exact curative effects are available. The commonly used drugs for the treatment of NAFLD in clinical practice are statins, such drugs, inevitably increase the burden on the live. Compared to statins, traditional Chinese medicines are believed to be "all natural" with fewer side effects, are associated with strong patient compliance. Accordingly, a great deal of clinical studies have shown that Xuefu Zhuyu decoction (XFZYD) can significantly improve the clinical symptoms and enhance the therapeutic effect. Meanwhile, a system review and meta-analysis are conducted by us to further clarify the effectiveness and safety of XFZYD for NAFLD. METHODS: We will apply to database mainly range from the English literature searches Cochrane Library, PubMed, excerpt medica database, and Web of Science to the Chinese literature China national knowledge infrastructure, Chinese biomedical literature database, VIP, and Wanfang database, randomized controlled trials (RCTs) are enrolled to evaluate the effectiveness and safety of XFZYD in the treatment of NAFLD, the enrollment of RCTs is from the establishment of the database to February 01, 2021. Simultaneously we will retrieval clinical registration tests and grey literatures. The 2 researchers worked independently on literature selection, data extraction, and quality assessment. The dichotomous data is expressed in terms of relative risk, the continuous is represented by mean difference or standard mean difference, whether there is heterogeneity is the factor that determines the synthesis of data in fixed effect model or random effect model. Alanine aminotransferase (ALT) or Aspartic acid aminotransferase (AST) coupled with Glutamyltransferase (GGT) is considered as one of the main indicators of the NAFLD, while the pathology, imaging and diagnosis of metabolic syndrome are also auxiliary results. The last, meta-analysis was conducted by RevMan software version 5.3. RESULTS: This study will provide evidence for treatment of NAFLD with XFZYD in terms of effectiveness and safety. CONCLUSION: This systematic review aims to confirm the efficacy and safety of XFZYD in the treatment of NAFLD. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/7CWRK.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Humanos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34162313

RESUMO

The paper presents the results of the study on the transport systems in metropolises by stating the interdisciplinary problems and prospects of applying the environmental and economic approach to the optimization of transport communication in megacities. The main problems of transport communications in large cities have been considered. The world experience in managing transport systems is analyzed. Priority directions for the implementation of environmental and economic tasks of transport industry management using the economic and mathematical approach have been established. It has been established that the performance indicators of the functioning of the megalopolis transport system depend on the work of the service provider. The most effective solution is to ensure that vehicles are working properly, that the vehicles are fully loaded and that they are on schedule. Performance indicators of the functioning of the megalopolis transport system on the part of the consumer of services: the coefficient of determination was 0.9493, the static probability p = 0.2067 standard deviation was 7.9428, the variance did not exceed 0.1015. The correlation of actual and planned results exceeded r2>0.7051; and was described by the equation y = 1.6746 + 0.844x. Logistic models for performance improvement of the transportation system were offered.


Assuntos
Comunicação , Meio Ambiente , Transportes/economia , Cidades , Modelos Teóricos
14.
Artigo em Inglês | MEDLINE | ID: mdl-33979017

RESUMO

Li-CO2 batteries are regarded as next-generation high-energy-density electrochemical devices. However, the greatest challenge arises from the formation of the discharge product, Li2 CO3 , which would accumulate and deactivate heterogenous catalysts to cause huge polarization. Herein, Ru(bpy)3 Cl2 was employed as a solution-phase catalyst for Li-CO2 batteries and proved to be the most effective one screened so far. Spectroscopy and electrochemical analyses elucidate that the RuII center could interact with both CO2 and amorphous Li2 C2 O4 intermediate, thus promoting electroreduction process and delaying carbonate transformation. As a result, the charge potential is reduced to 3.86 V and over 60 discharge/charge cycles are achieved with a fixed capacity of 1000 mAh g-1 at a current density of 300 mA g-1 . Our work provides a new avenue to improve the electrochemical performance of Li-CO2 batteries with efficient mobile catalysts.

