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1.
Sci Rep ; 13(1): 21500, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057507

RESUMO

In high energy heavy-ion collisions, the high speed valence charges will produce intense electromagnetic fields within the resulting quark-gluon plasma. Utilizing the AMPT model, this paper presents a comprehensive analysis of the magnetic field distribution generated from non-central collisions between [Formula: see text] nuclei at [Formula: see text]. The initial geometric parameters of the collision and the electric conductivity of the quark-gluon plasma have a dominant influence on the evolution of the magnetic field, while the plasma diffusion and the CME effect have a lesser impact and only slightly involve the original magnetic field by inducing new magnetic fields. This finding suggests that the dynamics of the quark-gluon plasma can be roughly decoupled from the effect of the electromagnetic field.

2.
Cells ; 12(22)2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37998374

RESUMO

COVID-19 emerged as a worldwide pandemic in early 2020, and while the rapid development of safe and efficacious vaccines stands as an extraordinary achievement, the identification of effective therapeutics has been less successful. This process has been limited in part by a lack of human-relevant preclinical models compatible with therapeutic screening on the native virus, which requires a high-containment environment. Here, we report SARS-CoV-2 infection and robust viral replication in PREDICT96-ALI, a high-throughput, human primary cell-based organ-on-chip platform. We evaluate unique infection kinetic profiles across lung tissue from three human donors by immunofluorescence, RT-qPCR, and plaque assays over a 6-day infection period. Enabled by the 96 devices/plate throughput of PREDICT96-ALI, we also investigate the efficacy of Remdesivir and MPro61 in a proof-of-concept antiviral study. Both compounds exhibit an antiviral effect against SARS-CoV-2 in the platform. This demonstration of SARS-CoV-2 infection and antiviral dosing in a high-throughput organ-on-chip platform presents a critical capability for disease modeling and therapeutic screening applications in a human physiology-relevant in vitro system.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Antivirais/farmacologia , Pulmão , Replicação Viral
3.
BMC Biol ; 21(1): 231, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37867192

RESUMO

BACKGROUND: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. RESULTS: Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. CONCLUSIONS: Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.


Assuntos
Splicing de RNA , Espermatogênese , Masculino , Humanos , Espermatogênese/genética , Proteínas de Ligação a RNA/genética , Processamento Alternativo , Meiose/genética , RNA Mensageiro
4.
Opt Lett ; 48(11): 2797-2800, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37262213

RESUMO

Measurement-device-independent quantum key distribution can remove all possible detector side channels, and is robust against state preparation flaws when further combined with the loss-tolerant method. However, the secure key rate in this scenario is relatively low, thus hindering its practical application. Here, we first present a four-intensity decoy-state protocol where the signal intensity is modulated only in Z basis for key generation while the decoy intensities are modulated in both Z and X bases for parameter estimation. Moreover, we adopt collective constraint and joint-study strategy in statistical fluctuation analysis. We have also experimentally demonstrated this protocol and the result indicates high performance and good security for practical applications.

5.
Data Brief ; 48: 109045, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37006391

RESUMO

Mimosa diplotricha (Fabaceae) and Mimosa diplotricha var. inermis are invasive taxa introduced in the Chinese mainland in the 19th century. M. diplotricha has been listed in the list of highly invasive species in China, which has seriously endangered the growth and reproduction of local species. As a poisonous plant, M. diplotricha var. inermis, a variant of M. diplotricha, will also endanger the safety of animals. We report the complete chloroplast genome sequence of M. diplotricha and M. diplotricha var. inermis. The chloroplast genome of M. diplotricha is 164,450 bp long and the chloroplast genome of M. diplotricha var. inermis is 164,445 bp long. Both M. diplotricha and M. diplotricha var. inermis contain a large single-copy region (LSC) of 89,807 bp and a small single-copy (SSC) region of 18,728 bp. The overall GC content of the two species is both 37.45%. A total of 84 genes were annotated in the two species, namely 54 protein-coding genes, 29 tRNA genes, and one rRNA gene. The phylogenetic tree based on the chloroplast genome of 22 related species showed that Mimosa diplotricha var. inermis is most closely related to M. diplotricha, while the latter clade is sister to Mimosa pudica, Parkia javanica, Faidherbia albida, and Acacia puncticulata. Our data provide a theoretical basis for the molecular identification, genetic relationships, and invasion risk monitoring of M. diplotricha and M. diplotricha var. inermis.

