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Transparent piezoelectrics are highly desirable for numerous hybrid ultrasound-optical devices ranging from photoacoustic imaging transducers to transparent actuators for haptic applications1-7. However, it is challenging to achieve high piezoelectricity and perfect transparency simultaneously because most high-performance piezoelectrics are ferroelectrics that contain high-density light-scattering domain walls. Here, through a combination of phase-field simulations and experiments, we demonstrate a relatively simple method of using an alternating-current electric field to engineer the domain structures of originally opaque rhombohedral Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT) crystals to simultaneously generate near-perfect transparency, an ultrahigh piezoelectric coefficient d33 (greater than 2,100 picocoulombs per newton), an excellent electromechanical coupling factor k33 (about 94 per cent) and a large electro-optical coefficient γ33 (approximately 220 picometres per volt), which is far beyond the performance of the commonly used transparent ferroelectric crystal LiNbO3. We find that increasing the domain size leads to a higher d33 value for the [001]-oriented rhombohedral PMN-PT crystals, challenging the conventional wisdom that decreasing the domain size always results in higher piezoelectricity8-10. This work presents a paradigm for achieving high transparency and piezoelectricity by ferroelectric domain engineering, and we expect the transparent ferroelectric crystals reported here to provide a route to a wide range of hybrid device applications, such as medical imaging, self-energy-harvesting touch screens and invisible robotic devices.
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A cattle pangenome representation was created based on the genome sequences of 898 cattle representing 57 breeds. The pangenome identified 83 Mb of sequence not found in the cattle reference genome, representing 3.1% novel sequence compared with the 2.71-Gb reference. A catalog of structural variants developed from this cattle population identified 3.3 million deletions, 0.12 million inversions, and 0.18 million duplications. Estimates of breed ancestry and hybridization between cattle breeds using insertion/deletions as markers were similar to those produced by single nucleotide polymorphism-based analysis. Hundreds of deletions were observed to have stratification based on subspecies and breed. For example, an insertion of a Bov-tA1 repeat element was identified in the first intron of the APPL2 gene and correlated with cattle breed geographic distribution. This insertion falls within a segment overlapping predicted enhancer and promoter regions of the gene, and could affect important traits such as immune response, olfactory functions, cell proliferation, and glucose metabolism in muscle. The results indicate that pangenomes are a valuable resource for studying diversity and evolutionary history, and help to delineate how domestication, trait-based breeding, and adaptive introgression have shaped the cattle genome.
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The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intraovarian mammalian target of rapamycin-C-type natriuretic peptide pathway, activated by follicle-stimulating hormone, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mammalian target of rapamycin in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.
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Aquaporinas , Junções Íntimas , Animais , Feminino , Aquaporinas/genética , Hormônio Foliculoestimulante , Gonadotropinas , Bombas de Íon , Mamíferos , Serina-Treonina Quinases TOR/genética , Camundongos , Peptídeo Natriurético Tipo C/metabolismoRESUMO
BACKGROUND: Enhanced glycolysis is a crucial metabolic event that drives the development of liver fibrosis, but the molecular mechanisms have not been fully understood. Lactate is the endproduct of glycolysis, which has recently been identified as a bioactive metabolite binding to G-protein-coupled receptor 81 (GPR81). We then questioned whether GPR81 is implicated in the development of liver fibrosis. METHODS: The level of GPR81 was determined in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and in transforming growth factor beta 1 (TGF-ß1)-activated hepatic stellate cells (HSCs) LX-2. To investigate the significance of GPR81 in liver fibrosis, wild-type (WT) and GPR81 knockout (KO) mice were exposed to CCl4, and then the degree of liver fibrosis was determined. In addition, the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) was supplemented in CCl4-challenged mice and TGF-ß1-activated LX-2 cells to further investigate the pathological roles of GPR81 on HSCs activation. RESULTS: CCl4 exposure or TGF-ß1 stimulation significantly upregulated the expression of GPR81, while deletion of GPR81 alleviated CCl4-induced elevation of aminotransferase, production of pro-inflammatory cytokines, and deposition of collagen. Consistently, the production of TGF-ß1, the expression of alpha-smooth muscle actin (α-SMA) and collagen I (COL1A1), as well as the elevation of hydroxyproline were suppressed in GPR81 deficient mice. Supplementation with DHBA enhanced CCl4-induced liver fibrogenesis in WT mice but not in GPR81 KO mice. DHBA also promoted TGF-ß1-induced LX-2 activation. Mechanistically, GPR81 suppressed cAMP/CREB and then inhibited the expression of Smad7, a negative regulator of Smad3, which resulted in increased phosphorylation of Smad3 and enhanced activation of HSCs. CONCLUSION: GPR81 might be a detrimental factor that promotes the development of liver fibrosis by regulating CREB/Smad7 pathway.
