RESUMO
Heimler syndrome (HS) is a rare autosomal recessive hereditary disease that is caused by biallelic variants in peroxisomal biogenic factor 1 gene (PEX1), peroxisomal biogenic factor 6 gene (PEX6) or peroxisomal biogenic factor 26 gene (PEX26), resulting in intracellular peroxisomal dysfunction (PBDs). We report a patient with HS with a new compound heterozygous PEX1 variant. Exon sequencing was used to screen pathologic variants in the patient. Retinal characteristics and serum metabolome alterations were evaluated. Scanning laser ophthalmoscope showed a large area of retinal choroidal atrophy at the posterior pole of the retina, with scattered patchy subretinal pigmentation. Optical coherence tomography showed fovea atrophy accompanied by retinal retinoschisis in the right eye and macular retinoschisis and edema in the left eye. The electroretinogram showed obviously reduced amplitudes of a-waves and b-waves under photopic and scotopic conditions in both eyes. Visual field tests showed a reduced central visual field in both eyes. Exon sequencing identified the compound heterozygous variant including c.2966T > C and c.1670+1G > T of the PEX1 gene, with the latter being novel. Nontargeted determination of total lipid metabolites and targeted determination of medium- and long-chain fatty acids in the serum of the patient and his healthy sibling were tested. This study identified a new compound heterozygous PEX1 variant, expanding our understanding of phenotypes in HS.
Assuntos
Retinosquise , Humanos , ATPases Associadas a Diversas Atividades Celulares/genética , Retina/metabolismo , Atrofia , Proteínas de Membrana/genéticaRESUMO
Anterior segment dysgenesis is a severe developmental eye disorder that leads to blindness in children. The exact mechanisms underlying this condition remain elusive. Recently, an increasing amount of studies have focused on genes and signal transduction pathways that affect anterior segment dysgenesis;these factors include transcription factors, developmental regulators, extracellular matrix genes, membrane-related proteins, cytoskeleton proteins and other associated genes. To date, dozens of gene variants have been found to cause anterior segment dysgenesis. However, there is still a lack of effective treatments. With a broader and deeper understanding of the molecular mechanisms underlying anterior segment development in the future, gene editing technology and stem cell technology may be new treatments for anterior segment dysgenesis. Further studies on the mechanisms of how different genes influence the onset and progression of anterior segment dysgenesis are still needed.
Assuntos
Segmento Anterior do Olho , Anormalidades do Olho , Criança , Humanos , Segmento Anterior do Olho/metabolismo , Anormalidades do Olho/genética , Anormalidades do Olho/metabolismo , Fatores de Transcrição/genética , Biologia MolecularRESUMO
The CRISPR/Cas9 system has been harnessed to cleave a targeted DNA fragment via its Cas nuclease activity under the direction of guide RNA for rendering gene insertions, deletions, and point mutations in basic research and clinical applications. There are a number of vehicles, including lipofectamine, viruses, and nanoparticles, that can deliver the CRISPR/Cas9 system, but all these methods face numerous challenges during their application in life science contexts. Here, we focus on the delivery of CRISPR/Cas9 via nanoparticles because this method has shown great advantages in terms of safety, simplicity and flexibility.
Assuntos
Edição de Genes , Nanopartículas , Sistemas CRISPR-Cas/genética , Técnicas de Transferência de Genes , RNA Guia de Cinetoplastídeos/genéticaRESUMO
BACKGROUND: Polycystic kidney disease (PKD) represents the most prevalent inherited progressive kidney disorder in humans. Due to complexity of the genetic network behind the disease, the molecular mechanisms of PKD are still poorly understood yet. OBJECTIVES: This study aimed to develop a ciliogenesis-associated gene network for PKD patients and comprehensively understand the molecular mechanisms underlying the disease. METHOD: The potential hub genes were selected based on the differential expression analysis from the GEO database. Meanwhile, the primary hub genes were further elucidated by both in vivo and in vitro experiments. RESULTS: In this study, we established a comprehensive differentially expressed genes profile (including GNAS, PI4KB, UMOD, SLC7A13, and MIOX) for PKD patients compared with the control specimen. At the same time, enrichment analysis was utilized to demonstrate that the G-protein-related signaling and cilia assembling signaling pathways were closely associated with PKD development. The further investigations of the interaction between 2 genes (GNAS and PI4KB) with in vivo and in vitro analyses revealed that PI4KB functioned as a downstream factor for GNAS and spontaneously activated the phosphorylation of Akt into p-Akt for ciliogenesis in PKD formation. The PI4KB depletion mutant zebrafish model displayed a PKD phenotype as well as absence of primary cilia in the kidney. CONCLUSIONS: Collectively, our work discovered an innovative potential signaling pathway model for PKD formation, which provided a valuable insight for future study of the mechanism of this disease.
