Experimental verification about treatment of Bu-Shen-Yi-Jing-Fang in Alzheimer's disease by the analysis of the feasible signaling pathway of network pharmacology.

CONTEXT: Bu-shen-yi-jing-fang (BSYJF) has been reported to reduce amyloid-ß (Aß)1-42 deposition in the brain of APP/PS1 mice and ameliorate cognitive function. However, its neuroprotective mechanism remains unclear. OBJECTIVE: This study aims to investigate whether BSYJF exerts a protective effect on Aß1-42-induced oxidative stress injury and explore its possible mechanism. MATERIALS AND METHODS: The platform databases TCMSP, Swiss, TTD, DrugBank, and GeneCards were used to mine the targets of Alzheimer's disease (AD) and BSYJF. The platform databases STRING and Metascape were used to build the interaction network of the target protein, and Cytoscape software was used to analyze this network and screen out the key pathways. Aß1-42-treated SKNMC cells were established to verify the mechanism of BSYJF and the key proteins. The downstream proteins and antioxidants as well as apoptosis and ferroptosis of the PI3K/AKT/Nrf2 signaling pathway were validated using an in vitro SKNMC cell model experiment. The expression levels of related proteins were detected using Western blotting. Flow cytometry and immunofluorescence staining were used to analyze apoptosis and ferroptosis. RESULTS: Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis considered the key signal pathways, mainly involving the PI3K/AKT signaling pathway. Experimental validation demonstrated that BSYJF treatment markedly increased the activity of the PI3K/AKT pathway, which could exert anti-AD effects. CONCLUSIONS: Our data provided compelling evidence that the protective effects of BSYJF might be associated with their regulation of the PI3K/AKT/Nrf2 signaling pathway. These studies offered a potential therapy for natural herbal medicine treatment of AD.

Suppressed thermal transport in silicon nanoribbons by inhomogeneous strain.

Nanoscale structures can produce extreme strain that enables unprecedented material properties, such as tailored electronic bandgap1-5, elevated superconducting temperature6,7 and enhanced electrocatalytic activity8,9. While uniform strains are known to elicit limited effects on heat flow10-15, the impact of inhomogeneous strains has remained elusive owing to the coexistence of interfaces16-20 and defects21-23. Here we address this gap by introducing inhomogeneous strain through bending individual silicon nanoribbons on a custom-fabricated microdevice and measuring its effect on thermal transport while characterizing the strain-dependent vibrational spectra with sub-nanometre resolution. Our results show that a strain gradient of 0.112% per nanometre could lead to a drastic thermal conductivity reduction of 34 ± 5%, in clear contrast to the nearly constant values measured under uniform strains10,12,14,15. We further map the local lattice vibrational spectra using electron energy-loss spectroscopy, which reveals phonon peak shifts of several millielectron-volts along the strain gradient. This unique phonon spectra broadening effect intensifies phonon scattering and substantially impedes thermal transport, as evidenced by first-principles calculations. Our work uncovers a crucial piece of the long-standing puzzle of lattice dynamics under inhomogeneous strain, which is absent under uniform strain and eludes conventional understanding.

Modification of the electrokinetic motion of microalgae through light illumination for viability assessment.

The viability detection of microalgae with the electrokinetic (EK) technique shows vast applications in the biology and maritime industry. However, due to the slight variations in the EK properties between alive and dead microalgae cells, the accuracy and practicability of this technique is limited. In this paper, the light illumination pretreatment was conducted to modify the EK velocity of microalgae for enhancing the EK difference. The effects of the illumination time and light color on the EK velocities of Chlorella vulgaris and Isochrysis galbana were systematically measured, and the EK differences between alive and dead cells were calculated and compared. The results indicate that under light illumination, the photosynthesis of the alive cells leads to the amplification of the zeta potential, leading toward increase in the EK difference along with the illumination time. By using light with different color spectra to treat the microalgae, it was found that the EK difference changes with the light color according to the following order: white light > red light > blue light > green light. The difference in EK potential with exposure to white light treatment surpasses over 10-fold in comparison to those without such treatment. The light pretreatment technique, as illustrated in this study, offers an advantageous strategy to enhance the EK difference between living and dead cells, proving beneficial in the field of microalgae biotechnology.

