GO/Cu Nanosheet-Integrated Hydrogel Platform as a Bioactive and Biocompatible Scaffold for Enhanced Calvarial Bone Regeneration.

Purpose: The treatment of craniofacial bone defects caused by trauma, tumors, and infectious and degenerative diseases is a significant issue in current clinical practice. Following the rapid development of bone tissue engineering (BTE) in the last decade, bioactive scaffolds coupled with multifunctional properties are in high demand with regard to effective therapy for bone defects. Herein, an innovative bone scaffold consisting of GO/Cu nanoderivatives and GelMA-based organic-inorganic hybrids was reported for repairing full-thickness calvarial bone defect. Methods: In this study, motivated by the versatile biological functions of nanomaterials and synthetic hydrogels, copper nanoparticle (CuNP)-decorated graphene oxide (GO) nanosheets (GO/Cu) were combined with methacrylated gelatin (GelMA)-based organic-inorganic hybrids to construct porous bone scaffolds that mimic the extracellular matrix (ECM) of bone tissues by photocrosslinking. The material characterizations, in vitro cytocompatibility, macrophage polarization and osteogenesis of the biohybrid hydrogel scaffolds were investigated, and two different animal models (BALB/c mice and SD rats) were established to further confirm the in vivo neovascularization, macrophage recruitment, biocompatibility, biosafety and bone regenerative potential. Results: We found that GO/Cu-functionalized GelMA/ß-TCP hydrogel scaffolds exhibited evidently promoted osteogenic activities, M2 type macrophage polarization, increased secretion of anti-inflammatory factors and excellent cytocompatibility, with favorable surface characteristics and sustainable release of Cu2+. Additionally, improved neovascularization, macrophage recruitment and tissue integration were found in mice implanted with the bioactive hydrogels. More importantly, the observations of microCT reconstruction and histological analysis in a calvarial bone defect model in rats treated with GO/Cu-incorporated hydrogel scaffolds demonstrated significantly increased bone morphometric values and newly formed bone tissues, indicating accelerated bone healing. Conclusion: Taken together, this BTE-based bone repair strategy provides a promising and feasible method for constructing multifunctional GO/Cu nanocomposite-incorporated biohybrid hydrogel scaffolds with facilitated osteogenesis, angiogenesis and immunoregulation in one system, with the optimization of material properties and biosafety, it thereby demonstrates great application potential for correcting craniofacial bone defects in future clinical scenarios.

Lead-free ferroelectrics with giant unipolar strain for high-precision actuators.

The trade-off between electrostrain and strain hysteresis for piezo/ferroelectric materials largely restrains the development of high precision actuators and remains unresolved over the past few decades. Here, a simple composition of (Bi0.5Na0.5)1-x/100Srx/100TiO3 in the ergodic relaxor state is collaboratively designed through the segregated domain structure with the ferroelectric core, local polarization heterogeneity, and defect engineering. The ferroelectric core can act as a seed to facilitate the field-induced nonpolar-to-polar transition. Together with the internal bias field caused by defect dipoles and adjusted through electric field cycling and heat treatment technology, a giant unipolar strain of 1.03% is achieved in the x = 30 ceramic with a low hysteresis of 27%, while the electric-field-independent large-signal piezoelectric strain coefficient of ~1000 pm/V and ultralow hysteresis of <10% can be obtained in the x = 35 ceramic. Intriguingly, the low-hysteresis high strain also exhibits near-zero remnant strain, excellent temperature and cycling stability.

Improved Energy Density at High Temperatures of FPE Dielectrics by Extreme Low Loading of CQDs.

