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1.
Protein Expr Purif ; 189: 105973, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34560256

RESUMO

The novel anti-PD-L1/TGFBR2-ECD fusion protein (BR102) comprises an anti-PD-L1 antibody (HS636) which is fused at the C terminus of the heavy chain to a TGF-ß1 receptor Ⅱ ectodomain (TGFBR2-ECD), and which can sequester the PD-1/PD-L1 pathway and TGF-ß bioactivity in the immunosuppressive tumor microenvironment. In the expression of TGFBR2-ECD wild-type fused protein (BR102-WT), a 50 kDa clipped species was confirmed to be induced by proteolytic cleavage at a "QKS" site located in the N-terminus of the ectodomain, which resulted in the formation of IgG-like clipping. The matrix metalloproteinase-9 was determined to be associated with BR102-WT digestion. In addition, it was observed that the N-glycosylation modifications of the fusion protein were tightly involved in regulating proteolytic activity and the levels of cleavage could be significantly suppressed by MMP-inhibitors. To avoid proteolytic degradation, eliminating protease-sensitive amino acid motifs and introducing potential glycosylation were performed. Three sensitive motifs were mutated, and the levels of clipping were strongly restrained. The mutant candidates exhibited similar binding affinities to hPD-L1 and hTGF-ß1 as well as highly purified BR102-WT2. Furthermore, the mutants displayed more significant proteolytic resistance than that of BR102-WT2 in the lysate incubation reaction and the plasma stability test. Moreover, the bifunctional candidate Mu3 showed an additive antitumor effect in MC38/hPD-L1 bearing models as compared to that of with anti-PD-L1 antibody alone. In conclusion, in this study, the protease-sensitive features of BR102-WT were well characterized and efficient optimization was performed. The candidate BR102-Mutants exhibited advanced druggability in drug stability and displayed desirable antitumor activity.

2.
J Colloid Interface Sci ; 607(Pt 1): 502-513, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34509121

RESUMO

HYPOTHESIS: The Landau-Levich-Derjaguin (LLD) theory is widely applied to predict the film thickness in the dip-coating process. However, the theory was designed only for flat plates and thin fibers. Fifty years ago, White and Tallmadge attempted to generalize the LLD theory to thick rods using a numerical solution for a static meniscus and the LLD theory to forcedly match their numeric solution with the LLD asymptotics. The White-Talmadge solution has been criticized for not being rigorous yet widely used in engineering applications mostly owing to the lack of alternative solutions. A new set of experiments significantly expanding the range of White-Tallmadge conditions showed that their theory cannot explain the experimental results. We then hypothesized that the results of LLD theory can be improved by restoring the non-linear meniscus curvature in the equation. With this modification, the obtained equation should be able to describe static menisci on any cylindrical rods and the film profiles observed at non-zero rod velocity. EXPERIMENT: To test the hypothesis, we distinguished capillary forces from viscous forces by running experiments with different rods and at different withdrawal velocities and video tracking the menisci profiles and measuring the weight of deposited films. The values of film thickness were then fitted with a mathematical model based on the modified LLD equation. We also fitted the meniscus profiles. FINDINGS: The results show that the derived equation allows one to reproduce the results of the LLD theory and go far beyond those to include rods of different radii. A new set of experimental data together with the White-Tallmadge experimental data are explained with the modified LLD theory. A set of simple formulas approximating numeric results have been derived. These formulas can be used in engineering applications for the prediction of the coating thickness.

