Explore the vast range of titles available.

Therapeutic tumor neoantigen vaccines have been widely studied given their good safety profile and ability to avoid central thymic tolerance. However, targeting antigen‐presenting cells (APCs) and inducing robust neoantigen‐specific cellular immunity remain challenges. Here, a safe and broad‐spectrum neoantigen vaccine delivery system is proposed (GP‐Neoantigen) based on β‐1,3‐glucan particles (GPs) derived from Saccharomyces cerevisiae and coupling peptide antigens with GPs through convenient click chemistry. The prepared system has a highly uniform particle size and high APC targeting specificity. In mice, the vaccine system induced a robust specific CD8+ T cell immune response and humoral immune response against various conjugated peptide antigens and showed strong tumor growth inhibitory activity in EG7·OVA lymphoma, B16F10 melanoma, 4T1 breast cancer, and CT26 colon cancer models. The combination of the toll‐like receptors (TLRs) agonist PolyI:C and CpG 2395 further enhanced the antitumor response of the particle system, achieving complete tumor clearance in multiple mouse models and inducing long‐term rejection of reinoculated tumors. These results provide the broad possibility for its further clinical promotion and personalized vaccine treatment. A broad‐spectrum neoantigen vaccine delivery system (GP‐Neoantigen) based on β‐1,3‐glucan particles (GPs) derived from Saccharomyces cerevisiae induces a robust cellular and humoral immune response against conjugated peptide antigens and strongly inhibits tumor growth, with which complete tumor clearance and long‐term rejection of reinoculated tumors can be achieved in multiple mouse tumor models.

Large-diameter titanium dioxide nanotubes (TNTs) have shown promise in preserving osteoblast function under oxidative stress (OS) in vitro. However, their ability to enhance osteogenesis in vivo under OS conditions and the underlying mechanisms remain unclear. This study aimed to evaluate the osteogenic potential of 110 nm TNTs (TNT110) compared to 30 nm TNTs (TNT30) in an aging rat model exhibiting OS, and to investigate the mechanisms involved. Surface properties of TNTs were characterized, and in vitro and in vivo experiments were conducted to assess their osteoinductive effects under OS. Transcriptomic, proteomic analyses, and Western blotting were performed to investigate the protective mechanisms of TNT110 on osteoblasts. Protein adsorption studies focused on the roles of fibronectin (FN) and albumin (BSA) in modulating osteoblast behavior on TNT110. In both in vitro and in vivo experiments, TNT110 significantly improved new bone formation and supported osteoblast survival under OS conditions. Subsequent ribonucleic acid sequencing results indicated that TNT110 tended to attenuate inflammatory responses and reactive oxygen species (ROS) expression while promoting endoplasmic reticulum (ER) stress and extracellular matrix receptor interactions, all of which are crucial for osteoblast survival and functionality. Further confirmation indicated that the cellular behavior changes of osteoblasts in the TNT110 group could only occur in the presence of serum. Moreover, proteomic analysis under OS conditions revealed the pivotal roles of FN and BSA in augmenting TNT110's resistance to OS. Surface pretreatment of TNT110 with FN/BSA alone could beneficially influence the early adhesion, spreading, ER activity, and ROS expression of osteoblasts, a trend not observed with TNT30. TNT110 effectively protects osteoblast function in the OS microenvironment by modulating protein adsorption, with FN and BSA synergistically enhancing osteogenesis. These findings suggest TNT110's potential for use in implants for elderly patients.

Animal experiments suggest that selenium (Se) may alleviate cadmium (Cd) toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. In black shale regions such as Enshi and Zhuxi County, residents who long‐term consume local rice may surpass safe Se and Cd intake levels. Significantly high median blood Se (B‐Se) and urine selenium (U‐Se) levels were detected in these areas, measuring 416.977 μg/L and 352.690 μg/L and 104.527 μg/L and 51.820 μg/L, respectively. Additionally, the median blood Cd (B‐Cd) and urine Cd (U‐Cd) levels were markedly elevated at 4.821 μg/L and 3.848 μg/L and at 7.750 μg/L and 7.050 μg/L, respectively, indicating substantial Cd exposure. Nevertheless, sensitive liver and kidney biomarkers in these groups fall within healthy reference ranges, suggesting a potential antagonistic effect of Se on Cd in the human body. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. However, within the healthy ranges, residents in the Enshi study area had significantly greater median levels of serum creatinine and cystatin C, measuring 67.3 μmol/L and 0.92 mg/L, respectively, than those in Zhuxi did (53.6 μmol/L and 0.86 mg/L). In cases of excessive Se and Cd exposure, high Se and Cd levels impact the filtration function of the human kidney to some extent. Plain Language Summary Se is an essential trace element for humans. However, excessive intake of Se can harm humans. Cd is a carcinogen and a chronic potent nephrotoxin that mostly accumulates in the human liver and kidneys. Animal experiments suggest that Se may alleviate Cd toxicity in animal liver and kidneys, but its effect on human liver and kidneys remains uncertain. In China, areas with black shale exposure have shown elevated levels of Se and Cd. According to the USEPA (U.S. Environmental Protection Agency) evaluation method, the soil and rice in these areas pose significant risks. Our results suggested that the exposed black shale areas are simultaneously enriched with Se and Cd. However, residents in these areas were exposed to excessive Se and Cd long‐term without significant damage to liver and kidney functions. Therefore, the USEPA method may not accurately assess Cd risk in exposed black shale areas. The risk assessment of heavy metals in high‐Se geological background areas cannot be separated from human health surveys. Our study provides evidence for the antagonistic effects of Se and Cd on the human body. Key Points Residents in exposed black shale areas consume excessive Se and Cd through local rice Human liver and kidney functions are not significantly damaged in exposed black shale areas The USEPA method may not accurately assess Cd risk in exposed black shale areas

