Search

Statin induced myopathy (SIM) is a main deleterious effect leading to the poor treatment compliance, while the preventive or therapeutic treatments are absent. Mounting evidences demonstrated that vitamin D plays a vital role in muscle as a direct modulator. The deficiency of vitamin D was considered as a cause of muscle dysfunction, whereas the supplementation resulted in a remission. However, there is no causal proof that vitamin D supplementation rescues SIM. Here, using the mice model of simvastatin-induced myopathy, we investigated the role of vitamin D supplementation and the mechanisms associated with mitochondria. Results indicated that simvastatin administration (80 mg/kg) impaired skeletal muscle with the increased serum creatine kinase (CK) level and the declined grip strength, which were alleviated by vitamin D supplementation. Moreover, vitamin D supplementation rescued the energy metabolism dysfunction in simvastatin-treated mice gastrocnemius by reducing the abnormal aggregation of muscular glycogen and lactic acid. Mitochondrial homeostasis plays a key role in the process of energy metabolism. Thus, the mitochondrial dysfunction is a mortal damage for the highly energy-requiring tissue. In our study, the mitochondrial cristae observed under transmission electron microscope (TEM) were lytic in simvastatin-treated gastrocnemius. Interestingly, vitamin D supplementation improved the mitochondrial cristae shape by regulating the expression of mitofusin-1/2 (MFN1/2), optic atrophy 1 (OPA1) and dynamin-related protein 1 (Drp1). As expected, the mitochondrial dysfunction and oxidative stress was mitigated by vitamin D supplementation. In conclusion, these findings suggested that moderate vitamin D supplementation rescued simvastatin induced myopathy via improving the mitochondrial cristae shape and function. • Vitamin D supplementation rescued simvastatin induced myopathy in mice. • Vitamin D supplementation improved the mitochondrial cristae shape. • Vitamin D supplementation mitigated mitochondrial dysfunction and oxidative stress in simvastatin-treated gastrocnemius. [ABSTRACT FROM AUTHOR]

• NO was reduced to N 2 by a integrated chemical- and biological- system. • Efficient regeneration of Fe(II)EDTA by sponge iron. • Part of NO reduced to NH 4 + by sponge iron and the consumption of exogenous NH 4 + decreased. • Anammox and NAFO played an important role in this system. Integrated Fe(II)EDTA absorption and anaerobic ammonia oxidation process can remove NO from flue gas, but Fe(II)EDTA was easily oxidized to Fe(III)EDTA which is not capable of binding NO. Regeneration of Fe(II)EDTA is the key to this process. A novel autotrophic up-flow bioreactor with sponge iron bed was developed. During 80-day continuous operation of the reactor, NO was almost completely reduced to N 2 with the average removal rate of 7.57 mM/d, and N 2 O in the off gas was lower than the limit of detection. Since part of NO was chemically reduced to NH 4 + by sponge iron, the ratio of NO-N removal to NH 4 +-N consumption was up to 5. Sponge iron worked excellently on in-situ regeneration of Fe(II)EDTA, and the average loss rate of Fe2+ was only 0.190 mM/d. Results of microbial community structure analysis showed that the microbial community diversity decreased gradually as the reactor running. The relative abundance of Candidatus Kuenenia, the dominant anammox genus in seed sludge, changed from 4.48% to 0.78%. The formation of a symbiotic system, in which AnAOB and denitrification bacteria dominated, showed that anammox and nitrate-dependent anaerobic ferrous oxidation (NAFO) played an important role in the biological process of NO reduction. The autotrophic up-flow bioreactor with sponge iron bed can provide a potential process for NO removal from flue gas. [ABSTRACT FROM AUTHOR]

In this paper, we study a class of (ω , c) -periodic time varying impulsive differential equations and establish the existence and uniqueness results for (ω , c) -periodic solutions of homogeneous problem as well as nonhomogeneous problem. [ABSTRACT FROM AUTHOR]

Problem: The role of the long non‐coding RNA (lncRNA) actin filament associated protein 1 antisense RNA1 (AFAP1‐AS1) in the etiology of endometriosis is unknown. Method of Study: Expression of epithelial‐mesenchymal transition (EMT) markers was quantified using qRT‐PCR, immunohistochemistry, and Western blotting. The proliferation, migration, and invasion of ectopic endometrial epithelial cells and Ishikawa cells were evaluated by MTT, EdU, wound healing, and transwell assays. Inflammatory cytokine levels were detected by ELISA. Luciferase assays were used to measure activity of the ZEB1 promoter site pGL3‐P886. Results: AFAP1‐AS1 levels were much higher in ectopic endometrial tissues than that in eutopic tissues. Expression of ZEB1, E‐cadherin, and keratin was obviously higher in eutopic tissues than those in ectopic tissues. In contrast, expression of vimentin and N‐cadherin was significantly lower in eutopic tissue than those in ectopic tissues. After knockdown of AFAP1‐AS1, the morphology of endometrial epithelial cells varied from spindle fiber shaped to polygon epithelioid and proliferation, migration, and invasion were each inhibited. The knockdown of AFAP1‐AS1 significantly inhibited expression from promoter site pGL3‐P886 of the EMT‐related transcription factor ZEB1. The size of subcutaneous tumours in nude mice was significantly reduced after down‐regulation of AFAP1‐AS1 expression. Conclusion: Higher expression of AFAP1‐AS1 positively correlated with greater EMT in ectopic endometrium of patients with endometriosis. Knockdown of AFAP1‐AS1 inhibited E2‐induced activity of promoter site pGL3‐P886 of transcription factor ZTB1, suggesting that AFAP1‐AS1 knockdown inhibited growth of endometrial epithelial cells and that pathogenesis may be correlated with EMT. [ABSTRACT FROM AUTHOR]

