Activation of the G protein-coupled sulfakinin receptor inhibits blood meal intake in the mosquito Aedes aegypti.

Little is known about the blood-feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO-K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein-coupled (i.e., calcium-mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.

Metagenomics reveals the potential transmission risk of resistomes from urban park environment to human.

Urban parks play a significant role in urban ecosystems and are strongly associated with human health. Nevertheless, the biological contamination of urban parks - opportunistic pathogens and antibiotic resistance genes (ARGs) - has been poorly reported. Here, metagenomic and 16 S rRNA sequencing methods were used to study the distribution and assembly of opportunistic pathogens and ARGs in soil and water from nine parks in Lanzhou city, and further compared them with local human gut microbiomes to investigate the potential transmission risk. Our results revealed that the most important type of drug resistance in urban parks was multidrug resistance, with various resistance mechanisms. Approximately half of ARGs were shared between human gut and park environment, and it was noteworthy that cross-species transmission might exist among some high-risk ARGs, such as mepA and mdtE, with a significant enrichment in human gut. Metagenomic binning uncovered several bacterial genomes carrying adjacent ARGs, MGEs, and virulence genes, indicating a possibility that these genes may jointly transfer among different environments, particularly from park environment to human. Our results provided a reference point for the management of environmental pollutants in urban parks.

Gut microbiome and antibiotic resistance genes in plateau model animal (Ochotona curzoniae) exhibit a relative stability under cold stress.

Antibiotic resistance genes (ARGs) carried by gut pathogens may pose a threat to the host and ecological environment. However, few studies focus on the effects of cold stress on intestinal bacteria and ARGs in plateau animals. Here, we used 16S rRNA gene sequencing and gene chip technique to explore the difference of gut microbes and ARGs in plateau pika under 4 °C and 25 °C. The results showed that tetracycline and aminoglycoside resistance genes were the dominant ARGs in pika intestine. Seven kinds of high-risk ARGs (aadA-01, aadA-02, ermB, floR, mphA-01, mphA-02, tetM-02) existed in pika's intestine, and cold had no significant effect on the composition and structure of pika's intestinal ARGs. The dominant phyla in pika intestine were Bacteroidetes and Firmicutes. Cold influenced 0.47 % of pika intestinal bacteria in OTU level, while most other bacteria had no significant change. The diversity and community assembly of intestinal bacteria in pika remained relatively stable under cold conditions, while low temperature decreased gut microbial network complexity. In addition, low temperature led to the enrichment of glycine biosynthesis and metabolism-related pathways. Moreover, the correlation analysis showed that eight opportunistic pathogens (such as Clostridium, Staphylococcus, Streptococcus, etc.) detected in pika intestine might be potential hosts of ARGs.

High-Efficiency Alkyl Ketene Dimer Emulsions Stabilized by Polyaluminum Chloride and Chitosan Complex.

Based on the interaction of polyaluminum chloride (PAC) and chitosan (CTS) at the molecular level, an organic/inorganic composite material was designed for the preparation of alkyl ketene dimer (AKD) emulsion. This paper aimed to explore the influence of PAC/CTS on the physicochemical properties, microstructure, and sizing efficiency of AKD emulsions. The PAC/CTS complex forms a denser adsorption layer at the oil-water interface at the microscopic level. With the increase in CTS concentration, the AKD emulsions displayed excellent stability after high-speed centrifugation. In addition, the addition of CTS can effectively improve the sizing efficiency of the emulsion. Therefore, this study proposed a strategy of PAC/CTS as an emulsifier, and the related interaction mechanism was explored, which further expands the application of inorganic/organic composites in the field of colloidal chemistry.

Development and validation of a glioma prognostic model based on telomere-related genes and immune infiltration analysis.

