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1.
Proc Natl Acad Sci U S A ; 118(3)2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33431677

RESUMO

Hepatitis C virus (HCV) is a major worldwide health burden, and a preventive vaccine is needed for global control or eradication of this virus. A substantial hurdle to an effective HCV vaccine is the high variability of the virus, leading to immune escape. The E1E2 glycoprotein complex contains conserved epitopes and elicits neutralizing antibody responses, making it a primary target for HCV vaccine development. However, the E1E2 transmembrane domains that are critical for native assembly make it challenging to produce this complex in a homogenous soluble form that is reflective of its state on the viral envelope. To enable rational design of an E1E2 vaccine, as well as structural characterization efforts, we have designed a soluble, secreted form of E1E2 (sE1E2). As with soluble glycoprotein designs for other viruses, it incorporates a scaffold to enforce assembly in the absence of the transmembrane domains, along with a furin cleavage site to permit native-like heterodimerization. This sE1E2 was found to assemble into a form closer to its expected size than full-length E1E2. Preservation of native structural elements was confirmed by high-affinity binding to a panel of conformationally specific monoclonal antibodies, including two neutralizing antibodies specific to native E1E2 and to its primary receptor, CD81. Finally, sE1E2 was found to elicit robust neutralizing antibodies in vivo. This designed sE1E2 can both provide insights into the determinants of native E1E2 assembly and serve as a platform for production of E1E2 for future structural and vaccine studies, enabling rational optimization of an E1E2-based antigen.

2.
J Chem Neuroanat ; 112: 101916, 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33373660

RESUMO

The expressions of different temporal patterns of bone morphogenetic proteins (BMPs) have changed after ischemic strokes, and ischemic preconditioning-induced neuroprotection was attenuated when BMP7 was inhibited. In the previous study, the neuroprotection of isoflurane postconditioning (ISPOC) against cerebral ischemia-reperfusion (I/R) injury has been addressed, with particular relevance to the role of BMP7. Consequently, in the present study, we continued to explore the mechanisms involved in the BMP7 signal mediated the neuroprotection of ISPOC. A rat model of the middle cerebral artery occlusion was used in this study. Rats were administered 1.5 % isoflurane, 60 min after 90 min of ischemia, followed by a 24 h reperfusion period. The 1.5 % ISPOC significantly ameliorated the cerebral infarct volumes, neurologic deficit scores, damaged neurons, and apoptotic neurons. Moreover, ISPOC unregulated the expressions of BMP7, p-Smad1/5/9, and p-p38. Whereas, the neuroprotective effect was weakened by LDN-193189 and SB203580, respectively, a BMP7/Smad1/5/9 and p38MAPK signaling pathway inhibitor. Furthermore, LDN-193189 downregulated the expression of p-p38. The present results of this study indicated that the neuroprotection of 1.5 % isoflurane postconditioning to cerebral ischemia-reperfusion injury is related to the activating of BMP7/Smad1/5/9 and p38MAPK signal pathway.

3.
Ying Yong Sheng Tai Xue Bao ; 31(9): 3033-3039, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345504

RESUMO

We examined the correlation between changes of root morphology and endogenous hormones in intercropping systems of wheat and faba bean under different phosphorus levels by hydroponics. Compared with monocropping wheat (MW), the intercropping of wheat and faba bean (W∥F) significantly increased root length of wheat, reduced root average diameter of wheat, and increased root surface area under the condition of 1/2P (low P) level. At the conventional phosphorus level, intercropping significantly reduced root average diameter of wheat, and increased root length and root surface area. Compared with monocropping faba bean (MF), W∥F significantly promoted the growth of faba bean root and increased root surface area of faba bean. At the level of 1/2P, intercropping significantly increased the content of auxin (IAA), abscisic acid (ABA), sali-cylic acid (SA) and jasmonic acid (JA). At the conventional phosphorus level, intercropping could significantly increase the content of IAA, ABA and JA in wheat root, while no significant difference in the SA content of wheat root between monocropping and intercropping wheat was found. Intercropping could increase the content of ABA and SA in faba bean roots, but did not affect IAA and JA contents of faba bean roots. There was no significant correlation between the contents of endogenous hormones (IAA, ABA, SA and JA) and root morphology (root length, root average diameter and root surface area) of wheat and faba bean roots in wheat or faba bean monocropping system. In wheat and faba bean intercropping system, there was a positive correlation between IAA contents of wheat and faba bean and their root length and root surface area. W∥F enhanced IAA of wheat and faba bean root, which was an important factor driving the change of root morphology in the intercropping system of wheat and faba bean.


