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1.
Carbohydr Polym ; 276: 118730, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34823766

RESUMO

Achyranthes bidentata is a traditional Chinese medicine used to treat osteoporosis. AB90, a crude saccharide from A. bidentata, showed excellent osteoprotective effects in ovariectomized rats, and ABW90-1, an oligosaccharide purified from AB90, stimulated significant differentiation of osteoblasts. However, the osteogenic effects and underlying mechanisms of ABW90-1 have remained unknown. In the present study, we found that ABW90-1 significantly promoted ALP activity, mineralization, and the expression of osteogenic markers in MC3T3-E1 cells. ABW90-1 showed strong binding with the WNT signaling complex and BMP2 based on number of interactions, hydrogen bond length, and binding energy in silico. ABW90-1 significantly increased the expression of active-ß-catenin, p-GSK-3ß, LEF-1, BMP2, and p-SMAD1. Importantly, the osteogenic effects of ABW90-1 were partially suppressed by DKK-1 and Noggin, which are specific inhibitors of the WNT and BMP signaling pathways, respectively. Collectively, these findings suggest that ABW90-1 has osteogenic effects through crosstalk between WNT/ß-catenin and BMP2/SMAD1 signaling pathways.

2.
Viruses ; 13(12)2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34960691

RESUMO

Dear Professor Remi N. Charrel and Professor Jerome Depaquit, we thank you for your interest in our research and for your kind suggestions [...].

3.
Neuroimage ; 245: 118685, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34740794

RESUMO

Pain perception varies widely among individuals due to the varying degrees of biological, psychological, and social factors. Notably, sex differences in pain sensitivity have been consistently observed in various experimental and clinical investigations. However, the neuropsychological mechanism underlying sex differences in pain sensitivity remains unclear. To address this issue, we quantified pain sensitivity (i.e., pain threshold and tolerance) using the cold pressure test and negative emotions (i.e., pain-related fear, pain-related anxiety, trait anxiety, and depression) using well-established questionnaires and collected magnetic resonance imaging (MRI) data (i.e., high-resolution T1 structural images and resting-state functional images) from 450 healthy subjects. We observed that, as compared to males, females exhibited lower pain threshold and tolerance. Notably, sex differences in pain sensitivity were mediated by pain-related fear and anxiety. Specifically, pain-related fear and anxiety were the complementary mediators of the relationship between sex and pain threshold, and they were the indirect-only mediators of the relationship between sex and pain tolerance. Besides, structural MRI data revealed that the amygdala subnuclei (i.e., the lateral and basal nuclei in the left hemisphere) volumes were the complementary mediators of the relationship between sex and pain-related fear, which further influenced pain sensitivity. Altogether, our results provided a comprehensive picture of how negative emotions (especially pain-related negative emotions) and related brain structures (especially the amygdala) contribute to sex differences in pain sensitivity. These results deepen our understanding of the neuropsychological underpinnings of sex differences in pain sensitivity, which is important to tailor a personalized method for treating pain according to sex and the level of pain-related negative emotions for patients with painful conditions.

4.
Front Cell Infect Microbiol ; 11: 739496, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778103

RESUMO

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06-0.12 µg/ml), posaconazole (0.06-0.12 µg/ml), amphotericin B (0.25-1 µg/ml), and 5-flucytosine (range, <0.06-0.12 µg/ml), whereas four isolates showed high MICs (≥4 µg/ml) for echinocandins. Strains with high MIC values for azoles showed common ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.


Assuntos
Antifúngicos , Farmacorresistência Fúngica , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida , Humanos , Testes de Sensibilidade Microbiana , Saccharomycetales
5.
Plant Sci ; 313: 111070, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34763863

RESUMO

R-loops, consisting of a DNA:RNA hybrid and a single-stranded DNA (ssDNA), form naturally as functional chromosome structures and are crucial in many vital biological processes. However, disrupted R-loop homeostasis will threat to the integrity and stability of genome. As the endonuclease, RNase H1 can efficiently recognize and remove excess R-loops to protect organisms from DNA damage induced by R-loop over-accumulation. Here, we investigated the function of RNase H1 in Physcomitrium (Physcomitrella) patens to illustrate its important role in the evolution of plants. We found that PpRNH1A dysfunction seriously affected shoot growth and branch formation in P. patens, revealing a noticeable functional difference between PpRNH1A and AtRNH1A of Arabidopsis. Furthermore, auxin signaling was significantly affected at the transcriptional level in PpRNH1A mutant plants, as a result of the accumulation of R-loops at several auxin-related genes. This study provides evidence that PpRNH1A regulates the development of P. patens by controlling R-loop formation at specific loci to modulate the transcription of auxin-related genes. It also highlights the interspecific functional differences between early land plants and vascular plants, despite crucial and conserved role of RNase H1 played in maintaining R-loop homeostasis.


