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Global pandemics caused by viruses cause widespread panic and economic losses. The lack of specific antivirals and vaccines increases the spreading of viral diseases worldwide. Thus, alternative strategies are required to manage viral outbreaks. Here, we develop a CRISPR activation (CRISPRa) system based on polymeric carriers to prevent respiratory virus infection in a mouse model. A polyaspartate grafted with 2-(diisopropylamino) ethylamine (DIP) and nuclear localization signal peptides (NLS-MTAS fusion peptide) was complexed with plasmid DNA (pDNA) encoding dCas9-VPR and sgRNA targeting IFN-λ. The pH-sensitive DIP and NLS-MTAS groups were favor of endo-lysosomal escape and nuclear localization of pDNA, respectively. They synergistically improved gene transfection efficiency, resulting in significant reporter gene expression and IFN-λ upregulation in lung tissue. In vitro and in vivo prophylactic experiments showed that the non-viral CRISPRa system could prevent infection caused by H1N1 viruses with minimal inflammatory responses, presenting a promising prophylactic approach against respiratory virus infections.

In this paper, we consider double ramification cycles with orbifold targets. An explicit formula for double ramification cycles with orbifold targets, which is parallel to and generalizes the one known for the smooth case, is provided. Some applications for orbifold Gromov--Witten theory are also included., Comment: 49 pages; typo fixed; overall expression improved; comments are welcome!

Mixed-space cluster expansion (MSCE), a first-principles method to simultaneously model the configuration-dependent short-ranged chemical and long-ranged strain interactions in alloy thermodynamics, has been successfully applied to binary FCC and BCC alloys. However, the previously reported MSCE method is limited to binary alloys with cubic crystal symmetry on a single sublattice. In the current work, MSCE is generalized to systems with multiple sublattices by formulating compatible reciprocal space interactions and combined with a crystal-symmetry-agnostic algorithm for the calculation of constituent strain energy. This generalized approach is then demonstrated in a hypothetical HCP system and Mg-Zn alloys. The current MSCE can significantly improve the accuracy of the energy parameterization and account for all the fully relaxed structures regardless of lattice distortion. The generalized MSCE method makes it possible to simultaneously analyze the short- and long-ranged configuration-dependent interactions in crystalline materials with arbitrary lattices with the accuracy of typical first-principles methods.

Sustainable intensification needs to optimize irrigation and fertilization strategies while increasing crop yield. To enable more precision and effective agricultural management, a bi-level screening and bi-level optimization framework is proposed. Irrigation and fertilization dates are obtained by upper-level screening and upper-level optimization. Subsequently, due to the complexity of the problem, the lower-level optimization uses a data-driven evolutionary algorithm, which combines the fast non-dominated sorting genetic algorithm (NSGA-II), surrogate-assisted model of radial basis function and Decision Support System for Agrotechnology Transfer to handle the expensive objective problem and produce a set of optimal solutions representing a trade-off between conflicting objectives. Then, the lower-level screening quickly finds better irrigation and fertilization strategies among thousands of solutions. Finally, the experiment produces a better irrigation and fertilization strategy, with water consumption reduced by 44%, nitrogen application reduced by 37%, and economic benefits increased by 7 to 8%.

Deparia chinensis (Ching) X.S.Guo & C.Du in Chen (2016: 18). ≡ Dryoathyrium chinense Ching in Jin (1988: 36). Lectotype (designated by Hsu and Kuo in Kuo et al. 2018):— CHINA. Chongqing [Szechuan]: Chengkou [Chen-kou Hsien], 2100 m, 17 October 1958, T. L.Tai 106702 (PE barcode 00049936 [photo!], isolectotypes HNWP barcode 0219360 [photo!], IBK barcode 00034139 [photo!], IBSC barcode 0676556 [photo!], NAS barcode 00082856 [photo!], PE barcode 00049937 [photo!], SZ barcodes 00149268 [photo!] & 00149269 [photo!], WUK barcode 0130652 [photo!]). – Dryoathyrium chinense Ching (1974: 214), not validly published, with two gatherings indicated as types, contrary to Art. 40.2. – Dryoathyrium chinense Ching in Hsieh (1985: 153), not validly published, with the identity of the type not explicitly indicated, contrary to Art. 40 Note 2. – Deparia chinensis (Ching) Z.R.Wang in He et al. (2013: 422), new combination not validly published, with incorrect reference to basionym, contrary to Art. 41.5. – Deparia chinensis (Ching) T.C.Hsu & L.Y.Kuo in Kuo et al. (2018: 651), isonym., Published as part of Zhang, Jian-Hang, Du, Cheng, Applequist, Wendy L. & Liao, Shuai, 2023, An overview on the valid publication and typification of Dryoathyrium chinense and Deparia chinensis (Athyriaceae, Aspleniineae, Polypodiales), pp. 67-69 in Phytotaxa 579 (1) on page 68, DOI: 10.11646/phytotaxa.579.1.8, http://zenodo.org/record/7532153, {"references":["Chen, Y. - S. (2016) The Checklist of Shaanxi Vascular Plants. Higher Education Press, Beijing, 525 pp.","Jin, S. - Y. (1988) Bibliography of new taxa (Cormophytes) and type specimens in the herbaria of China (I). Bulletin of Botanical Research, Harbin, Supplement: 1 - 117.","Kuo, L. - Y., Ebihara, A., Hsu, T. - C., Rouhan, G., Huang, Y. - M., Wang, C. - N., Chiou, W. - L. & Kato, M. (2018) Infrageneric Revision of the Fern Genus Deparia (Athyriaceae, Aspleniineae, Polypodiales). Systematic Botany 43: 645 - 655. https: // doi. org / 10.1600 / 036364418 X 697364","Ching, R. - C. (1974) Dryoathyrium Ching. In: Editorial Committee of Flora Tsinlingensis (Eds.) Flora Tsinlingensis 2. Science Press, Beijing, pp. 100 - 101 & 213 - 215.","Hsieh, Y. - T. (1985) The taxonomy of Dryoathyrium Ching in China. Bulletin of Botanical Research, Harbin 5 (3): 147 - 157. Available from: https: // bbr. nefu. edu. cn / CN / abstract / abstract 1781. shtml (accessed 12 January 2022)","He, Z. - R., Wang, Z. - R. & Kato, M. (2013) Deparia Hooker & Greville. In: Wu, Z. - Y., Raven, P. H. & Hong, D. - Y. (Eds.) Flora of China 2 - 3. Science Press, Beijing & Missouri Botanical Garden Press, St. Louis, pp. 418 - 442. Available from: http: // www. efloras. org / florataxon. aspx? flora _ id = 2 & taxon _ id = 109640 (accessed 12 January 2022)"]}