Near-unity quantum yield and long-term emission stability in halide perovskite nanocrystal glass composite.

Metal halide perovskites are promising optoelectronic materials due to their outstanding luminescent properties. However, the instability of perovskites has long been the bottleneck to their practical applications. Here Cs4PbBr6 nanocrystals based glass composite (Cs4PbBr6 NCs@glass) are successfully prepared, which displays green emission color (520 nm), narrow bandwidth (23 nm) and a near-unity photoluminescence quantum yield (PLQY). The H2O molecules permeating in the lattice of Cs4PbBr6 were found to be a crucial role in the subband energy emission. The Cs4PbBr6 NCs@glass has excellent emission stability; maintains 93 % of initial PL intensity after ultraviolet light irradiation for over 5000 h. In addition, by adjusting the halogen content, we have achieved tunable emission color from blue (450 nm) to green (520 nm) and red (670 nm) on Cs4PbX6 NCs@glass (X = Cl, Br, I), which covers up to 127 % of the National Television Systems Board (NTSC) standard system. Our finding indicates the commercial applications of perovskite materials in lighting and display.

A murine model of DC-SIGN humanization exhibits increased susceptibility against SARS-CoV-2.

To generate a new murine model for virus, DC-SIGN gene in murine was humanized. In this study, we successfully generated a humanized C57BL/6N mouse model expressing human DC-SIGN (hDC-SIGN) using CRISPR/Cas9 technology, and evaluated its characters and susceptibility to virus. The humanized mice could survival as usual, and with normal physiological index just like the wild-type mice. Whereas, we found significant differences in the intestinal flora and metabolic profiles between wild-type mice and humanized mice. Following intranasal infection with SARS-CoV-2, hDC-SIGN mice exhibited significantly increased viral loads in the lungs and nasal turbinates, along with more severe lung damage. This phenomenon may be associated with differential lipid metabolism and Fcγ receptor-mediated phagocytosis in two mouse models. This study provides a useful tool for investigating the mechanisms of coronavirus infection and potential drug therapies against novel coronavirus.

An immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment.

BACKGROUND: In recent years, the emergence of immunotherapy has renewed therapeutic modality. Different from traditional anti-tumor therapy, immune-related adverse events of skin, gastrointestinal tract, liver, lung, endocrine glands commonly occurred. At present, only one case of immune-related adverse event of Behcet's-like syndrome following pembrolizumab treatment was reported in USA, and no one is reported in China. CASE PRESENTATION: Here, we report a rare case of Behcet's-like symptom following pembrolizumab treatment. A 43-year-old female was diagnosed as lymph node and bone metastasis of adenocarcinoma with unknown primary lesion, probably being of pulmonary origin. She was treated with pembrolizumab 200 mg every three weeks in combination with chemotherapy for 6 cycles, followed by pembrolizumab monotherapy maintenance. However, she developed Behcet's-like syndrome with oral ulcer, genital uler, phlebitis, and vision loss after 9 cycles of pembrolizumab treatment. She was treated with prednisone 5 mg orally three times a day. Two weeks later, dose of glucocorticoid gaven to the patient gradually decreased with improved symptoms. After a treatment-free withdrawal period, the patient requested to continue pembrolizumab treatment. Unfortunately, the above symptoms recurred on the second day following pembrolizumab treatment, and glucocorticoid was taken once again. The symptoms improved and the condition was under control. CONCLUSIONS: In view of the exponential growth of immunocheckpoint inhibitors (ICIs) in a variety of tumors, we should be alert to related adverse events, especially the rare rheumatic manifestations.

