Functional role of Ash2l in oxLDL induced endothelial dysfunction and atherosclerosis.

Endothelial injury and dysfunction in the artery wall fuel the process of atherosclerosis. As a key epigenetic regulator, Ash2l (Absent, small, or homeotic-Like 2) is involved in regulating vascular injury and its complications. However, the role of Ash2l in atherosclerosis has not yet been fully elucidated. Here, we found increased Ash2l expression in high-cholesterol diet-fed ApoE-/- mice and oxidized LDL (oxLDL) treated endothelial cells (ECs). Furthermore, Ash2l promoted the scavenger receptors transcription by catalyzing histone H3 lysine 4 (H3K4) trimethylation at the promoter region of transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) and triggered the activation of the pro-inflammatory nuclear factor-kappa B (NF-κB) by enhancing interaction between CD36 and toll-like receptor 4 (TLR4). Meanwhile, enhanced expression of scavenger receptors drove more oxLDL uptake by ECs. In vivo studies revealed that ECs-specific Ash2l knockdown reduced atherosclerotic lesion formation and promoted fibrous cap stability in the aorta of ApoE-/- mice, which was partly associated with a reduced endothelial activation by suppressing scavenger receptors and the uptake of lipids by ECs. Collectively, our findings identify Ash2l as a novel regulator that mediates endothelial injury and atherosclerosis. Targeting Ash2l may provide valuable insights for developing novel therapeutic candidates for atherosclerosis.

An Evaluation of the Impact of 60Co Irradiation on Volatile Organic Compounds of Olibanum Using Gas Chromatography Ion Mobility Spectrometry.

Olibanum is a resinous traditional Chinese medicine that is directly used as a powder. It is widely used in China and is often combined with other traditional Chinese medicine powders to promote blood circulation and relieve pain, as well as to treat rheumatism, rheumatoid arthritis, and osteoarthritis. Powdered traditional Chinese medicine is often easily contaminated by microorganisms and 60Co irradiation is one of the good sterilization methods. Volatile organic compounds (VOCs) are the main active ingredient of olibanum. The aim of this study was to validate the optimum doses of 60Co irradiation and its effect on VOCs. 60Co irradiation was applied in different doses of 0 kGy, 1.5 kGy, 3.0 kGy, and 6.0 kGy. Changes in VOCs were detected using gas chromatography ion mobility spectrometry. A total of 81 VOCs were identified. The odor fingerprint results showed that, with an increase in irradiation dose, most of the VOCs of olibanum changed. Through principal component analysis, cluster analysis, and partial least squares discriminant analysis, it was demonstrated that, at 1.5 kGy, the impact of radiation on the VOCs of olibanum was minimal, indicating this is a relatively good irradiation dose. This study provides a theoretical basis for the irradiation processing and quality control of resinous medicinal materials such as olibanum and it also provides a good reference for irradiation technology development and its application to functional foods, thus making it both significant from a research perspective and useful from an application perspective.

Development of chemiluminescent lab-on-fiber immunosensors for rapid point-of-care testing of anti-SARS-CoV-2 antibodies and evaluation of longitudinal immune response kinetics following three-dose inactivation virus vaccination.

Developing reliable, rapid, and quantitative point-of-care testing (POCT) technology of SARS-CoV-2-specific antibodies and understanding longitudinal vaccination response kinetics are highly required to restrain the ongoing coronavirus disease 2019 (COVID-19) pandemic. We demonstrate a novel portable, sensitive, and rapid chemiluminescent lab-on-fiber detection platform for detection of anti-SARS-CoV-2 antibodies: the chemiluminescent lab-on-fiber immunosensor (c-LOFI). Using SARS-CoV-2 Spike S1 RBD protein functionalized fiber bio-probe, the c-LOFI can detect anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies with high sensitivity based on their respective horseradish peroxidase-labeled secondary antibodies. The limits of detection of anti-SARS-CoV-2 IgG and IgM antibodies were 0.6 and 0.3 ng/ml, respectively. The c-LOFI was successfully applied for direct detection of anti-SARS-CoV-2 antibodies in whole blood samples with simple dilution, which can serve as a finger prick test to rapidly detect antibodies. Furthermore, the longitudinal immune response (>12 months) kinetics following three-dose inactivated virus vaccines was evaluated based on anti-SARS-CoV-2 IgG detection results, which can provide important significance for understanding the immune mechanism against COVID-19 and identify individuals who may benefit from the vaccination and booster vaccination. The c-LOFI has great potential to become a sensitive, low-cost, rapid, high-frequency POCT tool for the detection of both SARS-CoV-2-specific antibodies and other biomarkers.

