An NIR-IIb emissive transmembrane voltage nano-indicator for the optical monitoring of electrophysiological activities in vivo.

In vivo transmembrane-voltage detection reflected the electrophysiological activities of the biological system, which is crucial for the diagnosis of neuronal disease. Traditional implanted electrodes can only monitor limited regions and induce relatively large tissue damage. Despite emerging monitoring methods based on optical imaging have access to signal recording in a larger area, the recording wavelength of less than 1000 nm seriously weakens the detection depth and resolution in vivo. Herein, a Förster resonance energy transfer (FRET)-based nano-indicator, NaYbF4:Er@NaYF4@Cy7.5@DPPC (Cy7.5-ErNP) with emission in the near-infrared IIb biological window (NIR-IIb, 1500-1700 nm) is developed for transmembrane-voltage detection. Cy7.5 dye is found to be voltage-sensitive and is employed as the energy donor for the energy transfer to the lanthanide nanoparticle, NaYbF4:Er@NaYF4 (ErNP), which works as the acceptor to achieve electrophysiological signal responsive NIR-IIb luminescence. Benefiting from the high penetration and low scattering of NIR-IIb luminescence, the Cy7.5-ErNP enables both the visualization of action potential in vitro and monitoring of Mesial Temporal lobe epilepsy (mTLE) disease in vivo. This work presents a concept for leveraging the lanthanide luminescent nanoprobes to visualize electrophysiological activity in vivo, which facilitates the development of an optical nano-indicator for the diagnosis of neurological disorders.

Focused Ultrasound-Responsive Nanocomposite with Near-Infrared II Mechanoluminescence for Spatiotemporally Selective Immune Activation in Lymph Nodes.

The immune regulation of the lymphatic system, especially the lymph node (LN), is of great significance for the treatment of diseases and the inhibition of pathogenic organisms spreading in the body. However, achieving precise spatiotemporal control of immune cell activation in LN in vivo remains a challenge due to tissue depth and off-target effects. Furthermore, minimally invasive and real-time feedback methods to monitor the regulation of the immune system in LN are lacking. Here, focused ultrasound responsive immunomodulator loaded nanoplatform (FURIN) with near-infrared II (NIR-II) luminescence is designed to achieve spatiotemporally controllable immune activation in LN in vivo. The NIR-II persistent luminescence of FURIN can track its delivery in LN through bioimaging. Under focused ultrasound (FUS) stimulation, the immunomodulator encapsulated in FURIN can be released locally in the LN to activate immune cells such as dendritic cells and the NIR-II mechanoluminescence of FURIN provides real-time optical feedback signals for immune activation. This work points to a FUS mediated, spatiotemporal selective immune activation strategy in vivo with the feedback control of luminescence signals via ultrasound responsive nanocomposite, which is of great significance in improving the efficacy and reducing the side effect of immune regulation for the development of potential immunotherapeutic methods in the future.

A bone-targeting near-infrared luminescence nanocarrier facilitates alpha-ketoglutarate efficacy enhancement for osteoporosis therapy.

Osteoporosis (OP), which largely increases the risk of fractures, is the most common chronic degenerative orthopedic disease in the elderly due to the imbalance of bone homeostasis. Alpha-ketoglutaric acid (AKG), an endogenous metabolic intermediate involved in osteogenesis, plays critical roles in osteogenic differentiation and mineralization and the inhibition of osteoclastogenic differentiation. However, the low bioavailability and poor bone-targeting efficiency of AKG seriously limit its efficacy in OP treatment. In this work, a bone-targeting, near-infrared emissive lanthanide luminescence nanocarrier loaded with AKG (ß-NaYF4:7%Yb, 60%Nd@NaLuF4@mSiO2-EDTA-AKG, abbreviated as LMEK) is developed for the enhancement of AKG efficacy in OP therapy. By utilizing the NIR-II luminescence (>1000 nm) of LMEK, whole-body bone imaging with high spatial resolution is achieved to confirm the bone enrichment of AKG noninvasively in vivo. The results reveal that LMEK exhibits a remarkable OP therapeutic effect in improving the osseointegration of the surrounding bone in the ovariectomized OP mice models, which is validated by the enhanced inhibition of osteoclast through hypoxia-inducible factor-1α suppression and promotion of osteogenic differentiation in osteoblast. Notably, the dose of AKG in LMEK can be reduced to only 0.2 % of the dose when pure AKG is used in therapy, which dramatically improves the bioavailability of AKG and mitigates the metabolism burden. This work provides a strategy to conquer the low utilization of AKG in OP therapy, which not only overcomes the challenges in AKG efficacy for OP treatment but also offers insights into the development and application of other potential drugs for skeletal diseases. STATEMENT OF SIGNIFICANCE: Alpha-ketoglutarate (AKG) is an intermediate within the Krebs cycle, participating in diverse metabolic and cellular processes, showing potential for osteoporosis (OP) therapy. However, AKG's limited bioavailability and inefficient bone-targeting hinder its effectiveness in treating OP. Herein, a near-infrared emissive nanocarrier is developed that precisely targets bones and delivers AKG, bolstering its effectiveness in OP therapy. Thanks to this efficient bone-targeting delivery, the AKG dosage is reduced to 0.2 % of the conventional treatment level. This marks the first utilization of a bone-targeting nanocarrier to amplify AKG's bioavailability and OP therapy efficacy. Furthermore, the mechanism of AKG-loaded nanocarrier regulating the biological behavior of osteoclasts and osteoblasts mediated is tentatively explored.

