Semiparametric pseudo-score and pseudo-likelihood for evaluating correlate of protection in vaccine trials.

In vaccine clinical trials, vaccine efficacy endpoint analysis is usually associated with in high cost or extended study duration, due to the generally low infection rate. Correlate of protection (CoP), which refers to surrogate endpoint, usually immunological response, that can reliably predict the treatment effect, provides a more efficient and less costly approach to evaluate the vaccine. To handle the challenge of the missingness in the unobserved surrogate immune biomarker, the pseudo-score (PS) method, semiparametric method and pseudo-likelihood (PL) method demonstrated their advantages on different aspects. In this article, we propose new methodologies to combine the advantages of PS and PL with semiparametric methods respectively, to achieve higher estimate efficiency, allow continuous baseline predictor variable, and handle multiple surrogate markers. The advantage of our methodologies are demonstrated by a simulation study in different settings and applied to a case study, which eventually can improve the chance of a successful trial.

A functional mixed model for scalar on function regression with application to a functional MRI study.

Motivated by a functional magnetic resonance imaging (fMRI) study, we propose a new functional mixed model for scalar on function regression. The model extends the standard scalar on function regression for repeated outcomes by incorporating subject-specific random functional effects. Using functional principal component analysis, the new model can be reformulated as a mixed effects model and thus easily fit. A test is also proposed to assess the existence of the subject-specific random functional effects. We evaluate the performance of the model and test via a simulation study, as well as on data from the motivating fMRI study of thermal pain. The data application indicates significant subject-specific effects of the human brain hemodynamics related to pain and provides insights on how the effects might differ across subjects.

Biphasically Modulating the Activity of Carboxypeptidase G2 with Ultrasound.

BACKGROUND/AIMS: Carboxypeptidase G2 (CPG2) has been used for cancer prodrug therapy to realize the targeted release of active drugs, but there yet lacks a means to modulate the CPG2 activity. Here ultrasound was used to modulate the CPG2 activity. METHODS: The activity of insonated CPG2 was determined, and then underlying biochemical (i.e., monomer, dimer and conformation) and ultrasonic (i.e., heat and cavitation) mechanisms were explored. RESULTS: Ultrasound (1.0 MHz) increased or decreased the enzymatic activity; the activity decreased as zero- or first-order kinetics, depending on the intensity. L1 (10 W/cm2 for 200 s) improved the activity via increasing the specific activity. L2 or L3 (20 W/cm2 for 1200 or 3000 s) decreased the activity via disassembling the dimer, degrading the monomer, inducing glycosylation, transforming conformation and decreasing the specific activity. An increase or a slight decrease of activity attributable to 10 W/cm2 was reversible, but the activity decrease due to 20 W/cm2 was irreversible. The enzymatic modulation was realized via cavitation. CONCLUSION: Ultrasound can biphasically modulate the CPG2 activity, and can be employed in the CPG2-prodrug therapy to adjust the release and moles of active drugs.

[Effective Ingredients of Yangjing Zhongyu Decoction Regulated Androgen Biosyntheses by Mitogen-Activated Protein Kinase Pathway in Porcine Granulose Cells].