Tea is one of the most popular non-alcoholic beverages, while tea plant is also an important cash crop in the world. Somatic embryogenesis (SE) is a powerful tool for producing large scale vegetative propagation, but the unestablished SE regeneration system greatly impedes the mass production of tea seedlings, and thereby affecting the development of tea industry. In this study, we established a high-efficiency direct SE system in tea including somatic embryo initiation, maturation and germination. Somatic embryo initiation was affected by tea cultivars, explant age and plant growth regulator. Cotyledons of tea seeds at 270 days after flowering had the highest globular embryos induction efficiency as explant. Somatic embryos were induced well in embryos initiation medium adding 1 mg/L NAA and 0.5 mg/L 6-BA. The optimum induction rate from globular embryos to cotyledonary embryos was 12.62 ± 1.57%, when the globular embryos was transferred to the hormone-free medium supplemented with 2 g/L activated carbon. Mature embryos germinated to produce plantlet on MS medium with 1 mg/L 6-BA and 0.1 mg/L NAA with a generation frequency of 20.2 ± 0.1%. In addition, six SE-related genes were identified, and the expression level of these genes during the SE of tea were analyzed by quantitative real-time RT-PCR (qRT-PCR). These genes showed higher expression level in the initiation embryo stage than maturated embryo stage, which deduced that these genes are crucial during the initiation of SE in tea. Taken together, the establishment of a direct SE regeneration system for tea plant would confer to large-scale propagation and genetic improvement of tea plant as well as studies about SE-related genes would lay the foundation for further clarifying the molecular mechanism of SE in tea plant. [Display omitted] • A stable and high-efficiency direct somatic embryogenesis regeneration system was established in tea plant. • The somatic embryogenesis efficiency of tea plant is greatly influenced by explant age, genotypes and the composition of culture medium. • Regeneration plantlets of tea plant via direct somatic embryogenesis system can be achieved after approximately 7 months. • Some key genes related to somatic embryogenesis presented higher expression levels at the early stage of somatic embryogenesis. [ABSTRACT FROM AUTHOR]

Highly dense CaCu 3 Ti 4 O 12 (CCTO) ceramics co-doped by ZnO and Al 2 O 3 were synthesized by spark plasma sintering (SPS) at 750 °C for 10 min, and then annealed at 1000 °C for 3 h. The homogeneous microstructures were achieved, and the grain size was suppressed to around 2 μm. Dramatically enhanced electrical properties of CCTO ceramics were obtained when 1 mol% ZnO and Al 2 O 3 were co-doped. The breakdown field was improved to 12.13 kV/cm and the nonlinear coefficient was increased to 6.59, accompanying with a low dielectric loss of 0.02 at around 1 kHz, which were ascribed to the elevation of Schottky barrier height from 0.54 eV to 0.80 eV. Comparing with the pure CCTO sample, the activation energy of grain boundary obtained from the impedance spectra increases from 0.64 eV to 0.92 eV. Additionally, the grain and grain boundary resistance were also discussed based on the Cole-Cole plot, from which the grain boundary resistance was found to be increased significantly from 3.8 × 105 Ω to 4.0 × 106 Ω after co-doping. • Homogenous microstructures of CCTO were obtained by SPS. • Dramatically improved breakdown field of ∼12 kV/cm and dielectric loss of ∼0.02 were achieved by co-doping Zn, Al. • The schottky barrier height of grain boundary was elevated from 0.54 eV to 0.80 eV. • Correlation between grain boundary activation energy and schottky barrier height was proposed. [ABSTRACT FROM AUTHOR]

Lithium-sulfur (Li-S) batteries are highly regarded as leading contenders to traditional lithium-ion batteries owing to their impressive energy density and low cost. Unfortunately, the serious issues such as shuttle effect of polysulfides and lithium dendrite growth hinder the practical application of Li-S batteries. Our previous investigation has demonstrated that natural protein exhibits considerable capability in improving of Li-S battery performance. Herein, zein (corn protein) and polyvinylidene fluoride-co-hexafluoropropylene (PVDF) are combined to create an interpenetrating structure (zein@PVDF) that works as an interlayer on a commercial separator. The results indicate that the zein@PVDF interlayer effectively enhances thermal stability, wettability, and polysulfide-trapping capability of the separator. Consequently, Li-S batteries equipped with the zein@PVDF-modified separator exhibit enhanced rate performance and extended cycle life. In particular, after 500 cycles, the battery with zein@PVDF-modified separator demonstrates a higher capacity retention rate (∼450 mAh g−1, ∼62 %) in comparison with that of Li-S cells with the commercial separator (∼150 mAh g−1, 16 %). This work provides a new pathway in the design of effective modifications of the separator for improving of performance Li-S batteries. [Display omitted] • An interlayer with an interpenetrating structure of zein and a polar polymer. • The modified separator is created on a commercial separator. • The separator shows enhanced thermal stability and wettability. • The separator effectively traps polysulfides and enhances Li + transport. • The Li-S battery with the separator shows improved capacity and cycling stability. [ABSTRACT FROM AUTHOR]

Polymer-based dielectric films with excellent physicochemical and electrical properties are widely designed for energy storage applications of electrostatic capacitors. In this work, the energy storage capabilities of the poly(vinylidene fluoride-co-hexafluoropropylene)/boron nitride nanosheets (P(VDF-HFP)/BNNSs) composites were manipulated via a self-made nanosecond electric pulse (nsEP) assisted solution-casting platform. The nsEP induces dipole interactions and dielectrophoretic forces, achieving a high horizontal orientation degree (∼78 %) of BNNSs within the composite. Experimental and simulation results demonstrate that this reorientation of BNNSs alleviates electric field distortion at the BNNSs/polymer matrix interface, suppresses the electron propagation path, and significantly improves dielectric properties, breakdown field, and energy density. Specifically, under the nsEP of 80 V/mm, the P(VDF-HFP)/BNNSs composite presents an elevated breakdown field of 521 MV/m and an improved energy density of 10.3 J/cm3, which are 9.5 % and 40.1 % enhancement in comparison to the untreated samples. This work introduces an innovative approach to fabricate P(VDF-HFP)/BNNSs composites, and provides a new route on the improvement of high-energy-density PVDF-based films. [Display omitted] • Nanosecond electric pulse was employed for P(VDF-HFP)/BNNSs composite fabrication. • Horizontal orientation degree of BNNSs in P(VDF-HFP)/BNNSs composites reaches 78 %. • Breakdown field of P(VDF-HFP)/BNNSs was boosted by 9.5 % after nsEP treatment. • Energy density of P(VDF-HFP)/BNNSs was enhanced by 40.1 % after using 80 V/mm nsEP. [ABSTRACT FROM AUTHOR]

