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1.
Talanta ; 275: 126148, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705016

RESUMO

Latent fingerprints, as one of the most frequently encountered traces in crime scene investigation and also one of the largest sources of forensic evidence, can play a critical role in determining the identity of a person who may be involved in a crime. Due to the invisible characteristic of latent fingerprints, exploring efficient techniques to visualize them (especially the ones resided on metallic surfaces) while retain the biological and chemical information (e.g., touch DNA) has become a multidisciplinary research focus. Herein we reported a new and highly sensitive electrochemical interfacial strategy of simultaneously developing and enhancing latent fingerprints on stainless steel based on synchronous electrodeposition and electrochromism of manganese oxides in a neutral aqueous electrolyte. By utilizing a specially designed device for electrochemical testing and image capture, a series of electrochemical measurements, physical characterization and image analysis have been applied to evaluate the feasibility, development accuracy and enhancement efficacy of the proposed electrochemical system. The qualitative and quantitative analysis on the in situ and ex situ fingerprint images indicates that the three levels of fingerprint features can be precisely developed and effectively enhanced. Forensic DNA typing has also been performed to reveal actual impact of the proposed electrochemical system on subsequent analysis of touch DNA in fingerprint residues. The ratio of detected loci after electrochemical treatment reaches up to 98.5 %, showing non-destructive nature of this fingerprint development and enhancement technique.

2.
Cell Genom ; : 100421, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38697122

RESUMO

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8 weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.

3.
Cell Metab ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38701776

RESUMO

Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks. Training elicited substantial changes in the adrenal gland, brown adipose, colon, heart, and skeletal muscle. The colon showed non-linear response dynamics, whereas mitochondrial pathways were downregulated in brown adipose and adrenal tissues. Protein acetylation increased in the liver, with a shift in lipid metabolism, whereas oxidative proteins increased in striated muscles. Exercise-upregulated networks were downregulated in human diabetes and cirrhosis. Knockdown of the central network protein 17-beta-hydroxysteroid dehydrogenase 10 (HSD17B10) elevated oxygen consumption, indicative of metabolic stress. We provide a multi-omic, multi-tissue, temporal atlas of the mitochondrial response to exercise training and identify candidates linked to mitochondrial dysfunction.

4.
Sci Rep ; 14(1): 8719, 2024 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622207

RESUMO

Occult hemorrhages after trauma can be present insidiously, and if not detected early enough can result in patient death. This study evaluated a hemorrhage model on 18 human subjects, comparing the performance of traditional vital signs to multiple off-the-shelf non-invasive biomarkers. A validated lower body negative pressure (LBNP) model was used to induce progression towards hypovolemic cardiovascular instability. Traditional vital signs included mean arterial pressure (MAP), electrocardiography (ECG), plethysmography (Pleth), and the test systems utilized electrical impedance via commercial electrical impedance tomography (EIT) and multifrequency electrical impedance spectroscopy (EIS) devices. Absolute and relative metrics were used to evaluate the performance in addition to machine learning-based modeling. Relative EIT-based metrics measured on the thorax outperformed vital sign metrics (MAP, ECG, and Pleth) achieving an area-under-the-curve (AUC) of 0.99 (CI 0.95-1.00, 100% sensitivity, 87.5% specificity) at the smallest LBNP change (0-15 mmHg). The best vital sign metric (MAP) at this LBNP change yielded an AUC of 0.6 (CI 0.38-0.79, 100% sensitivity, 25% specificity). Out-of-sample predictive performance from machine learning models were strong, especially when combining signals from multiple technologies simultaneously. EIT, alone or in machine learning-based combination, appears promising as a technology for early detection of progression toward hemodynamic instability.


