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1.
bioRxiv ; 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38712231

RESUMEN

Single-cell multiomic techniques have sparked immense interest in developing a comprehensive multi-modal map of diverse neuronal cell types and their brain wide projections. However, investigating the spatial organization, transcriptional and epigenetic landscapes of brain wide projection neurons is hampered by the lack of efficient and easily adoptable tools. Here we introduce Projection-TAGs, a retrograde AAV platform that allows multiplex tagging of projection neurons using RNA barcodes. By using Projection-TAGs, we performed multiplex projection tracing of the mouse cortex and high-throughput single-cell profiling of the transcriptional and epigenetic landscapes of the cortical projection neurons. Projection-TAGs can be leveraged to obtain a snapshot of activity-dependent recruitment of distinct projection neurons and their molecular features in the context of a specific stimulus. Given its flexibility, usability, and compatibility, we envision that Projection-TAGs can be readily applied to build a comprehensive multi-modal map of brain neuronal cell types and their projections.

2.
Nat Commun ; 15(1): 4122, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750027

RESUMEN

Visual information is important for accurate spatial coding and memory-guided navigation. As a crucial area for spatial cognition, the medial entorhinal cortex (MEC) harbors diverse spatially tuned cells and functions as the major gateway relaying sensory inputs to the hippocampus containing place cells. However, how visual information enters the MEC has not been fully understood. Here, we identify a pathway originating in the secondary visual cortex (V2) and directly targeting MEC layer 5a (L5a). L5a neurons served as a network hub for visual processing in the MEC by routing visual inputs from multiple V2 areas to other local neurons and hippocampal CA1. Interrupting this pathway severely impaired visual stimulus-evoked neural activity in the MEC and performance of mice in navigation tasks. These observations reveal a visual cortical-entorhinal pathway highlighting the role of MEC L5a in sensory information transmission, a function typically attributed to MEC superficial layers before.


Asunto(s)
Corteza Entorrinal , Neuronas , Navegación Espacial , Corteza Visual , Animales , Corteza Entorrinal/fisiología , Corteza Visual/fisiología , Navegación Espacial/fisiología , Ratones , Neuronas/fisiología , Masculino , Ratones Endogámicos C57BL , Estimulación Luminosa , Región CA1 Hipocampal/fisiología , Región CA1 Hipocampal/citología , Vías Visuales/fisiología , Percepción Visual/fisiología
3.
Drug Saf ; 47(5): 465-474, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38441749

RESUMEN

INTRODUCTION: Systemic inflammatory response syndrome (SIRS) is one of the most serious complications in patients undergoing percutaneous nephrolithotomy (PCNL). Although glucocorticoids are increasingly used during PCNL, few studies have been concerned about the association between glucocorticoids and postoperative SIRS. The study aims to explore whether preoperative use of glucocorticoids is associated with SIRS after PCNL. METHODS: A total of 1259 patients who underwent PCNL between January 2015 and April 2021 were enrolled in the retrospective cohort study. Risk factors for post-PCNL SIRS were identified by univariate and multivariate regression analysis. To further explore the association between preoperative administration of glucocorticoids and SIRS, 113 pairs of patients were matched for the confounding factors using propensity score matching (PSM) analysis. The odds ratios (OR) and 95 % confidence intervals (CI) for the above variables were analyzed. RESULTS: The incidence of SIRS after PCNL was 9.6 % (121/1259) and the patients who suffered from postoperative SIRS had longer hospital stays and higher hospital costs (all p < 0.05). Multivariate logistic regression analysis indicated that female, preoperative leukocyte count, insertion of central vein catheter, serum albumin, preoperative high-sensitive C-reactive protein/albumin ratio, preoperative transfusion, preoperative administration of glucocorticoids were independent risk factors for SIRS (all p < 0.05). After minimization, the effects of confounding factors by PSM, preoperative administration of glucocorticoids was significantly correlated with SIRS in patients after PCNL (OR=2.44, 95 %CI: 1.31-4.55, p = 0.005). CONCLUSION: Preoperative administration of glucocorticoids is an independent risk factor for SIRS in patients undergoing PCNL.