Assuntos
Triticum , Vicia faba , Hormônios , Fósforo , Raízes de Plantas
4.
PLoS One ; 15(11): e0241914, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33206683

RESUMO

Alternative splicing (AS) is a post-transcriptional process common in plants and essential for regulation of environmental fitness of plants. In the present study, we focus on the AS events in poplar leaves to understand their effects on plant growth and development. The hybrid poplar (P.alba×P.glandulosa cv.84K) leaves were collected for RNA extraction. The extracted RNA was sequenced using on an Illumina HiSeq™ 2000 platform. Using the Populus trichocarpa genome as the reference, a total of 3810 AS genes were identified (9225 AS events), which accounted for 13.51% of all the expressed genes. Intron retention was the most common AS event, accounting for 43.86% of all the AS events, followed by alternative 3' splice sites (23.75%), alternative 5' splice sites (23.71%), and exon skipping (8.68%). Chromosomes 10 had the most condensed AS events (33.67 events/Mb) and chromosome 19 had the least (12.42 events/Mb). Association analysis showed that AS in the poplar leaves was positively correlated with intron length, exon number, exon length, and gene expression level, and was negatively correlated with GC content. AS genes in the poplar leaves were associated mainly with inositol phosphate metabolism and phosphatidylinositol signaling system pathways that would be significant on wooden plant production.


Assuntos
Processamento Alternativo , Quimera/genética , Proteínas de Plantas/genética , Populus/crescimento & desenvolvimento , Sequenciamento Completo do Genoma/métodos , Quimera/crescimento & desenvolvimento , Cromossomos de Plantas/genética , Éxons , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , Íntrons , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Populus/genética , Sítios de Splice de RNA
5.
Taiwan J Obstet Gynecol ; 59(6): 910-915, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33218411

RESUMO

OBJECTIVE: To retrospectively analyze the incidence of chromosomal polymorphisms in prenatal cytogenetic diagnostic cases and the effect of the clinical manifestation of these fetuses. MATERIALS AND METHODS: 490 fetuses with chromosomal polymorphisms among 9996 pregnant women who underwent prenatal cytogenetic diagnosis were included in this study and were set as group 1. Other 500 pregnant women, whose fetuses were with normal karyotypes, were randomly selected from the remaining pregnant women and set as group 2. Clinical information and outcomes and maternal serum screening results of group 1 were compared with group 2. RESULTS: The frequency of fetal chromosomal polymorphism was 4.90% (490/9996). The most common variants observed were 1/9/16 qh± (2.27%, 227/9996), followed by inv(9) (0.90%, 90/9996). 94.62% (264/279) of fetal chromosomal variants were inherited from parents. No statistical difference was found in clinical information and outcomes and maternal serum screening results between group 1 and group 2. CONCLUSION: The fetus with chromosomal polymorphism has no impact on serum markers of second trimester screening and does not play an important role for the clinical outcome of the current pregnancy either, whether it is inherited from the parents or a de novo mutation.

6.
J Clin Oncol ; 38(35): 4138-4148, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33026938

RESUMO

PURPOSE: Patients with advanced esophageal cancer have a poor prognosis and limited treatment options after first-line chemotherapy. PATIENTS AND METHODS: In this open-label, phase III study, we randomly assigned (1:1) 628 patients with advanced/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, that progressed after one prior therapy, to pembrolizumab 200 mg every 3 weeks for up to 2 years or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). Primary end points were overall survival (OS) in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10, in patients with squamous cell carcinoma, and in all patients (one-sided α 0.9%, 0.8%, and 0.8%, respectively). RESULTS: At final analysis, conducted 16 months after the last patient was randomly assigned, OS was prolonged with pembrolizumab versus chemotherapy for patients with CPS ≥ 10 (median, 9.3 v 6.7 months; hazard ratio [HR], 0.69 [95% CI, 0.52 to 0.93]; P = .0074). Estimated 12-month OS rate was 43% (95% CI, 33.5% to 52.1%) with pembrolizumab versus 20% (95% CI, 13.5% to 28.3%) with chemotherapy. Median OS was 8.2 months versus 7.1 months (HR, 0.78 [95% CI, 0.63 to 0.96]; P = .0095) in patients with squamous cell carcinoma and 7.1 months versus 7.1 months (HR, 0.89 [95% CI, 0.75 to 1.05]; P = .0560) in all patients. Grade 3-5 treatment-related adverse events occurred in 18.2% of patients with pembrolizumab versus 40.9% in those who underwent chemotherapy. CONCLUSION: Pembrolizumab prolonged OS versus chemotherapy as second-line therapy for advanced esophageal cancer in patients with PD-L1 CPS ≥ 10, with fewer treatment-related adverse events.

