Babesiosis is a zoonotic parasitic disease caused by tick-borne Babesia species. Currently, more than 100 species of Babesia have been characterized, including at least 4 species that may infect humans. Babesiosis is prevalent across the world, and humans are commonly susceptible to babesiosis. The incidence of babesiosis appears an obvious seasonal distribution, and peaks in summer and autumn. Recently, the number of reported babesiosis cases has increased year by year with the improvement of diagnostic and monitoring capabilities, and the range of animal hosts has continued to expand. However, effective prevention and control of babesiosis remain challenging because of the lack of highly effective specific drugs and available vaccines. This review summarizes the pathogenic characteristics, epidemiological characteristics, epidemic process of babesiosis, and influencing factors of its epidemic, with an emphasis on natural and social factors, so as to provide the scientific evidence for risk assessment of babesiosis and formulation of babesiosis control strategy.

Atherosclerotic cardiovascular diseases(ASCVD)are chronic progressive diseases characterized by endothelial dysfunction,and their traditional therapies have limitations.In recent years,nanocarrier systems have demonstrated significant advantages in targeted delivery,enhancing drug safety and efficacy,thereby offering new strategies for precise diagnosis and treatment of ASCVD.Nanomaterials,including polymer nanoparticles,lipid nanoparticles,inorganic nanoparticles and bio-inspired nanoparticles,can effectively intervene key pathological processes of ASCVD.They achieve therapeutic effects by regulating macrophage balance,preserving endothelial cell function,maintaining smooth muscle cell contractile phenotype and modulating platelet activity.This review summarizes the application characteristics and research progress of different types of nanomaterials in the prevention and treatment of ASCVD,and provides insights into the challenges and future prospects of this field.

Atherosclerotic cardiovascular diseases(ASCVD)are chronic progressive diseases characterized by endothelial dysfunction,and their traditional therapies have limitations.In recent years,nanocarrier systems have demonstrated significant advantages in targeted delivery,enhancing drug safety and efficacy,thereby offering new strategies for precise diagnosis and treatment of ASCVD.Nanomaterials,including polymer nanoparticles,lipid nanoparticles,inorganic nanoparticles and bio-inspired nanoparticles,can effectively intervene key pathological processes of ASCVD.They achieve therapeutic effects by regulating macrophage balance,preserving endothelial cell function,maintaining smooth muscle cell contractile phenotype and modulating platelet activity.This review summarizes the application characteristics and research progress of different types of nanomaterials in the prevention and treatment of ASCVD,and provides insights into the challenges and future prospects of this field.