Background: Gliomas are the most prevalent primary brain tumors, and patients typically exhibit poor prognoses. Increasing evidence suggests that telomere maintenance mechanisms play a crucial role in glioma development. However, the prognostic value of telomere-related genes in glioma remains uncertain. This study aimed to construct a prognostic model of telomere-related genes and further elucidate the potential association between the two. Methods: We acquired RNA-seq data for low-grade glioma (LGG) and glioblastoma (GBM), along with corresponding clinical information from The Cancer Genome Atlas (TCGA) database, and normal brain tissue data from the Genotype-Tissue Expression (GTEX) database for differential analysis. Telomere-related genes were obtained from TelNet. Initially, we conducted a differential analysis on TCGA and GTEX data to identify differentially expressed telomere-related genes, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses on these genes. Subsequently, univariate Cox analysis and log-rank tests were employed to obtain prognosis-related genes. Least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis were sequentially utilized to construct prognostic models. The model's robustness was demonstrated using receiver operating characteristic (ROC) curve analysis, and multivariate Cox regression of risk scores for clinical characteristics and prognostic models were calculated to assess independent prognostic factors. The aforementioned results were validated using the Chinese Glioma Genome Atlas (CGGA) dataset. Finally, the CIBERSORT algorithm analyzed differences in immune cell infiltration levels between high- and low-risk groups, and candidate genes were validated in the Human Protein Atlas (HPA) database. Results: Differential analysis yielded 496 differentially expressed telomere-related genes. GO and KEGG pathway analyses indicated that these genes were primarily involved in telomere-related biological processes and pathways. Subsequently, a prognostic model comprising ten telomere-related genes was constructed through univariate Cox regression analysis, log-rank test, LASSO regression analysis, and multivariate Cox regression analysis. Patients were stratified into high-risk and low-risk groups based on risk scores. Kaplan-Meier (K-M) survival analysis revealed worse outcomes in the high-risk group compared to the low-risk group, and establishing that this prognostic model was a significant independent prognostic factor for glioma patients. Lastly, immune infiltration analysis was conducted, uncovering notable differences in the proportion of multiple immune cell infiltrations between high- and low-risk groups, and eight candidate genes were verified in the HPA database. Conclusions: This study successfully constructed a prognostic model of telomere-related genes, which can more accurately predict glioma patient prognosis, offer potential targets and a theoretical basis for glioma treatment, and serve as a reference for immunotherapy through immune infiltration analysis.

Impact of Ae-GRD on Ivermectin Resistance and Its Regulation by miR-71-5p in Aedes aegypti.

iGABAR, a member of the Cys-loop ligand-gated ion channel superfamily, is a significant target of the insecticide ivermectin (IVM). GRD is the potential subunit of the insect iGABAR. However, little information about GRD in Ae. aegypti has been reported. In this study, we involved cloning and characterizing the iGABAR subunit GRD of Ae. aegypti (Ae-GRD). Sequence analysis indicated that Ae-GRD, as part of the cysteine-loop ligand-gated ion channel family, is similar to other insect GRD. RNA interference (RNAi) was employed to explore IVM resistance in Ae. aegypti, resulting in a significant reduction in Ae-GRD expression (p < 0.05), and the mortality of Ae. aegypti adults with Ae-GRD knockdown was significantly decreased after exposure to ivermectin. Bioinformatics prediction identified miR-71-5p as a potential regulator of Ae-GRD. In vitro, dual-luciferase reporter assays confirmed that Ae-GRD expression was regulated by miR-71-5p. Microinjection of miR-71-5p mimics upregulated miR-71-5p expression and downregulated Ae-GRD gene expression, reducing mortality by 34.52% following IVM treatment. Conversely, microinjection of a miR-71-5p inhibitor decreased miR-71-5p expression but did not affect the susceptibility to IVM despite increased Ae-GRD expression (p < 0.05). In conclusion, Ae-GRD, as one of the iGABA receptor subunits, is a potential target of ivermectin. It may influence ivermectin resistance by modulating the GABA signaling pathway. The inhibition of Ae-GRD expression by miR-71-5p decreased ivermectin resistance and consequently lowered the mortality rate of Ae. aegypti mosquitoes. This finding provides empirical evidence of the relationship between Ae-GRD and its miRNA in modulating insecticide resistance, offering novel perspectives for mosquito control strategies.

[Prognostic Significance of Progression of Disease within 24 Months in Mantle Cell Lymphoma].

