Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 337
Filtrar
1.
Parasite ; 31: 34, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38949636

RESUMO

Wild rodents serve as reservoirs for Cryptosporidium and are overpopulated globally. However, genetic data regarding Cryptosporidium in these animals from China are limited. Here, we have determined the prevalence and genetic characteristics of Cryptosporidium among 370 wild rodents captured from three distinct locations in the southern region of Zhejiang Province, China. Fresh feces were collected from the rectum of each rodent, and DNA was extracted from them. The rodent species was identified by PCR amplifying the vertebrate cytochrome b gene. Cryptosporidium was detected by PCR amplification and amplicon sequencing the small subunit of ribosomal RNA gene. Positive samples of C. viatorum and C. parvum were further subtyped by analyzing the 60-kDa glycoprotein gene. A positive Cryptosporidium result was found in 7% (26/370) of samples, involving five rodent species: Apodemus agrarius (36), Niviventer niviventer (75), Rattus losea (18), R. norvegicus (155), and R. tanezumi (86). Their respective Cryptosporidium positive rates were 8.3%, 5.3%, 11.1%, 7.1%, and 7.0%. Sequence analysis confirmed the presence of three Cryptosporidium species: C. parvum (4), C. viatorum (1), and C. muris (1), and two genotypes: Cryptosporidium rat genotype IV (16) and C. mortiferum-like (4). Additionally, two subtypes of C. parvum (IIdA15G1 and IIpA19) and one subtype of C. viatorum (XVdA3) were detected. These results demonstrate that various wild rodent species in Zhejiang were concurrently infected with rodent-adapted and zoonotic species/genotypes of Cryptosporidium, indicating that these rodents can play a role in maintaining and dispersing this parasite into the environment and other hosts, including humans.


Title: Transmission interspécifique de Cryptosporidium chez les rongeurs sauvages de la région sud de la province chinoise du Zhejiang et son impact possible sur la santé publique. Abstract: Les rongeurs sauvages servent de réservoirs à Cryptosporidium et ont des grandes populations à l'échelle mondiale. Cependant, les données génétiques concernant Cryptosporidium chez ces animaux en Chine sont limitées. Ici, nous avons déterminé la prévalence et les caractéristiques génétiques de Cryptosporidium parmi 370 rongeurs sauvages capturés dans trois endroits distincts de la région sud de la province du Zhejiang, en Chine. Des excréments frais ont été collectés dans le rectum de chaque rongeur et l'ADN en a été extrait. L'espèce de rongeur a été identifiée par amplification par PCR du gène du cytochrome b des vertébrés. Cryptosporidium a été détecté par amplification PCR et séquençage d'amplicons de la petite sous-unité du gène de l'ARN ribosomal. Les échantillons positifs de C. viatorum et C. parvum ont ensuite été sous-typés en analysant le gène de la glycoprotéine de 60 kDa. Un résultat positif pour Cryptosporidium a été trouvé dans 7 % (26/370) des échantillons, impliquant cinq espèces de rongeurs : Apodemus agrarius (36), Niviventer niviventer (75), Rattus losea (18), R. norvegicus (155) et R. tanezumi (86). Leurs taux respectifs de positivité pour Cryptosporidium étaient de 8,3 %, 5,3 %, 11,1 %, 7,1 % et 7,0 %. L'analyse des séquences a confirmé la présence de trois espèces de Cryptosporidium : C. parvum (4), C. viatorum (1) et C. muris (1), et de deux génotypes : Cryptosporidium génotype IV de rat (16) et C. mortiferum-like (4). De plus, deux sous-types de C. parvum (IIdA15G1 et IIpA19) et un sous-type de C. viatorum (XVdA3) ont été détectés. Ces résultats démontrent que diverses espèces de rongeurs sauvages du Zhejiang sont simultanément infectées par des espèces/génotypes de Cryptosporidium zoonotiques et adaptés aux rongeurs, ce qui indique que ces rongeurs peuvent jouer un rôle dans le maintien et la dispersion de ce parasite dans l'environnement et d'autres hôtes, y compris les humains.


