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The quality of fermented plant leaves is closely related to the interleaf microorganisms and their metabolic activities. In this experiment, a multi-omics analysis was applied to investigate the link between the structural composition of the phyllosphere microbial community and the main metabolites during the fermentation process. It was found that the whole fermentation process of cigar leaves could be divided into three stages, in which the Mid-Stage was the most active period of microbial metabolic activities and occupied an important position. Staphylococcus, Brevundimonas, Acinetobacter, Brevibacterium, Pantoea, Aspergillus, Wallemia, Meyerozyma, Sampaiozyma, Adosporium and Trichomonascus played important roles in this fermentation. Staphylococcus and Aspergillus are the microorganisms that play an important role in the fermentation process. Staphylococcus were strongly correlated with lipids and amino acids, despite its low abundance, Stenotrophomonas is importantly associated with terpene and plays a significant role throughout the process. It is worth noting that Wapper exists more characteristic fungal genera than Filler and is more rapid in fermentation progress, which implies that the details of the fermentation process should be adjusted appropriately to ensure stable quality when faced with plant leaves of different genotypes. This experiment explored the relationship between metabolites and microorganisms, and provided a theoretical basis for further optimizing the fermentation process of plant leaves and developing techniques to improve product quality. Biomarker is mostly present in the pre-fermentation phase, but the mid-fermentation phase is the most important part of the process.
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Transition-metal phosphates/phosphides showcase significant promise for energy-related applications because of their high theoretical electrochemical characteristics. However, sluggish electro/ion transfer rates and kinetically unfavorable reaction sites hinder their application at high mass loading. Herein, a self-supporting electrode based on transition-metal phosphates was successfully fabricated via a one-step electrodeposition process. The nanosheet structure of transition-metal phosphates, formed by interconnecting nanoparticles, effectively mitigates the impact of stress and achieves a high mass-loading (21 mg cm-2) of the electrode. Additionally, the oxygen vacancy-rich and porous nanostructure of transition-metal phosphates endows the as-prepared electrodes with a significantly increased conductivity and fast ion migration rate for enhancing electrochemical kinetics. Consequently, the as-fabricated transition-metal phosphate electrode displays the highest areal specific capacity of 39.2F cm-2. Furthermore, the asymmetric supercapacitor achieves a maximum energy density of 0.79 mWh cm-2 and a high capacity retention of 93.0 % for 10000 cycles under 60 mA cm-2. This work provides an ideal strategy for fabricating flexible electrodes with high mass loading and synthesizing transition-metal phosphate electrodes rich in oxygen vacancies.
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The gut microbiome plays a key role in regulating the gut-skin axis, and host genetics partially influence this regulation. The study investigated the role of gut microbiota and host genetics in the gut-skin axis, focusing on the unusual "coffee-like" color phenotype observed in TYRP1 mutant Oujiang Color Common Carp. We employed comparative high-throughput omics data from wild-type and mutant fish to quantify the influence of both genetics and gut microbes on skin transcriptomic expression and blood metabolites. We found 525 differential metabolites (DMs) and 45 distinct gut microbial genera in TYRP1 mutant fish compared to wild type. Interaction and causal mediation analyses revealed a complex interplay. The TYRP1 mutation likely triggers an inflammatory pathway involving Acinetobacter bacteria, Leukotrience-C4 and Spermine. This inflammatory response appears to be counterbalanced by an anti-inflammatory cardiovascular genetic network. The net effect is the upregulation of COMT, PLG, C2, C3, F10, TDO2, MHC1, and SERPINF2, leading to unusual coffee-like coloration. This study highlights the intricate interplay between gut microbiota, host genetics, and metabolic pathways in shaping complex phenotypes.
