Inflammatory microenvironment regulation and osteogenesis promotion by bone-targeting calcium and magnesium repletion nanoplatform for osteoporosis therapy.

Osteoporosis is the most common bone metabolic disease that affects the health of middle-aged and elderly people, which is hallmarked by imbalanced bone remodeling and a deteriorating immune microenvironment. Magnesium and calcium are pivotal matrix components that participate in the bone formation process, especially in the immune microenvironment regulation and bone remodeling stages. Nevertheless, how to potently deliver magnesium and calcium to bone tissue remains a challenge. Here, we have constructed a multifunctional nanoplatform composed of calcium-based upconversion nanoparticles and magnesium organic frameworks (CM-NH2-PAA-Ald, denoted as CMPA), which features bone-targeting and pH-responsive properties, effectively regulating the inflammatory microenvironment and promoting the coordination of osteogenic functions for treating osteoporosis. The nanoplatform can efficaciously target bone tissue and gradually degrade in response to the acidic microenvironment of osteoporosis to release magnesium and calcium ions. This study validates that CMPA possessing favorable biocompatibility can suppress inflammation and facilitate osteogenesis to treat osteoporosis. Importantly, high-throughput sequencing results demonstrate that the nanoplatform exerts a good inflammatory regulation effect through inhibition of the nuclear factor kappa-B signaling pathway, thereby normalizing the osteoporotic microenvironment. This collaborative therapeutic strategy that focuses on improving bone microenvironment and promoting osteogenesis provides new insight for the treatment of metabolic diseases such as osteoporosis.

Intranasal Delivery of Near-Infrared and Magnetic Dual-Response Nanospheres to Rapidly Produce Antidepressant-Like and Cognitive Enhancement Effects.

Restricted by synaptic plasticity, dopamine receptor (DR) upregulation takes a long time to work. Moreover, the impact of the blood-brain barrier (BBB) on delivery efficiency restricts the development of drugs. Taking inspiration from snuff bottles, a convenient, fast-acting, and nonaddictive nasal drug delivery system has been developed to rapidly reshape the balance of synaptic transmitters. This optical and magnetic response system called CFs@DP, comprised of carbonized MIL-100 (Fe) frameworks (CFs) and domperidone (DP), which can enter the brain via nasal administration. Under dual stimulation of near-infrared (NIR) irradiation and catecholamine-induced complexation, CFs@DP disintegrates to release iron ions and DP, causing upregulation of the dopamine type 1 (D1), type 2 (D2) receptors, and brain-derived neurotrophic factor (BDNF) to achieve a therapeutic effect. In vivo experiments demonstrate that the DR density of mice (postnatal day 50-60) increased in the prefrontal cortex (PFC) and the hippocampus (HPC) after 10 days of therapy, resulting in antidepressant-like and cognitive enhancement effects. Interestingly, the cognitive enhancement effect of CFs@DP is even working in noniron deficiency (normal fed) mice, making it a promising candidate for application in enhancing learning ability.

Efficient CsPbBr3 Perovskite Light-Emitting Diodes via Novel Multi-Step Ligand Exchange Strategy Based on Zwitterionic Molecules.

Perovskite nanocrystals have absorbed increasing interest, especially in the field of optoelectronics, owing to their unique characteristics, including their tunable luminescence range, robust solution processability, facile synthesis, and so on. However, in practice, due to the inherent instability of the traditional long-chain insulating ligands surrounding perovskite quantum dots (PeQDs), the performance of the as-fabricated QLED is relatively disappointing. Herein, the zwitterion 3-(decyldimethylammonio)propanesulfonate (DLPS) with the capability of double passivating perovskite quantum dots could effectively replace the original long-chain ligand simply through a multistep post-treatment strategy to finally inhibit the formation of defects. It was indicated from theexperimental results that the DLPS, as one type of ligand with the bimolecular ion, was very adavntageous in replacing long-chain ligands and further suppressing the formation of defects. Finally, the perovskite quantum dots with greatly enhanced PLQY as high as 98% were effectively achieved. Additionally, the colloidal stability of the corresponding PeQDs has been significantly enhanced, and a transparent colloidal solution was obtained after 45 days under ambient conditions. Finally, the as-fabricated QLEDs based on the ligand-exchanged PeQDs exhibited a maximum brightness of 9464 cd/m2 and an EQE of 12.17%.

