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Ubiquitination is the specific modification of target proteins in cells by ubiquitin molecules, which is under the action of a series of special enzymes such as ubiquitin-activating enzymes, binding, and ligase enzymes. Ubiquitination plays an essential role in anthocyanin accumulation in plants. There are few studies on the coloring of pear peel by ubiquitin ligase E3. In this study, an E3 ubiquitin ligase protein PpPUB59 with seven WD40 repeats was cloned. And the function of PpPUB59 on the ubiquitination and protein stability of PpBBX24 and Ppbbx24-del, and the possible action mechanism in the anthocyanin accumulation of 'Red Zaosu' was studied. Our results showed that the WD40 repeats were verified to be the key domain interacting with the VP domain of BBX protein. PpPUB59 could degrade PpBBX24 in vitro by interacting with the VP domain but could not degrade the mutant PpBBX24-del without the VP domain. Dual luciferase assay showed that Ppbbx24-del could activate the PpCHS promoter, while PpPUB59 did not interfere with this activation; PpBBX24 could not activate the promotor of PpCHS but could suppress the activation of PpHY5; when the PpPUB59 was co-expressed with PpBBX24 and PpHY5, the activation roles of PpHY5 in the promotor of PpCHS was not recovered. BiFC and yeast two-hybrid experiments showed that PpPUB59 could also interact with PpHY5, which may make it ubiquitinated and degraded by 26S proteasome. In conclusion, PpPUB59 played an essential role in pear anthocyanin accumulation by ubiquitinating the associated transcription factors. These findings clarified the mutant mechanism of the 'Red Zaosu' pear at the post-translational modification level and enriched the regulation theory of the pear anthocyanin accumulation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest in relation to the manuscript titled “Mechanism difference of PpPUB59 ubiquitination regulating anthocyanin accumulation in ‘Zaosu’ pear and its red bud mutation”., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Amidst the therapeutic quandaries associated with triple-negative breast cancer (TNBC), an aggressive malignancy distinguished by its immune resistance and limited treatment avenues, the urgent need for innovative solutions is underscored. To conquer the dilemma, we present a groundbreaking approach that ingeniously employs DNA-fragments-containing exosomes (DNA-Exo) and the concept of "biological logic-gates" to achieve precise homing and controlled selective activation of ferroptosis and stimulator interferon genes (STING) pathways. Leveraging insights from our previous research, a nano-Trojan-horse, Fe 0 @HMON@DNA-Exo, is engineered via in situ Fe 0 synthesis within the glutathione (GSH)-responsiveness degradable hollow mesoporous organosilica nanoparticles (HMON) and subsequently enveloped in DNA-Exo derived from 7-ethyl-10-hydroxycamptothecin (SN38)-treated 4T1 cells. Emphasizing the precision of our approach, the DNA-Exo ensures specific 'homing' to TNBC cells, rendering a targeted delivery mechanism. Concurrently, the concept of "biological logic-gates" is employed to dictate a meticulous and selective activation of STING in antigen-presenting cells (APCs) under OR logic-gating with robust immune response and Fe 0 -based ferroptosis in TNBC cells under AND logic-gating with reactive oxygen species (ROS) storm generation. In essence, our strategy exhibits great potential in transforming the "immunologically cold" nature of TNBC, enabling precise control over cellular responses, illuminating a promising therapeutic paradigm that is comprehensive and productive in pursuing precision oncology and paving the way for personalized TNBC therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Under international advocacy for a low-carbon and healthy lifestyle, ambient PM2.5 pollution poses a dilemma for urban residents who wish to engage in outdoor exercise and adopt active low-carbon commuting. In this study, an Urban Air Health Navigation System (UAHNS) was designed and proposed to assist users by recommending routes with the least PM2.5 exposure and dynamically issuing early risk warnings based on topologized digital maps, an application programming interface (API), an eXtreme Gradient Boosting (XGBoost) model, and two-step spatial interpolation. A test of the UAHNS's functions and applications was carried out in Wuhan city. The results showed that, compared with trained random forest (RF), LightGBM, Adaboost models, etc., the XGBoost model performed better, with an R 2 exceeding 0.90 and an RMSE of approximately 15.74 μg/m 3 , based on data from national air and meteorological