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Autoimmune regulator (Aire) and TGF-ß signaling play important roles in central tolerance and peripheral tolerance, respectively, by eliminating or suppressing the activity of autoreactive T cells. We previously demonstrated that dnTGFßRII mice develop a defect in peripheral tolerance and a primary biliary cholangitis (PBC)-like disease. We hypothesized that by introducing the Aire gene to this model, we would observe a more severe PBC phenotype. Interestingly, however, we demonstrated that, while dnTGFßRII Aire-/- mice do manifest key histological and serological features of autoimmune cholangitis, they also develop mild to moderate interface hepatitis and show high levels of alanine transaminase (ALT) and antinuclear antibodies (ANA), characteristics of autoimmune hepatitis (AIH). To further understand this unique phenotype, we performed RNA sequencing (RNA-seq) and flow cytometry to explore the functional pathways and immune cell pathways in the liver of dnTGFßRII Aire-/- mice. Our data revealed enrichments of programmed cell death pathways and predominant CD8+ T cell infiltrates. Depleting CD8+ T cells using an anti-CD8α antibody significantly alleviated hepatic inflammation and prolonged the life span of these mice. Finally, RNA-seq data indicated the clonal expansion of hepatic CD8+ T cells. In conclusion, these mice developed an autoreactive CD8+ T-cell-mediated autoimmune cholangitis with concurrent hepatitis that exhibited key histological and serological features of the AIH-PBC overlap syndrome, representing a novel model for the study of tolerance and autoimmune liver disease. © 2023 The Pathological Society of Great Britain and Ireland.
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Colangite , Hepatite Autoimune , Cirrose Hepática Biliar , Camundongos , Animais , Hepatite Autoimune/genética , Hepatite Autoimune/metabolismo , Cirrose Hepática Biliar/genética , Cirrose Hepática Biliar/metabolismo , Linfócitos T CD8-Positivos , Colangite/genética , Colangite/metabolismoRESUMO
Three novel diterpenoid alkaloids, comprising two C19 -diterpenoid alkaloids (1 and 2) and one C20 -diterpenoid alkaloid (3), were isolated from Delphinium ajacis, alongside the six known compoundsâ (4-9). Their structures were elucidated by spectroscopic methods (MS, UV, IR, 1D and 2D NMR) and chemical properties. Simultaneously, the anti-inflammatory properties of all compoundsâ (1-9) was conducted, focusing on nitric oxide (NO) production in LPS-induced BV-2 cells. The results indicated compoundsâ 1-3, 7, and 8 have potential anti-inflammatory activity.
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Alcaloides , Delphinium , Diterpenos , Delphinium/química , Espectroscopia de Ressonância Magnética , Alcaloides/farmacologia , Alcaloides/química , Diterpenos/farmacologia , Diterpenos/química , Anti-Inflamatórios/farmacologia , Estrutura MolecularRESUMO
There is a potential risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread through human contact with seafood and the inanimate materials contaminated by the virus. In this study, we examined the stability of the virus in artificial seawater (ASW) and on the surface of selected materials. SARS-CoV-2 (3.75 log10 TCID50 ) in ASW at 22â maintained infectious about 3 days and at 4â the virus survived more than 7 days. It should be noticed that viable virus at high titer (5.50 log10 TCID50 ) may survive more than 20 days in ASW at 4â and for 7 days at 22â. SARS-CoV-2 on stainless steel and plastic bag maintained infectious for 3 days, and on nonwoven fabric for 1 day at 22â. In addition, the virus remained infectious for 9 days on stainless steel and non-woven fabric, and on plastic bag for 12 days at 4â. It is important to highlight the role of inanimate material surfaces as a source of infection and the necessity for surface decontamination and disinfection.
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COVID-19 , SARS-CoV-2 , Humanos , Plásticos , Água do Mar , Aço InoxidávelRESUMO
Hyperpigmented skin diseases such as melasma, freckles, and melanosis usually mar the appearance of patients. Traditional herbal medicines are highly accepted in inhibiting skin pigmentation, with advantages of high efficiency, low cost, and low side effects. Selaginellin (SEL), one of the active compounds of selaginella, has been proved to be exhibit antineoplastic, antioxidant, antisenescence, and antiapoptosis activities. In this study, we found that SEL can inhibit melanogenesis in vitro and in vivo. A mechanism study found that SEL inhibits melanogenesis through inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway, then down-regulating the expression of microphthalmia-associated transcription factor (MITF) and downstream genes tyrosinase (TYR) and tyrosinase-related protein 2 (TYRP2). UVB-activated paracrine function of fibroblasts and keratinocytes promotes melanogenesis of melanocytes. Interestingly, SEL antagonizes UVB-activated paracrine function of fibroblasts and keratinocytes. These findings indicate that SEL can be a potential whitening compound to inhibit melanogenesis.