Background: Edible fungi (mushrooms) have attracted much more concerns due to their abundant nutritions and functional bioactive substances like polysaccharides. Objective: In this study, the anti-oxidation and anti-aging activities of polysaccharide fraction (LDP-1) from the wild Lactarius deliciosus fruiting bodies were systematically evaluated using Caenorhabditis elegans (C. elegans) as a model. Methods: Lifetime determination of C. elegans (survival status) was observed via microscope. Effects of LDP-1 on C. elegans induced by heat and oxidative stress were, respectively, performed in an artificial climate chamber and Juglone solution. Determination of lipofuscin levels in C. elegans was observed by laser confocal scanning microscopy. Determination of reactive oxygen species in C. elegans in vivo was conducted via fluorescence spectrophotometer reader. Results: The results revealed that LDP-1 could significantly extend the lifespan of C. elegans, and the lifetime of C. elegans treated with 1,000 μg/mL LDP-1 could be prolonged by 32.8% compared with the control. The survival rates of the experimental C. elegans under heat shock and oxidative stress conditions were clearly improved after treated with 1,000 μg/mL LDP-1 (40 and 19.8%, respectively), while under the same circumstances all the C. elegans in the blank group died. Fluorescence microscopy analysis confirmed that LDP-1 could effectively reduce the accumulation of lipofuscin and reactive oxygen free radicals in C. elegans, where the respective maximum reduction reached 22.8 and 42.7% compared with the control. Conclusion: These results indicate that LDP-1 had favorable antioxidant and anti-aging effects, which could be explored as potential dietary additives to renovate oxidative damage and slow down aging process.

Ophthalmologic care is inaccessible to many people due to a variety of factors, including the availability of providers, cost of equipment for ophthalmologic care, and transportation to clinics and appointments. Because many causes of blindness are both highly prevalent and preventable once identified, it is essential to address gaps in care for underserved populations. We developed a novel 3D-printed mobile retinal camera. In this study, we organized recurring student-run screening events around New York City that took place in community centers and churches, at which we utilized our device to take retinal images. Our screening events reached a diverse population of New Yorkers, disproportionately those with lower household income, many of whom had not had recent eye exams. To validate the device for use in telehealth ophthalmologic visits, we transmitted the images to a remote ophthalmologist for evaluation and compared the result with an on-site attending physician's dilated eye exam. The subjective assessment indicated that 97% of images captured with the mobile retinal camera were acceptable for telehealth analysis. Remote image assessment by achieved 92% sensitivity and 83% specificity in detecting optic disc cupping, compared to the gold-standard on-site dilated eye exam. In addition, the device was portable, affordable, and able to be used by those with relatively little ophthalmologic training. We have demonstrated the utility of this affordable mobile retinal camera for telehealth ophthalmologic evaluation during community screening events that reached an underserved population to detect disease and connect with long-term care.

A component-optimized chemo-dynamic nanoagent achieved an enhanced tumour cell-selective chemo-dynamic therapy with minimal side effects in a glioma mouse model.

Background Achieving negative margins for melanoma in situ, lentigo maligna type can be challenging, particularly on cosmetically sensitive areas. Objective To assess the utility of intraoperative frozen section margin assessment using a teledermatopathology system in the treatment of head and neck lentigo maligna. Methods and materials Over a 6 year period, 96 patients with lentigo maligna had surgical excisions. The margins were assessed intraoperatively with frozen sections prepared in the manner used in Mohs surgery. The surgeon guided the frozen section slides around the margin while a dermatopathologist assessed the margin remotely. Results In 2/96 (2.1%) cases, the safety margin was positive (frozen sections were false negative). In 1 further case (1%) there was a recurrence of the melanoma 13 months following the excision. Conclusion The described method is effective in treating melanoma in situ, lentigo maligna type with clearance rates similar to previous studies for Mohs surgery.

