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Atherosclerosis (AS) is a chronic inflammatory disorder characterized by arterial intimal lipid plaques. Small interfering ribonucleic acid (siRNA)-based therapies, with their ability to suppress specific genes with high targeting precision and minimal side effects, have shown great potential for AS treatment. However, targets of siRNA therapies based on macrophages for AS treatment are still limited. Olfactory receptor 2 (Olfr2), a potential target for plaque formation, was discovered recently. Herein, anti-Olfr2 siRNA (si-Olfr2) targeting macrophages was designed, and the theranostic platform encapsulating si-Olfr2 to target macrophages within atherosclerotic lesions was also developed, with the aim of downregulating Olfr2, as well as diagnosing AS through photoacoustic imaging (PAI) in the second near-infrared (NIR-II) window with high resolution. By utilization of a reactive oxygen species (ROS)-responsive nanocarrier system, the expression of Olfr2 on macrophages within atherosclerotic plaques was effectively downregulated, leading to the inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 β (IL-1β) secretion, thereby reducing the formation of atherosclerotic plaques. As manifested by decreased Olfr2 expression, the lesions exhibited a significantly alleviated inflammatory response that led to reduced lipid deposition, macrophage apoptosis, and a noticeable decrease in the necrotic areas. This study provides a proof of concept for evaluating the theranostic nanoplatform to specifically deliver si-Olfr2 to lesional macrophages for AS diagnosis and treatment.

Pipeline corrosion, leading to water quality deterioration, leakage, and related issues, severely disrupts residents' daily lives and economic activities. The effect of CO2addition on pipeline corrosion is being explored in this study. It delves into the protective mechanisms that arise from bicarbonate ions within CO2treated systems, aiming to mitigate pipeline corrosion. According to the study, the corrosion behavior of the iron matrix surface can be revealed through electrochemical testing methods. Due to the presence of CO2, the metal formed a dense passivation layer, leading to a significant shift in the electrode potential on the surface of the pipe in the positive direction. The metal inside the pipe is fundamentally prevented from dissolving, forming a passive state and thus achieving corrosion protection. A comprehensive understanding of the corrosion mechanism and product transformation is achieved by examining morphological changes and corrosion interface features and analyzing the composition of corrosion products. Combined with the analysis of the effect of CO2on the microbial community, the presence of CO2effectively reduced the biological corrosion in the pipeline. This study underscores the crucial role of varying HCO3-concentrations in safeguarding iron against corrosion in CO2treated systems.

Byline: Jian. Wei, Yuefeng. Hu, Jianan. Yu, Chao. Yin, Guang. Chen, Long. Jin Aims: To investigate the predictive value of hepatic venous pressure gradient (HVPG) and the efficacy and significance [...]

The interplay between drug and polymer chemistry and its impact on drug release from an amorphous solid dispersion (ASD) is a relatively underexplored area. Herein, the release rates of several drugs of diverse chemistry from hydroxypropyl methylcellulose acetate succinate (HPMCAS)-based ASDs were explored using surface area normalized dissolution. The tendency of the drug to form an insoluble complex with HPMCAS was determined through coprecipitation experiments. The role of pH and the extent of drug ionization were probed to evaluate the role of electrostatic interactions in complex formation. Relationships between the extent of complexation and the drug release rate from an ASD were observed, whereby the drugs could be divided into two groups. Drugs with a low extent of insoluble complex formation with HPMCAS tended to be neutral or anionic and showed reasonable release at pH 6.8 even at higher drug loadings. Cationic drugs formed insoluble complexes with HPMCAS and showed poor release when formulated as an ASD. Thus, and somewhat counterintuitively, a weakly basic drug showed a reduced release rate from an ASD at a bulk solution pH where it was ionized, relative to when unionized. The opposite trend was observed in the absence of polymer for the neat amorphous drug. In conclusion, electrostatic interactions between HPMCAS and lipophilic cationic drugs led to insoluble complex formation, which in turn resulted in ASDs with poor release performance.

Purpose: Cellular configurations with ZPR more suitable for cylindrical sandwich shell in which the structure needs undergo pure cylindrical bending. To date, research in the vibration response of cylindrical sandwich shell is still a challenging task. This article proposes one method for free vibration analysis of sandwich cylindrical shells consisting of elastic-isotropic skin and a zero Poisson's ratio cellular core was proposed. Method: The free vibration characteristics of the sandwich cylindrical shells has been studied using classical thin shell theory. Theoretical models of the effective mechanical performances of the cellular core are established by homogenization methods. The accuracies of theoretical predictions are validated by the finite element method and comparing with others from some available literatures. Results and Conclusions: Based on the theoretical predictions, the influences on effective mechanical performances of the cellular core and natural frequencies of the sandwich cylindrical shell caused by geometric parameters are evaluated in detail. These geometrical parameters provide different contributions to the effective mechanical properties and dynamic response, which can lead to separate designs for improving their dynamic characteristics.

Near-infrared-II fluorescence imaging (NIR-II FI) has become a powerful imaging technique for disease diagnosis owing to its superiorities, including high sensitivity, high spatial resolution, deep imaging depth, and low background interference. Despite the widespread application of conjugated polymer nanoparticles (CPNs) for NIR-II FI, most of the developed CPNs have quite low NIR-II fluorescence quantum yields based on the energy gap law, which makes high-sensitivity and high-resolution imaging toward deep lesions still a huge challenge. This work proposes a nanoengineering strategy to modulate the size of CPNs aimed at optimizing their NIR-II fluorescence performance for improved NIR-II phototheranostics. By adjusting the initial concentration of the synthesized conjugated polymer, a series of CPNs with different particle sizes are successfully prepared via a nanoprecipitation approach. Results show that the NIR-II fluorescence brightness of CPNs gradually amplifies with decreasing particle size, and the optimal CPNs, NP0.2, demonstrate up to a 2.05-fold fluorescence enhancement compared with the counterpart nanoparticles. With the merits of reliable biocompatibility, high photostability, and efficient light–heat conversion, the optimal NP0.2 has been successfully employed for NIR-II FI-guided photothermal therapy both in vitro and in vivo. Our work highlights an effective strategy of nanoengineering to improve the NIR-II performance of CPNs, advancing the development of NIR-II FI in life sciences.

