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1.
Cell ; 162(3): 564-79, 2015 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-26232226

RESUMO

During differentiation, human embryonic stem cells (hESCs) shut down the regulatory network conferring pluripotency in a process we designated pluripotent state dissolution (PSD). In a high-throughput RNAi screen using an inclusive set of differentiation conditions, we identify centrally important and context-dependent processes regulating PSD in hESCs, including histone acetylation, chromatin remodeling, RNA splicing, and signaling pathways. Strikingly, we detected a strong and specific enrichment of cell-cycle genes involved in DNA replication and G2 phase progression. Genetic and chemical perturbation studies demonstrate that the S and G2 phases attenuate PSD because they possess an intrinsic propensity toward the pluripotent state that is independent of G1 phase. Our data therefore functionally establish that pluripotency control is hardwired to the cell-cycle machinery, where S and G2 phase-specific pathways deterministically restrict PSD, whereas the absence of such pathways in G1 phase potentially permits the initiation of differentiation.


Assuntos
Ciclo Celular , Células-Tronco Embrionárias/citologia , Redes Reguladoras de Genes , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Diferenciação Celular , Ciclina B2/metabolismo , Células-Tronco Embrionárias/metabolismo , Epigênese Genética , Humanos , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/metabolismo , Proteína Supressora de Tumor p53/metabolismo
2.
Nano Lett ; 24(14): 4158-4164, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38557108

RESUMO

As a quasi-layered ferrimagnetic material, Mn3Si2Te6 nanoflakes exhibit magnetoresistance behavior that is fundamentally different from their bulk crystal counterparts. They offer three key properties crucial for spintronics. First, at least 106 times faster response compared to that exhibited by bulk crystals has been observed in current-controlled resistance and magnetoresistance. Second, ultralow current density is required for resistance modulation (∼5 A/cm2). Third, electrically gate-tunable magnetoresistance has been realized. Theoretical calculations reveal that the unique magnetoresistance behavior in the Mn3Si2Te6 nanoflakes arises from a magnetic field induced band gap shift across the Fermi level. The rapid current induced resistance variation is attributed to spin-orbit torque, an intrinsically ultrafast process (∼nanoseconds). This study suggests promising avenues for spintronic applications. In addition, it highlights Mn3Si2Te6 nanoflakes as a suitable platform for investigating the intriguing physics underlying chiral orbital moments, magnetic field induced band variation, and spin torque.

3.
Muscle Nerve ; 69(5): 597-603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38488306

RESUMO

INTRODUCTION/AIMS: Muscle strength, functional status, and muscle enzymes are conventionally used to evaluate disease status in idiopathic inflammatory myopathies (IIM). This study aims to investigate the role of quantitative muscle ultrasound in evaluating disease status in IIM patients. METHODS: Patients with IIM, excluding inclusion body myositis, were recruited along with age- and sex-matched healthy controls (HC). All participants underwent muscle ultrasound and clinical assessments. Six limb muscles were unilaterally scanned using a standardized protocol, measuring muscle thickness (MT) and echo intensity (EI). Results were compared with HC, and correlations were made with outcome measures. RESULTS: Twenty IIM patients and 24 HC were recruited. The subtypes of IIM were dermatomyositis (6), necrotizing myositis (6), polymyositis (3), antisynthetase syndrome (3), and nonspecific myositis (2). Mean disease duration was 8.7 ± 6.9 years. There were no significant differences in demographics and anthropometrics between patients and controls. MT of rectus femoris in IIM patients was significantly lower than HC. Muscle EI of biceps brachii and vastus medialis in IIM patients were higher than HC. There were moderate correlations between MT of rectus femoris and modified Rankin Scale, Physician Global Activity Assessment, and Health Assessment Questionnaire, as well as between EI of biceps brachii and Manual Muscle Testing-8. DISCUSSION: Muscle ultrasound can detect proximal muscle atrophy and hyperechogenicity in patients with IIM. The findings correlate with clinical outcome measures, making it a potential tool for evaluating disease activity of patients with IIM in the late phase of the disease.


