Radiotherapy Resistance of 3D Bioprinted Glioma via ITGA2/p-AKT Signaling Pathway.

Due to the inherent radiation tolerance, patients who suffered from glioma frequently encounter tumor recurrence and malignant progression within the radiation target area, ultimately succumbing to treatment ineffectiveness. The precise mechanism underlying radiation tolerance remains elusive due to the dearth of in vitro models and the limitations associated with animal models. Therefore, a bioprinted glioma model is engineered, characterized the phenotypic traits in vitro, and the radiation tolerance compared to 2D ones when subjected to X-ray radiation is assessed. By comparing the differential gene expression profiles between the 2D and 3D glioma model, identify functional genes, and analyze distinctions in gene expression patterns. Results showed that 3D glioma models exhibited substantial alterations in the expression of genes associated with the stromal microenvironment, notably a significant increase in the radiation tolerance gene ITGA2 (integrin subunit A2). In 3D glioma models, the knockdown of ITGA2 via shRNA resulted in reduced radiation tolerance in glioma cells and concomitant inhibition of the p-AKT pathway. Overall, 3D bioprinted glioma model faithfully recapitulates the in vivo tumor microenvironment (TME) and exhibits enhanced resistance to radiation, mediated through the ITGA2/p-AKT pathway. This model represents a superior in vitro platform for investigating glioma radiotherapy tolerance.

Molecular Crystals Constructed by Polar Molecular Cages: A Promising System for Exploring High-performance Infrared Nonlinear Optical Crystals.

Polar molecular crystals, with their densely stacked polar nonlinear optical (NLO) active units, are favored for their large second harmonic generation (SHG) responses and birefringence. However, their potential for practical applications as Infrared (IR) NLO materials has historically been underappreciated due to the weak inter-molecular interaction forces that may compromise their physicochemical properties. In this study, we propose molecular crystals with polar molecular cages as a treasure-house for the development of superior IR NLO materials and a representative system, binary chalcogenide molecular crystals, composed of [P4 Sn ] (n=3-9) polar molecular cages, is introduced. These crystals may not only achieve wide band gap, large SHG response, and birefringence in a single structure, but also exhibit favorable physicochemical properties. We subsequently obtained a polar molecular crystal, α-P4 S5 , which demonstrated exceptional IR optical properties, including a strong SHG response (1.1×AGS), wide band gap (3.02 eV), large birefringence (0.134@2050 nm), and a broad transmission range (0.41-14.7 µm). Moreover, it showed excellent water resistance and hardness. These findings highlight the potential of polar molecular crystals as a promising platform for the development of high-performance IR NLO materials.

Mg(C3 O4 H2 )(H2 O)2 : A New Ultraviolet Nonlinear Optical Material Derived from KBe2 BO3 F2 with High Performance and Excellent Water-Resistance.

Acquiring high-performance ultraviolet (UV) nonlinear optical (NLO) materials that simultaneously exhibit a strong second harmonic generation (SHG) coefficients, as short as possible SHG phase-matching (PM) wavelength and non-hygroscopic properties has consistently posed a significant challenge. Herein, through multicomponent modification of KBe2 BO3 F2 (KBBF), an excellent UV NLO crystal, Mg(C3 O4 H2 )(H2 O)2 , was successfully synthesized in malonic system. This material possesses a unique 2D NLO-favorable electroneutral [Mg(C3 O4 H2 )3 (H2 O)2 ]∞ layer, resulting in the rare coexistence of a strong SHG response of 3×KDP (@1064 nm) and short PM wavelength of 200 nm. More importantly, it exhibits exceptional water resistance, which is rare among ionic organic NLO crystals. Theoretical calculations revealed that its excellent water-resistant may be originated from its small available cavity volumes, which is similar to the famous LiB3 O5 (LBO). Therefore, excellent NLO properties and stability against air and moisture indicate it should be a promising UV NLO crystal.

Two-dimensional TiO nanosheets with photothermal effects for wound sterilization.

