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To identify long non-coding RNAs (lncRNAs) and their potential roles in hepatic fibrosis in rat liver issues induced by CCl4, lncRNAs and genes were analyzed in fibrotic rat liver tissues by RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Differentially expressed (DE) lncRNAs (DE-lncRNAs) and genes were subjected to bioinformatics analysis and used to construct a co-expression network. We identified 10 novel DE-lncRNAs that were downregulated during the hepatic fibrosis process. The cis target gene of DE-lncRNA, XLOC118358, was Met, and the cis target gene of the other nine DE-lncRNAs, XLOC004600, XLOC004605, XLOC004610, XLOC004611, XLOC004568, XLOC004580 XLOC004598, XLOC004601, and XLOC004602 was Nox4. The results of construction of a pathway-DEG co-expression network show that lncRNA-Met and lncRNAs-Nox4 were involved in oxidation-reduction processes and PI3K/Akt signaling pathway. Our results identified 10 DE-lncRNAs related to hepatic fibrosis, and the potential roles of DE-lncRNAs and target genes in hepatic fibrosis might provide new therapeutic strategies for hepatic fibrosis.

The COVID-19 pandemic is currently spreading widely around the world, causing huge threats to public safety and global society. This study analyzes the spatiotemporal pattern of the COVID-19 pandemic in China, reveals China's epicenters of the pandemic through spatial clustering, and delineates the substantial effect of distance to Wuhan on the pandemic spread. The results show that the daily new COVID-19 cases mostly occurred in and around Wuhan before March 6, and then moved to the Grand Bay Area (Shenzhen, Hong Kong and Macau). The total COVID-19 cases in China were mainly distributed in the east of the Huhuanyong Line, where the epicenters accounted for more than 60% of the country's total in/on 24 January and 7 February, half in/on 31 January, and more than 70% from 14 February. The total cases finally stabilized at approximately 84,000, and the inflection point for Wuhan was on 14 February, one week later than those of Hubei (outside Wuhan) and China (outside Hubei). The generalized additive model-based analysis shows that population density and distance to provincial cities were significantly associated with the total number of the cases, while distances to prefecture cities and intercity traffic stations, and population inflow from Wuhan after 24 January, had no strong relationships with the total number of cases. The results and findings should provide valuable insights for understanding the changes in the COVID-19 transmission as well as implications for controlling the global COVID-19 pandemic spread.

This study collected 183 Hemerocallis varieties to conduct numerical classification of flower color and provide valuable baseline data and foundational theory for normalization and precision of Hemerocallis. The color CIELab phenotypes were collected via colorimeter (CR-10 Plus), which separately measured three sepal and petal parts (throat, eye and limb). The colors of experimental samples were artificially named by the Royal Horticultural Society Colour Chart (RHSCC). All the data were analyzed using R software. The results showed that the throat was predominantly green-yellow, light yellow and yellow; green-yellow accounted for the largest proportion of sepals (67.76%) and petals (69.40%). The eye was more abundant, and there were significant differences between sepals and petals. The limb was clustered into five color groups (orange, yellow, pink, red and purple); the yellow group had the most varieties for both sepals and petals, containing 57.38% and 55.74%, respectively. Both sepals and petals had significant differences (p

TW-37 is a novel, potent and non-peptide Bcl-2 small-molecule inhibitor. Its activity in colorectal cancer (CRC) cells is studied. In both HCT-116 cells and primary human colon cancer cells, treatment with TW-37 at only nM concentration efficiently inhibited cell survival and proliferation. TW-37 also induced caspase-3/9 and apoptosis activation in CRC cells. Feedback autophagy activation was observed in TW-37-treated CRC cells. Reversely pharmacological autophagy inhibition or Beclin-1 knockdown by targeted-shRNA potentiated TW-37-induced apoptosis and killing of CRC cells. In vivo, intravenous injection of TW-37 inhibited HCT-116 tumor growth in mice. TW-37's anti-tumor activity was further potentiated against Beclin-1-silenced HCT-116 tumors. Together, targeting Bcl-2 family protein by TW-37 efficiently inhibits CRC cell growth in vitro and in vivo. Inhibition of feedback autophagy activation could further sensitize TW-37.

We investigated the inter-day effects of price limits policies that are employed in agent-based simulations. To isolate the impact of price limits from the impact of other factors, we built an artificial stock market with higher frequency price limits hitting. The trading mechanisms in this market are the same as the trading mechanisms in China's stock market. Then, we designed a series of simulations with and without price limits policy. The results of these simulations demonstrate that both upper and lower price limits can cause a volatility spillover effect and a trading interference effect. The process of price discovery will be delayed if upper price limits are imposed on a stock market; however, this phenomenon does not occur when lower price limits are imposed.

There is a great challenge in combining soil proximal spectra and remote sensing spectra to improve the accuracy of soil organic carbon (SOC) models. This is primarily because mixing of spectral data from different sources and technologies to improve soil models is still in its infancy. The first objective of this study was to integrate information of SOC derived from visible near-infrared reflectance (Vis-NIR) spectra in the laboratory with remote sensing (RS) images to improve predictions of topsoil SOC in the Skjern river catchment, Denmark. The second objective was to improve SOC prediction results by separately modeling uplands and wetlands. A total of 328 topsoil samples were collected and analyzed for SOC. Satellite Pour l'Observation de la Terre (SPOT5), Landsat Data Continuity Mission (Landsat 8) images, laboratory Vis-NIR and other ancillary environmental data including terrain parameters and soil maps were compiled to predict topsoil SOC using Cubist regression and Bayesian kriging. The results showed that the model developed from RS data, ancillary environmental data and laboratory spectral data yielded a lower root mean square error (RMSE) (2.8%) and higher R2 (0.59) than the model developed from only RS data and ancillary environmental data (RMSE: 3.6%, R2: 0.46). Plant-available water (PAW) was the most important predictor for all the models because of its close relationship with soil organic matter content. Moreover, vegetation indices, such as the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), were very important predictors in SOC spatial models. Furthermore, the 'upland model' was able to more accurately predict SOC compared with the 'upland & wetland model'. However, the separately calibrated 'upland and wetland model' did not improve the prediction accuracy for wetland sites, since it was not possible to adequately discriminate the vegetation in the RS summer images. We conclude that laboratory Vis-NIR spectroscopy adds critical information that significantly improves the prediction accuracy of SOC compared to using RS data alone. We recommend the incorporation of laboratory spectra with RS data and other environmental data to improve soil spatial modeling and digital soil mapping (DSM).

Price limit trading rules are adopted in some stock markets (especially emerging markets) trying to cool off traders' short-term trading mania on individual stocks and increase market efficiency. Under such a microstructure, stocks may hit their up-limits and down-limits from time to time. However, the behaviors of price limit hits are not well studied partially due to the fact that main stock markets such as the US markets and most European markets do not set price limits. Here, we perform detailed analyses of the high-frequency data of all A-share common stocks traded on the Shanghai Stock Exchange and the Shenzhen Stock Exchange from 2000 to 2011 to investigate the statistical properties of price limit hits and the dynamical evolution of several important financial variables before stock price hits its limits. We compare the properties of up-limit hits and down-limit hits. We also divide the whole period into three bullish periods and three bearish periods to unveil possible differences during bullish and bearish market states. To uncover the impacts of stock capitalization on price limit hits, we partition all stocks into six portfolios according to their capitalizations on different trading days. We find that the price limit trading rule has a cooling-off effect (object to the magnet effect), indicating that the rule takes effect in the Chinese stock markets. We find that price continuation is much more likely to occur than price reversal on the next trading day after a limit-hitting day, especially for down-limit hits, which has potential practical values for market practitioners.

