RESUMO
Evidence regarding the role of dietary patterns in metabolic syndrome (MetS) is limited. The mechanistic links between dietary patterns, insulin resistance, and MetS are not fully understood. This study aimed to evaluate the associations between dietary patterns and the risk of MetS in a Chinese population using a longitudinal design. Data from the China Health and Nutrition Survey, a nationally representative survey, were analyzed. MetS cases were identified based on biomarker data collected in 2009. Factor analysis was employed to identify dietary patterns, while logistic regression models were utilized to examine the association between dietary patterns and MetS. Mediation models were applied to assess multiple mediation effects. Two dietary patterns were revealed by factor analysis. Participants in the higher quartiles of the traditional Chinese dietary pattern had lower odds of MetS than those in the lowest quartile (Q1) (OR = 0.58, 95%CI: 0.48, 0.69 for Q4; OR = 0.75, 95%CI: 0.63, 0.89 for Q3). Conversely, participants in the higher quartiles of the modern Chinese dietary pattern had higher odds of MetS compared to those in the lowest quartile (Q1) (OR = 1.40, 95%CI: 1.17, 1.68 for Q4; OR = 1.27, 95%CI: 1.06, 1.52 for Q3). Significant associations between dietary patterns and MetS were mediated by insulin resistance. Therefore, dietary patterns in Chinese adults are associated with MetS, and these associations appear to be mediated through insulin resistance. These findings underscore the critical role of dietary patterns in the development of MetS and establish a foundation for culturally tailored dietary interventions aimed at reducing rates the prevalence of MetS among Chinese adults.
Assuntos
Dieta , Resistência à Insulina , Síndrome Metabólica , Humanos , Síndrome Metabólica/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Dieta/efeitos adversos , Fatores de Risco , Povo Asiático , Idoso , Inquéritos Nutricionais , Comportamento Alimentar , Padrões Dietéticos , População do Leste AsiáticoRESUMO
BACKGROUND: The congenital ventricular outflow tract malformations (CVOTMs) is a major congenital heart diseases (CHDs) subtype, and its pathogenesis is complex and unclear. Lipid metabolic plays a crucial role in embryonic cardiovascular development. However, due to the limited types of detectable metabolites in previous studies, findings on lipid metabolic and CHDs are still inconsistent, and the possible mechanism of CHDs remains unclear. METHODS: The nest case-control study obtained subjects from the multicenter China Teratology Birth Cohort (CTBC), and maternal serum from the pregnant women enrolled during the first trimester was utilized. The subjects were divided into a discovery set and a validation set. The metabolomics of CVOTMs and normal fetuses were analyzed by targeted lipid metabolomics. Differential comparison, random forest and lasso regression were used to screen metabolic biomarkers. RESULTS: The lipid metabolites were distributed differentially between the cases and controls. Setting the selection criteria of P value < 0.05, and fold change (FC) > 1.2 or < 0.833, we screened 70 differential metabolites. Within the prediction model by random forest and lasso regression, DG (14:0_18:0), DG (20:0_18:0), Cer (d18:2/20:0), Cer (d18:1/20:0) and LPC (0:0/18:1) showed good prediction effects in discovery and validation sets. Differential metabolites were mainly concentrated in glycerolipid and glycerophospholipids metabolism, insulin resistance and lipid & atherosclerosis pathways, which may be related to the occurrence and development of CVOTMs. CONCLUSION: Findings in this study provide a new metabolite data source for the research on CHDs. The differential metabolites and involved metabolic pathways may suggest new ideas for further mechanistic exploration of CHDs, and the selected biomarkers may provide some new clues for detection of COVTMs.