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Tetracloreto de Carbono , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Células Estreladas do Fígado , Cirrose Hepática , Camundongos Knockout , Receptores Acoplados a Proteínas G , Transdução de Sinais , Proteína Smad7 , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/patologia , Cirrose Hepática/etiologia , Cirrose Hepática/induzido quimicamente , Camundongos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Células Estreladas do Fígado/metabolismo , Proteína Smad7/metabolismo , Proteína Smad7/genética , Fator de Crescimento Transformador beta1/metabolismo , Masculino , Humanos , Linhagem Celular , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Deleção de GenesRESUMO
BACKGROUND: The angiographic features of moyamoya disease (MMD) and atherosclerosis-associated moyamoya vasculopathy (AS-MMV) are similar, but the etiology and clinical treatment strategies are different. Differentiating MMD from AS-MMV helps to choose the appropriate treatment. PURPOSE: To investigate the feasibility of a nomogram based on high-resolution vessel wall (HR-VWI) MRI features to differentiate MMD from AS-MMV. STUDY TYPE: Retrospective. SUBJECTS: One hundred and two patients with MMD (N = 52) or AS-MMV (N = 50) in the training cohort (9-72 years; 54 females) and 70 patients with MMD (N = 42) or AS-MMV (N = 28) in the validation cohort (7-69 years; 33 females). FIELD STRENGTH/SEQUENCE: 3-T, three-dimensional time-of-flight MR angiography (3D-TOF-MRA), spin echo high-resolution 3D T1-weighted imaging (3D-T1WI), 3D T2-weighted imaging (3D-T2WI), and contrast-enhanced 3D-T1WI. ASSESSMENT: Image assessment was performed by three neuroradiologists (with 10, 15, and 18 years of experience). Demographic characteristic and image features were evaluated and compared. Independent factors of MMD were screened to construct a nomogram model in the training cohort. The validation cohort was used to validated its generality. STATISTICAL TESTS: Interclass correlation coefficient (ICC), kappa, t-test, χ2 test, receiver operating characteristic (ROC) curve, area under the curve (AUC), calibration curve and concordance index (C-index). A P-value <0.05 was considered statistically significant. RESULTS: Significant differences were observed between MMD and AS-MMV in terms of age, vessel outer diameter, vessel wall thickening pattern, maximum thickness, dot sign, and anterior cerebral artery (ACA) involved. Age, outer diameter, dot sign, and ACA involved were independent factors. The C-index was 0.886 in the training cohort and 0.859 in the validation cohort. The ROC demonstrated high diagnostic efficacy with an AUC of 0.884 in the training cohort and 0.857 in the validation cohort. DATA CONCLUSION: A nomogram model based on age, vessel outer diameter, dot sign and ACA involved may effectively distinguish MMD from AS-MMV with good reliability and accuracy. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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N1-methyladenosine (m1A) is a post-transcriptionally modified RNA molecule that plays a pivotal role in the regulation of various biological functions and activities. Especially in cancer cell invasion, proliferation and cell cycle regulation. Over recent years, there has been a burgeoning interest in investigating the m1A modification of RNA. Most studies have focused on the regulation of m1A in cancer enrichment areas and different regions. This review provides a comprehensive overview of the methodologies employed for the detection of m1A modification. Furthermore, this review delves into the key players in m1A modification, known as the "writers," "erasers," and "readers." m1A modification is modified by the m1A methyltransferases, or writers, such as TRMT6, TRMT61A, TRMT61B, TRMT10C, NML, and, removed by the demethylases, or erasers, including FTO and ALKBH1, ALKBH3. It is recognized by m1A-binding proteins YTHDF1, TYHDF2, TYHDF3, and TYHDC1, also known as "readers". Additionally, we explore the intricate relationship between m1A modification and its regulators and their implications for the development and progression of specific types of cancer, we discuss how m1A modification can potentially facilitate the discovery of novel approaches for cancer diagnosis, treatment, and prognosis. Our summary of m1A methylated adenosine modification detection methods and regulatory mechanisms in various cancers provides useful insights for cancer diagnosis, treatment, and prognosis. Video Abstract.
