The antivirulence activity, transcriptomics of EGCG and its protective effects on zebrafish infected by Aeromonas hydrophila.

Background: Aeromonas hydrophila is an important pathogen that mainly harms aquatic animals and exhibits resistance to a variety of antibiotics. This study investigated the effect of epigallocatechin-3-gallate (EGCG) on the virulence factors of A.hydrophila and its impact on adhesion, invasion, and cytotoxicity in Caco-2 cells. The potential mechanism of antibacterial activity of EGCG was investigated by transcriptomic analysis. Results: EGCG not only inhibited the production of biofilm, hemolytic activity, motility, and protease activity of A.hydrophila, but also reduced its adhesion, invasion, and cytotoxicity in Caco-2 cells. Transcriptomic analysis indicated that the antimicrobial activity of EGCG may be achieved by weakening the chemotaxis and stress response of the bacteria, as well as inhibiting the TonB system. Animal studies demonstrated that EGCG can significantly improve the survival rate and organs damage of zebrafish infected with A.hydrophila. Conclusion: EGCG would be a potential alternative drug for the prevention and treatment of A. hydrophila infections by anti-virulence mechanism.

Downhole parameter prediction method based on multi-layer water injection model and historical data-based model parameter identification.

Wireless communication has become a preferred direction for the development of layered water injection tools due to its low cost and high reliability. However, the wireless system relies on the underground battery for power supply，and each communication will consume a significant amount of energy. In order to save energy consumption, the wireless system adopts the intermittent sleep communication mode, with intervals of usually more than one month. During the idle time of communication, the downhole parameters such as pressure and flowrate will change as the pressure and flowrate at the wellhead. Therefore, it is crucial to predict downhole parameters based on the wellhead pressure and flowrate. In this study, a downhole parameter prediction method based on multi-layer water injection model is proposed. A multilayer injection prediction model was established based on the hydraulic analysis of the tubing string, and the model parameters were identified and updated using the historical data uploaded each time. The pressure and flow rate measured at the wellhead were used as inputs to the model, and the recursive relationship between layers in the multilayer model was utilized to predict downhole parameters for each layer. A model parameter optimization method based on time-weighting is proposed in order to address the gradual changes in model parameters during water injection. This method assigns greater weight to more recent historical data, resulting in optimized model parameters. Experimental results show that the proposed method can effectively predict the flowrate and pressure of each layer, with a prediction deviation of less than 5% F.S., which provides technical support for the application and popularization of the wireless layered water injection system.

Haze Exposure Changes the Skin Fungal Community and Promotes the Growth of Talaromyces Strains.

Haze pollution has been a public health issue. The skin microbiota, as a component of the first line of defense, is disturbed by environmental pollutants, which may have an impact on human health. A total of 74 skin samples from healthy students were collected during haze and nonhaze days in spring and winter. Significant differences of skin fungal community composition between haze and nonhaze days were observed in female and male samples in spring and male samples in winter based on unweighted UniFrac distance analysis. Phylogenetic diversity whole-tree indices and observed features were significantly increased during haze days in male samples in winter compared to nonhaze days, but no significant difference was observed in other groups. Dothideomycetes, Capnodiales, Mycosphaerellaceae, etc. were significantly enriched during nonhaze days, whereas Trichocomaceae, Talaromyces, and Pezizaceae were significantly enriched during haze days. Thus, five Talaromyces strains were isolated, and an in vitro culture experiment revealed that the growth of representative Talaromyces strains was increased at high concentrations of particulate matter, confirming the sequencing results. Furthermore, during haze days, the fungal community assembly was better fitted to a niche-based assembly model than during nonhaze days. Talaromyces enriched during haze days deviated from the neutral assembly process. Our findings provided a comprehensive characterization of the skin fungal community during haze and nonhaze days and elucidated novel insights into how haze exposure influences the skin fungal community. IMPORTANCE Skin fungi play an important role in human health. Particulate matter (PM), the main haze pollutant, has been a public environmental threat. However, few studies have assessed the effects of air pollutants on skin fungi. Here, haze exposure influenced the diversity and composition of the skin fungal community. In an in vitro experiment, a high concentration of PM promoted the growth of Talaromyces strains. The fungal community assembly is better fitted to a niche-based assembly model during haze days. We anticipate that this study may provide new insights on the role of haze exposure disturbing the skin fungal community. It lays the groundwork for further clarifying the association between the changes of the skin fungal community and adverse health outcomes. Our study is the first to report the changes in the skin fungal community during haze and nonhaze days, which expands the understanding of the relationship between haze and skin fungi.

