Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Quantum dot-based single-virus tracking has become a practical method to explore the molecular mechanism of virus entry into cells,because it can realize virion imaging in living cells.Mink enteritis virus(MEV)is a single-stranded DNA virus with strong environmental resistance,which has caused huge economic losses for the global mink farming industry.Although epidemio-logic and clinical aspects of MEVs have been studied,the mechanisms by which it infect target cells remain unclear.In this study,we implemented quantum dot labeling of mink enteritis virus u-sing the biotin-streptomycin affinity system and monitored the viral infection process in host cells.We found that MEV first attaches to the cell membrane and enters the cell by endocytosis.Live cell images showed quantum dot(QD)-MEV movement along microtubules,and viral infection was also inhibited by treatment with the microtubule inhibitor nocodazole,whereas the addition of the microfilament inhibitor CytoD had no effect on infection,suggesting that MEV transport is de-pendent on microtubules rather than microfilaments.Another imaging results showed that MEV co-localized with Rab5 and Rab7 in host cells,suggesting that the endosomal system is required for MEV internalization.Biochemical analyses showed that viral infection was significantly inhibited after pretreatment of host cells with the endosomal acidification inhibitors NH4 Cl and chloro-quine,suggesting that MEV invasion requires an acidic environment in the endosomes.Our results indicated that MEV enters early and late endosomes after entering the cell membrane,and that in-tracellular translocation is microtubule-dependent,which may in turn uncover a novel target for antiviral treatment.

Objective To analyze the characteristics of acupoint selection in treatment for func-tional constipation.Methods Clinical literature on acupuncture and electroacupuncture therapy for functional constipation from January 1,2013,to December 31,2023,was retrieved from CNKI.The acupuncture prescriptions were collected and organized,and data mining techniques were employed to analyze the patterns of acupoint selection.Results A total of 182 articles were included,yielding 123 acupuncture prescriptions involving 92 acupoints with usage frequency of 967 times.The top 10 acu-points in frequency were Tianshu(158 times),Shangjuxu(138 times),Dachangshu(61 times),Zu-sanli(60 times),Zhigou(57 times),Fujie(57 times),Guanyuan(35 times),Zhongwan(34 times),Qihai(34 times),and Quchi(28 times).The meridians of the selected acupoints for acu-puncture treatment of functional constipation were mainly involved in stomach,bladder,Ren,and spleen meridians.Association rule analysis revealed that the combination of Tianshu-Shangjuxu had the highest occurrence probability(75.82％),followed by Tianshu-Dachangshu(33.52％)and Tianshu-Zusanli(32.97％).Cluster analysis of acupoints showed that the main acupoints selected for acu-puncture treatment of functional constipation could be divided into 10 clusters,including primary acu-points,acupoints for various syndrome types,acupoints for regulating spirit,and acupoints for regula-ting sympathetic nerves.Conclusion Acupuncture treatment for functional constipation should follow the principles of holistic treatment and syndrome differentiation,combined with the methods of selecting acupoints based on their upper-lower,proximal-distal,and anterior-posterior relationships.The acu-point selection patterns identified in this study can provide important references for clinical treatment of functional constipation,offer guidance for practitioners in acupoint selection,facilitate precise treatment,and promote early patient recovery.

Quantum dot-based single-virus tracking has become a practical method to explore the molecular mechanism of virus entry into cells,because it can realize virion imaging in living cells.Mink enteritis virus(MEV)is a single-stranded DNA virus with strong environmental resistance,which has caused huge economic losses for the global mink farming industry.Although epidemio-logic and clinical aspects of MEVs have been studied,the mechanisms by which it infect target cells remain unclear.In this study,we implemented quantum dot labeling of mink enteritis virus u-sing the biotin-streptomycin affinity system and monitored the viral infection process in host cells.We found that MEV first attaches to the cell membrane and enters the cell by endocytosis.Live cell images showed quantum dot(QD)-MEV movement along microtubules,and viral infection was also inhibited by treatment with the microtubule inhibitor nocodazole,whereas the addition of the microfilament inhibitor CytoD had no effect on infection,suggesting that MEV transport is de-pendent on microtubules rather than microfilaments.Another imaging results showed that MEV co-localized with Rab5 and Rab7 in host cells,suggesting that the endosomal system is required for MEV internalization.Biochemical analyses showed that viral infection was significantly inhibited after pretreatment of host cells with the endosomal acidification inhibitors NH4 Cl and chloro-quine,suggesting that MEV invasion requires an acidic environment in the endosomes.Our results indicated that MEV enters early and late endosomes after entering the cell membrane,and that in-tracellular translocation is microtubule-dependent,which may in turn uncover a novel target for antiviral treatment.