This paper explores a method of managing the risk of the stock index futures market and the cross-market through analyzing the effectiveness of price limits on the Chinese Stock Index 300 futures market. We adopt a cross-market artificial financial market (include the stock market and the stock index futures market) as a platform on which to simulate the operation of the CSI 300 futures market by changing the settings of price limits. After comparing the market stability under different price limits by appropriate liquidity and volatility indicators, we find that enhancing price limits or removing price limits both play a negative impact on market stability. In contrast, a positive impact exists on market stability if the existing price limit is maintained (increase of limit by10%, down by 10%) or it is broadened to a proper extent. Our study provides reasonable advice for a price limit setting and risk management for CSI 300 futures.

Swell-shrink characteristic soils exhibit a high susceptibility to cracking during the drying process, which poses a significant risk of various geological disasters. Among these, the occurrence of drying shrinkage acts as a prerequisite for the cracking phenomenon. Therefore, it is of utmost importance to comprehend the specific characteristics associated with the drying shrinkage mechanism. To investigate the drying shrinkage behavior of swell-shrink characteristic soils, a series of drying shrinkage experiments were conducted on long strip samples of red clay and expansive soil. Utilizing three-dimensional digital image correlation (DIC) technology, the surface displacement, strain, and anisotropic shrinkage rates of the soil samples during the drying process were obtained, and the size effect on the drying shrinkage of swell-shrink characteristic soil were analyzed. The research findings are as follows: The displacement development of the soil samples in the X and Y directions can be divided into two stages: a linear growth stage and a stable displacement stage. In the Z direction, the soil surface deformation can be divided into three stages: soil surface arching, vertical shrinkage, and shrinkage stabilization. The drying shrinkage of swell-shrink characteristic soil exhibits anisotropy, with the vertical shrinkage rate being the largest, followed by the longitudinal and then the transverse directions. Additionally, the soil sample shrinkage exhibits a size effect, whereby the shrinkage rates in all directions increase with increasing sample width and thickness. During the drying shrinkage process, the stress state on the soil surface evolves from initial tensile strain to subsequent compressive strain. The strain at different positions and times within the soil sample is not uniform, resulting in the non-uniformity and anisotropy of the sample shrinkage. This study provides important insights into the cracking mechanism of swell-shrink characteristic soils and serves as a valuable reference for related laboratory experiments, which will contribute to better prediction and control the geological hazards caused by the drying shrinkage of swell-shrink characteristic soils., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aortic aneurysms (AA) and aorta dissection (AD) are life-threatening conditions with a rising incidence and high mortality rate. Recent research has linked non-coding RNAs to the regulation of AA and AD progression. In this study, we performed circRNA sequencing, microRNA (miRNA) sequencing, and messenger RNA (mRNA) sequencing on plasma samples from AA and AD patients to identify the key circRNA-miRNA-mRNA axis involved in the transition from AA to AD. Our results showed elevated levels of circ_0000006 and circ_0000160, along with decreased levels of hsa-let-7e-5p in AD samples compared to AA samples. Predictive analysis suggested that circ_0000006 and circ_0000160 potentially target hsa-let-7e-5p, which in turn may bind to the mRNA of Ubiquilin 4 (UBQLN4). In an AD cell model using vascular smooth muscle cells (VSMCs), silencing circ_0000006 and circ_0000160 attenuated the effects of platelet-derived growth factor (PDGF)-induced phenotypic changes, proliferation, and migration. This effect was partially reversed by inhibiting hsa-let-7e-5p. Furthermore, we found that overexpression of UBQLN4 counteracted the effects of hsa-let-7e-5p, suggesting UBQLN4 as a downstream mediator of hsa-let-7e-5p. In an animal model of AD, knockdown of circ_0000006 and circ_0000160 also showed protective effects against aortic septation. Overall, our findings indicate that the upregulation of circ_0000006 and circ_0000160 contributes to the progression from AA to AD by influencing abnormal phenotypic changes, migration, and proliferation of VSMCs. The Hsa-let-7e-5p/UBQLN4 axis may play a critical role in AD development. Targeting circ_0000006 and circ_0000160 could be a potential therapeutic strategy for preventing the progression of AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The workload of breast cancer pathological diagnosis is very heavy. The purpose of this study is to establish a nomogram model based on pathological images to predict the benign and malignant nature of breast diseases and to validate its predictive performance., Methods: In retrospect, a total of 2,723 H&E-stained pathological images were collected from 1,474 patients at Qingdao Central Hospital between 2019 and 2022. The dataset consisted of 509 benign tumor images (adenosis and fibroadenoma) and 2,214 malignant tumor images (infiltrating ductal carcinoma). The images were divided into a training set (1,907) and a validation set (816). Python3.7 was used to extract the values of the R channel, G channel, B channel, and one-dimensional information entropy from all images. Multivariable logistic regression was used to select variables and establish the breast tissue pathological image prediction model., Results: The R channel value, B channel value, and one-dimensional information entropy of the images were identified as independent predictive factors for the classification of benign and malignant pathological images (P < 0.05). The area under the curve (AUC) of the nomogram model in the training set was 0.889 (95% CI: 0.869, 0.909), and the AUC in the validation set was 0.838 (95% CI: 0.7980.877). The calibration curve results showed that the calibration curve of this nomogram model was close to the ideal curve. The decision curve results indicated that the predictive model curve had a high value for auxiliary diagnosis., Conclusion: The nomogram model for the prediction of benign and malignant breast diseases based on pathological images demonstrates good predictive performance. This model can assist in the diagnosis of breast tissue pathological images., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Grounded in the cultural context of Chinese filial piety, this study employs structural equation model to analyze survey data from elderly participants. It explores the effect and path of progeny-parents family travel on the elderly's sense of well-being and examines the mediating roles of generational interaction, optimistic emotion, and psychological resilience. The findings indicate that progeny-parents family travel positively influences the well-being of the elderly, with generational interaction, optimistic emotion, and psychological resilience serving as intermediary roles. Theoretically, this study enriches the localized perspective of family travel's psychological and behavioral impact on the elderly. It elucidates the spillover effects of family travel within the framework of filial piety culture, delineates the mechanisms by which family travel enhances elderly well-being, and offers theoretical insights for businesses to develop customized family travel products and services., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To investigate the effect of aerobic exercise intervention to inhibit cardiomyocyte apoptosis and thus improve cardiac function in myocardial infarction (MI) mice by regulating CTGF expression through miR-133a-3p., Methods: Male C57/BL6 mice, 7-8 weeks old, were randomly divided into sham-operated group (S group), sham-operated +aerobic exercise group (SE group), myocardial infarction group (MI group) and MI + aerobic exercise group (ME group). The mice were anesthetized the day after training and cardiac function was assessed by cardiac echocardiography. Myocardial collagen volume fraction (CVF%) was analyzed by Masson staining. Myocardial CTGF, Bax and Bcl-2 were detected by Western blotting, and myocardial miR-133a-3p was measured by RT-qPCR., Results: Compared with the S group, miR-133a-3p, Bcl-2 and EF were significantly decreased and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly increased in the MI group. Compared with the MI group, miR-133a-3p, Bcl-2 and EF were significantly increased, cardiac function was significantly improved, and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly decreased in ME group. The miR-133a-3p was significantly lower and CTGF was significantly higher in the H2O2 intervention group compared with the control group of H9C2 rat cardiomyocytes. miR-133a-3p was significantly higher and CTGF was significantly lower in the AICAR intervention group compared to the H2O2 intervention group. Compared with the control group of H9C2 rat cardiomyocytes, CTGF, Bax and Bax/Bcl-2 were significantly increased and Bcl-2 was significantly decreased in the miR-133a-3p inhibitor intervention group; CTGF, Bax and Bax/Bcl-2 were significantly decreased and Bcl-2 was significantly upregulated in the miR-133a-3p mimics intervention group., Conclusion: Aerobic exercise down-regulated CTGF expression in MI mouse myocardium through miR-133a-3p, thereby inhibiting cardiomyocyte apoptosis and improving cardiac function., Competing Interests: The authors declare that they have no completing interests., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This paper investigates the international accounting network memberships' impact on audit fees. We find that, firstly, the audit fees charged by the member audit firms are significantly higher; secondly, if the revenue, ranking or audit and accounting business share of the international network the audit firm join is higher, the charge is also higher. Additional results show that economic policy uncertainty will intensify this positive relationship, and member audit firms charge higher fees by improving their overseas expertise. We also find that international network memberships will reduce abnormal audit fees, and improve the quality of financial reports., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Few empirical studies have specifically examined the underlying mechanisms of the "healthy context paradox" in Chinese cultural context. By constructing a moderated mediation model, the present study investigated the relationship between bullying victimization and academic adjustment, as well as the mediating effects of subjective well-being and the moderating role of classroom-level victimization. A sample of 631 adolescents (Mage = 13.75, SD = 0.74, 318 boys) were recruited from four schools in Hubei, Southern China. Results show that: (1) classroom-level victimization moderates the relationship between bullying victimization and academic adjustment. (2) Classroom-level victimization moderates the association through subjective well-being. This study confirms the healthy context paradox of bullying victimization and first reveals the mechanism of the mediating role of subjective well-being. Understanding the mechanisms that contribute to the health