7.
Int Ophthalmol ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070270

RESUMO

BACKGROUND: Cyclocryotherapy and transscleral cyclophotocoagulation are commonly used procedures for the treatment of refractory glaucoma, but still with many complications. Ultrasound cyclo plasty (UCP) is a novel technique that determines a selective and more precise coagulation necrosis of the ciliary body to reduce intraocular pressure (IOP), but its efficacy and safety have been less investigated in Chinese population. This study aimed to evaluate the clinical efficacy and safety of UCP in Chinese patients with refractory glaucoma. METHODS: We designed a prospective, before-after study involving 36 eyes of 36 patients with refractory glaucoma that underwent uneventful UCP. Mean IOP, mean IOP reduction and subjective pain scale scores before and after UCP were compared to evaluate the efficacy of UCP in these patients. Procedural success defined as no abnormality of the treatment sites, and complications were recorded, along with confirmation of the safety of UCP. RESULTS: The 36 UCP patients had a mean IOP of 53.61 ± 12.4 mmHg and a mean VAS score of 5.69 ± 3.02 preoperatively. Successful operation was achieved in 28 patients, with a success rate of 77.8%. In the follow-up observation at day 1, day 7, and month 1, 2, 3 and 6 postoperatively, both mean IOP and mean VAS score were significantly lower than those before operation (both P < 0.0001). The median baseline IOP reduction ranged from 22 to 36%. The mean reduction was 42.5% in 36 patients when taking IOP at the last follow-up visit as the last. No significant changes in visual acuity were achieved in 4 patients after UCP, and no adverse outcomes were present in other patients after timely treatment of complications such as conjunctival hyperemia, subconjunctival hemorrhage, or hyphema. CONCLUSIONS: UCP is a novel yet reliable option for Chinese patients with refractory glaucoma since its high efficacy and safety.

8.
Biochem Biophys Res Commun ; 533(4): 1393-1399, 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33092792

RESUMO

Cytosolic carboxypeptidases (CCPs) comprise a unique subfamily of M14 carboxypeptidases and are erasers of the reversible protein posttranslational modification- polyglutamylation. Potent inhibitors for CCPs may serve as leading compounds targeting imbalanced polyglutamylation. However, no efficient CCP inhibitor has yet been reported. Here, we showed that 2-phosphonomethylpentanedioic acid (2-PMPA), a potent inhibitor of the distant M28 family member glutamate carboxypeptidase II (GCPII), rather than the typical M14 inhibitor 2-benzylsuccinic acid, could efficiently inhibit CCP activities. 2-PMPA inhibited the recombinant Nna1 (a.k.a. CCP1) for hydrolyzing a synthetic peptide in a mixed manner, with Ki and Ki' being 0.11 µM and 0.24 µM respectively. It inhibited Nna1 for deglutamylating tubulin, the best-known polyglutamylated protein, with an IC50 of 0.21 mM. Homology modeling predicted that the R-form of 2-PMPA is more favorable to bind Nna1, unlike that GCPII prefers to S-form. This work for the first time identified a potent inhibitor for CCP family.

9.
Am J Transl Res ; 12(8): 4456-4466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32913519

RESUMO

Lung cancer, a leading cause of cancer-related mortalities worldwide and non-small cell lung cancer (NSCLC) is the main subtype of lung cancer. As a first-line chemotherapeutic drug used for NSCLC, acquired resistance retarded the clinical application of cisplatin (DDP). We herein reported long non-coding RNA SNHG9 was over-expressed in NSCLC tissues and cell lines compared with normal lung tissues and cell line; Increased SNHG9 was also observed in DDP resistant NSCLC tissues and cell lines compared with their DDP sensitive counterparts. Elevated expression of SNHG9 was associated with lower overall survival (OS) rate in NSCLC patients. Besides, silence of SNHG9 suppressed DDP resistance of NSCLC cells. Furthermore, CAPRIN1 was positively regulated by SNHG9 and mediated the promoting role of SNHG9 in DDP resistance of NSCLC cells. SNHG9 could be used as a potential target for DDP resistant NSCLC therapy.

