RESUMO
Plant innate immunity is capable of combating diverse and ever evolving pathogens. The plasticity of innate immunity could be boosted by RNA processing. Arabidopsis thaliana CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5 (CPR5), a key negative immune regulator, is a component of the nuclear pore complex. Here we further identified CPR5 as a component of RNA processing complexes. Through genetic screening, we found that RNA splicing activator NineTeen Complex and RNA polyadenylation factor CLEAVAGE AND POLYADENYLATION SPECIFICITY FACTOR, coordinately function downstream of CPR5 to activate plant immunity. CPR5 and these two regulators form a complex that is localized in nuclear speckles, an RNA processing organelle. Intriguingly, we found that CPR5 is an RNA-binding protein belonging to the Transformer 2 (Tra2) subfamily of the serine/arginine-rich family. The RNA recognition motif of CPR5 protein binds the Tra2-targeted RNA sequence in vitro and is functionally replaceable by those of Tra2 subfamily proteins. In planta, it binds RNAs of CPR5-regulated alternatively spliced genes (ASGs) identified by RNA-seq. ARGONAUTE 1 (AGO1) is one of the ASGs and, consistent with this, the ago1 mutant suppresses the cpr5 phenotype. These findings reveal that CPR5 is an RNA-binding protein linking RNA processing with plant immunity.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Membrana/metabolismo , Imunidade Vegetal/genética , Processamento Pós-Transcricional do RNA , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, and the development of novel therapeutic strategies for HNSCC requires a profound understanding of tumor cells and the tumor microenvironment (TME). Additionally, HNSCC has a poor prognosis, necessitating the use of genetic markers for predicting clinical outcomes in HNSCC. In this study, we performed single-cell sequencing analysis on tumor tissues from seven HNSCC patients, along with one adjacent normal tissue. Firstly, the analysis of epithelial cell clusters revealed two clusters of malignant epithelial cells, characterized by unique gene expression patterns and dysregulated signaling pathways compared to normal epithelial cells. Secondly, the examination of the TME unveiled extensive crosstalk between fibroblasts and malignant epithelial cells, potentially mediated through ligand-receptor interactions such as COL1A1-SDC1, COL1A1-CD44, and COL1A2-SDC1. Furthermore, transcriptional heterogeneity was observed in immune cells present in the TME, including macrophages and dendritic cells. Finally, leveraging the gene expression profiles of malignant epithelial cells, we developed a prognostic model comprising six genes, which we validated using two independent datasets. These findings shed light on the heterogeneity within HNSCC tumors and the intricate interplay between malignant cells and the TME. Importantly, the developed prognostic model demonstrates high efficacy in predicting the survival outcomes of HNSCC patients.
Assuntos
Carcinoma , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Neoplasias de Cabeça e Pescoço/genética , Células Epiteliais , Microambiente Tumoral/genéticaRESUMO
LiNi0.8Mn0.1Co0.1O2 with high nickel content plays a critical role in enabling lithium metal batteries (LMBs) to achieve high specific energy density, making them a prominent choice for electric vehicles (EVs). However, ensuring the long-term cycling stability of the cathode electrolyte interfaces (CEIs), particularly at fast-charge conditions, remains an unsolved challenge. The decay mechanism associated with CEIs and electrolytes in LMB at high current densities is still not fully understood. To address this issue, in situ Fourier transform infrared (FTIR) is employed to observe the dynamic process of formation/disappearance/regeneration of CEIs during charge and discharge cycles. These dynamic processes further exacerbate the instability of CEIs as current density increases, leading to rupture and dissolution of CEIs and subsequent deterioration in battery performance because of continuous electrolyte reactions. Additionally, the dynamic changes occurring within individual components of CEIs at different cycling stages and various current densities are also discussed. The results demonstrate that excellent capacity retention at small current density is attributed to enrichment of inorganic compounds (Li2CO3, LiF, etc.) and rendering better stability and smaller expansion of CEIs. The key to achieving excellent electrochemical performance at high current densities lies on protecting CEIs, mainly inorganic components.