context paradox is crucial for developing targeted intervention strategies for individuals who experience ongoing bullying., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Green finance promotes the optimization of industrial structure and continuous improvement of ecological environment by supporting the development of green industries. Based on the panel data of 30 provinces in China from 2012 to 2020, this paper uses the entropy weight TOPSIS method to measure the development level of green finance and the level of industrial structure optimization in China, and constructs a panel data model to empirically test the impact of green finance on the upgrading of China's industrial structure. The study finds that there is still an imbalance and insufficiency in the development of green finance and industrial structure optimization in China. From 2012 to 2020, the development level of green finance and the level of industrial structure optimization in China have been continuously rising, but there is obvious heterogeneity, showing an eastern>central>western spatial pattern. Empirical analysis results show that at the significance level of 1‰, the development of green finance has a significant promoting effect on the rationalization and upgrading of the industrial structure. However, there is significant heterogeneity in the impact of green finance on industrial structure optimization. In terms of regional heterogeneity, at the significance level of 1‰, the role of green finance in promoting the optimization of industrial structure in central and western China is higher than that in eastern China, and the impact of green finance on China's industrial structure shows a spatial pattern of western>central>eastern China. In terms of industry heterogeneity, at the significance level of 1‰, green finance has a significant promoting effect on the development of green industries, and a significant inhibiting effect on the development of high-energy-consuming industries. Specifically, in the green industry, green finance has the greatest promoting effect on the communication and other electronic equipment manufacturing industry; in the high-energy-consuming industry, green finance has the greatest inhibiting effect on the black metal smelting and rolling processing industry, and the smallest impact on the petroleum, coal and other fuel processing industry. Finally, based on this, policy suggestions for green finance to support the optimization of industrial structure are proposed from two dimensions: government and financial institutions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As an extension of traditional bullying, cyberbullying emerges with the increasing popularity of the internet, and seriously affects the health of students. However, fewer studies have explored the potential influencing mechanisms of cyberbullying victimization from a positive psychology perspective. Therefore, based on the positive youth development theory, this study will explore the potential mediator and moderator in the relationship between positive youth development (PYD) attributes and cyberbullying victimization through a longitudinal design. 719 students (Mage = 15.95 years, SD = 0.76, 45.2% boy) participated in the study and completed self-report questionnaires on relevant variables. The result found that students' level of PYD significantly and negatively predicted the level of cyberbullying victimization. Meanwhile, SEM analysis showed that PYD influenced individuals' cyberbullying victimization by affecting their internet gaming disorder (IGD), while depression levels moderated the relationship between PYD and IGD. This study examines cyberbullying victimization from a positive psychology orientation, with potential prevention and intervention value., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Protective color restoration of faded digital pathology images based on color transfer algorithm., Methods: Twenty fresh tissue samples of invasive breast cancer from the pathology department of Qingdao Central Hospital in 2021 were screened. After HE staining, HE stained sections were irradiated with sunlight to simulate natural fading, and every 7 days was a fading cycle, and a total of 8 cycles were experienced. At the end of each cycle, the sections were digitally scanned to retain clear images, and the color changes of the sections during the fading process were recorded. The color transfer algorithm was applied to restore the color of the faded images; Adobe Lightroom Classic software presented the histogram of the image color distribution; UNet++ cell recognition segmentation model was used to identify the color restored images; Natural Image Quality Evaluator (NIQE), Information Entropy (Entropy), and Average Gradient (AG) were applied to evaluate the quality of the restored images., Results: The restored image color met the diagnostic needs of pathologists. Compared with the faded images, the NIQE value decreased (P<0.05), Entropy value increased (P<0.01), and AG value increased (P<0.01). The cell recognition rate of the restored image was significantly improved., Conclusion: The color transfer algorithm can effectively repair faded pathology images, restore the color contrast between nucleus and cytoplasm, improve the image quality, meet the diagnostic needs and improve the cell recognition rate of the deep learning model., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Both the number of dust explosion accidents and the resulting number of casualties have increased dramatically in recent years. To reduce this risk of dust explosions, we use the functional resonance analysis method (FRAM) to analyze the cause of the dust explosion accident at the Kunshan factory and propose barrier measures to prevent such accidents. The functional units that changed in the production system during the accident and how these functional units coupled to eventually cause the dust explosion were examined and explained. In addition, barrier measures were developed for functional units that changed during production and emergency systems defined to block the propagation of changes between functions and prevent resonance. Through case study, the identification of key functional parameters in both triggering the initial explosion and in then allowing its spread are key to define barriers to prevent a recurrence of such an event. FRAM uses system function coupling instead of traditional linear causality to explain the accident process, and develops barrier measures for changing function units, providing a novel thinking strategy and method for the analysis of accidents and their prevention., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A new type of paste filling material was created using fluorogypsum, a byproduct of hydrofluoric acid, as the raw material to address the issue of the filling material's high cost. The effects of five factors, including gangue, fly ash, fluorogypsum, lime content, and mass concentration on the physical and mechanical properties of filling material were also examined. In addition to analyzing slump and extension changes, the filler's mineral composition and microstructure were examined using SEM and XRD examinations. The results show that the best ratio of the developed filling material was 1000g coal gangue, 300g fly ash, 300g fluorogypsum, and 50g lime and mass concentration is 78%, and its compressive strength can reach 4-5MPa at 28 days. Raw materials such as gangue and fly ash will have a certain influence on the mechanical properties of the filling material. The hydration products of the developed filling material prepared by XRD and SEM were ettringite, calcium sulfate dihydrate, and calcium silicate hydrate gel. The new fluorogypsum-based paste filling material can be used to consolidate loose rock strata and fill goaf. It solves the problem of disposal of industrial waste fluoropgypsum and also solves the problem of coal mine gangue stacking, which has a far-reaching influence on ecological environment management., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Chun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Drought is a major factor that limiting mung bean development. To clarify the molecular mechanism of mung bean in response to drought stress, 2 mung bean groups were established, the experimental group (drought-treated) and the control group (normal water management). With prominent difference of 2 groups in stomatal conductance, relative water content and phenotype, leaf samples were collected at 4 stages, and the physiological index of MDA, POD, chlorophyll, and soluble proteins were estimated. RNA-seq was used to obtain high quality data of samples, and differentially expressed genes were identified by DESeq2. With GO and KEGG analysis, DEGs were enriched into different classifications and pathways. WGCNA was used to detect the relationship between physiological traits and genes, and qPCR was performed to confirm the accuracy of the data. We obtained 169.49 Gb of clean data from 24 samples, and the Q30 of each date all exceeded 94%. In total, 8963 DEGs were identified at 4 stages between the control and treated samples, and the DEGs were involved in most biological processes. 1270 TFs screened from DEGs were clustered into 158 TF families, such as AP2, RLK-Pelle-DLSVA, and NAC TF families. Genes related to physiological traits were closely related to plant hormone signaling, carotenoid biosynthesis, chlorophyll metabolism, and protein processing. This paper provides a large amount of data for drought research in mung bean., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Deep neuromuscular blockade provides better surgical workspace conditions in laparoscopic surgery, but it is still not clear whether it improves perioperative outcomes, not to mention its role in other types of surgeries. We performed this systematic review and meta-analysis of randomized controlled trials to investigate whether deep neuromuscular blockade versus other more superficial levels of neuromuscular blockade provides improved perioperative outcomes in adult patients in all types of surgeries. Medline, Embase, Cochrane Central Register of Controlled Trials, and Google Scholar were searched from inception to June 25, 2022. Forty studies (3271 participants) were included. Deep neuromuscular blockade was associated with an increased rate of acceptable surgical condition (relative risk [RR]: 1.19, 95% confidence interval [CI]: [1.11, 1.27]), increased surgical condition score (MD: 0.52, 95% CI: [0.37, 0.67]), decreased rate of intraoperative movement (RR: 0.19, 95% CI: [0.10, 0.33]), fewer additional measures to improve the surgical condition (RR: 0.63, 95% CI: [0.43, 0.94]), and decreased pain score at 24 h (MD: -0.42, 95% CI: [-0.74, -0.10]). There was no significant difference in the intraoperative blood loss (MD: -22.80, 95% CI: [-48.83, 3.24]), duration of surgery (MD: -0.05, 95% CI: [-2.05, 1.95]), pain score at 48 h (MD: -0.49, 95% CI: [-1.03, 0.05]), or length of stay (MD: -0.05, 95% CI: [-0.19, 0.08]). These indicate that deep neuromuscular blockade improves surgical conditions and prevents intraoperative movement, and there is no sufficient evidence that deep neuromuscular blockade is associated with intraoperative blood loss, duration of surgery, complications, postoperative pain, and length of stay. More high-quality randomized controlled trials are needed, and more attention should be given to complications and the physiological mechanism behind deep neuromuscular blockade and postoperative outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