Objective:To explore the prognostic value of long non-coding RNA (lncRNA) AL445524.1 in hepatocellular carcinoma (HCC) and its regulatory effect on liver cancer cells.Methods:Based on the TCGA database, bioinformatics analysis was conducted to assess the expression levels of AL445524.1 in HCC. Using the median expression level of AL445524.1 as the cut-off value, 343 HCC patients were divided into high expression group and low expression group. Survival analysis was performed using Kaplan-Meier curves. Univariate and multivariate Cox proportional hazards regression models were employed to analyze the relationship between AL445524.1 expression, other clinical characteristics, and patients' prognosis, identifying independent risk factors for the prognosis of HCC patients. Based on the results of the multivariate analysis, patients with complete data were randomly divided into a testing set ( n=215) and a training set ( n=92) in a 7∶3 ratio using a random number table method, and a nomogram prognostic prediction model for HCC was constructed. Receiver operator characteristic (ROC) curves were plotted to calculate the area under the curve (AUC) to analyze and validate the predictive performance of the model. Functional enrichment analysis was conducted on the differentially expressed genes regulated by AL445524.1. The expression level of AL445524.1 in liver cancer cells was detected using RT-PCR. Human hepatoma cell lines HCCLM3 were divided into si-AL445524.1-1, si-AL445524.1-2, si-AL445524.1-3 and si-NC groups. The CCK-8 assay was used to assess cell proliferation capability; cell scratch and Transwell assays were performed to evaluate cell migration and invasion abilities; and flow cytometry was utilized to detect cell apoptosis. Results:The expression of AL445524.1 in liver cancer tissues was significantly higher than that in para-carcinoma tissues (4.38±1.26 vs. 2.08±0.45, t=24.58, P<0.001). Kaplan-Meier survival analysis showed that the 5-year overall survival (OS) rate for HCC patients in high AL445524.1 expression group ( n=170) was 37.37%, and that of patients in low AL445524.1 expression group ( n=173) was 58.38%, with a statistically significant difference ( χ2=8.83, P=0.003). Multivariate analysis showed that tumor recurrence ( HR=2.58, 95% CI: 1.64-4.07, P<0.001), clinical stage ( HR=2.49, 95% CI: 1.63-3.81, P<0.001), and AL445524.1 expression ( HR=1.23, 95% CI: 1.06-1.41, P=0.010) were independent factors affecting the prognosis of HCC patients. A nomogram prognostic prediction model was constructed based on tumor recurrence, clinical stage, and AL445524.1 expression, with the model risk score calculated as: risk score=0.774×tumor recurrence+0.753×clinical stage+0.231×AL445524.1. The prediction model C-index values of 0.726, 0.660, and 0.678 in the training set, testing set, and overall set, respectively. ROC curve analysis showed that the AUC values for the 1-year OS rates in the training set, testing set, and overall set were 0.746, 0.630, and 0.684, respectively; the AUC values for the 3-year OS rates were 0.778, 0.736, and 0.743; and the AUC values for the 5-year OS rates were 0.794, 0.760, and 0.774. In the training set, the test set and the overall set, the predictive performance of the model score in predicting the 5-year OS rate of patients was superior to the individual predictions of AL445524.1 expression, clinical stage and tumor recurrence alone (all P<0.05). The 5-year overall survival (OS) rates of high-risk group ( n=154) and low-risk group ( n=153) were 33.54% and 77.73%, respectively, with a statistically significant difference ( χ2=28.97, P<0.001). GO and KEGG enrichment analysis suggested that the differential expression of AL445524.1 genes in high and low expression groups was mainly related to lipid metabolism and oxidation. GSEA analysis showed that the oxidative phosphorylation pathway was significantly enriched in HCC patients with high expression of AL445524.1. In vitro experiments showed that AL445524.1 expression was higher in liver cancer cells (1.97±0.14) compared to normal liver cells (1.00±0.10), with a statistically significant difference ( t=11.62, P=0.007). Silencing AL445524.1 could significantly inhibit the proliferation, migration, and invasion of liver cancer cells and promote apoptosis. In the CCK-8 proliferation experiment, the A450 values of the si-NC, si-AL445524.1-1, si-AL445524.1-2, and si-AL445524.1-3 groups after 24 hours were 0.433±0.012, 0.377±0.020, 0.383±0.020, and 0.423±0.005, respectively, with a statistically significant difference ( F=20.51, P<0.001). Additionally, the cell proliferation in the si-AL445524.1-1, si-AL445524.1-2, and si-AL445524.1-3 groups was lower than that in the si-NC group (all P<0.001). The cell scratch assay showed that the scratch healing rates of the above 4 groups were 33.60%±6.15%, 21.60%±4.30%, 26.40%± 4.60%, and 27.30%±2.60%, respectively, with a statistically significant difference ( F=42.71, P<0.001). The scratch healing rates of the si-AL445524.1-1, si-AL445524.1-2, and si-AL445524.1-3 groups were also significantly lower than that of the si-NC group (all P<0.001). Transwell migration and invasion experiments revealed that the number of migrated cells in the above 4 groups were 293.50±14.80, 110.50±10.28, 132.44±5.57, and 115.25±8.66, respectively, with a statistically significant difference ( F=374.16, P<0.001). The number of migrated cells in the si-AL445524.1-1, si-AL445524.1-2, and si-AL445524.1-3 groups were significantly lower than that in the si-NC group (all P<0.001). For the invasion assay, the number of invaded cells in the above 4 groups were 247.00±9.49, 119.00±5.57, 153.25±5.85, and 163.67±5.51, respectively, with a statistically significant difference ( F=218.14, P<0.001). The number of invaded cells in the si-AL445524.1-1, si-AL445524.1-2, and si-AL445524.1-3 groups were also significantly lower than that in the si-NC group (all P<0.001). Flow cytometry showed that the apoptosis rates of the above 4 groups were 1.70%±0.08%, 2.17%±0.11%, 2.38%±0.08%, and 2.02%±0.27%, respectively, with a statistically significant difference ( F=29.36, P<0.001). The apoptosis rate in the si-AL445524.1-1, si-AL445524.1-2, and si-AL445524.1-3 groups were significantly higher than that in the si-NC group (all P<0.001) . Conclusion:AL445524.1 can serve as a prognostic marker for HCC. The AL445524.1-related prognostic prediction model demonstrates high accuracy in predicting the 5-year OS rate of HCC patients. Patients with high AL445524.1 expression have poorer survival prognosis. Silencing AL445524.1 can inhibit liver cancer cell proliferation, migration, and invasion while promoting apoptosis, which may be related to cellular lipid metabolism or oxidative phosphorylation.

