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

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

Objective To investigate the effects of advanced maternal age(AMA)on synaptic pruning of the hippocampus of offspring rats.Methods Offspring of 3-month-old SD female rats and 3-month-old SD male rats were designated as the appropriate age group(Ctl group),while offspring of 12-month-old SD female rats and 3-month-old SD male rats were assigned to AMA group.Hippocampal tissues from both groups(n=3 per group at each time point)were subjected to Golgi staining on postnatal days(P)7,28,and 60.Dendritic complexity,spine density(DS),and morphology of immature brain neurons at different age stages were compared between the two groups.Results Compared with Ctl group,the dendritic length of AMA group on P7,P28,and P60 was significantly shortened,and the average number of intersections between dendrites and concentric circles on P28 and P60 was also significantly decreased(P<0.05).Compared with Ctl group,the dendritic spine density of AMA group was significantly decreased on P7,P28,and P60.Notably,the density of thin-shaped dendritic spines in AMA group was increased on P7,whereas the densities of stubby-shaped and mushroom-shaped dendritic spines were decreased(P<0.05).On P28 in AMA group,the densities of thin-shaped and mushroom-shaped dendritic spines were significantly increased compared with Ctl group,while the density of stubby-shaped dendritic spines was significantly decreased(P<0.05).The densities of stubby-shaped and mushroom-shaped dendritic spine were markedly lower in AMA group on P60 than those in Ctl group(P<0.05).Conclusions During postnatal brain development periods,there were abnormalities in synaptic pruning in the hippocampal region of the offspring of the AMA,which manifested as reduced dendritic complexity,decreased dendritic spine density,and disorganized dendritic spine morphology.It could be one of the key mechanisms underlying brain dysfunction in the offspring of AMA.

Alcoholic liver disease(ALD)is a liver disease caused by long-term heavy drinking and one of the most common causes of liver-related morbidity and mortality.According to Chinese medicine,the development of ALD is mainly related to alcoholism,and the evolution of its pathology is a gradually aggravating process.Wine-heat injures the liver,without obvious organic lesions at the initial stage,and as the disease progresses to different stages,internal dampness appears,dampness depresses and transforms into heat,and Qi stagnation and blood stasis are gradually aggravated,which affects the functions of various internal organs,directly or indirectly,and creates a complex mechanism of crosstalk between the liver and other organs,which leads to the pathological condition of This leads to the pathological state of multi-organ dysfunction.Modern research has found that long-term alcohol abuse not only causes direct damage to the liver,but also leads to progression to end-stage liver disease by altering the intestinal barrier function and intestinal microbial community,and producing kidney damage and cardiac function.This article reviewed recent studies on the interactions between the liver and other organs in light of the Chinese and Western pathogenesis of alcoholic liver disease and the theory of organ crosstalk,and introduces potential strategies for the treatment of alcoholic liver disease,which will provide a reference for the discovery of new therapeutic avenues.

Aim To investigate the effect of triptolide(TP)on corticosterone(CORT)-induced depression-like behaviors in mice and explore the antidepressant mechanism of TP based on the CREB/BDNF/TrkB sig-naling pathway.Methods Sixty 8-week-old male C57BL/6J mice were randomly divided into five groups:control group,CORT group,TP groups of low and high doses(10,30 μg·kg-1),and fluoxetine(FLU)group(10 mg·kg-1).Except for the control group,the other groups received subcutaneous injec-tions of CORT for three consecutive weeks to establish the model of depression.During the last two weeks of modeling,normal saline,TP and FLU were adminis-tered via intraperitoneal injection respectively.After the administration,depression-like behaviors in mice were assessed using forced swimming test,tail suspen-sion test,and sucrose preference test.Biochemical methods were used to measure the levels of SOD and MDA in the hippocampus and prefrontal cortex(PFC).Cell apoptosis was detected by TUNEL meth-od.Immunohistochemistry,immunofluorescence,and Western blotting were employed to detect the expres-sion of apoptosis/autophagy-related proteins,synaptic structure markers,and proteins related to the CREB/BDNF/TrkB signaling pathway.Results TP signifi-cantly ameliorated CORT-induced depression-like be-haviors in mice,mainly manifested by reduced immo-bility time in the tail suspension test and forced swim-ming test,and increased sucrose preference rate.TP alleviated CORT-induced oxidative stress by increasing SOD levels and reducing MDA production in brain tis-sue.Additionally,TP also inhibited apoptosis and ex-cessive autophagy of neurons in the hippocampus and prefrontal cortex,maintained synaptic plasticity,and significantly upregulated the expression of p-CREB,BDNF,and TrkB.Conclusions TP exhibits potential antidepressant effect in mice by upregulating the CREB/BDNF/TrkB signaling pathway,reducing oxida-tive stress,inhibiting excessive neuronal apoptosis and autophagy,and improving synaptic plasticity.