Traditional Herb (Moxa) Modified Zinc Oxide Nanosheets for Quick, Efficient and High Tissue Penetration Therapy of Fungal Infection.

Fungal infection possesses the characteristics of high invasion depth and easy formation of a biofilm under the skin, which greatly hinders the treatment process. Here, traditional Chinese medicine moxa is carbonized and modified with zinc oxide (ZnO) nanosheets to synthesize carbonized moxa@ZnO (CMZ) with the dual response properties of yellow light (YL) and ultrasound (US) for synergistic antifungal therapy. CMZ with narrow bandgap can respond to long-wavelength YL that is highly safe and helpful for skin repair. Simultaneously, CMZ with a piezoelectric effect can further enhance the photocatalytic efficiency under the stimulation of US with high tissue penetration. Gene mechanism investigation indicates that when exposed to US and YL irradiation, CMZ-based therapy can adjust the expression of genes associated with fungal virulence, metabolic activity, mycelial growth and biofilm development, thus efficaciously eradicating planktonic Candida albicans (C. albicans) and mature biofilm. Importantly, despite the 1.00 cm thick tissue barrier, CMZ can rapidly eliminate 99.9% of C. albicans within 4 min, showing a satisfactory deep fungicidal efficacy. The in vivo therapeutic effect of this strategy is demonstrated in both open wound and deep cutaneous infection tests, speaking of dramatically better efficacy than the traditional fungicide ketoconazole (KTZ).

Traditional Scraping (Gua Sha) Combined with Copper-Curcumin Nanoparticle Oleogel for Accurate and Multi-Effective Therapy of Androgenic Alopecia.

Androgenetic alopecia (AGA) is a prevalent systemic disease caused by diverse factors, for which effective treatments are currently limited. Herein, the oleogel (OG) containing copper-curcumin (CuR) nanoparticles is developed, designated as CuRG, which is also combined with traditional naturopathic scraping (Gua Sha, SCR) as a multifunctional therapy for AGA. With the assistance of lipophilic OG and SCR, CuR can efficaciously penetrate the epidermal and dermal regions where most hair follicles (HFs) reside, thereby releasing curcumin (CR) and copper ions (Cu2+) subcutaneously to facilitate hair regeneration. Concomitantly, the mechanical stimulation induced by SCR promotes the formation of new blood vessels, which is conducive to reshaping the microenvironment of HFs. This study validates that the combination of CuRG and SCR is capable of systematically interfering with different pathological processes, ranging from improvement of perifollicular microenvironment (oxidative stress and insufficient vascularization), regulation of inflammatory responses to degradation of androgen receptor, thus potentiating hair growth. Compared with minoxidil, a widely used clinical drug for AGA therapy, the designed synergistic system displays augmented hair regeneration in the AGA mouse model.

Microenvironment-Responsive Metal-Phenolic Nanozyme Release Platform with Antibacterial, ROS Scavenging, and Osteogenesis for Periodontitis.