Healing of large calvarial bone defects remains challenge but may be improved by stimulating bone regeneration of implanted cells. The aim of this study is to specially co-activate transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF-A) genes expressions in pre-osteoblast MC3T3-E1 cells through the non-viral CRISPR activation (CRISPRa) system to promote osteogenesis. A cationic copolymer carrying nucleus localizing peptides and proton sponge groups dimethyl-histidine was synthesized to deliver CRISPRa system into MC3T3-E1 cells with high cellular uptake, lysosomal escape, and nuclear translocation, which activated VEGF-A and TGF-β1 genes expressions and thereby additively or synergistically induced several osteogenic genes expressions. A tunable dual-crosslinked hydrogel was developed to implant the above engineered cells into mice calvaria bone defect site to promote bone healing

The therapeutic effect of photodynamic therapy (PDT) is highly dependent on the intracellular production of reactive oxygen species (ROS). However, the ROS generated by photosensitizers can be consumed by the highly concentrated glutathione (GSH) in tumor cells, severely impairing the therapeutic effect of PDT. Herein, we synthesized a GSH-scavenging copolymer to deliver photosensitizer chlorin e6 (Ce6). The pyridyl disulfide groups, which have faster reactivity with the thiol groups of GSH than other disulfide groups, were grafted onto a hydrophobic block to encapsulate the Ce6. Under NIR irradiation, the Ce6 generated ROS to kill tumor cells, and the pyridyl disulfide groups depleted the GSH to prevent ROS consumption, which synergistically enhanced the therapeutic effect of PDT.

Fungi play an important role in dying wastewater treatment. In this work, the mycelia of Lactarius deliciosus exhibited an excellent capacity in decolorizing coomassie brilliant blue (CBB). The results demonstrated that the mycelia could treat CBB with high concentrations over a broad range of pH and temperature. The decolorization rate of 99.19% and the removal rate of 16.31 mg·L−1·h were realized. The mycelia could be recycled from decolorizing process for 19 times, indicating a good re-usability. It verified that the lignin peroxidase (121.65 U·L−1) and manganese peroxidase (36.77 U·L−1) were involved in the degradation and decolorization process of CBB. Toxicity assessments indicated the seed germination rate was up to 82.22% while inhibition to Escherichia coli decreased dramatically and no significant effect on Caenorhabditis elegans growth was found. The removal of CBB was a synergistic process accomplished by adsorption and biodegradation. The mycelia could be used for eco-friendly CBB treatment.

In this study, the deposition and characteristics of Si- and Ti-series multilayer coatings with respective glass/Si3N4/NiCr/Ag/NiCr/Si3N4 and glass/TiO2/ZnSnO3/ZnO/Ag/NiCrOx/ZnSnO3/Si3N4 structures were investigated. Experimental analyses were performed, and the optical performance and thermal stability of the coatings were assessed. The as-deposited Si- and the Ti-series samples exhibited optimal shading coefficient of 0.49 and 0.57, respectively. Thermal annealing in air was performed to analyze the thermal stability and oxidation resistance of the samples. The Si- and Ti-series samples prevented the failure of low-emissivity properties at 700 and 600 °C, respectively. In addition to high transparency, the Si-series samples exhibited improved low-emissivity properties, reduced light pollution, and superior thermal stability compared to the Ti-series samples. The use of Si3N4 and NiCr layers effectively prevented the oxidation and cracking of the Ag layer upon heat treatment. This study presents the characteristics of Si- and Ti-series samples for energy-saving building applications.

SUMMARYInformation flow through neural circuits is continuously modified by context-dependent learning. In the nematode Caenorhabditis elegans, pairing specific odors with food deprivation results in aversion to the odor. Here we identify cell-specific mechanisms of insulin/IGF receptor signaling that integrate sensory information with food context during aversive olfactory learning. Using a conditional allele of the insulin/IGF receptor DAF-2, we show that aversive learning to butanone, an odor sensed only by the AWCON olfactory neuron, requires DAF-2 in AWCON. Learning requires an axonally-localized DAF-2c isoform and the insulin receptor substrate (IRS) protein IST-1, but is partly independent of the FoxO transcription factor DAF-16. Upon food deprivation, the unconditioned stimulus for learning, DAF-2 expression increases post-transcriptionally through an insulin- and ist-1-dependent process. Aversive learning suppresses odor-regulated glutamate release from AWCON in wild-type animals but not in ist-1 mutants, suggesting that localized insulin signaling drives presynaptic depression to generate an aversive memory.