6.
Ying Yong Sheng Tai Xue Bao ; 34(4): 1123-1129, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37078333

RESUMO

Taking straws of corn, wheat, and millet as raw materials, we pretreated them with alkaline hydrogen peroxide, and then hydrolyzed by cellulase and xylanase. We selected the total sugar content in the hydrolysate as the indicator to evaluate the hydrolysis of the straws from three crop species, and further optimized the conditions. Then, the hydrolysates of three types of crop straws were used as carbon source for Chlorella sorokiniana culture to assess their effects on microalgal cultivation. The results showed that the optimal hydrolysis conditions for the three crop straws were identified as solid-liquid ratio of 1:15, temperature of 30 ℃, and treatment time of 12 h. Under such optimal condition, the total sugar contents increased up to 1.677, 1.412, and 1.211 g·L-1 in the corn, millet and wheat straw hydrolysate, respectively. The hydrolysates from the three crop straw could significantly increase both algal biomass and lipid content of C. sorokiniana. Corn straw hydrolysate had the best effect, with high levels of algal biomass (1.801 g·L-1) and lipid content (30.1%). Therefore, we concluded that crop straw hydrolysates as carbon source could significantly promote microalgal biomass and lipid enrichment. The results could lay the foundation for the efficient conversion and utilization of straw lignocellulose raw materials, provide new knowledge for the resource utilization of agricultural wastes, as well as the theoretical basis for the efficient cultivation of microalgae using crop straw hydrolysates.


Assuntos
Chlorella , Hidrólise , Lipídeos , Carbono , Açúcares , Biomassa
7.
Front Genet ; 14: 1036467, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36992701

RESUMO

Purpose: To study the accuracy of non-invasive chromosomal screening (NICS) results, in normal chromosomes and chromosomal rearrangement groups and to investigate whether using trophoblast cell biopsy along with NICS, to choose embryos for transfer can improve the clinical outcomes of assisted pregnancy. Methods: We retrospectively analyzed 101 couples who underwent preimplantation genetic testing at our center from January 2019 to June 2021 and collected 492 blastocysts for trophocyte (TE) biopsy. D3-5 blastocyst culture fluid and blastocyst cavity fluid were collected for the NICS. Amongst them, 278 blastocysts (58 couples) and 214 blastocysts (43 couples) were included in the normal chromosomes and chromosomal rearrangement groups, respectively. Couples undergoing embryo transfer were divided into group A, in which both the NICS and TE biopsy results were euploid (52 embryos), and group B, in which the TE biopsy results were euploid and the NICS results were aneuploid (33 embryos). Results: In the normal karyotype group, concordance for embryo ploidy was 78.1%, sensitivity was 94.9%, specificity was 51.4%, the positive predictive value (PPV) was 75.7%, and the negative predictive value (NPV) was 86.4%. In the chromosomal rearrangement group, concordance for embryo ploidy was 73.1%, sensitivity was 93.3%, specificity was 53.3%, the PPV was 66.3%, and the NPV was 89%. In euploid TE/euploid NICS group, 52 embryos were transferred; the clinical pregnancy rate was 71.2%, miscarriage rate was 5.4%, and ongoing pregnancy rate was 67.3%. In euploid TE/aneuploid NICS group, 33 embryos were transferred; the clinic pregnancy rate was 54.5%, miscarriage rate was 5.6%, and ongoingpregnancy rate was 51.5%. The clinical pregnancy and ongoing pregnancy rates were higher in the TE and NICS euploid group. Conclusion: NICS was similarly effective in assessing both normal and abnormal populations. Identification of euploidy and aneuploidy alone may lead to the wastage of embryos due to high false positives. More suitable reporting methods for NICS and countermeasures for a high number of false positives in NICS are needed. In summary, our results suggest that combining biopsy and NICS results could improve the outcomes of assisted pregnancy.

