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1.
J R Soc Interface ; 21(214): 20230625, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38715322

RESUMEN

Peer effects can directly or indirectly rely on interaction networks to drive people to follow ideas or behaviours triggered by a few individuals, and such effects can be largely improved by targeting the so-called influential individuals. In this article, we study the current most promising seeding strategy used in field experiments, the one-hop strategy, where the underlying interaction networks are generally too impractical or prohibitively expensive to be obtained, and propose an individual-centralized seeding approach to target influential seeds in information-limited networks. The presented strategy works by reasonable follow-up questions to respondents, such as Who do you think has more connections/friends?, and constructs the seeding set by those nodes with the most nominations. In this manner, the proposed method could acquire more information about the studied interaction network from the inference of respondents without surveying additional individuals. We evaluate our strategy on networks from various experimental datasets. Results show that the obtained seeds are much more influential compared to the one-hop strategy and other methods. We also show how the proposed approach could be implemented in field studies and potentially provide better interventions in real scenarios.


Asunto(s)
Modelos Teóricos , Humanos
2.
Am J Clin Nutr ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38729573

RESUMEN

BACKGROUND: Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVE: Our study aims to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS: This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS: The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1 and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95%CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18 to 26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95%CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR[95%CI]: 0.85[0.76-0.94]), PUFAs 20:4 (0.84[0.75-0.94]) and 24:2 (0.87[0.78-0.97]) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 [0.61-0.99] (P= 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS: These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

3.
PLoS One ; 19(5): e0302753, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38739634

RESUMEN

Leprosy has a high rate of cripplehood and lacks available early effective diagnosis methods for prevention and treatment, thus novel effective molecule markers are urgently required. In this study, we conducted bioinformatics analysis with leprosy and normal samples acquired from the GEO database(GSE84893, GSE74481, GSE17763, GSE16844 and GSE443). Through WGCNA analysis, 85 hub genes were screened(GS > 0.7 and MM > 0.8). Through DEG analysis, 82 up-regulated and 3 down-regulated genes were screened(|Log2FC| > 3 and FDR < 0.05). Then 49 intersection genes were considered as crucial and subjected to GO annotation, KEGG pathway and PPI analysis to determine the biological significance in the pathogenesis of leprosy. Finally, we identified a gene-pathway network, suggesting ITK, CD48, IL2RG, CCR5, FGR, JAK3, STAT1, LCK, PTPRC, CXCR4 can be used as biomarkers and these genes are active in 6 immune system pathways, including Chemokine signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, T cell receptor signaling pathway, Natural killer cell mediated cytotoxicity and Leukocyte transendothelial migration. We identified 10 crucial gene markers and related important pathways that acted as essential components in the etiology of leprosy. Our study provides potential targets for diagnostic biomarkers and therapy of leprosy.


Asunto(s)
Biomarcadores , Redes Reguladoras de Genes , Lepra , Lepra/genética , Lepra/microbiología , Humanos , Biomarcadores/metabolismo , Biología Computacional/métodos , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Mapas de Interacción de Proteínas/genética , Transducción de Señal
4.
Pharmacol Res ; : 107214, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38763328

RESUMEN

Studies have shown that the microbiota-gut-brain axis is highly correlated with the pathogenesis of depression in humans. However, whether independent oral microbiome that do not depend on gut microbes could affect the progression of depression in human beings remains unclear, neither does the presence and underlying mechanisms of the microbiota-oral-brain axis in the development of the condition. Hence this study that encompasses clinical and animal experiments aims at investigating the correlation between oral microbiota and the onset of depression via mediating the microbiota-oral-brain axis. We compared the oral microbial compositions and metabolomes of 87 patients with depressive symptoms versus 70 healthy controls. We found that the oral microbial and metabolic signatures were significantly different between the two groups. Significantly, germ-free (GF) mice transplanted with saliva from mice exposing to chronic restraint stress (CRS) displayed depression-like behavior and oral microbial dysbiosis. This was characterized by a significant differential abundance of bacterial species, including the enrichment of Pseudomonas, Pasteurellaceae, and Muribacter, as well as the depletion of Streptococcus. Metabolomic analysis showed the alternation of metabolites in the plasma of CRS-exposed GF mice, especially Eicosapentaenoic Acid. Furthermore, oral and gut barrier dysfunction caused by CRS-induced oral microbiota dysbiosis may be associated with increased blood-brain barrier permeability. Pseudomonas aeruginosa supplementation exacerbated depression-like behavior, while Eicosapentaenoic Acid treatment conferred protection against depression-like states in mice. These results suggest that oral microbiome and metabolic function dysbiosis may be relevant to the pathogenesis and pathophysiology of depression. The proposed microbiota-oral-brain axis provides a new way and targets for us to study the pathogenesis of depression.