OBJECTIVE: To investigate the effect of progression of disease within 24 months (POD24) on overall survival (OS) in patients with mantle cell lymphoma (MCL), and compare the clinical characteristics between POD24 and non-POD24 patients. METHODS: A retrospective analysis was performed on 50 MCL patients with treatment indications and regular treatment who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to August 2020. According to the occurrence of POD24, the patients were grouped for prognostic evaluation and clinical characteristics comparison. RESULTS: Univariate Cox regression analysis showed that POD24, PLT, albumin, MIPI score, ECOG PS score, LDH were the factors influencing OS in newly diagnosed MCL patients (all P < 0.05). The results of multivariate Cox regression analysis showed that POD24ï¼»HR=16.797(95%CI : 3.671-76.861),P < 0.001ï¼½, albumin<40 g/Lï¼»HR=3.238(95%CI :1.095-9.572),P =0.034ï¼½ and ECOG PS score≥2ï¼»HR=4.005(95%CI :1.033-15.521),P =0.045ï¼½ were independent risk factors influencing OS in MCL patients. The incidence of PLT<100×109/L (33.3% vs 5.9%, P =0.033) and ECOG PS score ≥2 (45.5% vs 5.9%, P =0.040) were significantly higher in POD24 patients than those in non-POD24 patients. CONCLUSION: POD24 is an independent poor prognostic factor affecting the OS of MCL patients, and the patients with PLT<100×109/L and ECOG PS score≥2 at diagnosis have a higher probability of POD24.

Fabrication and characterization of an alginate-based film incorporated with cinnamaldehyde for fruit preservation.

Sodium alginate (SA) is widely used in the food, biomedical, and chemical industries due to its biocompatibility, biodegradability, and excellent film-forming properties. This article introduces a simple method for preparing uniform alginate-based packaging materials with exceptional properties for fruit preservation. The alginate was uniformly crosslinked by gradually releasing calcium ions triggered by the sustained hydrolysis of gluconolactone (GDL). A cinnamaldehyde (CA) emulsion, stabilized by xanthan without the use of traditional surfactants, was tightly incorporated into the alginate film to enhance its antimicrobial, antioxidant, and UV shielding properties. The alginate-based film effectively blocked ultraviolet rays in the range of 400-200 nm, while allowing for a visible light transmittance of up to 70 %. Additionally, it showed an increased water contact angle and decreased water vapor permeability. The alginate-based film was also employed in the preparation of coated paper through the commonly used coating process in the papermaking industry. The alginate-based material displayed excellent antioxidant properties and antimicrobial activity against Escherichia coli, Staphylococcus aureus and Botrytis cinerea, successfully extending the shelf life of strawberries to 7 days at room temperature. This low-cost and facile method has the potential to drive advancements in the food and biomedical fields by tightly incorporating active oil onto a wide range of biomacromolecule substrates.

Circulating interleukins concentrations and post-stroke depression: A systematic review and meta-analysis.

Interleukins may play a role in supporting the diagnosis of post-stroke depression (PSD). Here, eight databases were employed to search for studies on circulating interleukins concentrations in patients with PSD. A total of 45 studies exploring circulating interleukins in PSD and stroke patients without depression (NPSD) were included in the retrieval database, including IL-1(5), IL-1ß (10), IL-2(6), IL-6(35), IL-10(7), IL-17(5), IL-18(6). Then, the RevMan 5.4 software was used for meta-analysis. The results of the meta-analysis showed that the PSD patients have higher concentrations of IL-1, IL-4, IL-6, and lower concentrations of IL-10 than NPSD patients. Additionally, the circulating IL-1, IL-6, and IL-18 concentrations in PSD patients were significantly higher than those in NPSD patients in the acute phase; the circulating IL-6 and IL-17 concentrations in PSD patients were significantly higher than those in NPSD patients at discharge; the PSD patients have lower concentrations sin IL-2 but higher concentrations in IL-6 and IL-17 than NPSD patients at the 3rd and 6th month. Our research provides evidence that circulating interleukins may have clinical utility as a biomarker for identifying PSD.