8.
Huan Jing Ke Xue ; 43(9): 4576-4586, 2022 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-36096598

RESUMO

In October-November 2020, the phytoplankton and the aquatic environment from 62 sites in the mainstream of the Qinhe River and the largest tributary of the Qinhe River (Danhe River) in the Jincheng region were investigated to clarify the spatial pattern of phytoplankton communities and their driving factors. A total of 7 phyla and 47 species of phytoplankton were identified in the Qinhe River basin and were composed of Cryptophyta, Chlorophyta, Pyrrophyta, Chrysophyta, Bacillariophyta, Cyanophyta, and Crytophyta. Six dominant species in the Qinhe River included:Chlorella vulgaris, Cryptomonas erosa, Chroomonas acuta, Cyclotella stelligera, Chlorococcum, and Euglena viridis. Six dominant species in the Danhe River included:C. erosa, Frustulia vulgaris, E. viridis, C. vulgaris, Trachelomonas oblonga Lemm, and C. stelligera. The Shannon-Wiener diversity index (H') varied from 0.35 to 3.15, with a mean value 1.40. The Pielou evenness index (J) varied from 0.24 to 1.00, with a mean value of 0.68. H' values in the Qinhe River were higher than those in the Danhe River. J values were relatively low in the middle reaches of the Qinhe River and middle-low reaches of the Danhe River. The results in the Qinhe River through a canonical correspondence analysis (CCA) showed that the percent of forest land at a 300 m buffer was the driving factor of Chlorococcum in Chlorophyta, and nitrate, total phosphorus, and the percent of forest land at the 300 m buffer were the driving factors of E. viridis. Cyclotella stelligera was mainly influenced by the percent of urban land and water temperature, whereas C. vulgaris, C. erosa, and C. acuta were mainly influenced by the percent of farmland and residential land at the 300 m buffer. The results in the Danhe River via CCA showed that C. erosa and C. stelligera were mainly influenced by pH and sulfate, E. viridis was mainly influenced by the percent of urban land and grass land, T. oblonga Lemm was mainly influenced by chloride and the percent of forest land, F. vulgaris was mainly influenced by water temperature and the percent of farmland, and C. vulgaris was mainly influenced by ammonia and the percent of farmland.


Assuntos
Chlorella vulgaris , Clorófitas , Diatomáceas , Fitoplâncton , Rios/química , Estações do Ano , Água
9.
J Cell Physiol ; 237(11): 4317-4325, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36161883

RESUMO

Mammalian oocytes are arrested at the diplotene stage of prophase I during fetal or postnatal development. It was reported that cyclin-dependent kinases (CDK1) was the sole CDK to drive the resumption of meiosis and CDK2 was dispensable for meiosis progression in mouse oocytes according to the conditional knockout studies. However, a recent study showed that CDK2 activity is essential for meiotic division and gametogenesis by means of gene-directed mutagenesis, which avoids the compensatory activation of other CDKs. Taken the compensatory effect between CDKs after gene knockout, the physiological function of CDK2 activity in oocyte maturation remains unclear. To address this issue, we applied a specific small-molecule inhibitor to restrain CDK2 activity transiently during oocyte meiotic maturation. Surprisingly, transient inhibition of CDK2 activity severely prevented the meiosis I completion although the meiotic resumption was not affected. Then we found that CDK2 activity was required for establishment of normal spindle and chromosome dynamics. Notably, CDK2 inhibition interrupted the anaphase-promoting complex/cyclosome (APC/C)-dependent degradation pathway by maintaining the activation of spindle assembly checkpoint (SAC). Interestingly, CDK2 inhibition prevented the egg activation as well. Overall, our data demonstrate that CDK2 kinase activity is required for proper dynamics of spindle and chromosomes, whose disturbance induces the continuous SAC activation and subsequent inactivation of APC/C activity in oocyte meiosis.


Assuntos
Meiose , Oócitos , Camundongos , Animais , Oócitos/metabolismo , Oogênese , Ciclossomo-Complexo Promotor de Anáfase/genética , Quinases Ciclina-Dependentes/genética , Mamíferos/metabolismo
10.
Front Endocrinol (Lausanne) ; 13: 907874, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017318

