Network pharmacology analysis and molecular docking using the Chinese herbal agent WYHX formula (according to Yan Dexin): Management of coronary artery disease.

BACKGROUND: The therapeutic impact of the Wenyang Huoxue (WYXH) formula on coronary atherosclerotic heart disease (CHD) is well established, yet the precise mechanisms are currently not fully understood. This study provides preliminary insights into the potential mechanisms underlying the therapeutic effects of the formula on CHD by utilizing network pharmacology and molecular docking technology. MATERIALS AND METHODS: The primary active constituents and their corresponding action targets for the formula were retrieved from the TCMSP database. Utilizing Cytoscape 3.9.1 software, a network linking the components of the formula to their respective targets was constructed. Information was collected from Genecards, OMIM, TTD, and DrugBank databases to identify targets related to CHD. The common targets shared by the formula and CHD were then imported into the STRING database to create a protein-protein interaction (PPI) network. Following this, enrichment analyses were performed on the shared targets using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, molecular docking was conducted on the primary active compounds and the core targets. RESULTS: The network encompassing the components and targets of the formula comprises a total of 311 nodes and 895 edges. Compounds exhibiting higher degree centrality consist of quercetin, ß-sitosterol, and kaempferol. In the PPI network, proteins with elevated degree centrality are protein kinase B (AKT1), epidermal growth factor receptor (EGFR), and mitogen-activated protein kinase 3 (MAPK3). The results of GO and KEGG enrichment analyses reveal that the biological processes associated with the efficacy of the formula in treating CHD primarily involve positive regulation of gene expression, hypoxia response, and lipopolysaccharide response, among others. The signaling pathways primarily involved include phosphatidylinositol 3-kinase and protein kinase B (PI3K-AKT), MAPK3, tumor necrosis factor (TNF), and so on. Molecular docking results demonstrate a strong affinity between quercetin, ß-sitosterol, and kaempferol with AKT1, EGFR, and MAPK3. CONCLUSION: We showed for the first time that AKT1, EGFR, and MAPK3 are potential targets influenced by the WYHX formula in CHD treatment. The therapeutic effects could possibly involve signaling pathways such as the PI3K-AKT, MAPK, TNF, and AGE-RAGE pathways.

RhB-Embedded Mn-MOF with Cyclotriphosphazene Skeleton as Dual-Emission Sensor for Putrescine as well as Smart Fluorescent Response of Aromatic Diamines and Nitrophenol.

Luminescent metal-organic framework composites with multiple luminescence emissions have been efficient sensing platforms. Herein, a fluorescent sensor (RhB@1-0.4) with dual-emission fluorescence properties was prepared by introducing rhodamine B (RhB) into the framework of complex 1, [Mn2.5(HCPCP)(H2O)4]·(CH3CN)0.5 [HCPCP = hexa-(4-carboxyl-phenoxy)-cyclotriphosphazene and CH3CN = acetonitrile), which is a novel crystalline two-dimensional (2D) coordinated organic framework material. It is a highly desirable material, realizing a ratiometric fluorescence response to putrescine with a high signal-to-noise ratio, and the detection limit can be as low as 6.8 µM. In addition, RhB@1-0.4 exhibited a better fluorescent sensing performance for aromatic diamines and nitrophenols compared with that of complex 1. It is a potential functionalized MOF material for the application of multichannel fluorescence sensing.

The role of anthraquinone-2-sulfonate on intra/extracellular electron transfer of anaerobic nitrate reduction.

