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1.
Nature ; 628(8006): 93-98, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382650

RESUMO

Defects at the top and bottom interfaces of three-dimensional (3D) perovskite photoabsorbers diminish the performance and operational stability of perovskite solar cells owing to charge recombination, ion migration and electric-field inhomogeneities1-5. Here we demonstrate that long alkyl amine ligands can generate near-phase-pure 2D perovskites at the top and bottom 3D perovskite interfaces and effectively resolve these issues. At the rear-contact side, we find that the alkyl amine ligand strengthens the interactions with the substrate through acid-base reactions with the phosphonic acid group from the organic hole-transporting self-assembled monolayer molecule, thus regulating the 2D perovskite formation. With this, inverted perovskite solar cells with double-side 2D/3D heterojunctions achieved a power conversion efficiency of 25.6% (certified 25.0%), retaining 95% of their initial power conversion efficiency after 1,000 h of 1-sun illumination at 85 °C in air.

2.
Nature ; 623(7988): 732-738, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37769785

RESUMO

Monolithic perovskite/silicon tandem solar cells are of great appeal as they promise high power conversion efficiencies (PCEs) at affordable cost. In state-of-the-art tandems, the perovskite top cell is electrically coupled to a silicon heterojunction bottom cell by means of a self-assembled monolayer (SAM), anchored on a transparent conductive oxide (TCO), which enables efficient charge transfer between the subcells1-3. Yet reproducible, high-performance tandem solar cells require energetically homogeneous SAM coverage, which remains challenging, especially on textured silicon bottom cells. Here, we resolve this issue by using ultrathin (5-nm) amorphous indium zinc oxide (IZO) as the interconnecting TCO, exploiting its high surface-potential homogeneity resulting from the absence of crystal grains and higher density of SAM anchoring sites when compared with commonly used crystalline TCOs. Combined with optical enhancements through equally thin IZO rear electrodes and improved front contact stacks, an independently certified PCE of 32.5% was obtained, which ranks among the highest for perovskite/silicon tandems. Our ultrathin transparent contact approach reduces indium consumption by approximately 80%, which is of importance to sustainable photovoltaics manufacturing4.

3.
Lab Invest ; 104(3): 100326, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38237739

RESUMO

To better understand the pathogenesis of acute type A aortic dissection, high-sensitivity liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS)-based proteomics and phosphoproteomics approaches were used to identify differential proteins. Heat shock protein family B (small) member 6 (HSPB6) in aortic dissection was significantly reduced in human and mouse aortic dissection samples by real-time PCR, western blotting, and immunohistochemical staining techniques. Using an HSPB6-knockout mouse, we investigated the potential role of HSPB6 in ß-aminopropionitrile monofumarate-induced aortic dissection. We found increased mortality and increased probability of ascending aortic dissection after HSPB6 knockout compared with wild-type mice. Mechanistically, our data suggest that HSPB6 deletion promoted vascular smooth muscle cell apoptosis. More importantly, HSPB6 deletion attenuated cofilin activity, leading to excessive smooth muscle cell stiffness and eventually resulting in the development of aortic dissection and rupture. Our data suggest that excessive stiffness of vascular smooth muscle cells caused by HSPB6 deficiency is a new pathogenetic mechanism leading to aortic dissection.


Assuntos
Dissecção Aórtica , Espectrometria de Massas em Tandem , Camundongos , Humanos , Animais , Cromatografia Líquida , Dissecção Aórtica/genética , Miócitos de Músculo Liso/metabolismo , Camundongos Knockout , Modelos Animais de Doenças , Proteínas de Choque Térmico HSP20/metabolismo
4.
Microb Pathog ; 192: 106713, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38810765

RESUMO

Newcastle disease virus (NDV) is the pathogen of a zoonosis that is primarily transmitted by poultry and has severe infectivity and a high fatality rate. Many studies have focused on the role of the NDV fusion (F) protein in the cell-cell membrane fusion process. However, little attention has been given to the heptad repeat region, HR4, which is located in the NDV F2 subunit. Here, site-directed mutants were constructed to study the function of the NDV F protein HR4 region and identify the key amino acids in this region. Nine conserved amino acids were substituted with alanine or the corresponding amino acid of other aligned paramyxoviruses. The desired mutants were examined for changes in fusogenic activity through three kinds of membrane fusion assays and expression and proteolysis through IFA, FACS and WB. The results showed that when conserved amino acids (L81, Y84, L88, L91, L92, P94, L95 and I99) were replaced with alanine, the fusogenic activity of the F protein was abolished, possibly because of failed protein expression not only on the cell surface but also inside cells. These data indicated that the conserved amino acids above in NDV F HR4 are critical for normal protein synthesis and expression, possibly for the stability of the F protein monomer, formation of trimer and conformational changes.