Periodontitis is a chronic inflammatory disease deriving from dental plaque, characterized by the excessive accumulation of reactive oxygen species (ROS), matrix metalloproteinase (MMP) and other substances, resulting in the destruction of periodontal tissues. At present, the main therapeutic modalities, such as local mechanical debridement and antibiotic delivery, are not only difficult to solve the intractable bacterial biofilm effectively but also tricky to ameliorate the excessive inflammatory response as well as regenerate the impaired periodontal tissues. Herein, we have proposed the TM/BHT/CuTA hydrogel system formed by the self-assembly of the copper-based nanozyme (copper tannic acid coordination nanosheets, CuTA NSs) and the triglycerol monostearate/2,6-di-tert-butyl-4-methylphenol (TM/BHT) hydrogel. The negatively charged TM/BHT/CuTA can retain at the inflammation sites with a positive charge through electrostatic adsorption and hydrolyze in response to the increasing MMP of periodontitis, realizing the on-demand release of the CuTA nanozyme. The released CuTA nanozyme has antibacterial and antiplaque properties. Meanwhile, as a metal-phenolic nanozyme, it can scavenge multiple ROS by simulating the cascade process of superoxide dismutase (SOD) and catalase (CAT). Further, the CuTA nanozyme can modulate the macrophage polarization from M1 phenotype to M2 phenotype through the Nrf2/NF-κB pathway, which reduces the pro-inflammatory cytokines, increases the anti-inflammatory cytokines, and promotes the expression of osteogenetic genes successively, thus relieving the inflammation and accelerating the tissue regeneration of periodontitis. Altogether, this multifunctional nanozyme on-demand release platform (TM/BHT/CuTA) provides a desirable strategy for the treatment of periodontitis.

Research progress of stimuli-responsive ZnO-based nanomaterials in biomedical applications.

Zinc oxide nanoparticles (ZnO NPs), an attractive oxide semiconductor material, are widely used in the biomedical field due to their good biosafety and economy. The proposal of stimuli-responsive materials provides a new way for the further application of single ZnO-based nanomaterials that cannot meet the ever-changing requirements. In this review, the emerging advances in exogenous stimuli (light, ultrasound, mechanical force, etc.) and endogenous stimuli (pH, enzymes, etc.) responsive systems of ZnO-based nanomaterials in biomedical applications are highlighted. First, the basic characteristics, response mechanisms and construction principles of single-stimulus-responsive ZnO-based nanomaterials, as well as their recent advances in tissue repair, medical devices and theranostics are summarized. Subsequently, the design method of multi-stimuli-responsive ZnO-based biomaterials is discussed, and the application advantages of multi-functional responsive systems are explained by analyzing typical cases of biomedical applications of multi-responsive strategies. Finally, we discuss the prospects for the design and development of stimuli-responsive ZnO-based biomaterials for biomedical applications and point out their advantages as well as the places that need to be further improved. The current review may provide a useful reference for researchers interested in constructing such abundant, inexpensive and widely applicable multi-stimuli-responsive materials.

Metal-Organic-Framework-Based Hydrogen-Release Platform for Multieffective Helicobacter Pylori Targeting Therapy and Intestinal Flora Protective Capabilities.

Helicobacter pylori (H. pylori) infection is the leading cause of chronic gastritis, peptic ulcer, and gastric cancer. Antibiotics, as traditional method for eliminating H. pylori, have no targeting effect, which causes serious bacterial resistance and gut dysbacteriosis. Moreover, antibiotics can hardly address hyperactive inflammatory response or damaged gastric mucosal barrier caused by H. pylori infection. Here, a pH-responsive metal-organic framework hydrogen-generation nanoparticle (Pd(H) @ ZIF-8) is reported, which is encapsulated with ascorbate palmitate (AP) hydrogel. Both in vitro and in vivo experiments demonstrate that the outer AP hydrogel can target and adhere to the inflammatory site through electrostatic interactions, and is then hydrolyzed by matrix metalloproteinase (MMP) enriching in inflammatory sites. The released Pd(H) @ ZIF-8 nanoparticles are further decomposed by gastric acid to generate zinc ions (Zn2+ ) and hydrogen, thus effectively killing H. pylori, alleviating inflammation and restoring impaired gastric mucosa simultaneously. Unexpectedly, this metal-organic framework hydrogen-generation platform (Pd(H) @ ZIF-8 @ AP) also has an effect toward avoiding the imbalance of intestinal flora, which thus provides a more precise, effective, and healthy strategy for the treatment of H. pylori infection.

