In recent years, the leaf beetle
has broken out in the northern grasslands of Inner Mongolia, its management still mainly depends on chemical control using traditional insecticides or with novel ...action. The study was aim to identify mutation locus associated with resistance to diamide insecticides in field population of
, to provide a reference for rational selection of insecticides and to avoid the rapid resistance development to diamide insecticides. We cloned the full length of the ryanodine receptor gene of
(
), constructed 3D model and transmembrane regions by homologous modeling based on deduced amino acid sequence. Two potential mutation loci (Gly4911Glu and Ile4754Met) and allelic mutation frequencies were detected in individuals of
. In addition, their binding patterns to two diamide insecticides (chlorantraniliprole, cyantraniliprole) were analyzed separately using a molecular docking method. The full-length cDNA sequence of
(GenBank accession number: OP828593) was obtained by splicing and assembling, which is 15,399 bp in length and encodes 5,133 amino acids. The amino acid similarity of
with that of other Coleopteran insects were 86.70%-91.33%, which possessed the typical structural characteristics. An individual resistance allelic mutation frequency test on fifty field leaf beetles has identified 12% and 32% heterozygous individuals at two potential mutation loci Gly4911Glu and Ile4754Met, respectively. The affinity of the I4754M mutant model of
for chlorantraniliprole and cyantraniliprole was not significantly different from that of the wild type, and all had non-covalent interactions such as hydrogen bonding, hydrophobic interactions and π-cation interactions. However, the G4911E mutant model showed reduced affinity and reduced mode of action with two diamide insecticides, thus affecting the binding stability of the ryanodine receptor to the diamide insecticides. In conclusion, the G4911E mutation in
may be a potential mechanism for the development of resistance to diamide insecticides on
and should be a key concern for resistance risk assessment and reasonable applications of diamide insecticides for control in future. Moreover, this study could provide a reference for ryanodine receptor structure-based insecticides design.
Induction of tumor cell senescence has become a promising strategy for anti-tumor immunotherapy, but fibrotic matrix severely blocks senescence inducers penetration and immune cells infiltration. ...Herein, we designed a cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V), which can directionally deliver valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets. In detail, DOX is conjugated with hyaluronic acid (HA) via diselenide bonds (Se-Se) to form HSD micelles, while CAFs-sensitive peptide is grafted onto the HSD to form a hydrophilic polymer, which is coated on Val nanocrystals (VNs) surface for improving the stability and achieving responsive release. Once arriving at tumor microenvironment and touching CAFs, HSD-P@V disintegrates into VNs and HSD micelles due to sensitive peptide detachment. VNs can degrade the extracellular matrix, leading to the enhanced penetration of HSD. HSD targets tumor cells, releases DOX to induce senescence, and recruits effector immune cells. Furthermore, senescent cells are cleared by the recruited immune cells to finish the integrated anti-tumor therapy. In vitro and in vivo results show that the nano-assembly remarkably inhibits tumor growth as well as lung metastasis, and extends tumor-bearing mice survival. This work provides a promising paradigm of programmed delivering multi-site nanomedicine for cancer immunotherapy.
Cancer-associated fibroblasts (CAFs) triggered structure-transformable nano-assembly (HSD-P@V) was constructed for directionally delivering valsartan (Val, CAFs regulator) and doxorubicin (DOX, senescence inducer) to the specific targets, thus enhancing tumor immunotherapy.
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Dong people in Southwest China are officially recognised as an ethnic group, but there has been a lack of population genetic research on this group, especially based on mitochondrial DNA data.
To ...study the sequences and haplogroups of the mitochondrial DNA control region in a typical Dong population, and to provide help for the construction of a forensic mitochondrial DNA analysis reference database in East Asia.
The sequences of the mitochondrial DNA control region were analysed in 200 individuals of Dong in Guizhou. The haplotype frequencies, haplogroup distribution and paired Fst values of Guizhou Dong and 51 other populations in the world were calculated and explained to explore the genetic polymorphism and population relationships.
