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More than 80% of the world's populations are at risk of vector-borne diseases, with mosquito-borne diseases as a significant global public health problem. Mosquito populations control is critical to interrupting the transmission of mosquito-borne diseases. This review summarizes the physical attributes, smell, vision, touch, and hearing of mosquitoes to unravel the preferences of female mosquitoes, and describes the mechanisms underlying the best male mating by female mosquitoes, so as to provide new insights into management of mosquito-borne diseases.

Objective: To investigate the feasibility of constructing the risk index of Echinococcus infection based on the classification of echinococcosis lesions, so as to provide insights into the management of echinococcosis., Methods: The imaging data of echinococcosis cases were collected from epidemiological surveys of echinococcosis in China from 2012 to 2016, and the detection of incident echinococcosis cases was captured from the annual echinococcosis prevention and control reports across provinces (autonomous regions) and Xinjiang Production and Construction Corps in China from 2017 to 2022. After echinococcosis lesions were classified, a risk index of Echinococcus infection was constructed based on the principle of discrete distribution marginal probability and multi-group classification data tests. The correlation between the risk index of Echinococcus infection and the detection of incident echinococcosis cases was evaluated in the provinces (autonomous regions and corps) from 2017 to 2022, and the correlations between the short and medium-term risk indices and between the medium and long-term risk indices of Echinococcus infection were examined using a univariate linear regression model., Results: A total of 4 014 echinococcosis cases in China from 2012 to 2016 were included in this study. The short-, medium- and long-term risk indices of E. granulosus infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ 2 = 4.12 to 708.65, all P values < 0.05), with high short- (0.058), medium- (0.137) and long-term risk indices (0.104) in Tibet Autonomous Region, and the short-, medium- and long-term risk indices of E. multilocularis infection varied in echinococcosis-endemic provinces (autonomous regions and corps) of China (χ 2 = 6.74 to 122.60, all P values < 0.05), with a high short-term risk index in Sichuan Province (0.016) and high medium- (0.009) and long-term risk indices in Qinghai Province (0.018). There were no significant correlations between the risk index of E. granulosus infection and the detection of incident cystic echinococcosis cases during the study period ( t = -0.518 to 2.265, all P values > 0.05), and strong correlations were found between the risk indices of E. multilocularis infection and the detection of incident alveolar echinococcosis cases (including mixed type) in 2018, 2020, 2021, 2022, during the period from 2017 through 2020, from 2017 through 2021, from 2017 through 2022 (all r values > 0.7, t = 2.521 to 3.692, all P values < 0.05). Linear regression models were established between the risk index of E. multilocular infection and the detection of alveolar echinococcosis cases (including mixed type), and the models were all statistically significant ( b = 0.214 to 2.168, t = 2.458 to 3.692, F = 6.044 to 13.629, all P values < 0.05). The regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. granulosus infection were 2.339 and 0.765, and the regression coefficients for the correlations between the medium- and short-term, and between the long- and medium-term risk indices of E. multilocular infection were 0.280 and 1.842, with statistical significance seen in both the regression coefficients and regression models ( t = 16.479 to 197.304, F = 271.570 to 38 928.860, all P values < 0.05)., Conclusions: The risk index of Echinococcus infection has been successfully established based on the classification of echinococcosis lesions, which may provide insights into the prevention and control, prediction, diagnosis and treatment, and classified management of echinococcosis.

Objective To investigate whether vitamin D3 (VD3) can alleviate Helicobacter pylori (Hp) infection by reducing blood lipids and inhibiting the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway. Methods High-cholesterol mouse model and Hp infected mouse model were established. Each was treated with VD3 via oral administration for 8 weeks. Real-time quantitative PCR was used to detect the expression of vitamin D receptor (VDR), insulin-induced gene 2 (Insig-2), and gastrin mRNA. Western blot analysis was used to examine the expression of JAK, STAT3, and cyclooxygenase-2 (COX2) proteins in gastric tissues. Biochemical analyses were performed to measure serum cholesterol levels, and ELISA was utilized to evaluate serum gastrin, interleukin 6 (IL-6), and IL-8 levels, along with histopathological examination of liver and gastric tissues using HE staining. Results After oral administration of VD3, the levels of VDR and Insig-2 in mouse liver tissue significantly increased in the high cholesterol group and the high cholesterol combined with Hp infection group. And the expression of serum gastrin decreased. The expression of JAK, STAT3 in gastric tissues reduced, as did the expression of COX2. Serum cholesterol levels decreased, with no significant changes in IL-6 levels, but a reduction in IL-8 levels. Compared to the control group, the high cholesterol combined with Hp infection group showed reduced hepatic ballooning degeneration and alleviated gastric tissue inflammation. In addition, inflammation in gastric tissue was also reduced in the cholesterol group and the Hp infection group. Conclusion VD3 alleviates gastritis by enhancing the activity of VDR in liver tissues, blocking the JAK/STAT3 signaling pathway, and inhibiting the expression of inflammatory factors.

Objective: To investigate the activity of Acorus tatarinowii extracts against dust mites, and to isolate and characterize active ingredient of A. tatarinowii extracts., Methods: The essential oil components were extracted from A. tatarinowii rhizome powder by rotary evaporation with methanol as solvents, followed by petroleum ether extraction and rotary evaporation. The essential oil was mixed with Tween-80 at a ratio of 1:1 and diluted into concentrations of 1.000 00%, 0.500 00%, 0.250 00%, 0.125 00%, 0.062 50% and 0.031 25%, while diluted Tween-80 served as controls. A. tatarinowii essential oil at each concentration (200 μL) was transferred evenly to filter papers containing 100 adult mites, with each test repeated in triplicate, and controls were assigned for each concentration. Following treatment at 25 °C and 75% relative humidity for 24 h, the mean corrected mortality of mites was calculated. The essential oil components were separated by silica gel column chromatography, and the essential oil was prepared in the positive column of medium pressure; and then, each component was collected. Silica gel column chromatography was run with the mobile phase that consisted of petroleum ether solution containing 10% ethyl acetate and pure ethyl acetate, detection wavelength of 254 nm, positive silica gel column as the chromatography column, and room temperature as the column temperature. Each component of the purified A. tatarinowii essential oil was diluted into 1.000 00% for acaricidal tests. The components with less than 100% acaricidal activity were discarded, and the remaining components were diluted into 50% of the previous-round tests for subsequent acaricidal tests. The components with acaricidal activity were subjected to high-performance liquid chromatography, liquid chromatography-mass spectrometry and pulsed-Fourier transform nuclear magnetic resonance spectroscopy. The structure of active monomer compounds was determined by standard spectral library retrieval and literature review., Results: A. tatarinowii essential oil at concentrations of 1.000 00%, 0.500 00%, 0.250 00% and 0.125 00% killed all dust mites, and the corrected mortality was all 100%. Exposure to A. tatarinowii extracts at an effective concentration of 0.062 50% for 24 hours resulted in 94.33% mortality of dust mites. Six components (A to F) were separated using gel column chromatography, and components D and E both showed a 100% acaricidal activity against dust mites at a concentration of 0.50000%. In addition, Component D was identified as isoeugenol methyl ether, and Component E as β-asarinol., Conclusions: The extract of A. tatarinowii essential oil has acaricidal activity, and the isoeugenol methyl ether shows a remarkable acaricidal activity against dust mites.

Objective To confirm that Hantaan virus (HTNV) can infect BEAS-2B human normal lung epithelial cells and examine the host immune response and metabolic changes induced by HTNV infection by transcriptomic analysis. Methods Western blotting, quantitative real-time PCR and immunofluorescence assay were used to assess the viral load in BEAS-2B cells, and RNA sequencing was employed for transcriptomic analysis. Results Following the infection of BEAS-2B cells with HTNV, there was an increase in the expression of HTNV nucleocapsid protein (NP) and small segment (S) over time. A transcriptomic analysis of these infected cells at 48-hour mark identified 328 genes that were differentially expressed. GO and KEGG enrichment analysis revealed that these differences were primarily associated with interferon response and innate immune pattern recognition receptor pathways. Protein-protein interaction network analysis identified several genes related to innate immune responses, including four genes encoding disintegrin and metalloproteinase with thrombospondin motifs. Metabolic pathway analysis showed three genes related to terpenoid backbone biosynthesis, two genes related to glycolysis/gluconeogenesis and two genes related to steroid hormone biosynthesis. Subcellular localization analysis indicated that many of the differentially expressed genes were located in mitochondria. Conclusion HTNV is capable of effectively infecting BEAS-2B cells, making them a suitable in vitro model for studying HTNV infection in human lung epithelial. By utilizing bioinformatics methods to screen for differentially expressed genes and metabolic pathways associated with HTNV infection, researchers can establish a theoretical foundation for investigating the molecular mechanisms underling HTNV infection.

Allergic rhinitis (AR), a common disease in otolaryngology, is a key risk factor for poorly controlled asthma and many complications, although it is not life-threatening. The negative impact of AR on social productive forces and human health is no less than that of asthma. Dendritic cells (DCs) play an important role in AR. In addition to sharing some of DC's biological characteristics, DCs-derived exosomes (DEXs) can promote the priming and activation of T cells and the maturation and differentiation of T helper type 2 (Th2) cells. Multiple signaling pathways in AR can be modulated by DEXs, which present allergens and participate in allergic immune responses. Anti-allergic drugs can be carried by DEXs to alleviate allergic airway inflammation and treat Th2-mediated AR effectively. Therefore, DEXs are crucial in the pathogenesis and treatment of AR.

