ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

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.

Fermented traditional Chinese medicine(TCM) has a long history of medicinal use, such as Sojae Semen Praeparatum, Arisaema Cum Bile, Pinelliae Rhizoma Fermentata, red yeast rice, and Jianqu. Fermentation technology was recorded in the earliest TCM work, Shen Nong's Classic of the Materia Medica. Microorganisms are essential components of the fermentation process. However, the contamination of fermented TCM by toxigenic fungi and mycotoxins due to unstandardized fermentation processes seriously affects the quality of TCM and poses a threat to the life and health of consumers. In this paper, the characteristics, microbial composition, and mycotoxin profile of fermented TCM are systematically summarized to provide a theoretical basis for its quality and safety control.
Fermentation ; Mycotoxins/analysis* ; Drugs, Chinese Herbal/analysis* ; Fungi/classification* ; Bacteria/genetics* ; Drug Contamination ; Medicine, Chinese Traditional

Aim To explore the effect of salvianolic acid B(SalB)on improving non-alcoholic fatty liver by regulating Lcn2.Methods In vivo experiments,8-week-old male C57BL/6J mice were fed with regular maintenance diet as the control group,while 8-week-old ApoE-/-mice were fed with high-fat diet and random-ly divided into the model group and SalB group.After eight weeks of feeding,mice in the SalB group were ga-vaged with SalB at a low dose of 15 mg·kg-1·d-1 and a high dose of 30 mg·kg-1·d-1,while mice in the control and model groups were gavaged with equal doses of normal saline.The results of liver RNA-seq revealed differentially expressed genes between the model group and the SalB group.HE staining and Oil Red O staining were used to observe pathological chan-ges in liver tissue.The kit was used to detect lipid,ox-idative stress,and inflammation in serum and liver tis-sue.RT-qPCR was employed to detect the mRNA lev-els of Lcn2,SREBP-1C,and enzymes related to lipid synthesis.In vitro experiments established a NAFLD model by inducing L02 and LX-2 cells with palmitic acid(PA)for 24 hours,and the effect of SalB on non-alcoholic fatty liver in vitro was detected by co treat-ment of SalB(30 pmol·L-1)and PA(0.2 mmol·L-1).The assay kit was used to detect the content of TC and TG in L02 cells,the cell oil red O staining to detect the accumulation of lipids in L02 cells,and RT-qPCR to detect the mRNA levels of Lcn2,SREBP-1 C,and genes related to lipid metabolism in LX-2 cells.Results The biochemical indicators of serum and liver in the model group were abnormal,with elevated levels of lipid,inflammation,and oxidative stress in liver tis-sue.Large areas of lipid vacuoles and deposition were observed,and PA induced L02 cells also exhibited sig-nificant lipid accumulation.These liver lesions were significantly improved after intervention with SalB.The effect of SalB on regulating lipid metabolism and in-flammation was found from RNA-seq.The mRNA lev-els of liver and LX-2 cells showed significant upregula-tion of Lcn2,SREBP-1 C,and enzymes related to lipid metabolism in the model group,and markedly downreg-ulation in the SalB group.Conclusions SalB can im-prove non-alcoholic fatty liver,and its mechanism may be related to down-regulating the expression of Lcn2,SREBP-1 C,and lipid synthase.

Aim To explore the effect of salvianolic acid B(SalB)on improving non-alcoholic fatty liver by regulating Lcn2.Methods In vivo experiments,8-week-old male C57BL/6J mice were fed with regular maintenance diet as the control group,while 8-week-old ApoE-/-mice were fed with high-fat diet and random-ly divided into the model group and SalB group.After eight weeks of feeding,mice in the SalB group were ga-vaged with SalB at a low dose of 15 mg·kg-1·d-1 and a high dose of 30 mg·kg-1·d-1,while mice in the control and model groups were gavaged with equal doses of normal saline.The results of liver RNA-seq revealed differentially expressed genes between the model group and the SalB group.HE staining and Oil Red O staining were used to observe pathological chan-ges in liver tissue.The kit was used to detect lipid,ox-idative stress,and inflammation in serum and liver tis-sue.RT-qPCR was employed to detect the mRNA lev-els of Lcn2,SREBP-1C,and enzymes related to lipid synthesis.In vitro experiments established a NAFLD model by inducing L02 and LX-2 cells with palmitic acid(PA)for 24 hours,and the effect of SalB on non-alcoholic fatty liver in vitro was detected by co treat-ment of SalB(30 pmol·L-1)and PA(0.2 mmol·L-1).The assay kit was used to detect the content of TC and TG in L02 cells,the cell oil red O staining to detect the accumulation of lipids in L02 cells,and RT-qPCR to detect the mRNA levels of Lcn2,SREBP-1 C,and genes related to lipid metabolism in LX-2 cells.Results The biochemical indicators of serum and liver in the model group were abnormal,with elevated levels of lipid,inflammation,and oxidative stress in liver tis-sue.Large areas of lipid vacuoles and deposition were observed,and PA induced L02 cells also exhibited sig-nificant lipid accumulation.These liver lesions were significantly improved after intervention with SalB.The effect of SalB on regulating lipid metabolism and in-flammation was found from RNA-seq.The mRNA lev-els of liver and LX-2 cells showed significant upregula-tion of Lcn2,SREBP-1 C,and enzymes related to lipid metabolism in the model group,and markedly downreg-ulation in the SalB group.Conclusions SalB can im-prove non-alcoholic fatty liver,and its mechanism may be related to down-regulating the expression of Lcn2,SREBP-1 C,and lipid synthase.

Tacrolimus is the first immunosuppressive choice for organ transplantation.It is also used in the immunotherapy of many non-transplant diseases.Because of its large individual variabilities and narrow treatment window,the individualized administration for tacrolimus taking advantage of population pharmacokinetics is necessary.This article aims to summarize population pharmacokinetics studies of tacrolimus in patients with non-transplant diseases and its influencing factors,and to provide a reference for rational use of tacrolimus.

Tacrolimus is the first immunosuppressive choice for organ transplantation.It is also used in the immunotherapy of many non-transplant diseases.Because of its large individual variabilities and narrow treatment window,the individualized administration for tacrolimus taking advantage of population pharmacokinetics is necessary.This article aims to summarize population pharmacokinetics studies of tacrolimus in patients with non-transplant diseases and its influencing factors,and to provide a reference for rational use of tacrolimus.

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 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