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Rong Liu,1,* Min Zhu,2,* Jiaojiao Chen,3 Junwei Gai,2 Jing Huang,2 Yingqun Zhou,1 Yakun Wan,2 Chuantao Tu4 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2Shanghai Novamab Biopharmaceuticals Co., Ltd, Shanghai, 201318, People’s Republic of China; 3Department of Gastroenterology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, 200434, People’s Republic of China; 4Department of Gastroenterology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chuantao Tu; Yakun Wan, Email tuchuantao@hotmail.com; ykwan@novamab.comBackground: No agents are currently available for the treatment or reversal of liver fibrosis. Novel antifibrotic therapies for chronic liver diseases are thus urgently needed. Connective tissue growth factor (CTGF) has been shown to contributes profoundly to liver fibrogenesis, which makes CTGF as a promising target for developing antifibrotic agents.Methods: In this study, we identified a novel nanobody (Nb) against human CTGF (anti-CTGF Nb) by phage display using an immunized camel, which showed high affinity and specificity in vitro. LX-2 cells, the immortalized human hepatic stellate cells, were induced by transforming growth factor beta1 (TGFβ 1) as an in vitro model of liver fibrosis to verify the antifibrotic activity of the anti-CTGF Nb.Results: Our data demonstrated that anti-CTGF Nb effectively alleviated TGFβ 1-induced LX-2 cell proliferation, activation, and migration, and promoted the apoptosis of activated LX-2 cells in response to TGFβ 1. Moreover, the anti-CTGF Nb remarkably reduced the levels of TGFβ 1, Smad2, and Smad3 expression in LX-2 stellate cells stimulated by TGFβ 1.Conclusion: Taken together, we successfully identified a novel Nb against human CTGF, which exhibited antifibrotic effects in vitro by regulating the biological functions of human stellate cells LX-2.Graphical Abstract: Keywords: nanobody, connective tissue growth factor, liver fibrosis, hepatic stellate cells

ObjectivesChlorophyll content and water content are key physiological indicators of crop growth, and their non-destructive detection is a key technology to realize the monitoring of crop growth status such as drought stress. This study took maize as an object to develop a hyperspectral-based approach for the rapid and non-destructive acquisition of the leaf chlorophyll content and water content for drought stress assessment.MethodsDrought treatment experiments were carried out in a greenhouse of the College of Agriculture, Guangxi University. Maize plants were subjected to drought stress treatment at the seedling stage (four leaves). Four drought treatments were set up for normal water treatment [CK], mild drought [W1], moderate drought [W2], and severe drought [W3], respectively. Leaf samples were collected at the 3rd, 6th, and 9th days after drought treatments, and 288 leaf samples were collected in total, with the corresponding chlorophyll content and water content measured in a standard laboratory protocol. A pair of push-broom hyperspectral cameras were used to collect images of the 288 seedling maize leaf samples, and image processing techniques were used to extract the mean spectra of the leaf lamina part. The algorithm flow framework of "pre-processing - feature extraction - machine learning inversion" was adopted for processing the extracted spectral data. The effects of different pre-processing methods, feature wavelength extraction methods and machine learning regression models were analyzed systematically on the prediction performance of chlorophyll content and water content, respectively. Accordingly, the optimal chlorophyll content and water content inversion models were constructed. Firstly, 70% of the spectral data was randomly sampled and used as the training dataset for training the inversion model, whereas the remaining 30% was used as the testing dataset to evaluate the performance of the inversion model. Subsequently, the effects of different spectral pre-processing methods on the prediction performance of chlorophyll content and water content were compared. Different feature wavelengths were extracted from the optimal pre-processed spectra using different algorithms, then their capabilities in preserve the information useful for the inversion of leaf chlorophyll content and water content were compared. Finally, the performances of different machine learning regression model were compared, and the optimal inversion model was constructed and used to visualize the chlorophyll content and water content. Additionally, the construction of vegetation coefficients were explored for the inversion of chlorophyll content and water content and evaluated their inversion ability. The performance evaluation indexes used include determination coefficient and root mean squared error (RMSE).Results and DiscussionsWith the aggravation of stress, the reflectivity of leaves in the wavelength range of 400~1700 nm gradually increased with the degree of drought stress. For the inversion of leaf chlorophyll content and water content, combining stepwise regression (SR) feature extraction with Stacking regression could obtain an optimal performance for chlorophyll content prediction, with an R2 of 0.878 and an RMSE of 0.317 mg/g. Compared with the full-band stacking model, SR-Stacking not only improved R2 by 2.9%, reduced RMSE by 0.0356mg/g, but also reduced the number of model input variables from 1301 to 9. Combining the successive projection algorithm (SPA) feature extraction with Stacking regression could obtain the optimal performance for water content prediction, with an R2 of 0.859 and RMSE of 3.75%. Compared with the full-band stacking model, SPA-Stacking not only increased R2 by 0.2%, reduced RMSE by 0.03%, but also reduced the number of model input variables from 1301 to 16. As the newly constructed vegetation coefficients, normalized difference vegetation index(NDVI) [(R410-R559)/(R410+R559)] and ratio index (RI) (R400/R1171) had the highest accuracy and were significantly higher than the traditional vegetation coefficients for chlorophyll content and water content inversion, respectively. Their R2 were 0.803 and 0.827, and their RMSE were 0.403 mg/g and 3.28%, respectively. The chlorophyll content and water content of leaves were visualized. The results showed that the physiological parameters of leaves could be visualized and the differences of physiological parameters in different regions of the same leaves can be found more intuitively and in detail.ConclusionsThe inversion models and vegetation indices constructed based on hyperspectral information can achieve accurate and non-destructive measurement of chlorophyll content and water content in maize leaves. This study can provide a theoretical basis and technical support for real-time monitoring of corn growth status. Through the leaf spectral information, according to the optimal model, the water content and chlorophyll content of each pixel of the hyperspectral image can be predicted, and the distribution of water content and chlorophyll content can be intuitively displayed by color. Because the field environment is more complex, transfer learning will be carried out in future work to improve its generalization ability in different environments subsequently and strive to develop an online monitoring system for field drought and nutrient stress.

