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Hepatocellular carcinoma (HCC) remains a health challenge with increasing incidence worldwide. Radiofrequency ablation (RFA) is a potentially curative option for patients with early-stage HCC. However, the high rate of tumor recurrence limits long-term survival when the tumors are larger than 2 cm and undergoing insufficient RFA (iRFA). Notably, in situ tumor necrosis due to thermal ablation is assumed to be a source of antigens that induce antitumor immunity. Therefore, mounting studies and trials have attempted to provide a rational and effective therapeutic strategy combining RFA and immunotherapy to treat HCC. Nowadays, many controversies and challenges with this combined therapeutic strategy remain to be resolved, such as the indications for adjuvant immunotherapy along with RFA in early HCC, the sequence of the two treatments in advanced HCC, and the optimal timing of immunotherapy before or after RFA. In addition, individualized treatment strategies need to be perfected for patients with HCC.

The intensive application of chlorantraniliprole (CAP) leaves residues in the environment, posing a potential threat to non-target organisms. In the present study, we investigated the adverse effects of sublethal CAP exposure on Bombyx mori. Sublethal CAP (0.02 mg/L) was shown to induce the release of intracellular Ca

Recently, the emerging role of circular RNAs (circRNAs) in tumor development and progression has been a topic of great interest. Nevertheless, the effects of hepatic stellate cell (HSC)-derived exosomes in hepatocellular carcinoma (HCC) remain unclear. Here, we aim to explore the potential effect of HSC exosome-derived circWDR25 on the aggressiveness of HCC. Firstly, a microarray analysis of circRNAs was performed to profile and identify the differentially expressed circRNAs derived from HSC exosomes activated by HCC cells. Subsequently, the roles of circWDR25 in HCC tumor growth and aggressiveness were confirmed through in vitro and in vivo functional experiments. Moreover, RNA pull-down, dual-luciferase reporter assays, and fluorescent in situ hybridization (FISH) were performed to determine interactions in the circWDR25-miR-4474-3p-ALOX15 loop. Immunohistochemical analysis was also performed on a microarray of HCC tissues and peritumoral tissues. We found that overexpressed peritumoral circWDR25 was associated with survival and recurrence in patients with HCC and promoted the progression of HCC cells both in vitro and in vivo. Mechanistically, both exogenous and HSC exosomal-derived circWDR25 regulated the expression of ALOX15 by sponging miR-4474-3p and ultimately inducing an epithelial-to-mesenchymal transition (EMT) in HCC cells. Moreover, exogenous and HSC exosomal-derived circWDR25 promoted the expression of CTLA-4 in HSCs and PD-L1 in HCC cells. In conclusion, circWDR25 facilitated HCC cell proliferation and invasion via the circWDR25/miR-4474-3p/ALOX15 and EMT axes and it promoted the expression of CTLA-4 in HSCs and PD-L1 in HCC cells, thus providing insights into the mechanism of tumor aggressiveness mediated by HSC-derived exosomal circWDR25.

As a new type of biologically compatible material, TiO2 NPs are widely used in the industry as additives, drug carriers, and components of skin care products. Due to their wide use, residual TiO2 NPs in the environment are a safety concern that has attracted extensive attention. In this study, the ovarian cell line BmN of the model organism Bombyx mori was used to reveal the damaging effects of TiO2 NPs exposure. The results demonstrated that TiO2 NPs exhibited a dose-dependent effect on the relative cell viability, with significant toxic effects being observed above 20 mg/L. Oxidative damage analysis showed that ROS accumulated significantly in BmN cells after exposure to TiO2 NPs (P ≤ 0.05) and induced DNA damage. Further analysis revealed that the transcriptional levels of key superoxide dismutase genes (SOD) decreased significantly, while the transcriptions of key genes of the MAPK/NF-κB signaling pathway (P38, MEK, ERK and REL) and the downstream inflammatory factor genes (IL6 and TNFSF5) were all significantly up-regulated (P ≤ 0.05). Overall, our results indicate that exposure to TiO2 NPs leads to reduced transcription of antioxidant genes, accumulation of peroxides, and inflammation. These findings provide valuable data for the safety evaluation of environmental residues of TiO2 NPs.

