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1.
BMC Infect Dis ; 24(1): 371, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566017

RESUMO

BACKGROUND: There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. METHODS: BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student's t-test. RESULTS: The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. CONCLUSIONS: Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.


Assuntos
Interleucina-6 , Lipopolissacarídeos , Células B de Memória , Ácidos Teicoicos , Camundongos , Animais , Camundongos Endogâmicos BALB C , Staphylococcus aureus , Imunização , Vacinação , Peptídeos
2.
Lasers Med Sci ; 38(1): 277, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38012462

RESUMO

This study aimed to compare higher-order aberrations (HOAs) after small incision lenticule extraction (SMILE) in patients with different angle kappa. This is a retrospective report in which 341 right eyes of 341 patients who were subjected to SMILE, which used coaxially sighted corneal light reflex (CSCLR) as the treatment zone centered, treated by the same experienced surgeon (LHB) for correction of myopia and myopic astigmatism, preoperative and postoperative spherical equivalent (SE), angle kappa, total higher-order aberrations (total HOA), spherical aberration (SA), vertical coma (VC), horizontal coma (HC), oblique trefoil (OT), and horizontal trefoil (HT), were compared. SMILE showed outstanding performance in terms of safety, efficacy, and predictability. In addition, a comparison of preoperative and postoperative HOAs exhibited the difference of total HOA (P < 0.01), SA (P < 0.01), VC (P < 0.01), and HC (P < 0.01), which was statistically significant; however, for OT and HT with the longer follow-up time, the statistical difference gradually decreased. For stratification of angle kappa into groups based on decantation, angle kappa was divided into three major groups: r < 0.1 mm, 0.1 ≤ r < 0.2 mm, and r ≥ 0.2 mm; the changes of SA (F = 4.127, P = 0.021) and OT (F = 3.687, P = 0.031) exhibited significant difference after 1 year of SMILE. We performed a correlation analysis of all preoperative and postoperative parameters, and the results indicated that the preoperative total HOA was negatively correlated with preoperative cylindrical diopter (DC), and postoperative total HOA, SA, and coma were affected by spherical diopter (DS) and SE. Moreover, we also found a significant difference of SA and VC in the early postoperative with preoperative. SA was positively correlated with Y values and r of 1 year after SMILE. All of the analyzed parameters in the three groups, except for the trefoil, gradually increased over time; however, the trefoil could gradually stabilize over time. We also divided angle kappa into four groups by quadrants; the result showed that the effects of higher-order aberrations were markedly different from the various quadrants. Patients with large angle kappa were able to increase VC and SA postoperatively, and higher HOAs were more significant in patients with high myopia. The differences in quadrants exhibited a diversity of HOAs; this could be attributed to the corneal surface reestablishment and the alteration of angle kappa, but the trend was not apparent. Although all patients displayed increased HOAs after SMILE, the potential application of CSCLR as the treatment zone centered still showed excellent safety, efficacy, and predictability.


Assuntos
Miopia , Ferida Cirúrgica , Humanos , Acuidade Visual , Estudos Retrospectivos , Coma , Refração Ocular , Miopia/cirurgia , Lasers de Excimer
3.
Cell Commun Signal ; 18(1): 169, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109187