• Eight urea-electricity-heat-cooling multi-generation systems are proposed. • Energy, exergy, economic, and environmental performance are comparative analyzed. • The optimal system is based on the chemical looping ammonia generation process. • The lowest emission of 0.013 tons of carbon dioxide per ton of urea synthesis is achieved. The Haber-Bosch process for urea production is known for its significant carbon emissions. While the chemical looping ammonia generation method presents a potential alternative, its technical and economic feasibility still requires further investigation. This paper conducts a comparative analysis of eight renewable energy-driven urea-electricity-heat-cooling multi-generation systems by developing their energy, exergy, economic, and environmental evaluation models. Considering the fluctuation in renewable energy resources, an annual evaluation of the different systems is conducted based on a monthly time scale. The results indicate that systems based on the Haber-Bosch process have higher average energy and exergy efficiencies of 60–80 % and 40–50 %, respectively. For the chemical looping ammonia generation process, the respective efficiencies are 50–70 % and 30–40 %. Additionally, the system integrating the Haber-Bosch reaction, reduction reactor, and solid oxide fuel cell yields the highest energy and exergy efficiencies among the eight systems, at 68.2 % and 45.78 %, respectively. However, it is inferior to the multi-generation system integrating the chemical looping ammonia generation process in terms of economic and environmental performance. In addition, the system integrating the chemical looping ammonia generation process and solid oxide fuel cell has the shortest discounted payback period of 8 years, with annual revenue and net present value of 32.63 and 11.66 MUSD, respectively. While the operating expenditures of the Haber-Bosch (12.6–15.7 MUSD) are lower than those of the chemical looping ammonia generation process (14.0–17.5 MUSD), its capital expenditures (382.0–410.8 MUSD) are significantly higher than those of the chemical looping ammonia generation process (302.4–307.3 MUSD). Furthermore, the conducted environmental evaluation shows that the multi-generation system integrating the chemical looping ammonia generation process and reduction reactor exhibits lower overall carbon emissions (0.013 t CO 2 /t urea) compared to the state-of-the-art method of oxy-fuel coal-fired power plant for urea synthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] • An pioneering work to exploit metal-phenolic network complexes as a novel type of bio-fillers. • A new platform to design advanced immunomodulatory biocomposites with additional multifunctions. • Effects of tannic acid/Mg2+ modified scaffold on immune response and osteogensis in vivo. • An innovative strategy to combine immunomodulatory, antibacterial, or osteogenic functions for scaffolds. Here, we exploited the potential applications of metal-phenolic networks (MPNs) as a novel type of filler for next-generation multi-functional immunomodulatory biocomposites. Tannic acid (TA) and Mg2+ were selected as the model phenolic ligand and metal ion, respectively, and used to assemble MPN particles, and a TA-Mg/polycaprolactone (PCL) composite nanofibrous scaffold was then prepared by blending electrospinning. Measurements of the resultant composite scaffold verified strong hydrogen-bonding interactions between TA motifs and PCL chains and the good dispersity of MPN particles throughout the substrate. Due to the pH-responsive disassembly kinetics of MPN complexes, both TA and Mg2+ displayed pH-responsive sustained release behaviour, thus eliciting significant biological effects. Specifically, TA and Mg2+ synergistically generated an anti-inflammatory micro-environment, which was beneficial for osteogenesis, and Mg2+ directly stimulated the osteogenic differentiation of stem cells. Consequently, the composite membrane significantly enhanced in vivo osteogenic performance when used as a barrier membrane to guide bone tissue regeneration. One unique advantage of this filler is that it combines the functions of both metal ions and phenolic ligands. By selecting different phenolic ligands and metal ions, a series of novel MPN-based fillers with unique functions could be easily obtained, suggesting that this system has a wide range of potential applications for next-generation multi-functional biocomposites. [ABSTRACT FROM AUTHOR]

Despite the progress made with the recent clinical use of the anticancer compound cabazitaxel, the efficacy in patients remains unsatisfactory, largely due to the high in vivo toxicity of the agent. Therefore, strategies that achieve favorable outcomes and good safety profiles will greatly expand the repertoire of this potent agent. Here, we propose a combinatorial strategy to reform the cabazitaxel agent and the use of sequential supramolecular nanoassembly with liposomal compositions to assemble a prodrug-formulated liposome, termed lipoprodrug, for safe and effective drug delivery. Reconstructing cabazitaxel with a polyunsaturated fatty acid (i.e. , docosahexaenoic acid) via a hydrolyzable ester bond confers the generated prodrug with the ability to be readily integrated into the lipid bilayer of liposomes for systemic administration. The resulting lipoprodrug scaffold showed significantly sustained drug release profiles and improved pharmacokinetics in rats as well as a reduction in systemic toxicity in vivo. Notably, the lipoprodrug outperformed free cabazitaxel in terms of in vivo therapeutic efficacy in multiple separate tumor xenograft-bearing mouse models, one of which was a patient-derived xenograft model. Surprisingly, the lipoprodrug was able to reduce tumor invasiveness and reprogram the tumor immunosuppressive microenvironment by proinflammatory macrophage polarization. Our findings validate this lipoprodrug approach as a simple yet effective strategy for transforming the highly toxic cabazitaxel agent into an efficacious nanomedicine with excellent in vivo tolerability. This approach could also be applied to rescue other drugs or drug candidates that have failed in clinical trials due to poor pharmacokinetic properties or unacceptable toxicity in patients. Image 1 • PUFAylation of anticancer cabazitaxel drug facilitated the incorporation of the drug into liposomal formulation. • The liposomal prodrug (termed lipoprodrug) was established for the drug optimization. • Lipoprodrug scaffold showed sustained drug release profiles in vitro and improved pharmacokinetics in vivo. • Lipoprodrug potentiated the efficacy of cabazitaxel in multiple mice models, including a patient-derived xenograft model. • Lipoprodrug remarkably alleviated the toxicity with a high safety margin relative to cabazitaxel in animals. [ABSTRACT FROM AUTHOR]

What is the expression pattern of microRNA (miRNA) in exosomes isolated from eutopic endometrial stromal cells (EuESC) of women with endometriosis-associated infertility? Small RNA sequencing was conducted in exosomes isolated from EuESC of women with endometriosis-associated infertility (n = 3) and normal endometrial stromal cells (NESC) of fertile women without endometriosis (n = 3). The differentially expressed miRNA in exosomes derived from EuESC and NESC were identified. The functions of the differentially expressed miRNA were analysed by gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Small RNA sequencing showed that the percentages of exosomal miRNA in the total small RNA isolated from EuESC and NESC were not significantly different (P = 0.7804). A total of 49 differentially expressed miRNA (fold change >1.5 and P < 0.05) were identified, including 26 up-regulated and 23 down-regulated in EuESC exosomes as compared with NESC exosomes. Functional analysis revealed that 12 miRNA were predicted to target homeobox A10 (HOXA10) and/or the leukaemia inhibitory factor (LIF) 3' untranslated region (UTR). Both HOXA10 and LIF mRNA expression levels were significantly decreased in EuESC compared with NESC (P = 0.0222 and 0.0395, respectively). In addition, the predicated target genes of these differentially expressed exosomal miRNA were significantly (P < 0.05) enriched in 76 pathways, including the MAPK and Wnt signalling pathways. The differential expression patterns of exosomal miRNA were identified. Many exosomal miRNA may be involved in regulating the endometrial receptivity of women with endometriosis-associated infertility. [ABSTRACT FROM AUTHOR]