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Carpas , Microbioma Gastrointestinal , Mutación , Pigmentación de la Piel , Animales , Carpas/genética , Carpas/microbiología , Carpas/metabolismo , Pigmentación de la Piel/genética , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Transcriptoma , Piel/metabolismo , Piel/microbiologíaRESUMEN
BACKGROUND: Lower respiratory tract infection (LRTI) has long been an important threat to people's life and health, so the rapid diagnosis of LRTI is of great significance in clinical treatment. In recent years, the development of the sequencing technology provides a new direction for the rapid diagnosis of LRTI. In this review, the advantages and disadvantages of second-generation sequencing techniques represented by metagenomics next-generation sequencing (mNGS) and droplet digital polymerase chain reaction (ddPCR) in LRTI were reviewed. Furthermore, it offers insights into the future trajectory of this technology, highlighting its potential to revolutionise the field of respiratory infection diagnostics. OBJECTIVE: This review summarises developments in mechanistic research of second-generation sequencing technology their relationship with clinical practice, providing insights for future research. METHODS: Authors conducted a search on PubMed and Web of Science using the professional terms 'Lower respiratory tract infection' and 'droplet digital polymerase chain reaction' and 'metagenomics next generation sequencing'. The obtained literature was then roughly categorised based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. RESULTS: Different studies discussed the application of second-generation sequencing technology in LRTI from different angles, including the detection of pathogens of LRTI by mNGS and ddPCR, the prediction ability of drug-resistant bacteria, and comparison with traditional methods. We try to analyse the advantages and disadvantages of the second-generation sequencing technology by combing the research results of mNGS and ddPCR. In addition, the development direction of the second-generation sequencing technology is prospected.
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Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds.
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Factor de Crecimiento Epidérmico , Hidrogeles , Cicatrización de Heridas , Factor de Crecimiento Epidérmico/química , Cicatrización de Heridas/efectos de los fármacos , Hidrogeles/química , Animales , Humanos , Adhesivos Tisulares/química , Adhesivos/química , Ratas , Agua/químicaRESUMEN
Microplastics (MPs) have been widely found in the environment and have exerted non-negligible impacts on the environment and human health. Extensive research has shown that MPs can act as carriers for viruses and interacts with them in various ways. Whether MPs influence the persistence, transmission and infectivity of virus has attracted global concern in the context of increasing MPs contamination. This review paper provides an overview of the current state of knowledge regarding the interactions between MPs and viruses in aquatic environments. Latest progress and research trends in this field are summarized based on literature analysis. Additionally, we discuss the potential risks posed by microplastic-associated viruses to human health and the environmental safety, highlighting that MPs can affect viral transmission and infectivity through various pathways. Finally, we underscores the need for further research to address key knowledge gaps, such as elucidating synergistic effects between MPs and viruses, understanding interactions under real environmental conditions, and exploring the role of biofilms in virus-MPs interactions. This review aims to contribute to a deeper understanding on the transmission of viruses in the context of increasing MPs pollution in water, and promote actions to reduce the potential risks.
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Objective: There is limited research on the relationship between the frequency of plant-based food intake and the risk of cardiovascular disease (CVD) among elderly Chinese. This study aims to evaluate the association between plant-based dietary index (PDI) and CVD risks, providing evidence for elderly Chinese to reduce CVD risks by increasing the frequency of plant-based food consumption. Methods: This study analyzed data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2011-2018, employing a multivariate modified Poisson regression model, trend tests, and restricted cubic spline (RCS) analysis to assess the linear and non-linear relationship between the PDI and CVD risks. Subgroup analyses and interaction tests were conducted to evaluate the robustness and population-specificity of the results. Results: This study included a total of 1,414 elderly Chinese, and at the end of follow-up, 487 participants had developed CVD. The multivariate modified Poisson regression model revealed a negative association between PDI and CVD risks [RR = 0.983, 95%CI = (0.970, 0.997)]. Similarly, the multivariate trend test (p = 0.031) and RCS analysis (P for nonlinear = 0.600) indicated a linear relationship between PDI and CVD risks. Subgroup analyses showed that the relationship between PDI and CVD risk was not influenced by gender, BMI, smoking, alcohol use, or exercise. Conclusion: The PDI was negatively correlated with CVD risks, indicating that increasing the frequency of plant-based food intake in the diet may reduce CVD risks among elderly Chinese.