RESUMO

BACKGROUND: Jumonji AT-rich interactive domain 1B(JARID1B) has been shown to be upregulated in many human cancers and plays a critical role in the development of cancers cells. Nevertheless, its functional role in colorectal cancer (CRC) progression is not fully understood. METHODS: Herein, JARID1B expression levels were detected in clinical CRC samples by western blotting and qRT-PCR. DLD-1 cells with JARID1B knockdown or overexpression by stably transfected plasmids were used in vitro and in vivo study. Colony formation, 5-ethynyl-20-deoxyuridine (EdU) and Real Time Cellular Analysis (RTCA) assays were used to detect cell proliferation and growth. Transcriptome and CHIP assays were used to examine the molecular biology changes and molecular interaction in these cells. Nude mice was utilized to study the correlation of JARID1B and tumor growth in vivo. RESULTS: Here, we first observed that JARID1B was significantly upregulated in CRC tissue compared to adjacent normal tissues. In CRC patients, JARID1B high expression was positively relation with poor overall survival. Multivariate analyses revealed that high JARID1B expression was an independent predictive marker for the poor prognosis of CRC. In addition, we found that JARID1B promoted CRC cells proliferation by Wnt/ß-catenin signaling pathway. Further studies demonstrated CDX2 as a downstream target of JARID1B, and our data demonstrated that CDX2 is crucial for JARID1B -mediated Wnt/ß-catenin signaling pathway. Mechanistically, we demonstrated that JARID1B regulated CDX2 expression through demethylation of H3K4me3. CONCLUSIONS: CDX2 inhibited by JARID1B-derived H3K4me3 methylation promoted cells proliferation of CRC via Wnt/ß-catenin signaling pathway. Therefore, our studies provided a novel insight into the role of JARID1B in CRC cells proliferation and potential new molecular target for treating CRC. Video abstract.


Assuntos
Fator de Transcrição CDX2/metabolismo , Neoplasias Colorretais/patologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Via de Sinalização Wnt , Animais , Fator de Transcrição CDX2/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Progressão da Doença , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Lisina/metabolismo , Masculino , Metilação , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Nucleares/genética , Regiões Promotoras Genéticas/genética , Proteínas Repressoras/genética , Análise de Sobrevida , Regulação para Cima/genética
4.
Cell Mol Biol (Noisy-le-grand) ; 65(4): 1-5, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31078145

RESUMO

To analyze the effects of blastocysts on the 5th day (D5) and 6th day (D6) of frozen-thawed blastocyst transplantation on pregnancy outcome and provide evidence for further improvement of the strategy. This study included transfers from the Reproductive Medicine Center of the Second Affiliated Hospital of Wenzhou Medical University during freeze-thaw cycles from January 2016 to December 2017. They were divided into D5 group (1616 cases) and D6 group (619 cases) according to blastocyst formation and development. Each group was further divided into 5 groups according to the quality of the blastocyst and the number of transplants, making a total of 10 groups. Following the frozen transplantation cycle, the transplanting rate was significantly higher for D5 (41.73%) than for D6 (23.98%) (P < 0.05); the ongoing pregnancy rate (47,40%) was also significantly higher than that of D6 (28.43%) (P < 0.05).In the frozen-thawed blastocyst resuscitation transplantation, compared to D6 blastocysts, D5 blastocysts were more conducive to blastocyst implantation and could be used to achieve better clinical pregnancy outcome. In blastocyst selection, a single D5 excellent blastocyst transplant is preferred. Only at the 6th day of non-excellent D6, 2 blastocysts are recommended for transplantation.


Assuntos
Blastocisto/citologia , Desenvolvimento Embrionário , Congelamento , Adulto , Transferência Embrionária , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Resultado da Gravidez , Fatores de Tempo , Adulto Jovem
5.
Proc Natl Acad Sci U S A ; 111(15): 5574-9, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24706897

RESUMO

The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 (Sp1), a major transcription factor that controls expression of lens-specific genes such as ß-crystallins, was positively regulated by SUMO1 but negatively regulated by SUMO2. SUMO2 was found to inhibit Sp1 functions through several mechanisms: sumoylating it at K683 to attenuate DNA binding, and at K16 to increase its turnover. SUMO2 also interfered with the interaction between Sp1 and the coactivator, p300, and recruited a repressor, Sp3 to ß-crystallin gene promoters, to negatively regulate their expression. Thus, stable SUMO1, but diminishing SUMO2/3, during lens development is necessary for normal lens differentiation. In support of this conclusion, SUMO1 and Sp1 formed complexes during early and later stages of lens development. In contrast, an interaction between SUMO2/3 and Sp1 was detected only during the initial lens vesicle stage. Together, our results establish distinct roles of different SUMO isoforms and demonstrate for the first time, to our knowledge, that Sp1 acts as a major transcription factor target for SUMO control of cell differentiation.