Assuntos
Sistema Cardiovascular , Hipovolemia , Humanos , Hipovolemia/diagnóstico , Pressão Negativa da Região Corporal Inferior , Sinais Vitais , Biomarcadores
5.
Nat Commun ; 15(1): 2813, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561336

RESUMO

CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved protein, is known to play a critical role in chromatin structure. Post-translational modifications (PTMs) diversify the functions of protein to regulate numerous cellular processes. However, the effects of PTMs on the genome-wide binding of CTCF and the organization of three-dimensional (3D) chromatin structure have not been fully understood. In this study, we uncovered the PTM profiling of CTCF and demonstrated that CTCF can be O-GlcNAcylated and arginine methylated. Functionally, we demonstrated that O-GlcNAcylation inhibits CTCF binding to chromatin. Meanwhile, deficiency of CTCF O-GlcNAcylation results in the disruption of loop domains and the alteration of chromatin loops associated with cellular development. Furthermore, the deficiency of CTCF O-GlcNAcylation increases the expression of developmental genes and negatively regulates maintenance and establishment of stem cell pluripotency. In conclusion, these results provide key insights into the role of PTMs for the 3D chromatin structure.


Assuntos
Genoma , Processamento de Proteína Pós-Traducional , Fator de Ligação a CCCTC/metabolismo , Diferenciação Celular , Cromatina
6.
Foods ; 13(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38672952

RESUMO

Abuse of herbicides in food safety is a vital concern that has an influence on the sustainable development of the world. This work presents, a modified ionization method with separation of the sample and carrier gas inlets, which was utilized for efficient ionization and analyte transfer of herbicides in crops. The working parameters of voltage, injective distance, desorption temperature, and the carrier gas flow rate were optimized to achieve the high efficiency of the transfer and ionization of the analyte. When it was applied in the analysis of herbicides in laboratory, the method exhibited excellent performance in achieving the quantitative detection of herbicides in solutions and residues spiked in an actual matrix with a limit of quantification of 1-20 µg/kg and relative standard deviations of less than 15%. Although a simple QuEchERS process was used, the programmable heating platform ensured efficient gasification and transfer of the target analyte, with the advantages of high speed and selectivity, avoiding the noted matrix effect. The method exhibited a relatively acceptable performance by using air as the discharged gas (open air). It could be used to monitor herbicide residues in the growth stage via on-site non-destructive analysis, which obtained low LODs by dissociating the herbicides from the crops without any pretreatment. It showed great potential for the supervision of the food safety market by achieving non-destructive detection of crops anytime and anywhere. This finding may provide new insights into the determination of pesticide emergence and rice quality assessment.

7.
Sci Total Environ ; 931: 172768, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38670359

RESUMO

The accumulation of contaminants like PAHs in soil due to industrialization, urbanization, and intensified agriculture poses environmental challenges, owing to their persistence, hydrophobic nature, and toxicity. Thus, the degradation of PAHs has attracted worldwide attention in soil remediation. This study explored the effect of noble metal and temperature on the degradation of various polycyclic aromatic hydrocarbons (PAHs) in soil, as well as the types of reactive radicals generated and mechanism. The Fe-Pd/AC and Fe-Pt/AC activated persulfate exhibited high removal efficiency of 19 kinds of PAHs, about 79.95 % and 83.36 %, respectively. Fe-Pt/AC-activated persulfate exhibits superior degradation efficiency than that on Fe-Pd/AC-activated persulfate, due to the higher specific surface area and dispersity of Pt particles, thereby resulting in increased reactive radicals (·OH, SO4-· and ·OOH). Additionally, thermal activation enhances the degradation of PAHs, with initial efficiencies of 64.20 % and 55.49 % on Fe-Pd/AC- and Fe-Pt/AC-activated persulfate systems respectively, increasing to 76.05 % and 73.14 % with elevated temperatures from 21.5 to 50 °C. Metal and thermal activation facilitate S2O82- activation, generating reactive radicals, crucial for the degradation of PAHs via ring opening and oxygen hydrogenation reactions, yielding low-ring oxygen-containing derivatives such as organic acids, keto compounds, ethers, and esters. Furthermore, understanding the impact of parameters such as activation temperature and the types of noble metals on the degradation of PAHs within the activated persulfate system provides a theoretical foundation for the remediation of PAH-contaminated soil.