Systemic inflammatory response syndrome (SIRS) is a frequent and severe complication in patients underwent percutaneous nephrolithotomy (PCNL), which can be challenging to diagnose early, potentially leading to delayed treatment. Identifying SIRS risk factors and promptly treating high-risk patients is crucial. Glucocorticoids are commonly used to prevent SIRS in clinical practice, and this study aims to investigate whether preoperative glucocorticoid administration is associated with SIRS after PCNL. In total, 1259 patients underwent PCNL and were enrolled in the study. The study utilized both propensity score matching (PSM) analysis and regression analysis to identify risk factors for post-PCNL SIRS. The incidence of SIRS after PCNL was 9.6 % in the study and patients with postoperative SIRS had longer hospital stays and higher hospital costs. After minimizing the potential influence of confounding factors through the use of PSM, we found a significant association between the preoperative use of glucocorticoids and the occurrence of SIRS in patients undergoing PCNL. Based on our analysis, we can conclude that the preoperative administration of glucocorticoids represents an independent risk factor for the development of SIRS in these patients.


Asunto(s)
Nefrolitotomía Percutánea , Humanos , Femenino , Nefrolitotomía Percutánea/efectos adversos , Glucocorticoides/efectos adversos , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Factores de Riesgo
4.
Mol Nutr Food Res ; 68(6): e2300443, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38456781

RESUMEN

SCOPE: Gut microbiota can convert a variety of alkaloids and TMAO into TMA, which is then transported by the blood to the liver, and converted into TMAO. In recent years, TMAO has attracted wide attention as a metabolic risk factor in cardiovascular disease, diabetes, and other diseases. However, it is still unclear about the role of gut microbial metabolite TMA in the adverse health impacts of TMAO. METHODS AND RESULTS: Male C57BL/6J is treated with intraperitoneal (i.p.) or oral TMAO for 8 weeks, the area under the OGTT curve of oral group is significantly increased by about 15% compared to the control and injection groups. Serum triglyceride levels in the oral group are significantly higher by 28.2% and 24.6% than those in the control and injection groups, respectively. Meanwhile, cholesterol content in serum is significantly elevated by 27.6% and 30.7%. Similarly, proinflammatory factors gene expressions are significantly increased with oral but not i.p. TMAO intervention. Furthermore, transformation in HepG2 cells shows that TMAO could not be converted into TMA by hepatocytes. CONCLUSION: The adverse effects of TMAO on glucose and lipid metabolism in C57BL/6J mice may act through gut microbiota metabolite TMA.


Asunto(s)
Microbioma Gastrointestinal , Ratones , Animales , Masculino , Ratones Endogámicos C57BL , Metabolismo de los Lípidos , Glucosa/farmacología , Metilaminas , Colina/farmacología
5.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(2): 211-215, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38442942

RESUMEN

Sepsis is a fatal organ dysfunction caused by the uncontrolled inflammatory response of the host to infection. Excessive inflammatory reaction is the core factor in the occurrence and development of sepsis, the degree of organ dysfunction is directly related to the prognosis of sepsis. Timely intervention of excessive inflammatory response and alleviation of organ function damage are essential to improve the prognosis of sepsis. Maresin-1 (MaR-1) is a newly discovered endogenous specific pro-inflammatory resolution mediator, which plays a role of anti-inflammatory, pro-inflammatory regression and organ protection in sepsis, and may be a new target for the treatment of sepsis. This article reviews the research progress of the role of MaR-1 in the regulation of inflammation and organ protection in sepsis, in order to provide reference for the clinical development of new drugs for the treatment of sepsis.


Asunto(s)
Insuficiencia Multiorgánica , Sepsis , Humanos , Insuficiencia Multiorgánica/prevención & control , Sepsis/tratamiento farmacológico , Inflamación
6.
Proc Natl Acad Sci U S A ; 121(7): e2311703121, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38315863

RESUMEN

Global polls have shown that people in high-income countries generally report being more satisfied with their lives than people in low-income countries. The persistence of this correlation, and its similarity to correlations between income and life satisfaction within countries, could lead to the impression that high levels of life satisfaction can only be achieved in wealthy societies. However, global polls have typically overlooked small-scale, nonindustrialized societies, which can provide an alternative test of the consistency of this relationship. Here, we present results from a survey of 2,966 members of Indigenous Peoples and local communities among 19 globally distributed sites. We find that high average levels of life satisfaction, comparable to those of wealthy countries, are reported for numerous populations that have very low monetary incomes. Our results are consistent with the notion that human societies can support very satisfying lives for their members without necessarily requiring high degrees of monetary wealth.


