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1.
Proc Natl Acad Sci U S A ; 120(49): e2203241120, 2023 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-38015839

RESUMO

The Lysinibacillus sphaericus proteins Tpp49Aa1 and Cry48Aa1 can together act as a toxin toward the mosquito Culex quinquefasciatus and have potential use in biocontrol. Given that proteins with sequence homology to the individual proteins can have activity alone against other insect species, the structure of Tpp49Aa1 was solved in order to understand this protein more fully and inform the design of improved biopesticides. Tpp49Aa1 is naturally expressed as a crystalline inclusion within the host bacterium, and MHz serial femtosecond crystallography using the novel nanofocus option at an X-ray free electron laser allowed rapid and high-quality data collection to determine the structure of Tpp49Aa1 at 1.62 Å resolution. This revealed the packing of Tpp49Aa1 within these natural nanocrystals as a homodimer with a large intermolecular interface. Complementary experiments conducted at varied pH also enabled investigation of the early structural events leading up to the dissolution of natural Tpp49Aa1 crystals-a crucial step in its mechanism of action. To better understand the cooperation between the two proteins, assays were performed on a range of different mosquito cell lines using both individual proteins and mixtures of the two. Finally, bioassays demonstrated Tpp49Aa1/Cry48Aa1 susceptibility of Anopheles stephensi, Aedes albopictus, and Culex tarsalis larvae-substantially increasing the potential use of this binary toxin in mosquito control.


Assuntos
Bacillaceae , Bacillus , Culex , Praguicidas , Animais , Bacillaceae/química , Bacillaceae/metabolismo , Controle de Mosquitos , Larva/metabolismo
2.
Gastroenterology ; 165(1): 133-148.e17, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36907523

RESUMO

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma (PDA), with its highly metastatic propensity, is one of the most lethal subtypes of pancreatic cancer. Although recent large-scale transcriptomic studies have demonstrated that heterogeneous gene expressions play an essential role in determining molecular phenotypes of PDA, biological cues for and consequences of distinct transcriptional programs remain unclear. METHODS: We developed an experimental model that enforces the transition of PDA cells toward a basal-like subtype. We combined epigenome and transcriptome analyses with extensive in vitro and in vivo evaluations of tumorigenicity to demonstrate the validity of basal-like subtype differentiation in association with endothelial-like enhancer landscapes via TEA domain transcription factor 2 (TEAD2). Finally, we used loss-of-function experiments to investigate the importance of TEAD2 in regulating reprogrammed enhancer landscape and metastasis in basal-like PDA cells. RESULTS: Aggressive characteristics of the basal-like subtype are faithfully recapitulated in vitro and in vivo, demonstrating the physiological relevance of our model. Further, we showed that basal-like subtype PDA cells acquire a TEAD2-dependent proangiogenic enhancer landscape. Genetic and pharmacologic inhibitions of TEAD2 in basal-like subtype PDA cells impair their proangiogenic phenotypes in vitro and cancer progression in vivo. Last, we identify CD109 as a critical TEAD2 downstream mediator that maintains constitutively activated JAK-STAT signaling in basal-like PDA cells and tumors. CONCLUSIONS: Our findings implicate a TEAD2-CD109-JAK/STAT axis in the basal-like differentiated pancreatic cancer cells and as a potential therapeutic vulnerability.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Diferenciação Celular , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição de Domínio TEA , Neoplasias Pancreáticas
3.
Small ; 19(9): e2205048, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36534830

RESUMO

Repositioning is a common guideline for the prevention of pressure injuries of bedridden or wheelchair patients. However, frequent repositioning could deteriorate the quality of patient's life and induce secondary injuries. This paper introduces a method for continuous multi-site monitoring of pressure and temperature distribution from strategically deployed sensor arrays at skin interfaces via battery-free, wireless ionic liquid pressure sensors. The wirelessly delivered power enables stable operation of the ionic liquid pressure sensor, which shows enhanced sensitivity, negligible hysteresis, high linearity and cyclic stability over relevant pressure range. The experimental investigations of the wireless devices, verified by numerical simulation of the key responses, support capabilities for real-time, continuous, long-term monitoring of the pressure and temperature distribution from multiple sensor arrays. Clinical trials on two hemiplegic patients confined on bed or wheelchair integrated with the system demonstrate the feasibility of sensor arrays for a decrease in pressure and temperature distribution under minimal repositioning.