Assuntos
Animais Selvagens , Criptosporidiose , Cryptosporidium , Fezes , Doenças dos Roedores , Roedores , Animais , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Criptosporidiose/transmissão , China/epidemiologia , Cryptosporidium/genética , Cryptosporidium/isolamento & purificação , Cryptosporidium/classificação , Fezes/parasitologia , Doenças dos Roedores/parasitologia , Doenças dos Roedores/epidemiologia , Doenças dos Roedores/transmissão , Animais Selvagens/parasitologia , Ratos/parasitologia , Roedores/parasitologia , Prevalência , Saúde Pública , Reservatórios de Doenças/parasitologia , Reservatórios de Doenças/veterinária , Filogenia , Humanos , DNA de Protozoário/isolamento & purificação , Murinae/parasitologia , Reação em Cadeia da Polimerase , Zoonoses/parasitologia , Zoonoses/transmissão , Zoonoses/epidemiologia , Genótipo
2.
Mater Horiz ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007354

RESUMO

Metal ion interference therapy (MIIT) has emerged as a promising approach in the field of nanomedicine for combatting cancer. With advancements in nanotechnology and tumor targeting-related strategies, sophisticated nanoplatforms have emerged to facilitate efficient MIIT in xenografted mouse models. However, the diverse range of metal ions and the intricacies of cellular metabolism have presented challenges in fully understanding this therapeutic approach, thereby impeding its progress. Thus, to address these issues, various amplification strategies focusing on ionic homeostasis and cancer cell metabolism have been devised to enhance MIIT efficacy. In this review, the remarkable progress in Fe, Cu, Ca, and Zn ion interference nanomedicines and understanding their intrinsic mechanism is summarized with particular emphasis on the types of amplification strategies employed to strengthen MIIT. The aim is to inspire an in-depth understanding of MIIT and provide guidance and ideas for the construction of more powerful nanoplatforms. Finally, the related challenges and prospects of this emerging treatment are discussed to pave the way for the next generation of cancer treatments and achieve the desired efficacy in patients.

3.
Heliyon ; 10(12): e33334, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39021918

RESUMO

Shrews play a crucial role as repositories for diverse pathogens linked to zoonotic infectious diseases. However, the genetic information regarding Cryptosporidium in Chinese shrews remains unexplored. The objectives of this study were twofold: to determine the occurrence rate of Cryptosporidium spp. in wild shrews residing in the southern part of Zhejiang Province, China, and to investigate their genetic characteristics. A total of 282 wild shrews were captured between April and October of 2023. The detection of Cryptosporidium in fecal samples, collected from each animal's rectum, was performed using PCR and sequencing of the partial small subunit of ribosomal RNA (SSU rRNA) gene. The 60-kDa glycoprotein (gp60) gene was utilized to further subtype the positive samples of C. viatorum and C. parvum. All animals were identified as Suncus murinus, and a positive result for Cryptosporidium was obtained in 14.2 % (40/282) of the samples. The following species and genotypes were identified: C. ratti (n = 19), C. parvum (n = 2), C. viatorum (n = 1), Cryptosporidium rat genotype IV (n = 13), and Cryptosporidium skunk genotype (n = 5). Furthermore, the subtypes IIdA15G1 and XVdA3 were detected within C. parvum and C. viatorum, respectively. Molecular evidence indicates that S. murinus is concurrently infected with rodent-adapted and zoonotic species/genotypes, actively contributing to the dissemination of cryptosporidiosis.

