Two Fluorescent Probes for Recognition of Acetylcholinesterase: Design, Synthesis, and Comparative Evaluation.

In this study, two "on-off" probes (BF2-cur-Ben and BF2-cur-But) recognizing acetylcholinesterase (AChE) were designed and synthesized. The obtained probes can achieve recognition of AChE with good selectivity and pH-independence with a linear range of 0.5~7 U/mL and 0.5~25 U/mL respectively. BF2-cur-Ben has a lower limit of detection (LOD) (0.031 U/mL), higher enzyme affinity (Km = 16 ± 1.6 µM), and higher inhibitor sensitivity. A responsive mechanism of the probes for AChE was proposed based on HPLC and mass spectra (MS) experiments, as well as calculations. In molecular simulation, BF2-cur-Ben forms more hydrogen bonds (seven, while BF2-cur-But has only four) and thus has a more stable enzyme affinity, which is mirrored by the results of the comparison of Km values. These two probes could enable recognition of intracellular AChE and probe BF2-cur-Ben has superior cell membrane penetration due to its higher log p value. These probes can monitor the overexpression of AChE during apoptosis of lung cancer cells. The ability of BF2-cur-Ben to monitor AChE in vivo was confirmed by a zebrafish experiment.

Doping Ferrocene-Based Conjugated Microporous Polymers with 7,7,8,8-Tetracyanoquinodimethane for Efficient Photocatalytic CO2 Reduction.

The design and synthesis of organic photocatalysts remain a great challenge due to their strict structural constraints. However, this could be mitigated by achieving structural flexibility by constructing permanent porosity into the materials. Conjugated microporous polymers (CMPs) are an emerging class of porous materials with an amorphous, three-dimensional network structure, which makes it possible to integrate the elaborate functional groups to enhance photocatalytic performance. Here, we report the synthesis of a novel CMP, named TAPFc-TFPPy-CMP, constructed by 1,1'3,3'-tetra(4-aminophenyl)ferrocene (TAPFc) and 1,3,6,8-tetrakis(4-formylphenyl)pyrene (TFPPy) monomers. The integration of the p-type dopant 7,7,8,8-tetracyanoquinodimethane (TCNQ) into the TAPFc-TFPPy-CMP improved the light adsorption performance, leading to a decrease in the optical bandgap from 2.00 to 1.43 eV. The doped CMP (TCNQ@TAPFc-TFPPy-CMP) exhibited promising catalytic activity in photocatalytic CO2 reduction under visible light, yielding 546.8 µmol g-1 h-1 of CO with a selectivity of 96% and 5.2 µmol g-1 h-1 of CH4. This represented an 80% increase in the CO yield compared to the maternal TAPFc-TFPPy-CMP. The steady-state photoluminescence (PL) and fluorescence lifetime (FL) measurements reveal faster carrier separation and transport after the doping. This study provides guidance for the development of organic photocatalysts for the utilization of renewable energy.

Current status of emergency medical service use in ST-segment elevation myocardial infarction in China: Findings from China Acute Myocardial Infarction (CAMI) Registry.

BACKGROUND: The mortality rate of myocardial infarction in China has increased dramatically in the past three decades. Although emergency medical service (EMS) played a pivotal role for the management of patients with ST-segment elevation myocardial infarction (STEMI), the corresponding data in China are limited. METHODS: An observational analysis was performed in 26,305 STEMI patients, who were documented in China acute myocardial infarction (CAMI) Registry and treated in 162 hospitals from January 1st, 2013 to January 31th, 2016. We compared the differences such as demographic factors, social factors, medical history, risk factors, socioeconomic distribution and treatment strategies between EMS transport group and self-transport group. RESULTS: Only 4336 patients (16.5%) were transported by EMS. Patients with symptom onset outside, out-of-hospital cardiac arrest and presented to province-level hospital were more likely to use EMS. Besides those factors, low systolic blood pressure, severe dyspnea or syncope, and high Killip class were also positively related to EMS activation. Notably, compared to self-transport, use of EMS was associated with a shorter prehospital delay (median, 180 vs. 245 min, P < 0.0001) but similar door-to-needle time (median, 45 min vs. 52 min, P = 0.1400) and door-to-balloon time (median, 105 min vs. 103 min, P = 0.1834). CONCLUSIONS: EMS care for STEMI is greatly underused in China. EMS transport is associated with shorter onset-to-door time and higher rate of reperfusion, but not substantial reduction in treatment delays or mortality rate. Targeted efforts are needed to promote EMS use when chest pain occurs and to set up a unique regionalized STEMI network focusing on integration of prehospital care procedures in China. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01874691), retrospectively registered June 11, 2013.

