A Noncationic Biocatalytic Nanobiohybrid Platform for Cytosolic Protein Delivery Through Controlled Perturbation of Intracellular Redox Homeostasis.

Intracellular delivery of proteins has largely been relying on cationic nanoparticles to induce efficient endosome escape, which, however, poses serious concerns on the inflammatory and cytotoxic effects. Herein, a versatile noncationic nano biohybrid platform is introduced for efficient cytosolic protein delivery by utilizing a nano-confined biocatalytic reaction. This platform is constructed by co-immobilizing glucose oxidase (GOx) and the target protein into nanoscale hydrogen-bonded organic frameworks (HOFs). The biocatalytic reaction of nano-confined GOx is leveraged to induce controlled perturbation of intracellular redox homeostasis by sustained hydrogen peroxide (H2O2) production and diminishing the flux of the pentose phosphate pathway (PPP). This in turn induces the endosome escape of nanobiohybrids. Concomitantly, GOx-mediated hypoxia leads to overexpression of azo reductase that initiated the materials' self-destruction for releasing target proteins. These biological effects collectively induce highly efficient cytosolic protein delivery. The versatility of this delivery platform is further demonstrated for various types of proteins, different protein loading approaches (in situ immobilization or post-adsorption), and in multiple cell lines. Finally, the protein delivery efficiency and biosafety are demonstrated in a tumor-bearing mouse model. This nanohybrid system opens up new avenues for intracellular protein delivery and is expected to be extensively applicable for a broad range of biomolecuels.

Tadpole-Like Carbon Nanotube with Fe Nanoparticle Encapsulated at the Head and Zn Single-Atom Anchored on the Body: One-Pot Carbonization for Tetramodal Synergistic Cancer Therapy.

Precise integration of diverse therapeutic approaches into nanomaterials is the key to the development of multimodal synergistic cancer therapy. In this work, tadpole-like carbon nanotubes with Fe nanoparticle encapsulated at the head and Zn single-atom anchored on the body (Fe@CNT-Zn) is precisely designed and facilely prepared via one-pot carbonization. In vitro studies revealed the integration of chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT) in Fe@CNT-Zn as well as the near-infrared light (NIR)-responsive cascade therapeutic efficacy. Furthermore, in vivo studies demonstrated the NIR-triggered cascade-amplifying synergistic cancer therapy in a B16 tumor-bearing mouse model. The results not only showcased the Fe@CNT-Zn as a potential tetramodal therapeutic platform, but also demonstrated a proof-of-concept on metal-organic framework-based "one stone for multiple birds" strategy for in situ functionalization of carbon materials.

Differential pressure sensors based on transfer-free piezoresistive layered PdSe2thin films.

Piezoresistive layered two-dimensional (2D) crystals offer intriguing promise as pressure sensors for microelectromechanical systems (MEMS) due to their remarkable strain-induced conductivity modulation. However, integration of the conventional chemical vapor deposition grown 2D thin films onto a micromachined silicon platform requires a complex transfer process, which degrades their strain-sensing performance. In this study, we present a differential pressure sensor built on a transfer-free piezoresistive PdSe2polycrystalline film deposited on a SiNxmembrane by plasma-enhanced selenization of a metal film at a temperature as low as 200 °C. Based on the resistance change and finite element strain analysis of the film under membrane deflection, we show that a 7.9 nm thick PdSe2film has a gauge factor (GF) of -43.3, which is ten times larger than that of polycrystalline silicon. The large GF enables the development of a diaphragm pressure sensor with a high sensitivity of 3.9 × 10-4kPa-1within the differential pressure range of 0-60 kPa. In addition, the sensor with a Wheatstone bridge circuit achieves a high voltage sensitivity of 1.04 mV·kPa-1, a rapid response time of less than 97 ms, and small output voltage variation of 8.1 mV in the temperature range of 25 °C to 55 °C. This transfer-free and low-temperature grown PdSe2piezoresistive thin film is promising for MEMS transducer devices.

Discovery of a photosensitizing PI3K inhibitor for tumor therapy: Design, synthesis and in vitro biological evaluation.

In drug development, optical triggering of cancer therapy is increasingly used. Herein, we report a novel photosensitive PI3K inhibitor FD2157, which bears a photoprotecting moiety and can be efficiently cleaved with enhanced anticancer activity upon short-term light irradiation. In biological assessment, FD2157 exhibited remarkably enhanced anticancer activity in inhibition of PI3K pathway against melanoma cell lines upon light irradiation (4 min). Hence, this photosensitive PI3K inhibitor FD2157 may represent a valuable tool compound for studying the PI3K pathway and further optimization toward light-triggered cancer treatment.

