Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Background With the rapid industrialization, cadmium has become a primary heavy metal pollutant in cultivated land soil in China, which seriously affects human health. Previous studies have found that cadmium exposure associates with cognitive dysfunction in individuals, but there is a lack of research on the mechanism of cadmium exposure associated cognitive impairment in offspring in early life which is more vulnerable to various toxins and crucial for development of the neuro. Objective To explore the potential mechanism of brain-derived neurotrophic factor/tyrosine kinase receptor B (BDNF-TrkB) signaling pathway in cognitive dysfunction in mice after cadmium exposure in early-life. Methods Twelve 8-week-old C57BL/6 pregnant mice were randomly divided into 2 groups, namely control group and cadmium exposure group, with 6 mice in each group. The exposure period was from pregnancy day 4.5 to lactation day 21 (E4.5-P21), during which distilled water or cadmium chloride solution (2.5 mg·kg⁻¹·d⁻¹) was given. After lactation, the offspring of the control group and the cadmium exposure group were given distilled water until 8 weeks of age. Then the toxicity effects of cadmium exposure on mice were evaluated by body weight and selected biochemical indicators. The cadmium content in brain was detected and the learning and memory ability was tested by Y maze and Morris water maze to evaluate cognitive function of offspring mice. Histopathological changes of the hippocampus were observed after Nissl staining and Golgi staining. The mRNA and protein expression levels of the BDNF-TrkB pathway and synapse were detected by real-time quantitative PCR (qPCR) and Western blot. Results Compared with the control group, no significant change was found in body weight, liver or kidney function in the cadmium exposure group (P> 0.05). However, compared with the control group, the cadmium content in brain was increased in the cadmium exposure group (P<0.001). The behavioral changes associated with cognitive dysfunction were positive in the cadmium exposure group (all P<0.05). The histopathological observation after Nissl staining showed abnormal tissue structure, decreased number of neurons and increased karyopyknosis in the cadmium exposure group (P<0.01).The spine density of Golgi staining was decreased in the cadmium exposure group (P<0.001). The BDNF-TrkB pathway-related mRNA and the synapse-related mRNA in the hippocampus were reduced in the cadmium exposure group (all P<0.05). The expression levels of BDNF-TrkB pathway-related proteins and synapse-related proteins in the hippocampus were also reduced in the cadmium exposure group (P<0.05). Conclusion Early-life cadmium exposure may induce synaptic dysplasia and lead to cognitive dysfunction by down-regulating the BDNF-TrkB signaling pathway in mice.

ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

Chronic active Epstein-Barr virus (CAEBV) infection with renal involvement is not common. The paper reported a child of multisystem-compromised CAEBV infection with the onset of IgA nephropathy (IgAN). The child presented with intermittent gross hematuria, and renal biopsy showed focal proliferative IgAN, administered methylprednisolone pulse followed by oral prednisolone treatment. Intermittent increase of blood Epstein-Barr virus (EBV) load and abnormal EBV antibody, pneumonia caused by EBV and Staphylococcus aureus-mixed infection, periappendiceal abscess, and pancytopenia occurred during treatment follow-up. The CAEBV infection was considered. Echocardiography suggested pulmonary hypertension. Head CT presented multiple calcifications in the bilateral basal ganglia. Bone marrow biopsy showed bone marrow EBV-DNA 6.5×10 3 copies per liter. Immunohistochemistry of renal biopsy showed about 50 CD8 + (scattered +) cells per high power field (HPF), about 40 CD4 + (focal +) cells per HPF (local), CD68 + (-), latent membrane protein 1 (-), EBV-encoded small RNA (scattered +) approximately 25 cells per HPF. The lymphocyte subsets infected with EBV showed CD4 + T cells EBV-DNA 3.4×10 4 copies per 1 million cells, CD8 + T cells EBV-DNA 3.3×10 5 copies per 1 million cells, B cells EBV-DNA 1.25×10 4 copies per 1 million cells, NK cells/NK T cells EBV-DNA 2.3×10 4 copies per 1 million cells. The clinical diagnosis was CAEBV infection and EBV-associated IgAN. The patient currently receives oral prednisone treatment, and it is recommended to undergo hematopoietic stem cell transplantation and treatment is under follow up.