Design, synthesis, and evaluation of a carboxylesterase detection probe with therapeutic effects.

In this study, a lysosomal targeting fluorescent probe recognition on CEs was designed and synthesized. The obtained probe BF2-cur-Mor demonstrated excellent selectivity, sensitivity, pH-independence, and enzyme affinity towards CEs within 5 min. BF2-cur-Mor could enable recognition of intracellular CEs and elucidate that the CEs content of different cancer cells follows the rule of HepG2 > HCT-116 > A549 > HeLa, and the CEs expression level of hepatoma cancer cells far exceeds that of normal hepatic cells, being in good agreement with the previous reports. The ability of BF2-cur-Mor to monitor CEs in vivo was confirmed by zebrafish experiment. BF2-cur-Mor exhibits some pharmacological activity in that it can induce apoptosis in hepatocellular carcinoma cells but is weaker in normal hepatocyte cells, being expected to be a potential "diagnostic and therapeutic integration" tool for the clinical diagnosis of CEs-related diseases.

Vision-driven metasurfaces for perception enhancement.

Metasurfaces have exhibited unprecedented degree of freedom in manipulating electromagnetic (EM) waves and thus provide fantastic front-end interfaces for smart systems. Here we show a framework for perception enhancement based on vision-driven metasurface. Human's eye movements are matched with microwave radiations to extend the humans' perception spectrum. By this means, our eyes can "sense" visual information and invisible microwave information. Several experimental demonstrations are given for specific implementations, including a physiological-signal-monitoring system, an "X-ray-glasses" system, a "glimpse-and-forget" tracking system and a speech reception system for deaf people. Both the simulation and experiment results verify evident advantages in perception enhancement effects and improving information acquisition efficiency. This framework can be readily integrated into healthcare systems to monitor physiological signals and to offer assistance for people with disabilities. This work provides an alternative framework for perception enhancement and may find wide applications in healthcare, wearable devices, search-and-rescue and others.

Cognitive function and its associated factors among patients with cancer pain: a multicentre cross-sectional study in China.

OBJECTIVE: This research aimed to assess the levels of cognitive function and its contributing factors among individuals experiencing cancer pain (CP) in mainland China. DESIGN: A descriptive, cross-sectional study. SETTING: The investigation was undertaken within three tertiary oncology hospitals. PARTICIPANTS: We included 220 hospitalised individuals who reported experiencing cancer-related pain and consented to complete the research questionnaires. OUTCOME MEASURES: The collected data encompassed sociodemographic and clinical variables, augmented by results from validated questionnaires. Cognitive impairment (CI) was evaluated using the Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog) scale, with scores ranging from 0 to 148. Sleep quality, depression and anxiety were assessed through the Pittsburgh Sleep Quality Index, the Patient Health Questionnaire-9 and the Generalised Anxiety Disorder-7, respectively. A binary logistic regression model was used to identify factors associated with CI in individuals with CP. RESULTS: Of the 225 individuals approached, 220 (97.8%) participated in the study. The mean FACT-Cog score for those with CP was 101.29 (SD=25.24; range=25-148). The prevalence of CI among these individuals was 35.90%. Sleep quality was rated below medium in 45% of participants with CP. More than moderate pain was reported by 28.2%, with 64.6% experiencing depression and 38.6% experiencing anxiety. Increased odds of developing CI were observed in those with CP (OR 1.422, 95% CI 1.129 to 1.841), depression (OR 1.119, 95% CI 1.029 to 1.2117), anxiety (OR 1.107, 95% CI 1.005 to 1.220), advancing age (OR 1.042, 95% CI 1.013 to 1.073), poor sleep quality (OR 1.126, 95% CI 1.013 to 1.252) and a history of smoking (OR 3.811, 95% CI 1.668 to 8.707). CONCLUSIONS: CI associated with CP is notably prevalent in China. Those older, with a smoking history, inadequate sleep, more severe pain, depression and anxiety, have a heightened risk of CI. Consequently, interventions need to be personalised, addressing these key determinants.