Assuntos
Diferenciação Celular/fisiologia , Células Epiteliais/fisiologia , Regulação da Expressão Gênica/fisiologia , Cristalino/crescimento & desenvolvimento , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Fator de Transcrição Sp1/metabolismo , Sumoilação/fisiologia , Animais , Western Blotting , Imunoprecipitação da Cromatina , Primers do DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Fatores de Crescimento de Fibroblastos/metabolismo , Imuno-Histoquímica , Imunoprecipitação , Cristalino/citologia , Camundongos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
6.
Clin Nucl Med ; 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39010313

RESUMO

ABSTRACT: We reported imaging findings with a peculiar tau accumulation pattern in a 56 year-old woman with frontotemporal dementia caused by Q351R mutation in the microtubule-associated protein tau (MAPT) gene. She had a 10-year history of gradually worsening memory loss. 18F-FDG PET demonstrated hypometabolism in medial temporal lobes, but 18F-florbetapir PET manifested no abnormal amyloid beta deposition, which ruled out Alzheimer disease. 18F-florzolotau PET showed tau proteins accumulated in medial temporal lobes, basal ganglia brainstem, and cerebellum. The pattern is different from other known MAPT gene mutation. Multitracer imaging can help differentiate between Alzheimer disease and frontotemporal dementia caused by MAPT mutation.

7.
Technol Health Care ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38943413

RESUMO

BACKGROUND: About 186 million people in the world suffer from infertility, and there is one infertile couple in every 4-6 couples. It is thus essential to find effective psychological treatment. OBJECTIVE: To conduct a systematic review of previous meta-analyses on mindfulness-based therapy outcomes in infertile female patients and a meta-analysis of studies nested within these meta-analyses. METHODS: Randomized controlled trials (RCTS) on the efficacy of mindset-based interventions in infertile female patients were retrieved from PubMed, The Cochrane Library, Embase, Web of Science, CNI, VIP Database, and Wanfang Database until March 1, 2023. Two researchers screened the literature, extracted data according to inclusion and exclusion criteria, and conducted quality control according to Cochrane Handbook 5.1.0. When there was ambiguity, a third party determined it. The meta-analysis was performed using RevMan 5.3 software. RESULT: 14 randomized controlled trials involving 1784 patients were included. Meta-analysis showed that compared with conventional care, mindfulness-based intervention can effectively relieve anxiety in female infertility patients [SMD =-2.25, 95% CI (-2.90, -1.60), P< 0.00001], depression [SMD =-2.25, 95% CI (-2.99, -1.52), P< 0.00001], perceived stress [SMD =-0.99, 95% CI (-1.27, -0.71), P< 0.00001], improved quality of life, physiological function [MD = 14.03, 95% CI (11.98, 16.07), P< 0.00001], Role limitations due to physical problems [MD = 11.30, 95% CI (5.71, 16.90), P< 0.0001], vitality [MD = 11.55, 95% CI (9.46, 13.65), P< 0.00001], mental health [MD = 17.32, 95% CI (15.29, 19.35), P< 0.00001]. CONCLUSION: Existing evidence shows that mindfulness therapy can effectively relieve the anxiety and depression of infertile women, reduce the level of stress, and improve the quality of life and sleep quality. However, due to the limited quantity and quality of the literature, multi-center, large-sample, and high-quality randomized controlled studies should be conducted in the future.