Assuntos
Líquidos Iônicos , Cadeiras de Rodas , Humanos , Temperatura , Tecnologia sem Fio , Pele
4.
Small ; 19(32): e2206839, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37069777

RESUMO

Peripheral nerve injuries cause various disabilities related to loss of motor and sensory functions. The treatment of these injuries typically requires surgical operations for improving functional recovery of the nerve. However, capabilities for continuous nerve monitoring remain a challenge. Herein, a battery-free, wireless, cuff-type, implantable, multimodal physical sensing platform for continuous in vivo monitoring of temperature and strain from the injured nerve is introduced. The thin, soft temperature, and strain sensors wrapped around the nerve exhibit good sensitivity, excellent stability, high linearity, and minimum hysteresis in relevant ranges. In particular, the strain sensor integrated with circuits for temperature compensation provides reliable, accurate strain monitoring with negligible temperature dependence. The system enables power harvesting and data communication to wireless, multiple implanted devices wrapped around the nerve. Experimental evaluations, verified by numerical simulations, with animal tests, demonstrate the feasibility and stability of the sensor system, which has great potential for continuous in vivo nerve monitoring from an early stage to complete regeneration.


Assuntos
Fontes de Energia Elétrica , Próteses e Implantes , Animais , Temperatura , Tecnologia sem Fio
5.
Lasers Med Sci ; 38(1): 272, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37991524

RESUMO

With an increasing demand for noninvasive skin rejuvenation techniques, several light-based devices have been introduced. Due to its ability to deliver thermal energy from the superficial to deeper levels of the dermis, a combined triple-wavelength laser (755 nm, 810 nm, and 1064 nm) can be used for skin rejuvenation. The objective of this study was to assess the effectiveness and safety of a combined triple-wavelength laser for skin rejuvenation. A total of 28 female patients seeking skin rejuvenation treatment were included. All patients underwent five consecutive treatment sessions at a two-week interval. Clinical improvement of aging-related cutaneous change was noted by the treating dermatologists and patients. Biopsies were performed on the faces of consenting patients before and two weeks after the final treatment. Significant clinical improvements were observed by both patients and evaluating dermatologists. Based on the patient satisfaction questionnaire, 78% of patients reported a self-assessed improvement of more than 25%. Additionally, 86% of patients showed an improvement of more than 25% on objective assessment by dermatologists. Histopathological findings revealed increased collagen and elastic bundles throughout the dermis. Except for transient pain during treatment, no serious adverse effects were reported. The findings of this study suggest that the combined triple-wavelength laser may be an effective and safe nonablative option for skin rejuvenation.


Assuntos
Rejuvenescimento , Pele , Humanos , Feminino , Administração Cutânea , Biópsia , Lasers
6.
Sensors (Basel) ; 23(14)2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37514943

RESUMO

This paper proposes a physics-informed neural network (PINN) for predicting the early-age time-dependent behaviors of prestressed concrete beams. The PINN utilizes deep neural networks to learn the time-dependent coupling among the effective prestress force and the several factors that affect the time-dependent behavior of the beam, such as concrete creep and shrinkage, tendon relaxation, and changes in concrete elastic modulus. Unlike traditional numerical algorithms such as the finite difference method, the PINN directly solves the integro-differential equation without the need for discretization, offering an efficient and accurate solution. Considering the trade-off between solution accuracy and the computing cost, optimal hyperparameter combinations are determined for the PINN. The proposed PINN is verified through the comparison to the numerical results from the finite difference method for two representative cross sections of PSC beams.