A considerable amount of evidence suggests that parental marital conflict is an important factor in adolescents' internet gaming disorder (IGD). However, the mechanism underlying this relationship remains unclear. Therefore, the purpose of this study is to explore the relationship between parental marital conflict and IGD among Chinese adolescents, and whether this relationship is mediated by deviant peer affiliation and teacher-student relationship. There were 698 Chinese adolescents that took part in the study (51.58% male; Mage = 13.52). They completed self-report questionnaires regarding perception of parental marital conflict, deviant peer affiliation, teacher-student relationship and IGD. Structural equation model (SEM) was used to examine the relationship between parental marital conflict and adolescents' IGD, as well as the mediating roles of deviant peer affiliation and teacher-student relationship. Correlation analysis showed a positive correlation between parental marital conflict, deviant peer affiliation, and IGD, as well as a negative correlation between them and teacher-student relationship. The results of the SEM showed that parental marital conflict not only predicts adolescent IGD directly, but also through the mediation effects of deviant peer affiliation and teacher-student relationship. Additionally, deviant peer affiliation and teacher-student relationship not only play an independent but also a sequential mediating effect in the relationship between parental marital conflict and IGD. The relationship between parental marital conflict and IGD is mediated by deviant peer affiliation and teacher-student relationship, which has potential prevention and intervention value for adolescent IGD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To explore the association between the physical health (PH) and physical activity behavior (PAB) of children aged 3 to 6 years, and to provide a basis for the scientific planning of children's physical activity behavior in kindergarten., Methods: A total of 18041 children in China aged 3 to 6 years were selected as the research subject. The PH monitoring indicators were measured according to "The National Physical Fitness Measurement Standards Manual" (Preschool Children Version) (NPFMSM), and PAB was reported by teachers. The chi-square test was used to test for differences in PH and PAB across groups, the percentile method was used to rank PAB, correlation analysis was used to analyze the association between components of PH and PAB, and multiple linear regression was used to determine the independent association between PAB and PH., Results: Participants in this study exhibited poor PH status, and the detection rates of failure were 16.4% for boys and 16.8% for girls, and showed a decreasing trend with increasing age. The grade difference and sex difference in PH components were statistically significant (P<0.01). PAB changes to static activities with increasing age, mainly to static indoor physical activities (SIPAs). The regression effects of the total duration of physical activity (TDPA) and dynamic physical activity (DPA) on PH score and physical fitness (PF) score were significant (P < 0.01) but not statistically significant with static physical activity (SPA) (P>0.05). Dynamic outdoor physical activity (DOPA) is the core factor affecting children's PH, and is significantly positively correlated with the components of PH., Conclusion: PAB in kindergarten can improve children's PH, and reasonable planning of PAB in kindergarten has a targeted effect on PH promotion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Xiong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Growing evidence has indicated that the characteristics of gut microbiota are associated with acute ischemic stroke (AIS). Phlegm-heat syndrome (PHS), a specific pathological state of the AIS, is one of the common traditional Chinese syndromes of stroke. The long duration of PHS in patients with AIS could lead to poor clinical outcomes. Gut microbiota characteristics in patients with both AIS and PHS, and their relationship remains unknown. This study was designed to investigate the alterations in gut microbiota in patients with AIS and PHS through a cross-sectional study. Fecal samples were collected from 10 patients with AIS and non-PHS (ntAIS), 7 patients with AIS and PHS (tAIS), and 10 healthy controls (HC). Samples were profiled via Illumina sequencing of the 16S rRNA V3-V4. Stroke severity was assessed at admission by the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS); their correlation with gut microbiota was investigated. The alpha-diversity of the bacterial communities was significantly higher in the fecal samples of patients with tAIS than in patients with ntAIS (Shannon index, P = 0.037). In addition, the combined tAIS and ntAIS group (tntAIS) exhibited higher microbiotic diversity when compared with HC (chao1, P = 0.019). The structure of intestinal microbiota was effectively distinguished between the tAIS and ntAIS group (ANOSIM, r = 0.337, P = 0.007). Additionally, the gut microbiota structure was significantly different between the tntAIS and HC groups (ANOSIM, r = 0.217, P = 0.005). The genera, Ruminococcaceae&#95; UCG&#95;002 and Christensenellaceae&#95;R-7&#95;group, were implicated in the discrimination of PHS from non-PHS. The order Lactobacillales and family Lachnospiraceae were significantly negatively correlated with NIHSS and mRS at admission (P < 0.05). By contrast, the order Desulfovibrionales, families Christensenellaceae and Desulfovibrionaceae, and genera Ruminococcaceae UCG-014 and Ruminococcaceae UCG-002 were significantly positively correlated with NIHSS and mRS at admission (P < 0.05). This study is the first to profile the characteristics of gut microbiota in patients with AIS and PHS, compared with those with non-PHS. The genera, Ruminococcaceae&#95; UCG&#95;002 and Christensenellaceae&#95;R-7&#95;group, may be objective indicators of this traditional Chinese medicine (TCM) syndrome in AIS. Furthermore, it provides a microbe-inspired biological basis for TCM syndrome differentiation., Competing Interests: The authors have declared that no competing interests exist.

Internet gaming disorder (IGD) is a social problem that cannot be ignored. Considerable research has shown that IGD can impede the healthy physical and mental development of adolescents. Based on positive youth development theory and stage-environment fit theory, the current study explored the mediating effect of depression and the moderating effect of gender to determine the association between positive youth development (PYD) and IGD. A sample of 1970 Chinese adolescents aged 11-18 years (1021 boys, 940 girls, and 10 unidentifiable individuals) completed questionnaires related to PYD, depression, IGD, and their background information. The results revealed that PYD negatively predicted IGD. After controlling for gender and age, this study found that depression mediated the relationship between PYD and IGD. Furthermore, gender moderated the relationship between depression and IGD. Boys with depressive symptoms were more likely to indulge in IGD than girls. This research contributes to a more thorough understanding of how PYD decreases the risk of IGD. These findings suggest that cultivating PYD attributes is a promising approach to prevent or reduce depression and IGD among adolescents in mainland China., Competing Interests: The authors have declared that no competing interests exist.