Design, synthesis and in vitro biological evaluation of 2-aminopyridine derivatives as novel PI3Kδ inhibitors for hematological cancer.

Phosphoinositide-3-kinase (PI3K) involves in regulation of proliferation, cell cycle, and apoptosis, and is overexpressed in most of human malignant tumors. Therefore, the development of PI3K inhibitors has attracted great interest in tumor treatment. In this study, we designed and synthesized a series of 2-aminopyridine derivatives via a bioisosterism strategy. Among them, compound MR3278 showed superior PI3Kδ inhibitory activity (IC50 = 30 nM), as well as higher inhibitory activity to most of AML cells (e.g., MOLM-16 and Mv-4-11 cells with IC50 values of 2.6 µM and 3.7 µM, respectively) than Idelalisib. Further cell studies indicated that MR3278 could induce G2/M phase arrests and cell apoptosis of Mv-4-11 cells via PI3K dependent pathway in a dose dependent manner. In addition, in silico physicochemical and ADMET evaluation revealed its drug-like properties with satisfactory toxicity profiles. These results indicate that MR3278 can be identified as a promising new lead compound to the current PI3Kδ inhibitor and is worthy of further profiling.

Thickness-dependent carrier transport of PdSe2films grown by plasma-assisted metal selenization.

Atomically thin narrow-bandgap layered PdSe2has attracted much attention due to its rich and unique electrical properties. For silicon-compatible device integration, direct wafer-scale preparation of high-quality PdSe2thin film on a silicon substrate is highly desired. Here, we present the low-temperature synthesis of large-area polycrystalline PdSe2films grown on SiO2/Si substrates by plasma-assisted metal selenization and investigate their charge carrier transport behaviors. Raman analysis, depth-dependent x-ray photoelectron spectroscopy, and cross-sectional transmission electron microscopy were used to reveal the selenization process. The results indicate a structural evolution from initial Pd to intermediate PdSe2-xphase and eventually to PdSe2. The field-effect transistors fabricated from these ultrathin PdSe2films exhibit strong thickness-dependent transport behaviors. For thinner films (4.5 nm), a record high on/off ratio of 104was obtained. While for thick ones (11 nm), the maximum hole mobility is about 0.93 cm2V-1S-1, which is the record high value ever reported for polycrystalline films. These findings suggest that our low-temperature-metal-selenized PdSe2films have high quality and show great potential for applications in electrical devices.

Discovery and identification of a novel PI3K inhibitor with enhanced CDK2 inhibition for the treatment of triple negative breast cancer.

Blocking the PI3K pathway has been recognized as a promising strategy for cancer therapy. Herein, we report the discovery of novel PI3K inhibitors utilizing 7-azaindole-based fragment-oriented growth. Among them, compound FD2056 stands out as the most promising candidate, maintaining potent inhibitory activity against PI3K and enhanced CDK2 inhibition, and showing moderate selectivity among 108 kinases. In cellular assays, the inhibitor FD2056 demonstrated superior anti-proliferative profiles over reference compounds against TNBC cells and significantly increased apoptosis of MDA-MB-231 cells in a dose-dependent manner. Moreover, FD2056 showed more efficacious anti-TNBC activity than the corresponding drugs BKM120 and CYC202 at an oral dose of 15 mg/kg in the MDA-MB-231 xenograft model, inhibiting tumor growth by 43% with no observable toxic effects. All these results suggest that FD2056 has potential for further development as a promising anticancr compound, and co-targeting PI3K and CDK2 pathways may provide an alternative therapeutic strategy for the treatment of TNBC.

Research Progress of Bioinspired Structural Color in Camouflage.

Bioinspired structural color represents a burgeoning field that draws upon principles, strategies, and concepts derived from biological systems to inspire the design of novel technologies or products featuring reversible color changing mechanisms, with significant potential applications for camouflage, sensors, anticounterfeiting, etc. This mini-review focuses specifically on the research progress of bioinspired structural color in the realm of camouflage. Firstly, it discusses fundamental mechanisms of coloration in biological systems, encompassing pigmentation, structural coloration, fluorescence, and bioluminescence. Subsequently, it delineates three modulation strategies-namely, photonic crystals, film interference, and plasmonic modulation-that contribute to the development of bioinspired structural color materials or devices. Moreover, the review critically assesses the integration of bioinspired structural color materials with environmental contexts, with a particular emphasis on their application in camouflage. Finally, the paper outlines persisting challenges and suggests future development trends in the camouflage field via bioinspired structural color.