A total of 180 haplotypes were detected, with frequencies of 0.005-0.02. All haplotypes were assigned to 97 different haplogroups. The haplotype diversity and random matching probability were 0.998643 and 0.00635, respectively. The paired Fst values and correlation p values of 52 populations showed that the Guizhou Dong had the closest genetic relationship with the Henan Han and the Guizhou Miao in China, and were closest to the Punjab population in Pakistan and the Kashmiri population when compared with the world populations.
Our study was based on the matrilineal genetic structure of Guizhou Dong to study mitochondrial DNA, which was helpful to promote the establishment of the forensic DNA reference database in East Asia and provide reference for anthropological research.
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As a major part of the modern
Eurasian or Altaic language family, most of the Mongolic and Tungusic languages were mainly spoken in northern China, Mongolia, and southern Siberia, but some were also ...found in southern China. Previous genetic surveys only focused on the dissection of genetic structure of northern Altaic-speaking populations; however, the ancestral origin and genomic diversification of Mongolic and Tungusic-speaking populations from southwestern East Asia remain poorly understood because of the paucity of high-density sampling and genome-wide data. Here, we generated genome-wide data at nearly 700,000 single-nucleotide polymorphisms (SNPs) in 26 Mongolians and 55 Manchus collected from Guizhou province in southwestern China. We applied principal component analysis (PCA), ADMIXTURE,
statistics,
analysis,
, TreeMix, Fst, and ALDER to infer the fine-scale population genetic structure and admixture history. We found significant genetic differentiation between northern and southern Mongolic and Tungusic speakers, as one specific genetic cline of Manchu and Mongolian was identified in Guizhou province. Further results from ADMIXTURE and
statistics showed that the studied Guizhou Mongolians and Manchus had a strong genetic affinity with southern East Asians, especially for inland southern East Asians. The
-based estimates of ancestry admixture proportion demonstrated that Guizhou Mongolians and Manchus people could be modeled as the admixtures of one northern ancestry related to northern Tungusic/Mongolic speakers or Yellow River farmers and one southern ancestry associated with Austronesian, Tai-Kadai, and Austroasiatic speakers. The
-based phylogeny and neighbor-joining tree further confirmed that Guizhou Manchus and Mongolians derived approximately half of the ancestry from their northern ancestors and the other half from southern Indigenous East Asians. The estimated admixture time ranged from 600 to 1,000 years ago, which further confirmed the admixture events were mediated
the Mongolians Empire expansion during the formation of the Yuan dynasty.
We previously demonstrated that baicalin had efficacy against gouty arthritis (GA) by oral administration. In this paper, a novel baicalin-loaded microemulsion-based gel (B-MEG) was prepared and ...assessed for the transdermal delivery of baicalin against GA. The preparation method and transdermal capability of B-MEG was screened and optimized using the central composite design, Franz diffusion cell experiments, and the split-split plot design. Skin irritation tests were performed in guinea pigs. The anti-gout effects were evaluated using mice. The optimized B-MEG comprised of 50 % pH 7.4 phosphate buffered saline, 4.48 % ethyl oleate, 31.64 % tween 80, 13.88 % glycerin, 2 % borneol, 0.5 % clove oil and 0.5 % xanthan gum, with a baicalin content of (10.42 ± 0.08) mg/g and particle size of (15.71 ± 0.41) nm. After 12 h, the cumulative amount of baicalin permeated from B-MEG was (672.14 ± 44.11) μg·cm−2. No significant skin irritation was observed following B-MEG application. Compared to the model group, B-MEG groups significantly decreased the rate of auricular swelling (P < 0.01) and number of twists observed in mice (P < 0.01); and also reduced the rate of paw swelling (P < 0.01) and inflammatory cell infiltration in a mouse model of GA. In conclusion, B-MEG represents a promising transdermal carrier for baicalin delivery and can be used as a potential therapy for GA.