RESUMO

Background: Establishing a successful pregnancy depends on the endometrium and the embryo. It is estimated that suboptimal endometrial receptivity account for one-third of implantation failures. Despite the indepth understanding of the processes associated with embryo-endometrial cross-talk, little progress has been achieved for diagnosis and treatments for suboptimal endometrial receptivity. Methods: This retrospective study included women undergoing their first frozen-thawed embryo transfer (FET) cycles at our reproductive medicine center from March 2021 to August 2021. Transvaginal three-dimensional (3D) ultrasound was performed in the morning on the day of embryo transfer for all the thawed embryo transfer patients, to evaluate endometrial receptivity, including endometrial thickness, echogenicity, volume, movement and blood flow. Results: A total number of 562 patients of FET with 315 pregnancies (56.0%) was analyzed. It was found that only the echo of the endometrial central line was different between the pregnant group and non-pregnant group. Other parameters, such as endometrial thickness, volume, endometrial peristalsis, or the endometrial blood flow were not statistically different between the two groups. Then, according to the relationship between the different groups and the clinical pregnancy rate, a score of 0 to 2 was respectively scored. The sum of the scores for the six items was the patient's endometrial receptivity score. It showed that the clinical pregnancy rate increased as the endometrial receptivity score increased, and when the receptivity score reaches at least 5, the clinical pregnancy rate is significantly improved (63.7% versus 49.5%, P=0.001). Conclusion: We developed an endometrial receptivity scoring system and demonstrated its validity. It may aid clinicians in choosing the useful marker in clinical practice and for informing further research.


Assuntos
Endométrio , Peristaltismo , Transferência Embrionária/métodos , Endométrio/diagnóstico por imagem , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Ultrassonografia
11.
J Environ Manage ; 317: 115381, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35751237

RESUMO

Application of zero-valent iron (ZVI) has become one of the most promising innovative technologies for the remediation of environmental pollutants. However, ZVI may suffer from the low intrinsic reactivity toward refractory pollutants, which seriously restricts its practical application in fields. Therefore, strategies have been developing to enhance the reactivity of ZVI. Until now, the most commonly used strategies include pretreatment of ZVI, synthesis of highly-active ZVI-based materials and additional auxiliary measures. In this review, a systematic and comprehensive summary of these commonly used strategies has been conducted for the following purposes: (1) to understand the fundamental mechanisms of the selected approaches; (2) to point out their advantages and shortcomings; (3) to illustrate the main problems of their large-scale application; (4) to forecast the future trend of developing ZVI technologies. Overall, this review is devoted to providing a fundamental understanding on the mechanism for enhancing the reactivity of ZVI and facilitating the practical application of ZVI technologies in fields.


Assuntos
Recuperação e Remediação Ambiental , Poluentes Químicos da Água , Ferro
12.
Mol Biol Rep ; 49(5): 4095-4099, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35536498

RESUMO

BACKGROUND: Picea brachytyla is a unique tree species in China. Due to being extensively exploited in the past, it is listed as Vulnerable in the IUCN Red List. It is mainly distributed across the Hengduan and Daba-Qinglin mountains and has been found in other areas including Sichuan Province and Qinghai Province, China. Microsatellites, or simple sequence repeats (SSRs), are widely used in correlational studies of genetic protection. Few markers have been developed for P. brachytyla because of the small number of trees and scholarly resources available for study. METHODS AND RESULTS: The genomic DNA of P. brachytyla was sequenced using the DNBSEQ platform, and unigenes were obtained after assembly and deredundancy. Of the 100 primer pairs screened, we isolated 10 useful microsatellite loci from P. brachytyla genes. The observed and expected heterozygosity values ranged from 0.173 (P24) to 0.788 (P79; mean 0.469) and 0.199 (P87) to 0.911 (P79; mean 0.700), respectively. Polymorphism-information content (PIC) ranged from 0.190 (P84) to 0.904 (P79; mean 0.666). Only P84 and P72 were in a Hardy-Weinberg equilibrium (P > 0.05) in the different P. brachytyla populations. All the levels of linkage disequilibrium (LD) were high for the 10 SSR loci indicating that there were no autocorrelations among the 10 SSR loci. CONCLUSIONS: The novel polymorphic microsatellite markers showed high polymorphism for P. brachytyla. These polymorphic microsatellites can provide a basis for future conservation and genetic research on this rare plant species.