8.
ACS Appl Mater Interfaces ; 16(22): 29257-29266, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38781456

RESUMO

Triboelectric polymers have attracted extensive attention due to their great electron-accepting and electron-donating properties in contact electrification as well as their flexible and low-cost merits and have become promising electrode materials in triboelectric nanogenerators (TENGs). However, most research has exclusively focused on improving the electron capture capability of the triboelectric layer, neglecting to enhance the electron-donating capability, which leads to a low output performance of TENG and limits its practical application. In this study, we developed a method to fabricate highly tribo-positive Nylon-11 film through roll-to-roll processing. Paired with the poly(tetrafluoroethylene) triboelectric layer, the transferred charge density of contact-separation TENG based on Nylon-11 film prepared by this method reaches 291.1 µC/m2, which has been improved by 12.4% compared with the conventional compression molding sample. The novel fabricating method can regulate the surface functional groups to achieve higher surface potential and obtain a favorable pseudohexagonal crystal phase, leading to an increasing transferred charge density in triboelectrification. Additionally, it has been analyzed that higher chemical potential of materials can facilitate the transfer of electrons from the triboelectric polymer surface. This study provides a nonadditive, simple, and effective strategy to fabricate excellent tribo-positive material, which can significantly enhance the performance of TENG.

9.
ACS Nano ; 18(5): 4467-4477, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38263634

RESUMO

The energy conversion efficiency of a triboelectric nanogenerator (TENG) is severely limited by the charge density of triboelectric materials, while drastic and unavoidable charge decay happens during contact due to the insufficient charge retention capacity of positive triboelectric materials. Here, elaborately synthesized acid-ion-doped pyridine-based polybenzimidazole processing with strong charge retention capability is demonstrated to couple with negatively corona-polarized electrets. As illustrated by thermal stimulation and an ion mass spectrometer, the formation of acid-ion chimerism processes high activation energy for stored charges, and the selective anion migration can compensate the escape of polarized charge. Accordingly, the charge density can reach up to 596 µC m-2 and the charge retention rate reaches 49.7%, which is so far the highest intrinsic charge density obtained in the open air. Thus, the ionic chimerism strategy provides an effective way to suppress the charge escaping in the open air and gives a great expandable avenue for the material challenges of TENG's practical deployment.

10.
Nat Commun ; 15(1): 819, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280902

RESUMO

Lightweight flexible piezoelectric polymers are demanded for various applications. However, the low instinctively piezoelectric coefficient (i.e. d33) and complex poling process greatly resist their applications. Herein, we show that introducing dynamic pressure during fabrication is capable for poling polyvinylidene difluoride/barium titanate (PVDF/BTO) composites with d33 of ~51.20 pC/N at low density of ~0.64 g/cm3. The melt-state dynamic pressure driven energy implantation induces structure evolutions of both PVDF and BTO are demonstrated as reasons for self-poling. Then, the porous material is employed as pressure sensor with a high output of ~20.0 V and sensitivity of ~132.87 mV/kPa. Besides, the energy harvesting experiment suggests power density of ~58.7 mW/m2 can be achieved for 10 N pressure with a long-term durability. In summary, we not only provide a high performance lightweight, flexible piezoelectric polymer composite towards sustainable self-powered sensing and energy harvesting, but also pave an avenue for electrical-free fabrication of piezoelectric polymers.

11.
Carbohydr Polym ; 305: 120535, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36737188

RESUMO

In this paper, we proposed a novel and green strategy based on water evaporation induced in-situ interfacial compatibilization (WEIC) mechanism for fabricating high-strength and all-natural lignocellulose/starch composites. This mechanism exploits the natural compatibility of the lignocellulose and starch and was tested through an internal mixing process with regulated water evaporation. Specifically, we revealed that a restrained layer was in-situ formed at the interface of the lignocellulose and starch during the internal mixing process; a faster water evaporation rate thickens this restrained layer, restricts the starch's molecular movement and significantly increases the composite's mechanical properties. The highest tensile strength and Young's modulus of the composites achieved are 21.7 ± 0.8 MPa and 2.2 ± 0.1 GPa, respectively, superior to many existing starch/lignocellulose composites. Thus, this work provides new insight into the compatibilization of various hydrophilic polysaccharides and paves new avenues for developing greener and more facile methods to fabricate all-polysaccharide composites.