4.
Int J Biol Macromol ; 276(Pt 1): 133459, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945333

RESUMO

A new polysaccharide, named SP40015A01, was obtained from Saposhnikoviae Radix by water extraction, isolation and purification. SP40015A01 (9.7 × 105 Da) is composed of Rhamnose (Rha), Galacturonic acid (GalA), Galactose (Gal), and Arabinose (Ara) with the proportion of 1.6:85.6:5.8:7.6. The backbone of SP40015A01 is composed of 3-α-GalAp, 2-α-GalAp, 2,3-ß-GalAp and 2,3-ß-Galp, and branched at C3 of 2,3-ß-GalAp, C3 of 2,3-ß-Galp. Zebrafish experiments were used to explore the immunomodulatory activity of SP40015A01. Results showed that SP40015A01 could significantly improve the neutrophils density of immunocompromised zebrafish and reduce the content of nitric oxide (NO) and interleukin-1ß (IL-1ß). This study demonstrated that SP40015A01 has significant immunomodulatory activity, which can improve the neutrophils density and reduce inflammatory factor content, suggesting SP40015A01 may be a potential immunomodulator in Saposhnikoviae Radix (SR) for treatment of hypoimmunity related disease. This study supplemented the research on the polysaccharide components in traditional Chinese medicine and provided a scientific explanation for the development and clinical applications of SR.

5.
Diabetologia ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819467

RESUMO

AIMS/HYPOTHESIS: Mutations in Isl1, encoding the insulin enhancer-binding protein islet-1 (ISL1), may contribute to attenuated insulin secretion in type 2 diabetes mellitus. We made an Isl1E283D mouse model to investigate the disease-causing mechanism of diabetes mellitus. METHODS: The ISL1E283D mutation (c. 849A>T) was identified by whole exome sequencing on an early-onset type 2 diabetes family and then the Isl1E283D knockin (KI) mouse model was created and an IPGTT and IPITT were conducted. Glucose-stimulated insulin secretion (GSIS), expression of Ins2 and other ISL1 target genes and interacting proteins were evaluated in isolated pancreas islets. Transcriptional activity of Isl1E283D was evaluated by cell-based luciferase reporter assay and electrophoretic mobility shift assay, and the expression levels of Ins2 driven by Isl1 wild-type (Isl1WT) and Isl1E283D mutation in rat INS-1 cells were determined by RT-PCR and western blotting. RESULTS: Impaired GSIS and elevated glucose level were observed in Isl1E283D KI mice while expression of Ins2 and other ISL1 target genes Mafa, Pdx1, Slc2a2 and the interacting protein NeuroD1 were downregulated in isolated islets. Transcriptional activity of the Isl1E283D mutation for Ins2 was reduced by 59.3%, and resulted in a marked downregulation of Ins2 expression when it was overexpressed in INS-1 cells, while overexpression of Isl1WT led to an upregulation of Ins2 expression. CONCLUSIONS/INTERPRETATION: Isl1E283D mutation reduces insulin expression and secretion by regulating insulin and other target genes, as well as its interacting proteins such as NeuroD1, leading to the development of glucose intolerance in the KI mice, which recapitulated the human diabetic phenotype. This study identified and highlighted the Isl1E283D mutation as a novel causative factor for type 2 diabetes, and suggested that targeting transcription factor ISL1 could offer an innovative avenue for the precise treatment of human type 2 diabetes.

6.
PLoS Pathog ; 20(5): e1012214, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38722857

RESUMO

Epithelial cells function as the primary line of defense against invading pathogens. However, bacterial pathogens possess the ability to compromise this barrier and facilitate the transmigration of bacteria. Nonetheless, the specific molecular mechanism employed by Mycobacterium tuberculosis (M.tb) in this process is not fully understood. Here, we investigated the role of Rv2569c in M.tb translocation by assessing its ability to cleave E-cadherin, a crucial component of cell-cell adhesion junctions that are disrupted during bacterial invasion. By utilizing recombinant Rv2569c expressed in Escherichia coli and subsequently purified through affinity chromatography, we demonstrated that Rv2569c exhibited cell wall-associated serine protease activity. Furthermore, Rv2569c was capable of degrading a range of protein substrates, including casein, fibrinogen, fibronectin, and E-cadherin. We also determined that the optimal conditions for the protease activity of Rv2569c occurred at a temperature of 37°C and a pH of 9.0, in the presence of MgCl2. To investigate the function of Rv2569c in M.tb, a deletion mutant of Rv2569c and its complemented strains were generated and used to infect A549 cells and mice. The results of the A549-cell infection experiments revealed that Rv2569c had the ability to cleave E-cadherin and facilitate the transmigration of M.tb through polarized A549 epithelial cell layers. Furthermore, in vivo infection assays demonstrated that Rv2569c could disrupt E-cadherin, enhance the colonization of M.tb, and induce pathological damage in the lungs of C57BL/6 mice. Collectively, these results strongly suggest that M.tb employs the serine protease Rv2569c to disrupt epithelial defenses and facilitate its systemic dissemination by crossing the epithelial barrier.