Psathrosterols C-E, highly conjugated ergosterol derivatives from Psathyrella rogueiana with anti-inflammatory and immunosuppressive activity.

Three new ergosterols featuring with a highly conjugated ring system, psathrosterols C-E (1-3), have been isolated from the fungus Psathyrella rogueiana. The structures with the absolute configurations were elucidated by means of spectroscopic methods and single crystal X-ray diffraction. Compounds 1-3 exhibit inhibitory activity against NO production with IC50 values ranging from 8.4 to 21.8 µM. Compound 1 inhibits the LPS-induced proliferation of B lymphocyte cells with an IC50 value of 12.3 µM.

A cell atlas of the adult female Aedes aegypti midgut revealed by single-cell RNA sequencing.

Aedes aegypti is a primary vector for transmitting various arboviruses, including Yellow fever, dengue and Zika virus. The mosquito midgut is the principal organ for blood meal digestion, nutrient absorption and the initial site of arbovirus infection. Although a previous study delineated midgut's transcriptome of Ae. aegypti at the single-nucleus resolution, there still lacks an established protocol for isolating and RNA sequencing of single cells of Ae. aegypti midgut, which is required for investigating arbovirus-midgut interaction at the single-cell level. Here, we established an atlas of the midgut cells for Ae. aegypti by single-cell RNA sequencing. We annotated the cell clusters including intestinal stem cells/enteroblasts (ISC/EB), cardia cells (Cardia), enterocytes (EC, EC-like), enteroendocrine cells (EE), visceral muscle (VM), fat body cells (FBC) and hemocyte cells (HC). This study will provide a foundation for further studies of arbovirus infection in mosquito midgut at the single-cell level.

Trophoblastic signals facilitate endometrial interferon response and lipid metabolism, ensuring normal decidualization.

The decidua plays a crucial role in providing structural and trophic support to the developing conceptus before placentation. Following embryo attachment, embryonic components intimately interact with the decidual tissue. While evidence indicates the participation of embryo-derived factors in crosstalk with the uterus, the extent of their impact on post-implantation decidual development requires further investigation. Here, we utilize transgenic mouse models to selectively eliminate primary trophoblast giant cells (pTGCs), the embryonic cells that interface with maternal tissue at the forefront. pTGC ablation impairs decidualization and compromises decidual interferon response and lipid metabolism. Mechanistically, pTGCs release factors such as interferon kappa (IFNK) to strengthen the decidual interferon response and lipoprotein lipase (LPL) to enhance lipid accumulation within the decidua, thereby promoting decidualization. This study presents genetic and metabolomic evidence reinforcing the proactive role of pTGC-derived factors in mobilizing maternal resources to strengthen decidualization, facilitating the normal progression of early pregnancy.

Role of arylalkylamine N-acetyltransferase 7 in reproduction and limb pigmentation of Aedes aegypti.

Arylalkylamine N-acetyltransferase (aaNAT) is a crucial enzyme that catalyses the transfer of acetyl groups from acetyl coenzyme A to arylalkylamines and arylamines. Evolutionary studies have identified a distinct class of aaNATs specific to mosquitoes, yet their functions remain elusive. This study focuses on Ae-aaNAT7, a mosquito-unique gene in Aedes aegypti (Diptera:Culicidae), to explore its functionality. Temporal and spatial expression analysis of Ae-aaNAT7 mRNA revealed high expression during embryonic development and in first-instar larvae, with notable expression in the limbs of adult mosquitoes based on tissue expression profiling. By further employing CRISPR/Cas9 technology for loss-of-function studies, our investigation revealed a reduction in the area of white spotting in the limbs of Ae-aaNAT7 mutant adult mosquitoes. Further investigation revealed a significant decrease in the fecundity and hatchability of the mutants. Dissection of the ovaries from Ae-aaNAT7 heterozygous mutants showed a noticeable reduction in the oocyte area compared with wild type. Dissection of the exochorion of the eggs from Ae-aaNAT7 homozygous mutants consistently revealed a striking absence of mature embryos. In addition, RNA interference experiments targeting Ae-aaNAT7 in males resulted in a reduction in fecundity, but no effect on hatchability was observed. These collective insights underscore the substantial impact of Ae-aaNAT7 on reproduction and its pivotal contribution to adult limb pigmentation in Ae. aegypti. These revelations offer insights pivotal for the strategic design of future insecticide targets.