Novel combretastatin A-4 derivative containing aminophosphonates as dual inhibitors of tubulin and matrix metalloproteinases for lung cancer treatment.

Here, sixteen novel conjugates containing tubulin inhibitor and matrix metalloproteinase inhibitor was synthesized together with their activity evaluated. Among them, 9e exhibited the most potent activity against various human cancer cells (IC50 values was 0.19-0.42 µM) as well as multidrug-resistant tumor cells (A549/CDDP and MCF-7/DOX) and also showed significantly lower cytotoxic activity toward human normal liver cells LO2 in comparison with that of CA-4. Interestingly, 9e not only strongly inhibited tubulin polymerization, and induced cell apoptosis and cell cycle arrest in G2/M stage, but also remarkably displayed inhibition of cell migration against A549 cells in vitro, and exhibited a moderate activity toward MMP-2, MMP-3 and MMP-9, respectively. Moreover, the significant down-regulation in the levels of Bcl-2 protein and up-regulated levels of proteins, such as Bax, p53 and caspase-3, indicated that 9e can induce apoptosis via mitochondria-dependent apoptosis pathway. Additionally, 9e can also cause ER stress demonstrating as up-regulation express of proteins (CHOP, p-eIF2a, and p-PERK). Importantly, 9e displayed significant in vivo antitumor efficacy in A549 xenograft models without inducing apparent systemic toxicity. Collectively, this work indicated that compound 9e, a dual MMPs and tubulin inhibitor, is a novel and promising agent for cancer therapy.

Eucommia ulmoides bark extract reduces blood pressure and inflammation by regulating the gut microbiota and enriching the Parabacteroides strain in high-salt diet and N(omega)-nitro-L-arginine methyl ester induced mice.

Hypertension is a major threat to human health. Eucommia ulmoides Oliv. (EU) is a small tree and EU extract is widely used to improve hypertension in East Asia. However, its major constituents have poor absorption and stay in the gut for a long time. The role of the gut microbiota in the anti-hypertensive effects of EU is unclear. Here, we examined the anti-hypertensive effects of EU in high-salt diet and N(omega)-nitro-L-arginine methyl ester (L-NAME) induced mice. After receiving EU for 6 weeks, the blood pressure was significantly reduced and the kidney injury was improved. Additionally, EU restored the levels of inflammatory cytokines, such as serum interleukin (IL)-6 and IL-17A, and renal IL-17A. The diversity and composition of the gut microbiota were influenced by administration of EU; 40 significantly upregulated and 107 significantly downregulated amplicon sequence variants (ASVs) were identified after administration of EU. ASV403 (Parabacteroides) was selected as a potential anti-hypertensive ASV. Its closest strain XGB65 was isolated. Furthermore, animal studies confirmed that Parabacteroides strain XGB65 exerted anti-hypertensive effects, possibly by reducing levels of inflammatory cytokines, such as renal IL-17A. Our study is the first to report that EU reduces blood pressure by regulating the gut microbiota, and it enriches the Parabacteroides strain, which exerts anti-hypertensive effects. These findings provide directions for developing novel anti-hypertensive treatments by combining probiotics and prebiotics.

Hepatoid Adenocarcinoma of the Lung: A Systematic Review of the Literature From 1981 to 2020.

OBJECTIVES: We report the first case of hepatoid adenocarcinoma of the lung (HAL) with PIK3CA mutation. In addition, we analyzed data from HAL cases over the past 40 years to study its main treatment methods, prognosis, and the relationship between prognosis and the serum alpha-fetoprotein (AFP) level before treatment. METHODS: We report a 66-year-old male case who was diagnosed with locally advanced HAL with PIK3CA mutation and carried out a systematic literature search for HAL cases documented between 1981 and 2020. General patient information including case characteristics was extracted and summarized. The median OS (mOS) of HAL patients was determined using the KM survival curve. The Cox proportional hazards regression model was used to evaluate the effect of tumor size, location, and serum AFP value before treatment and radical surgery (RS) on the prognosis of patients. RESULTS: A total of 46 studies including 51 HAL patients was included in our review. Our study revealed that 52.9% of tumors were located in the upper lobe of the right lung. The proportion of serum AFP-positive patients before treatment, early-stage patients (TNM stage I and II), and patients who had received surgery were 69.2%, 34.1%, and 40%, respectively. The mOS of HAL patients was 16.0 months. The 2-year and 5-year survival rates of the patients were 35.3% and 8.0%, respectively. In the subgroup analysis, the 2-year survival rate for patients who received RS was 62.5%, while for patients who were unable to undergo RS, it was only 12.5% (p = 0.009). The Cox proportional hazards regression model indicated that RS can significantly improve the prognosis of HAL patients (p = 0.011), although the location and size of tumor as well as the serum AFP value before treatment had no significant effect on their prognosis (p = 0.82, p = 0.96, p = 0.25). CONCLUSIONS: HAL patients have a poor prognosis, and the survival benefits for patients receiving chemoradiotherapy or chemotherapy alone appear to be limited. We demonstrate statistically for the first time that pretreatment serum AFP values are not related to the prognosis of HAL patients and RS can significantly improve patient prognosis.