Assuntos
Mutagênese Sítio-Dirigida , Vírus da Doença de Newcastle , Proteínas Virais de Fusão , Internalização do Vírus , Vírus da Doença de Newcastle/genética , Vírus da Doença de Newcastle/metabolismo , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/metabolismo , Animais , Substituição de Aminoácidos , Linhagem Celular , Mutação , Proteólise , Fusão de Membrana
5.
Perfusion ; : 2676591241278629, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39171903

RESUMO

BACKGROUND: The modality of thoracoabdominal aortic repair (TAAR) is mainly based on left heart bypass (LHB) in western countries, while in our team, it is mainly based on a unique technique, normothermic iliac perfusion, and there is a lack of systematic reports and long-term results. To describe the operative technique and summarize the patient characteristics and outcomes of TAAR with normothermic iliac perfusion in our team in the last decade. Meanwhile, to explore the influence of different previous surgical history on prognosis. METHODS: 137 consecutive patients who received TAAR with normothermic iliac perfusionby single surgeon from 2012 to 2022 were retrospectively analyzed. Operative details were described and data were grouped according to previous surgical history. Early operative mortality and adverse events were summarized. Survival over time was estimated by the Kaplan-Meier curve. RESULTS: The average age of the cohort was 42.39 ± 11.76 years old, 70.07% were male. 63 (46%) patients had no previous surgery, 53 (39%) patients had total arch replacement with frozen elephant trunk (TAR_FET), and 21 (15%) patients had thoracic endovascular aortic repair (TEVAR). Operative mortality was 4.38%, the incidence of early paraplegia was 6.57%, and previous surgery had no significant effect on prognosis (p = .294). Cumulative survival was 92.1% at 3 years and 90.8% at 5 years. CONCLUSIONS: The normothermic iliac perfusionfor TAAR is feasible regardless of previous surgery, as long as there are no complicating factors. And the early outcomes are satisfactory and the long-term outcomes are reliable.

6.
Angew Chem Int Ed Engl ; : e202407398, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39082226

RESUMO

As the most advanced non-viral delivery system, lipid nanoparticles (LNPs) were approved by the FDA, propelling the advancements of gene therapy. However, their clinical applications are hampered by the potential immunogenicity of the lipid components that trigger immune-related adverse events, like inflammation and allergy. Herein, we formulate various dLNPs with diminished immunogenicity by incorporating dexamethasone (Dex) into liver-, spleen-, and lung-targeting LNPs formulations that exhibit excellent abilities to target specific organs and deliver various types of RNA, such as mRNA and siRNA. In vivo investigations demonstrate unparalleled advantages in safety compared to conventional LNPs, showing promising potential in the development of RNA therapeutics. Intriguingly, the encapsulation of runt-related transcription factor-1 siRNA (siRUNX1) into lung-targeting dLNPs (dLNPs@siRUNX1) demonstrates remarkable advantages in the treatment of pulmonary fibrosis through the synergy of gene therapy and drug therapy. This research establishes secure and universal platforms for the precise delivery of nucleic acid therapeutics, showcasing promising clinical applications in gene therapy.

7.
Angew Chem Int Ed Engl ; 63(17): e202319400, 2024 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-38284300

RESUMO

Peptidoglycan, an essential component within the cell walls of virtually all bacteria, is composed of glycan strands linked by stem peptides that contain D-amino acids. The peptidoglycan biosynthesis machinery exhibits high tolerance to various D-amino acid derivatives. D-amino acid derivatives with different functionalities can thus be specifically incorporated into and label the peptidoglycan of bacteria, but not the host mammalian cells. This metabolic labeling strategy is highly selective, highly biocompatible, and broadly applicable, which has been utilized in various fields. This review introduces the metabolic labeling strategies of peptidoglycan by using D-amino acid derivatives, including one-step and two-step strategies. In addition, we emphasize the various applications of D-amino acid derivative-based metabolic labeling, including bacterial peptidoglycan visualization (existence, biosynthesis, and dynamics, etc.), bacterial visualization (including bacterial imaging and visualization of growth and division, metabolic activity, antibiotic susceptibility, etc.), pathogenic bacteria-targeted diagnostics and treatment (positron emission tomography (PET) imaging, photodynamic therapy, photothermal therapy, gas therapy, immunotherapy, etc.), and live bacteria-based therapy. Finally, a summary of this metabolic labeling and an outlook is provided.