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 explore the benefits of transradial diagnostic cerebral angiography in elderly patients and its correlation with morphometric parameters of the aortic arch.Methods:Clinical data and aortic arch CTA imaging parameters of patients who underwent cerebral angiography at the Department of Neurosurgery, Beijing Hospital, between May 2022 and April 2023 were retrospectively analyzed.The study aimed to compare the time taken for angiography via radial artery access in elderly patients versus younger patients, as well as via femoral artery access, and to evaluate the associated aortic arch morphology parameters.Results:A total of 101 patients' data were analyzed, with 67 males(66.3%)and an average age of 63.4±12.0 years.Among them, 69 patients(68.3%)were aged 60 and above.The arterial approach for 44 patients(43.6%)was radial, while 57 cases(56.4%)used the femoral artery approach.In the elderly group, 14 cases(20.6%), 31 cases(45.6%), and 23 cases(33.8%)had type Ⅲ aortic arch, respectively.For younger patients, 17 cases(53.1%), 12 cases(37.5%), and 3 cases(9.4%)fell into these categories.The distribution difference was statistically significant( χ2=12.765, P=0.002).Elderly patients had a larger aortic arch width angle compared to younger patients(106°±12°and 100°±12°, t=2.334, P=0.022).The time for whole-brain angiography via radial artery was shorter for elderly patients than via femoral artery(39.8±29.5 minutes and 52.2±28.4 minutes, respectively, t=1.845, P=0.070).In young patients, there was no significant time difference between the two approaches(42.3±30.4 minutes for radial artery and 34.6±11.2 minutes for femoral artery, t=1.026, P=0.313).In the type Ⅱ aortic arch group, the average times for transradial and transfemoral approaches were 38.1±21.7 minutes and 46.7±32.2 minutes, respectively( t=1.020, P=0.314).The average times for the type Ⅲ aortic arch group were 41.9±37.3 minutes and 48.9±20.7 minutes, respectively.Correlation analysis revealed a significant negative correlation between the duration of radial artery access and the distance from the origin of the innominate artery to the left subclavian artery(Pearson correlation coefficien( r=-0.372, P=0.014). Conclusions:In elderly patients, particularly those with type Ⅱ or Ⅲ aortic arch or a wide aortic arch, diagnostic cerebral angiography using transradial access is preferable to femoral access.The distance between the innominate artery and the left subclavian artery origin could impact the duration of the procedure.

Objective: Conebeam CT (CBCT) was used to measure the palatine between the maxillary first and second molars. The proximal and distal palatal widths of the maxillary first and second molar and the palatal mucosal thickness and bone tissue thickness when microscrew implant anchorage nail were implanted at different angles provided a reference for the clinical selection of microscrew implant placement. Methods: The image data of 90 adult patients were selected as the research object, and the jaw bone was reconstructed by scanning. In maxillary palatine, selection of distances at 12 mm, 14 mm, 16 mm, and 18 mm from the palatal apex of maxillary first molar between the maxillary first and second molar were used as measurement, measured the proximal and distal palatal widths of maxillary first and second molar and the palatal mucosal thickness and bone tissue thickness when microscrew implant anchorage nails were implanted at 30 °, 45 °, 60 °, and 90 °. SPSS 26.0 software was used for one-way ANOVA and LSD pair comparison. Results: The larger the angle of the microscrew implant anchorage nail was, the smaller the proximal and distal medial widths between the maxillary first and second molar, and the difference was statistically significant (P < 0.05). Compared with the 90° direction, the proximal and distal medial widths of the microscrew implant anchorage nail were larger in the 60° direction. The greater the angle of implantation, the smaller the mucosal thickness and the greater the bone tissue thickness, and the results showed a significant difference (P < 0.001). Compared with the direction of 30° and 45°, the mucosal thickness at the direction of 60° was smaller, and the bone tissue thickness was larger. The higher the position of the microscrew implant anchorage nail, the greater the width of the proximal and distal medial, and the difference was statistically significant (P < 0.05). Compared with the positions 12 and 14 mm from the palatal tip, the proximal and distal medial widths of the microscrew implant anchorage nail were larger. The higher the implant position was, the greater the mucosal thickness and the smaller the bone tissue thickness. The results showed a significant difference (P < 0.001). Compared with the position of 18 mm from the palatal tip of the maxillary first molar, the mucosal thickness was smaller and the bone tissue thickness was larger. Conclusion It is most appropriate to implant microscrew implant anchorage nail at least 10 mm in length in the direction of 60° at the palatal apex 16 mm from the maxillary first molar in palatine between the first and second molar.

The biocompatibility of nanomaterials has attracted much attention. Graphene oxide (GO) is a nanomaterial widely used in biomedicine, but its toxicity can not be ignored. In this study, the effect of GO on the blood system (the hemolysis rate, the fragility of erythrocyte, and acetylcholinesterase activity) was systematically investigated. The results showed that the hemolysis rate of erythrocytes was lower than 8% when the GO concentration was below 100 μg/mL (P<0.01). GO at low concentration levels (<5 μg/mL) had no significant effect on the fragility of erythrocytes, but GO at high concentration (10 μg/mL) increased the fragility of erythrocytes (P=0.01). Moreover, GO increased the activity of acetylcholinesterase on erythrocytes. The concentration of 20 μg/mL graphene oxide with the size >5 μm (LGO) increased the activity of acetylcholinesterase by 42.67% (P<0.05). Then molecular dynamics simulation was used to study how GO interacted with acetylcholinesterase and increased its activity. The results showed that GO was attached to the cell membrane, thus may provide an electronegative environment that helps the hydrolysate to detach from the active sites more quickly so as to enhance the activity of acetylcholinesterase.
Acetylcholinesterase ; Erythrocytes ; Graphite ; Nanostructures