Low Duty-Cycling MAC Protocol for Low Data-Rate Medical Wireless Body Area Networks.

Wireless body area networks (WBANs) are severely energy constrained, and how to improve the energy efficiency so as to prolong the network lifetime as long as possible is one of the most important goals of WBAN research. Low data-rate WBANs are promising to cut down the energy consumption and extend the network lifetime. Considering the characteristics and demands of low data-rate WBANs, a low duty-cycling medium access control (MAC) protocol is specially designed for this kind of WBAN in this paper. Longer superframes are exploited to cut down the energy consumed on the transmissions and receptions of redundant beacon frames. Insertion time slots are embedded into the inactive part of a superframe to deliver the frames and satisfy the quality of service (QoS) requirements. The number of the data subsections in an insertion time slot can be adaptively adjusted so as to accommodate low data-rate WBANs with different traffic. Simulation results show that the proposed MAC protocol performs well under the condition of low data-rate monitoring traffic.

An Energy-Efficient MAC Protocol for Medical Emergency Monitoring Body Sensor Networks.

Medical emergency monitoring body sensor networks (BSNs) monitor the occurrence of medical emergencies and are helpful for the daily care of the elderly and chronically ill people. Such BSNs are characterized by rare traffic when there is no emergency occurring, high real-time and reliable requirements of emergency data and demand for a fast wake-up mechanism for waking up all nodes when an emergency happens. A beacon-enabled MAC protocol is specially designed to meet the demands of medical emergency monitoring BSNs. The rarity of traffic is exploited to improve energy efficiency. By adopting a long superframe structure to avoid unnecessary beacons and allocating most of the superframe to be inactive periods, the duty cycle is reduced to an extremely low level to save energy. Short active time slots are interposed into the superframe and shared by all of the nodes to deliver the emergency data in a low-delay and reliable way to meet the real-time and reliable requirements. The interposition slots can also be used by the coordinator to broadcast network demands to wake-up all nodes in a low-delay and energy-efficient way. Experiments display that the proposed MAC protocol works well in BSNs with low emergency data traffic.

A MAC protocol for medical monitoring applications of wireless body area networks.

Targeting the medical monitoring applications of wireless body area networks (WBANs), a hybrid medium access control protocol using an interrupt mechanism (I-MAC) is proposed to improve the energy and time slot utilization efficiency and to meet the data delivery delay requirement at the same time. Unlike existing hybrid MAC protocols, a superframe structure with a longer length is adopted to avoid unnecessary beacons. The time slots are mostly allocated to nodes with periodic data sources. Short interruption slots are inserted into the superframe to convey the urgent data and to guarantee the real-time requirements of these data. During these interruption slots, the coordinator can break the running superframe and start a new superframe. A contention access period (CAP) is only activated when there are more data that need to be delivered. Experimental results show the effectiveness of the proposed MAC protocol in WBANs with low urgent traffic.

NIR-II Absorption/Emission Dual Function Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy.

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near-infrared window (NIR-II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real-time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid-responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti-inflammatory agent, Ti3C2-BSA-CQ4T-H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications.

Dual regulation of osteosarcoma hypoxia microenvironment by a bioinspired oxygen nanogenerator for precise single-laser synergistic photodynamic/photothermal/induced antitumor immunity therapy.

The hypoxic tumor microenvironment (TME) of osteosarcoma (OS) is the Achilles' heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the hypoxia. Herein, we proposed a "reducing expenditure of O2 and broadening sources" dual-strategy and constructed ultrasmall IrO2@BSA-ATO nanogenerators (NGs) for decreasing the O2-consumption and elevating the O2-supply simultaneously. As O2 NGs, the intrinsic catalase (CAT) activity could precisely decompose the overexpressed H2O2 to produce O2 in situ, enabling exogenous O2 infusion. Moreover, the cell respiration inhibitor atovaquone (ATO) would be at the tumor sites, effectively inhibiting cell respiration and elevating oxygen content for endogenous O2 conservation. As a result, IrO2@BSA-ATO NGs systematically increase tumor oxygenation in dual ways and significantly enhance the antitumor efficacy of PDT. Moreover, the extraordinary photothermal conversion efficiency allows the implementation of precise photothermal therapy (PTT) under photoacoustic guidance. Upon a single laser irradiation, this synergistic PDT, PTT, and the following immunosuppression regulation performance of IrO2@BSA-ATO NGs achieved a superior tumor cooperative eradicating capability both in vitro and in vivo. Taken together, this study proposes an innovative dual-strategy to address the serious hypoxia problem, and this microenvironment-regulable IrO2@BSA-ATO NGs as a multifunctional theranostics platform shows great potential for OS therapy.

A Novel Activatable Nanoradiosensitizer for Second Near-Infrared Fluorescence Imaging-Guided Safe-Dose Synergetic Chemo-Radiotherapy of Rheumatoid Arthritis.