ABSTRACT Eleven push-out experimental specimens were analyzed based on the orthogonal design method to investigate the effects of a checkered steel plate pattern height, position of pattern and transverse stirrup [...]

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) is a weakly acidic polymer that is widely used in the formulation of amorphous solid dispersions (ASDs). While the pH-dependent solubility of HPMCAS is widely recognized, the role of other solution properties, including buffer capacity, is less well understood in the context of ASD dissolution. The goal of this study was to elucidate the rate-limiting steps for drug and HPMCAS release from ASDs formulated with two poorly water soluble model drugs, indomethacin and indomethacin methyl ester. The surface area normalized release rate of the drug and/or polymer in a variety of media was determined. The HPMCAS gel layer apparent pH was determined by incorporating pH sensitive dyes into the polymer matrix. Water uptake extent and rate into the ASDs were measured gravimetrically. For neat HPMCAS, the rate-limiting step for polymer dissolution was observed to be the polymer solubility at the polymer–solution interface. This, in turn, was impacted by the gel layer pH which was found to be substantially lower than the bulk solution pH, varying with medium buffer capacity. For the ASDs, the HPMCAS release rate was found to control the drug release rate. However, both drugs reduced the polymer release rate with indomethacin methyl ester having a larger impact. In low buffer capacity media, the presence of the drug had less impact on release rates when compared to observations in higher strength buffers, suggesting changes in the rate-limiting steps for HPMCAS dissolution. The observations made in this study can contribute to the fundamental understanding of acidic polymer dissolution in the presence and absence of a molecularly dispersed lipophilic drug and will help aid in the design of more in vivorelevant release testing experiments.

With the increase in service temperature of aero-engine hot components, the requirements for the high-temperature performance and processability of the powder metallurgy (PM) superalloys used for preparing turbine disks also increase. To overcome the bottlenecks that constrain the preparation and microstructure control of PM superalloys, this work investigates the impacts of hot compression parameters on the hot deformation behavior and microstructure evolution of a novel PM superalloy, FGH4113A. Hot compression tests were conducted on the FGH4113A alloy, which underwent hot isostatic pressing, within a temperature range of 1050 °C–1150 °C and at a consistent true strain rate ranging from 0.001s−1to 1s−1. The results reveal that the flow stress decreases progressively with the reduction of strain rate and the rise in temperature. Optimal hot deformation conditions are identified at a temperature of 1110 °C with strain rates ranging from 0.1s−1to 1s−1, and a temperature of 1130 °C with strain rates between 0.01s−1and 0.1s−1. Within these optimal regimes, grains are uniform, and the average grain size is maintained within10μm. Grain evolution during hot compression involves original grain deformation, followed by recrystallization, subsequent grain coarsening, and then deformation again. Additionally, the γ′ area fraction diminishes with an increase in deformation temperature. Specifically, as the deformation temperature raises from 1050 °C to 1110 °C, and subsequently to 1150 °C, at a rate of 0.001s−1, the primary γ′ area fraction diminishes progressively from 6.2 % to 3.0 % and ultimately to zero. Above 1130 °C, the γ′ area fraction remained largely unaffected by variations in strain rate. These insights are pivotal, offering both experimental data and theoretical perspectives for optimal microstructure control in PM superalloys.

The development of near-infrared-II (NIR-II)-absorbing nano-agents for NIR-II photoacoustic imaging (PAI)-guided photothermal therapy (PTT) provides opportunities to advance the development of deep tissue photo-theranostics. Despite the superiority of semiconducting polymer nanoparticles (SPNs) for NIR-II PAI and PTT, their limited photoacoustic/photothermal performance makes achieving effective in vivophototheranostics still a huge challenge. In this work, we propose a noncovalent conformational lock (NCL)-based molecular engineering strategy to improve the NIR-II photoacoustic/photothermal performance of SPNs for high-efficiency phototheranostics in vivo. The introduction of NCL is favorable to improve the backbone planarity of the semiconducting polymer to enhance the light-harvesting capability, resulting in amplified NIR-II photo-acoustic/photothermal output. By virtue of the low toxicity, suitable size, and improved photophysical properties, the optimal SPN3 not only can be efficiently internalized by 4T1 cancer cells to kill the cells under NIR-II light excitation but also light up the tumor profile viaNIR-II PAI after systemic administration, which further guides the NIR-II PTT for efficient tumor ablation. Our investigation therefore provides a unique molecular design strategy to amplify the NIR-II photo-acoustic/photothermal signals of SPNs for improved in vivophototheranostics.

This paper revisits the thesis of Levine (1991) on the positive contribution of the financial market on the rate of economic growth. According to the author, the stock market performs, because it facilitates the formation of capital by increasing the liquidity of the market. In contrast, the economy private financial markets would be less effective. Such a conclusion is yet far from obvious. From the model of Levine (1991), we examine the equilibrium proportion invested in high-return (illiquid) projects and we show that the self-financing economy can record a growth rate higher than that of the economy of financial markets. Regardless of the stock market, economic growth is related to the interactions between the aversion to risk and the parameters of the set of production.

Preserving cellular integrity while eliminating algae cells constitutes a pivotal aspect in the removal of algae within potable water treatment facilities. The effect of calcium peroxide (CaO2) as a pre-oxidizer on water containing Microcystis aeruginosaand its algal removal performance and reaction mechanism were investigated in this study. CaO2was found to be highly effective in removing algae, requiring only a small amount to eliminate algal cells while preserving their cellular integrity. At 1.0 mM CaO2, the algal cell damage rate was 19.2 % with mild oxidation and slight damage to cellular integrity. Dissolved organic carbon decreased to 75.9 % and 13.5 % of the original after pre-oxidation and enhanced coagulation at 1.0 mM CaO2, respectively. Higher CaO2concentrations improved coagulation and reduced disinfection by-products (DBPs) precursors. Notably, CaO2was more effective in reducing the formation of carbonaceous disinfection by-products compared to nitrogenous disinfection by-products. The formation of most DBPs by chloramination was less than that by chlorination, except for trichloromethane, which was first founded. This study showed that CaO2had great potential for application in the treatment of algae-laden water.