Dual-target platinum(IV) complexes exhibit antiproliferative activity through DNA damage and induce ER-stress-mediated apoptosis in A549 cells.

Platinum(II)-based chemotherapeutics are commonly used to treat various types of solid tumors, such as lung cancers. However, these compounds can cause serious side effects, including nephrotoxicity and ototoxicity, which affect the quality of life of patients. In our work, four novel dual target platinum(IV) complexes were designed and synthesized. In vitro results indicated that the title platinum(IV) complexes exhibited effective antitumor activities against the tested cancer cells and had lower toxicity and resistance factors than oxaliplatin and cisplatin. Further mechanistic experiments demonstrated that complex 11 accumulated in mitochondria and induced an elevation in ROS and an ER stress response via mitochondrial dysfunction. Notably, complex 11 significantly modulated the expression levels of proapoptosis proteins including cleaved-Caspase-3, Bax, and p53, and decreased the level of the prosurvival protein Bcl-2. Together, these results suggested that complex 11 might be a potential lead compound for future cancer therapy due to its potency and selectivity.

Size-Controlled and Super Long-Term Stable Lignin Nanospheres through a Facile Self-Assembly Strategy from Kraft Lignin.

In diverse fields, much attention has been concentrated on the preparation of lignin nanospheres with various structures. Here we report a facile self-assembly strategy for preparing super long-term stable hollow and solid nanospheres based on lignin fractionation. We found that different lignins obtained at different pHs during fractionation can form nanospheres with different particle sizes and structures. The self-assembled and formation mechanisms of the nanospheres were surveyed by dynamic light scattering (DLS), elemental analysis, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The analysis results showed that the phenolic hydroxyl groups and the intermolecular π-π interaction play a decisive effect in the formation of nanospheres. This study can not only facilitate the advance of lignin-based nanotechnologies but also provide a broad prospect for the use of black liquor.

Comparative Evaluation of Organic Acid Pretreatment of Eucalyptus for Kraft Dissolving Pulp Production.

Pretreatment is an essential process for the extensive utilization of lignocellulose materials. The effect of four common organic acid pretreatments for Kraft dissolving pulp production was comparatively investigated. It was found that under acidic conditions, hemicellulose can be effectively removed and more reducing sugars can be recovered. During acetic acid pretreatment, lignin that was dissolved in acetic acid could form a lignin-related film which would alleviate cellulose hydrolysis, while other organic acids caused severe cellulose degradation. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffractometry (XRD) were used to characterize the pretreated chips in the process. Lignin droplets were attached to the surface of the treated wood chips according to the SEM results. The FTIR spectrum showed that the lignin peak signal becomes stronger, and the hemicellulose peak signal becomes weaker with acid pretreatment. The XRD spectrum demonstrated that the crystallinity index of the wood chips increased. The acetic acid pretreatment process-assisted Kraft process achieved higher yield (31.66%) and higher α-cellulose (98.28%) than any other organic acid pretreatment. Furthermore, extensive utilization of biomass was evaluated with the acetic acid pretreatment-assisted Kraft process. 43.8% polysaccharide (12.14% reducing sugar and 31.66% dissolving pulp) and 22.24% lignin (0.29% acetic acid lignin and 21.95% sulfate lignin) were recovered during the process. Biomass utilization could reach 66.04%. Acetic acid pretreatment is a promising process for extensive biomass utilization.

A New Deep Learning Model for Fault Diagnosis with Good Anti-Noise and Domain Adaptation Ability on Raw Vibration Signals.

Intelligent fault diagnosis techniques have replaced time-consuming and unreliable human analysis, increasing the efficiency of fault diagnosis. Deep learning models can improve the accuracy of intelligent fault diagnosis with the help of their multilayer nonlinear mapping ability. This paper proposes a novel method named Deep Convolutional Neural Networks with Wide First-layer Kernels (WDCNN). The proposed method uses raw vibration signals as input (data augmentation is used to generate more inputs), and uses the wide kernels in the first convolutional layer for extracting features and suppressing high frequency noise. Small convolutional kernels in the preceding layers are used for multilayer nonlinear mapping. AdaBN is implemented to improve the domain adaptation ability of the model. The proposed model addresses the problem that currently, the accuracy of CNN applied to fault diagnosis is not very high. WDCNN can not only achieve 100% classification accuracy on normal signals, but also outperform the state-of-the-art DNN model which is based on frequency features under different working load and noisy environment conditions.