Assuntos
Proteínas de Bactérias , Caderinas , Células Epiteliais , Mycobacterium tuberculosis , Serina Proteases , Caderinas/metabolismo , Mycobacterium tuberculosis/patogenicidade , Mycobacterium tuberculosis/metabolismo , Animais , Humanos , Camundongos , Serina Proteases/metabolismo , Serina Proteases/genética , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Células A549 , Tuberculose/microbiologia , Tuberculose/metabolismo , Feminino
7.
Plant Mol Biol ; 114(3): 50, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656412

RESUMO

Amylose biosynthesis is strictly associated with granule-bound starch synthase I (GBSSI) encoded by the Waxy gene. Mutagenesis of single bases in the Waxy gene, which induced by CRISPR/Cas9 genome editing, caused absence of intact GBSSI protein in grain of the edited line. The amylose and amylopectin contents of waxy mutants were zero and 31.73%, while those in the wild type were 33.50% and 39.00%, respectively. The absence of GBSSI protein led to increase in soluble sugar content to 37.30% compared with only 10.0% in the wild type. Sucrose and ß-glucan, were 39.16% and 35.40% higher in waxy mutants than in the wild type, respectively. Transcriptome analysis identified differences between the wild type and waxy mutants that could partly explain the reduction in amylose and amylopectin contents and the increase in soluble sugar, sucrose and ß-glucan contents. This waxy flour, which showed lower final viscosity and setback, and higher breakdown, could provide more option for food processing.


Assuntos
Amilose , Edição de Genes , Hordeum , Proteínas de Plantas , Sintase do Amido , Amilose/metabolismo , Hordeum/genética , Hordeum/metabolismo , Edição de Genes/métodos , Sintase do Amido/genética , Sintase do Amido/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sistemas CRISPR-Cas , Amilopectina/metabolismo , Sacarose/metabolismo , Açúcares/metabolismo , Regulação da Expressão Gênica de Plantas , Mutação , beta-Glucanas/metabolismo , Plantas Geneticamente Modificadas , Solubilidade
8.
BMC Microbiol ; 24(1): 113, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575881

RESUMO

BACKGROUND: Cryptosporidium is a highly pathogenic parasite responsible for diarrhea in children worldwide. Here, the epidemiological status and genetic characteristics of Cryptosporidium in children with or without diarrhea were investigated with tracking of potential sources in Wenzhou City, China. METHODS: A total of 1032 children were recruited, 684 of whom had diarrhea and 348 without, from Yuying Children's Hospital in Wenzhou, China. Samples of stool were collected from each participant, followed by extraction of DNA, genotyping, and molecular identification of Cryptosporidium species and subtypes. RESULTS: Twenty-two of the 1032 (2.1%) children were infected with Cryptosporidium spp. with 2.5% (17/684) and 1.4% (5/348) in diarrhoeic and asymptomatic children, respectively. Four Cryptosporidium species were identified, including C. parvum (68.2%; 15/22), C. felis (13.6%; 3/22), C. viatorum (9.1%; 2/22), and C. baileyi (9.1%; 2/22). Two C. parvum subtypes named IIdA19G1 (n = 14) and IInA10 (n = 1), and one each of C. felis (XIXa) and C. viatorum (XVaA3g) subtype was found as well. CONCLUSIONS: This is the first research that identified Cryptosporidium in children of Wenzhou, China, using PCR. Identification of zoonotic C. parvum, C. felis, C. viatorum, and their subtypes indicate potential cross-species transmission of Cryptosporidium between children and animals. Additionally, the presence of C. baileyi in children suggests that this species has a wider host range than previously believed and that it possesses the capacity to infect humans.