ZnO varistor ceramics are synthesized by spark plasma sintering (SPS), and then annealed in a conventional furnace in air atmosphere. Dense microstructure with more than 98% of theoretical density is achieved, and homogenous ZnO grains with typical second phases such as Zn 7 Sb 2 O 12 spinel, Zn 2 Bi 3 Sb 3 O 14 pyrochlore are observed from X-ray diffraction spectra (XRD) and scanning electron microscopy (SEM). In addition, a metallic Bi phase is also observed, which is resulted from the reduction of Bi 2 O 3 because of inherent low oxygen partial pressure of SPS, and it can be reoxidized after a post-annealing process. The breakdown field of the optimum ZnO varistor ceramic is 725 V/mm with a nonlinear coefficient of 53.5, which stems from its high Schottky barrier height of 0.60 eV. In analysis of dielectric spectra from 173 K to 293 K, two relaxation peaks with activation energy of 0.22 eV and 0.48–0.54 eV can be observed, which are attributed to the intrinsic zinc interstitial and defect of grain boundary or intergranular phase, respectively. The grain boundary resistances are discussed according to Cole-Cole plot, from which the activation energy controlling resistance at the grain boundary is determined to be 0.87 eV. [ABSTRACT FROM AUTHOR]

Modern electronics and electrical systems demand efficient operation of dielectric polymer‐based capacitors at high electric fields and elevated temperatures. Here, polyimide (PI) dielectric composites prepared from in situ polymerization in the presence of inorganic nanofillers are reported. The systematic manipulation of the dielectric constant and bandgap of the inorganic fillers, including Al2O3, HfO2, TiO2, and boron nitride nanosheets, reveals the dominant role of the bandgap of the fillers in determining and improving the high‐temperature capacitive performance of the polymer composites, which is very different from the design principle of the dielectric polymer composites operating at ambient temperature. The Al2O3‐ and HfO2‐based PI composites with concomitantly large bandgap and moderate dielectric constants exhibit substantial improvement in the breakdown strength, discharged energy density, and charge–discharge efficiency when compared to the state‐of‐the‐art dielectric polymers. The work provides a design paradigm for high‐performance dielectric polymer nanocomposites for electrical energy storage at elevated temperatures. [ABSTRACT FROM AUTHOR]

Environmentally-friendly polymers which can be recycled and reused at the end of life are urgently needed for the development of advanced high-voltage direct current (HVDC) systems. Polymer nanocomposites have attracted considerable attention owing to their unique features arising from synergistic combination of inorganic fillers and polymer matrices. Here we describe thermoplastic poly(ether imide) (PEI) nanocomposites that contain boron nitride nanosheets (BNNSs). It is found that the polymer nanocomposites exhibit simultaneous improvements in multiple physical properties, such as the DC electrical breakdown strength, volume resistivity, mechanical strength and thermal stability, along with substantial reduction in loss tangent, compared with neat PEI. A great improvement in thermal conductivity has been attributed to the presence of BNNSs in the composites, which improves heat dissipation in comparison with neat polymers. The composite approach provides a promising solution for alleviating temperature-gradient distribution and addressing heat accumulation issues in HVDC equipment, and enables broader applications of insulation materials in HVDC systems operated under high voltages. [ABSTRACT FROM AUTHOR]

Abstract It is of crucial importance to develop novel dielectric materials with high discharge energy densities to meet the urgent requirements in the rapid advances in modern electronics and electrical power systems. In this work, we describe a new class of sandwich-structured ceramic-polymer nanocomposites base on poly(vinylidene fluoride- co -hexafluoropropylene) exhibiting outstanding energy storage performance. The central layer of the composite consists of MgO nanowires to offer high breakdown strength, whereas the outer layers contain BaTiO 3 nanofibers to provide improved dielectric constant of the composites. The systematic investigation gave the composites with 2 wt% MgO in the central layer and 20 wt% BaTiO 3 in the outer layers to yield the best energy density of 15.55 J cm−3 with a charge-discharge efficiency of 68% at the Weibull breakdown strength of 416 MV m−1. It is found that the trilayered nanocomposite exhibits superior energy storage performance as compared to the corresponding single-layered composite films. The result demonstrates the uniqueness of the layered structure to incorporate multiple inorganic components into polymer with enhanced collective properties for energy applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Polyoxypropylene surfactant was used to prepare nanoemulsions using the phase inversion composition (PIC) method. • Polyoxypropylene surfactant are more effective than conventional surfactant in nanoemulsion formation by the PIC method. • The obtained nanoemulsions will be an important candidate for the application in enhanced oil recovery. Emulsification using phase inversion composition (PIC) was achieved by changing the composition of surfactants at a constant temperature. The method has great potential to scale up applications due to the ease in the formation of nanoemulsions and the relatively low energy involved. Surfactants containing composition-sensitive polyoxyethylene (POE) chains are widely used to prepare nanoemulsions using the PIC method. It is, therefore, anticipated that surfactants containing composition-sensitive polyoxypropylene (POP) chains can also be used to prepare nanoemulsions using the PIC method. The POP surfactant D230-2OA, containing short POP chains, was obtained from the electrostatic interactions between hydrophilic POP diamine (D230) and hydrophobic oleic acid (OA). The synthesized D230-2OA was used as an emulsifier in the preparation of the n -dodecane-in-water nanoemulsion using the PIC method. The effects of D230-2OA concentration, oil-to-surfactant weight ratio, and NaCl concentration on the droplet size of the nanoemulsions was investigated using dynamic light scattering (DLS). The morphology of the nanoemulsion was characterized using cryogenic transmission electron microscopy (cryo-TEM). The wettability of the crude oil–saturated quartz plate before and after treatment with nanoemulsions was obtained using contact angle measurement. A core flooding experiment demonstrated the efficiency of the diluted nanoemulsion in enhanced oil recovery, with an additional recovery of 21.30%. The nanoemulsion prepared with the POP surfactant as the emulsifier using the PIC method has wide application in petroleum recovery. [ABSTRACT FROM AUTHOR]