3.
Nat Commun ; 12(1): 6471, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34753932

RESUMO

Very recently, increasing attention has been focused on non-Abelian topological charges, e.g., the quaternion group Q8. Different from Abelian topological band insulators, these systems involve multiple entangled bulk bandgaps and support nontrivial edge states that manifest the non-Abelian topological features. Furthermore, a system with an even or odd number of bands will exhibit a significant difference in non-Abelian topological classification. To date, there has been scant research investigating even-band non-Abelian topological insulators. Here, we both theoretically explore and experimentally realize a four-band PT (inversion and time-reversal) symmetric system, where two new classes of topological charges as well as edge states are comprehensively studied. We illustrate their difference in the four-dimensional (4D) rotation sense on the stereographically projected Clifford tori. We show the evolution of the bulk topology by extending the 1D Hamiltonian onto a 2D plane and provide the accompanying edge state distributions following an analytical method. Our work presents an exhaustive study of four-band non-Abelian topological insulators and paves the way towards other even-band systems.

4.
BMC Plant Biol ; 21(1): 526, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758750

RESUMO

BACKGROUND: Wall-associated kinase (WAK)/WAK-like (WAKL) is one of the subfamily of receptor like kinases (RLK). Although previous studies reported that WAK/WAKL played an important role in plant cell elongation, response to biotic and abiotic stresses, there are no systematic studies on RcWAK/RcWAKL in rose. RESULTS: In this study, we identified a total of 68 RcWAK/RcWAKL gene family members within rose (Rosa chinensis) genome. The RcWAKs contained the extracellular galacturonan-binding domain and calcium-binding epidermal growth factor (EGF)-like domain, as well as an intracellular kinase domains. The RcWAKLs are missing either calcium-binding EGF-like domain or the galacturonan-binding domain in their extracellular region. The phylogenetic analysis showed the RcWAK/RcWAKL gene family has been divided into five groups, and these RcWAK/RcWAKL genes were unevenly distributed on the 7 chromosomes of rose. 12 of RcWAK/RcWAKL genes were significantly up-regulated by Botrytis cinerea-inoculated rose petals, where RcWAK4 was the most strongly expressed. Virus induced gene silencing of RcWAK4 increased the rose petal sensitivity to B. cinerea. The results indicated RcWAK4 is involved in the resistance of rose petal against B. cinerea. CONCLUSION: Our study provides useful information to further investigate the function of the RcWAK/RcWAKL gene family and breeding research for resistance to B. cinerea in rose.

5.
Oxid Med Cell Longev ; 2021: 3137066, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777682

RESUMO

Background: Osteoarthritis (OA) is a progressive illness that destroys cartilage. Oxidative stress is a major contributor of OA, while endoplasmic reticulum (ER) stress is the key cellular damage under oxidative stress in chondrocytes. Echinacoside (ECH) is the main extract and active substance of Cistanche, with potent antioxidative stress (OS) properties, and currently under clinical trials in China. However, its function in OA is yet to be determined. Purpose: We aimed to explore the specific role of ECH in the occurrence and development of OA and its underlying mechanism in vivo and in vitro. Methods: After the mice were anesthetized, the bilateral medial knee joint meniscus resection was performed to establish the DMM model. TBHP was used to induce oxidative stress to establish the OA model in chondrocytes in vitro. Western blot and RT-PCR were used to evaluate the level of ER stress-related biomarkers such as p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP and apoptosis-related proteins such as BAX, Bcl-2, and cleaved caspase-3. Meanwhile, we used SO staining, immunofluorescence, and immunohistochemical staining to evaluate the pharmacological effects of ECH in mice in vivo. Results: We demonstrated the effectiveness of ECH in suppressing ER stress and restoring ECM metabolism in vitro. In particular, ECH was shown to suppress tert-Butyl hydroperoxide- (TBHP-) induced OS and subsequently lower the levels of p-PERK/PERK, GRP78, ATF4, p-eIF2α/eIF2α, and CHOP in vitro. Simultaneously, ECH reduced MMP13 and ADAMTS5 levels and promoted Aggrecan and Collagen II levels, suggesting ECM degradation suppression. Moreover, we showed that ECH mediates its cellular effects via upregulation of Sirt1. Lastly, we confirmed that ECH can protect against OA in mouse OA models. Conclusion: In summary, our findings indicate that ECH can inhibit ER stress and ECM degradation by upregulating Sirt1 in mouse chondrocytes treated with TBHP. It can also prevent OA development in vivo.