Here, we develop a simple, efficient, bacmid-based, selection marker-free method for gene deletion and editing in baculovirus genomes. Specifically, based on pFastbac1, a donor plasmid with long left and right homology arms but without a reporter was constructed for disrupting ie1, an essential baculovirus gene. Instead of ligating with a plasmid, the homology arms were introduced to the polyhedrin locus of BmNPV bacmid using the BmNPV bac-to-bac expression system. Two viruses generated from the modified bacmid and unmodified BmNPV bacmid were then used to co-infect BmN cells in order that recombination takes place at the ie1 locus between them. Finally, without multiple rounds of purification, total cellular DNA was isolated, transformed into Cacl

Mitochondrial genomes (mitogenomes) have been widely used for studies on phylogenetic relationships and molecular evolutionary biology. Here, the complete mitogenome sequence of Spilosoma lubricipedum (Noctuoidea: Erebidae: Arctiinae) was determined (total length 15,375 bp) and phylogenetic analyses S. lubricipedum were inferred from available noctuid sequence data. The mitogenome of S. lubricipedum was found to be highly A + T-biased (81.39%) and exhibited negative AT- and GC-skews. All 13 protein-coding genes (PCGs) were initiated by ATN codons, except for cox1 with CGA. All tRNAs exhibited typical clover-leaf secondary structures, except for trnS1. The gene order of the S. lubricipedum mitogenome was trnM-trnI-trnQ-nad2. The A + T-rich region of S. lubricipedum contained several conservative features common to noctuid insects. Phylogenetic analysis within Noctuoidea was carried out based on mitochondrial data. Results showed that S. lubricipedum belonged to Erebidae and the Noctuoidea insects could be divided into five well-supported families (Notodontidae + (Erebidae + (Nolidae + (Euteliidae + Noctuidae)))).

Boron-doped diamond (BDD) has proved to be an ideal anode material for the electrolysis of organic sewage. However, the existing two dimensional BDD electrodes with small active area and low mass transfer rates, limit their further improvement in degradation efficiency. In this paper, a novel three dimensional macroporous BDD (3D-BDD) foam electrode with a structure of evenly distributed pores and interconnected networks in which wastewater can flow freely was prepared using a simple and reproducible method. Compared to two dimensional BDD electrodes of the same geometry, the electro-active surface area of 3D-BDD electrode increased by ˜20 times, and the electrochemical oxidation reaction rate constant of RB-19 increased by ˜350 times. Under optimized conditions, the energy consumption reduced to a minimum of 0.03 kWh(gTOC) −1, and the MCE reach a maximum of 325.86%.

A Ni/Cu/boron-doped diamond (Ni/Cu/BDD) complex electrode for non-enzymatic glucose electrochemical detection was prepared by a simple two-step heat treatment method. Scanning electron microscopy (SEM), Raman spectroscopy and electrochemical workstation were used to characterize the surface morphology, composition and electrochemical properties of the electrode, respectively. The results showed that Ni reacted with BDD under high temperature catalytic conditions forming a porous structure, and stabilized Cu on the surface of BDD due to the superior wettability between Cu and Ni. Compared to Ni/BDD and Cu/BDD electrodes, Ni/Cu/BDD electrode exhibited enhanced catalytic activity in glucose detection, such as an extremely wide detection range (0.022–18.3 mM), high sensitivity (1007.688 μAmM−1 cm−2, which was 1.28 times higher than that of the Ni/BDD electrode), great selectivity and excellent long-term stability (93.3% after one month).

