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Although hepatocellular carcinoma (HCC) is one of the deadliest health burdens worldwide, few drugs are available for its clinical treatment. However, in recent years, major breakthroughs have been made in the development of new drugs due to intensive fundamental research and numerous clinical trials in HCC. Traditional systemic therapy schemes and emerging immunotherapy strategies have both advanced. Between 2017 and 2020, the United States Food and Drug Administration (FDA) approved a variety of drugs for the treatment of HCC, including multikinase inhibitors (regorafenib, lenvatinib, cabozantinib, and ramucirumab), immune checkpoint inhibitors (nivolumab and pembrolizumab), and bevacizumab combined with atezolizumab. Currently, there are more than 1000 ongoing clinical trials involving HCC, which represents a vibrant atmosphere in the HCC drug research and development field. Additionally, traditional Chinese medicine approaches are being gradually optimized. This review summarizes FDA-approved agents for HCC, elucidates promising agents evaluated in clinical phase I/II/III trials and identifies emerging targets for HCC treatment. In addition, we introduce the development of HCC drugs in China. Finally, we discuss potential problems in HCC drug therapy and possible future solutions and indicate future directions for the development of drugs for HCC treatment.

The fall armyworm (FAW), native to the Americas, has rapidly invaded the whole of Southern China since January 2019. In addition, it can survive and breed in the key maize- and rice- growing area of the Yangtze River Valley. Furthermore, this pest is also likely to continue infiltrating other cropping regions in China, where food security is facing a severe threat. To understand the potential infestation area of newly-invaded FAW from the Yangtze River Valley, we simulated and predicted the possible flight pathways and range of the populations using a numerical trajectory modelling method combining meteorological data and self-powered flight behavior parameters of FAW. Our results indicate that the emigration of the first and second generations of newly-invaded FAW initiating from the Yangtze River Valley started on 20 May 2019 and ended on 30 July 2019. The spread of migratory FAW benefitted from transport on the southerly summer monsoon so that FAW emigrants from the Yangtze River Valley can reach northern China. The maize-cropping areas of Northeastern China, the Korean Peninsula and Japan are at a high risk. This study provides a basis for early warning and a broad picture of FAW migration from the Yangtze River Valley.

Transgenic cotton that has been engineered to produce insecticidal toxins from Bacillus thuringiensis (Bt) and so to resist the pest cotton bollworm (Helicoverpa armigera) has been widely planted in Asia. Analysis of the population dynamics of H. armigera from 1992 to 2007 in China indicated that a marked decrease in regional outbreaks of this pest in multiple crops was associated with the planting of Bt cotton. The study area included six provinces in northern China with an annual total of 3 million hectares of cotton and 22 million hectares of other crops (corn, peanuts, soybeans, and vegetables) grown by more than 10 million resource-poor farmers. Our data suggest that Bt cotton not only controls H. armigera on transgenic cotton designed to resist this pest but also may reduce its presence on other host crops and may decrease the need for insecticide sprays in general.

Insect chemosensory proteins (CSPs) have been proposed to capture and transport hydrophobic chemicals from air to olfactory receptors in the lymph of antennal chemosensilla. They may represent a new class of soluble carrier protein involved in insect chemoreception. However, their specific functional roles in insect chemoreception have not been fully elucidated. In this study, we report for the first time three novel CSP genes (AlinCSP1-3) of the alfalfa plant bug Adelphocoris lineolatus (Goeze) by screening the antennal cDNA library. The qRT-PCR examinations of the transcript levels revealed that all three genes (AlinCSP1-3) are mainly expressed in the antennae. Interestingly, these CSP genes AlinCSP1-3 are also highly expressed in the 5(th) instar nymphs, suggesting a proposed function of these CSP proteins (AlinCSP1-3) in the olfactory reception and in maintaining particular life activities into the adult stage. Using bacterial expression system, the three CSP proteins were expressed and purified. For the first time we characterized the types of sensilla in the antennae of the plant bug using scanning electron microscopy (SEM). Immunocytochemistry analysis indicated that the CSP proteins were expressed in the pheromone-sensitive sensilla trichodea and general odorant-sensitive sensilla basiconica, providing further evidence of their involvement in chemoreception. The antennal activity of 55 host-related semiochemicals and sex pheromone compounds in the host location and mate selection behavior of A. lineolatus was investigated using electroantennogram (EAG), and the binding affinities of these chemicals to the three CSPs (AlinCSP1-3) were measured using fluorescent binding assays. The results showed several host-related semiochemicals, (Z)-3-hexen-1-ol, (E)-2-hexen-1-al and valeraldehyde, have a high binding affinity with AlinCSP1-3 and can elicit significant high EAG responses of A. lineolatus antennae. Our studies indicate the three antennae-biased CSPs may mediate host recognition in the alfalfa plant bug A. lineolatus.