Clinical analysis of the efficacy of radiation therapy for primary high-grade gliomas guided by biological rhythms.

OBJECTIVE: High-grade glioma (HGG) patients frequently encounter treatment resistance and relapse, despite numerous interventions seeking enhanced survival outcomes yielding limited success. Consequently, this study, rooted in our prior research, aimed to ascertain whether leveraging circadian rhythm phase attributes could optimize radiotherapy results. METHODS: In this retrospective analysis, we meticulously selected 121 HGG cases with synchronized rhythms through Cosinor analysis. Post-surgery, all subjects underwent standard radiotherapy alongside Temozolomide chemotherapy. Random allocation ensued, dividing patients into morning (N = 69) and afternoon (N = 52) radiotherapy cohorts, enabling a comparison of survival and toxicity disparities. RESULTS: The afternoon radiotherapy group exhibited improved overall survival (OS) and progression-free survival (PFS) relative to the morning cohort. Notably, median OS extended to 25.6 months versus 18.5 months, with P = 0.014, with median PFS at 20.6 months versus 13.3 months, with P = 0.022, post-standardized radiotherapy. Additionally, lymphocyte expression levels in the afternoon radiation group 32.90(26.10, 39.10) significantly exceeded those in the morning group 31.30(26.50, 39.20), with P = 0.032. CONCLUSIONS: This study underscores the markedly prolonged average survival within the afternoon radiotherapy group. Moreover, lymphocyte proportion demonstrated a notable elevation in the afternoon group. Timely and strategic adjustments of therapeutic interventions show the potential to improve therapeutic efficacy, while maintaining vigilant systemic immune surveillance. A comprehensive grasp of physiological rhythms governing both the human body and tumor microenvironment can refine treatment efficacy, concurrently curtailing immune-related damage-a crucial facet of precision medicine.

Silver Nanoparticles In Situ Enhanced Electrochemiluminescence of the Porphyrin Organic Matrix for Highly Sensitive and Rapid Monitoring of Tetracycline Residues.

Accurate monitoring of tetracycline (TC) residues in the environment is crucial for avoiding contaminant risk. Herein, a novel TC biosensor was facilely designed by integrating silver nanoparticles (Ag NPs) into the porphyrin metal-organic matrix (Ag@AgPOM) as a bifunctional electrochemiluminescence (ECL) probe. Different from the step-by-step synthesis of the co-reaction accelerator and ECL emitter, the co-reaction accelerators Ag NPs were in situ-grown on the surface of 5,10,15,20-tetrakis (4-carboxyphenyl) porphyrin (TCPP) via a simple one-pot approach. Symbiotic Ag NPs on Ag@AgPOM formed an intimate interface and increased the collision efficiency of the ECL reaction, achieving the ECL enhancement of TCPP. Under the optimized conditions, the ternary ECL biosensor showed a wide linear detection range toward TC with a low detection limit of 0.14 fmol L-1. Compared with the traditional HPLC and ELISA methods, satisfied analytical adaptability made this sensing strategy feasible to monitor TC in complex environmental samples.

[Toxic effect and mechanism of Tripterygium glycosides on ovarian germline stem cells of mice in vitro by Notch signaling pathway].