6.
Front Cell Dev Biol ; 9: 745621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805156

RESUMO

Intervertebral disc degeneration (IDD) is a major cause of low back pain (LBP), but there is still a lack of effective therapy. Multiple studies have reported that endoplasmic reticulum (ER) stress and extracellular matrix (ECM) degradation exert an enormous function on the occurrence and development of IDD. Autophagy can effectively repair ER stress and maintain ECM homeostasis. Eicosapentaenoic acid (EPA) can specifically induce autophagy. The purpose of this study is to demonstrate that EPA can promote autophagy, reduce ECM degradation and ER stress in vitro, thereby reducing cell apoptosis, and the protective effects of EPA in an IDD-rat model in vivo. Western blot and immunofluorescence were used to detect the autophagic flux, ER stress, ECM degradation, and apoptosis in nucleus pulposus cells (NPCs) treated by EPA. We also used puncture-induced IDD rats as experimental subjects to observe the therapeutic effect of EPA on IDD. Our findings indicated that EPA can effectively improve the autophagy activity in NPCs, inhibit the endoplasmic reticulum stress process, reduce the degree of cell apoptosis, and exert protective effects on the anabolism and catabolism of ECM. In addition, in vivo investigations demonstrated that EPA ameliorated the progression of puncture-induced IDD in rats. In conclusion, this study revealed the intrinsic mechanisms of EPA's protective role in NPCs and its potential therapeutic significance for the treatment of IDD.

7.
Proc Natl Acad Sci U S A ; 118(48)2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34810248

RESUMO

Synaptotagmin 1 (syt1) is a Ca2+ sensor that regulates synaptic vesicle exocytosis. Cell-based experiments suggest that syt1 functions as a multimer; however, biochemical and electron microscopy studies have yielded contradictory findings regarding putative self-association. Here, we performed dynamic light scattering on syt1 in solution, followed by electron microscopy, and we used atomic force microscopy to study syt1 self-association on supported lipid bilayers under aqueous conditions. Ring-like multimers were clearly observed. Multimerization was enhanced by Ca2+ and required anionic phospholipids. Large ring-like structures (∼180 nm) were reduced to smaller rings (∼30 nm) upon neutralization of a cluster of juxtamembrane lysine residues; further substitution of residues in the second C2-domain completely abolished self-association. When expressed in neurons, syt1 mutants with graded reductions in self-association activity exhibited concomitant reductions in 1) clamping spontaneous release and 2) triggering and synchronizing evoked release. Thus, the juxtamembrane linker of syt1 plays a crucial role in exocytosis by mediating multimerization.

8.
Toxicol Res (Camb) ; 10(5): 1013-1021, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34733486

RESUMO

Circular RNAs (circRNAs), is a novel type of endogenous non-coding RNAs (ncRNAs) participated in the pathogenesis of many diseases. Beryllium is one of the carcinogenesis elements. However, the mechanism and function of circRNAs in human bronchial epithelial cells (16HBE) induced by beryllium sulfate (BeSO4) was rarely reported. Therefore, the high-throughput RNA sequencing analysis was performed to detect the circRNA profiles between control groups and BeSO4-induced groups. Furthermore, circRNA-miRNA-mRNA network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and PPI network analysis were used for bioinformatics analysis. CircRNA sequencing analysis revealed that 36 circRNAs were up-regulated and 35 circRNAs were down-regulated in the BeSO4-exposed groups. The selected circRNAs were verified by real-time fluorescent quantitative PCR (qRT-PCR). Hsa_circ_0004214 and hsa_circ_0003586 were validated to be up-regulated, hsa_circ_0047958, hsa_circ_0001944, and hsa_circ_0008982 were down-regulated. The circRNA-miRNA-mRNA network annotated the key signaling pathway including cellular senescence, TNF signaling pathway, NF-kappa B signaling pathway, HIF-1 signaling pathway, and Hippo signaling pathway. The PPI network indicated the most circRNAs might participate in the BeSO4 toxicity by acting as a sponge for the miR-663b through JAK-STAT signaling pathway. In summary, our study suggests that circRNAs may play roles in the mechanism of beryllium toxicity.