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Neoplasias , Humanos , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/metabolismo , RNA/genética , RNA/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Metilação , Homólogo AlkB 1 da Histona H2a Dioxigenase/metabolismo , Homólogo AlkB 3 da Dioxigenase Dependente de alfa-Cetoglutarato/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismoRESUMO
N4-acetylcytidine (ac4C) is a highly conserved chemical modification widely found in eukaryotic and prokaryotic RNA, such as tRNA, rRNA, and mRNA. This modification is significantly associated with various human diseases, especially cancer, and its formation depends on the catalytic activity of N-acetyltransferase 10 (NAT10), the only known protein that produces ac4C. This review discusses the detection techniques and regulatory mechanisms of ac4C and summarizes ac4C correlation with tumor occurrence, development, prognosis, and drug therapy. It also comments on a new biomarker for early tumor diagnosis and prognosis prediction and a new target for tumor therapy. Video Abstract.
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Neoplasias , RNA , Humanos , RNA/metabolismo , Citidina/genética , RNA Mensageiro/genética , Neoplasias/genéticaRESUMO
BACKGROUND: Cervical spondylosis (CS), including myelopathy and radiculopathy, is the most common degenerative cervical spine disease. This study aims to evaluate the clinical outcomes of unilateral biportal endoscopy (UBE) compared to those of conventional anterior cervical decompression and fusion (ACDF) for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. METHODS: A prospective, randomized, controlled, noninferiority trial was conducted. The sample consisted of 131 patients who underwent UBE or ACDF was conducted between September 2021 and September 2022. Patients with cervical nerve roots or coexisting spinal cord compression symptoms and imaging-defined unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs were randomized into two groups: a UBE group (n = 63) and an ACDF group (n = 68). The operative time, blood loss, length of hospital stay after surgery, and perioperative complications were recorded. Preoperative and postoperative modified Japanese Orthopaedic Association (mJOA) scale scores, visual analog scale (VAS) scores, neck disability index (NDI) scores, and recovery rate (RR) of the mJOA were utilized to evaluate clinical outcomes. RESULTS: The hospital stay after surgery was significantly shorter in patients treated with UBE than in those treated with ACDF (p < 0.05). There were no significant differences in the neck or arm VAS score, NDI score, mJOA score, or mean RR of the mJOA between the two groups (p < 0.05). Only mild complications were observed in both groups, with no significant difference (p = 0.30). CONCLUSION: UBE can significantly relieve pain and disability without severe complications, and most patients are satisfied with this technique. Consequently, this procedure can be used safely and effectively as an alternative to ACDF for treating unilateral cervical radiculopathy or coexisting cervical myelopathy induced by unilateral cervical herniated discs. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry on 02/08/2023 ( http://www.chictr.org.cn , #ChiCTR2300074273).
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Vértebras Cervicais , Descompressão Cirúrgica , Endoscopia , Radiculopatia , Doenças da Medula Espinal , Fusão Vertebral , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Radiculopatia/cirurgia , Radiculopatia/etiologia , Descompressão Cirúrgica/métodos , Estudos Prospectivos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Fusão Vertebral/métodos , Endoscopia/métodos , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/diagnóstico por imagem , Resultado do Tratamento , Idoso , Adulto , Espondilose/cirurgia , Espondilose/complicações , Espondilose/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/complicaçõesRESUMO
Intestinal epithelial cells (IECs) play crucial roles in forming an essential barrier, providing host defense against pathogens and regulating nutrients absorption. Milk-derived extracellular vesicles (EVs) within its miRNAs are capable of modulating the recipient cell function. However, the differences between colostrum and mature milk EVs and their biological function in attenuating intestinal epithelial cell injury remain poorly understood. Thus, we carried out the present study to characterize the difference between colostrum and mature milk-derived miRNA of EVs and the effect of colostrum and mature milk EVs on the proliferation, apoptosis, proinflammatory cytokines and intestinal epithelial barrier related genes in IEC-6 induced by LPS. Differential expression of 329 miRNAs was identified between colostrum and mature milk EVs, with 185 miRNAs being downregulated and 144 upregulated. In addition, colostrum contains a greater number and protein concentration of EVs than mature milk. Furthermore, compared to control, EVs derived from colostrum significantly inhibited the expression of apoptosis- (Bax, p53, and caspase-3) and proinflammatory-related genes (TNFα, IL6, and IL1ß). EVs derived from mature milk did not affect expression of apoptosis-related genes (Bax, p53, bcl2, and caspase-3). The EVs derived