RESUMO
Placental chorion/labyrinth trophoblasts are energy demanding which is met by the mitochondrial oxidative phosphorylation. Exercise enhances placental development and mitochondrial biogenesis, but the underlying mechanisms remain poorly understood. To address, female C57BL/6 J mice were randomly assigned into two groups: a control group and an exercise (EX) group. All animals were acclimated to treadmill exercise for 1 week before mating, but only the EX group was subjected to daily exercise during pregnancy from embryonic day (E) 1.5 to E16.5. Placenta were collected at E18.5 for biochemical and histochemical analyses, and primary trophoblast cells were isolated from the E18.5 placenta for further analyses. The data showed that exercise during pregnancy promoted the expression of syncytiotrophoblast cell markers, indicating trophoblast cell differentiation, which was closely associated with elevated mitochondrial biogenesis and oxidative metabolism in the E18.5 placenta. In addition, exercise during pregnancy activated peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α), which was associated with upregulated placental α-ketoglutarate and the expression of isocitrate dehydrogenases and ten-eleven translocations, facilitating DNA demethylation of the Pgc1a promoter. Furthermore, exercise upregulated fibronectin type III domain containing 5 expression and the secretion of its cleaved form, irisin, which is known to activate PGC-1α. These data suggest that exercise-induced activation of PGC-1α, via epigenetic modifications, is responsible for promoting mitochondrial energy metabolism and chorion/labyrinth trophoblast development.
Assuntos
Fibronectinas , Placentação , Animais , Feminino , Camundongos , Gravidez , Fibronectinas/genética , Fibronectinas/metabolismo , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Placenta/metabolismo , Fatores de Transcrição/genética , Trofoblastos/metabolismoRESUMO
Two metal borate-carbonates, M6[Cd2(CO3)2(B12O18)(OH)6] [M = K (1), Rb (2)], were obtained under surfactant-thermal conditions. In 1 and 2, each cyclic [(B12O18)(OH)6]6- anion captures two CdCO3 in two sides of the rings and finally forms the unusual (CdCO3)2@[(B12O18)(OH)6] cluster. Both 1 and 2 show moderate birefringence. Density functional theory calculations indicate that carbonate groups have a major contribution to electron-related optical transition.
RESUMO
AIMS: The survival of inoculated Escherichia coli on Fuji apples in Washington State orchards was studied, considering evaporative cooling, canopy location, year, and region, with the examination of sunlight exposure and inoculation levels in year 2. METHODS AND RESULTS: Rifampicin-resistant E. coli was applied to Fuji apples. Initial concentrations for the high-inoculation study were 7.4 ± 0.3 log10 CFU per apple and 3.4 ± 0.3 log10 CFU per apple for the low-inoculation study. Enumeration of E. coli was conducted at 0, 2, 10, 18, 34, 42, 58, 82, 106, and 154 h after inoculation. Results were analyzed using Tukey's honest significance difference test and a log-linear model. Log-linear, Weibull, and Biphasic models characterized E. coli die-off patterns for high and low inoculations. The application of evaporative overhead cooling water did not significantly influence E. coli survival on Fuji apples; inoculation level and sunlight exposure were significant factors in a log-linear model. E. coli decreased by 5.5 ± 1.3 and 3.3 ± 0.4 log10 CFU per apple for high and low inoculated apples, respectively, by 154 h. The Biphasic model best explained the die-off pattern for high and low-inoculated Fuji apples. CONCLUSIONS: Overhead evaporative cooling, a useful fruit quality practice, did not impact the survival of generic E. coli on Fuji apple surfaces. The significant impact of sunlight exposure and inoculation levels on die-off highlights the importance of ultraviolet radiation in risk reduction and the need for various inoculum concentrations in preharvest field studies.
RESUMO
H2A.Z, the most evolutionarily conserved variant of histone H2A, plays a pivotal role in chromatin remodeling and contributes significantly to gene transcription and genome stability. However, the role of H2A.Z in the silkworm (Bombyx mori) remains unclear. In this study, we cloned the BmH2A.Z from B. mori. The open reading frame of BmH2A.Z is 390 bp, encoding 129 amino acids, with a confirmed molecular weight of 13.4 kDa through prokaryotic expression analysis. Sequence analysis revealed that BmH2A.Z has a conserved H2A.Z domain and is closely related to the systemic evolution of other known H2A.Zs. The expression profile of BmH2A.Z at various developmental stages of the B. mori exhibited the highest expression level in the 1st instar, followed by the grain stage and the 2nd instar, and the lowest expression level in the moth. The highest transcript level of BmH2A.Z was observed in the head, with relatively lower levels detected in the blood than in the other tissues under consideration. In addition, the upregulation of BmH2A.Z resulted in the amplified expression of B. mori nucleopolyhedrovirus (BmNPV) genes, thus facilitating the proliferation of BmNPV. This study establishes a foundation for investigating the role of BmH2A.Z in B. mori and its participation in virus-host interactions.