10.
Medicine (Baltimore) ; 99(37): e22124, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925763

RESUMO

RATIONALE: This study aimed to report 1 family case with novel Y chromosome structural variations by an established next-generation sequencing (NGS) method using unique STSs. PATIENT CONCERNS: The case studied was from a family with a father and son (the proband). G-band staining was used for karyotype analysis. Y chromosome microdeletions were detected by sequence-tagged site (STS)-PCR analysis and a new NGS screening strategy. DIAGNOSES: Semen analysis showed that the proband was azoospermic. The patient had an abnormal karyotype (45,X[48%]/46,XY[52%]). His father exhibited a normal karyotype. STS-PCR analysis showed that the proband had a deletion of the AZFb+c region, and his father had no deletion of STS markers examined. The sequencing method revealed that the patient had DNA sequence deletions from nt 20099846 to nt 28365090 (8.3 Mb), including the region from yel4 to the Yq terminal, and his father exhibited a deletion of b1/b3 and duplication of gr/gr. INTERVENTIONS: The proband was advised to undergo genetic counseling, and consider the use of sperm from a sperm bank or adoption to become a father. OUTCOMES: The proband was azoospermic. AZFc partial deletions may produce a potential risk for large AZFb+c deletions or abnormal karyotypes causing spermatogenic failure in men. LESSONS: The NGS method can be considered a clinical diagnostic tool to detect Y chromosome microdeletions. The partial AZFc deletions and/or duplications can be a risk of extensive deletions in offspring.


Assuntos
Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Masculino , Sitios de Sequências Rotuladas , Aberrações dos Cromossomos Sexuais
11.
Medicine (Baltimore) ; 99(39): e22340, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991447

RESUMO

RATIONALE: Apert syndrome (AS) is an autosomal dominant inheritance pattern of the most severe craniosynostosis syndrome. AS is characterized by synostosis of cranial sutures and acrocephaly, including brachycephaly, midfacial hypoplasia, and syndactyly of the hands and feet. Patients with AS often present with craniosynostosis, severe syndactyly, and skin, skeletal, brain, and visceral abnormalities. PATIENT CONCERNS: A pregnant Chinese woman presented with a fetus at 23 + 5 weeks of gestation with suspected AS in a prenatal ultrasound examination. Following ultrasound, the pregnancy underwent spontaneous abortion. Gene sequencing was performed on the back skin of the dead fetus. DIAGNOSIS: The diagnosis of AS was confirmed on the basis of clinical manifestations of the fetus, and a de novo mutation in the fibroblast growth factor receptor 2 (FGFR2) gene was identified. INTERVENTIONS: The couple finally chose to terminate the pregnancy based on the ultrasonic malformations and the risk of the parents having a neonate with AS in the future is small. However, any future pregnancy must be assessed by prenatal diagnosis. OUTCOMES: The dead fetus presented with bilateral skull deformation. Additionally, there were bilateral changes to the temporal bone caused by inwards movement leading to concave morphology, a "clover" sign, and syndactyly from the index finger/second toe to the little finger/little toe. AS was diagnosed by genetic testing, which showed a p.S137W (c.410C>G, chr10:123279677) mutation in the FGFR2 gene. LESSONS: Clinicians should be aware that there are a variety of ultrasound findings for AS. Therefore, genetic testing should be used when appropriate to confirm diagnosis of AS.


