Objective:To study the resistance of Aedes albopictus to commonly used insecticides in Hangzhou, and to investigate the polymorphism distribution characteristics of voltage-gated sodium channel (VGSC) and acetylcholinesterase (AchE) 1 (Ace-1) genes in Aedes albopictus in the region, providing a scientific basis for control of Aedes albopictus in Hangzhou. Methods:From May to June 2023, Aedes albopictus larvae and pupae were collected from residential areas across divided different urban areas by directions in Hangzhou. They were reared in the laboratory, and their resistance to malathion, propoxur, pyrethroid insecticides (permethrin, deltamethrin, and beta-cypermethrin) was evaluated using the World Health Organization-recommended adult mosquito contact tube method. The 24 h mortality rates of adult mosquito of 98% - 100% was susceptible, 80% - < 98% was suspected resistance, < 80% was resistant. Genomic DNA was extracted from adult Aedes albopictus, and mutations in the VGSC and Ace-1 genes were detected through PCR amplification and Sanger sequencing. Results:The 24 h mortality rates of adult Aedes albopictus exposed to 0.5% malathion, 0.05% propoxur, 0.4% permethrin, 0.03% deltamethrin, and 0.08% beta-cypermethrin in Hangzhou were 100% (75/75), 96.00% (72/75), 41.43% (29/70), 17.33% (13/75), and 32.86% (23/70), respectively. A total of 146 surviving Aedes albopictus were tested for VGSC gene mutations at diagnostic doses of pyrethroid insecticides. Among them, 6 Aedes albopictus (4.11%) had a gene mutation at position V1016, and 146 Aedes albopictus (100%) had a gene mutation at position F1534. A total of 63 Aedes albopictus that died at diagnostic doses of pyrethroid insecticides were analyzed for VGSC gene mutations. No gene mutation was detected at position V1016, while 63 Aedes albopictus (100%) had a gene mutation at position F1534. One non synonymous mutation was detected at position V1016 of the VGSC gene, which was a heterozygous mutation of V1016V to V1016V/G. Two non synonymous mutations were detected at position F1534 of the VGSC gene, namely F1534F to F1534S or a F1534F/S heterozygous mutation. No Ace-1 gene mutation was detected in all Aedes albopictus exposed to 0.05% propoxur ( n = 75). Conclusions:The Aedes albopictus in Hangzhou has developed resistance to permethrin, deltamethrin, and beta-cypermethrin. It shows suspected resistance to propoxur and sensitivity to malathion. Moreover, a high frequency of mutations in the VGSC gene has been observed in these mosquitoes. It is crucial to enhance resistance monitoring in Aedes albopictus populations in Hangzhou and to implement the rational rotation of chemical insecticides to slow down the progress of drug resistance.

Escherichia coli(E.coli)is a key pathogenic bacterium responsible for postpartum endo-metritis,with its colonization in the reproductive tract closely associated with endometrial damage and disruption of the ovarian cycle.This ultimately leads to infertility,causing significant economic losses to the dairy industry.Macrophages play a pivotal role in the inflammatory response.This study aims to investigate the mRNA expression profile of bovine bone marrow-derived macropha-ges following E.coli infection using RNA sequencing(RNA-seq)technology.Additionally,it seeks to identify the biological functions and signaling pathways of differentially expressed genes(DEGs)through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The results demonstrated that E.coli infection induced differential expression of 4 522 genes,with 2 141 upregulated and 2 381 downregulated.These genes were primarily asso-ciated with inflammatory responses,where TLR2,TLR4,NLRP3,and PTGS2 played pivotal roles.PGD2 synthesis was mediated by TLR2,TLR4,and NLRP3.Transcriptome sequencing of bovine bone marrow-derived macrophages infected with E.coli and treated with a PGD2 inhibitor revealed a marked downregulation of TLR2 and TLR4 gene expression.qPCR validation results were highly consistent with the RNA-seq findings.This study elucidates the interactive regulatory roles of TLR2,TLR4,and NLRP3 in conjunction with PGD2,which collectively modulate bovine endome-tritis.These findings offer significant molecular insights that enhance our understanding of the pathological mechanisms underlying bovine endometritis,thereby informing its prevention and treatment strategies.