Assuntos
Sequência de Aminoácidos , Bombyx , Clonagem Molecular , Histonas , Proteínas de Insetos , Animais , Bombyx/genética , Bombyx/metabolismo , Bombyx/virologia , Histonas/metabolismo , Histonas/genética , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Larva/genética , Larva/metabolismo , Larva/crescimento & desenvolvimento , Filogenia , Nucleopoliedrovírus/genética , Alinhamento de SequênciaRESUMO
BACKGROUND: Aquatic products are rich in nutrients and unique in flavor, and are popular among the public. However, aquatic products are extremely susceptible to quality degradation during storage, of which odor deterioration is the most obvious and influential aspect. Odor deterioration in aquatic products is widespread and severely affects overall flavor and quality. In this study, odor deterioration and flavor-related quality degradation of tilapia during cold storage are discussed, focusing on the changes in volatile compounds and the evolution of free fatty acids (FFAs), free amino acids (FAAs), nucleotides, and microbial diversity. RESULTS: A total of 63 volatile compounds were detected by gas chromatography-mass spectrometry, including 11 hydrocarbons, 10 alcohols, 6 aldehydes, 8 ketones, 6 esters, 9 aromatics, 3 phenols, and 10 other compounds. Microbial diversity analysis revealed that Acinetobacter, Psychrobacter, Vagococcus, and Myroides were the main dominant species of tilapia at the end of cold storage and predicted that microorganisms could influence the flavor of tilapia by participating in important metabolic pathways. Meanwhile, the evolution of FFAs, FAAs, and nucleotides also had a significant impact on odor deterioration, as evidenced by the contribution of unsaturated fatty acids (such as oleic acid and linoleic acid), Lys, and off-flavor nucleotides (HxR and Hx) to the undesirable flavor. Oxidation of oleic acid and linoleic acid resulted in changes in aldehydes, with Lys, HxR, and Hx being key flavor precursors and off-flavor contributors. CONCLUSION: This study contributes to a comprehensive overview of odor deterioration and the evolution of flavor-related quality in tilapia during cold storage, providing new insights into the regulation of overall flavor and quality. © 2023 Society of Chemical Industry.
Assuntos
Tilápia , Compostos Orgânicos Voláteis , Animais , Armazenamento de Alimentos , Ácidos Graxos não Esterificados/análise , Aminoácidos/química , Aldeídos/análise , Ácidos Linoleicos , Ácidos Oleicos , Compostos Orgânicos Voláteis/químicaRESUMO
Listeria monocytogenes biofilms formed on food-contact surfaces within food-processing facilities pose a significant challenge, serving as persistent sources of cross-contamination. In this review, we examined documented cases of foodborne outbreaks and recalls linked to L. monocytogenes contamination on equipment surfaces and in the food production environment, provided an overview of the prevalence and persistence of L. monocytogenes in different food-processing facilities, and discussed environmental factors influencing its biofilm formation. We further delved into antimicrobial interventions, such as chemical sanitizers, thermal treatments, biological control, physical treatment, and other approaches for controlling L. monocytogenes biofilms on food-contact surfaces. This review provides valuable insights into the persistent challenge of L. monocytogenes biofilms in food processing, offering a foundation for future research and practical strategies to enhance food safety.
Assuntos
Biofilmes , Microbiologia de Alimentos , Listeria monocytogenes , Listeria monocytogenes/fisiologia , Biofilmes/crescimento & desenvolvimento , Manipulação de Alimentos/métodos , Contaminação de Alimentos/prevenção & controle , Contaminação de Equipamentos/prevenção & controleRESUMO
This research examined the effects of sodium alginate (SA) and vitamin C (Vc) soaking of pearl gentian grouper before waterless transportation from the perspectives of serum parameters, oxidative stress, muscle quality, and gill tissue morphology. After the fish reached semi-dormancy with a cooling rate of 3 °C/h, fish (420 ± 25 g) were distributed to 4 treatments as follows: S1 group (50 mg/L Vc and 0.1% SA were added), S2 group (50 mg/L Vc and 0.3% SA were added), S3 group (50 mg/L Vc and 0.5% SA were added), and control group (without soaking in protective fluid). After oxygenated packaging, samples were taken at 0, 8, and 16 h of waterless transportation and 12 h after rehydration, respectively. It was found that after 16 h of waterless transport, compared with the control group, cortisol, glucose, blood urea nitrogen (BUN), uric acid (UA), creatinine (CREA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) levels were significantly decreased (p < 0.05), while albumin, lysozyme (LZM), muscle pH, and total free amino acid (TFAA) contents were significantly elevated (p < 0.05) in the S3 group. Moreover, by gill tissue microscopy, it was found that the protective solution of group S3 did not cause serious deleterious morphological changes to the gill epithelium. The results showed that the grouper was soaked by protective fluid before waterless could maintain surface moisture, reduce gill and kidney function and oxidative stress damage, and maintain the stability of muscle quality. This study provides a novel transportation method for waterless preservation, which helps to reduce transportation costs and improve transportation efficiency.