Silkworm (Bombyx mori) is an important economic insect and an attractive model system. A series of autophagy-related genes (Atgs) are involved in the autophagic process, and these Atgs have been proved to play important roles in the development. Atg7 stands at the hub of two ubiquitin-like systems involving Atg8 and Atg12 in the autophagic vesicle. In the present study, we cloned and characterized a BmAtg7 gene in Bombyx mori. The open reading frame (ORF) of BmAtg7 was 1908 bp in length, and it encoded a polypeptide of 635 amino acids. BmAtg7 was highly expressed in the posterior silk gland, fatbody, and epidermis. The expression profile of BmAtg7 in the fatbody showed an increasing tendency from day 1 of the 5th instar to the prepupal stage. After chlorantraniliprole (CAP) exposure, the transcriptional level of BmAtg7 was continuously decreased. After depletion of BmAtg7 by RNAi, the expressions of BmAtg7, BmAtg8, and BmEcr were all downregulated, while the expression of BmJHBP2 was upregulated. However, depletion of BmAtg7 did not prevent the metamorphosis of silkworm from larvae to pupae, while the occurrence of such process was delayed. After the 20-hydroxyecdysone (20E) treatment, the expression characteristics of these four genes (BmAtg7, BmAtg8, BmEcr and BmJHBP2) were contrary to the results after depletion of BmAtg7. Our results suggested that although CAP exposure could significantly inhibit the expression of BmAtg7 continuously, the changes of BmAtg7 was not the key factor in CAP-induced metamorphosis defects.

As a new type of biologically compatible material, TiO

The neonicotinoid insecticide acetamiprid is widely applied for pest control in agriculture production, and its exposure often results in adverse effects on a non-target insect, Bombyx mori. However, only few studies have investigated the effects of exposure to sublethal doses of neonicotinoid insecticides on gut microbiota and susceptibility to pathogenic bacteria. In this study, we aimed to explore the possible mechanisms underlying the acetamiprid-induced compositional changes in gut microbiota of silkworm and reduced host resistance against detrimental microbes. This study indicated that sublethal dose of acetamiprid activated the dual oxidase-reactive oxygen species (Duox-ROS) system and induced ROS accumulation, leading to dysregulation of intestinal immune signaling pathways. The evenness and structure of bacterial community were altered. Moreover, after 96 h of exposure to sublethal dose of acetamiprid, several bacteria, such as Pseudomonas sp (Biotype A, DOP-1a, XW34) and Staphylococcus sp (RCB1054, RCB314, X302), invaded the silkworm hemolymph. The survival rate and bodyweight of the acetamiprid treated silkworm larvae inoculated with Enterobacter cloacae (E. cloacae) were significantly lower than the acetamiprid treatment group, suggesting that acetamiprid reduced silkworm resistance against pathogens. These findings indicated that acetamiprid disturbed gut microbial homeostasis of Bombyx mori, resulting in changes in gut microbial community and susceptibility to detrimental microbes.

The accurate prediction of storm surge disasters’ direct economic losses plays a positive role in providing critical support for disaster prevention decision-making and management. Previous researches on storm surge disaster loss assessment did not pay much attention to the overfitting phenomenon caused by the data scarcity and the excessive model complexity. To solve these problems, this paper puts forward a new evaluation system for forecasting the regional direct economic loss of storm surge disasters, consisting of three parts. First of all, a comprehensive assessment index system was established by considering the storm surge disasters’ formation mechanism and the corresponding risk management theory. Secondly, a novel data augmentation technique, k-nearest neighbor-Gaussian noise (KNN-GN), was presented to overcome data scarcity. Thirdly, an ensemble learning algorithm XGBoost as a regression model was utilized to optimize the results and produce the final forecasting results. To verify the best-combined model, KNN-GN-based XGBoost, we conducted cross-contrast experiments with several data augmentation techniques and some widely-used ensemble learning models. Meanwhile, the traditional prediction models are used as baselines to the optimized forecasting system. The experimental results show that the KNN-GN-based XGBoost model provides more precise predictions than the traditional models, with a 64.1% average improvement in the mean absolute percentage error (MAPE) measurement. It could be noted that the proposed evaluation system can be extended and applied to the geography-related field as well.