Electrostatic capacitors, with the advantages of high-power density, fast charging-discharging, and outstanding cyclic stability, have become important energy storage devices for modern power electronics. However, the insulation performance of the dielectrics in capacitors will significantly deteriorate under the conditions of high temperatures and electric fields, resulting in limited capacitive performance. In this paper, we report a method to improve the high-temperature energy storage performance of a polymer dielectric for capacitors by incorporating an extremely low loading of 0.5 wt% carbon quantum dots (CQDs) into a fluorene polyester (FPE) polymer. CQDs possess a high electron affinity energy, enabling them to capture migrating carriers and exhibit a unique Coulomb-blocking effect to scatter electrons, thereby restricting electron migration. As a result, the breakdown strength and energy storage properties of the CQD/FPE nanocomposites are significantly enhanced. For instance, the energy density of 0.5 wt% CQD/FPE nanocomposites at room temperature, with an efficiency (η) exceeding 90%, reached 9.6 J/cm3. At the discharge energy density of 0.5 wt%, the CQD/FPE nanocomposites remained at 4.53 J/cm3 with an efficiency (η) exceeding 90% at 150 °C, which surpasses lots of reported results.

Manganese self-boosting hollow nanoenzymes with glutathione depletion for synergistic cancer chemo-chemodynamic therapy.

Chemodynamic therapy (CDT) has outstanding potential as a combination therapy to treat cancer. However, the effectiveness of CDT in the treatment of solid tumors is limited by the overexpression of glutathione (GSH) in the tumor microenvironment (TME). GSH overexpression diminishes oxidative stress and attenuates chemotherapeutic drug-induced apoptosis in cancer cells. To counter these effects, a synergistic CDT/chemotherapy cancer treatment, involving the use of a multifunctional bioreactor of hollow manganese dioxide (HMnO2) loaded with cisplatin (CDDP), was developed. Metal nanoenzymes that can auto-degrade to produce Mn2+ exhibit Fenton-like, GSH-peroxidase-like activity, which effectively depletes GSH in the TME to attenuate the tumor antioxidant capacity. In an acidic environment, Mn2+ catalyzed the decomposition of intra-tumor H2O2 into highly toxic ·OH as a CDT. HMnO2 with large pores, pore volume, and surface area exhibited a high CDDP loading capacity (>0.6 g-1). Treatment with CDDP-loaded HMnO2 increased the intratumor Pt-DNA content, leading to the up-regulation of γ-H2Aχ and an increase in tumor tissue damage. The decreased GSH triggered by HMnO2 auto-degradation protected Mn2+-generated ·OH from scavenging to amplify oxidative stress and enhance the efficacy of CDT. The nanoenzymes with encapsulated chemotherapeutic agents deplete GSH and remodel the TME. Thus, tumor CDT/chemotherapy combination therapy is an effective therapeutic strategy.

Integration of Ultrathin Hafnium Oxide with a Clean van der Waals Interface for Two-Dimensional Sandwich Heterostructure Electronics.

Integrating high-κ dielectrics with a small equivalent oxide thickness (EOT) with two-dimensional (2D) semiconductors for low-power consumption van der Waals (vdW) heterostructure electronics remains challenging in meeting both interface quality and dielectric property requirements. Here, we demonstrate the integration of ultrathin amorphous HfOx sandwiched within vdW heterostructures by the selective thermal oxidation of HfSe2 precursors. The self-cleaning process ensures a high-quality interface with a low interface state density of 1011-1012 cm-2 eV-1. The synthesized HfOx displays excellent dielectric properties with an EOT of ∼1.5 nm, i.e., a high κ of ∼16, an ultralow leakage current of 10-6 A/cm2, and an impressively high breakdown field of 9.5 MV/cm. This facilitates low-power consumption vdW heterostructure MoS2 transistors, demonstrating steep switching with a low subthreshold swing of 61 mV/decade. This one-step integration of high-κ dielectrics into vdW sandwich heterostructures holds immense potential for developing low-power consumption 2D electronics while meeting comprehensive dielectric requirements.

Oxygen self-supplying small size magnetic nanoenzymes for synergistic photodynamic and catalytic therapy of breast cancer.

In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic-photodynamic combination therapy.

Highly Flexible, High-Performance, and Stretchable Piezoelectric Sensor Based on a Hierarchical Droplet-Shaped Ceramics with Enhanced Damage Tolerance.