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Melaninas , Proteínas Quinases Ativadas por Mitógeno , Humanos , Melanócitos , Fator de Transcrição Associado à Microftalmia/genética , Fator de Transcrição Associado à Microftalmia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Transdução de SinaisRESUMO
Contact prelithiation is an important strategy to compensate the initial capacity loss of lithium-ion batteries. However, the dead Li generated from inadequate Li conversion reduces the cycling stability of rechargeable batteries. Herein a mono-solvent dimethyl carbonate (DMC) electrolyte was employed in contact prelithiation for the first time. We discover that the low-organic-content raw electrolyte interphase (REI) induced by this electrolyte on Li source and anode is a mixed ion/electron conductor. Therefore, electron channels can be maintained even when the Li source has been completely wrapped by the DMC-derived REI. As a result, an outstanding Li source utilization of 92.8 % and a negligible dead Li yield can be realized. This strategy renders batteries with a very high initial Coulombic efficiency (90.0 %) and an excellent capacity retention (94.9 %) over 210â cycles, highlighting the significance of REI for effective contact prelithiation.
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The frequent detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in healthcare environments, accommodations, and wastewater has attracted great attention to the risk of viral transmission by environmental fomites. However, the process of SARS-CoV-2 adsorption to exposed surfaces in high-risk environments remains unclear. In this study, we investigated the interfacial dynamics of single SARS-CoV-2 pseudoviruses with plasmonic imaging technology. Through the use of this technique, which has high spatial and temporal resolution, we tracked the collision of viruses at a surface and differentiated their stable adsorption and transient adsorption. We determined the effect of the electrostatic force on virus adhesion by correlating the solution and surface chemistry with the interfacial diffusion velocity and equilibrium position. Viral adsorption was found to be enhanced in real scenarios, such as in simulated saliva. This work not only describes a plasmonic imaging method to examine the interfacial dynamics of a single virus but also provides direct measurements of the factors that regulate the interfacial adsorption of SARS-CoV-2 pseudovirus. Such information is valuable for understanding virus transport and environmental transmission and even for designing anticontamination surfaces.
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COVID-19 , SARS-CoV-2 , Fômites , HumanosRESUMO
OBJECTIVE: To investigate the role of HELQ in chemo-resistance of epithelial ovarian carcinoma (EOC), which is a critical factor of patients' prognosis. METHODS: Immunohistochemistry, survival analysis of our 87 EOC patients and bioinformatics analysis of The Cancer Genome Atlas (TCGA) datasets (Nature, 2011) disclosed the clinical importance of HELQ expression. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western Blot analyses of EOC tissue were used to confirm it. Ectopic overexpression and RNA interference knockdown of HELQ were carried out in OVCAR3 and A2780 cell lines, respectively, to determine the effect of altered HELQ expression on cellular response to cisplatin by CCK8 assay. The DNA repair capacity of these cells was evaluated by using host-cell reactivation assay. Western Blot analyses were carried out to determine the effect of HLEQ on the DNA repair genes by using cells with altered HELQ expression. RESULTS: HELQ expression associates with response of EOC patients to platinum-based chemotherapy and their overall survival (OS), disease free survival (DFS). HELQ overexpression or knockdown, respectively, increased and decreased the cellular resistance to cisplatin, DNA repair activity, and expression of DNA repair proteins of Nucleotide excision repair (NER) pathway. CONCLUSIONS: HELQ plays an important role in regulating the expression of DNA repair proteins NER pathway which, in turn, contributes to cellular response to cisplatin and patients' response to platinum-based chemotherapy. Our results demonstrated that HELQ could serve as a novel indicator for chemo-resistance of EOC, which can predict the prognosis of the disease.