Assuntos
Ácido Ascórbico , Bass , Animais , Ácido Ascórbico/farmacologia , Ácido Ascórbico/metabolismo , Bass/metabolismo , Alginatos/farmacologia , Alginatos/metabolismo , Brânquias/metabolismo , Estresse Oxidativo , Antioxidantes/metabolismo , Catalase/metabolismo , Vitaminas/farmacologia , Superóxido Dismutase/metabolismo , Músculos/metabolismo , Malondialdeído/metabolismo , Glutationa Peroxidase/metabolismoRESUMO
OBJECTIVE: The waterless transport of live fish has changed the present situation of live-fish transport. However, the waterless transport environment may cause stress in fish. This research evaluated the effect of tea polyphenol-trehalose (TPT) coating solutions on Turbot Scophthalmus maximus during waterless transport. METHODS: After cold acclimation, Turbot were coated and subsequently transported in a waterless environment for 18 h. Physiological and biochemical parameters were measured, including lysozyme (LZM) and immunoglobulin M (IgM) activities, serum creatinine (Cr) and uric acid (UA) concentrations, and nutritional flavor. RESULT: The results showed that the nonspecific immunity of Turbot was inhibited during the waterless transport; the LZM activity first increased and then decreased, and the serum Cr and UA concentrations significantly increased. In addition, the waterless transport promoted the breakdown of Turbot flesh proteins, leading to changes in nucleotides and free amino acids (FAAs). After waterless transport, the LZM and IgM activities in the TPT-treated Turbot were higher than those in the control group (CK), and the changes in FAA content and nucleotides were smaller than those observed in the CK group. CONCLUSION: This study shows that the use of TPT coating solution can reduce the impact of waterless transportation stress on the immune and metabolic functions of Turbot and can maintain the meat quality and flavor of Turbot.
Assuntos
Linguados , Polifenóis , Estresse Fisiológico , Animais , Polifenóis/farmacologia , Polifenóis/química , Estresse Fisiológico/efeitos dos fármacos , Meios de Transporte , Aquicultura/métodosRESUMO
Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.
Assuntos
Glicosídeos , Picrorhiza , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Linhagem Celular Tumoral , Picrorhiza/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Medicamentos de Ervas Chinesas/química , TriterpenosRESUMO
Intestinal remodelling is dynamically regulated by energy metabolism. Exercise is beneficial for gut health, but the specific mechanisms remain poorly understood. Intestine-specific apelin receptor (APJ) knockdown (KD) and wild-type male mice were randomly divided into two subgroups, with/without exercise, to obtain four groups: WT, WT with exercise, APJ KD and APJ KD with exercise. Animals in the exercise groups were subjected to daily treadmill exercise for 3 weeks. Duodenum was collected at 48 h after the last bout of exercise. AMP-activated protein kinase (AMPK) α1 KD and wild-type mice were also utilized for investigating the mediatory role of AMPK on exercise-induced duodenal epithelial development. AMPK and peroxisome proliferator-activated receptor γ coactivator-1 α were upregulated by exercise via APJ activation in the intestinal duodenum. Correspondingly, exercise induced permissive histone modifications in the PR domain containing 16 (PRDM16) promoter to activate its expression, which was dependent on APJ activation. In agreement, exercise elevated the expression of mitochondrial oxidative markers. The expression of intestinal epithelial markers was downregulated due to AMPK deficiency, and AMPK signalling facilitated epithelial renewal. These data demonstrate that exercise-induced activation of the APJ-AMPK axis facilitates the homeostasis of the intestinal duodenal epithelium. KEY POINTS: Apelin receptor (APJ) signalling is required for improved epithelial homeostasis of the small intestine in response to exercise. Exercise intervention activates PRDM16 through inducing histone modifications, enhanced mitochondrial biogenesis and fatty acid metabolism in duodenum. The morphological development of duodenal villus and crypt is enhanced by the muscle-derived exerkine apelin through the APJ-AMP-activated protein kinase axis.