OBJECTIVE: To study the molecular mechanism of Yangjing Zhongyu Decoction (YZD) n-butanol extracts (ZDC) and ethyl acetate extracts (YSYZ) in reducing androgen in porcine granulose cells by mitogen-activated protein kinase (MAPK) pathway. METHODS: Porcine granulose cells were isolated and cultured. They were inoculated by MAPK inhibitor PD98059 at different concentrations, and then they were divided into the blank control group (0), 1, 3, 10, and 25 micromol/L groups. After 24-h culture the cytochrome P450c17a (CYP17) mRNA expression level was detected using Real-time fluorescent quantitative PCR. Contents of androgen (testosterone) in the supernate were detected using RIA and optimal PD98059 concentration screened. After intervened by 10 micromol/L PD98059 for 24 h, the culture solution was intervened by effective ingredients of with or without YZD or YSYZ at various concentrations (0, 1 , 5, 25, 50 mg/mL) at various time points (3, 6, 18, 24 h). Expression levels of p-ERK1/2, c-Fos and CYP17 were detected by Western blot. Testosterone content in the supernate was determined by radioimmunoassay (RIA). RESULTS: Ten pLmol/L PD98059 could obviously decrease p-ERK1/2 protein expression and increase CYP17 mRMA expression, and elevate testosterone content in the supernate (P < 0.05). ZDC and YSYZ at 25 ng/mL could increase p-ERK1/2 protein expression and c-Fos levels, and reduce CYP17 protein expression, and lower testosterone content in the supernate after 6-h intervention (P < 0.01). CONCLUSION: Effective ingredients of YZD could reduce androgen production in porcine granulose cells through increasing activities of MAPK.

Resolving the dynamics of chrysolaminarin regulation in a marine diatom: A physiological and transcriptomic study.

Diatom containing different active biological macromolecules are thought to be an excellent microbial cell factory. Phaeodactylum tricornutum, a model diatom, is a superb chassis organism accumulating chrysolaminarin with important bioactivities. However, the characteristic of chrysolaminarin accumulation and molecular mechanism of the fluctuated chrysolaminarin in diatom are still unknown. In this study, physiological data and transcriptomic analysis were carried out to clarify the mechanism involved in chrysolaminarin fluctuation. The results showed that chrysolaminarin content fluctuated, from 7.41 % dry weight (DW) to 40.01 % DW during one light/dark cycle, increase by day and decrease by night. The similar fluctuated characteristic was also observed in neutral lipid content. Genes related to the biosynthesis of chrysolaminarin and neutral lipid were up-regulated at the beginning of light-phase, explaining the accumulation of these biological macromolecules. Furthermore, genes involved in carbohydrate degradation, cell cycle, DNA replication and mitochondria-localized ß-oxidation were up-regulated at the end of light phase and at the beginning of dark phase hinting an energy transition of carbohydrate to cell division during the dark period. Totally, our findings provide important information for the regulatory mechanism in the diurnal fluctuation of chrysolaminarin. It would also be of great help for the mass production of economical chrysolaminarin in marine diatom.

Rural Workplace Sustainable Development of Smart Rural Governance Workplace Platform for Efficient Enterprise Performances.

In the long developmental process, China's agriculture has transformed from organic agriculture to inorganic agriculture. New technologies have made the modernization of agriculture possible. However, most older people who are engaged in agriculture may not completely understand the modernization of agriculture. Based on the limitations of traditional image target detection methods, a deep learning-based pest target detection and recognition method is proposed from a blockchain perspective, to analyze and research agricultural data supervision and governance and explore the effectiveness of deep learning methods in crop pest detection and recognition. The comparative analysis demonstrates that the average precision (AP) of GA-CPN-LAR (global activation-characteristic pyramid network-local activation region) increases by 4.2% compared with other methods. Whether under the Inception or ResNet-50 backbone networks, the AP of GA-CPN-LAR is significantly better than other methods. Compared with the ResNet-50 backbone network, GA-CPN-LAR has higher accuracy and recall rates under Inception. Precision-recall curve measurement shows that the proposed method can significantly reduce the false detection rate and missed detection rate. The GA-CPN-LAR model proposed here has a higher AP value on the MPD dataset than the other target detection methods, which can be increased by 4.2%. Besides, the accuracy and recall of the GA-CPN-LAR method corresponding to two representative pests under the initial feature extractor are higher than the MPD dataset baseline. In addition, the research results of the MPD dataset and AgriPest dataset also show that the pest target detection method based on convolutional neural networks (CNNs) has a good presentation effect and can significantly reduce false detection and missed detection. Moreover, the pest regulation based on blockchain and deep learning comprehensively considers global and local feature extraction and pattern recognition, which positively impacts the conscientization of agricultural data processing and promotes the sustainable development of rural areas.