Assuntos
Biomarcadores , Cardiopatias Congênitas , Metabolômica , Humanos , Feminino , Gravidez , Estudos de Casos e Controles , Metabolômica/métodos , Biomarcadores/sangue , Adulto , Cardiopatias Congênitas/sangue , China , Lipídeos/sangue , Obstrução do Fluxo Ventricular Externo/sangue , Primeiro Trimestre da Gravidez/sangue , Metabolismo dos LipídeosRESUMO
Cold stress negatively impacts the growth, development, and quality of Camellia sinensis (Cs, tea) plants. CBL-interacting protein kinases (CIPK) comprise a pivotal protein family involved in plant development and response to multiple environmental stimuli. However, their roles and regulatory mechanisms in tea plants (Camellia sinensis (L.) O. Kuntze) remain unknown. Here we show that CsCBL-interacting protein kinase 11 (CsCIPK11), whose transcript abundance was significantly induced at low temperatures, interacts and phosphorylates tau class glutathione S-transferase 23 (CsGSTU23). CsGSTU23 was also a cold-inducible gene and has significantly higher transcript abundance in cold-resistant accessions than in cold-susceptible accessions. CsCIPK11 phosphorylated CsGSTU23 at Ser37, enhancing its stability and enzymatic activity. Overexpression of CsCIPK11 in Arabidopsis thaliana resulted in enhanced cold tolerance under freezing conditions, while transient knockdown of CsCIPK11 expression in tea plants had the opposite effect, resulting in decreased cold tolerance and suppression of the C-repeat-binding transcription factor (CBF) transcriptional pathway under freezing stress. Furthermore, the transient overexpression of CsGSTU23 in tea plants increased cold tolerance. These findings demonstrate that CsCIPK11 plays a central role in the signaling pathway to cold signals and modulates antioxidant capacity by phosphorylating CsGSTU23, leading to improved cold tolerance in tea plants.
RESUMO
2D conjugated covalent organic frameworks (c-COFs) provide an attractive foundation as organic electrodes in energy storage devices, but their storage capability is long hindered by limited ion accessibility within densely π-π stacked interlayers. Herein, two kinds of 2D c-COFs based on dioxin and dithiine linkages are reported, which exhibit distinct in-plane configurations-fully planar and undulated layers. X-ray diffraction analysis reveals wavy square-planar networks in dithiine-bridged COF (COF-S), attributed to curved CâSâC bonds in the dithiine linkage, whereas dioxin-bridged COF (COF-O) features densely packed fully planar layers. Theoretical and experimental results elucidate that the undulated stacking within COF-S possesses an expanded layer distance of 3.8 Å and facilitates effective and rapid Li+ storage, yielding a superior specific capacity of 1305 mAh g-1 at 0.5 A g-1, surpassing that of COF-O (1180 mAh g-1 at 0.5 A g-1). COF-S also demonstrates an admirable cycle life with 80.4% capacity retention after 5000 cycles. As determined, self-expanded wavy-stacking geometry, S-enriched dithiine in COF-S enhances the accessibility and redox activity of Li storage, allowing each phthalocyanine core to store 12 Li+ compared to 8 Li+ in COF-O. These findings underscore the elements and stacking modes of 2D c-COFs, enabling tunable layer distance and modulation of accessible ions.
RESUMO
The pursuit of discovering new high-temperature superconductors that diverge from the copper-based model1-3 has profound implications for explaining mechanisms behind superconductivity and may also enable new applications4-8. Here our investigation shows that the application of pressure effectively suppresses the spin-charge order in trilayer nickelate La4Ni3O10-δ single crystals, leading to the emergence of superconductivity with a maximum critical temperature (Tc) of around 30 K at 69.0 GPa. The d.c. susceptibility measurements confirm a substantial diamagnetic response below Tc, indicating the presence of bulk superconductivity with a volume fraction exceeding 80%. In the normal state, we observe a strange metal behaviour, characterized by a linear temperature-dependent resistance extending up to 300 K. Furthermore, the layer-dependent superconductivity observed hints at a unique interlayer coupling mechanism specific to nickelates, setting them apart from cuprates in this regard. Our findings provide crucial insights into the fundamental mechanisms underpinning superconductivity, while also introducing a new material platform to explore the intricate interplay between the spin-charge order, flat band structures, interlayer coupling, strange metal behaviour and high-temperature superconductivity.