Aim To detect the mechanism of Wenshen Jianpi recipe(WSJPR)regulating the autophagy by p70S6K signaling pathway on alleviating podocyte inju-ry in diabetic nephropathy(DN)rats.Methods DN model rats induced by streptozotocin were divided into five groups with six rats in each group:model control group,low dose group(7.5 g·kg-1·d-1),medium dose group(15 g·kg-1·d-1),high dose group(30 g·kg-1·d-1),and positive control group(25 mg·kg-1·d-1).In addition,six normal rats were used as negative control group(isotonic NaCl solution 10 mL·kg-1·d-1).All the rats were given continuous ga-vage for eight weeks.Fasting blood glucose,urine al-bumin/creatinine ratio(UACR)and blood viscosity were determined.The changes of podocyte ultrastruc-ture and autophagosome in each group were observed by transmission electron microscopy(TEM).The pro-tein levels of signaling pathway factor p70S6K and au-tophagy factor p62 in renal tissues of rats in each group were detected by Western blot.Besides,p62 expres-sion was observed by immunohistochemistry.Results WSJPR could decrease fasting blood glucose and UACR,and improve the indexes of blood viscosity in rats.TEM indicated that WSJPR could significantly improve the podocyte ultrastructure and autophagy level in DN rats.Western blot showed that the expression level of signaling pathway factor p70S6K and autophagy factor p62 in the kidney of DN rats increased signifi-cantly compared with blank control group(P＜0.01).The expression level of p70S6K and p62 in WSJPR groups decreased compared with model control group(P＜0.05).Among them,the medium-dose group of WSJPR had the most significant change.Immunohisto-chemical results showed that the level of autophagy fac-tor p62 in kidney tissue of DN rats increased compared with the control group.WSJPR had a certain inhibitory effect on p62 expression in DN rats.Conclusion WSJPR might restore cell homeostasis by inhibiting p70S6K level,reducing the expression of autophagy factor p62 and enhancing autophagy level in renal tis-sue of DN rats.

Aim To investigate the effect of p-AMPK activity on autophagy in different subtypes of MDA-MB-231(triple-negative breast cancer cells)and MCF-7(estrogen receptor-positive cells)and its regulatory mechanism.Methods MDA-MB-231 cells were trea-ted with EBSS,Baf-A1,and EBSS+Baf-A1 for four hours,and MCF-7 cells for eight hours.The effects of autophagy on cell proliferation and apoptosis were ob-served,mitochondrial morphology was examined,and the expression of autophagy markers LC3B,P62,LAMP1,TOM20,AMPK,p-AMPK,ULK1,and Bec-lin1/VPS34 proteins was detected.The autophagy pathway was validated by inhibiting AMPK activity.Results Breast cancer cells underwent autophagy af-ter starvation induction(EBSS),with inconsistent au-tophagy processes observed in different subtypes of breast cancer cells.Autophagy inhibited cell prolifera-tion.In MDA-MB-231 cells,autophagy led to an in-crease in p-AMPK levels and a decrease in ULK1 lev-els,initiating autophagy through p-AMPK activation of ULK1.In MCF-7 cells,both p-AMPK and ULK1 levels decreased after autophagy,suggesting that autophagy might not be mediated by p-AMPK activation.Conclu-sions MDA-MB-231 cells primarily initiate autophagy by directly activating ULK1 by p-AMPK,independent of the MTOR pathway.In MCF-7 cells autophagy might be triggered by inhibiting MTOR through AMPK activity or directly activating MTOR through other up-stream factors.Regulating p-AMPK activity based on the autophagy pathways in different cell subtypes could enable more precise targeting and treatment of different types of breast cancer.