To combat multidrug-resistant bacteria, researchers have poured into the development and design of antimicrobial agents. Here, low-cost two-dimensional (2D) antibacterial material titanium monoxide nanosheets (TiO NSs) were prepared by an ultrasonic-assisted liquid-phase exfoliation method. When cultured with bacteria, TiO NSs showed intrinsic antimicrobial capacity, possibly due to membrane damage caused by the sharp edges of TiO NSs. Under near-infrared (NIR) laser irradiation, TiO NSs showed high photothermal conversion efficiency (PTCE) and sterilization efficiency. By combining these two antibacterial mechanisms, TiO NSs exhibited a strong killing effect on Gram-negative Escherichia coli (E. coli) and Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). Especially after treatment with TiO NSs (150 µg mL-1) +near-infrared (NIR) light irradiation, both bacteria were completely killed. In vivo experiments on wound repair of bacterial infection further confirmed its antibacterial effect. In addition, TiO NSs had no obvious toxicity or side effects, so as a kind of broad-spectrum 2D antibacterial nanoagent, TiO NSs have broad application prospects in the field of pathogen infection.

Cu-GA-coordination polymer nanozymes with triple enzymatic activity for wound disinfection and accelerated wound healing.

During the past few years, bacterial infection and oxidative stress have become important issues for wound healing. However, the emergence of numerous drug-resistant superbugs has had a serious impact on the treatment of infected wounds. Presently, the development of new nanomaterials has become one of the most important approaches to the treatment of drug-resistant bacterial infections. Herein, coordination polymer copper-gallic acid (Cu-GA) nanorods with multi-enzyme activity is successfully prepared for efficient wound treatment of bacterial infection, which can effectively promote wound healing. Cu-GA can be efficiently prepared by a simple solution method and had good physiological stability. Interestingly, Cu-GA shows enhanced multienzyme activity (peroxidase, glutathione peroxidase, and superoxide dismutase), which can produce a large number of reactive oxygen species (ROS) under acidic conditions while scavenging ROS under neutral conditions. In acidic environment, Cu-GA possesses POD (peroxidase)-like and glutathione peroxidase (GSH-Px)-like catalytic activities that is capable of killing bacteria; but in neutral environment, Cu-GA exhibits superoxide dismutase (SOD)-like catalytic activity that can scavenge ROS and promote wound healing. In vivo studies show that Cu-GA can promote wound infection healing and have good biosafety. Cu-GA contributes to the healing of infected wounds by inhibiting bacterial growth, scavenging reactive oxygen species, and promoting angiogenesis. STATEMENT OF SIGNIFICANCE: Cu-GA-coordinated polymer nanozymes with multienzyme activity were successfully prepared for efficient wound treatment of bacterial infection, which could effectively promote wound healing. Interestingly, Cu-GA exhibited enhanced multienzyme activity (peroxidase, glutathione peroxidase, and superoxide dismutase), which could produce a large number of reactive oxygen species (ROS) under acidic conditions and scavenge ROS under neutral conditions. In vitro and in vivo studies demonstrated that Cu-GA was capable of killing bacteria, controlling inflammation, and promoting angiogenesis.

Design of the Ionic Organic Nonlinear Optical Material NH4 [LiC3 H(CH3 )O4 ] with Ultrawide Band Gap and Moderate Birefringence.

Ionic organic crystals containing organic planar π-conjugated units has become one of the hot spots as nonlinear optical (NLO) materials. However, although this type of ionic organic NLO crystals commonly have remarkable second harmonic generation (SHG) responses, they also suffer from overlarge birefringences and relatively small band gaps that be hardly beyond 6.2 eV. Herein, a flexible π-conjugated [C3 H(CH3 )O4 ]2- unit was theoretically revealed, showing great potential for designing NLO crystals with balanced optical properties. Accordingly, through the reasonable NLO-favourable layered design, a new ionic organic material, NH4 [LiC3 H(CH3 )O4 ], was successfully obtained. As expected, it achieves not only a large SHG effect (4×KDP), but also a suitable birefringence (0.06@546 nm) and an ultrawide band gap (>6.5 eV). This study provides a new flexible π-conjugated NLO-active unit, contributing to design more ionic organic NLO materials with excellent balanced optical properties.

Crosstalk between microglia and neural stem cells influences the relapse of glioblastoma in GBM immunological microenvironment.

Interactions between immunocytes and Neural Stem Cells (NSCs) in glioblastoma multiforme still remains unclear. Here, microglial cells and NSCs in peri-tumoral tissue were analyzed via single-cell whole-transcriptome sequencing. Results showed that two clusters of putative NSCs (the EGFR+BCAN+ cell cluster, and the FABPT+H19+ cell cluster) exhibited immune-related functions. Two clusters of putative microglia (the XIST+PDK4+ and APOC1+CCL3+ cell clusters) exhibited the function of glial cell activation. The results of ligand receptor network analysis disclosed significant interactions between the APOC1+CCL3+ microglia and the NSCs. Correlation analysis on the overall survival (OS) and relapse-free survival (RFS) with 102 potential molecular targets in the TCGA database showed that a much larger number of molecules were correlated with RFS than with OS (34.31% vs. 8.82%), nine of them were validated in clinical specimens. In conclusion, crosstalk between APOC1+CCL3+ microglia and multiple molecule-labeled NSCs distal to the tumor core play certain roles on the recurrence of GBM.

