In order to reduce the silique shattering loss of rapeseed mechanical harvesting process, based on the state of force on the silique during rapeseed harvesting reel branch, Ningza 1810, Zhenyou 8 and Fengyou 306 were used as research objects, and the experimental research on the factors affecting rapeseed siliques shattering was carried out using the swing impact method. The experimental analysis showed that: rapeseed varieties, silique moisture content, silique growth position, collision material, impact speed, force position and other factors had significant effects on silique shattering. The impact velocity was less than 1.5m·s-1, the difference on the effect of each factor on pod-shattering was not significant, it was not easy to shatter when the moisture content of rapeseed silique was higher. The impact resistance of the front side of rapeseed was 2 to 4 times that of the bonding surface of rapeseed petals, the shattering rate of the top rapeseed silique was twice that of the bottom siliques, when siliques were supported, they were more likely to shatter under external forces than when they were unsupported. The experimental study of the mechanical properties of rapeseed siliques was carried out using the impending fracture method, the experimental analyses showed that the support position and force position of the silique, the loading speed and the growth position of the silique had a significant effect on the mechanical properties of the silique. The maximum cracking force was higher and bending strength was stronger when the body of the silique was supported, which the range of the maximum cracking force were 3.05N to 4.16N, and the bending strength range were 8.48 MPa to 11.57 MPa. The maximum cracking force and bending strength of the silique was stronger when the front side of the silique petal was pressurized than when the bonding surface of the petal was pressurized. Based on Pearson's correlation and grey correlation analysis, the morphological characteristics of rapeseed siliques were ranked in order of their influence on the performance of siliques in terms of the angle between silique and stalk, stalk diameter, petal thickness, beak length, silique thickness, silique width and silique length. This study can be used as a reference for the design and optimization of the rapeseed harvesting reel branch mechanism and the selection of machine harvestable rapeseed varieties.

A variable speed anti-tangling reel mechanism was designed to address the problems of tangling, hanging and rewinding of the tassel wheel and the high paddling loss in the current Chinese rape combine harvester cutting table. The kinematic equations of the reel mechanism were developed, and the analysis showed that the speed in the entry stage is low and the speed in the exit stage is high, and the attitude of the reel teeth change with the rape plant movement during the whole paddling process. A single-factor test and a multi-factor regression orthogonal combination test were carried out using the cutting table loss rate of rape harvesting as the evaluation index. The main and secondary factors affecting the cutting table loss of the variable speed reel were obtained as the reel speed, the machine travel speed and the ground angle of the frame. A mathematical model of regression of cutter loss and the main influencing factors was established, with the coefficient of determination R2 = 0.9918. The optimal combination of parameters for the variable speed reel was obtained with the lowest cutting table loss rate in rape harvesting as the optimization target: reel speed 25r/min, frame parallel to the ground and implement travel speed 0.7m/s. Field validation tests and comparative tests of cutting table loss of the two reels were carried out. The test results show that the regression mathematical model of the cutting table loss is more accurate, and the cutting table loss is reduced by 13.9% with the variable speed reel compared to the cam-action reel, and there are no problems with the paddle teeth hanging and tangling during the paddling process.

Hospital-based programs democratize mRNA therapeutics by facilitating the processes to translate a novel RNA idea from the bench to the clinic. Because mRNA is essentially biological software, therapeutic RNA constructs can be rapidly developed. The generation of small batches of clinical grade mRNA to support IND applications and first-in-man clinical trials, as well as personalized mRNA therapeutics delivered at the point-of-care, is feasible at a modest scale of cGMP manufacturing. Advances in mRNA manufacturing science and innovations in mRNA biology, are increasing the scope of mRNA clinical applications.

The present study aimed to analyze novel mechanisms underlying Nrf2-mediated anti-apoptosis in periodontal ligament stem cells (PDLSCs) in the periodontitis oxidative microenvironment. We created an oxidative stress model with H2O2-treated PDLSCs. Herein, we used real-time PCR, western blotting, TUNEL staining, fluorogenic assay and transfer genetics to confirm the degree of oxidative stress and apoptosis as well as the Nrf2 function. Surprisingly, we demonstrated that with up-regulated ROS and MDA levels, the effect of oxidative stress was obvious under H2O2 treatment. Anti-oxidative molecules were changed after the H2O2 exposure, whereby the anti-oxidative signaling of Nrf2 was activated with the increase of its downstream effectors, HO-1, NQO1 and γ-GCS. Additionally, the apoptosis levels gradually increased with oxidative stress and changes in the caspase-9, caspase-3, Bax and c-Fos levels, but not with caspase-8 and down-regulated Bcl-2. The enhanced antioxidant effect could not resist the occurrence of apoptosis. Furthermore, Nrf2 overexpression effectively improved the anti-oxidative levels and increased cell proliferation. At the same time, overexpression effectively restrained TUNEL staining and decreased the molecular levels of caspase-9, caspase-3, et al, but not that of caspase-8. By contrast, silencing the expression Nrf2 levels had the opposite effect. Collectively, Nrf2 alleviates PDLSCs via its effects on anti-oxidative and anti-intrinsic apoptosis by the activation of anti-oxidative enzymes.