Quantitative and detailed spatiotemporal patterns of drought in China during 2001-2013.

Investigation of spatiotemporal patterns of drought is essential to understand the mechanism and influencing factors of drought occurrence and development. Due to the differences in designation of various drought indices, it remains a great challenge to obtain an accurate result in spatiotemporal patterns investigation of drought. In this study, a quantitative drought monitoring index (i.e., Integrated Surface Drought Index, ISDI) was used to identify spatiotemporal patterns of drought and the drought variation trend at the pixel level during 2001-2013 over China. Eco-geographical regionalization was used as an evaluation unit to distinguish the ecological and climatic background of drought over the whole country. The results showed that the spatial distribution of drought intensity has a strong correlation with eco-geographical regionalization in China. The severe drought areas were mainly concentrated in sub-humid regions and semi-arid regions of medium temperate zones, and humid regions of middle subtropical zones. The regions with higher drought probabilities were most distributed in the south and north of China, while the regions in central and western China exhibited lower drought probabilities. The most obvious decreasing trend of ISDI from 2001 to 2013 was located in the northeast of China and south of the Yangtze River. This decrease in ISDI over time indicates a trend for progressive aggravation of drought severity in these areas. This study shows great promise in informing the future drought prevention measures and management policies under the background of more frequent extreme climate events.

[Effect of economic structure adjustment on pollution emission: a case study of COD].

Economic structure adjustment is an important means to reduce the emissions of pollutants. For quantitative analysis of the effect of economic structure adjustment on the reduction of pollution emission, the country was divided into four sub-regions, eastern, northeastern, central and western, and the industry was divided into 39 sectors. Taking chemical oxygen demand (COD) as an example, the influences of regional structure and industry structure adjustment on total emission reduction and emission intensity were analyzed through building a model. The results showed that, in 2000-2010: (1) COD emissions in China were reduced from 1 445 x 10(4) t to 1 238 x 10(4) t, with a total emission of 14 950 x 10(4) t in 11 years, among which the emissions from eastern area occupied the largest proportion, accounting for 35.6%. (2) In the industrial COD emissions, emission from paper and paper products was the largest, accounting for 35.8% of the industrial COD emissions. (3) The economic structure changes in the four areas reduced the COD emissions by 420 x 10(4) t, resulting in a decrease of 1.29% in COD emission intensity. (4) Industrial internal structure changes reduced the COD emissions by 533 x 10(4) t, leading to a decrease of 3.1% in COD emission intensity. The research results have certain reference value in guiding the Chinese economic structure adjustment and achieving the targets of energy-saving and emission reduction.

[Establishment and application of pollutant discharge-environment quality model].

In order to explore the mutual influence between pollutant discharge and environment quality, relation models of pollutant discharge and environmental quality were established, and the relationship was divided into four types, low pollutant discharge-high environmental quality, high pollutant discharge-high environmental quality, high pollutant discharge-low environmental quality, and low pollutant discharge-low environmental quality. The evolution paths from one type into another were also discussed. The regional data in 2005 and 2010 was used to validate the pollutant discharge-environmental quality models. The results showed that most regions of China belonged to the high pollutant discharge-low environmental quality type, and the pollutant discharge- environmental quality type didn't vary too much during the 2005-2010 period. In the majority of provinces, the environmental quality index was higher than the pollutant discharge index, and the pollutant discharge quantity overflowed the environmental capacity. The reduction of pollutant discharge quantity should be the most important environmental problem in China. At present, China is in a critical period of environmental governance, and excessive disturbance from economic system to the environment system should be prevented. The results should be helpful for understanding the regional environmental quality situation, on the implementation of pollutant discharge reduction, and the improvement of environmental quality.

[Advance in preoperative radiochemotherapy for resectable rectal cancer].

The aim of preoperative radiotherapy for rectal cancer is to improve the local control rate, increase the possibility for sphincter preservation, and improve the survival and the quality of life. Randomized clinical trials have shown that combining radical surgery with preoperative radiochemotherapy is more effective in improving the local control rate as compared with radical surgery or preoperative radiotherapy alone. With introduction of more effective novel chemotherapeutic agents and schemes of their combination, multimodal treatment with preoperative radiochemotherapy will be applied individually to treat selected patients, which is expected to further enhance the therapeutic effect of rectal cancer. This article reviewed the current status and development of preoperative radiochemotherapy for rectal cancer.