To improve the electron (e-) transfer efficiency, exogenous redox mediators (RMs) were usually employed to enhance the denitrification efficiency due to the electron shuttling. Previous studies were mainly focused on how to improve the extracellular electron transfer (EET) by exogenous RMs. However, the intracellular electron transfer (IET), another crucial e- transfer pathway, of biological denitrification was scarcely reported, especially for the relationship between the denitrification and IET. In this study, Coenzyme Q, Complexes I, II and III were determined as the core components in the IET chain of denitrification by using four specific respiration chain inhibitors (RCIs). Anthraquinone-2-sulfonate (AQS) partially recovered the IET of denitrification from NO3--N to N2 gas when the RCIs were added. Specifically, the generations of N2 gas were improved by 9.68%-18.25% in the experiments with RCIs and AQS, comparing to that with RCIs. nrfA gene was not detected by reverse transcription-polymerase chain reaction, suggesting that Klebsiella oxytoca strain could not conduct dissimilatory nitrate reduction to ammonium. Nitrate assimilation was considered as the main NH4+-N formation way of K. oxytoca strain. The two e- transfer pathways of denitrification were constructed and the roles of AQS on the IET and EET of denitrification were specifically discussed. The results of this study provided a better understanding of the e- transfer pathways of denitrification, and suggested a potential practical use of exogenous RM on bio-treatment of nitrate-containing wastewater.

Comparison of Mortality Predictive Models of Sepsis Patients Based on Machine Learning.

Objective To compare the performance of five machine learning models and SAPS II score in predicting the 30-day mortality amongst patients with sepsis. Methods The sepsis patient-related data were extracted from the MIMIC-IV database. Clinical features were generated and selected by mutual information and grid search. Logistic regression, Random forest, LightGBM, XGBoost, and other machine learning models were constructed to predict the mortality probability. Five measurements including accuracy, precision, recall, F1 score, and area under curve (AUC) were acquired for model evaluation. An external validation was implemented to avoid conclusion bias. Results LightGBM outperformed other methods, achieving the highest AUC (0.900), accuracy (0.808), and precision (0.559). All machine learning models performed better than SAPS II score (AUC=0.748). LightGBM achieved 0.883 in AUC in the external data validation. Conclusions The machine learning models are more effective in predicting the 30-day mortality of patients with sepsis than the traditional SAPS II score.

Repeatability and Reproducibility of Quantitative Assessment of the Retinal Microvasculature Using Optical Coherence Tomography Angiography Based on Optical Microangiography.

OBJECTIVE: The aim of this study was to determine the repeatability and reproducibility of optical coherence tomography angiography (OCTA) based on optical microangiography (OMAG) measurements of macular vessels in normal eyes. METHODS: In this prospective cohort study, 40 eyes of 40 healthy volunteers underwent repeated OCTA (Cirrus HD-OCT 5000 angiography system, Carl Zeiss Meditec, Inc.) scans on two separate visit days. On each visit day, the eyes were scanned three times. The following parameters were used to quantitatively describe the OCTA images of the superficial vascular network: vessel area density (VAD), vessel skeleton density (VSD), vessel diameter index (VDI), vessel perimeter index (VPI), vessel complexity index (VCI), flux, and foveal avascular zone (FAZ). Coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for evaluating intravisit and intervisit repeatability, as well as interobserver reproducibility. RESULTS: The measurements showed high repeatability [CVs ⪕ 4.2% (intravisit) and ⪕ 4.6% (intervisit)] and interobserver reproducibility (ICCs ⪖ 0.923) for all parameters. CONCLUSION: This study demonstrated good repeatability and reproducibility of OCTA based on OMAG for the measurement of superficial vessel parameters in normal eyes.

[Spatial-Temporal Evolution and Prediction of Carbon Storage in Jiuquan City Ecosystem Based on PLUS-InVEST Model].