Underground storage of natural gas has the characteristics of clean and low-carbon, and has the ability to provide sustainable and stable supply. It is a very high-quality green energy that can increase the storage efficiency of gas storage through fracturing, achieving the sustainable development goal of "Carbon Peaking and Carbon Neutrality". The accurate evaluation of the fracability of a reservoir is an important prerequisite for reservoir fracturing design and post fracturing productivity evaluation. At present, research on fracability is mainly based on qualitative characterization or quantitative evaluation based on rock mechanics and fracturing construction parameters, which cannot fully reflect the rock composition and structure of each stage. Firstly, based on logging data, this paper analyzes the evolution laws of strain energy such as elastic properties, pre-peak dissipation energy, and post-peak fracture energy during the transition of rock materials from plastic deformation to brittle fracture in an energy perspective, and determines the key energy that affects the brittle characteristics of rocks. Secondly, a brittleness index evaluation approach has been established that can comprehensively reflect the mechanical properties of rocks during pre-peak deformation and post-peak damage stages. In addition, this article focuses on the impact of reservoir stratigraphic environment by combining the influence of geo-stresses with the rock brittleness index, and proposes a new method for evaluating reservoir fracability. Finally, this paper conducts a study on the fracability evaluation of three wells in a gas storage facility in eastern China. The results indicate that low modulus and fracability coefficient are beneficial for fracturing, thereby improving the gas production and peak shaving ability of gas storage.

Currently, there is no specific treatment for COVID-19 proven by clinical trials. WHO and CDC guidelines therefore endorse supportive care only. However, frontline clinicians have been applying several virus-based and host-based therapeutics in order to combat SARS-CoV-2. Medications from COVID-19 case reports, observational studies and the COVID-19 Treatment Guideline issued by the China's National Health Commission (7^th edition published March 3^rd, 2020. Edited translation attached) are evaluated in this review. Key evidence from relevant in vitro researches, animal models and clinical studies in SARS-CoV-2, SARS-CoV and MERS-CoV are examined. Antiviral therapies remdesivir, lopinavir/ritonavir and umifenovir, if considered, could be initiated before the peak of viral replication for optimal outcomes. Ribavirin may be beneficial as an add-on therapy and is ineffective as a monotherapy. Corticosteroids use should be limited without indicating comorbidities. IVIG is not recommended due to lack of data in COVID-19. Xuebijing may benefit patients with complications of bacterial pneumonia or sepsis. The efficacy of interferon is unclear due to conflicting outcomes in SARS and MERS studies. Chloroquine and hydroxychloroquine have shown in vitro inhibition of SARS-CoV-2 and may be beneficial as both prophylactic and treatment therapy. For patients who developed cytokine release syndrome, interleukin-6 inhibitors may be beneficial. Given the rapid disease spread and increasing mortality, active treatment with readily available medications may be considered timely prior to disease progression.

This study was first time designed to investigate the effect of oxidation on protein digestion and transport properties in boiled sea cucumber body wall (BSCBW) via simulated digestion combine with everted-rat-gut-sac models. Boiling heat treatments led to protein oxidation in SCBW, manifested by increases in free radical intensity, thiobarbituric acid reactive substances, carbonyl groups, disulfide bonds, dityrosine bonds, advanced glycation end products, protein hydrophobicity and aggregation, declines in free sulfhydryl group, and secondary structure transition from α-helix to β-sheet. Boiling for 2 h caused the anti-digestion collagen unfolding, provided the action site for protease, and improved the protein digestion and transport levels. On the contrary, excessive oxidative modification of 4 h-BSCBW resulted in decreased protein digestion and transport levels. From the perspective of texture, digestion and transport properties, boiling for 2 h can obtain sea cucumber products with better edible and digestible properties, which is considered to be a better processing condition.

Cynomorium songaricum is an important endangered plant with significant medicinal and edible values. However, the lack of resources and quality variation have limited the comprehensive developments and sustainable utilization of C. songaricum. Here, we evaluated chemical and genetic traits of C. songaricum from the highly suitable habitat regions simulated with species distribution models. The PCA and NJ tree analyses displayed intraspecific variation in C. songaricum, that could be divided into two ecotypes: ecotype I and ecotype II. Furthermore, the LC-MS/MS-based metabolomic was used to identify and analyze the metabolites of two ecotypes. The results indicated that a total of 589 compounds were detected, 236 of which were significantly different between the two ecotypes. Specifically, the relative content and the kind of flavonoids were more abundant in ecotype I, which were closely associated with the medicinal activities. In contrast, amino acids and organic acids were more enriched in ecotype II, which may provide better nutritional quality and unique flavor. In summary, our findings demonstrate the ecotype division and chemical diversity of C. songaricum in China from different geographical regions and provide a reference for the development of germplasm and directed plant breeding of endangered medicinal plants.