monitoring stations. Further, the two-step spatial interpolation model was adopted to dynamically generate pollution distribution at a spatial resolution of 300 m*300 m. Then, an exposure comparison was performed under randomly selected commuting routes and times in Wuhan, showing the recommended routes for lower PM2.5 exposure made effectively help. And the route difference ratios of about 14.9 % and 16.9 % for riding and walking, respectively. Finally, the UAHNS platform was integrally realized for Wuhan, consisting of a real-time PM2.5 query, a one-hour PM2.5 prediction function at any location, health navigation on city map, and a personalized health information query., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Psoriasis is an immune-mediated skin disease where the IL-17 signaling pathway plays a crucial role in its development. Chronic circadian rhythm disorder in psoriasis pathogenesis is gaining more attention. The relationship between IL and 17 signaling pathway and skin clock genes remains poorly understood., Methods: GSE121212 with psoriatic lesion and healthy controls was used as the exploration cohort for searching analysis. Datasets GSE54456, GSE13355, GSE14905, GSE117239, GSE51440, and GSE137218 were applied to validation analysis. Single-cell RNA sequencing (scRNA-seq) dataset GSE173706 was used to explore the F3 expression and related pathway activities in single-cell levels. Through intersecting with high-expression DEGs, F3 was selected as the signature skin circadian gene in psoriasis for further investigation. Functional analyses, including correlation analyses, prediction of transcription factors, protein-protein interaction, and single gene GSEA to explore the potential roles of F3. ssGSEA algorithm was performed to uncover the immune-related characteristics of psoriasis. We further explored F3 expression in the specific cell population in scRNA-seq dataset, besides this, AUCell analysis was performed to explore the pathway activities and the results were further compared between the specific cell cluster. Immunohistochemistry experiment, RT-qPCR was used to validate the location and expression of F3, small interfering RNA (siRNA) transfection experiment in HaCaT, and transcriptome sequencing analysis were applied to explore the potential function of F3., Results: F3 was significantly down-regulated in psoriasis and interacted with IL-17 signaling pathway. Low expression of F3 could upregulate the receptor of JAK-STAT signaling, thereby promoting keratinocyte inflammation., Conclusion: Our research revealed a bidirectional link between the skin circadian gene F3 and the IL-17 signaling pathway in psoriasis, suggesting that F3 may interact with the IL-17 pathway by activating JAK-STAT within keratinocytes and inducing abnormal intracellular inflammation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Exposure scenario and receptor behavior significantly affect PM2.5 exposure quantity of persons and resident groups, which in turn influenced indoor or outdoor air quality & health management. An Internet of Things (IoT) system, EnvironMax+, was developed to accurately and conveniently assess residential dynamic PM2.5 exposure state. A university community "QC", as the application area, was divided into four exposure scenarios and five groups of residents. Low-cost mobile sensors and indoor/outdoor pollution migration (IOP) models jointly estimated multi-scenario real-time PM2.5 concentrations. Questionnaire was used to investigate residents' indoor activity characteristics. Mobile application (app) "Air health management (AHM)" could automatic collect residents' activity trajectory. At last, multi-scenario daily exposure concentrations of each residents-group were obtained. The results showed that residential exposure scenario was the most important one, where residents spend about 60 % of their daily time. Closing window was the most significant behavior affecting indoor contamination. The annual average PM2.5 concentration in the studied scenarios: residential scenario (RS) < public scenario (PS) < outdoor scenario (OS) < catering scenario (CS). Except for CS, the outdoor PM2.5 in other scenarios was higher than indoor by 5-10 μg/m 3 . The multi-scenario population weighted annual average exposure concentration was 37.1 μg/m 3 , which was 78 % of the annual average outdoor concentration. The exposure concentration of 5 groups: cooks > outdoor workers > indoor workers > students > the elderly, related to their daily activity time proportion in different exposure scenario., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Immunogenicity improvement is a valuable strategy for tumor