Age-period-cohort analysis of long-term trends in ischemic stroke mortality in China caused by specific risk factors from 1990 to 2019.

OBJECTIVE: To study the primary risk factors for the long-term trends of mortality rates in ischemic stroke (IS) in China. METHODS: Using the Global Burden of Disease Study 2019 (GBD 2019) database, research was conducted on the 11 primary risk factors for the mortality rates of IS in China from 1990 to 2019. This study employed Joinpoint regression software and the Age-Period-Cohort (APC) method to evaluate the trends of mortality rates divided by age, period, and cohort over time. RESULTS: From 1990 to 2019, the age-standardized mortality rate (ASMR) caused by a diet high in red meat and high body-mass index (BMI) in China showed an upward trend. ASMR increased first and then decreased due to smoking, diet high in sodium, particulate matter pollution, high fasting plasma glucose, and high systolic blood pressure. Low-density lipoprotein cholesterol (LDL-C), kidney dysfunction, low temperature, and lead exposure remained relatively stable during this period. In the 35-45 age group, the mortality rate of IS due to high LDL-C was up to about 60%, and smoking affected men more than women. Overall, high LDL-C, high systolic blood pressure, and particulate matter pollution were the most common risk factors in patients with IS. The risk of death rose with age. The period and cohort relative risks showed that metabolic risk factors had the greatest impact on the mortality of IS. CONCLUSION: Metabolic risk factors have become the primary risk factors for the ASMR of IS in China. Relevant authorities should pay attention to their long-term effects on IS. Effective public health policies and interventions should be implemented to reduce the burden of IS.

Chinese expert consensus statement on the clinical application of AFP/AFP-L3%/DCP using GALAD and GALAD-like algorithm in HCC.

BACKGROUND: Primary hepatocellular carcinoma (HCC) is one of the most prevalent world-wide malignancies. Half of the newly developed HCC occurs in China. Optimizing the strategies for high-risk surveillance and early diagnosis are pivotal for improving 5-year survival. Constructing the scientific non-invasive detection technologies feasible for medical and healthcare institutions is among the key routes for elevating the efficacies of HCC identification and follow-up. RESULTS: Based on the Chinese and international guidelines, expert consensus statements, literatures and evidence-based clinical practice experiences, this consensus statement puts forward the clinical implications, application subjects, detection techniques and results interpretations of the triple-biomarker (AFP, AFP-L3%, DCP) based GALAD, GALAD like models for liver cancer. CONCLUSIONS: The compile of this consensus statement aims to address and push the reasonable application of the triple-biomarker (AFP, AFP-L3%, DCP) detections thus to maximize the clinical benefits and help improving the high risk surveillance, early diagnosis and prognosis of HCC.

Short-term efficacy of stenting as a rescue therapy for acute atherosclerotic occlusion in anterior cerebral circulation.