Assuntos
Criptosporidiose , Cryptosporidium , Criança , Animais , Humanos , Cryptosporidium/genética , Criptosporidiose/epidemiologia , Criptosporidiose/parasitologia , Diarreia/epidemiologia , China/epidemiologia , Fezes/parasitologia , Genótipo , Probabilidade
9.
ACS Nano ; 18(17): 11449-11461, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644575

RESUMO

Bimetallic alloy nanoparticles have garnered substantial attention for diverse catalytic applications owing to their abundant active sites and tunable electronic structures, whereas the synthesis of ultrafine alloy nanoparticles with atomic-level homogeneity for bulk-state immiscible couples remains a formidable challenge. Herein, we present the synthesis of RuxCo1-x solid-solution alloy nanoparticles (ca. 2 nm) across the entire composition range, for highly efficient, durable, and selective CO2 hydrogenation to CH4 under mild conditions. Notably, Ru0.88Co0.12/TiO2 and Ru0.74Co0.26/TiO2 catalysts, with 12 and 26 atom % of Ru being substituted by Co, exhibit enhanced catalytic activity compared with the monometallic Ru/TiO2 counterparts both in dark and under light irradiation. The comprehensive experimental investigations and density functional theory calculations unveil that the electronic state of Ru is subtly modulated owing to the intimate interaction between Ru and Co in the alloy nanoparticles, and this effect results in the decline in the CO2 conversion energy barrier, thus ultimately culminating in an elevated catalytic performance relative to monometallic Ru and Co catalysts. In the photopromoted thermocatalytic process, the photoinduced charge carriers and localized photothermal effect play a pivotal role in facilitating the chemical reaction process, which accounts for the further boosted CO2 methanation performance.

10.
Zhongguo Zhong Yao Za Zhi ; 49(2): 498-508, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403325

RESUMO

To fully understand whether Saposhnikoviae Radix polysaccharides(SP) can be metabolized in gastric fluid and the meta-bolic behavior, this study systematically analyzed the metabolites in simulated gastric fluid of SP by high-performance liquid chromatography-ion trap time-of-flight mass spectrometry(HPLC-IT-TOF-MS) technology in combination with zebrafish immune activity evaluation. Based on the obtained accurate relative molecular mass, chromatographic retention behavior, MS fragmentation patterns, refe-rence standards, and relevant literature reports, 19 metabolites were analyzed and identified. Among them, five monosaccharides and 14 oligosaccharides were generated as metabolites. Several reducing sugars, including mannose, glucose, rhamnose, and xylose, were accurately identified in the gastric fluid metabolites. Zebrafish pharmacological evaluation results indicated that SP maintained good immune activity after gastric fluid metabolism, with the most significant increase in immune cell density observed at W3(simulated gastric fluid metabolism for 2 hours). Among the gastric fluid metabolites, M1 and M3(Hex-Hex-Man) may be most closely related to pharmacological activity and could be further studied as potential active fragments.


Assuntos
Medicamentos de Ervas Chinesas , Peixe-Zebra , Humanos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Raízes de Plantas/química , Polissacarídeos/análise , Medicamentos de Ervas Chinesas/química
11.
ACS Nano ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332473

RESUMO

Sono-immunotherapy faces challenges from poor immunogenicity and low response rate due to complex biological barriers. Herein, we prepared MCTH nanocomposites (NCs) consisting of disulfide bonds (S-S) doped mesoporous organosilica (MONs), Cu-modified protoporphyrin (CuPpIX), mitochondria-targeting triphenylphosphine (TPP), and CD44-targeting hyaluronic acid (HA). MCTH NCs efficiently accumulate at the tumor site due to the overexpressed CD44 receptors on the membrane of the cancer cells. Under the function of HAase and glutathione (GSH), MCTH degrades and exposes TPP to deliver CuPpIX to the mitochondrial site and induce a reactive oxygen species (ROS) burst in situ under ultrasound irradiations, thereby causing severe mitochondria dysfunction. This cascade-targeting ability of MCTH NCs not only reinforces oxidative stress in cancer cells but also amplifies immunogenic cell death (ICD) to stimulate the body's immune response and alleviate the tumor immunosuppressive microenvironment. These NCs significantly enhance the infiltration of immune cells into the tumor, particularly CD8+ T cells, for a powerful antitumor sono-immunotherapy. The proposed cascade-targeting strategy holds promise for strengthening sono-immunotherapy for prostate cancer treatment and overcoming the limitations of traditional immunotherapy.