15.
J Control Release ; 335: 1-20, 2021 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-33991600

RESUMO

Multidrug resistance (MDR) of cancer is a persistent problem in chemotherapy. Scientists have considered the overexpressed efflux transporters responsible for MDR and chemotherapy failure. MDR extremely limits the therapeutic effect of chemotherapy in cancer treatment. Many strategies have been applied to solve this problem. Multifunctional nanoparticles may be one of the most promising approaches to reverse MDR of tumor. These nanoparticles can keep stability in the blood circulation and selectively accumulated in the tumor microenvironment (TME) either by passive or active targeting. The stimuli-sensitive or organelle-targeting nanoparticles can release the drug at the targeted-site without exposure to normal tissues. In order to better understand reversal of MDR, three main strategies are concluded in this review. First strategy is the synergistic effect of chemotherapeutic drugs and ABC transporter inhibitors. Through directly inhibiting overexpressed ABC transporters, chemotherapeutic drugs can enter into resistant cells without being efflux. Second strategy is based on nanoparticles circumventing over-expressed efflux transporters and directly targeting resistance-related organelles. Third approach is the combination of multiple therapy modes overcoming cancer resistance. At last, numerous researches demonstrated cancer stem-like cells (CSCs) had a deep relation with drug resistance. Here, we discuss two different drug delivery approaches of nanomedicine based on CSC therapy.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Nanomedicina , Neoplasias/tratamento farmacológico , Microambiente Tumoral
16.
Sci China Life Sci ; 64(8): 1236-1280, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33893979

RESUMO

Evolutionary developmental biology, or Evo-Devo for short, has become an established field that, broadly speaking, seeks to understand how changes in development drive major transitions and innovation in organismal evolution. It does so via integrating the principles and methods of many subdisciplines of biology. Although we have gained unprecedented knowledge from the studies on model organisms in the past decades, many fundamental and crucially essential processes remain a mystery. Considering the tremendous biodiversity of our planet, the current model organisms seem insufficient for us to understand the evolutionary and physiological processes of life and its adaptation to exterior environments. The currently increasing genomic data and the recently available gene-editing tools make it possible to extend our studies to non-model organisms. In this review, we review the recent work on the regulatory signaling of developmental and regeneration processes, environmental adaptation, and evolutionary mechanisms using both the existing model animals such as zebrafish and Drosophila, and the emerging nonstandard model organisms including amphioxus, ascidian, ciliates, single-celled phytoplankton, and marine nematode. In addition, the challenging questions and new directions in these systems are outlined as well.

17.
Int J Mol Sci ; 22(9)2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33919240

RESUMO

Tunicates include diverse species, as they are model animals for evolutionary developmental biology study. The embryonic development of tunicates is known to be extensively regulated by transcription factors (TFs). Styela clava, the globally distributed invasive tunicate, exhibits a strong capacity for environmental adaptation. However, the TFs were not systematically identified and analyzed. In this study, we reported 553 TFs categorized into 60 families from S. clava, based on the whole genome data. Comparison of TFs analysis among the tunicate species revealed that the gene number in the zinc finger superfamily displayed the most significant discrepancy, indicating this family was under the highly evolutionary selection and might be related to species differentiation and environmental adaptation. The greatest number of TFs was discovered in the Cys2His2-type zinc finger protein (zf-C2H2) family in S. clava. From the point of temporal view, more than half the TFs were expressed at the early embryonic stage. The expression correlation analysis revealed the existence of a transition for TFs expression from early embryogenesis to the later larval development in S. clava. Eight Hox genes were identified to be located on one chromosome, exhibiting different arrangement and expression patterns, compared to Ciona robusta (C. intestinalis type A). In addition, a total of 23 forkhead box (fox) genes were identified in S. clava, and their expression profiles referred to their potential roles in neurodevelopment and sensory organ development. Our data, thus, provides crucial clues to the potential functions of TFs in development and environmental adaptation in the leathery sea squirt.


Assuntos
Regulação da Expressão Gênica , Fatores de Transcrição/genética , Urocordados/metabolismo , Animais , Perfilação da Expressão Gênica , Análise de Sequência de RNA , Urocordados/genética
18.
BMC Womens Health ; 21(1): 167, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879147

RESUMO

BACKGROUND: Catamenial pneumothorax is characterized by spontaneous recurring pneumothorax during menstruation, which is a common clinical manifestation of thoracic endometriosis syndrome. There are still controversies about its pathogenesis. CASE PRESENTATION: A 43-year-old woman with a history of endometriosis came to our hospital due to recurring pneumothorax during menstruation. Uniportal Video-assisted Thoracoscopic Surgery (VATS) exploration was performed on the eve of menstruating. We thoroughly explored the diaphragm, visceral and parietal pleura: The lung surface was scattered with yellowish-brown implants; no bullae were found; multiple diaphragmatic defects were found on the dome. And surprisingly, we caught a fascinating phenomenon: Bubbles were slipping into pleural cavity through diaphragmatic defects. We excised the diaphragmatic lesions and wedge resected the right upper lung lesion; cleared the deposits and flushed the thoracic cavity with pure iodophor. Diaphragmatic lesions confirmed the presence of endometriosis, and interestingly enough, microscopically, endometrial cells were shedding with impending menses. After a series of intraoperative operations and postoperative endocrine therapy, the disease did not recur after a period of follow-up. CONCLUSION: We have witnessed the typical signs of catamenial pneumothorax at the accurate timing: Not only observed the process of gas migration macroscopically, but also obtained pathological evidence of diaphragmatic periodic perforation microscopically, which is especially precious and confirms the existing theory that retrograde menstruation leads to diaphragmatic endometriosis, and the diaphragmatic fenestration is obtained due to the periodic activities of ectopic endometrium.