Nasopharyngeal carcinoma (NPC) has a 10–15% recurrence rate, while no long term or durable treatment options are currently available. Single-cell profiling in recurrent NPC (rNPC) may aid in designing effective anticancer therapies, including immunotherapies. For the first time, we profiled the transcriptomes of ∼60,000 cells from four primary NPC and two rNPC cases to provide deeper insights into the dynamic changes in rNPC within radiation fields. Heterogeneity of both immune cells (T, natural killer, B, and myeloid cells) and tumor cells was characterized. Recurrent samples showed increased infiltration of regulatory T cells in a highly immunosuppressive state and CD8+ T cells in a highly cytotoxic and dysfunctional state. Enrichment of M2-polarized macrophages and LAMP3+ dendritic cells conferred enhanced immune suppression to rNPC. Furthermore, malignant cells showed enhanced immune-related features, such as antigen presentation. Elevated regulatory T cell levels were associated with a worse prognosis, with certain receptor-ligand communication pairs identified in rNPC. Even with relatively limited samples, our study provides important clues to complement the exploitation of rNPC immune environment and will help advance targeted immunotherapy of rNPC.

Supplementary Material 1

Insulin/insulin-like growth factor (IGF) receptor signaling (IIS) supports context-dependent learning in vertebrates and invertebrates. Here, we identify cell-specific mechanisms of IIS that integrate sensory information with food context to drive synaptic plasticity and learning. In the nematode Caenorhabditis elegans, pairing food deprivation with an odor such as butanone suppresses attraction to that odor. We find that aversive olfactory learning requires the insulin receptor substrate (IRS) protein IST-1 and atypical signaling through the insulin/IGF-1 receptor DAF-2. Cell-specific knockout and rescue demonstrate that DAF-2 acts in the AWC

Although small interfering RNA (siRNA) therapy has achieved great progress, unwanted gene inhibition in normal tissues severely limits its extensive clinical applications due to uncontrolled siRNA biodistribution. Herein, a spatially controlled siRNA activation strategy is developed to achieve tumor-specific siRNA therapy without gene inhibition in the normal tissues. The quaternary ammonium moieties are conjugated to amphiphilic copolymers via reactive oxygen species (ROS)-sensitive thioketal (TK) linkers for co-delivery of siRNA and photosensitizer chlorin e6 (Ce6), showing excellent siRNA complexation capacity and near infrared (NIR)-controlled siRNA release. In the normal tissue, siRNAs are trapped and degraded in the endo-lysosomes due to the unprotonatable property of quaternary ammonium moiety, showing the siRNA activity "off" state. When NIR irradiation is spatially applied to the tumor tissue, the NIR irradiation/Ce6-induced ROS trigger siRNA endo-lysosomal escape and cytosolic release through the photochemical internalization effect and cleavage of TK bonds, respectively, showing the siRNA activity "on" state. The siRNA-mediated glutathione peroxidase 4 gene inhibition enhances ROS accumulation. The synergistic antitumor activity of Ce6 photodynamic therapy and gene inhibition is confirmed in vivo. Spatially controlled tumor-specific siRNA activation and co-delivery with Ce6 using unprotonatable and ROS-sensitive cationic nanocarriers provide a feasible strategy for tumor-specific siRNA therapy with synergistic drug effects.

Liver disease, particularly viral hepatitis and hepatocellular carcinoma (HCC), is a global healthcare burden and leads to more than 2 million deaths per year worldwide. Despite some success in diagnosis and vaccine development, there are still unmet needs to improve diagnostics and therapeutics for viral hepatitis and HCC. The emerging clustered regularly interspaced short palindromic repeat/associated proteins (CRISPR/Cas) technology may open up a unique avenue to tackle these two diseases at the genetic level in a precise manner. Especially, liver is a more accessible organ over others from the delivery point of view, and many advanced strategies applied for nanotheranostics can be adapted in CRISPR‐mediated diagnostics or liver gene editing. In this review, the focus is on these two aspects of viral hepatitis and HCC applications. An overview on CRISPR editor development and current progress in clinical trials is first given, followed by highlighting the recent advances integrating the merits of gene editing and nanotheranostics. The promising systems that are used in other applications but may hold potentials in liver gene editing are also discussed. This review concludes with the perspectives on rationally designing the next‐generation CRISPR approaches and improving the editing performance., Herein, the clustered regularly interspaced short palindromic repeat (CRISPR) nanotheranostics developed for viral hepatitis and hepatocellular carcinoma are reviewed, and rational design considerations for the next‐generation nanomedicine approaches to advance liver gene editing are discussed, highlighting their significances in clinical applications.

The controllable degradation of silica nanoparticles in anticancer therapy remains challenging. Here, we offer the first report that a thioketal (TK)-bond-containing bridged organoalkoxysilane has been synthesized. This allows for the fabrication of reactive oxygen species (ROS)-sensitive, degradable, bridged silsesquioxane nanoparticles (BS-NPs). These TK-bridged BS-NPs have a uniform size of 50 nm and are able to encapsulate a small molecule drug - metformin - using a reverse micro-emulsion method. After surface modification with a targeting peptide (RGD), these metformin-loaded BS-NPs exhibited a homologous tumor aggregation ability, leading to the efficient transport of metformin into the tumor cells. When combined with a clinically feasible fasting therapy, the RGD-decorated, metformin-loaded, ROS-responsive degradable BS-NPs remarkably increased the tumor sensitivity to metformin by 10 times compared with free metformin. The synergistic effects of metformin-loaded BS-NPs and fasting-induced hypoglycemia were verified through in vitro and in vivo experiments. This effect occurred by down-regulating the expression of pro-survival proteins pGSK3β and MCL-1. Collectively, these results demonstrate that the ROS-sensitive organosilica nanocarrier is a promising nanoplatform for drug delivery and provides an alternative approach for the combinatorial therapy of metformin and fasting therapy.