Purpose: The study aimed to explore the efficacy and safety of the Neuroform EZ stent in treating acute anterior circulation large artery occlusion. Methods: The clinical data of 42 consecutive patients with acute anterior circulation large atherosclerotic occlusion who were treated with the Neuroform EZ stent from January 2018 to August 2019 in our stroke care center, including baseline characteristics, images, therapeutic condition, and follow-up data were retrospectively analyzed. Results: There were 42 mechanical thrombectomy (MT) failure cases of intracranial atherosclerotic stenosis with rescue Neuroform EZ stent implantation, of which 78.6% (33/42) had a good prognosis and 88.1% (37/42) showed no re-stenosis at follow-up. The average time from puncture to recanalization is 79.50 ± 14.19 min. The successful rate of intraoperative stent release is 97.6%, while there is one case of stent displacement, three cases of thrombus escape, and six cases of hemorrhage. Conclusion: Rescue therapy of the Neuroform EZ stent for acute anterior circulation large atherosclerotic occlusion can archive good short-term imaging and clinical results, while long-term follow-up is still needed to verify.

Burden of ischemic stroke in mainland China and Taiwan province from 1990 to 2019: with forecast for the next 11 years.

Ischemic stroke is featured with high incidence, mortality, and disability. The aim of this study is to use Global Burden of Disease database to describe and compare the burden of ischemic stroke in mainland China and Taiwan province and to further predict the expected changes in the next 11 years using statistical modeling methods. Information on ischemic stroke incidence and mortality in China (mainland and Taiwan province) during 1990-2019 was obtained from the Global Burden of Disease database to analyze the effects of region, gender, and age on the incidence and mortality of ischemic stroke in China. The autoregressive integrated moving average model was used to predict the age-standardized incidence rate and age-standardized mortality rate of ischemic stroke in males and females in mainland China and Taiwan province in the next 11 years. The period from 1990 to 2019 witnessed an overall upward trend in the number of incidence and deaths in mainland China and Taiwan province. In 2019, there were nearly 2.87 million ischemic incidence cases with stroke in mainland China, with more female patients than male in the age group of over 60 years. Among the nearly 1.03 million deaths, the death toll of men under the age of 85 years was higher than that of women, while in Taiwan province, the number of incidence was 28 771, with more female patients of all ages than male. Among the 6788 deaths, the death toll of men under the age of 80 years was higher than that of women. In 2019, the age group with the highest number of patients in the two regions was 65-69 years, while the highest number of deaths was found in people aged 85 years and above. As our autoregressive integrated moving average model predicted, the age-standardized incidence rate value of ischemic stroke is expected to be 163.23/100 000 persons in mainland China by 2030, which would continue to increase, while the age-standardized mortality rate value of ischemic stroke is expected to be 16.41/100 000 persons in Taiwan province by 2030, which showed a decreasing trend. Disease burden of ischemic stroke is still increasing in mainland China and Taiwan province, and health resources should be deployed to implement effective prevention and control strategies, taking into account region, gender, and age.

Solasonine ameliorates cerebral ischemia-reperfusion injury via suppressing TLR4/MyD88/NF-κB pathway and activating AMPK/Nrf2/HO-1 pathway.

Solasonine (SS), the main active ingredient of Solanum nigrum L., has been reported to possess a variety of pharmacological properties. A recent study demonstrated a neuroprotective effect of SS in a mouse nerve injury model. However, its protective effects on cerebral ischemia/reperfusion injury (CIRI) remain to be elucidated. We investigated herein the in vitro and in vivo neuroprotective effects of SS. Primary hippocampal neurons were exposed to oxygen and glucose deprivation/reoxygenation (OGD/R) to construct an in vitro model while rats were treated with middle cerebral artery occlusion/reperfusion (MCAO/R) to establish an in vivo CIRI model. The results showed that SS reduced OGD/R-induced inflammatory responses of neurons by blocking secretion of TNF-α, IL-1ß and IL-6. Moreover, SS ameliorated OGD/R-induced oxidative stress in neurons by decreasing the level of ROS and MDA and increasing the activity of SOD and GPx. We also found that SS protected neurons from OGD/R-induced apoptosis by down-regulating bax and cleaved caspase-3 and up-regulating bcl-2. The in vivo results revealed that SS administration reduced the infarct volume and alleviated the neurological deficit of MCAO/R rats as well as diminished neuronal damages in these rats. Our investigation on the underlying mechanisms indicated that the neuroprotective effect of SS on CIRI may be associated with the TLR4/MyD88/NF-κB and AMPK/Nrf2/HO-1 pathways. Taken together, these findings demonstrate that SS ameliorates CIRI via suppressing TLR4/MyD88/NF-κB pathway and activating AMPK/Nrf2/HO-1 pathway.