In the field of Human-Computer Interaction (HCI), speech emotion recognition technology plays an important role. Facing a small number of speech emotion data, a novel speech emotion recognition method based on feature construction and ensemble learning is proposed in this paper. Firstly, the acoustic features are extracted from the speech signal and combined to form different original feature sets. Secondly, based on Light Gradient Boosting Machine (LightGBM) and Sequential Forward Selection (SFS) method, a novel feature selection method named L-SFS is proposed. And then, the softmax regression model is used to learn automatically the weights of the four single weak learners including Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Extreme Gradient Boosting (XGBoost) and LightGBM. Lastly, based on the learned automatically weights and the weighted average probability voting strategy, an ensemble classification model named Sklex is constructed, which integrates the above four single weak learners. In conclusion, the method reflects the effectiveness of feature construction and the superiority and stability of ensemble learning, and gets good speech emotion recognition accuracy., Competing Interests: The authors have declared that no competing interests exist.

Background: Neuronal dysfunction plays an important role in the high prevalence of HIV-associated neurocognitive disorders (HAND) in people with HIV (PWH). Transcranial direct current stimulation (tDCS)-with its capability to improve neuronal function-may have the potential to serve as an alternative therapeutic approach for HAND. Brain imaging and neurobehavioral studies provide converging evidence that injury to the anterior cingulate cortex (ACC) is highly prevalent and contributes to HAND in PWH, suggesting that ACC may serve as a potential neuromodulation target for HAND. Here we conducted a randomized, double-blind, placebo-controlled, partial crossover pilot study to test the safety, tolerability, and potential efficacy of anodal tDCS over cingulate cortex in adults with HIV, with a focus on the dorsal ACC (dACC)., Methods: Eleven PWH (47-69 years old, 2 females, 100% African Americans, disease duration 16-36 years) participated in the study, which had two phases, Phase 1 and Phase 2. During Phase 1, participants were randomized to receive ten sessions of sham (n = 4) or cingulate tDCS (n = 7) over the course of 2-3 weeks. Treatment assignments were unknown to the participants and the technicians. Neuropsychology and MRI data were collected from four additional study visits to assess treatment effects, including one baseline visit (BL, prior to treatment) and three follow-up visits (FU1, FU2, and FU3, approximately 1 week, 3 weeks, and 3 months after treatment, respectively). Treatment assignment was unblinded after FU3. Participants in the sham group repeated the study with open-label cingulate tDCS during Phase 2. Statistical analysis was limited to data from Phase 1., Results: Compared to sham tDCS, cingulate tDCS led to a decrease in Perseverative Errors in Wisconsin Card Sorting Test (WCST), but not Non-Perseverative Errors, as well as a decrease in the ratio score of Trail Making Test-Part B (TMT-B) to TMT-Part A (TMT-A). Seed-to-voxel analysis with resting state functional MRI data revealed an increase in functional connectivity between the bilateral dACC and a cluster in the right dorsal striatum after cingulate tDCS. There were no differences in self-reported discomfort ratings between sham and cingulate tDCS., Conclusions: Cingulate tDCS is safe and well-tolerated in PWH, and may have the potential to improve cognitive performance and brain function. A future study with a larger sample is warranted., Competing Interests: The authors have declared that no competing interests exist.

As an important part of the second defense line of the power system, the Security and Stability Control System (SSCS) is of great significance to ensure the reliable operation of the power system. However, SSCS still lacks an effective security mechanism and is easily accessed by attackers, thus posing a threat to the stable and reliable operation of the power system. To tackle this issue, we propose a blockchain-based identity authentication scheme for Intelligent Electronic Devices (IEDs) of SSCS. We first propose an identity authentication system model for IEDs and design the deployment of consortium chain nodes on IEDs, with architectural characteristics of SSCS and the working scenario of IEDs taken into consideration. The consortium chain is used to store credentials required for authentication, ensuring that they are tamper-proof. We combine IP address, port number and physical ID, and propose the unique identification of IEDs, with a data structure designed for the identification. We also propose a lightweight identity authentication method based on renewable hash chains, with hash chains used as one-time authentication passwords, and introduce a renewal mechanism of hash chains. Further, the detailed processes of registration and authentication phase are designed. Finally, the security analysis shows that our identity authentication scheme can resist various attacks, and the feasibility of our scheme is verified by experiments., Competing Interests: The authors have declared that no competing interests exist.

Asamitocins are maytansinoids produced by Actinosynnema pretiosum ssp. auranticum ATCC 31565 (A. pretiosum ATCC 31565), which have a structure similar to that of maytansine, therefore serving as a precursor of maytansine in the development of antibody-drug conjugates (ADCs). Currently, there are more than 20 known derivatives of ansamitocins, among which ansamitocin P-3 (AP-3) exhibits the highest antitumor activity. Despite its importance, the application of AP-3 is restricted by low yield, likely due to a substrate competition mechanism underlying the synthesis pathways of AP-3 and its byproducts. Given that N-demethylansamitocin P-3, the precursor of AP-3, is regulated by asm25 and asm10 to synthesize AGP-3 and AP-3, respectively, asm25 is predicted to be an inhibitory gene for AP-3 production. In this study, we inactivated asm25 in A. pretiosum ATCC 31565 by CRISPR-Cas9-guided gene editing. asm25 depletion resulted in a more than 2-fold increase in AP-3 yield. Surprisingly, the addition of isobutanol further improved AP-3 yield in the asm25 knockout strain by more than 6 times; in contrast, only a 1.53-fold increase was found in the WT strain under the parallel condition. Thus, we uncovered an unknown function of asm25 in AP-3 yield and identified asm25 as a promising target to enhance the large-scale industrial production of AP-3., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this research was to systematically investigate the effects of endothelial mesenchymal transition (EndMT) induced by hypoxia on the skin microvascular remodeling of systemic sclerosis (SSc) and the underlying mechanism., Methods: Skin tissues from SSc patients and controls were collected for isobaric tags for the relative and absolute quantification (iTRAQ)-based proteomics and immunohistochemical test. Human microvascular endothelial cell line-1 (HMEC-1) cultured in hypoxic or normal conditions was treated by tamoxifen or bevacizumab., Results: The iTRAQ-based proteomics indicated a significantly upregulated hypoxia-inducible factor-1 (HIF-1) signal in SSc samples. The immunohistochemical results demonstrated the significant downregulation of CD31, the positive staining of α-smooth muscle actin (α-SMA), HIF-1α, and vascular endothelial growth factor (VEGF-a) in SSc skin tissues, compared with control samples. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside a marked increase in the expression of α-SMA and fibronectin, as well as a distinct upregulation of HIF-1α and VEGF-a, when compared with those under normal conditions. It is noteworthy that the inhibition of HIF-1α by tamoxifen effectively downregulated the hypoxic induction of VEGF-a and α-SMA while rescuing the hypoxic suppression of CD31. In addition, the VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31, as a tamoxifen intervention, but did not reduce HIF-1α., Conclusion: These results suggest that the HIF-1α/VEGF signaling pathway can have a critical role in mediating the effect of hypoxia-induced EndMT on the skin microvascular remodeling of SSc., Competing Interests: The authors have declared that no competing interests exist.

A previous study has documented that stressful life events is positively related to Internet gaming disorder (IGD) among adolescents. However, the mechanism underlying this relationship remains unclear. The current study examined whether the link between stressful life events and adolescent IGD was moderated by neuroticism and whether the interaction of stressful life events and neuroticism supported the diathesis stress model or differential susceptibility model. To this end, self-report questionnaires were distributed. Participants were 927 Chinese adolescents (meanage = 14.53 years, 51.02% male). After controlling for adolescent gender, age, family economic situation, and family socioeconomic status, the results revealed that stressful life events could be positively associated with adolescent IGD and that this link is moderated by neuroticism. Moreover, the results of interaction effects supported the "diathesis stress" model. The above findings contributed to a better understanding of how and when stressful life events increase the risk of IGD and provided new evidence for the diathesis stress hypothesis., Competing Interests: The authors have declared that no competing interests exist.