Assuntos
Miosite de Corpos de Inclusão , Miosite , Polimiosite , Humanos , Miosite/complicações , Miosite/diagnóstico por imagem , Músculo Esquelético , Polimiosite/patologia , Miosite de Corpos de Inclusão/patologia , Atrofia Muscular/patologia
4.
PLoS Comput Biol ; 19(7): e1011321, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37486948

RESUMO

The phase separation model for transcription suggests that transcription factors (TFs), coactivators, and RNA polymerases form biomolecular condensates around active gene loci and regulate transcription. However, the structural details of condensates remain elusive. In this study, for Nanog, a master TF in mammalian embryonic stem cells known to form protein condensates in vitro, we examined protein structures in the condensates using residue-level coarse-grained molecular simulations. Human Nanog formed micelle-like clusters in the condensate. In the micelle-like cluster, the C-terminal disordered domains, including the tryptophan repeat (WR) regions, interacted with each other near the cluster center primarily via hydrophobic interaction. In contrast, hydrophilic disordered N-terminal and DNA-binding domains were exposed on the surface of the clusters. Electrostatic attractions of these surface residues were responsible for bridging multiple micelle-like structures in the condensate. The micelle-like structure and condensate were dynamic and liquid-like. Mutation of tryptophan residues in the WR region which was implicated to be important for a Nanog function resulted in dissolution of the Nanog condensate. Finally, to examine the impact of Nanog cluster to DNA, we added DNA fragments to the Nanog condensate. Nanog DNA-binding domains exposed to the surface of the micelle-like cluster could recruit more than one DNA fragments, making DNA-DNA distance shorter.


Assuntos
Micelas , Triptofano , Animais , Humanos , DNA/genética , Células-Tronco Embrionárias/metabolismo , Fatores de Transcrição/genética , Triptofano/metabolismo
5.
Arch Insect Biochem Physiol ; 115(1): e22083, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288495

RESUMO

Due to the high prevalence of diabetes mellitus, researchers have conducted numerous experimental animal studies. However, the mammalian diabetes model is cumbersome and expensive to operate, while the cheap and simple common silkworm diabetes model has the disadvantage of a short cycle time. Since the growth of silkworms is greatly affected by environmental factors, we extended the five-age cycle of silkworms by lowering the ambient temperature to establish a novel low-temperature silkworm diabetes model. Our goal was to determine whether the low-temperature feeding of a high-sugar diet to silkworms could serve as an effective animal model for diabetes. Also, we aimed to resolve certain issues concerning the normal temperature silkworm diabetes model, such as the short time frame for experiments and erratic fluctuations in blood sugar levels. Silkworms weighing between 0.9 and 1.0 g at the beginning of the fifth instar were selected, and we created diabetic silkworms by feeding mulberry leaves containing 4% glucose daily in a 16-20°C environment. When the silkworms were kept at a cooler temperature, the fifth instar stage lasted for an additional 9-11 days. In the model group, 83.3% of the silkworms had blood glucose levels greater than 7.8 mmol/L, while the total prevalence of diabetic silkworms was 89.8%. Moreover, JNK phosphorylation expression rose in the model group, while PI3K expression fell. Additionally, the JNK and PI3K signaling pathway expressions matched diabetic signals. Therefore, using silkworms to create a diabetes model in a cool environment is a straightforward and cost-effective approach to studying diabetes in animals.


Assuntos
Bombyx , Diabetes Mellitus , Morus , Animais , Bombyx/metabolismo , Temperatura , Fosfatidilinositol 3-Quinases/metabolismo , Mamíferos
6.
BMC Vet Res ; 20(1): 161, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678268

RESUMO

BACKGROUND: SARS-CoV-2 is believed to have originated from a spillover event, where the virus jumped from bats to humans, leading to an epidemic that quickly escalated into a pandemic by early 2020. Despite the implementation of various public health measures, such as lockdowns and widespread vaccination efforts, the virus continues to spread. This is primarily attributed to the rapid emergence of immune escape variants and the inadequacy of protection against reinfection. Spillback events were reported early in animals with frequent contact with humans, especially companion, captive, and farmed animals. Unfortunately, surveillance of spillback events is generally lacking in Malaysia. Therefore, this study aims to address this gap by investigating the presence of SARS-CoV-2 neutralising antibodies in wild rodents in Sarawak, Malaysia. RESULTS: We analysed 208 archived plasma from rodents collected between from 2018 to 2022 to detect neutralising antibodies against SARS-CoV-2 using a surrogate virus neutralisation test, and discovered two seropositive rodents (Sundamys muelleri and Rattus rattus), which were sampled in 2021 and 2022, respectively. CONCLUSION: Our findings suggest that Sundamys muelleri and Rattus rattus may be susceptible to natural SARS-CoV-2 infections. However, there is currently no evidence supporting sustainable rodent-to-rodent transmission.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Animais , COVID-19/veterinária , COVID-19/epidemiologia , COVID-19/imunologia , Malásia/epidemiologia , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Ratos/virologia , Anticorpos Neutralizantes/sangue , Estudos Soroepidemiológicos , Bornéu/epidemiologia , Roedores/virologia
7.
Mol Cell ; 62(4): 603-17, 2016 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-27184079

