Search

Terrestrial dissolved organic matter (tDOM) holds great promise for controlling cyanobacteria blooms through watershed management. To identify tDOM that could inhibit the growth, photosynthesis and colony formation, unicellular Microcystis aeruginosa Kützing (FACHB-469) was cultivated and treated with varying concentrations of gallic acid, proline and tea polyphenols at different levels of iron. The results indicated that gallic acid and tea polyphenols could inhibit Microcystis growth by suppressing photosynthesis and colony formation by reducing extracellular polysaccharides (EPS) secretion. However, proline had no significant effect on the growth, photosynthesis, colony size and EPS content of Microcystis. Transcriptome analysis showed Microcystis may optimize the internal energy transfer mode of photosynthesis through the change of phycobilisome at different levels of iron. In addition, Microcystis adapted to different iron concentration environments by regulating the expression of genes associated with iron uptake and transport. These findings suggest that the effects of plant species on algal blooms should be considered in reforestation of watershed. This consideration necessitates finding a balance between the costs and benefits of controlling cyanobacteria blooms using tDOM.

The Heilongjiang River is one of the largest rivers in the cool temperate zone and has an abundant fish source. To date, the microbiota community in water samples and fish guts from the Heilongjiang River is still unclear. In the present study, water samples and fish guts were collected from four locations of the Heilongjiang River during both the dry season and the wet season to analyze the spatio-temporal dynamics of microbiota communities in the water environment and fish guts through 16s ribosome RNA sequencing. The water qualities showed seasonal changes in which the pH value, dissolved oxygen, and total dissolved solids were generally higher during the dry season, and the water temperature was higher during the wet season. RDA indicated that higher pH values, dissolved oxygen, and total dissolved solids promoted the formation of microbiota communities in the water samples of the dry season, while higher water temperature positively regulated the formation of microbiota communities in the water samples of the wet season. LEFSe identified five biomarkers with the most abundant difference at the genus level, of which TM7a was upregulated in the water samples of the dry season, and SM1A02, Rheinheimera, Gemmatimonas, and Vogesella were upregulated in the water samples of the wet season. Pearson analysis revealed that higher pH values and dissolved oxygen positively regulated the formation of TM7a and negatively regulated the formation of SM1A02, Rheinheimera, Gemmatimonas, and Vogesella (p < 0.05), while higher water temperature had the opposite regulatory roles in the formation of these biomarkers. The relative abundance of microbiota diversity in fish guts varies greatly between different fish species, even if the fishes were collected from the same water source, indicating that dietary habits and fish species may be key factors, affecting the formation and construction of microbiome community in fish gut. P. glenii, P. lagowskii, G. cynocephalus, and L. waleckii were the main fish resources, which were collected and identified from at least six sample points. RDA indicated that the microbiota in the water environment regulated the formation of microbiota community in the guts of G. cynocephalus and L. waleckii and had limited regulated effects on P. glenii and P. lagowskii. The present study identified the regulatory effects of water qualities on the formation of microbiota communities in the water samples and fish guts, providing valuable evidence for the protection of fish resources in the Heilongjiang River.

This study aimed to analyze the structure of polysaccharides from eight different Dendrobium species and their protective effects on gastric mucosa. Ultraviolet (UV) analysis showed that the contents of eight polysaccharides ranged from 51.89 ± 6.91% to 80.57 ± 11.63%; the degree of acetylation ranged from 0.17 ± 0.03 to 0.48 ± 0.03. High-performance liquid chromatography (HPLC) results showed that these polysaccharides were mainly composed of mannose (Man) and glucose (Glc) with a small amount of galactose (Gal) and arabinose (Ara), and the monosaccharide ratios of different Dendrobium species were different. High-performance size exclusion chromatography—multi angle light scattering—refractive index detector (HPSEC-MALS-RID) showed that the molecular weight (Mw) of all Dendrobium polysaccharides was >1 × 105 Da; D. huoshanense had the lowest molecular weight. Subsequently, an ethanol injured GES-1 cell model was constructed to evaluate the gastric mucosal protective potential of polysaccharides from eight different Dendrobium species. The results showed that the protective effect of the low concentration 50 μg/mL DHP treatment group was similar to that of the control group (p > 0.05), and the cell viability could reach 97.32% of that of the control group. Based on the polysaccharide composition, different kinds of Dendrobium have different degrees of migration and repair effects on GES-1 damaged cells, and the effect of DHP is slightly better than that of other varieties (83.13 ± 1.05%). Additionally, Dendrobium polysaccharides alleviated ethanol-induced oxidative stress and inflammatory response in gastric mucosal cells by enhancing the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase) and reducing the levels of malondialdehyde and reactive oxygen species. Overall, DHP can most effectively protect gastric mucosa. These findings enhance our understanding of the relationship between the structure and biological activity of Dendrobium polysaccharides, providing a foundation for the quality control of Dendrobium. Furthermore, these findings offer theoretical support for the development of Dendrobium polysaccharides as nutraceuticals to treat digestive system diseases.

Introduction: As an important part of ship manufacturing, parts are of great significance in the calculation of its reliability level.Methods: To achieve rapid damage detection of ship parts, a method for measuring the reliability level of ship casting and forging parts based on spectral subtraction and vibration-acoustic principles was proposed. This method improves the spectral subtraction method by adding a percussion vibration signal and time-frequency analysis, and uses the principle of resonance acoustics to complete the construction of the test platform to obtain the natural frequency of the part and achieve non-destructive testing of the part.Results: The results show that using the Fabric data set as the task data set for experiments, the accuracy of the research method is 98.54%; the uncertainty is 5.58; the sensitivity detection is 0.26 μm. In the comparison of the spectrogram of the sound signal after noise reduction, this method has fewer yellow spots remaining on the spectrogram of the noise reduction sound signal, and almost no excess noise remains. In the comparison of modal simulation data of ship parts, the maximum relative error between the simulation data obtained by this method and the natural frequency value obtained from the experimental data is 2.3%, and there is no value exceeding 2.5%, so the error is small.Discussion: The above results show that this method can obtain more accurate natural frequencies of parts, can effectively calculate the reliability level of ship casting and forging parts, and provides a new method reference for the safe operation of ships.