A systematic study of the effect of Al2O3 doping concentration in targets on the structure and optoelectronic characteristics of sputtered MgZnO films was conducted. The films were prepared on glass substrates by radio frequency magnetron sputtering from a MgZnO target mixed with 0–4 wt.% Al2O3. X-ray diffraction analysis demonstrated that the Al-doped MgZnO films had a highly (002) preferred orientation with only one intense diffraction peak. The electrical properties of the Al-doped MgZnO films were dependent on the Al2O3 concentration. Optimal results of Al-doped MgZnO films were obtained at an Al2O3-doping concentration of 2 wt.%, with low resistivity of 2.82 × 10−3 Ω-cm and high transmittance of 91% in the visible region. Outstanding electrical properties were achieved because of the significantly increased carrier concentration. The optical bandgap of the Al-doped MgZnO films showed a short-wavelength shift with increased Al2O3-doping concentration. The low electrical resistivity and high transparency of Al-doped MgZnO films indicated their potential as transparent conductive oxide window materials for UV optoelectronic devices.

The clustered regularly interspaced short palindromic repeats (CRISPR)/associated protein 9 (CRISPR/Cas9) gene editing technology, as a revolutionary breakthrough in genetic engineering, offers a promising platform to improve the treatment of various genetic and infectious diseases because of its simple design and powerful ability to edit different loci simultaneously. However, failure to conduct precise gene editing in specific tissues or cells within a certain time may result in undesirable consequences, such as serious off-target effects, representing a critical challenge for the clinical translation of the technology. Recently, some emerging strategies using genetic regulation, chemical and physical strategies to regulate the activity of CRISPR/Cas9 have shown promising results in the improvement of spatiotemporal controllability. Herein, in this review, we first summarize the latest progress of these advanced strategies involving cell-specific promoters, small-molecule activation and inhibition, bioresponsive delivery carriers, and optical/thermal/ultrasonic/magnetic activation. Next, we highlight the advantages and disadvantages of various strategies and discuss their obstacles and limitations in clinical translation. Finally, we propose viewpoints on directions that can be explored to further improve the spatiotemporal operability of CRISPR/Cas9.

The evolutions of the surface morphologies, cross-sectional microstructures, and mechanical properties of two types of Ag-based alloy wires with different Au contents under a 105 A/cm2 electrical current density across various times were compared in this study. Ag-based alloy wires that contain 8 wt% Au and 15 wt% Au with 3 wt% Pd were produced via rapid drawing and multiple annealing processes to replace commercial Au-bonded wires in the electronic packaging industry. The surface morphologies of these wires were revealed by scanning electron microscopy (SEM), and cross-sectional microstructures were analyzed by electron back scattering diffraction (EBSD). The SEM observations showed grain- and step-like structures in the Ag–8Au–3Pd and Ag–15Au–3Pd wires after a 5-h treatment, respectively. EBSD results revealed a change in the main preferred orientation from slender grains to equiaxed grains because the high-angle grain boundaries (HAGB) were reduced, and the twin boundaries (TB) were multiplied along the drawing direction. In terms of mechanical properties, Ag–15Au–3Pd wire showed better breaking loads and elongations than Ag–8Au–3Pd wire. The Au effect in Ag-based alloy wires reduced the atomic diffusion to stabilize grain structures and induce a dislocation accumulation, which subsequently improved the mechanical properties by retaining and forming HAGBs, LAGBs, and TBs under high current stressing.

Zn–Ti–O films were co-sputtered from Zn and Ti targets and then annealed at temperatures ranging from 600 °C to 900 °C for 2 h under an air atmosphere. The [Ti]/([Ti]+[Zn]) ratio decreased from 75.52 to 28.26 as the Zn-target power increased from 25 W to 75 W. The phase transition of the films strongly depended on the [Ti]/([Ti]+[Zn]) ratio. High [Ti]/([Ti]+[Zn]) ratios led to the coexistence of ZnTiO3, Zn2Ti3O8, and rutile TiO2 phases. Zn2Ti3O8 gradually became the major crystalline phase as the [Ti]/([Ti]+[Zn]) ratio and rutile TiO2 and ZnTiO3 phases decreased. The aforementioned phases disappeared when the [Ti]/([Ti]+[Zn]) ratio was especially low. In their place, Zn2TiO4 and even ZnO phases developed. The dielectric constant of the films increased with increasing [Ti]/([Ti]+[Zn]) ratio. However, extremely high [Ti]/([Ti]+[Zn]) ratios increased the dielectric loss of the films. The film mainly composed of the Zn2Ti3O8 phase exhibited optimal dielectric properties, including a dielectric constant and loss equal to 40.1 and 0.0304, respectively, at 1 MHz.

In this study, solitary waves passing over a submerged breakwater are investigated both experimentally and numerically. A total of 9 experimental conditions are carried out, including different incident wave heights and water depths. Numerical simulations are performed using a high-order finite-difference model solving Navier-Stokes (N-S) equations. The predicted water wave elevation, velocity and pressure show good agreement with experimental data, verifying the accuracy and capacity of the numerical model. Furthermore, parametric studies are conducted by numerical modelling to examine the effects of the geometrical features of submerged dike on hydrodynamic characteristics around the breakwater.