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Despite many nano-based strategies devoted to delivering cisplatin for tumor therapy, its clinical benefits are compromised by poor tissue penetration and limited DNA adducts formation of the drug. ...Herein, a cisplatin loading nanomotor based janus structured Ag-polymer is developed for cisplatin delivery of deeper tissue and increased DNA adducts formation. The nanomotor displayed a self-propelled tumor penetration fueled by hydrogen peroxide (H.sub.2O.sub.2) in tumor tissues, which is catalytically decomposed into a large amount of oxygen bubbles by Ag nanoparticles (NPs). Notably, cisplatin could elevate the intracellular H.sub.2O.sub.2 level through cascade reactions, further promote the degradation of Ag NPs accompanied with the Ag.sup.+ release, which could downregulate intracellular Cl.sup.- through the formation of AgCl precipitate, thereby enhancing cisplatin dechlorination and Pt-DNA formation. Moreover, polymer can also inhibit the activity of ALKBH2 (a Fe.sup.2+-dependent DNA repair enzyme) by chelating intracellular Fe.sup.2+ to increase the proportion of irreparable Pt-DNA cross-links. It is found that deep tissue penetration, as well as the increased formation and maintenance of Pt-DNA adducts induced by the nanomotor afford 80% of tumor growth inhibition with negligible toxicity. This work provides an important perspective of resolving chemotherapeutic barriers for boosting cisplatin therapy.
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(Joannis) is a pest species with serious outbreaks in the Inner Mongolian grasslands in recent years, and its larvae and eggs are extremely cold-tolerant. To gain a deeper understanding of the ...molecular mechanism of its cold-tolerant stress response, we performed de novo transcriptome assembly of
via RNA-Seq and compared the differentially expressed genes (DEGs) of first- and second-instar larvae grown and developed indoors and outdoors, respectively. The results show that cold tolerance in
is associated with changes in gene expression mainly involved in the glycolysis/gluconeogenesis pathway, the fatty acid biosynthesis pathway and the production of heat shock proteins (HSPs). Compared with the control group (indoor), the genes associated with gluconeogenesis, fatty acid biosynthesis and HSP production were up-regulated in the larvae grown and developed outdoors. While the changes in these genes were related to the physiological metabolism and growth of insects, it was hypothesized that the proteins encoded by these genes play an important role in cold tolerance in insects. In addition, we also investigated the expression of genes related to the metabolic pathway of HSPs, and the results show that the HSP-related genes were significantly up-regulated in the larvae of
grown and developed outdoors compared with the indoor control group. Finally, we chose to induce significant expression differences in the Hsp70 gene (
,
and
) via RNAi to further illustrate the role of heat stress proteins in cold tolerance on
larvae. The results show that separate and mixed injections of
,
and
significantly reduced expression levels of the target genes in
larvae. The super-cooling point (SCP) and the body fluid freezing point (FP) of the test larvae were determined after RNAi using the thermocouple method, and it was found that silencing the Hsp70 genes significantly increased the SCP and FP of
larvae, which validated the role of heat shock proteins in the cold resistance of
larvae. Our findings provide an important theoretical basis for further excavating the key genes and proteins in response to extremely cold environments and analyzing the molecular mechanism of cold adaptation in insects in harsh environments.
•The lectin microarray was used to select lectins.•Lectins selected were immobilized on magnetic particles.•Five lectins (e.g. VVA, ConA, STL, LEL and LCA) were positive by lectin microarray.•The ...structure of carbohydrate chains might contain GlaNAc, mannose, GlcNAc and LacNAc.
Ginger-derived glycoproteins are a widely distributed group of biological macromolecules with multiple functions. To date, the structure of ginger-derived glycoproteins has not been clarified with regard to their complexity, their sequence diversity and their uneven micro-distribution. In this study, a lectin microarray was used to evaluate 37 types of lectins and determine the optimal lectins that can conjugate with glycoproteins based on the fluorescence intensity. Subsequently, the lectins were immobilized on magnetic beads, coupled with glycoproteins to enrich ginger-derived glycoproteins, and evaluated using SDS-PAGE. Our results showed that five lectins (e.g. VVA, ConA, STL, LEL, and LCA) were selected by the lectin microarray and that VVA showed the highest fluorescence intensity. In addition, it is indicated that the structure of the carbohydrate chains might contain GlaNAc, mannose, GlcNAc, and LacNAc.