7.
J Orthop Sci ; 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37953191

RESUMO

BACKGROUND: Various operative methods for the treatment of Morton's neuroma have been discussed, and osteotomy of the metatarsal bone has been reported recently. However, there has been no report of pedobarographic changes after metatarsal osteotomy. Pedobarographic changes of other metatarsal area after the surgery may cause transfer metatarsalgia, and thorough analysis of the pedobarographic data should be performed peri-operatively. The purpose of this study is to investigate the post-operative pedobarographic changes of sliding osteotomy of the 3rd metatarsal bone for treating Morton's neuroma. METHODS: Forty patients (45 feet) who underwent metatarsal sliding osteotomy of the 3rd metatarsal bone for treating Morton's neuroma from November 2013 to December 2021 were retrospectively reviewed. Proximal sliding osteotomy was performed at the proximal 3rd metatarsal bone through dorsal approach. Clinical outcomes were evaluated with American Orthopaedic Foot and Ankle Society Lesser Metatarsophalangeal Interphalangeal Scale (AOFAS LMIS), Foot Function Index (FFI), and Visual Analogue Scale (VAS). Plain radiograph and pedobarogram were performed to evaluate the radiologic and pedobarographic outcomes. RESULTS: AOFAS score was improved from 52.8 ± 9.0 (18-62) to 88.8 ± 9.8 (78-100) and FFI was improved from 61.8 ± 4.9 (50-70) to 32.2 ± 5.1 (23-42) on average. The 3rd metatarsal bone was shortened by 3.1 ± 0.8 mm and dorsally shifted by 1.5 ± 0.4 mm after the surgery. Plantar intermetatarsal distances between 2nd and 3rd and 3rd and 4th metatarsal heads were significantly increased post-operatively. Average forefoot pressure and maximum pressure of the 2nd to 4th metatarsal head were not significantly changed between pre-operatively and post-operatively. CONCLUSION: Proximal metatarsal sliding osteotomy of the 3rd metatarsal bone shows a satisfactory result in both clinical and pedobarographical evaluations. It could be an effective treatment of permanent indirect decompression of Morton's neuroma with avoiding recurred neuroma, adhesion of tissue, paresthesia, and transfer metatarsalgia.

8.
Int J Mol Sci ; 24(4)2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36834911

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disorder associated with cognitive decline. Despite worldwide efforts to find a cure, no proper treatment has been developed yet, and the only effective countermeasure is to prevent the disease progression by early diagnosis. The reason why new drug candidates fail to show therapeutic effects in clinical studies may be due to misunderstanding the cause of AD. Regarding the cause of AD, the most widely known is the amyloid cascade hypothesis, in which the deposition of amyloid beta and hyperphosphorylated tau is the cause. However, many new hypotheses were suggested. Among them, based on preclinical and clinical evidence supporting a connection between AD and diabetes, insulin resistance has been pointed out as an important factor in the development of AD. Therefore, by reviewing the pathophysiological background of brain metabolic insufficiency and insulin insufficiency leading to AD pathology, we will discuss how can insulin resistance cause AD.


Assuntos
Doença de Alzheimer , Resistência à Insulina , Humanos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Resistência à Insulina/fisiologia , Insulina
9.
Nature ; 539(7627): 43-47, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27680699

RESUMO

BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi-step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals-50 unit cells per edge, on average-has impeded structural characterization by conventional means. Here we report the structure of Lysinibacillus sphaericus BinAB solved de novo by serial-femtosecond crystallography at an X-ray free-electron laser. The structure reveals tyrosine- and carboxylate-mediated contacts acting as pH switches to release soluble protoxin in the alkaline larval midgut. An enormous heterodimeric interface appears to be responsible for anchoring BinA to receptor-bound BinB for co-internalization. Remarkably, this interface is largely composed of propeptides, suggesting that proteolytic maturation would trigger dissociation of the heterodimer and progression to pore formation.


Assuntos
Bacillus/química , Toxinas Bacterianas/química , Culicidae , Inseticidas/química , Larva , Lasers , Animais , Sítios de Ligação , Cristalização , Cristalografia por Raios X , Culicidae/metabolismo , Concentração de Íons de Hidrogênio , Larva/química , Larva/metabolismo , Modelos Moleculares , Multimerização Proteica , Proteólise , Tirosina/química
10.
Sensors (Basel) ; 22(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36236677

RESUMO

This paper presents an experimental validation of deep learning-based direction-of-arrival (DoA) estimation by using realistic data collected via universal software radio peripheral (USRP). Deep neural network (DNN) and convolutional neural network (CNN) structures are designed to estimate the DoA. Two types of data are used for training networks. One is the data synthesized by the signal model, and the other is the data collected by USRP. Here, the signal model considers both mutual coupling and multipath signals. Experimental results show that the estimation performance is most accurate when training DNN and CNN with the collected data. Furthermore, the estimation tends to be poor in the indoor environment, which suffers from the strong non-line-of-sight (NLoS) signals.