Among various inflammatory factors/mediators, autocrine and paracrine prostaglandin 2 (PGE2), which are abundant in various tumors, promote the proliferation and chemoresistance of cancer cells. Th...

The mushroom polysaccharides are important substances with variety of functions, especially to the human body's immunomodulation effects. In this work, a polysaccharide fraction (LDP-1) was extracted and purified from the fruiting bodies of a rare wild Lactarius deliciosus. LDP-1 with molecular weight of 9.8 × 105 Da showed an obvious immunological activity to the RAW 264.7 cells. It had no significant suppressive but promotive effects on proliferation of the macrophages. The production of nitric oxide (NO) presented a concentration-dependent manner after treated with the LDP-1, and the maximum yield of NO was 39.15 μM. LDP-1 could promote the phagocytic uptake ability of the RAW 264.7 cells significantly, and many of the antennas produced around the cells correspondingly. The cytokines of TNF-α, IL-1β and IL-6 were secreted increasingly in a concentration-dependent manner, which were 4.83, 17.8 and 11 times than that of the control, respectively. Western blotting analysis confirmed that NF-κB levels in the nucleus were increased while cytoplasmic inhibitor of NF-κB (IκB-α) degraded after treated with the LDP-1, indicating the RAW 264.7 cells probably be stimulated by LDP-1 through activating the IκB-α-NF-κB pathway. These results demonstrated that LDP-1 could be used as a kind of immunomodulatory agent for healthcare potentially.

In this study, the microstructure and performance of different Ag-based conductive wires were investigated. Ag-based wires that contain 8, 15, 20, and 28 wt% Au were produced by multiple drawing and rapid annealing processes to substitute commercial gold wires in electronic packaging industries. The cross-sectional gain structures observed using focused ion beam showed the formation of a slender granular structure at the center, and the outer portion changed from equiaxed to elongated grains with the increase in Au content. High-resolution transmission electron microscopy showed a remarkable decrease in the twin thickness and stacking defect of 9R structures dissociated from incoherent twin boundaries. Electron backscatter diffraction analysis revealed that slender grains at the center showed strong crystallographic orientation, and the equiaxed grains near the surface were in the preferred orientation. The high Au solute concentration in Ag-based wires induced strong interaction on dislocations, thereby resulting in the formation of low-angle grain boundaries (LAGBs) and nano-twins. Ternary Ag-based alloy wires exhibited high strength and hardness but low conductivity and elongation with the increase in Au content because relatively the high LAGB density and Au solute atoms caused strengthening and electron scattering.

A novel heteroglycan TLH-G was successfully isolated from Tricholoma lobayense cultivated in south China. TLH-G was composed of five monosaccharides, namely, mannose, rhamnose, glucuronic acid, glu...

Xiaoxia Li,1,* Hong Xiao,1,* Chaowen Lin,2,3,* Weitong Sun,1 Teng Wu,1 Jin Wang,4 Bin Chen,3 Xia Chen,2 Du Cheng1 1PCFM Lab of Ministry of Education, School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 510275, People’s Republic of China; 2Department of Cardiovascular Medicine, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, People’s Republic of China; 3Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, People’s Republic of China; 4Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, People’s Republic of China *These authors contributed equally to this work Background: Atherosclerosis is a major cardiovascular disease that causes ischemia of the heart, brain, or extremities, and can lead to infarction. The hypolipidemic agent atorvastatin calcium (Ato) alleviates atherosclerosis by reducing plasma lipid and inflammatory factors. However, the low bioavailability of Ato limits its widespread use and clinical effectiveness. Curcumin (Cur), a natural polyphenol with antioxidation and anti-inflammation bioactivities, has potential anti-atherosclerosis activity and may reduce Ato-induced cytotoxicity.Materials and methods: Liposomes modified using a targeting ligand (E-selectin-binding peptide) were prepared to co-deliver Ato and Cur to dysfunctional endothelial cells (ECs) overexpressing E-selectin. Molecules involved in the inhibition of adhesion (E-selectin and intercellular cell adhesion molecule-1 [ICAM-1]) and inflammation (IL-6 and monocyte chemotactic protein 1 [MCP-1]) in human aortic endothelial cells were evaluated using real-time quantitative PCR, flow cytometry, and immunofluorescence staining. The antiatherosclerosis effects of liposomes co-loaded with Ato and Cur invivo were evaluated using ApoE knockout (ApoE-/-) mice.Results: Targeted liposomes delivered Ato and Cur to dysfunctional ECs, resulting in synergistic suppression of adhesion molecules (E-selectin and ICAM-1) and plasma lipid levels. Moreover, this treatment reduced foam cell formation and the secretion of inflammatory factors (IL-6 and MCP-1) by blocking monocyte migration into the intima. In addition, Cur successfully reduced Ato-inducible cytotoxicity.Conclusion: Both invitro and invivo experiments demonstrated that cell-targeted co-delivery of Ato and Cur to dysfunctional ECs drastically reduces atherosclerotic lesions with fewer side effects than either Ato or Cur alone. Keywords: combined therapy, atorvastatin calcium, curcumin, antiatherosclerosis, targeted codelivery