Omnidirectional broadband phase modulation by total internal reflection.

Phase modulation plays a crucial role in shaping optical fields and physical optics. However, traditional phase modulation techniques are highly dependent on angles and wavelengths, limiting their applicability in smart optical systems. Here, we propose a first-principle theory for achieving constant phase modulation independent of incident angle and wavelength. By utilizing a hyperbolic metamaterial and engineering-specific optical parameters, different reflective phase jumps are achieved and tailored for both transverse electric (TE) and transverse magnetic (TM) waves. The aimed reflection phase difference between TE and TM waves can be thus achieved omnidirectionally and achromatically. As an example, we propose a perfect omnidirectional broadband reflection quarter wave plate. This work provides fundamental insights into manipulating optical phases through optical parameter engineering.

Exogenous melatonin enhances the tolerance of tiger nut (Cyperus esculentus L.) via DNA damage repair pathway under heavy metal stress (Cd2+) at the sprout stage.

Heavy metal (HM) stress is a non-negligible abiotic stress that seriously restricts crop yield and quality, while the sprout stage is the most sensitive to stress and directly impacts the growth and development of the later stage. Melatonin (N-acetyl-5-methoxytryptamine), as an exogenous additive, enhances stress resistance due to its ability to oxidize and reduce. However, few reports on exogenous melatonin to tiger nuts under HM stress have explored whether exogenous melatonin enhances plants' resistance to heavy metals. Here, "Jisha 2″ was used as material, with a stress concentration of 5 mg/L and 100 µmol/L of CdCl2 to explore whether exogenous melatonin enhances plant resistance and molecular mechanism. The result revealed that stress limits growth, while melatonin alleviated the sprout damage under stress from the phenotypes. Moreover, stress-enhanced reactive oxygen species (ROS) accumulation and membrane lipid peroxidation, while melatonin-increased ROS reduce damage via the analysis of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) and malondialdehyde (MDA) content, hydrogen peroxide (H2O2), superoxide anion (O2-), and Electrolyte leakage (El). Further results indicated that HM leads to DNA damage while exogenous melatonin will repair the damage by analyzing random amplified polymorphic DNA (RAPD), DNA cross-linking, 8-hydroxy-20-deoxyguanine level, and relative density of apurinic sites. Furthermore, gene expression in the DNA-repaired pathway exhibited similar results. These results applied that exogenous melatonin released the hurt caused by HM stress, with DNA repair and ROS balance serving as candidate pathways. This study elucidated the mechanism of melatonin's influence and provided theoretical insights into its application in tiger nuts.

Spatial characteristics of VOCs and their ozone and secondary organic aerosol formation potentials in autumn and winter in the Guanzhong Plain, China.