Carbon-Phosphorus Coupling Governs Microbial Effects on Nutrient Acquisition Strategies by Four Crops.

Plants adjust root morphological and/or exudation traits in response to phosphorus (P) mobilization mediated by microorganisms. We hypothesized that straw application coupled with P fertilization would influence microbial P and then root nutrient-acquisition strategies related to crop growth. Root morphological (length and average diameter) and exudation traits (acid phosphatase and carboxylates) of Brassica chinensis, Solanum lycopersicum, Lactuca sativa, and Vigna unguiculata in response to microbial P dynamics were characterized in no-P and P-fertilized soil with/without straw addition. Straw addition increased the growth of fungi and bacteria, stimulating microbial P immobilization at day 24. The high microbial abundance was associated with four tested crops having short roots in straw-amended compared with no-straw soil at day 24. In straw-amended soil, B. chinensis and S. lycopersicum shifted toward root P-acquisition strategies based on fast elongation and strong carboxylate exudation from days 24 to 40. Such effective root P-acquisition strategies together with microbial P release increased shoot P content in S. lycopersicum in straw-amended compared with those without straw at day 40. Conversely, L. sativa and V. unguiculata produced short roots in response to the stable (or even increased) microbial P after straw addition till day 40. In straw-amended soil, high P application stimulated root elongation and carboxylate exudation in L. sativa and V. unguiculata, whereas carboxylate exudation by S. lycopersicum was decreased compared with the straw-amended but non-fertilized treatment at day 40. In summary, root P-acquisition strategies in response to microbial P differed among the tested crop species. Phosphorus fertilization needs to be highlighted when returning straw to enhance P-use efficiency in vegetable cropping systems.

Effect of nitrogen application rate on soil fungi community structure in a rice-fish mutualistic system.

Rice-fish mutualistic production systems rationalise the use of water and soil resources in an improved approach to sustainable food production. However, drivers of fungi community structure in paddy soil, including effects of nitrogen (N) application rate, are unclear in these systems. Here, we assessed soil fungi community and soil physicochemical responses in paddy soil to contrasting rates of N application in a rice-fish system. To clarify the mutualistic effects, the rice-fish system was compared with a standard rice monoculture under a 325.5 kg ha-1 N application rate. The results showed that N application rate affected abundance of paddy soil fungi (P < 0.05). Alpha diversity and richness of fungi were lower in the rice-fish system, but evenness increased with a decrease in N application rate, while the rate of N determined diversity of soil fungi in the rice-fish system. Dominant genera in the two systems differed, and soil physicochemical properties were more important drivers of soil fungi community structure in the rice-fish mutualistic system than in rice monoculture. Total N, available N and P regulated the abundance of dominant fungi. Our results indicate that management of soil fungi may contribute to sustainable agricultural production.

Increased planting density of Chinese milk vetch (Astragalus sinicus) weakens phosphorus uptake advantage by rapeseed (Brassica napus) in a mixed cropping system.

Neighbouring plants can affect plant growth through altering root morphological and physiological traits, but how exactly root systems respond to neighbouring plants with varied density, determining nutrient uptake and shoot growth is poorly understood. In a pot-based experiment, rapeseed was grown alone (single rapeseed), or mixed with 3, 6, or 15 Chinese milk vetch plants. As controls, monocropped Chinese milk vetch was grown at the same planting density, 3, 6, or 15 plants per pot. Root interaction between rapeseed and Chinese milk vetch facilitated phosphorus (P) uptake in rapeseed grown with 3 plants of Chinese milk vetch. As the planting density of Chinese milk vetch in mixture increased, there was a decrease in citrate concentration and acid phosphatase activity but an increase in the total root length of Chinese milk vetch per pot, resulting in decreases in rapeseed root biomass, total root length and P uptake when rapeseed was grown with 6 or 15 Chinese milk vetch plants relative to rapeseed grown with 3 plants. These results demonstrate that the enhanced nutrient utilization induced by root interaction at low planting densities was eliminated by the increased planting density of the legume species in rapeseed/Chinese milk vetch mixed cropping system, suggesting that root/rhizosphere management through optimizing legume planting density is important for improving crop productivity and nutrient-use efficiency.