Background: To determine the prevalence of food allergy (FA) and factors associated with these occurrences in different populations from different regions., Materials and Methods: The literature search will be conducted via Pubmed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), Vip and Wanfang databases. Ratio rate (RR), odds ratio (OR) and 95% confidence intervals (CIs) will be adopted to evaluate prevalence and factors for FA in different populations from different regions. When the heterogeneity is small (I2<50%), the fixed effect model will be analyzed, otherwise, random effects model analysis will be performed. When the heterogeneity is large (I2≥50%), Meta regression will be used to explore the sources of inter-study heterogeneity. When the heterogeneity is large (I2≥50%) and the results are statistically significant (P<0.05), subgroup analysis will be analyzed based on age, gender, race/region, literature quality and other factors. Funnel plots will be used to reflect reporting bias and the Begg's test will be used to test the symmetry of the funnel plots. When publication bias occurs, "cut-and-fill" method will be adopted to adjust publication bias. And sensitivity analysis will be performed for all outcome indicators., Discussion: This meta-analysis will evaluate the prevalence of FA and factors associated with these occurrences in different populations from different regions on the basis of existing evidences. Our study may be crucial to analyze similarities and differences regarding FA between different individuals from diverse regions and eventually define preventive or diagnostic approaches specifically tailored to certain populations and regions., Systematic Review Registration: OSF registration number: 10.17605/OSF.IO/VQXU9., Competing Interests: The authors have declared that no competing interests exist.

The risk spillover among financial markets has been noticeably investigated in a burgeoning number of literature. Given those doctrines, we scrutinize the impact persistence of volatility spillover and illiquidity spillover of Chinese commodity markets in this paper. Based on the sample from 2010 to 2020, we reveal that there is a cross-market spillover of volatility and illiquidity in China and also, interactions between volatility and illiquidity in different financial markets are pronounced. More importantly, we demonstrate that different commodity markets have different responsiveness to stock market shocks, which embeds their market characteristics. Specifically, we discover that the majority of the traders in gold market might be hedger and therefore gold market is more sensitive to stock market illiquidity shock and thus the shock impact in persistent. On the other hand, agricultural markets like corn and soybean markets might be dominated by investors and thus those markets respond to the stock market volatility shocks and the shock impact in persistent over 10 periods given the first period of risk shock happening. In fact, different Chinese commodity markets' responsiveness towards Chinese stock market risk shocks indicates the stock market risk impact persistence in Chinese commodity markets. This result can help policymakers to understand the policy propagation effect according to this risk spillover channel and risk impact persistence mechanism in China., Competing Interests: The authors have declared that no competing interests exist.

To identify long non-coding RNAs (lncRNAs) and their potential roles in hepatic fibrosis in rat liver issues induced by CCl4, lncRNAs and genes were analyzed in fibrotic rat liver tissues by RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Differentially expressed (DE) lncRNAs (DE-lncRNAs) and genes were subjected to bioinformatics analysis and used to construct a co-expression network. We identified 10 novel DE-lncRNAs that were downregulated during the hepatic fibrosis process. The cis target gene of DE-lncRNA, XLOC118358, was Met, and the cis target gene of the other nine DE-lncRNAs, XLOC004600, XLOC004605, XLOC004610, XLOC004611, XLOC004568, XLOC004580 XLOC004598, XLOC004601, and XLOC004602 was Nox4. The results of construction of a pathway-DEG co-expression network show that lncRNA-Met and lncRNAs-Nox4 were involved in oxidation-reduction processes and PI3K/Akt signaling pathway. Our results identified 10 DE-lncRNAs related to hepatic fibrosis, and the potential roles of DE-lncRNAs and target genes in hepatic fibrosis might provide new therapeutic strategies for hepatic fibrosis., Competing Interests: The authors have declared that no competing interests exist.

Background: We conducted an overview of systematic reviews (SRs) summarizing the best evidence regarding the effect of COVID-19 on maternal and child health following Cochrane methods and PRISMA statement for reporting (PROSPERO-CRD42020208783)., Methods: We searched literature databases and COVID-19 research websites from January to October 2020. We selected relevant SRs reporting adequate search strategy, data synthesis, risk of bias assessment, and/or individual description of included studies describing COVID-19 and pregnancy outcomes. Pair of reviewers independently selected studies through COVIDENCE web-software, performed the data extraction, and assessed its quality through the AMSTAR-2 tool. Discrepancies were resolved by consensus. Each SR's results were synthesized and for the most recent, relevant, comprehensive, and with the highest quality, by predefined criteria, we presented GRADE evidence tables., Results: We included 66 SRs of observational studies out of 608 references retrieved and most (61/66) had "critically low" overall quality. We found a relatively low degree of primary study overlap across SRs. The most frequent COVID-19 clinical findings during pregnancy were fever (28-100%), mild respiratory symptoms (20-79%), raised C-reactive protein (28-96%), lymphopenia (34-80%), and pneumonia signs in diagnostic imaging (7-99%). The most frequent maternal outcomes were C-section (23-96%) and preterm delivery (14-64%). Most of their babies were asymptomatic (16-93%) or presented fever (0-50%), low birth weight (5-43%) or preterm delivery (2-69%). The odds ratio (OR) of receiving invasive ventilation for COVID-19 versus non-COVID-19 pregnant women was 1.88 (95% Confidence Interval [CI] 1.36-2.60) and the OR that their babies were admitted to neonatal intensive care unit was 3.13 (95%CI 2.05-4.78). The risk of congenital transmission or via breast milk was estimated to be low, but close contacts may carry risks., Conclusion: This comprehensive overview supports that pregnant women with COVID-19 may be at increased risk of adverse pregnancy and birth outcomes and low risk of congenital transmission., Competing Interests: The authors have declared that no competing interests exist.

Spatial inhibition of return (IOR) refers to the phenomenon by which individuals are slower to respond to stimuli appearing at a previously cued location compared to un-cued locations. Here with a group of older adults (n = 56, 58-80 (67.9±5.2) year old, 31 females, 18.7±3.6 years of education), we provide evidence supporting the notion that spatial IOR is mildly impaired in individuals with mild cognitive impairment (MCI) or mild Alzheimer's disease (AD), and the impairment is detectable using a double cue paradigm. Furthermore, reduced spatial IOR in high-risk healthy older individuals is associated with reduced memory and other neurocognitive task performance, suggesting that the double cue spatial IOR paradigm may be useful in detecting MCI and early AD., Competing Interests: The authors have declared that no competing interests exist.

Wide Area Protection System (WAPS) undertakes the important task of maintaining system reliability and stability when the power system is subject to abnormal or predetermined unstable conditions. The existing WAPS adopts a centralized mechanism to record and audit communication messages, which faces the risk of excessive authority and tampering with communication records and audit logs, thus making it impossible to achieve true transparency and fairness. Due to the involvement of multiple parties and equipment maintained by different manufacturers in the communication of WAPS, there are difficulties in tracing the cause of the accident and determining the at-fault party following misoperations and miss trips. To address this issue, we propose a semi-centralized blockchain system with multi-chain for auditing communications of WAPS. We first propose a semi-centralized system architecture according to the system architecture and management requirements of WAPS. Then, we utilize the blockchain network as a self-recording channel to achieve tamper-proof and non-repudiation verification interaction. We also design a multi-chain structure and classification node mechanism to meet the communication auditing requirements of multiple WAPS. We have designed a new block structure that conforms to the communication protocol of WAPS. To reduce the storage burden caused by the ever-expanding blockchain ledger, we propose a deletable blockchain scheme while maintaining the integrity and security of blockchain. Analysis and experiments show that the proposed blockchain system can support the secure, transparent, tamper-proof and traceable communication recording and auditing of WAPS along with high performance., Competing Interests: The authors have declared that no competing interests exist.