Microwave-Induced Behavior and Digestive Properties of the Lotus Seed Starch-Chlorogenic Acid Complex.

The effect of chlorogenic acid (CA) on the dielectric response of lotus seed starch (LS) after microwave treatment, the behavior and digestive characteristics of the resulting starch/chlorogenic acid complex (LS-CA) at different degrees of gelatinization and the inhibition of α-amylase by chlorogenic acid were investigated. The variation in dielectric loss factor, ε″, and dielectric loss tangent, tanδε, of the microwave thermal conversion indicated that LS-CA had a more efficient microwave-energy-to-thermal-energy conversion efficiency than LS. This gelatinized LS-CA to a greater extent at any given temperature between 65 and 85 °C than LS, and it accelerated the degradation of the starch crystalline structure. The greater disruption of the crystal structure decreased the bound water content and increased the thermal stability of LS-CA compared to LS. The simulated in vitro digestion found that the presence of the LS-CA complex improved the slow-digestion property of lotus seed starch by increasing its content of resistant and slowly digested starch. In addition, the release of chlorogenic acid during α-amylase hydrolysis further slowed starch digestion by inhibiting α-amylase activity. These findings provide a foundation for understanding the correlation between the complex behavior and digestive properties of naturally polyphenol-rich, starch-based foods, such as LS, under microwave treatment, which will facilitate the development of starch-based foods with tailored digestion rates, lower final degrees of hydrolysis and glycemic indices.

The enhanced sensing properties of MOS-based resistive gas sensors by Au functionalization: a review.

Gas sensors are essential for detecting toxic gases that can harm social life or industrial production. Traditional metal oxide semiconductor (MOS)-based sensors suffer from shortcomings such as high operating temperature and slow response time, which limits their detection capabilities. Thus, there is a need to improve their performance. One useful technique is noble metal functionalization, which can effectively enhance the response/recovery time, sensitivity and selectivity, sensing response, and optimum operating temperature of MOS gas sensors. Among the noble metals, Au NPs are considered a promising material for forming composite sensing materials to achieve better sensing performance. This paper aims to review and discuss the recent research on Au-decorated MOS-based sensors, including Au/n-type MOS-based sensors, Au/p-type MOS-based sensors, Au/MOS/carbon composite materials, and Au/MOS/perovskite composite materials. The sensing mechanism of Au-functionalized MOS-based materials will also be examined.

Retraction: Radical Covalent Organic Frameworks Associated with Liquid Na-K toward Dendrite-Free Alkali Metal Anodes.

10.1002/advs.202203058 Adv. Sci. 2022, 9, 2203058 The above article from Advanced Science, published online on 21 July 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202203058), has been retracted by agreement between the authors, the Editor-in-Chief, Kirsten Severing, and Wiley-VCH GmbH. The retraction has been agreed as the article is based on research results and data that the authors were not authorized to use. Moreover, the majority of co-authors have been listed despite insufficient qualification for contributorship.

Retraction: Dual-Ion Stabilized Layered Structure of O-V-OforZero-Strain Potassium Insertion and Extraction.

10.1002/advs.202202550 Adv. Sci.2022, 9, 2202550 The above article from Advanced Science, published online on 5 June 2022 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/advs.202202550), has been retracted by agreement between the authors, the Editor-in-Chief, Kirsten Severing, and Wiley-VCH GmbH. The retraction has been agreed as the article is based on research results and data that the authors were not authorized to use. Moreover, the majority of co-authors have been listed despite insufficient qualification for contributorship.

Citri Reticulatae Pericarpium-Reynoutria japonica Houtt. herb pair suppresses breast cancer liver metastasis by targeting ECM1-mediated cholesterol biosynthesis pathway.