immunotherapy. However, immunosuppressive factors bestow tolerogenic phenotype on tumor-infiltrating DCs, which exhibit weak antigen presentation and strong anti-inflammatory cytokines secretion abilities, limiting the effectiveness of tumor immunotherapy even if the tumor has adequate immunogenicity. Herein, we designed a programmable releasing versatile hydrogel platform (PIVOT) to sculpt tumor immunogenicity, increase intratumoral DCs and cDC1s abundance, and reverse the tolerogenic phenotype of DCs, thus promoting their maturation for boosting innate and adaptive immune responses. Responsive to tumoral reactive oxygen species (ROS), the hydrogel splits and promotes the activation of DCs and macrophages. Then, oxaliplatin is first released from PIVOT to sculpt tumor immunogenicity by inducing immunogenic cell death (ICD) and causing tumoral DNA fragments exposure simultaneously. Subsequently, the impaired DNA fragments bind to high mobility group protein 1 (HMGB1) forming the DNA-HMGB1 complex. Moreover, exogenous FMS-like tyrosine kinase 3 ligand (Flt-3L) recruits masses of DCs, especially cDC1s, which will endocytose the complex benefiting from TIM-3 blockade (αTIM3) that can reverse tolerogenic DCs. Finally, the endocytosis activates the cGAS-STING pathway of cDC1s, which promotes the secretion of type I IFN that triggers innate immune responses, and CXCL9 which recruits CD8 + effector T cells to initiate the following adaptive immune response against tumor progress. PIVOT achieves nearly 90 % tumor growth inhibition and induces systemic antitumor immune responses. In conclusion, this study focuses on ICD-mediated tumor immunogenicity sculpture and nucleic acid endocytosis-involved tolerogenic DCs reversal, providing a novel paradigm for enhancing DCs-based antitumor immune responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: The abnormal polarisation of microglial cells (MGs) following retinal ischemia/reperfusion (RIR) initiates neuroinflammation and progressive death of retinal ganglion cells (RGCs), causing increasingly severe and irreversible visual dysfunction. Roflumilast (Roflu) is a promising candidate for treating neuroinflammatory diseases. This study aimed to explore whether Roflu displayed a cytoprotective effect against RIR-induced neuroinflammation and to characterise the underlying signalling pathway., Methods: The effects and mechanism of Roflu against RIR injury were investigated in C57BL/6J mice and the BV2 cell line. We used quantitative real-time PCR and enzyme-linked immunosorbent assay to examine the levels of inflammatory factors. Furthermore, haematoxylin and eosin and immunofluorescence (IF) stainings were used to assess the morphology of the retina and the states of MGs and RGCs. Reactive oxygen species (ROS) levels were examined using a ROS assay kit, while whole-genome sequencing analysis was conducted to identify altered pathways and molecules. Western blotting and IF staining were used to quantify the proteins associated with the nuclear factor erythroid 2-related factor 2 (Nrf2)/stimulator of interferon gene (STING)/nuclear factor kappa beta (NF-κB) pathway., Results: MG polarisation includes the pro-inflammatory and neurotoxic M1 phenotype as well as the anti-inflammatory and neuroprotective M2 phenotype. Roflu significantly attenuated MG activation and contributed to a shift in the MG phenotype from M1 to M2. Moreover, Roflu decreased ROS release and increased heme oxygenase 1 and NAD(P)H quinone oxidoreductase 1 expression. In vitro and in vivo experiments validated that Roflu exerted its neuroprotective effects primarily by upregulating the Nrf2/STING/NF-κB pathway. However, these effects were abrogated when the Nrf2 expression was inhibited by pharmacological or genetic manipulation., Conclusions: Roflu suppressed RIR-induced neuroinflammation by driving the shift of MG polarisation from M1 to M2 phenotype, which was mediated by the upregulation of the Nrf2/STING/NK-κB pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Trigeminal neuralgia (TN) is a stubborn head and face neuropathic pain with complex pathogenesis. Patients with TN have a significantly increased risk of central neurodegeneration, which manifests as cognitive impairment and memory loss, but the specific mechanism underlying central nervous degeneration is still unclear. This study aimed to explore central neurodegeneration and its possible mechanism of action in TN rats based on changes in the brain fatty acid content and microglia-related neuroinflammation. Using a TN neuropathic pain model established by us, we found that TN rats have obvious cognitive impairment. Furthermore, changes in the brain fatty acid content were analyzed