Objective To prepare monoclonal antibodies against the envelope protein extracellular domain (Eecto) of Zika virus (ZIKV) in mice. Methods A prokaryotic expression plasmid, pET28a-ZIKV-Eecto of ZIKV Eecto, was constructed, transformed into Escherichia coli BL21 and induced by isopropyl β-D-thiogalactoside (IPTG). The recombinant Eecto protein was expressed in the form of inclusion bodies, and purified proteins were obtained through denaturation, renaturation and ultrafiltration. After three rounds of immunization with the Eecto protein, the serum of BALB/c mice was obtained and the titer of polyclonal antibodies in serum was determined. The reactivity of polyclonal antibodies was analyzed with Western blotting and immunofluorescence assay in HEK293T cells expressing the ZIKV prME. Spleen cells from mice with higher antibody titers were prepared and fused with SP2/0 myeloma cells. The hybridoma cells secreting antibodies were screened through the limited dilution method, and the ascites containing antibody were harvested for titer measurement and subclass analysis. The Eecto from the envelope proteins of Japanese encephalitis virus (JEV), Yellow fever virus (YFV), Dengue virus (DENV1-4), and Tick borne encephalitis virus (TBEV) were coated and used to analyze the cross-reactivity of ZIKV monoclonal antibodies by ELISA. Further specificity analysis was conducted on antibodies with high titers and strong specificity. Results The plasmid pET28a-ZIKV-Eecto was successfully constructed. The purified Eecto protein was obtained with good immunogenicity. Four monoclonal antibodies were prepared and screened, namely 1D6, 4F11, 4H7, and 4F8. Among them, 1D6, 4H7, and 4F8 are IgG (K) type antibodies, and 4F11 is an IgM (K) antibody. The ascitic fluid titer of 1D6 was higher than 1:10 8 . Antibodies 1D6 and 4H7 are ZIKV-specific and showed no cross-reactivity with other Flaviviruses. Conclusion The mice monoclonal antibodies against ZIKV-Eecto are produced successfully, which will provide experimental materials for the establishment of ZIKV detection methods and the study of its pathogenesis.

Objective To evaluate the toxicology of targeting human epidermal growth factor receptor-2 chimeric antigen receptor T (HER2-CAR-T) cells and to provide a safety basis for the clinical evaluation of HER2-CAR-T cell therapy. Methods The recombinant lentiviral vector was used to generate HER2-CAR-T cells. Soft agar colony formation assay was used to observe the colony formation of HER2-CAR-T cells, and the colony formation rate was statistically analyzed. The HER2-CAR-T cell suspension was co-incubated with rabbit red blood cell suspension, and the hemolysis of red blood cells was evaluated by direct observation and microplate reader detection. The HER2-CAR-T cell preparation was injected into the ear vein of male New Zealand rabbits, and the stimulating effect of HER2-CAR-T cells on the blood vessels of the animals was observed by staining of tissue sections. The vesicular stomatitis virus envelope glycoprotein (VSV-G) gene of pMD 2.G vector was used as the target sequence, and the safety of the lentiviral vector was verified by real-time fluorescence quantitative PCR. The heart, liver, lung, and kidney of mice receiving HER2-CAR-T cell infusion were collected, and the lesions were observed by HE staining. Results The HER2-CAR-T cells were successfully prepared. These cells did not exhibit soft agar colony formation ability in vitro, and the HER2-CAR-T cell preparation did not cause hemolysis in New Zealand rabbit red blood cells. After the infusion of HER2-CAR-T cells into the ear vein of New Zealand rabbits, no obvious vascular stimulation response was found, and no specific amplification of VSV-G was detected. No obvious lesions were found in the heart, liver, lung and kidney tissues of the treatment group. Conclusion The prepared HER2-CAR-T cells have reliable safety.

Objective To investigate the liver injury induced by chronic intermittent hypoxia (CIH) activation of NOD-like receptor pyrin domain containing protein 1 (NLRP1) inflammasome. Methods C57BL/6 male mice were randomly divided into control group and CIH group. Mice in CIH group were put into CIH chamber for molding (8 hours a day for 4 weeks). After 4 weeks of molding, liver tissue cells was observed by HE staining, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of mice were detected by kit. The levels of reactive oxygen species (ROS) in liver tissue were detected by dihydroethidine (DHE). The expression and localization of NLRP1, apoptosis speck-like protein containing a caspase activation and recruiting domain (ASC) and caspase-1 were detected by immunohistochemical staining. The protein expressions of NLRP1, ASC, caspase-1, interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were detected by Western blot analysis. The serum levels of IL-1β and TNF-α were detected by ELISA. Results Compared with the control group, the CIH group exhibited significant pathological changes in hepatocytes. Hepatocytes showed signs of rupture and necrosis, accompanied by inflammatory cell aggregation. Furthermore, the levels of ALT, AST, ROS, IL-1β and TNF-α were elevated, along with increased protein expressions of NLRP1, ASC, caspase-1, IL-1β and TNF-α. Conclusion CIH causes liver injury by activating NLRP1 inflammasome.

Tuberculosis (TB) remains one of the biggest infectious killers worldwide. Vaccine is the most satisfactory tool for prevention of TB; however, Bacillus Calmette-Guérin (BCG), the widely used vaccine in clinical for the prevention of TB, has limitations in protective effects. Development of novel TB vaccines is therefore of urgent need. Currently, there are 15 novel TB vaccine candidates in clinical trials, including live-attenuated vaccines, inactivated vaccines, subunit vaccines and viral-vectored vaccines, which open the door for the ultimate target of the End TB Strategy. This review summarizes the latest advances in the development of TB vaccines in global clinical trials, so as to provide insights into TB control.

Objective: To investigate the prevalence of tick-borne rickettsial infections in selected areas of Liupanshui City, Guizhou Province, 2023, so as to provide insights into the management of tick-borne rickettsioses in the city., Methods: Ticks were captured from the body surface of bovines and sheep in Gaoxing Village, Dashan Township, Liupanshui City, Guizhou Province during the period between April and June, 2023, and tick species were identified using morphological and molecular biological techniques. In addition, tick-borne Rickettsia was identified using a nested PCR assay, including spotted fever group rickettsiae (SFGR), Coxiella spp., Anaplasma spp., Ehrlichia spp., and Orientia spp., and positive amplified fragments were sequenced and aligned with known sequences accessed in the GenBank database., Results: A total of 200 ticks were collected and all tick species were identified as Rhipicephalus microplus . Nestle PCR assay combined with sequencing identified ticks carrying Candidatus Rickettsia jingxinensis (40.50%), Coxiella burnetii (1.50%), and Coxiella -like endosymbionts (27.00%), and Anaplasma spp., Ehrlichia spp. or Orientsia spp. was not detected., Conclusions: R. microplus carried Candidatus R. jingxinensis , C. burnetii , and Coxiella -like endosymbionts in selected areas of Liupanshui City, Guizhou Province. Intensified monitoring of tickborne rickettsial infections is needed in livestock and humans to reduce the damages caused by rickettsioses.

Objective To investigate the effect of 3-deazaadenosine (3-DAA), an N 6 -methyladenosine (m 6 A) methylation modification inhibitor, on the replication of the Japanese encephalitis virus (JEV). Methods Neuro2a mouse neuroblastoma cells, N9 mouse microglial cells, and BHK baby hamster kidney cells were exposed to JEV and then treated with 3-DAA. JEV was also injected into the footpad of adult C57BL/6 mice, which were then administered 3-DAA intraperitoneally. Real-time quantitative PCR was utilized to measure mRNA expression levels of JEV, interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), inducible nitric oxide synthase (iNOS), arginase 1 (Arg1), interferon (IFN)-α, IFN-β, IFN-γ, and C-X-C motif chemokine ligand 10 (CXCL10) in the cells and mouse brain tissues. Western blot analysis was used to detect JEV protein expression in the cells and mouse brain tissues. Furthermore, the survival of the mice was monitored and pathological changes in mouse brains were observed via hematoxylin and eosin (HE) staining. Results 3-DAA had a dose-dependent effect on the replication of RNA and protein expression of JEV in both BHK, N9, Neuro 2α cells and mouse brain tissues, which resulted in rapid progression of JEV infection in mice and a decrease in their survival rate. Furthermore, 3-DAA suppressed the expression of inflammatory factors such as IL-6, TNF-α, CXCL10, IL-1β and iNOS, thus weakening the immune response. Conclusion 3-DAA promotes JEV infection and hastens death of infected cells and mice, indicating that m 6 A modification may negatively regulate JEV replication.

Natural killer (NK) cells directly lysis the virus-infected cells through rapidly releasing cytotoxic mediators and cytokines. The balance between inhibitory and activated receptors on the surface of NK cells, as well as the corresponding ligands expressed on target cells are involved in the regulation of the cytotoxic function of NK cells. NKG2A is one of the highly anticipated inhibitory receptors expressed on NK cells, which can inhibit the cytotoxicity of NK cells to autologous normal tissue cells through interacting with the ligand HLA-E. The studies have shown that HLA-E is overexpressed on virus-infected cells and forms a complex with peptides derived from viral proteins. The interaction of HLA-E and NKG2A can regulate the functions of NK cells, participateing the pathogenesis process of virus infectious diseases. This review outlines the characteristics of the molecular interaction between NKG2A and HLA-E, as well as the mechanisms of NKG2A-HLA-E axis in regulating NK cell responses.

Hematopoietic stem cells (HSCs) posses the potential for highly self-renewal, proliferation and multi-lineage differentiation. HSC transplantation has long been the primary method for treating hematologic disorders and autoimmune diseases, and the ability to rebuild the immune system after transplantation is a key indicator of success. To enhance the reconstruction ability of the immune system after transplantation, current research focuses on genetic engineering and the use of HSCs modified by clustered regularly interspaced short palindromic repeats (CRISPR) gene editing technology as a source of transplant cells. This article summaries the biological characteristics, regulatory mechanism, ability to differentiate into immune cells, as well as the application and advance in the treatment of blood disorders, immune deficiencies, cancers and other related diseases, aiming to provide references for the research on relevant diseases.