from mature milk significantly inhibited the expression of proinflammatory-related genes (TNFα and IL6). Western blot analysis also indicated that colostrum and mature milk EVs significantly decreased the apoptosis of IEC-6 cells. The EdU assay results showed that colostrum and mature milk EVs significantly increased the proliferation of IEC-6 cells. The expression of intestinal barrier-related genes (TJP1, CLDN1, OCLN, CDX2, MUC2, and IGF1R) was significantly promoted in IEC-6 cells after colostrum and mature milk EVs addition. Importantly, colostrum and mature milk EVs significantly relieved the LPS-induced inhibition of proliferation and intestinal barrier-related genes expression and attenuated apoptosis and proinflammatory responses induced by LPS in IEC-6 cells. Flow cytometry and Western blot analysis also indicated that colostrum and mature milk EVs significantly affect the apoptosis of IEC-6 cells induced by LPS. The results also indicated that EVs derived from colostrum had better effects on inhibiting the apoptosis- and proinflammatory cytokines-related genes expression. However, the EVs derived from mature milk exhibited beneficial effects on intestinal epithelial barrier protection. The present study will provide a better understanding of the role of EVs derived from colostrum and milk in dairy cows with different responses in the regulation of intestinal cells function, and also presents new evidence for the change of EVs cargos during various stages of lactation.
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Vesículas Extracelulares , Leite , Animais , Feminino , Gravidez , Bovinos , Colostro , Lipopolissacarídeos/farmacologia , Caspase 3 , Fator de Necrose Tumoral alfa , Interleucina-6 , Proteína Supressora de Tumor p53 , Proteína X Associada a bcl-2 , Células EpiteliaisRESUMO
Industrial wastewater discharged into sewer systems is often characterized by high nitrate contents and low C/N ratios, resulting in high treatment costs when using conventional activated sludge methods. This study introduces a partial denitrification-anammox (PD/A) granular process to address this challenge. The PD/A granular process achieved an effluent TN level of 3.7 mg/L at a low C/N ratio of 2.3. Analysis of a typical cycle showed that the partial denitrification peaked within 15 min and achieved a nitrate-to-nitrite transformation ratio of 86.9%. Anammox, which was activated from 15 to 120 min, contributed 86.2% of the TN removal. The system exhibited rapid recovery from post-organic shock, which was attributed to significant increases in protein content within TB-EPS. Microbial dispersion and reassembly were observed after coexistence of the granules, with Thauera (39.12%) and Candidatus Brocadia (1.25%) identified as key functional microorganisms. This study underscores the efficacy of PD/A granular sludge technology for treating low-C/N nitrate wastewater.
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Desnitrificação , Nitratos , Esgotos , Águas Residuárias , Nitratos/metabolismo , Águas Residuárias/química , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Nitrogênio/metabolismo , Carbono/química , Reatores BiológicosRESUMO
Lactate dehydrogenase A (LDHA) primarily catalyzes the conversion between lactic acid and pyruvate, serving as a key enzyme in the aerobic glycolysis pathway of sugar in tumor cells. LDHA plays a crucial role in the occurrence, development, progression, invasion, metastasis, angiogenesis, and immune escape of tumors. Consequently, LDHA not only serves as a biomarker for tumor diagnosis and prognosis but also represents an ideal target for tumor therapy. Although LDHA inhibitors show great therapeutic potential, their development has proven to be challenging. In the development of LDHA inhibitors, the key active sites of LDHA are emphasized. Nevertheless, there is a relative lack of research on the amino acid residues around the active center of LDHA. Therefore, in this study, we investigated the amino acid residues around the active center of LDHA. Through structure comparison analysis, five key amino acid residues (Ala30, Met41, Lys131, Gln233, and Ala259) were identified. Subsequently, the effects of these five residues on the enzymatic properties of LDHA were investigated using site-directed mutagenesis. The results revealed that the catalytic activities of the five mutants varied to different degrees in both the reaction from lactic acid to pyruvate and pyruvate to lactic acid. Notably, the catalytic activities of LDHAM41G and LDHAK131I were improved, particularly in the case of LDHAK131I. The results of the molecular dynamics analysis of LDHAK131I explained the reasons for this phenomenon. Additionally, the optimum temperature of LDHAM41G and LDHAQ233M increased from 35 °C to 40 °C, whereas in the reverse reaction, the optimum temperature of LDHAM41G and LDHAK131I decreased from 70 °C to 60 °C. These findings indicate that Ala30, Met41, Lys131, Gln233, and Ala259 exert diverse effects on the catalytic activity and optimum temperature of LHDA. Therefore, these amino acid residues, in addition to the key catalytic site of the active center, play a crucial role. Considering these residues in the design and screening of LDHA inhibitors may lead to the development of more effective inhibitors.