9.
Nat Metab ; 3(11): 1569-1584, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34750570

RESUMO

The Hedgehog (Hh) signalling pathway plays a critical role in regulating liver lipid metabolism and related diseases. However, the underlying mechanisms are poorly understood. Here, we show that the Hh signalling pathway induces a previously undefined long non-coding RNA (Hilnc, Hedgehog signalling-induced long non-coding RNA), which controls hepatic lipid metabolism. Mutation of the Gli-binding sites in the Hilnc promoter region (HilncBM/BM) decreases the expression of Hilnc in vitro and in vivo. HilncBM/BM and Hilnc-knockout mice are resistant to diet-induced obesity and hepatic steatosis through attenuation of the peroxisome proliferator-activated receptor signalling pathway, as Hilnc directly interacts with IGF2BP2 to enhance Pparγ mRNA stability. Furthermore, we identify a potential functional human homologue of Hilnc, h-Hilnc, which has a similar function in regulating cellular lipid metabolism. These findings uncover a critical role of the Hh-Hilnc-IGF2BP2 signalling axis in lipid metabolism and suggest a potential therapeutic target for the treatment of diet-induced hepatic steatosis.

10.
Front Plant Sci ; 12: 738880, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759939

RESUMO

The TRICHOME BIREFRINGENCE-LIKE (TBL) family is an important gene family engaged in the O-acetylation of cell wall polysaccharides. There have been a few reports showing that TBL participated in the resistance against phytopathogens in Arabidopsis and rice. However, no relevant studies in rose (Rosa sp.) have been published. In this study, a genome-wide analysis of the TBL gene family in rose was presented, including their phylogenetic relationships, gene structure, chromosomal positioning, and collinearity analysis. The phylogenetic analysis revealed a total of 50 RcTBL genes in the rose genome, and they are unevenly distributed across all seven chromosomes. The occurrence of gene duplication events suggests that both the whole genome duplication and partial duplication may play a role in gene duplication of RcTBLs. The analysis of Ka/Ks showed that the replicated RcTBL genes underwent mainly purifying selection with limited functional differentiation. Gene expression analysis indicated that 12 RcTBLs were down-regulated upon the infection of Botrytis cinerea, the causal agent of the gray mold disease of rose. These RcTBLs may be a sort of candidate genes for regulating the response of rose to B. cinerea. Through virus-induced gene silencing, RcTBL16 was shown to be associated with susceptibility to gray mold in rose. Through this study, meaningful information for further studies on the function of the TBL protein family in rose is provided.

11.
Neurochem Res ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779994

RESUMO

Epilepsy is one of the most common chronic neurological diseases. There is increasing evidence for ferroptosis playing an important role in the occurrence and development of epilepsy. Vitamin E is a common fat-soluble antioxidant that can regulate ferroptosis. The aim of this study was to investigate the effects of vitamin E on ferroptosis of hippocampal neurons in epileptic rats. Sixty-four male Sprague-Dawley (SD) rats were randomly divided into control, pentylenetetrazol (PTZ; 35 mg/kg), vitamin E (200 mg/kg) + PTZ, and Ferrostatin-1 (Fer-1; 2.5 µmol/kg) + PTZ groups, with drugs administered intraperitoneally 15 times every other day for 29 days. The behavioral manifestations (epileptic score, latency, and number of seizures in 30 min) and EEG changes were observed and recorded. Nissl staining and electrophysiological recording were used to assess neuronal damage and excitability in the hippocampal CA1 region, respectively. The levels of iron, glutathione (GSH), and malondialdehyde (MDA) in the hippocampus were assessed by spectrophotometry. Immunofluorescence staining was used to detect lipoxygenase 15 (15-LOX) expression. Western blot was used to determine glutathione peroxidase 4 (GPX4) and 15-LOX protein levels. Vitamin E treatment was associated with decreased epileptic grade, seizure latency, and number of seizures in the PTZ-kindled epileptic model. Vitamin E treatment also decreased 15-LOX expression, inhibited MDA and iron accumulation, and increased GPX4 and GSH expression. In conclusion, vitamin E can reduce neuronal ferroptosis and seizures by inhibiting 15-LOX expression.