Objective: To construct an evaluation index system for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept, so as to provide insights into the control and elimination of mountain-type zoonotic visceral leishmaniasis using the One Health approach., Methods: A preliminary evaluation index system was constructed based on literature review, panel discussions and field surveys. Thirty-three experts were selected from 7 provincial disease control and prevention centers in Beijing Municipality, Hebei Province, Shanxi Province, Henan Province, Sichuan Province, Shaanxi Province and Gansu Province where mountain-type zoonotic visceral leishmaniasis was endemic, and two rounds of expert consultations were conducted to screen the indicators. The positive coefficient, degree of concentration, degree of coordination, and authority of the experts were calculated, and the normalized weights of each index were calculated with the analytic hierarchy process., Results: The response rates of questionnaires during two rounds of expert consultation were both 100.00% (33/33), and the authority coefficients of the experts were 0.86 and 0.88, respectively. The coefficients of coordination among experts on the rationality, importance, and operability of the indicators were 0.392, 0.437, 0.258, and 0.364, 0.335, 0.263, respectively (all P values < 0.05). Following screening, the final evaluation index system included 3 primary indicators, 17 secondary indicators, and 50 tertiary indicators. The normalized weights of primary indicators "external environment", "internal support" and "comprehensive control" were 16.98%, 38.73% and 44.29%, respectively. Among the secondary indicators of the primary indicator "external environment", the highest weight was seen for natural environment (66.67%), and among the secondary indicators of the primary indicator "internal support", the lowest weight was seen for the scientific research for visceral leishmaniasis control (8.26%), while other indicators had weights of 12.42% to 13.38%. Among the secondary indicators of the primary indicator "comprehensive control", the weight was 16.67% for each indicator., Conclusions: An evaluation index system has been constructed for the capability of comprehensive control of mountain-type zoonotic visceral leishmaniasis based on the One Health concept. In addition to assessment of the effect of conventional mountain-type zoonotic visceral leishmaniasis control measures, this index system integrates the importance of top-level design, organizational management, and implementation of control measures, and includes indicators related to multi-sectoral cooperation.

Cancer associated fibroblasts (CAFs) are one of the main components of tumor microenvironment (TME). In TME, the interaction between tumor cells and non-tumor cells or among non tumor cells can promote the occurrence and development of tumors. CAFs can interact with a variety of immune cells and promote the occurrence and development of tumors by inhibiting the function of adaptive immune cells and reshaping the immune microenvironment in TME. The interaction between CAFs and macrophages and the induction of macrophage polarization towards M2 type play an important role in promoting tumor occurrence and development. This article reviews the research progress of CAF in promoting the polarization of M2 macrophages.

Mycobacterium tuberculosis heat resistant antigen (MTB-HAg) is a polypeptide antigen released from Mycobacterium tuberculosis (MTB) H37Ra to the supernatant after being autoclaved at 121 DegreesCelsius for 20 minutes. γδ T cells are unconventional T cells widely distributed in non-lymphoid tissues. They secrete cytokines such as TNF-α and IFN-γ, and play an important role in the immune response against MTB infection. MTB-HAg can effectively stimulate the proliferation and activation of γδ T cells in vitro, enabling them to participate more efficiently in the anti-TB infection process. Therefore, MTB-HAg is a potential target for the design of novel TB vaccines or drugs. However, due to its complex composition, it is still unknown which component of MTB-HAg stimulates the anti-MTB infection function of γδ T cells.

Objective: To investigate the prevalence and epidemiological characteristics of taeniasis and cysticercosis among residents in Tibetan agricultural areas of Sichuan Province, so as to provide insights for the prevention and control of taeniasis and cysticercosis., Methods: From 2016 to 2022, Kangding City, Daocheng County, Derong County, Ruoergai County and Muli Tibetan Autonomous County were sampled from Tibetan agricultural areas of Ganzi Tibetan Autonomous Prefecture, Aba Tibetan and Qiang Autonomous Prefecture and Liangshan Yi Autonomous Prefecture in Sichuan Province, and 1 to 6 townships were sampled from each county (district), followed by 4 to 7 villages sampled from each township. Primary school children were sampled using a cluster sampling method, and permanent residents at ages of over 16 years were randomly sampled from each village. Participants' demographics, history of tapeworm excretion during the past year and clinical symptoms and signs of cysticercosis were collected through questionnaire surveys, and participants' stool and venous blood samples were collected. Taenia eggs were detected in stool samples using the direct smear method, and deworming was performed among taeniasis patients with areca nut-squash seeds. The tapeworm species were identified using a multiplex PCR assay, and serum specific IgG antibody against cysticercus was detected using enzyme-linked immunosorbent assay (ELISA)., Results: A total of 5 249 respondents participated in the questionnaire survey, including 603 respondents (11.5%) with a self-reported history of proglottids secretion during the past year. A total of 3 976 residents were subjected to stool examinations, and the detection of Taenia eggs was 6.5%. Of 258 participants undergoing deworming, there were 403 cases (94.2%) with excretions of Taenia worms or proglottids. The mean prevalence of taeniasis was 10.9% (439/4 043), and there were gender-, age- and region-specific prevalence rates of taeniasis (χ 2 = 36.73, 126.31 and 163.41, all P values < 0.05). Multiplex PCR assays detected 41 cases with T. solium infections (12.5%), 197 cases with T. saginata infections (59.9%) and 91 cases with T. asiatica infections (27.6%) among 329 patients undergoing deworming, and there were region-specific prevalence rates of T. solium , T. saginata and T. asiatica infections (χ 2 = 45.39, P < 0.05). In addition, the sero-prevalence of anti-cysticercus IgG antibody was 7.0% (345/4 933), and there were age- and region-specific sero-prevalence rates of anti-cysticercus IgG antibody (χ 2 = 13.49 and 51.76, both P values < 0.05)., Conclusions: Multiple Taenia species are prevalent in Tibetan agricultural areas of Sichuan Province and the sero-prevalence of anti-cysticercus antibody is high among residents. Monitoring and control of taeniasis and cysticercosis should be strengthened.

Objective To construct a recombinant poxvirus vector vaccine, rVTTδTK-RBD, and to evaluate its safety and immunogenicity. Methods The receptor-binding domain (RBD) gene was synthesized with reference to the gene sequence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was inserted into the polyclonal site of the self-constructed recombinant plasmid pSTKE, to construct the recombinant poxvirus shuttle vector pSTKE-RBD. This was then transfected into BHK-21 cells pre-infected with the vaccinia virus Tiantan strain (VTT). The recombinant poxvirus rVTTδTK-RBD was successfully obtained after several rounds of fluorescence phage screening. The effect of rVTTδTK-RBD on the body mass of BALB/c mice was detected after immunizing mice by intra-nasal vaccination. The levels of specific and neutralizing antibodies produced by rVTTδTK-RBD on BALB/c mice were analyzed after immunizing mice intramuscularly. The effect of rVTTδTK-RBD on T cell subsets in BALB/c mice was detected by flow cytometry. Results Through homologous recombination, enhanced green fluorescent protein (EGFP) screening marker, and multiple rounds of fluorescent phosphorescence phage screening, a recombinant poxvirus rVTTδTK-RBD, expressing RBD with deletions in the thymidine kinase (TK) gene, was successfully obtained, which was validated by PCR. The in vivo experiments on BALB/c mice showed that rVTTδTK-RBD was highly immunogenic against SARS-CoV-2 and significantly reduced toxicity to the body compared to the parental strain VTT. Conclusion The recombinant poxvirus vaccine rVTTδTK-RBD against SARS-CoV-2 is successfully constructed and obtained, with its safety and immunogenicity confirmed through various experiments.

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.

Objective To prepare mouse monoclonal antibodies against the ectodomain of E2 (E2ecto) glycoprotein of Western equine encephalitis virus (WEEV). Methods A prokaryotic expression plasmid pET-28a-WEEV E2ecto was constructed and transformed into BL21 (DE3) competent cells. E2ecto protein was expressed by IPTG induction and presented mainly as inclusion bodies. Then the purified E2ecto protein was prepared by denaturation, renaturation and ultrafiltration. BALB/c mice were immunized with the formulated E2ecto protein using QuickAntibody-Mouse5W as an adjuvant via intramuscular route, boosted once at an interval of 21 days. At 35 days post-immunization, mice with antibody titer above 1×10 4 were inoculated with E2ecto intraperitoneally, and spleen cells were fused with SP2/0 cells three days later. Hybridoma cells secreting specific monoclonal antibodies were screened by the limited dilution method, and ascites were prepared after intraperitoneal inoculation of hybridoma cells. The subtypes and titers of the antibodies in ascites were assayed by ELISA. The biological activity of the mAb was identified by immunofluorescence assay(IFA) on BHK-21 cells which were transfected with eukaryotic expression plasmid pCAGGS-WEEV-CE3E2E1. The specificity of the antibodies were evaluated with E2ecto proteins from EEEV and VEEV. Results Purified WEEV E2ecto protein was successfully expressed and obtained. Four monoclonal antibodies, 3G6G10, 3D7G2, 3B9E8 and 3D5B7, were prepared, and their subtypes were IgG2c(κ), IgM(κ), IgM(κ) and IgG1(κ), respectively. The titers of ascites antibodies 3G6G10, 3B9E8 and 3D7G2 were 10 5 , and 3D5B7 reached 10 7 . None of the four antibody strains cross-reacted with other encephalitis alphavirus such as VEEV and EEEV. Conclusion Four strains of mouse mAb specifically binding WEEV E2ecto are successfully prepared.