Surgical treatment improves overall survival of hepatocellular carcinoma with extrahepatic metastases after conversion therapy: a multicenter retrospective study.

Systemic therapy is typically the primary treatment choice for hepatocellular carcinoma (HCC) patients with extrahepatic metastases. Some patients may achieve partial response (PR) or complete response (CR) with systemic treatment, leading to the possibility of their primary tumor becoming resectable. This study aimed to investigate whether these patients could achieve longer survival through surgical resection of their primary tumor. We retrospectively collected data from 150 HCC patients with extrahepatic metastases treated at 15 different centers from January 1st, 2015, to November 30th, 2022. We evaluated their overall survival (OS) and progress-free survival (PFS) and analyzed risk factors impacting both OS and PFS were analyzed. Patients who received surgical treatment had longer OS compared to those who did not (median OS 16.5 months vs. 11.3 months). However, there was no significant difference in progression-free survival between the two groups. Portal vein invasion (P = 0.025) was identified as a risk factor for poor prognosis in patients, while effective first-line treatment (P = 0.039) and surgical treatment (P = 0.005) were protective factors. No factors showed statistical significance in the analysis of PFS. Effective first-line treatment (P = 0.027) and surgical treatment (P = 0.006) were both independent protective factors for prolonging patient prognosis, while portal vein invasion was an independent risk factor (P = 0.044). HCC patients with extrahepatic metastases who achieve PR/CR with conversion therapy may experience longer OS through surgical treatment. This study is the first to analyze the clinical outcomes of patients receiving surgical treatment for HCC with extrahepatic metastases.

Stable Interstrand Cross-Links Generated from the Repair of 1,N6-Ethenoadenine in DNA by α-Ketoglutarate/Fe(II)-Dependent Dioxygenase ALKBH2.

DNA cross-links severely challenge replication and transcription in cells, promoting senescence and cell death. In this paper, we report a novel type of DNA interstrand cross-link (ICL) produced as a side product during the attempted repair of 1,N6-ethenoadenine (εA) by human α-ketoglutarate/Fe(II)-dependent enzyme ALKBH2. This stable/nonreversible ICL was characterized by denaturing polyacrylamide gel electrophoresis analysis and quantified by high-resolution LC-MS in well-matched and mismatched DNA duplexes, yielding 5.7% as the highest level for cross-link formation. The binary lesion is proposed to be generated through covalent bond formation between the epoxide intermediate of εA repair and the exocyclic N6-amino group of adenine or the N4-amino group of cytosine residues in the complementary strand under physiological conditions. The cross-links occur in diverse sequence contexts, and molecular dynamics simulations rationalize the context specificity of cross-link formation. In addition, the cross-link generated from attempted εA repair was detected in cells by highly sensitive LC-MS techniques, giving biological relevance to the cross-link adducts. Overall, a combination of biochemical, computational, and mass spectrometric methods was used to discover and characterize this new type of stable cross-link both in vitro and in human cells, thereby uniquely demonstrating the existence of a potentially harmful ICL during DNA repair by human ALKBH2.

Impact of antifibrotic therapy on disease progression, all-cause mortality, and risk of acute exacerbation in non-IPF fibrosing interstitial lung diseases: evidence from a meta-analysis of randomized controlled trials and prospective controlled studies.