12.
J Oncol ; 2022: 4537021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36276280

RESUMO

According to statistics released by the WHO, China has the highest prevalence of myopia in the world, with a frequency that is 1.5 times higher than the global average. Asians have the highest prevalence of myopia worldwide. The Ministry of Education and the State General Administration of Sports "2010 National Student Physical Fitness and Health Research Results" show that the incidence of poor vision among primary and secondary school students in China is 67.3%, and elementary school students' vision has decreased by 40.9%. Low vision among youth has become a major cause of affecting the quality of the population and improving national physical fitness; therefore, how to improve and enhance the vision level of youth has become a major issue for the government, sports, and educators face as a major issue. In order to address this issue, this research suggests a deep learning-based vision monitoring and risk prediction model for high myopia eyes and develops a deep artificial neural network that unsupervised learns essential characteristics of physiological time-series data.

13.
Aging (Albany NY) ; 14(15): 6128-6148, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35951367

RESUMO

The male abnormal gene family 21 (mab21), was initially identified in C. elegans. Since its identification, studies from different groups have shown that it regulates development of ocular tissues, brain, heart and liver. However, its functional mechanism remains largely unknown. Here, we demonstrate that Mab21L1 promotes survival of lens epithelial cells. Mechanistically, Mab21L1 upregulates expression of αB-crystallin. Moreover, our results show that αB-crystallin prevents stress-induced phosphorylation of p53 at S-20 and S-37 through abrogating the activation of the upstream kinases, ATR and CHK1. As a result of suppressing p53 activity by αB-crystallin, Mab21L1 downregulates expression of Bak but upregulates Mcl-1 during stress insult. Taken together, our results demonstrate that Mab21L1 promotes survival of lens epithelial cells through upregulation of αB-crystallin to suppress ATR/CHK1/p53 pathway.


Assuntos
Cristalinas , Cristalino , Animais , Caenorhabditis elegans/metabolismo , Cristalinas/genética , Células Epiteliais/metabolismo , Cristalino/metabolismo , Masculino , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
14.
Nat Commun ; 13(1): 4083, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-35835779

RESUMO

Triboelectric polymer with high charge density is the foundation to promote the wide range of applications of triboelectric nanogenerators. This work develops a method to produce triboelectric polymer based on repeated rheological forging. The fluorinated ethylene propylene film fabricated by repeated forging method not only has excellent mechanical properties and good transmittance, but also can maintain an ultrahigh tribo-charge density. Based on the film with a thickness of 30 µm, the output charge density from contact-separation nanogenerator reaches 352 µC·m-2. Then, the same film is applied for the nanogenerator with air-breakdown mode and a charge density of 510 µC·m-2 is further achieved. The repeated forging method can effectively regulate the composition of surface functional groups, the crystallinity, and the dielectric constants of the fluorinated ethylene propylene, leading to the superior capability of triboelectrification. Finally, we summarize the key parameters for elevating the electrification performance on the basis of molecular structure and related fabrication crafts, which can guide the further development of triboelectric polymers.

15.
Arch Gynecol Obstet ; 284(3): 757-64, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21614496

RESUMO

PURPOSE: Reduction of serum total testosterone (TT) is associated with pregnancy rate in polycystic ovary syndrome (PCOS) women receiving metformin, but most of the studies focus on the changes of basal levels of TT. The aim of this study was to evaluate whether the TT level around the ovulation period is related to the outcome of pregnancy in women with PCOS. METHODS: In total, 30 non-obese PCOS women with clomiphene citrate (CC) resistance from the Medical College's Reproductive Health Center were enrolled and randomly assigned to be treated with placebo (Group 1) or metformin (850 mg) (Group 2) twice daily for 3 months as the pre-treatment. Then, metformin alone was administered with CC, human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) to induce ovulation for 3 months in Group 1. In Group 2, CC/HMG/HCG was used to induce ovulation for 3 months without metformin. Follicle-stimulating hormone, luteinizing hormone, estradiol and TT levels before and after ovulation in pregnant cycles and non-pregnant cycles were evaluated over the course of treatment. RESULTS: A total of 26 subjects completed 65 cycles. The TT levels after ovulation in the pregnant cycles were significantly lower than in the non-pregnant cycles in both groups (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: The level of TT after ovulation may be of prognostic value for pregnancy in non-obese women with PCOS and CC resistance during treatment.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Clomifeno/uso terapêutico , Fármacos para a Fertilidade Feminina/uso terapêutico , Menotropinas/uso terapêutico , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Testosterona/sangue , Adulto , Resistência a Medicamentos , Quimioterapia Combinada , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Folículo Ovariano/diagnóstico por imagem , Indução da Ovulação/métodos , Projetos Piloto , Gravidez , Taxa de Gravidez , Prognóstico , Substâncias para o Controle da Reprodução/uso terapêutico , Ultrassonografia
16.
J Leukoc Biol ; 110(6): 1091-1099, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33993518