RESUMO

Identifying pairwise RNA-RNA interactions is key to understanding how RNAs fold and interact with other RNAs inside the cell. We present a high-throughput approach, sequencing of psoralen crosslinked, ligated, and selected hybrids (SPLASH), that maps pairwise RNA interactions in vivo with high sensitivity and specificity, genome-wide. Applying SPLASH to human and yeast transcriptomes revealed the diversity and dynamics of thousands of long-range intra- and intermolecular RNA-RNA interactions. Our analysis highlighted key structural features of RNA classes, including the modular organization of mRNAs, its impact on translation and decay, and the enrichment of long-range interactions in noncoding RNAs. Additionally, intermolecular mRNA interactions were organized into network clusters and were remodeled during cellular differentiation. We also identified hundreds of known and new snoRNA-rRNA binding sites, expanding our knowledge of rRNA biogenesis. These results highlight the underexplored complexity of RNA interactomes and pave the way to better understanding how RNA organization impacts biology.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA Fúngico/genética , RNA Mensageiro/genética , RNA Neoplásico/genética , RNA Ribossômico/genética , RNA Nucleolar Pequeno/genética , Saccharomyces cerevisiae/genética , Transcriptoma , Sítios de Ligação , Diferenciação Celular , Biologia Computacional , Reagentes de Ligações Cruzadas/química , Bases de Dados Genéticas , Células-Tronco Embrionárias/metabolismo , Ficusina/química , Regulação Fúngica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Células HeLa , Humanos , Conformação de Ácido Nucleico , Estabilidade de RNA , RNA Fúngico/química , RNA Fúngico/metabolismo , RNA Mensageiro/química , RNA Mensageiro/metabolismo , RNA Neoplásico/química , RNA Neoplásico/metabolismo , RNA Ribossômico/química , RNA Ribossômico/metabolismo , RNA Nucleolar Pequeno/química , RNA Nucleolar Pequeno/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Saccharomyces cerevisiae/metabolismo
8.
Neurol Sci ; 45(7): 3449-3459, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38270729

RESUMO

INTRODUCTION: There is an increasing need for a reproducible and sensitive outcome measure in patients with hereditary transthyretin amyloidosis (ATTRv) with polyneuropathy (PN) due to the emergence of disease modifying therapies. In the current study, we aimed to investigate the role of quantitative muscle ultrasound (QMUS) as a disease biomarker in ATTRv-PN. METHODS: Twenty genetically confirmed ATTRv amyloidosis patients (nine symptomatic, 11 pre-symptomatic) were enrolled prospectively between January to March 2023. Muscle ultrasound was performed on six muscles at standardized locations. QMUS parameters included muscle thickness (MT) and muscle echo intensity (EI). Twenty-five age- and sex-matched healthy controls were recruited for comparison. Significant QMUS parameters were correlated with clinical outcome measures. RESULTS: Muscle volume of first dorsal interosseus (FDI) muscle [measured as cross-sectional area (CSA)] was significantly lower in symptomatic patients compared to healthy controls and pre-symptomatic carriers (98.3 ± 58.0 vs. 184.4 ± 42.5 vs. 198.3 ± 56.8, p < 0.001). EI of biceps and FDI for symptomatic ATTRv-PN patients were significantly higher compared to the other two groups (biceps: 76.4 ± 10.8 vs. 63.2 ± 11.5 vs. 59.2 ± 9.0, p = 0.002; FDI: 48.2 ± 7.5 vs. 38.8 ± 7.5 vs. 33.0 ± 5.3, p < 0.001). CSA of FDI and EI of biceps and FDI correlated with previous validated outcome measures [polyneuropathy disability score, neuropathy impairment score, Karnofsky performance scale, Rasch-built overall disability scale, European quality of life (QoL)-5 dimensions and Norfolk QoL questionnaire-diabetic neuropathy]. CONCLUSION: QMUS revealed significant difference between ATTRv amyloidosis patients and healthy controls and showed strong correlation with clinical outcome measures. QMUS serves as a sensitive and reliable biomarker of disease severity in ATTRv-PN.