RESUMO
BACKGROUND: Selenium nanoparticles (SeNPs) are increasingly gaining attention due to its characteristics of low toxicity, high activity, and stability. Additionally, Bacillus licheniformis, as a probiotic, has achieved remarkable research outcomes in diverse fields such as medicine, feed processing, and pesticides, attracting widespread attention. Consequently, evaluating the activity of probiotics and SeNPs is paramount. The utilization of probiotics to synthesize SeNPs, achieving large-scale industrialization, is a current hotspot in the field of SeNPs synthesis and is currently the most promising synthetic method. To minimize production costs and maximize yield of SeNPs, this study selected agricultural by-products that are nutrient-rich, cost-effective, and readily available as culture medium components. This approach not only fulfills industrial production requirements but also mitigates the impact on downstream processes. RESULTS: The experimental findings revealed that SeNPs synthesized by B. licheniformis F1 exhibited a spherical morphology with diameters ranging from 110 to 170 nm and demonstrating high stability. Both the secondary metabolites of B. licheniformis F1 and the synthesized SeNPs possessed significant free radical scavenging ability. To provide a more robust foundation for acquiring large quantities of SeNPs via fermentation with B. licheniformis F1, key factors were identified through single-factor experiments and response surface methodology (RSM) include a 2% seed liquid inoculum, a temperature of 37 â, and agitation at 180 rpm. Additionally, critical factors during the optimization process were corn powder (11.18 g/L), soybean meal (10.34 g/L), and NaCl (10.68 g/L). Upon validating the optimized conditions and culture medium, B. licheniformis F1 can synthesize nearly 100.00% SeNPs from 5 mmol/L sodium selenite. Subsequently, pilot-scale verification in a 5 L fermentor using the optimized medium resulted in a shortened fermentation time, significantly reducing production costs. CONCLUSION: In this study, the efficient production of SeNPs by the probiotic B. licheniformis F1 was successfully achieved, leading to a significant reduction in fermentation costs. The exploration of the practical applications of this strain holds significant potential and provides valuable guidance for facilitating the industrial-scale implementation of microbial synthesis of SeNPs.
Assuntos
Bacillus licheniformis , Meios de Cultura , Fermentação , Probióticos , Selênio , Bacillus licheniformis/metabolismo , Selênio/metabolismo , Meios de Cultura/química , Probióticos/metabolismo , Nanopartículas/química , Nanopartículas Metálicas/químicaRESUMO
Dilated cardiomyopathy (DCM) causes heart failure and sudden death. Epigenetics is crucial in cardiomyopathy susceptibility and progression; however, the relationship between epigenetics, particularly DNA methylation, and DCM remains unknown. Therefore, this study identified aberrantly methylated differentially expressed genes (DEGs) associated with DCM using bioinformatics analysis and characterized their clinical utility in DCM. DNA methylation expression profiles and transcriptome data from public datasets of human DCM and healthy control cardiac tissues were obtained from the Gene Expression Omnibus public datasets. Then an epigenome-wide association study was performed. DEGs were identified in both DCM and healthy control cardiac tissues. In total, 3,353 cytosine-guanine dinucleotide sites annotated to 2,818 mRNAs were identified, and 479 DCM-related genes were identified. Subsequently, core genes were screened using logistic, least absolute shrinkage and selection operator, random forest, and support vector machine analyses. The overlapping of these genes resulted in DEGs with abnormal methylation patterns. Cross-tabulation analysis identified 8 DEGs with abnormal methylation. Real-time quantitative polymerase chain reaction confirmed the expression of aberrantly methylated DEGs in mice. In DCM murine cardiac tissues, the expressions of SLC16A9, SNCA, PDE5A, FNDC1, and HTRA1 were higher compared to normal murine cardiac tissues. Moreover, logistic regression model associated with aberrantly methylated DEGs was developed to evaluate the diagnostic value, and the area under the receiver operating characteristic curve was 0.949, indicating that the diagnostic model could reliably distinguish DCM from non-DCM samples. In summary, our study identified 5 DEGs through integrated bioinformatic analysis and in vivo experiments, which could serve as potential targets for further comprehensive investigation.