Intense d-p Hybridization in Nb3 O15 Tripolymer Induced the Largest Second Harmonic Generation Response and Birefringence in Germanates.

We herein report two asymmetric germanate crystals, KNbGe3 O9 and K3 Nb3 Ge2 O13 , with different structures and optical properties derived from divergent polymerized forms of GeO4 and NbO6 groups. Remarkably, K3 Nb3 Ge2 O13 achieved a rare combination of the strongest second harmonic generation (SHG) response of 17.5×KDP @ 1064 nm and the largest birefringence of 0.196 @ 546 nm in germanates. It features unique [Nb3 O12 ]∞ tubular chains constructed by circular Nb3 O15 tripolymers. Theoretical calculations reveal that the d-p interactions in the Nb3 O15 group are responsible for outstanding optical properties. This work emphasizes the significance of the polymerizable functional units in obtaining high-performance nonlinear optical (NLO) crystals.

NaHSO4·H2O: A Promising Deep-Ultraviolet Nonlinear-Optical Bisulfate with Large Birefringence and a Second-Harmonic-Generation Effect.

Searching on the functional building units with ultrawide band gaps, large hyperpolarizabilities, and strong anisotropies is the key to finding new deep-ultraviolet (DUV) nonlinear-optical (NLO) materials. In this study, the polar covalent tetrahedral unit [SO3(OH)]- is studied by theoretical calculation and its excellent DUV optical properties are revealed. Moreover, we thoroughly investigate the known bisulfates, finding a promising DUV NLO crystal, NaHSO4·H2O. It exhibits a large second-harmonic-generation (SHG) response of 1.5 times that of KH2PO4 and a short cutoff edge (shorter than 190 nm). Meanwhile, it has the largest birefringence of 0.042 at 546 nm among the DUV NLO sulfates. Our study suggests that bisulfates should be fresh and ideal DUV NLO candidates.

Directional Construction of New Nonlinear Optical Bifunctional Units through Molecular Engineering Design Inspired by the B3O7-Typed Configuration.

Studies on new functional structural units with both large hyperpolarizability and high anisotropy are essentially important for finding high-performance nonlinear optical (NLO) materials and enriching the material systems. Under the guidance of the "structure-analogue" strategy, the work utilizes the molecular engineering approach to direct the construction of target units, BC2N5O2 and B(C2N5)2 units. The BC2N5O2 unit with a highly analogous structure to the B3O7 group and its derivate B(C2N5)2 unit with a configuration of B5O10 group are designed as NLO-active units. Furthermore, two compounds with these new NLO-active units, BC2N5H6(OH)2·H2O (I) and B(C2N5H6.5)2(NO3)2 (II), are synthesized, successfully. These compounds exhibit excellent properties with second-harmonic generation (SHG) responses ranging from 0.5 to 5.9 times that of KDP and large birefringence (ΔnI = 0.181 @ 546.1 nm and ΔnII = 0.148 @ 546.1 nm). Theoretical calculations prove that the BC2N5O2 and B(C2N5)2 units make great contributions to the SHG effects and birefringence, which confirms that the BC2N5O2 and B(C2N5)2 units are novel NLO bifunctional units and could be excellent fundamental building blocks to construct amounts of novel NLO and birefringence crystals. Our studies would enlighten the research studies on biguanide complexes of boron.

A flexible functional module to regulate ultraviolet optical nonlinearity for achieving a balance between a second-harmonic generation response and birefringence.

Rigid planar π-conjugated groups are adopted for designing ultraviolet (UV) nonlinear optical (NLO) materials extensively. However, for these UV NLO crystals, the realization of a strong second harmonic generation (SHG) response is commonly accompanied by undesired overlarge birefringence. Herein, we propose a new functional gene, the flexible π-conjugated (C3H2O4)2- group, for designing a UV NLO crystal with a balance between the SHG response and birefringence. Furthermore, the combination of low-coordinated and high-coordinated alkali cations with the flexible (C3H2O4)2- group results in finding a new mixed alkali malonate, KLi(C3H2O4)·H2O (KLMW). As expected, KLMW exhibits a strong SHG efficiency (3 × KDP) and moderate birefringence (0.103 @ 1064 nm). In addition, it has a short UV cut-off edge of 231 nm and can be conveniently grown from solution. More importantly, it realized fourth harmonic generation with type-I phase-matching. Therefore, these excellent properties make KLMW a potential practical UV NLO material.