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Canine adenovirus type 1 (CAdV-1) is a double-stranded DNA virus, which is the causative agent of fox encephalitis. The
Fiber
protein is one of the structural proteins in CAdV-1, which mediates ...virion binding to the coxsackievirus and adenovirus receptor on host cells. The suspected virus was cultured in the MDCK cells, and it was determined through the cytopathic effects, sequencing and electron microscopy. The informatics analysis of the
Fiber
was done using online bioinformatics servers. The CAdV-1-JL2021 strain was isolated successfully, and were most similar to the CAdV-1 strain circulating in Italy. The occurrence of negative selection and recombination were found in the CAdV-1-JL2021 and CAdV-2-AC_000020.1. Host cell membrane was its subcellular localization. The CAdV-1-JL2021
Fiber
(ON164651) had 6 glycosylation sites and 107 phosphorylation sites, exerted adhesion receptor-mediated virion attachment to host cell, which was the same as CAdV-2-AC_000020.1 Fiber. The
Fiber
tertiary structure of the CAdV-1-JL2021 and CAdV-2-AC_000020.1 was different, but they had the same coxsackievirus and adenovirus receptor. “VATTSPTLTFAYPLIKNNNH” were predicted to be the potential CAdV-1 B cell linear epitope. The MHC-I binding peptide “KLGVKPTTY” were both presented in the CAdV-1-JL2021 and CAdV-2-AC_000020.1 Fiber and it is useful to design the canine adenovirus vaccine.
X-chromosomes show a specific genetic mode, which makes genetic markers on the X-chromosome play crucial roles in forensic research and human evolution. Dong group, one of 55 minority groups in ...China, live in Guizhou, Guangxi, and Hunan provinces. Even though some genetic data of Y chromosomal short tandem repeats (STRs) and autosomal insertion/deletion polymorphism (InDels) in Dong groups have been reported, there is little research about X-STRs in the Dong group.
Purposes of this study are to investigate allelic distributions and forensic statistical parameters of 19 X-STRs in the Guizhou Dong group, and explore the genetic composition of the Guizhou Dong group and its phylogenetic relationships with other reference populations.
Five hundred and seven Dongs (272 males and 235 females) living in Guizhou province were typed using the AGCU X19 STR kit. Allelic frequencies and forensic parameters of 19 X-STRs in the Guizhou Dong group were calculated. Population genetic analyses of Guizhou Dong and another 17 reference populations were conducted using D
A
genetic distances, phylogenetic tree, principal component analysis, and multidimensional scaling.
A total of 230 alleles of 19 X-STRs were identified in all Dongs. The frequencies of 19 loci ranged from 0.0013 to 0.6838. The values for cumulative power of discrimination in males (PDM), cumulative power of discrimination in females (PDF), and four different kinds of mean exclusion chance (MEC_Kruger, MEC_Kishida, MEC_Desmarais, and MEC_Desmarais_du) for the 19 X-STRs in all individuals were 0.999999999999761, 0.9999999999999999999993951, 0.999999964841617, 0.999999999997261, 0.999999999997297, and 0.999999993623172, respectively. Besides, genetic polymorphisms of seven linkage clusters ranged from 0.9381 to 0.9963. In addition, these seven groups showed high polymorphism information content (PIC), PDM, PDF, MEC_Kruger, MEC_Kishida, MEC_Desmarais, and MEC_Desmarais_duo. Population genetic analyses of Guizhou Dong and another 17 reference populations showed that the Guizhou Dong group had close genetic relationships with surrounding Tai-Kadai-speaking, Hmong-Mien-speaking, and Han groups.
Nineteen X-STRs displayed high genetic diversities and could be employed for forensic personal identification and paternity analysis in the Guizhou Dong group. Close genetic affinities between Guizhou Dong and surrounding populations were observed based on the 19 X-STRs in 17 reference populations.
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