Assuntos
Neuropatias Amiloides Familiares , Músculo Esquelético , Polineuropatias , Ultrassonografia , Humanos , Neuropatias Amiloides Familiares/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Polineuropatias/diagnóstico por imagem , Idoso , Biomarcadores , Adulto
9.
Dysphagia ; 39(4): 541-551, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38117313

RESUMO

Stroke is the leading cause of death and disability among adults. The incidence of stroke per 100, 000 patient-years was 2875. As many as 37% to 78% of patients with acute strokes suffer dysphagia. Dysphagia can easily lead to inhalation pneumonia, dehydration, malnutrition, and other serious complications, affecting the quality of life of stroke patients and increasing their mortality. Effective prevention and treatment of post-stroke dysphagia are of great significance to improving the prognosis and quality of life of patients. Some studies have shown that Pharyngeal cavity electrical stimulation-assisted swallowing (PCES-assisted swallowing) has a positive effect on patients with post-stroke dysphagia. This study will evaluate the effects of PCES-assisted swallowing on post-stroke dysphagia, including swallowing function, withdrawal rate of nasal feeding tubes, duration of hospitalization, and so on. Randomized controlled trials (RCTs) of PCES-assisted swallowing in the treatment of post-stroke dysphagia were searched in eight databases, including Cochrane Library, Embase, PubMed, Web of Science, Chinese Biomedical Literature Database, VIP Information Resource System, CNKI, and Wanfang Medical Science. The retrieval time was from the database establishment to June 2022. Rayyan was used to screen the retrieved literature risk of bias for included studies and was calculated using ROB2.0. The RevMan 5.3 software was used for the meta-analysis with the standard mean difference (SMD) and 95% confidence interval (CI). The model type was a random effect model, The risk ratio (RR) was used as the effect size for the two categorical variables. The swallowing function scores, withdrawal rate of nasal feeding tubes, and Length of stay (LOS) of the intervention and control groups were extracted, and the results of the meta-analysis were presented using a forest plot. Six studies from 2010 to 2018 with a total of 341 people were included in the meta-analysis. All studies reported quantitative outcome measures for the severity of dysphagia, and some reported the withdrawal rate of nasal feeding tubes, LOS, and penetration-aspiration-scale (PAS). The overall swallowing function of the PCES group was better than that of the control group (SMD = - 0.20, 95%CI - 0.38 to - 0.03, P = 0.02). In terms of the severity of dysphagia, there was a statistically significant difference in the Dysphagia Severity Rating scale (DSRS) between the Pharyngeal cavity electrical stimulation (PCES) group and the control group (SMD = - 0.24, 95%CI - 0.48 to 0, P = 0.05). The PCES group nasal feeding withdrawal rate of nasal feeding tubes was higher than the control group (RR = 2.88, 95% CI 1.15 to 7.26, P = 0.02). There was no significant difference in the LOS between the PCES group and the control group (SMD = - 0.19, 95%CI - 0.44 to 0.07, P = 0.15). This systematic review and meta-analysis provide reasonably reliable evidence that PCES-assisted swallowing can improve nasogastric feeding swallowing function and the withdrawal rate of nasal feeding tubes in patients with post-stroke dysphagia. However, the evidence for reducing oral feeding, aspiration, and length of hospitalization stay is lacking, and further studies are needed.


Assuntos
Transtornos de Deglutição , Terapia por Estimulação Elétrica , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Transtornos de Deglutição/fisiopatologia , Acidente Vascular Cerebral/complicações , Terapia por Estimulação Elétrica/métodos , Deglutição/fisiologia , Idoso , Masculino , Reabilitação do Acidente Vascular Cerebral/métodos , Feminino , Faringe/fisiopatologia , Pessoa de Meia-Idade , Resultado do Tratamento
10.
J Asian Nat Prod Res ; : 1-9, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38853517

RESUMO

Investigation of the fruits of Rhododendron molle G. Don led to the isolation of three new grayanane-type diterpenoids, rhodomolleins LIV-LVI (1-3). The structures and absolute configurations of new compounds were fully elucidated by spectroscopic analysis and single-crystal X-ray diffraction, including HRESIMS, 1 D and 2 D NMR data. Compounds 1-3 were evaluated for analgesic activities utilizing an acetic acid-induced writhing test in mice. Compound 1 showed a significant antinociceptive effect with writhe inhibition rates of 72.9% and 100% at doses of 6 mg/kg and 20 mg/kg in mice, respectively. The binding mode of 1 to N-ethylmaleimide-sensitive factor (NSF, PDB: 6IP2) was explored by molecular docking, indicating the presence of hydrogen bond interactions which account for its analgesic activity.