Advancement of sulfur (S) cathode of lithium-sulfur (Li-S) batteries is hindered by issues such as insulating nature of sulfur, sluggish redox kinetics, polysulfide dissolution and shuttling. To address these issues, we initiate a study on applying an important amino acid of protein, arginine (Arg), as a functional additive into S cathode. Based on our simulation study, the positively charged Arg facilitates strong interactions with polysulfides. The experimental results indicate that the interaction enable capability of trapping polysulfides within the S cathode, responsible for reducing shuttle effects. Furthermore, the positively charged Arg also promotes efficient ion diffusion and polysulfides conversion. The new findings include that, with addition of only 1 wt % Arg, the resultant cathode demonstrates effectively enhanced electrolyte wettability, polysulfide adsorption and redox kinetics, leading to enhanced rate performance and long-term cycling stability. This study highlights the great potential of amino acids being able to act as effective functional bio-additives in S cathode, paving a new way to high-performance and sustainable energy storage solutions., (© 2025 Wiley-VCH GmbH.)

Background: Previous studies have discussed the correlation between mechanical power (MP) and lung injury. However, evidence regarding the relationship between MP and postoperative pulmonary complications (PPCs) in children remains limited, specifically during one-lung ventilation (OLV)., Objectives: Propensity score matching was employed to generate low MP and high MP groups to verify the relationship between MP and PPCs. Multivariable logistic regression was performed to identify risk factors of PPCs in young children undergoing video-assisted thoracic surgery (VATS)., Design: A retrospective study., Setting: Single-site tertiary children's hospital., Patients: Children aged ≤2 years who underwent VATS between January 2018 and February 2023., Interventions: None., Main Outcome Measures: The incidence of PPCs., Results: Overall, 581 (median age, 6 months [interquartile range: 5-9.24 months]) children were enrolled. The median [interquartile range] MP during OLV were 2.17 [1.84 to 2.64) J min-1. One hundred and nine (18.76%) children developed PPCs. MP decreased modestly during the study period (2.63 to 1.99 J min-1; P < 0.0001). In the propensity score matched cohort for MP (221 matched pairs), MP (median MP 2.63 vs. 1.84 J min-1) was not associated with a reduction in PPCs (adjusted odds ratio, 1.43; 95% CI, 0.87 to 2.37; P = 0.16). In the propensity score matched cohort for dynamic components of MP (139 matched pairs), dynamic components (mean 2.848 vs. 4.162 J min-1) was not associated with a reduction in PPCs (adjusted odds ratio, 1.62; 95% CI, 0.85 to 3.10; P  = 0.15).The multiple logistic analysis revealed PPCs within 7 days of surgery were associated with male gender, OLV duration >90 min, less surgeon's experience and lower positive end-expiratory pressure (PEEP) value., Conclusions: MP and dynamic components were not associated with PPCs in young children undergoing VATS, whereas PPCs were associated with male gender, OLV duration >90 min, less surgeon's experience and lower PEEP value., Trial Registration: ChiCTR2300074649., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the European Society of Anaesthesiology and Intensive Care.)

This study aimed to probe if xylooligosaccharide (XOS) could act as an antimetabolite to impact the cell cycle and antibiotic tolerance of avian pathogenic Escherichia coli (APEC). We firstly measured the bacteriostasis of XOS against APEC O78 and its effect on the growth of APEC O78 growing on different medium. Afterwards, the effects of XOS on xylose operon activation along with the cell cycle and antibiotic tolerance of APEC O78 were analyzed. The results showed that XOS caused no inhibitory circle against APEC O78 and did not affect (P > 0.05) the growth of APEC O78 growing on LB medium. Besides, APEC O78 was unable to grow on M9 medium (carbon-free) added with XOS. However, XOS exerted a similar role as xylose in increasing (P < 0.05) the expression of certain xylose operon genes including xylose isomerase (XylA)-encoding gene (xylA) and xylose-binding periplasmic protein (XylF)-encoding gene (xylF) in APEC O78. The molecular docking simulation revealed that the major monomer components (xylobiose, xylotriose and xylotetraose) of XOS had stable binding potentials to both XylA and XylF proteins of E. coli, as supported by the low binding free energy and the formation of considerable hydrogen bonds between them. The subsequent analysis showed that XOS altered certain cell cycle-related genes expression, especially elevated (P < 0.05) nrdB expression and decreased ihfB expression to a degree. Moreover, XOS played a similar role as 2-deoxy-glucose (a glucose analogue serving as a typical antimetabolite) in lowering (P < 0.05) the number of ampicillin-tolerant APEC O78. Collectively, XOS had no direct bacteriostasis against APEC and could not be metabolized/utilized by APEC O78. However, it might become an analogue of xylose and then activate xylose transport- and metabolism-related proteins in APEC O78, thus functioning as a potential antimetabolite and exerting antimetabolic actions. This could at least partially interpret the observed roles of XOS in interfering with the cell cycle and diminishing the antibiotic tolerance of APEC O78. The above findings expand the knowledges about the functions of XOS and provide a basis for exploring novel strategies to reduce the antibiotic tolerance of APEC., Competing Interests: DISCLOSURES 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 Authors. Published by Elsevier Inc. All rights reserved.)

Immuno-oncology has become a revolutionary strategy for cancer treatment. Therapeutic interventions based on adaptive immunity through immune checkpoint therapy or chimeric antigen receptor (CAR) T cells have received clinical approval for monotherapy and combination treatment in various cancers. Although these treatments have achieved clinical successes, only a minority of cancer patients show a response, highlighting the urgent need to discover new therapeutic molecules that could be exploited to improve clinical outcomes and pave the way for the next generation of immunotherapy. Given the critical role of the innate immune system against infection and cancer, substantial efforts have been dedicated to developing novel anticancer therapeutics that target these pathways. Targeting the stimulator of interferon genes (STING) pathway is a powerful strategy to generate a durable antitumor response, and activation of the adaptor protein STING induces the initiation of transcriptional cascades, thereby producing type I interferons, pro-inflammatory cytokines and chemokines. Various STING agonists, including natural or synthetic cyclic dinucleotides (CDNs), have been developed as anticancer therapeutics. However, since most CDNs are confined to intratumoral administration, there has been a great interest in developing non-nucleotide agonists for systemic treatment. Here, we review the current development of STING-activating therapeutics in both preclinical and clinical stages., (© 2024 Wiley-VCH GmbH.)