The precise theranostics of rheumatoid arthritis (RA) remains a formidable challenge in clinical practice. Exploring novel applications of contemporary therapeutic approaches like chemo-radiotherapy is promising as a highly effective strategy for RA. Herein, a novel activatable nanoradiosensitizer-40 (denoted as IRnR-40) is developed, based on encapsulating the clinically approved drugs cisplatin (DDP) and indocyanine green (ICG) within a gelatin shell to achieve second near-infrared fluorescence (NIR-II FL) imaging-guided safe-dose synergetic chemo-radiotherapy. The high concentration of matrix metalloproteinase-9 (MMP-9) in the RA microenvironment plays a pivotal role in triggering the responsive degradation of IRnR-40, leading to the rapid release of functional molecules DDP and ICG. The released ICG serves the dual purpose of illuminating the inflamed joints to facilitate accurate target volume delineation for guiding radiotherapy, as well as acting as a real-time reporter for quantifying the release of DDP to monitor efficacy. Meanwhile, the released DDP achieves highly effective synergistic chemotherapy and radiosensitization for RA via the dual reactive oxygen species (ROS)-mediated mitochondrial apoptotic pathway. To sum up, this activatable nanoradiosensitizer IRnR-40 is believed to be the first attempt to achieve efficient NIR-II FL imaging-guided safe-dose chemo-radiotherapy for RA, which provides a new paradigm for precise theranostics of refractory benign diseases.

Potato glycoside alkaloids exhibit antifungal activity by regulating the tricarboxylic acid cycle pathway of Fusarium solani.

Fusarium solani is a pathogenic fungus that causes significant harm, leading to crop yield reduction, fruit quality reduction, postharvest decay, and other diseases. This study used potato glycoside alkaloids (PGA) as inhibitors to investigate their effects on the mitochondrial structure and tricarboxylic acid (TCA) cycle pathway of F. solani. The results showed that PGA could inhibit the colony growth of F. solani (54.49%), resulting in the disappearance of the mitochondrial membrane and the loss of contents. PGA significantly decreased the activities of aconitase (ACO), isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), succinate dehydrogenase (SDH), fumarase (FH), malate dehydrogenase (MDH), succinyl-CoA synthetase (SCS), and increased the activity of citrate synthase (CS) in F. solani. After PGA treatment, the contents of acetyl coenzyme A (CoA), citric acid (CA), malic acid (L-MA), and α-ketoglutaric acid (α-KG) in F. solani were significantly decreased. The contents of isocitric acid (ICA), succinyl coenzyme A (S-CoA), succinic acid (SA), fumaric acid (FA), and oxaloacetic acid (OA) were significantly increased. Transcriptomic analysis showed that PGA could significantly affect the expression levels of 19 genes related to TCA cycle in F. solani. RT-qPCR results showed that the expression levels of ACO, IDH, α-KGDH, and MDH-related genes were significantly down-regulated, and the expression levels of SDH and FH-related genes were significantly up-regulated, which was consistent with the results of transcriptomics. In summary, PGA can achieve antifungal effects by reducing the tricarboxylic acid cycle's flow and regulating key genes' expression levels. This study reveals the antifungal mechanism of PGA from the perspective of TCA cycle, and provides a theoretical basis for the development and application of PGA as a biopesticide.

Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by excessive proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and accumulation of inflammatory cytokines. Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) dual-model imaging-guided multi-treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin-nanoparticles (MNPs), hydrogen gas (H2), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT.

A novel NIR-II FL/ PA imaging-guided synergistic photothermal-immune therapy: Biomineralizing nanosystems integrated with anti-tumor and bone repair.

Advanced stages of breast cancer are frequently complicated by bone metastases, which cause significant cancer-related bone destruction and mortality. However, the early precise theranostics of bone metastasis remains a formidable challenge in clinical practice. Herein,a novel all-in-one nanotheranostic system (ABI NYs) combining NIR-II FL/PA dual-modal imaging with photothermal-immunity therapeutic functionalities in one component was designed to precisely localize bone metastasis microscopic lesions and achieve complete tumor ablation at an early stage. The surface modification of the nanosystem with ibandronate (IBN) facilitates both passive and active targeting, significantly improving the detection rate of bone metastasis and suppressing the bone resorption. Superior photothermal performance produces sufficient heat to kill tumor cells while stimulating the upregulation of heat shock proteins 70 (HSP70), which triggers the immunogenic cell death (ICD) effect and the anti-tumor immune response. These all-in-one nanosystems precisely demonstrated early lesion localization in bone metastases and total tumor ablation with a single integration via "one-component, multi-functions" technique. To sum up, ABI NYs, as novel biomineralizing nanosystems integrated with anti-tumor and bone repair, present a synergistic therapy strategy, providing insight into the theranostics of bone metastases and clinical research.