Objective:To study the resistance of Aedes albopictus to commonly used insecticides in Hangzhou, and to investigate the polymorphism distribution characteristics of voltage-gated sodium channel (VGSC) and acetylcholinesterase (AchE) 1 (Ace-1) genes in Aedes albopictus in the region, providing a scientific basis for control of Aedes albopictus in Hangzhou. Methods:From May to June 2023, Aedes albopictus larvae and pupae were collected from residential areas across divided different urban areas by directions in Hangzhou. They were reared in the laboratory, and their resistance to malathion, propoxur, pyrethroid insecticides (permethrin, deltamethrin, and beta-cypermethrin) was evaluated using the World Health Organization-recommended adult mosquito contact tube method. The 24 h mortality rates of adult mosquito of 98% - 100% was susceptible, 80% - < 98% was suspected resistance, < 80% was resistant. Genomic DNA was extracted from adult Aedes albopictus, and mutations in the VGSC and Ace-1 genes were detected through PCR amplification and Sanger sequencing. Results:The 24 h mortality rates of adult Aedes albopictus exposed to 0.5% malathion, 0.05% propoxur, 0.4% permethrin, 0.03% deltamethrin, and 0.08% beta-cypermethrin in Hangzhou were 100% (75/75), 96.00% (72/75), 41.43% (29/70), 17.33% (13/75), and 32.86% (23/70), respectively. A total of 146 surviving Aedes albopictus were tested for VGSC gene mutations at diagnostic doses of pyrethroid insecticides. Among them, 6 Aedes albopictus (4.11%) had a gene mutation at position V1016, and 146 Aedes albopictus (100%) had a gene mutation at position F1534. A total of 63 Aedes albopictus that died at diagnostic doses of pyrethroid insecticides were analyzed for VGSC gene mutations. No gene mutation was detected at position V1016, while 63 Aedes albopictus (100%) had a gene mutation at position F1534. One non synonymous mutation was detected at position V1016 of the VGSC gene, which was a heterozygous mutation of V1016V to V1016V/G. Two non synonymous mutations were detected at position F1534 of the VGSC gene, namely F1534F to F1534S or a F1534F/S heterozygous mutation. No Ace-1 gene mutation was detected in all Aedes albopictus exposed to 0.05% propoxur ( n = 75). Conclusions:The Aedes albopictus in Hangzhou has developed resistance to permethrin, deltamethrin, and beta-cypermethrin. It shows suspected resistance to propoxur and sensitivity to malathion. Moreover, a high frequency of mutations in the VGSC gene has been observed in these mosquitoes. It is crucial to enhance resistance monitoring in Aedes albopictus populations in Hangzhou and to implement the rational rotation of chemical insecticides to slow down the progress of drug resistance.

Escherichia coli(E.coli)is a key pathogenic bacterium responsible for postpartum endo-metritis,with its colonization in the reproductive tract closely associated with endometrial damage and disruption of the ovarian cycle.This ultimately leads to infertility,causing significant economic losses to the dairy industry.Macrophages play a pivotal role in the inflammatory response.This study aims to investigate the mRNA expression profile of bovine bone marrow-derived macropha-ges following E.coli infection using RNA sequencing(RNA-seq)technology.Additionally,it seeks to identify the biological functions and signaling pathways of differentially expressed genes(DEGs)through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses.The results demonstrated that E.coli infection induced differential expression of 4 522 genes,with 2 141 upregulated and 2 381 downregulated.These genes were primarily asso-ciated with inflammatory responses,where TLR2,TLR4,NLRP3,and PTGS2 played pivotal roles.PGD2 synthesis was mediated by TLR2,TLR4,and NLRP3.Transcriptome sequencing of bovine bone marrow-derived macrophages infected with E.coli and treated with a PGD2 inhibitor revealed a marked downregulation of TLR2 and TLR4 gene expression.qPCR validation results were highly consistent with the RNA-seq findings.This study elucidates the interactive regulatory roles of TLR2,TLR4,and NLRP3 in conjunction with PGD2,which collectively modulate bovine endome-tritis.These findings offer significant molecular insights that enhance our understanding of the pathological mechanisms underlying bovine endometritis,thereby informing its prevention and treatment strategies.

