Sufficient dimension reduction and prediction through cumulative slicing PFC

<p>In this article, a new method named cumulative slicing principle fitted component (CUPFC) model is proposed to conduct sufficient dimension reduction and prediction in regression. Based on the classical PFC methods, the CUPFC avoids selecting some parameters such as the specific basis function form or the number of slices in slicing estimation. We develop the estimator of the central subspace in the CUPFC method under three error-term structures and establish its consistency. The simulations investigate the effectiveness of the new method in prediction and reduction estimation with other competitors. The results indicate that the new proposed method generally outperforms the existing PFC methods no matter how the predictors are truly related to the response. The application to real data also verifies the validity of the proposed method.</p

DataSheet_1_MiR-199a-3p-regulated alveolar macrophage-derived secretory autophagosomes exacerbate lipopolysaccharide-induced acute respiratory distress syndrome.pdf

PurposeAcute respiratory distress syndrome (ARDS) is a prevalent illness in intensive care units. Extracellular vesicles and particles released from activated alveolar macrophages (AMs) assist in ARDS lung injury and the inflammatory process through mechanisms that are unclear. This study investigated the role of AM-derived secretory autophagosomes (SAPs) in lung injury and microRNA (MiR)-199a-3p-regulated inflammation associated with ARDS in vitro and in a murine model.MethodsThe ARDS model in mouse was established by intratracheal LPS lipopolysaccharide (LPS) injection. The agomirs or antagomirs of MiR-199a-3p were injected into the caudal vein to figure out whether MiR-199a-3p could influence ARDS inflammation and lung injury, whereas the mimics or inhibitors of MiR-199a-3p, siRNA of Rab8a, or PAK4 inhibitor were transfected or applied to RAW264.7 cells to evaluate the mechanism of SAP release. Culture supernatants of RAW264.7 cells treated with LPS or bronchoalveolar lavage fluid from mice were collected for the isolation of SAPs.ResultsWe found that MiR-199a-3p was over-expressed in the lungs of ARDS mice. The MiR-199a-3p antagomir alleviated, whereas the MiR-199a-3p agomir exacerbated LPS-induced inflammation in mice by promoting AM-derived SAP secretion. In addition, MiR-199a-3p over-expression exacerbated LPS-induced ARDS via activating Rab8a, and Rab8a silencing significantly suppressed the promoting influence of the MiR-199a-3p mimic on SAP secretion. Furthermore, MiR-199a-3p mimic activated Rab8a by directly inhibiting PAK4 expression.ConclusionThe novel finding of this study is that MiR-199a-3p participated in the regulation of SAP secretion and the inflammatory process via targeting of PAK4/Rab8a, and is a potential therapeutic candidate for ARDS treatment.</p

Data_Sheet_1_Circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis: a two-step bidirectional Mendelian randomization study.docx

BackgroundThe relationship between gut microbiota and the occurrence of cholecystitis remains unclear. Existing research lacks a clear understanding of how circulating vitamin levels modulate this relationship. Therefore, our study aims to investigate whether circulating vitamin levels mediate the causal relationship between gut microbiota and cholecystitis using a two-step bidirectional Mendelian randomization approach.MethodsIn this study, we initially employed Linkage Disequilibrium Score Regression (LDSC) analysis to assess the genetic correlation of five circulating vitamin level genome-wide association study (GWAS) summary datasets, thereby avoiding potential sample overlap. Subsequently, we conducted a two-step analysis to investigate the causal effects between gut microbiota and cholecystitis. In the second step, we explored the causal relationship between circulating vitamin levels and cholecystitis and identified the mediating role of vitamin D. The primary method used for causal analysis was the inverse variance-weighted approach. We performed additional sensitivity analyses to ensure result robustness, including the cML-MA method and reverse Mendelian randomization (MR) analysis.ResultsAn increment of one standard deviation in RuminococcaceaeUCG003 was associated with a 25% increased risk of cholecystitis (OR = 1.25, 95%CI = 1.01–1.54, p = 0.04), along with a 3% decrease in 25-hydroxyvitamin D levels (OR = 0.97, 95%CI = 0.944–0.998, p = 0.04). However, following the rigorous Bonferroni correction, every one standard deviation decrease in circulating vitamin D levels was associated with a 33% increased risk of cholecystitis (OR = 0.67, 95%CI = 0.49–0.90, p = 0.008, Padjust = 0.04). Thus, the potential link between gut microbiota and cholecystitis risk might be mediated by circulating vitamin D levels (proportion mediated = 5.5%). Sensitivity analyses provided no evidence of pleiotropy.ConclusionOur study results suggest that an elevated abundance of specific gut microbiota is associated with an increased susceptibility to cholecystitis, with the causal relationship being mediated by circulating vitamin D levels. Further large-scale randomized controlled trials are necessary to validate the causal effects of gut microbiota on cholecystitis risk. This study provides novel insights into cholecystitis prevention through the regulation of gut microbiota.</p