using gas chromatography-mass spectrometry (GC-MS). It was found that the docosahexaenoic acid (DHA) content in the central nervous system (CNS) of TN rats was significantly decreased compared to that in the CNS of Sham rats. An important component in maintaining brain cognition, DHA also plays a key role in regulating central neuroinflammation. Here, by continuous supplementation of DHA, the CNS DHA content was increased to a certain extent in TN rats. The cognitive impairment of TN rats was improved after restoring the central DHA level; this may be related to the improvement of neuroinflammation through the DHA-mediated regulation of microglial polarization. Overall, this study provides a theoretical basis for explaining the pathogenesis of central neurodegeneration in TN. It also suggests DHA as a target for protecting the CNS of patients with TN from damage., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Human galectin 3 (Gal-3) has been implicated to play important roles in different biological recognition processes such as tumor growth and cancer metastasis. High-affinity Gal-3 ligands are desirable for functional studies and as inhibitors for potential therapeutic development. We report here a facile synthesis of β-cyclodextrin (CD)-based Tn and TF antigen-containing multivalent ligands via a click reaction. Binding studies indicated that the synthetic multivalent glycan ligands demonstrated a clear clustering effect in binding to human Gal-3, with up to 153-fold enhanced relative affinity in comparison with the monomeric glycan ligand. The GalNAc (Tn antigen) containing heptavalent ligand showed the highest affinity for human Gal-3 among the synthetic ligands tested, with an EC 50 of 1.4 μM in binding to human Gal-3. A cell-based assay revealed that the synthetic CD-based multivalent ligands could efficiently inhibit Gal-3 binding to human airway epithelial cells, with an inhibitory capacity consistent with their binding affinity measured by SPR. The synthetic cyclodextrin-based ligands described in this study should be valuable for functional studies of human Gal-3 and potentially for therapeutic applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Cell therapy offers a promising paradigm for heart tissue regeneration. Human induced pluripotent stem cells (hiPS) and their cardiac derivatives are emerging as a novel treatment for post-myocardial infarction repair. However, the immature phenotype and function of hiPS-derived cardiomyocytes (hiPS-CMs), particularly poor electrical coupling, limit their potential as a therapy. Herein, we developed a hybrid gold nanoparticle (AuNP)-hyaluronic acid (HA) hydrogel matrix encapsulating hiPS-CMs to overcome this limitation. Methacrylate-modified-HA was used as the backbone and crosslinked with a matrix metalloproteinase-2 (MMP-2) degradable peptide to obtain a MMP-2-responsive hydrogel; RGD peptide was introduced as an adhesion point to enhance biocompatibility; AuNPs were incorporated to regulate the mechanical and topological properties of the matrix by significantly increasing its stiffness and surface roughness, thereby accelerating gap junction formation in hiPS-CMs and orchestrating calcium handling via the α n β1integrin-mediated ILK-1/p-AKT/GATA4 pathway. Transplanted AuNP-HA-hydrogel-encapsulated-hiPS-CMs developed more robust gap junctions in the infarcted mice heart and resynchronized electrical conduction of the ventricle post-myocardial infarction. The hiPS-CMs delivered by the hydrogels exerted stronger angiogenic effects, which also contributed to the recovery process. This study provides insight into constructing an injectable biomimetic for structural and functional renovation of the injured heart., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Intimal hyperplasia-induced restenosis is a common response to vascular endothelial damage caused by mechanical force or other stimulation, and is closely linked to vascular remodeling. Curcumin, a traditional Chinese medicine, exhibits potent protective effects in cardiovascular diseases; for example, it attenuates vascular remodeling. Although the suppressive effects of curcumin on diseases caused by vascular narrowing have been investigated, the underlying mechanisms remain unknown. Long non-coding RNAs (lncRNAs) regulate various pathological processes and affect the action of drugs. In the present study, we found that the curcumin remarkably downregulated the expression of lncRNA H19 and thereby inhibited intimal hyperplasia-induced vascular restenosis. Furthermore, the inhibition of the expression of H19 by curcumin resulted in the inactivation of the Wnt/β-catenin signaling. Overall, we show that