Objectives: In order to enhance clinical improvement of periodontal defects, the addition of enamel matrix derivatives (EMD) to open flap debridement (OFD) has been investigated. The aim of this systematic review is to figure out whether such a combination, in comparison to the treatment with OFD alone has some effects on the following outcomes: clinical attachment level gain, probing depth reduction, and gingival recessions increase., Methods: Electronic databases (PubMed, Embase, Web of Science, and Cochrane) were searched for randomized controlled trials in humans addressing the use of a combination of OFD and EMD versus a control group with OFD alone for the treatment of periodontal defects, with a minimum of 6 months of follow-up; meta-analysis and trial sequential analysis were then performed., Results: From a total of 204 records screened by title and abstract, 13 studies were read full-text and eight out of them included in the meta-analysis. Some significant differences have been demonstrated both for clinical attachment level gain and probing depth reduction between test and control groups., Conclusions: In the treatment of periodontal defects, the addition of EMD to OFD seems to be beneficial in terms of clinical attachment level gain, probing depth reduction, promoting periodontal regeneration. However, such results should be considered with caution because of the small number of studies included in the meta-analysis and their heterogeneity., (© 2024 Wiley Periodicals LLC.)

To create a healthier indoor environment via sustainable technologies, there is a growing demand for constructing high-performance air filters from natural materials. Addressing this need, we have fabricated high-performance protein air filters with a tailored frame-channel structure via electrospinning. The innovative feature of the protein air filter is generated by adding a small amount of an organic salt, tetrabutylammonium chloride (TBAC), to modulate the denaturation of zein for tuning electrical charge distribution and hydrophilicity of the protein solutions. The results highlight that the optimized filter with 1.0 wt% TBAC exhibits a denser nanofiber assembly on the frame and a sparser arrangement on the channel. Functionally, the filter demonstrates ultralow pressure drop (ca. 9.04 Pa) that is only a third of that observed in unmodified formulation and commercial air filters, while it maintains high filtration efficiency in capturing PM 2.5 (99.42% ± 0.30%) and PM 0.3 (98.25 ± 0.39%). More importantly, the filter indicates multifunctional perspectives, e.g., high removal efficiency for formaldehyde (HCHO) and PM 2.5 under high airflow rates (up to 8 L/min) or after prolonged testing period (120 min). Our design of the frame-channel structure for the protein air filter marks a leap forward in developing biomass-based structural materials.

The immunosuppressive tumor microenvironment (TME) remains a major obstacle to tumor control and causes suboptimal responses to immune checkpoint blockade (ICB) therapy. Thus, developing feasible therapeutic strategies that trigger inflammatory responses in the TME could improve the ICB efficacy. Mitochondria play an essential role in inflammation regulation and tumor immunogenicity induction. Herein, we report the discovery and characterization of a class of small molecules that can recapitulate aqueous self-assembly behavior, specifically target cellular organelles (e.g., mitochondria), and invigorate tumor cell immunogenicity. Mechanistically, this nanoassembly platform dynamically rewires mitochondria, induces endoplasmic reticulum stress, and causes apoptosis/paraptosis-associated immunogenic cell death. After treatment, stressed and dying tumor cells can act as prophylactic or therapeutic cancer vaccines. In preclinical mouse models of cancers with intrinsic or acquired resistance to PD-1 blockade, the local administration of nanoassemblies inflames the immunologically silent TME and synergizes with ICB therapy, generating potent antitumor immunity. This chemically programmed small-molecule immune enhancer acts distinctly from regular cytotoxic therapeutics and offers a promising strategy for synchronous and dynamic tailoring of innate immunity to achieve traceless cancer therapy and overcome immunosuppression in cancers., (© 2024. The Author(s).)

Aims: To investigate whether gamma-aminobutyric acid (GABA) supplementation improves insulin resistance during olanzapine treatment in mice and to explore the underlying mechanisms., Materials and Methods: Insulin resistance and body weight gain were induced in mice by 10 weeks of olanzapine treatment. Simultaneously, the mice were administered GABA after 4 weeks of olanzapine administration., Results: We found that mice treated with olanzapine had lower GABA levels in serum and subcutaneous white adipose tissue (sWAT). GABA supplementation restored GABA levels and improved olanzapine-induced lipid metabolism disorders and insulin resistance. Chronic inflammation in adipose tissue is one of the main contributors to insulin resistance. We found that GABA supplementation inhibited olanzapine-induced adipose tissue macrophage infiltration and M1-like polarization, especially in sWAT. In vitro studies showed that stromal vascular cells, rather than adipocytes, were sensitive to GABA. Furthermore, the results suggested that GABA improves olanzapine-induced insulin resistance at least in part through a GABA B receptor-dependent pathway., Conclusions: These findings suggest that targeting GABA may be a potential therapeutic approach for olanzapine-induced metabolic disorders., (© 2024 John Wiley & Sons Ltd.)

Effective anticancer immunity depends on properly activating multiple stepwise events in the cancer-immunity cycle. An immunologically "cold" tumor microenvironment (TME) engenders immune evasion and refractoriness to conventional checkpoint blockade immunotherapy. Here, we combine nanoparticle formulations and an in situ formed hydrogel scaffold to treat accessible tumors locally and to stimulate systemic immunity against metastatic tumor lesions. The nanoparticles encapsulate poly(ε-caprolactone)-derived cytotoxic chemotherapy and adjuvant of Toll-like receptor 7/8 through a reactive oxygen species (ROS)-cleavable linker that can be self-activated by the coassembled neighboring photosensitizer following near-infrared (NIR) laser irradiation. Further development results in syringeable, NIR light-responsive, and immunogenic hydrogel (iGEL) that can be implanted peritumorally and deposited into the tumor surgical bed. Upon NIR laser irradiation, the generated ROS induces iGEL degradation and bond cleavage in the polymer-drug conjugates, triggering the immunogenic cell death cascade in cancer cells and spontaneously releasing encapsulated agents to rewire the cancer-immunity cycle. Notably, upon application in multiple preclinical models of melanoma and triple-negative breast cancer, which are aggressive and refractory to conventional immunotherapy, iGEL induces durable remission of established tumors, extends postsurgical tumor-free survival, and inhibits metastatic burden. The result of this study is a locally administrable immunogenic hydrogel for triggering host systemic immunity to improve immunotherapeutic efficacy with minimal off-target side effects.