Data_Sheet_1_Metabolites Identification of Bioactive Compounds Daturataturin A, Daturametelin I, N-Trans-Feruloyltyramine, and Cannabisin F From the Seeds of Datura metel in Rats.DOC

<p>Datura metel L. is a widely used traditional herbal medicine, and withanolides and amides are the two groups of main bioactive constituents in Datura metel seeds. This study aimed to elucidate the metabolism of four representative bioactive compositions containing daturataturin A (1), daturametelin I (2), N-trans-feruloyltyramine (3), and cannabisin F (4) in rats. After separately oral administration of 20 mg/kg withanolides (1, 2) and amides (3, 4) to rats, a total of 12, 24, and 21 metabolites were detected in the plasma, urine, and fecal samples, respectively. Among them, three hydroxylated metabolites, 1-M3, 2-M2, and 3-M5, were detected in plasma and rat liver microsome incubation system in high abundance. Two metabolites of 1 and 2 were unambiguously identified by comparing with reference standards. Particularly, the methylated metabolite 27α-methoxy-(22R)-22,26-epoxy-27-[(β-D-glucopyranosyl)oxy]ergosta-2,4,6,24-tetraene-1,26-dione (daturametelin L) is a new compound. The withanolides could readily get hydroxylation or methylation metabolism. Meanwhile, the phase II metabolism (glucuronidation or sulfation) was the major reaction for the amides. This is the first study on in vivo metabolism of these active compounds in seeds of Datura metel.</p

MOESM2 of EZH2 promotes DNA replication by stabilizing interaction of POLδ and PCNA via methylation-mediated PCNA trimerization

Additional file 2: Figure S2 (related to Fig. 2). A: Flow cytometry shows the cell cycle distribution of hDPCs from one donor at the indicated time points after release from serum deprivation. B: Immunoblot demonstrates the expression of CYCLIN D1 and CYCLIN A2, indicating G1 phase and S phase, respectively. α-TUBULIN was used a loading control of whole lysate. C: Statistical analysis of the EZH2-positive ratio (Left, n = 3) and Pearson’s correlation coefficient of EZH2 with DAPI (right, each dot represents one cell). D: Statistical analysis of the PLA-positive ratio (left, n = 5). The PLA signals are associated with DAPI on a single-cell basis (***P < 0.001

MOESM3 of EZH2 promotes DNA replication by stabilizing interaction of POLδ and PCNA via methylation-mediated PCNA trimerization

Additional file 3: Figure S3. Uncut immunoblots from the immunoprecipitation experiment

Effects of Climate and Rodent Factors on Hemorrhagic Fever with Renal Syndrome in Chongqing, China, 1997–2008

<div><p>China has the highest global incidence of hemorrhagic fever with renal syndrome (HFRS), constituting 90% of the cases in the world. Chongqing, located in the Three Gorges Reservoir Region, has been experiencing differences in the occurrence of HFRS from 1997 to 2008. The current study was designed to explore the effects of climate and rodent factors on the transmission of HFRS in Chongqing. Data on monthly HFRS cases, rodent strains, and climatic factors were collected from 1997 to 2008. Spatio-temporal analysis indicated that most HFRS cases were clustered in central Chongqing and that the incidence of HFRS decreased from 1997 to 2008. Poisson regression models showed that temperature (with lagged months of 0 and 5) and rainfall (with 2 lagged months) were key climatic factors contributing to the transmission of HFRS. A zero-inflated negative binomial model revealed that rodent density was also significantly associated with the occurrence of HFRS in the Changshou district. The monthly trend in HFRS incidence was positively associated with rodent density and rainfall and negatively associated with temperature. Possible mechanisms are proposed through which construction of the dam influenced the incidence of HFRS in Chongqing. The findings of this study may contribute to the development of early warning systems for the control and prevention of HFRS in the Three Gorges Reservoir Region.</p></div

Temporal pattern of HFRS occurrence from 1997 to 2008.

<p>(A) Annual and monthly trends of HFRS incidence in the study area; (B) Seasonal trend of HFRS incidence in the study area. HFRS: hemorrhagic fever with renal syndrome. Case numbers for each month are presented as mean ± standard error of mean.</p

Spatial distribution of HFRS occurrence from 1997 to 2008.

<p>WS: Wushan; FJ: Fengjie; YY: Yunyang; KX: Kaixian; WZ: Wanzhou; SZ: Shizhu; ZX: Zhongxian; FD: Fengdu; WL: Wulong; FL: Fuling; CS: Changshou; YB: Yubei; BN: Banan. TGD: Three Gorges Dam. HFRS: hemorrhagic fever with renal syndrome. Central region includes the districts of ZX, CS, SZ, FL, FD, and WL. The rest of districts are designated as periphery region.</p

Association between climatic factors and HFRS incidence in Chongqing City from 1997 to 2008, analyzed by Poisson regression models.

<p>HFRS: hemorrhagic fever with renal syndrome; GDP: gross domestic product; Lx: the lagged months.</p><p>Association between climatic factors and HFRS incidence in Chongqing City from 1997 to 2008, analyzed by Poisson regression models.</p