curcumin suppresses intimal hyperplasia via the H19/Wnt/β-catenin pathway, implying that H19 is a critical molecule in the suppression of intimal hyperplasia after balloon injury by curcumin. These insights should be useful for potential application of curcumin as a therapeutic intervention in vascular stenosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Simulation of flow diverter (FD) treated aneurysm can evaluate treatment efficacy and aid treatment planning. However, explicit modeling of thin wires of FD impose extremely high demand of computational resources and time, which limit its use in time-sensitive presurgical planning. One alternative approach is to model FD as homogenous porous medium, which saves time but with compromise in accuracy. We proposed a new method to model FD as heterogeneous and anisotropic porous medium whose properties were determined from local porosity. The new method was validated by comparing with PIV measurement from an in-vitro phantom. Simulation result was in good agreement with experimental measurement. Four patient cases were further analyzed to compare the new method with the homogenous porous media method. Results showed that in patient cases with curved artery, new method was preferred over the homogenous method, as the assumption of homogenous porosity led to overpredicted flow reduction effect by as much as 87.9%, which may lead to overoptimistic decision making and poor prognosis. Our new method can provide timely and accurate simulation to aid in the treatment planning of aneurysms., (Copyright © 2021. Published by Elsevier Ltd.)

Since the 5-year survival rate of pancreatic cancer is only 10.0%, new therapies are urgently needed. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis specifically on tumor cells, nevertheless its clinical application was seriously restricted by resistance and short in vivo half-life. Herein, a novel multifunctional R6ST protein equipped with cell penetrating peptides R6, intrinsic apoptosis inducing tetrapeptide AVPI and soluble TRAIL was designed and constructed. Then, it was recruited to prepare self-sustained nanoplatform (SSN) to reverse TRAIL-resistance of pancreatic cancer through simultaneously promoting extrinsic and intrinsic apoptotic pathway, as well to elongate circulation time. Once administrated, high tumor accumulation and cellular uptake of SSN were achieved through prolonged circulation time, targeting ability of soluble TRAIL to death receptors and positive-charged R6, and further enhanced through reversed upregulation of death receptors on TRAIL-resistant tumor cells by the cumulated artesunate released in cytoplasm as a positive feedback loop. Furthermore, this loop simultaneously promoted extrinsic apoptosis of TRAIL fragment via the upregulated death receptors on TRAIL-resistant pancreatic cancer cells and intrinsic apoptosis of AVPI tetrapeptide via the efficient accumulation and uptake of R6ST on SSN. Hence, SSN exhibited synergistic antitumor effect and provided a new strategy for TRAIL-resistant pancreatic cancer therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Leflunomide, an immunosuppressive disease-modifying anti-rheumatic drug (DMARD), is widely used in the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PA) as well as multiple sclerosis. However, its role in myasthenia gravis (MG) has not yet been clearly explored. Here, we investigated the effect of leflunomide on experimental autoimmune myasthenia gravis (EAMG) in vivo and in vitro. The results demonstrated that leflunomide alleviated the severity of EAMG associated with reduced serum total anti-acetylcholine receptor (AChR) IgG levels. During the development of EAMG, the increase of follicular helper T cells (Tfh) 1, Tfh 17 cells and decrease of follicular regulatory T cells (Tfr) were reversely altered after leflunomide administration. Our work further found that leflunomide might inhibit Tfh cells through the IL-21/STAT3 pathway to reduce the secretion of antibodies by B cells. In addition, leflunomide rebuilt the balance of Th1/Th2/Th17/Treg subsets. These results suggested that leflunomide ameliorated EAMG severity by regulating humoral immune responses and Th cell profiles thereby providing a novel effective treatment strategy for MG., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: To block transmission of measles, the China Ministry of Health endorsed the "2006-2012 National Measles Elimination Action Plan (NMEAP)" on November 11, 2006, while no published studies used mathematical models to assess the impact of this action. Also, the problem of residuals autocorrelation due to auto-correlated infectious disease data is often ignored in