12.
Adv Sci (Weinh) ; 11(16): e2308316, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38380506

RESUMO

Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.


Assuntos
Neoplasias da Mama , Ouro , Hipertermia Induzida , Receptor ErbB-2 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , Humanos , Camundongos , Animais , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Hipertermia Induzida/métodos , Ouro/química , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Prata/química , Linhagem Celular Tumoral , Modelos Animais de Doenças , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Proliferação de Células/efeitos dos fármacos
13.
J Clin Neurol ; 20(1): 37-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38179630

RESUMO

BACKGROUND AND PURPOSE: The eye-movement examination can be applied as a noninvasive method to identify multiple-system atrophy (MSA). Few studies have investigated eye movements during the early stage of MSA with predominant parkinsonism (MSA-P). We aimed to determine the characteristic oculomotor changes in the early stage of MSA-P. METHODS: We retrospectively selected 17 patients with MSA-P and 40 with Parkinson's disease (PD) with disease durations of less than 2 years, and 40 age-matched healthy controls (HCs). Oculomotor performance in the horizontal direction was measured in detail using videonystagmography. RESULTS: We found that the proportions of patients with MSA-P and PD exhibiting abnormal eye movements were 82.4% and 77.5%, respectively, which were significantly higher than that in the HCs (47.5%, p<0.05). Compared with HCs, patients with MSA-P presented significantly higher abnormal proportions of fixation and gaze-holding (17.6% vs. 0%), without-fixation (47.1% vs. 0%), prolonged latency in reflexive saccades (29.4% vs. 5.0%), memory-guided saccades (93.3% vs. 10.0%), and catch-up saccades in smooth-pursuit movement (SPM, 41.2% vs. 0) (all p<0.05). Compared with those with PD, patients with MSA-P presented a significantly higher proportion of catch-up saccades in SPM (41.2% vs. 2.5%, p<0.001). CONCLUSIONS: MSA-P presented the characteristic of catch-up saccades in SPM in the early stage, which may provide some value in differentiating MSA-P from PD.

14.
Phys Chem Chem Phys ; 26(5): 4208-4217, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38230688

RESUMO

Through extensive density functional theory (DFT) calculations, our investigation delves into the stability, electrical characteristics, and magnetic behavior of monolayers (MLs) of MSi2N4. Computational analyses indicate intrinsic antiferromagnetic (AFM) orders within the MSi2N4 MLs, as a result of direct exchange interactions among transition metal (M) atoms. We further find that CrSi2N4 and CoSi2N4 MLs with primitive cells (pcells) exhibit half-metallic properties, with respective spin-ß electron gaps of 3.661 and 2.021 eV. In contrast, MnSi2N4 and FeSi2N4 MLs with pcells act as semiconductors, having energy gaps of 0.427 and 0.282 eV, respectively. When the SOC is considered, the CrSi2N4, MnSi2N4 and FeSi2N4 MLs are metals, while the CoSi2N4 ML is a semiconductor. Our findings imply the dynamics and thermodynamic stability of MSi2N4 MLs. We have also explored the influence of carrier doping on the electromagnetic attributes of MSi2N4 MLs. Interestingly, charge doping could transform CrSi2N4, MnSi2N4, and CoSi2N4 MLs from their original AFM state into a ferromagnetic (FM) order. Moreover, carrier doping transformed CrSi2N4 and CoSi2N4 MLs from spin-polarized metals to half-metals (HMs). It is of particular note that doping of CrSi2N4 MLs with +0.9 e per pcell or more holes caused a switch in the easy axis (EA) to the [001] axis. The demonstrated intrinsic AFM order, excellent thermodynamic and kinetic stability, adjustable magnetism, and half-metallicity of the MSi2N4 family suggest its promising potential for applications in the realm of spintronics.