Most of follicles undergo a degenerative process called follicular atresia. This process directly affects the egg production of laying hens and is regulated by external and internal factors. External factors primarily include nutrition and environmental factors. In follicular atresia, internal factors are predominantly regulated at 3 levels; organic, cellular and molecular levels. At the organic level, the hypothalamic-pituitary-ovary (HPO) axis plays an essential role in controlling follicular development. At the cellular level, gonadotropins and cytokines, as well as estrogens, bind to their receptors and activate different signaling pathways, thereby suppressing follicular atresia. By contrast, oxidative stress induces follicular atresia by increasing ROS levels. At the molecular level, granulosa cell (GC) apoptosis is not the only factor triggering follicular atresia. Autophagy is also known to give rise to atresia. Epigenetics also plays a pivotal role in regulating gene expression in processes that seem to be related to follicular atresia, such as apoptosis, autophagy, proliferation, and steroidogenesis. Among these processes, the miRNA regulation mechanism is well-studied. The current review focuses on factors that regulate follicular atresia at organic, cellular and molecular levels and evaluates the interaction network among these levels. Additionally, this review summarizes atretic follicle characteristics, in vitro modeling methods, and factors preventing follicular atresia in laying hens.

With the increasingly high requirements for wearable and flexible devices, traditional inorganic capacitors cannot meet the flexible demand of next-generation electronic devices. In this work, the energy storage property of all-inorganic flexible films has been systematically studied. PbZrO3(PZO) and Al2O3(AO) are selected as the antiferroelectric layer and insulating layer, respectively. The heterostructured films are prepared on the fluorphlogopite (F-Mica) substrate by chemical solution deposition. The microstructure, polarization behavior, and energy storage performances are investigated. The results demonstrate that the AO/PZO/AO/PZO/AO (APAPA) multilayered thin film possesses a greatly improved energy storage density (Wrec) of 28.1 J/cm3with an excellent energy storage efficiency (η) of 80.1%, which is ascribed to the enhanced breakdown strength and large difference in polarization. Furthermore, the capacitive films exhibit good stability under a wide working temperature range of 25–140 °C and an electric fatigue endurance of 107cycles. Besides, the energy storage performances are almost unchanged after 104bending cycles, demonstrating an excellent mechanical bending endurance. This work sheds light on the preparation technology and improvement of the dielectric energy storage performance for all-inorganic flexible multilayered thin films.

ABSTRACTObjectives:Glucocorticoid receptor (GR) expressed in hippocampus is critical for the homeostasis of stress responses and susceptible to epigenetic modulation caused by maternal factors. Here we show that maternal methyl nutrition causes sex-biased changes in hippocampal expression of GR exon 1 mRNA variants, associated with promoter DNA methylation, across two offspring generations in rats.Methods:Three-month-old female Sprague–Dawley rats (F0) were fed a diet supplemented with 1% betaine throughout the gestation and lactation. F0 dams and their F1 and F2 offspring of both sexes at weaning were used in the study.Results:A sex-specific transgenerational effect was observed. F2 females, but not males, followed the same pattern of their grand dams showing increased mRNA expression of total GR and its exons 1.4, 1.7, 1.10 and 1.11 variants coincided with promoter DNA hypomethylation in the hippocampus. However, F1 females, but not males, exhibited an opposite pattern, showing decreased expression of GR and its mRNA variants accompanied with promoter hypermethylation. The protein content of phospho-GR and BDNF/ERK in the hippocampus displayed the same sex and generation specificity.Discussion:These results indicate that maternal betaine exerts transgenerational effects on hippocampal GR expression and BDNF/ERK pathway in female rat offspring, with generation-dependent patterns of DNA methylation on alternative GR promoters.

Films with excellent mechanical properties and antimicrobial activity have potential applications in food preservation. The antimicrobial film was prepared by blending probiotic Bacillus velezensis906 metabolites (906), potassium sorbate (PS), and polyvinyl alcohol (PVA). The film was characterized using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and thermal stability analysis. The mechanical, barrier, and antimicrobial properties of the film were tested. The results of the physicochemical analysis indicated that, compared to the pure PVA film, the film's mechanical properties decreased, while its barrier properties and hydrophobicity increased with the addition of PS and 906, respectively. The results of the antimicrobial tests revealed that the blend film exhibited significant antimicrobial activity against Vibrio parahaemolyticus, Psychrobacter maritimus, Oceanobacillus kimchii, Pseudomonas aeruginosa, and Listeria monocytogenes. SEM demonstrated good fusion between the components of the PVA/PS/906 film, resulting in a dense and crack-free structure. FTIR suggested that PS and 906 enhance molecular interactions within the film matrix. XRD revealed that the film was crystallized, with 906 increasing the crystallinity of the bonds between the film components. Thermal analysis indicated the thermal stability of the films was enhanced. Consequently, the PVA/PS/906 blend film shows significant potential for application in the preservation of aquatic products.

In order to solve the issue of localised electric field concentration in high-voltage direct current cable accessories, a method for preparing a composite material with high conductivity and nonlinear conductivity properties is proposed. The authors employed homemade calcium copper titanate @ zinc oxide (CCTO@ZnO) as a filler and glycidyl methacrylate (GMA) as a grafted small molecule to co-regulate the non-linear conductivity of silicone rubber (SiR). The results indicate that doping CCTO@ZnO can enable SiR to acquire non-linear conduction properties and grafting GMA can significantly enhance the conductivity of SiR. However, both doping CCTO@ZnO and grafting GMA have a negative impact on the breakdown performance of SiR. Simulation results indicate that reinforced insulators made from doped and grafted co-modified composites can improve the distribution of electric fields in cable accessories.