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Domínio Catalítico , Inibidores Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Aminoácidos/química , Aminoácidos/metabolismo , L-Lactato Desidrogenase/antagonistas & inibidores , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/química , Lactato Desidrogenase 5/metabolismo , Lactato Desidrogenase 5/antagonistas & inibidores , Lactato Desidrogenase 5/química , Ácido Pirúvico/metabolismo , Ácido Pirúvico/química , Mutagênese Sítio-Dirigida , Simulação de Dinâmica MolecularRESUMO
BACKGROUND: The epigenetic mechanisms involved in the progression of pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. This study aimed to identify key transcription factors (TFs) through multiomics sequencing to investigate the molecular mechanisms of TFs that play critical roles in PDAC. METHODS: To characterise the epigenetic landscape of genetically engineered mouse models (GEMMs) of PDAC with or without KRAS and/or TP53 mutations, we employed ATAC-seq, H3K27ac ChIP-seq, and RNA-seq. The effect of Fos-like antigen 2 (FOSL2) on survival was assessed using the Kaplan-Meier method and multivariate Cox regression analysis for PDAC patients. To study the potential targets of FOSL2, we performed Cleavage Under Targets and Tagmentation (CUT&Tag). To explore the functions and underlying mechanisms of FOSL2 in PDAC progression, we employed several assays, including CCK8, transwell migration and invasion, RT-qPCR, Western blotting analysis, IHC, ChIP-qPCR, dual-luciferase reporter, and xenograft models. RESULTS: Our findings indicated that epigenetic changes played a role in immunosuppressed signalling during PDAC progression. Moreover, we identified FOSL2 as a critical regulator that was up-regulated in PDAC and associated with poor prognosis in patients. FOSL2 promoted cell proliferation, migration, and invasion. Importantly, our research revealed that FOSL2 acted as a downstream target of the KRAS/MAPK pathway and recruited regulatory T (Treg) cells by transcriptionally activating C-C motif chemokine ligand 28 (CCL28). This discovery highlighted the role of an immunosuppressed regulatory axis involving KRAS/MAPK-FOSL2-CCL28-Treg cells in the development of PDAC. CONCLUSION: Our study uncovered that KRAS-driven FOSL2 promoted PDAC progression by transcriptionally activating CCL28, revealing an immunosuppressive role for FOSL2 in PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Animais , Camundongos , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Regulação para Cima , Cromatina , Ligantes , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/patologia , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Quimiocinas CC/metabolismo , Antígeno 2 Relacionado a Fos/genética , Antígeno 2 Relacionado a Fos/metabolismo , Neoplasias PancreáticasRESUMO
Dielectric energy storage polymers play a vital role in advanced electronics and electrical systems, due to their high breakdown strength, excellent reliability, and easy fabrication. However, the low dielectric constant and poor thermal resistance of dielectric polymers limit their energy storage density and working temperatures, making them less versatile for broader applications. In this work, a novel carboxylated poly (p-phenylene terephthalamide) (c-PPTA) is synthesized and employed to simultaneously enhance the dielectric constant and thermal resistance of polyetherimide (PEI), leading to a discharged energy density of 6.4 J cm-3 at 150 °C. The introduction of c-PPTA molecules effectively reduces the Πï£¿Π stacking effect and increases the average chain spacing between polymer molecules, which is conducive to improving the dielectric constant. Additionally, c-PPTA molecules with stronger positive charges and high dipole moments can capture electrons, resulting in reduced conduction loss and enhanced breakdown strength at high temperatures. The coiled capacitor fabricated with the PEI/c-PPTA film exhibits superior capacitance performances and higher working temperatures compared to commercial metalized PP capacitors, demonstrating great potential for dielectric polymers in high-temperature electronic and electrical energy storage systems.