Arson is classified as a violent crime,and often involves accelerants that significantly increase casualties and property damage.These accelerants,typically flammable liquids with low saturated vapor pressure,present volatile characteristic components in fire residues,making evidence preservation critical for accurate forensic analysis.In this study,the preservation performance of AMPAC(American KAPAC polyester sampling bags)and polyethylene(PE)evidence bags were evaluated under simulated field conditions(40 oC)through gas chromatography-mass spectrometry(GC-MS)technique,focusing on background interference,sealing integrity,and cross-contamination.The results demonstrated that AMPAC bags exhibited minimal background interference(C12?C14 alkanes detected after 3?7 days)and effective gasoline sealing,though slight losses of C2?C3 alkylbenzenes and trace cross-contamination were observed.In contrast,PE bags showed significant background hydrocarbons(C15?C19 alkanes)and pronounced gasoline component losses,including C2?C4 alkylbenzenes,naphthalenes,and indenes.Notably,severe cross-contamination of gasoline markers was detected in adjacent blank PE bags,with characteristic components such as C2?C4 alkylbenzenes,naphthalenes,methylnaphthalenes,dimethylnaphthalenes,indenes,indanes,methylindenes,and dimethylindenes identified,indicating substantial cross-contamination issues in PE evidence bags.Microstructural analysis revealed superior sealing in AMPAC bags attributed to their smooth,dense surface morphology compared to PE's rougher,porous structure.This study established a comprehensive evaluation framework for fire residue evidence containers,and found that PE bags were unsuitable for long-term gasoline evidence preservation due to compromised integrity.These findings provided critical references for forensic container selection in fire investigations.

Nitrofurantoin(NFT)is a nitrofuran antibiotic commonly used as a veterinary drug to treat bacterial infections in animals.However,due to the low solubility and bioaccumulation properties,NFT is prone to leave excessive residues in animal-derived foods and water systems,posing serious threats to human health and ecosystems.Therefore,there is an urgent need to develop an efficient and rapid detection method for NFT.In this work,nitrogen-doped carbon nanomaterials with unique bowl-like structures(N-CNBs)were synthesized via a hydrothermal-carbonization method.The morphology,surface structure,and specific surface area of N-CNBs were characterized using transmission electron microscopy(TEM),scanning electron microscopy(SEM),and X-ray photoelectron spectroscopy(XPS).The N-CNB modified glassy carbon electrode(N-CNB/GCE)was prepared,and the electrochemical test revealed that the N-CNB/GCE exhibited higher conductivity and larger electrochemical active surface area compared to bare GCE and nitrogen-doped hollow carbon nanosphere-modified electrode(N-HCNS/GCE).Additionally,the N-CNB/GCE demonstrated superior electrocatalytic activity toward NFT.An NFT electrochemical sensor was constructed based on N-CNB/GCE.The detection conditions of the sensor were optimized,and differential pulse voltammetry(DPV)was employed for NFT detection under optimal experimental conditions.The established NFT electrochemical sensor had a wide linear range of 0.4-500 μmol/L,a low detection limit(S/N=3)of 0.015 μmol/L and high selectivity,with excellent stability and reproducibility.The practical feasibility of this sensor was confirmed by analysis of NFT in milk and tap water samples,with spiked recoveries ranging from 94.2%to 108.9%.

Objective: This study aims to evaluate the clinical benefits of the integrated optical and magnetic surgical navigation system in assisting transforaminal endoscopic lumbar discectomy (TELD) for the treatment of lumbar disc herniation (LDH). Methods: A retrospective analysis was conducted on patients who underwent TELD for LDH at Beijing Chaoyang Hospital, Capital Medical University from November 2022 to December 2023. Patients treated with the integrated optical and magnetic surgical navigation system were defined as the navigation-guided TELD (Ng-TELD) group (30 cases), while those treated with the conventional x-ray fluoroscopy method were defined as the control group (31 cases). Record and compare baseline characteristics, surgical parameters, efficacy indicators, and adverse events between the 2 patient groups. Results: The average follow-up duration for the 61 patients was 11.8 months. Postoperatively, both groups exhibited significant relief from back and leg pain, which continued to improve over time. At the final follow-up, patients’ lumbar function and quality of life had significantly improved compared to preoperative levels (p < 0.05). The Ng-TELD group had significantly shorter total operation time (58.43 ± 12.37 minutes vs. 83.23 ± 25.90 minutes), catheter placement time (5.83 ± 1.09 minutes vs. 15.94 ± 3.00 minutes), decompression time (47.17 ± 11.98 minutes vs. 67.29 ± 24.23 minutes), and fewer intraoperative fluoroscopies (3.20 ± 1.45 vs. 16.58 ± 4.25) compared to the control group (p < 0.05). There were no significant differences between the groups in terms of efficacy evaluation indicators and hospital stay. At the final follow-up, the excellent and good rate of surgical outcomes assessed by the MacNab criteria was 98.4%, and the overall adverse event rate was 8.2%, with no statistically significant differences between the groups (p > 0.05). Conclusion This study demonstrates that the integrated optical and magnetic surgical navigation system can reduce the complexity of TELD, shorten operation time, and minimize radiation exposure for the surgeon, highlighting its promising clinical potential.