The emerging metasurfaces with the exceptional capability of manipulating an arbitrary wavefront have revived the holography with unprecedented prospects. However, most of the reported metaholograms ...suffer from limited polarization controls for a restrained bandwidth in addition to their complicated meta-atom designs with spatially variant dimensions. Here, we demonstrate a new concept of vectorial holography based on diatomic metasurfaces consisting of metamolecules formed by two orthogonal meta-atoms. On the basis of a simply linear relationship between phase and polarization modulations with displacements and orientations of identical meta-atoms, active diffraction of multiple polarization states and reconstruction of holographic images are simultaneously achieved, which is robust against both incident angles and wavelengths. Leveraging this appealing feature, broadband vectorial holographic images with spatially varying polarization states and dual-way polarization switching functionalities have been demonstrated, suggesting a new route to achromatic diffractive elements, polarization optics, and ultrasecure anticounterfeiting.
The emerging meta-holograms rely on arrays of intractable meta-atoms with various geometries and sizes for customized phase profiles that can precisely modulate the phase of a wavefront at an optimal ...incident angle for given wavelengths. The stringent and band-limited angle tolerance remains a fundamental obstacle for their practical application, in addition to high fabrication precision demands. Utilizing a different design principle, we determined that facile metagrating holograms based on extraordinary optical diffraction can allow the molding of arbitrary wavefronts with extreme angle tolerances (near-grazing incidence) in the visible-near-infrared regime. By modulating the displacements between uniformly sized meta-atoms rather than the geometrical parameters, the metagratings produce a robust detour phase profile that is irrespective of the wavelength or incident angle. The demonstration of high-fidelity meta-holograms and in-site polarization multiplexing significantly simplifies the metasurface design and lowers the fabrication demand, thereby opening new routes for flat optics with high performances and improved practicality.
Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of ...this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness.
Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored.
IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects.
Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.
Acute pancreatitis (AP) is a sudden inflammatory reaction, caused by the activation of pancreatic enzymes in the pancreas, and in severe cases can lead to systemic inflammation and multiple organ ...failure. Oxidative stress contributed to the further deterioration of inflammation and played an important role in AP development. Bilirubin has been found to exert antioxidative, anti-inflammatory, and anti-apoptotic effects in a series of diseases accompanied by a high level of oxidative stress. However, the therapeutic effects of bilirubin for AP management have not yet been demonstrated. Additionally, the poor solubility and potential toxicity of bilirubin also limit its application. Thus, we developed bilirubin encapsulated silk fibrin nanoparticles (BRSNPs) to study the protective effects and mechanisms of bilirubin nanomedicine for the treatment of AP. BRSNPs could selectively delivery to the inflammatory lesion of the pancreas and release bilirubin in an enzyme-responsive manner. In the model of AP caused by L-Arginine hyperstimulation, BRSNPs exerted strong therapeutic effects against AP by the reduction of oxidative stress, decreased expression of pro-inflammatory cytokines, and impaired recruitment of macrophages and neutrophils. The mechanism study indicated that BRSNPs protected acinar cells against extensive oxidative damage and inflammation through inhibiting NF-κB pathway and activating the Nrf2/HO-1 pathway. Collectively, for the first time, this study demonstrated that bilirubin nanomedicine, BRSNPs, are effective in alleviating experimental acute pancreatitis, and the mechanisms are associated with its inhibition of NF-κB regulated pro-inflammatory signaling and activation of Nrf2-regulated cytoprotective protein expression.
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•Bilirubin nanomedicine holds potent therapeutic potentials aginst acute pancreatitis.•Silk firboin based nanoparticle release the bilirubin in an enzyme resposnive manner.•Bilirubin nanomedicine selectively accumulate at the inflammatory pancreas.•Bilirubin nanomedicine suppressed oxidative stress by activating Nrf2/HO-1 pathway.•Bilirubin nanomedicine reduced inflammation by inhibiting NF-κB pathway.
Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus. The combination of insulin (Ins) with liraglutide (Lir) has a greater potential for preventing DN than ...monotherapy. However, the renal protective effect of the combined Ins/Lir therapy is largely compromised due to their short half-lives after subcutaneous injection. Herein, a glucose-responsive hydrogel was designed in situ forming the dynamic boronic esters bonds between phenylboronic acid-grafted γ-Polyglutamic acid (PBA-PGA) and konjac glucomannan (KGM). It was hypothesized that the KGM/PBA-PGA hydrogel as the delivery vehicle of Ins/Lir would enhance the combinational effect of the latter on preventing the DN progress. Scan electronic microscopy and rheological studies showed that KGM/PBA-PGA hydrogel displayed good glucose-responsive property. Besides, the glucose-sensitive release profile of either Ins or Lir from KGM/PBA-PGA hydrogel was uniformly displayed at hyperglycemic level. Furthermore, the preventive efficacy of KGM/PBA-PGA hydrogel incorporating insulin and liraglutide (Ins/Lir-H) on DN progress was evaluated on streptozotocin-induced rats with diabetic mellitus (DM). At 6 weeks after subcutaneous injection of Ins/Lir-H, not only the morphology of kidneys was obviously recovered as shown by ultrasonography, but also the renal hemodynamics was significantly improved. Meanwhile, the 24-h urinary protein and albumin/creatinine ratio were well modulated. Inflammation and fibrosis were also largely inhibited. Besides, the glomerular NPHS-2 was obviously elevated after treatment with Ins/Lir-H. The therapeutic mechanism of Ins/Lir-H was highly associated with the alleviation of oxidative stress and activation of autophagy. Conclusively, the better preventive effect of the combined Ins/Lir via KGM/PBA-PGA hydrogel on DN progress was demonstrated as compared with their mixed solution, suggesting KGM/PBA-PGA hydrogel might be a potential vehicle of Ins/Lir to combat the progression of DN.
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Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes ...treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated β-cyclodextrin (β-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host–guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.
Diabetic wounds are challenging to heal due to complex pathogenic abnormalities. Routine treatment with acid fibroblast growth factor (aFGF) is widely used for diabetic wounds but hardly offers a ...satisfying outcome due to its instability. Despite the emergence of various nanoparticle-based protein delivery approaches, it remains challenging to engineer a versatile delivery system capable of enhancing protein stability without the need for complex preparation. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and Epigallocatechin-3-gallate (EGCG) was constructed and applied in the healing of diabetic wounds. First, the binding patterns of EGCG and aFGF were predicted by molecular docking analysis. Then, the characterizations demonstrated that AE-NPs displayed higher stability in hostile conditions than free aFGF by enhancing the binding activity of aFGF to cell surface receptors. Meanwhile, the AE-NPs also had a powerful ability to scavenge reactive oxygen species (ROS) and promote angiogenesis, which significantly accelerated full-thickness excisional wound healing in diabetic mice. Besides, the AE-NPs suppressed the early scar formation by improving collagen remodeling and the mechanism was associated with the TGF-β/Smad signaling pathway. Conclusively, AE-NPs might be a potential and facile strategy for stabilizing protein drugs and achieving the scar-free healing of diabetic wounds.
Diabetic chronic wound is among the serious complications of diabetes that eventually cause the amputation of limbs. Herein, a polyphenol-driven facile assembly of nanosized coacervates (AE-NPs) composed of aFGF and EGCG was constructed. The EGCG not only acted as a carrier but also possessed a therapeutic effect of ROS scavenging. The AE-NPs enhanced the binding activity of aFGF to cell surface receptors on the cell surface, which improved the stability of aFGF in hostile conditions. Moreover, AE-NPs significantly accelerated wound healing and improved collagen remodeling by regulating the TGF-β/Smad signaling pathway. Our results bring new insights into the field of polyphenol-containing nanoparticles, showing their potential as drug delivery systems of macromolecules to treat diabetic wounds.
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Owing to its good air stability and high refractive index, two-dimensional (2D) noble metal dichalcogenide shows intriguing potential for versatile flat optics applications. However, light field ...manipulation at the atomic scale is conventionally considered unattainable because the small thickness and intrinsic losses of 2D materials completely suppress both resonances and phase accumulation effects. Here, we demonstrate that losses of structured atomically thick PtSe2 films integrated on top of a uniform substrate can be utilized to create the spots of critical coupling, enabling singular phase behaviors with a remarkable π phase jump. This finding enables the experimental demonstration of atomically thick binary meta-optics that allows an angle-robust and high unit thickness diffraction efficiency of 0.96%/nm in visible frequencies (given its thickness of merely 4.3 nm). Our results unlock the potential of a new class of 2D flat optics for light field manipulation at an atomic thickness.