Organic small molecule-based phototheranostics hold great promise for clinical translation by virtue of their distinct chemical structure, easy reproducibility, and high purity. However, reported molecular agents typically have relatively low optical absorbances, particularly over the near-infrared (NIR) region, and this limits their phototheranostic performance. Herein, we first exploit a diradicaloid molecular structure for enhancing NIR absorption to facilitate efficient photoacoustic imaging (PAI)-guided photothermal therapy (PTT). The donor–acceptor interaction in the diradicaloid molecule (DRM) leads to strong charge transfer resulting on obvious diradical characteristics, which is beneficial for NIR absorption. The DRM possesses excellent light-harvesting ability, with a mass extinction coefficient of ∼220 L g–1cm–1, which is much higher than those (∼5–100 L g–1cm–1) of typical organic molecules. After assembling into nanoparticles, they show good water dispersibility, good photostability, and impressive performance for PAI-guided PTT in vitroand in vivo. The impressive in vitroand in vivoperformances show that developing small molecules with diradicaloid structures can be an effective approach for enhancing NIR harvesting capability for biomedical applications.

Periodically driven Floquet quantum systems could provide a promising platform to investigate novel physics out of equilibrium1, but the drive generically heats the system to a featureless infinite-temperature state2–4. Fortunately, for high driving frequency, the heat absorption rate has been theoretically predicted to be exponentially small, giving rise to a long-lived prethermal regime that exhibits all the intriguing properties of Floquet systems5–8. Here we experimentally observe Floquet prethermalization using NMR techniques and probe the heating rate. We first show the relaxation of a far-from-equilibrium initial state to a long-lived prethermal state, well described by a time-independent ‘prethermal’ Hamiltonian. By measuring the autocorrelation of this prethermal Hamiltonian we can further experimentally confirm the predicted exponentially slow heating rate. More strikingly, we find that, on the timescale at which the prethermal Hamiltonian picture breaks down, the Floquet system still possesses other quasiconservation laws. Our results demonstrate that it is possible to realize robust Floquet engineering, thus enabling the experimental observation of non-trivial Floquet phases of matter.

Efficient and stable Pt-free electrocatalysts for oxygen reduction reaction (ORR) are indispensable for future fuel cells. Herein, we describe a heterostructure of Pd nanocrystals (PdNCs) on N-doped Ag nanowires (NWs) synthesized using a direct epitaxial growth strategy with a Pd loading of only 9.5 wt.%. The PdAg bimetallic heterostructure showed the highest mass activity among reported PdAg-based ORR electrocatalysts and exhibited excellent stability, with only a 1.5 mV decay in the half-wave potential even after 20000 cycles of continuous testing. The remarkably enhanced activity and durability can be attributed to the distinct advantages of the ultrasmall PdNCs, cocatalysts of N-doped AgNWs, and their heterointerfaces. This work reveals that the epitaxial growth of a heterostructure on a stable support is a promising strategy for promoting catalytic performance.

In this contribution, we present the results of recent neutron irradiation campaign performed in the material test reactor BR2 (Belgium) on pure tungsten. We have applied various irradiation conditions and sample geometry to assess the effect of neutron irradiation on hardness, bending, tensile and fracture mechanical properties. The investigated material is a commercially pure tungsten plate fabricated according to the international thermonuclear experimental reactor (ITER) specification for the application in the divertor plasma-facing components. The neutron irradiation covers a large span of temperatures and damage doses, ranging from 600 to 1200 °C and 0.1–1 dpa. The obtained mechanical properties were analyzed to deduce the shift of the ductile to brittle transition temperature (DBTT) applying bending, tensile and fracture toughness-testing procedures. Then, a correlation of the fracture toughness with the change of the hardness was established. The obtained results are compared with the already published results on another ITER specification grade produced in the form of a rod. The presented and discussed results show that the performance of the compared grades in terms of the irradiation-induced embrittlement is similar, and that the irradiation in the high-temperature region (600–800 °C) causes a considerable DBTT shift already at 0.2–0.5 dpa.

Photodynamic therapy (PDT) synergized photothermal therapy (PTT) shows superior clinical application prospects than single PDT or PTT. On the other hand, multimodal imaging can delineate comprehensive information about the lesion site and thus help to improve therapy accuracy. However, integrating all these functions into one single molecule is challenging, let alone balancing and maximizing the efficacy of each function. Herein, a near-infrared (NIR) small molecule (ETTC) with an “acceptor–donor–acceptor” structure was designed and synthesized by coupling rigity and flexibility to simultaneously achieve NIR-II fluorescence imaging (NIR-II FLI), photoacoustic imaging, PTT and PDT. The efficacy of each functionality was well balanced and optimized (NIR-II quantum yield: 3.0%; reactive oxygen species generation: 3.2-fold higher than ICG; photothermal conversion efficiency: 52.8%), which may be attributed to the coupling of the rigid and flexible structures in ETTC to tactically manipulate the energy dissipation paths (non-radiative against radiative decay). As a proof-of-concept, under the effective guidance of local-tumor imaging by PA and whole-body imaging by NIR-II FL, complete tumor eradication was achieved viaPDT and PTT combinational therapy. This work provides a novel perspective into conceiving and developing single molecule for efficient versatile biomedical applications.