Objective:This study aimed to assess left atrial function in adults across various age groups using 4-dimensional automated left atrial quantification(4D Auto LAQ)technology.The study also aimed to compare the differences in two-dimensional(2D)and four-dimensional(4D)strains of the left atrium among different age groups, with the goal of enhancing the clinical utility of 4D Auto LAQ.Methods:A total of 409 healthy volunteers were recruited for the research.Two-dimensional and four-dimensional images were obtained using a GE Vivid E95 ultrasound system with a 4Vc four-dimensional probe.The study examined variations in 2D and 4D ultrasound parameters across various age groups.Furthermore, the relationship between left atrial reservoir strain(LASr), Left atrial conduit strain(LAScd), left atrial contraction strain(LASct), and age was explored.Results:The study involved 409 volunteers, with 217 males and 192 females, who were categorized into three age groups: young(18-45 years, n=56), middle-aged(46-65 years, n=202), and elderly(>65 years, n=151).Conventional ultrasound measurements indicated changes in left atrial anterior-posterior diameter with age progression: (31.70±3.65)mm for the young group, (34.02±3.91)mm for the middle-aged group, and(35.2±4.37)mm for the elderly group( P<0.01).The 2D and 4D left atrial parameters across the age groups were as follows: LASr(2D)(%): 37.48±7.51, 30.95±8.23, 26.9±7.56( P<0.01); LA VImax(ml/m 2): 23.54±5.79, 26.33±7.6, 28.99±8.15( P<0.01); LASr(%): 31.2±17.07, 22.5±8.59, 19.49±7.47( P<0.01).Both 2D and 4D left atrial parameters exhibited significant associations with age.Specifically, the correlations between LASr(2D)(%), LAScd(2D)(%), LASr(%), LAScd(%), and age were -0.429, 0.580, -0.354, 0.298, respectively( P<0.01). Conclusions:The 4D Auto LAQ technology is efficient in assessing left atrial function across various age groups, with age playing a significant role in influencing left atrial parameters.When compared to other ultrasound parameters, both 2D and 4D left atrial strain parameters have the ability to detect differences at an early stage, making them suitable for the early screening, evaluation, and monitoring of age-related left atrial dysfunction, especially in the elderly population.