8.
Poult Sci ; 103(6): 103715, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38652954

RESUMO

Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.

9.
Proc Natl Acad Sci U S A ; 121(18): e2312111121, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38657041

RESUMO

Class II histone deacetylases (HDACs) are important in regulation of gene transcription during T cell development. However, our understanding of their cell-specific functions is limited. In this study, we reveal that class IIa Hdac4 and Hdac7 (Hdac4/7) are selectively induced in transcription, guiding the lineage-specific differentiation of mouse T-helper 17 (Th17) cells from naive CD4+ T cells. Importantly, Hdac4/7 are functionally dispensable in other Th subtypes. Mechanistically, Hdac4 interacts with the transcription factor (TF) JunB, facilitating the transcriptional activation of Th17 signature genes such as Il17a/f. Conversely, Hdac7 collaborates with the TF Aiolos and Smrt/Ncor1-Hdac3 corepressors to repress transcription of Th17 negative regulators, including Il2, in Th17 cell differentiation. Inhibiting Hdac4/7 through pharmacological or genetic methods effectively mitigates Th17 cell-mediated intestinal inflammation in a colitis mouse model. Our study uncovers molecular mechanisms where HDAC4 and HDAC7 function distinctively yet cooperatively in regulating ordered gene transcription during Th17 cell differentiation. These findings suggest a potential therapeutic strategy of targeting HDAC4/7 for treating Th17-related inflammatory diseases, such as ulcerative colitis.


Assuntos
Diferenciação Celular , Colite , Histona Desacetilases , Correpressor 1 de Receptor Nuclear , Células Th17 , Animais , Células Th17/citologia , Células Th17/metabolismo , Células Th17/imunologia , Histona Desacetilases/metabolismo , Histona Desacetilases/genética , Camundongos , Colite/genética , Colite/metabolismo , Colite/imunologia , Transcrição Gênica , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Correpressor 2 de Receptor Nuclear/metabolismo , Correpressor 2 de Receptor Nuclear/genética , Interleucina-17/metabolismo , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Humanos , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Interleucina-2/metabolismo
10.
Environ Sci Technol ; 58(17): 7469-7479, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38557082

RESUMO

Trivalent arsenicals such as arsenite (AsIII) and methylarsenite (MAsIII) are thought to be ubiquitous in flooded paddy soils and have higher toxicity than pentavalent forms. Fungi are widely prevalent in the rice rhizosphere, and the latter is considered a hotspot for As uptake. However, few studies have focused on alleviating As toxicity in paddy soils using fungi. In this study, we investigated the mechanism by which the protein TaGlo1, derived from the As-resistant fungal strain Trichoderma asperellum SM-12F1, mitigates AsIII and MAsIII toxicity in paddy soils. Taglo1 gene expression in Escherichia coli BL21 conferred strong resistance to AsIII and MAsIII, while purified TaGlo1 showed a high affinity for AsIII and MAsIII. Three cysteine residues (Cys13, Cys18, and Cys71) play crucial roles in binding with AsIII, while only two (Cys13 and Cys18) play crucial roles for MAsIII binding. TaGlo1 had a stronger binding strength for MAsIII than AsIII. Importantly, up to 90.2% of the homologous TaGlo1 proteins originate from fungi by GenBank searching. In the rhizospheres of 14 Chinese paddy soils, Taglo1 was widely distributed and its gene abundance increased with porewater As. This study highlights the potential of fungi to mitigate As toxicity and availability in the soil-rice continuum and suggests future microbial strategies for bioremediation.