12.
Front Nutr ; 8: 709211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746201

RESUMO

Background and Aims: Sarcopenia is negatively associated with clinical outcomes. However, the definitions of sarcopenia are inconsistent across international consensuses. Thus, the purpose of this study is to compare the impact of the basic definition components of sarcopenia and their combinations in post-operative complications and overall survival, aiming to find the best sarcopenia definition to stratify the prognosis in an Asian population. Methods: A total of 1,307 patients who underwent curative surgery for gastric cancer from July 2014 to May 2019 were prospectively included. The basic sarcopenia components were measured pre-operatively, including low skeletal muscle mass index (LSMI), low skeletal muscle radiodensity (LSMD), low handgrip strength (LHGS), and low gait speed (LGS). Among them, LSMI and LSMD were measured using a CT post-processing software, LHGS was measured using an electronic hand dynamometer, and LGS was represented by a 6-m walk speed. Results: For the single basic component, the muscle function parameters (LHGS or LGS) but not the muscle composition parameters (LSMI or LSMD) showed associations with post-operative complications and mortality. For the combination of the basic combinations, all statistically significant combinations included at least one muscle function parameter. The combination of muscle composition (LSMI or LSMD) and muscle function (LHGS or LGS) had a significantly higher area under the curve in the prediction of post-operative complications compared with the combinations of two muscle function parameters (LSMI plus LSMD) or two muscle composition parameters (LHGS plus LGS). Conclusions: Compared with muscle composition parameters (LSMI and LSMD), muscle function parameters (LHGS and LGS) are better predictors of post-operative complications and overall survival, which should be considered as the principal determinant in the sarcopenia definition. The definition of sarcopenia consists of muscle function (LHGS or LGS) and muscle composition (LSMI or LSMD) separately, which is better than the combination of the two muscle function parameters (LHGS plus LGS) or two muscle composition parameters (LSMI plus LSMD).

13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(5): 825-831, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34622600

RESUMO

Objective: To establish an animal model of reflux renal damage through bladder outlet obstruction. Methods: Sixty male C57BL/6 mice aged 6-8 weeks were randomly assigned to a control group, a sham operation group, and a partial bladder outlet obstruction (PBOO) group, with 20 mice in each group. Laparotomy were performed on the PBOO mice under anesthesia in order to separate the bladder necks and to perform guided partial ligation of the bladder neck with a metal rod of 0.3 mm diameter. Mice in the sham operation group had laparotomy and had their bladder necks separated without ligation. The control group did not receive any treatment. 7 days after the surgery, 12 surviving mice were randomly selected from each group to observe the general changes of the bladder, ureter, renal pelvis and kidney. Retrograde urography was performed through the bladder. Kidney tissues were extracted for histopathological analysis. The expression levels of Vimentin, proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were examined with Western blot, immunohistochemistry and immunofluorescence staining tests, respectively. Results: Compared with the control and sham operation group, the bladder, ureter, and renal pelvis of the mice in the PBOO group were significantly enlarged, vesicoureteral reflux was more obvious, the kidney volume and mass increased ( P<0.001), and renal parenchyma became thinner ( P<0.000 1). Histopathological staining showed glomerular atrophy, renal tubule expansion, tubulointerstitial inflammatory cell infiltration, glomerular basement membrane hyperplasia and obvious interstitial fibrosis. Western blot, immunofluorescence and immunohistochemistry staining showed that the expression levels of Vimentin, PCNA and α-SMA in kidney tissue were elevated ( P<0.000 1). Conclusion: After PBOO, the bladder, ureter, and kidney of the mice showed obvious morphological alteration and presented reflux renal fibrosis-like damage. This can be used as an animal model to study the pathological alteration mechanism and therapeutic measures of renal fibrosis caused by bladder outlet obstruction.