BACKGROUND: Nintedanib and pirfenidone are preferred pharmacological therapies for patients with idiopathic pulmonary fibrosis (IPF). However, evidence favoring antifibrotic therapy in patients with non-IPF fibrosing interstitial lung diseases (ILD) is limited. OBJECTIVE: To investigate the effects of antifibrotic therapy on disease progression, all-cause mortality, and acute exacerbation (AE) risk in patients with non-IPF fibrosing ILDs. DESIGN: Meta-analysis. DATA SOURCES AND METHODS: Electronic databases were searched for articles published before 28 February 2023. Studies that evaluated the efficacy of antifibrotic agents in patients with fibrosing ILDs were selected. The primary outcome was the disease progression risk, and the secondary outcomes included all-cause mortality and AE risk. The GRADE criteria were used for the certainty of evidence assessment. RESULTS: Nine studies with 1990 participants were included. Antifibrotic therapy reduced the rate of patients with disease progression (five trials with 1741 subjects; relative risk (RR), 0.56; 95% CI, 0.42-0.75; p < 0.0001; I2 = 0; high-certainty evidence). Antifibrotic therapy did not significantly decrease all-cause mortality (nine trials with 1990 subjects; RR, 0.76; 95% CI, 0.55-1.03; p = 0.08; I2 = 0; low-certainty evidence). However, in patients with progressive fibrosing ILDs (PF-ILD), antifibrotic therapy decreased all-cause mortality (four trials with 1100 subjects; RR, 0.69; 95% CI, 0.48-0.98; p = 0.04; I2 = 0; low-certainty evidence). CONCLUSION: Our study supports the use of antifibrotic agents in patients with PF-ILDs, which could slow disease progression and decrease all-cause mortality. TRIAL REGISTRATION: This study protocol was registered with PROSPERO (registration number: CRD42023411272).

Reexamination of Damping in Sliding Friction.

Friction is responsible for about one-third of the primary energy consumption in the world. So far, a thorough atomistic understanding of the frictional energy dissipation mechanisms is still lacking. The Amontons' law states that kinetic friction is independent of the sliding velocity while the Prandtl-Tomlinson model suggests that damping is proportional to the relative sliding velocity between two contacting objects. Through careful analysis of the energy dissipation process in atomic force microscopy measurements, here we propose that damping force is proportional to the tip oscillation speed induced by friction. It is shown that a physically well-founded damping term can better reproduce the multiple peaks in the velocity-dependent friction force observed in both experiments and molecular dynamics simulations. Importantly, the analysis gives a clear physical picture of the dynamics of energy dissipation in different friction phases, which provides insight into long-standing puzzles in sliding friction, such as velocity weakening and spring-stiffness-dependent friction.

Three-way decisions in generalized intuitionistic fuzzy environments: survey and challenges.

Enhancing decision-making under risks is crucial in various fields, and three-way decision (3WD) methods have been extensively utilized and proven to be effective in numerous scenarios. However, traditional methods may not be sufficient when addressing intricate decision-making scenarios characterized by uncertain and ambiguous information. In response to this challenge, the generalized intuitionistic fuzzy set (IFS) theory extends the conventional fuzzy set theory by introducing two pivotal concepts, i.e., membership degrees and non-membership degrees. These concepts offer a more comprehensive means of portraying the relationship between elements and fuzzy concepts, thereby boosting the ability to model complex problems. The generalized IFS theory brings about heightened flexibility and precision in problem-solving, allowing for a more thorough and accurate description of intricate phenomena. Consequently, the generalized IFS theory emerges as a more refined tool for articulating fuzzy phenomena. The paper offers a thorough review of the research advancements made in 3WD methods within the context of generalized intuitionistic fuzzy (IF) environments. First, the paper summarizes fundamental aspects of 3WD methods and the IFS theory. Second, the paper discusses the latest development trends, including the application of these methods in new fields and the development of new hybrid methods. Furthermore, the paper analyzes the strengths and weaknesses of research methods employed in recent years. While these methods have yielded impressive outcomes in decision-making, there are still some limitations and challenges that need to be addressed. Finally, the paper proposes key challenges and future research directions. Overall, the paper offers a comprehensive and insightful review of the latest research progress on 3WD methods in generalized IF environments, which can provide guidance for scholars and engineers in the intelligent decision-making field with situations characterized by various uncertainties.

Direct observation of carbon slurry flow behavior and its effect on electrochemical performance in a microfluidic electrochemical flow capacitor.