Assuntos
Cardiomiopatia Dilatada , Biologia Computacional , Metilação de DNA , Perfilação da Expressão Gênica , Cardiomiopatia Dilatada/genética , Metilação de DNA/genética , Humanos , Animais , Camundongos , Epigênese Genética , Transcriptoma/genética , Masculino , Regulação da Expressão Gênica/genéticaRESUMO
BACKGROUND: Intraoperative persistent hypotension (IPH) during pancreaticoduodenectomy (PD) is linked to adverse postoperative outcomes, yet its risk factors remain unclear. AIM: To clarify the risk factors associated with IPH during PD, ensuring patient safety in the perioperative period. METHODS: A retrospective analysis of patient records from January 2018 to December 2022 at the First Affiliated Hospital of Nanjing Medical University identified factors associated with IPH in PD. These factors included age, gender, body mass index, American Society of Anesthesiologists classification, comorbidities, medication history, operation duration, fluid balance, blood loss, urine output, and blood gas parameters. IPH was defined as sustained mean arterial pressure < 65 mmHg, requiring prolonged deoxyepinephrine infusion for > 30 min despite additional deoxyepinephrine and fluid treatments. RESULTS: Among 1596 PD patients, 661 (41.42%) experienced IPH. Multivariate logistic regression identified key risk factors: increased age [odds ratio (OR): 1.20 per decade, 95% confidence interval (CI): 1.08-1.33] (P < 0.001), longer surgery duration (OR: 1.15 per additional hour, 95%CI: 1.05-1.26) (P < 0.01), and greater blood loss (OR: 1.18 per 250-mL increment, 95%CI: 1.06-1.32) (P < 0.01). A novel finding was the association of arterial blood Ca2+ < 1.05 mmol/L with IPH (OR: 2.03, 95%CI: 1.65-2.50) (P < 0.001). CONCLUSION: IPH during PD is independently associated with older age, prolonged surgery, increased blood loss, and lower plasma Ca2+.
RESUMO
The increasing discharge of antibiotic wastewater leads to increasing water pollution. Most of these antibiotic wastewaters are persistent, strongly carcinogenic, easy to bioaccumulate, and have other similar characteristics, seriously jeopardizing human health and the ecological environment. As a commonly used wastewater treatment technology, non-homogeneous electro-Fenton technology avoids the hazards of H2O2 storage and transportation as well as the loss of desorption and reabsorption. It also facilitates electron transfer on the electrodes and the reduction of Fe3+ on the catalysts, thereby reducing sludge production. However, the low selectivity and poor activity of electro-synthesized H2O2, along with the low concentration of its products, combined with the insufficient activity of electrically activated H2O2, results in a low âOH yield. To address the above problems, composites of layered bimetallic hydroxides and carbon materials were designed and prepared in this paper to enhance the performance of electro-synthesized H2O2 and non-homogeneous electro-Fenton by changing the composite mode of the materials. Three composites, NiFe layered double hydroxides (LDHs)/reduced graphene oxide (rGO), NiMn LDHs/rGO, and NiMnFe LDHs/rGO, were constructed by the electrostatic self-assembly of exfoliated LDHs with few-layer graphene. The LDHs/rGO was loaded on carbon mats to construct the electro-Fenton cathode materials, and the non-homogeneous electro-Fenton oxidative degradation of organic pollutants was realized by the in situ electrocatalytic reduction of O2 to âOH. Meanwhile, the effects of solution pH, applied voltage, and initial concentration on the performance of non-homogeneous electro-Fenton were investigated with ceftazidime as the target pollutant, which proved that the cathode materials have an excellent electro-Fenton degradation effect.
RESUMO
Spermatogonial stem cell (SSC) self-renewal and differentiation provide foundational support for long-term, steady-state spermatogenesis in mammals. Here, we have investigated the essential role of RNA exosome associated DIS3 ribonuclease in maintaining spermatogonial homeostasis and facilitating germ cell differentiation. We have established male germ-cell Dis3 conditional knockout (cKO) mice in which the first and subsequent waves of spermatogenesis are disrupted. This leads to a Sertoli cell-only phenotype and sterility in adult male mice. Bulk RNA-seq documents that Dis3 deficiency partially abolishes RNA degradation and causes significant increases in the abundance of transcripts. This also includes pervasively transcribed PROMoter uPstream Transcripts (PROMPTs), which accumulate robustly in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that Dis3 deficiency in spermatogonia significantly disrupts RNA metabolism and gene expression, and impairs early germline cell development. Overall, we document that exosome-associated DIS3 ribonuclease plays crucial roles in maintaining early male germ cell lineage in mice.
