Objective To investigate the effects of Echinococcus multilocularis infection on levels of memory T (Tm) cells and their subsets in lymph nodes of mice at different stages of infection, so as to provide new insights into immunotherapy for alveolarechinococcosis. MethodsTwenty-four C57BL/6J mice aged 6 to 9 weeks were randomly divided into the infection group and the control group, of 12 mice in each group. Mice in the infection group were administered with 3 000 E. multilocularis protoscoleces via portal venous injection, while animals in the control group were administered with an equal volume of physiological saline. Three mice from each group were sacrificed 4, 12 weeks and 24 weeks post-infection, and lymph nodes were sampled and stained with hematoxylin and eosin (HE) to investigate the histopathological changes of mouse lymph nodes in the infection group. The expression and localization of T lymphocyte surface markers CD3, CD4, and CD8 were observed in mouse lymph nodes using immunohistochemical staining. In addition, lymphocyte suspensions were prepared from mouse lymph nodes in both groups at different time points post-infection, and the levels of Tm cell subsets and their secreted cytokines were detected using flow cytometry. Results HE staining showed diffuse structural alterations in the subcapsular cortical and paracortical regions of mouse lymph nodes in the infection group 4 weeks post-infection with E. multilocularis. Immunohistochemical staining detected CD3, CD4 and CD8 expression in mouse lymph nodes in both groups. Flow cytometry revealed higher proportions of CD4⁺ Tm cells [(55.3 ± 4.8)% vs. (38.8 ± 6.1)%; t = -4.259, P < 0.05] and CD4⁺ tissue-resident Tm (Trm) cells [(57.7 ± 3.7)% vs. (34.1 ± 11.2)%; t = -3.990, P < 0.05] in mouse lymph nodes in the infection group than in the control group 4 weeks post-infection, and higher proportions of CD4⁺ Tm cells [(34.6 ± 3.2)% vs. (23.3 ± 7.5)%; t = -2.764, P < 0.05] and CD4⁺ Trm cells [(44.0 ± 1.9)% vs. (31.2 ± 1.5)%; t = -4.039, P < 0.05] in mouse lymph nodes in the infection group than in the control group 24 weeks post-infection. The proportions of CD8⁺ Tm cells were higher in the infection group than in the control group 4 weeks [(56.8 ± 2.7)% vs. (43.9 ± 5.2)%; t = -4.416, P < 0.01] and 12 weeks post-infection [(25.4 ± 2.7)% vs. (12.0 ± 2.6)%; t = -2.552, P < 0.05], while the proportions of tumor necrosis factor (TNF)-α⁺ CD4⁺ T cells [(15.7 ± 5.0)% vs. (49.4 ± 6.4)%; t = 7.150, P < 0.01], TNF-α⁺CD8⁺ T cells [(20.7 ± 5.5)% vs. (57.5 ± 8.4)%; t = -6.694, P < 0.01], and TNF-α⁺ CD8⁺ Tm cells [7.0% (1.0%) vs. 31.0% (11.0%); Z = -2.236, P < 0.05] were lower in the infection group than in the control group 24 weeks post-infection. Conclusions Tm cells levels are consistently increased in lymph nodes of mice at different stages of E. multilocularis infection, with Trm cells as the predominantly elevated subset. The impaired capacity of CD8⁺ Tm cells to secrete the effector molecule TNF-α in mouse lymph nodes at the late-stage infection may facilitate chronic parasitism of E. multilocularis.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Immunotherapy is an important breakthrough in canc-er treatment.Unfortunately,low drug concentration in tumor sites almost ineffectively initiates immune responses and thereby severely limits immune therapy applications in clinics.Nanoma-terials are well-recognized drug delivery system in cancer thera-py.Nanographene oxide(NGO)have shown immense perti-nence for anti-cancer drug delivery owing to their ultra-high sur-face area,chemical stability,good biocompatibility and excel-lent photosensitivity.In addition,functionalized modifications on the surface of NGO increase tumor targeting and minimize cy-totoxicity.This study focuses on reviewing the literature and up-dates on NGO in drug delivery and discussing the possibilities and challenges of NGO in cancer synergetic therapy.