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Cancer is the second leading cause of death globally. Despite some successes, conventional cancer treatments are insufficient to address the growing problem of drug resistance in tumors and to achieve efficient treatment outcomes. Therefore, there is an urgent need to explore new therapeutic options. Ferroptosis, a type of iron- and reactive oxygen species-dependent regulated cell death, has been closely associated with cancer development and progression. Non-coding RNAs (ncRNAs) are a class of RNAs that do not code for proteins, and studies have demonstrated their involvement in the regulation of ferroptosis in cancer. This review aims to explore the molecular regulatory mechanisms of ncRNAs involved in ferroptosis in cancer and to emphasize the feasibility of ferroptosis and ncRNAs as novel therapeutic strategies for cancer. We conducted a systematic and extensive literature review using PubMed, Google Scholar, Web of Science, and various other sources to identify relevant studies on ferroptosis, ncRNAs, and cancer. A deeper understanding of ferroptosis and ncRNAs could facilitate the development of new cancer treatment strategies.
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Integrated wound care through sequentially promoting hemostasis, sealing, and healing holds great promise in clinical practice. However, it remains challenging for regular bioadhesives to achieve integrated care of dynamic wounds due to the difficulties in adapting to dynamic mechanical and wet wound environments. Herein, we reported a type of dehydrated, physical double crosslinked microgels (DPDMs) which were capable of in situ forming highly stretchable, compressible and tissue-adhesive hydrogels for integrated care of dynamic wounds. The DPDMs were designed by the rational integration of the reversible crosslinks and double crosslinks into micronized gels. The reversible physical crosslinks enabled the DPDMs to integrate together, and the double crosslinked characteristics further strengthen the formed macroscopical networks (DPDM-Gels). We demonstrated that the DPDM-Gels simultaneously possess outstanding tensile (â¼940 kJ/m3) and compressive (â¼270 kJ/m3) toughness, commercial bioadhesives-comparable tissue-adhesive strength, together with stable performance under hundreds of deformations. In vivo results further revealed that the DPDM-Gels could effectively stop bleeding in various bleeding models, even in an actual dynamic environment, and enable the integrated care of dynamic skin wounds. On the basis of the remarkable mechanical and appropriate adhesive properties, together with impressive integrated care capacities, the DPDM-Gels may provide a new approach for the smart care of dynamic wounds. STATEMENT OF SIGNIFICANCE: Integrated care of dynamic wounds holds great significance in clinical practice. However, the dynamic and wet wound environments pose great challenges for existing hydrogels to achieve it. This work developed robust adhesive hydrogels for integrated care of dynamic wounds by designing dehydrated, physical double crosslinked microgels (DPDMs). The reversible and double crosslinks enabled DPDMs to integrate into macroscopic hydrogels with high mechanical properties, appropriate adhesive strength and stable performance under hundreds of external deformations. Upon application at the injury site, DPDM-Gels efficiently stopped bleeding, even in an actual dynamic environment and showed effectiveness in integrated care of dynamic wounds. With the fascinating properties, DPDMs may become an effective tool for smart wound care.
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Hidrogeles , Adhesivos Tisulares , Cicatrización de Heridas , Hidrogeles/química , Animales , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Cicatrización de Heridas/efectos de los fármacos , Reactivos de Enlaces Cruzados/química , Microgeles/química , Resistencia a la Tracción , Ratas Sprague-DawleyRESUMEN
Salt stress seriously affects crop growth, leading to a decline in crop quality and yield. Application of exogenous substances to improve the salt tolerance of crops and promote their growth under salt stress has become a widespread and effective means. Eugenol is a small molecule of plant origin with medicinal properties such as antibacterial, antiviral, and antioxidant properties. In this study, tobacco seedlings were placed in Hoagland's solution containing NaCl in the presence or absence of eugenol, and physiological indices related to stress tolerance were measured along with transcriptome sequencing. The results showed that eugenol improved the growth of tobacco seedlings under salt stress. It promoted carbon and nitrogen metabolism, increased the activities of nitrate reductase (NR), sucrose synthase (SS), and glutamine synthetase (GS) by 31.03, 5.80, and 51.06%. It also activated the enzymatic and non-enzymatic antioxidant systems, reduced the accumulation of reactive oxygen species in the tobacco seedlings, and increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) by 24.38%, 18.22%, 21.60%, and 28.8%, respectively. The content of glutathione (GSH) was increased by 29.49%, and the content of superoxide anion (O2-) and malondialdehyde (MDA) were reduced by 29.83 and 33.86%, respectively. Promoted osmoregulation, the content of Na+ decreased by 34.34, K+ increased by 41.25%, and starch and soluble sugar increased by 7.72% and 25.42%, respectively. It coordinated hormone signaling in seedlings; the content of abscisic acid (ABA) and gibberellic acid 3 (GA3) increased by 51.93% and 266.28%, respectively. The transcriptome data indicated that the differentially expressed genes were mainly enriched in phenylpropanoid biosynthesis, the MAPK signaling pathway, and phytohormone signal transduction pathways. The results of this study revealed the novel role of eugenol in regulating plant resistance and provided a reference for the use of exogenous substances to alleviate salt stress.