Assuntos
Picea , China , Desequilíbrio de Ligação/genética , Repetições de Microssatélites/genética , Picea/genética , Polimorfismo Genético/genética
13.
Opt Express ; 30(5): 8126-8135, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35299560

RESUMO

Quantum random access code (QRAC) serves the communication task to encode a long message into a quantum system and allow the receiver to decode the initial information with a higher success probability than classical random access code (RAC). Here, we present an experimental demonstration of sequential 3 → 1 QRAC in the prepare-transform-measure scenario with one sender and three independent receivers. The experimental results show that, in the 3 → 1 QRAC scenario, three receivers can independently decode the initial information with an average success probability higher than the classical RAC.

14.
Opt Lett ; 47(3): 665-668, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35103698

RESUMO

Measurement-device-independent quantum key distribution (MDI-QKD) can remove all detection side channels but still makes additional assumptions on sources that can be compromised through uncharacterized side channels in practice. Here, we combine a recently proposed reference technique to prove the security of MDI-QKD against possible source imperfections and/or side channels. This requires some reference states and an upper bound on the parameter that describes the quality of the sources. With this formalism we investigate the asymptotic performance of single-photon sources, and the results show that the side channels have a great impact on the key rates.

15.
Opt Lett ; 47(23): 6285-6288, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37219228

RESUMO

Tomography is a very beneficial and fundamental technique in the fields of quantum information and quantum optics, which can be applied to infer information about quantum states or quantum processes. In quantum key distribution (QKD), tomography can be proposed to improve the secure key rate by taking full advantage of data from both matched and mismatched measurement outcomes to characterize quantum channels accurately. However, to date, no experimental work has been conducted on it. In this work, we study tomography-based QKD (TB-QKD), and for the first time, to the best of our knowledge, carry out proof-of-principle experimental demonstrations by implementing Sagnac interferometers to simulate different transmission channels. Furthermore, we compare it with reference-frame-independent QKD (RFI-QKD) and demonstrate that TB-QKD can significantly outperform RFI-QKD in certain channels, e.g., amplitude damping channel or probabilistic rotation channel.

16.
BMJ Open ; 12(9): e056691, 2022 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-36691208

RESUMO

INTRODUCTION: Fracture is a disease with a high incidence worldwide. Foot and ankle fractures are common among fractures of the lower extremities. Foot and ankle fractures usually require surgical fixation and a period of fixed treatment, which can lead to decreased bone density. Although transcutaneous electrical acupoint stimulation (TEAS) is widely used for movement system diseases, there is minimal evidence to show the effectiveness of TEAS on patients after surgical fixation of ankle and foot fractures. This trial aims to evaluate whether TEAS can reduce bone loss in patients with immobilisation after ankle and foot fractures. METHODS AND ANALYSIS: A randomised controlled trial will be conducted in which 60 patients will be randomly divided into two groups: (a) the control group will be treated according to the routine procedures of basic orthopaedics treatment; (b) in the treatment group, bilateral SP36, BL23 and ST36 will be performed on the basis of the control group, and the test will be performed for 30 min every other day for a total of 8 weeks. Bone turnover markers will be used as primary outcome. Secondary outcomes are composed of blood phosphorus, blood calcium and bone mineral density. Treatment safety will be monitored and recorded. ETHICS AND DISSEMINATION: This trial is approved by the Ethics Committee of Beijing University of Chinese Medicine (2020BZYLL0611) and the Ethics Committee of Beijing Luhe Hospital (2020-LHKY-055-02), and inpatients who meet the following diagnostic and inclusion criteria are eligible to participate in this study. TRIAL REGISTRATION NUMBER: ChiCTR 2000039944.


Assuntos
Fraturas do Tornozelo , Traumatismos do Tornozelo , Humanos , Fraturas do Tornozelo/cirurgia , Pontos de Acupuntura , Resultado do Tratamento , Extremidade Inferior , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Toxicology ; 464: 153013, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34718031

RESUMO

Patulin is a secondary metabolite mainly secreted by fungi and is the most common mycotoxin found in apples and apple-based products. For the past few years, numerous studies suggested the wide distribution and toxicity of patulin. In this study, we investigated the toxic effect of patulin on mouse oocytes and its possible mechanisms. The results showed that patulin treatment did not affect meiotic resumption, but inhibited oocyte maturation as indicated by failure of first polar body extrusion. Further mechanistic study showed that patulin treatment disturbed normal spindle assembly, chromosome alignment and morphology. We also found increased oxidative stress by testing the level of ROS and decreased mitochondrial membrane potential, indicating mitochondria dysfunction. In summary, our results suggest that patulin treatment causes oocyte meiotic arrest by disturbing normal spindle assembly and chromosome alignment, which may be caused by dysfunctions of mitochondria.