RESUMO

The interaction of the solo H3K79 methyltransferase DOT1-like (DOT1L) and its regulatory factor ALL1-fused gene from chromosome 10 protein (AF10) is crucial for the transcription of developmental genes such as HOXA in acute leukemia. The octapeptide motif and leucine zipper region of AF10 is responsible for binding DOT1L and catalyzing H3K79 monomethylation to demethylation. However, the characteristics of the mechanism between DOT1L and AF10 are not clear. Here, we present the crystal structures of coiled-coil regions of DOT1L-AF10 and AF10-inhibitory peptide, demonstrating the inhibitory peptide could form a compact complex with AF10 via a different recognition pattern. Furthermore, an inhibitory peptide with structure-based optimization is identified and decreases the HOXA gene expression in a human cell line. Our studies provide an innovative pharmacologic basis for therapeutic intervention in leukemia.


Assuntos
Antineoplásicos/farmacologia , Histona-Lisina N-Metiltransferase/química , Proteínas de Homeodomínio/biossíntese , Modelos Moleculares , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/química , Regulação Neoplásica da Expressão Gênica/fisiologia , Histona-Lisina N-Metiltransferase/metabolismo , Humanos , Leucemia Mieloide Aguda/metabolismo , Conformação Proteica
17.
ACS Appl Mater Interfaces ; 13(31): 37252-37261, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34318675

RESUMO

With the rapid development of wearable electronics, piezoelectric materials have received great attention owing to their potential solution to the portable power source. To enhance the output capability and broaden the application, it is highly desired for the design of piezoelectric materials with a three-dimensional and porous structure to facilitate strain accumulation. Herein, enlightened by hierarchical structures in nature, a hierarchically nested network was constructed in polyvinylidene fluoride (PVDF) foam via solid-state shear milling and salt-leaching technology. The as-prepared foam exhibited two hierarchical levels of pores with diameters of 20∼50 µm and 0.3∼4 µm, by which the porosity and flexibility were significantly enhanced, while the highest piezoelectric output reached 11.84 V and 217.78 nA. As a proof-of-concept, the PVDF piezoelectric foam can also be used to monitor human movement toward the different magnitude of strain and frequency, and simultaneously collect energy in a multidimensional stress field for energy harvesting. This work provides a simple and convenient design idea for the preparation of energy harvesters, which have great application potential as a mechanical energy harvester or self-powered sensor in wearable electronic devices.

18.
ACS Appl Mater Interfaces ; 13(9): 11480-11488, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33625833

RESUMO

Flexible and stretchable strain sensors are crucial components for wearable electronics that can detect and quantify the stimuli from the environment and thus realize the rapid feedback and control of smart devices. However, reconciliation of the conflict between resourceful design of conductive networks and large-scale production in the industry still faces a huge challenge. Herein, we present a new flow-manipulated strategy to prepare a wearable strain sensor featuring a helically intersected conductive network, which exhibited easy integration, multidimensional sensibility, and robust mechanical properties. From visualization of simulation and verification of experimental results, the helically intersected conductive network formed in an elastomer ring can simultaneously reflect the static and dynamic mechanical responses with a tunable gauge factor (10.41-31.12), wide linear region (0-40o), mechanical robustness (σs = ∼7 MPa, ε = ∼1400%), and rapid response time (∼300 ms). We further constructed a control system based on smart rings and demonstrated its application in controlling industrial robotic arms and remote-controlled cars. Looking ahead, this kind of a smart ring will be more widely used in space and underwater exploration, intelligent robotics, and human-machine interface technologies.