As critical precursors of tropospheric ozone (O3) and secondary organic aerosol (SOA), volatile organic compounds (VOCs) largely influence air quality in urban environments. In this study, measurements of 102 VOCs at all five major cities in the Guanzhong Plain (GZP) were conducted during Sep.09-Oct. 13, 2017 (autumn) and Nov. 14, 2017-Jan. 19, 2018 (winter) to investigate the characteristics of VOCs and their roles in O3 and SOA formation. The average concentrations of total VOCs (TVOCs) at Xi'an (XA), Weinan (WN), Xianyang (XY), Tongchuan (TC), and Baoji (BJ) sites were in the range of 55.2-110.2 ppbv in autumn and 42.4-74.3 ppbv in winter. TVOCs concentrations were reduced by 22.4%-43.5% from autumn to winter at XA, WN and BJ. Comparatively low concentrations of TVOCs were observed in XY and TC, ranging from 53.5 to 62.7 ppbv across the sampling period. Alkanes were the major components at all sites, accounting for 26.4%-48.9% of the TVOCs during the sampling campaign, followed by aromatics (4.2%-26.4%). The average concentration of acetylene increased by a factor of up to 4.8 from autumn to winter, indicating the fuel combustion in winter heating period significantly impacted on VOCs composition in the GZP. The OH radical loss rate and maximum incremental reactivity method were employed to determine photochemical reactivities and ozone formation potentials (OFPs) of VOCs, respectively. The VOCs in XA and WN exhibited the highest reactivities in O3 formation, with the OFP of 168-273 ppbv and the OH loss rates of 19.3-40.8 s-1. Alkenes and aromatics primarily related to on-road and industrial emissions contributed 57.8%-76.3% to the total OFP. The contribution of aromatics to the SOA formation at all sites reached 94.1%-98.6%. Considering the potential source-area of VOCs, regional transport of VOCs occurred within the GZP cities.

On-site rapid and simultaneous detection of acetamiprid and fipronil using a dual-fluorescence lab-on-fiber biosensor.

A dual-fluorescence lab-on-fiber biosensor was developed for the rapid and simultaneous on-site determination of acetamiprid and fipronil, based on time-resolved effect and indirect competitive immunoassay principle. The optical fiber modified with two hapten-protein conjugates serves as a bifunctional bio-probe. The dual-color fluorescent reporters were prepared via labeling acetamiprid and fipronil antibodies with Cy5.5 and Alexa Fluor 555, which were excited at 635-nm and 520-nm laser wavelengths, respectively. In the presence of targets, the binding sites of corresponding antibodies were occupied and less antibodies were connected to the probe surface, resulting in the reduction of fluorescence signal. The concentration of acetamiprid and fipronil was determined by measuring the fluorescence signals at 568 nm and 702 nm (emission wavelengths), respectively. Under optimal conditions, the linear response range was 14.2-225.4 ng/L for acetamiprid and 25.1-162.8 ng/L for fipronil, and the limit of detection was 6.51 ng/L and 17.8 ng/L for acetamiprid and fipronil, respectively. The method was successfully applied to the simultaneous detection of acetamiprid and fipronil in three environmental samples, and the recoveries were between 90 and 128%. The dual-fluorescence lab-on-fiber biosensor provides a feasible platform for simultaneous and rapid detection of multiple pesticide residues. A dual-fluorescence lab-on-fiber biosensor was developed for the rapid and simultaneous on-site determination of acetamiprid and fipronil. A bifunctional bio-probe was prepared from the optical fiber modified with two hapten-protein conjugates. Acetamiprid and fipronil antibodies were labeled with different fluorophores and used as dual-color fluorescent reporters.

Rapid, label-free, and sensitive point-of-care testing of anti-SARS-CoV-2 IgM/IgG using all-fiber Fresnel reflection microfluidic biosensor.

The ongoing global pandemic of SARS-CoV-2 has promoted to develop novel serological testing technologies since they can be effectively complementary to RT-PCR. Here, a new all-fiber Fresnel reflection microfluidic biosensor (FRMB) was constructed through combining all-fiber optical system, microfluidic chip, and multimode fiber bio-probe. The transmission of the incident light and the collection and transmission of Fresnel reflection light are achieved using a single-multi-mode fiber optic coupler (SMFC) without any other optical separation elements. This compact design greatly simplifies the whole system structure and improves light transmission efficiency, which makes it suitable for the label-free, sensitive, and easy-to-use point-of-care testing (POCT) of targets in nanoliter samples. Based on Fresnel reflection mechanism and immunoassay principle, both the SARS-CoV-2 IgM and IgG antibodies against the SARS-CoV-2 spike protein could be sensitively quantified in 7 min using the secondary antibodies-modified multimode fiber bio-probe. The FRMB performs in one-step, is accurate, label-free, and sensitive in situ/on-site detection of SARS-CoV-2 IgM or IgG in serum with simple dilution only. The limits of detection of SARS-CoV-2 IgM and SARS-CoV-2 IgG were 0.82 ng/mL and 0.45 ng/mL, respectively. Based on our proposed theory, the affinity constants of SARS-CoV-2 IgM or IgG antibody and their respective secondary antibodies were also determined. The FRMB can be readily extended as a universal platform for the label-free, rapid, and sensitive in situ/on-site measurement of other biomarkers and the investigation of biomolecular interaction.