11.
Foot Ankle Surg ; 28(4): 464-470, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34838426

RESUMO

BACKGROUND: Transfer metatarsalgia is a potential complication of hallux valgus surgery. This study aimed to investigate the shortened first metatarsal length and elevation and to compare groups with and without second transfer metatarsalgia after Scarf osteotomy. METHODS: The first metatarsal length of 123 feet was measured via the Maestro's method using the metatarsal axial length and the relative second metatarsal protrusion to the first metatarsal. Metatarsal elevation was measured using the first metatarsal angle. RESULTS: Second transfer metatarsalgia occurred after Scarf osteotomy in 11 (8.9%) feet. When baseline characteristics were considered in propensity score matching, the 11 feet were compared with the 33 feet in the control group. The group with transfer metatarsalgia showed a more shortened first metatarsal axial length (-4.1 ± 1.8 mm vs. -2.5 ± 2.2 mm, p = 0.032), a significantly longer relative second metatarsal protrusion (+5.8 ± 2.6 mm vs. +1.2 ± 2.6 mm, p < 0.001), and a significantly lower first metatarsal angle (18.1 ± 4.3° vs. 21.5 ± 4.0°, p = 0.012) than the control group postoperatively. CONCLUSIONS: To avoid iatrogenic transfer metatarsalgia, first metatarsal length shortening should be minimized to at least less than 4.0 mm. Furthermore, the metatarsal parabola should be retained.


Assuntos
Hallux Valgus , Ossos do Metatarso , Metatarsalgia , Hallux Valgus/complicações , Hallux Valgus/diagnóstico por imagem , Hallux Valgus/cirurgia , Humanos , Doença Iatrogênica , Ossos do Metatarso/diagnóstico por imagem , Ossos do Metatarso/cirurgia , Metatarsalgia/diagnóstico por imagem , Metatarsalgia/etiologia , Metatarsalgia/cirurgia , Osteotomia/efeitos adversos , Osteotomia/métodos , Resultado do Tratamento
12.
J Am Chem Soc ; 143(29): 11180-11190, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34264077

RESUMO

Catalyst-transfer polymerization has revolutionized the field of polymer synthesis due to its living character, but for a given catalyst system, the polymer scope is rather narrow. Herein we report a highly efficient Suzuki-Miyaura catalyst-transfer polymerization (SCTP) that covers a wide range of monomers from electron-rich (donor, D) to electron-deficient (acceptor, A) (hetero)arenes by rationally designing boronate monomers and using commercially available Buchwald RuPhos and SPhos Pd G3 precatalysts. Initially, we optimized the controlled polymerization of 3,4-propylenedioxythiophene (ProDOT), benzotriazole (BTz), quinoxaline (QX), and 2,3-diphenylquinoxaline (QXPh) by introducing new boronates, such as 4,4,8,8-tetramethyl-1,3,6,2-dioxazaborocane and its N-benzylated derivative, to modulate the reactivity and stability of the monomers. As a result, PProDOT, PBTz, PQX, and PQXPh were prepared with controlled molecular weight and narrow dispersity (D < 1.29) in excellent yield (>85%). A detailed investigation of the polymer structures using 1H NMR and MALDI-TOF spectrometry supported the chain-growth mechanism and the high initiation efficiency of the SCTP method. In addition, the use of RuPhos-Pd showing excellent catalyst-transfer ability on both D/A monomers led to unprecedented controlled D-A statistical copolymerization, thereby modulating the HOMO energy level (from -5.11 to -4.80 eV) and band gap energy (from 1.68 to 1.91 eV) of the resulting copolymers. Moreover, to demonstrate the living nature of SCTP, various combinations of D-A and A-A block copolymers (PBTz-b-PProDOT, PQX-b-PProDOT, and PQX-b-PBTz) were successfully prepared by the sequential addition method. Finally, simple but powerful one-shot D-A block copolymerization was achieved by maximizing the rate difference between a fast-propagating pinacol boronate donor and a slow-propagating acceptor to afford well-defined poly(3-hexylthiophene)-b-poly(benzotriazole).