Assuntos
Proteínas Quinases Ativadas por AMP , Transdução de Sinais , Camundongos , Masculino , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Receptores de Apelina , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Homeostase , Mucosa Intestinal/metabolismoRESUMO
The innate immune system has developed sophisticated strategies to defense against infections. Host cells utilize the recognition machineries such as toll-like receptors and nucleotide binding and oligomerization domain-like receptors to identify the pathogens and alert immune system. However, some pathogens have developed tactics to evade host defenses, including manipulation of host inflammatory response, interference with cell death pathway, and highjack of phagocytosis signaling for a better survival and colonization in host. Enterohemorrhagic Escherichia coli (EHEC) is a notorious foodborne pathogen that causes severe tissue damages and gastrointestinal diseases, which has been reported to disturb host immune responses. Diverse bioactive compounds such as flavonoids, phenolic acids, alkaloids, saccharides, and terpenoids derived from food varieties and probiotics have been discovered and investigated for their capability of combating bacterial infections. Some of them serve as novel antimicrobial agents and act as immune boosters that harness host immune system. In this review, we will discuss how EHEC, specifically E. coli O157:H7, hijacks the host immune system and interferes with host signaling pathway; and highlight the promising role of food-derived bioactive compounds and probiotics in harnessing host innate immunity and eliminating E. coli O157:H7 infection with multiple strategies.
Assuntos
Escherichia coli Êntero-Hemorrágica , Infecções por Escherichia coli , Escherichia coli O157 , Enteropatias , Probióticos , Humanos , Escherichia coli O157/fisiologia , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/microbiologia , Imunidade InataRESUMO
The prevalence of inflammatory bowel disease (IBD) is increasing, which is concerning because IBD is a known risk factor for the development of colorectal cancer. Emerging evidence highlights environmental factors, particularly dietary factors and gut microbiota dysbiosis, as pivotal inducers of IBD onset. Goji berry, an ancient tonic food and a nutraceutical supplement, contains a range of phytochemicals such as polysaccharides, carotenoids, and polyphenols. Among these phytochemicals, L. barbarum polysaccharides (LBPs) are the most important functional constituents, which have protective effects against oxidative stress, inflammation, and neurodegeneration. Recently, the beneficial effects of goji berry and associated LBPs consumption were linked to prebiotic effects, which can prevent dysbiosis associated with IBD. This review assessed pertinent literature on the protective effects of goji berry against IBD focusing on the gut microbiota and their metabolites in mediating the observed beneficial effects.
Assuntos
Doenças Inflamatórias Intestinais , Lycium , Humanos , Prebióticos , Disbiose/prevenção & controle , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/prevenção & controle , Polissacarídeos/farmacologia , Compostos Fitoquímicos/farmacologiaRESUMO
OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.
Assuntos
Síndrome da Imunodeficiência Adquirida , Coinfecção , Tuberculose , Humanos , Vacina BCG , Coinfecção/epidemiologia , Prevalência , Fatores de Risco , Tuberculose/epidemiologia , China/epidemiologiaRESUMO
Patients undergoing kidney transplantation have a poor response to vaccination and a higher risk of disease progression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of vaccine doses and antibody titer tests against the mutant variant in these patients remains unclear. We retrospectively analyzed the risk of SARS-CoV-2 infection in a single medical center according to vaccine doses and immune responses before the outbreak. Among 622 kidney transplant patients, there were 77 patients without vaccination, 26 with one dose, 74 with two doses, 357 with three, and 88 with four doses. The vaccination status and infection rate proportion were similar to the general population. Patients undergoing more than three vaccinations had a lower risk of infection (odds ratio = 0.6527, 95% CI = 0.4324-0.9937) and hospitalization (odds ratio = 0.3161, 95% CI = 0.1311-0.7464). Antibody and cellular responses were measured in 181 patients after vaccination. Anti-spike protein antibody titer of more than 1,689.3 BAU/mL is protective against SARS-CoV-2 infection (odds ratio = 0.4136, 95% CI = 0.1800-0.9043). A cellular response by interferon-γ release assay was not correlated with the disease (odds ratio = 1.001, 95% CI = 0.9995-1.002). In conclusion, despite mutant strain, more than three doses of the first-generation vaccine and high antibody titers provided better protection against the omicron variant for a kidney transplant recipient.