15.
Biochim Biophys Acta Mol Cell Res ; 1871(3): 119681, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280406

RESUMO

Bladder cancer (BC) is one of the most common cancers worldwide. Although the treatment and survival rate of BC are being improved, the risk factors and the underlying mechanisms causing BC are incompletely understood. Squalene monooxygenase (SQLE) has been associated with the occurrence and development of multiple cancers but whether it contributes to BC development is unclear. In this study, we performed bioinformatics analysis on paired BC and adjacent non-cancerous tissues and found that SQLE expression is significantly upregulated in BC samples. Knockdown of SQLE impairs viability, induces apoptosis, and inhibits the migration and invasion of BC cells. RNA-seq data reveals that SQLE deficiency leads to dysregulated expression of genes regulating proliferation, migration, and apoptosis. Mass spectrometry-directed interactome screening identifies proliferating cell nuclear antigen (PCNA) as an SQLE-interacting protein and overexpression of PCNA partially rescues the impaired viability, migration, and invasion of BC cells caused by SQLE knockdown. In addition, we performed xenograft assays and confirmed that SQLE deficiency inhibits BC growth in vivo. In conclusion, these data suggest that SQLE promotes BC development and SQLE inhibition may be therapeutically useful in BC treatment.


Assuntos
Esqualeno Mono-Oxigenase , Neoplasias da Bexiga Urinária , Humanos , Antígeno Nuclear de Célula em Proliferação/genética , Esqualeno Mono-Oxigenase/genética , Neoplasias da Bexiga Urinária/genética , Apoptose/genética , Biologia Computacional
16.
Neuron ; 112(3): 458-472.e6, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38056455

RESUMO

Maladaptation in balancing internal energy needs and external threat cues may result in eating disorders. However, brain mechanisms underlying such maladaptations remain elusive. Here, we identified that the basal forebrain (BF) sends glutamatergic projections to glutamatergic neurons in the ventral tegmental area (VTA) in mice. Glutamatergic neurons in both regions displayed correlated responses to various stressors. Notably, in vivo manipulation of BF terminals in the VTA revealed that the glutamatergic BF → VTA circuit reduces appetite, increases locomotion, and elicits avoidance. Consistently, activation of VTA glutamatergic neurons reduced body weight, blunted food motivation, and caused hyperactivity with behavioral signs of anxiety, all hallmarks of typical anorexia symptoms. Importantly, activation of BF glutamatergic terminals in the VTA reduced dopamine release in the nucleus accumbens. Collectively, our results point to overactivation of the glutamatergic BF → VTA circuit as a potential cause of anorexia-like phenotypes involving reduced dopamine release.


Assuntos
Prosencéfalo Basal , Área Tegmentar Ventral , Camundongos , Animais , Área Tegmentar Ventral/fisiologia , Dopamina/fisiologia , Anorexia , Fenótipo , Neurônios Dopaminérgicos/fisiologia
17.
Small ; 20(9): e2304147, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37875665

RESUMO

Room-temperature gallium-based liquid metals (RT-GaLMs) have garnered significant interest recently owing to their extraordinary combination of fluidity, conductivity, stretchability, self-healing performance, and biocompatibility. They are ideal materials for the manufacture of flexible electronics. By changing the composition and oxidation of RT-GaLMs, physicochemical characteristics of the liquid metal can be adjusted, especially the regulation of rheological, wetting, and adhesion properties. This review highlights the advancements in the liquid metals used in flexible electronics. Meanwhile related characteristics of RT-GaLMs and underlying principles governing their processing and applications for flexible electronics are elucidated. Finally, the diverse applications of RT-GaLMs in self-healing circuits, flexible sensors, energy harvesting devices, and epidermal electronics, are explored. Additionally, the challenges hindering the progress of RT-GaLMs are discussed, while proposing future research directions and potential applications in this emerging field. By presenting a concise and critical analysis, this paper contributes to the advancement of RT-GaLMs as an advanced material applicable for the new generation of flexible electronics.