Assuntos
Acrocefalossindactilia/genética , Acrocefalossindactilia/patologia , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Aborto Espontâneo , Acrocefalossindactilia/diagnóstico , Feminino , Humanos , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
12.
J Virol ; 94(22)2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32878891

RESUMO

An effective vaccine for hepatitis C virus (HCV) is a major unmet need, and it requires an antigen that elicits immune responses to key conserved epitopes. Based on structures of antibodies targeting HCV envelope glycoprotein E2, we designed immunogens to modulate the structure and dynamics of E2 and favor induction of broadly neutralizing antibodies (bNAbs) in the context of a vaccine. These designs include a point mutation in a key conserved antigenic site to stabilize its conformation, as well as redesigns of an immunogenic region to add a new N-glycosylation site and mask it from antibody binding. Designs were experimentally characterized for binding to a panel of human monoclonal antibodies (HMAbs) and the coreceptor CD81 to confirm preservation of epitope structure and preferred antigenicity profile. Selected E2 designs were tested for immunogenicity in mice, with and without hypervariable region 1, which is an immunogenic region associated with viral escape. One of these designs showed improvement in polyclonal immune serum binding to HCV pseudoparticles and neutralization of isolates associated with antibody resistance. These results indicate that antigen optimization through structure-based design of the envelope glycoproteins is a promising route to an effective vaccine for HCV.IMPORTANCE Hepatitis C virus infects approximately 1% of the world's population, and no vaccine is currently available. Due to the high variability of HCV and its ability to actively escape the immune response, a goal of HCV vaccine design is to induce neutralizing antibodies that target conserved epitopes. Here, we performed structure-based design of several epitopes of the HCV E2 envelope glycoprotein to engineer its antigenic properties. Designs were tested in vitro and in vivo, demonstrating alteration of the E2 antigenic profile in several cases, and one design led to improvement of cross-neutralization of heterologous viruses. This represents a proof of concept that rational engineering of HCV envelope glycoproteins can be used to modulate E2 antigenicity and optimize a vaccine for this challenging viral target.


Assuntos
Hepacivirus/genética , Hepacivirus/imunologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , Antígenos Virais/química , Antígenos Virais/genética , Antígenos Virais/imunologia , Linhagem Celular , Epitopos/química , Epitopos/imunologia , Feminino , Células HEK293 , Hepatite C/imunologia , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Anticorpos Anti-Hepatite C/imunologia , Humanos , Imunogenicidade da Vacina , Camundongos , Modelos Moleculares , Testes de Neutralização , Conformação Proteica , Proteínas do Envelope Viral/genética , Vacinas contra Hepatite Viral/imunologia
13.
Opt Lett ; 45(13): 3805-3808, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32630959

RESUMO

We firstly demonstrated a tunable 2.1 µm pumped mid-infrared type-II phase-matching BaGa4Se7 (BGSe) optical parametric oscillator (OPO). A signal tuning range of 3.82-3.99 µm was achieved. With a signal light produced by the BGSe OPO serving as seed, the ZnGeP2 (ZGP) optical parametric amplifier (OPA) was first introduced. A 4.35 W mid-infrared laser was obtained in the novel type-II BGSe OPO with a ZGP OPA system, which was pumped by a 24 W 1 kHz Q-switched Ho:YAG laser. The beam quality factor M2 of the whole system is ∼2.3, which is over a 50% promotion on the previous M2 results of single BGSe OPO.

14.
Medicine (Baltimore) ; 99(28): e20813, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664073

RESUMO

INTRODUCTION: As one of the most common causes of male infertility, asthenozoospermia mainly shows low sperm motility, accounting for 81.84% of male infertility patients. Recently, there has been a notable increase for relationship between genetic testing and asthenozoospermia. In this report, we design to provide clues to prove relationship between dynein heavy chain gene 5 (DNAH5) gene alterations and asthenozoospermia. This also provides a reference for patients to choose a reasonable treatment plan or genetic counseling to assist reproductive reproduction. PATIENTS CONCERN: In the present study, we screened 143 patients with asthenozoospermia for variants in DNAH5 gene. We used high-throughput targeted gene sequencing technology and the data were assessed by bioinformatics analysis. DIAGNOSIS: We found 1 of 143 asthenozoospermia patients was detected as carrying DNAH5 compound heterozygous variants (c.3502G>A and c.2578-11_2578-7del). OUTCOMES: The variation c.2578-11_2578-7del was predicted in silico to not affect the splicing by HSF3. The variation c.3502G > A (p.E1168K) may cause disease by Mutationtaster software. They may contribute to a risk of male infertility in Chinese patients. CONCLUSIONS: We discussed the possible association between mutations in DNAH5 and asthenospermia for the first time in Chinese people. If confirmed in larger samples and different races, this result was meaningful for a better diagnosis of asthenospermia patients.