Assuntos
Cílios/genética , Redes Reguladoras de Genes , Doenças Renais Policísticas/genética , Linhagem Celular , Cílios/metabolismo , Cílios/patologia , Humanos , Doenças Renais Policísticas/metabolismo , Doenças Renais Policísticas/patologia , Mapas de Interação de Proteínas , Transdução de Sinais , TranscriptomaRESUMO
Improving the extremely low temperature operation of rechargeable batteries is vital to the operation of electronics in extreme environments, where systems capable of high-rate discharge are in short supply. Herein, we demonstrate the holistic design of dual-graphite batteries, which circumvent the sluggish ion-desolvation process found in typical lithium-ion batteries during discharge. These batteries were enabled by a novel electrolyte, which simultaneously provides high electrochemical stability and ionic conductivity at low temperature. The dual-graphite cells, when compared to industry-type graphite ⥠LiCoO2 full-cells demonstrated an 11â times increased capacity retention at -60 °C for a 10 C discharge rate, indicative of the superior kinetics of the "dual-ion" storage mechanism. These trends are further supported by galvanostatic intermittent titration technique (GITT) and electrochemical impedance spectroscopy (EIS) measurements at reduced temperature. This work provides a new design strategy for extreme low-temperature batteries.
RESUMO
Effective granular sample manipulation with a portable and visualizable microfluidic device is significant for lots of applications, such as point-of-care testing and cargo delivery. Herein, we report a portable microfluidic device for controlled particle focusing, migration and double-emulsion droplet release via thermal fields. The device mainly contains a microfluidic chip, a microcontroller with a DC voltage control unit, a built-in microscope with a video transmission unit and a smartphone. Five microheaters located at the bottom of the microfluidic chip are used to unevenly heat fluids and then induce thermal buoyancy flow and a thermocapillary effect, and the experiments can be conveniently visualized through a smartphone, which provides convenient sample detection in outdoor environments. To demonstrate the feasibility and multifunctionality of this device, the focusing manipulation of multiple particles is first analyzed by using silica particles and yeast cells as experimental samples. We can directly observe the particle focusing states on the screen of a smartphone, and the particle focusing efficiency can be flexibly tuned by changing the control voltage of the microheater. Then the study focus is transferred to single-particle migration. By changing the voltage combinations applied on four strip microheaters, the single particle can migrate at predetermined trajectory and speed, showing attractiveness for those applications needing sample transportation. Finally, we manipulate the special three-phase flow system of double-emulsion drops in thermal fields. Under the combined effect of the thermocapillary effect and increased instability, the shell of double-emulsion droplets gradually thins and finally breaks, resulting in the release of samples in inner cores. The core release speed can also be flexibly adjusted by changing the control voltage of the microheater. These three experiments successfully demonstrate the effectiveness and multifunctionality of this thermally actuated microfluidic device on granular manipulation. Therefore, this portable microfluidic device will be promising for lots of applications, such as analytical detection, microrobot actuation and cargo release.