Based on the background of carbon peaking and carbon neutrality goal strategies, it is important to explore the impact of land use change on carbon storage and the drivers of spatial variation in carbon storage in the Northwest Arid Zone, which is vital to improve the carbon sink increment of the regional ecosystem and promote the regional carbon breakeven. The arid region of northwest China is an extremely fragile natural ecology, and with the rapid advancement of new urbanization, the rate of land use change has accelerated significantly, which has a certain impact on the carbon storage and fixation capacity of ecosystems. The PLUS-InVEST model was used to simulate the spatial and temporal evolution characteristics of carbon storage under natural development, intensive development, water resource constraint, and ecological protection scenarios in Jiuquan City in 2035, and the parameter optimal geographic detector model was used to analyze the spatial divergence drivers of carbon storage. The results showed that:① the area of cultivated land, watershed, and construction land in Jiuquan City showed a significant increasing trend from 1990 to 2020, whereas the area of the remaining land use types showed a decreasing trend. ② The carbon storage in Jiuquan City increased from 7 722 808.1 t to 7 784 371 t from 1990 to 2020, and the conversion of grassland into unused land was the main cause of the loss of regional carbon storage, accounting for 85% of the total loss. ③ All four development scenarios in 2035 showed an increasing trend of carbon storage, among which the ecological protection scenario had the most significant increase, with an increment of 76 989.29 t. ④ The degree of land use, population density, GDP density, and NDVI were the main driving factors of the spatial variation in carbon storage in Jiuquan City, among which the degree of land use had the strongest explanatory power (q value of 0.849), and the interaction of natural and anthropogenic factors enhanced the explanatory power of each factor on the spatial variation in carbon storage. The results of the study can provide a scientific basis and decision basis for the integrated ecosystem management and territorial space optimization in Jiuquan City.

[Ecological network optimization of Jiuquan City, Gansu, China based on complex network theory and circuit model]. / åŸºäºŽå¤æ‚ç½‘ç»œç†è®ºå’Œç”µè·¯æ¨¡åž‹çš„é ’æ³‰å¸‚ç”Ÿæ€ç½‘ç»œä¼˜åŒ–.

Building a scientific and reasonable ecological network is the key for optimizing the pattern of territorial development and protection, and is of great significance for ensuring regional ecological security and promoting the virtuous cycle of ecosystems. In previous studies, nodal attack method (destruction of ecological source area) was often used in the "robustness" evaluation of ecological networks. Actually, the ecological corridor is more fragile than the source area, and thus the nodal attack method is not reasonable. In this study, taking Jiuquan City as the research area, based on the circuit model to construct the ecological network, we carried out the topology optimization of ecological network by using three strategies (random edge increase, node degree and priority edge increase with low node intermedium number) in complex network theory. We compared and analyzed the "robustness" of ecological network before and after optimization by constructing edge attack strategy, and selected the best network optimization strategy. The results showed that 65 ecological source areas were identified in Jiuquan City, with a total area of 20275.15 km2, and that grassland accounted for 89.5% of the source area. We identified 179 ecological corridors with a total length of 6387.16 km, 158 ecological barrier points with a total area of 1385.5 km2. The unused land accounted for 92.2% of the total barrier points area. We identified 63 ecological pinch points, mainly concentrated in the source edge and corridor intersection. Among them, the spatial distribution of 11 barrier points and pinch points was consistent, which was the key area to be repaired in ecological network optimization. The three optimization strategies had significantly improved the stability of ecological network in Jiuquan City. The relative size of the maximum connected subgraph and the edge connected rate of the ecological network of the optimization strategy of adding edges according to degree were all the most stable under random attack mode and deliberate attack mode, which was the best optimization scheme for ecological network in Jiuquan City.

A multi-source behavioral and physiological recording system for cognitive assessment.

Cognitive assessment has a broad application prospect, including estimate of childhood neuro development and maturation, diagnosis of neurodegenerative diseases, and selection for special profession. With the development of computer technique and behavioral recording sensors, the method of cognitive assessment has been replaced from paper scale test to human-computer interaction. We can not only obtain the results of tasks, but also make it possible to acquire multiple behavioral and physiological data during the task. However, there is still a strong challenge of recording multi-source data synchronously during multi-dimensional cognitive assessments. Therefore, we built a multi-source cognitive assessment system can record multi-pattern behavioral and physiological data and feedback at different spatiotemporal levels. Under this system, we developed a multi-source diagnostic toolset for cognitive assessment, including eye tracking, hand movement, EEG and human-computer interaction data during the cognitive task. 238 participants with different mental disorders were assessed using this system. The results showed that our diagnostic toolset can be used to study the behavioral abnormalities of patients with mental disorders through the characteristics of multi-source data. Furthermore, this system can provide some objective diagnostic criteria such as behavioral characters and EEG features for diagnosis of mental disorders.