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Antioxidantes , Eugenol , Regulación de la Expresión Génica de las Plantas , Nicotiana , Reguladores del Crecimiento de las Plantas , Estrés Salino , Plantones , Transducción de Señal , Nicotiana/efectos de los fármacos , Nicotiana/metabolismo , Nicotiana/genética , Plantones/efectos de los fármacos , Plantones/metabolismo , Plantones/crecimiento & desarrollo , Antioxidantes/metabolismo , Transducción de Señal/efectos de los fármacos , Eugenol/farmacología , Eugenol/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Estrés Salino/efectos de los fármacos , Reguladores del Crecimiento de las Plantas/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Tolerancia a la Sal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Introduction: To characterize the influence of female-specific hormones on women's thyroid function, the study investigated the influence of extra progestin from oral contraceptives on inducing thyroid dysfunction. Methods: Sixty female Wistar rats were divided into six groups based on levonorgestrel or desogestrel administration as the main active agents: control, low (0.0039 mg*20-fold), medium (0.0039 mg*100-fold), high (0.0318 mg*100-fold) levonorgestrel (pure product); and low (0.0083 mg*20-fold) and high (0.0083 mg*100-fold) desogestrel (pure product). Progestin was administered by gavage every 4 days for 1 month. Statistical analysis was performed using one-way analysis of variance and the Kruskal-Wallis test. Results: Following levonorgestrel gavage, serum free T4 and thyroidstimulating hormone levels were significantly lower in the experimental group than that in the control group (p=0.013 and 0.043). After desogestrel gavage, the serum free T4 and free T3 levels were lower in the experimental group than that in the control group (p=0.019 and 0.030). Thyroid hormone antibody concentrations were lower in rats administered levonorgestrel and desogestrel than that in control rats. Moreover, exposure to progestin upregulated the expression of the thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid. Discussion: Progestin stimulation enhanced the proliferation of follicular epithelial cells in rat thyroid tissues. Progestin exposure could cause thyroid dysfunction by upregulating the transcription of thyroid-stimulating hormone receptor and sodium iodide symporter in thyroid, thus inducing pathomorphological changes in rats' thyroid.