RESUMO
The treatment of tumors in developing countries, especially those with poor medical conditions, remains a significant challenge. Herein, a novel solvent-exchange strategy to prepare adhesive hydrogels for the concurrent treatment of tumors through synchronous ethanol ablation and local chemotherapy is reported. First, a poly (gallic acid-lipoic acid) (PGL) ethanol gel is prepared that can undergo solvent exchange with water to form a hydrogel in situ. PGL ethanol gel deposited on the wet tissue can form a hydrogel in situ to effectively repel interfacial water and establish a tight contact between the hydrogel and tissue. Additionally, the functional groups between the hydrogels and tissues can form covalent and non-covalent bonds, resulting in robust adhesion. Furthermore, this PGL ethanol gel demonstrates exceptional capacity to effectively load antitumor drugs, allowing for controlled and sustained release of the drugs locally and sustainably both in vitro and in vivo. In addition, the PGL ethanol gel can combine ethanol ablation and local chemotherapy to enhance the antitumor efficacy in vitro and in vivo. The PGL ethanol gel-derived hydrogel shows robust wet bioadhesion, drug loading, sustained release, good biocompatibility and biodegradability, easy preparation and usage, and cost-effectiveness, which make it a promising bioadhesive for diverse biomedical applications.
Assuntos
Etanol , Hidrogéis , Solventes , Hidrogéis/química , Etanol/química , Animais , Camundongos , Solventes/química , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Modelos Animais de Doenças , Adesivos/química , Humanos , Técnicas de Ablação/métodosRESUMO
GaSe is an important member of the post-transition-metal chalcogenide family and is an emerging two-dimensional (2D) semiconductor material. Because it is a van der Waals material, it can be fabricated into atomic-scale ultrathin films, making it suitable for the preparation of compact, heterostructure devices. In addition, GaSe possesses unusual optical and electronic properties, such as a shift from an indirect-bandgap single-layer film to a direct-bandgap bulk material, rare intrinsic p-type conduction, and nonlinear optical behaviors. These properties make GaSe an appealing candidate for the fabrication of field-effect transistors, photodetectors, and photovoltaics. However, the wafer-scale production of pure GaSe single-crystal thin films remains challenging. This study develops an approach for the direct growth of nanometer-thick GaSe films on GaAs substrates by using molecular beam epitaxy. It yields smooth thin GaSe films with a rare γ'-polymorph. We analyze the formation mechanism of γ'-GaSe using density-functional theory and speculate that it is stabilized by Ga vacancies since the formation enthalpy of γ'-GaSe tends to become lower than that of other polymorphs when the Ga vacancy concentration increases. Finally, we investigate the growth conditions of GaSe, providing valuable insights for exploring 2D/three-dimensional (3D) quasi-van der Waals epitaxial growth.
RESUMO
As a new energy harvesting technology, triboelectric nanogenerators are widely used for vibration mechanical energy harvesting. However, the current schemes ignore the composite characteristics of vibration, with problems such as utilization and low collection efficiency. In this paper, a random resonance cantilever beam triboelectric nanogenerator (RCB-TENG) with dual-mode coupled is presented, the working mode is a coupling form of in-plane sliding and vertical contact-separation that can effectively collect complex vibration energy in transverse and longitudinal directions. The influences of the structural parameters of the RCB-TENG and different dielectric materials on the output performance are systematically investigated. The single vibration module achieved a power density of 463.56 mW/m2 and a transfer charge of 10.7 µC at a vibration frequency of 46 Hz, an increase in power density, and a transfer charge of 4.94 and 3.82 times, respectively, compared to the conventional contact-separation mode. Finally, the RCB-TENG was tested in practice, and it was observed that nine 1 W commercial LED bulbs and 500 5 mm diameter LED lamps were successfully lit. This work offers new ideas for distributed energy harvesting technologies and holds broad promise in the field of energy harvesting from wind, water, wave, and random vibrations caused by mechanical energy.