11.
J Med Virol ; 95(8): e28987, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37501648

RESUMO

Rotavirus is the leading causative viral agent of pediatric acute gastroenteritis globally, infecting mostly children 5 years old and below. Data on rotavirus prevalence in Malaysia is scarce, despite the WHO's recommendation for continuous rotavirus surveillance, and has underestimated the need for national rotavirus vaccination. Characteristics of the current rotavirus strains in Malaysia have to be determined to understand the rotavirus epidemiology and vaccine compatibility. This study sought to determine the genetic relatedness of Sarawak rotavirus strains with global strains and to determine the antigenic coverage and epitope compatibility of Rotarix and RotaTeq vaccines with the Sarawak rotavirus strains via in silico analysis. A total of 89 stool samples were collected from pediatric patients (<5 years old) with acute gastroenteritis at private hospitals in Kuching, Sarawak. Rotavirus was detected using reverse transcription-polymerase chain reaction. Positive amplicons were analyzed using nucleotide sequencing before phylogenetic analyses and assessment of epitope compatibility. Genotyping revealed G1P[8] (1/13; 7.7%), G3P[8] (3/13; 23%), G9P[4] (1/13; 7.7%), and G9P[8] (3/13; 23%), G9P[X] (1/13; 7.7%), GXP[4] (1/13; 7.7%), and GXP[8] (3/13; 23%) in samples. All wild-type Sarawak rotavirus strains, with the exception of G1, showed variations in their phylogenetic and antigenic epitope characteristics.


Assuntos
Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Animais , Cavalos/genética , Suínos , Malásia/epidemiologia , Filogenia , Genótipo , Epidemiologia Molecular , Gastroenterite/epidemiologia , Antígenos Virais/genética , Epitopos , Fezes
12.
Opt Express ; 31(17): 27914-27926, 2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37710857

RESUMO

We report on the continuous-wave (CW) operation of 1D terahertz quantum cascade (THz QC) microlaser arrays working on various bound states in the continuum (BICs). We first created a quasi-BIC state by breaking the inversion symmetry of the microlaser array, which enables flexible control of the radiation efficiency. The optimized multi-periods array exhibits single-mode emission with the maximum output power of 21 mW (at 30 K), and the maximum operation temperature (Tcw) of 45 K. To further increase Tcw, we created a hybrid-BIC state by hybridizing a quasi-BIC generated in a few-periods array and a high-Q surface plasmon polariton mode formed in an unbiased array. The hybridization minimizes the pumping area with no obvious degradation of the threshold current density. The reduced pumping area, together with the discrete distribution of microlasers, significantly decreases the device thermal resistance. Such scheme improves the Tcw up to 79 K with a low beam divergence of 17°×17°, and the output power remains 3.4 mW at 20 K. Our work provides a novel solution to control the output power, the operating temperature, and the beam quality of THz QC lasers in CW mode.

13.
Acta Neuropathol ; 145(6): 717-731, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36964213

RESUMO

Cerebral amyloid-ß (Aß) accumulation due to impaired Aß clearance is a pivotal event in the pathogenesis of Alzheimer's disease (AD). Considerable brain-derived Aß is cleared via transporting to the periphery. The liver is the largest organ responsible for the clearance of metabolites in the periphery. Whether the liver physiologically clears circulating Aß and its therapeutic potential for AD remains unclear. Here, we found that about 13.9% of Aß42 and 8.9% of Aß40 were removed from the blood when flowing through the liver, and this capacity was decreased with Aß receptor LRP-1 expression down-regulated in hepatocytes in the aged animals. Partial blockage of hepatic blood flow increased Aß levels in both blood and brain interstitial fluid. The chronic decline in hepatic Aß clearance via LRP-1 knockdown specific in hepatocytes aggravated cerebral Aß burden and cognitive deficits, while enhancing hepatic Aß clearance via LRP-1 overexpression attenuated cerebral Aß deposition and cognitive impairments in APP/PS1 mice. Our findings demonstrate that the liver physiologically clears blood Aß and regulates brain Aß levels, suggesting that a decline of hepatic Aß clearance during aging could be involved in AD development, and hepatic Aß clearance is a novel therapeutic approach for AD.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Fígado/metabolismo , Fígado/patologia , Camundongos Transgênicos , Modelos Animais de Doenças
14.
Phys Rev Lett ; 131(16): 166703, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37925723