Assuntos
Fertilidade , Espermatogônias , Testículo , Animais , Masculino , Camundongos , Diferenciação Celular , Complexo Multienzimático de Ribonucleases do Exossomo/metabolismo , Complexo Multienzimático de Ribonucleases do Exossomo/genética , Exossomos/metabolismo , Fertilidade/genética , Infertilidade Masculina/genética , Camundongos Knockout , Estabilidade de RNA/genética , Células de Sertoli/metabolismo , Espermatogênese , Espermatogônias/metabolismo , Espermatogônias/citologia , Testículo/metabolismoRESUMO
DIS3L, a catalytic exoribonuclease associated with the cytoplasmic exosome complex, degrades cytoplasmic RNAs and is implicated in cancers and certain other diseases in humans. Epididymis plays a pivotal role in the transport, maturation, and storage of sperm required for male fertility. However, it remains unclear whether DIS3L-mediated cytoplasmic RNA degradation plays a role in epididymis biology and functioning. Herein, we fabricated a Dis3l conditional knockout (Dis3l cKO) mouse line in which DIS3L was ablated from the principal cells of the initial segment (IS). Morphological analyses showed that spermatogenesis and IS differentiation occurred normally in Dis3l cKO mice. Additionally, the absence of DIS3L had no dramatic influence on the transcriptome of IS. Moreover, the sperm count, morphology, motility, and acrosome reaction frequency in Dis3l cKO mice were comparable to that of the control, indicating that the Dis3l cKO males had normal fertility. Collectively, our genetic model demonstrates that DIS3L inactivation in the IS is nonessential for sperm maturation and male fertility.
RESUMO
Xanthomonas campestris pv. campestris (Xcc) is a significant phytopathogen causing black rot disease in crucifers. Its virulence relies heavily on the type III secretion system (T3SS), facilitating effector translocation into plant cells. The type III effectors (T3Es) disrupt cellular processes, promoting pathogen proliferation. However, only a few T3Es from Xcc have been thoroughly characterized. In this study, we further investigated two effectors using the T3Es-deficient mutant and the Arabidopsis protoplast system. XopE2Xcc triggers Arabidopsis immune responses via an unidentified activator of the salicylic acid (SA) signaling pathway, whereas XopLXcc suppresses the expression of genes associated with patterns-triggered immunity (PTI) and the SA signaling pathway. These two effectors exert opposing effects on Arabidopsis immune responses. Additionally, we examined the relationship between the specific domains and functions of these two effector proteins. Our findings demonstrate that the N-myristoylation motif and N-terminal domain are essential for the subcellular localization and virulence of XopE2Xcc and XopLXcc, respectively. These novel insights enhance our understanding of the pathogenic mechanisms of T3Es and contribute to developing effective strategies for controlling bacterial disease.
RESUMO
Shear banding is much dependent on the glass-glass interfaces (GGIs) in metallic nanoglasses (NGs). Nevertheless, the current understanding of the glass phase of GGIs is not well established for controlling the shear banding in NGs. In this study, Co-P NGs are investigated by molecular dynamics simulations to reveal the phenomenon of elemental segregation in the GGI regions where the content of Co is dominant. Specifically, Co segregation results in the formation of GGIs, whose atomic structures are comparatively less dense than those present in the interiors of glassy grains. It is suggested that the Co segregation significantly reduces the shear resistance of GGIs. Thus, such compositional heterogeneity influences the mechanical properties of Co-P NGs. Particularly, shear banding is much altered through enhancing the Co segregation in the GGI regions, which leads to improvements in the ductility of Co-P NGs. This study advances knowledge of the formation of the GGI phase in NGs, which could enable GGI engineering in enhancing the mechanical properties of NGs.
RESUMO
Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.