Abstract Background ETS transcription factors, known as the E26 transformation-specific factors, assume a critical role in the regulation of various vital biological processes in animals, including cell differentiation, the cell cycle, and cell apoptosis. However, their characterization in mollusks is currently lacking. Results The current study focused on a comprehensive analysis of the ETS genes in blood clam Tegillarca granosa and other mollusk genomes. Our phylogenetic analysis revealed the absence of the SPI and ETV subfamilies in mollusks compared to humans. Additionally, several ETS genes in mollusks were found to lack the PNT domain, potentially resulting in a diminished ability of ETS proteins to bind target genes. Interestingly, the bivalve ETS1 genes exhibited significantly high expression levels during the multicellular proliferation stage and in gill tissues. Furthermore, qRT-PCR results showed that Tg-ETS-14 (ETS1) is upregulated in the high total hemocyte counts (THC) population of T. granosa, suggesting it plays a significant role in stimulating hemocyte proliferation. Conclusion Our study significantly contributes to the comprehension of the evolutionary aspects concerning the ETS gene family, while also providing valuable insights into its role in fostering hemocyte proliferation across mollusks.

In this study, the oral bioavailability of Pb, Cd, and As in three types of traditional Chinese medicines (TCMs) and TCM decoctions were investigated through in vitro PBET digestion/MDKC cell model. Furthermore, a novel cumulative risk assessment model associated with co-exposure of heavy metal(loid)s in TCM and TCM decoction based on bioavailability was developed using hazard index (HI) for rapid screening and target organ toxicity dose modification of the HI (TTD) method for precise assessment. The results revealed that the bioavailability of Pb, Cd, and As in three types of TCM and TCM decoction was 5.32–72.49% and 4.98–51.97%, respectively. After rapid screening of the co-exposure health risks of heavy metal(loid)s by the HI method, cumulative risk assessment results acquired by TTD method based on total metal contents in TCMs indicated that potential health risks associated with the co-exposure of Pb, Cd, and As in Pheretima aspergillum (E. Perrier) and Oldenlandia diffusa (Willd.) Roxb were of concern. However, considering both the factors of decoction and bioavailability, TTD-adjusted HI outcomes for TCMs in this study were

Abstract Delay tolerant networks (DTNs) refer to a kind of novel wireless mobile network, where there is no constant end‐to‐end connection between network nodes due to frequent movement, sparse distribution and limited communication range of nodes. Instead of the traditional store‐forward routing strategy, in DTNs, the new store‐carry‐forward routing strategy is adopted for data transmission. Therefore, how to select the best next‐hop node among network nodes is the main challenge of the routing in DTNs. To this end, here, a k‐step double Q‐learning routing (K‐DQLR) algorithm is proposed, which integrates the multi‐step and double Q‐learning algorithms to make an unbiased, accurate and efficient routing decision in DTNs. Besides, a new dynamic reward mechanism is proposed, which combines the number of routing hops and the node centrality to adopt the dynamic network environment of DTNs. The simulation results show that K‐DQLR can significantly increase the delivery ratio while reducing the delivery delay and overhead compared with the related state‐of‐the‐art routing protocols of DTNs.

Natural polysaccharides are important active biomolecules. However, the analysis and structural characterization of polysaccharides are challenging tasks that often require multiple techniques and maps to reflect their structural features. This study aimed to propose a new heart-cutting two-dimensional liquid chromatography (2D–LC) method for separating and analyzing polysaccharides to explore the multidimensional information of polysaccharide structure in a single map. That is, the first-dimension liquid chromatography (1D–LC) presents molecular-weight information, and the second-dimension liquid chromatography (2D–LC) shows the fingerprints of polysaccharides. In this 2D–LC system, the size-exclusion chromatography–hydrophilic interaction chromatography (SEC–HILIC) model was established. Coupling with a charged aerosol detector (CAD) eliminated the need for the derivatization of the polysaccharide sample, allowing the whole process to be completed within 80 min. The methods were all validated in terms of precision, linearity, stability, and repeatability. The capability of the new 2D-LC method was demonstrated in determining various species of natural polysaccharides. Our experimental data demonstrated the feasibility of the whole systematic approach, opening the door for further applications in the field of natural polysaccharide analysis.

Polygonum multiflorum Thunb. (PM) and derived products are broadly utilized in Chinese traditional medicine. According to our previous research, PM mostly contains polysaccharides, which display a wide range of biological activities. Two water-soluble polysaccharides (PMPs-1 and PMPs-2) were obtained from PM by DEAE-Cellulose and Sephadex G-100 column chromatography. Colorimetry, HPGPC-MALLS-RID, HPLC-PDA, methylation, FT-IR, NMR, and SEM were used to characterize these polysaccharides. PMPs-1 and PMPs-2 had average molecular weights of 255.5 and 55.7 kDa, respectively. PMPs-1 consisted of Man, Glc, Gal, and Ara at 0.9:78.6:1.0:1.6 and was a glucan with → 4)-Glcp-(1 → as a backbone. Meanwhile, PMPs-2, an acidic polysaccharide, comprised Rha, GalA, Glc, Gal, and Ara at 3.2:20.3:2.7:1.0:8.3. PMPs-1 and PMPs-2 significantly improved the proliferation of RAW 264.7 cells and induced NO, TNF-α, and IL-6 release. This study reveals that these two polysaccharides can be explored as novel immunomodulators and provide a basis for further development of PM in food and pharmaceutical industries.

Houttuyniae herba has a long history of medicinal and edible homology in China. It has the functions of clearing heat and detoxifying, reducing swelling and purulent discharge, diuresis, and relieving gonorrhea. It is mainly distributed in the central, southeastern, and southwestern provinces of China. Houttuyniae herba has been designated by the National Ministry of Health of China as a dual-use plant for both food and medicine. Comprising volatile oils, flavonoids, and alkaloids as its primary constituents, Houttuyniae herba harbors aristolactams, a prominent subclass of alkaloids. Notably, the structural affinity of aristolactams to aristolochic acids is discernible, the latter known for its explicit toxicological effects. Additionally, the safety study on Houttuyniae herba mainly focused on the ethanol, methanol, or aqueous extract. In this study, both zebrafish and mice were used to evaluate the acute toxicity of the total alkaloids extracts from Houttuyniae herba (HHTAE). The zebrafish experiment showed that a high concentration (0.1 mg/mL) of HHTAE had a lethal effect on zebrafish embryos. Furthermore, the mice experiment results showed that, even at a higher dose of 2000 mg/kg, HHTAE was not toxic. In conclusion, HHTAE was of low safety risk.