Reusable optofluidic point-of-care testing platform with lyophilized specific antibody for fluorescence detection of cholylglycine in serum.

A reusable optofluidic point-of-care testing platform (OPOCT) was successfully constructed through integrating evanescent wave fluorescence technology into an all-fiber-based optofluidic system. The compact design of the OPOCT allows it to be portable and suitable for on-site sensitive determination of biomarkers in serum without complicated and costly procedures. The sensitivity of 90.9 pM for antibody determination is observed thanks to the high transmission efficiency of excitation light and fluorescence in the OPOCT. The affinity constant between cholylglycine (CG) and anti-CG antibody was quantified using this platform based on the proposed theory. Using the lyophilized fluorescence-labeled specific antibody and reusable fiber optic biosensor, the OPOCT is applied to the one-step sensitive determination of CG in serum, which eliminates the dearth associated with liquid reagent handling, disposable biosensors, and user intervention. A limit of detection of 0.025 µg/mL for CG is obtained, which is far more than adequate for meeting diagnostic requirements. The matrix effect of serum samples on the evanescent wave-based optofluidic biosensor can be effectively reduced by simple dilution of serum samples. The performance of the OPOCT also compared favorably with that of a commercial turbidimetric inhibition immunoassay through analyzing multiple serum samples. This platform is ready to expand to measure any other biomarker by using its specific antibody. The simplicity, sensitivity, cost-effectiveness, and robustness of the OPOCT enable the early diagnosis of disease and making a timely clinical decision. Graphical abstract .

Reusable chemiluminescent fiber optic aptasensor for the determination of 17ß-estradiol in water samples.

A reusable fiber optic chemiluminescent aptasensor (FOCA) is reported for the rapid and sensitive on-site detection of 17ß-estradiol (E2), an endocrine-disrupting compound frequently found in water samples. The E2-ovalbumin conjugate (E2-OVA) was covalently immobilized onto the optical fiber as a biorecognition element as well as a transducer. The affinity constant of the E2/aptamer complex was determined to be 1.35 × 106 M-1 using the FOCA. An indirect competitive assay was then developed for E2 detection. A certain concentration of HRP-E2 aptamers pre-reacted with samples containing E2 in various concentrations. Part of HRP-E2 aptamers specially bound to the sensor surface after introduction of the mixture. This catalyzed the chemiluminescece reaction of a chemiluminescent system composed of luminol and H2O2. A higher concentration of E2 led to less HRP-E2 aptamer bound to the biosensor surface, thus resulting in less chemiluminescence. Highly sensitive detection of E2 was achieved under optimal conditions, and the limit of detection is 48 ng ·L-1 (0.18 nM). The whole analytical process, including measurement and regeneration, can be performed in <15 min. The robustness of the biosensor allows its application to multiple assays with little activity loss. The selectivity, recovery, and accuracy of the sensor was demonstrated by evaluating its response to potentially interfering endocrine disruptors in spiked water samples. Graphical abstract Schematic diagram of the fiber optic chemiluminescent aptasensor system (A), detection mechanism of 17ß-estradiol (B), and its application for detection of 17ß-estradiol with rapidity and sensitivity (C and D).

Double aspheric imaging design with unconstrained object to image mapping.

An imaging design approach for optical systems consisting of two aspheres which is free of astigmatism is presented in this paper. A set of implicit differential equations is derived from generalized ray tracing. The solution of the derived equations provides the profiles of the two aspheres as well as the object to image mapping. The obtained design can be used as a good starting point for optimization. Particular examples are given.

