This paper considers variable selection and identification of dynamic additive nonlinear systems via kernel-based nonparametric approaches, where the number of variables and additive functions may be ...large. Variable selection aims to find which additive functions contribute and which do not. The proposed variable selection consists of two successive steps. At the first step, one estimates each additive function by kernel-based nonparametric identification approaches without suffering from the curse of dimensionality. At the second step, a nonnegative garrote estimator is applied to identify which additive functions are nonzero by utilizing the obtained nonparametric estimates of each function. Under weak conditions, the nonparametric estimates of each additive function can achieve the same asymptotic properties as for 1D nonparametric identification based on kernel functions. It is also established that the nonnegative garrote estimator turns a consistent estimate for each additive function into a consistent variable selection with probability one as the number of samples tends to infinity. Two simulation examples are presented to verify the effectiveness of the variable selection and identification approaches proposed in the paper.
Background
We compared efficacy and safety of paclitaxel/capecitabine therapy followed by capecitabine for maintenance (PACX) versus cisplatin/capecitabine therapy (XP) in advanced gastric cancer.
...Methods
Multicenter, randomized, phase III trial was conducted in China (December 2009–February 2014). Adults (
n
= 320) with histologically confirmed, untreated metastatic/unresectable gastric or gastroesophageal junction adenocarcinoma; with ≥ 1 measureable lesions according to Response Evaluation Criteria in Solid Tumors 1.0 criteria; Karnofsky performance score ≥ 70 and life expectancy ≥ 3 months were randomized (1:1) to PACX or XP. PACX group received paclitaxel 80 mg/m
2
intravenous on days 1 and 8; capecitabine 1000 mg/m
2
orally BD on days 1–14, followed by a 7-day rest interval for 4 cycles, followed by maintenance capecitabine at same dosage/schedule until disease progression, unendurable adverse events or death. XP group received cisplatin intravenous 80 mg/m
2
on day 1 and capecitabine at same dosage/schedule as PACX group per cycle for 6 cycles.
Results
Median progression-free survival (5.0 versus 5.3 months; hazard ratio 95% CI: 0.906; 0.706–1.164;
p
= 0.44) and overall survival (12.5 versus 11.8 months; hazard ratio: 0.878 0.685–1.125;
p
= 0.30) were not significantly different between PACX and XP groups. Objective response rate was significantly higher (43.1 versus 28.8%;
p
= 0.012) and disease control rate was similar (77.5 versus 72.5%;
p
= 0.75) in PACX versus XP, respectively. Quality of life was significantly improved in PACX versus XP after three treatment cycles. Many treatment-related adverse events were significantly lesser in PACX than XP.
Conclusions
First-line chemotherapy with PACX is effective with milder toxicities in advanced gastric cancer, but could not replace XP.
The purpose of this study was to assess the potential effects of polysaccharides from edible mushroom Grifola frondosa (GFP) on lipid metabolic disorders and gut microbiota dysbiosis, and elucidate ...their possible regulatory mechanisms on lipid and cholesterol metabolism in high-fat diet (HFD)-exacerbated hyperlipidemic and hypercholesterolemic rats. Results showed that oral administration of GFP markedly alleviated dyslipidaemia through decreasing the serum levels of total triglycerides, total cholesterol, and free fatty acids, and significantly suppressing hepatic lipid accumulation and steatosis. Besides, the excretion of fecal bile acids was also promoted by oral administration of GFP. Metagenomic analysis revealed that GFP supplementation (400 mg kg-1 day-1) resulted in significant structure changes on gut microbiota in HFD-fed rats, in particular modulating the relative abundance of functionally relevant microbial phylotypes compared with the HFD group. Key microbial phylotypes responding to GFP intervention were identified to strongly correlate with the lipid metabolism disorder associated parameters using the correlation network based on Spearman's correlation coefficient. Serum and hepatic lipid profiles were found positively correlated with Clostridium-XVIII, Butyricicoccus and Turicibacter, but negatively correlated with Helicobater, Intestinimonas, Barnesiella, Parasutterella, Ruminococcus and Flavonifracter. Moreover, GFP treatment (400 mg kg-1 day-1) regulated the mRNA expression levels of the genes responsible for hepatic lipid and cholesterol metabolism. Oral supplementation of GFP markedly increased the mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acid (BA) synthesis and excretion from the liver. These findings illustrated that GFP could ameliorate lipid metabolic disorders through modulating specific gut microbial phylotypes and regulating hepatic lipid and cholesterol metabolism related genes, and therefore could be used as a potential functional food ingredient for the prevention or treatment of hyperlipidemia.