practice., Methods: Based on monthly counts of measles in 31 Chinese provinces during 2004-2016, a spatiotemporal auto-correlated mixed model was developed to assess the intervention effects over 10 years after the NMEAP, after controlling for seasonality and time-varying socioeconomic and meteorological factors. The first-order autoregression dynamic relationship was used to adjust the bias of conditional covariance in Quasi-likelihood function due to temporal autocorrelation and the spatial autoregressive term was used to capture the neighbor effects of adjacent provinces., Results: There were a similar seasonal pattern and spatial differences of measles incidence among provinces, yet the spatiotemporal pattern was diminished after the intervention. The introduction of the NMEAP was associated with a reduction of 51.03% [excess risk (ER%) = -51.03%, 95% CI: -62.32% to -36.37%] in measles morbidity on average during the 10-year intervention period. The intervention effect varied with time. The significant effect was observed 15 months after the intervention onset, and then gradually increased to a stable level, but was weakened slightly after 2012. The effect of birth rate and meteorological factors on measles morbidity reduced after the NMEAP., Conclusions: There was clear evidence that prominent progress towards a goal of measles elimination had been achieved after the intervention, while the resurgence after 2012 indicated the goal for measles elimination by 2012 had not been reached., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A novel sulfidogenic acid mine drainage (AMD) treatment system with a sulfur reduction process was developed. During the 220-d operation, >99.9% of 380-mg/L ferric, 150-mg/L aluminum, 110-mg/L zinc, 20-mg/L copper and 2.5-mg/L lead ions, and 42.6-44.4% of 100-mg/L manganese ions in the synthetic AMD were step-by-step removed in the developed system with three pre-posed metal precipitators and a sulfur reduction reactor. Among them, zinc, copper and lead ions were removed by the biogenic hydrogen sulfide that produced through elemental sulfur reduction; while ferric, aluminum and manganese ions were removed by the alkali precipitation. Compared with the reported sulfate reduction reactors, the sulfur reduction reactor significantly reduced the chemical cost by 25.6-78.9% for sulfide production, and maintained a high sulfide production rate (1.12 g S 2- /L-d). The pH level in the sulfidogenic reactor driven by sulfur-reducing bacteria posed a significant effect on the sulfide production rate. Under a nearly neutral condition (pH 7.0-7.5), elemental sulfur dissolved into polysulfide to increase the bioavailability of S 0 . At acidic conditions (pH < 6.0), polysulfide formation was limited and sulfate reduction became dominant. Therefore, maintaining the sulfidogenic reactor driven by sulfur-reducing bacteria at neutral condition is essential to realize high-rate and low-cost AMD treatment. Moreover, the escape of residual hydrogen sulfide from the system was eliminated by employing a 17% recirculation from effluent to the sulfidogenic reactor., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Members of the genus Rhodiola L. have been widely used in Tibetan medicines for preventing and treating acute mountain sickness (AMS) for a long time. However, the pharmacological mechanisms of these medicines in treating AMS remain unclear. To address this problem, an integrative method combining ultra-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS)analysis and network pharmacology was employed. First, the chemical profiles of Dazhu Hongjingtian (DZ, a Chinese medicine preparation composed of R. kirilowii (Regel) Maxim) were identified or tentatively characterized. Second, the targets of DZ were predicted using the SwissTargetPrediction and STITCH databases; the targets of AMS were also collected from the Drugbank and TTD databases. Then, networks between targets and compounds or diseases were constructed by Cytoscape 3.6.1. Third, GO and pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 40 ingredients of 53 compounds in DZ might be biologically active. These activities were related to the regulatory effects of the ingredients on 68 significant signaling pathways, such as the inflammation pathway, apoptosis pathway, HIF-1 signaling pathway, and others, by targeting 33 proteins, including PTGS2 and PTGS1, ALOX5 and ALOX15, BCL2 and BCL2L1, the protein kinase C (PKC) family and HIF1A, among others., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The risk of cardiovascular events in patients with chronic kidney disease is tremendously increased due to vascular calcification. Local vascular