Assuntos
Astenozoospermia/genética , Dineínas/metabolismo , Mutação/genética , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Dineínas do Axonema/genética , Biologia Computacional/instrumentação , Humanos , Infertilidade Masculina/etiologia , Masculino , Polimorfismo de Nucleotídeo Único/genética , Motilidade Espermática/genética
15.
Dalton Trans ; 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32613984

RESUMO

We report a robust room temperature ferroelectric (FE) state in (1 - x)Pb0.99Nb0.02[(Zr0.57Sn0.43)0.933Ti0.067]0.98O3-xZnO ((1 - x)PNZST-xZnO) composites, where PNZST shows a predominant antiferroelectric (AFE) nature due to ZnO-induced internal strain. Upon heating, a FE-AFE transition occurs and generates high pyroelectric performance. The composite with x = 0.1 shows a peak pyroelectric coefficient of p = 2450.7 × 10-4 C m-2 K-1 and figures of merit of current responsivity Fi = 926.9 × 10-10 m V-1, voltage responsivity Fv = 1334.3 × 10-2 m2 C-1, and detectivity Fd = 1194.8 × 10-5 Pa-1/2, which are about two orders of magnitude higher than those of most perovskite pyroelectric oxides. More interestingly, the FE-AFE transition temperature, i.e., the temperature corresponding to peak pyroelectric performance, is tunable in a wide temperature range from 30 °C to 65 °C. This work not only provides a promising material candidate for high performance pyroelectric devices, but also an alternative idea to develop ferroelectric and pyroelectric properties based on antiferroelectric materials.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32700452

RESUMO

The current protein interaction method is time consuming and cumbersome or the instrument is expensive. A new method that is convenient, fast, and high throughput needs to be studied urgently. The purpose of this study was to establish a homogeneous immunoassay to detect the interaction between insulin-like growth factor-1 receptor-ß (IGF1R-ß) and suppressor of cytokine signaling 1 (SOCS1). The recombinant vectors IGF1R-ß/pENTER and SOCS1/pENTER were constructed and transfected into 293T cells. Based on homogeneous immunoassay technology, we established a suitable method. The signal intensity in the 293T lysate that overexpressed IGF1R-ß and SOCS1, respectively, was compared with the signal intensity in the simultaneous expression of IGF1R-ß and SOCS1. The interaction between IGF1R-ß and SOCS1 was verified in vitro. The detection system for the interaction between IGF1R-ß and SOCS1 was established. Compared with other methods, homogeneous immunoassay has the advantages of being rapid and sensitive, having higher sensitivity, and easy to operate. The interaction between IGF1R-ß and SOCS1 was tested to verify the feasibility of this method and prove its practicability and sensitivity. This new method can be used as a high-throughput platform for protein-protein interaction, with the advantages of trace detection, short detective time, and high detective sensitivity.

17.
Opt Express ; 28(11): 17056-17063, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32549515

RESUMO

We report an idler-resonant, continuous-wave (CW) seed injected, optical parametric oscillator (OPO) based on cadmium selenide (CdSe). The CdSe OPO was pumped by a 2.09 µm ns-pulsed laser and injection-seeded by a 2.58 µm CW laser. The idler-resonant oscillator was designed to maximize the optical-to-optical conversion efficiency and optimize the beam quality. The injected seed laser was designed to reduce the pump threshold. With this setup, the average idler output power of 802 mW was obtained corresponding to a pulse energy of 0.8 mJ at the wavelength of 11.01 µm and linewidth (FWHM) of 0.6 cm-1, optical-to-optical conversion efficiency of 4.4%, quantum conversion efficiency of 23.3%, beam quality of M2x = 1.23, M2y = 1.12, and pulse width of 21 ns. In addition, by turning the angle of the CdSe, wavelength tuning of 10.55-11.98 µm was achieved.