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Cisplatino/farmacologia , DNA Helicases/metabolismo , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/enzimologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/enzimologia , Antineoplásicos/farmacologia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , DNA Helicases/biossíntese , DNA Helicases/deficiência , DNA Helicases/genética , Reparo do DNA , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Técnicas de Silenciamento de Genes , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Taxa de SobrevidaRESUMO
Regulatory sequences and transposable elements (TEs) account for a large proportion of the genomic sequences of species; however, their roles in gene transcription, especially tissue-specific expression, remain largely unknown. Pigs serve as an excellent animal model for studying genomic sequence biology due to the extensive diversity among their wild and domesticated populations. Here, we conducted an integrated analysis using H3K27ac ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data from 10 different tissues of seven fetuses and eight closely related adult pigs. We aimed to annotate the regulatory elements and TEs to elucidate their associations with histone modifications and mRNA expression across different tissues and developmental stages. Based on correlation analysis between mRNA expression and H3K27ac and H3K4me3 peak activity, results indicated that H3K27ac exhibited stronger associations with gene expression than H3K4me3. Furthermore, 1.45% of TEs overlapped with either the H3K27ac or H3K4me3 peaks, with the majority displaying tissue-specific activity. Notably, a TE subfamily (LTR4C_SS), containing binding motifs for SIX1 and SIX4, showed specific enrichment in the H3K27ac peaks of the adult and fetal ovaries. RNA-seq analysis also revealed widespread expression of TEs in the exons or promoters of genes, including 4 688 TE-containing transcripts with distinct development stage-specific and tissue-specific expression. Of note, 1 967 TE-containing transcripts were enriched in the testes. We identified a long terminal repeat (LTR), MLT1F1, acting as a testis-specific alternative promoter in SRPK2 (a cell cycle-related protein kinase) in our pig dataset. This element was also conserved in humans and mice, suggesting either an ancient integration of TEs in genes specifically expressed in the testes or parallel evolutionary patterns. Collectively, our findings demonstrate that TEs are deeply embedded in the genome and exhibit important tissue-specific biological functions, particularly in the reproductive organs.
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Elementos de DNA Transponíveis , Transcriptoma , Humanos , Masculino , Camundongos , Animais , Suínos/genética , Elementos de DNA Transponíveis/genética , Histonas/genética , Histonas/metabolismo , RNA Mensageiro , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Transativadores/genética , Transativadores/metabolismoRESUMO
Label-free probing of the material composition of (bio)nano-objects directly in solution at the single-particle level is crucial in various fields, including colloid analysis and medical diagnostics. However, it remains challenging to decipher the constituents of heterogeneous mixtures of nano-objects with high sensitivity and resolution. Here, we present deep-learning plasmonic scattering interferometric microscopy, which is capable of identifying the composition of nanoparticles automatically with high throughput at the single-particle level. By employing deep learning to decode the quantitative relationship between the interferometric scattering patterns of nanoparticles and their intrinsic material properties, this technique is capable of high-throughput, label-free identification of diverse nanoparticle types. We demonstrate its versatility in analyzing dynamic surface chemical reactions on single nanoparticles, revealing its potential as a universal platform for nanoparticle imaging and reaction analysis. This technique not only streamlines the process of nanoparticle characterization, but also proposes a methodology for a deeper understanding of nanoscale dynamics, holding great potential for addressing extensive fundamental questions in nanoscience and nanotechnology.
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Lysidrhodosides A-I (1-9), nine acylphloroglucinol glucoside derivatives along with three known analogues (10-12) were isolated from the leaves of Lysidice rhodostegia. Their structures and absolute configuration were elucidated by spectroscopic data analysis (NMR, UV, IR, HR-ESI-MS), single-crystal X-ray diffraction, and acid hydrolysis with HPLC analysis. Notably, compounds 7-9 represent the first examples of 3-methylbutyryl phloroglucinol glucoside dimers isolated from this plant. Additionally, compounds 1-12 were assessed for their inhibitory effects on nitric oxide (NO) in the LPS-induced BV-2 cells. The results showed that compounds 6 and 12 significantly inhibited the production of the inflammatory mediator NO, with an inhibitory rate of 95.96 and 91.13% at a concentration of 50 µM, respectively.