Assuntos
Bryopsida/crescimento & desenvolvimento , Bryopsida/genética , Diferenciação Celular/genética , Ácidos Indolacéticos/metabolismo , Brotos de Planta/crescimento & desenvolvimento , Brotos de Planta/genética , Ribonuclease H/genética , Diferenciação Celular/fisiologia
6.
Mol Plant ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619328

RESUMO

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-mediated gene editing is revolutionizing plant research and crop breeding. Here, we present an effective and streamlined pipeline for arrayed CRISPR library construction and demonstrate it is suitable for small- to large-scale genome editing in plants. This pipeline introduces artificial PCR fragment-length markers for distinguishing guide RNAs (gRNAs) (FLASH), and a group of 12 constructs harboring different FLASH tags are co-transformed into plants each time. The identities of gRNAs in Agrobacterium mixtures and transgenic plants can therefore be read out by detecting the FLASH tags, a process that requires only conventional PCR and gel electrophoresis rather than sequencing. We generated an arrayed CRISPR library targeting all 1,072 members of the receptor-like kinase (RLK) family in rice. One-shot transformation generated a mutant population that covers gRNAs targeting 955 RLKs, and 74.3% (710/955) of the target genes had three or more independent T0 lines. Our results indicate that the FLASH tags act as bona fide surrogates for the gRNAs and are tightly (92.1%) associated with frameshift mutations in the target genes. In addition, the FLASH pipeline allows for rapid identification of unintended editing events without corresponding T-DNA integrations and generates high-order mutants of closely related RLK genes. Furthermore, we showed that the RLK mutant library enables rapid discovery of defense-related RLK genes. This study introduces an effective pipeline for arrayed CRISPR library construction and provides genome-wide rice RLK mutant resources for functional genomics.

7.
Opt Express ; 29(19): 30237-30243, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34614750

RESUMO

Optical properties of InGaN-based red LED structure, with a blue pre-well, are reported. Two emission peaks located at 445.1 nm (PB) and 617.9 nm (PR) are observed in the PL spectrum, which are induced by a low-In-content blue InGaN single quantum well (SQW) and the red InGaN double quantum wells (DQWs), respectively. The peak shift of PB with increase of excitation energy is very small, which reflects the built-in electric field of PB-related InGaN single QW is remarkably decreased, being attributed to the significant reduction of residual stress in the LED structure. On the other hand, the PR peak showed a larger shift with increase of excitation energy, due to both the screening of built-in electric field and the band filling effect. The electric field in the red wells is caused by the large lattice mismatch between high-In-content red-emitting InGaN and surrounding GaN. In addition, the anomalous temperature dependences of the PR peak are well elucidated by assuming that the red emission comes from quasi-QD structures with deep localized states. The deep localization suppresses efficiently the escape of carriers and then enhances the emission in the red, leading to high internal quantum efficiency (IQE) of 24.03%.

8.
Plant Cell Rep ; 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34694441

RESUMO

KEY MESSAGE: ipa1 enhances rice drought tolerance mainly through activating the ABA pathway. It endows rice seedlings with a more developed root system, smaller leaf stomata aperture, and enhanced carbon metabolism. Drought is a major abiotic stress to crop production. IPA1 (IDEAL PLANT ARCHITECTURE 1)/OsSPL14 encodes a transcription factor and has been reported to function in both rice ideal plant architecture and biotic resistance. Here, with a pair of IPA1 and ipa1-NILs (Near Iso-genic Lines), we found that ipa1 could significantly improve rice drought tolerance at seedling stage. The ipa1 plants had a better-developed root system and smaller leaf stomatal aperture. Analysis of carbon-nitrogen metabolism-associated enzyme activity, gene expression, and metabolic profile indicated that ipa1 could tip the carbon-nitrogen metabolism balance towards an increased carbon metabolism pattern. In both the control and PEG-treated conditions, ABA content in the ipa1 seedlings was significantly higher than that in the IPA1 seedlings. Expression of the ABA biosynthesis genes was detected to be up-regulated, whereas the expression of ABA catabolism genes was down-regulated in the ipa1 seedlings. In addition, based on yeast one-hybrid assay and dual-luciferase assay, IPA1 was found to directly activate the promoter activity of OsHOX12, a transcription factor promoting ABA biosynthesis, and OsNAC52, a positive regulator of the ABA pathway. The expression of OsHOX12 and OsNAC52 was significantly up-regulated in the ipa1 plants. Combined with the previous studies, our results suggested that ipa1 could improve rice seedling drought tolerance mainly through activating the ABA pathway and that regulation of the ipa1-mediated ABA pathway will be an important strategy for improving drought resistance of rice.