18.
Medicine (Baltimore) ; 99(23): e20561, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32502024

RESUMO

Nonobstructive azoospermia (NOA) is a severe form of male infertility. The molecular basis of NOA is still poorly understood. The aim of this study was to explore the associations between single nucleotide polymorphisms (SNPs) of the TATA-box binding protein associated factor 4b (TAF4B) gene and NOA. A total of 100 Han Chinese patients with NOA and 100 healthy men as controls were recruited. Targeted gene capture sequencing was performed. A total of 11 TAF4B SNPs were screened in the NOA and control subjects. Six synonymous and 4 nonsynonymous variants were detected. The c.11G>T (p.G4V) mutation was detected only in NOA patients. Polymorphism Phenotyping v2 and Sorting Intolerant From Tolerant analysis indicated that the p.G4V mutation influenced the protein structure of TAF4B. Haplotype analysis showed that the candidate SNPs did not independently associate with NOA and were found at extremely low frequencies in the subject population. Mutation Taster analysis indicated that the c.11G>T/p.G4V mutation was damaging. WebLogo analysis showed that the residue at amino acid 4 was relatively conserved. The p.Gly4Val substitution may affect the structure of the TAF4B protein. The c.11G>T mutation of the TAF4B gene may be associated with NOA in a Chinese population. Bioinformatics analysis indicated this variation may play an important role in the process of spermatogenesis.


Assuntos
Azoospermia/genética , Fatores Associados à Proteína de Ligação a TATA/genética , Fator de Transcrição TFIID/genética , Adulto , Estudos de Casos e Controles , China , Humanos , Masculino , Mutação , Polimorfismo de Nucleotídeo Único , Adulto Jovem
19.
Mol Genet Genomic Med ; 8(9): e1372, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32573075

RESUMO

BACKGROUND: Isolated hypogonadotropic hypogonadism (IHH) and Kallmann syndrome (KS) are rare genetic diseases that cause male infertility. The chromodomain helicase DNA-binding protein 7 (CHD7) gene is commonly associated with KS and IHH. We speculated that CHD7 variants may be associated with male infertility. METHODS: Two hundred males with azoospermia and 120 with oligozoospermia were recruited. The patients underwent clinical examination and reproductive hormone testing. A panel of genes including CHD7 and others related to spermatogenic failure was sequenced by targeted-gene exome sequencing. RESULTS: Three patients with severe oligozoospermia had CHD7 variants (a detection rate of 0.94% (3/320)). After prediction software analysis, two of the variants c.3464G>A (p.R1155H) and c.4516G>A (p.G1506S) were predicted to be likely pathogenic. Although predicted to be benign, the variants of c.2824A>G (p.T942A) located in the chromodomain 2 could not be excluded as disease causing. The patients with variants had small testicular volumes. In particular, the testes of the patient with a p.G1506S variant varied in size (left, 8 ml; right, 4.5 ml). Two patients (patients 31 and 120) had low E2 levels and two (patients 83 and 120) had low T levels. Ultimately, these variants were classified as "variants of unknown significant" that may be associated with male infertility. CONCLUSIONS: There may be a relationship between the CHD7 gene missense variants and male infertility. These variants are easier to find in patients with azoospermia and severe oligospermia whose testosterone levels are decreased.

20.
Mol Pharm ; 2020 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-32530637

RESUMO

Two well-defined synthetic polyphosphazene immunoadjuvants, PCPP and PCEP, were studied for their ability to potentiate the immune response to the hepatitis C virus (HCV) E2 glycoprotein antigen in vivo. We report that PCEP induced significantly higher serum neutralization and HCV-specific IgG titers in mice compared to other adjuvants used in the study: PCPP, Alum, and Addavax. PCEP also shifted the response toward the desirable balanced Th1/Th2 immunity, as evaluated by the antibody isotype ratio (IgG2a/IgG1). The in vivo results were analyzed in the context of antigen-adjuvant molecular interactions in the system and in vitro immunostimulatory activity of formulations. Asymmetric flow field flow fractionation (AF4) and dynamic light scattering (DLS) analysis showed that both PCPP and PCEP spontaneously self-assemble with the E2 glycoprotein with the formation of multimeric water-soluble complexes, which demonstrates the role of polyphosphazene macromolecules as vaccine delivery vehicles. Intrinsic in vitro immunostimulatory activity of polyphosphazene adjuvants, which was assessed using a mouse macrophage cell line, revealed comparable activities of both polymers and did not provide an explanation of their in vivo performance. However, PCEP complexes with E2 displayed greater stability against agglomeration and improved in vitro immunostimulatory activity compared to those of PCPP, which is in line with superior in vivo performance of PCEP. The results emphasize the importance of often neglected antigen-polyphosphazene self-assembly mechanisms in formulations, which can provide important insights on their in vivo behavior and facilitate the establishment of a structure-activity relationship for this important class of immunoadjuvants.

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