ABSTRACTTumor immunity is closely associated with the prognosis of tumors, including osteosarcoma (OS). The aim of the present study was to construct an immune-related prognostic index (PI) to predict the prognosis of OS. Herein, OS expression data were sourced from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. We divided the OS patients into nonmetastatic and metastatic groups, allowing differentially immune-related genes (DIRGs) to be selected. After DIRGs were further investigated by enrichment analysis, four keys prognostic IRGs (CD79A, CSF3R, MTNR1B and NPPC) were identified using a Cox proportional hazards model. Then, an immune-related prognostic index was constructed. Finally, gene set enrichment analysis (GSEA) was employed to further explore the underlying mechanisms. The difference in tumor-infiltrating immune cell (TIIC) abundance was also discussed. In our study, eight upregulated genes and 30 downregulated genes were identified. Several Gene Ontology (GO) terms and the most significantly enriched KEGG pathways were immune-associated functions and pathways. Four genes, including CD79A, CSF3R, MTNR1B and NPPC, were used to establish a risk assessment model for evaluating OS prognosis. GSEA revealed that the risk score was related to cytokine receptor interaction and to the chemokine and B cell receptor signaling pathways. Furthermore, high risk markedly related to the infiltration of several immune cell types, including M2 macrophages, naïve CD4 T cells, and CD8 T cells. In sum, we developed a survival model for OS. The underlying molecular mechanisms of the high-risk group may affect immune-related biological processes and TIICs.Abbreviations TARGET: Therapeutically Applicable Research To Generate Effective Treatments; PI: Prognostic index; OS: Osteosarcoma; DIRGs: Differentially immune-related genes; GSEA: Gene set enrichment analysis; TIIC: Tumor-infiltrating immune cell.

Precise diagnosis and effective treatment of gliomas still remain a huge challenge. Photoacoustic-guided photothermal therapy (PTT) has unique advantages over conventional techniques for brain tumor theranostics, but existing nanoagents for photoacoustic imaging (PAI)-guided PTT are mainly organic small molecules or inorganic nanoparticles, which have the limitations of poor photostability and biocompatibility. Besides, the restricted absorption in the first near-infrared window (NIR-I) of the most existing nanoagents compromises their effectiveness for deep tissue PAI and PTT. We herein develop novel semiconducting polymer nanoparticles (SPNs) that are strongly absorptive in the second NIR window (NIR-II) to alleviate these problems. With the merits of excellent photoacoustic and photothermal performance, high photostability, proper size, and low toxicity, SPNs not only show efficient cellular uptake for PAI and PTT toward U87 glioma cells but also demonstrate effective accumulation in both subcutaneous tumors and brain tumors upon intravenous injection, thereby realizing efficient PAI-guided PTT toward gliomas under NIR-II light irradiation.

In this study, we present a new hybrid functional denoted as xOPBE, which is optimized at the 6-311+G(2d,p) basis set and designed with a specific aim of providing accurate 13C chemical shifts. By mixing the Hartree–Fock exchange into the OPBE functional, xOPBE provides a significantly improved overall performance as compared to its parent OPBE functional, while OPBE was shown previously as an excellent functional for 13C chemical shifts. Even in the case of the 1-adamantyl cation, for which OPBE completely fails in reproducing the experimental results, xOPBE still performs very well with similar accuracy as the standard CCSD(T) method with a large basis set. Our results also demonstrate that xOPBE not only can improve quantitatively the description of the correct assignments given by OPBE but also can revert OPBE’s incorrect assignments qualitatively. Thus, we would like to recommend the use of xOPBE for routine evaluations of 13C chemical shifts.

ABSTRACTTumorigenic cancer stem cells (CSCs) exist in various tumors including the cutaneous squamous cell carcinoma (cSCC) as a minor subpopulation and are tightly associated with metastasis and therapeutic resistance. Better understanding of CSCs properties is essential for the novel therapeutic strategy targeted toward these cancers. The cSCC stem cells (cSCCSCs) were enriched from a cSCC cell line A431 by repeated sphere culture, and identified via the expression analysis of stemness marker genes and CD44 proteolysis. MiR-199a-5p was previously reported to be related with the proteolysis modulation of CD44, so the specific regulation mechanisms were verified by overexpression in vitroand in vivo. MiR-199a-5p is under-expressed in cSCCSCs and functions as a tumor suppressive molecule. Overexpression of miR-199a-5p reduced the stemness of cSCCSCs and inhibited cell proliferation. By targeting the deacetylase Sirt1, miR-199a-5p inhibited cellular proteolysis of CD44 and reduced the CD44 intracellular domain (CD44ICD) release and nuclear translocation. Overexpression of CD44ICD reversed the effects of miR-199a-5p overexpression or Sirt1 silencing, and increased the transcriptional expression of stemness genes. Our results revealed that the miR-199a-5p/Sirt1/CD44ICD signaling pathway regulates cSCCSCs progression by affecting its migration ability and tumorigenicity, therefore can be utilized to develop a curative approach for cSCC.Abbreviations: CSCs: cancer stem cells; cSCC cutaneous squamous cell carcinoma; cSCCSCs: cSCC stem cells; CD44ICD: CD44 intracellular domain; HA: hyaluronic acid; HNSCC: hand and neck squamous cell carcinoma; ESCC: esophageal squamous cell carcinoma;MMPs: matrix metalloproteinases; SFM: sphere formation medium; EGF: epidermal growth factor; bFGF: basic fibroblast growth factor; BSA: bovine serum albumin; CCK-8: cell counting kit-8

Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients experience recurrence. Recent evidence suggests that perioperative KRAS-mutated circulating tumor DNA (ctDNA) may have prognostic value. Therefore, we conducted a systematic review and meta-analysis to explore the prognostic significance of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC.

In destructive earthquakes, embankment seismic damages were widely distributed, and researches on embankment seismic hazard, fragility, and probability risk assessment have important significance to improve highway seismic performance and for regional disaster prevention and mitigation capacities. Embankment seismic damages were divided into five grades, and the maximum lateral permanent displacement rate on the top surface εmaxwas selected as the embankment seismic damage parameter. Taking the Xi’an–Baoji expressway K1125 + 470 embankment as an example, we carried out a seismic hazard assessment based on CPSHA, a fragility assessment based on IDA and PSDA, and a probability risk assessment based on a hazard curve. On the basis of risk acceptability, a risk management method was put forward, which was suitable for the seismic design of new embankments and seismic strengthening of existing embankments, and verified the positive effect of a retaining wall on the embankment seismic performance. The results show that the seismic hazard assessment results of the Xi’an–Baoji expressway were higher than those of the fourth-generation seismic zoning map; when the PGA reached 0.8 g, the exceedance probability of severe damage was as high as 99.995%; the probability risk of severe damage in the next 50 years was 36.46%. However, the probability risk of severe damage of the embankment with the retaining wall was found to be 21.17%, indicating that a retaining wall can significantly reduce the embankment seismic damage risk. The embankment seismic damage risk was divided into high, medium, and low levels: medium risk and low risk were acceptable, and high risk was unacceptable.