Abstract Background Access to biologically available nitrogen is a key constraint on plant growth in both natural and agricultural settings. Variation in tolerance to nitrogen deficit stress and productivity in nitrogen limited conditions exists both within and between plant species. However, our understanding of changes in different phenotypes under long term low nitrogen stress and their impact on important agronomic traits, such as yield, is still limited. Results Here we quantified variation in the metabolic, physiological, and morphological responses of a sorghum association panel assembled to represent global genetic diversity to long term, nitrogen deficit stress and the relationship of these responses to grain yield under both conditions. Grain yield exhibits substantial genotype by environment interaction while many other morphological and physiological traits exhibited consistent responses to nitrogen stress across the population. Large scale nontargeted metabolic profiling for a subset of lines in both conditions identified a range of metabolic responses to long term nitrogen deficit stress. Several metabolites were associated with yield under high and low nitrogen conditions. Conclusion Our results highlight that grain yield in sorghum, unlike many morpho-physiological traits, exhibits substantial variability of genotype specific responses to long term low severity nitrogen deficit stress. Metabolic response to long term nitrogen stress shown higher proportion of variability explained by genotype specific responses than did morpho-pysiological traits and several metabolites were correlated with yield. This suggest, that it might be possible to build predictive models using metabolite abundance to estimate which sorghum genotypes will exhibit greater or lesser decreases in yield in response to nitrogen deficit, however further research needs to be done to evaluate such model.

Abstract Background Dietary magnesium deficiency, which is common in modern diet, has been associated with osteoarthritis (OA) susceptibility. Despite this clinical association, no study has addressed if dietary magnesium deficiency accelerates OA development, especially at molecular level. This study aimed to explore aggravating effects of dietary magnesium deficiency on cartilage damage in an injury-induced murine OA model and to determine the underlying mechanism. Methods Twelve-week-old C57BL/6J mice subject to injury-induced OA modeling were randomized into different diet groups in which the mice were fed a diet with daily recommended magnesium content (500 mg/kg) or diets with low magnesium content (100 or 300 mg/kg). Articular cartilage damage was evaluated using the OARSI score. To determine molecular mechanisms in vitro, mouse chondrocytes were treated with media of low magnesium conditions at 0.1 and 0.4 mM, compared with normal magnesium condition at 0.7 mM as control. Anabolic and catabolic factors, autophagy markers, β-catenin, Wnt ligands, and a magnesium channel transient receptor potential cation channel subfamily member 7 (TRPM7) were analyzed by quantitative real-time PCR and immunoblotting. Autolysosomes were detected by DALGreen staining via fluorescence microscopy and autophagosomes were evaluated by transmission electron microscopy. Autophagy markers, β-catenin, and TRPM7 were assessed in vivo in the mouse cartilage, comparing between dietary magnesium deficiency and normal diet, by immunohistochemistry. Results Dietary magnesium deficiency aggravated injury-induced cartilage damage, indicated by significant higher OARSI scores. Autophagy markers LC3-II and Beclin-1 were decreased both in low magnesium diet-fed mice and low magnesium-treated chondrocytes. The number of autolysosomes and autophagosomes was also reduced under low magnesium conditions. Moreover, magnesium deficiency induced decreased anabolic and increased catabolic effect of chondrocytes which could be restored by autophagy activator rapamycin. In addition, reduced autophagy under low magnesium conditions is mediated by activated Wnt/β-catenin signaling. The expression of TRPM7 also decreased in low magnesium diet-fed mice, indicating that downstream changes could be regulated through this channel. Conclusions Dietary magnesium deficiency contributes to OA development, which is mediated by reduced autophagy through Wnt/β-catenin signaling activation. These findings indicated potential benefits of adequate dietary magnesium for OA patients or those individuals at high risk of OA.

Before use as medicines, most traditional Chinese medicine (TCM) plants are processed and decocted. During processing, there may be some changes in pesticide residues in TCM. In recent years, reports have studied the changes of pesticides during the processes of boiling, drying and peeling of TCM materials but have rarely involved special processing methods for TCM, such as ethanol extraction and volatile oil extraction. The changes of carbendazim, carbofuran, pyridaben and tebuconazole residues in common processing methods for P. cablin products were systemically assessed in this study. After each processing step, the pesticides were quantitated by UPLC-MS/MS. The results showed amount decreases in various pesticides to different extents after each processing procedure. Processing factor (PF) values for the four pesticides after decoction, 75% ethanol extraction and volatile oil extraction were 0.02~0.75, 0.40~0.98 and 0~0.02, respectively, which indicated that residual pesticide concentrations may depend on the processing technique. A risk assessment according to the hazard quotient with PF values showed that residual pesticide amounts in P. cablin were substantially lower than levels potentially posing a health risk. Overall, these findings provide insights into the safety assessment of P. cablin.

Traditional Chinese medicine (TCM) is the key to unlock treasures of Chinese civilization. TCM and its compound play a beneficial role in medical activities to cure diseases, especially in major public health events such as novel coronavirus epidemics across the globe. The chemical composition in Chinese medicine formula is complex and diverse, but their effective substances resemble “mystery boxes”. Revealing their active ingredients and their mechanisms of action has become focal point and difficulty of research for herbalists. Although the existing research methods are numerous and constantly updated iteratively, there is remain a lack of prospective reviews. Hence, this paper provides a comprehensive account of existing new approaches and technologies based on previous studies with an in vitro to in vivo perspective. In addition, the bottlenecks of studies on Chinese medicine formula effective substances are also revealed. Especially, we look ahead to new perspectives, technologies and applications for its future development. This work reviews based on new perspectives to open horizons for the future research. Consequently, herbal compounding pharmaceutical substances study should carry on the essence of TCM while pursuing innovations in the field.

In our previous study, we have isolated Lactoplantibacillus plantarum L3 (GenBank accession No. MT781360) which can secret bacteriocin L3 with broad-spectrum antibacterial activities. This work aimed to illustrate the antibacterial mechanism of bacteriocin L3 and predict the functionalities of the L. plantarum L3 strain through whole genome analysis. Preliminary exploration of the bacteriostatic mechanism showed that bacteriocin L3 destroyed the cell membrane integrity and led to the extravasation of the cell contents, leading to cell death. The sequencing results showed that the genome of Lactobacillus plantarum L3 was 3 187 020 bp in size, with a GC content of 44.57%. Overall, 3 024 encoding genes were annotated, with a sequence length of 2 679 162 bp, accounting for 84.06% of the total genome length. The strain has strong reproductive and metabolic abilities and high safety. The bacteriocin gene cluster analysis showed that the bacteriocins L3 belonged to the class IIb bacteriocins. This work might provide a theoretical basis for the application of this strain in the food industry, especially its potential use in dairy products.

As a miraculous Xinjiang Uyghur customary traditional Chinese medicine (TCM), Chicory (Cichorium glandulosum Boiss.et Huet and Cichorium intybus L.) has been found to have therapeutic potential for metabolic diseases in recent years. Although it is widely used as an ethnic medicine, there is still a lack of targeted quality control indicators in quality standards. Hence, this study was conducted to further develop a strategy to reveal bioactive-chemical quality markers based on the existing foundation. First, through the comparative screening of fingerprint profiles of a large amount of Cichorium glandulosum Boiss.et Huet and Cichorium intybus L., superiority components were found to be potential indicators of chemical quantitative properties for the roots and above-ground parts. The results of content determination showed that their contents differed among different species and parts. Second, the potential dominant components were further confirmed using network pharmacology and molecular docking techniques. Again, the results of RAW264.7 cells and L02 cells experiments showed that chicory acid and lactucin were the main components that could reflect the anti-inflammatory and uric acid-lowering potential of chicory. Finally, under this strategy, this study reveals that cichoric acid and lactucin have the properties of quality markers and quality control of chicory. In a word, this work contributes to the quality control, standard improvement, and rational clinical use of chicory.