BACKGROUND: Liver metastasis is a frequent event in breast cancer that causes low survival rate and poor prognosis. Citri Reticulatae Pericarpium-Reynoutria japonica Houtt. (CR), a traditional Chinese herb pair, is used for the treatment of breast cancer liver metastasis or cholesterol gallstone disease in clinics. PURPOSE: This study attempted to investigate the potential therapeutic target and mechanism of CR herb pair on breast cancer liver metastasis. METHODS: The anti-metastatic and cholesterol-lowering activities of CR extract were evaluated in triple-negative breast cancer (TNBC) cell lines and an experimental liver metastasis model. The role of extracellular matrix protein 1 (ECM1) in the cholesterol biosynthesis pathway was determined by the knockdown and overexpression of ECM1 gene of TNBC cells. Changes in the gene and protein expression levels of ECM1 and the cholesterol biosynthesis pathway after CR treatment were detected in vitro and in vivo by real-time PCR and Western blot. RESULTS: The invasive and metastatic potentials and hypercholesterol levels of TNBC cells were positively associated with ECM1 expression. ECM1 knockdown reduced tumor cholesterol levels via downregulating cholesterol biosynthesis genes, including ACAT2, HMGCS1, HMGCR, MVK, and MVD, whereas ECM1 overexpression elicited the opposite effects. CR herb pair exerts the potential therapeutic effects on TNBC liver metastasis, which is partially mediated by disrupting ECM1-activated cholesterol biosynthesis process in TNBC cells. CONCLUSION: This study reveals that ECM1 is a novel target for the activation of cholesterol biosynthesis to promote TNBC liver metastasis occurrence. CR herb pair, an ECM1 inhibitor, maybe be considered to serve as an adjuvant therapeutic drug for liver metastasis in clinical practice.

A questionnaire to assess the health information literacy of patients with intermediate-stage chronic kidney disease.

AIM: To investigate the status and influencing factors of health information literacy in patients with intermediate-stage chronic kidney disease (CKD). DESIGN: A prospective clinical study. METHODS: We used a CKD health information literacy questionnaire to survey 130 patients with intermediate-stage CKD and valuate their health needs and health knowledge. We performed the study in strict accordance with the Guidelines for Clinical Trial Protocols. We registered the study in the Chinese Clinical Trial Registration Center (registration No. ChiCTR2100053103; approval No. K56-1). RESULTS: The overall health information literacy of CKD was relatively low. Low education level, advanced age and unemployment were influencing factors. The scores of assessment ability, literacy awareness, application ability, integration ability and CKD health knowledge reserve were relatively low. The generalized linear model showed that the older the men, the lower their health information literacy.

Electrospun TiO2 Nanofibers Featuring Surface Oxygen Vacancies as a Multifunctional Interlayer for High-Performance Lithium-Sulfur Batteries in a Wide Temperature Range.

Despite great achievements having been made in lithium-sulfur batteries (LSBs), further improvements regarding rate performance, cycle life, and operating temperature are needed for realistic applications. Herein, we developed a simple electrospun method for the preparation of TiO2 coaxial nanofiber (TCNFs)-modified Celgard separators to suppress the polysulfide shuttling. LSBs with a TCNF/Celgard separator display excellent electrochemical performance. For an areal sulfur loading of 2.5 mg cm-2, the cells exhibited a capacity of 1279 mA h g-1 at 0.5 A g-1, remained 798 mA h g-1 at 2.5 A g-1, and low-capacity decay of 0.057% per cycle within 1000 cycles. At 50 and -10 °C, the capacity of the cells is maintained at 932 and 931 mA h g-1 after 80 cycles at 0.5 A g-1, respectively. Detailed structural analysis and theoretical calculations revealed that the hollow-structured TCNFs offer high density of accessible electropositive Ti sites and oxygen vacancies and thus enables efficient trapping of polysulfides and facilitates Li+ transfer, leading to excellent performance. The simplicity of this strategy and the diversity of hollow-structured metal oxides holds great promise to design separators for high-performance LSBs.