9.
Front Hum Neurosci ; 15: 681193, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34658812

RESUMO

Spatial memory is an important cognitive function for human daily life and may present dysfunction or decline due to aging or clinical diseases. Functional near-infrared spectroscopy neurofeedback (fNIRS-NFB) is a promising neuromodulation technique with several special advantages that can be used to improve human cognitive functions by manipulating the neural activity of targeted brain regions or networks. In this pilot study, we intended to test the feasibility of fNIRS-NFB to enhance human spatial memory ability. The lateral parietal cortex, an accessible cortical region in the posterior medial hippocampal-cortical network that plays a crucial role in human spatial memory processing, was selected as the potential feedback target. A placebo-controlled fNIRS-NFB experiment was conducted to instruct individuals to regulate the neural activity in this region or an irrelevant control region. Experimental results showed that individuals learned to up-regulate the neural activity in the region of interest successfully. A significant increase in spatial memory performance was found after 8-session neurofeedback training in the experimental group but not in the control group. Furthermore, neurofeedback-induced neural activation increase correlated with spatial memory improvement. In summary, this study preliminarily demonstrated the feasibility of fNIRS-NFB to improve human spatial memory and has important implications for further applications.

10.
Hepatology ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510484

RESUMO

BACKGROUND AND AIMS: Aging exacerbates liver neutrophil infiltration and alcohol-associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA-223 (miR-223), and their contribution to ALD pathogeneses. APPROACH AND RESULTS: Young and aged myeloid-specific Sirt1 knockout mice were subjected to chronic-plus-binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking who presented with acute intoxication were analyzed. Neutrophilic Sirt1 and miR-223 expression were down-regulated in aged mice compared with young mice. Deletion of the Sirt1 gene in myeloid cells including neutrophils exacerbated chronic-plus-binge ethanol-induced liver injury and inflammation and down-regulated neutrophilic miR-223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C/EBPα deacetylation by directly interacting with C/EBPα, a key transcription factor that controls miR-223 biogenesis, and subsequently elevated miR-223 expression in neutrophils. Importantly, down-regulation of SIRT1 and miR-223 expression was also observed in circulating neutrophils from middle-aged and elderly subjects compared with those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic SIRT1 expression in young and middle-aged patients, with a greater reduction in the latter group. The neutrophilic SIRT1 expression correlated with neutrophilic miR-223 and serum alanine transaminase levels in those patients. CONCLUSIONS: Aging increases the susceptibility of alcohol-induced liver injury in mice and humans through the down-regulation of the neutrophilic SIRT1-C/EBPα-miR-223 axis, which could be a therapeutic target for the prevention and/or treatment of ALD.

11.
Angew Chem Int Ed Engl ; 60(47): 25013-25019, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34523206

RESUMO

We present a coral-like FeP composite with FeP nanoparticles anchored and dispersed on a nitrogen-doped 3D carbon framework (FeP@NC). Due to the highly continuous N-doped carbon framework and a spring-buffering graphitized carbon layer around the FeP nanoparticle, a sodium-ion battery with the FeP@NC composite exhibits an ultra-stable cycling performance at 10 A g-1 with a capacity retention of 82.0 % in 10 000 cycles. Also, particle refinement leads to a capacity increase during cycling. The FeP nanoparticles go through a refining-recombination process during the first cycle and present a global refining trend after dozens of cycles, which results in a gradually increase in graphitization degree and interface magnetization, and further provides more active sites for Na+ storage and contributes to a rising capacity with cycling. The capacity ascending phenomenon can also extend to lithium-ion batteries.