Near-Infrared Light and Upconversion Nanoparticle Defined Nitric Oxide-Based Osteoporosis Targeting Therapy.

Osteoporosis is one of the most common diseases affecting bone metabolism. Nitric oxide (NO), an endogenous gas molecule involved in osteogenesis, can effectively promote the proliferation and differentiation of osteoblasts. Although exogenous NO can reverse osteoporosis to a certain extent, the transitory half-life and short diffusion radius of NO severely limit its application. In this work, a gas generation nanoplatform of NO with bone targeting property (UCPA) is developed based on the upconversion nanoparticles (UCNPs) that can convert 808 nm near-infrared (NIR) light into UV/blue light, and further stimulate the NO donor (BNN) to release NO. With an adjustment of the output power of the 808 nm NIR, the amount of released NO can be precisely controlled. Both in vitro and in vivo experiments demonstrate the favorable affinity of UCPA to bone due to the modification of alendronate; thus, it can directly release NO in bone and reverse osteoporosis. In addition, the cellular uptake of nanocomposites and intracellular NO release can be observed in preosteoblasts, thereby promoting their differentiation efficiently.

Electrical and visible light dual-responsive ZnO nanocomposite with multiple wound healing capability.

The healing process of open wounds is a competition between cells and bacteria. Therefore, a strategy that can quickly remove bacteria and promote cell proliferation to accelerate wound healing is urgently needed. Inspired by photoelectric synergy tactics, we improved both the optical and electrical response of zinc oxide (ZnO) through the modification of polydopamine (PDA) and reduced graphene oxide (rGO), thus obtaining a ZnO composite named PDA-rGO-ZnO (PrZ). Combined with the photoelectric double stimulation, the sterilization target could be completed from multiple physical levels simultaneously. More importantly, the band gap of ZnO was considerably narrowed by PDA encapsulation. The encapsulated ZnO thus could be effectively excited by pure yellow light (YL) with a moderate long wavelength, which fundamentally improved its safety in exerting photocatalytic antibacterial properties. In addition, we found that electrical stimulation (ES) could not only help to clear bacteria, but also facilitate the formation of new blood vessels. Animal experiments further showed that PrZ efficaciously regulated the immune response around the wound surface, promoted cell proliferation and the formation of collagen fibers, thereby accelerating wound healing.

ZnO/CPAN Modified Contact Lens with Antibacterial and Harmful Light Reduction Capabilities.

Compared with traditional glasses, the comfortable and convenient contact lens (CL) has seen an upsurge among the public. However, due to the lack of antibacterial properties of ordinary CLs, the risk of eye infection is greatly increased accordingly. On the other hand, ordinary CLs also cannot effectively reduce the short-wavelength blue light emitted from electronic products, such as mobile phones and computers. Aiming at the above two problems, zinc oxide (ZnO)/cyclized polyacrylonitrile (CPAN) composites are developed for CL modification. After loading with ZnO/CPAN (ZC), the CL shows a broad-spectrum antibacterial property. Further experiments also prove that it can block UVB, UVA, as well as blue light selectively, under the premise of ensuring hydrophilicity and certain transparency. Theoretically, this ZC-decorated CL can fundamentally reduce the damage to the eyes from harmful light emitted by light-emitting diodes and the secretion of pro-inflammatory factors, which is thus a promising eye protection strategy for modern society.

Jelly-Inspired Injectable Guided Tissue Regeneration Strategy with Shape Auto-Matched and Dual-Light-Defined Antibacterial/Osteogenic Pattern Switch Properties.