Stretchable self-powered sensors are of significant interest in next-generation wearable electronics. However, current strategies for creating stretchable piezoelectric sensors based on piezoelectric polymers or 0-3 piezoelectric composites face several challenges such as low piezoelectric activity, low sensitivity, and poor durability. In this paper, a biomimetic soft-rigid hybrid strategy is used to construct a new form of highly flexible, high-performance, and stretchable piezoelectric sensor. Inspired by the hinged bivalve Cristaria plicata, hierarchical droplet-shaped ceramics are manufactured and used as rigid components, where computational models indicate that the unique arched curved surface and rounded corners of this bionic structure can alleviate stress concentrations. To ensure electrical connectivity of the piezoelectric phase during stretching, a patterned liquid metal acts as a soft circuit and a silicone polymer with optimized wettability and stretchability serves as a soft component that forms a strong mechanical interlock with the hierarchical ceramics. The novel sensor design exhibits excellent sensitivity and durability, where the open circuit voltage remains stable after 5000 stretching cycles at 60% strain and 5000 twisting cycles at 180°. To demonstrate its potential in heathcare applications, this new stretchable sensor is successfully used for wireless gesture recognition and assessing the progression of knee osteoarthritis.

Quasi-Zero-Dimensional Ferroelectric Polarization Charges-Coupled Resistance Switching with High-Current Density in Ultrascaled Semiconductors.

Ferroelectric memristors hold immense promise for advanced memory and neuromorphic computing. However, they face limitations due to low readout current density in conventional designs with low-conductive ferroelectric channels, especially at the nanoscale. Here, we report a ferroelectric-mediated memristor utilizing a 2D MoS2 nanoribbon channel with an ultrascaled cross-sectional area of <1000 nm2, defined by a ferroelectric BaTiO3 nanoribbon stacked on top. Strikingly, the Schottky barrier at the MoS2 contact can be effectively tuned by the charge transfers coupled with quasi-zero-dimensional polarization charges formed at the two ends of the nanoribbon, which results in distinctive resistance switching accompanied by multiple negative differential resistance showing the high-current density of >104 A/cm2. The associated space charges in BaTiO3 are minimized to ∼3.7% of the polarization charges, preserving nonvolatile polarization. This achievement establishes ferroelectric-mediated nanoscale semiconductor memristors with high readout current density as promising candidates for memory and highly energy-efficient in-memory computing applications.

The FJQR Has Synergistic Effect with Fluoropyrimidine in the Maintenance Treatment for HER-2 Negative Gastric Cancer.

INTRODUCTION: Maintenance therapy aimed to strengthen the first-line chemotherapy and improve quality of life is needed for gastric cancer (GC). Currently, many clinical studies have confirmed the important role of fluoropyrimidine in the maintenance stage. Our team has created patented prescriptions "Fuzheng jiedu Quyu Method" recipe (FJQR), which was considered as an adjuvant therapeutic scheme (reduce toxicity and increase the efficacy of chemotherapy). This study aimed to evaluate the efficacy and safety of FJQR combined with fluoropyrimidine as a maintenance treatment in HER-2 negative GC patients. METHODS: We performed the analysis of 129 patients with HER-2 negative GC who entered the maintenance stage in our hospital and Tianjin Cancer Hospital between January 2018 and December 2020. Out of the 129 eligible patients, 64 were categorized into the maintenance treatment group with FJQR+fluoropyrimidine, and 65 patients were assigned to the control group if they received fluoropyrimidine alone. Capecitabine was orally 1000mg/m2, Qd, half an hour after meals, and FGQR was 15g Bid after capecitabine. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), overall remission rate (ORR), quality of Life (QOL), TCM syndrome and safety. RESULTS: The mPFS in the treatment group was significantly prolonged compared with the control group (6.3 vs. 5.0 months, p = 0.03), while the mOS was not substantially improved (11.4 vs. 10.5 months, p = 0.38). Gastrointestinal symptoms and pain became better in the treatment group. The number of distant metastatic organs, first-line chemotherapy cycles, and lymph node metastasis were independent risk predictors for PFS. Blood stasis syndrome may be the protective factor. In terms of safety, treatment-related adverse events (AEs) in the treatment group were relatively lighter, and the incidence of grade III-IV AEs could be significantly reduced. CONCLUSION: FJQR and fluoropyrimidine have synergistic effects as maintenance treatment in HER-2 negative GC, with good efficacy and safety.