Homocysteine (Hcy) is an intermediate in the one-carbon metabolism that donates methyl groups for methylation processes involved in epigenetic gene regulation. Although poor oocyte quality in polycystic ovarian syndrome (PCOS) patients is associated with elevated Hcy concentration in serum and follicular fluid, whether Hcy directly affects oocyte quality and its mechanisms are poorly understood. Here we show that Hcy treatment impaired oocyte quality and developmental competence, indicated by significantly reduced survival rate, polar body extrusion rate, and cleavage rate. Hcy treatment resulted in mitochondrial dysfunction, with increased production of mitochondrial ROS, reduced mtDNA copy number, and the expression of 7 out of 13 mtDNA-encoded genes and 2 ribosome RNA genes, 12S rRNA and 16S rRNA. Upon Hcy treatment, the expression of one-carbon metabolic enzymes and DNMT1 was enhanced. Interestingly, DNA methyltransferase inhibitor 5'AZA rescued Hcy-induced mitochondrial dysfunction, impaired oocyte quality and developmental competence. Concurrently, expression of one-carbon metabolic enzymes and methylation status of mtDNA coding sequences were also normalized, at least partially, by 5'AZA treatment. Our findings not only extend the understanding about how Hcy induces poor oocyte quality, but also contribute to a novel angle of identifying targets for enhancing the quality of oocyte from PCOS patients.

Smart manufacturing refers to integrating new generation information technologies and advanced manufacturing technologies to improve enterprise efficiency, increase customer satisfaction and enhance market competitiveness. Cloud manufacturing (CMfg) is a typical paradigm of smart manufacturing. With the rapid deployment and application of various CMfg systems, it is extremely urgent and significant to implement the standardized semantic description of manufacturing resources (MRs) characterized by geographical dispersion, high autonomy, and heterogeneity. In this paper, a metadata based manufacturing resource ontology modeling method is proposed to solve the consistency description problem of MRs in cloud. Firstly, the characteristic attributes of MRs in CMfg systems are analyzed, and a metadata-based manufacturing resource ontology-modeling framework is constructed. Then, a manufacturing resource domain ontology (MR_Onto) and a metadata model (MR_Meta) are designed, the mapping rules between them are discussed. Finally, a prototype tool describing manufacturing resources is developed, the feasibility and effectiveness of the proposed method and the developed tool are verified in an application case.

Machine tool is one of the most important manufacturing resources for manufacturing enterprises. Taking into account the machine tool’s common characteristics of decentralization and heterogeneity in cloud manufacturing (CMfg) environment, it is difficult to precisely find an appropriate machine tool from massive manufacturing service candidates to a customized manufacturing demand in CMfg. This paper proposes a multi-quality model for characterizing a manufacturing demand and a capability model for describing a manufacturing cloud service supported by machine tools, and constructs a mapping mechanism between the two proposed models. Based on the grey correlation theory, a machine tool supply–demand matching method is put forward. Finally, a case study is conducted to validate the feasibility of the proposed method.

Photoacoustic (PA) imaging and tracking of stem cells plays an important role in the real-time assessment of cell-based therapies. Nevertheless, the limitations of conventional inorganic PA contrast agents and the narrow range of the excitation wavelength in the first near-infrared (NIR-I) window hamper the applications of PA imaging in living subjects. Herein, we report the design and synthesis of a second near-infrared (NIR-II) absorptive organic semiconducting polymer (OSP)-based nanoprobe (OSPN+) for PA imaging and tracking of stem cells. Comparison studies in biological tissue show that NIR-II light excited PA imaging of the OSPN+has significantly higher signal-to-noise ratio than NIR-I light excited PA imaging, thereby demonstrating the superiority of the OSPN+for deep tissue imaging. With good biocompatibility, appropriate size, and optimized surface property, the OSPN+shows enhanced cellular uptake for highly efficient PA labeling of stem cells. In vivoinvestigations reveal significant NIR-II PA contrast enhancement of the transplanted OSPN+-labeled human mesenchymal stem cells by 40.6- and 21.7-fold in subcutaneous and brain imaging, respectively, compared with unlabeled cases. Our work demonstrates a class of OSP-based nanomaterials for NIR-II PA stem cell imaging to facilitate a better understanding and evaluation of stem cell-based therapies.

Hydrogen sulfide (H2S) is a versatile modulator in mitochondria and involved in numerous diseases caused by mitochondrial dysfunction. Therefore, many efforts have been made to develop fluorescent probes for mitochondrial H2S detection. However, these cationic small molecule probes are inapplicable for in vivo imaging because of the shallow tissue penetration and poor biostability. Herein, a ratiometric upconversion luminescence nanoprobe with an acid-activated targeting strategy is developed for detecting and bioimaging of mitochondrial H2S. The merocyanine triphenylamine-merocyanine (TPAMC)-modified upconversion nanophosphors, acting as the targeting and response component, are encapsulated into a pH-sensitive husk, composed of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(poly(ethylene glycol))-2000] (DSPE-PEG) and poly(l-histidine)-b-PEG, which improved the nanoprobe’s stability during transport in vivo. Under lysosomal pH, the PEG shell is interrupted and the targeting sites are exposed to further attach to mitochondria. Taking advantage of the luminescence resonance energy transfer process between TPAMC and upconversion nanophosphors, the ratiometric detection of mitochondrial H2S can be achieved with high selectivity and sensitivity. Cellular testing reveals the precise targeting to mitochondria via a lysosome delivery process. Importantly, the nanoprobe can be used for monitoring mitochondrial H2S levels in living cells and colon cancer mouse models.