Assuntos
Poluentes do Solo , Solo , Solo/química , Arsenitos , Microbiologia do Solo , Oryza
11.
Urolithiasis ; 52(1): 50, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38554174

RESUMO

The purpose of this study was to evaluate the efficacy and safety of flexible ureteroscopy with holmium laser lithotripsy in the management of calyceal diverticular calculi. In this study, we retrospectively analyzed the clinical data of 27 patients with calyceal diverticular calculi admitted to the Department of Urology of the Zigong First People's Hospital from May 2018 to May 2021. Intraoperatively, the diverticular neck was found in all 27 patients, but flexible ureterorenoscopy lithotripsy was not performed in 2 cases because of the slender diverticular neck, and the success rate of the operation was 92.6%. Of the 25 patients with successful lithotripsy, the mean operative time was 76.9 ± 35.5 (43-200) min. There were no serious intraoperative complications such as ureteral perforation, mucosal avulsion, or hemorrhage. Postoperative minor complications (Clavien classification I-II) occurred in 4 (16%) patients. The mean hospital stay was 4.4 ± 1.7 (3-12) days. The stone-free rate was 80% at the 1-month postoperative follow-up. After the second-stage treatment, the stone-free rate was 88%. In 22 cases with complete stone clearance, no stone recurrence was observed at 5.3 ± 2.6 (3-12) months follow-up. This retrospective study demonstrated that flexible ureterorenoscopy with holmium laser is a safe and effective choice for the treatment of calyceal diverticular calculi, because it utilizes the natural lumen of the human body and has the advantages of less trauma, fewer complications, and a higher stone-free rate.


Assuntos
Divertículo , Cálculos Renais , Lasers de Estado Sólido , Litotripsia a Laser , Cálculos Ureterais , Humanos , Ureteroscopia/efeitos adversos , Estudos Retrospectivos , Lasers de Estado Sólido/efeitos adversos , Cálculos Renais/terapia , Ureteroscópios , Litotripsia a Laser/efeitos adversos , Divertículo/cirurgia , Divertículo/complicações , Complicações Pós-Operatórias , Cálculos Ureterais/complicações , Resultado do Tratamento
12.
Mil Med ; 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537150

RESUMO

INTRODUCTION: Detection of occult hemorrhage (OH) before progression to clinically apparent changes in vital signs remains an important clinical problem in managing trauma patients. The resource-intensiveness associated with continuous clinical patient monitoring and rescue from frank shock makes accurate early detection and prediction with noninvasive measurement technology a desirable innovation. Despite significant efforts directed toward the development of innovative noninvasive diagnostics, the implementation and performance of the newest bedside technologies remain inadequate. This poor performance may reflect the limitations of univariate systems based on one sensor in one anatomic location. It is possible that when signals are measured with multiple modalities in multiple locations, the resulting multivariate anatomic and temporal patterns of measured signals may provide additional discriminative power over single technology univariate measurements. We evaluated the potential superiority of multivariate methods over univariate methods. Additionally, we utilized machine learning-based models to compare the performance of noninvasive-only to noninvasive-plus-invasive measurements in predicting the onset of OH. MATERIALS AND METHODS: We applied machine learning methods to preexisting datasets derived using the lower body negative pressure human model of simulated hemorrhage. Employing multivariate measured physiological signals, we investigated the extent to which machine learning methods can effectively predict the onset of OH. In particular, we applied 2 ensemble learning methods, namely, random forest and gradient boosting. RESULTS: Analysis of precision, recall, and area under the receiver operating characteristic curve showed a superior performance of multivariate approach to that of the univariate ones. In addition, when using both invasive and noninvasive features, random forest classifier had a recall 95% confidence interval (CI) of 0.81 to 0.86 with a precision 95% CI of 0.65 to 0.72. Interestingly, when only noninvasive features were employed, the results worsened only slightly to a recall 95% CI of 0.80 to 0.85 and a precision 95% CI of 0.61 to 0.73. CONCLUSIONS: Multivariate ensemble machine learning-based approaches for the prediction of hemodynamic instability appear to hold promise for the development of effective solutions. In the lower body negative pressure multivariate hemorrhage model, predictions based only on noninvasive measurements performed comparably to those using both invasive and noninvasive measurements.