Semiconducting polymer (SP) is a promising photothermal agent in the antitumor application, but the co-delivery of the second near-infrared window (NIR-II)-based SPs with chemotherapeutic drug (e.g., doxorubicin (DOX)) remains a challenge. Here, SPs were firstly improved via backbone and alkyl side-chain engineering, and afterward, SPs and pH-sensitive prodrug copolymer self-assembled into a nanoparticle for a photoacoustic (PA)-imaging guided combination of photothermal therapy and chemotherapy. SP-encapsulated nanoparticles exhibited a high photothermal conversion efficiency of 45% at a relatively low power level of NIR irradiation (0.3 W/cm2 for 5 min). DOX was rapidly released in response to the acidic lysosomal environment. PA and fluorescence imaging confirmed that the photothermal therapy effectively drove DOX penetration inside tumor tissue, and it resulted in the killing of the surviving tumor cells from hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo. Overall, the co-delivery of the SP and DOX using pH-sensitive nanoparticles represents a feasible strategy for photothermal therapy with potentially synergistic drug effects. Statement of significance Recent years have yielded great progress in semiconducting polymers (SPs)-based photothermal therapy for anticancer treatment. However, studies about molecular weight and side-chain of SPs on photothermal conversion efficiency are limited, and investigation of controlled codelivery with chemotherapeutic drug is lacking. Here, we improved the SPs performance via backbone and side-chain engineering, and afterward offered a pH-sensitive DOX-conjugated amphiphilic copolymer to encapsulate SPs. SP-encapsulated nanoparticles exhibited high photothermal conversion efficiency at a clinically feasible power level of NIR irradiation. NIR irradiation-generated hyperthermia not only killed tumor cells but also promoted DOX penetration inside the tumor tissue to ablate the tumor cells that survived hyperthermia. The synergistic effect of SP-based photothermal therapy and DOX-induced chemotherapy was verified in vivo.

Multi-element (CrHfNbTaTiVZr)N coatings were prepared through the magnetron sputtering of an equimolar CrHfNbTaTiVZr alloy target. This study determined the influences of N2-to-total (N2 + Ar) ratios (RN) on the composition, structure, mechanical properties, and electrical performance of the coatings. Coating thickness decreased from 898 nm to 128 nm with increasing RN from 0% to 100%. The alloy coating has bundles of fibrous structures with remarkable void boundaries. The coating changed from amorphous phase to face-centered cubic (FCC) phase with (111) preferred orientation, then to FCC phase with (200) preferred orientation, and finally to near-amorphous phase as RN increased from 0% to 100%. The microstructure of the nitride coatings transformed from a columnar structure with rough faceted tops and void boundaries into a dense and small structure with smooth domed tops. The grain size of the nitride coatings also decreased with RN. Accordingly, the electrical performance at high RN was poor. The nitride coating deposited at RN = 60% had the highest hardness of 16.6 GPa and the lowest friction coefficient of 0.52, owing to structural densification and grain refinement.

Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. MicroRNAs (miRNAs) are known to be important regulators of GC. This study aims to investigate the role of miRNA (miR)-497 in GC. We demonstrated that the expression of miR-497 was downregulated in human GC tissues. After N-methyl-N-nitrosourea treatment, the incidence of GC in miR-497 knockout mice was significantly higher than that in wild-type mice. miR-497 overexpression suppressed GC cell proliferation, cell-cycle progression, colony formation, anti-apoptosis ability, and cell migration and invasion capacity. Additionally, miR-497 overexpression decreased the expression levels of cell division cycle 42 (CDC42) and integrin β1 (ITGB1) and inhibited the phosphorylation of focal adhesion kinase (FAK), paxillin (PXN), and serine-threonine protein kinase (AKT). Furthermore, overexpression of miR-497 inhibited the metastasis of GC cells in vivo, which could be counteracted by CDC42 restoration. Furthermore, the focal adhesion of GC cells was found to be regulated by miR-497/CDC42 axis via ITGB1/FAK/PXN/AKT signaling. Collectively, it is concluded that miR-497 plays an important role in the repression of GC tumorigenesis and progression, partly via the CDC42/ITGB1/FAK/PXN/AKT pathway., Graphical abstract, This study reports that the defect in miR-497 promotes the malignant transformation of gastric epithelial cells, and miR-497 is a regulator for the CDC42/ITGB1/FAK/PXN/AKT pathway. These demonstrations provide a novel explanation of the tumorigenesis and progression of gastric cancer and provide clues for the prevention and treatment of this deadly disease.

Aluminum-doped zinc oxide (AZO) was cosputtered from ZnO and Al targets on glass substrates at room temperature. The effect of Al-target power and annealing atmosphere on structural and optoelectronic properties of AZO films was investigated.[Al]/[Zn] ratio increased to 0.258 when the Al-target power increased to 250 W. At a fixed Al-target power of 200 W, the [Al]/[Zn] ratio was 0.104 and the as-deposited AZO film demonstrated a low resistivity of 3.19 × 10−4 Ω-cm and high transmittance of approximately 90% in the visible region. After annealing at 500 °C in forming gas (5% H2 in Ar) atmosphere, the resistivity of the AZO film can be further reduced to 9.38 × 10−5 Ω-cm. Given its low-temperature process and good optoelectronic properties, sputtered AZO films that use ZnO and Al targets have high potential in various optoelectronic devices.