Assuntos
Endometriose , Pneumotórax , Adulto , Endometriose/complicações , Endometriose/cirurgia , Feminino , Humanos , Menstruação , Pneumotórax/etiologia , Pneumotórax/cirurgia , Cirurgia Torácica Vídeoassistida
19.
Mol Biotechnol ; 63(7): 613-620, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33880702

RESUMO

MicroRNAs (miRNAs) regulate multicellular processes and diverse signaling pathways in organisms. The detection of the spatiotemporal expression of miRNA in vivo is crucial for uncovering the function of miRNA. However, most of the current detecting techniques cannot reflect the dynamics of miRNA sensitively in vivo. Here, we constructed a miRNA-induced CRISPR-Cas9 platform (MICR) used in marine chordate Ciona. The key component of MICR is a pre-single guide RNA (sgRNA) flanked by miRNA-binding sites that can be released by RNA-induced silencing complex (RISC) cleavage to form functional sgRNA in the presence of complementary miRNA. By using the miRNA-inducible CRISPR-on system (MICR-ON), we successfully detected the dynamic expression of a miRNA csa-miR-4018a during development of Ciona embryo. The detected patterns were validated to be consistent with the results by in situ hybridization. It is worth noting that the expression of csa-miR-4018a was examined by MICR-ON to be present in additional tissues, where no obvious signaling was detected by in situ hybridization, suggesting that the MICR-ON might be a more sensitive approach to detect miRNA signal in living animal. Thus, MICR-ON was demonstrated to be a sensitive and highly efficient approach for monitoring the dynamics of expression of miRNA in vivo and will facilitate the exploration of miRNA functions in biological systems.

20.
Aging (Albany NY) ; 13(8): 11470-11490, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33864447

RESUMO

BACKGROUNDS: A major side effect of statin, a widely used drug to treat hyperlipidemia, is skeletal myopathy through cell apoptosis. The aim of this study is to investigate the roles of microRNA in statin-induced injury. METHODS: Apolipoprotein E knockout (ApoE-/-) mice were administered with simvastatin (20 mg/kg/day) for 8 weeks. Exercise capacity was evaluated by hanging grid test, forelimb grip strength, and running tolerance test. RESULTS: In cultured skeletal muscle cells, statin increased the levels of miR-1a but decreased the levels of mitogen-activated protein kinase kinase kinase 1 (MAP3K1) in a time or dose dependent manner. Both computational target-scan analysis and luciferase gene reporter assay indicated that MAP3K1 is the target gene of miR-1a. Statin induced cell apoptosis of skeletal muscle cells, but abolished by downregulating of miR-1a or upregulation of MAP3K1. Further, the effects of miR-1a inhibition on statin-induced cell apoptosis were ablated by MAP3K1 siRNA. In ApoE-/- mice, statin induced cell apoptosis of skeletal muscle cells and decreased exercise capacity in mice infected with vector, but not in mice with lentivirus-mediated miR-1a gene silence. CONCLUSION: Statin causes skeletal injury through induction of miR-1a excessive expression to decrease MAP3K1 gene expression.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , MAP Quinase Quinase Quinase 1/genética , MicroRNAs/metabolismo , Fibras Musculares Esqueléticas/patologia , Doenças Musculares/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hiperlipidemias/tratamento farmacológico , Camundongos , Camundongos Knockout para ApoE , MicroRNAs/agonistas , MicroRNAs/antagonistas & inibidores , Fibras Musculares Esqueléticas/efeitos dos fármacos , Doenças Musculares/diagnóstico , Doenças Musculares/genética , Doenças Musculares/patologia , Condicionamento Físico Animal , Cultura Primária de Células , RNA Interferente Pequeno/metabolismo , Sinvastatina/efeitos adversos , Regulação para Cima/efeitos dos fármacos
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