The research takes the composite foundation of the Lintao oil depot belonging to the Gansu branch of PetroChina treated with compaction piles in the collapsible loess region as the research background. A large number of compaction piles dispersed in the composite foundation are simplified using the equivalent continuum method. Discrete piles arranged in a triangular shape are simplified in the model, where the annular piles and compacted soil are arranged alternately, which can provide new ideas for the three-dimensional calculation mode of composite foundation and greatly improve the convergence and computational efficiency of the finite element model. To more realistically reflect the actual situation, the soil-structure and fluid–structure interactions, the material and the contact nonlinearities are considered, and a large-scale three-dimensional calculation model, which includes the composite foundation, concrete foundation, tank and liquid, is established. A sensitivity analysis is used to analyze the sensitivity of the elastic modulus, internal friction angle and cohesion of the composite foundation. The sensitivity of a single factor is evaluated based on the absolute value of the slope of the result-parameter curve; the relative sensitivity of various parameters is discussed according to the dimensionless sensitivity. The results show that for composite foundation, an increase in the friction angle or the cohesion of the foundation will significantly increase the safety factor. The sensitivity of the friction angle is greater than that of cohesion, and the sensibility of the elasticity modulus on the stability is very small. The results suggest that the accuracy of the mechanical parameter selection should be considered in the research on the stability of composite foundations. Measures to increase the angle of internal friction should be preferentially taken and increasing the cohesion should be considered secondary to improve the stability and safety reserve of composite foundation.

Adenosine-to-inosine RNA editing (ATIRE) is a common form of ribonucleic acid (RNA) editing, which has highlighted the importance of ATIRE in tumors. However, its role in bladder cancer (BLCA) remains poorly understood. To study ATIRE impact on BLCA patient prognosis, we obtained ATIRE, gene expression, and clinical data from the Cancer Genome Atlas (TCGA) database for 251 patients, randomly dividing them into training and testing groups. Univariate proportional hazards model (COX) regression identified prognosis-associated ATIRE loci, while the least absolute shrinkage and selection operator (LASSO) selected final loci to construct prognostic models and generate ATIRE scores. We developed a nomogram to predict BLCA patients’ overall survival (OS) and analyzed the effect of ATIRE editing levels on host gene expression. We also compared immune cell infiltration and drug treatment between patients with high and low ATIRE scores. The ATIRE prognostic prediction model was constructed using ten ATIRE loci that are closely associated with BLCA survival. Patients with high ATIRE scores showed significantly worse OS than those with low ATIRE scores. Furthermore, the nomogram, which incorporates the ATIRE score, can better predict the prognosis of patients. Multiple functional and pathway changes associated with immune responses, as well as significant differences in immune cell infiltration levels and response to drug therapy were observed between patients with high and low ATIRE scores. This study represented the first comprehensive analysis of the role of ATIRE events in BLCA patient prognosis and provided new insights into potential prognostic markers for BLCA research.

Developing versatile and easily prepared nanomaterials with both imaging and therapeutic properties have received significant attention in cancer diagnostics and therapeutics. Here, we facilely fabricated Gd3+-chelated poly(isobutylene-alt-maleic anhydride) (PMA) framework pendent with perylene-3,4,9,10-tetracarboxylic diimide (PDI) derivatives and poly(ethylene glycol) (PEG) as an efficient theranostic platform for dual-modal photoacoustic imaging (PAI) and magnetic resonance imaging (MRI)-guided photothermal therapy. The obtained polymeric nanoparticles (NPs) chelated with Gd3+(PMA–PDI–PEG–Gd NPs) exhibited a high T1relaxivity coefficient (13.95 mM–1s–1) even at the higher magnetic fields. After 3.5 h of tail vein injection of PMA–PDI–PEG–Gd NPs, the tumor areas showed conspicuous enhancement in both photoacoustic signal and T1-weighted MRI intensity, indicating the efficient accumulation of PMA–PDI–PEG–Gd NPs owing to the enhanced permeation and retention effect. In addition, the excellent tumor ablation therapeutic effect in vivo was demonstrated with living mice. Overall, our work illustrated a straightforward synthetic strategy for engineering multifunctional polymeric nanoparticles for dual-modal imaging to obtain more accurate information for efficient diagnosis and therapy.

Chalcone synthases (CHS, EC 2.3.1.74) are key enzymes that catalyze the first committed step in flavonoid biosynthesis. In this study, we isolated a chalcone synthase, named NtCHS6,from Nicotiana tabacum.This synthase shared high homology with the NSCHSL(Y14507) gene and contained most of the conserved active sites that are in CHS proteins. The phylogenetic analysis suggested that NtCHS6 protein shared a large genetic distance with other SolanaceaeCHS proteins and was the most closely-related to an uncharacterized CHS from Solanum lycopersicum.The expression analysis indicated that NtCHS6was abundantly expressed in leaves, especially in mature leaves. By scrutinizing its upstream promoter sequences, multiple cis-regulatory elements involved in light and drought responsive were detected. Furthermore, NtCHS6expression decreased significantly under dark treatment and increased significantly under drought stress. Our results suggested that NtCHS6expression exhibited both light responsiveness and drought responsiveness, and might play important roles in ultraviolet protection and drought tolerance.

Semiconducting polymer nanoparticles (SPNs) have emerged as an alternative class of optical nanoagents for imaging applications. However, the general preparation method of SPNs is nanoprecipitation, which is likely to encounter the issue of nanoparticle dissociation. We herein report nondissociable near-infrared (NIR)-absorbing organic semiconducting nanoparticles for in vivo photoacoustic (PA) and fluorescence imaging. The nanoparticles are self-assembled from an amphiphilic semiconducting oligomer (ASO) that has a hydrophobic semiconducting oligomer backbone attached by hydrophilic poly(ethylene glycol) (PEG) side chains. The ASO has a higher structural stability and brighter PA signals compared to those of its counterpart nanoparticles synthesized by nanoprecipitation. The small size and the PEG-passivated surface of the ASO allow it to passively target to and efficiently accumulate in the tumor of living mice, permitting tumor imaging with high signal-to-background ratios. Our study provides new NIR-absorbing organic nanoparticles for PA and fluorescence imaging, which also have the potential to be used as a drug carrier for theranostics.