The roots of Polygonum multiflorum Thunb (PM) have a long history of usage in traditional Chinese medicine and are still widely utilized today. PM in raw or processed form has different biological activities and is commonly used to treat different diseases. Polysaccharides are the main component of PM, and it is unclear whether their physicochemical properties and activities change after processing. In this study, the polysaccharides from thirty-one raw PM (RPMPs) and nine processed PM (PPMPs) were extracted, and the physicochemical properties and immunomodulatory activity in vitro of polysaccharide samples were evaluated. Results showed that RPMPs and PPMPs had significant differences in physicochemical properties. RPMPs and PPMPs were both composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, and arabinose. However, RPMPs and PPMPs had significant differences in their yields, molecular weight (Mw), and the molar ratio of Glc/GalA (p < 0.05), which can be used to distinguish raw and processed PM. The fingerprint of monosaccharide composition was analyzed by chemometrics, and it was further demonstrated that Glc and GalA could be used as differential markers. The immunomodulatory activity assays indicated that RPMPs and PPMPs could significantly enhance phagocytosis and mRNA expression of cytokines in RAW 264.7 cells. In addition, the immunomodulatory activity of PPMPs with lower Mw was significantly better than that of RPMPs. This study furthers the understanding of the polysaccharides from raw and processed PM and provides a reference for improving the quality standard of PM.

Internet memes have become widely used by people for online communication and interaction, particularly through social media. Interest in meme-generation research has been increasing rapidly. In this study, we address the problem of meme generation as an image captioning task, which uses an encoder–decoder architecture to generate Chinese meme texts that match image content. First, to train the model on the characteristics of Chinese memes, we collected a dataset of 3,000 meme images with 30,000 corresponding humorous Chinese meme texts. Second, we introduced a Chinese meme generation system that can generate humorous and relevant texts from any given image. Our system used a pre-trained ResNet-50 for image feature extraction and a state-of-the-art transformer-based GPT-2 model to generate Chinese meme texts. Finally, we combined the generated text and images to form common image memes. We performed qualitative evaluations of the generated Chinese meme texts through different user studies. The evaluation results revealed that the Chinese memes generated by our model were indistinguishable from real ones.

Arsenic in environmental health has caused public concerns all over the world. However, high levels of arsenic residues in medicinal animals have not received enough attention. Medicinal earthworms are consumed widely in China, but its arsenic potential health risks to humans are unknown. This work investigated the total concentration, bioaccessibility, and speciation of arsenic in earthworms by ICP-MS and HPLC-ICP-MS to evaluate its potential health risks to humans. Arsenic was found in all earthworms at concentrations ranging from 0.4 to 53.6 mg kg−1. The bioaccessibility of arsenic (bAs) varied significantly and ranged from 12.1 to 69.1%, with inorganic arsenic (iAs, including As(III) and As(V)) as the predominant species. Furthermore, a small amount of arsenobetaine (AB) was found. The estimated daily intake dose (EDI), hazard quotient (HQ), and carcinogenic risk (CR) of arsenic in most of the samples exceeded the safe threshold level. Results from this study indicated that the potential health risks by the consumption of earthworms may not be negligible. Herein, recommendations for the use of earthworms and regulatory recommendations for arsenic limit standards were proposed. This study reminds us that more control and monitoring of arsenic in medicinal animals should be carried out.

Introduction: Pretreatment inflammatory markers were applied to predict the prognosis of colorectal cancer. However, the role of these markers in predicting survival in patients with synchronous colorectal liver metastasis (CLM) is rarely reported. Notably, lymphocyte-to-monocyte ratio (LMR) was mainly reported in hematologic malignancies and is worth to be further explored to predict the survival of synchronous CLM. Methods: Totally, 196 patients who were diagnosed with synchronous CLM were enrolled. Their clinical and laboratory data before treatment were collected, retrospectively. Univariate and multivariate analyses were performed to analyze the inflammatory biomarkers. Results: LMR ( P = .002) and lactate dehydrogenase (LDH) ( P = .017) were significantly related to the progression-free survival (PFS). More factors such as neutrophil-to-lymphocyte ratio (NLR) ( P = .011), carbohydrate antigen 19-9 (CA19-9) ( P = .001), number of metastatic foci ( P = .006), and adjuvant chemotherapy ( P = .027) were correlated with overall survival (OS). In multivariate analysis, LMR remained statistically associated with PFS ( P = .003). Regarding OS, LMR ( P = .016) and LDH ( P = .013) were significantly independent predictive factors. Conclusions: The higher LMR and lower LDH were strongly correlated with better survival in synchronous CLM patients. In addition, the result also indicated that enhanced LMR was related to better PFS. The LMR and LDH can be used to predict prognosis of the synchronous CLM.

In the present study, 168 pesticides in 1,017 samples of 10 Chinese herbal medicines (CHMs) were simultaneously determined by high-performance liquid (HPLC-MS/MS) and gas (GC-MS/MS) chromatography–tandem mass spectrometry. A total of 89.2% of the samples encompassed one or multiple pesticide residues, and the residue concentrations in 60.5% of samples were less than 0.02 mg kg−1, revealing the relatively low residue levels. The hazard quotient and hazard index methods were used to estimate the health risk for consumers. For a more accurate risk assessment, the exposure frequency and exposure duration of CHMs were involved into the exposure assessment, which was obtained from a questionnaire data of 20,917 volunteers. The results of chronic, acute, and cumulative risk assessment indicated that consumption of CHMs is unlikely to pose a health risk to consumers. Ranking the risk of detected pesticides revealed that phorate, BHC, triazophos, methidathion, terbufos, and omethoate posed the highest risk. Our results also showed that pollution of the aboveground medicinal part was more serious. Although exposure to pesticides in tested CHMs was below dangerous levels, more strict controlled management should be carried out for banned pesticides due to the high detection rate and illegal use in the actual planting practice.