The COVID-19 pandemic is currently spreading widely around the world, causing huge threats to public safety and global society. This study analyzes the spatiotemporal pattern of the COVID-19 pandemic in China, reveals China's epicenters of the pandemic through spatial clustering, and delineates the substantial effect of distance to Wuhan on the pandemic spread. The results show that the daily new COVID-19 cases mostly occurred in and around Wuhan before March 6, and then moved to the Grand Bay Area (Shenzhen, Hong Kong and Macau). The total COVID-19 cases in China were mainly distributed in the east of the Huhuanyong Line, where the epicenters accounted for more than 60% of the country's total in/on 24 January and 7 February, half in/on 31 January, and more than 70% from 14 February. The total cases finally stabilized at approximately 84,000, and the inflection point for Wuhan was on 14 February, one week later than those of Hubei (outside Wuhan) and China (outside Hubei). The generalized additive model-based analysis shows that population density and distance to provincial cities were significantly associated with the total number of the cases, while distances to prefecture cities and intercity traffic stations, and population inflow from Wuhan after 24 January, had no strong relationships with the total number of cases. The results and findings should provide valuable insights for understanding the changes in the COVID-19 transmission as well as implications for controlling the global COVID-19 pandemic spread., Competing Interests: The authors have declared that no competing interests exist.

This study provides new perspectives on urban development and conservation by exploring the spatial interaction between ecosystem services and urbanization. Limited studies have discussed the interaction between ecosystem services and urbanization; therefore, in this research, the spatial relationship between ecosystem services and urbanization is explored by taking the urban agglomeration in Central Yunnan as an example, and land-use data and economic and social data from 2009 and 2018 are used to determine the interactive impact of urbanization on the urban ecosystem. It is shown that (1) the spatial distribution of the urbanization level of the urban agglomeration in Central Yunnan has significant regional differences, showing a decreasing trend from the urbanized area to the surrounding areas. (2) Another factor with obvious regional differences is the spatial distribution of ecosystem services, which is similar to urbanization in spatial distribution. This difference is mainly caused by the impact of the urbanization level and the change in land use. (3) The spatial distribution and local agglomeration of urbanization and the ecosystem service value of urban agglomeration in Central Yunnan are very similar, and there is a significant negative correlation between the urbanization level and ecosystem service value. The research results have guiding significance for future urban and ecological development in Central Yunnan city., Competing Interests: The authors have declared that no competing interests exist.

The endoplasmic reticulum (ER) membrane protein complex (EMC) is a conserved protein complex involved in inserting the transmembrane domain of membrane proteins into membranes in the ER. EMC3 is an essential component of EMC and is important for rhodopsin synthesis in photoreceptor cells. However, the in vivo function of Emc3 in bipolar cells (BCs) has not been determined. To explore the role of Emc3 in BCs, we generated a BC-specific Emc3 knockout mouse model (named Emc3 cKO) using the Purkinje cell protein 2 (Pcp2) Cre line. Although normal electroretinography (ERG) b-waves were observed in Emc3 cKO mice at 6 months of age, Emc3 cKO mice exhibited reduced b-wave amplitudes at 12 months of age, as determined by scotopic and photopic ERG, and progressive death of BCs, whereas the ERG a-wave amplitudes were preserved. PKCa staining of retinal cryosections from Emc3 cKO mice revealed death of rod BCs. Loss of Emc3 led to the presence of the synaptic protein mGLuR6 in the outer nuclear layer (ONL). Immunostaining analysis of presynaptic protein postsynaptic density protein 95 (PSD95) revealed rod terminals retracted to the ONL in Emc3 cKO mice at 12 months of age. In addition, deletion of Emc3 resulted in elevated glial fibrillary acidic protein, indicating reactive gliosis in the retina. Our data demonstrate that loss of Emc3 in BCs leads to decreased ERG response, increased astrogliosis and disruption of the retinal inner nuclear layer in mice of 12 months of age. Taken together, our studies indicate that Emc3 is not required for the development of BCs but is important for long-term survival of BCs., Competing Interests: The authors have declared that no competing interests exist.

Long-term chemical fertilizer input causes soil organic matter losses, structural compaction, and changes in soil water and nutrient availability, which have been subdued in the most of dry farmland in China. The concept of "more efficiency with less fertilizer input" has been proposed and is urgently needed in current agriculture. Application of chemical fertilizer combined with organic manure (OM) could be a solution for soil protection and sustainable production of dry-land maize (Zea mays. L). Field research over three consecutive years on the Loess Plateau of China was conducted to evaluate the integrated effects of chemical fertilizer strategies and additional OM input on soil nutrients availability and water use in maize. The results showed that, after harvest, soil bulk density decreased significantly with OM application, concomitant with 11.9, 18.7 and 97.8% increases in topsoil total nitrogen, organic matter, and available phosphorus contents, respectively, compared with those under equal chemical NPK input. Water use in the 1.0-1.5 m soil profile was improved, therefore, the soil conditions were better for maize root growth, leaf area and shoot biomass of individual maize plants increased significantly with OM application. Optimized NPK strategies increased grain yield and water use efficiency by 18.5 and 20.6%, respectively, compared to only chemical NP input. Furthermore, additional OM input promoted yield and water use efficiency by 8.9 and 5.8%, respectively. Addition of OM promotes sustainable soil and maize grain productivity as well as friendly soil environmental management of dry land farming., Competing Interests: The authors have declared that no competing interests exist.

The characteristics of urban spatial structure and the objective evaluation of the development level of urban economy have always been the concern of urban researchers, However, the spatial relationship between urban spatial structure and urban economic development level is often deliberately ignored. Through the point of interest (POI), the identification framework is constructed, the spatial structure of the city is identified and evaluated, and the Geographically Weighted Regression analysis is carried out with the distribution of unit GDP (Gross Domestic Product) in this study. The research shows that Kunming and Guiyang are polycentric spatial structures and Kunming's structure is more significant. Kunming's economic level is generally higher than Guiyang, but the unit area cannot be compared. The city center will promote the development of the central area in this city, and the more urban centers are distributed within the geographical and spatial range, the greater contribution would have to economic development. In addition, the results of this study will have a positive impact on urban planning and construction, and will also provide a new perspective for the study of cities and related disciplines., Competing Interests: The authors have declared that no competing interests exist.

Pollution source parameter identification (PSPI) is significant for pollution control, since it can provide important information and save a lot of time for subsequent pollution elimination works. For solving the PSPI problem, a large number of pollution sensor nodes can be rapidly deployed to cover a large area and form a wireless sensor network (WSN). Based on the measurements of WSN, least-squares estimation methods can solve the PSPI problem by searching for the solution that minimize the sum of squared measurement noises. They are independent of the measurement noise distribution, i.e., robust to the noise distribution. To search for the least-squares solution, population-based parallel search techniques usually can overcome the premature convergence problem, which can stagnate the single-point search algorithm. In this paper, we adapt the relatively newly presented artificial bee colony (ABC) algorithm to solve the WSN-based PSPI problem and verifies its feasibility and robustness. Extensive simulation results show that the ABC and the particle swarm optimization (PSO) algorithm obtained similar identification results in the same simulation scenario. Moreover, the ABC and the PSO achieved much better performance than a traditionally used single-point search algorithm, i.e., the trust-region reflective algorithm., Competing Interests: The authors have declared that no competing interests exist.