Analysing changes in vegetation seasonality of terrestrial ecosystems is important to understand ecological responses to global change. Based on over three decades of observations by the series of Advanced Very High Resolution Radiometer (AVHRR) sensors, the Global Inventory Modelling and Mapping Studies (GIMMS) Normalized Difference Vegetation Index (NDVI) dataset has been widely used for monitoring vegetation trends. However, it is not well known how robust long-term trends in vegetation seasonality derived from GIMMS NDVI are, given inevitable influences from sensor and processing artefacts. Here we analyse long-term seasonality trends in the GIMMS third generation (NDVI3g) record (1982–2013). Changes in vegetation seasonality are decomposed into changes in duration (related to growing season length) and timing (related to peak growing season). We compare seasonality trends from the previous version (NDVI3g v0) with those in the subsequently released version (NDVI3g v1) and, for their common period, with those derived from MODerate Resolution Imaging Spectroradiometer (MODIS) collection 6 NDVI. We find that NDVI3g v0 shows marked seasonality trends for 1982–2013 over more than one-third of the global vegetated area. Long-term trends based on v1 are generally consistent with v0, but v1 shows a strong trend towards earlier timing across the Arctic regions that is absent in v0. NDVI3g v0, v1, and MODIS all point towards an increased duration across the tundra of North Asia and later timing across North Africa. However, several discrepancies are also found between the NDVI datasets. For example, for the North-American tundra, MODIS shows earlier and v0 later timing, while MODIS shows an increased duration and v1 a reduced duration. For North Africa, v0 and v1 exhibit a reduced duration that is absent in MODIS. We conclude that both the primary observations and the subsequent processing can have a marked influence on inferred seasonality trends, and propose that the robustness of trends should be examined and corroborated using alternative data sources wherever possible.

Members of the genus Treron (Columbidae) are widely distributed in southern Asia and the Indo-Malayan Region but their relationships are poorly understood. Better knowledge of the systematic status of this genus may help studies of historical biogeography and taxonomy. The complete mitochondrial genome of T. curvirostra was characterized, a first for the genus. It is 17,414 base pairs in length, containing two rRNAs, 22 tRNAs, 13 protein coding genes (PCGs), and one D-loop with a primary structure that is similar to that found in most members of Columbidae. Most PCGs start with the common ATG codon but are terminated by different codons. The highest value of the Ka/Ks ratio within 13 PCGs was found in ATP8 with 0.1937, suggesting that PCGs of the mitochondrial genome tend to be conservative in Columbidae. Moreover, the phylogenetic relationships within Columbidae, which was based on sequences of 13 PCGs, showed that (T. curvirostra + Hemiphaga novaeseelandiae) were clustered in one clade, suggesting a potentially close relationship between Treron and Hemiphaga. However, the monophyly of the subfamilies of Columbidae recognized by the Interagency Taxonomic Information System could not be corroborated. Hence, the position of the genus Treron in the classification of Columbidae may have to be revised.

This study aimed to explore the toxicity of environmental residues of graphene oxide nanoparticles (GONPs) to reproduction of Lepidopteron insects using both ovary cell line (BmN) and individual female Bombyx mori as the research subjects. The results showed that GONPs dose dependently affect BmN cells. At higher concentrations (>25 mg/L), GONPs led to oxidative stress, ROS accumulation and DNA damage in BmN cells and significantly reduced their survival rate (p ≤ 0.05). Moreover, feeding female B. mori larvae with mulberry leaves treated with 25 mg/L GONPs significantly decreased their gonadosomatic index (GSI) by 40.84%, and increased oxidation levels and antioxidant enzyme activity in silkworm ovary tissues. Pathological analysis found that exposure to GONPs decreased the numbers of both oogonia and oocytes in ovarian tissues, increased the formation of peroxisome and vacuoles in follicle cells, reduced the transcription of genes (Vg, Ovo, Sxl-s, Sxl-l, and Otu) related to ovarian development in B. mori by 0.61, 0.65, 0.75, 0.72, and 0.42-fold, respectively, and lowered the amount of spawning by 52.25%. Overall, these results revealed that GONPs exposure is toxic to the reproduction of B. mori. The underlying mechanism is that oxidative stress due to GONPs causes oxidative damage to DNA, damages ovarian tissues, as well as hinders B. mori development and spawning. Thus, this study provides important experimental data for safety evaluation of reproductive toxicity due to GONPs exposure.