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Fabaceae , Glucosídeos , Glucosídeos/farmacologia , Estrutura Molecular , Floroglucinol/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Espectroscopia de Ressonância Magnética , Fabaceae/química , Óxido NítricoRESUMO
The gastrointestinal tract is essential for food digestion, nutrient absorption, waste elimination, and microbial defense. Single-cell transcriptome profiling of the intestinal tract has greatly enriched our understanding of cellular diversity, functional heterogeneity, and their importance in intestinal tract development and disease. Although such profiling has been extensively conducted in humans and mice, the single-cell gene expression landscape of the pig cecum remains unexplored. Here, single-cell RNA sequencing was performed on 45â¯572 cells obtained from seven cecal samples in pigs at four different developmental stages (days (D) 30, 42, 150, and 730). Analysis revealed 12 major cell types and 38 subtypes, as well as their distinctive genes, transcription factors, and regulons, many of which were conserved in humans. An increase in the relative proportions of CD8 + T and Granzyme A (low expression) natural killer T cells (GZMA low NKT) cells and a decrease in the relative proportions of epithelial stem cells, Tregs, RHEX + T cells, and plasmacytoid dendritic cells (pDCs) were noted across the developmental stages. Moreover, the post-weaning period exhibited an up-regulation in mitochondrial genes, COX2 and ND2, as well as genes involved in immune activation in multiple cell types. Cell-cell crosstalk analysis indicated that IBP6 + fibroblasts were the main signal senders at D30, whereas IBP6 - fibroblasts assumed this role at the other stages. NKT cells established interactions with epithelial cells and IBP6 + fibroblasts in the D730 cecum through mediation of GZMA-F2RL1/F2RL2 pairs. This study provides valuable insights into cellular heterogeneity and function in the pig cecum at different development stages.
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Ceco , Intestinos , Humanos , Camundongos , Animais , Suínos , Ceco/metabolismo , Trato Gastrointestinal , Perfilação da Expressão Gênica/veterinária , Células EpiteliaisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: A widely used traditional prescription, Yi-Gan San (YGS) is a remedy for neurodegenerative disorders. The formulation consists of seven Chinese medicinal materials in specific proportions, namely Uncariae Ramulus cum Uncis (Uncaria rhynchophylla (Miq.) Miq. ex Havil.), Bupleuri Radix (Bupleurum chinense DC.), Angelicae Sinensis Radix (Angelica sinensis (Oliv.) Diels), Chuanxiong Rhizoma (Ligusticum wallichii Franch.), Poria (Poria cocos (Schw.) Wolf), Atractylodis Macrocephalae Rhizoma (Atractylodes macrocephala Koidz.) and Glycyrrhizae Radix et Rhizoma (Glycyrrhiza uralensis Fisch.). Using YGS has been shown to alleviate various behavioural and psychological symptoms of dementia (BPSD). AIM OF THIS REVIEW: The goal of this review is to give up-to-date information about the traditional uses, chemistry, pharmacology and clinical efficacy of YGS based on the scientific literature and to learn the current focus and provide references in the next step. MATERIALS AND METHODS: The database search room was accessed using the search terms "Yi-Gan San" and "Yokukansan" to obtain results from resources such as Web of Science, PubMed, Google Scholar and Sci Finder Scholar. We not only consulted the literature of fellow authors for this review but also explored classical medical books. RESULTS: YGS has been used to cure neurosis, sleeplessness, night weeping and restlessness in infants. Its chemical components primarily consist of triterpenes, flavonoids, phenolics, lactones, alkaloids and other types of compounds. These active ingredients displayed diverse pharmacological activities to ameliorate BPSD by regulating serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmission. In addition, YGS showed neuroprotective, antistress, and anti-inflammatory effects. The majority of cases of neurodegenerative disorders are treated with YGS, including Alzheimer's disease and dementia with Lewy bodies. CONCLUSIONS: Based on previous studies, YGS has been used as a traditional prescription in East Asia, such as Japan, Korea and China, and it has diverse chemical compounds and multiple pharmacological activities. Nevertheless, few experimental studies have focused on chemical and quantitative YGS studies, suggesting that further comprehensive research on its chemicals and quality assessments is critical for future evaluations of drug efficacy.