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Desogestrel , Levonorgestrel , Progestinas , Ratas Wistar , Glándula Tiroides , Animales , Femenino , Ratas , Progestinas/farmacología , Progestinas/efectos adversos , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismo , Levonorgestrel/farmacología , Desogestrel/administración & dosificación , Desogestrel/farmacología , Tiroxina/sangre , Hormonas Tiroideas/sangre , Pruebas de Función de la TiroidesRESUMEN
OBJECTIVE: To assess the utility of combined neutrophil-to-lymphocyte ratio (NLR) and D-dimer detection in determining the severity and short-term prognosis of acute cardiogenic cerebral embolism (ACCE) in older adults. METHODS: We selected 202 elderly non-valvular atrial fibrillation patients hospitalized at the Third Affiliated Hospital of Anhui Medical University from April 1, 2020, to April 1, 2023. They were divided into an observation group (69 cases combined with ACCE) and a control group (133 cases with non-valvular atrial fibrillation alone) based on whether acute cardioembolic cerebral embolism occurred. According to the National Institutes of Health Stroke Scale (NIHSS), the observation group was divided into a mild cerebral infarction group (MICI group), a moderate cerebral infarction group (MOCI group), and a severe cerebral infarction group (SCI group), with 26 cases, 29 cases, and 14 cases, respectively. According to the modified Rankin scale (mRS), after 3 months, 30 cases were divided into the good prognosis group and 39 cases were divided into the poor prognosis group. We detected and compared the differences in D-dimer and NLR levels among different groups of patients, as well as differences in some important laboratory indicators. Logistic regression analysis was used to identify factors influencing the short-term prognosis of patients with acute cardioembolic cerebral infarction, and ROC curves were plotted to evaluate the value of D-dimer and NLR in predicting the short-term prognosis of patients with acute cardioembolic cerebral infarction. RESULTS: The levels of D-dimer and NLR in peripheral blood in SCI group [1.82 (0.58-6.71) mg/l, 4.55 (3.14,7.21)] were higher than those in MOCI group [1.16 (0.65-1.90) mg/l, 3.84 (2.31,6.68)] and MICI group [0.53 (0.32-0.90) mg/l, 2.46 (2.09-3.79)]. The difference between groups was statistically significant (P < 0.05). Logistic regression analysis showed that D-dimer and NLR were independent risk factors for poor prognosis in patients with acute cardiogenic cerebral embolism (OR values were 1.772 and 1.603, and 95 %CI were 1.060-2.963 and 1.100-2.338, respectively, both P < 0.05). The AUC for the prediction of poor prognosis in acute cardioembolic stroke by combining D-dimer and NLR was 0.812 [95 % CI: 0.710-0.914], higher than the individual detections of D-dimer at 0.756 [95% CI: 0.642-0.869] and NLR at 0.733 [95 % CI: 0.613-0.854]. CONCLUSION: Peripheral blood D-dimer combined with NLR detection is helpful for the risk stratification and short-term prognosis assessment of patients with acute cardiogenic cerebral embolism. Clinical detection is of great significance for the prevention and monitoring of disease development.
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Fibrilación Atrial , Biomarcadores , Productos de Degradación de Fibrina-Fibrinógeno , Linfocitos , Neutrófilos , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Humanos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Masculino , Anciano , Femenino , Pronóstico , Biomarcadores/sangre , Anciano de 80 o más Años , Recuento de Linfocitos , Factores de Tiempo , Factores de Riesgo , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/sangre , Fibrilación Atrial/complicaciones , Estudios Retrospectivos , Medición de Riesgo , Embolia Intracraneal/sangre , Embolia Intracraneal/diagnóstico , Embolia Intracraneal/etiología , Factores de Edad , Evaluación de la DiscapacidadRESUMEN
This study demonstrated that both copper oxide nanoparticles (CuO-NPs) and copper nanoparticles (Cu-NPs) can cause swelling, inflammation, and cause damage to the mitochondria of alveolar type II epithelial cells in mice. Cellular examinations indicated that both CuO-NPs and Cu-NPs can reduce cell viability and harm the mitochondria of human bronchial epithelial cells, particularly Beas-2B cells. However, it is clear that CuO-NPs exhibit a more pronounced detrimental effect compared with Cu-NPs. Using bafilomycin A1 (Bafi A1), an inhibitor of lysosomal acidification, was found to enhance cell viability and alleviate mitochondrial damage caused by CuO-NPs. Additionally, Bafi A1 also reduces the accumulation of dihydrolipoamide S-acetyltransferase (DLAT), a marker for mitochondrial protein toxicity, induced by CuO-NPs. This observation suggests that the toxicity of CuO-NPs depends on the distribution of copper particles within cells, a process facilitated by the acidic environment of lysosomes. The release of copper ions is thought to be triggered by the acidic conditions within lysosomes, which aligns with the lysosomal Trojan horse mechanism. However, this association does not seem to be evident with Cu-NPs.
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Supervivencia Celular , Cobre , Lisosomas , Macrólidos , Nanopartículas del Metal , Mitocondrias , Cobre/toxicidad , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Animales , Humanos , Nanopartículas del Metal/toxicidad , Macrólidos/toxicidad , Ratones , Supervivencia Celular/efectos de los fármacos , Línea Celular , MasculinoRESUMEN
BACKGROUND & AIMS: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. METHODS: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected with the pAAV/HBV1.2 plasmid. We assessed the HBV load by measuring the levels of various markers including hepatitis B surface antigen, hepatitis B envelope antigen, hepatitis B core antigen, HBV DNA, and HBV RNA. RESULTS: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice. CONCLUSION: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.