The generation of genetically modified mouse models derived from gene targeting (GT) in mouse embryonic stem (ES) cells (mESCs) has greatly advanced both basic and clinical research. Our previous finding that gene targeting at the Myh9 exon2 site in mESCs has a pronounced high homologous recombination (HR) efficiency (>90%) has facilitated the generation of a series of nonmuscle myosin II (NM II) related mouse models. Furthermore, the Myh9 gene locus has been well demonstrated to be a new safe harbor for site-specific insertion of other exogenous genes. In the current study, we intend to investigate the molecular biology underlying for this high HR efficiency from other aspects. Our results confirmed some previously characterized properties and revealed some unreported observations: 1) The comparison and analysis of the targeting events occurring at the Myh9 and several widely used loci for targeting transgenesis, including ColA1, HPRT, ROSA26, and the sequences utilized for generating these targeting constructs, indicated that a total length about 6 kb with approximate 50% GC-content of the 5' and 3' homologous arms, may facilitate a better performance in terms of GT efficiency. 2) Despite increasing the length of the homologous arms, shifting the targeting site from the Myh9 exon2, to intron2, or exon3 led to a gradually reduced GT frequency (91.7, 71.8 and 50.0%, respectively). This finding provides the first evidence that the HR frequency may also be associated with the targeting site even in the same locus. Meanwhile, the decreased trend of the GT efficiency at these targeting sites was consistent with the reduced percentage of simple sequence repeat (SSR) and short interspersed nuclear elements (SINEs) in the sequences for generating the targeting constructs, suggesting the potential effects of these DNA elements on GT efficiency; 3) Our series of targeting experiments and analyses with truncated 5' and 3' arms at the Myh9 exon2 site demonstrated that GT efficiency positively correlates with the total length of the homologous arms (R = 0.7256, p<0.01), confirmed that a 2:1 ratio of the length, a 50% GC-content and the higher amount of SINEs for the 5' and 3' arms may benefit for appreciable GT frequency. Though more investigations are required, the Myh9 gene locus appears to be an ideal location for identifying HR-related cis and trans factors, which in turn provide mechanistic insights and also facilitate the practical application of gene editing., Competing Interests: The authors have declared that no competing interests exist

Mollusk shell matrix proteins are important for the formation of organic frameworks, crystal nucleation, and crystal growth in Pinctada fucata martensii (P. f. martensii). MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play important roles in many biological processes, including shell formation. In this study, we obtained the full-length sequence of Pif97-like gene in P. f. martensii (PfmPif97-like). PfmPif97-like was mainly distributed in mantle pallial and mantle edge. Correlation analysis indicated that the average shell thickness and weight showed a positive correlation with PfmPif97-like expression (P < 0.05). The inner surface of the nacreous layer and prismatic layer showed atypical growth when we knocked down the expression of PfmPif97-like by RNA interference (RNAi). We used a luciferase reporter assay to identify that miR-9b-5p of P. f. martensii (Pfm-miR-9b-5p) downregulated the expression of PfmPif97-like by interacting with the 3'-untranslated region (UTR) while we obtained the same result by injecting the Pfm-miR-9b-5p mimics in vivo. After injecting the mimics, we also observed abnormal growth in nacre layer and prismatic layer which is consistent with the result of RNAi. We proposed that PfmPif97-like regulated by Pfm-miR-9b-5p participates in shell formation of P. f. martensii. These findings provide important clues about the molecular mechanisms that regulate biomineralization in P. f. martensii., Competing Interests: The authors have declared that no competing interests exist.

Q fever is a worldwide zoonosis caused by Coxiella burnetii. Human Q fever is typically acquired through inhalation of contaminated aerosols, resulting in an initial pulmonary infection. In this study, BALB/c mice were infected with C. burnetii via an intratracheal (IT) route using a non-invasive aerosol pulmonary delivery device to directly place the living C. burnetii organisms into the lungs of the mice. The bacterial loads, pathological lesions, and antibody and cellular responses were analyzed and compared with those of mice infected via an intraperitoneal (IP) route. Compared with mice infected via an IP route, mice infected via an IT route exhibited a higher bacterial load and more severe pathological lesions in the heart and lungs at days 3 and 7 post-infection (pi). The levels of interferon-γ and IL-12p70 in the serum of mice infected via the IT route were significantly higher than those of mice infected via the IP route at day 3 pi. In conclusion, this murine model of acute C. burnetii infection via IT inoculation closely resembles the natural route of C. burnetii infection than that of IP injection. Thus, this newly developed model will be useful for investigating the pathogenesis and immunity of C. burnetii aerosol infection, as well as for the evaluation of therapeutic drugs and preventive vaccines of Q fever., Competing Interests: The authors have declared that no competing interests exist.

Systemic lupus erythematosus (SLE) is a chronic, remitting, and relapsing, inflammatory disease involving multiple organs, which exhibits abnormalities of both the innate and adaptive immune responses. A limited number of transcriptomic studies have characterized the gene pathways involved in SLE in an attempt to identify the key pathogenic drivers of the disease. In order to further advance our understanding of the pathogenesis of SLE, we used a novel Bayesian network algorithm to hybridize knowledge- and data-driven methods, and then applied the algorithm to build an SLE gene network using transcriptomic data from 1,760 SLE patients' RNA from the two tabalumab Phase III trials (ILLUMINATE-I & -II), the largest SLE RNA dataset to date. Further, based on the gene network, we carried out hub- and key driver-gene analyses for gene prioritization. Our analyses identified that the JAK-STAT pathway genes, including JAK2, STAT1, and STAT2, played essential roles in SLE pathogenesis, and reaffirmed the recent discovery of pathogenic relevance of JAK-STAT signaling in SLE. Additionally, we showed that other genes, such as IRF1, IRF7, PDIA4, FAM72C, TNFSF10, DHX58, SIGLEC1, and PML, may be also important in SLE and serve as potential therapeutic targets for SLE. In summary, using a hybridized network construction approach, we systematically investigated gene-gene interactions based on their transcriptomic profiles, prioritized genes based on their importance in the network structure, and revealed new insights into SLE activity., Competing Interests: Thomas Dörner has received grant support from Chugai, Janssen, Novartis, and Sanofi. He has received consultancy support from AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, Roche, Samsung, and UCB, and speaker bureau fees from Eli Lilly and Company and Roche. Michelle Petri has received consultancy support from Eli Lilly and Company. Daniel Wallace has received consulting support from Amgen, Eli Lilly and Company, EMD Merck Serono, and Pfizer. Yupeng Li, Richard Higgs, Robert Hoffman, Ernst Dow, Xiong Liu, Brian Eastwood, Bradley Miller and Yushi Liu are employees and stockholders of Eli Lilly and Company. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Preclinical studies showed that antibiotic exposure played a role in clinical outcomes in patients with chemotherapy via modulation of microbiota. However, it remains unknown whether antibiotic exposure during the bevacizumab therapy affects the clinical outcomes in metastatic colorectal cancer(mCRC) patients. This study aimed to examine the association between the antibiotic medication and the clinical outcomes in mCRC patients with bevacizumab therapy., Methods: This retrospective cohort analysis included 147 mCRC patients treated with bevacizumab. The hazard ratio of death was estimated using three Cox proportional hazards models with (1) never vs ever; (2) never vs 1-6 days and 7-40 days;(3) increase per day, and further tested using propensity score matching (PSM) and landmark analysis. A smooth curve technique was used to explore the shape of dose-response relationship., Results: Compared with the non-antibiotic group, antibiotic exposure was inversely associated with the mortality in the antibiotic group after adjustment for demographic and other potential confounders (a history of medication: HR, 0.650(95%CI: 0.360 to 1.173); an increase per day: HR, 0.967(CI: 0.924 to 1.011); 1-6 days: HR, 0.859(CI: 0.441 to 1.674); 7-40 days: HR, 0.474(CI: 0.225 to 0.999); P for trend = 0.040). A test for the interaction between sex was statistically significant (p = 0.016). A similar result was found as measured by landmark and PSM analysis. Significant negative dose-response relationship was shown by smooth curve analysis in the male patients but not female after adjustment for confounders(p = 0.028). No association was found between the antibiotic medication and adverse events of bevacizumab., Conclusion: Antibiotic exposure could be inversely associated with the mortality in mCRC patients treated with bevacizumab., Competing Interests: The authors have declared that no competing interests exist.