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Angelica sinensis , Atractylodes , Medicamentos de Ervas Chinesas , Glycyrrhiza uralensis , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Angelica sinensis/química , PrescriçõesRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the Podocarpus species belong to the Podocarpaceae family and are largely distributed in the southern hemisphere. Beside the commercially and ecologically valuable, plants of the Podocarpus species are also used in traditional medicines in some countries for treating asthma, fever, venereal diseases, eye diseases, etc. AIM OF THE STUDY: In recent decades, the identities and pharmacological activities of phytochemicals extracted from Podocarpus plants have been widely studied. However, there have been no comprehensive and systematic reviews. This article aims to systematically review the latest research on the putative mechanisms underlying pharmacological actions of phytochemicals from the Podocarpus species, as well as to lay a foundation for promoting the development of plant resources from this genus, further drug research, and product development. MATERIALS AND METHODS: A comprehensive search of PubMed, Google Scholar, Web of Science, Elsevier and CNKI databases was conducted using the keywords "Podocarpus", "traditional usage", "phytochemistry", "pharmacology", "nagilactone", etc. Related papers published among July 1964 to February 2023 were collected to summarize the research progress. All plant names were determined through the "The Plant List" (http://www.theplantlist.org/). RESULTS: To date, 262 chemical constituents have been isolated and identified from 26 Podocarpus plants; among these, norditerpene bilactone is the main pharmacologically active component. Norditerpene bilactones are reported to have anti-cancer, anti-inflammatory, antioxidant, antibacterial, anti-tyrosinase, neuroprotective, anti-plasmodial, anti-mutagenic, and anti-atherosclerotic properties as well as other pharmacological activities, which support its traditional uses. CONCLUSION: Extensive studies on phytochemistry and pharmacology of Podocarpus species lead to discovery of a series of hopeful leading compounds with unique chemical structure, especially the nor- and bis-norditerpenoid dilactones with four isoprene units. These compounds have been proved to possess various pharmacological activities. This review will provide a reference for further research and promote the idea of combining modern research with traditional medicinal applications of Podocarpus plants.
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Plantas Medicinais , Etnofarmacologia , Fitoterapia , Medicina Tradicional , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/químicaRESUMO
This paper introduces professor SUN Shen-tian's clinical thoughts and his characteristics of acupuncture techniques for the treatment of depression based on "psychosomatic medicine". Professor SUN, the master of traditional Chinese medicine, believes that depression refers to comorbidity of "heart mind" and "body", resulting from the "body-mind" disharmony, specially dominated by the emotional disorder. This disease is located in the brain, with the injury of mind and closely related to the heart and liver dysfunction. In pathogenesis, the dysfunction of brain mind and the unhealthy conditions of body and mind are involved. The treatment should focus on "regulating the mind, improving the intelligence, co-modulating the abdominal and brain functions and treating the physical and mental disorders". Baihui (GV 20), Ningshen (Extra) and emotional area on the head are selected as the main points to benefit the intelligence and calming down the mind; the abdominal region 1 and region 8 of "Sun's abdominal acupuncture" are used as the main points of the abdomen to regulate the brain functions. The point prescription is modified according to the symptoms and etiologies. The repeated transcranial acupuncture stimulation and electroacupuncture at low frequency (2 Hz) are crucial to the therapeutic effect. Reliving anxious emotions is specially considered before acupuncture, and the mind is protected and deqi is consolidated during acupuncture.
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Terapia por Acupuntura , Acupuntura , Humanos , Depressão/terapia , Pontos de Acupuntura , Terapia por Acupuntura/métodos , Medicina Tradicional ChinesaRESUMO
Five new sesquiterpenoids (1-5), elephantmollides A-E, along with four known compounds (6-9), were isolated from the whole plants of E. mollis. Their planar structures were elucidated using the spectroscopic methods, including HRESIMS, IR, UV, and NMR (1H, 13C, DEPT, HSQC, HMBC, 1H-1H COSY). The relative configurations of them were partially deduced by the NOESY experiment, and the absolute configurations were assigned by comparing the calculated electronic circular dichroism (ECD) results with the experimental data. In addition, cytotoxic activities of 1-9 against HepG2 cells ware tested, and compounds 1-9 exhibited cytotoxic activities with IC50 values ranging from 6.7 to 25.8 µM.
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EpsteinâBarr virus (EBV)-associated gastric cancer (GC) manifests an intriguing immunotherapy response. However, the cellular basis for EBV-imprinted tumour immunity and on-treatment response remains undefined. This study aimed to finely characterize the dynamic tumour immune contexture of human EBV (+) GC treated with immunochemotherapy by longitudinal scRNA-seq and paired scTCR/BCR-seq. EBV (+) GC exhibits an inflamed-immune phenotype with increased T-cell and B-cell infiltration. Immunochemotherapy triggers clonal revival and reinvigoration of effector T cells which step to determine treatment response. Typically, an antigen-specific ISG-15+CD8+ T-cell population is highly enriched in EBV (+) GC patients, which represents a transitory exhaustion state. Importantly, baseline intratumoural ISG-15+CD8+ T cells predict immunotherapy responsiveness among GC patients. Re-emerged clonotypes of pre-existing ISG-15+CD8+ T cells could be found after treatment, which gives rise to a CXCL13-expressing effector population in responsive EBV (+) tumours. However, LAG-3 retention may render the ISG-15+CD8+ T cells into a terminal exhaustion state in non-responsive EBV (+) tumours. In accordance, anti-LAG-3 therapy could effectively reduce tumour burden in refractory EBV (+) GC patients. Our results delineate a distinct implication of EBV-imprinted on-treatment T-cell immunity in GC, which could be leveraged to optimize the rational design of precision immunotherapy.