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Electrostatic dielectric capacitors are essential components in advanced electronic and electrical power systems due to their ultrafast charging/discharging speed and high power density. A major challenge, however, is how to improve their energy densities to effectuate the next-generation applications that demand miniaturization and integration. Here, we report a high-entropy stabilized Bi2Ti2O7-based dielectric film that exhibits an energy density as high as 182 J cm-3 with an efficiency of 78% at an electric field of 6.35 MV cm-1. Our results reveal that regulating the atomic configurational entropy introduces favourable and stable microstructural features, including lattice distorted nano-crystalline grains and a disordered amorphous-like phase, which enhances the breakdown strength and reduces the polarization switching hysteresis, thus synergistically contributing to the energy storage performance. This high-entropy approach is expected to be widely applicable for the development of high-performance dielectrics.
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China is an epidemic area of hepatitis E, and the serum prevalence data is very important for formulating prevention and control strategies. However, almost all related research in the past decade are cross-sectional studies. In this study, we analyzed the serological data from 2012 to 2021 in Chongqing for 10 consecutive years. We found that the positive rate of hepatitis E IgG antibody increased gradually, from 1.61% in January 2012 to 50.63% in December 2021. The autoregressive integrated moving average model was used to predict the trend, and it was found that it will continue to show an upward trend in the recent future. In contrast, the positive rate of IgM and clinical incidence of hepatitis E showed a relatively stable trend. Although the positive rate of antibodies gradually increased with age, there was no significant difference in the age distribution of the subjects each year. Therefore, these results suggest that the accumulated infection of hepatitis E in Chongqing may be gradually increasing, but the clinical incidence rate remains unchanged, which provides a new concern for formulating prevention and control strategies.
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Vírus da Hepatite E , Hepatite E , Humanos , Hepatite E/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Estudos Soroepidemiológicos , Fatores de Tempo , China/epidemiologia , Anticorpos Anti-Hepatite , Imunoglobulina G , Imunoglobulina MRESUMO
We describe an application where graphene oxide nanoparticles (GONs) enable combined inhibition of Pseudorabies Virus (PRV) through delivery of a CRISPR/Cas9 system for targeted cleaving of a PRV genome and direct interaction with viral particles. The sheeted GONs could load CRISPR plasmid DNA (pDNA) to form a small sized, near-spheroidal GONs-CRISPR complex, which enables CRISPR pDNA efficient intracellular delivery and transient expression under serum conditions. Cell studies showed that GONs-CRISPR could allow rapid cellular uptake, endolysosomes escape, and nucleus transport within 3 h. Virus studies demonstrated that the pure GONs have antiviral activity and GONs-CRISPR could significantly inhibit PRV replication and result in progeny PRV decreasing by approximately 4000 times in infected host cells. Transmission electron microscopy (TEM) imaging showed that GONs-CRISPR could destroy the PRV structures by directly interacting with viral particles. This GONs-based strategy may extend the advanced application of the CRISPR system for antiviral action.
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Herpesvirus Suídeo 1 , Nanopartículas , Animais , Herpesvirus Suídeo 1/genética , Sistemas CRISPR-Cas/genética , Replicação Viral , Antivirais/farmacologiaRESUMO
Coronavirus disease 2019 (COVID-19) continues to take a heavy toll on personal health, healthcare systems, and economies around the globe. Scientists are expending tremendous effort to develop diagnostic technologies for detecting positive infections within the shortest possible time, and vaccines and drugs specifically for the prevention and treatment of COVID-19 disease. At the same time, emerging novel variants have raised serious concerns about vaccine efficacy. The SARS-CoV-2 nucleocapsid (N) protein plays an important role in the coronavirus life cycle, and participates in various vital activities after virus invasion. It has attracted a large amount of attention for vaccine and drug development. Here, we summarize the latest research of the N protein, including its role in the SARS-CoV-2 life cycle, structure and function, and post-translational modifications in addition to its involvement in liquid-liquid phase separation (LLPS) and use as a basis for the development of vaccines and diagnostic techniques.