The relationship between farmers' entrepreneurial behavior and macroeconomics based on the probit regression model and entrepreneurial psychological capital.

At present, the research on the influence mechanism of psychological capital on farmers' entrepreneurial behavior is relatively mature. However, the relationship between farmers' entrepreneurial behavior and macroeconomics by entrepreneurial psychological capital (PsyCap) is still unclear. Based on this, firstly, this work analyzes the entrepreneurial PsyCap in detail. Secondly, the research hypothesis is put forward and a conceptual model is implemented. A questionnaire is designed to analyze the current situation of farmers' entrepreneurial PsyCap and entrepreneurial behavior. Finally, a structural equation model (SEM) is implemented to explore the relationship between farmers' entrepreneurial behavior and macroeconomics. The path test of the SEM is utilized to obtain the following. Macroeconomic growth has a significant positive impact on entrepreneurial behavior. Macroeconomics can affect farmers' entrepreneurial behavior to varying degrees by affecting the four entrepreneurial PsyCap of farmers' subjective cognition, Tenacity, hope and open-mindedness. This indicates that entrepreneurial PsyCap plays an intermediary role between farmers' entrepreneurial behavior and macroeconomics. The purpose of this work is to explore the relationship among farmers' entrepreneurial behavior, macroeconomics, and the role of entrepreneurial PsyCap through empirical analysis, thereby providing a theoretical reference for the subsequent country's optimization of farmers' entrepreneurial strategies.

Effects of laminarin zwitterionic carboxylate and sulfonate on the intestinal barrier function and gut microbiota.

Ulcerative colitis (UC) has become a global chronic disease that keeps increasing. This study was to explore the treatment effectiveness of two functional zwitterionic laminarins, zwitterionic sulfonate (LZS) and zwitterionic carboxylate (LZC), in dextran sulfate sodium (DSS) induced mouse model. FT-IR and NMR techniques were used to characterize the aforementioned functional zwitterion. Compared to UC mice, the composition and diversity of gut microbiota were significantly increased in the treated mice. Specifically, the composition of Bacteroidetes increased and the level of Firmicutes decreased. Moreover, we demonstrated the alleviation of colitis by LZS and LZC reflected by the improved integrity of intestinal mucosa, which includes increased number of goblet cells, mucin protein production, maintenance of collagens, as well as the lower extent of intestinal fibrosis. These findings indicated the potentials of LZC and LZS as promising agents to prevent colitis via adjusting gut microbiota and maintaining intestinal barrier integrity.

Cryptotanshinone Regulates Androgen Synthesis through the ERK/c-Fos/CYP17 Pathway in Porcine Granulosa Cells.

The aim of the study is to investigate the molecular mechanism behind androgen reduction in porcine granulosa cells (pGCs) with Salvia miltiorrhiza Bunge extract cryptotanshinone. PGCs were isolated from porcine ovaries and identified. Androgen excess model of the pGCs was induced with the MAPK inhibitor PD98059 and then treated with cryptotanshinone. The testosterone level was measured by radioimmunoassay in the culture media. The protein levels of P-ERK1/2, c-Fos, and CYP17 in the cells were measured by western blot. Cryptotanshinone decreased the concentration of testosterone and the protein level of CYP17 and increased the protein levels of P-ERK1/2 and c-Fos in the androgen excess mode. After the c-Fos gene was silenced by infection with c-Fos shRNA lentivirus, we measured the mRNA expression by quantitative RT-PCR and protein level by western blot of P-ERK1/2, c-Fos, and CYP17. This showed that the mRNA expression and protein level of P-ERK1/2 and c-Fos were significantly reduced in the shRNA-c-Fos group compared to the scrambled group, while those of CYP17 were significantly increased. So we concluded that cryptotanshinone can significantly reduce the androgen excess induced by PD98059 in pGCs. The possible molecular mechanism for this activity is regulating the ERK/c-Fos/CYP17 pathway.