Semiparametric functional data analysis for longitudinal/clustered data: theory and application

Semiparametric models play important roles in the field of biological statistics. In this dissertation, two types of semiparametic models are to be studied. One is the partially linear model, where the parametric part is a linear function. We are to investigate the two common estimation methods for the partially linear models when the data is correlated  longitudinal or clustered. The other is a semiparametric model where a latent covariate is incorporated in a mixed effects model. We will propose a semiparametric approach for estimation of this model and apply it to the study on colon carcinogenesis. First, we study the profilekernel and backfitting methods in partially linear models for clustered/longitudinal data. For independent data, despite the potential rootn inconsistency of the backfitting estimator noted by Rice (1986), the two estimators have the same asymptotic variance matrix as shown by Opsomer and Ruppert (1999). In this work, theoretical comparisons of the two estimators for multivariate responses are investigated. We show that, for correlated data, backfitting often produces a larger asymptotic variance than the profilekernel method; that is, in addition to its bias problem, the backfitting estimator does not have the same asymptotic efficiency as the profilekernel estimator when data is correlated. Consequently, the common practice of using the backfitting method to compute profilekernel estimates is no longer advised. We illustrate this in detail by following Zeger and Diggle (1994), Lin and Carroll (2001) with a working independence covariance structure for nonparametric estimation and a correlated covariance structure for parametric estimation. Numerical performance of the two estimators is investigated through a simulation study. Their application to an ophthalmology dataset is also described. Next, we study a mixed effects model where the main response and covariate variables are linked through the positions where they are measured. But for technical reasons, they are not measured at the same positions. We propose a semiparametric approach for this misaligned measurements problem and derive the asymptotic properties of the semiparametric estimators under reasonable conditions. An application of the semiparametric method to a colon carcinogenesis study is provided. We find that, as compared with the corn oil supplemented diet, fish oil supplemented diet tends to inhibit the increment of bcl2 (oncogene) gene expression in rats when the amount of DNA damage increases, and thus promotes apoptosis

Complete genome of Phenylobacterium zucineum – a novel facultative intracellular bacterium isolated from human erythroleukemia cell line K562

<p>Abstract</p> <p>Background</p> <p><it>Phenylobacterium zucineum </it>is a recently identified facultative intracellular species isolated from the human leukemia cell line K562. Unlike the known intracellular pathogens, <it>P. zucineum </it>maintains a stable association with its host cell without affecting the growth and morphology of the latter.</p> <p>Results</p> <p>Here, we report the whole genome sequence of the type strain HLK1^T. The genome consists of a circular chromosome (3,996,255 bp) and a circular plasmid (382,976 bp). It encodes 3,861 putative proteins, 42 tRNAs, and a 16S-23S-5S rRNA operon. Comparative genomic analysis revealed that it is phylogenetically closest to <it>Caulobacter crescentus</it>, a model species for cell cycle research. Notably, <it>P. zucineum </it>has a gene that is strikingly similar, both structurally and functionally, to the cell cycle master regulator CtrA of <it>C. crescentus</it>, and most of the genes directly regulated by CtrA in the latter have orthologs in the former.</p> <p>Conclusion</p> <p>This work presents the first complete bacterial genome in the genus <it>Phenylobacterium</it>. Comparative genomic analysis indicated that the CtrA regulon is well conserved between <it>C. crescentus </it>and <it>P. zucineum</it>.</p

Epigenetic modification and inheritance in sexual reversal of fish

Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model—a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD—we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish

Generalization of PhaseNet in Shandong and its application to the Changqing M4.1 earthquake sequenceKey points