Comparison of total corneal power measurements obtained with different devices after myopic keratorefractive surgery.

AIM: To analyze the differences, agreements, and correlation among total corneal power parameters generated by different instruments after myopic keratorefractive surgery. METHODS: The prospective cross-sectional study included patients who underwent myopic keratorefractive surgery and received measurements of corneal power 3mo after surgery. Automated keratometer was used for the measurement of simulated keratometry (SimK), swept-source optical coherence tomography (SS-OCT) based biometer for total keratometry (TK), anterior segment-OCT for real keratometry (RK), and Scheimpflug keratometer for the true net power (TNP), the total corneal refractive power (TCRP) and equivalent K-readings (EKR). The differences among these parameters were analyzed, and the agreements and correlation between SimK and other total corneal power parameters were investigated. RESULTS: A total of 70 eyes of 70 patients after myopic keratorefractive surgery were included. The evaluated corneal power parameters were as follows: SimK 38.32±1.93 D, TK 37.54±2.12 D, RK 36.64±2.09 D, TNP 36.56±1.97 D, TCRP 36.70±2.01 D, and EKR 37.55±2.00 D. Pairwise comparison showed that there were significant differences (P<0.001) among all parameters except for between TK and EKR, RK and TNP, RK and TCRP (P=1.000, 1.000, 1.000, respectively). The limits of agreement between SimK and TK, RK, TNP, TCPR, and EKR were 1.08, 1.08, 1.43, 1.48, and 1.73 D, respectively. All parameters showed good correlation with SimK, and the correlation coefficients were 0.995, 0.994, 0.983, 0.982, and 0.975. CONCLUSION: Among the corneal power parameters after myopic keratorefractive surgery, the value of SimK is the largest, followed by TK and EKR, with TCRP, RK, and TNP being the smallest. The differences among the parameters may be attributable to the different calculation principles. Correct understanding and evaluation of corneal power parameters can provide a theoretical basis for taking advantage of the total corneal power to improve the accuracy of intraocular lens calculation after keratorefractive surgery.

Acceleration of biotic decolorization and partial mineralization of methyl orange by a photo-assisted n-type semiconductor.

In this study, a n-type semiconductor perylene diimide (PDI) was coupled with biodegradation to accelerate the biotic decolorization and mineralization of methyl orange (MO) under light condition. The decolorization rates (k1) of MO in pure and mixed cultures with PDI were promoted by 1.35 and 1.79 folds, respectively, comparing to the cultures without PDI. The total mineralization efficiency of 4-aminobenzenesulfonic acid (4-ABA) was achieved to 22.10 ± 0.84% when in the presence of PDI. The quinone-like group and oxidation-reduction capacity of PDI were detected by Fourier transform infrared spectroscopy and cyclic voltammetry, respectively, but the enhancement on the biotic decolorization of MO was not promoted under dark condition indicating that microbial extracellular electron transfer was not promoted. The 4-ABA was confirmed to be partially mineralized when the PDI exposure to light. The generated free radicals i.e., h+, ⸱OH, was demonstrated as active species to accelerate the decolorization and mineralization of MO by ESR test and radical quenching experiments. The bond breaking of MO and 4-ABA molecules were successfully predicted by density functional theory calculations and were further proven by liquid-chromatography mass spectra. The synergistic mechanism of decolorization and mineralization of MO by microorganism and photocatalysis was proposed. Moreover, High-throughput sequencing and Live/dead cell results indicated that the presence of PDI has no obvious toxicity to the microorganisms and will not change the microbial communities during the short-term treatment period. The results of study provided a biological intimate photocatalytic material and suggested a feasible way for its combination with biodegradation of azo dyes.

Associations between pain and depressive symptoms: A longitudinal study of Chinese adolescents.