13.
Parasite Immunol ; 43(1): e12799, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33058167

RESUMO

AIMS: To date, a Toxoplasma gondii vaccine for clinical use remains unavailable, though multiple vaccine candidates have been suggested. In our previous studies, unadjuvanted virus-like particles (VLPs) vaccines expressing multiple T. gondii antigens were confirmed to be protective against T. gondii challenge infection. Yet, the protective efficacy of adjuvanted T. gondii VLP in comparison with the unadjuvanted counterpart requires elucidation. METHODS AND RESULTS: In the present study, mice were immunized with the multi-antigenic VLP vaccines (TG146 VLP) with or without CpG adjuvants and their protective efficacies were compared. CpG-adjuvanted TG146 VLP vaccine elicited enhanced T gondii-specific IgG and IgA antibody responses in the sera, mucosal tissue and the brain compared to unadjuvanted VLPs vaccine. Inclusion of CpG adjuvant in vaccines also induced greater CD4+ and CD8+ T-cell responses, as well as B cell and germinal centre B cell responses from splenocytes and mesenteric lymph nodes. Pro-inflammatory cytokine response and cyst counts in the brain were drastically diminished in mice immunized with CpG-adjuvanted VLP vaccines. CONCLUSION: Our results demonstrated that CpG-adjuvanted T. gondii VLPs can significantly enhance the protective efficacy of vaccines against T. gondii infection.


Assuntos
Adjuvantes Imunológicos/farmacologia , Anticorpos Antiprotozoários/sangue , Oligodesoxirribonucleotídeos/farmacologia , Vacinas Protozoárias/imunologia , Toxoplasma/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Ilhas de CpG/genética , Feminino , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Oligodesoxirribonucleotídeos/administração & dosagem , Proteínas de Protozoários/imunologia , Vacinação , Vacinas de Partículas Semelhantes a Vírus/imunologia
14.
Eur Heart J ; 41(2): 239-252, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31419281

RESUMO

AIMS: Proprotein convertase subtilisin/kexin type-9 (PCSK9), a molecular determinant of low-density lipoprotein (LDL) receptor (LDLR) fate, has emerged as a promising therapeutic target for atherosclerotic cardiovascular diseases. However, the precise mechanism by which PCSK9 regulates the internalization and lysosomal degradation of LDLR is unknown. Recently, we identified adenylyl cyclase-associated protein 1 (CAP1) as a receptor for human resistin whose globular C-terminus is structurally similar to the C-terminal cysteine-rich domain (CRD) of PCSK9. Herein, we investigated the role of CAP1 in PCSK9-mediated lysosomal degradation of LDLR and plasma LDL cholesterol (LDL-C) levels. METHODS AND RESULTS: The direct binding between PCSK9 and CAP1 was confirmed by immunoprecipitation assay, far-western blot, biomolecular fluorescence complementation, and surface plasmon resonance assay. Fine mapping revealed that the CRD of PCSK9 binds with the Src homology 3 binding domain (SH3BD) of CAP1. Two loss-of-function polymorphisms found in human PCSK9 (S668R and G670E in CRD) were attributed to a defective interaction with CAP1. siRNA against CAP1 reduced the PCSK9-mediated degradation of LDLR in vitro. We generated CAP1 knock-out mice and found that the viable heterozygous CAP1 knock-out mice had higher protein levels of LDLR and lower LDL-C levels in the liver and plasma, respectively, than the control mice. Mechanistic analysis revealed that PCSK9-induced endocytosis and lysosomal degradation of LDLR were mediated by caveolin but not by clathrin, and they were dependent on binding between CAP1 and caveolin-1. CONCLUSION: We identified CAP1 as a new binding partner of PCSK9 and a key mediator of caveolae-dependent endocytosis and lysosomal degradation of LDLR.


Assuntos
Aterosclerose/genética , Proteínas de Transporte/genética , LDL-Colesterol/sangue , Mutação , Pró-Proteína Convertase 9/genética , Receptores de LDL/sangue , Animais , Aterosclerose/metabolismo , Proteínas de Transporte/metabolismo , DNA/genética , Análise Mutacional de DNA , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Pró-Proteína Convertase 9/metabolismo
15.
Microb Pathog ; 142: 104090, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32097746