Assuntos
Exposição Materna , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Nascimento Prematuro , Humanos , Feminino , Gravidez , China/epidemiologia , Exposição Materna/efeitos adversos , Adulto , Nascimento Prematuro/epidemiologia , Estudos Prospectivos , Resultado da Gravidez/epidemiologia , Didrogesterona/efeitos adversos , Progesterona , Coorte de Nascimento , Recém-Nascido , Aborto Espontâneo/epidemiologia , Aborto Espontâneo/induzido quimicamente , Natimorto/epidemiologia , Recém-Nascido de Baixo Peso , Estudos Longitudinais , Incidência , Adulto JovemRESUMO
Acting as a growth regulator, Indole-3-acetic acid (IAA) is an important phytohormone that can be produced by several Bacillus species. However, few studies have been published on the comprehensive evaluation of the strains for practical applications and the effects of selenium species on their IAA-producing ability. The present study showed the selenite reduction strain Bacillus altitudinis LH18, which is capable of producing selenium nanoparticles (SeNPs) at a high yield in a cost-effective manner. Bio-SeNPs were systematically characterized by using DLS, zeta potential, SEM, and FTIR. The results showed that these bio-SeNPs were small in particle size, homogeneously dispersed, and highly stable. Significantly, the IAA-producing ability of strain was differently affected under different selenium species. The addition of SeNPs and sodium selenite resulted in IAA contents of 221.7 µg/mL and 91.01 µg/mL, respectively, which were 3.23 and 1.33 times higher than that of the control. This study is the first to examine the influence of various selenium species on the IAA-producing capacity of Bacillus spp., providing a theoretical foundation for the enhancement of the IAA-production potential of microorganisms.
Assuntos
Bacillus , Ácidos Indolacéticos , Selênio , Ácidos Indolacéticos/metabolismo , Bacillus/metabolismo , Bacillus/efeitos dos fármacos , Selênio/química , Selênio/farmacologia , Selênio/metabolismo , Nanopartículas/química , Tamanho da PartículaRESUMO
ABSTRACT An alternative transcription start site (ATSS) is a major driving force for increasing the complexity of transcripts in human tissues. As a transcriptional regulatory mechanism, ATSS has biological significance. Many studies have confirmed that ATSS plays an important role in diseases and cell development and differentiation. However, exploration of its dynamic mechanisms remains insufficient. Identifying ATSS change points during cell differentiation is critical for elucidating potential dynamic mechanisms. For relative ATSS usage as percentage data, the existing methods lack sensitivity to detect the change point for ATSS longitudinal data. In addition, some methods have strict requirements for data distribution and cannot be applied to deal with this problem. In this study, the Bayesian change point detection model was first constructed using reparameterization techniques for two parameters of a beta distribution for the percentage data type, and the posterior distributions of parameters and change points were obtained using Markov Chain Monte Carlo (MCMC) sampling. With comprehensive simulation studies, the performance of the Bayesian change point detection model is found to be consistently powerful and robust across most scenarios with different sample sizes and beta distributions. Second, differential ATSS events in the real data, whose change points were identified using our method, were clustered according to their change points. Last, for each change point, pathway and transcription factor motif analyses were performed on its differential ATSS events. The results of our analyses demonstrated the effectiveness of the Bayesian change point detection model and provided biological insights into cell differentiation.
Assuntos
Teorema de Bayes , Diferenciação Celular , Sítio de Iniciação de Transcrição , Diferenciação Celular/genética , Humanos , Cadeias de Markov , Método de Monte Carlo , Modelos Genéticos , Algoritmos , Simulação por ComputadorRESUMO
Coxiella burnetii (C. burnetii) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.