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Vacinas contra COVID-19 , Proteínas do Nucleocapsídeo , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , COVID-19/prevenção & controle , Teste para COVID-19RESUMO
BACKGROUND: This study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE). PATIENTS AND METHODS: A single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded. RESULTS: Acalculous cholecystitis was found in 66 patients (57.89%) with acute HE. The incidence in males was 63.95%, which was significantly higher than in females (39.29%) (P = 0.022). The mean length of hospital stay and the incidence of spontaneous peritonitis in patients with cholecystitis (20.12 ± 9.43 days and 9.09%, respectively) were significantly higher than those in patients without cholecystitis (12.98 ± 7.26 days and 0%, respectively) (P < 0.001 and P = 0.032). Albumin, total bile acid, bilirubin, cholinesterase, and prothrombin activity in patients with cholecystitis were significantly inferior to those in patients without cholecystitis (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.003, respectively). After correction by multivariate analysis, albumin and total bile acid were found to be closely related to acalculous cholecystitis in HE. CONCLUSION: Acalculous cholecystitis is very common in patients with acute HE, and may serve as a predictor of increased peritonitis, synthetic decompensation, and longer hospital stay.
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Colecistite Acalculosa , Colecistite , Hepatite E , Peritonite , Masculino , Feminino , Humanos , Colecistite Acalculosa/complicações , Hepatite E/complicações , Doença Aguda , Colecistite/complicações , Colecistite/epidemiologia , Peritonite/etiologia , Ácidos e Sais BiliaresRESUMO
BACKGROUND: There is bidirectional communication between the gut microbiota and the brain. Empirical evidence has demonstrated sex differences in both the gut microbiome and the brain. However, the effects of sex on the gut microbiota-brain associations have yet to be determined. We aim to elucidate the sex-specific effects of gut microbiota on brain and cognition. METHODS: One hundred fifty-seven healthy young adults underwent brain structural, perfusion, functional and diffusion MRIs to measure gray matter volume (GMV), cerebral blood flow (CBF), functional connectivity strength (FCS) and white matter integrity, respectively. Fecal samples were collected and 16S amplicon sequencing was utilized to assess gut microbial diversity. Correlation analyses were conducted to test for sex-dependent associations between microbial diversity and brain imaging parameters, and mediation analysis was performed to further characterize the gut microbiota-brain-cognition relationship. RESULTS: We found that higher gut microbial diversity was associated with higher GMV in the right cerebellum VI, higher CBF in the bilateral calcarine sulcus yet lower CBF in the left superior frontal gyrus, higher FCS in the bilateral paracentral lobule, and lower diffusivity in widespread white matter regions in males. However, these associations were absent in females. Of more importance, these neuroimaging biomarkers significantly mediated the association between gut microbial diversity and behavioral inhibition in males. CONCLUSIONS: These findings highlight sex as a potential influential factor underlying the gut microbiota-brain-cognition relationship, and expose the gut microbiota as a biomarker-driven and sex-sensitive intervention target for mental disorders with abnormal behavioral inhibition.
Assuntos
Microbioma Gastrointestinal , Adulto Jovem , Humanos , Masculino , Feminino , Microbioma Gastrointestinal/fisiologia , Encéfalo/diagnóstico por imagem , Cognição/fisiologia , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
Materials exhibiting high energy/power density are currently needed to meet the growing demand of portable electronics, electric vehicles and large-scale energy storage devices. The highest energy densities are achieved for fuel cells, batteries, and supercapacitors, but conventional dielectric capacitors are receiving increased attention for pulsed power applications due to their high power density and their fast charge-discharge speed. The key to high energy density in dielectric capacitors is a large maximum but small remanent (zero in the case of linear dielectrics) polarization and a high electric breakdown strength. Polymer dielectric capacitors offer high power/energy density for applications at room temperature, but above 100 °C they are unreliable and suffer from dielectric breakdown. For high-temperature applications, therefore, dielectric ceramics are the only feasible alternative. Lead-based ceramics such as La-doped lead zirconate titanate exhibit good energy storage properties, but their toxicity raises concern over their use in consumer applications, where capacitors are exclusively lead free. Lead-free compositions with superior power density are thus required. In this paper, we introduce the fundamental principles of energy storage in dielectrics. We discuss key factors to improve energy storage properties such as the control of local structure, phase assemblage, dielectric layer thickness, microstructure, conductivity, and electrical homogeneity through the choice of base systems, dopants, and alloying additions, followed by a comprehensive review of the state-of-the-art. Finally, we comment on the future requirements for new materials in high power/energy density capacitor applications.