Periodontitis is a bacterial infectious disease leading to the loss of periodontal supporting tissues and teeth. The current guided tissue regeneration (GTR) membranes for periodontitis treatments cannot effectively promote tissue regeneration for the limited antibacterial properties and the excessively fast degradation rate. Besides, they need extra tailoring according to variform defects before implantation, leading to imprecise match. This study proposed an injectable sodium alginate hydrogel composite (CTP-SA) doped with cubic cuprous oxide (Cu2O) and polydopamine-coated titanium dioxide (TiO2@PDA) nanoparticles for GTR. Inspired by the gelation process of the jelly, the phase change (liquid to solid) of CTP-SA after injection could automatch variform bone defects. Meanwhile, CTP-SA exhibited broad-spectrum antibacterial capabilities under blue light (BL) irradiation, including Streptococcus mutans (one of the most abundant bacteria in oral biofilms). Moreover, the reactive oxygen species released under BL excitation could accelerate the oxidation of Cu+ to Cu2+. Afterward, osteogenesis could be enhanced through two factors simultaneously: the stimulation of newly formed Cu2+ and the photothermal effect of CTP-SA under near-infrared (NIR) irradiation. Collectively, through this dual-light (blue and NIR) noninvasive regulation, CTP-SA could switch antibacterial and osteogenic modes to address requirements of patients at different healing stages, thereby realizing the customized GTR procedures.

Tremella-Like ZnO@Col-I-Decorated Titanium Surfaces with Dual-Light-Defined Broad-Spectrum Antibacterial and Triple Osteogenic Properties.

The growing population of peri-implant diseases (PIDs) has become a public obsession, mainly due to the lack of antibacterial ability and osteogenic promotion of titanium (Ti) implants. Herein, inspired by tremella, we reported zinc oxide (ZnO)@collagen type I (Col-I)-decorated Ti for PIDs treatments. Compared with pure Ti implants, ZnO@Col-I-decorated Ti could be activated by a safe visible yellow light and showed excellent broad-spectrum antibacterial properties. The proliferation and osteogenic gene expression of bone marrow mesenchymal stem cells (BMSCs) indicated that the triple osseointegration of implants was realized through (I) the remarkedly improved surface hydrophilicity of ZnO@Col-I-decorated Ti, (II) the function of Col-I, and (III) the excellent near-infrared (NIR)-induced photothermal performance of ZnO. Collectively, the proposed dual-light-defined ZnO@Col-I coating was a promising implant surface modification system to provide customized treatments for each PID patient.

Slice-based Learning: A Programming Model for Residual Learning in Critical Data Slices.

In real-world machine learning applications, data subsets correspond to especially critical outcomes: vulnerable cyclist detections are safety-critical in an autonomous driving task, and "question" sentences might be important to a dialogue agent's language understanding for product purposes. While machine learning models can achieve high quality performance on coarse-grained metrics like F1-score and overall accuracy, they may underperform on critical subsets-we define these as slices, the key abstraction in our approach. To address slice-level performance, practitioners often train separate "expert" models on slice subsets or use multi-task hard parameter sharing. We propose Slice-based Learning, a new programming model in which the slicing function (SF), a programming interface, specifies critical data subsets for which the model should commit additional capacity. Any model can leverage SFs to learn slice expert representations, which are combined with an attention mechanism to make slice-aware predictions. We show that our approach maintains a parameter-efficient representation while improving over baselines by up to 19.0 F1 on slices and 4.6 F1 overall on datasets spanning language understanding (e.g. SuperGLUE), computer vision, and production-scale industrial systems.

Study on the blocking temperature of mixed magnetic films by Monte Carlo simulation.

The blocking temperature (TB) of the ferromagnetic and antiferromagnetic mixed films has been studied by Monte Carlo method. TB is found in the simulation, which is discussed with the energy of system and the spin configuration. The calculated results indicate that TB may be produced in the antiferromagnetic coupling system with small number of spins. The effect of little external field and the value of x on TB are also considered. It is found that TB increases with decreasing little external field and the value of x.