To analyze genetic characters of migratory dragonflies, we used 10 microsatellite markers and a partial sequence of the mitochondrial gene Cytb to investigate genetic diversity and demographic history among 19 populations of P. flavescens in eastern the monsoon region of China. In a Bayesian clustering analysis of the microsatellite data, three distinct clades were present, and each population consisted of a mixture of individuals from the three clusters. An AMOVA of the data from both the microsatellite loci and Cytb revealed that genetic variation was mainly within each population. For the 543 individuals from the 19 regions, 77 unique haplotypes were obtained by DnaSP 4.0, and a median-joining network showed no obvious geographical pattern and displayed high gene flow and minimal population genetic structure among the 19 populations. According to a Mantel test, there was no significant association between genetic distance and geographic distribution and no isolation by distance. Mismatch distribution and neutrality tests showed no demographic expansion for the 19 populations. Microsatellite and mitochondrial DNA data suggested there was high gene flow and low differentiation among the populations. These results will help provide valuable information to study the migratory route of insects, especially important agricultural pests.

Insects interact with their environment and respond to the changes in host plant conditions using semiochemicals. Such ecological interactions are facilitated by the olfactory sensilla and the use of olfactory recognition proteins. The cotton aphid Aphis gossypii can change its phenotype in response to ecological conditions. They reproduce mainly as wingless asexual morphs but develop wings to find mates or new plant hosts under the influence of environmental factors such as temperature, plant nutrition and population density. Two groups of small soluble proteins, odorant binding proteins (OBPs) and chemosensory proteins (CSPs) are believed to be involved in the initial biochemical recognition steps in semiochemical perception. However, the exact molecular roles that these proteins play in insect olfaction remain to be discovered. In this study, we compared the transcriptomes of three asexual developmental stages (wingless spring and summer morphs and winged adults) and characterised 9 OBP and 9 CSP genes. The gene structure analysis showed that the number and length of introns in these genes are much higher and this appears to be unique feature of aphid OBP and CSP genes in general. Another unique feature in aphids is a higher abundance of CSP transcripts than OBP transcripts, suggesting an important role of CSPs in aphid physiology and ecology. We showed that some of the transcripts are overexpressed in the antennae in comparison to the bodies and highly expressed in the winged aphids compared to wingless morphs, suggesting a role in host location. We examined the differential expression of these olfactory genes in ten aphid species and compared the expression profile with the RNA-seq analyses of 25 pea aphid transcriptome libraries hosted on AphidBase.

The codling moth Cydia pomonella is a major pest of global significance impacting pome fruits and walnuts. It threatens the apple industry in the Loess Plateau and Bohai Bay in China. Sterile insect technique (SIT) could overcome the limitations set by environmentally compatible area-wide integrated pest management (AW-IPM) approaches such as mating disruption and attract-kill that are difficult to suppress in a high-density pest population, as well as the development of insecticide resistance. In this study, we investigated the effects of X-ray irradiation (183, 366, 549 Gy) on the fecundity and fertility of a laboratory strain of C. pomonella, using a newly developed irradiator, to evaluate the possibility of X-rays as a replacement for Cobalt60 (60Co-γ) and the expanded future role of this approach in codling moth control. Results show that the 8th-day is the optimal age for irradiation of male pupae. The fecundity decreased significantly as the dosage of radiation increased. The mating ratio and mating number were not influenced. However, treated females were sub-sterile at a radiation dose of 183 Gy (20.93%), and were almost 100% sterile at a radiation dose of 366 Gy or higher. Although exposure to a radiation dose of 366 Gy resulted in a significant reduction in the mating competitiveness of male moths, our radiation biology results suggest that this new generation of X-ray irradiator has potential applications in SIT programs for future codling moth control.