inflammation significantly promotes vascular calcification. A previous study has shown that puerarin inhibits calcification of mouse vascular smooth muscle cells (VSMCs) in vitro, but whether puerarin can inhibit vascular calcification in vivo and the underlying mechanisms remain unclear. In this study, we found that rat VSMCs treated with calcifying medium showed more mineral deposition, and this effect was inhibited by puerarin in a dose-dependent manner, as detected by alizarin red staining and calcium content assay. Puerarin also prevented the trans-differentiation of VSMCs into osteoblast-like cells, indicated by down-regulation of bone-related genes including Runx2 and BMP2. In vivo study of uremic rats induced by renal nephrectomy further confirmed the inhibitory effect of puerarin on vascular calcification in uremic rats. Puerarin treatment significantly prevented mineral deposition in rat aortas and down-regulated the expression of Runx2 and BMP2. Furthermore, we detected the levels of pro-inflammatory cytokines including IL-1β, IL-6, IL-18 and TNFα in vitro and in vivo. The levels of IL-1β were remarkably increased in both calcified VSMCs and aortas of uremic rats, while puerarin treatment markedly decreased the expression of IL-1β. In addition, we found that puerarin reduced IL-1β possibly through targeting NLRP3/Caspase1/IL-1β and NF-κB signaling pathways and inhibiting the generation of reactive oxygen species. Taken together, we demonstrated that puerarin has the capability of inhibiting vascular calcification in uremic rats by inhibiting inflammation., (Copyright © 2019. Published by Elsevier B.V.)

To overcome irradiation-dependence of cancer phototherapy, a near infrared aza-BODIPY-based photothermogenic photosensitizer BDY with 2-Pyridone group has been synthesized for imaging-guided photothermal synergistic sustainable photodynamic therapy. Multifunctional water-soluble BDY nanoparticles (NPs), with high photothermal conversion efficiency of 35.7% and excellent singlet oxygen ( 1 O 2 ) generation ability, are prepared by self-assembling. The reversible transformation between 2-pyridone moiety and its endoperoxide form endows BDY with continuous 1 O 2 generation ability under illumination and non-illumination conditions. Simultaneously, BDY NPs exhibit excellent tumor targeting properties by enhanced permeability and retention (EPR) effect and photoacoustic imaging (PAI) ability. Furthermore, the photothermal assisted sustainable photodynamic therapy can significantly inhibit tumor growth (93.4% inhibition) with almost no side effects by intermittent laser illumination. The finding highlights that this photothermal synergistic sustainable phototherapy presents great potential for clinical applications., (Copyright © 2018. Published by Elsevier Ltd.)

Ultrasmall Cu 2 ZnSnS 4 (CZTS) nanocrystals with high near infrared (NIR) photothermal conversion abilities and peroxidase-mimic properties are synthesized and functionalized with bovine serum albumin (BSA) for rapid clearance multifunctional theranostic platform. Due to the presence of Cu (I) of CZTS@BSA, H 2 O 2 could be decomposed to produce highly reactive oxygen species (ROS), catalyzed by intrinsic peroxidase like activity of CZTS. The CZTS@BSA possesses high NIR absorption and excellent photoacoustic (PA) imaging abilities. The as-prepared CZTS@BSA is also reported as an efficient T1 contrast agent for in vivo MR imaging. Therefore, in vivo distribution and rapid renal clearance of CZTS@BSA are successfully tracked by PA/MR dual-modal-imaging and further proved by ICP-MS analysis. Systemic acute toxicity evaluation indicates CZTS@BSA have good biocompatibility to normal tissues and blood. All results reveal that CZTS@BSA could act as a rapid clearance theranostic nanoplatform for dual-modal-imaging guided tumor PTT., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Hemodynamics has been recognized as an important factor in the development, growth, and rupture of cerebral aneurysms, and investigated by computational fluid dynamics techniques using a single phase approach. However, flow-dependent cell transport and interactions are usually ignored in single phase models, in which blood is usually treated as a single phase Newtonian fluid. For getting better insight into the underlying pathology of intracranial aneurysm, cell transport and interactions should be covered in hemodynamic studies. In the present study, a multiphase hemodynamic model incorporating cell transport and interactions was developed, in which blood was modeled as multiphase fluid having a continuous phase (plasma) and two particulate phases (erythrocytes and leukocytes). The model showed