Waveforms of seismic events, extracted from January 2019 to December 2021 were used to construct a test dataset to investigate the generalizability of PhaseNet in the Shandong region. The results show that errors in the picking of seismic phases (P- and S-waves) had a broadly normal distribution, mainly concentrated in the ranges of −0.4–0.3 s and −0.4–0.8 s, respectively. These results were compared with those published in the original PhaseNet article and were found to be approximately 0.2–0.4 s larger. PhaseNet had a strong generalizability for P- and S-wave picking for epicentral distances of less than 120 km and 110 km, respectively. However, the phase recall rate decreased rapidly when these distances were exceeded. Furthermore, the generalizability of PhaseNet was essentially unaffected by magnitude. The M4.1 earthquake sequence in Changqing, Shandong province, China, that occurred on February 18, 2020, was adopted as a case study. PhaseNet detected more than twice the number of earthquakes in the manually obtained catalog. This further verified that PhaseNet has strong generalizability in the Shandong region, and a high-precision earthquake catalog was constructed. According to these precise positioning results, two earthquake sequences occurred in the study area, and the southern cluster may have been triggered by the northern cluster. The focal mechanism solution, regional stress field, and the location results of the northern earthquake sequence indicated that the seismic force of the earthquake was consistent with the regional stress field

Strength and Environmental Behaviours of Municipal Solid Waste Incineration Fly Ash for Cement-Stabilised Soil

Many sandy soil foundations need to be solidified during traffic construction in Guangxi, China. Because it has a similar chemical composition as cement, municipal solid waste incineration fly ash (MSWIFA) can strengthen sandy soil. However, the chloride ions and heavy metals in MSWIFA may have a negative influence on the solidification of sandy soil. Thus, FA resource use faces great challenges. This study evaluates the feasibility of using MSWIFA to solidify sandy soil. The acetic acid buffer solution method was used in the leaching test to simulate the weak acid groundwater environment in the Guangxi karst landform. The effects of the treatment methods (washing with ferrous sulphate solution, pre-treatment of organics via chelation, and adding sugarcane ash) on the strength and environmental characteristics of fly ash cement-stabilised soil (FACS) are discussed in detail. The results indicate that the FACS unconfined compressive strength (UCS) decreased by 24.82&ndash;46.64% when 5% cement was replaced with FA. Sugarcane ash effectively improved the strength of FACS by more than 10%. The leaching concentrations of Zn and Cu in the FACS meet the concentration limit set by GB 16889-2008. The leaching concentrations of Cr and Pb after washing with 6% ferrous sulphate solution were reduced by more than 30%. Meanwhile, the FACS strength developed faster. Organic chelating agents solidified most heavy metals

Winter Green Manure Decreases Subsoil Nitrate Accumulation and Increases N Use Efficiencies of Maize Production in North China Plain

Planting a deep-rooted green manure (GM) (more than 1.0 m depth) greatly improves soil fertility and reduces the loss of nutrients. However, few studies have examined the response of soil nitrogen (N) distribution in the soil profile and subsoil N recovery to the long-term planting and incorporation of deep-rooted GM. Based on a 12-year (2009–2021) experiment of spring maize-winter GMs rotation in the North China Plain (NCP), this study investigated the effects of different GMs that were planted over the winter, including ryegrass (RrG, Lolium L.) (>1.0 m), Orychophragmus violaceus (OrV, Orychophragmus violaceus L.) (>0.8 m), and hairy vetch (VvR, Vicia villosa Roth.) (>1.0 m), on the spring maize yield, N distribution in the deep soil profile, N use efficiencies, functional gene abundances involving soil nitrification–denitrification processes and N2O production. Compared with the winter fallow, the maize yield significantly increased by 11.6% after 10 years of green manuring, and water storage in 0–200 cm soil profile significantly increased by 5.0–17.1% at maize seedling stage. The total N content in the soil layer at 0–90 cm increased by 15.8–19.7%, while the nitrate content in the deep soil layer (80–120 cm) decreased by 17.8–39.6%. Planting GM significantly increased the N recovery rate (10.4–32.7%) and fertilizer N partial productivity (4.6–13.3%). Additionally, the topsoil N functional genes (ammonia-oxidizing archaea amoA, ammonia-oxidizing bacterial amoA, nirS, nirK) significantly decreased without increasing N2O production potential. These results indicated that long-term planting of the deep-rooted GM effectively reduce the accumulation of nitrates in the deep soil and improve the crop yield and N use efficiencies, demonstrating a great value in green manuring to improve the fertility of the soil, increase the crop yield, and reduce the risk of N loss in NCP

Total Glucosides of Paeony Alleviate Cell Apoptosis and Inflammation by Targeting the Long Noncoding RNA XIST/MicroRNA-124-3p/ITGB1 Axis in Renal Ischemia/Reperfusion Injury