Titanium (Ti) implants have been widely used for the treatment of tooth loss due to their excellent biocompatibility and mechanical properties. However, modifying the biological properties of these implants to increase osteointegration remains a research challenge. Additionally, the continuous release of various metal ions in the oral microenvironment due to fluid corrosion can also lead to implant failure. Therefore, simultaneously improving the bioactivity and corrosion resistance of Ti-based materials is an urgent need. In recent decades, micro-arc oxidation (MAO) has been proposed as a surface modification technology to form a surface protective oxide layer and improve the comprehensive properties of Ti. The present study doped nano silicon nitride (Si 3 N 4 ) particles into the Ti surface by MAO treatment to improve its corrosion resistance and provide excellent osteoinduction by enhancing alkaline phosphatase activity and osteogenic-related gene expression. In addition, due to the presence of silicon, the Si 3 N 4 -doped materials showed excellent angiogenesis properties, including the promotion of cell migration and tubule formation, which play essential roles in early recovery after implantation.

Prostate cancer (PCa) is the second most common cancer in men, causing more than 300,000 deaths every year worldwide. Due to their superior cell-killing ability and the relative simplicity of their preparation, immunotoxin molecules have great potential in the clinical treatment of cancer, and several such molecules have been approved for clinical application. In this study, we adopted a relatively simple strategy based on a single-domain antibody (sdAb) and an improved Pseudomonas exotoxin A (PE) toxin (PE24X7) to prepare a safer immunotoxin against prostate-specific membrane antigen (PSMA) for PCa treatment. The designed anti-PSMA immunotoxin, JVM-PE24X7, was conveniently prepared in its soluble form in an Escherichia coli (E. coli) system, avoiding the complex renaturation process needed for immunotoxin preparation by the conventional strategy. The product was very stable and showed a very strong ability to bind the PSMA receptor. Cytotoxicity assays showed that this molecule at a very low concentration could kill PSMA-positive PCa cells, with an EC50 value (concentration at which the cell viability decreased by 50%) of 15.3 pM against PSMA-positive LNCaP cells. Moreover, this molecule showed very good killing selectivity between PSMA-positive and PSMA-negative cells, with a selection ratio of more than 300-fold. Animal studies showed that this molecule at a very low dosage (5 × 0.5 mg/kg once every three days) completely inhibited the growth of PCa tumors, and the maximum tolerable dose (MTD) was more than 15 mg/kg, indicating its very potent tumor-treatment ability and a wide therapeutic window. Use of the new PE toxin, PE24X7, as the effector moiety significantly reduced off-target toxicity and improved the therapeutic window of the immunotoxin. The above results demonstrate that the designed anti-PSMA immunotoxin, JVM-PE24X7, has good application value for the treatment of PCa.

Antibody drug conjugates (ADCs) have become an important modality of clinical cancer treatment. However, traditional ADCs have some limitations, such as reduced permeability in solid tumors due to the high molecular weight of monoclonal antibodies, difficulty in preparation and heterogeneity of products due to the high drug/antibody ratio (4–8 small molecules per antibody). Miniaturized ADCs may be a potential solution, although their short circulation half-life may lead to new problems. In this study, we propose a novel design strategy for miniaturized ADCs in which drug molecules and small ligand proteins are site-specifically coupled via a bifunctional poly(ethylene glycol) (PEG) chain. The results showed that the inserted PEG chains significantly prolonged the circulation half-life but also obviously reduced the cytotoxicity of the conjugates. Compared with the conjugate ZHER2-SMCC-MMAE (HM), which has no PEG insertion, ZHER2-PEG4K-MMAE (HP4KM) and ZHER2-PEG10K-MMAE (HP10KM) with 4 or 10 kDa PEG insertions have 2.5- and 11.2-fold half-life extensions and 4.5- and 22-fold in vitro cytotoxicity reductions, respectively. The combined effect leads to HP10KM having the most ideal tumor therapeutic ability at the same dosages in the animal model, and its off-target toxicity was also reduced by more than 4 times compared with that of HM. These results may indicate that prolonging the half-life is very helpful in improving the therapeutic capacity of miniaturized ADCs. In the future, the design of better strategies that can prolong half-life without affecting cytotoxicity may be useful for further improving the therapeutic potential of these molecules.