AIMS: Pain and depressive symptoms are prevalent in adolescents. Data on the association between pain and depressive symptoms in the general adolescent population are limited. The purpose of this study was to investigate the prospective associations of headache, stomachache, and other nonspecific pain with depressive symptoms in a large sample of Chinese adolescents. METHODS: A total of 7072 adolescents who participated in the baseline survey and were followed up 1 year later were included in the prospective analysis. Participants completed a self-administered questionnaire to assess three types of pain (headache, stomachache, and other nonspecific pain) and demographics. Depressive symptoms were assessed by the Center for Epidemiology Studies Depression Scale. Logistic regression models were conducted to evaluate the associations between pain and depressive symptoms. RESULTS: The prevalence and incidence rates of depressive symptoms significantly increased with elevated pain frequencies. After adjusting for insomnia symptoms and other adolescent and family covariates, frequent headache (OR=2.39, 95% CI =1.37-4.16) and other nonspecific pain (sometimes pain: OR=1.57, 95% CI =1.14-2.15; frequent pain: OR=2.78, 95% CI =1.33-5.82) were significantly associated with increased risk of depressive symptoms 1 year later. Study limitation: Pain and depressive symptoms were self-reports. CONCLUSIONS: The findings suggest that frequent pain is associated with subsequent depressive symptoms. Further research is needed to determine the causal relationship between pain and depressive symptoms in adolescents.

[Computed tomographic classification of posterior condylar tibial plateau fractures].

OBJECTIVE: To study the new computed tomographic (CT) classification, surgical approaches and clinical efficacy of posterior condylar tibial plateau fractures. METHODS: From January 2006 to July 2009, a total of 39 patients of posterior condylar tibial plateau fractures were treated by posteromedial and posterolateral knee approaches. There were 23 males and 16 females. The mean age was 41.6 years old (range: 28 - 68). Among all patients, the causes were traffic accidents (n = 26), falls (n = 9) and other injuries (n = 4). By CT classification, there were type I with posteromedial condylar tibial plateau split fracture (n = 7), type II with posterolateral condylar tibial plateau split fracture (n = 5), type III with posterolateral condylar tibial plateau depression fracture (n = 11), type IV with posterolateral condylar tibial plateau split depression fracture (n = 2) and type V with posteromedial split and posterolateral condylar tibial plateau depression fracture (n = 14). RESULTS: The mean follow-up period was 18.1 months (range: 12 - 30). The radiographic bony union time was 11 - 16 weeks (mean: 15.2) and the full weight-bearing time 12 - 20 weeks (mean: 15.6). No infection, knee varus/valgus, nerve injury or screw loosening/breakage was found. Bony union was achieved in all cases. According to the Rasmussen functional scoring, the results were excellent in 20, good in 14 and fair in 5. And the excellent and good rate was 87.2%. The radiological results were graded with the Rasmussen score to evaluate the reduction of fracture. The outcome was excellent in 28, good in 8 and fair in 3. And the excellent and good rate was 92.3%. CONCLUSION: This new CT classification scheme of posterior condylar tibial plateau fractures can significantly improve the reliability, guide the clinicians to select appropriate treatment plans and design an ideal regimen of operative approach and internal fixation.

[Simulation of Lanzhou urban land expansion based on multi-agent model]. / åŸºäºŽå¤šæ™ºèƒ½ä½“æ¨¡åž‹çš„å °å·žå¸‚åŸŽé•‡ç”¨åœ°æ‰©å±•æ¨¡æ‹Ÿ.