Assuntos
Proteínas de Bactérias , Coxiella burnetii , Lisossomos , Fosfatidilinositol 3-Quinases , Fosfatos de Fosfatidilinositol , Canais de Potencial de Receptor Transitório , Vacúolos , Animais , Humanos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Coxiella burnetii/metabolismo , Coxiella burnetii/crescimento & desenvolvimento , Coxiella burnetii/genética , Células HeLa , Interações Hospedeiro-Patógeno , Lisossomos/metabolismo , Lisossomos/microbiologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatos de Fosfatidilinositol/metabolismo , Febre Q/microbiologia , Canais de Potencial de Receptor Transitório/metabolismo , Canais de Potencial de Receptor Transitório/genética , Vacúolos/microbiologia , Vacúolos/metabolismoRESUMO
Ligand-protected metal clusters possess hybrid properties that seamlessly combine an inorganic core with an organic ligand shell, imparting them exceptional chemical flexibility and unlocking remarkable application potential in diverse fields. Leveraging chemical flexibility to expand the library of available materials and stimulate the development of new functionalities is becoming an increasingly pressing requirement. This Review focuses on the origin of chemical flexibility from the structural analysis, including intra-cluster bonding, inter-cluster interactions, cluster-environments interactions, metal-to-ligand ratios, and thermodynamic effects. In the introduction, we briefly outline the development of metal clusters and explain the differences and commonalities of M(I)/M(I/0) coinage metal clusters. Additionally, we distinguish the bonding characteristics of metal atoms in the inorganic core, which give rise to their distinct chemical flexibility. Section 2 delves into the structural analysis, bonding categories, and thermodynamic theories related to metal clusters. In the following sections 3 to 7, we primarily elucidate the mechanisms that trigger chemical flexibility, the dynamic processes in transformation, the resultant alterations in structure, and the ensuing modifications in physical-chemical properties. Section 8 presents the notable applications that have emerged from utilizing metal clusters and their assemblies. Finally, in section 9, we discuss future challenges and opportunities within this area.
RESUMO
OBJECTIVES: The translocation of intestinal flora has been linked to the colonization of diverse and heavy lower respiratory flora in patients with septic ARDS, and is considered a critical prognostic factor for patients. METHODS: On the first and third days of ICU admission, BALF, throat swab, and anal swab were collected, resulting in a total of 288 samples. These samples were analyzed using 16S rRNA analysis and the traceability analysis of new generation technology. RESULTS: On the first day, among the top five microbiota species in abundance, four species were found to be identical in BALF and throat samples. Similarly, on the third day, three microbiota species were found to be identical in abundance in both BALF and throat samples. On the first day, 85.16% of microorganisms originated from the throat, 5.79% from the intestines, and 9.05% were unknown. On the third day, 83.52% of microorganisms came from the throat, 4.67% from the intestines, and 11.81% were unknown. Additionally, when regrouping the 46 patients, the results revealed a significant predominance of throat microorganisms in BALF on both the first and third day. Furthermore, as the disease progressed, the proportion of intestinal flora in BALF increased in patients with enterogenic ARDS. CONCLUSIONS: In patients with septic ARDS, the main source of lung microbiota is primarily from the throat. Furthermore, the dynamic trend of the microbiota on the first and third day is essentially consistent.It is important to note that the origin of the intestinal flora does not exclude the possibility of its origin from the throat.
Assuntos
Bactérias , Líquido da Lavagem Broncoalveolar , Microbiota , Faringe , RNA Ribossômico 16S , Síndrome do Desconforto Respiratório , Sepse , Humanos , Masculino , Feminino , Síndrome do Desconforto Respiratório/microbiologia , Pessoa de Meia-Idade , Faringe/microbiologia , RNA Ribossômico 16S/genética , Líquido da Lavagem Broncoalveolar/microbiologia , Idoso , Sepse/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/genética , Alvéolos Pulmonares/microbiologia , Adulto , Unidades de Terapia Intensiva , Microbioma GastrointestinalRESUMO
Background: With improving survival after pancreatic cancer (PC) resection, questions emerge concerning risk and patterns of metachronous tumors. We aimed to determine the incidence of multiple primary cancers among postoperative PC survivors. Methods: Patients undergoing PC surgery from 1975 to 2020 were identified in the Surveillance, Epidemiology, and End Results (SEER) registry. Standardized incidence ratios (SIRs) compared observed-to-expected cancers based on U.S. population rates. Cumulative incidence of secondary tumors was analyzed with Cox regression and cancer-specific survival with Kaplan-Meier curves. Results: Of 6,100 resected PC patients, 267 (4.38%) developed multiple cancers over 6.2 years median follow-up period. Subsequent malignancies showed a rising cumulative incidence extending beyond 5 years. Lung cancer was the predominant second primary in both males (n=36, SIR 1.87) and females (n=32, SIR 2.17). Prostate (n=33) and breast (n=25) cancers were also common. Risk varied by latency period and gender. Conclusions: Postoperative PC patients face a measurable risk for secondary cancers. Enhanced long-term surveillance has the potential to improve early detection and outcomes in this survivor population. Our data provides real-world evidence which could help inform surveillance guidelines in the future.