Assuntos
Mitocôndrias/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Patulina/toxicidade , Animais , Feminino , Meiose/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Mitocôndrias/patologia , Oócitos/patologia , Espécies Reativas de Oxigênio/metabolismo
18.
Cell Death Dis ; 12(10): 883, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580275

RESUMO

Protein phosphatase 6 (PP6) is a member of the PP2A-like subfamily, which plays significant roles in numerous fundamental biological activities. We found that PPP6C plays important roles in male germ cells recently. Spermatogenesis is supported by the Sertoli cells in the seminiferous epithelium. In this study, we crossed Ppp6cF/F mice with AMH-Cre mice to gain mutant mice with specific depletion of the Ppp6c gene in the Sertoli cells. We discovered that the PPP6C cKO male mice were absolutely infertile and germ cells were largely lost during spermatogenesis. By combing phosphoproteome with bioinformatics analysis, we showed that the phosphorylation status of ß-catenin at S552 (a marker of adherens junctions) was significantly upregulated in mutant mice. Abnormal ß-catenin accumulation resulted in impaired testicular junction integrity, thus led to abnormal structure and functions of BTB. Taken together, our study reveals a novel function for PPP6C in male germ cell survival and differentiation by regulating the cell-cell communication through dephosphorylating ß-catenin at S552.


Assuntos
Domínio Catalítico , Deleção de Genes , Fosfoproteínas Fosfatases/metabolismo , Células de Sertoli/metabolismo , Espermatogênese , Animais , Apoptose , Epididimo/metabolismo , Éxons/genética , Infertilidade Masculina/genética , Integrases/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfoproteínas Fosfatases/deficiência , Fosfoproteínas/metabolismo , Fosforilação , Proteoma/metabolismo , Espermatozoides/metabolismo , Testículo/metabolismo , Testículo/patologia , beta Catenina/metabolismo
19.
ACS Med Chem Lett ; 12(8): 1325-1332, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34408808

RESUMO

Non-covalent inhibitors of the main protease (Mpro) of SARS-CoV-2 having a pyridinone core were previously reported with IC50 values as low as 0.018 µM for inhibition of enzymatic activity and EC50 values as low as 0.8 µM for inhibition of viral replication in Vero E6 cells. The series has now been further advanced by consideration of placement of substituted five-membered-ring heterocycles in the S4 pocket of Mpro and N-methylation of a uracil ring. Free energy perturbation calculations provided guidance on the choice of the heterocycles, and protein crystallography confirmed the desired S4 placement. Here we report inhibitors with EC50 values as low as 0.080 µM, while remdesivir yields values of 0.5-2 µM in side-by-side testing with infectious SARS-CoV-2. A key factor in the improvement is enhanced cell permeability, as reflected in PAMPA measurements. Compounds 19 and 21 are particularly promising as potential therapies for COVID-19, featuring IC50 values of 0.044-0.061 µM, EC50 values of ca. 0.1 µM, good aqueous solubility, and no cytotoxicity.

20.
Opt Lett ; 46(15): 3729-3732, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34329267

RESUMO

The measurement-device-independent quantum key distribution (MDI-QKD) can be immune to all detector side-channel attacks. Moreover, it can be easily implemented combining with the matured decoy-state methods under current technology. It, thus, seems a very promising candidate in practical implementation of quantum communications. However, it suffers from a severe finite-data-size effect in most existing MDI-QKD protocols, resulting in relatively low key rates. Recently, Jiang et al. [Phys. Rev. A103, 012402 (2021).PLRAAN1050-294710.1103/PhysRevA.103.012402] proposed a double-scanning method to drastically increase the key rate of MDI-QKD. Based on Jiang et al.'s theoretical work, here we for the first time, to the best of our knowledge, implement the double-scanning method into MDI-QKD and carry out corresponding experimental demonstration. With a moderate number of pulses of 1010, we can achieve 150 km secure transmission distance, which is impossible with all former methods. Therefore, our present work paves the way toward practical implementation of MDI-QKD.

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