Assuntos
Bactérias , Peptidoglicano , Peptidoglicano/metabolismo , Bactérias/metabolismo , Aminoácidos/química , Parede Celular/metabolismo
8.
Environ Res ; 216(Pt 1): 114139, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36084678

RESUMO

Hexachlorobutadiene (HCBD) was listed as a new persistent organic pollutant for global regulation under Stockholm Convention in 2015, and there has been scarce information on its atmospheric concentrations, distributions, and emission sources. HCBD air samples were collected and analyzed to characterize concentrations and distributions at high elevation and urban sites as well as emission source locations in Northern China. We found ambient concentrations of HCBD in Northern China averaged at 34 ± 16 and 36 ± 28 pptv at urban sites in Jinan and Tai'an, respectively, and 31 ± 21 pptv at a high-elevation site Mount Tai. HCBD concentrations at the high elevation and urban sites were found to be affected by long-range transport under the influence of the East Asian monsoon climate. Over potential sources areas, we found concentrations of 76 ± 33 pptv in a mixed factory park, 59 ± 21 pptv in a rubber plant and 74 ± 8 pptv in a municipal solid waste (MSW) landfill area, which were all several times higher than in urban sites. The large concentration gradient across the various environments revealed strong emission sources of HCBD, especially over MSW landfill and Cl-compound production and application areas. An emission rate of 9.2 × 104 kg/yr and an oxidation rate of 32.9 kg/yr for HCBD were estimated for the mixed factory park. OH and Cl are much more active in reaction with HCBD than other oxidants in the atmosphere. Dry deposition and oxidation removed about 5.3% and 0.04%, respectively, of the emitted, suggesting that ∼95% of the emitted HCBD remaining in the atmosphere and could be transported for redistribution. Our findings revealed significant emission sources of HCBD in northern China, which was in turn affected by major sources in East-central China. The regional influence of HCBD pollution warrants serious concerns and points to the need to develop mitigation strategies.


Assuntos
Poluentes Atmosféricos , Poluentes Orgânicos Persistentes , Monitoramento Ambiental , Butadienos , Atmosfera , Resíduos Sólidos , China , Poluentes Atmosféricos/análise
9.
Clin J Sport Med ; 32(6): e647-e651, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36315830

RESUMO

ABSTRACT: Ischiofemoral impingement is a distinct pathologic finding with abnormal osseous contact between the ischium and the lesser trochanter of the femur. Lesser trochanter excision has been recommended for recalcitrant ischiofemoral impingement through an open or endoscopic approach; however, no study has included ischial tuberosity osteophyte resection and refixation of the hamstring tendon. We report an endoscopic procedure involving ischial tuberosity osteophyte resection with refixation of the partially detached hamstring insertion through a posterior approach in the prone position. Using this technique, it is easier to reach the lesion and less likely to injure the sciatic nerve. The postoperative pain score (visual analogy score) was significantly decreased, the modified Harris hip score increased from 39 preoperatively to 86 postoperatively, and there was no adverse effect on the hamstring tendon.


Assuntos
Impacto Femoroacetabular , Músculos Isquiossurais , Osteófito , Humanos , Ísquio/cirurgia , Osteófito/diagnóstico por imagem , Osteófito/cirurgia , Fêmur/cirurgia , Fêmur/patologia , Endoscopia , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Impacto Femoroacetabular/patologia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia
10.
J Am Chem Soc ; 142(11): 5177-5183, 2020 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-32100536

RESUMO

The insufficient intracellular H2O2 level in tumor cells is closely associated with the limited efficacy of chemodynamic therapy (CDT). Despite tremendous efforts, engineering CDT agents with a straightforward and secure H2O2 supplying ability remains a great challenge. Inspired by the balance of H2O2 generation and elimination in cancer cells, herein, a nanozyme-based H2O2 homeostasis disruptor is fabricated to elevate the intracellular H2O2 level through facilitating H2O2 production and restraining H2O2 elimination for enhanced CDT. In the formulation, the disruptor with superoxide dismutase-mimicking activity can convert O2•- to H2O2, promoting the production of H2O2. Simultaneously, the suppression of catalase activity and depletion of glutathione by the disruptor weaken the transformation of H2O2 to H2O. Thus, the well-defined system could perturb the H2O2 balance and give rise to the accumulation of H2O2 in cancer cells. The raised H2O2 level would ultimately amplify the Fenton-like reaction-based CDT efficiency. Our work not only paves a way to engineer alternative CDT agents with a H2O2 supplying ability for intensive CDT but also provides new insights into the construction of bioinspired materials.