good agreement with experimental data and observations in the literature, and was applied to four patient-specific aneurysms in a pulsatile manner. Leukocyte accumulations were predicted at locations with flow disturbance and low wall shear stress. The concentrations of leukocyte at accumulation sites were found to exceed 200 to 500% of normal physiological level on three unstable aneurysms, including two ruptured aneurysms and a growing aneurysm where accumulation was observed near a daughter sac and a secondary aneurysm. This suggested that aneurysms with complex secondary flow patterns could be prone to leukocyte accumulation on the wall. As this is the first study to characterize cell transport and interactions in aneurysm hemodynamics, our model can serve as a foundation for future intracranial aneurysm models., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Chlamydia abortus (C. abortus) is an obligate intracellular pathogen that causes abortion in pigs and poses a zoonotic risk in pregnant women. Although attenuated and inactivated vaccines are available, they do not provide complete protection in animals underlining the need to develop new vaccines. In this study, we tested the hypothesis that intramuscular immunization with an ompA-based phage-mediated DNA chlamydial vaccine candidate will induce significant antigen-specific cellular and humoral immune responses. Thus, groups of piglets (five per group) were immunized intramuscularly with the phage-MOMP vaccine (λ-MOMP) or a commercial live-attenuated vaccine (1B vaccine) or a GFP-expressing phage (λ-GFP) or phosphate buffered saline (PBS) (control) and antigen-specific cell-mediated and humoral immune responses were evaluated. By day 63 post-immunization, the λ-MOMP vaccine elicited significantly higher (P<0.05) levels of antigen-specific serum IgG antibody responses than the 1B vaccine or control did. Also, piglets immunized with λ-MOMP vaccine had significantly higher (P<0.05) MOMP-specific lymphocyte proliferative responses compared to those immunized with the 1B vaccine or control. Furthermore, the total T-cell numbers (CD3+) and the proportion of CD4+ and CD8+ T-cell subsets as well as the ratio of CD4+/CD8+ T cells elicited following immunization were comparable between the λ-MOMP- and 1B-vaccinated animals on both days 63 and 70. Interestingly, although the proportion of CD3+CD4-CD8- double negative T cells on day 63 was significantly higher (P<0.05) in the 1B vaccine group compared to the λ-MOMP-immunized group, there was a significant decrease in the proportion of this T-cell population on day 70 in the 1B compared to the λ-MOMP vaccinated group. These results indicate that the λ-MOMP DNA vaccine is capable of inducing antigen-specific cellular and humoral immune responses that may provide protective immunity against a live challenge infection with C. abortus., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Apolipoprotein E (apoE) is an important plasma protein in cholesterol homeostasis and plays a key role in the pathogenesis of glomerulosclerosis (GS). Gelatinases include matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). The abnormal expressions of gelatinases are implicated in the pathogenesis of extracellular matrix accumulation. All-trans retinoic acid (ATRA) is an import biological agent which can play a protective role against GS. We performed this investigation to explore whether ATRA could regulate the expressions of gelatinases and apoE in the glomerulus of GS rats. 120 Wistar rats were randomly divided into three groups: sham operation group (SHO), glomerulosclerosis model group without treatment (GS) and GS model group treated with ATRA (GA). The GS disease was established by uninephrectomy and adriamycin injection. At the end of 9 and 13 weeks, the relevant samples were collected and determined. Compared with GS group at 9/13 weeks, values of 24-hour urine total protein, 24-hour urine excretion for albumin, blood urea nitrogen, serum creatinine and glomerulosclerosis index, and protein expressions of apoE, transforming growth factor-βl (TGF-β1), α-smooth muscle actin, collagen-IV and fibronectin in glomerulus and mRNA expressions of apoE and TGF-β1 in renal tissue were significantly down-regulated by ATRA (each P<0.01). However, the expressions of MMP-2 and MMP-9 (mRNA, protein and activity) were enhanced in GA group than those in GS group. In conclusion, gelatinases are associated with apoE expression, and ATRA can increase the gelatinases expressions and reduce the accumulation of apoE in glomerulus of GS rats, but the detailed mechanism needs to be elucidated in the future., (Copyright © 2011 Elsevier Inc. All rights reserved.)