Asunto(s)
Renta , Satisfacción Personal , Humanos , Pobreza , Sociedades , Problemas Sociales
7.
BMC Vet Res ; 20(1): 43, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38308297

RESUMEN

BACKGROUND: Bovine viral diarrhea (BVD) is an acute febrile infectious disease caused by the bovine viral diarrhea virus (BVDV), which has brought huge economic losses to the world's cattle industry. At present, commercial inactivated BVDV vaccines may cause some adverse reactions during use. This study aims to develop a safer and more efficient inactivated BVDV vaccine. METHODS: Here, we described the generation and preclinical efficacy of a hydrogen peroxide (H2O2) inactivated BVDV type 1 vaccine in mice, and administered it separately with commercial vaccine (formaldehyde inactivated) in mice to study its efficacy. RESULTS: The BVDV type 1 IgG, IFN- γ, IL-4 and neutralizing antibody in the serum of the H2O2 inactivated vaccine group can be maintained in mice for 70 days. The IgG level reached its maximum value of 0.67 on the 42nd day, significantly higher than the commercial formaldehyde inactivated BVDV type 1 vaccine. IFN- γ and IL-4 reached their maximum values on the 28th day after immunization, at 123.16 pg/ml and 143.80 pg/ml, respectively, slightly higher than commercial vaccines, but the effect was not significant. At the same time the BVDV-1 neutralizing antibody titer reached a maximum of 12 Nu on the 42nd day post vaccination. CONCLUSIONS: The H2O2 inactivated BVDV vaccine has good safety and immunogenicity, which provides a potential solution for the further development of an efficient and safe BVDV vaccine.


Asunto(s)
Diarrea Mucosa Bovina Viral , Enfermedades de los Bovinos , Virus de la Diarrea Viral Bovina Tipo 1 , Virus de la Diarrea Viral Bovina , Vacunas Virales , Animales , Bovinos , Ratones , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Diarrea/veterinaria , Formaldehído , Peróxido de Hidrógeno , Inmunoglobulina G , Interleucina-4 , Vacunas de Productos Inactivados
8.
Biomed Chromatogr ; 38(4): e5829, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38351664

RESUMEN

The imbalance of steroid hormones is closely related to the occurrence and development of hepatocellular carcinoma (HCC). However, most research has focused on steroid hormone receptors, and reports about the relationship between the serum concentration of cortisol and the development of HCC are rare. The aim of this research was to establish a simple, specific, sensitive and reliable liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for the quantitation of cortisol in human serum and to compare the level of cortisol in serum between 221 HCC patients and 183 healthy volunteers. The results showed that the correlation coefficients of the linear regression with a weighing factor of 1/x2 ranged from 0.9933 to 0.9984 over the range of 2-1,000 ng/ml. The inter- and intra-day precision and accuracy were <10%. The matrix effect and recovery of cortisol were 94.9-102.5% and 96.3-99.8%, respectively. The concentration of cortisol in HCC patients was significantly higher than that in healthy volunteers (p < 0.05) and was not affected by sex, age, menopause or α-fetoprotein (AFP) level. The present study reveals that elevated cortisol might promote the progression of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Femenino , Humanos , Hidrocortisona , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida con Espectrometría de Masas , Esteroides
9.
Environ Toxicol ; 39(5): 2596-2609, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38205898

RESUMEN

Cell senescence, glycolysis, and mitochondrial deficit jointly regulate the development of septic acute kidney injury (SAKI). This study aimed to explore the role of circular RNA HIPK3 (circHIPK3) in mitochondrial function in SAKI. The SAKI mouse model was established by Candida albicans infection, followed by Western blot assay, measurements of serum lactate, and adenosine triphosphate (ATP), 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimi-dazolylcarbocyanine iodide (JC-1) staining and flow cytometry. Human renal tubular epithelial cells were treated with lipopolysaccharide to establish the SAKI cell model, followed by cell counting kit-8 assay, tests of hexokinase activity, lactate production, oxygen consumption rate, extracellular acidification rate, ATP, and JC-1 staining, and Western blot assay. The roles of mitochondrial pyruvate carrier 1 (MPC1) were validated by kidney function tests, hematoxylin and eosin staining, periodic acid-Schiff staining, and SA-ß-gal staining. circHIPK3 downregulation reduced glycolysis and mitochondrial dysfunction both in vivo and in vitro through the microRNA (miR)-148b-3p/DNMT1/3a/Klotho axis. Inhibition of miR-148b-3p or Klotho increased glycolysis and mitochondrial dysfunction. Knockdown of MPC1 increased lactate content and decreased ATP levels and MMP both in vivo and in vitro. Collectively, circHIPK3, in concert with the miR-148b-3p/DNMT1/3a/Klotho axis, increased glycolysis, and inhibited the negative regulation of lactate production by MPC1, and aggravated mitochondrial dysfunction and cell senescence in SAKI.