Assuntos
Antineoplásicos/uso terapêutico , Peróxido de Hidrogênio/metabolismo , Estruturas Metalorgânicas/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Amitrol (Herbicida)/química , Amitrol (Herbicida)/uso terapêutico , Amitrol (Herbicida)/toxicidade , Animais , Antineoplásicos/química , Antineoplásicos/toxicidade , Catalase/antagonistas & inibidores , Catálise , Linhagem Celular Tumoral , Tratamento Farmacológico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Inibidores Enzimáticos/toxicidade , Feminino , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/toxicidade , Camundongos , Nanopartículas/química , Nanopartículas/toxicidade , Oxirredução , Polietilenoglicóis/química , Polietilenoglicóis/uso terapêutico , Polietilenoglicóis/toxicidade
11.
Angew Chem Int Ed Engl ; 59(13): 5108-5115, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-31960567

RESUMO

Sepsis, characterized by immoderate production of multiple reactive oxygen and nitrogen species (RONS), causes high morbidity and mortality. Despite progress made with nanozymes, efficient antioxidant therapy to eliminate these RONS remains challenging, owing largely to the specificity and low activity of exploited nanozymes. Herein, an enzyme-mimicking single-atom catalyst, Co/PMCS, features atomically dispersed coordinatively unsaturated active Co-porphyrin centers, which can rapidly obliterate multiple RONS to alleviate sepsis. Co/PMCS can eliminate O2.- and H2 O2 by mimicking superoxide dismutase, catalase, and glutathione peroxidase, while removing . OH via the oxidative-reduction cycle, with markedly higher activity than nanozymes. It can also scavenge . NO through formation of a nitrosyl-metal complex. Eventually, it can reduce proinflammatory cytokine levels, protect organs from damage, and confer a distinct survival advantage to the infected sepsis mice.


Assuntos
Materiais Biomiméticos/química , Catalase/química , Glutationa Peroxidase/química , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sepse/metabolismo , Superóxido Dismutase/química , Animais , Antioxidantes/química , Antioxidantes/metabolismo , Materiais Biomiméticos/metabolismo , Catalase/metabolismo , Catálise , Cobalto/química , Complexos de Coordenação/química , Complexos de Coordenação/metabolismo , Citocinas/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Ferro/química , Camundongos , Modelos Animais , Oxirredução , Porfirinas/química , Superóxido Dismutase/metabolismo
12.
Chem Soc Rev ; 47(11): 4017-4072, 2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29611579

RESUMO

DNA metallization has witnessed tremendous growth and development, from the initial simple synthesis aimed at manufacturing conductive metal nanowires to the current fabrication of various nanostructures for applications in areas as diverse as nanolithography, energy conversion and storage, catalysis, sensing, and biomedical engineering. To this, our aim here was to present a comprehensive review to summarize the research activities on DNA metallization that have appeared since the concept was first proposed in 1998. We start with a brief presentation of the basic knowledge of DNA and its unique advantages in the template-directed growth of metal nanomaterials, followed by providing a systematic summary of the various synthetic methods developed to date to deposit metals on DNA scaffolds. Then, the leverage of DNAs with different sequences, conformations, and structures for tuning the synthesis of feature-rich metal nanostructures is discussed. Afterwards, the discussion is divided around the applications of these metal nanomaterials in the fields mentioned above, wherein the key role DNA metallization plays in enabling high performance is emphasized. Finally, the current status and some future prospects and challenges in this field are summarized. As such, this review would be of great interest to promote the further development of DNA metallization by attracting researchers from various communities, including chemistry, biology, physiology, material science, and nanotechnology as well as other disciplines.