RESUMO

Finding tunable van der Waals (vdW) ferromagnets that operate at above room temperature is an important research focus in physics and materials science. Most vdW magnets are only intrinsically magnetic far below room temperature and magnetism with square-shaped hysteresis at room temperature has yet to be observed. Here, we report magnetism in a quasi-2D magnet Cr_{1.2}Te_{2} observed at room temperature (290 K). This magnetism was tuned via a protonic gate with an electron doping concentration up to 3.8×10^{21} cm^{-3}. We observed nonmonotonic evolutions in both coercivity and anomalous Hall resistivity. Under increased electron doping, the coercivities and anomalous Hall effects (AHEs) vanished, indicating a doping-induced magnetic phase transition. This occurred up to room temperature. DFT calculations showed the formation of an antiferromagnetic (AFM) phase caused by the intercalation of protons which induced significant electron doping in the Cr_{1.2}Te_{2}. The tunability of the magnetic properties and phase in room temperature magnetic vdW Cr_{1.2}Te_{2} is a significant step towards practical spintronic devices.

15.
BMC Cancer ; 23(1): 808, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644421

RESUMO

BACKGROUND: Glioblastoma (GBM) is the most malignant glioma, with poor survival rates and prognosis. Several studies have reported the abnormal expression of circular RNAs (circRNAs) and their functions in the malignant biological behavior of GBM. However, such research is still in the preliminary stages, and further study is needed to confirm the therapeutic potential of circRNAs in GBM. METHODS: RNA-seq was performed using four tumor tissues from patients with GBM and their adjacent non-tumor brain tissues to screen differentially expressed circRNAs. Fluorescence in situ hybridization assay was used to examine the location of circ_0021350 in glioma cells. In addition, a series of biological function assays were employed to verify the oncogenic role of circ_0021350 in GBM. Quantitative reverse transcription PCR was used to examine circular, micro- (miRNA), and messenger RNA (mRNA) levels. Furthermore, dual-luciferase reporter, RNA pull-down, and RNA binding protein immunoprecipitation assays were applied to verify the interaction between circ_0021350 and its downstream effectors. RESULTS: Circ_0021350 was significantly elevated in GBM tissues and glioma cells. Overexpression of circ_0021350 promoted glioma cell proliferation and metastatic ability; silencing of circ_0021350 had the opposite effect. Mechanistic analysis revealed that circ_0021350 sponged miR-1207-3p to regulate PIK3R3, whose overexpression reversed the reduction in the malignant biological behavior of glioma cells caused by silencing circ_0021350. CONCLUSION: Our findings suggest that circ_0021350 is an oncogenic circRNA in GBM, and the circ_0021350/miR-1207-3p/PIK3R3 axis may serve as a potential therapeutic target in GBM treatment.


Assuntos
Glioblastoma , Glioma , MicroRNAs , Humanos , Glioblastoma/genética , Hibridização in Situ Fluorescente , RNA Circular/genética , Oncogenes , MicroRNAs/genética , Fosfatidilinositol 3-Quinases
16.
Virol J ; 20(1): 176, 2023 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-37550752

RESUMO

SARS-CoV-2 is a zoonotic betacoronavirus that was first reported at the dawn of 2019 in Wuhan, China and has since spread globally, causing an ongoing pandemic. Anthroponotic transmission was reported early, with confirmed infections reported in 26 species to date, including dogs and cats. However, there is a paucity of reports on the transmission of SARS-CoV-2 to companion animals, and thus, we aimed to estimate the seroprevalence of SARS-CoV-2 in dogs and cats in Sarawak, Malaysia. From August 2022 to 2023, we screened plasma samples of 172 companion animals in Sarawak, Malaysia, using a species-independent surrogate virus neutralization test. Our findings revealed the presence of neutralizing antibodies of SARS-CoV-2 in 24.5% (27/110) of dogs and 24.2% (15/62) of cats. To the best of our knowledge, this is the first report of the seroprevalence of SARS-CoV-2 in companion animals in Malaysia. Our findings emphasize the need for pet owners to distance themselves from their pets when unwell, and a strategy must be in place to monitor SARS-CoV-2 in companion animals to assess the potential impact of the virus on companion animals.