Insects use their sensitive and selective olfactory system to detect outside chemical odorants, such as female sex pheromones and host plant volatiles. Several groups of olfactory proteins participate in the odorant detection process, including odorant binding proteins (OBPs), chemosensory proteins (CSPs), odorant receptors (ORs), ionotropic receptors (IRs) and sensory neuron membrane proteins (SNMPs). The identification and functional characterization of these olfactory proteins will enhance our knowledge of the molecular basis of insect chemoreception. In this study, we report the identification and differential expression profiles of these olfactory genes in the black cutworm moth Agrotis ipsilon. In total, 33 OBPs, 12 CSPs, 42 ORs, 24 IRs, 2 SNMPs and 1 gustatory receptor (GR) were annotated from the A. ipsilon antennal transcriptomes, and further RT-PCR and RT-qPCR revealed that 22 OBPs, 3 CSPs, 35 ORs, 14 IRs and the 2 SNMPs are uniquely or primarily expressed in the male and female antennae. Furthermore, one OBP (AipsOBP6) and one CSP (AipsCSP2) were exclusively expressed in the female sex pheromone gland. These antennae-enriched OBPs, CSPs, ORs, IRs and SNMPs were suggested to be responsible for pheromone and general odorant detection and thus could be meaningful target genes for us to study their biological functions in vivo and in vitro.

Aphis gossypii , one of the most important agricultural pests in the world, can cause serious economic losses in the main crop-producing areas. To clarify issues such as the genetic differentiation, genetic structure, and demographic history of A. gossypii populations, we used 10 nuclear microsatellite loci (SSR) and two mitochondrial gene sequences ( COI and Cytb ) to investigate genetic diversity and population structure of A. gossypii populations that were collected from 33 sampling sites in China from different climatic zones. SSR and mtDNA data suggested low to moderate levels of genetic diversity. A star-shaped network of mtDNA haplotypes indicated that the maternal ancestor of China cotton aphids likely originated in Xinjiang. The POPTREE, STRUCTURE and principal coordinate analysis (PCoA) revealed two genetic clusters: an eastern and a western region group. Isolation by distance (IBD) results showed a positive correlation between geographic distance and genetic distance in the vast eastern region but not in the western region. Neutrality testing and mismatch distribution analysis provided strong evidence for a recent rapid expansion in most populations. Genetic bottleneck was not detected in A. gossypii populations of China. The present work can help us to develop strategies for managing this pest.

Spodoptera frugiperda, an invasive pest, has a huge impact on food production in Asia and Africa. The potential and advantages of sterile insect techniques for the permanent control of S. frugiperda have been demonstrated, but the methods for their field application are still unavailable. For the purposes of this study, male pupae of S. frugiperda were irradiated with an X-ray dose of 250 Gy to examine the effects of both the release ratio and the age of the irradiated males on the sterility of their offspring. The control effect of the irradiated male release ratio on S. frugiperda was evaluated using field-cage experiments in a cornfield. The results showed that when the ratio of irradiated males to non-irradiated males reached 12:1, the egg-hatching rate of the offspring of S. frugiperda decreased to less than 26%, and there was also no significant difference in mating competitiveness among the different ages. Field-cage testing showed that when irradiated males were released at ratios of 12:1–20:1 to normal males, the leaf protection effect for the corn reached 48–69% and the reduction in the insect population reached 58–83%. In this study, an appropriate release ratio is suggested, and the mating competitiveness of irradiated and non-irradiated males of S. frugiperda is investigated, thus providing a theoretical basis for the use of sterile insect techniques to control S. frugiperda.