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.

Characterization of beta subunit variants of recombinant human chorionic gonadotrophin.

Human chorionic gonadotropin (hCG), an endogenous glycoprotein hormone, has been widely used for the treatment of infertility and corpus luteum defect in women. The biological specificity of hCG is essentially determined by its beta (ß-) subunit, whereas the alpha (α-) subunit is a common subunit shared among the gonadotropin family. In development of a therapeutic recombinant hCG, the purity analysis showed that the beta (ß-) subunit has two variants, ß1 and ß2. Structural characterization using a combination of analytical techniques has demonstrated that ß1-subunit is derived from non-glycosylation at Asn 13, whereas ß2-subunit is a normal species with complete N-glycosylation at both Asn 13 and Asn 30. In vivo Bioactivity evaluation of the r-hCG fractions with various ratios of ß1-and ß2-subunits showed that incomplete glycosylation at Asn 13 potentially reduced the biological activity of r-hCG to promote uterus growth. Although hCG has a long history of medicinal use, this is the first report to identify the structural difference of hCG ß-subunit variants, as well as to preliminary establish the structure-activity relationship of this variation. The obtained results also suggest the importance of variant characterization and necessary quality control of product variants during the development of recombinant protein therapeutics.

High-performance infrared photodetectors based on InAs/InAsSb/AlAsSb superlattice for 3.5†µm cutoff wavelength spectra.

High-performance infrared p-i-n photodetectors based on InAs/InAsSb/AlAsSb superlattices on GaSb substrate have been demonstrated at 300K. These photodetectors exhibit 50% and 100% cut-off wavelength of ∼3.2 µm and ∼3.5 µm, respectively. Under -130 mV bias voltage, the device exhibits a peak responsivity of 0.56 A/W, corresponding to a quantum efficiency (QE) of 28%. The dark current density at 0 mV and -130 mV bias voltage are 8.17 × 10-2 A/cm2 and 5.02 × 10-1 A/cm2, respectively. The device exhibits a saturated dark current shot noise limited specific detectivity (D*) of 3.43 × 109 cm·Hz1/2/W (at a peak responsivity of 2.5 µm) under -130 mV of applied bias.

Intercalation Doped Multilayer-Graphene-Nanoribbons for Next-Generation Interconnects.

Copper-based interconnects employed in a wide range of integrated circuit (IC) products are fast approaching a dead-end due to their increasing resistivity and diminishing current carrying capacity with scaling, which severely degrades both performance and reliability. Here we demonstrate chemical vapor deposition-synthesized and intercalation-doped multilayer-graphene-nanoribbons (ML-GNRs) with better performance (more than 20% improvement in estimated delay per unit length), 25%/72% energy efficiency improvement at local/global level, and superior reliability w.r.t. Cu for the first time, for dimensions (down to 20 nm width and thickness of 12 nm) suitable for IC interconnects. This is achieved through a combination of GNR interconnect design optimization, high-quality ML-GNR synthesis with precisely controlled number of layers, and effective FeCl3 intercalation doping. We also demonstrate that our intercalation doping is stable at room temperature and that the doped ML-GNRs exhibit a unique width-dependent doping effect due to increasingly efficient FeCl3 diffusion in scaled ML-GNRs, thereby indicating that our doped ML-GNRs will outperform Cu even for sub-20 nm widths. Finally, reliability assessment conducted under accelerated stress conditions (temperature and current density) established that highly scaled intercalated ML-GNRs can carry over 2 × 108 A/cm2 of current densities, whereas Cu interconnects suffer from immediate breakdown under the same stress conditions and thereby addresses the key criterion of current carrying capacity necessary for an alternative interconnect material. Our comprehensive demonstration of highly reliable intercalation-doped ML-GNRs paves the way for graphene as the next-generation interconnect material for a variety of semiconductor technologies and applications.

An ultra energy-efficient hardware platform for neuromorphic computing enabled by 2D-TMD tunnel-FETs.