5.
Biomater Sci ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38764365

RESUMEN

Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.

6.
Coron Artery Dis ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38767051

RESUMEN

BACKGROUND: Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. METHODS: This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. RESULTS: A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. CONCLUSION: Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.

7.
J Colloid Interface Sci ; 668: 540-550, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38691963

RESUMEN

Photocatalysis is considered as an environmentally friendly and sustainable method as it can produce active species to degrade pollutants. However, its applications are hindered by the turbidity of pollutants and the requirements for continuous or repeated in situ irradiation. To avoid the need for continuous in situ irradiation in the photocatalytic process, herein we report the doping of Cu(II) ions into zinc gallate (ZnGa2O4) as traps to capture photo-generated electrons. In this way, long lifetime charge release and separation were effectively achieved for the persistent degradation of organic dyes in wastewater. The Cu(II) doped ZnGa2O4 (ZGC) nanoparticles with a small size about 7.7 nm synthesized via a hydrothermal method exhibited a persistent photocatalytic activity with continuous production of reactive oxygen species for at least 96 h without in situ irradiation due to its unique electronic structure and carrier transport path, and enabled to degrade 82.2 % of rhodamine B in 1 h. Further investigation revealed that the doped Cu(II) ions occupied the octahedral sites of ZGC and highly increased the persistent production and availability of active species for the persistent degradation of organic dyes under pre-illuminated conditions.

8.
Infect Med (Beijing) ; 3(2): 100103, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38764728

RESUMEN

Background: Given the preventable nature of most healthcare-associated infections (HAIs), it is crucial to understand their characteristics and temporal patterns to reduce their occurrence. Methods: A retrospective analysis of medical record cover pages from a Chinese hospital information system was conducted for surgery inpatients from 2010 to 2019. Association rules mining (ARM) was employed to explore the association between disease, procedure, and HAIs. Joinpoint models were used to estimate the annual HAI trend. The time series of each type of HAI was decomposed to analyze the temporal patterns of HAIs. Results: The study included data from 623,290 surgery inpatients over 10 years, and a significant decline in the HAI rate was observed. Compared with patients without HAIs, those with HAIs had a longer length of stay (29 days vs. 9 days), higher medical costs (96226.57 CNY vs. 22351.98 CNY), and an increased risk of death (6.42% vs. 0.18%). The most common diseases for each type of HAI differed, although bone marrow and spleen operations were the most frequent procedures for most HAI types. ARM detected that some uncommon diagnoses could strongly associate with HAIs. The time series pattern varied for each type of HAI, with the peak occurring in January for respiratory system infections, and in August and July for surgical site and bloodstream infections, respectively. Conclusions: Our findings demonstrate that HAIs impose a significant burden on surgery patients. The differing time series patterns for each type of HAI highlight the importance of tailored surveillance strategies for specific types of HAI.