Objective. Renal ischemia/reperfusion injury (RI/RI) is the main cause of acute kidney injury. Total glucosides of paeony (TGP) are a traditional Chinese medicine. This study was aimed at exploring the role of TGP in RI/RI and its underlying mechanism of action. Methods. Rat RI/RI models were constructed by surgical operation. Serum creatinine (Scr) and blood urea nitrogen (BUN) were used to evaluate renal function. The levels of proinflammatory cytokines were detected by ELISA. RI/RI was simulated by hypoxia/reoxygenation (H/R) treatment in renal cells in vitro. The lncRNA XIST (XIST) expression was analyzed by qRT-PCR. Then, the viability and apoptosis of renal cells were detected by MTT and flow cytometry assay. Additionally, dual-luciferase reporter assay was used to determine the interactions among XIST, microRNA-124-3p (miR-124-3p), and ITGB1. Results. TGP improved renal function and inhibited inflammatory responses after RI/RI. XIST expression was highly expressed in rat RI/RI models and H/R-treated renal cells, whereas treatment with TGP downregulated the XIST expression. Additionally, TGP increased viability and attenuated apoptosis and inflammation of H/R-treated renal cells via inhibiting XIST. Moreover, XIST was competitively bound to miR-124-3p, and ITGB1 was a target of miR-124-3p. miR-124-3p overexpression or ITGB1 inhibition rescued the reduction effect on viability and mitigated the promoting effects on cell apoptosis and inflammation caused by XIST overexpression in H/R-treated renal cells. Conclusions. In vivo, TGP attenuated renal dysfunction and inflammation in RI/RI rats. In vitro, TGP inhibited XIST expression to modulate the miR-124-3p/ITGB1 axis, alleviating the apoptosis and inflammation of H/R-treated renal cells

Schisandrin B Attenuates Cancer Invasion and Metastasis Via Inhibiting Epithelial-Mesenchymal Transition

<div><h3>Background</h3><p>Metastasis is the major cause of cancer related death and targeting the process of metastasis has been proposed as a strategy to combat cancer. Therefore, to develop candidate drugs that target the process of metastasis is very important. In the preliminary studies, we found that schisandrin B (Sch B), a naturally-occurring dibenzocyclooctadiene lignan with very low toxicity, could suppress cancer metastasis.</p> <h3>Methodology</h3><p>BALB/c mice were inoculated subcutaneously or injected via tail vein with murine breast cancer 4T1 cells. Mice were divided into Sch B-treated and control groups. The primary tumor growth, local invasion, lung and bone metastasis, and survival time were monitored. Tumor biopsies were examined immuno- and histo-pathologically. The inhibitory activity of Sch B on TGF-β induced epithelial-mesenchymal transition (EMT) of 4T1 and primary human breast cancer cells was assayed.</p> <h3>Principal Findings</h3><p>Sch B significantly suppressed the spontaneous lung and bone metastasis of 4T1 cells inoculated s.c. without significant effect on primary tumor growth and significantly extended the survival time of these mice. Sch B did not inhibit lung metastasis of 4T1 cells that were injected via tail vein. Delayed start of treatment with Sch B in mice with pre-existing tumors did not reduce lung metastasis. These results suggested that Sch B acted at the step of local invasion. Histopathological evidences demonstrated that the primary tumors in Sch B group were significantly less locally invasive than control tumors. In vitro assays demonstrated that Sch B could inhibit TGF-β induced EMT of 4T1 cells and of primary human breast cancer cells.</p> <h3>Conclusions</h3><p>Sch B significantly suppresses the lung and bone metastasis of 4T1 cells via inhibiting EMT, suggesting its potential application in targeting the process of cancer metastasis.</p> </div

Sch B prolongs mouse survival time in dose-dependent manner.

<p>Mice (n = 8 for each group) receiving Sch B (100, 30, 10 mg/kg body weight) or vehicle every day for total 7 doses, and primary tumors were resected on day 10. (A) Mouse survival time. (B) Mouse body weight. (C) Tumor weight resected on day 10. *, P<0.05, **, P<0.01, Sch B versus control group.</p