13.
Microorganisms ; 12(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38543530

RESUMO

Afforestation plays a pivotal role in ecosystem restoration, exemplified by the Saihanba Mechanized Forest Farm, the world's largest planted forest; however, the assembly mechanisms and interactions of soil microbial communities in such forests remain inadequately understood. This study aimed to elucidate the impact of different afforestation tree species, namely Larix gmelinii var. principis-rupprechtii, Picea asperata, and Pinus sylvestris var. mongolica, on soil bacterial diversity and community structure in comparison to grassland. Sixty soil samples were collected at a 20 cm depth, and high-throughput sequencing was employed to identify bacterial communities and assess their interactions with environmental factors. A total of 6528 operational taxonomic units (OTUs) were identified, with Solirubrobacter, Conexibacter, Bacillus, Massilia, Gaiella, Acidibacter, and Vicinamibacter being the dominant genera. Afforestation significantly impacted soil bacterial alpha diversity, with notable influence from key soil chemical properties, including available phosphorus (AP), cation exchange capacity (CEC), and the carbon-to-nitrogen ratio of soil organic matter (SOM-C/N). The Mantel test highlighted pH, the Normalized Difference Vegetation Index (NDVI), and spatial variable (dbMEM) as primary environmental factors influencing dominant bacterial genera. The bacterial community structure demonstrated deterministic homogeneous selection, wherein SOM-C/N emerged as a significant factor influencing the dissimilarity of soil bacterial communities. Furthermore, plantation soils exhibited a more complex network structure than grassland soil, highlighting the crucial role of bacterial communities in vegetation changes and providing valuable insights into their response to environmental factors during the reforestation process.

14.
Microbiol Spectr ; 12(5): e0295523, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38497713

RESUMO

In this study, we first time sequenced and analyzed the 16S rRNA gene data of predator ladybird beetles Novius pumilus and globally distributed invasive pest Icerya aegyptiaca at different stages, and combined data with bacterial genome sequences in N. pumilus to explored the taxonomic distribution, alpha and beta diversity, differentially abundant bacteria, co-occurrence network, and putative functions of their microbial community. Our finding revealed that Candidatus Walczuchella, which exhibited a higher abundance in I. aegyptiaca, possessed several genes in essential amino acid biosynthesis and seemed to perform roles in providing nutrients to the host, similar to other obligate symbionts in scale insects. Lactococcus, Serratia, and Pseudomonas, more abundant in N. pumilus, were predicted to have genes related to hydrocarbon, fatty acids, and chitin degradation, which may assist their hosts in digesting the wax shell covering the scale insects. Notably, our result showed that Lactococcus had relatively higher abundances in adults and eggs compared to other stages in N. pumilus, indicating potential vertical transmission. Additionally, we found that Arsenophonus, known to influence sex ratios in whitefly and wasp, may also function in I. aegyptiaca, probably by influencing nutrient metabolism as it similarly had many genes corresponding to vitamin B and essential amino acid biosynthesis. Also, we observed a potential horizontal transfer of Arsenophonus between the scale insect and its predator, with a relatively high abundance in the ladybirds compared to other bacteria from the scale insects.IMPORTANCEThe composition and dynamic changes of microbiome in different developmental stages of ladybird beetles Novius pumilus with its prey Icerya aegyptiaca were detected. We found that Candidatus Walczuchella, abundant in I. aegyptiaca, probably provide nutrients to their host based on their amino acid biosynthesis-related genes. Abundant symbionts in N. pumilus, including Lactococcus, Serratia, and Pseudophonus, may help the host digest the scale insects with their hydrocarbon, fatty acid, and chitin degrading-related genes. A key endosymbiont Arsenophonus may play potential roles in the nutrient metabolisms and sex determination in I. aegyptiaca, and is possibly transferred from the scale insect to the predator.