Hepatocellular carcinoma (HCC) is well characterized as a heterogeneous disease. Its late-stage diagnosis and chemotherapy resistance make it one of the refractory tumors in China. Natural killer (NK) cells play a significant role in immune surveillance. However, NK cells become dysfunctional in the progression of HCC, leading to tumor immune escape. This article reviews the recent progress on different strategies of NK cell-based immunotherapy in treating HCC, including direct adoptive NK cell transfer, gene engineering in NK cell, NK cell receptor targeting, immunosuppressive microenvironment modification, and tumor toxicity enhancement by cytokines or traditional Chinese medicine. These NK cell-based strategies have shown promising therapeutic potential.

Objective: To establish a snail control approach for spraying chemicals with drones against Oncomelania hupensis in complex snail habitats in hilly regions, and to evaluate its molluscicidal effect., Methods: The protocol for evaluating the activity of spraying chemical molluscicides with drones against O. hupensis snails was formulated based on expert consultation and literature review. In August 2022, a pretest was conducted in a hillside field environment (12 000 m 2 ) north of Dafengji Village, Dacang Township, Weishan County, Yunnan Province, which was assigned into four groups, of no less than 3 000 m 2 in each group. In Group A, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with drones at a dose of 40 g/m 2 , and in Group B, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with drones at a dose of 40 g/m 2 , while in Group C, environmental cleaning was not conducted and 5% niclosamide ethanolamine salt granules were sprayed with knapsack sprayers at a dose of 40 g/m 2 , and in Group D, environmental cleaning was performed, followed by 5% niclosamide ethanolamine salt granules sprayed with knapsack sprayers at a dose of 40 g/m 2 . Then, each group was equally divided into six sections according to land area, with Section 1 for baseline surveys and sections 2 to 6 for snail surveys after chemical treatment. Snail surveys were conducted prior to chemical treatment and 1, 3, 5, 7 days post-treatment, and the mortality and corrected mortality of snails, density of living snails and costs of molluscicidal treatment were calculated in each group., Results: The mortality and corrected mortality of snails were 69.49%, 69.09%, 53.57% and 83.48%, and 68.58%, 68.17%, 52.19% and 82.99% in groups A, B, C and D 14 days post-treatment, and the density of living snails reduced by 58.40%, 63.94%, 68.91% and 83.25% 14 days post-treatment relative to pre-treatment in four groups, respectively. The median concentrations of chemical molluscicides were 37.08, 35.42, 42.50 g/m 2 and 56.25 g/m 2 in groups A, B, C and D, and the gross costs of chemical treatment were 0.93, 1.50, 0.46 Yuan per m 2 and 1.03 Yuan per m 2 in groups A, B, C and D, respectively., Conclusions: The molluscicidal effect of spraying 5% niclosamide ethanolamine salt granules with drones against O. hupensis snails is superior to manual chemical treatment without environmental cleaning, and chemical treatment with drones and manual chemical treatment show comparable molluscicidal effects following environmental cleaning in hilly regions. The cost of chemical treatment with drones is slightly higher than manual chemical treatment regardless of environmental cleaning. Spraying 5% niclosamide ethanolamine salt granules with drones is recommended in complex settings with difficulty in environmental cleaning to improve the molluscicidal activity and efficiency against O. hupensis snails.

Objective To investigate the expressions of IL-18, IL-18 binding protein isoform a (IL-18BPa) and IL-18 receptor α (IL-18Rα) in blood CD4 + Th2 cells of patients with allergic rhinitis (AR) and the effects of allergens on their expressions. Methods Blood samples of AR patients and healthy control subjects (HCs) were collected. Peripheral blood mononuclear cells (PBMCs) and CD4 + T cells sorted by immunomagnetic beads were stimulated by crude extract of Artemisia sieversiana wild allergen (ASWE), Platanus pollen (PPE) and house dust mite extract (HDME). Flow cytometry was used to detect the expression of IL-18, IL-18BPa and IL-18Rα in CD4 + Th2 cells, and BioPlex was used to detect the level of plasma IL-4 and analyze its correlation with the proportion of IL-18 + Th2 cells. Results Compared with HCs, the proportion of IL-18 + cells was increased in Th2 cells of AR patients; MFI of IL-18 was increased, while that of IL-18Rα was decreased. Moreover, allergens induced IL-18 and IL-18Rα expression in sorted CD4 + Th2 cells of HCs and induced IL-18Rα in that of AR patients. Additionally, elevated plasma IL-4 level was found in AR patients, which was moderately correlated with the percentage of IL-18 + Th2 cells. Conclusion Allergens may be involved in the pathogenesis of AR by inducing expression of IL-18 in peripheral blood CD4 + Th2 cells.

Objective: To investigate the HIV-1 genotype and distribution of newly diagnosed HIV-1 cases in Fujian Province in 2020, so as to provide insights into formulation of the precise AIDS control strategy in the province., Methods: Newly diagnosed HIV-1 cases without antiretroviral therapy (excluding AIDS patients) were randomly sampled from each city of Fujian Province in 2020 at a proportion of 50% of the mean number of HIV-infected cases reported across 9 cities of Fujian Province during the past three years. Subjects' demographic and epidemiological data were collected and blood samples were collected. The HIV-1 pol gene was amplified using nested reverse-transcription PCR assay, and the gene sequences were used for HIV-1 genotyping and phylogenetic analysis. The gene sequences were uploaded to the HIV Drug Resistance Database (http://hivdb.stanford.edu) for genotypic drug resistance assays, and the scores and level of HIV drug resistance were estimated using the HIVDB Algorithm version 9.5., Results: A total of 1 043 newly diagnosed HIV-1 cases were reported in Fujian Province in 2020, and 936 gene sequences were successfully obtained following sequencing of blood samples. There were 9 HIV-1 genotypes characterized in blood samples from 936 newly diagnosed HIV-1 cases, with CRF07&#95;BC (52.1%) and CRF01&#95;AE (30.4%) as predominant subtypes, followed by CRF08&#95;BC (4.9%), CRF55&#95;01B (3.0%), subtype C (2.5%), subtype B (2.1%), CRF85&#95;BC (1.7%), CRF59&#95;01B (0.3%) and CRF65&#95;CPX (0.1%), and unidentified subtypes were found in 26 blood samples. HIV-1 drug resistance was detected in 43 out of the 936 newly diagnosed HIV-1 cases, with 4.6% prevalence of HIV-1 drug resistance prior to therapy, and the highest drug resistance was found in the HIV CRF59&#95;01B subtype, followed by in CRF08&#95;BC, B, C, CRF01&#95;AE, CRF07&#95;BC and other subtypes, with a significant difference in the genotype-specific prevalence of HIV-1 drug resistance (χ 2 = 45.002, P < 0.05)., Conclusions: There was a HIV-1 genotype diversity in Fujian Province in 2020, and emerging recombinant and drug-resistant HIV-1 strains were detected and spread across patients and regions. Monitoring of HIV-1 genotypes is recommended to be reinforced for timely understanding of the transmission and spread of novel recombinant and drug-resistant HIV-1 strains.

Objective: To establish a surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin, so as to provide insights into creation of a sensitive and highly efficient surveillance and early warning system for schistosomiasis., Methods: National and international publications, documents, laws and regulations pertaining to schistosomiasis control were retrieved with keywords including schistosomiasis, surveillance, early warning and control interventions from 2008 to 2022, and a thematic panel discussion was held to preliminarily construct surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin. The index system was then comprehensively scored and screened using the Delphi method, and the weight of each index was determined using analytic hierarchy process and the modified proportional allocation method. In addition, the credibility of the Delphi method was evaluated using positive coefficient, authority coefficient, degree of concentration and degree of coordination of experts., Results: Following two rounds of expert consultation, a surveillance and early warning index system for schistosomiasis transmission risk in endemic areas along the middle and lower reaches of the Yangtze River basin was preliminarily constructed, including 3 primary indicators, 9 secondary indicators and 41 tertiary indicators. The normalized weights of primary indicators epidemics, natural and social factors and comprehensive control were 0.639 8, 0.145 6 and 0.214 6, respectively, and among all secondary indicators, snail status (0.321 3) and schistosomiasis prevalence (0.318 5) had the highest combined weights, while social factors had the lowest combined weight (0.030 4). Of all tertiary indicators, human egg-positive rate (0.041 9), number of acute schistosomiasis cases (0.041 5), number of stool-positive bovine and sheep (0.041 1), and prevalence of Schistosoma japonicum in free-ranging livestock (0.041 1) had the highest combined weights. During two rounds of consultation, the positive coefficient of experts was both 100%, and the authority coefficient was both 0.9 and greater, while the coordination coefficients were 0.338 to 0.441 and 0.426 to 0.565 (χ 2 = 22.875 to 216.524, both P values < 0.05)., Conclusions: The established surveillance and early warning index system for schistosomiasis transmission risk along the middle and lower reaches of the Yangtze River basin is of great scientific values and authority, which may provide insights into construction of the sensitive and highly efficient surveillance and early warning system for schistosomiasis in the context of low prevalence and low intensity of infection in China.

Since the outbreak of corona virus disease 2019 (COVID-19), viral strains have mutated and evolved. Vaccine research is the most direct and effective way to control COVID-19. According to different production mechanisms, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines included inactivated virus vaccine, live attenuated vaccine, mRNA vaccine, DNA vaccine, viral vector vaccine, virus-like particle vaccine and protein subunit vaccine. Among them, viral protein subunit vaccine has a wide application prospect due to its high safety and effectiveness. Viral nucleocapsid protein has high immunogenicity and low variability which could be a new direction for vaccine production. We summarized the current development of vaccine research by reviewing the current progress, vaccine safety and vaccine immune efficiency. It is hoped that the proposed possible development strategies could provide a reference for epidemic prevention work in future.