Oocyte-specific deletion of ovarian genes using Cre/loxP technology provides an excellent tool to understand their physiological
roles during folliculogenesis, oogenesis, and preimplantation ...embryonic development. We have generated a transgenic mouse
line expressing improved Cre recombinase (iCre) driven by the mouse growth differentiation factor-9 ( GDF-9 ) promoter. The resulting transgenic mouse line was named GDF-9-iCre mice. Using the floxed ROSA reporter mice, we found that Cre recombinase was expressed in postnatal ovaries, but not in heart, liver, spleen, kidney,
and brain. Within the ovary, the Cre recombinase was exclusively expressed in the oocytes of primordial follicles and follicles
at later developmental stages. The expression of iCre of GDF-9-iCre mice was shown to be earlier than the Cre expression of Zp3Cre and Msx2Cre mice, in which the Cre gene is driven by zona pellucida protein 3 ( Zp3 ) promoter and a homeobox gene Msx2 promoter, respectively, in the postnatal ovary. Breeding wild-type males with heterozygous floxed germ cell nuclear factor (GCNF) females carrying the GDF-9-iCre transgene did not produce any progeny having the floxed GCNF allele, indicating that complete deletion of the floxed GCNF allele can be achieved in the female germline by GDF-9-iCre mice. These results suggest that GDF-9-iCre mouse line provides an excellent genetic tool for understanding functions of oocyte-expressing genes involved in folliculogenesis,
oogenesis, and early embryonic development. Comparison of the ontogeny of the Cre activities of GDF-9-iCre, Zp3Cre, and Msx2Cre transgenic mice shows there is sequential Cre activity of the three transgenes that will allow inactivation of a target gene
at different points in folliculogenesis.
•A study considering the effect of structural columns on masonry structures.•A model to reflect the nonlinear behavior of the masonry wall.•Parametric analysis on the seismic performance of masonry ...structures.
Masonry structures often exhibit poor seismic performance during earthquakes owing to their low material strength, structural integrity, and ductility. To address the mechanism of in-plane damage and collapse of masonry walls subjected to earthquake ground motion, three full-size brick walls, one with structural columns and two without structural columns, were designed and constructed in this experimental study to quantitatively investigate the effect of structural columns on the seismic performance of masonry walls. Quasi-static tests of masonry walls subjected to cyclic lateral loading were conducted using electrohydraulic servo actuators. The in-plane damage evolution and failure mode of the masonry walls under lateral loading were investigated. A numerical model with a novel plastic damage constitutive model of masonry was established. The accuracy of this model and the calculation results were verified by comparing them with the crack development and mechanical property curves obtained from the experiments. Based on the numerical model, a parametric analysis was conducted to investigate the influence of critical factors, such as mortar strength, vertical load, and height-to-width ratio, on the seismic performance of masonry structures. The test results showed that structural columns can effectively improve the performance of masonry structures. Properly installed structural columns can improve the peak load-bearing capacity, ductility, and energy dissipation of masonry structures. The masonry damage constitutive model used in this study could simulate the damage to masonry wall specimens well and reflect the hysteretic curves of the specimens within an acceptable range of accuracy. Thus, it provides a valuable reference for physical experiments. An appropriate mortar strength and vertical compressive stress can effectively enhance the load-bearing capacity of masonry structures within a certain range. For structural column walls. Walls with mortar strengths (average compressive strength) of 12.5 MPa, 10 MPa, 7.5 MPa, and 5 MPa showed an increase in peak bearing capacity of 26.2 %, 23.9 %, 18.5 %, and 9.4 %, respectively, compared to walls with mortar strengths (average compressive strength) of 2.5 Mpa. The aspect ratio had a significant impact on the shear load-bearing capacity of the masonry walls. An increase in the aspect ratio led to a transition from shear failure to flexural failure and a subsequent decrease in shear load-bearing capacity. For masonry walls with structural columns, increasing the diameter of the longitudinal steel in the structural columns can enhance the load-bearing capacity of the masonry wall, resulting in a significant improvement in its overall performance.
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