Aim To explore the feasibility of the cloud exposure system for in vitro exposure experiments on inhalation toxicology.Methods Calu-3 cells cultured at the air-liquid interface(ALI)were exposed to three concentrations of lipopolysaccha-ride(LPS):high,medium,and low(800,400,200 mg·L-1)by the cloud exposure system,and phosphate buffer solu-tion(PBS)was used as a negative control group for one expo-sure,while the high concentration of LPS was used to expose Calu-3 cells for five times.Calu-3 cells were exposed to phos-phate buffer solution(PBS)once as negative control group and to high concentration of LPS solution for five times,and the ac-tivity of Calu-3 cells,the release of lactate dehydrogenase(LDH),TEER,mucin MUC5AC,and the expression of inflam-matory factors IL-6,IL-8 and TNF-α were detected 3 h and 24 h after the end of the exposure,respectively.Results Compared with the PBS-negative control group,after exposure to the Calu-3 cell model at the air-liquid interface with three concentrations of LPS,high,medium,and low,there were no significant changes in the activity and LDH release,but the cellular electrical resist-ance value was reduced,and the barrier function of the cells was impaired;with the increase of the exposure concentration,the LPS promoted the expression of the cellular mucin MUC5AC,which led to a decrease in the expression of cellular IL-6,IL-8,and a decrease in the expression of TNF-α.Expression of IL-6 and IL-8 decreased and TNF-α expression increased;as the fre-quency of exposure increased,LPS inhibited the expression of mucin and increased the expression of IL-6;an increase in the frequency of exposure along with a prolongation of post-exposure assay time resulted in an increase in the expression of cellular IL-8 and TNF-a.Conclusions The ALI cloud exposure ap-proach can effectively reflect the cellular response to positive subjects,and this in vitro exposure can be used in subsequent exposure experiments to evaluate the inhalation toxicity of com-pounds.

Aim To investigate the role of ferrostatin-1(Fer-1)in adriamycin(ADR)induced podocyte inju-ry.Methods Western blot and RT-qPCR were used to detect the expression of the ferroptosis signaling pathway and podocyte injury-related proteins in podo-cytes treated with ADR and Fer-1.The therapeutic effect of Fer-1 on podocytes was screened by CCK-8;malondialdehyde(MDA),glutathione(GSH)and Fe2+kit were used to evaluate the lipid peroxidation level of podocytes.A mouse model of ADR nephropa-thy was constructed in vivo,and the expression of fer-roptosis related proteins in mouse glomerular podocytes was detected by Western blot and RT-qPCR.The fer-roptosis level of kidney was evaluated by immunohisto-chemistry staining of 4-HNE.Results The expression level of ACSL4,a marker related to ferroptosis,was significantly up-regulated.GPX4 and SLC7A11 were significantly down-regulated in podocytes under ADR stimulation.Compared with the ADR group,Fer-1 in-tervention could partially restore the anomalous change of ferroptosis related protein and improve the expression level of podocellular damage protein desmin.The re-sults of MDA,GSH and Fe2+showed that Fer-1 could improve the lipid peroxidation level of podocytes.The expression level of ACSL4 was significantly up-regula-ted and GPX4 and SLC7A11 were significantly up-reg-ulated in the ADR model group.IHC staining of 4-HNE increased in ADR model group.Conclusions Adriamycin promotes podocyte injury by induced ferrop-tosis,and inhibiting ferroptosis may be a potential strat-egy to prevent the progression of ADR nephropathy.

Protein methylation is a common post-translational modification in organisms.For a long time,research on protein methylation mainly focused on arginine and lysine,and there were few reports on histidine methylation.However,recent studies have emphasized that histidine methylation is also a widespread and highly conserved modification,occurring at the Nπ and Nτ sites of the histidine imidazole ring,catalyzed by specific protein histidine methyltransferases(PHMTs).Here,we review the history and significant advances in histidine methylation in recent years,particularly highlighting several known histidine methyltransferases.These methyltransferases,through specific molecular mechanisms,are re-sponsible for precise methylation modifications on histidine residues,playing crucial roles in processes such as cell movement,tumor cell proliferation,and protein translation.Additionally,this article discus-ses the research methods for histidine methylation,especially the application of mass spectrometry,which plays a vital role in advancing histidine methylation research.Although the veil of histidine methylation is gradually being lifted,a complete understanding of this modification and its functional mechanisms still poses challenges.Therefore,this article also presents new insights into the current dilemmas in histidine methylation research and future research priorities,hoping to uncover more secrets of histidine methyla-tion in the future.This could expand the protein methylation modification network and provide new per-spectives and strategies for elucidating disease mechanisms and developing new therapeutic approaches.

Polyorchidism is a rare congenital malformation of the urogenital system, in which a man has three or more testes, and the excess testes are usually located in the scrotum. A case of polyorchidism was reported in this paper. The patient presented with a scrotal mass, and ultrasonography showed an echogenic mass resembling testicular tissue in the right scrotum. A palpable mass in the right lower pole of the testis was found during the operation and completely removed. Pathological examination showed that the nodule parenchyma was seminiferous tubules under the microscope, and the nodule was covered with a white structure, which was considered as polytorchidism. Six months after the operation, the bilateral testis and epididymis were normal.