The ovarian germline stem cells(OGSCs) cultured in the optimized culture system were used as the research object to observe the effect of Tripterygium glycosides(TG) on OGSCs and explore the mechanism of reproductive toxicity by the Notch signaling pathway. Cell counting kit-8(CCK-8) was used to observe the viability level of OGSCs in mice cultured in vitro by TG of 3.75, 7.5, and 15 µg·mL~(-1). Immunofluorescence technology and reverse transcription-polymerase chain reaction(RT-PCR) were used to detect the protein and gene expression level of OGSCs marker mouse vasa homologue(MVH) and octamer-binding transcription factor 4(Oct4) by TG of 3.75 µg·mL~(-1). RT-PCR detected the gene expression of neurogenic locus Notch homolog protein 1(Notch1), Hes family BHLH transcription factor 1(Hes1), and jagged canonical Notch ligand 1(Jagged1). The RNA was extracted for transcriptome analysis to analyze the mechanism of action of TG intervention on OGSCs. 3.75 µg·mL~(-1) of TG was combined with 40 ng·mL~(-1) Notch signaling pathway γ-secretagocin agonist jagged canonical notch ligand(Jagged) for administration. CCK-8 was used to detect the viability level of OGSCs. Double immunofluorescence technology was used to detect the protein co-expression of MVH with Hes1, Notch1, and Jagged1. The results showed that compared with the blank group, the TG administration group significantly inhibited the activity of OGSCs(P<0.01 or P<0.001). It could reduce the protein and gene expression of OGSC markers, namely MVH and Oct4(P<0.05, P<0.01, or P<0.001). It could significantly inhibit the gene expression of Notch1, Hes1, and Jagged1(P<0.001). Transcriptomic analysis showed that TG affected the growth and proliferation of OGSCs by intervening Jagged1, a ligand associated with the Notch signaling pathway. The experimental results showed that the combination of Notch signaling pathway γ-secretagorein agonist Jagged could significantly alleviate the decrease in OGSC viability induced by TG(P<0.001) and significantly increased the OGSC viability compared with the TG group(P<0.001). It also could significantly increase the co-expression of MVH/Jagged1, MVH/Hes1, and MVH/Notch1 proteins(P<0.01 or P<0.001). It suggested that TG play the role of γ-secretagorease inhibitors by downregulating the OGSC markers including MVH and Oct4 and Notch signaling pathway molecules such as Notch1, Hes1, and Jagged1, participate in the OGSC pathway, and mediate reproductive toxicity caused by the Notch signaling pathway.

Immune protection of three serine protease inhibitors vaccine in mice against Rhipicephalus sanguineus.

Bioactive molecules in tick saliva are considered to be key to successful feeding and further the transmission of tick-borne pathogens. Problems such as pathogen transmission and animal weight loss result in tick infestation can cause tremendous economic losses to the livestock industry. Therefore, the development of a universal tick vaccine is urgently needed. In this paper, three serine protease inhibitor (serpin) proteins RMS-3, L7LRK7 and L7LTU1 were analyzed with bioinformatics methods. Subsequently the proteins were expressed and purified, and inoculated into Kunming mice for immune protection analysis. The amino acid sequence similarities between RMS-3, L7LRK7 and L7LTU1 were up to 90% in Rhipicephalus sanguineus. The recombinant RMS-3 + L7LRK7 + L7LTU1 showed anticoagulant reaction function and could inhibit the activity of CD4+ lymphocytes, when inoculated into Kunming mice. Additionally, After the immunized mice were challenged with Rhipicephalus sanguineus, the percentage of larvae and nymphs that were fully engorged dropped to 40.87% (P < 0.05) and 87.68% (P > 0.05) in the RmS-3 + L7LRK7 immune group, 49.57% (P < 0.01) and 52.06% (P < 0.05) in the RmS-3 + L7LTU1 group, and 45.22% (P < 0.05) and 60.28% (P < 0.05) in the RmS-3 + L7LRK7 + L7LTU1 immune group, in comparison with the control group. These data indicate that RmS-3 + L7LRK7 + L7LTU1 has good immune protection and has the potential to be developed into a vaccine against the larvae and nymphs of R. sanguineus.

Experience of multi-disciplinary treatment of multiple cerebellar diffuse large B-cell lymphoma: A case report.