Objective : To explore the role of long non-coding RNA XR_378418 (LncRNA XR_378418) in the bi- ological behavior of hepatic stellate cells line JS-1 and to probe the potential molecular mechanism of LncRNA XR _378418 involved in liver fibrosis based on transcriptome sequencing． Methods : In this study，the recombinant plasmid of pcDNA-LncRNA XR_378418 and control plasmid pcDNA-NC were constructed and transfected into JS-1 cells respectively．Then，the expression level of LncRNA XR_378418 was analyzed by quantitative real-time PCR (RT-qPCR) ．The effect of overexpression of LncRNA XR_378418 on proliferation and migration of JS-1 cells were detected by cell counting kit-8 assay ( CCK-8 ) and scratch assay，respectively． Finally，by high-throughput se- quencing analysis，the effect of XR_378418 on the transcriptomics of JS-1 cells was analyzed. Results : T-qPCR results showed that the expression level of LncRNA XR_378418 in the overexpression group was significantly higher than that in the control group (P＜0. 05) ．The results of CCK-8 and scratch experiment suggested that the prolifer- ation and migration in the pcDNA-LncRNA XR _ 378418 group significantly increased． Furthermore ，the high- throughput sequencing analysis showed that a total of 248 genes were screened by gene differential analysis ，of which 127 were up-regulated ，and 117 were down-regulated． Gene Ontology ( GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that LncRNA XR_378418 could regulate cell adhesion，autophagy and Ca2 + signaling，etc． Conclusion LncRNA XR_378418 promotes the proliferation and migration of JS-1 cells and affects the expression of genes related to cell adhesion and calcium signaling in JS-1 cells.

Bovine leukemia virus(BLV)mainly causes bovine B-cell malignant lymphoma,which causes immunosuppression and leads animals susceptible to other diseases.BLV has been detected all over the world except in Western Europe.Antibodies to BLV have been detected in humans,and reverse transcribed DNA of BLV were detected in breast tissue sections and lung tumors,which in-dicate that BLV is a potential zoonotic disease.At present,there are no effective treatment methods or commercial vaccines for BLV.An in-depth understanding of the development of BLV detection technology will help researchers choose suitable detection methods,avoid invalid detection results,and meet the requirements of disease prevention and control.In view of this,this paper reviews 19 detection technologies of BLV including cytology detection,nucleic acid detection,and serology de-tection.The advantages,disadvantages,and scope of application were also analyzed,which provide theoretical guidance for the prevention and control of bovine leukemia.

The eutR gene deletion mutant of Salmonella enteritidis was successfully constructed by homologous recombination.Through the study of its biochemical characteristics,motility,resist-ance to stress in vitro and survival ability in RAW 264.7 cells,it was found that the biochemical characteristics and motility of the eutR gene deletion mutant of Salmonella enteritidis had no sig-nificant change compared with the wild type of Salmonella enteritidis.The ability of eutR gene de-letion strain of Salmonella enteritidis to resist acid,alkali and oxidation was significantly reduced,while the ability to resist heat was not significantly changed;the survival ability of eutR gene dele-tion strain in RAW 264.7 cells was significantly reduced compared with the wild type.In order to further analyze the effect of eutR gene on the expression of virulence factors of Salmonella enterit-idis,the relative expression levels of invH,ssav,ssrA,xthA,orf245,sodC,lrp,mrr1 and hflk virulence genes of the deletion strain and the wild strain were detected by SYBR Green PCR.It was found that the expression of the virulence factors mentioned above in the eutR gene deletion strain of Salmonella enteritidis was significantly down-regulated compared with that in the wild-type strain.The LD50 of the eutR gene-deleted strain of Salmonella enteritidis was determined by ani-mal experiments,and the results showed that the LD50 of the eutR gene-deleted strain was higher than that of the wild-type strain,indicating that the eutR gene could affect the virulence of Salmonella.This study clarified the effect of eutR gene on the survival ability,some biological characteristics and virulence of Salmonella enteritidis in macrophages,and provided a new gene knockout target for the development of attenuated Salmonella enteritidis genetic engineering vac-cine.