Conducting realistic interactions while communicating efficiently in online conferences is highly desired but challenging. In this work, we propose a novel pixel-style virtual avatar for interacting with virtual objects in virtual conferences that can be generated in real-time. It consists of a 2D segmented head video stream for real-time facial expressions and a 3D point cloud body for realistic interactions, both of which are generated from RGB video input of a monocular webcam. We obtain a human-only video stream with a human matting method and generate the 3D avatar’s arms with a 3D pose estimation method, which improves the stereoscopic realism and sense of interaction of conference participants while interacting with virtual objects. Our approach fills the gap between 2D video conferences and 3D virtual avatars and combines the advantages of both. We evaluated our pixel-style avatar by conducting a user study; the result proved that the efficiency of our method is superior to other various existing avatar types.

BackgroundTo compare perioperative and oncological outcomes of pancreatic duct adenocarcinoma (PDAC) after laparoscopic versus open pancreaticoduodenectomy (LPD vs. OPD), we performed a meta-analysis of currently available propensity score matching studies and large-scale retrospective cohorts to compare the safety and overall effect of LPD to OPD for patients with PDAC.MethodsA meta-analysis was registered at PROSPERO and the registration number is CRD42021250395. PubMed, Web of Science, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched based on a defined search strategy to identify eligible studies before March 2021. Data on operative times, blood loss, 30-day mortality, reoperation, length of hospital stay (LOS), overall morbidity, Clavien–Dindo ≥3 complications, postoperative pancreatic fistula (POPF), blood transfusion, delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), and oncologic outcomes (R0 resection, lymph node dissection, overall survival, and long-term survival) were subjected to meta-analysis.ResultsOverall, we identified 10 retrospective studies enrolling a total of 11,535 patients (1,514 and 10,021 patients underwent LPD and OPD, respectively). The present meta-analysis showed that there were no significant differences in overall survival time, 1-year survival, 2-year survival, 30-day mortality, Clavien-Dindo ≥3 complications, POPF, DGE, PPH, and lymph node dissection between the LPD and OPD groups. Nevertheless, compared with the OPD group, LPD resulted in significantly higher rate of R0 resection (OR: 1.22; 95% CI 1.06–1.40; p = 0.005), longer operative time (WMD: 60.01 min; 95% CI 23.23–96.79; p = 0.001), lower Clavien–Dindo grade ≥III rate (p = 0.02), less blood loss (WMD: −96.49 ml; 95% CI −165.14 to −27.83; p = 0.006), lower overall morbidity rate (OR: 0.65; 95% CI 0.50 to 0.85; p = 0.002), shorter LOS (MD = −2.73; 95% CI −4.44 to −1.03; p = 0.002), higher 4-year survival time (p = 0.04), 5-year survival time (p = 0.001), and earlier time to starting adjuvant chemotherapy after surgery (OR: −10.86; 95% CI −19.42 to −2.30; p = 0.01).ConclusionsLPD is a safe and feasible alternative to OPD for patients with PDAC, and compared with OPD, LPD seemed to provide a similar OS.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/#recordDetails.

BackgroundRobotic distal pancreatectomy (RDP) and laparoscopic distal pancreatectomy (LDP) are the two principal minimally invasive surgical approaches for patients with pancreatic body and tail adenocarcinoma. The use of RDP and LDP for pancreatic ductal adenocarcinoma (PDAC) remains controversial, and which one can provide a better R0 rate is not clear.MethodsA comprehensive search for studies that compared robotic versus laparoscopic distal pancreatectomy for PDAC published until July 31, 2021, was conducted. Data on perioperative outcomes and oncologic outcomes (R0-resection and lymph node dissection) were subjected to meta-analysis. PubMed, Cochrane Central Register, Web of Science, and EMBASE were searched based on a defined search strategy to identify eligible studies before July 2021.ResultsSix retrospective studies comprising 572 patients (152 and 420 patients underwent RDP and LDP) were included. The present meta-analysis showed that there were no significant differences in operative time, tumor size, and lymph node dissection between RDP and LDP group. Nevertheless, compared with the LDP group, RDP results seem to demonstrate a possibility in higher R0 resection rate (p

The traditional Chinese herbal medicine Eupatorium fortunei Turcz. (E. fortunei) has been widely adopted to treat nausea, diabetes, siriasis, and poor appetite. However, E. fortunei contains multiple pyrrolizidine alkaloids (PAs). This study aimed to investigate the hepatotoxicity of total alkaloids in E. fortunei (EFTAs) and identify the toxic mechanisms of EFTAs on hepatocytes. Liquid chromatography with a tandem mass spectrometry assay with reference standards indicated that EFTAs mainly consisted of eight PAs whose content accounted for 92.38% of EFTAs. EFTAs markedly decreased mouse body and liver weights and increased the contents of AST and ALT. The histopathological assays demonstrated that, after exposition to EFTAs, the structures of hepatocytes were damaged and the fibrosis and apoptosis in hepatocytes were accelerated. Moreover, EFTAs increased the serum level of inflammatory cytokines and aggravated circulating oxidative stress. A combination of hepatic proteomics and metabolomics was used to investigate the toxic mechanisms of EFTAs. The study revealed that EFTAs seriously disrupted glycerophospholipid metabolism by upregulating the contents of lysophosphatidylglycerol acyltransferase 1 and phosphatidylinositol and downregulating the contents of choline/ethanolamine kinase beta, choline-ethanolamine phosphotransferase 1, phospholipase D4, 1-acylglycerophosphocholine, phosphatidylcholine, and dihydroxyacetone phosphate in the liver, resulting in detrimental inflammation, fibrosis, and apoptosis. This study revealed that EFTAs induced severe hepatotoxicity by disrupting glycerophospholipid metabolism.

Portal hypertension is a common manifestation in late-to-end-stage liver diseases and can cause severe complications such as ascites, hepatic encephalopathy, etc. However, an early diagnosis of portal hypertension is often difficult as it can be asymptomatic. Though the gold standard to diagnose portal hypertension is hepatic vein catheterization, ultrasound elastography is regarded as a noninvasive alternative that can be used to accurately predict portal hypertension and a few further complications such as gastro-esophageal varices. Since ultrasound elastography is available in most medical centers, and is cheaper and noninvasive, studying its function in predicting portal hypertension is of paramount importance. Therefore, this review generalized the results of recently published articles in order to establish the indicators that were related to diagnostic and prediction efficiency. Our study found that various technologies of ultrasound elastography could be used to predict portal hypertension with satisfactory diagnostic sensitivity, specificity, accuracy, and AUC. Meanwhile, we also recognized similar diagnostic efficiency of ultrasound elastography in gastro-esophageal varices.