RESUMO
The bHLH family, as a superfamily of transcription factors (TFs), has special functional characteristics in plants and plays a crucial role in a plant's growth and development and helping the plant cope with various stresses. In this study, 128 bHLH family genes were screened in the birch (B. platyphylla) genome using conservative domain scan and blast analysis. These genes are clustered into 21 subfamilies based on the phylogenetic tree construction and are unevenly distributed among the 14 birch chromosomes. In all, 22 segmental duplication pairs with 27 BpbHLH genes were identified. The duplications were distributed on eight chromosomes. Analysis of gene structures and protein motifs revealed intra-group conservation of BpbHLHs. Of the BpbHLH family genes, 16 contain only one intron each. The BPChr14G06667 gene contains the most introns, that is, 19. The cis-elements, which respond to plant hormones, light, defense, and stress, were found on the promoter of BHLH family genes. As per RNA-seq data analysis, under PEG osmotic stress, most BpbHLH genes were differentially expressed, and eight were highly differentially expressed. The qRT-PCR analysis results further indicated that BPChr06G09475 was the gene with the highest expression level in leaves, roots, and stems, and that the expression of these eight genes was higher in leaves than in roots and stems and upregulated in all three tissues under osmotic stress compared to the controls. The above analysis suggests that the BpbHLH family genes have a certain biological effect under drought stress that provides a basis for molecular breeding for stress resistance in birch.
RESUMO
We compared the relationship between sedentary activity (SA) and physical activity (PA) with bone mineral density (BMD) and body fat percentage in the United States and found a negative association between SA and BMD and a positive association with body fat percentage. A positive association between PA and BMD and a negative association with body fat percentage. SA and PA are associated with changes in skeletal parameters and body fat percentage, and we aimed to investigate and compare the relationship between SA, PA and bone mineral density (BMD) and body fat percentage in men and women. We assessed the relationship between SA, PA and BMD and body fat percentage in 9787 Americans aged 20-59 years (mean age 38.28 ± 11.39 years) from NHANES 2011-2018. BMD and body fat percentage were measured by dual-energy X-ray bone densitometry (DXA). We used multiple linear regression models to examine the relationships between SA, PA and lumbar spine BMD and total body fat percentage, adjusted for a large number of confounding factors. After adjusting for race/ethnicity, age, alcohol and smoking behavior, body mass index (BMI), total protein, blood calcium, blood uric acid, cholesterol, blood phosphorus, vitamin D, and blood urea nitrogen, SA was negatively associated with lumbar spine BMD (ß = - 0.0011 95% CI - 0.0020 to - 0.0002, P = 0.022), and SA was positively associated with total fat percentage (ß = PA was positively associated with lumbar BMD (ß = 0.0046 95% CI 0.0010 to 0.0082, P = 0.012) and there was a negative association between PA and body fat percentage (ß = - 1.177 95% CI - 1.326 to -1.027, P < 0.001). Our results show that physical activity is a key component of maintaining bone health in both men and women and is strongly associated with lower body fat percentages. Sedentary activity is negatively correlated with bone density and is strongly associated with an increase in body fat percentage. Healthcare policy makers should consider reducing sedentary activity and increasing physical activity when preventing osteoporosis and obesity.
Assuntos
Densidade Óssea , Osteoporose , Masculino , Humanos , Feminino , Estados Unidos/epidemiologia , Adulto , Pessoa de Meia-Idade , Inquéritos Nutricionais , Absorciometria de Fóton , Exercício Físico , Índice de Massa Corporal , Vértebras LombaresRESUMO
HSPA8 (heat shock protein family A (Hsp70) member 8) plays a significant role in the autophagic degradation of proteins, however, its effect on protein stabilization and anti-bacterial autophagy remains unknown. Here, it is discovered that HSPA8, as a binding partner of RHOB and BECN1, induce autophagy for intracellular bacteria clearance. Using its NBD and LID domains, HSPA8 physically binds to RHOB residues 1-42 and 89-118 as well as to BECN1 ECD domain, preventing RHOB and BECN1 degradation. Intriguingly, HSPA8 contains predicted intrinsically disordered regions (IDRs), and drives liquid-liquid phase separation (LLPS) to concentrate RHOB and BECN1 into HSPA8-formed liquid-phase droplets, resulting in improved RHOB and BECN1 interactions. Our study reveals a novel role and mechanism of HSPA8 in modulating anti-bacterial autophagy, and highlights the effect of LLPS-related HSPA8-RHOB-BECN1 complex on enhancing protein interaction and stabilization, which improves the understanding of autophagy-mediated defense against bacteria.