12.
Microorganisms ; 9(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34361971

RESUMO

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been used in the field of clinical microbiology since 2010. Compared with the traditional technique of biochemical identification, MALDI-TOF MS has many advantages, including convenience, speed, accuracy, and low cost. The accuracy and speed of identification using MALDI-TOF MS have been increasing with the development of sample preparation, database enrichment, and algorithm optimization. MALDI-TOF MS has shown promising results in identifying cultured colonies and rapidly detecting samples. MALDI-TOF MS has critical research applications for the rapid detection of highly virulent and drug-resistant pathogens. Here we present a scientific review that evaluates the performance of MALDI-TOF MS in identifying clinical pathogenic microorganisms. MALDI-TOF MS is a promising tool in identifying clinical microorganisms, although some aspects still require improvement.

13.
Signal Transduct Target Ther ; 6(1): 304, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404759

RESUMO

A comprehensive analysis of the humoral immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in understanding COVID-19 pathogenesis and developing antibody-based diagnostics and therapy. In this work, we performed a longitudinal analysis of antibody responses to SARS-CoV-2 proteins in 104 serum samples from 49 critical COVID-19 patients using a peptide-based SARS-CoV-2 proteome microarray. Our data show that the binding epitopes of IgM and IgG antibodies differ across SARS-CoV-2 proteins and even within the same protein. Moreover, most IgM and IgG epitopes are located within nonstructural proteins (nsps), which are critical in inactivating the host's innate immune response and enabling SARS-CoV-2 replication, transcription, and polyprotein processing. IgM antibodies are associated with a good prognosis and target nsp3 and nsp5 proteases, whereas IgG antibodies are associated with high mortality and target structural proteins (Nucleocapsid, Spike, ORF3a). The epitopes targeted by antibodies in patients with a high mortality rate were further validated using an independent serum cohort (n = 56) and using global correlation mapping analysis with the clinical variables that are associated with COVID-19 severity. Our data provide fundamental insight into humoral immunity during SARS-CoV-2 infection. SARS-CoV-2 immunogenic epitopes identified in this work could also help direct antibody-based COVID-19 treatment and triage patients.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , Imunidade Humoral , SARS-CoV-2/imunologia , Proteínas não Estruturais Virais/imunologia , COVID-19/mortalidade , Estado Terminal , Intervalo Livre de Doença , Epitopos/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Masculino , Análise Serial de Proteínas , Taxa de Sobrevida
14.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3222-3227, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396740

RESUMO

The present study analyzed the current Chinese medicinal health products and Chinese patent medicines effective in boosting memory,aiming at providing references for the formulation and development of memory-boosting health products. The information on memory-boosting health products published by the Department of Special Food Safety Supervision and Management,the State Administration for Market Regulation( SAMR) was collected and the Chinese patent medicines on DRUGDATAEXPY were searched. Microsoft Excel and the TCMISS were used to statistically analyze the characteristics of formulations. A total of 212 memory-boosting health products were obtained from SAMR,including 83 ones containing Chinese medicinal materials. Twelve Chinese herbal medicines showed a usage frequency ≥ 8,with 151 times in use. In DRUGDATAEXPY,258 similar Chinese patent medicines were collected.Twelve Chinese herbal medicines showed a usage frequency ≥ 58,with 907 times in use. Through unsupervised hierarchical entropybased clustering of the above-mentioned Chinese medicinal health products and Chinese patent medicines separately,5 and 12 new formulas were obtained. The selection of Chinese herbal medicines for the new formulas was consistent with the principles of traditional Chinese medicine( TCM) theories,i. e.,tonifying kidney and marrow,benefiting Qi,nourishing Yin,resolving phlegm,and eliminating stasis. According to TCM theories,syndrome differentiation of the users was conducted,and the formulas were designed following the correspondence of syndromes with formulas and Chinese herbal medicines. This study is expected to provide new ideas and methods for the development of Chinese medicinal health products and accurately guide practical applications to exert the advantages of TCM in health care based on syndrome differentiation and improve the effect of Chinese medicinal health products.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos sem Prescrição , China , Humanos , Medicina Tradicional Chinesa , Síndrome
15.
Zhongguo Zhong Yao Za Zhi ; 46(13): 3234-3239, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34396742