9.
Nano Lett ; 24(20): 6165-6173, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38717317

RESUMEN

Dynamic therapies, which induce reactive oxygen species (ROS) production in situ through endogenous and exogenous stimulation, are emerging as attractive options for tumor treatment. However, the complexity of the tumor substantially limits the efficacy of individual stimulus-triggered dynamic therapy. Herein, bimetallic copper and ruthenium (Cu@Ru) core-shell nanoparticles are applied for endo-exogenous stimulation-triggered dynamic therapy. The electronic structure of Cu@Ru is regulated through the ligand effects to improve the adsorption level for small molecules, such as water and oxygen. The core-shell heterojunction interface can rapidly separate electron-hole pairs generated by ultrasound and light stimulation, which initiate reactions with adsorbed small molecules, thus enhancing ROS generation. This synergistically complements tumor treatment together with ROS from endogenous stimulation. In vitro and in vivo experiments demonstrate that Cu@Ru nanoparticles can induce tumor cell apoptosis and ferroptosis through generated ROS. This study provides a new paradigm for endo-exogenous stimulation-based synergistic tumor treatment.


Asunto(s)
Apoptosis , Cobre , Especies Reactivas de Oxígeno , Rutenio , Cobre/química , Cobre/farmacología , Humanos , Especies Reactivas de Oxígeno/metabolismo , Animales , Rutenio/química , Rutenio/farmacología , Apoptosis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ligandos , Ferroptosis/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/farmacología
10.
Chem Res Toxicol ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38771128

RESUMEN

Lung cancer is the main cause of cancer deaths around the world. Nitrosamine 4-(methyl nitrosamine)-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific carcinogen of lung cancer. Abundant evidence implicates long noncoding RNAs (lncRNAs) in tumorigenesis. Yet, the effects and mechanisms of lncRNAs in NNK-induced carcinogenesis are still unclear. In this study, we discovered that NNK-induced transformed Beas-2B cells (Beas-2B-NNK) showed increased cell migration and proliferation while decreasing rates of apoptosis. RNA sequencing and differentially expressed lncRNAs analyses showed that lncRNA PSMB8-AS1 was obviously upregulated. Interestingly, silencing the lncRNA PSMB8-AS1 in Beas-2B-NNK cells reduced cell proliferation and migration and produced cell cycle arrest in the G2/M phase along with a decrease in CDK1 expression. Conclusively, our results demonstrate that lncRNA PSMB8-AS1 could promote the malignant characteristics of Beas-2B-NNK cells by regulating CDK1 and affecting the cell cycle, suggesting that it may supply a new prospective epigenetic mechanism for lung cancer.

11.
Anal Chem ; 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38755966

RESUMEN

Nanogap-based plasmonic metal nanocrystals have been applied in surface-enhanced Raman scattering detection, while the closed and insufficient electromagnetic fields as well as the nonreproducible Raman signal of the substrate greatly restrict the actual application. Herein, a highly uniform Au/AgAu monolayer with abundant nanogaps and huge electromagnetic enhancement is prepared, which shows ultrasensitive and reproducible SERS detection. Au/AgAu with an inner nanogap is first prepared based on Au nanotriangles, and the nanogap is opened from the three tips via a subsequent etching process. The open-gap Au/AgAu displays much higher SERS efficiency than Au and Au/AgAu with an inner nanogap on detecting crystal violet due to the open-gap induced electromagnetic enhancement and improved molecular absorption. Furthermore, the open-gap Au/AgAu monolayer is prepared via interfacial self-assembly, which shows further improved SERS due to the dense and strong hotspots in the nanocavities induced by the electromagnetic coupling between adjacent open gaps. The monolayer possesses excellent signal stability, uniformity, and reproducibility. The analytic enhancement factor and relative standard deviation reach to 2.12 × 108 and 4.65% on detecting crystal violet, respectively. Moreover, the monolayer achieves efficient detection of thiram in apple juice, biphenyl-4-thiol, 4-mercaptobenzoic, melamine, and a mixed solution of four different molecules, showing great promise in practical detection.