Carbon slurries have been used as "flowable electrodes" in various electrochemical systems, and the slurry flow characteristics play an important role in the system electrochemical performance. For example, in an electrochemical flow capacitor (EFC), activated carbon particles must pass electrical charge from a stationary electrode to surrounding particles via particle-electrode and particle-particle interactions to store energy in the electric double layer. So far, particle behaviors under a continuous flow condition have not been observed due to the slurry's opacity, and studies of the device's performance thus have been mainly on a bulk level. To understand the relation between the hydrodynamic behavior and the electrochemical performance of carbon slurries, we have constructed a microfluidic EFC (µ-EFC) using transparent materials. The µ-EFC allows for direct observation of particle interactions in flowing carbon slurries using high-speed camera recording, and concurrent measurements of the electrochemical performance via chronoamperometry. The results indicate an interesting dependence of the particle cluster interaction on the flowrate, and its effect on the slurry charging/discharging behavior. It is found that an optimal flowrate could exist for better electrochemical performance.

Evaluating Prognostic Bias of Critical Illness Severity Scores Based on Age, Sex, and Primary Language in the United States: A Retrospective Multicenter Study.

OBJECTIVES: Although illness severity scoring systems are widely used to support clinical decision-making and assess ICU performance, their potential bias across different age, sex, and primary language groups has not been well-studied. DESIGN SETTING AND PATIENTS: We aimed to identify potential bias of Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) IVa scores via large ICU databases. SETTING/PATIENTS: This multicenter, retrospective study was conducted using data from the Medical Information Mart for Intensive Care (MIMIC) and eICU Collaborative Research Database. SOFA and APACHE IVa scores were obtained from ICU admission. Hospital mortality was the primary outcome. Discrimination (area under receiver operating characteristic [AUROC] curve) and calibration (standardized mortality ratio [SMR]) were assessed for all subgroups. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: A total of 196,310 patient encounters were studied. Discrimination for both scores was worse in older patients compared with younger patients and female patients rather than male patients. In MIMIC, discrimination of SOFA in non-English primary language speakers patients was worse than that of English speakers (AUROC 0.726 vs. 0.783, p < 0.0001). Evaluating calibration via SMR showed statistically significant underestimations of mortality when compared with overall cohort in the oldest patients for both SOFA and APACHE IVa, female patients (1.09) for SOFA, and non-English primary language patients (1.38) for SOFA in MIMIC. CONCLUSIONS: Differences in discrimination and calibration of two scores across varying age, sex, and primary language groups suggest illness severity scores are prone to bias in mortality predictions. Caution must be taken when using them for quality benchmarking and decision-making among diverse real-world populations.

Portal Vein Pressure Estimation and Portal Hypertension Discrimination Based on Subharmonic Scattering of Ultrasound Contrast Agent Microbubbles.

OBJECTIVE: The acquisition of real-time portal vein pressure (PVP) is important for portal hypertension (PH) discrimination to monitor disease progress and select treatment options. To date, the PVP evaluation approaches are either invasive or noninvasive but with less stability and sensitivity. METHODS: We customized an open ultrasound scanner to explore in vitro and in vivo the ultrasound contrast agent SonoVue microbubbles' subharmonic characteristics with acoustic pressure and local ambient pressure, and obtained promising results of PVP measurements in canine models with induced PH by ligation or embolization of portal vein. RESULTS: In in vitro experiments, the highest correlations between the subharmonic amplitude of SonoVue microbubbles and ambient pressure were observed at acoustic pressures of 523 kPa and 563 kPa (r = -0.993, -0.993, P<0.05, respectively). The correlation coefficients between absolute subharmonic amplitudes and PVP (10.7-35.4 mmHg) were the highest among existing studies using microbubbles as pressure sensors (r values ranged from -0.819 to -0.918). The PH (>16 mmHg) diagnostic capacity also achieved a high level (563 kPa, sensitivity = 93.3%, specificity = 91.7%, accuracy = 92.6%). CONCLUSION: This study proposes a promising measurement for PVP with the highest accuracy, sensitivity, and specificity in an in vivo model compared to existing studies. Future investigations are planned to assess the feasibility of this technique in clinical practice. SIGNIFICANCE: This is the first study that comprehensively investigates the role of the subharmonic scattering signals from SonoVue microbubbles in evaluating PVP in vivo. It represents a promising alternative to invasive measurements for portal pressure.

Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

The prognostic value of age-adjusted Charlson comorbidity index in laparoscopic resection for hilar cholangiocarcinoma.

The prognostic role of the Age-Adjusted Charlson Comorbidity Index (ACCI) in hilar cholangiocarcinoma patients undergoing laparoscopic resection is unclear. To evaluate ACCI's effect on overall survival (OS) and recurrence-free survival (RFS), we gathered data from 136 patients who underwent laparoscopic resection for hilar cholangiocarcinoma at Zhengzhou University People's Hospital between 1 June 2018 and 1 June 2022. ACCI scores were categorized into high ACCI (ACCI > 4.0) and low ACCI (ACCI ≤ 4.0) groups. We examined ACCI's association with OS and RFS using Cox regression analyses and developed an ACCI-based nomogram for survival prediction. Our analysis revealed that higher ACCI scores (ACCI > 4.0) (HR = 2.14, 95%CI: 1.37-3.34) were identified as an independent risk factor significantly affecting both OS and RFS in postoperative patients with hilar cholangiocarcinoma (p < 0.05). TNM stage III-IV (HR = 7.42, 95%CI: 3.11-17.68), not undergoing R0 resection (HR = 1.58, 95%CI: 1.01-2.46), hemorrhage quantity > 350 mL (HR = 1.92, 95%CI: 1.24-2.97), and not receiving chemotherapy (HR = 1.89, 95%CI: 1.21-2.95) were also independent risk factors for OS. The ACCI-based nomogram accurately predicted the 1-, 2-, and 3-year OS rates, with Area Under the Curve (AUC) values of 0.818, 0.844, and 0.924, respectively. Calibration curves confirmed the nomogram's accuracy, and decision curve analysis highlighted its superior predictive performance. These findings suggest that a higher ACCI is associated with a worse prognosis in patients undergoing laparoscopic resection for hilar cholangiocarcinoma. The ACCI-based nomogram could aid clinicians in making accurate predictions about patient survival and facilitate individualized treatment planning.

Network pharmacology analysis and experimental validation of Anemarrhenae Rhizoma in treating Alzheimer's disease. / çŸ¥æ¯æ²»ç–—é˜¿å°”èŒ¨æµ·é»˜ç— ç½‘ç»œè¯ç†å­¦ç ”ç©¶åŠå®žéªŒéªŒè¯.