Asunto(s)
Lesión Renal Aguda , Bencimidazoles , Carbocianinas , MicroARNs , Enfermedades Mitocondriales , Ratones , Animales , Humanos , ARN Circular/genética , MicroARNs/genética , Mitocondrias , Lesión Renal Aguda/genética , Adenosina Trifosfato , Lactatos
10.
Neural Regen Res ; 19(9): 2036-2040, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38227533

RESUMEN

JOURNAL/nrgr/04.03/01300535-202409000-00036/figure1/v/2024-01-16T170235Z/r/image-tiff Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory responses. Moreover, anti-inflammatory treatment has shown partial effectiveness in alleviating depression symptoms. Lycium barbarum polysaccharide (LBP), derived from Goji berries, exhibits notable antioxidative and anti-inflammatory properties. In our recent double-blinded randomized placebo-controlled trial, we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold depression. It is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory cytokines. In the double-blinded randomized controlled trial, we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo group. In the LBP group, adolescents were given 300 mg/d LBP. A 6-week follow up was completed by 24 adolescents, comprising 14 adolescents from the LBP group (15.36 ± 2.06 years, 3 men and 11 women) and 10 adolescents from the placebo group (14.9 ± 1.6 years, 2 men and 8 women). Our results showed that after 6 weeks of treatment, the interleukin-17A level in the LBP group was lower than that in the placebo group. Network analysis showed that LBP reduced the correlations and connectivity between inflammatory factors, which were associated with the improvement in depressive symptoms. These findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level, thereby exerting an antidepressant effect.

11.
Adv Healthc Mater ; 13(3): e2301945, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37897223

RESUMEN

Polymer-based hemostatic materials/devices have been increasingly exploited for versatile clinical scenarios, while there is an urgent need to reveal the rational design/facile approach for procoagulant surfaces through regulating blood-material interactions. In this work, degradable powders (PLPS) and thermoresponsive gels (F127-PLPS) are readily developed as promising hemostatic materials for versatile clinical applications, through tuning blood-material interactions with optimized grafting of cationic polylysine: the former is facilely prepared by conjugating polylysine onto porous starch particle, while F127-PLPS is prepared by the simple mixture of PLPS and commercial thermosensitive polymer. In vitro and in vivo results demonstrate that PLPS2 with the optimal-/medium content of polylysine grafts achieve the superior hemostatic performance. The underlying procoagulant mechanism of PLPS2 surface is revealed as the selective fibrinogen adsorption among the competitive plasma-protein-adsorption process, which is the foundation of other blood-material interactions. Moreover, in vitro results confirm the achieved procoagulant surface of F127-PLPS through optimal PLPS2 loading. Together with the tunable thermoresponsiveness, F127-PLPS exhibits outstanding hemostatic utilization in both femoral-artery-injury and renal-artery-embolization models. The work thereby pioneers an appealing approach for generating versatile polymer-based hemostatic materials/devices.