Assuntos
Bactérias , Besouros , Simbiose , Animais , Besouros/microbiologia , Bactérias/classificação , Bactérias/genética , Bactérias/metabolismo , Bactérias/isolamento & purificação , RNA Ribossômico 16S/genética , Transferência Genética Horizontal , Filogenia , Feminino , Microbiota
15.
JCI Insight ; 9(6)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358827

RESUMO

Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to CF, a life-threating autosomal recessive genetic disease. While recently approved Trikafta dramatically ameliorates CF lung diseases, there is still a lack of effective medicine to treat CF-associated liver disease (CFLD). To address this medical need, we used a recently established CF rabbit model to test whether sotagliflozin, a sodium-glucose cotransporter 1 and 2 (SGLT1/2) inhibitor drug that is approved to treat diabetes, can be repurposed to treat CFLD. Sotagliflozin treatment led to systemic benefits to CF rabbits, evidenced by increased appetite and weight gain as well as prolonged lifespan. For CF liver-related phenotypes, the animals benefited from normalized blood chemistry and bile acid parameters. Furthermore, sotagliflozin alleviated nonalcoholic steatohepatitis-like phenotypes, including liver fibrosis. Intriguingly, sotagliflozin treatment markedly reduced the otherwise elevated endoplasmic reticulum stress responses in the liver and other affected organs of CF rabbits. In summary, our work demonstrates that sotagliflozin attenuates liver disorders in CF rabbits and suggests sotagliflozin as a potential drug to treat CFLD.


Assuntos
Fibrose Cística , Hepatopatias , Animais , Coelhos , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Hepatopatias/complicações , Glicosídeos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/complicações
16.
Sci Rep ; 14(1): 4478, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396140

RESUMO

Glycosylation is currently considered to be an important hallmark of cancer. However, the characterization of glycosylation-related gene sets has not been comprehensively analyzed in glioma, and the relationship between glycosylation-related genes and glioma prognosis has not been elucidated. Here, we firstly found that the glycosylation-related differentially expressed genes in glioma patients were engaged in biological functions related to glioma progression revealed by enrichment analysis. Then seven glycosylation genes (BGN, C1GALT1C1L, GALNT13, SDC1, SERPINA1, SPTBN5 and TUBA1C) associated with glioma prognosis were screened out by consensus clustering, principal component analysis, Lasso regression, and univariate and multivariate Cox regression analysis using the TCGA-GTEx database. A glycosylation-related prognostic signature was developed and validated using CGGA database data with significantly accurate prediction on glioma prognosis, which showed better capacity to predict the prognosis of glioma patients than clinicopathological factors do. GSEA enrichment analysis based on the risk score further revealed that patients in the high-risk group were involved in immune-related pathways such as cytokine signaling, inflammatory responses, and immune regulation, as well as glycan synthesis and metabolic function. Immuno-correlation analysis revealed that a variety of immune cell infiltrations, such as Macrophage, activated dendritic cell, Regulatory T cell (Treg), and Natural killer cell, were increased in the high-risk group. Moreover, functional experiments were performed to evaluate the roles of risk genes in the cell viability and cell number of glioma U87 and U251 cells, which demonstrated that silencing BGN, SDC1, SERPINA1, TUBA1C, C1GALT1C1L and SPTBN5 could inhibit the growth and viability of glioma cells. These findings strengthened the prognostic potentials of our predictive signature in glioma. In conclusion, this prognostic model composed of 7 glycosylation-related genes distinguishes well the high-risk glioma patients, which might potentially serve as caner biomarkers for disease diagnosis and treatment.


Assuntos
Glioma , Humanos , Glicosilação , Prognóstico , Glioma/genética , Contagem de Células , Sobrevivência Celular
17.
Cell Biosci ; 14(1): 27, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38388523