RESUMO

Toxoplasmosis is an intracellular parasitic disease caused by the protozoa Toxoplasma gondii, which affects about half of the world's population. In spite of the strenuous endeavors, a T. gondii vaccine for clinical use remains unreported to date. In the present study, we generated virus-like particles (VLPs) containing T. gondii apical membrane antigen 1 (AMA1) and assessed its efficacy in a murine model. VLPs were characterized using western blot and TEM. T. gondii-specific IgG and IgA antibody responses in sera, germinal center B cell responses in spleen, brain cyst counts and their sizes were determined. Elevated T. gondii-specific IgG and IgA antibody responses were observed from the sera of AMA1 VLP-immunized mice. Immunization with AMA1 VLPs enhanced T. gondii-specific antibody-secreting cell responses and germinal center B cell responses upon antigen stimulation. Brain tissue analysis revealed that AMA1 VLP-immunization reduced cyst formation and its size compared to control. Also, VLP-immunized mice were less susceptible to body weight loss and displayed enhanced survival rate compared to the control group. Our results demonstrated that the immune response induced by T. gondii AMA1 VLPs confer partial protection against T. gondii infection and provides important insight into potential T. gondii vaccine design strategy.

16.
Parasite Immunol ; 42(6): e12716, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249951

RESUMO

AIMS: Neuroinflammation can manifest upon infection with the neurotropic parasite Toxoplasma gondii (ME49), which can lead to brain injury and cognitive dysfunction. Rhoptry organelle proteins (ROPs) secreted by T gondii play critical roles in host invasion. METHODS AND RESULTS: In this study, influenza virus-like particles (VLPs) expressing T gondii ROP4 or ROP13 were generated to assess vaccination-induced changes in intracranial pro-inflammatory cytokines and antibody responses upon T gondii challenge infection. Compared to ROP13 VLPs, ROP4VLPs vaccination significantly limited the production of pro-inflammatory cytokines IFN-γ and IL-6 in the brains of mice. Reduced pro-inflammatory cytokine responses by ROP4 VLPs and ROP13 VLPs correlated with significantly increased T gondii-specific IgG and IgA antibody responses in the brain, as well as IgG, IgG1 and IgM antibody responses in the sera. CONCLUSION: We concluded that influenza T gondii VLP vaccination induces antibody responses in sera and brain, which may contribute to the significant reduction of neuroinflammation during T gondii infection.


Assuntos
Anticorpos Antiprotozoários/sangue , Encéfalo/imunologia , Proteínas de Membrana/imunologia , Proteínas de Protozoários/imunologia , Toxoplasma/imunologia , Vacinação , Vacinas de Partículas Semelhantes a Vírus/imunologia , Animais , Encéfalo/parasitologia , Linhagem Celular , Feminino , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Inflamação/imunologia , Interferon gama/imunologia , Interleucina-6/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Células Sf9
17.
Parasite Immunol ; 42(11): e12781, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32738150

RESUMO

AIMS: Merozoite surface protein 8 (MSP-8) of Plasmodium parasites plays an important role in erythrocyte invasion and is a potential malaria vaccine candidate. METHODS AND RESULTS: In this study, virus-like particles (VLPs) expressing MSP-8 of Plasmodium berghei on the surface of influenza virus matrix protein 1 (M1) core protein were generated for vaccine efficacy assessment. Mice were intramuscularly (IM) immunized with MSP-8 VLPs twice and challenge-infected with P. berghei. We found that VLP vaccination elicited higher levels of P. berghei-specific IgG antibody response in the sera, along with blood CD4+ and CD8+ T-cell response enhancement compared to the naïve control mice. CD4+ and CD8+ effector memory T-cell and memory B-cell responses in the spleen were found to be higher in VLP-immunized mice compared to control mice. VLP vaccination significantly reduced inflammatory cytokine (IFN-γ) response in the spleen and parasitemia levels in blood compared to naïve control mice. CONCLUSIONS: These results indicate that MSP-8 containing virus-like particles could be a vaccine candidate for blood-stage vaccine design.