Colorectal cancer is a common malignant tumor in gastrointestinal tract. Its onset and development are associated with its own characteristics as well as the tumor microenvironment (TME) in which tumor-associated macrophages (TAMs) are the most abundant immune cells. After being recruited to the tumor site and stimulated by different signals in TME, TAMs can grow into two different subtypes, namely M1 and M2. TAMs are mainly manifested as M1 macrophages in the early stage of colorectal cancer, mediating the immune response to inhibit tumor growth. In the late stage, TAMs mainly grow into M2 macrophages, showing the ability to suppress immunity, stimulate the proliferation of tumor cells and tumor angiogenesis, and promote the invasion and metastasis of tumor cells. It has been found that intervention in TAMs polarization can regulate its relationship with the onset and development of colorectal cancer.

Objective To investigate the role of proanthocyanidins (PC) in lipopolysaccharide (LPS)-induced inflammatory response and its possible mechanism in RAW264.7 macrophages. Methods RAW264.7 macrophages were cultured and treated with PBS and different concentrations of PC for 24 hours, followed by 1 μg/mL LPS for 6 hours. Real-time PCR was used to detect the mRNA expression of interleukin1β (IL-1β), IL-6, monocyte chemoattractant protein 1 (MCP-1), tumor necrotic factor α (TNF-α), IL-4 and arginase 1 (Arg1) in RAW264.7 macrophages. Flow cytometry was used to detect the effects of PBS group, LPS group and PC combined with LPS group on M1 and M2 polarization of macrophages. The protein expressions of silenced information regulator 1 (SIRT1), nuclear factor kappa B p65(NF-κB p65) and acetylated NF-κB p65 (Ace-p65) were detected by Western blot analysis after different concentrations of PC treatment. Co-immunoprecipitation assay was used to detect the binding effect of SIRT1 to NF-κB p65 in macrophages treated with PC. Results Compared with PBS group, the mRNA expression of macrophage pro-inflammatory cytokines IL-1β, IL-6, MCP-1 and TNF-α decreased and the mRNA expression of anti-inflammatory factors IL-4 and Arg1 increased in PC group. Compared with LPS group, PC combined with LPS group could significantly inhibit M1 polarization and promote M2 polarization of macrophages. With the increase of PC concentration, the expression of SIRT1 was up-regulated, and NF-κB p65 protein did not change significantly. The expression of Ace-p65 protein decreased significantly when treated with high concentration of PC. Conclusion PC can significantly alleviate the LPS-induced inflammatory response by up-regulating the expression of SIRT1 and inhibiting NF-κB pathway in RAW264.7 macrophages.

Platelets not only have hemostatic function, but can also directly or indirectly recognize pathogenic microorganisms and the signals they produce to capture and destroy them through membrane receptors. They can collaborate with various components of the body's immune system by releasing of intraplatelet particulate matter, cytokines and chemokines to perform bactericidal functions. And it can also play a bactericidal role by swallowing pathogens, releasing antimicrobial proteins and chemokines and activating and enhancing other specialized anti-inflammatory cells bactericidal effect, such as leukocytes and so on. However, the bacteriostatic composition and bacteriostatic mechanism of platelets remain unclear, so attention should be paid to the immune mechanism and bacteriostatic effect of platelets.

Objective To explore the effect of knocking down Rho-associated coiled-coil kinase (ROCK2) gene on the cognitive function of amyloid precursor protein/presenilin-1 (APP/PS1) double transgenic mice and its mechanism. Methods APP/PS1 double transgenic mice were randomly divided into AD model group (AD group), ROCK2 gene knock-down group (shROCK2 group), ROCK2 gene knock-down control group (shNCgroup), and wild-type C57BL/6 mice of the same age served as the wild-type control (WT group). Morris water maze and Y maze were employed to test the cognitive function of mice. Neuron morphology was detected by Nissl staining. Immunofluorescence histochemical staining was used to detect the expression of phosphorylated dynamin-related protein 1 (p-Drp1) and mitochondrial fusion 1 (Mfn1). Western blot analysis was used to detect the expression ROCK2, cleaved-caspase-3 (c-caspase-3), B-cell lymphoma 2 (Bcl2), Bcl2-related protein X (BAX), p-Drp1, mitochondrial fission 1 (Fis1), optic atrophy 1 (OPA1), Mfn1 and Mfn2. Results Compared with AD group mice, the expression of ROCK2 in shROCK2 group mice was significantly reduced; the cognitive function was significantly improved with the number of neurons in the hippocampal CA3 and DG areas increasing, and nissl bodies were deeply stained; the expression of c-caspase-3 and BAX was decreased, while the expression of Bcl2 was increased; the expression of mitochondrial division related proteins p-Drp1 and Fis1 were decreased, while the expression of mitochondrial fusion-related proteins OPA1, Mfn1 and Mfn2 were increased. Conclusion Knock-down of ROCK2 gene can significantly improve the cognitive function and inhibit the apoptosis of nerve cells of APP/PS1 mice. The mechanism may be related to promoting mitochondrial fusion and inhibiting its division.

Monocytes are important target cells of various hemorrhagic fever viruses. In viral hemorrhagic fevers (VHFs), monocytes can be infected by viruses and produce different kinds of cytokines, which contribute to the antiviral immune response and participation in the immunopathogenesis of VHFs. During the pathogenesis of various VHFs (early stage), monocytes change in cell counting, subpopulation distribution and expression of surface molecules with an activated phenotype. Several hemorrhagic fever viruses can infect monocytes and induce immune response, which may play an important role in immunopathological injury. Monocytes and the cytokines they produce may interact with platelets and vascular endothelial cells, contributing to disease progression.

Objective To express the monkeypox virus (MPXV) A23R protein in Escherichia coli and purify by Ni-NTA affinity column, and to prepare mouse antiserum against MPXV A23R. Methods The recombinant plasmid pET-28a-MPXV-A23R was constructed and transformed into Escherichia coli BL21 to induce the expression of A23R protein. After optimizing the conditions of expression, A23R protein was highly expressed. Recombinant A23R protein was purified by Ni-NTA affinity column and identified by Western blot analysis. The purified protein was used to immunize mice for preparing the A23R polyclonal antibody, and the antibody titer was detected by ELISA. Results The expression of A23R recombinant protein reached the peak under the induced conditions of 0.6 mmol/L isopropyl-β-D-thiogalactoside (IPTG), 37 DegreesCelsius and 20 hours. The purity of the protein was about 96.07% and was identified by Western blot analysis. The mice were immunized with recombinant protein, and the titer of antibody reached 1:102 400 at the 6th week after immunization. Conclusion MPXV A23R is expressed highly and purified with a high purity and its antiserum from mouse is obtained with a high titre.

Objective To prepare specific mouse monoclonal antibody (mAb) against human adenovirus type 55 Hexon protein (HAdV55 Hexon). Methods The Hexon genes of HAdV55, 3, 4, 7, 16 and 21 were chemically synthesized as templates for PCR amplification. The prokaryotic expression plasmids pET28a-HAdV55 Hexon and eukaryotic expression plasmids pCAGGS-HAdV3, 4, 7, 16, 21 and 55 Hexon were constructed respectively. The pET28a-HAdV55 Hexon plasmid was transformed into E. coli competent cell BL21 (DE3) and was induced by IPTG. After the purified inclusion body was denatured and renatured, Hexon55 protein was purified by tangential flow filtration system. pCAGGS-HAdV55 Hexon was used to immunize BALB/c mice by cupping, and HAdV55 Hexon protein was used to booster immunization. The anti-HAdV55 Hexon mAb was prepared by hybridoma technique and the titer and subclass were determined. The specificity of antibody was identified by Western blot using HEK293T cells transfected with pCAGGS-HAdV55 Hexon and by immunofluorescence assay (IFA) using BHK cells transfected with pCAGGS-HAdV55 Hexon. Both clones with high titer were selected, and the cross-reactivity of pCAGGS-HAdV3, 4, 7, 16, 21 and 55 Hexon transfected cells were analyzed by Western blot analysis and IFA. Results PET28a-HAdV55 Hexon and pCAGGS-HAdV55 Hexon, 3, 4, 7, 16 and 21 expression plasmids were successfully constructed. BL21 transformed with pET28a-HAdV55 Hexon was induced by IPTG. The HAdV55 Hexon protein was mainly expressed in the form of inclusion body. After denaturation and renaturation, the purified HAdV55 Hexon protein was obtained by ultrafiltration. Six hybridoma cell lines secreting HAdV55 Hexon mAb were obtained. The antibody subclass analysis showed that 2 strains were IgG2a subtypes and 4 strains were IgG2b. Two specific HAdV55 Hexon antibodies with high titer were obtained, and there was no cross-reactivity with HAdV3, 4, 7, 16, 21 Hexon. Conclusion The specific mice mAb against HAdV55 Hexon provides an experimental basis for establishing its antigen detection method.

Objective To investigate a convenient and quantitative solution to activation levels and functional characterization of CAR-T cells by inserting T cell activity-responsive promoter (TARP) nanoluciferase reporter gene system into a lentiviral plasmid containing the gene encoding the chimeric antigen receptor (CAR). Methods The recombinant plasmid was constructed by using whole gene synthesis and molecular cloning techniques. The lentivirus was packaged and was infected with human primary T lymphocytes. Flow cytometry was used to detected the positive rate of lentivirus-infected T cells. The functional characterization of CAR-T cells was identified by luciferase reporter gene system, Western blot, flow cytometry, and small animal live imaging techniques. Results The results of enzyme digestion identification and the plasmid sequencing showed that the recombinant plasmids were constructed, and flow cytometry displayed the normal preparation of CAR-T cells. This system could dynamically respond to the activation of CAR-T cells by luciferase reporter gene system. The functional assay in vitro confirmed that the system could reflect the exhaustion of CAR-T cells, and the small animal live imaging results demonstrated that the system can be used as a tracer of CAR-T cells in mice. Conclusion TARP nanoluciferase reporter gene system provides a more convenient, sensitive and quantitative method for evaluating CAR-T cells activation level, exhaustion phenotype and tracing.