To determine the systematic status of family Limacodidae within Lepidoptera, the complete mitochondrial genome (mitogenome) of Thosea sinensis (Lepidoptera: Zygaenoidea: Limacodidae) was sequenced. The genome is 15,544 base pairs (bp), including 13 protein-coding genes (PCGs), two ribosomal RNAs (rRNAs), 22 transfer RNAs (tRNAs), and an AT-rich region. These characteristics are similar to of other lepidopterans. The gene order of T. sinensis is identical to that of Ditrysia lepidopterans. The nucleotide composition of the T. sinensis mitochondrial genome is highly biased toward A + T nucleotides (81.1%) and exhibits negative AT and GC skew. All the other 13 PCGs except cox1 are initiated by ATN codons. All tRNA genes are folded into the typical cloverleaf secondary structure, except for trnS1, which lacked the dihydrouridine (DHU) stem. There are 20 intergenic spacer regions ranging from 1 to 56 bp in length, and two gene overlap regions throughout the entire genome. The AT-rich region includes the ATAGA motif, followed by a 19-bp poly T stretch, a microsatellite-like (AT)10, and a poly-A element. Analysis of phylogenetic relationships indicated that T. sinensis belongs to the Limacodidae, and the monophyly of each lepidopteran family was well supported.

Acetamiprid is a new neonicotinoid insecticide widely used in the prevention and control of pests in agriculture. However, its residues in the environment affect the cocooning of the silkworm, Bombyx mori (B. mori), a non-target insect. To investigate the mechanism of damage, B. mori larvae were fed with trace amounts of acetamiprid (0.15 mg/L). At 96 h after exposure, the larvae showed signs of poisoning and decreased body weight, resulting in reduced survival and ratio of cocoon shell. At 48 h and 96 h after exposure, the residues in the posterior silk gland (PSG), which is responsible for synthesizing silk fibroin, were 0.72 μg/mg and 1.21 μg/mg, respectively, as measured by high performance liquid chromatography, indicating that acetamiprid can accumulate in the PSG. Moreover, pathological sections and transmission electron microscopy also demonstrate the damage of the PSG by acetamiprid. Digital gene expression (DGE) and KEGG pathway enrichment analysis revealed that genes related to metabolism, stress responses and inflammation were significantly up-regulated after exposure. Quantitative RT-PCR analysis showed that the transcript levels of FMBP-1 and FTZ-F1 (transcription factors for synthesizing silk protein) were up-regulated by 2.55-and 1.56-fold, respectively, and the transcript levels of fibroin heavy chain ( Fib-H), fibroin light chain (Fib-L), P25, Bmsage and Bmdimm were down-regulated by 0.75-, 0.76-, 0.65-, 0.44- and 0.40-fold, respectively. The results indicate that accumulated acetamiprid causes damage to the PSG and leads to reduced expression of genes responsible for synthesizing silk fibroin. Our data provide reference for evaluating the safety of acetamiprid residues in the environment for non-target insects.

Diamond with a 3D porous macrostructure has a combination of outstanding intrinsic physicochemical properties and unique structural advantages, which is highly promising for wide-scale practical applications. In this paper, a novel macroscopic porous structure of diamond foam (DF) prepared by hot filament chemical vapor deposition (HFCVD) is proposed for thermal management. The continuous diamond film coated on macroporous Cu foam (CF) substrate forms a monolith of 3D interconnected diamond network, which can act as an effective conductive highway for heat transfer, leading to an exceptional thermal transport property significantly superior to that of CF. Then, DF was further infiltrated with epoxy resin as a thermal conducting filler through the vacuum impregnation process. The thermal conductivity of DF/epoxy composite significantly increased up to 10-fold from 0.23 (neat epoxy) to 2.28 W/m K even with a fairly low diamond loading of 1.2 wt%. The further finite element analysis indicates that the formation of 3D interconnected heat conduction network is advantageous to dissipate heat efficiently in practical application. This work opens up new opportunities toward realizing the application of macroporous DFs and their composites for the use in heat dissipation and the future development of high-performance thermal management systems. Keywords: Diamond film, Chemical vapor deposition, Macroporous, Epoxy-matrix composite, 3D interconnected, Thermal management