13.
Angew Chem Int Ed Engl ; 58(45): 16236-16242, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31456332

RESUMO

Nanozymes have emerged as a new generation of antibiotics with exciting broad-spectrum antimicrobial properties and negligible biotoxicities. However, their antibacterial efficacies are unsatisfactory due to their inability to trap bacteria and their low catalytic activity. Herein, we report nanozymes with rough surfaces and defect-rich active edges. The rough surface increases bacterial adhesion and the defect-rich edges exhibit higher intrinsic peroxidase-like activity compared to pristine nanozymes due to their lower adsorption energies of H2 O2 and desorption energy of OH*, as well as the larger exothermic process for the whole reaction. This was demonstrated using drug-resistant Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus in vitro and in vivo. This strategy can be used to engineer nanozymes with enhanced antibacterial function and will pave a new way for the development of alternative antibiotics.


Assuntos
Antibacterianos/farmacologia , Dissulfetos/química , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Molibdênio/química , Peroxidases/química , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/química , Infecções por Escherichia coli/microbiologia , Peróxido de Hidrogênio/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estafilocócicas/microbiologia
14.
J Nanosci Nanotechnol ; 18(4): 3012-3017, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29442988

RESUMO

Silver nanowires with high yield, uniform size and high aspect ratio were successfully synthesized by a simple and effective polyol method under low temperature and quiescent conditions, adopting CuCl2·2H2O as the nucleation control agent for the first time. The synthesized silver nanowires were characterized by X-ray powder diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and UV-Vis diffuse reflectance spectroscopy (DRS). The results indicate that the silver nanowires were composed of face-centered cubic structure of pure metallic silver with high crystallinity. And the silver nanowires have an average length of 80~100 µm and an average diameter of 40~80 nm. Thus, the aspect ratio of the nanowires was greater than 1000. In addition, the influence on the morphology and structure of the silver nanowires were investigated for reaction temperature, mole ratio of PVP:AgNO3, molecular weight of PVP and mole ratio of control agent CuCl2 · 2H2O:AgNO3. Finally, the optimum reaction condition were obtained for the preparation of the silver nanowires with high aspect ratio.

15.
Chemistry ; 23(54): 13518-13524, 2017 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-28741846

RESUMO

Skin cancers caused by UV irradiation have been a major public health problem. One simple and effective way to avoid the above detrimental effects is the use of UV-protective sunscreens. However, there has been considerable concern with the issue of the production of reactive oxygen species (ROS) through the photodegradation of commercial UV filters. Herein, for the first time, it is reported that the integration of ZnO nanoparticles and CeOx nanoparticles into hollow microspheres (ZnO/CeOx HMS) could provide broad-spectrum UV protection and scavenge generated ROS under UV irradiation. Benefiting from the cooperative effect of the hollow structure and the antioxidative activity of CeOx , ROS generated under UV irradiation could be confined to a limited space and effectively conversion into nontoxic molecules is catalyzed as a consequence of increased collision frequency. Therefore, both primary, direct UV-induced damage and secondary ROS toxicity could be greatly reduced.


Assuntos
Espécies Reativas de Oxigênio/metabolismo , Protetores Solares/química , Raios Ultravioleta , Animais , Catálise , Sobrevivência Celular/efeitos dos fármacos , Cério/química , Vermelho Congo/química , Feminino , Citometria de Fluxo , Células HEK293 , Humanos , Nanopartículas Metálicas/química , Camundongos , Microscopia de Fluorescência , Fotólise , Espécies Reativas de Oxigênio/química , Pele/patologia , Pele/efeitos da radiação , Protetores Solares/farmacologia , Óxido de Zinco/química
16.
Clin Lab ; 60(4): 587-97, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24779292

RESUMO

BACKGROUND: Primary hepatic carcinoma (PHC) is currently one of the most common worldwide causes of cancer death. Golgi protein 73 (GP73) has been proposed as potential diagnostic marker. However, it is controversial because of inconsistent diagnostic accuracy in different studies. The aim of this study was to assess the diagnostic accuracy of GP73 for PHC. METHODS: All the studies relating to the diagnostic accuracy of GP73 for patients with PHC from 1978 to January 2013 were collected. Methodological quality was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). The overall diagnostic sensitivity, specificity, and area under the receiver operating characteristic curve were used to evaluate the diagnostic accuracy of GP73 using Meta-DiSc statistical software. RESULTS: Altogether 5,637 subjects were included in the 25 selected studies. The sensitivity and specificity (95% confidence interval) of GP73 was 0.75 (0.73-0.76) and 0.84 (0.83 - 0.86), respectively. The area under the summary receiver operating characteristic curve (AUC) and Q* index of GP73 was 0.8616 and 0.8021. CONCLUSIONS: Serum GP73 has a relatively high diagnostic accuracy in primary hepatic carcinoma with better sensitivity and high specificity than AFP.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma/sangue , Neoplasias Hepáticas/sangue , Proteínas de Membrana/sangue , Ensaio de Imunoadsorção Enzimática , Humanos , Curva ROC , alfa-Fetoproteínas/metabolismo
17.
Nanoscale Horiz ; 9(7): 1070-1071, 2024 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-38695198