Objective External examination of a clinical risk score to predict persistent postconcussive symptoms (PPCS) in a pediatric emergency department (ED). Methods Prospective cohort study of 5- to 18-year-old patients diagnosed with an acute concussion. Risk factors were collected at diagnosis and participants (n  = 85) were followed to determine PPCS 30 days postinjury. Univariate logistic regression analyses were completed to examine associations of risk factors with PPCS. Results Headache and total clinical risk score were associated with increased odds of PPCS in the univariate analyses, OR 3.37 (95% CI 1.02, 11.10) and OR 1.25 (95% CI 1.02, 1.52), respectively. Additionally, teenage age group, history of prolonged concussions, and risk group trended toward association with PPCS, OR 4.79 (95% CI 0.93, 24.7), OR 3.41 (95% CI 0.88, 13.20), and OR 2.23 (95% CI 0.88, 5.66), respectively. Conclusion Our study supports the use of multiple variables of a clinical risk score to assist with ED risk stratification for pediatric patients at risk for PPCS. [ABSTRACT FROM AUTHOR]

In order to study the influence of wind velocity on the safe working limit time of miners in a humid and hot mine, five experienced mine workers were selected as subjects to exercise labor simulations with moderate intensity under 24 different mine environments simulated by an artificial microclimate room. While recording the experimental time, their physiological indicators were measured: heart rate and rectal temperature, therefore to determine safe working limit time of the miners. There are 4 groups of wind velocity are set: static wind(wind velocity less than 0.2 m/s), low velocity wind(1 m/s), medium velocity wind(2.5 m/s), high velocity wind(4 m/s), 3 groups of temperature are set: 26, 30, 34 ℃, 2 groups of relative humidity are set: 70%, 90%. According to the experimental data, the Cox regression method and survival function method are used to analyze the effect of wind velocity on the safe working limit time and the recommended value of safe working limit time is given. The result shows that: the influence of wind velocity on miners’ safe working limit time is greater than relative humidity but less than temperature. Among the four wind velocity types, the order of survival rate decline rate from high to low is: static wind>low velocity wind>medium velocity wind>high velocity wind. Increasing wind velocity can effectively increase the value of the safe working limit time, but the effect is not great when the wind velocity reaches 2.5 m/s.