RESUMO

This study summarized and analyzed the current acne-relieving Chinese medicinal health products and Chinese patent medicines,aiming at providing references for the formulation and development of acne-relieving health products. The information on acne-relieving health products published by the Department of Special Food Safety Supervision and Management,the State Administration for Market Regulation( SAMR) was retrieved,and the Chinese patent medicines on DRUGDATAEXPY were searched. Microsoft Excel and the Traditional Chinese Medicine Inheritance Support System V2. 5( TCMISS) were employed to statistically analyze the characteristics of formulations. Forty-three acne-relieving health products were obtained,including 40 ones containing Chinese herbal medicines. Six Chinese herbal medicines showed a usage frequency ≥8,with 61 times in use totally,including Salviae Miltiorrhizae Radix et Rhizoma( 13),Lonicerae Japonicae Flos( 12),Taraxaci Herba( 11),ALOE( 9),Carthami Flos( 8),and Rhei Radix et Rhizoma( 8). A total of 29 Chinese patent medicines with similar efficacy were collected in DRUGDATAEXPY. Nine Chinese herbal medicines showed a usage frequency ≥6,with 63 times in use,including Rhei Radix et Rhizoma( 10),Glycyrrhizae Radix et Rhizoma( 8),Scutellariae Radix( 8),Lonicerae Japonicae Flos( 7),Angelicae Sinensis Radix( 6),Paeoniae Radix Rubra( 6),Astragali Radix( 6),Paeoniae Radix Alba( 6),and Gardeniae Fructus( 6). Through unsupervised hierarchical entropy-based clustering of the above-mentioned Chinese medicinal health products and Chinese patent medicines,five and three new formulas were obtained,respectively. The selection of Chinese herbal medicines was consistent with the principles of traditional Chinese medicine( TCM) theories in relieving acne,i. e.,dispelling exterior wind,ventilating lungs,clearing heat,dissipating mass,promoting diuresis,relaxing bowels,removing toxin,activating blood,resolving stasis,eliminating phlegm,and regulating Qi. According to the " lung governing skin and body hair" and " interior-exterior relationship between lung and large intestine" in TCM theories,the idea that acne could be treated by relieving constipation was proposed,which provided new methods and references for the research and development of Chinese medicinal health products.


Assuntos
Acne Vulgar , Medicamentos de Ervas Chinesas , Acne Vulgar/tratamento farmacológico , China , Glycyrrhiza , Humanos , Medicina Tradicional Chinesa , Medicamentos sem Prescrição
16.
Front Neuroinform ; 15: 683735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335218

RESUMO

Independent component analysis (ICA) is a multivariate approach that has been widely used in analyzing brain imaging data. In the field of functional near-infrared spectroscopy (fNIRS), its promising effectiveness has been shown in both removing noise and extracting neuronal activity-related sources. The application of ICA remains challenging due to its complexity in usage, and an easy-to-use toolbox dedicated to ICA processing is still lacking in the fNIRS community. In this study, we propose NIRS-ICA, an open-source MATLAB toolbox to ease the difficulty of ICA application for fNIRS studies. NIRS-ICA incorporates commonly used ICA algorithms for source separation, user-friendly GUI, and quantitative evaluation metrics assisting source selection, which facilitate both removing noise and extracting neuronal activity-related sources. The options used in the processing can also be reported easily, which promotes using ICA in a more reproducible way. The proposed toolbox is validated and demonstrated based on both simulative and real fNIRS datasets. We expect the release of the toolbox will extent the application for ICA in the fNIRS community.

17.
Front Mol Biosci ; 8: 698975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307458

RESUMO

Renal ischemia/reperfusion (I/R), a major cause of acute kidney injury (AKI), is a serious clinical event in patients during post-renal transplantation. I/R is associated with renal dysfunction and tubular apoptosis, and calcium (Ca2+) overload has been reported to be a crucial factor on tubular apoptosis in I/R injury (IRI). The canonical transient receptor potential channel 6 (TRPC6), a type of non-selective Ca2+ channel, is involved in many renal diseases. Our earlier study identified that TRPC6-mediated Ca2+ influx plays a novel role in suppressing cytoprotective autophagy triggered by oxidative stress in primary tubular epithelial cells (TECs). This study explored the potential beneficial impact of TRPC6 knockout (TRPC6-/-) and the relevant cellular mechanisms against I/R-induced AKI in mice. Measuring changes of renal function, apoptotic index, and autophagy in mouse kidneys that suffered 24 h reperfusion after 40 min ischemia and working in vitro with TECs that suffered 24 h reoxygenation after 24 h hypoxia, we found that 1) IRI tissues had increased TRPC6 expression and TRPC6 knockout significantly ameliorated renal damage induced by IRI; 2) TRPC6 knockout enhanced the level of autophagy and alleviated the depolarization of mitochondrial membrane potential (ψm, MMP) and apoptotic changes upon IRI; and 3) IRI tissues had increased p-AKT and p-ERK1/2 expressions, while TRPC6 knockout could markedly reduce the phosphorylation of AKT and ERK1/2. These discoveries suggest that, by reducing Ca2+ overload, the underlying protective mechanism of TRPC6-/- may be involved in down-regulation of PI3K/AKT and ERK signaling, which is likely to provide a new avenue for future AKI therapies.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34320378