Protopanaxadiol ameliorates NAFLD by regulating hepatocyte lipid metabolism through AMPK/SIRT1 signaling pathway.

Non-alcoholic fatty liver disease (NAFLD) has become one of the main chronic liver diseases worldwide. Protopanaxadiol (PPD), an active compound derived from Gynostemma pentaphyllum, has been found able to improve free fatty acid-induced lipid accumulation in hepatocytes. However, the efficacy of PPD on NAFLD and the underlying mechanism remains unknown. In this study, the mice were fed with a high-fat diet for 22 weeks to induce the NAFLD model, and then were treated with PPD by gavage for 8 weeks. Moreover, AML12 and HepG2 cells induced by free fatty acids for 24 h, were treated with different doses of PPD and/or AMPK or SIRT1 inhibitor to explore the pharmacological mechanism of PPD. The results showed that mice with PPD treatment had significantly reduced liver weight and serum aminotransferase levels, less severe hepatosteatosis, and inflammatory cell infiltration in liver tissues when compared with the model mice. PPD also reversed the down-regulated activation of AMPK and SIRT1 expression as well as the change of lipid metabolism-related molecules in the mice liver tissues. Consistently, the in vitro experiments showed the effect of PPD in ameliorating lipid accumulation in hepatocytes. The inhibitor of AMPK or SIRT1 suppressed the AMPK and SIRT1 signaling and markedly diminished the anti-steatosis effect of PPD. In conclusion, our results prove the ameliorating impact of PPD on NAFLD and also reveal the involvement of regulation of AMPK/SIRT1 signaling pathway-mediated lipid metabolism in the underlying mechanism, suggesting PPD as a potential natural compound for the treatment of NAFLD.

Loganin attenuates neuroinflammation after ischemic stroke and fracture by regulating α7nAChR-mediated microglial polarization.

Fracture in acute stage of ischemic stroke can increase inflammatory response and enhance stroke injury. Loganin alleviates the symptoms of many inflammatory diseases through its anti-inflammatory effect, but its role in ischemic stroke and fracture remains to be explored. Here, mice were handled with permanent middle cerebral artery occlusion (pMCAO) followed by tibial fracture 1 day later to establish a pMCAO+fracture model. Loganin or Methyllycaconitine (MLA, a specific a7nAchR inhibitor) were intragastrically administered 2 or 0.5 h before pMCAO, respectively. And mouse motor function and infarct volume were evaluated 3 days after pMCAO. We found that loganin alleviated the neurological deficit, cerebral infarction volume, and neuronal apoptosis (NeuN+ TUNEL+ ) in mice with pMCAO+fracture. And loganin suppressed pMCAO+fracture-induced neuroinflammation by promoting M2 microglia polarization (Iba1+ CD206+ ) and inhibiting M1 microglia polarization (Iba1+ CD11b+ ). While administration with MLA reversed the protective effect of loganin on pMCAO+fracture-induced neurological deficit and neuroinflammation. Next, LPS was used to stimulate BV2 microglia to simulate pMCAO+fracture-induced inflammatory microenvironment in vitro. Loganin facilitated the transformation of LPS-stimulated BV2 cells from M1 pro-inflammatory state (CD11b+ ) to M2 anti-inflammatory state (CD206+ ), which was antagonized by treatment with MLA. And loganin induced autophagy activation in LPS-stimulated BV2 cells by activating a7nAchR. Moreover, treatment with rapamycin (an autophagy activator) neutralized the inhibitory effect of MLA on loganin induced transformation of BV2 cells to M2 phenotype. Furthermore, BV2 cells were treated with LPS, LPS + loganin, LPS + loganin+MLA, or LPS + loganin+MLA+ rapamycin to obtain conditioned medium (CM) for stimulating primary neurons. Loganin reduced the damage of primary neurons caused by LPS-stimulated BV2 microglia through activating a7nAchR and inducing autophagy activation. In conclusion, loganin played anti-inflammatory and neuroprotective roles in pMCAO + fracture mice by activating a7nAchR, enhancing autophagy and promoting M2 polarization of microglia.