Microwave thermotherapy(MWTT),as a treatment for tumors,lacks specificity and requires sensitizers.Most reported microwave sensitizers are single metal-organic frameworks(MOFs),which must be loaded with ionic liquids to enhance the performance in MWTT.Meanwhile,MWTT is rarely combined with other treatment modalities.Here,we synthesized a novel Fe-Cu bimetallic organic framework FeCuMOF(FCM)by applying a hydrothermal method and further modified it with methyl polyethylene glycol(mPEG).The obtained FCM@PEG(FCMP)showed remarkable heating performance under low-power microwave irradiation;it also acted as a novel nanospheres enzyme to catalyze H2O2 decompo-sition,producing abundant reactive oxygen species(ROS)to deplete glutathione(GSH)and prevent ROS clearance from tumor cells during chemodynamic treatment.The FCMP was biodegradable and demonstrated excellent biocompatibility,allowing it to be readily metabolized without causing toxic effects.Finally,it was shown to act as a suitable agent for T2 magnetic resonance imaging(MRI)in vitro and in vivo.This new bimetallic nanostructure could successfully realize two tumor treatment modalities(MWTTand chemodynamic therapy)and dual imaging modes(T2 MRI and microwave thermal imaging).Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and pro-vides a reference for developing new microwave sensitizers.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Objective To observe the effect of myocardial transcription factor MRTF-A on myocardium inflammation and its mechanism.Methods Totally 30 rats were randomly divided into the sham,ischemia-reperfusion (myocardial ischemia 30 min and reperfusion 2 h),and MRTF-A groups(myocardial ischemia 30 min and reperfusion 2 h & Lentivirus infection MRTF-A) (n=10 each group).Serum myocardial enzyme activity was detected by biochemical analysis,myocardial infarct size detected by TTC,and degree of myocardial injury was measured by HE staining.The TLR4 and TRIF expression was analyzed by immunohistochemistry and qPCR.Results Compared with the sham group,the MRTF-A group significantly increased the activity of serum myocardial enzymes CK-MB and LDH (P＜0.05).The infarct area of myocardial tissue was gray-white,and the infarct area was (54.31±3.07)％ (P ＜ 0.05).Myocardial fibrosis was disorder,myocardial cell was swollen and burst,and inflammatory cell infiltration was obvious.Protein and mRNA expressions of TRL4 and TRIF were significantly up-regulated (P＜0.05).Compared with the ischemia-reperfusion group,the levels of CK-MB and LDH were significantly reduced after myocardial infection with MRTF-A (P＜0.05).The myocardial infarction area was significantly reduced to (16.74±4.26)％ (P＜ 0.05).The myocardial structure was nearly normal with mild edema.Protein and mRNA expression of TRL4 and TRIF decreased significantly (P＜0.05).Conclusions The overexpression of transcription factor MRTF-A in myocardial cells alleviates the myocardial ischemia reperfusion injury by inhibiting the TLR4/TRIF signaling pathway and reducing the serum myocardial enzyme activity and myocardial damage.

A deficit in spatial memory has been taken as an early predictor of Alzheimer's disease (AD) or mild cognitive impairment (MCI). The uncinate fasciculus (UF) is a long-range white-matter tract that connects the anterior temporal lobe with the orbitofrontal cortex (OFC) in primates. Previous studies have shown that the UF impairment associated with spatial memory deficits may be an important pathological change in aging and AD, but its exact role in spatial memory is not well understood. The pathway arising from the postrhinal cortex (POR) and projecting to the ventrolateral orbitofrontal cortex (vlOFC) performs most of the functions of the UF in rodents. Although the literature suggests an association between spatial memory and the regions connected by the POR-vlOFC pathway, the function of the pathway in spatial memory is relatively unknown. To further illuminate the function of the UF in spatial memory, we dissected the POR-vlOFC pathway in mice. We determined that the POR-vlOFC pathway is a glutamatergic structure, and that glutamatergic neurons in the POR regulate spatial memory retrieval. We also demonstrated that the POR-vlOFC pathway specifically transmits spatial information to participate in memory retrieval. These findings provide a deeper understanding of UF function and dysfunction related to disorders of memory, as in MCI and AD.
Animals ; Glutamic Acid ; physiology ; Male ; Mental Recall ; physiology ; Mice, Inbred C57BL ; Neural Pathways ; cytology ; physiology ; Neuroanatomical Tract-Tracing Techniques ; Neurons ; physiology ; Prefrontal Cortex ; cytology ; physiology ; Spatial Memory ; physiology ; Temporal Lobe ; cytology ; physiology

Antineoplastic Agents ; Dasatinib ; Humans ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Protein Kinase Inhibitors ; Pyrimidines/therapeutic use*