12.
Virulence ; 15(1): 2350904, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38725098

RESUMEN

Fusobacterium nucleatum (F. nucleatum) is closely correlated with tumorigenesis in colorectal cancer (CRC). We aimed to investigate the effects of host norepinephrine on the carcinogenicity of F. nucleatum in CRC and reveal the underlying mechanism. The results revealed that both norepinephrine and bacterial quorum sensing (QS) molecule auto-inducer-2 (AI-2) were positively associated with the progression of F. nucleatum related CRC (p < 0.01). In vitro studies, norepinephrine induced upregulation of QS-associated genes and promoted the virulence and proliferation of F. nucleatum. Moreover, chronic stress significantly increased the colon tumour burden of ApcMin/+ mice infected with F. nucleatum (p < 0.01), which was decreased by a catecholamine inhibitor (p < 0.001). Our findings suggest that stress-induced norepinephrine may promote the progression of F. nucleatum related CRC via bacterial QS signalling. These preliminary data provide a novel strategy for the management of pathogenic bacteria by targeting host hormones-bacterial QS inter-kingdom signalling.


Asunto(s)
Neoplasias Colorrectales , Fusobacterium nucleatum , Norepinefrina , Percepción de Quorum , Transducción de Señal , Percepción de Quorum/efectos de los fármacos , Fusobacterium nucleatum/patogenicidad , Fusobacterium nucleatum/efectos de los fármacos , Fusobacterium nucleatum/fisiología , Animales , Neoplasias Colorrectales/microbiología , Norepinefrina/farmacología , Ratones , Humanos , Progresión de la Enfermedad , Infecciones por Fusobacterium/microbiología , Virulencia , Homoserina/análogos & derivados , Homoserina/metabolismo , Ratones Endogámicos C57BL , Masculino , Lactonas
13.
J Environ Manage ; 359: 121051, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38723507

RESUMEN

Straw return is an effective measure to promote sustainable agriculture by significantly improving soil fertility. At present, few studies have been conducted on the most effective carbon enhancing management measures for various crops. Therefore, we conducted a meta-analysis using data collected from 184 literature sources, comprising 3297 data sets to analyze the carbon increase effects of straw returning in three main crops (rice, maize, and wheat) in China and to explore the influence mechanism of natural factors, soil properties, straw return measures, and cropping systems on the carbon enhancement effect. The study showed that straw return significantly increased soil organic carbon and the rate of increase was higher for wheat at 15.88% (14.74%-17.03%) than for rice at 12.7% (11.5%-13.91%) and maize at 12.42% (11.42%-13.42%), with varying degrees of improvement in other soil physicochemical properties. Natural factors have the greatest impact on the carbon increasing effect of rice fields, reaching 28.8%, especially at temperature between 10 °C and 15 °C, less than 800 mm precipitation, low latitude, and short frost-free period. Maize and wheat are most affected by soil properties, reaching 41% and 34.5% respectively. Furthermore, field management practices also play a pivotal role, organic carbon increasing obviously was observed when the C/N ratio of exogenous nutrients is bigger than 20 with the low initial organic matter. Shallow tillage and less than 7.5 t hm-2 straw returning with 3-10 years to the field are ideal for rice and maize. Crop rotation, especially in drylands, increased soil organic carbon more significantly than continuous. The results of our analysis can provide valuable insights into the effect of straw return on carbon increase. In the future, the soil carbon can be improved by adopting rational cropping patterns and straw return measures with taking into account climate and soil characteristics for different crops.


Asunto(s)
Agricultura , Carbono , Productos Agrícolas , Suelo , Suelo/química , Carbono/análisis , China , Agricultura/métodos , Productos Agrícolas/crecimiento & desarrollo , Zea mays/crecimiento & desarrollo , Granjas , Triticum/crecimiento & desarrollo , Oryza/crecimiento & desarrollo
14.
J Hosp Infect ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38705476