This study was designed to evaluate the correlation between immune antibodies and pelvic inflammatory disease(PID)using retrospective analysis.Cases were selected from 171 patients who met the diagnosis of PID in Liuzhou People's Hospital of Guangxi Province from January 2022 to March 2023,and the PID patients were further divided into simple PID group(53 cases)and in PID combined with reproductive tract infection group(118 cases)according to the presence or absence of reproductive tract infections,while 83 cases of women who did not meet the specific diagnostic criteria of PID and did not have reproductive tract infections were selected as the control group during the same period.The positive rate of immune antibodies in the three groups were observed and compared to explore the relationship between immune antibodies and PID.Data showed that the positive rates of immune antibodies were significantly higher in the PID alone group and the PID combined with reproductive tract infection group than that in the control group.Furthermore,the positive rate of immune antibody TPOAb was significant difference in the PID combined with reproductive tract infection group and the PID alone group(P<0.05).In conclusion,TPOAb is closely associated with reproductive tract infections.

Objective:To investigate the distribution and seasonal fluctuations of flies in Hangzhou, study the resistance of Musca domestica ( M. domestica) to five commonly used sanitary insecticides and changing patterns in Hangzhou and provide a basis for scientific control of flies. Methods:From April to November 2023, the cage trap method was used for ecological monitoring of flies. From May to June 2023, the swing net method was used to collect M. domestica from various districts (counties and cities) in Hangzhou. After indoor breeding, the resistance of F1 generation female adult flies to five commonly used sanitary insecticides was determined using the micro-drop method. Probit regression model was used to calculate the median lethal dose (LD 50), 95% confidence interval ( CI) and virulence regression equation. Results:In 2023, the fly density in Hangzhou was 5.99 flies/cage, with a higher density of flies belonging to the Sarcophagus family (2.39 flies/cage), making it the dominant fly species in Hangzhou. Among different monitoring points, the fly density in Linping District was relatively high (20.97 flies/cage). In different habitats, the fly density in agricultural markets was relatively high (fly density from April to November: 2.86, 5.39, 8.86, 16.86, 31.32, 6.39, 3.75 and 1.89 flies/cage). The seasonal fluctuation of fly density showed a unimodal pattern, with the higher density in August (13.45 flies/cage). The M. domestica population in Hangzhou was sensitive to dichlorvos [resistance ratio ( RR): 3.08 times]. Different degrees of resistance were developed to propoxur, deltamethrin, beta-cypermethrin, and beta-cyhalothrin. The degree of resistance from high to low was propoxur (> 336.36 times), beta-cypermethrin (906.61 times), beta-cyhalothrin (432.29 times), and deltamethrin (72.56 times). Based on the monitoring results from 2003 to 2023, the RR of dichlorvos reached the higher level in 2008 (33.47 times) and gradually decreased to a sensitive level. The resistance level of propoxur had been at an extremely high level over the years. Three types of pyrethroid insecticides all had high resistance. Conclusions:The species of flies in the Sarcophagus family are the dominant population in Hangzhou, and M. domestica has developed high resistance to four commonly used insecticides except for dichlorvos. The use of physical control techniques is advocated to reduce the use of chemical pesticides, and prevent the continuous increase of resistance in M. domestica.