The mechanism of immunoregulation by Lycium barbarum polysaccharides (LBPs) was assessed by studying the effect of LBP on the immunity and the gut microbiota. LBP isolated and purified in this study was composed of nine monosaccharides, with an Mw 1,207 kDa. LBP showed immunomodulatory activity in cyclophosphamide (Cy)-treated mice by restoring the damaged immune organs and adjusting the T lymphocyte subsets. We also found that LBP increased the diversity of the gut microbiota and the relative abundances of bacteria, such as Rickenellaceae, Prevotellaceae, Bifidobacteriaceae, and so on, which were positively associated with immune traits. In addition, Caco2 cells model was used to explore the intestinal absorption of LBP. Results showed that LBP was hardly absorbed in the intestine, which suggesting that most LBP may interact with gut microbiota. These findings suggest that the immune response induced by LBP is associated with the regulation of the gut microbiota.

Abstract Background Lycium barbarum (wolfberry) has been widely cultivated in China, particularly in northwest regions. However, the fruit size and taste of L. barbarum from different habitats are quite different. Traditionally, only the fruit of L. barbarum produced in Ningxia province is recorded as an authentic herb, although the detailed mechanism responsible for this remains obscure. Polysaccharides are considered major active ingredients in L. barbarum which is crucial for its quality evaluation. Methods In this study, we assessed the yield, monosaccharide composition, molecular weight, and conformation of L. barbarum polysaccharides (LBPs) collected from different regions of China. The antioxidant and immune activities of LBPs were also determined as its quality indicator. Results Our results showed that the similarity values of monosaccharide composition were larger than 0.926, and the Mw of the two fractions (peaks 1–2) in LBPs were ranging from 1.36 × 106 to 2.01 × 106 (peak 1), and 6.85 × 104 to 10.30 × 104 (peak 2) which indicated that the structure of LBPs were similar. In addition, results showed that there was no significant difference in antioxidant and immune activities of nine LBPs from different regions. However, the yield of LBPs from Qinghai Province (low atmospheric temperature, high altitude) was significantly lower (p

Abstract Background During maize early kernel development, the dramatic transcriptional reprogramming determines the rate of developmental progression, and phytohormone plays critical role in these important processes. To investigate the phytohormone levels and transcriptome reprogramming profiles during maize early kernel development, two maize inbreds with similar genetic background but different mature kernel sizes (ILa and ILb) were used. Results The levels of indole-3-acetic acid (IAA) were increased continuously in maize kernels from 5 days after pollination (DAP) to 10 DAP. ILa had smaller mature kernels than ILb, and ILa kernels had significantly lower IAA levels and significantly higher SA levels than ILb at 10 DAP. The different phytohormone profiles correlated with different transcriptional reprogramming in the two kernels. The global transcriptomes in ILa and ILb kernels were strikingly different at 5 DAP, and their differences peaked at 8 DAP. Functional analysis showed that the biggest transcriptome difference between the two kernels is those response to biotic and abiotic stresses. Further analyses indicated that the start of dramatic transcriptional reprogramming and the onset of significantly enriched functional categories, especially the “plant hormone signal transduction” and “starch and sucrose metabolism”, was earlier in ILa than in ILb, whereas more significant enrichment of those functional categories occurred at later stage of kernel development in ILb. Conclusions These results indicate that later onset of the significantly enriched functional categories, coincide with their stronger activities at a later developmental stage and higher IAA level, are necessary for young kernels to undergo longer mitotic activity and finally develop a larger kernel size. The different onset times and complex interactions of the important functional categories, especially phytohormone signal, and carbohydrate metabolism, form the most important molecular regulators mediating maize early kernel development.

With the diversification of product types and the development of complex CNC system functions, reconfigurable, and extensible CNC system must be developed to meet the needs of industrial production in the new era. To optimize the original architecture between the CNC system and the machine tool, and to improve the integration level of the industrial control system, an integrated parallel CNC system which could control multiple CNC machine tools based on high performance multi-core processor is proposed in this paper. Based on the virtualize container technology, the functional modules of the CNC system, such as the interpreter module and interpolation module, operate separately on each Docker containers. The system scheduling module uniformly schedules above functional modules and caches the data generated by each module to maximize the processing efficiency and resource utilization. For the modeling of system architecture, the colored Petri nets are used to establish the models of CNC system and task scheduling. Two strategies of task scheduling which based on task dependencies and data flow are presented to determine the priority of system function threads. According to the developed test platform, the real time of the virtual system environment, real-time system environment, and the communication module of integrated CNC are analyzed. Furthermore, test results show that the proposed integrated parallel CNC system has the ability of centralized control of two machine tools synchronously.

Perca fluviatilis is an economically important species of freshwater fish. To understand the genetic structure of P. fluviatilis in China, 268 samples were collected from Wulungu Lake (WL), Jili Lake (JL), the Wulungu River (WR), and the Kalaeerqisi River (KR). These samples were then analyzed using microsatellite markers. A total of 98,425 microsatellite markers were developed based on the genomic data, and 29 polymorphic microsatellite markers were selected to analyze genetic diversity in this study. The number of alleles (Na) and observed heterozygosity (Ho) per population ranged from 4.621 (KR) to 11.172 (WL) and from 0.510 (KR) to 0.716 (JL), respectively. The results of the polymorphic information content (PIC) showed that the WL, JL, and WR populations were highly polymorphic (PIC≥ 0.5) and that the KR population was moderately polymorphic (0.25 ≤ PIC < 0.5). The genetic differentiation coefficient (Fst) among the four P. fluviatilis populations was 0.074, indicating moderate genetic differentiation among the populations in Xinjiang. The reason for the significant difference between the rivers and lakes could be the presence of a dam blocking the flow of P. fluviatilis. The development of microsatellite markers provides support for population genetics in the future. The evaluation of the genetic structure of P. fluviatilis in Xinjiang provides a reference for the reproduction and conservation of P. fluviatilis.

Beyond its role as an oxygen transport protein, the homodimer hemoglobin of blood clam Tegillarca granosa (Tg-HbI) has been found to possess antibacterial activity. However, the mechanism of antibacterial activity of Tg-HbI remain to be investigated. In this study, we investigated the effects of Cu2+ on the structure, peroxidase activity, and antibacterial ability of Tg-HbI. Tg-HbI was significantly inactivated by Cu2+ in a non-competitive inhibition manner, following first-order reaction kinetics. The Spectroscopy results showed that Cu2+ changed the iron porphyrin ring and the coordination of heme with proximal histidine of Tg-HbI, and increased the hydrophobicity of heme pocket. We found that proline could stabilize the heme pocket structure of Tg-HbI, hence, protect peroxidase activity and antimicrobial activity of Tg-HbI against damage by Cu2+. Our results suggest that Cu2+ inhibits the peroxidase and antibacterial activity of Tg-HbI by destroying its heme pocket structure and Tg-HbI probably plays an antibacterial role through its peroxidase activity. This result could provide insights into the antibacterial mechanism of Tg-HbI.