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Linfócitos T CD8-Positivos , Infecções por Vírus Epstein-Barr , Humanos , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4/genética , Exaustão das Células T , ImunoterapiaRESUMO
Studying the localized electrocatalytic activity of heterogeneous electrocatalysts is crucial for understanding electrocatalytic reactions and further improving their performance. However, correlating the electrocatalytic activity with the microscopic structure of two-dimensional (2D) electrocatalysts remains a great challenge due to the lack of in situ imaging techniques and methods of tuning structures with atomic precision. Here, we present a general method of probing the layer-dependent electrocatalytic activity of 2D materials in situ using a plasmonic imaging technique. Unlike the existing methods, this approach was used to visualize the surface charge density and electrocatalytic activity of single 2D MoS2 nanosheets, enabling the correlation of layer-dependent electrocatalytic activity with the surface charge density of single MoS2 nanosheets. This work provides insights into the electrocatalytic mechanisms of 2D transition metal dichalcogenides, and our approach can serve as a promising platform for investigating electrocatalytic reactions at the heterogeneous interface, thus guiding the rational design of high-performance electrocatalysts.
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This 33-color panel delineates immune phenotypes of the major lymphocyte subsets in murine tissues. The panel identifies surface markers for cell activation, differentiation, and exhaustion, and chemokine receptors, in CD4 T cells, CD8 T cells, γδ T cells, NK cells, NKT cells and B cells in spleen and liver. This panel was designed to include only surface markers to avoid the need for fixation and permeabilization steps. Cells were analyzed on a full spectrum flow cytometer, 5-Laser Aurora system (Cytek Biosciences). This panel enables in-depth immunophenotyping of murine lymphocytes in immune and non-immune tissues of mice. It could be a tool for systematic analysis of immune cell response to infectious diseases and immune disorders.
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Células Matadoras Naturais , Subpopulações de Linfócitos , Animais , Linfócitos B , Biomarcadores/análise , Citometria de Fluxo , Imunofenotipagem , CamundongosRESUMO
Contact prelithiation is strongly considered for compensating the initial capacity loss of lithium-ion batteries, exhibiting great potential for ultralong cycle life of working batteries and the application of large-scale energy-storage systems. However, the utilization of the sacrificial Li source for contact prelithiation is low (<65%). Herein the fundamental mechanism of contact prelithiation is described from the perspective of the Li source/anode interfaces by regulating the initial contact state, and a clear illustration of the pathogeny for capacity attenuation is successfully delivered. Specifically, creating plentiful electron channels is an access to making contact prelithiation with a higher Li utilization, as the mitigated local current density that reduces the etching of Li dissolution and SEI extension on electron channels. A vacuum thermal evaporation for depositing the Li film enables the contact interface to possess an adequate electron channel construction, rendering a Li utilization of 91.0%, and the dead Li yield is significantly reduced in a working battery.
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Background: The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance. Methods: This was a multicenter study and included 277 histologically confirmed CIN3 women who underwent cold knife conization (CKC) from January 2019 to December 2020. The methylation levels of PAX1 (PAX1m) and ZNF582 (ZNF582m) were determined by quantitative methylation-specific polymerase chain reaction (qMSP) and expressed in ΔCp. Receiver operating characteristic curves were used to evaluate predictive accuracy. Results: The final pathological results in 48 (17.33%) patients were inflammation or low-grade squamous intraepithelial lesion (LSIL), 190 (68.59%) were high-grade squamous intraepithelial lesion (HSIL), and 39 (14.08%) were squamous cervical cancer (SCC). PAX1m and ZNF582m increased as lesions progressed from inflammation/LSIL, HSIL, to SCC. PAX1 and ZNF582 methylation yielded better prediction performance compared with common screening strategies, whether individually or combined. A 4.33-fold increase in the probability of inflammation/LSIL was observed in patients with lower ZNF582 methylation levels (ΔCpZNF582â ≥ 19.18). A 6.53-fold increase in SCC risk was observed in patients with elevated ZNF582 methylation (ΔCpZNF582â < 7.09). Conclusions: DNA methylation would be an alternative screening method to triage and predict the final outcome of conization in CIN3 cases.