Assuntos
AutofagiaRESUMO
Hyperbolic phonon polaritons (HPhPs) can be supported in materials where the real parts of their permittivities along different directions are opposite in sign. HPhPs offer confinements of long-wavelength light to deeply subdiffractional scales, while the evanescent field allows for interactions with substrates, enabling the tuning of HPhPs by altering the underlying materials. Yet, conventionally used noble metal and dielectric substrates restrict the tunability of this approach. To overcome this challenge, here we show that doped semiconductor substrates, e.g., InAs and CdO, enable a significant tuning effect and dynamic modulations. We elucidated HPhP tuning with the InAs plasma frequency in the near-field, with a maximum difference of 8.3 times. Moreover, the system can be dynamically modulated by photo-injecting carriers into the InAs substrate, leading to a wavevector change of ~20%. Overall, the demonstrated hBN/doped semiconductor platform offers significant improvements towards manipulating HPhPs, and potential for engineered and modulated polaritonic systems.
RESUMO
Amblyopia is visual impairment characterized by a structurally normal eye showing significantly lower visual acuity than the fellow eye. Traditional treatment of amblyopia includes patching the good eye to force the amblyopic eye to work during normal daily activities; however, this approach is are limited by low compliance. Recently, researchers proposed a new treatment for amblyopia: video game playing. In the current review, we discuss whether video game playing can treat amblyopia, whether video game playing could better treat amblyopia than traditional treatments, and how the video game treats amblyopia and its possible mechanism. Based on results from our literature review and meta-analysis, we suggest there is strong evidence for the effectiveness of video game treatments. Moreover, multiple factors within and outside of video games could influence the treatment effect.
Assuntos
Ambliopia , Jogos de Vídeo , Baixa Visão , Ambliopia/terapia , Humanos , Resultado do Tratamento , Acuidade VisualRESUMO
BACKGROUND: The pathogenesis of inflammatory bowel diseases (IBD) is multifactorial, and diagnostic and treatment strategies for IBD remain to be developed. RhoB regulates multiple cell functions; however, its role in colitis is unexplored. RESULTS: Here, we found RhoB was dramatically increased in colon tissues of ulcerative colitis (UC) patients and mice with DSS-induced colitis. Compared with wild type mice, RhoB+/- and RhoB-/- mice developed milder DSS-induced colitis and increased goblet cell numbers and IEC proliferation. Decreased RhoB promoted goblet cell differentiation and epithelial regeneration through inhibiting Wnt signaling pathway and activating p38 MAPK signaling pathway. Moreover, increased SCFA-producing bacteria and SCFA concentrations were detected in intestinal microbiome of both RhoB+/- and RhoB-/- mice and upregulated SCFA receptor expression was also observed. CONCLUSIONS: Taken together, a higher level of RhoB is associated with UC, which also contributes to UC development through modulating cell signaling and altering intestinal bacterial composition and metabolites. These observations suggest that RhoB has potential as a biomarker and a treatment target for UC. Video Abstract.
Assuntos
Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Proteína rhoB de Ligação ao GTP/metabolismo , Animais , Biomarcadores , Colite/induzido quimicamente , Colite/patologia , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Sulfato de Dextrana , Humanos , Camundongos , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Host cells use several anti-bacterial pathways to defend against pathogens. Here, using a uropathogenic Escherichia coli (UPEC) infection model, we demonstrate that bacterial infection upregulates RhoB, which subsequently promotes intracellular bacteria clearance by inducing LC3 lipidation and autophagosome formation. RhoB binds with Beclin 1 through its residues at 118 to 140 and the Beclin 1 CCD domain, with RhoB Arg133 being the key binding residue. Binding of RhoB to Beclin 1 enhances the Hsp90-Beclin 1 interaction, preventing Beclin 1 degradation. RhoB also directly interacts with Hsp90, maintaining RhoB levels. UPEC infections increase RhoB, Beclin 1 and LC3 levels in bladder epithelium in vivo, whereas Beclin 1 and LC3 levels as well as UPEC clearance are substantially reduced in RhoB+/- and RhoB-/- mice upon infection. We conclude that when stimulated by UPEC infections, host cells promote UPEC clearance through the RhoB-Beclin 1-HSP90 complex, indicating RhoB may be a useful target when developing UPEC treatment strategies.