Basic helix-loop-helix (bHLH) transcription factors play various important roles in plant growth and development. In this study, a AabHLH48 was identified in the floral organ of Adonis amurensis, a perennial herb that can naturally complete flowering at extreme low temperatures. AabHLH48 was widely expressed in various tissues or organs of A. amurensis and was localized in the nucleus. Overexpression of AabHLH48 promotes early flowering in Arabidopsis under both photoperiod (12 h light/12 h dark and 16 h light/8 h dark) and temperature (22 and 18 °C) conditions. Transcriptome sequencing combined with quantitative real-time PCR analysis showed that overexpression of AabHLH48 caused a general upregulation of genes involved in floral development in Arabidopsis, especially for AtAGAMOUS-LIKE 8/FRUITFULL (AtAGL8/FUL). The yeast one-hybrid assay revealed that AabHLH48 has transcriptional activating activity and can directly bind to the promoter region of AtAGL8/FUL. These results suggest that the overexpression of AabHLH48 promoting early flowering in Arabidopsis is associated with the upregulated expression of AtAGL8/FUL activated by AabHLH48. This indicates that AabHLH48 can serve as an important genetic resource for improving flowering-time control in other ornamental plants or crops., 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 GmbH. All rights reserved.)

Endometriosis (EMs)-related infertility commonly has decreased endometrial receptivity and normal decidualization is the basis for establishing and maintaining endometrial receptivity. However, the potential molecular regulatory mechanisms of impaired endometrial decidualization in patients with EMs have not been fully clarified. We confirmed the existence of reduced endometrial receptivity in patients with EMs by scanning electron microscopy and quantitative real-time PCR. Here we identified an lncRNA, named BMPR1B-AS1, which is significantly downregulated in eutopic endometrium in EMs patients and plays an essential role in decidual formation. Furthermore, RNA pull-down, mass spectrometry, RNA immunoprecipitation, and rescue analyses revealed that BMPR1B-AS1 positively regulates decidual formation through interaction with the RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Downregulation of IGF2BP2 led to a decreased stability of BMPR1B-AS1 and inhibition of activation of the SMAD1/5/9 pathway, an inhibitory effect which diminished decidualization in human endometrial stromal cells (hESCs) decidualization. In conclusion, our identified a novel regulatory mechanism in which the IGF2BP2-BMPR1B-AS1-SMAD1/5/9 axis plays a key role in the regulation of decidualization, providing insights into the potential link between abnormal decidualization and infertility in patients with EMs, which will be of clinical significance for the management and treatment of infertility in patients with EMs., (© 2024 Federation of American Societies for Experimental Biology.)

Fundamentally suppressing Li dendrite growth is known to be critical for realizing the potential high energy density for Li-metal batteries (LMBs). Inspired by the ionic transport function of proteins, we previously discovered that utilizing natural proteins was able to stabilize the Li anode but have not demonstrated how a specific amino acid of the protein enabled the function. In this study, we decorate the separator with Leucine ( Leu ) amino acid assisted by poly(acrylic acid) (PAA) for effectively stabilizing the Li-metal anode, so as to dramatically improve the cycling performance of LMBs. The decorated separator improves electrolyte wettability and effectively suppresses Li dendrite growth. As a result, the amino acid-enabled separator prolongs the cycle life of the symmetrical Li|Li cells, exhibits higher Coulombic efficiency in the Li|Cu cells, and improves the cycling performance in LMBs with the LiFePO 4 cathode. This work is an initial study on applying a specific amino acid of proteins to enhance the performance of batteries, providing a new strategy on guiding Li + deposition, and laying an important foundation for functional separator design of high-energy-density batteries.

Anesthesia/surgery have been identified as potential factors contributing to perioperative neurocognitive disorders, with a notably heightened risk observed in aging populations. One of the primary drivers of this impairment is believed to be neuroinflammation, specifically inflammation of hippocampal microglia. Dietary restriction has demonstrated a favorable impact on cognitive impairment across various disorders, primarily by quelling neuroinflammation. However, the precise influence of dietary restriction on perioperative neurocognitive disorders remains to be definitively ascertained. This investigation aims to explore the effects of dietary restriction on perioperative neurocognitive disorders and propose innovative therapeutic strategies for their management. The model of perioperative neurocognitive disorder was induced through exploratory laparotomy under isoflurane anesthesia. Cognitive performance was evaluated using the open field test, Barnes maze test, and fear conditioning test. The enzyme-linked immunosorbent assay (ELISA) was employed to quantify concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in both serum and hippocampal samples. The Western blot technique was utilized to assess expression levels of hippocampal PSD 95, Synaptophysin, TLR4, MyD88, and NF-kB p65. Microglial polarization was gauged using a combination of reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence labeling techniques. We conducted 16S rRNA sequencing to investigate the impact of dietary restriction on the intestinal flora of aged mice following anesthesia/surgery. Our findings indicate that dietary restrictions have the potential to ameliorate anesthesia/surgery-induced cognitive dysfunction. This effect is achieved through the modulation of gut microbiota, suppression of inflammatory responses in hippocampal microglia, and facilitation of neuronal repair and regeneration., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Akebia saponin D (ASD) is a bioactive triterpenoid saponin extracted from Dipsacus asper Wall. ex DC.. This study aimed to investigate the effects of ASD on allergic airway inflammation. Human lung epithelial BEAS-2B cells and bone marrow-derived mast cells (BMMCs) were pretreated with ASD (50, 100 and 200 μΜ) and AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) (1 mM), and then stimulated with lipopolysaccharide (LPS) or IL-33. Pretreatment with ASD and AICAR significantly inhibited TNF-α and IL-6 production from BEAS-2B cells, and IL-13 production from BMMCs. Moreover, pretreatment with ASD and AICAR significantly increased p-AMPK expression in BEAS-2B cells. Inhibition of AMPK by siRNA and compound C partly abrogated the suppression effect of ASD on TNF-α, IL-6, and IL-13 production. Asthma murine model was induced by ovalbumin (OVA) challenge and treated with ASD (150 and 300 mg/kg) or AICAR (100 mg/kg). Infiltration of eosinophils, neutrophils, monocytes, and lymphocytes, and production of TNF-α, IL-6, IL-4, and IL-13 were attenuated in ASD and AICAR treated mice. Lung histopathological changes were also ameliorated after ASD and AICAR treatment. Additionally, it showed that treatment with ASD and AICAR increased p-AMPK expression in the lung tissues. In conclusion, ASD exhibited protective effects on allergic airway inflammation through the induction of AMPK activation., (© 2024. The Author(s) under exclusive licence to The Japanese Society of Pharmacognosy.)