Bio-based hydrophobic coating modified cotton fabrics with durable flame retardancy are of high interest in the application of oil-water separation for not only avoiding the use of hazardous ...substances but also improving the fire safety during use. Herein, phytic acid@Polyurushiol‑titanium complex coated cotton fabric was developed using the facile dip-coating method involving the sequential immersion in the solution of poly(ethyleneimine), phytic acid, titanium oxide, and urushiol. The underlying coating accommodated abundance of phytic acid, which imparted excellent flame retardancy to cotton fabric, and the top coating composed of the polyurushiol‑titanium complex endowed cotton fabric with high hydrophobicity that the water contact angle (WCA) was up to 149.8°. The hydrophobicity also guaranteed effective protection of the underlying phytic acid against chemical solvents and abrasion. Besides, the hydrophobic coating allowed cotton fabric for good self-cleaning and effective oil-water separation. Therefore, the preparation of phytic acid@polyurushiol‑titanium complex coated cotton fabric offers a promising approach to construct durable biomass-coated cellulose-based fabric with multifunctionality.
Because of their misuse and poor management, antibiotics pose a significant threat to the ecological environment and human health. The development of highly sensitive and effective sensors to detect ...such environmental contaminants is a crucial and challenging task. As a new class of desirable biocompatible materials, biological metal‐organic frameworks are considered as a viable platform for sensing applications. Herein, we report the synthesis of biological luminescent metal‐organic framework Zn6Ad4(BPDC‐(OH)2)4n (JNU‐104) using adenine (Ad) and 2,2′‐dihydroxy‐1,1′‐biphenyl‐4,4′‐dicarboxylic acid BPDC‐(OH)2 as organic linkers. JNU‐104 serves as a robust and sensitive luminescent sensor for detecting tetracycline antibiotics in aqueous media with low limits of detection (LODs) of 0.023, 0.029 and 0.024 μM for tetracycline (TC), oxytetracycline (OTC), and chlortetracycline (CTC), respectively. Furthermore, the MOF‐based test strips show a rapid and visualizable luminescence response to tetracycline antibiotics, making JNU‐104 a promising candidate for practical applications in sensing.
We report the synthesis of a stable biological luminescent metal‐organic framework (bio‐LMOF) using adenine and 2,2′‐dihydroxy‐1,1′‐biphenyl‐4,4′‐dicarboxylic acid as organic linkers. This bio‐LMOF serves as a robust and sensitive luminescent sensor for detecting tetracycline antibiotics in aqueous media with low limits of detection.
With 432 513 samples from UK Biobank dataset, multivariable linear/logistic regression were used to estimate the relationship between psoriasis/psoriatic arthritis (PsA) and estimated bone mineral ...density (eBMD)/osteoporosis, controlling for potential confounders. Here, confounders were set in three ways: model0 (including age, height, weight, smoking and drinking), model1 (model0 +regular physical activity) and model2 (model1 +medication treatments). The eBMD was derived from heel ultrasound measurement. And 4904 patients with psoriasis and 847 patients with PsA were included in final analysis. Mendelian randomisation (MR) approach was used to evaluate the causal effect between them.