Assuntos
Fibra de Carbono/química , Elastômeros/química , Polietilenos/química , Dispositivos Eletrônicos Vestíveis , Condutividade Elétrica , Desenho de Equipamento , Humanos , Conformação Molecular , Simulação de Dinâmica Molecular , Robótica/métodos
19.
Int J Biol Macromol ; 174: 42-51, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33497694

RESUMO

The development and utilization of inorganic material biosynthesis have evolved into single macromolecular systems. A putative cystathionine γ-lyase of bacteria Stenotrophomonas maltophilia (smCSE) is a newly identified biomolecule that enables the synthesis of nanomaterials. Due to the lack of structural information, the mechanism of smCSE biosynthesis remains unclear. Herein, we obtain two atomic-resolution smCSE-form X-ray structures and confirm that the conformational changes of Tyr108 and Lys206 within the enzyme active sites are critical for the protein-driven synthesis of metal sulfide quantum dots (QDs). The structural stability of tetramer and the specificity of surface amino acids are the basis for smCSE to synthesize quantum dots. The size of QD products can be regulated by predesigned amino acids and the morphology can be controlled through proteolytic treatments. The growth rate is enhanced by the stabilization of a flexible loop in the active site, as shown by the X-ray structure of the engineered protein which fused with a dodecapeptide. We further prove that the smCSE-driven route can be applied to the general synthesis of other metal sulfide nanoparticles. These results provide a better understanding of the mechanism of QD biosynthesis and a new perspective on the control of this biosynthesis by protein modification.


Assuntos
Cistationina gama-Liase/metabolismo , Cistationina gama-Liase/ultraestrutura , Pontos Quânticos/química , Aminoácidos , Bactérias/metabolismo , Cistationina gama-Liase/química , Substâncias Macromoleculares , Metais , Nanoestruturas , Stenotrophomonas maltophilia/enzimologia , Stenotrophomonas maltophilia/metabolismo , Sulfetos/química
20.
Am J Cancer Res ; 11(10): 4807-4825, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765294

RESUMO

Deubiquitinase (DUB) zinc finger RANBP2-type containing 1 (ZRANB1) has been reported to have a close relationship with cancers. However, its underlying role and molecular mechanisms in hepatocellular carcinoma (HCC) remain elusive. In this study, we demonstrated that ZRANB1 was highly expressed in HCC tissues. Additionally, ZRANB1 overexpression was correlated with poorer survival and ZRANB1 could be an independent predictor of poor prognosis for HCC patients. Through gain- and loss-of-function assays, we examined the oncogenic role of ZRANB1 in regulating HCC cell growth and metastasis in vitro and in vivo. To identify the downstream targets of ZRANB1 in regulating HCC tumorigenesis, we performed RNA-seq and demonstrated that Lysyl oxidase-like 2 (LOXL2) was the most significantly downregulated gene after ZRANB1 knockdown. Furthermore, the scatter plots indicated a significant positive correlation between ZRANB1 and LOXL2 expression in clinical HCC specimens. We also demonstrated that ZRANB1 knockdown downregulated the expression of LOXL2 and suppressed HCC growth and metastasis in vitro and in vivo. The effects of ZRANB1 knockdown were reversed by LOXL2 overexpression. More importantly, ZRANB1 regulated LOXL2 through specificity protein 1 (SP1) and SP1 overexpression rescued the suppression of HCC growth and metastasis induced by ZRANB1 knockdown. Mechanistically, ZRANB1 bound with SP1 directly and stabilized the SP1 protein by deubiquitinating it. The expression patterns of ZRANB1, SP1 and LOXL2 were evaluated in HCC patients. In summary, our research highlights a novel role of ZRANB1 in the tumorigenesis of HCC and suggests a new candidate prognostic biomarker for HCC treatment.

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