Objective The aim of this study was to investigate the prognostic value of body composition indicators in evaluating the development risk of gestational diabetes mellitus(GDM).Methods A total of 1431 pregnant women who were registered and underwent prenatal examinations in the Clinical Nutrition Department of Guizhou Hospital of Beijing Jishuitan Hospital were selected in this study from January 2018 to September 2021.Among them,263 participants were diagnosed with GDM(GDM group),and 1168 healthy individuals underwent physical examinations were enrolled as Con group.Results The GDM detection rate was 18.38%(263/1431).Logistic regression analysis showed that age and percent body fat were risk factors for the development of GDM.The area under the ROC curve of percent body fat for GDM prediction was 0.732,with sensitivity,specificity of 67.7%,68.3%.Conclusions High percentage of body fat during pregnancy is a risk factor for the development of GDM in late pregnancy,and the risk of developing diabetes during pregnancy can be predicted by the percentage of body fat index.

Objective To observe the value of MRI combined with serum carbohydrate antigen 125(CA125)and human epididymis protein 4(HE4)for differential diagnosis of type Ⅰ and Ⅱ epithelial ovarian cancers(EOC).Methods Totally 87 EOC patients were retrospectively enrolled.According to pathology,35 cases of type Ⅰ EOC were taken as type Ⅰ group,while 52 cases of type Ⅱ EOC were taken as type Ⅱ group.Conventional MRI manifestations and apparent diffusion coefficient(ADC)value of lesions,as well as CA125 and HE4 were compared between groups,and their efficacy for differential diagnosis of type Ⅰ and Ⅱ EOC were analyzed.Results Significant differences of conventional MRI manifestations of lesions,including composition,mural nodules,peritoneal diffusion and lymph node metastasis,of ADC value of lesions,also of patients'CA125 and HE4 were found between groups(all P＜0.05).The area under the curve(AUC)of conventional MRI manifestations and ADC value of lesions,patients'CA125 and HE4 for distinguishing typeⅠ and type Ⅱ EOC was 0.694,0.730,0.670 and 0.708,respectively,while of the combination of the above four was 0.865,higher than that of each one alone(Z=3.008,2.138,3.005,2.746,all P＜0.05).Conclusion MRI combined with CA125 and HE4 was helpful for differential diagnosis of type Ⅰ and Ⅱ EOC.

TROP-2, a tumor-associated antigen, has been implicated in the progression of various epithelial tumors. Due to its favorable expression profile, TROP-2 has emerged as a promising target for antibody-drug conjugates (ADCs) based anti-tumor therapies. Although ADCs have shown efficacy in cancer treatment, their application in solid tumors is hindered by their high molecular weight, poor tumor penetration, and release of cytotoxic molecules. Therefore, a recombinant immunotoxin was developed based on a shark-derived variable domain of immunoglobulin new antigen receptor (VNAR) antibody. VNARs are only one-tenth the size of IgG antibodies and possess remarkable tissue penetration capabilities and high stability. In this study, a shark VNAR phage display library was created, leading to the identification of shark VNAR-5G8 that targets TROP-2. VNAR-5G8 exhibited a high affinity and cellular internalization ability towards cells expressing high levels of TROP-2. Epitope analysis revealed that VNAR-5G8 recognizes a hidden epitope consisting of CRD and TY-1 on TROP-2. Subsequently, VNAR-5G8 was fused with a truncated form of Pseudomonas exotoxin (PE38) to create the recombinant immunotoxin (5G8-PE38), which exhibited significant anti-tumor activity in vitro and in vivo. Overall, this study highlights the promise of 5G8-PE38 as a valuable candidate for cancer therapy.