Xylooligosaccharide (XOS) is known as a prebiotic, however, it is unknown whether XOS can directly protect against bacterial infection. This study aimed to investigate the direct inhibitory effects of XOS on Salmonella Typhimurium colonization and the inductive impairments in gut health and growth performance in broilers. We first probed the inhibitory effects of XOS on S. Typhimurium adhesion and its induction of intestinal epithelial cell (IPEC-J2) injuries. Afterward, 168 one-day-old yellow-feathered broilers were randomly divided into 3 groups (7 replicates/group): negative control (NC, received a basal diet), positive control (PC, received a basal diet with S. Typhimurium challenge) and XOS group (PC birds + 1,500 mg/kg XOS). All birds except those in NC were orally challenged with S. Typhimurium from 8 to 10 d of age. Parameters were analyzed on d 11. The results showed that XOS inhibited S. Typhimurium adhesion and the inductive injuries of IPEC-J2 cells by lowering (P < 0.05) certain adhesion-related genes expression of this bacterium. It also alleviated S. Typhimurium-induced increase (P < 0.05) in the expression of certain inflammatory cytokines and tight junction (TJ) proteins of IPEC-J2 cells. Supplementing XOS to S. Typhimurium-challenged broilers attenuated the elevations (P < 0.05) in S. Typhimurium colonization of ileal mucosa and its translocation to the liver and spleen, as well as increased (P < 0.05) certain TJ proteins expression of ileum. Besides, XOS addition normalized S. Typhimurium-induced impairments (P < 0.05) in ileal morphology, final body weight and average daily gain in broilers. Collectively, supplemental XOS directly suppressed intestinal colonization of S. Typhimurium by diminishing its adhesiveness and subsequently mitigated destructions in intestinal barriers, thus contributing to weaken growth retardation in challenged broilers. Our findings provide a new insight into the mechanisms of XOS limiting Salmonella infection in chickens., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Immunotherapy holds great promise for the treatment of aggressive and metastatic cancers; however, currently available immunotherapeutics, such as immune checkpoint blockade, benefit only a small subset of patients. A photoactivatable toll-like receptor 7/8 (TLR7/8) nanoagonist (PNA) system that imparts near-infrared (NIR) light-induced immunogenic cell death (ICD) in dying tumor cells in synchrony with the spontaneous release of a potent immunoadjuvant is developed here. The PNA consists of polymer-derived proimmunoadjuvants ligated via a reactive oxygen species (ROS)-cleavable linker and polymer-derived photosensitizers, which are further encapsulated in amphiphilic matrices for systemic injection. In particular, conjugation of the TLR7/8 agonist resiquimod to biodegradable macromolecular moieties with different molecular weights enabled pharmacokinetic tuning of small-molecule agonists and optimized delivery efficiency in mice. Upon NIR photoirradiation, PNA effectively generated ROS not only to ablate tumors and induce the ICD cascade but also to trigger the on-demand release of TLR agonists. In several preclinical cancer models, intravenous PNA administration followed by NIR tumor irradiation resulted in remarkable tumor regression and suppressed postsurgical tumor recurrence and metastasis. Furthermore, this treatment profoundly shifted the tumor immune landscape to a tumoricidal one, eliciting robust tumor-specific T cell priming in vivo. This work highlights a simple and cost-effective approach to generate in situ cancer vaccines for synergistic photodynamic immunotherapy of metastatic cancers.

Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 μg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.

Clusterin (CLU) is a stress-responding protein associated with cytoprotection in a broad range of pathological processes. However, clusterin's function in diabetes-induced endothelial dysfunction has not been defined. Herein, using two diabetes models, we investigated the role of clusterin in endothelial dysfunction triggered by diabetes and the molecular mechanisms involved. The results revealed that clusterin overexpression inhibited ICAM-1/VCAM-1 expression in aortas and improved endothelium-dependent vasodilatation in db/db diabetic mice and streptozotocin (STZ)-induced diabetes models. Consistently, in vitro, adenoviral clusterin overexpression reduced the expression of a range of pro-inflammatory cytokines and suppressed monocyte adhesion to endothelial cells subjected to high glucose and high palmitate. Further study indicated that clusterin overexpression mitigated mitochondrial excessive fission and reduced mitochondrial ROS production. Conversely, silencing clusterin aggravated mitochondrial fission and endothelial inflammatory activation in high glucose-exposed endothelial cells. Accumulating evidence indicates that impaired mitochondrial dynamics plays a considerable role in promoting endothelial dysfunction in diabetic subjects. Therefore, treatments targeting mitochondrial undue fission may be promising measures to prevent vascular complications of diabetes. Furthermore, AMP-activated protein kinase (AMPK) activation contributed to the modulation of mitochondrial dynamics executed by clusterin. Mechanistically, clusterin promoted the phosphorylation of AMPKα and its downstream target acetyl-CoA carboxylase (ACC), while the inhibition of AMPKα negated the improvement in mitochondrial dynamics provided by clusterin overexpression. Over all, these findings suggest that clusterin exerts beneficial effects in endothelial cells under diabetic conditions via inhibiting mitochondrial fragmentation mediated by AMPK., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ruthenium complexes have attracted a surge of interest as anticancer drug candidates because of their low toxicity, diversity in mode-of-actions and non-cross drug resistance with conventional platinum-based agents. Despite remarkable advances, only a limited number of ruthenium complexes have been demonstrated to kill cancer cells and suppress metastasis simultaneously. Here, two organometallic tetranuclear Ru(II) arene complexes (Ru-1 and Ru-2) have been synthesized and evaluated for their in vitro activity against a panel of human cancer cell lines, including a cisplatin-resistant human lung cancer A549 cell line. A superior cytotoxic activity of the ruthenium complexes compared to cisplatin across distinct cell lines was observed. Further examination of the mechanism indicated that anticancer activity was accomplished by inducing apoptosis in cancer cells. In addition, we found that such compounds exhibited promising antimetastatic activity and reduced the invasiveness of cancer cells. Importantly, choosing Ru-1 as a target compound, a significantly enhanced safety profile relative to cisplatin in animals was validated, suggesting that these complexes can be used as promising candidates for cancer therapy and deserve further investigation., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)