Objective: The aim of the study was to evaluate the diagnostic value of contrast-enhanced ultrasound (CEUS) in distinguishing between benign and malignant cervical lymph nodes in patients with nasopharyngeal carcinoma (NPC).Material and Methods: A total of 144 NPC patients with enlarged superficial cervical lymph nodes underwent CEUS examination. The comparison of CEUS image characteristics between malignant and benign cervical lymph nodes was performed in this study as well. We analyzed parameters of the time–intensity curve (TIC), which includes time to peak (TP), area under the gamma curve (AUC), and peak intensity (PI). Furthermore, receiver operating characteristic (ROC) curve analysis was also investigated to evaluate the diagnostic value of CEUS.Result: We conducted 144 lymph node examinations in total, where 64 cases were biopsy-proven benign nodules and 80 cases were biopsy-proven metastatic nodules. The vast majority of the benign nodes displayed centrifugal perfusion (96.88%, 62/64) and homogeneous enhancement (93.75%, 60/64), while most of the malignant nodes showed centripetal perfusion (92.50%, 74/80) and inhomogeneous 80.00% (64/80). In addition, quantitative analysis showed that CEUS parameters including PI, TP, and AUC in benign lymph nodes (12.51 ± 2.15, 23.79 ± 11.80, and 1110.33 ± 286.17, respectively) were significantly higher than that in the malignant nodes (10.51 ± 2.98, 16.52 ± 6.95, and 784.09 ± 340.24, respectively). The assistance of the three aforementioned parameters and CEUS image characteristics would result in an acceptable diagnostic value.Conclusion: Our results suggest that imaging perfusion patterns as well as quantitative parameters obtained from CEUS provide valuable information for the evaluation of cervical lymph nodes in NPC patients.

Background: Prognostic nutritional index (PNI), combining albumin and lymphocyte counts, which represent the nutritional and immune status, was considered as an effective predictor for the patient's prognosis after surgery. To comprehensively analyze the relative effectiveness of prognostic performance of pretreatment PNI in esophageal cancer (EC), we performed this meta-analysis.Methods: We performed a systematic search in PubMed, Embase, CNKI, and Web of Science. The hazard ratios (HRs) or odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were extracted to explore the correlation between PNI and the post-operative survival of patients with EC, including overall survival (OS), recurrence-free survival (RFS), and post-operative complications. The Newcastle–Ottawa Scale (NOS) was applied to estimate the quality of the included studies. The Begg's test was applied to assess the publication bias.Results: A total of 13 articles with 3,543 patients, were included in our meta-analysis, and nine studies reported OS in 2,731 EC patients. The pooled results of the nine studies suggested that EC patients with a low PNI would have a worse overall survival (HR = 1.14, 95% CI 0.99–1.31, p < 0.05). The integrated results also indicated that the PNI was a negative predictor for RFS.Conclusion: This meta-analysis indicated a high correlation between PNI and post-operative survival of EC. EC patients with low PNI values tend to have worse OS and may be at a higher risk of EC recurrence. However, more relevant researches are needed to confirm the association between PNI and post-operative complications of EC.

Aim: The purpose of this study was to assess the ability of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of cancerous lymph nodes.Methods: Contrast-enhanced ultrasonography was performed in the cervical nodules of included patients, and the diagnoses were confirmed by pathological examination. Contrast-enhanced ultrasonography images and parameters of head and neck lymphomas were compared with those of cancerous lymph nodes. Besides, receiver operating characteristic curve was operated to access the diagnostic value of CEUS.Results: Finally, a total of 63 head and neck lymphomas and 80 cervical cancerous lymph nodes were enrolled in this study. Results showed that the CEUS images of lymphoma were mainly characterized by homogeneous enhancement (71.43%), and approximately half of them were centripetal perfusion (58.73%), whereas most CEUS images of cancerous lymph nodes were inhomogeneous enhancement (82.50%) and centripetal perfusion (92.50%). Quantitative analysis of CEUS parameters indicated that PI (derived peak intensity) and AUC (area under the curve) of lymphomas were both lower than those of cancerous lymph nodes (PI: 8.78 vs. 10.51, AUC: 652.62 vs. 784.09, respectively) (P < 0.05). Receiver operating characteristic analysis showed that the sensitivity of CEUS parameters in the differential diagnosis was significant (80.00%), although the specificity was not high (47.62%). When parameters were combined with the image features, the accuracy of diagnosis was greatly improved (from 0.655 to 0.899).Conclusion: Contrast-enhanced ultrasonography could be a promising tool for the differential diagnosis of head and neck lymphomas and cancerous lymph nodes.

High arsenic residues make Cordyceps sinensis a concern in China. Arsenic toxicity is related to its species. Many studies have evaluated the toxicity of total arsenic, but few have studied its species. In this study, the species of arsenic in C. sinensis and its potential health risk were investigated. SEC-HPLC-ICP-MS was used to analysis of arsenic in C. sinensis and unknown arsenic (uAs) was discovered. Additionally, arsenic in C. sinensis was mainly found in alkali-soluble proteins. The trend of arsenic transformation indicated that unknown arsenic in C. sinensis may be converted into free inorganic arsenic, which enhanced toxicity. The result of risk assessment indicated that there were potential health risks of uAs. Hereon, we proposed recommendations for the use of C. sinensis and regulatory recommendations for arsenic standards. This study contributed to the toxicity reveal, safety evaluation, and risk assessment of arsenic in C. sinensis.

Glyptothorax annandalei belongs to the family of Sisoridae, Glyptothorax. It is distributed in the Yarlung Zangbo River of southwestern China. In this study, we first published the complete mitochondrial genome sequence of Glyptothorax annandalei, which was 16,541 bp in length. This genome consists of two rRNA genes, 22 tRNA genes, 13 protein-coding genes (PCGs), and a putative control region. The overall base composition was for A(31.25%,) for T(25.67%), for C(27.66%), for G(15.42%). The PCGs start with a traditional ATG except for COX1 start with GTG, respectively, and end with stop codon TAA, TAG, or a single T base. All tRNA have the typical clover-leaf structure. The phylogenetic tree of the whole mitogenome sequence is constructed by maximum likelihood (ML) method and the phylogenetic relationship among the family Sisoridae is further analyzed. We expect to provide the theoretical basis for the further study of the phylogenetic relationship, taxonomic status, conservation and management of genetic resources of Sisoridae catfishes.