RESUMO

BACKGROUND: Sodium-Glucose cotransporter 1 and 2 (SGLT1/2) belong to the family of glucose transporters, encoded by SLC5A1 and SLC5A2, respectively. SGLT2 is almost exclusively expressed in the renal proximal convoluted tubule cells. SGLT1 is expressed in the kidneys but also in other organs throughout the body. Many SGLT inhibitor drugs have been developed based on the mechanism of blocking glucose (re)absorption mediated by SGLT1/2, and several have gained major regulatory agencies' approval for treating diabetes. Intriguingly these drugs are also effective in treating diseases beyond diabetes, for example heart failure and chronic kidney disease. We recently discovered that SGLT1 is upregulated in the airway epithelial cells derived from patients of cystic fibrosis (CF), a devastating genetic disease affecting greater than 70,000 worldwide. RESULTS: In the present work, we show that the SGLT1 upregulation is coupled with elevated endoplasmic reticulum (ER) stress response, indicated by activation of the primary ER stress senor inositol-requiring protein 1α (IRE1α) and the ER stress-induced transcription factor X-box binding protein 1 (XBP1), in CF epithelial cells, and in epithelial cells of other stress conditions. Through biochemistry experiments, we demonstrated that the spliced form of XBP1 (XBP1s) acts as a transcription factor for SLC5A1 by directly binding to its promoter region. Targeting this ER stress → SLC5A1 axis by either the ER stress inhibitor Rapamycin or the SGLT1 inhibitor Sotagliflozin was effective in attenuating the ER stress response and reducing the SGLT1 level in these cellular model systems. CONCLUSIONS: The present work establishes a causal relationship between ER stress and SGLT1 upregulation and provides a mechanistic explanation why SGLT inhibitor drugs benefit diseases beyond diabetes.

18.
G3 (Bethesda) ; 14(4)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38366555

RESUMO

Sanguinoderma infundibulare is a newly discovered species of Ganodermataceae known to have high medicinal and ecological values. In this study, the whole-genome sequencing and comparative genomic analyses were conducted to further understand Ganodermataceae's genomic structural and functional characteristics. Using the Illumina NovaSeq and PacBio Sequel platforms, 88 scaffolds were assembled to obtain a 48.99-Mb high-quality genome of S. infundibulare. A total of 14,146 protein-coding genes were annotated in the whole genome, with 98.6% of complete benchmarking universal single-copy orthologs (BUSCO) scores. Comparative genomic analyses were conducted among S. infundibulare, Sanguinoderma rugosum, Ganoderma lucidum, and Ganoderma sinense to determine their intergeneric differences. The 4 species were found to share 4,011 orthogroups, and 24 specific gene families were detected in the genus Sanguinoderma. The gene families associated with carbohydrate esterase in S. infundibulare were significantly abundant, which was reported to be involved in hemicellulose degradation. One specific gene family in Sanguinoderma was annotated with siroheme synthase, which may be related to the typical characteristics of fresh pore surface changing to blood red when bruised. This study enriched the available genome data for the genus Sanguinoderma, elucidated the differences between Ganoderma and Sanguinoderma, and provided insights into the characteristics of the genome structure and function of S. infundibulare.


Assuntos
Genoma , Genômica , Sequenciamento Completo do Genoma
19.
Nat Commun ; 15(1): 1492, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374032

RESUMO

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Adulto , Humanos , Feminino , Masculino , Idoso , Formação de Anticorpos , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , Demografia , Vacinação
20.
Nat Commun ; 15(1): 1427, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365776

RESUMO

Electrochemical carbon dioxide reduction reaction using sustainable energy is a promising approach of synthesizing chemicals and fuels, yet is highly energy intensive. The oxygen evolution reaction is particularly problematic, which is kinetically sluggish and causes anodic carbon loss. In this context, we couple CO2 electrolysis with hydrogen oxidation reaction in a single electrochemical cell. A Ni(OH)2/NiOOH mediator is used to fully suppress the anodic carbon loss and hydrogen oxidation catalyst poisoning by migrated reaction products. This cell is highly flexible in producing either gaseous (CO) or soluble (formate) products with high selectivity (up to 95.3%) and stability (>100 h) at voltages below 0.9 V (50 mA cm-2). Importantly, thanks to the "transferred" oxygen evolution reaction to a water electrolyzer with thermodynamically and kinetically favored reaction conditions, the total polarization loss and energy consumption of our H2-integrated CO2 reduction reaction, including those for hydrogen generation, are reduced up to 22% and 42%, respectively. This work demonstrates the opportunity of combining CO2 electrolysis with the hydrogen economy, paving the way to the possible integration of various emerging energy conversion and storage approaches for improved energy/cost effectiveness.

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