Asunto(s)
Hemostáticos , Polietilenos , Polilisina , Polipropilenos , Polvos , Hemostáticos/farmacología , Geles , Almidón
12.
Artículo en Inglés | MEDLINE | ID: mdl-38086068

RESUMEN

ABSTRACT: The high level of oxidative stress induced by angiotensin II (AngII) is the main pathophysiological process that promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) and induces vascular remodeling. LncRNA Metastasis-related lung adenocarcinoma transcript 1 (MALAT1) has been determined to play an important role in the modulation of oxidative stress and the development of cardiovascular diseases. Nevertheless, the function and underlying mechanism of MALAT1 in restenosis induced by hypertensive angioplasty remain unclear. AngII increased the expression of MALAT1 in VSMCs. We found that anti-sense oligonucleotide lncRNA MALAT1 (ASO-MALAT1) could inhibit AngII induced reactive oxygen species (ROS) production and VSMCs proliferation and migration by inducing the expression of glutathione peroxidase 4 (GPX4), which can be reversed by siRNA-GPX4. And GPX4 overexpression can inhibit the proliferation and migration of VSMCs induced by AngII. In addition, we found that the process by which MALAT1 knockdown induces GPX4 expression involves nuclear factor erythrocyte 2 related factor 2 (Nrf2). Overexpression of Nrf2 can increase the expression of GPX4, and down-regulation of GPX4 by ML385 (Nrf2 inhibitor) blocked the protective effect of ASO-MALAT1 on AngII-induced proliferation and migration of VSMCs. Ferrostatin-1 (Fer-1, ip 5mg/kg per day for 2 weeks), a GPX4 agonist, significantly inhibited neointimal formation in spontaneously hypertensive rat (SHR) by the inhibition of oxidative stress. In conclusion, these data imply that ASO-MALAT1 suppresses the AngII-induced oxidative stress, proliferation and migration of VSMCs by activating Nrf2/GPX4 antioxidant signaling. GPX4 may be a potential target for the therapeutic intervention of hypertensive vascular restenosis.

13.
Expert Opin Drug Metab Toxicol ; 19(12): 1015-1021, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38059472

RESUMEN

OBJECTIVES: To compare the pharmacokinetic and safety of the test group capecitabine tablets (0.5 g) and the reference group capecitabine tablets (0.5 g). METHODS: This study was registered at www.chinadrugtrials.org.cn under the registration number CTR20220138. 48 subjects with solid tumor were recruited and randomized to receive either the test group or the reference group at a dose of 2 g per cycle for three cycles of the entire trial. RESULTS: The point estimate of the geometric mean ratio of Cmax for the subject and reference groups was 1.0670, which was in the range of 80.00%-125.00%. And the upper limit of 95% confidence interval was -0.0450 < 0. The statistics of geometric mean ratio of AUC0-t and AUC0-∞ (test group/reference group) and their 90% confidence intervals were in the range of 80.00%-125.00%, thus the test group was bioequivalent to the reference group under the conditions of this postprandial test. There were no major or serious adverse events. Conclusion: The pharmacokinetic profiles of capecitabine under postprandial conditions were consistent between the two groups. The two groups were bioequivalent and had a similar favorable safety profile in Chinese patients with solid tumor.


Asunto(s)
Neoplasias , Humanos , Equivalencia Terapéutica , Capecitabina/efectos adversos , Comprimidos , Estudios Cruzados , Área Bajo la Curva , Neoplasias/tratamiento farmacológico , China , Voluntarios Sanos
14.
Nat Prod Res ; : 1-7, 2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37850447

RESUMEN

A new aromatic polyketide, alternaphenol B2 (1), and four known compounds (2-5) were isolated from the coral-derived fungus Parengyodontium album SCSIO SX7W11. Their structures were elucidated by high-resolution mass spectrometry, 1D and 2D NMR spectroscopy and comparison with reported literatures. Compounds 1 and 2 exhibited selective inhibitory activity against isocitrate dehydrogenase mutant R132H (IDH1m), with IC50 values of 41.9 and 27.7 µM, respectively. Our findings thus provide a fresh incentive for investigation on IDH1m inhibitors as lead compounds for cancer treatment.