Evaluation of the Robustness Verification of Downstream Production Process for Inactivated SARS-CoV-2 Vaccine and Different Chromatography Medium Purification Effects.

BACKGROUND: Large-scale vaccine production requires downstream processing that focuses on robustness, efficiency, and cost-effectiveness. METHODS: To assess the robustness of the current vaccine production process, three batches of COVID-19 Omicron BA.1 strain hydrolytic concentrated solutions were selected. Four gel filtration chromatography media (Chromstar 6FF, Singarose FF, Bestarose 6B, and Focurose 6FF) and four ion exchange chromatography media (Maxtar Q, Q Singarose, Diamond Q, and Q Focurose) were used to evaluate their impact on vaccine purification. The quality of the vaccine was assessed by analyzing total protein content, antigen content, residual Vero cell DNA, residual Vero cell protein, and residual bovine serum albumin (BSA). Antigen recovery rate and specific activity were also calculated. Statistical analysis was conducted to evaluate process robustness and the purification effects of the chromatography media. RESULTS: The statistical analysis revealed no significant differences in antigen recovery (p = 0.10), Vero HCP residue (p = 0.59), Vero DNA residue (p = 0.28), and BSA residue (p = 0.97) among the three batches of hydrolytic concentrated solutions processed according to the current method. However, a significant difference (p < 0.001) was observed in antigen content. CONCLUSIONS: The study demonstrated the remarkable robustness of the current downstream process for producing WIBP-CorV vaccines. This process can adapt to different batches of hydrolytic concentrated solutions and various chromatography media. The research is crucial for the production of inactivated SARS-CoV-2 vaccines and provides a potential template for purifying other viruses.

Clinical efficacy of Camrelizumab combined with first-line chemotherapy in extensive-stage small-cell lung cancer.

Objective: Exploring the clinical efficacy of camrelizumab in combination with first-line chemotherapy in patients with extensive-stage small-cell lung cancer (ES-SCLC). Methods: The clinical data of 35 patients with ES-SCLC who received camrelizumab combined with EC or EP regimen in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from January 2020 to January 2023 were retrospectively analyzed. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were OS, ORR and DCR. SPSS 25.0 software was used for statistical analysis, Kaplan-Meier curve and Log-Rank test analysis, and survival curve was drawn. Results: The median PFS of 35 patients with SCLC was 7.4 months (95 % CI 6.75-9.81 months), .and the median OS was 12.5 months (95% CI,11.71-16.90 months). The ORR and DCR were 65.7 % and 74.3 %, respectively. Adverse events (AEs) were mainly concentrated in grade 1-2, and the probability of occurrence of grade 3 or above was low. Reactive Cutaneous Capillary Endothelial Proliferation (RCCEP) was the most common, followed by nausea &vomit and anemia. The other common AEs included abnormal thyroid function, decreased neutrophil count, skin rash and leucopenia. Conclusion: Camrelizumab in combination with first-line chemotherapy regimens prolonged OS and PFS in SCLC patients and showed efficacy and safety in real-world data.

Effects of Ionic Liquid Content on the Electrical Properties of PVDF Films by Fused Deposition Modeling.

In this study, polyvinylidene fluoride (PVDF) composite films were prepared by fused deposition modeling, and the effects of ionic liquid (IL) content on the printability, crystallization behavior, and electrical properties of melted PVDF were systematically investigated. The results show that the addition of IL increased the temperature sensitivity of melted PVDF and decreased its viscosity, while IL acted as a plasticizer to lower the melting point of PVDF and improve its FDM printability. The imidazole cations in IL had electrostatic interactions with the -CF2- groups in PVDF, which promoted the transformation of the nonpolar phase to the polar phase in PVDF; thus, the addition of IL was beneficial to the increase in the polar ß phase. The PVDF with 20 wt.% IL contained the highest proportion of ß phase content (32.59%). Moreover, the increase in polar ß-phase content also increased the polarization strength of PVDF and improved its ferroelectric properties. PVDF with 10 wt.% IL had the highest residual polarization strength (16.87 µC/m2).