Objective To investigate the relationship between disease courses and severity and monocyte subsets distribution and surface CD31 intensity in patients of hemorrhagic fever with renal syndrome (HFRS). Methods Peripheral blood samples from 29 HFRS patients and 13 normal controls were collected. The dynamic changes of classical monocyte subsets (CD14 ++ CD16 - ), intermediated monocyte subsets (CD14 ++ CD16 + ) and non-classical monocyte subsets (CD14 + CD16 ++ ) and the mean fluorescent intensity (MFI) of CD31 on monocyte subsets were detected by multiple-immunofluorescent staining and flow cytometry. Results In acute phase of HFRS, the ratio of classical monocyte subsets to total monocytes was dramatically decreased compared to convalescent phase and normal control. It was still much lower in convalescent phase compared to normal controls. The ratio of classical monocyte subsets to total monocytes were decreased in HFRS patients compared to that in normal control, whereas there was no difference between severe/critical groups and mild/moderate groups. On the contrary, the ratio of intermediate monocyte subsets to total monocytes in acute phase of HFRS was significantly increased compared to convalescent phase and normal control. The ratio of intermediate monocyte subsets to total monocytes were increased in HFRS patients compared to that in normal control, whereas no difference was found between severe/critical groups and mild/moderate groups. Phases or severity groups had no difference in ratio of non-classical monocyte subsets to total monocytes. Additionally, the ratio of classical monocyte subsets had a tendency to decline and that of intermediate monocyte subsets showed an increase both to total monocytes between the acute and convalescent phases in 11 HFRS patients with paired-samples. Moreover, in acute phase of HFRS, the mean fluorescent intensity (MFI) of CD31 on three monocyte subsets all decreased, specifically classical monocyte subsets showed the highest MFI of CD31 while the normal control reported the highest MFI of CD31 in non-classical monocyte subsets. In convalescent phase, the MFI of CD31 on classical and intermediated monocyte subsets were both lower than that of normal control, while MFI of CD31 was still significantly lower than normal control on non-classical monocyte subsets. Finally, MFI of CD31 on classical and intermediated monocyte subsets in severe/critical group were both lower than those in mild/moderate group, showing no statistical difference in MFI of CD31 on non-classical monocyte subset across groups of different disease severity. Conclusion The ratio of classical and intermediated monocyte subsets to total monocytes are correlated with the course of HFRS, and so are the surface intensity of CD31 on these monocyte subsets with the disease course and severity. The surface intensity of CD31 on non-classical monocyte subsets, however, is correlated only with the course of the disease. Together, the underlying mechanisms for the observed changes in monocyte subsets in HFRS patients should be further investigated.

Objective To investigate the effect of Echinococcus granulosus cyst fluid(EgCF) on the cytoskeletal rearrangement and phagocytosis and the migration of macrophages induced by lipopolysaccharide(LPS). Methods Peritoneal macrophages of C57BL/6 mice were isolated and cultured in vitro, and divided into control group and LPS group and LPS combined with EgCF group. After 48 hours of treatment, filamentous actin (F-actin) changes were observed with rhodamine-labelled phalloidin staining and fluorescence microscopy; Transwell TM chamber was used to test cell migration ability and flow cytometry to test cell phagocytosis. After 1 hour of treatment, PI3K and AKT, phosphorylated AKT (p-AKT), Rac1, guanosine triphospho-Rac1 (GTP-Rac1), WASP and Arp2 protein expressions were detected with Western blot analysis. Results Compared with the control group, after LPS stimulation, macrophages were deformed significantly; pseudopodia increased; actin cytoskeleton increased and was more distributed in pseudopodia; the ability of migration and phagocytosis were significantly improved, and the expression of PI3K, p-AKT, GTP-Rac1, WASP and Arp2 proteins significantly increased. EgCF treatment caused cell shrinkage and disappearance of pseudopodia protrusions of LPS-activated cells, and led to the reduced phagocytic and migratory of cells; the protein expression of PI3K, p-AKT, GTP-Rac1, WASP and Arp2 decreased significantly compared with the LPS group. Conclusion LPS induces the migration and enhances phagocytosis of macrophages while EgCF inhibits these effects, which is related to actin cytoskeleton rearrangement.

Macrophage as a crucial component of innate immunity, plays an important role in inflammation and infection immunity. Notch signal pathway is a highly conserved pathway, which regulates cellular fate and participates in numerous pathological processes. At present, a lot of literature has confirmed the role of Notch signaling in regulating the differentiation, activation and metabolism of macrophage during inflammation and infection. This review focuses on how Notch signaling promotes macrophage pro-inflammatory and anti-infective immune function in different inflammatory and infectious diseases. In this regulation, Notch signaling interact with TLR signaling in macrophages or inflammatory-related cytokines including IL-6, IL-12, and TNF-α. Additionally, the potential application and challenges of Notch signaling as a therapeutic target against inflammation and infectious diseases are also discussed.

Objective: To explore the improvements of high-fat intake on lung injury induced by Paragonimus proliferus infection in rats, and to preliminarily explore the mechanisms underlying the role of cytochrome P450 4A1 (CYP 4A1) in the improve ments., Methods: SD rats were randomly assigned into three groups, including the normal control group ( n = 10), the infection and normal diet group ( n = 12) and the infection and high-fat diet group ( n = 12). Rats in the normal control group were fed with normal diet and without any other treatments, and animals in the infection and normal diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with normal diet, while rats in the infection and high-fat diet group were subcutaneously injected with 8 excysted metacercariae of P. proliferus via the abdominal wall, followed by feeding with high-fat diet. All rats were sacrificed 28 weeks post-infection, and serum samples and lung specimens were collected. Following hematoxylin-eosin (HE) staining of rat lung specimens, the rat lung injury was observed under an optical microscope, and alveolitis was evaluated using semi-quantitative scoring. Serum interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA), and the cytochrome P450 4A1 (CYP 4A1) expression was quantified in rat lung specimens at transcriptional and translational levels using quantitative real-time PCR (qPCR) and Western blotting assays., Results: Alveolar wall thickening, edema and inflammatory cell infiltration were alleviated 28 weeks post-infection with P. proliferus in rats in the infection and high-fat diet group relative to the infection and normal diet group, and no alveolar consolidation was seen in the infection and high-fat diet group. The semi-quantitative score of alveolitis was significantly higher in the infection and normal diet group [(2.200 ± 0.289) points] than in the normal control group [(0.300 ± 0.083) points] and the infection and high-fat diet group [(1.300 ± 0.475) points] (both P values < 0.05), and higher serum IL-1β [(151.586 ± 20.492)] pg/mL and TNF-α levels [(180.207 ± 23.379) pg/mL] were detected in the infection and normal diet group than in the normal control group [IL-1β: (103.226 ± 3.366) pg/mL; TNF-α: (144.807 ± 1.348) pg/mL] and the infection and high-fat diet group [IL-1β: (110.131 ± 12.946) pg/mL; TNF-α: (131.764 ± 27.831) pg/mL] (all P values < 0.05). In addition, lower CYP 4A1 mRNA (3.00 ± 0.81) and protein expression (0.40 ± 0.02) was quantified in lung specimens in the infection and normal diet group than in the normal control group [(5.03 ± 2.05) and (0.84 ± 0.14)] and the infection and high-fat diet group [(11.19 ± 3.51) and (0.68 ± 0.18)] (all P values < 0.05)., Conclusions: High-fat intake may alleviate lung injuries caused by P. proliferus infection in rats through up-regulating CYP 4A1 expression in lung tissues at both translational and transcriptional levels.

Objective To investigate the effect of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) on the proliferation, migration and tumor immune microenvironment of colorectal cancer cells and its possible molecular mechanism. Methods The Cancer Genome Atlas (TCGA) database was used to analyze the expression levels of IGF2BP2 and MYC in colorectal cancer and adjacent tissues. The expression of IGF2BP2 in HCT-116 and SW480 human colorectal cancer cells was silenced by RNA interference (RNAi), and the silencing effect was detected by quantitative real-time PCR. After knocking down IGF2BP2, colony formation assay, CCK-8 assay and 5-ethynyl-2'-deoxyuridine (EdU) assay were employed to detect cell colony formation and proliferation ability. Transwell TM assay was used to detect cell migration ability. Quantitative real-time PCR was used to detect the mRNA expression of IGF2BP2, MYC, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and interleukin-10 (IL-10). The protein expression of IGF2BP2 and MYC was detected by western blot. The binding ability of IGF2BP2 and MYC in HCT-116 cells was detected by quantitative real-time PCR after RNA immunoprecipitation. Results The results of TCGA database showed that the expression of IGF2BP2 and MYC in colorectal cancer tissues was significantly higher than that in adjacent tissues, and the survival time of colorectal cancer patients with high expression of IGF2BP2 was shorter. After silencing IGF2BP2, the viability, proliferation and migration of HCT-116 and SW480 cells were decreased. The mRNA expression of MYC, TGF-β and IL-10 in IGF2BP2 knockdown group was significantly decreased, while the expression of TNF-α mRNA was increased. The expression of MYC protein and the stability of MYC mRNA were significantly decreased. RIP-qPCR results showed that IGF2BP2 could bind to MYC mRNA. Conclusion Knockdown of IGF2BP2 inhibits colorectal cancer cell proliferation, migration and promotes tumor immunity by down-regulating MYC expression.