Assuntos
COVID-19 , Doenças do Gato , Doenças do Cão , Animais , Gatos , Cães , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/veterinária , Animais de Estimação , Malásia/epidemiologia , Doenças do Gato/epidemiologia , Estudos Soroepidemiológicos , Doenças do Cão/epidemiologia
17.
J Sex Med ; 20(5): 645-650, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-36861333

RESUMO

BACKGROUND: The effects of pelvic organ prolapse (POP) and stress urinary incontinence (SUI) on sexual activity and female sexual dysfunction (FSD) remain unknown. How female sexual function is affected by surgery to treat SUI and/or POP remains controversial. AIM: The objectives of this study were to identify the prevalence of FSD and potential risk factors in women with POP and/or SUI and to assess whether pelvic floor surgery leads to alterations in female sexual function. METHODS: This investigation was prospective and observational. Informed consent was obtained from women who were scheduled to undergo pelvic floor surgery to manage POP and/or SUI at Peking University People's Hospital, which is an urban medical center. Sexual function was assessed by an investigator preoperatively and 12 months postoperatively. OUTCOMES: Sexual activity and sexual function before and after surgery were investigated with potential risk factors. Sexual function was measured by 2 validated questionnaires: the Female Sexual Function Index and the PISQ-12 (Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire Short Form). RESULTS: A total of 233 women were recruited, and all were ethnically Chinese. The average age was 63 years (range, 31-83), and 47.2% were sexually active. The lack of sexual activity before surgery was associated with increasing age (mean ± SD, 56.3 ± 9.5 vs 68.4 ± 8.1 years; P < .001) and postmenopausal status (70.0% vs 97.6%, P < .001). Among the sexually active women, 62.7% were diagnosed with FSD. Increasing age (58.6 ± 9.6 vs 52.3 ± 7.8 years, P < .001) and postmenopausal status (82.6% vs 48.8%, P < .001) were associated with the presence of FSD. Overall there was no significant difference between the PISQ-12 score before and 12 months after surgery (34.7 ± 6.7 vs 33.9 ± 6.6, P = .14). Lubrication of the vagina (P = .044) was an independent factor associated with the improvement in quality of sexual life after surgery. Menopause negatively affected the improvement in quality of sexual life after surgery (P = .024). CLINICAL IMPLICATIONS: Menopause and lubrication of the vagina might affect the improvement in sexual function after surgery. STRENGTHS AND LIMITATIONS: Strengths include the prospective design, validated questionnaires, and adequate follow-up time. As a limitation, this study is a single-center study that included only Chinese patients with advanced POP/SUI, so it may not be generalizable to other populations. CONCLUSION: Nearly half of women with symptomatic POP and/or SUI are still sexually active. Increasing age and menopause are associated with a lack of sexual activity. Premenopausal status and better lubrication of the vagina before surgery might lead to an improvement in sexual function after pelvic floor surgery.


Assuntos
Distúrbios do Assoalho Pélvico , Prolapso de Órgão Pélvico , Incontinência Urinária por Estresse , Incontinência Urinária , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Distúrbios do Assoalho Pélvico/complicações , Distúrbios do Assoalho Pélvico/epidemiologia , Distúrbios do Assoalho Pélvico/cirurgia , Qualidade de Vida , Comportamento Sexual , Incontinência Urinária por Estresse/cirurgia , Incontinência Urinária por Estresse/complicações , Prolapso de Órgão Pélvico/complicações , Prolapso de Órgão Pélvico/cirurgia , Inquéritos e Questionários
18.
PLoS Comput Biol ; 18(6): e1010195, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35653400