18.
Small ; 20(16): e2309637, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38010990

RESUMO

Copper-nitrogen-doped carbon-based nanocatalysts (Cu-NCs), containing atomically dispersed Cu-NxC4- x sites, are efficient in boosting the Fenton-like reaction. However, the mechanisms of the Fenton-like reaction, including the pH effect on the products and the effect of the coordination environment on catalytic activity, remain controversial, restricting the development of Cu-NCs. Cu-NCs are experimentally synthesized with Cu-N4 sites and prove that the Fenton-like reaction generates mainly hydroxyl radicals (·OH) in the acidic but ·OH and superoxide radicals (·O2 -) in the neutral. The density functional theory (DFT) calculations reveal that the catalytic activity of Cu-NCs in the Fenton-like reaction is associated with the adsorption strength of ·OH at the Cu site. Further investigation of the effect of the coordination environment of Cu-NCs indicates that the Cu-N2C2 site, which can enhance the ·OH adsorption strength, is an ideal catalyst site for the Fenton-like reaction. These results open the way to facilitating the catalytic activity of Cu-NCs in the Fenton-like reaction.

19.
J Sci Food Agric ; 104(1): 468-478, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37649238

RESUMO

BACKGROUND: The environmental pollution and ecological risks caused by the widespread use of antibiotics have attracted attention in recent years. Biochar materials have a rich pore diameter and can effectively adsorb pollutants from wastewater. However, biochar will experience high temperatures, freezing and thawing in nature, affecting its physicochemical properties and adsorption capacity. Three types of aged biochar were prepared by artificial simulated aging using soybean straw as raw material. The aged biochar's elemental composition and functional group species were investigated by characterization analysis, and their adsorption kinetics and adsorption isotherms were studied. RESULTS: The specific surface area and pore size of the three aged biochars were lower than those of fresh biochars. The increased number of oxygen-containing functional groups of the aged biochars formed a water cluster interaction with norfloxacin (NOR), which was unfavorable to the adsorption of NOR. The adsorption mechanism of biochar on NOR comprises pore filling, electrostatic interaction, ion exchange and complexation. CONCLUSION: The adsorption of NOR on biochar before and after aging was spontaneous and was described by quasi-second kinetics and the Langmuir equation. Different aging methods influenced the physicochemical properties and adsorption performance of biochar, and the adsorption capacity of biochar was significantly reduced after aging. Therefore, the influence of climatic factors needs to be considered when using biochar to remove target pollutants. © 2023 Society of Chemical Industry.


Assuntos
Poluentes Ambientais , Poluentes Químicos da Água , Adsorção , Águas Residuárias , Glycine max , Antibacterianos , Carvão Vegetal/química , Cinética , Poluentes Químicos da Água/química
20.
Environ Sci Pollut Res Int ; 31(5): 6977-6991, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38157173

RESUMO

Currently, waste management classification is a critical topic that concerns not only environmental protection, but also the advancement of a circular economy. To address this issue within the context of a circular economy, this study develops an uncooperative triumvirate paradigm consisting of "central regulation, local promotion, and universal participation." The model analyzes the strategy choices of both the central and local governments while using an evolutionary game method to encourage residents to promote waste separation. Using numerical simulations, this study examines the variables that impact the strategy choices of the three parties over time. The results show that (1) the desire of the central government, local governments, and citizens to engage has varying effects on each of these entities; the conduct of local government is significantly influenced by the preparedness of the central government, but residents' behavior is comparatively less influenced by the central government's intention; in comparison, it is mainly affected by psychological expectations of income and expenditure; (2) the impact of the local government and residents on each other is characterized by an unbalanced relationship, with the local government being more sensitive to residents' willingness to participate and changes in policy support being more sensitive; and (3) residents show more sensitivity to incentive funds, compensation, penalties, and benefit distribution coefficients. To promote waste separation in China, it is crucial to establish a reasonable expectation of ecological civilization, establish an efficient mechanism for environmental protection supervision, refine local waste separation programs, increase local governments' responsibility for promoting them, ensure legal methods for universal participation, and improve the regulatory mechanism for universal participation to protect the environment. In addition, it is essential to improve the education system for waste separation and continue research related to waste separation.


Assuntos
Conservação dos Recursos Naturais , Gerenciamento de Resíduos , Gerenciamento de Resíduos/métodos , Governo Local , China , Gastos em Saúde , Governo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...