15.
PeerJ ; 11: e16294, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37868061

RESUMEN

Ruminants such as cattle rely mainly on microbes in the rumen to digest cellulose and hemicellulose from forage, and the digestion products are mainly absorbed and utilized by the host in the form of short chain fatty acids (SCFAs). This study aimed to isolate acid-producing strains from the cattle rumen and investigate their functions. A total of 980 strains of acid-producing bacteria were isolated from cattle rumen contents using a medium supplemented with bromocresol green. Combined with the test of acid production ability and 16S rRNA amplicon sequencing technology, five strains were selected based on their ability to produce relatively high levels of acid, including Bacillus pumillus, Enterococcus hirae, Enterococcus faecium, and Bacillus subtilis. Sheep were treated by gavage with a mixed bacterial suspension. The results showed that mixed bacteria significantly increased the body weight gain and feed conversion rate of sheep. To investigate the function of acid-producing bacteria in sheep, we used 16S rDNA sequencing technology to analyze the rumen microbes of sheep. We found that mixed bacteria changed the composition and abundance of sheep rumen bacteria. Among them, the abundance of Bacteroidota, Actinobacteriota, Acidobacteriota, and Proteobacteria was significantly increased, and the abundance of Firmicutes was significantly decreased, indicating that the changes in gut microbiota changed the function of the sheep rumen. The acid-producing bacteria isolated in this study can effectively promote the growth of ruminants, such as cattle and sheep, and can be used as additives to improve breeding efficiency, which lays a foundation for subsequent research on probiotics.


Asunto(s)
Microbioma Gastrointestinal , Rumen , Bovinos , Animales , Ovinos/genética , Rumen/microbiología , ARN Ribosómico 16S/genética , Bacterias/genética , Rumiantes/genética , Microbioma Gastrointestinal/genética
16.
Amino Acids ; 55(11): 1487-1499, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37814028

RESUMEN

Apart from cancer, metabolic reprogramming is also prevalent in other diseases, such as bacterial infections. Bacterial infections can affect a variety of cells, tissues, organs, and bodies, leading to a series of clinical diseases. Common Pathogenic bacteria include Helicobacter pylori, Salmonella enterica, Mycobacterium tuberculosis, Staphylococcus aureus, and so on. Amino acids are important and essential nutrients in bacterial physiology and support not only their proliferation but also their evasion of host immune defenses. Many pathogenic bacteria or opportunistic pathogens infect the host and lead to significant changes in metabolites, especially the proteinogenic amino acids, to inhibit the host's immune mechanism to achieve its immune evasion and pathogenicity. Here, we review the regulation of host metabolism, while host cells are infected by some common pathogenic bacteria, and discuss how amino acids of metabolic reprogramming affect bacterial infections, revealing the potential adjunctive application of amino acids alongside antibiotics.


Asunto(s)
Infecciones Bacterianas , Mycobacterium tuberculosis , Humanos , Antibacterianos , Aminoácidos
17.
Medicine (Baltimore) ; 102(40): e35222, 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37800815

RESUMEN

Clear cell renal cell carcinoma (ccRCC) constitutes the most prevalent histopathologic subtype of renal cell carcinoma. The interplay between aging and cancer is complicated, and we provide a relatively new set of senescence genes that has not yet been used in the study of clear cell renal cell carcinoma. Our objective is to investigate the involvement of senescence in the development and diagnosis of ccRCC. RNA-seq and clinical data for ccRCC was obtained from the cancer genome atlas and gene expression omnibus databases. Consensus clustering analysis was performed to identify novel molecular subgroups. Tumor immune status was assessed using estimating stromal and immune cells in malignancy using expression data, microenvironment cell populations, and single-sample gene set enrichment analysis analyses. Functional analysis, including gene ontology, gene set variation analysis, and gene set enrichment analysis, was conducted to explore potential mechanisms. A prognostic risk model was constructed using the LASSO algorithm and multivariate Cox regression analysis. Decision trees and nomograms were developed for survival prediction. SenMayo classified ccRCC patients into 2 molecular subtypes with significantly different survival rates, and significant differences in their immune status, characterized by poor prognosis with relatively high immune status. Besides, the differentially expressed genes between the 2 subgroups were mainly enriched in immune-related pathways. The burden of aging tissues and cells may lead to immune dysregulation and drug resistance, which could contribute to poor prognosis in ccRCC patients. Risk models, decision trees, and nomogram for ccRCC survival prediction have great potential applications. In conclusion, our study establishes a clear association between aging in ccRCC and the immune microenvironment, demonstrating the predictive potential of senescence genes for ccRCC prognosis.