RESUMO

Allosteric communication between distant parts of proteins controls many cellular functions, in which metal ions are widely utilized as effectors to trigger the allosteric cascade. Due to the involvement of strong coordination interactions, the energy landscape dictating the metal ion binding is intrinsically rugged. How metal ions achieve fast binding by overcoming the landscape ruggedness and thereby efficiently mediate protein allostery is elusive. By performing molecular dynamics simulations for the Ca2+ binding mediated allostery of the calmodulin (CaM) domains, each containing two Ca2+ binding helix-loop-helix motifs (EF-hands), we revealed the key role of water-bridged interactions in Ca2+ binding and protein allostery. The bridging water molecules between Ca2+ and binding residue reduces the ruggedness of ligand exchange landscape by acting as a lubricant, facilitating the Ca2+ coupled protein allostery. Calcium-induced rotation of the helices in the EF-hands, with the hydrophobic core serving as the pivot, leads to exposure of hydrophobic sites for target binding. Intriguingly, despite being structurally similar, the response of the two symmetrically arranged EF-hands upon Ca2+ binding is asymmetric. Breakage of symmetry is needed for efficient allosteric communication between the EF-hands. The key roles that water molecules play in driving allosteric transitions are likely to be general in other metal ion mediated protein allostery.


Assuntos
Cálcio , Água , Sítios de Ligação , Cálcio/metabolismo , Calmodulina/metabolismo , Íons/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica , Conformação Proteica , Água/metabolismo
19.
PLoS Comput Biol ; 18(4): e1009578, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35381009

RESUMO

Residue-level coarse-grained (CG) models have become one of the most popular tools in biomolecular simulations in the trade-off between modeling accuracy and computational efficiency. To investigate large-scale biological phenomena in molecular dynamics (MD) simulations with CG models, unified treatments of proteins and nucleic acids, as well as efficient parallel computations, are indispensable. In the GENESIS MD software, we implement several residue-level CG models, covering structure-based and context-based potentials for both well-folded biomolecules and intrinsically disordered regions. An amino acid residue in protein is represented as a single CG particle centered at the Cα atom position, while a nucleotide in RNA or DNA is modeled with three beads. Then, a single CG particle represents around ten heavy atoms in both proteins and nucleic acids. The input data in CG MD simulations are treated as GROMACS-style input files generated from a newly developed toolbox, GENESIS-CG-tool. To optimize the performance in CG MD simulations, we utilize multiple neighbor lists, each of which is attached to a different nonbonded interaction potential in the cell-linked list method. We found that random number generations for Gaussian distributions in the Langevin thermostat are one of the bottlenecks in CG MD simulations. Therefore, we parallelize the computations with message-passing-interface (MPI) to improve the performance on PC clusters or supercomputers. We simulate Herpes simplex virus (HSV) type 2 B-capsid and chromatin models containing more than 1,000 nucleosomes in GENESIS as examples of large-scale biomolecular simulations with residue-level CG models. This framework extends accessible spatial and temporal scales by multi-scale simulations to study biologically relevant phenomena, such as genome-scale chromatin folding or phase-separated membrane-less condensations.


Assuntos
Simulação de Dinâmica Molecular , Software , Cromatina , DNA/química
20.
Environ Sci Technol ; 57(47): 18433-18442, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36719710

RESUMO

In drinking water distribution systems, the oxidation of zerovalent chromium, Cr(0), in iron corrosion scales by chlorine residual disinfectant is the dominant reaction to form carcinogenic hexavalent chromium, Cr(VI). This study investigates inhibitive corrosion control strategies through adjustments of chemical water parameters (i.e., pH, silicate, phosphate, calcium, and alkalinity) on Cr(VI) formation through oxidation of Cr(0)(s) by free chlorine under drinking water conditions. The results show that an increase in pH, silicate, alkalinity, and calcium suppressed Cr(VI) formation that was mainly attributed to in situ surface precipitation of new Cr(III) solids on the surface of Cr(0)(s), including Cr(OH)3(s), Cr2(SiO3)3(s), CrPO4(s), Cr2(CO3)3(s), and Cr10Ca(CO3)16(s). The Cr(III) surface precipitates were much less reactive with chlorine than Cr(0)(s) and suppressed the Cr redox reactivity. The concentration of surface Cr(III) solids was inversely correlated with the rate constant of Cr(VI) formation. Adding phosphate either promoted or inhibited the Cr(VI) formation, depending on the phosphate concentration. This study provides fundamental insight into the Cr(VI) formation mechanisms via Cr(0) oxidation by chlorine and the importance of surface precipitation of Cr(III) solids with different corrosion control strategies and suggests that increasing the pH/alkalinity and addition of phosphate or silicate can be effective control strategies to minimize Cr(VI) formation.


Assuntos
Água Potável , Poluentes Químicos da Água , Corrosão , Cálcio , Cloro , Poluentes Químicos da Água/análise , Cromo/análise , Oxirredução , Fosfatos , Silicatos
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