Using the four periods of land use data and socio-economic statistics of Lanzhou City in 1995, 2005, 2015 and 2018, we examined the evolution characteristics and driving forces of urban land use in Lanzhou, with expansion intensity index, Logistic regression, and principal component analysis method. Based on the multi-agent model, the expansion of urban land use in Lanzhou under multiple scenarios in 2025 was simulated using Netlogo software. The results showed that the intensity and scale of urban land expansion in Lanzhou City from 1995 to 2018 showed an increasing trend, with a total of 307 km2 of cultivated land and water area. The expansion of urban land in Lanzhou City was significantly related to regional GDP, social fixed asset investment, population density, population, policy, and terrain. The multi-agent model on the Netlogo software could simulate the expansion trend of urban land in Lanzhou, which provided a reliable simulation method for the expansion of valley-type cities. From 2020 to 2025, urban land use under the comprehensive development scenario, natural expansion development scenario, ecological and farmland protection development scenario all showed an increasing trend. The scale of expansion would range between 42.6-134.3 km2. The expansion mode would mainly be infilled expansion. Our results could provide decision support for the land space planning and ecological environment layout optimization for Lanzhou City.

Associations Between the Use of Renin-Angiotensin System Inhibitors and the Risks of Severe COVID-19 and Mortality in COVID-19 Patients With Hypertension: A Meta-Analysis of Observational Studies.

Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share a target receptor with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The use of ACEIs/ARBs may cause angiotensin-converting enzyme 2 receptor upregulation, facilitating the entry of SARS-CoV-2 into host cells. There is concern that the use of ACEIs/ARBs could increase the risks of severe COVID-19 and mortality. The impact of discontinuing these drugs in patients with COVID-19 remains uncertain. We aimed to assess the association between the use of ACEIs/ARBs and the risks of mortality and severe disease in patients with COVID-19. A systematic search was performed in PubMed, EMBASE, Cochrane Library, and MedRxiv.org from December 1, 2019, to June 20, 2020. We also identified additional citations by manually searching the reference lists of eligible articles. Forty-two observational studies including 63,893 participants were included. We found that the use of ACEIs/ARBs was not significantly associated with a reduction in the relative risk of all-cause mortality [odds ratio (OR) = 0.87, 95% confidence interval (95% CI) = 0.75-1.00; I 2 = 57%, p = 0.05]. We found no significant reduction in the risk of severe disease in the ACEI subgroup (OR = 0.95, 95% CI = 0.88-1.02, I 2 = 50%, p = 0.18), the ARB subgroup (OR = 1.03, 95% CI = 0.94-1.13, I 2 = 62%, p = 0.48), or the ACEI/ARB subgroup (OR = 0.83, 95% CI = 0.65-1.08, I 2 = 67%, p = 0.16). Moreover, seven studies showed no significant difference in the duration of hospitalization between the two groups (mean difference = 0.33, 95% CI = -1.75 to 2.40, p = 0.76). In conclusion, the use of ACEIs/ARBs appears to not have a significant effect on mortality, disease severity, or duration of hospitalization in COVID-19 patients. On the basis of the findings of this meta-analysis, there is no support for the cessation of treatment with ACEIs or ARBs in patients with COVID-19.

Acceleration of the bio-reduction of methyl orange by a magnetic and extracellular polymeric substance nanocomposite.

Extracellular electron transfer (EET) plays an important role in bio-reduction of environmental pollutants. Extracellular polymeric substances (EPS), a kind of biogenic macromolecule, contain functional groups responsible for acceleration of EET. In this study, azo dye-methyl orange (MO) was chosen as a model pollutant, and a Fe3O4 and EPS nanocomposite (Fe3O4@EPS) was prepared to evaluate its promotion on the bio-reduction of MO. The flower-like core-shell configuration of Fe3O4@EPS with a 12 nm of light layer of EPS was confirmed by TEM. The redox ability of EPS was well reserved on Fe3O4@EPS by FTIR and electrochemical test. The application of Fe3O4@EPS on sustained acceleration of MO decolorization were confirmed by batch experiments and anaerobic sequenced batch reactors. Due to biocompatibility of the biogenic shell, the as-prepared Fe3O4@EPS exhibited low toxic to microorganisms by the Live/dead cell test. Moreover, negligible leaching of EPS under high concentration of various anions and less than 10% of EPS was released under extreme acidic and basic pH condition. The results of study provided a new preparation method of biological intimate and environmentally friendly redox mediators and suggested a feasible way for its use on bio-reduction of pollutants.

