Ablative Radiotherapy Reprograms the Tumor Microenvironment of a Pancreatic Tumor in Favoring the Immune Checkpoint Blockade Therapy

The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.     

Lithiation MXene Derivative Skeletons for Wide-Temperature Lithium Metal Anodes

Lithium (Li) metal, as an appealing candidate for the next-generation of high-energy-density batteries, is plagued by its safety issue mainly caused by uncontrolled dendrite growth and infinite volume expansion. Developing new materials that can improve the performance of Li-metal anode is one of the urgent tasks. Herein, a new MXene derivative containing pure rutile TiO₂ and N-doped carbon prepared by heat-treating MXene under a mixing gas, exhibiting high chemical activity in molten Li, is reported. The lithiation MXene derivative with a hybrid of LiTiO₂-Li₃N-C and Li offers outstanding electrochemical properties. The symmetrical cell assembling lithiation MXene derivative hybrid anode exhibits an ultra-long cycle lifespan of 2000 h with an overpotential of ≈30 mV at 1 mA cm⁻², which overwhelms Li-based anodes reported so far. Additionally, long-term operations of 34, 350, and 500 h at 10 mA cm⁻² can be achieved in symmetrical cells at temperatures of −10, 25, and 50 °C, respectively. Both experimental tests and density functional theory calculations confirm that the LiTiO₂-Li₃N-C skeleton serves as a promising host for Li infusion by alleviating volume variation. Simultaneously, the superlithiophilic interphase of Li₃N guides Li deposition along the LiTiO₂-Li₃N-C skeleton to avoid dendrite growth.     

Ratiometric Detection of Glutathione Based on Disulfide Linkage Rupture between a FRET Coumarin Donor and a Rhodamine Acceptor

Abnormal levels of glutathione, a cellular antioxidant, can lead to a variety of diseases. We have constructed a near-infrared ratiometric fluorescent probe to detect glutathione concentrations in biological samples. The probe consists of a coumarin donor, which is connected through a disulfide-tethered linker to a rhodamine acceptor. Under the excitation of the coumarin donor at 405 nm, the probe shows weak visible fluorescence of the coumarin donor at 470 nm and strong near-infrared fluorescence of the rhodamine acceptor at 652 nm due to efficient Forster resonance energy transfer (FRET) from the donor to the acceptor. Glutathione breaks the disulfide bond through reduction, which results in a dramatic increase in coumarin fluorescence and a corresponding decrease in rhodamine fluorescence. The probe possesses excellent cell permeability, biocompatibility, and good ratiometric fluorescence responses to glutathione and cysteine with a self-calibration capability. The probe was utilized to ratiometrically visualize glutathione concentration alterations in HeLa cells and Drosophila melanogaster larvae.     

Effect of microwave heating time on the gel properties of chicken myofibrillar proteins and their formation mechanism

The present work was conducted to illustrate the mechanism of gel formation of myofibrillar proteins (MPs) under different microwave heating times. The results showed that the denaturation enthalpy (ΔH) of the MPs significantly decreased when the heating time increased from 3 to 9 s and then completely disappeared as the heating time progressed, indicating that the MPs gradually denatured and subsequently aggregated with increasing heating time, which was further verified by the changes in the secondary structure, electrophoretic bands, and gel properties (e.g., water holding capacity and textural profiles) of the MPs. Microstructural images indicated that the MP gel formed under 12 s had the most compact network, indicating that extended microwave heating time could induce quality deterioration of MP gels. Moreover, the hydrophobic forces, electrostatic forces, and disulphide bonds of the MPs gradually intensified with increasing microwave heating time, suggesting that both non-covalent and covalent bonds could promote molecular denaturation and subsequent aggregation of MPs. In addition, correlation analysis revealed that the changes in the molecular conformation of MPs induced by different microwave heating times could effectively regulate the formation of MP gels and their related properties.     

Interfacial microstructure and mechanical properties of Ti3SiC2 ceramic and TC11 alloy joint diffusion bonded with a Cu interlayer

Reliable joints of Ti₃SiC₂ ceramic and TC11 alloy were diffusion bonded with a 50 μm thick Cu interlayer. The typical interfacial structure of the diffusion boned joint, which was dependent on the interdiffusion and chemical reactions between Al, Si and Ti atoms from the base materials and Cu interlayer, was TC11/α-Ti + β-Ti + Ti₂Cu + TiCu/Ti₅Si₄ + TiSiCu/Cu(s, s)/Ti₃SiC₂. The influence of bonding temperature and time on the interfacial structure and mechanical properties of Ti₃SiC₂/Cu/TC11 joint was analyzed. With the increase of bonding temperature and time, the joint shear strength was gradually increased due to enhanced atomic diffusion. However, the thickness of Ti₅Si₄ and TiSiCu layers with high microhardness increased for a long holding time, resulting in the reduction of bonding strength. The maximum shear strength of 251 ± 6 MPa was obtained for the joint diffusion bonded at 850 °C for 60 min, and fracture primarily occurred at the diffusion layer adjacent to the Ti₃SiC₂ substrate. This work provided an economical and convenient solution for broadening the engineering application of Ti₃SiC₂ ceramic.     