Low dose radiation (LDR) is a relatively low dose, but it is important in the fields of occupational health, medical radiation protection and environmental protection. Therefore, the effects of LDR on DNA damage repair and its potential mechanisms have attracted increasing attention. LDR mainly acts on DNA molecules in direct or indirect ways, leading to DNA double strand breaks (DSBs), which then triggers DNA damage, forms cluster damage, and induces DNA damage repair, which has a potential impact on organisms. However, long-term LDR exposure may lead to dysfunction of the DNA repair system and increase the risk of accumulating DNA damage. LDR-induced DNA damage response is an adaptive response, with DNA damage repair being one of its main mechanisms. The repair of DSBs is particularly important, with the main repair methods including homologous recombination and non-homologous end joining. LDR may also trigger adaptive responses by activating immune cells, enhancing cellular antioxidant capacities, and through varies of specific biological mechanisms such as immune/inflammatory response and antioxidant responses. The biological effects of LDR mainly include cell stress response, cell cycle regulation and bystander effect. In the future, it is necessary to further explore the molecular mechanism of LDR's impact on organism health and evaluate its impact on radiation risk assessment and individualized protective measures, to better understand the basic principles of radiation biology and provide scientific basis for radiation protection, risk assessment and injury treatment.

BACKGROUND: Ovarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer. METHODS: LncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 ( SNAI2 ) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo . Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2 . RESULTS: AC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo . miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis. CONCLUSION AC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.
Animals ; Mice ; Humans ; Female ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Ovarian Neoplasms/metabolism* ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/genetics* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Snail Family Transcription Factors/metabolism*

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

Objective:To investigate the expression of inositol 1, 4, 5-triphate receptor (IP 3R)-glucose-regulated protein 75 (Grp75)-voltage dependent anion channel 1 (VDAC1)-mitochondrial Calcium uniporter (MCU) Calcium axis molecules in proteinuria and to explore its upstream regulator. Methods:Sixteen Sprague Dawley rats were divided into control group (6 rats) and Adriamycin (ADR) group (10 rats). Nephropathy rat model was established by single injection of ADR through tail vein.The glomerular expression of IP 3R, Grp75, VDAC1, MCU and the activation marker of mammalian target of Rapamycin complex 1 (mTORC1) were analyzed by immunohistochemical staining.In cultured mouse podocyte, ADR was used to induce podocyte injury, and the Everolimus of different concentrations was applied for intervention.The expression of the Calcium axis molecules and apoptosis marker was analyzed. Results:Compared with control group, the glomerular expression of IP 3R (0.02±0 vs.0, P<0.001), Grp75 (0.04±0 vs.0, P<0.001), VDAC1 (0.04±0 vs.0.01±0, P<0.001), and MCU (0.05±0.01 vs.0.01±0, P<0.001) were significantly increased in ADR-induced nephropathy rats, and the activation marker of mTORC1 (0.57±0.01 vs.0.18±0, P<0.001) was increased as well.In cultured mouse podocytes, compared with control group, the expression of Grp75 (1.89±1.17 vs.0.16±0.08, P=0.001), VDAC1 (1.59±0.34 vs.0.20±0.07, P=0.006), and MCU (1.56±0.38 vs.0.46±0.35, P=0.014) were obviously increased in ADR induced podocytes, and the activation marker of mTORC1 (2.12±0.08 vs.0.39±0.09, P<0.001) was also increased.Compared with the ADR induced podocytes, the expression of Grp75 (0.26±0.20 vs.1.89±1.17, P=0.001), VDAC1 (0.40±0.26 vs.1.59±0.34, P=0.014) and MCU (0.60±0.32 vs.1.56±0.38, P=0.029) in podocytes treated with ADR and 1.0 nmol/L Everolimus were remarkably decreased, accompanied with the decrease of mitochondrial calcium [(2 664.00±140.57) U vs.(3 025.16±180.92) U, P=0.023] and apoptosis marker cleaved Caspase-3 (0.55±0.28 vs.1.48±0.45, P=0.011). Conclusions:The over-production of IP 3R-Grp75-VDAC1-MCU Calcium axis molecules accompanied with the hyper-activation of mTORC1 was involved in ADR induced nephropathy rats.mTORC1 inhibitor decreased the expression of Calcium axis molecules in mouse podocytes, which might involve in the mechanism of mTORC1 inhibitor′s effects on podocyte.