Uncovering a Vital Band Gap Mechanism of Pnictides.

Pnictides are superior infrared (IR) nonlinear optical (NLO) material candidates, but the exploration of NLO pnictides is still tardy due to lack of rational material design strategies. An in-depth understanding structure-performance relationship is urgent for designing novel and eminent pnictide NLO materials. Herein, this work unravels a vital band gap mechanism of pnictides, namely P atom with low coordination numbers (2 CN) will cause the decrease of band gap due to the delocalization of non-bonding electron pairs. Accordingly, a general design paradigm for NLO pnictides, ionicity-covalency-metallicity regulation is proposed for designing wide-band gap NLO pnictides with maintained SHG effect. Driven by this idea, millimeter-level crystals of MgSiP2 are synthesized with a wide band gap (2.34 eV), a strong NLO performance (3.5 x AgGaS2 ), and a wide IR transparency range (0.53-10.3 µm). This work provides an essential guidance for the future design and synthesis of NLO pnictides, and also opens a new perspective at Zintl chemistry important for other material fields.

Sulfamide: A Promising Deep-Ultraviolet Nonlinear Optical Crystal Assembled from Polar Covalent [SO2 (NH2 )2 ] Tetrahedra.

For the first time, the polar covalent tetrahedron [SO2 (NH2 )2 ] is revealed as a new deep-ultraviolet (DUV) nonlinear optical (NLO)-active unit according to theoretical calculations. Furthermore, sulfamide consisting of polar [SO2 (NH2 )2 ] units was confirmed as an excellent candidate as a DUV NLO crystal. Sulfamide provides the optimal balance between composition, structure, and properties, in addition to a very short absorption of 160 nm. It achieves multiple optical performance records for non-π-conjugated DUV NLO materials, including the strongest second harmonic generation (SHG) efficiency (about 4 times that of KDP), the largest birefringence (obv.: 0.07@589.3 nm) and the shortest SHG wavelength predicted as 188 nm.

Central ß-turn increases the cell selectivity of imperfectly amphipathic α-helical peptides.

Although membrane lytic antimicrobial peptides (AMPs) show enormous potential for addressing mounting global antibiotic resistance, therapeutic applications are hindered by their weak antimicrobial activity, high toxicity, salt sensitivity and poor understanding of structure-activity relationships. To investigate the effects of different parameters on the biological activities of AMPs, a rational approach was adopted to design a series of short cationic α-helical peptides comprising the Ac-WxKyWxzzyKxWyK-NH2 sequence, where x: cationic residues (Arg or Lys), y: hydrophobic residues (Ala, Val, Ile or Leu), and zz: ß-turn (rigid D-Pro-Gly turn or flexible Gly-Gly turn). The peptides showed a more helical structure as the concentration of membrane-mimetic solution increased. The peptide RL with a central D-Pro-Gly turn (x: Arg, y: Lys, zz = D-Pro-Gly) exhibited broad-spectrum antimicrobial activities (2-8 µM) against ten types of clinically relevant microorganisms and even maintained its activity in the presence of physiological salts and showed excellent selectivity toward bacterial cells over human red blood cells and mammalian cells. However, the toxicity was increased after the removal of D-Pro-Gly turn. Additionally, the bactericidal activity was reduced when the D-Pro-Gly turn was replaced by a Gly-Gly turn. Fluorescence spectroscopy and electron microscopy analyses indicated that RL and its derivatives killed microbial cells by permeabilizing the cell membrane and damaging membrane integrity. In conclusion, these findings clearly generalized a potential method for designing or optimizing AMPs, and the peptide RL is a promising therapeutic candidate to combat antibiotic resistance. STATEMENT OF SIGNIFICANCE: We proposed a rational approach to design imperfectly amphiphilic peptides and identified RL (Ac-WRKLWRpGLKRWLK-NH2) in particular that shows strong antibacterial properties, low toxicity and high salt resistance. The ß-turn unit inserted into the central position of cationic α-helical peptides, especially the D-Pro-Gly turn, significantly increase the cell selectivity of the synthetic amphiphiles. The findings demonstrate a potential method for designing and/or optimizing AMPs, which would facilitate the development of strategies to design peptide-based antimicrobial biomaterials in a variety of biotechnological and clinical applications.