Effects of (Li0.5Sm0.5)/W co-substitution and sintering temperature on the structure and electrical properties of ultrahigh Curie temperature piezoceramics,Ca0.92(Li0.5Sm0.5)0.08Bi2Nb2-xWxO9

With co-substitution of (Li_0.5Sm_0.5) at A site and W at B site, the electrical properties of modified Ca_0.92(Li_0.5Sm_0.5)_0.08Bi₂Nb_2-xW_xO₉ [(CLS)BN-xW, x = 0, 0.015 and 0.03] piezoceramics with ultrahigh Curie temperature (T_C) of > 930 °C were enhanced dramatically. The increased resistivity induced by the co-substitution ensure them to be polarized under an enough high field. Combined with the increase of spontaneous ferroelectric polarization (P_S), the significant enhancements in the piezoelectric, dielectric and ferroelectric properties can be obtained in the composition x = 0.015. Furthermore, the piezoelectric activity (d₃₃) and bulk resistivity (ρ_b) of (CLS)BN-0.015 W can be further enhanced at an appropriate sintering temperature. This optimum composition sintered at 1170 °C shows ultrahigh T_C of ～948 °C, d₃₃ of ～17.3 pC/N and ρ_b of ～6.9 MΩ cm at 600 °C, which are comparable to those of the reported high-temperature Aurivillius piezoceramics with T_C > 850 °C.     

Structural Aspects and Prediction of Calmodulin-Binding Proteins

Calmodulin (CaM) is an important intracellular protein that binds Ca²⁺ and functions as a critical second messenger involved in numerous biological activities through extensive interactions with proteins and peptides. CaM’s ability to adapt to binding targets with different structures is related to the flexible central helix separating the N- and C-terminal lobes, which allows for conformational changes between extended and collapsed forms of the protein. CaM-binding targets are most often identified using prediction algorithms that utilize sequence and structural data to predict regions of peptides and proteins that can interact with CaM. In this review, we provide an overview of different CaM-binding proteins, the motifs through which they interact with CaM, and shared properties that make them good binding partners for CaM. Additionally, we discuss the historical and current methods for predicting CaM binding, and the similarities and differences between these methods and their relative success at prediction. As new CaM-binding proteins are identified and classified, we will gain a broader understanding of the biological processes regulated through changes in Ca²⁺ concentration through interactions with CaM.     

Effects of Cu on the corrosion behavior and microstructure of Mg–Zn–Ca bulk metallic glass

For the purpose of developing biodegradable magnesium alloys with suitable properties for biomedical applications, Mg–Zn–Ca–Cu metallic glasses were prepared by copper mold injection methods. In the present work, the effect of Cu doping on mechanical properties, corrosion behavior, and glass-forming ability of Mg₆₆Zn₃₀Ca₄ alloy was studied. The experimental findings demonstrated that the incorporation of Cu decreases the corrosion resistance of alloys, but increases the microhardness and degradation rate slightly. However, the addition of a trace amount of Cu can make the samples have antibacterial properties. Therefore, Mg–Zn–Ca–Cu has great advantages in clinical implantation and is the potential implant material.     

Enhanced electrochemical performance of LiNi0.8Co0.1Mn0.1O2 via titanium and boron co-doping

Titanium and boron are simultaneously introduced into LiNi_0.8Co_0.1Mn_0.1O₂ to improve the structural stability and electrochemical performance of the material. X-ray diffraction studies reveal that Ti⁴⁺ ion replaces Li⁺ ion and reduces the cation mixing; B³⁺ ion enters the tetrahedron of the transition metal layers and enlarges the distance of the [LiO₆] layers. The co-doped sample has spherical secondary particles with elongated and enlarged primary particles, in which Ti and B elements distribute uniformly. Electrochemical studies reveal the co-doped sample has improved rate performance (183.1 mAh·g^-1 at 1 C and 155.5 mAh·g^-1 at 10 C) and cycle stability (capacity retention of 94.7% after 100 cycles at 1 C). EIS and CV disclose that Ti and B co-doping reduces charge transfer impedance and suppresses phase change of LiNi_0.8Co_0.1Mn_0.1O_2.