RESUMEN

BACKGROUND: The environmental surveillance of air grilles in clinical areas has not been systematically analyzed. METHODS: Samples were collected from frequently-touched items (n=529), air supply (n=295) and exhaust (n=184) grilles in six medical and eleven surgical wards for the cultures of multidrug-resistant organisms (MDROs): methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenemase-producing Enterobacterales (CPE), and isolates were selected for whole-genome analysis (WGS). The contamination rates were correlated with the colonization pressures of the respective MDROs. RESULTS: From 3-October to 21-November 2023, 9.8% (99/1008) of the samples tested positive, with MRSA (24.2%,24/99), CRAB (59.6%,59/99), and CPE (2.0%,2/99), being the only detected MDROs. The contamination rate in air exhaust grilles (26.6%,49/184) was significantly higher than in air supply grilles (5.8%,17/295;p<0.001). The contamination rate of air exhaust grilles with any MDRO in acute medical wards (73.7%,14/19) was significantly higher than in surgical wards (12.5%,4/32;p<0.001). However, there was no difference in the contamination rate of air exhaust grilles between those located inside and outside the cohort cubicles for MDROs (27.1%,13/48 vs. 28.8%,30/104;p=0.823). Nevertheless, the weekly CRAB colonization pressure showed a significant correlation with the overall environmental contamination rate (r=0.878; 95%CI:0.136-0.986;p=0.004), as well as with the contamination rate in air supply grilles (r=0.960;95%CI:0.375-0.999;p<0.001) and air exhaust grilles (r=0.850;95%CI:0.401-0.980;p=0.008). WGS demonstrated clonal relatedness of isolates collected from patients and air exhaust grilles. CONCLUSIONS: Air grilles may serve as MDRO reservoirs. Cohort nursing in open cubicles may not completely prevent MDRO transmission through air dispersal, prompting the consideration of future hospital design.

15.
Small ; : e2401103, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709231

RESUMEN

The unsaturated amides are traditionally synthesized by acylation of carboxylic acids or hydration of nitrile compounds but are rarely investigated by hydroaminocarbonylation of alkynes using heterogeneous single-metal-site catalysts (HSMSCs). Herein, single-Pd-site catalysts supported on N-doping carbon (NC) with different nitrogen dimensions inherited from corresponding metal-organic-framework precursors are successfully synthesized. 2D NC-supported single-Pd-site (Pd1/NC-2D) exhibited the best performance with near 100% selectivity and 76% yield of acrylamide for acetylene hydroaminocarbonylation with better stability, superior to those of Pd1/NC-3D, single-metal-site/nanoparticle coexisting catalyst, and nanoparticle catalyst. The coordination environment and molecular evolution of the single-Pd-site during the process of acetylene hydroaminocarbonylation on Pd1/NC-2D are detailly illuminated by various characterizations and density functional theoretical calculations (DFT). DFT also showed the energy barrier of rate-determining step on Pd1/NC-2D is lower than that of Pd1/NC-3D. Furthermore, Pd1/NC-2D catalyst illustrated the general applicability of the hydroaminocarbonylation for various alkynes.

16.
Microbiol Spectr ; : e0379623, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38712963

RESUMEN

Cyclic GMP-AMP synthase (cGAS) is an important DNA pattern recognition receptor that senses double-stranded DNA derived from invading pathogens or self DNA in cytoplasm, leading to an antiviral interferon response. A tick-borne Bunyavirus, severe fever with thrombocytopenia syndrome virus (SFTSV), is an RNA virus that causes a severe emerging viral hemorrhagic fever in Asia with a high case fatality rate of up to 30%. However, it is unclear whether cGAS interacts with SFTSV infection. In this study, we found that SFTSV infection upregulated cGAS RNA transcription and protein expression, indicating that cGAS is an important innate immune response against SFTSV infection. The mechanism of cGAS recognizing SFTSV is by cGAS interacting with misplaced mitochondrial DNA in the cytoplasm. Depletion of mitochondrial DNA significantly inhibited cGAS activation under SFTSV infection. Strikingly, we found that SFTSV nucleoprotein (N) induced cGAS degradation in a dose-dependent manner. Mechanically, N interacted with the 161-382 domain of cGAS and linked the cGAS to LC3. The cGAS-N-LC3 trimer was targeted to N-induced autophagy, and the cGAS was degraded in autolysosome. Taken together, our study discovered a novel antagonistic mechanism of RNA viruses, SFTSV is able to suppress the cGAS-dependent antiviral innate immune responses through N-hijacking cGAS into N-induced autophagy. Our results indicated that SFTSV N is an important virulence factor of SFTSV in mediating host antiviral immune responses. IMPORTANCE: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne RNA virus that is widespread in East and Southeast Asian countries with a high fatality rate of up to 30%. Up to now, many cytoplasmic pattern recognition receptors, such as RIG-I, MDA5, and SAFA, have been reported to recognize SFTSV genomic RNA and trigger interferon-dependent antiviral responses. However, current knowledge is not clear whether SFTSV can be recognized by DNA sensor cyclic GMP-AMP synthase (cGAS). Our study demonstrated that cGAS could recognize SFTSV infection via ectopic mitochondrial DNA, and the activated cGAS-stimulator of interferon genes signaling pathway could significantly inhibit SFTSV replication. Importantly, we further uncovered a novel mechanism of SFTSV to inhibit innate immune responses by the degradation of cGAS. cGAS was degraded in N-induced autophagy. Collectively, this study illustrated a novel virulence factor of SFTSV to suppress innate immune responses through autophagy-dependent cGAS degradation.