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Virus de la Hepatitis B , Tolerancia Inmunológica , Ratones Noqueados , Factores de Crecimiento Nervioso , Factor de Transcripción STAT3 , Animales , Factores de Crecimiento Nervioso/metabolismo , Factores de Crecimiento Nervioso/genética , Virus de la Hepatitis B/inmunología , Ratones , Factor de Transcripción STAT3/metabolismo , Modelos Animales de Enfermedad , Humanos , Hepatocitos/metabolismo , Hepatocitos/virología , Hepatocitos/inmunología , Hepatitis B/inmunología , Hepatitis B/virología , Carga Viral , Antígenos de Superficie de la Hepatitis B/metabolismo , Antígenos de Superficie de la Hepatitis B/inmunología , Hígado/inmunología , Hígado/metabolismo , Hígado/virología , Ratones Endogámicos C57BL , Hepatitis B Crónica/inmunología , Hepatitis B Crónica/virologíaRESUMEN
We described the diagnosis and treatment of a patient with autoinflammatory disease, named "Deficiency in ELF4, X-linked (DEX)". A novel ELF4 variant was discovered and its pathogenic mechanism was elucidated. The data about clinical, laboratory and endoscopic features, treatment, and follow-up of a patient with DEX were analyzed. Whole exome sequencing and Sanger sequencing were performed to identify potential pathogenic variants. The mRNA and protein levels of ELF4 were analyzed by qPCR and Western blotting, respectively. The association of ELF4 frameshift variant with nonsense-mediated mRNA decay (NMD) in the pathogenesis DEX was examined. Moreover, RNA-seq was performed to identify the key molecular events triggered by ELF4 variant. The relationship between ELF4 and IFN-ß activity was validated using a dual-luciferase reporter assay and a ChIP-qPCR assay. An 11-year-old boy presented with a Behçet's-like phenotype. The laboratory abnormality was the most obvious in elevated inflammatory indicators. Endoscopy revealed multiple ileocecal ulcers. Intestinal histopathology showed inflammatory cell infiltrations. The patient was treated with long-term immunosuppressant and TNF-α blocker (adalimumab), which reaped an excellent response over 16 months of follow-up. Genetic analysis identified a maternal hemizygote frameshift variant (c.1022del, p.Q341Rfs*30) in ELF4 gene in the proband. The novel variant decreased the mRNA level of ELF4 via the NMD pathway. Mechanistically, insufficient expression of ELF4 disturbed the immune system, leading to immunological disorders and pathogen susceptibility, and disrupted ELF4-activating IFN-ß responses. This analysis detailed the clinical characteristics of a Chinese patient with DEX who harbored a novel ELF4 frameshift variant. For the first time, we used patient-derived cells and carried out transcriptomic analysis to delve into the mechanism of ELF4 variant in DEX.
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Mutación del Sistema de Lectura , Perfilación de la Expresión Génica , Niño , Humanos , Masculino , Secuenciación del Exoma , Predisposición Genética a la Enfermedad , Degradación de ARNm Mediada por Codón sin Sentido , Linaje , Proteínas Proto-Oncogénicas c-ets/genética , Factores de Transcripción/genética , TranscriptomaRESUMEN
OBJECTIVES: Patients with a septate uterus often have endometriosis, which can exacerbate their adverse pregnancy outcomes. We aimed to describe the clinical characteristics and treatment outcomes of patients with a septate uterus complicated by endometriosis. STUDY DESIGN: This retrospective study included patients who had a septate uterus complicated by endometriosis and were treated in Wuhan Tongji Hospital in the past 10 years. The characteristics of patients with a septate uterus and endometriosis were collected and described in terms of their preoperative and postoperative pregnancy outcomes. RESULTS: There were 24 cases with a complete septate uterus and 49 cases with an incomplete septate uterus.Combinations of other malformations are more common in patients with complete septate uterus. In patients with a septate uterus, endometriosis often affected the ovaries, most commonly the left side (P < 0.001). Non-significant difference in the staging of endometriosis between complete and incomplete septate uterus (P= 0.812). Surgical treatment greatly improved the reproductive function and increased the live birth rate of patients with a septate uterus complicated by endometriosis (P < 0.001). CONCLUSIONS: Compared to a septate uterus uncomplicated endometriosis, a septate uterus complicated by endometriosis significantly affects reproductive function. Surgical treatment can significantly improve the pregnancy outcomes of patients with a septate uterus and endometriosis. Clinicians should pay attention to timely diagnosing and treating these patients.