OBJECTIVES: To explore the mechanism of Anemarrhenae Rhizoma in treatment of Alzheimer's Disease (AD). METHODS: The active ingredients and targets of Anemarrhenae Rhizoma for treatment of AD were screened with network pharmacology methods, the protein-protein interaction (PPI) network was constructed and the core targets were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriching analysis was performed. The peripheral blood lymphocytes were extracted and lymphoblastoid cell lines (LCL) were constructed and an in vitro cell model of LCL-SKNMC was established. MTT and CCK-8 methods were used to quantify SKNMC/LCL cells, 2 ´, 7 ´-dichlorodihydrofluorescein diacetate (DCFH-DA) probe was used to detect reactive oxygen species (ROS), and immunofluorescence staining was used to detect the generation of Aß1-42 in a co-cultured model. Western blotting was used to detect protein expression in the co-culture model. The lifespan of N2 nematodes was observed under oxidative stress, normal state, and heat stress; ROS generated by N2 nematodes was detected by DCFH-DA probes. The paralysis time of CL4176 N2 nematodes was evaluated by paralysis assay, and Aß deposition in the pharynx was detected by Thioflavin S staining. RESULTS: Through network pharmacology, 15 potential active ingredients and 103 drug-disease targets were identified. PPI analysis showed that the Anemarrhenae Rhizoma might play anti-AD roles through albumin, Akt1, tumor necrosis factor, epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), mammalian target of rapamycin (mTOR), amyloid precursor protein (APP) and other related targets. KEGG analysis showed that the pharmacological effects of Anemarrhenae Rhizoma might involve the biological processes of Alzheimer's disease, endocrine resistance, insulin resistance; and neuroactive ligand-receptor interaction, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, calcium signaling pathway, AGE-RAGE signaling pathway in diabetes complications, neurotrophic factor signaling pathway and others. The in vitro cell experiments showed that Anemarrhenae Rhizoma was able to reduce the production of ROS and Aß1-42 (both P<0.01), inhibit the expression of ß-secretase 1 (BACE1), APP and Aß1-42 proteins (all P<0.05), up-regulate the expression of p-PI3K/PI3K, p-AKT/AKT, p-GSK3ß/GSK3ß in SKNMC cells (all P<0.05). The in vivo studies further confirmed that Anemarrhenae Rhizoma prolonged the lifespan of C. elegans under stress and normal conditions, reduced the accumulation of ROS and the toxicity of Aß deposition. CONCLUSIONS: Anemarrhenae Rhizoma may reduce the production of Aß in AD and inhibit its induced oxidative stress, which may be achieved by regulating the PI3K/Akt/GSK-3ß pathway.

Conformation-dependent lesion bypass of bulky arylamine-dG adducts generated from 2-nitrofluorene in epigenetic sequence contexts.

Sequence context influences structural characteristics and repair of DNA adducts, but there is limited information on how epigenetic modulation affects conformational heterogeneity and bypass of DNA lesions. Lesions derived from the environmental pollutant 2-nitrofluorene have been extensively studied as chemical carcinogenesis models; they adopt a sequence-dependent mix of two significant conformers: major groove binding (B) and base-displaced stacked (S). We report a conformation-dependent bypass of the N-(2'-deoxyguanosin-8-yl)-7-fluoro-2-aminofluorene (dG-FAF) lesion in epigenetic sequence contexts (d[5'-CTTCTC#G*NCCTCATTC-3'], where C# is C or 5-methylcytosine (5mC), G* is G or G-FAF, and N is A, T, C or G). FAF-modified sequences with a 3' flanking pyrimidine were better bypassed when the 5' base was 5mC, whereas sequences with a 3' purine exhibited the opposite effect. The conformational basis behind these variations differed; for -CG*C- and -CG*T-, bypass appeared to be inversely correlated with population of the duplex-destabilizing S conformer. On the other hand, the connection between conformation and a decrease in bypass for flanking purines in the 5mC sequences relative to C was more complex. It could be related to the emergence of a disruptive non-S/B conformation. The present work provides novel conformational insight into how 5mC influences the bypass efficiency of bulky DNA damage.

Surface charging and electrophoretic behavior of conductive polymer micro-droplets in conductive polymer liquid solutions.

This study investigates the surface charging and electrophoretic motion of polyethylene glycol-rich (PEG-rich) micro-droplets in dextran-rich solutions or dextran-rich micro-droplets in PEG-rich solutions. The electrophoretic velocities of the droplets were measured in a centimeter-sized chamber under an optical microscope. It was found that the direction of electrophoretic motion of both the PEG-rich droplets and dextran-rich droplets is opposite to the applied electric field, meaning that both the PEG-rich droplets and dextran-rich droplets are negatively charged. The electrophoretic velocity is independent of droplet size but proportional to the electric field strength. Increasing the NaCl concentration reduces the electrophoretic velocity of PEG-rich droplets and increases it for dextran-rich droplets, suggesting different surface charge changes due to ion affinity. The charge densities and velocities are affected by the PEG and dextran mass fractions. Physical models for droplet surface charging under different conditions were proposed to explain the experimental results.