Single freeform surface imaging design with unconstrained object to image mapping.

An imaging design approach which is free of third-order astigmatism for one freeform optical surface and the image is presented in this paper. A set of differential equations is derived from generalized ray tracing. The solution of the above derived equations provides the anastigmatic freeform optical surface, the image surface and the object to image mapping. The obtained design can be used as a good starting point for optimization. As an example, a reflective freeform surface is designed for a single reflective Head Mounted Display (HMD). This example has a 3 mm pupil, 15mm eye clearance, 24-degree diagonal full field of view, and the final design yields an average MTF of 62.6% across 17 field points.

Global research trends and hotspots on smoking and lung cancer from 1994-2023: A bibliometric analysis.

INTRODUCTION: Lung cancer is a significant cause of mortality, especially among smokers. Lung cancer and smoking are strongly associated, according to numerous studies. METHODS: Publications related to smoking and lung cancer were retrieved from the Science Citation Index Expanded (SCIE) database of the Web of Science Core Collection for the period 1994-2023. Descriptive and visual analyses were performed on the topics, journals, countries, institutions, authors, and citations of the publications. RESULTS: A total of 728 articles were retrieved from the Web of Science (WOS) SCIE database for the period January 1994 to December 2023, and the number of publications in the relevant literature demonstrated a progressive increase with time. A total of 647 articles were classified as experimental, while 81 were classified as reviews. The studies were published in 200 journals. The three journals that published the most articles were the American Journal of Epidemiology with 82 articles, Lung Cancer with 34 articles, and Cancer Causes and Control with 26 articles. The three most prolific countries were the United States (286 articles, 38.3%; 15879 citations), China (116 articles, 15.9%; 2911 citations), and France (75 articles, 10.3%; 3694 citations). The four most popular keywords in this field are 'early cancer detection', 'experimental', 'CT', and 'survival rate'. CONCLUSIONS: The findings of our study revealed key areas for focus in smoking and lung cancer research, having a view of supplying important data and motivation for further investigations.

Exploring risk factors and their differences on suicidal ideation and suicide attempts among depressed adolescents based on decision tree model.

BACKGROUND: Suicide has been recognized as a major global public health issue. Depressed adolescents are more prone to experiencing it. We explore risk factors and their differences on suicidal ideation and suicide attempts to further enhance our understanding of suicidal behavior. METHODS: 2343 depressed adolescents aged 12-18 from 9 provinces/cities in China participated in this cross-sectional study. We utilized decision tree model, incorporating 32 factors encompassing participants' suicidal behavior. The feature importance of each factor was measured using Gini coefficients. RESULTS: The decision tree model demonstrated a good fit with high accuracy (SI = 0.86, SA = 0.85 and F-Score (SI = 0.85, SA = 0.83). The predictive importance of each factor varied between groups with suicidal ideation and with suicide attempts. The most significant risk factor in both groups was depression (SI = 16.7 %, SA = 19.8 %). However, factors such as academic stress (SI = 7.2 %, SA = 1.6 %), hopelessness (SI = 9.1 %, SA = 5.0 %), and age (SI = 7.1 %, SA = 3.2 %) were more closely associated with suicidal ideation than suicide attempts. Factors related to the schooling status (SI = 3.5 %, SA = 10.1 %), total years of education (SI = 2.6 %, SA = 8.6 %), and loneliness (SI = 2.3 %, SA = 7.4 %) were relatively more important in the suicide attempt stage compared to suicidal ideation. LIMITATIONS: The cross-sectional design limited the ability to capture changes in suicidal behavior among depressed adolescents over time. Possible bias may exist in the measurement of suicidal ideation. CONCLUSION: The relative importance of each risk factor for suicidal ideation and attempted suicide varies. These findings provide further empirical evidence for understanding suicide behavior. Targeted treatment measures should be taken for different stages of suicide in clinical interventions.

Associations of cerebrospinal fluid complement proteins with Alzheimer's pathology, cognition, and brain structure in non-dementia elderly.