Antibody—drug conjugates (ADCs) play important roles in tumor therapy. However, traditional ADCs are limited by the extremely large molecular weight of the antibody molecules, which results in low permeability into solid tumors. The use of small ADCs may be expected to alleviate this problem, but this switch brings the new limitation of a greatly shortened blood circulation half-life. Here, we propose a new cleavable ADC design with excellent tumor tissue permeability and a long circulation half-life by fusing the small ADC ZHER2-MMAE with the Fc domain of the antibody for circulation half-life extension, and inserting a digestion sequence between them to release the small ADC inside tumors for better tumor penetration. The experimental results showed that the designed molecule Fc-U-ZHER2-MMAE has a significantly increased blood circulation half-life (7.1 h, 59-fold longer) compared to the small ADC ZHER2-MMAE, and significantly improved drug accumulation ability at tumor sites compared to the conventional full-length antibody-coupled ADC Herceptin-MMAE. These combined effects led to Fc-U-ZHER2-MMAE having significantly enhanced tumor treatment ability, as shown in mouse models of NCI-N87 gastric cancer and SK-OV-3 ovarian cancer, where Fc-U-ZHER2-MMAE treatment achieved complete regression of tumors in all or a portion of animals with no obvious side effects and an MTD exceeding 90 mg/kg. These data demonstrate the therapeutic advantages of this cleavable ADC strategy, which could provide a new approach for ADC design.

Biochar was prepared from the peanut shell. Then, it was mixed with the clay mineral kaolinite and stirred under the magnetic stirrer. The biochar derived from peanut shell supported with clay mineral kaolinite (B@K) was obtained. Adsorption experiments of dye Acid Orange 7 by B@K were conducted. The characteristics of B@K were determined by the elemental analyzer, specific surface area meter, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectrometer and the model axis-HS. The experimental results showed that a large number of oxygen-containing functional groups appear on the surface of B@K, which is beneficial for binding dye ions. The adsorption process fits well with the pseudo-second-order kinetic model. It indicated that the adsorption process was both physical adsorption and chemical adsorption. Chemical adsorption is the main adsorption process. Langmuir isotherm model can better describe the adsorption isothermal process of B@K on dye Acid Orange 7. The adsorption process is monolayer adsorption process.

Bioinspired bionic eyes should be self-driving, repairable and conformal to arbitrary geometries. Such eye would enable wide-field detection and efficient visual signal processing without requiring external energy, along with retinal transplantation by replacing dysfunctional photoreceptors with healthy ones for vision restoration. A variety of artificial eyes have been constructed with hemispherical silicon, perovskite and heterostructure photoreceptors, but creating zero-powered retinomorphic system with transplantable conformal features remains elusive. By combining neuromorphic principle with retinal and ionoelastomer engineering, we demonstrate a self-driven hemispherical retinomorphic eye with elastomeric retina made of ionogel heterojunction as photoreceptors. The receptor driven by photothermoelectric effect shows photoperception with broadband light detection (365 to 970 nm), wide field-of-view (180°) and photosynaptic (paired-pulse facilitation index, 153%) behaviors for biosimilar visual learning. The retinal photoreceptors are transplantable and conformal to any complex surface, enabling visual restoration for dynamic optical imaging and motion tracking. Luo et al. report a self-driven hemispherical retinomorphic eye that employs ionogel heterojunctions as photoreceptors. This photoreceptor exhibits broadband photosynapse, high conformability, retinal transplantation, and visual restoration for re-time optical imaging and motion tracking.

Research on bearing fault diagnosis generally uses a single signal processing method to extract features to a certain extent and then empirically judges the fault type at this stage. However, this approach has a poor fault feature extraction effect when the noise interference signal is large and subjective human errors. The diagnosis effect is determined by external interference and has no practical value. This paper proposes a rolling bearing fault diagnosis method based on singular spectrum analysis and a wide convolution kernel neural network, which can effectively extract the fault features of the rolling bearing crack fault signal with a strong noise interference and realize the efficient diagnosis of this kind of fault. Gaussian white noise is added to the standard bearing fault signal to construct the vibration signal with noise interference. Then, the noisy one-dimensional time series signal is preprocessed, including the data division into the training and test sets and the different kinds of numbering processing. Singular spectrum analysis is performed on the preprocessed data. Then, the denoised training set is used as input in a deep convolution neural network with a wide convolution kernel for feature extraction and model training. The trained diagnosis model is used for the fault prediction of the next test set, and the relevant diagnosis results are output. The test results show that this method can ensure the overall accuracy of more than 90% under the background of high noise, and the diagnosis rate of the model under various working conditions is stably maintained at more than 93%, without the collapse of diagnosis stability under the sudden change of noise. The advantages of model diagnosis efficiency and structural improvement fit are prominent.