17.
Medicine (Baltimore) ; 103(18): e37991, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38701321

RESUMEN

Several observational studies have found that exposure to sunlight reduces the risk of colorectal cancer (CRC). However, sun exposure remains ambiguous in its relationship to CRC. We carried out a Mendelian randomization (MR) study to explore the potential associations between them. We examined the exposure to sunlight summary statistics of the UK Biobank Consortium using a 2-sample MR analysis. Using data from the FinnGen consortium, we derived summary statistics for CRC. We conducted our analysis with various methods, incorporating inverse variance weighted (IVW) along with 4 other approaches. A Cochran Q statistic was used to measure the heterogeneity of instrumental variables (IVs). We screened 133 single nucleotide polymorphisms (SNPs) (time spent outdoors in summer), 41 SNPs (time spent outdoors in winter), and 35 SNPs (frequency of solarium/sunlamp use) representing sunlight exposure for MR analysis. All selected SNPs had an F-statistic >20, indicating that IVs did not weakly bias the results. The summer outdoor activity trait exhibited significant heterogeneity (Cochran Q statistic = 183.795, P = .002 < 0.05), but we found no horizontal polymorphisms or significant heterogeneity for the other exposure traits. According to IVW estimates, no causal association exists between time spent outdoors in summer and CRC (Odds Ratio, OR = 0.735, 95% confidence interval, CI = 0.494-1.017, P = .128 > 0.017). No causal relationship existed between time spent outdoors in winter and CRC, as indicated by Bonferroni-corrected adjusted p-values. The OR was 0.877 with a 95% CI of 0.334-2.299, and the P value was .789, more significant than the significance threshold of 0.017. The solarium/sunlamp use frequency was not associated with CRC (OR = 1.567, 95%CI = 0.243-10.119, P = .637 > .017). Also, an IVW with random effects was applied to determine the causal relationship between summer outdoor time and CRC. No causal association between summer outdoor time and CRC was found (OR = 0.735, 95% CI = 0.494-1.017, P = .128 > .017). Additionally, 4 additional analyses yielded similar results. The findings of our study suggest that exposure to sunlight may reduce CRC risk, but the causal relationship remains unsolved. There is no evidence to suggest that exposure to sunlight prevents CRC. Randomized, controlled trials are needed to determine whether sunlight exposure protects against CRC.


Asunto(s)
Neoplasias Colorrectales , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Luz Solar , Humanos , Luz Solar/efectos adversos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/etiología , Estaciones del Año , Factores de Riesgo
18.
Adv Mater ; : e2403876, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739951