Lower eBMD were observed in patients with PsA than in controls in both model0 (β-coefficient=-0.014, p=0.0006) and model1 (β-coefficient=-0.013, p=0.002); however, the association disappeared when conditioning on treatment with methotrexate or ciclosporin (model2) (β-coefficient=-0.005, p=0.28), mediation analysis showed that 63% of the intermediary effect on eBMD was mediated by medication treatment (p<2E-16). Patients with psoriasis without arthritis showed no difference of eBMD compared with controls. Similarly, the significance of higher risk of osteopenia in patients with PsA (OR=1.27, p=0.002 in model0) could be eliminated by conditioning on medication treatment (p=0.244 in model2). Psoriasis without arthritis was not related to osteopenia and osteoporosis. The weighted Genetic Risk Score analysis found that genetically determined psoriasis/PsA were not associated with eBMD (p=0.24 and p=0.88). Finally, MR analysis showed that psoriasis/PsA had no causal effect on eBMD, osteoporosis and fracture.
The effect of PsA on osteoporosis was secondary (eg, medication) but not causal. Under this hypothesis, psoriasis without arthritis was not a risk factor for osteoporosis.
Autopolyploidy is a valuable model for studying whole-genome duplication (WGD) without hybridization, yet little is known about the genomic structural and functional changes that occur in ...autopolyploids after WGD. Cyclocarya paliurus (Juglandaceae) is a natural diploid-autotetraploid species. We generated an allele-aware autotetraploid genome, a chimeric chromosome-level diploid genome, and whole-genome resequencing data for 106 autotetraploid individuals at an average depth of 60 × per individual, along with 12 diploid individuals at an average depth of 90 × per individual.
Autotetraploid C. paliurus had 64 chromosomes clustered into 16 homologous groups, and the majority of homologous chromosomes demonstrated similar chromosome length, gene numbers, and expression. The regions of synteny, structural variation and nonalignment to the diploid genome accounted for 81.3%, 8.8% and 9.9% of the autotetraploid genome, respectively. Our analyses identified 20,626 genes (69.18%) with four alleles and 9191 genes (30.82%) with one, two, or three alleles, suggesting post-polyploid allelic loss. Genes with allelic loss were found to occur more often in proximity to or within structural variations and exhibited a marked overlap with transposable elements. Additionally, such genes showed a reduced tendency to interact with other genes. We also found 102 genes with more than four copies in the autotetraploid genome, and their expression levels were significantly higher than their diploid counterparts. These genes were enriched in enzymes involved in stress response and plant defense, potentially contributing to the evolutionary success of autotetraploids. Our population genomic analyses suggested a single origin of autotetraploids and recent divergence (~ 0.57 Mya) from diploids, with minimal interploidy admixture.
Our results indicate the potential for genomic and functional reorganization, which may contribute to evolutionary success in autotetraploid C. paliurus.
Ganoderic acid A (GA) is one of the most abundant triterpenoids in Ganoderma lucidum, and has been proved to possess a wide range of beneficial health effects. The aim of the current study is to ...investigate the amelioration effects and mechanism of GA on improving hyperlipidemia in mice fed a high-fat diet (HFD). The results showed that GA intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, and ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation of lipid droplets in the liver induced by HFD-feeding was greatly alleviated by GA intervention. In addition, GA intervention also increased the level of short chain fatty acids (SCFAs) in the intestine and promoted the excretion of bile acids (BAs) through feces. High-throughput sequencing of bacterial full-length 16S rDNA revealed that daily supplementation with GA made significant structural changes in the gut microbial population of mice fed with HFD, in particular modulating the relative abundance of some function related microbial phylotypes. The relationships between lipid metabolic parameters and gut microbial phylotypes were also revealed by correlation analysis based on a heatmap and network. The result showed that 46 key gut microbial phylotypes (OTUs) were markedly correlated with at least one lipid metabolic parameter. Moreover, UPLC-QTOF/MS-based liver metabolomics showed that 111 biomarkers (47 up-regulated metabolites and 64 down-regulated metabolites) were significantly changed after high-dose GA intervention (75 mg kg
day
), compared with the HFD-fed hyperlipidemic mice. Metabolic pathway enrichment analysis of the differential hepatic metabolites demonstrated that GA intervention had significant regulatory effects on primary bile acid biosynthesis, fatty acid biosynthesis, amino sugar and nucleotide sugar metabolism, inositol phosphate metabolism, and so on. In addition, GA intervention regulated the mRNA levels of hepatic genes involved in fatty acid metabolism and bile acid homeostasis. These findings present new evidence supporting that GA from G. lucidum has the potential to alleviate lipid metabolic disorders and ameliorate the imbalance of gut microflora in a positive way.