Assuntos
Obstrução do Colo da Bexiga Urinária , Refluxo Vesicoureteral , Animais , Modelos Animais de Doenças , Rim , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obstrução do Colo da Bexiga Urinária/complicações , Refluxo Vesicoureteral/complicações
14.
Int J Gen Med ; 14: 6563-6571, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675623

RESUMO

Objective: To evaluate the feasibility, clinical efficacy and imaging results of preoperative traction (PT) followed by percutaneous kyphoplasty (PKP) combined with percutaneous cement discoplasty (PCD) for treating severe thoracolumbar osteoporotic vertebral compression fractures (OVCFs). Methods: A total of 13 patients with severe thoracolumbar OVCFs treated by PT followed by PKP combined with PCD were enrolled. General information, PT time, operation time, postoperative hospital stay, perioperative complications, visual analog scale (VAS) score, Oswestry disability index (ODI) score, local kyphosis angle, intervertebral angle (IVA), anterior vertebral height (AVH) and posterior vertebral height (PVH) were recorded. Results: The average VAS score at admission was 7.4±3.5, decreased to 4.3±1.7 after PT and 2.3±0.7 three days after operation, and 1.5±0.9 at last follow-up. The average ODI score was 73.7±21.4 before operation, decreased to 26.6±9.3 three days after operation and 13.7±7.1 at last follow-up. Compared to VAS and ODI scores at admission, these at the third day after operation and last follow-up were significantly different. At admission, the IVA was 3.4°±6.8°, the disc height was 5.7±1.2mm, the AVH was 10.7±3.2mm, and the PVH was 25.7±4.2 mm, which, after PT, changed to 8.1°±7.3°, 8.6±2.6mm, 18.5±2.8mm, and 26.2±7.1mm, respectively, and the differences were significant. The average kyphotic angle was 43.4°±17.8° at admission, and decreased to 26.3°±6.7° after PT, 17.5°±8.4° three days after operation and 19.1°±10.3° at last follow-up, and the differences were significant. Conclusion: PT followed by PKP combined with PCD for the treatment of severe thoracolumbar OVCFs was an effective and simple procedure with satisfactory short-term clinical outcomes by relieving pain and improving kyphosis.

15.
Front Plant Sci ; 12: 723294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650580

RESUMO

The accurate identification of apple leaf diseases is of great significance for controlling the spread of diseases and ensuring the healthy and stable development of the apple industry. In order to improve detection accuracy and efficiency, a deep learning model, which is called the Coordination Attention EfficientNet (CA-ENet), is proposed to identify different apple diseases. First, a coordinate attention block is integrated into the EfficientNet-B4 network, which embedded the spatial location information of the feature by channel attention to ensure that the model can learn both the channel and spatial location information of important features. Then, a depth-wise separable convolution is applied to the convolution module to reduce the number of parameters, and the h-swish activation function is introduced to achieve the fast and easy to quantify the process. Afterward, 5,170 images are collected in the field environment at the apple planting base of the Northwest A&F University, while 3,000 images are acquired from the PlantVillage public data set. Also, image augmentation techniques are used to generate an Apple Leaf Disease Identification Data set (ALDID), which contains 81,700 images. The experimental results show that the accuracy of the CA-ENet is 98.92% on the ALDID, and the average F1-score reaches .988, which is better than those of common models such as the ResNet-152, DenseNet-264, and ResNeXt-101. The generated test dataset is used to test the anti-interference ability of the model. The results show that the proposed method can achieve competitive performance on the apple disease identification task.