Objective: To investigate the dynamic expression of cluster of differentiation 47 (CD47) and its ligands signaling regulatory protein α (SIRPα) and thrombospondin-1 (TSP-1) in mice infected with Toxoplasma gondii in the second and third trimesters., Methods: C57BL/6J mice (6 to 8 weeks old) were used for modeling T. gondii infection in the first trimester, and the pregnant mice were randomly divided into the normal control and infection groups, of 10 mice in each group. Pregnant mice in the infection group were intraperitoneally injected with 150 T. gondii tachyzoites on gestational day (Gd) 6.5, while pregnant mice in the normal control group were intraperitoneally injected with the same volume of physiological saline at the same time. The uterine and placental specimens were collected from all pregnant mice on Gd12.5 and Gd18.5, and the pregnant outcomes were recorded. The pathological damages of mouse uterine and placental specimens were observed using hematoxylin-eosin (HE) staining on Gd12.5 and Gd18.5. The relative expression of CD47 , SIRPα , TSP-1 , surface antigen 1 ( SAG1 ), interferon-γ ( IFN-γ ), interleukin-2 ( IL-2 ), IL-4 and IL-13 mRNA was quantified in mouse uterine and placental specimens using real-time fluorescence quantitative PCR (qPCR) assay, and the CD47, SIRPα, TSP-1 expression was determined in mouse uterine and placental specimens using immunohistochemical staining., Results: As compared with those in the normal control group, the pregnant mice in the infection group showed back arching, bristling, trembling and listlessness during pregnancy, and several mice presented virginal bleeding and abortion. Pathological examinations showed inflammatory cell infiltration, congestion and necrosis in uterine and placental specimens of pregnant mice in the infection group, a higher abortion rate of pregnant mice was seen in the infection group than in the normal control group on Gd12.5 (χ 2 = 20.405, P < 0.001) and Gd18.5 (χ 2 = 28.644, P < 0.001). qPCR assay showed significant differences in the expression of CD47 , SIRP α, TSP-1 , SAG1 , INF-γ , IL-2 , IL-4 and IL-13 genes in mouse placental specimens between the normal control and infection groups on Gd12.5 and Gd18.5 [ F ' ( F ) = 37.511, 29.337, 97.343, 53.755, 67.188, 21.145, 8.658 and 13.930, all P values < 0.001]. Higher CD47 , SIRP α and TSP-1 gene expression was quantified in mouse placental specimens in the infection group than in the normal control group on Gd12.5 (all P values < 0.01), and lower CD47 , SIRPα and TSP-1 gene expression was quantified in the infection group than in the normal control group on Gd18.5 (all P values < 0.001), while higher SAG1 gene expression was detected in placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both P values < 0.01). In addition, higher INF-γ and IL-2 expression and lower IL-4 and IL-13 expression was detected in mouse placental specimens in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all P values < 0.001), and there were significant differences in the CD47 , SIRP α, TSP-1 , SAG1 , INF-γ , IL-2 , IL-4 and IL-13 gene expression in uterine specimens of pregnant mice between the normal control and infection groups on Gd12.5 and Gd18.5 [ H ( F ' and F ) = 14.951, 25.977, 18.711, 48.595, 39.318, 14.248 and 15.468, all P values < 0.01], and higher CD47 and TSP-1 expression was detected in mouse uterine specimens in the infection group than in the control group on Gd12.5 and Gd18.5 (all P values < 0.01); however, no significant difference was found in the SIRP α expression ( P > 0.05). Higher SAG1 expression was detected in uterine specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (both P values < 0.01), and higher INF -γ and IL-2 gene expression and lower IL-4 and IL-13 gene expression was found in the placental specimens of pregnant mice in the infection group than in the normal control group on Gd12.5 and Gd18.5 (all P values < 0.001). Spearman correlation analysis showed that the CD47 gene expression correlated positively with IFN-γ ( r s = 0.735, P < 0.05) and IL-2 ( r s = 0.655, P < 0.05) and negatively with IL-4 ( r s = -0.689, P < 0.05) and IL-13 expression ( r s = -0.795, P < 0.05) in the placental specimens of pregnant mice in the infection group on Gd12.5, and the CD47 gene expression correlated negatively with IFN -γ ( r s = -0.745, P < 0.05) and IL-2 expression ( r s = -0.816, P < 0.05) and positively with IL-4 ( r s = 0.704, P < 0.05) and IL-13 ( r s = 0.802, P < 0.05) in the placental specimens of pregnant mice in the infection group on Gd18.5. Immunohistochemical staining showed mild CD47, SIRPα and TSP-1 expression in uterine and placental specimens of pregnant mice in the normal control group on Gd12.5 and Gd18.5, strong CD47, SIRPα and TSP-1 expression in the placental specimens of pregnant mice in the infection group on Gd12.5 and strong CD47 and TSP-1 expression in the uterine specimens of pregnant mice in the infection group on Gd12.5., Conclusions: T. gondii infection in the first trimester may cause abnormal expression of CD47 and its ligands SIRPα and TSP-1 in the maternal-fetal interface of pregnant mice in the second and third trimesters, which may be associated with the immune escape of T. gondii at the maternal-fetal interface.

Fatty liver disease is one of the most prevalent chronic liver disease worldwide and the gut-liver axis is recognized as increasingly prominent in fatty liver disease. Intestinal dysfunction can affect the occurrence or progression of liver disease, therein, validating the critical role of the intestinal immune cells. Enormous literature reported that macrophages, lymphocyte, dendritic cells (DCs) and other immune cells in the gut as well as their subsets may regulate the fatty liver disease progression via different mechanisms, including disruption of intestinal barrier, dysregulation of intestinal lipid transporters and mediating immune cell migration to liver.

Objective: To investigate the prevalence and influencing factors of Blastocystis hominis infection among children with diarrhea under five years of age in Guangzhou City., Methods: Children with diarrhea under 5 years of age admitted to Guangzhou Children's hospital, Guangzhou Maternity and Child Healthcare Hospital and Guangzhou Women and Children's Medical Center during the period between January 1 and December 31, 2020, were enrolled. Participants' demographics, living environments and health status were collected using questionnaire surveys. Stool samples were collected from participants and nucleic acid was extracted. B. hominis infection was identified using PCR assay and sequence alignment, and the factors affecting B. hominis infection among children with diarrhea under 5 years of age were identified using univariate analysis and multivariate logistic regression analysis., Results: A total of 684 children with diarrhea under 5 years of age were enrolled, including 468 male children and 216 female children, with a mean age of (1.79 ± 1.12) years. The overall prevalence of B. hominis infection was 4.97% [34/684, 95% confidential interval (CI): (3.59%, 6.86%)] among participants, and there was no significant difference in the prevalence of B. hominis infection between children with chronic [7.52% (20/266), 95% CI: (4.92%, 11.33%)] and acute diarrhea [3.35% (14/418), 95% CI: (2.01%, 5.54%)] (χ 2 = 5.983, P = 0.014). Multivariate logistic regression analysis identified keeping pet [odds ratio ( OR ) = 6.298, 95% CI: (2.711, 14.633)], drinking non-tap water [ OR = 4.522, 95% CI: (1.769, 11.561)], lactose intolerance [ OR = 4.221, 95% CI : (1.043, 17.087)], antibiotic use [ OR = 0.125, 95% CI : (0.017, 0.944)] and chronic diarrhea [ OR = 2.172, 95% CI : (1.018, 4.637)] as factors affecting B. hominis infection among children with diarrhea under 5 years of age in Guangzhou City., Conclusions: B. hominis infections is detected in children with diarrhea under five years of age in Guangzhou City. Improving home environments and pet-keeping hygiene is recommended to reduce the likelihood of B. hominis infection among children.

Objective: To investigate the effect of recombinant Schistosoma japonicum egg ribonuclease SjCP1412 (rSjCP1412) on proliferation, cell cycle, apoptosis and activation of human hepatic stellate cells LX-2 in vitro , and explore the underlying mechanisms., Methods: The rSjCP1412 protein was expressed in Escherichia coli BL21 by prokaryotic expression, and the highly purified soluble rSjCP1412 protein was prepared by Ni NTA affinity chromatography and urea gradient refolding dialysis. Yeast RNA was digested using 12.5, 25.0, 50.0 µg rSjCP1412 proteins at 37 °C for 2, 3, 4 h, and the enzymatic products were electrophoresed on 1.5% agarose gel to observe the RNAase activity of rSjCP1412 protein. The proliferation of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was measured using CCK-8 assay, and the apoptosis of LX-2 cells stimulated by different doses of rSjCP1412 protein for 48 hours was detected using the Annexin V-FITC/PI double staining, while the percentage of LX-2 cells at G0/G1, S and G2/M phases of cell cycle following stimulation with different doses of rSjCP1412 protein for 48 h was detected by DAPI staining. The type I collagen, type III collagen and α-smooth muscle actin (α- SMA ) mRNA expression was quantified using quantitative florescent real-time PCR (qPCR) assay and Western blotting at transcriptional and translational levels in LX-2 cells following stimulation with different doses of rSjCP1412 protein for 48 h, while soluble egg antigen (SEA) served a positive control and PBS without rSjCP1412 protein as a normal control in the above experiments. The expression of collagen I, α-SMA and Smad4 protein was determined using Western blotting in LX-2 cells following stimulation with rSjCP1412 protein, transforming growth factor-β1 (TGF-β1) alone or in combination, to examine the signaling for the effect of rSjCP1412 protein on LX-2 cells., Results: The rSjCP1412 protein was successfully expressed and the highly purified soluble rSjCP1412 protein was prepared, which had a RNase activity. Compared with the normal group, the survival rates of LX-2 cells significantly decreased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein and SEA for 48 h ( F = 22.417 and 20.448, both P values < 0.05). The apoptotic rates of LX-2 cells significantly increased post-treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h ( F = 11.350, P < 0.05), and treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h resulted in arrest of LX-2 cells in G0/G1 phase ( F = 20.710, P < 0.05). Treatment with 12.5, 25.0, 50.0 µg/mL rSjCP1412 protein for 48 h caused a significant reduction in relative expression levels of collagen I ( F = 11.340, P < 0.05), collagen III ( F = 456.600, P < 0.05) and α- SMA mRNA ( F = 23.100, P < 0.05) in LX-2 cells, and both rSjCP1412 protein and SEA treatment caused a significant reduction in collagen I ( F = 1 302.000, P < 0.05), α-SMA ( F = 49.750, P < 0.05) and Smad4 protein expression ( F = 52.420, P < 0.05) in LX-2 cells. In addition, rSjCP1412 protein treatment inhibited collagen I ( F = 66.290, P < 0.05), α-SMA ( F = 31.300, P < 0.05) and Smad4 protein expression ( F = 27.010, P < 0.05) in LX-2 cells activated by TGF-β1., Conclusions: rSjCP1412 protein may induce apoptosis of LX-2 cells and inhibit proliferation, cell cycle and activation of LX-2 cells through down-regulating Smad4 signaling molecules.