Asunto(s)
Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Envejecimiento , Neoplasias Renales/genética , Expresión Génica , Pronóstico , Microambiente Tumoral/genética
18.
J Environ Manage ; 347: 119050, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37751664

RESUMEN

Upgrading of waste nitrogen sources is considered as an important approach to promote sustainable development. In this study, a multifunctional bio-electrochemical system with three chambers was established, innovatively achieving 2.02 g/L in-situ microbial protein (MP) production via hydrogen-oxidizing bacteria (HOB) in the protein chamber (middle chamber), along with over 2.9 L CO2/(L·d) consumption rate. Also, 69% chemical oxygen demand was degraded by electrogenic bacteria in the anode chamber, resulting in the 394.67 J/L electricity generation. Focusing on the NH4+-N migration in the system, the current intensity contributed 4%-9% in the anode and protein chamber, whereas, the negative effect of -6.69% on contribution was shown in the cathode chamber. On the view of kinetics, NH4+-N migration in anode and cathode chambers was fitted well with Levenberg-Marquardt equation (R2 > 0.92), along with the well-matched results of HOB growth in the protein chamber based on Gompertz model (R2 > 0.99). Further evaluating MPs produced by HOB, 0.45 g/L essential amino acids was detected, showing the better amino acid profile than fish and soybean. Multifunctional bio-electrochemical system revealed the economic potential of producing 6.69 €/m3 wastewater according to a simplified economic evaluation.


Asunto(s)
Fuentes de Energía Bioeléctrica , Animales , Fuentes de Energía Bioeléctrica/microbiología , Nitrógeno/metabolismo , Electricidad , Aguas Residuales , Bacterias/metabolismo , Hidrógeno , Electrodos
19.
Autoimmunity ; 56(1): 2259131, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37724530

RESUMEN

Sepsis-induced acute respiratory distress syndrome (ARDS) remains a major complication of death from bacterial infection. Regulatory T cells (Tregs) are important regulators in addressing lung injury. Considering the extensive research of circular RNAs (circRNAs), the role of circRNA in Treg modulation during ARDS remains unclear. In this study, patients with sepsis-induced ARDS along with non-ARDS controls were obtained, and bronchoalveolar lavage fluid (BALF) was collected as clinical samples. Additionally, cecal ligation and puncture (CLP) was performed to construct a septic ARDS model, and lung tissues as well as peripheral blood were collected. mRNA expressions were measured by RT-qPCR. ELISA was carried out to measure the concentration of inflammatory factors. A combination of online bioinformatics, dual-luciferase reporter, and RND pull-down assays was performed to verify interactions between microRNA (miRNA) and circRNA/mRNA. Tregs were measured by flow cytometry. Our data suggested that circFLNA was aberrantly elevated in ARDS, and depletion of circFLNA upregulated CD4+CD25+Foxp3+ Tregs and decreased inflammatory response. Additionally, miR-214-5p which binds with circFLNA, reversed circFLNA-induced effects in ARDS. Programmed cell death protein 1 (PD-1) is a downstream target gene of miR-214-5p, and abrogated the effects of miR-214-5p on regulating CD4+CD25+Foxp3+ Tregs and inflammatory response. In a word, circFLNA/miR-214-5p/PD-1 signaling is a novel pathway that modulates Tregs in ARDS.


Asunto(s)
Lesión Pulmonar Aguda , MicroARNs , Sepsis , Humanos , Lesión Pulmonar Aguda/genética , Factores de Transcripción Forkhead , MicroARNs/genética , Receptor de Muerte Celular Programada 1/genética , ARN Circular/genética , Sepsis/complicaciones , Sepsis/genética , Linfocitos T Reguladores
20.
Sci Adv ; 9(36): eadh2140, 2023 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-37683007

RESUMEN

Blue perovskite light-emitting diodes (LEDs) have shown external quantum efficiencies (EQEs) of more than 10%; however, devices that emit in the true blue-those that accord with the emission wavelength required for Rec. 2100 primary blue-have so far been limited to EQEs of ~6%. We focused here on true blue emitting CsPbBr3 colloidal nanocrystals (c-NCs), finding in early studies that they suffer from a high charge injection barrier, a problem exacerbated in films containing multiple layers of nanocrystals. We introduce a self-assembled monolayer (SAM) active layer that improves charge injection. We identified a bifunctional capping ligand that simultaneously enables the self-assembly of CsPbBr3 c-NCs while passivating surface traps. We report, as a result, SAM-based LEDs exhibit a champion EQE of ~12% [CIE of (0.132, 0.069) at 4.0 V with a luminance of 11 cd/m2], and 10-fold-enhanced operating stability relative to the best previously reported Rec. 2100-blue perovskite LEDs.

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