To investigate whether the recommendation to remove 15 lymph nodes that is used in the staging system is necessary to assess gastric cancer progression and to evaluate whether our metastatic lymph ...node ratio dividing method, adapted from the AJCC's (American Joint Committee on Cancer) 7(th) TNM staging system, is helpful for the patients with fewer than 15 harvested lymph nodes.
We performed a retrospective study of 1101 patients with histologically diagnosed gastric cancer who underwent a D2 gastrectomy at the Sun Yat-sen University Cancer Center between January 2001 and December 2010. The Kappa and Chi-squared tests were employed to compare the clinicopathological variables. The Kaplan-Meier method and Cox regression were employed for the univariate and multivariate survival analyses.
In the trial, 346, 601 and 154 patients had 0-14, 15-30 and more than 30 lymph nodes harvested, respectively. The median survival times of patients with different lymph nodes harvested in N0, N1, N2 and N3a groups were 45.43, 54.28 and 66.95 months (p=0.068); 49.22, 44.25 and 56.72 months (p<0.001), 43.94, 47.97 and 35.19 months (p=0.042); 32.88, 42.76 and 23.50 months (p=0.016). Dividing the patients who had fewer than 15 lymph nodes harvested by the metastatic lymph node ratio at 0, 0.13 and 0.40, the median survival times of these 4 groups were 70.6, 50.5, 53.5 and 30.7 months (p<0.001). After re-categorising these 4 groups into the N0, N1, N2, N3a groups, the histological grade, T staging, premier N staging, and restaged N staging were the independent prognostic factors.
Large numbers of lymph nodes harvested in radical gastrectomy do not cause stage migration. For those patients with a small number of harvested lymph nodes, their stage should be divided by the metastatic lymph node ratio, referred to in the TNM staging system, to assign them an accurate stage.
In our quest to leverage the capabilities of the emerging single-atom catalysts (SACs) for wastewater purification, we confronted fundamental challenges related to electron scarcity and instability. ...Through meticulous theoretical calculations, we identified optimal placements for nitrogen vacancies (Nv) and iron (Fe) single-atom sites, uncovering a dual-site approach that significantly amplified visible-light absorption and charge transfer dynamics. Informed by these computational insights, we cleverly integrated Nv into the catalyst design to boost electron density around iron atoms, yielding a potent and flexible photoactivator for benign peracetic acid. This exceptional catalyst exhibited remarkable stability and effectively degraded various organic contaminants over 20 cycles with self-cleaning properties. Specifically, the Nv sites captured electrons, enabling their swift transfer to adjacent Fe sites under visible light irradiation. This mechanism accelerated the reduction of the formed "peracetic acid-catalyst" intermediate. Theoretical calculations were used to elucidate the synergistic interplay of dual mechanisms, illuminating increased adsorption and activation of reactive molecules. Furthermore, electron reduction pathways on the conduction band were elaborately explored, unveiling the production of reactive species that enhanced photocatalytic processes. A six-flux model and associated parameters were also applied to precisely optimize the photocatalytic process, providing invaluable insights for future photocatalyst design. Overall, this study offers a molecule-level insight into the rational design of robust SACs in a photo-Fenton-like system, with promising implications for wastewater treatment and other high-value applications.
PDF