RESUMO

mTOR is a typical and conserved serine/threonine protein kinase that regulates cell growth and metabolism of organisms. Molting is a fundamental biological process in Chinese mitten crab (Eriocheir sinensis) and is monitored by a series of genes and pathways. The structural and functional characteristics of EsmTOR was investigated to determine the role of mTOR in the molting process of. The intact CDS of EsmTOR is 7449 bp in length and encodes a polypeptide consisting of 2482 amino acids. EsmTOR was expressed in all eight tissues examined during the three molting stages (postmolt, intermolt andpremolt), with levels fluctuating significantly during the molting. RNA interference of EsmTOR significantly delayed molting, indicating that mTOR may be involved in the molting process of E. sinensis. Meanwhile, a substantial downregulation was observed for the expression of upstream genes involved in amino acid transport (EsSLC7A5 and EsVATB) and downstream genes promoting ribosomal protein synthesis (EsS6K1) in the mTOR signaling pathway, as well as typical molt-related genes (EsMIH and EsEcR) after EsmTOR RNAi treatment. In addition, EsRheb, a molecular marker for tissue growth, was also significantly down-regulated. This study suggests that EsmTOR plays a fundamental role in molting regulation through the SLC7A5-V-ATPase-mTORC1 gene network.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Muda , Interferência de RNA , RNA Interferente Pequeno/genética , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Braquiúros , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
19.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(3): 421-428, 2021 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-34238419

RESUMO

Objective To analyze the radiological features of idiopathic pediatric meningiomas and explore their relationships with pathological grading,misdiagnoses,and blood loss during surgery.Methods We retrospectively reviewed 29 cases of pathologically confirmed pediatric meningiomas with pre-operative magnetic resonance imaging in Beijing Tiantan Hospital from November 2014 to July 2018.We assessed the imaging features to explore their relationships with pathological grading,misdiagnoses,and blood loss during surgery. Results Among the 29 cases,7 intraparenchymal meningiomas,5 extraparenchymal meningiomas,4 ventricular meningiomas,and 1 transcranial meningioma were misdiagnosed.Tumor location was significantly associated with possibility of misdiagnoses(P=0.021),and intraparenchymal tumors were most likely to be misdiagnosed.Twelve patients had positive dural tail sign,and 4 of them were misdiagnosed;16 patients did not have dural tail sign,and 12 of them were misdiagnosed.Fisher exact test showed that positive dural tail sign was associated with decreased possibility of misdiagnoses(one-sided P=0.034).Univariable regression analysis showed that the feature of tumor surrounding arteries or interfering with veins(P=0.020)and the tumor maximum diameter(P=0.001)had positively linear relationships with blood loss volume during surgery.Combining these two variables,the multivariable regression model showed better fitting performance($R_{ad}^2$=0.468).Conclusions Pediatric meningiomas are extremely rare,with scarce radiological characteristics.They are hard to diagnose,and the intraparenchymal meningiomas are very likely to be misdiagnosed and therefore should be treated with extra caution.Among all the radiological features,tumor surrounding arteries or interfering with veins and tumor maximum diameter were associated with increased blood loss during surgery.


Assuntos
Neoplasias Meníngeas , Meningioma , Criança , Humanos , Imageamento por Ressonância Magnética , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Estudos Retrospectivos
20.
Org Lett ; 23(13): 5192-5196, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34161105

RESUMO

6-Hydroxymethyl indolizidin-2-one amino acids were synthesized in 10 steps from l-serine by intramolecular ring opening of a symmetrical epoxide and lactam formation. X-ray analyses indicated the bicycles replicated ideal peptide type II' ß-turn central dihedral angle geometry. Inside a prostaglandin-F2α receptor modulator, the 6-hydroxymethyl analogue retained inhibitory activity on myometrial contractility.


Assuntos
Aminoácidos/síntese química , Dipeptídeos/química , Prostaglandinas/química , Aminoácidos/química , Fenômenos Bioquímicos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular
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