Hybrid nanoparticle-mediated simultaneous ROS scavenging and STING activation improve the antitumor immunity of in situ vaccines.

In situ vaccine (ISV) is a versatile and personalized local immunotherapeutic strategy. However, the compromised viability and function of dendritic cells (DCs) in a tumor microenvironment (TME) largely limit the therapeutic efficacy. We designed a hybrid nanoparticle-based ISV, which accomplished superior cancer immunotherapy via simultaneously scavenging reactive oxygen species (ROS) and activating the stimulator of interferon genes (STING) pathway in DCs. This ISV was constructed by encapsulating a chemodrug, SN38, into diselenide bond-bridged organosilica nanoparticles, followed by coating with a Mn2+-based metal phenolic network. We show that this ISV can activate the STING pathway through Mn2+ and SN38 comediated signaling and simultaneously scavenge preexisting H2O2 in the TME and Mn2+-catalyzed •OH by leveraging the antioxidant property of diselenide and polyphenol. This ISV effectively activated DCs and protected them from oxidative damage, leading to remarkable downstream T cell activation and systemic antitumor immunity. This work highlights a nanoparticle design that manipulates DCs in the TME for improving the ISV.

Diagnostic potential of trace metals concentration in expressed prostatic secretion and serum of patients with category IV prostatitis.

BACKGROUND: The National Institutes of Health (NIH) category IV prostatitis is a painless prostate gland inflammation, just as its name implies, this type of prostatitis is related with inflammation of the prostate, but most men are not conscious of it. However, category IV prostatitis is fairly common in general populations and reported having indirect relationships with prostate cancer. METHOD: We analyzed the concentration of zinc (Zn), copper (Cu), calcium (Ca) and magnesium (Mg) in expressed prostatic secretion (EPS) and serum of patients with category IV prostatitis and healthy controls, investigating the diagnostic potential of different metals in category IV prostatitis using a flame atomic absorption spectrometer (FAAS). RESULTS: Metal concentration combined clinical characteristics analysis suggested that average level of Zn, Ca, Mg were significantly lower in the EPS of patients with category IV prostatitis (P-value< 0.000), while Cu level raised obviously (P-value< 0.000). And in the serum, mean concentrations of Ca was also found to increase significantly in the patients with category IV prostatitis compared to healthy controls. Moreover, the correlation analysis indicated that age showed a positive correlation with EPS Zn, Ca, Mg concentration (P-value< 0.05), while albumin correlates with EPS Zn, Ca, Mg concentration reversely (P-value< 0.05) in patients with category IV prostatitis. CONCLUSION: Our report revealed that determination of the metal elements zinc, copper, calcium and magnesium in the serum and EPS could be a new and promising strategy for the rapid diagnosis of category IV prostatitis.

Controllable synthesized heterostructure photocatalyst Mo2C@C/2D g-C3N4: enhanced catalytic performance for hydrogen production.

Photocatalysis is a promising technology which can be applied in the fields of energy and environment. However, low charge separation efficiency has limited its commercial applications. In this work, we report a route to a controllable synthesized visible-light-driven heterostructure photocatalyst Mo2C@C/2D g-C3N4. The interfacial conductivity was improved by introducing Mo2C@C, which promoted the transportation of photogenerated carriers and suppressed their recombination. The optimal composite achieved a hydrogen (H2) generation rate of 2269.47 µmol g-1 h-1, and an external quantum efficiency (EQE) achieved 9.07% at λ = 405 nm. Thus, the great co-catalytic activity of Mo2C@C was unambiguously demonstrated.

Preparation of oligomeric beta-amyloid 1-42 and induction of synaptic plasticity impairment on hippocampal slices.

Impairment of synaptic connections is likely to underlie the subtle amnesic changes occurring at the early stages of Alzheimer s Disease (AD). beta-amyloid (A beta), a peptide produced in high amounts in AD, is known to reduce Long-Term Potentiation (LTP), a cellular correlate of learning and memory. Indeed, LTP impairment caused by A beta is a useful experimental paradigm for studying synaptic dysfunctions in AD models and for screening drugs capable of mitigating or reverting such synaptic impairments. Studies have shown that A beta produces the LTP disruption preferentially via its oligomeric form. Here we provide a detailed protocol for impairing LTP by perfusion of oligomerized synthetic A beta1-42 peptide onto acute hippocampal slices. In this video, we outline a step-by-step procedure for the preparation of oligomeric A beta(1-42;). Then, we follow an individual experiment in which LTP is reduced in hippocampal slices exposed to oligomerized A beta(1-42;) compared to slices in a control experiment where no A beta(1-42;) exposure had occurred.