RATIONALE: Primary central nervous system lymphoma (PCNSL) is a rare, highly malignant form of non-Hodgkin lymphoma categorized under the diffuse large B-cell type. It accounts for merely 1% of all non-Hodgkin lymphoma cases and comprises approximately 3% of all brain tumors. The involvement of the cerebellum is observed in only 9% of these cases. Recently, we came across an unusual instance: a young man presenting with multiple lesions located specifically within the cerebellum. PATIENT CONCERNS: A 26-year-old male was admitted to the hospital due to severe headaches. He has a medical history of sporadic headaches, accompanied by dizziness, nausea, and vomiting persisting for a month. Over the last 10 days, his headaches have intensified, coupled with decreased vision and protrusion of the eyeballs. Magnetic resonance imaging (MRI) revealed abnormal signals in both cerebellar hemispheres. DIAGNOSES, INTERVENTIONS, AND OUTCOMES: Diagnostic procedures included cerebellar biopsy, posterior fossa decompression, and lateral ventricle drainage. Histopathological examination identified diffuse large B-cell lymphoma (DLBCL) with high proliferative activity. To minimize neurotoxicity, chemotherapy involved intrathecal methotrexate (MTX) injections combined with the CHOP program. The patient has shown good tolerance to the treatment so far. LESSONS: While the definitive optimal treatment approach remains elusive, current chemotherapy centered on high-dose MTX stands as the standard induction therapy. Integrating surgery with radiotherapy and chemotherapy significantly extends patient survival.

MDR49 coding for both P-glycoprotein and TMOF transporter functions in ivermectin resistance, trypsin activity inhibition, and fertility in the yellow fever mosquito, Aedes aegypti.

This study investigated the function of the MDR49 gene in Aedes aegypti. MDR49 mutants were constructed using CRISPR/Cas9 technology; the mutation led to increased sensitivity to ivermectin (LC50: from 1.3090 mg L-1 to 0.5904 mg L-1), and a reduction in midgut trypsin activity. These findings suggest that the P-gp encoded by MDR49 confers resistance to ivermectin and impacts the reproductive function in Ae. aegypti. RNA interference technology showed that knockdown of MDR49 gene resulted in a significant decrease in the expression of VGA1 after a blood meal, as well as a decrease in the number of eggs laid and their hatching rate. LC-MS revealed that following ivermectin treatment, the MDR493d+2s/3d+2s strain larvae exhibited significantly higher drug concentrations in the head and fat body compared to the wild type. Modeling of inward-facing P-gp and molecular docking found almost no difference in the affinity of P-gp for ivermectin before and after the mutation. However, modeling of the outward-facing conformation demonstrated that the flexible linker loop between TM5 and TM6 of P-gp undergoes changes after the mutation, resulting in a decrease in trypsin activity and an increase in sensitivity to ivermectin. These results provide useful insights into ivermectin resistance and the other roles played by the MDR49 gene.

Roles of a newly lethal cuticular structural protein, AaCPR100A, and its upstream interaction protein, G12-like, in Aedes aegypti.

Mosquitoes form a vital group of vector insects, which can transmit various diseases and filarial worms. The cuticle is a critical structure that protects mosquitoes from adverse environmental conditions and penetration resistance. Thus, cuticle proteins can be used as potential targets for controlling the mosquito population. In the present study, we found that AaCPR100A is a structural protein in the soft cuticle, which has flexibility and elasticity allowing insects to move or fly freely, of Aedes aegypti. RNA interference (RNAi) of AaCPR100A caused high mortality in Aedes aegypti larvae and adults and significantly decreased the egg hatching rate. Transmission electron microscopy (TEM) analysis revealed that the larval microstructure had no recognizable endocuticle in AaCPR100A-deficient mosquitoes. A yeast two-hybrid assay was performed to screen proteins interacting with AaCPR100A. We verified that the G12-like protein had the strongest interaction with AaCPR100A using yeast two-hybrid and GST pull-down assays. Knockdown of G12-like transcription resulted in high mortality in Ae. aegypti larvae, but not in adults. Interestingly, RNAi of G12-like rescued the high mortality of adults caused by decreased AaCPR100A expression. Additionally, adults treated with G12-like dsRNA were found to be sensitive to low temperature, and their eggshell formation and hatching were decreased. Overall, our results demonstrated that G12-like may interacts with AaCPR100A, and both G12-like and AaCPR100A are involved in Ae. aegypti cuticle development and eggshell formation. AaCPR100A and G12-like can thus be considered newly potential targets for controlling the Ae. aegypti mosquito.