Assuntos
Antígenos de Protozoários/imunologia , Imunização , Vacinas Antimaláricas/imunologia , Malária/parasitologia , Plasmodium berghei/imunologia , Proteínas de Protozoários/imunologia , Animais , Antígenos de Protozoários/genética , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Parasitemia , Plasmodium berghei/genética , Plasmodium berghei/metabolismo , Proteínas de Protozoários/genética
18.
Nanotechnology ; 31(26): 265604, 2020 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-32176869

RESUMO

Despite increasing interest in tin disulfide (SnS2) as a two-dimensional (2D) material due to its promising electrical and optical properties, the surface treatment of silicon dioxide (SiO2) substrates prior to the atomic layer deposition (ALD) deposition of SnS2 has not been thoroughly studied. In this paper, we prepared two types of SiO2 substrates with and without using an O2 plasma surface treatment and compared the ALD growth behavior of SnS2 on the SiO2 substrates. The hydrophilic properties of the two SiO2 substrates were investigated by x-ray photoelectron spectroscopy and contact angle measurements, which showed that using an O2 plasma surface treatment tuned the surface to be more hydrophilic. ALD-grown SnS2 thin films on the two different SiO2 substrates were characterized by x-ray diffraction, Raman spectroscopy, atomic force microscopy, and x-ray photoelectron spectroscopy. To estimate the exact thickness of the ALD-grown SnS2 thin films, transmission electron microscopy was used. Our data revealed that using O2 plasma surface treatment increased the growth rate of the initial ALD stage. Thus, the ALD-grown SnS2 thin film on the SiO2 substrate treated with O2 plasma was thicker than the film grown on the non-treated SiO2 substrate.

19.
Nanotechnology ; 31(35): 355702, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32403092

RESUMO

Tin disulfide (SnS2) has emerged as a promising two-dimensional (2D) material due to its excellent electrical and optical properties. However, research into 2D SnS2 has mainly focused on its synthesis procedures and applications; its stability to humidity and temperature has yet to be studied. In this work, 2D SnS2 thin films were grown by atomic layer deposition (ALD) and characterized by various tools, such as x-ray diffraction, Raman analysis, and transmission electron spectroscopy. Characterization reveals that ALD-grown SnS2 thin films are a high-quality 2D material. After characterization, a four-inch-wafer-scale uniformity test was performed by Raman analysis. Owing to the quality, large-area growth enabled by the ALD process, 98.72% uniformity was obtained. Finally, we calculated the thermodynamic equations for possible reactions between SnS2 and H2O to theoretically presurmise the oxidation of SnS2 during accelerated humidity and temperature testing. After the accelerated humidity and temperature test, x-ray diffraction, Raman analysis, and Auger electron spectroscopy were performed to check whether SnS2 was oxidized or not. Our data revealed that 2D SnS2 thin films were stable at humid conditions.

20.
Plant Biotechnol J ; 17(7): 1369-1379, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30575262

RESUMO

Soybean (Glycine max [L.] Merr.) is a commodity crop highly valued for its protein and oil content. The high percentage of polyunsaturated fatty acids in soybean oil results in low oxidative stability, which is a key parameter for usage in baking, high temperature frying applications, and affects shelf life of packaged products containing soybean oil. Introduction of a seed-specific expression cassette carrying the Arabidopsis transcription factor WRINKLED1 (AtWRI1) into soybean, led to seed oil with levels of palmitate up to approximately 20%. Stacking of the AtWRI1 transgenic allele with a transgenic locus harbouring the mangosteen steroyl-ACP thioesterase (GmFatA) resulted in oil with total saturates up to 30%. The creation of a triple stack in soybean, wherein the AtWRI1 and GmFatA alleles were combined with a FAD2-1 silencing allele led to the synthesis of an oil with 28% saturates and approximately 60% oleate. Constructs were then assembled that carry a dual FAD2-1 silencing element/GmFatA expression cassette, alone or combined with an AtWRI1 cassette. These plasmids are designated pPTN1289 and pPTN1301, respectively. Transgenic events carrying the T-DNA of pPTN1289 displayed an oil with stearate levels between 18% and 25%, and oleate in the upper 60%, with reduced palmitate (<5%). While soybean events harboring transgenic alleles of pPTN1301 had similar levels of stearic and oleate levels as that of the pPTRN1289 events, but with levels of palmitate closer to wild type. The modified fatty acid composition results in an oil with higher oxidative stability, and functionality attributes for end use in baking applications.


Assuntos
Proteínas de Arabidopsis/genética , Glycine max/metabolismo , Palmitatos/análise , Plantas Geneticamente Modificadas/metabolismo , Sementes/química , Fatores de Transcrição/genética , Óleos de Plantas/química , Glycine max/genética
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