BACKGROUND: Cerebrospinal fluid (CSF) complement activation is a key part of neuroinflammation that occurs in the early stages of Alzheimer's disease (AD). However, the associations of CSF complement proteins with AD pathology, cognition, and structural neuroimaging biomarkers for AD have been rarely investigated. METHODS: A total of 210 participants (125 mild cognitive impairment [MCI] patients and 85 normal controls) were included from Alzheimer's Disease Neuroimaging Initiative (ADNI) database who measured AD pathology, cognition, and neuroimaging at baseline and every 12 months. The mixed-effect linear models were utilized to investigate longitudinal associations of CSF complement proteins with AD pathology, cognition, and neuroimaging in cognitively normal (CN) and mild cognitive impairment (MCI) subjects. Causal mediation analyses were conducted to explore the potential mediators between CSF complement proteins and cognitive changes. RESULTS: We found that the subjects with low CSF complement protein levels at baseline had worse outcomes in AD pathology, indicated by their lowest concentrations observed in A + and A + T + individuals. The reduced CSF complement proteins were associated with faster accumulation of tau among CN subjects and with cognitive decline and greater brain atrophy of specific regions among MCI subjects. Furthermore, mediation analyses showed that the effects of CSF complement proteins on cognitive performance were partially mediated by regional brain structures (mediation proportions range from 19.78 to 94.92%; p < 0.05). CONCLUSIONS: This study demonstrated that CSF complement proteins were involved in the early progression of AD. Our results indicated that regional brain atrophy might be a plausible way to connect CSF complement protein levels and cognition.

An Exploratory Study on the Rapid Detection of Volatile Organic Compounds in Gardenia Fruit Using the Heracles NEO Ultra-Fast Gas Phase Electronic Nose.

Gardenia fruit is a popular functional food and raw material for natural pigments. It comes from a wide range of sources, and different products sharing the same name are very common. Volatile organic compounds (VOCs) are important factors that affect the flavor and quality of gardenia fruit. This study used the Heracles NEO ultra-fast gas phase electronic nose with advanced odor analysis performance and high sensitivity to analyze six batches of gardenia fruit from different sources. This study analyzed the VOCs to find a way to quickly identify gardenia fruit. The results show that this method can accurately distinguish the odor characteristics of various gardenia fruit samples. The VOCs in gardenia fruit are mainly organic acid esters, ketones, and aldehyde compounds. By combining principal component analysis (PCA) and discriminant factor analysis (DFA), this study found that the hexanal content varied the most in different gardenia fruit samples. The VOCs allowed for the fruit samples to be grouped into two main categories. One fruit sample was quite different from the fruits of other origins. The results provide theoretical support for feasibility of rapid identification and quality control of gardenia fruit and related products in the future.

Association of peripheral immunity and cerebral small vessel disease in older adults without dementia: A longitudinal study.

This study explored the associations between peripheral immunity with cerebral small vessel diseases. Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative were investigated. Peripheral blood was obtained, and magnetic resonance imaging was performed to measure cerebral microbleeds (CMB), lacunar infarctions (LI), and white matter hyperintensities (WMH). Multivariable-adjusted regression models, linear mixed-effects models, and the Spearman correlations were used to evaluate the associations. At baseline, individuals with greater neutrophils (odds ratio [OR] =1.10, 95% confidence interval [CI] 1.00-1.20, p=0.042) and monocytes (OR=1.12, 95% CI 1.02-1.22, p=0.016) had higher WMH volume. On the contrary, a higher lymphocyte-to-monocyte ratio (LMR) was related to lower WMH volume (OR=0.91, 95% CI 0.82-1.00, p=0.041). Longitudinally, higher neutrophils (ρ=0.084, p=0.049) and NLR (ρ=0.111, p=0.009) predicted accelerated progression of WMH volume, while a greater LMR (ρ=-0.101, p=0.018) was linked to slower growth of WMH volume. Nevertheless, associations between peripheral immunity with CMB or LI were not observed at baseline and follow-up. Our study found that peripheral immune indexes could serve as convenient noninvasive biomarkers of WMH.