Efficient Biodegradation of Azo Dyes Catalyzed by the Anthraquinone-2-sulfonate and Reduced Graphene Oxide Nanocomposite.

An anthraquinone-2-sulfonate and reduced graphene oxide nanocomposite (AQS@rGO) was prepared and the improvement on the biotic reduction of a pollutant, i.e., azo dye, was demonstrated. Electron paramagnetic resonance signal of the semi-quinone radical in the well-dispersed solid AQS@rGO solution was detected. Although the as-prepared AQS@rGO has a negligible adsorption capacity toward methyl orange (MO) dye, the decolorization efficiencies in both flask experiments and sequencing operation reactors in the presence of AQS@rGO were increased by more than 1.5 times as compared to that with graphene oxide, and an efficient and continuable catalytic effect on the decolorization of azo dyes in seven operation periods was maintained. The catalytic effect on reduction was caused by the formation of a space-charge layer, which facilitates the efficient e- transfer from the conductive rGO sheets to the C=O of the AQS molecule. The results suggested that the AQS@rGO may act as an efficient insoluble redox mediator, which is important for the pollution control by accelerating the extracellular electron transfer.

Insights into Oxidation of the Ultrahigh Molecular Weight Polyethylene Artificial Joint Related to Lipid Peroxidation.

Oxidative degradation of ultrahigh molecular weight polyethylene (UHMWPE) bearings is one of the main factors that deteriorates their mechanical properties and abrasive wear resistance, which further results in the failure of total joint replacements. Absorption and diffusion of synovial fluids have been considered as causes of the oxidation of UHMWPE bearings. However, the role of synovial fluids in oxidation of UHMWPE remains elusive. In this work, we aimed to reveal the oxidation mechanism of UHMWPE joints with respect to squalene (a representative component of the synovial fluid). The UHMWPE doped in squalene showed slight oxidation, while severe oxidation was observed when squalene doped UHMWPE was exposed to oxygen atmosphere. Squalene manifested lipid peroxidation with notable oxidation products and oxygen-derived free radicals during thermo-oxidative aging. Lipid peroxidation was deduced to follow two routes including autoxidation and thermal oxidation. The aggressive free radicals of squalene abstracted hydrogen atoms from the UHMWPE chains, initiating the oxidation of UHMWPE artificial joints. These findings not only provide evidence for comprehending the process of squalene-induced UHMWPE oxidation but also are instructive to develop highly oxidative-resistant UHMWPE.

Cytomembrane-Mediated Transport of Metal Ions with Biological Specificity.

Metal ions are of significant importance in biomedical science. This study reports a new concept of cytomembrane-mediated biospecific transport of metal ions without using any other materials. For the first time, cytomembranes are exploited for two-step conjugation with metal ions to provide hybrid nanomaterials. The innate biofunction of cell membranes renders the hybrids with superior advantages over common vehicles for metal ions, including excellent biocompatibility, low immunogenic risk, and particularly specific biotargeting functionality. As a proof-of-concept demonstration, cancer cell membranes are used for in vivo delivery of various metal ions, including ruthenium, europium, iron, and manganese, providing a series of tumor-targeted nanohybrids capable of photothermal therapy/imaging, magnetic resonance imaging, photoacoustic imaging, and fluorescence imaging with improved performances. In addition, the special structure of the cell membrane allows easy accommodation of small-molecular agents within the nanohybrids for effective chemotherapy. This study provides a new class of metal-ion-included nanomaterials with versatile biofunctions and offers a novel solution to address the important challenge in the field of in vivo targeted delivery of metal ions.

Platelet-Mimicking Biotaxis Targeting Vasculature-Disrupted Tumors for Cascade Amplification of Hypoxia-Sensitive Therapy.