RESUMO

This article highlights the recent work of Castagnola, Armirotti, et al. (Nanoscale Horiz., 2024, https://doi.org/10.1039/D3NH00510K) on demonstrating that the widespread use of 10% fetal bovine serum in an in vitro assay cannot recapitulate the complexity of in vivo systemic administration.


Assuntos
Nanoestruturas , Coroa de Proteína , Nanoestruturas/química , Humanos , Coroa de Proteína/química , Animais , Bovinos
18.
Int J Dev Neurosci ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187446

RESUMO

BACKGROUND: The BCL11A gene is involved in disorders including intellectual disability syndrome (IDS), encodes a zinc finger protein highly expressed in haematopoietic and brain and acts as a transcriptional repressor of foetal haemoglobin (HbF). De novo variants in BCL11A have been associated with IDS, which is characterized by developmental delays, autism spectrum disorder (ASD) and speech and language delays. The reports of BCL11A gene variants are still limited worldwide, and additional cases are needed to expand the variant and phenotype spectrums. METHODS: The patient is a 5-year-old girl who was hospitalized due to developmental delays. After analysing her clinical and pathological characterizations, whole-exome sequencing (WES) was performed for pathogenic genetic variants of developmental delay and behavioural differences. Candidate variant in BCL11A gene was identified and further validated by Sanger sequencing. RESULTS: A heterozygous variant, c.1442delA (p.Glu481Glyfs*25), was identified in exon 4 of the BCL11A gene through WES. This variant results in a truncated expression of the encoded protein. This de novo variant was confirmed by Sanger sequencing. The language delay and behavioural differences were prominent in our patient. CONCLUSION: Our finding demonstrates that BCL11A variant may cause developmental delay and behavioural differences, expanding the genetic spectrum of the BCL11A gene.

19.
Front Pediatr ; 12: 1328063, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39026940

RESUMO

METTL23 belongs to a family of protein lysine methyltransferases that methylate non-histone proteins. Recently, the METTL23 gene has been reported to be related to an intellectual developmental disorder, autosomal recessive 44. Patients present with developmental delay, intellectual disability (ID), and variable dysmorphic features. Here, we report on a Chinese girl who presented with global developmental delay, abnormal brain structure, and multiple facial deformities, including a short/upturned nose with a sunken bridge, thin lips, and flat occiput. Whole-exome sequencing identified a novel variant (NM_001080510.5: c.322+1del) on the METTL23 gene. This variant was not collected on public human variants databases such as gnomAD, predicted to influence the splicing as a classical splicing variant, and classified as Pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Since patients with METTL23-related ID are rare, we summarize and compare the clinical phenotype of reported patients with METTL23 variants. Our report further expands the METTL23 variants and provides new evidence for clinical diagnosis of METTL23-related ID.

20.
Exploration (Beijing) ; 4(1): 20230019, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38854493

RESUMO

Calcium ions (Ca2+) are indispensable and versatile metal ions that play a pivotal role in regulating cell metabolism, encompassing cell survival, proliferation, migration, and gene expression. Aberrant Ca2+ levels are frequently linked to cell dysfunction and a variety of pathological conditions. Therefore, it is essential to maintain Ca2+ homeostasis to coordinate body function. Disrupting the balance of Ca2+ levels has emerged as a potential therapeutic strategy for various diseases, and there has been extensive research on integrating this approach into nanoplatforms. In this review, the current nanoplatforms that regulate Ca2+ homeostasis for cancer therapy are first discussed, including both direct and indirect approaches to manage Ca2+ overload or inhibit Ca2+ signalling. Then, the applications of these nanoplatforms in targeting different cells to regulate their Ca2+ homeostasis for achieving therapeutic effects in cancer treatment are systematically introduced, including tumour cells and immune cells. Finally, perspectives on the further development of nanoplatforms for regulating Ca2+ homeostasis, identifying scientific limitations and future directions for exploitation are offered.

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