Brain-like energy-efficient computing has remained elusive for neuromorphic (NM) circuits and hardware platform implementations despite decades of research. In this work we reveal the opportunity to significantly improve the energy efficiency of digital neuromorphic hardware by introducing NM circuits employing two-dimensional (2D) transition metal dichalcogenide (TMD) layered channel material-based tunnel-field-effect transistors (TFETs). Our novel leaky-integrate-fire (LIF) based digital NM circuit along with its Hebbian learning circuitry operates at a wide range of supply voltages, frequencies, and activity factors, enabling two orders of magnitude higher energy-efficient computing that is difficult to achieve with conventional material and/or device platforms, specifically the silicon-based 7 nm low-standby-power FinFET technology. Our innovative 2D-TFET based NM circuit paves the way toward brain-like energy-efficient computing that can unleash major transformations in future AI and data analytics platforms.

"Three birds, one stone" strategy of NIR-responsive CO/H2S dual-gas Nanogenerator for efficient treatment of osteoporosis.

Osteoporosis (OP), the most prevalent bone degenerative disease, has become a significant public health challenge globally. Current therapies primarily target inhibiting osteoclast activity or stimulating osteoblast activation, but their effectiveness remains suboptimal. This paper introduced a "three birds, one stone" therapeutic approach for osteoporosis, employing upconversion nanoparticles (UCNPs) to create a dual-gas storage nanoplatform (UZPA-CP) targeting bone tissues, capable of concurrently generating carbon monoxide (CO) and hydrogen sulfide (H2S). Through the precise modulation of 808 nm near-infrared (NIR) light, the platform could effectively control the release of CO and H2S in the OP microenvironment, and realize the effective combination of promoting osteogenesis, inhibiting osteoclast activity, and improving the immune microenvironment to achieve the therapeutic effect of OP. High-throughput sequencing results further confirmed the remarkable effectiveness of the nanoplatform in inhibiting apoptosis, modulating inflammatory response, inhibiting osteoclast differentiation and regulating multiple immune signaling pathways. The gas storage nanoplatform not only optimized the OP microenvironment with the assistance of NIR, but also restored the balance between osteoblasts and osteoclasts. This comprehensive therapeutic strategy focused on improving the bone microenvironment, promoting osteogenesis and inhibiting osteoclast activity provides an ideal new solution for the treatment of metabolic bone diseases.

Visible Light-Responsive Selenium Nanoparticles Combined with Sonodynamic Therapy to Promote Wound Healing.

In this paper, we synthesized selenium nanoparticles (SeNPs) that could be effectively excited by pure yellow light (YL) source to enhance antibacterial ability. Meanwhile, YL could also play the role of anti-inflammatory and promote wound healing. In addition, in order to overcome the problem of low penetration depth of photodynamic therapy (PDT), SeNPs were encapsulated with polyethylenimine (PEI), then modified with the sound sensitive agent indocyanine green (ICG), realizing the combined photoacoustic therapy to promote the healing of wounds infected by drug-resistant bacteria. The antibacterial efficiency of methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) reached more than 99% in in vitro and in vivo experiments within 10 min, which could safely and quickly kill drug-resistant bacteria to repair and heal wounds.

Photoresponsive Hydrogel-Coated Upconversion Cyanobacteria Nanocapsules for Myocardial Infarction Prevention and Treatment.

Myocardial infarction (MI) is a common disease that seriously threatens human health. It is noteworthy that oxygen is one of the key factors in the regulation of MI pathology procession: the controllable hypoxic microenvironment can enhance the tolerance of cardiac myocytes (CMs) and oxygen therapy regulates the immune microenvironment to repair the myocardial injury. Thus, the development of an oxygen-controllable treatment is critically important to unify MI prevention and timely treatment. Here, a hydrogel encapsulated upconversion cyanobacterium nanocapsule for both MI prevention and treatment is successfully synthesized. The engineered cyanobacteria can consume oxygen via respiration to generate a hypoxic microenvironment, resulting in the upregulation of heat shock protein70 (HSP70), which can enhance the tolerance of CMs for MI. When necessary, under 980 nm near-infrared (NIR) irradiation, the system releases photosynthetic oxygen through upconversion luminescence (UCL) to inhibit macrophage M1 polarization, and downregulates pro-inflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α), thereby repairing myocardial injury. To sum up, a photoresponsive upconversion cyanobacterium nanocapsule is developed, which can achieve MI prevention and treatment for only one injection via NIR-defined respiration and photosynthesis.

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.