RESUMEN

Sorption-based atmospheric water harvesting is an attractive technology for exploiting unconventional water sources. A critical challenge is how to facilitate fast and continuous collection of potable water from air. Here, a bio-based gel (CAL gel), resulting from the integration of a whole biomass-derived polymer network with lithium chloride is reported. A fast adsorption/desorption kinetics, with a water capture rate of 1.74 kg kg-1 h-1 at 30% relative humidity and a desorption rate of 1.98 kg kg-1 h-1, was simultaneously realized in one piece of CAL gel, because of its strong hygroscopicity, hydrophilic network, abundant water transport channels, photothermal conversion ability, and ∼200-µm-thick self-supporting bulky structure caused by multicomponent synergy. A solar-driven, drum-type, tunable, and portable harvester is designed that can harvest atmospheric water within a brief time. Under outdoor conditions, the harvester with CAL gels operates 36 switches (180°) per day realizes a water yield of 8.96 kg kggel -1 (18.87 g kgdevice -1). This portable harvester highlights the potential for fast and scalable atmospheric water harvesting in extreme environments. This article is protected by copyright. All rights reserved.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38749785

RESUMEN

BACKGROUND AND AIMS: This study aimed to explore potential hub genes and pathways of plaque vulnerability and to investigate possible therapeutic targets for acute coronary syndrome (ACS). METHODS AND RESULTS: Four microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs), weighted gene coexpression networks (WGCNA) and immune cell infiltration analysis (IIA) were used to identify the genes for plaque vulnerability. Then, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, Disease Ontology, Gene Ontology annotation and protein-protein interaction (PPI) network analyses were performed to explore the hub genes. Random forest and artificial neural networks were constructed for validation. Furthermore, the CMap and Herb databases were employed to explore possible therapeutic targets. A total of 168 DEGs with an adjusted P < 0.05 and approximately 1974 IIA genes were identified in GSE62646. Three modules were detected and associated with CAD-Class, including 891 genes that can be found in GSE90074. After removing duplicates, 114 hub genes were used for functional analysis. GO functions identified 157 items, and 6 pathways were enriched for the KEGG pathway at adjusted P < 0.05 (false discovery rate, FDR set at < 0.05). Random forest and artificial neural network models were built based on the GSE48060 and GSE34822 datasets, respectively, to validate the previous hub genes. Five genes (GZMA, GZMB, KLRB1, KLRD1 and TRPM6) were selected, and only two of them (GZMA and GZMB) were screened as therapeutic targets in the CMap and Herb databases. CONCLUSION: We performed a comprehensive analysis and validated GZMA and GZMB as a target for plaque vulnerability, which provides a therapeutic strategy for the prevention of ACS. However, whether it can be used as a predictor in blood samples requires further experimental verification.

20.
Artículo en Inglés | MEDLINE | ID: mdl-38581335

RESUMEN

Background: Elderly hospitalized patients often have dysphagia, which can cause a variety of complications, the most common being aspiration. Early detection and timely treatment by nurses are needed in the clinic. Objective: To assess the effect of the situational simulation teaching method in respiratory and cardiac arrest induced by aspiration in elderly patients. Design: This was a retrospective study. Setting: This study was performed in the Department of Geriatrics, The Third Hospital of Hebei Medical University. Participants: Fifty patients with aspiration-induced respiratory and cardiac arrest who were hospitalized in our hospital were chosen and divided into 2 groups according to the composition of rescue nursing staff, and each group had 25 cases. Interventions: The patients who were rescued by nurses without scenario simulation training were the control group (routine emergency nursing group). The patients who were rescued by nurses trained via the scenario simulation teaching method were the experimental group. Primary Outcome Measures: (1) Emergency rescue time, (2) survival rate, (3) duration of adverse events, and (4) nursing satisfaction of patients. Results: Compared to the control group, the emergency rescue time, the duration of asphyxia, duration of respiratory and cardiac arrest, and the duration of malignant arrhythmias caused by cardiac arrest in the experimental group was lower (P < .05), while the survival rate and nursing satisfaction of patients in the experimental group was higher (P < .05). Conclusion: The application of situational simulation teaching method in the rescue of patients with respiratory and cardiac arrest has outstanding effects, which can effectively improve the efficiency of first aid, significantly improve the efficiency and standardization of first aid, and control or prevent the occurrence of poor prognosis, which is worth popularizing.

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