Effect of Potato Glycoside Alkaloids on Energy Metabolism of Fusarium solani.

Fusarium solani is one of the primary pathogens causing root rot of wolfberry. The aims of this study were to investigate the inhibitory effect of potato glycoside alkaloids (PGA) on F. solani and its energy metabolism. In this study, the effects of PGA treatment on the growth and development of F. solani were investigated and the changes in the glycolytic pathway (EMP), ATPase activity, mitochondrial complex activity, mitochondrial structure, and energy charge level were analyzed to elucidate the possible antifungal mechanism of PGA on F. solani. The results showed that PGA treatment inhibited the colony growth, biomass, and spore germination of F. solani. PGA treatment reduced the glucose content and Hexokinase (HK) activity of F. solani, but increased the activity of Fructose-6-Phosphate Kinase (PFK) and Pyruvate Kinase (PK) and promoted the accumulation of pyruvic acid. In addition, PGA treatment inhibited the activities of H+-ATPase, Ca2+-ATPase, and mitochondrial complex IV, increased the mitochondrial inner membrane Ca2+ content and mitochondrial membrane permeability transition pore, and decreased the contents of ATP, ADP, and AMP as well as the energy charge. These results indicate that PGA treatment inhibits the growth and development of F. solani, activates the glycolysis pathway, inhibits ATPase activity and mitochondrial complex activity, and destroys the structure and function of mitochondrial membrane, resulting in a lower energy charge level.

A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management.

Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) mutation status over time challenge the design of effective EGFR tyrosine kinase inhibitor (TKI) treatment strategies for non-small cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for comprehensive tumor EGFR profiling in real time, particularly in lung cancer precision medicine trials. We report a positron emission tomography (PET) tracer, N-(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-18F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (18F-MPG), with high specificity to activating EGFR mutant kinase. We evaluate the feasibility of using 18F-MPG PET for noninvasive imaging and quantification of EGFR-activating mutation status in preclinical models of NSCLC and in patients with primary and metastatic NSCLC tumors. 18F-MPG PET in NSCLC animal models showed a significant correlation (R2 = 0.9050) between 18F-MPG uptake and activating EGFR mutation status. In clinical studies with NSCLC patients (n = 75), the concordance between the detection of EGFR activation by 18F-MPG PET/computed tomography (CT) and tissue biopsy reached 84.29%. There was a greater response to EGFR-TKIs (81.58% versus 6.06%) and longer median progression-free survival (348 days versus 183 days) in NSCLC patients when 18F-MPG PET/CT SUVmax (maximum standard uptake value) was ≥2.23 versus <2.23. Our study demonstrates that 18F-MPG PET/CT is a powerful method for precise quantification of EGFR-activating mutation status in NSCLC patients, and it is a promising strategy for noninvasively identifying patients sensitive to EGFR-TKIs and for monitoring the efficacy of EGFR-TKI therapy.

Development and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC.

To prepare and evaluate a new radiotracer 18F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of 18F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging. Ex vivo biodistribution assays were performed to quantify the accumulation of 18F-IRS in vivo. We also performed 18F-IRS PET/CT imaging of three patients with NSCLC. We labeled this small molecule with QD620 for flow cytometry and confocal imaging analyses. The uptakes of 18F-IRS by HCC827 and HCC827 tumors were significantly higher than those of H358, H1975 and H520, and they were reduced by the addition of 100 µM of gefitinib. Biodistribution experiments showed an accumulation of 18F-IRS in tumors of HCC827 xenografts. Flow cytometry and confocal imaging with QD620-IRS further demonstrated that binding specifically to HCC827 cells. 18F-IRS accumulation was preferential in the tumor, which was NSCLC with responsive EGFR exon 19 deleted. 18F-IRS showed high binding stability and specificity to 19 exon deleted EGFR mutation in vitro and vivo.

Outage Probability of MRC for κ-µ Shadowed Fading Channels under Co-Channel Interference.

In this paper, exact closed-form expressions are derived for the outage probability (OP) of the maximal ratio combining (MRC) scheme in the κ-µ shadowed fading channels, in which both the independent and correlated shadowing components are considered. The scenario assumes the received desired signals are corrupted by the independent Rayleigh-faded co-channel interference (CCI) and background white Gaussian noise. To this end, first, the probability density function (PDF) of the κ-µ shadowed fading distribution is obtained in the form of a power series. Then the incomplete generalized moment-generating function (IG-MGF) of the received signal-to-interference-plus-noise ratio (SINR) is derived in the closed form. By using the IG-MGF results, closed-form expressions for the OP of MRC scheme are obtained over the κ-µ shadowed fading channels. Simulation results are included to validate the correctness of the analytical derivations. These new statistical results can be applied to the modeling and analysis of several wireless communication systems, such as body centric communications.