Tumorous vasculature plays key roles in sustaining tumor growth. Vascular disruption is accompanied by internal coagulation along with platelet recruitment and the resulting suppression of oxygen supply. We intend to artificially create this physiological process to establish the mutual feedback between vascular disruption and platelet-mimicking biotaxis for the cascade amplification of hypoxia-dependent therapy. To prove this concept, mesoporous silica nanoparticles are co-loaded with a hypoxia-activated prodrug (HAP) and a vessel-disruptive agent and then coated with platelet membranes. Upon entering into tumors, our nanotherapeutic can disrupt local vasculature for tumor inhibition. This platelet membrane-coated nanoplatform shares the hemorrhage-tropic function with parental platelets and can be persistently recruited by the vasculature-disrupted tumors. In this way, the intratumoral vascular disruption and tumor targeting are biologically interdependent and mutually reinforced. Relying on this mutual feedback, tumorous hypoxia was largely promoted by more than 20-fold, accounting for the effective recovery of the HAP's cytotoxicity. Consequently, our bioinspired nanodesign has demonstrated highly specific and effective antitumor potency via the biologically driven cooperation among intratumoral vascular disruption, platelet-mimicking biotaxis, cascade hypoxia amplification, and hypoxia-sensitive chemotherapy. This study offers a paradigm of correlating the therapeutic design with the physiologically occurring events to achieve better therapy performance.

Quantitative evaluation of primary retinitis pigmentosa patients using colour Doppler flow imaging and optical coherence tomography angiography.

PURPOSE: To find the potential relation between changes in retinal large vessels and terminal vessels using colour Doppler flow imaging (CDFI) and optical coherence tomography angiography (OCTA) and to compare the respective advantages of CDFI and OCTA in evaluating vascular changes in retinitis pigmentosa (RP) patients. METHODS: A prospective series of case study was conducted to enrol RP patients and age-matched controls, who were, respectively, imaged by CDFI and OCTA. Repeatability and reproducibility of both CDFI and OCTA were performed among healthy volunteers. The central retinal artery (CRA) was detected by CDFI analysis to provide parameters of peak systolic velocity (PSV), end-diastolic velocity (EDV) and time-averaged maximum velocity (TAMV). Retinal parameters were evaluated from OCTA images, including vascular area density (VAD) of the superficial vascular layer, the fovea avascular zone (FAZ) area and retinal thickness. RP patients were separated into a high-vision group and a low-vision group, according to median vision (0.3, LogMAR 0.5). Multiple comparisons were used to analyse the data between groups. A correlation analysis was used to determine the correlation between CDFI and OCTA parameters. RESULTS: Twenty RP patients (40 eyes) and thirteen normal volunteers (26 eyes) were enrolled in this study. Repeatability and reproducibility of the measurements by CDFI had higher CVs, from 4.5% to 15.4%, than those measurements by OCTA (<5%). All the CDFI and OCTA parameters examined had significant reductions in RP patients compared to those in the controls (p < 0.01). Compared to the high-vision group, the low-vision group exhibited a statistically significant decrease in vascular parameters of the FAZ area, fovea VAD and parafovea nasal side VAD (p < 0.05); as well as in the parameters of the fovea thickness, and the parafovea nasal, superior and inferior side thickness (p < 0.05). From the correlation analysis, a significant association was found between the vision and CDFI parameters (PSV and time-averaged maximum velocity (TAMX), p < 0.05), and the vision and OCTA parameters (FAZ area, fovea and nasal side VAD, retinal thickness in all sides, p < 0.05). PSV and TAMX of the CRA were closely related to the OCTA superficial VAD in all sides, whereas the CDFI parameters showed poor correlation with retinal thickness. CONCLUSIONS: Colour Doppler flow imaging (CDFI) and OCTA parameters revealed a significant reduction in RP patients when compared to the controls. OCTA can detect vision-related microvascular and thickness changes around the macula between high- and low-vision groups, which happen earlier than the changes in large vessels. In addition to good repeatability and reproducibility, OCTA may have significant utility in the diagnosis and monitoring of disease progression in RP patients.