Using a quartz sand culture, comparisons were made between the T5 homozygous transgenic lines (HTLs) that overexpress StP5CS (GenBank accession number: JN606861) and their wild-type (WT) host cultivar to examine the differences in the growth and development traits, the concentrations of proline in vegetable soybean [Glycine max (L.) Merrill] under salt stress conditions. Moreover, the relative expression levels of two glutamine synthetase-related genes (GmGS1α1, GmGS1α2), two nodulation-related genes (GmENOD40-1, GmENOD40-2), and one leghemoglobin gene (GmLba) were also measured. The purpose of this research was to provide a theoretical basis for elucidating the mechanisms of nodulation and nitrogen fixation in the roots of transgenic plants under salt stress conditions. Compared with WT plants, the plant height and seed weight per plant of T5 HTLs significantly increased, and the contents of proline in various tissues of T5 HTLs were also significantly elevated. Quantitative real-time PCR (qRT-PCR) analysis indicated that the expression levels of GmGS1α1, GmGS1α2, GmENOD40-1, GmENOD40-2, and GmLba were significantly increased in T5 HTLs under salt stress conditions. These results indicate that the overexpression of StP5CS in T5 HTLs enhanced growth, nodulation and nitrogen fixation in transgenic vegetable soybean under salt stress conditions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Fatty liver may induce various complications including chronic hepatitis or liver cirrhosis, and is frequently occurred in obesity individuals. Advanced glycosylation end products (AGEs) were known to play a critical role in multiple liver diseases. This study, therefore, aimed to study the effect of AGEs on obesity, related liver cirrhosis and inflammation, on an obesity fatty liver rat model. MATERIALS AND METHODS: A total of 60 Sprague Dawley (SD) rats were randomly divided into control, model and AGEs inhibitor groups (n=20 each). AGEs level, body weight and liver function were examined in each animal, followed by hematoxylin-eosin (HE) staining to detect the pathological change of liver. Further Real-time PCR and enzyme-linked immunosorbent assay (ELISA) were employed to detect inflammatory cytokine levels including tumor necrosis factor (TNF)- a and interleukin (IL)-6. RESULTS: AGEs level was significantly elevated in obesity fatty liver model rats, which also had higher total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C) and high-density lipoprotein (HDL-C) levels, along with deteriorated liver function and higher TNF-α and IL-6 levels. The application of AGEs inhibitor aminoguanidine significantly improved liver functions and lower TNF-α or IL-6 levels when compared to the model group (p<0.05 in all cases). CONCLUSIONS: Obesity fatty liver can promote AGEs level, further causing pathological changes and increased secretion of inflammatory cytokines. The inhibition of AGEs can improve the metabolism of fatty acids, decrease inflammatory cytokines and benefit the treatment of obesity fatty liver. [ABSTRACT FROM AUTHOR]

Objective To investigate the role of CXCL5 in promoting gastric cancer and the potential molecular mechanisms. Methods We selected 83 gastric cancer patients as study objects and 40 healthy people who underwent physical examination as control. We compared the serum levels of CXCL5 between gastric cancer patients and healthy control, and the expression of CXCL5 and CXCR2 between tumor and paracarcinoma tissues. The effect of CXCL5 on ERK/MAPK, PI3K/AKT, NF-κB and WNT/β-catenin signals were examined. CXCL5-overexpressed and control MFC cells were injected subcutaneously into C57 mice to establish xenograft model. Tumor growth and survival curves were drawn. The expression of CXCL5, p-NF-κB and p-β-catenin and the number of CD4+ T, CD8+ T and CD56+CD16+ NK cells in xenograft tumor tissue were determined. Results CXCL5 expression in the serum of gastric cancer patients was significant higher than that in healthy controls (P < 0.05). The expression of CXCL5 and CXCR2 in tumor tissues were significantly higher than those in paracarcinoma normal tissues (P < 0.05). CXCL5 increased the expression of p-NF-κB and p-β-catenin in SNU126 and MFC cells (P < 0.05). In CXCL5 overexpression group, the tumor volume significantly increased and the survival of mice were significantly decreased, the expression levels of CXCL5, p-NF-κB and p-β-catenin were significantly higher, the number of CD4+T, CD8+T and CD56+CD16+ NK cells were significantly higher, compared with control mice (all P < 0.05). Conclusion CXCL5 may promote gastric cancer via modulating NF-κB and Wnt/β-catenin signaling-mediated inhibition of tumor immune.

With the continuous development and application of digital technology, higher vocational education is also facing the demand of digital transformation. The digital transformation of higher vocational education is the key to the high quality development of higher vocational education. In order to promote the digitization of education and enhance the adaptability of vocational education, it is necessary to continuously improve teachers’ ability and literacy. In order to adapt to and lead the digital new normal, it is an important starting point for the high-quality development of vocational education to build a comprehensive and multi-channel digital literacy of higher vocational teachers and the digital improvement path of classroom teaching. The research of this paper will provide guidance and reference for the cultivation of teachers’ digital literacy and the improvement of classroom teaching effect in higher vocational colleges.