Assuntos
COVID-19 , Transplante de Rim , Vacinas , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Estudos RetrospectivosRESUMO
Pyrrole-imidazole alkaloids (PIAs) constitute a highly diverse and densely functionalized subclass of marine natural products. Among them, the uncommon dimeric PIAs with ornate molecular architectures, attractive biological properties and interesting biosynthetic origin have spurred a considerable interest of chemists and biologists. The present review comprehensively summarized 84 dimeric PIAs discovered during the period from 1981 to September 2022, covering their source organisms, chemical structures, biological activities as well as biosynthesis. For a better understanding, these structurally intricate PIA dimers are firstly classified and presented according to their carbon skeleton features as well as biosynthesis pathways. Furthermore, relevant summaries focusing on the source organisms and the associated bioactivities of these compounds belonging to different chemical classes are also provided, which will help elucidate the fascinating chemistry and biology of these unusual PIA dimers.
Assuntos
Alcaloides , Produtos Biológicos , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Imidazóis/química , Pirróis/químicaRESUMO
Abnormalities of FGFR1 have been reported in multiple malignancies, suggesting FGFR1 as a potential target for precision treatment, but drug resistance remains a formidable obstacle. In this study, we explored whether FGFR1 acted a therapeutic target in human T-cell acute lymphoblastic leukemia (T-ALL) and the molecular mechanisms underlying T-ALL cell resistance to FGFR1 inhibitors. We showed that FGFR1 was significantly upregulated in human T-ALL and inversely correlated with the prognosis of patients. Knockdown of FGFR1 suppressed T-ALL growth and progression both in vitro and in vivo. However, the T-ALL cells were resistant to FGFR1 inhibitors AZD4547 and PD-166866 even though FGFR1 signaling was specifically inhibited in the early stage. Mechanistically, we found that FGFR1 inhibitors markedly increased the expression of ATF4, which was a major initiator for T-ALL resistance to FGFR1 inhibitors. We further revealed that FGFR1 inhibitors induced expression of ATF4 through enhancing chromatin accessibility combined with translational activation via the GCN2-eIF2α pathway. Subsequently, ATF4 remodeled the amino acid metabolism by stimulating the expression of multiple metabolic genes ASNS, ASS1, PHGDH and SLC1A5, maintaining the activation of mTORC1, which contributed to the drug resistance in T-ALL cells. Targeting FGFR1 and mTOR exhibited synergistically anti-leukemic efficacy. These results reveal that FGFR1 is a potential therapeutic target in human T-ALL, and ATF4-mediated amino acid metabolic reprogramming contributes to the FGFR1 inhibitor resistance. Synergistically inhibiting FGFR1 and mTOR can overcome this obstacle in T-ALL therapy.
Assuntos
Aminoácidos , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Linhagem Celular Tumoral , Antígenos de Histocompatibilidade Menor , Sistema ASC de Transporte de Aminoácidos/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Fator 4 Ativador da Transcrição/metabolismoRESUMO
OBJECTIVE: This study aimed to fill the current gap in the understanding of the knowledge, attitudes and behaviours (KAB) related to dietary Na among adult residents in Singapore. DESIGN: A cross-sectional online survey was conducted between October and December 2020 on 955 participants selected through random sampling. SETTING: The survey was conducted in Singapore. PARTICIPANTS: Participants were recruited from the Singapore Population Health Study Online Panel. RESULTS: Participants' mean age was 46·6 ± 14·1 years old and 58 % of them were females. Most of the participants were Chinese (82·1 %), 10·5 % were Indian and 4·5 % were Malay. Findings from the weighted data showed that most participants were aware of the health impact of high Na consumption. However, many participants were unaware of the recommended intake for salt (68%) and Na (83%), had misconceptions, and were unable to correctly use food labels to assess NA content (69%). Findings also alluded to the presence of knowledge gaps in the sources of Na in their diet. While 59 % of the participants reported to be limiting their consumption of Na, many reported facing barriers such as not knowing how to limit their Na intake. Participants also felt that there were limited options for low-Na foods when eating out and were lacking awareness of low-Na products. CONCLUSIONS: Findings highlighted substantial gaps in participants' knowledge and skills in managing their Na consumption. This suggests the need for more public education and improvements in the food environment.