Upregulation of highly reactive oxygen species (ROS) such as hypochlorite (ClO–) is associated with many pathological conditions including cardiovascular diseases, neuron degeneration, lung injury, and cancer. However, real-time imaging of ClO–is limited to the probes generally relying on fluorescence with shallow tissue-penetration depth. We here propose a self-assembly approach to develop activatable and degradable photoacoustic (PA) nanoprobes for in vivoimaging of ClO–. A near-infrared absorbing amphiphilic oligomer is synthesized to undergo degradation in the presence of a specific ROS (ClO–), which integrates a π-conjugated but ClO–oxidizable backbone with hydrophilic PEG side chains. This molecular architecture allows the oligomer to serve as a degradable nanocarrier to encapsulate the ROS-inert dye and self-assemble into structurally stable nanoparticles through both π–π stacking and hydrophobic interactions. The self-assembled nanoprobe exhibits sensitive and specific ratiometric PA signals toward ClO–, permitting ratiometric PA imaging of ClO–in the tumor of living mice.

•A bionic spider web microchannel structure design method was proposed.•Structural parameters and flow parameters was investigated.•Parameter coupling characteristics were analyzed and fitting equation was obtained.

The adverse effects of chronic heat stress (CHS)-induced fatty liver syndrome on laying hens during the egg-producing stages have been wildly documented. However, until nowadays, the CHS responses of growing laying hens as well as its alleviating effects of vitamin C are rarely reported. In this study, 12-wk-old laying hens were subjected to CHS at 36 °C for 10 h/d for 3 wk with or without dietary supplementation of 300 mg/kg vitamin C. Results showed that CHS significantly impaired the growth performances and the liver functions of birds, as characterized by reduced feed intake and body weight, increased hepatic lipid accumulation and serum concentrations of TG, ALT, and AST, as well as the abnormal expression patterns of the lipid metabolism-related genes. Vitamin C supplementation successfully mitigated the lipid accumulation, while showing no alleviating effect on the serum contents of ALT or AST, which are two key indicators of liver functions. Metabolomic analysis based on UPLC-Q-TOF/MS identified 173 differential metabolites from the HS and HSV group samples, and they are mainly enriched in the pathways related to the cellular components, vitamin and amino acid metabolism and energy substance metabolism. The results indicate that CHS-induced hepatic lipid deposition in growing laying hens is effectively alleviated by dietary supplementation of vitamin C, which is probably resulted from the alterations of hepatocellular metabolic patterns.The findings in this study not only extend our understandings about the CHS responses of growing laying hens, but also provide new clues and experimental basis for the salvaging of CHS and FLS disease in the poultry industry.Chronic heat stress (CHS)-induced fatty liver syndrome (FLS) is one of the major problems faced in poultry industry. However, the heat stress response as well as the alleviating strategies for growing laying hens is rarely concerned until nowadays. In this study, 12-wk-old laying hens were subjected to the CHS condition with or without dietary supplementation of 300 mg/kg vitamin C, we found that CHS can also remarkably impair the growth performance and liver functions and induce the hepatic lipid metabolism disorders in the growing laying hens. Vitamin C supplementation successfully mitigated the hepatic lipid accumulation, while showed no alleviating effect on the liver functions. Metabolomic analysis further identified 173 differential metabolites between CHS and HSV groups, which are mainly enriched in the pathways including the cellular components, vitamin and amino acid metabolism and the energy substance metabolism. The results suggest that vitamin C supplementation can effectively alleviate the hepatic lipid deposition in growing laying hens under CHS probably through altering their energy metabolism patterns.

High voltage polarization domains in functional dielectrics and the ability to orient them with an external applied electric field lead to the development of a variety of applications of energy conversion from energy harvesting to information storage and reading. Voids are often generated at the bond interface during the production process of polymer films, which can break down easily in the process of polarization with high voltage, but the voids inside dielectric materials play an important role in charge storage and maintenance if the materials are oriented to the application of electrostatic generator, sensor, actuator and transducer etc. Meanwhile, a polymer matrix doped with a small amount of nanoparticles can suppress charge formation and increase surface charge decay rate. Results obtained in this paper show that polymer materials with microvoids have better maintenance properties of space charge compared with nanocomposite polymer materials. The research result is of important reference value and practical significance in the field of insulation and applications of functional dielectric materials.

Objective: This study aimed to elucidate the antibacterial properties and therapeutic effect in refractory diabetic wound healing of a NanoAg-epidermal growth factor sustained-release carrier(NanoAg-EGF). Methods: as previous publishing, the sustained-release carrier of NanoAg-EGF can be conducted. The antibacterial properties and therapeutic effects of NanoAg-EGF were determined through in vitro bacterial growth inhibition experiments and in vivo wound healing experiments in diabetic rats. Results: In antibacterial experiments, NanoAg-EGF had strong properties of antibacterial which is similar to those of NanoAg (p>0.05). In diabetic wound healing experiments, NanoAg-EGF significantly shortened the wound healing time. Furthermore, at 3 days after wounding, the healing rate of each group was no different (p>0.05). However, at 7 and 13 days after wounding, with being higher than other four groups, the healing rates of sustained-release carrier treated diabetic rats were remarkable (p<0.05). Conclusion: NanoAg-EGF not only has good antibacterial properties, but can also promote rapid wound healing in diabetes.

A facile bottom-up method is reported here for the fabrication of N-doped graphene for oxygen reduction. It consists of a two-step calcination strategy and uses α-hydroxy acids (AHAs) as carbon source and melamine as nitrogen source. Three different AHAs, malic acid, tartaric acid, and citric acid, were chosen as the carbon sources. The prepared N-doped graphenes have a typical thin layered structure with a large specific surface area. It was found that the N content in the obtained N-doped graphenes varies from 4.12 to 8.11 at. % depending on the AHAs used. All of the samples showed high performance in oxygen reduction reaction (ORR). The N-doped graphene prepared from citric acid demonstrated the highest electrocatalytic activity, which is comparable to the commercial Pt/C and exhibited good durability, attributing to the high pyridinic N content in the composite.