Background: Wingless and Int-related protein (Wnt) ligands were aberrantly expressed in human diseases. However, the aberrant level of Wnt ligands have not been explored in serum. Here, we aimed to identify the WNT4 level in serum and explore its oncogenic role in colorectal cancer (CRC). Methods: Serum samples from 40 CRC patients and 28 healthy donors were collected to measure the levels of WNT4. CRC tissue samples from patients were collected to explore the resource of WNT4. Further, we used CRC cells and xenograft mouse model to explore the oncogenic role of WNT4. Findings: WNT4 was significantly upregulated in serum of colorectal cancer (CRC) patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, the elevated WNT4 in serum was downregulated after tumor resection. Next, we found that WNT4 could contributed to epithelial-to-mesenchymal transition and activated fibroblasts by activating WNT4/β-catenin pathway in vitro and in vivo; besides, angiogenesis was also induced via WNT4/β-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a β-catenin/TCF inhibitor. Interpretation: These data indicated that WNT4 may be a potential biomarker for CRC and provided evidence to support a critical role of WNT4 in promoting CRC cell metastasis by inducing epithelial-to-mesenchymal transition, activating fibroblasts and promoting angiogenesis in the colorectal tumor microenvironment. Funding Statement: This work was supported by the National Natural Science Foundation of China (grant number 81672387 and 81770899). Declaration of Interests: No potential conflicts of interest were disclosed. Ethics Approval Statement: Informed consents were signed by those patients and healthy donors before sample collection. All works were approved by the ethics review board of Renmin Hospital of Wuhan University and carried out in compliance with the Declaration of Helsinki of the World Medical Association.

Background Wingless and Int-related protein (Wnt) ligands are aberrantly expressed in patients with colorectal cancer (CRC). However, the aberrant level of Wnt ligands in serum have not been explored. Here, we aimed to identify the levels of WNT4 in serum and explored its oncogenic role in CRC. Methods The Oncomine database was used to analyze the relationship between WNT4 and the prognosis of CRC. ELISA was performed to measure WNT4 levels in serum and conditioned medium from fresh CRC tissues and adjacent normal tissues. Western blot and immunohistochemistry were carried out to measure the expression of WNT4 in human CRC tissues and adjacent normal tissues. The migration and invasion of CRC cells were determined by trans-well assay, and the effects of WNT4 on CRC invasion and metastasis in vivo were verified by tumor xenograft in nude mice. Cancer-associated fibroblasts (CAFs) and angiogenesis in subcutaneous nodules were detected by immunofluorescence (IF). In addition, the suspended spheres formation and tube formation assay were performed to explore the effects of WNT4 on CAFs and angiogenesis respectively. Results WNT4 was significantly upregulated in serum of CRC patients, and CRC tissues were identified as an important source of elevated WNT4 levels in CRC patients. Interestingly, elevated levels of WNT4 in serum were downregulated after tumor resection. Furthermore, we found that WNT4 contributed to epithelial-to-mesenchymal transition (EMT) and activated fibroblasts by activating the WNT4/β-catenin pathway in vitro and in vivo. Moreover, angiogenesis was induced via the WNT4/β-catenin/Ang2 pathway. Those effects could be reversed by ICG-001, a β-catenin/TCF inhibitor. Conclusion Our findings indicated that serum levels of WNT4 may be a potential biomarker for CRC. WNT4 secreted by colorectal cancer tissues promote the progression of CRC by inducing EMT, activate fibroblasts and promote angiogenesis through the canonical Wnt/β-catenin signalling pathway.

Codelivery of CRISPR-Cas9 and chlorin e6 achieved spatially controlled tumor-specific gene editing with synergistic drug effects., Controlled release of CRISPR-Cas9 ribonucleoprotein (RNP) and codelivery with other drugs remain a challenge. We demonstrate controlled release of CRISPR-Cas9 RNP and codelivery with antitumor photosensitizer chlorin e6 (Ce6) using near-infrared (NIR)– and reducing agent–responsive nanoparticles in a mouse tumor model. Nitrilotriacetic acid–decorated micelles can bind His-tagged Cas9 RNP. Lysosomal escape of nanoparticles was triggered by NIR-induced reactive oxygen species (ROS) generation by Ce6 in tumor cells. Cytoplasmic release of Cas9/single-guide RNA (sgRNA) was achieved by reduction of disulfide bond. Cas9/sgRNA targeted the antioxidant regulator Nrf2, enhancing tumor cell sensitivity to ROS. Without NIR irradiation, Cas9 was degraded in lysosomes and gene editing failed in normal tissues. The synergistic effects of Ce6 photodynamic therapy and Nrf2 gene editing were confirmed in vivo. Controlled release of CRISPR-Cas9 RNP and codelivery with Ce6 using stimuli-responsive nanoparticles represent a versatile strategy for gene editing with potentially synergistic drug effects.