Target pests of genetically engineered crops producing both defensive allelochemicals and Bacillus thuringiensis (Bt) toxins often sequentially or simultaneously uptake allelochemicals, Bt toxins, and/or insecticides. How the three types of toxins interact to kill pests remains underexplored. Here we investigated the interactions of Bt toxin Vip3A, plant allelochemical flavone, and insecticide emamectin benzoate in Spodoptera frugiperda. Simultaneous administration of flavone LC25 + Vip3A LC25, emamectin benzoate LC25 + Vip3A LC25, and flavone LC15 + emamectin benzoate LC15 + Vip3A LC15 but not flavone LC25 + emamectin LC25 yielded a mortality significantly higher than their expected additive mortality (EAM). One-day preexposure to one toxin at LC5 followed by 6-day exposure to the same toxin at LC5 plus another toxin at LC50 showed that the mortality of flavone LC5 + Vip3A LC50, emamectin benzoate LC5 + Vip3A LC50, and Vip3A LC5 + emamectin benzoate LC50, were significantly higher than their EAM, while that of flavone LC5 + emamectin benzoate LC50 was significantly lower than their EAM. No significant difference existed among the mortalities of Vip3A LC5 + flavone LC50, emamectin benzoate LC5 + flavone LC50, and their EAMs. The results suggest that the interactions of the three toxins are largely synergistic (inductive) or additive, depending on their combinations and doses.

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based studies using these datasets require thoughtful modification to sample selection and analytic strategies, relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings. This paper offers some practical guidance to the full analytical process, demonstrates methods for estimating causal treatment effects on several types of outcomes common to such studies, such as binary, count, time to event and longitudinally varying repeated measures outcomes, and aims to increase transparency and reproducibility. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insurees from 2001-2016.

Evidence indicates that the long noncoding RNAs are involved in the metformin-mediated anti-cancer processes. However, the potential effects of the long noncoding RNAs in metformin-mediated anti-tumor processes in esophageal squamous cell carcinomas (ESCC) are still elusive. This study uncovered that metformin decreases the level of long noncoding RNAs CCAT1 and SPRY4-IT1 thereby contributing to the down-regulation of c-Myc and vimentin. Also, the RNA level test of human ESCC tissue confirmed the positive correlation between CCAT1 and c-Myc. These findings demonstrated that metformin facilitated anti-cancer effects by targeting the 2 long noncoding RNAs (CCAT1 and SPRY4-IT1) and their consequential targets c-Myc and vimentin. Therefore, the CCAT1 and SPRY4-IT1 might act as novel molecular targets that mediate the anti-tumor effects in esophageal squamous cell carcinoma. This helps in predicting the treatment response of metformin in patients diagnosed with esophageal squamous cell carcinoma.

Numerous studies have shown that quinolones residues in the foods exceeding the MRL is harmful to the human health. There are some limitations in the existing methods for the residues, so we developed a new limit test method (TLC-SERS) to rapidly determine following residues: enrofloxacin(A), ciprofloxacin (B), ofloxacin(C), fleroxacin(D), sparfloxacin(E), enoxacin(F), gatifloxacin(G) and nadifloxacin(H). The residues can be preliminarily separated by TLC. Labeling the tested compounds’ position on the thin layer plate by their relative Rf under 254nm ultraviolet, and an appropriate amount of nanometer silver solution should be added to the position. The silver on the plate should be irradiated with 532nm laser to obtain SERS of the compounds. The results showed a significant differences of the 8 quinolones’ SERS; the LOD of the H, A, D, E, C, G, F and B were orderly 9.0, 12.6, 8.0, 19.0, 8.0, 8.4, 9.0 and 12.6 ng/mL, and the RSD≤4.9% for SERS of each quinolones.The limit test results of the 20 samples was consistent with that determined by the UPLC–MS/MS. The above results indicate that the TLC-SERS is specific, sensitive, stable, and accurate, providing a new reference for the rapid limit test of harmful residues in foods.

This prospective observational study aimed to describe voriconazole administrations and trough concentrations in patients with Child-pugh class C clinically, and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child-pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentration later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (P=0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor < 5), implying that CYP2C19 testing makes sense for precision medicine of Child-pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R^2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child-pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

Pancreatic cancer is the fourth most common cause of cancer mortality worldwide. Furthermore, patients with pancreatic cancer experience limited benefit from current chemotherapeutic approaches because of drug resistance. Therefore, an effective therapeutic strategy for patients with pancreatic cancer is urgently required. Deguelin is a natural chemopreventive drug that exerts potent antiproliferative activity in solid tumors by inducing cell death. However, the molecular mechanisms underlying this activity have not been fully elucidated. Here we show that deguelin blocks autophagy and induces apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells, and suppressing autophagy by chloroquine or silencing autophagy protein 5 enhanced doxorubicin-induced cell death. Similarly, inhibition of autophagy by deguelin also chemosensitized pancreatic cancer cell lines to doxorubicin. These findings suggest that deguelin has potent anticancer effects against pancreatic cancer and potentiates the anti-cancer effects of doxorubicin. These findings provide evidence that combined treatment with deguelin and doxorubicin represents an effective strategy for treating pancreatic cancer.