Background Chlorantraniliprole (CAP) is widely used in agriculture and forestry to prevent and control pests. The effects of environmental CAP residue on non-target insect metamorphosis have not been reported. Our research aimed to investigate the sublethal effect of CAP on larva-pupa transformation in silkworm, and explore the mechanism of sublethal CAP exposure-mediated pupation metamorphosis defects. Result Sublethal CAP exposure affected the growth and development of silkworm larvae and caused defects in pupation metamorphosis. After CAP exposure, formation the of prepupa procuticle, ecdysial membrane and new epidermis was inhibited. Also, the level of 20-hydroxyecdysone (20E) and mRNA levels of the 20E signaling pathway-related genes EcR, USP, E74, E75 and Ftz-f1 were significantly reduced. Moreover, genes involved in chitin synthesis, such as ChsA, CDA1 and CDA2, were downregulated. Injection of 20E led to the upregulation of chitin synthesis-related genes and increased formation of new epidermis in CAP-treated silkworm. However, injection of 20E failed to prevent downregulation of Ftz-f1 and the defects in pupation metamorphosis. Conclusion Our results suggested that 20E is a target hormone of CAP exposure-mediated epidermis formation phenotype. Ftz-f1 was silenced by CAP and might be a direct target gene of sublethal CAP exposure. Our study provided new evidence of the effects of sublethal CAP exposure on insect development and metamorphosis. © 2020 Society of Chemical Industry.

Acetamiprid is a new type of nicotinic insecticide that is widely used in pest control. Its environmental residues may cause silkworm cocooning disorder. In this study, silkworms that received continuous feeding of low concentration acetamiprid (0.15 mg/L) showed significantly decreased silk gland index and cocooning rate. Gene expression profiling of posterior silk glands (PSGs) revealed that the differentially expressed genes were significantly enriched in oxidative stress-related signal pathways with significant up-regulation. The contents of both H2O2 and MDA were increased, along with significantly elevated SOD and CAT activities, all of which reached maximal values at 48 h when H2O2 and MDA's contents were 10.46 and 7.98 nmol/mgprot, respectively, and SOD and CAT activities were 5.51 U/mgprot and 33.48 U/gprot, respectively. The transcription levels of antioxidant enzyme-related genes SOD, Mn-SOD, CuZn-SOD, CAT, TPX and GPX were all up-regulated, indicating that exposure to low concentration acetamiprid led to antioxidant response in silkworm PSG. The key genes in the FoxO/CncC/Keap1 signaling pathway that regulates antioxidant enzyme activity, FoxO, CncC, Keap1, NQO1, HO-1 and sMaf were all up-regulated during the whole process of treatment, with maximal values being reached at 72 h with 2.91, 1.46, 1.82, 2.52, 2.32 and 4.01 times of increases, respectively. These results demonstrate that exposure to low concentration acetamiprid causes oxidative stress in silkworm PSG, which may be the cause of cocooning disorder in silkworm. Our study provides a reference for the safety evaluation of environmental residues of acetamiprid on non-target insects.

A novel design of Al matrix composite reinforced with diamond coated spiral tungsten wire is proposed for thermal management. Fabrication techniques of the diamond film reinforced Al matrix composites consist of hot filament assisted chemical vapour deposition (HFCVD) for diamond film, low-cost cold pressing and vacuum sintering of Al matrix composites. The microstructure characteristics and thermal properties of the composites have been studied. Results show that the diamond film retains its high quality and integrity after the vacuum sintering process. Even such a low content of diamond films in the filler- at most 6.5 vol.% - provides a thermal conductivity of 294 W/mK, about 69% higher than that of sintered Al and 79% higher than that of 6.5 vol.% diamond particles reinforced Al matrix composite fabricated by the same powder metallurgy process. Finite element analysis of heat transfer within such a structure is conducted, revealing that the continuous and thick diamond framework provides continuous channels and effective thermal conductive pathways for heat transfer. This work displays a great potential of CVD diamond films reinforced metal matrix composites for thermal conduction applications.