Evaluación de la osteogénesis pos extracción en el alvéolo de rata: un modelo experimental / Osteogenic process evaluation following rat molar tooth extraction: an experimental model

coObjetivo: analizar la eficacia de un modelo experimental desarrollado en el laboratorio para evaluar radiográfica e histológicamente el proceso de osteogénesis y reparación alveolar. Materiales y métodos: se utilizaron 10 (n=10) ratas Wistar macho de aproximadamente 90 gramos de peso. Luego de anestesiados, se les realizó la extracción de dos molares superiores. Se formaron 2 grupos experimentales de 5 (n=5) ratas cada uno. Los maxilares fueron removidos, separados en mitade y fijados en una solución de formol-buffer al 10 por ciento. Resultados: en el grupo I se observaron imágenes radiolúcidas de los alvéolos vacíos. En los cortes histológicos se observaron imágenes compatibles con hemorragia y fibras periodontales remanentes. En el grupo II se encontraron imágenes radioopacas intraalveolares compatibles con tejido óseo. Los cortes histológicos revelaron el desarrollo de trabéculas óseas y espacios medulares que ocupaban casi la totalidad del espacio alveolar. Conclusiones: el modelo propuesto permitiría evaluar los cambios morfológicos producidos durante la osteogénesis posextracción. Adicionalmente, facilitaría la evaluación de los efectos producidos por diferentes condiciones experimentales.

Interaction of hypoxia inducible factor expression inhibition and P53 expression of patients with hepatic cellular cancer / 中国综合临床

Objective To investigate the correlation of hypoxia-inducible factors (HIF),P53 level and liver cancer infiltration in the microenvironment of the liver cancer pathological.Methods Flow cytometry was used to determine the P53 expression.Immunohistochemical method was applied to detect the expression of HIF characteristics,the correlation between Liver function (alanine amiotransferase (ALT),albumin (ALB),alpha fetoprotein(AFP))and HIF,P53.Results HIP positive rate in patients with encapsulated with incomplete,tumor diameter ≤ 5 cm and＞ 5 cm,tumor stage Ⅰ+Ⅱ and Ⅲ were 50.0％ (14/28) and 33.3％ (14/42),43.6 ％ (17/39)and 22.6％ (7/31),29.7％ (11/37)and 18.2％ (6/33)respectively.The HIF positive rate decrease in patients with capsular damage,tumor diameter increases (＞ 5 cm),Ⅲ patients,and differences between groups were statistically significant (P =0.040,0.030,0.030,respectively).P53 positive expression rate were 42.9％ (12/28) vs.83.3％ (35/42),51.3％ (20/39) vs.93.5％ (29/31),35.1％ (13/37) vs.69.7％ (23/33).The P53 positive expression in patients with capsular damage,tumor diameter increases (＞ 5 cm),Ⅲ patients with were relatively higher,the difference between groups was statistically significant (P =0.030,0.030,0.040,respectively).HIP positive rate in patient with past suffering from chronic hepatitis,cirrhosis and chronic AFP ＞ 35 ng/L,ALT ＞ 80 U/L were 36.2％ (21/58),27.9％ (17/61),27.1％ (14/51),28.2％ (11/39),lower than that of 58.3％ (7/12) in non-chronic hepatitis,non-cirrhotic 55.0％ (5/9),AFP ＜35 ng/L 58.0％ (11/19),ALT ＜ 80 U/L 51.6％ (16/31) of patients,the differences were statistically significant (P =0.046,0.047,0.037,0.045,respectively).P53 positive rate in patient with past sufering from chronic cirrhosis,AFP ＞ 35 ng/L,ALT ＞ 80 U/L,albumin ＜ 35 g/L were 82.0％ (50/61),74.5％ (38/51),69.2％ (27/39),73.7％ (42/57),respectively,higher than that of patient without chronic cirrhosis 44.4％ (4/9),or with AFP ＜ 35 ng/L 31.6％ (6/19),ALT ＜ 80 U/L 22.6％ (7/31),albumin ＞ 35 g/L 46.2％ (6/13).Tthe differences were statistically significant (P =0.037,0.040,0.032,0.041,respectively).Conclusion HIF and P53 might be the important factor in monitoring the development of hepatocellular carcinoma invasion.