Mechanistic insights into xanthomicrol as the active anti-HCC ingredient of Phytolacca acinosa Roxb.: A network pharmacology analysis and transcriptomics integrated experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Phytolacca acinosa Roxb. (PAR) is a Traditional Chinese Medicinal (TCM) plant with a broad global distribution encompassing 35 species, four of which are found in the People's Republic of China. It occupies a significant role in both Oriental and American traditional medicine, employed in treating a range of conditions such as edema, inflammation, dermatitis, and rheumatism. PAR is also used as a molluscicide and for addressing tumors and bronchitis. The plant is documented in the Chinese Pharmacopoeia and has a longstanding history in TCM, particularly for its diuretic properties and in treating ailments such as edema, swelling, and ulcers. Notably, PAR has demonstrated potent inhibitory effects against the A549 human lung cancer cell line, underscoring its potential in contributing to the development of novel cancer therapeutics. AIM OF THE STUDY: The research aims to elucidate the active components of PAR and their mechanisms in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Employing network pharmacology, this study predicted the principal active compounds and key targets of PAR. A holistic methodology incorporating biological network analysis, transcriptomics sequencing, molecular docking, and molecular dynamics (MD) simulations was utilized to forecast the effects of PAR on HCC, with empirical evidence supporting these findings. RESULTS: Network pharmacology identified xanthomicrol as the foremost active compound in PAR. The tumor-suppressive functions of PAR, as indicated by KEGG pathway analysis and transcriptomics sequencing, predominantly occur via the PI3K/AKT pathway. Molecular docking and dynamics simulations demonstrated the high affinity of xanthomicrol towards TNF, MMP9, PPARG, KDR, and MMP2. In vivo experiments verified the efficacy of xanthomicrol in curtailing HCC tumor growth, while in vitro assessments revealed its substantial impact on the proliferation and apoptosis of HepG2 and HCCLM3 cells. Moreover, the study indicates that xanthomicrol may modulate the expression of TNF, MMP9, PPARG, KDR, and MMP2 in HCC cells and inhibit the activation of the PI3K/AKT pathway. CONCLUSIONS: Xanthomicrol, a principal active component of PAR, has been identified to impede the growth of HCC by targeting the PI3K/Akt/MMP9 pathway. This insight could enhance therapeutic approaches for HCC.

Explore the Role of Frailty as a Contributor to the Association Between AT(N) Profiles and Cognition in Alzheimer's Disease.

Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent. Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty. Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-ß, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-ß/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status. Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty. Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment.

Associations of Frailty with Neuropsychiatric Symptoms of Alzheimer's Disease: A Longitudinal Study.

Background: Frailty is a vulnerability state increasing the risk of many adverse health outcomes, but little is known about the effects of frailty on neuropsychiatric health. Objective: To explore the associations between frailty and the risk of neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD), especially in its different clinical stages. Methods: We included 2,155 individuals assessed using modified frailty index-11 (mFI-11), Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The relationships between frailty and NPSs were explored with logistic regression models and Cox proportional hazard regression models. Causal mediation analyses were conducted to explore the mediation factors between frailty and NPSs. Results: Among mild cognitive impairment (MCI) participants, frailty was cross-sectionally associated with an increased risk of apathy, and longitudinally associated with increased risk of depression and apathy. Among AD participants, frailty was cross-sectionally associated with increased risk of depression and anxiety, and longitudinally associated with an increased risk of apathy. Among participants with cognitive progression, frailty was associated with increased risk of depression and apathy. In MCI participants, the influence of frailty on NPSs was partially mediated by hippocampus volume, whole brain volume, and monocytes, with mediating proportions ranging from 8.40% to 9.29%. Conclusions: Frailty was associated with NPSs such as depression, anxiety, and apathy among MCI, AD, and cognitive progression participants. Atrophy of the hippocampus and whole brain, as well as peripheral immunity may be involved in the potential mechanisms underlying the above associations.