Pareuchiloglanis kamengensis belongs to the family of Sisoridae, Pareuchiloglanis. It is distributed in the Yarlung Zangbo River, the Irrawaddy River, the Nujiang River, and the Lancang River in southwestern China. In this study, we first published the complete mitochondrial genome sequence of Pareuchiloglanis kamengensis, which was 16,589 bp in length. This genome consists of 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a non-coding A + T-rich region. The PCGs start with a traditional ATG except for COX1 and NAD3, which start with GTG and ATA instead, respectively, and end with stop codon TAA, TAG, TA, or a single T base. All tRNA have the typical clover-leaf structure. The phylogenetic tree of the whole mitogenome sequence is constructed by using neighbor-joining (NJ) method and the phylogenetic relationship among the family Sisoridae is further analyzed. We except to provide the theoretical basis for the further study of the phylogenetic relationship, taxonomic status, and conservation and management of genetic resources of Sisoridae catfishes.

In bone tissue engineering, three-dimensional printed biological scaffolds play an important role in the development of bone regeneration. The ideal scaffolds should have the ability to match the bone degradation rate and osteogenic ability. This article optimizes the unit cell model of the microstructure including spherical pore, gyroid, and topology to explore degradation performance of scaffolds. Boolean operation of array microstructure unit cells and selected part of a computer-aided design (CAD) femur model are adopted to create a reconstructed scaffold model. Polylactic acid/ β -tricalcium phosphate/hydroxyapatite scaffolds with spherical pore, gyroid, and topology-optimized structures are manufactured by three-dimensional printing utilizing the composition of bio-ink including polylactic acid, β -tricalcium phosphate, and hydroxyapatite. After degradation of the scaffolds in vitro for several days, the mechanical properties are analyzed to study the effects of different microstructures on the degradation properties. The results show that the gyroid scaffolds with favorable degradability still maintain excellent mechanical properties after degradation. Mechanical properties of the scaffolds with topology-optimized structure and spherical pore microstructure scaffolds have a significant decrease after degradation.

Background: B-cell leukemia/lymphoma-2 (BCL-2) protein is an important part of apoptotic pathway, which is overexpressed in chronic lymphocytic leukemia cells, non-Hodgkin lymphoma cells, and myeloma cells. Venetoclax (ABT-199/GDC-0199) is a highly selective bioavailable inhibitor of BCL-2 protein, which is more effective and less valid against BCL-xL in BCL2-dependent leukemia and lymphoma cell.Method: We searched PubMed database using retrieval keyword venetoclax, ABT-199, or GDC-0199 and investigated the data of the involved articles. Considering variability in different studies, the overall response rate was collected to assess the efficacy. Meanwhile, adverse events (AEs) were summarized, and event rates were calculated to assess the safety.Results: When patients were treated with venetoclax monotherapy, the most common AEs were nausea, diarrhea, neutropenia, fatigue and thrombocytopenia, and neutropenia. In addition, thrombocytopenia, anemia, febrile neutropenia, and leukopenia appeared more common and are considered as the severe AEs (defined as grade ≥ 3 AEs). Although the occurrence of thrombocytopenia was relatively high, it was not the most severe type. When compared with patients treated with venetoclax and other drugs, nausea, diarrhea, and thrombocytopenia were still the most common AEs occurrence in the patients of all the grade. The overall event rate was 73%, which is quite satisfactory.Conclusion: Venetoclax is a mild and efficient drug in treating advanced hematological malignancy, which can be specially fit for the chronic lymphocytic leukemia patients with del[17p], and AEs are well tolerable. Few tumor lysis syndrome occurred after taking the drugs. The AEs aroused by venetoclax, and the combination is well tolerable. Therefore, the use of venetoclax monotherapy or its combination with other therapies is desirable in hematological malignancy.

Metastatic melanoma is the most aggressive and obstinate skin cancer with poor prognosis. Variant novel applicable regimens have emerged during the past decades intensively, while the most profound approaches are oncogene-targeted therapy and T-lymphocyte mediated immunotherapy. Although targeted therapies generated remarkable and rapid clinical responses in the majority of patients, acquired resistance was developed promptly within months leading to tumor relapse. By contrast, immunotherapies elicited long-term tumor regression. However, the overall response rate was limited. In view of the above, either targeted therapy or immunotherapy cannot elicit durable clinical responses in large range of patients. Interestingly, the advantages and limitations of these regimens happened to be complementary. An increasing number of preclinical studies and clinical trials proved a synergistic antitumor effect with the combination of targeted therapy and immunotherapy, implying a promising prospect for the treatment of metastatic melanoma. In order to achieve a better therapeutic effectiveness and reduce toxicity in patients, great efforts need to be made to illuminate multifaceted interplay between targeted therapy and immunotherapy.

Like other important cereal crop in modern agricultural production, maize is also threatened by drought. And the drought stress during maize filling stage will directly affect the quality (protein or oil concentration) and also the weight of grain. Therefore, different from previous studies focusing on inbred lines and pot experiment at seedling stage, current study selected filling stage of the adult plant and planting maize in the experimental field. Two hybrids cultivars with different drought tolerant were used for drought and water treatment respectively. We performed transcriptome sequencing analysis of 4 groups, 12 samples, and obtained 651.08 million raw reads. Then the data were further processed by mapping to a reference genome, GO annotation, enrichment analysis and so on. Among them we focus on the different change trends of water treatment and drought treatment, and the different responses of two drought-tolerant cultivars to drought treatment. Through the analysis, several transcripts which encode nitrogen metabolic, protein phosphorylation, MYB,AP2/ERF, HB transcriptional factor, O-glycosyl hydrolases and organic acid metabolic process were implicated with maize drought stress. Our data will offer insights of the identification of genes involved in maize drought stress tolerance, which provides a theoretical basis for maize drought resistance breeding.

This article presents an online three-axis non-uniform rational B-splines preprocessing and feedrate scheduling method with chord error, axial velocity, acceleration, and jerk limitations. A preprocessing method is proposed to accurately locate the critical points by reducing pre-interpolation feedrate in feedrate limit violation regions. In the preprocessing stage, the non-uniform rational B-splines curve is subdivided into segments by the critical points and the corresponding feedrate constraints are obtained. A sliding look-ahead window-based feedrate scheduling method is proposed to generate smooth feedrate profile for the buffered non-uniform rational B-splines segments. The feedrate profile corresponding to each non-uniform rational B-splines block is constructed according to the block length and the given limits of acceleration and jerk. The feedrate modification method for non-schedulable short blocks is also described which aimed at avoiding feedrate discontinuity at the junction of two non-uniform rational B-splines blocks. With the proposed method, a successful feedrate profile could be generated with sufficient look-ahead trajectory length in the buffer, which enables that the preprocessing and feedrate planning to be performed progressively online. Simulation and experimental tests with different non-uniform rational B-splines curves are carried out to validate the feasibility and advantages of the proposed method. The results show that the proposed method is capable of making a balance between the machining efficiency, machining precision, and computational complexity.