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The metagenomic next-generation sequencing (mNGS) method is preferred for genotyping useful for the identification of organisms, illumination of metabolic pathways, and determination of microbiota. It can accurately obtain all the nucleic acid information in the test sample. Anthrax is one of the most important zoonotic diseases, infecting mainly herbivores and occasionally humans. The disease has four typical clinical forms, cutaneous, gastrointestinal, inhalation, and injection, all of which may result in sepsis or meningitis, with cutaneous being the most common form. Here, we report a case of cutaneous anthrax diagnosed by mNGS in a butcher. Histopathology of a skin biopsy revealed PAS-positive bacilli. Formalin-fixed paraffin-embedded (FFPE) tissue sample was confirmed the diagnosis of anthrax by mNGS. He was cured with intravenous penicillin. To our knowledge, this is the first case of cutaneous anthrax diagnosed by mNGS using FFPE tissue. mNGS is useful for identifying pathogens that are difficult to diagnose with conventional methods, and FFPE samples are simple to manage. Compared with traditional bacterial culture, which is difficult to cultivate and takes a long time, mNGS can quickly and accurately help us diagnose anthrax, so that anthrax can be controlled in a timely manner and prevent the outbreak of epidemic events.
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Carbunco , Enfermedades Cutáneas Bacterianas , Masculino , Humanos , Carbunco/diagnóstico , Adhesión en Parafina , Formaldehído/uso terapéutico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Metagenómica/métodos , Sensibilidad y EspecificidadRESUMEN
Calcium/calmodulin-dependent protein kinase IV (CaMK4) is a versatile serine/threonine kinase involved in various cellular functions. It regulates T-cell differentiation, podocyte function, tumor cell proliferation/apoptosis, ß cell mass, and insulin sensitivity. However, the underlying molecular mechanisms are complex and remain incompletely understood. The aims of this review are to highlight the latest advances in the regulatory mechanisms of CaMK4 underlying T-cell imbalance and parenchymal cell mass in multiple diseases. The structural motifs and activation of CaMK4, as well as the potential role of CaMK4 as a novel therapeutic target are also discussed.
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Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina , Humanos , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/metabolismo , Proteína Quinasa Tipo 4 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , AnimalesRESUMEN
Na3V2(PO4)2F3 is recognized as a promising cathode for high energy density sodium-ion batteries due to its high average potential of â¼3.95 V (vs Na/Na+). A high-voltage-resistant electrolyte is of high importance due to the long duration of 4.2 V (vs Na/Na+) when improving cyclability. Herein, a targeted electrolyte containing additives with two -C≡N groups like succinonitrile has been designed. In this design, one -C≡N group is accessible to the solvation sheath and enables the other -C≡N in dinitrile being exposed and subsequently squeezed into the electric double layer. Then, the squeezed -C≡N group is prone to a preferential adsorption on the electrode surface prior to the exposed -CH2/-CH3 in Na+-solvent and oxidized to construct a stable and electrically insulating interface enriched CN-/NCO-/Na3N. The Na3V2(PO4)2F3-based sodium-ion batteries within a high-voltage of 2-4.3 V (vs Na/Na+) can accordingly achieve an excellent cycling stability (e.g., 95.07% reversible capacity at 1 C for 1,5-dicyanopentane and 98.4% at 2 C and 93.0% reversible capacity at 5 C for succinonitrile after 1000 cycles). This work proposes a new way to design high-voltage electrolytes for high energy density sodium-ion batteries.