16.
Nucleic Acids Res ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664670

RESUMO

The success of protein engineering and design has extensively expanded the protein space, which presents a promising strategy for creating next-generation proteins of diverse functions. Among these proteins, the synthetic binding proteins (SBPs) are smaller, more stable, less immunogenic, and better of tissue penetration than others, which make the SBP-related data attracting extensive interest from worldwide scientists. However, no database has been developed to systematically provide the valuable information of SBPs yet. In this study, a database named 'Synthetic Binding Proteins for Research, Diagnosis, and Therapy (SYNBIP)' was thus introduced. This database is unique in (a) comprehensively describing thousands of SBPs from the perspectives of scaffolds, biophysical & functional properties, etc.; (b) panoramically illustrating the binding targets & the broad application of each SBP and (c) enabling a similarity search against the sequences of all SBPs and their binding targets. Since SBP is a human-made protein that has not been found in nature, the discovery of novel SBPs relied heavily on experimental protein engineering and could be greatly facilitated by in-silico studies (such as AI and computational modeling). Thus, the data provided in SYNBIP could lay a solid foundation for the future development of novel SBPs. The SYNBIP is accessible without login requirement at both official (https://idrblab.org/synbip/) and mirror (http://synbip.idrblab.net/) sites.

17.
Appl Opt ; 60(25): 7563-7573, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613222

RESUMO

In view of the functional requirements of high reliability and stability support of optical components of space remote sensors, a rigid-flexible, dual-mode coupling support structure for space-based rectangular curved prisms (SRCPs) was designed. In-depth studies of the support principle and engineering realization of the SRCPs and optimization of the flexible adhesive structure were performed. Static and dynamic simulations were conducted on the mirror subassembly by means of finite element analysis, and test verification was also performed. The tests revealed that the surface shape error of the mirror subassembly after mechanical testing was 0.021λ, the displacement of the mirror body was 0.008 mm, the inclination angle was ∼0.8'', the mass of the mirror subassembly was 4.79 kg, the fundamental frequency was 283 Hz, and the maximum amplification of the total rms acceleration was 4.37. All indexes were superior to those of the design requirements. On this basis, bonding tests and mechanical tests of a rectangular curved prism reflector, a rectangular curved prism, and a rectangular plane reflector employing this proposed support structure were continued. The test results verified the reliability, stability, and universal applicability of the proposed rigid-flexible, dual-mode peripheral bonding support structure.

18.
Chem Commun (Camb) ; 57(78): 10063-10066, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34514477

RESUMO

A nitrogen-based complex hydride is investigated for hydrogen isotope separation for the first time. The experimental results show that a lithium amide-lithium hydride composite (Li-N-H) possesses a distinct positive isotope effect with a separation factor of 1.42. The H-D exchange process in this system occurs at 373 K and can be accelerated with the increase of temperature.

19.
Am J Reprod Immunol ; : e13500, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34558137

RESUMO

A common genetic variant in the follicle stimulating hormone receptor gene (FSHR) 5'-untranslated region has been previously reported to influence FSHR gene expression. However, studies on the ovarian response to exogenous gonadotropin stimulation are limited. The aim of this study was to evaluate the association of variants at positions -29 of the FSHR gene with the ovarian response to exogenous FSH stimulation in Chinese women. The genotypes of the FSHR gene were assayed using the Sequenom MassARRAY system. Total RNA and protein was extracted from granulosa cells, and FSHR expression at the mRNA and protein levels was assessed using quantitative PCR and western blotting. Our data revealed that there was no association between the FSHR genotype at the -29 position and the outcome of controlled ovarian stimulation. The expression of FSHR, at both the mRNA and protein levels, was similar amongst the different FSHR genotypes assessed, but was significantly reduced in the low responders. These results indicate that the variants caused by mutations at position -29 are not associated with ovarian response, and the low ovarian response to gonadotropin stimulation may be caused by decreased FSHR expression.

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