Objective To investigate the effects of collagen peptides on the immune function of mice under the condition of X-ray irradiation combined with simulated weightlessness. Methods Mice were randomly divided into control group, modelling group and collagen peptide group. Mice in collagen peptide group were intraperitoneally injected with collagen peptide (600 mg/kg) once a day from the first day of the experiment, while mice in the other two groups were intraperitoneally injected with normal saline. On the fourth day of the experiment, mice in the modelling group and collagen peptide group were simultaneously exposed to X-ray irradiation (2 Gy) and hindlimb-unloaded simulated weightlessness by tail-suspension. On the 10th day of the experiment, the mice were terminated by cervical dislocation. Automated hematology analyzer was used to detect Leukocyte classification of peripheral blood. Splenic lymphocyte subsets, cell cycle and apoptosis of bone marrow cells were analyzed by flow cytometry. The expressions of 19 plasma cytokines were tested with liquid suspension chips. Results Compared with the control group, the modelling group had a significant reduction in the total number of white blood cells and lymphocytes in the peripheral blood, the total number of splenocyte and the number of T cells, CD4 + and CD8 + T cells, B cells, and natural killer (NK) cells in the spleen, an decrease in 18 cytokines in the plasma, and an increase in myelocyte apoptosis in mice of the modelling group. Compared with the modelling group, most immunological parameters had improved in the mice of the collagen peptide group except some cytokines. Conclusion Collagen peptides can effectively improve the immune function of mice under the condition of X-ray irradiation combined with simulated weightlessness.

Objective To construct and validate a prognostic model for lung adenocarcinoma based on bioinformatics of metabolic genes. Methods Lung adenocarcinoma-related data from The Cancer Genome Atlas (TCGA) database and gene expression omnibus (GEO) were acquired, and LASSO regression was used to construct multi-gene prognostic models and calculate risk-score (RS). Univariate and multivariate Cox independent prognostic analysis was performed. The area under receiver operating characteristic (ROC) curve (AUC) of the model was evaluated by ROC curve and survival analysis was performed. Nomogram were constructed to evaluate the feasibility of the model, and metabolic gene functional enrichment analysis was performed by GSEA. Tumor immune estimation resource (TIMER) database was used to analyze the correlation of patients RS with immune cell infiltration and with the expression of immune checkpoint molecules. Results The TCGA database was used to construct a prognostic model for lung adenocarcinoma based on 18 metabolism-related genes, and RS was used as an independent prognostic factor. The area under the ROC curve was 0.713. Survival analysis showed that overall survival was higher in the low-risk group compared to the high-risk group, and the prognostic model was associated with infiltration of immune cells and with the expression of immune checkpoint molecules. Conclusion RS is an independent prognostic factor in the prognostic model of lung adenocarcinoma with metabolic genes, suggesting a high prognostic value of this model.

Objective To investigate the therapeutic effects of eriodictyol on transgenic mice with five familial Alzheimer's disease (5×FAD) and the modulation of NOD-like receptor-pyrin domain containing 3 (NLRP3) inflammasome in microglia. Methods The 8-month-old 5×FAD mice were randomly divided into AD model group and eriodictyol-treated AD group. Same-aged wild-type C57BL/6J mice were randomly divided into wild-type (WT) control group and eriodictyol-treated WT group. Morris water maze and Y-maze experiments were performed to assess the cognitive function of each group of mice. Immunofluorescence histochemical staining was performed to detect the expression of NLRP3, caspase-1 and interleukin 18 (IL-18) in mouse brain tissue, and Western blot was performed to detect the protein levels of NLRP3, apoptosis-associated speckle-like protein containing a CARD (ASC), caspase-1, IL-18, IL-1β and ion calcium-binding adaptor molecule 1 (Iba-1) in mouse brain tissue. Results Compared with the WT group and the eriodictyol-treated WT group, cognitive function was significantly impaired in the AD group mice, and the expression of NLRP3, caspase-1, IL-18, ASC, IL-1β and Iba1 were increased in microglia of mouse brain tissue. After eriodictyol treatment, learning memory and cognitive function were improved, and the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18 and Iba1 were all down-regulated in the eriodictyol-treated AD group mice compared with the AD group mice. Conclusion Eriodictyol may improve cognitive function in animal models of AD by inhibiting the activation of the NLRP3 signaling pathway in microglia.

Macrophages are a class of innate immune cells with strong plasticity. They can polarize into different phenotypes, serving with various functions, such as phagocytosis and chemotaxis, which is involved in the development of diseases. RNA-binding protein quaking (QKI) regulates monocyte differentiation, macrophage polarization and various cellular functions through RNA splicing, translocation and expression. QKI regulates the differentiation of monocytes into macrophages, and QKI deficiency promotes the polarization of macrophages into M1 type, which exerts a pro-inflammatory phenotype. In contrast, QKI overexpression promotes macrophage polarization into M2 type. Additionally, QKI affects macrophage phagocytic receptor and chemokine expression. Due to the variations in tissue-resident macrophages' features, QKI modulates macrophages in the pathogenesis of diseases (atherosclerosis, inflammatory bowel disease, etc.) through diverse mechanisms, which mainly involves cyclicAMP response element binding protein (CREB) transcription factor regulation, signal transducer and activator of transcription 1/nuclear factor κB (STAT1/NF-κB) inflammatory signaling pathway and pre-mRNA splicing of phagocytic receptor.

Objective To investigate the effect of protein tyrosine phosphatase receptor type O (PTPRO) on the phagocytic activity of alveolar epithelial cells in LPS-induced acute lung injury. Methods Mice were randomly divided into the normal control group and LPS stimulation group. The infiltration of inflammatory cells was detected by HE staining. The cytokine TNF-α level in lung was analyzed by ELISA. Western blotting was performed to detect the effect of LPS on PTPRO protein expression in lung. After the expression of PTPRO in MLE-12 cells was silenced by siRNA in vitro, flow cytometry was used to detect the effects of LPS and PTPRO siRNA on the phagocytic activity of MLE-12 cells, and the effects of LPS and PTPRO siRNA on the expression of PTPRO, AKT and phosphorylated AKT protein were measured by Western blotting. Results After the establishment of murine acute lung injury model by LPS injection(1 mg/kg), the infiltrated polymorphonuclear leukocytes were markedly increased. The level of TNF-α in lung tissue and the expression of PTPRO in MLE-12 cells were both significantly increased after LPS stimulation. However, the activity of MLE-12 cells to phagocytose fluorescent microbeads was evidently decreased after silencing PTPRO. Furthermore, silencing PTPRO induced a remarkable decrease in the phosphorylation of AKT in MLE-12 cells. Conclusion PTPRO can promote phagocytic activity of MLE-12 cells via activating AKT signaling pathway.

Objective To investigate the regulation of Wnt5a/receptor tyrosine kinase-like orphan receptor 2 (ROR2) signaling pathway on macrophage autophagy induced by Bacille Calmette Guerin (BCG) infection. Methods RAW264.7 cells were infected with BCG at 0, 2, 6, 12 and 24 hours, and the expressions of Wnt5a, ROR2 and autophagy-related protein microtubule-associated protein 1 light chain 3II (LC3II ) were detected by Western blot analysis. After RAW264.7 cells were treated with ROR2 small interfering RNA and BCG infection respectively or together, the protein expressions of autophagy-related genes 5 (ATG5), P62, beclin-1, ATG7 and LC3II in RAW264.7 cells were tested by Western blot analysis. Autophagy flux was detected by mRFP-GFP-LC3 double-label adenovirus assay. Results Compared with the control group, Wnt5a, ROR2 and LC3II had the highest expression in RAW264.7 cells 6 hours after BCG infection. Compared with the non-infected control group, the expressions of autophagy-related proteins ATG5, P62, beclin-1, ATG7 and LC3II showed an increase, along with increased number of autophagosomes and autophagolysosomes in RAW264.7 cells infected with BCG. Compared with BCG infected group, the expressions of the above proteins observed a decrease, and the number of autophagosomes and autophagolysosomes both descended in the co-treatment group with knockdown ROR2 and BCG infection. Conclusion Knockdown of ROR2 can inhibit autophagy in macrophages induced by BCG infection.