Assuntos
Autofagossomos/metabolismo , Proteína Beclina-1/metabolismo , Infecções por Escherichia coli/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Infecções Urinárias/metabolismo , Escherichia coli Uropatogênica/crescimento & desenvolvimento , Proteína rhoB de Ligação ao GTP/metabolismo , Animais , Autofagossomos/genética , Autofagossomos/ultraestrutura , Proteína Beclina-1/genética , Linhagem Celular , Epitélio/metabolismo , Epitélio/microbiologia , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Feminino , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP90/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Proteínas Associadas aos Microtúbulos/metabolismo , Ligação Proteica , Estabilidade Proteica , RNA Interferente Pequeno , Proteínas Recombinantes , Bexiga Urinária/metabolismo , Bexiga Urinária/microbiologia , Infecções Urinárias/genética , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/patogenicidade , Proteína rhoB de Ligação ao GTP/genéticaRESUMO
Incorporating plasmonic nanostructures is a promising strategy to enhance both the optical and electrical characteristics of photovoltaic devices via more efficient harvesting of incident light. Herein, we report a facile fabrication scheme at low temperature for producing gold nanoparticles embedded in anatase TiO2 films, which can simultaneously improve the efficiency and stability of n-i-p planar heterojunction perovskite solar cells (PSCs). The PSCs based on rigid and flexible substrates with 0.2 wt % Au-TiO2/TiO2 dual electron transport layers (ETLs) achieved power conversion efficiencies up to 20.31 and 15.36%, superior to that of devices with TiO2 as a single ETL. Moreover, 0.2 wt % Au-TiO2/TiO2 devices demonstrated significant stability in light soaking, which is attributed to improved light absorption, low charge recombination loss, and enhanced carrier transport, and extraction with the plasmonic Au-TiO2/TiO2 dual ETL. The present work improves the practicability of high-performance and flexible PSCs by engineering the photogenerated carrier dynamics at the interface.
RESUMO
A facile aqueous-based fabrication scheme is developed for producing annealing-free anatase TiO2 (AF-TiO2) films that exhibit efficient electron transport properties in planar heterojunction perovskite solar cells (PSCs). AF-TiO2 films are fabricated by spin coating on a substrate a colloidal solution of anatase TiO2 nanoparticles (NPs) prepared via a low temperature hydrolytic sol-gel method. The resultant AF-TiO2 films show low electrical resistance, high transmittance in the visible and near-infrared regions and facilitation of high-quality perovskite film formation, which can be attributed to their homogeneous surface morphology and nanocrystallinity. The AF-TiO2 based PSCs achieve a power conversion efficiency (PCE) of 18.29 ± 0.18%, showing significant improvement compared to the control PSCs (PCE = 11.33 ± 0.32%) based on TiO2 films made by high-temperature annealing of amorphous TiO2 (HTA-TiO2).
RESUMO
Although some kinds of semiconductor metal oxides (SMOs) have been applied as electron selective layers (ESLs) for planar perovskite solar cells (PSCs), electron transfer is still limited by low electron mobility and defect film formation of SMO ESLs fabricated via low-temperature solution process. Herein, the C70 interlayer between TiO2 and (HC(NH2)2PbI3)x(CH3NH3PbCl3)1-x is prepared by spin-coating and low-temperature annealing for planar n-i-p PSCs. The resultant TiO2/C70 ESL shows good surface morphology, efficient electron extraction, and facilitation of high-quality perovskite film formation, which can be attributed to the suitable nanosize and the superior electronic property of C70 molecules. In comparison with pristine TiO2-based PSCs, the efficiency and hysteresis index are, respectively, enhanced 28% and reduced 76% by adding the C70 interlayer between TiO2 and perovskite on the basis of statistical data of more than 50 cells. With the main advantages of low-temperature process and optimized interface, the champion efficiency of PSCs on flexible substrates could exceed 12% in contrast with the above 18% on rigid substrate.