Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Receptor-interacting protein kinase 1 (RIPK1) plays an essential role in regulating the necroptosis and apoptosis in cerebral ischemia-reperfusion (I/R) injury. However, the regulation of RIPK1 kinase activity after cerebral I/R injury remains largely unknown. In this study, we found the downregulation of protein arginine methyltransferase 1 (PRMT1) was induced by cerebral I/R injury, which negatively correlated with the activation of RIPK1. Mechanistically, we proved that PRMT1 directly interacted with RIPK1 and catalyzed its asymmetric dimethylarginine, which then blocked RIPK1 homodimerization and suppressed its kinase activity. Moreover, pharmacological inhibition or genetic ablation of PRMT1 aggravated I/R injury by promoting RIPK1-mediated necroptosis and apoptosis, while PRMT1 overexpression protected against I/R injury by suppressing RIPK1 activation. Our findings revealed the molecular regulation of RIPK1 activation and demonstrated PRMT1 would be a potential therapeutic target for the treatment of ischemic stroke.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

A new alkaloid (1) and six known compounds (2-7) were isolated from the solid fermentation extract of the endophytic fungus Alternaria tenuissima Pas85 of Phragmites australis by silica gel column chromatography, Sephadex LH-20 column chromatography, high performance liquid chromatography and other chromatographic techniques. The structures of these compounds were determined by HREIMS, NMR, IR spectroscopy, and literature comparison, and the anti MRSA (methicillin-resistant Staphylococcus aureus) activity of 1-5 were tested. Compounds 1, 2, 3 and 4 exhibited certain inhibitory activity with MIC values of 64, 4, 32 and 32 μg·mL^-1, respectively, and compound 5 showed no significant inhibitory activity.

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

OBJECTIVE: To analyze factors associated with intestinal acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT) in children and to develop a prediction model for intestinal aGVHD after allo-HSCT in children. METHODS: The clinical data of 62 children who underwent allo-HSCT at the Department of Hematology of the People's Hospital of Xinjiang Uygur Autonomous Region from February 2018 to September 2021 were retrospectively analyzed. Intestinal aGVHD was evaluated according to the Mount Sinai Acute GVHD International Consortium (MAGIC) grading criteria, the variables were screened by LASSO (least absolute shrinkage and selection operator) regression analysis with 10-fold cross-validation, and developed a model for predicting intestinal aGVHD after allo-HSCT in children. RESULTS: A total of 33 (53.2%) of the 62 children developed intestinal aGVHD, of which 25 were degree II and 8 were degree III-IV. The results of screening variables by 10-fold cross-validated LASSO regression showed that the significant variables included ethnic minorities (OR =7.229; 95%CI: 2.337-22.354), platelet (PLT) (OR =0.971; 95%CI: 0.932-0.993), uric acid (UA) (OR =0.971; 95%CI: 0.935-0.988), C-reactive protein (CRP) (OR =1.217; 95%CI: 1.053-1.545), and viral infection (OR =10; 95%CI: 3.021-32.668), and these variables were independently associated with intestinal aGVHD in children (all P <0.05). A prediction model was constructed based on above variables. The area under the receiver operating characteristic (ROC) curve (AUC) of the model was calculated, and the AUC value was 0.985 (0.966-1), the Brier score was 0.055. The evaluation showed that the model has a high degree of discrimination and calibration. CONCLUSION Ethnic minorities, low PLT, low UA, high CRP, and viral infections are independently associated with intestinal aGVHD in children, and early attention should be paid to these high-risk children.
Humans ; Child ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Graft vs Host Disease/diagnosis* ; Risk Factors ; C-Reactive Protein ; Acute Disease

Objective: To analyze the immunological characteristics and antibody changes of patients infected with the Omicron BA.1 and evaluate the possibility of secondary infection. Methods: A total of 104 patients infected with Omicron BA.1 in the Jinnan District of Tianjin from January 8 to February 2, 2022, were included in the study. The control group and case group were matched 1∶1 based on age, sex and vaccination status. Serum was collected from the case group and control group at 3, 6 and 9 months after infection. The serum levels of interleukin4 (IL-4), IL-5 and interferon-gamma (IFN-γ), as well as the positive rates of IgG, IgG1 and IgG2, were detected by ELISA. Results: The highest concentration of IFN-γ in the case group at 6 months after infection was 145.4 pg/ml, followed by a decrease in concentration. The concentrations of IL-4 and IL-5 began to decrease at 6 months after infection (all P<0.001). There was no significant difference in the IgG2 positive rate between the case group and the control group at 6 months after BA.1 infection. However, at 9 months, there was a significant decrease compared to the control group (P=0.003). The ratio of IFN-γ/IL4 at 3 months after infection in the case group was lower than that in the control group (P<0.001). There was no significant difference in the ratio between the case group and the control group at 9 months after infection. Conclusion: The cellular immune function has been impaired at 3 months after infection with BA.1, and the specific cellular immune and humoral immune functions decrease significantly after 6 months, and the risk of secondary infection increases.
Adult ; Humans ; Immunity, Humoral ; Coinfection ; Interleukin-4 ; Interleukin-5 ; Immunoglobulin G ; Interferon-gamma