High-Precision Log-Ratio Spot Position Detection Algorithm with a Quadrant Detector under Different SNR Environments.

In atmospheric laser communication, a beam is transmitted through an atmospheric channel, and the photocurrent output from a quadrant detector (QD) used as the tracking sensor fluctuates significantly. To ensure uninterrupted communication and to adapt to such fluctuations, in this paper we apply logarithmic amplifiers to process the output signals of a QD. To further improve the measurement accuracy of the spot position, we firstly propose an integral infinite log-ratio algorithm (IILRA) and an integral infinity log-ratio algorithm based on the signal-to-noise ratio (BSNR-IILRA) through analysis of the factors influencing the measurement error considering the signal-to-noise ratio (SNR) parameter. Secondly, the measurement error of the two algorithms under different SNRs and their variations are analyzed. Finally, a spot position detection experiment platform is built to correctly and efficiently verify the two algorithms. The experimental results show that when the SNR is 54.10 dB, the maximum error and root mean square error of the spot position of the IILRA are 0.0054 mm and 0.0039 mm, respectively, which are less than half those of the center approximation algorithm (CAA). When the SNR is 23.88 dB, the maximum error and root mean square error of the spot position of the BSNR-IILRA are 0.0046 mm and 0.0034 mm, respectively, which are one-thirtieth and one-twentieth of the CAA, respectively. The spot position measurement accuracy of the two proposed algorithms is significantly improved compared with the CAA.

Low-dose X-ray enhanced tumor accumulation of theranostic nanoparticles for high-performance bimodal imaging-guided photothermal therapy.

BACKGROUND: Theranostic nanoparticles (NPs) have achieved rapid development owing to their capacity for personalized multimodal diagnostic imaging and antitumor therapy. However, the efficient delivery and bulk accumulation of NPs in tumors are still the decisive factors in improving therapeutic effect. It is urgent to seek other methods to alters tumor microenvironment (like vascular permeability and density) for enhancing the efficiency of nanoparticles delivery and accumulation at the tumor site. METHODS: Herein, we developed a Raman-tagged hollow gold nanoparticle (termed as HAuNP@DTTC) with surface-enhanced Raman scattering (SERS) property, which could be accumulated efficiently in tumor site with the pre-irradiation of low-dose (3 Gy) X-ray and then exerted highly antitumor effect in breast cancer model. RESULTS: The tumor growth inhibition (TGI) of HAuNP@DTTC-induced photothermal therapy (PTT) was increased from 60% for PTT only to 97%, and the lethal distant metastasis of 4T1 breast cancer (such as lung and liver) were effectively inhibited under the X-ray-assisted PTT treatment. Moreover, with the strong absorbance induced by localized surface plasmon resonance in near-infrared (NIR) region, the signals of Raman/photoacoustic (PA) imaging in tumor was also significantly enhanced after the administration of HAuNP@DTTC, indicating it could be used as the Raman/PA imaging and photothermal agent simultaneously under 808 nm laser irradiation. CONCLUSIONS: Our studied of the as-prepared HAuNP@DTTC integrated the Raman/PA imaging and PTT functions into the single platform, and showed the good prospects for clinical applications especially with the low-dose X-ray irradiation as an adjuvant, which will be a productive strategy for enhancing drug delivery and accumulation in tumor theranostics.

Asymmetric α-electrophilic difluoromethylation of ß-keto esters by phase transfer catalysis.

An efficient and enantioselective α-electrophilic difluoromethylation of ß-keto esters has been achieved by phase-transfer catalysis. This procedure is applicable to different kinds of ß-keto esters with a series of cinchona-derived C-2' aryl-substituted phase-transfer catalysts. The reaction gives the corresponding products in good enantioselectivities (up to 83% ee) and yields (up to 92%) with high C/O regioselectivities (up to 98 : 2). Moreover, the C/O selectivity of ß-keto esters could be easily reversed and controlled. This asymmetric difluoromethylation provided a novel and efficient way for introducing chiral C-CF2H groups.

Comparative efficacy and safety of glycerol versus mannitol in patients with cerebral oedema and elevated intracranial pressure: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Glycerol is thought to be superior to mannitol in the treatment of cerebral oedema and elevated intracranial pressure (ICP), particularly with safety concerns. However, the current evidence remains insufficient. Therefore, we aimed to compare the efficacy and safety of glycerol versus mannitol in this meta-analysis. METHODS: PubMed, EMBASE, Web of Science, CENTRAL, China National Knowledge Infrastructure, Wanfang Database, Chongqing VIP information, ClinicalTrials.gov, and the reference lists of relevant articles were searched for randomized controlled trials comparing glycerol and mannitol in patients with brain oedema and elevated ICP. Two investigators independently identified the articles, assessed the study quality and extracted data. Data analyses were performed using RevMan software. RESULTS AND DISCUSSION: Thirty trials involving 3144 patients met our inclusion criteria. Pooled data indicated that glycerol and mannitol had comparable effectiveness in controlling cerebral oedema (RR, 1.00; 95% CI, 0.97 to 1.03; p = .97), but the risks of acute kidney injury and electrolyte disturbances were significantly lower with glycerol (RR, 0.21; 95% CI, 0.16 to 0.27 and RR, 0.23; 95% CI, 0.17 to 0.30, respectively) than mannitol. Moreover, there seemed to be a lower probability of rebound ICP after the withdrawal of glycerol. Neither haemolysis nor elevated blood glucose levels were observed in the glycerol group. WHAT IS NEW AND CONCLUSION: Regarding the balance between efficacy and safety, glycerol could be an effective and more tolerable alternative therapy for cerebral oedema and elevated ICP than mannitol, especially for high-risk populations of renal failure.

Surface-anchored framework for generating RhD-epitope stealth red blood cells.

Rhesus D (RhD) is one of the most important immunogenic antigens on red blood cells (RBCs). However, the supply of RhD-negative blood frequently faces critical shortages in clinical practice, and the positive-to-negative transition of the RhD antigen remains a great challenge. Here, we developed an alternative approach for sheltering the epitopes on RhD-positive RBCs using a surface-anchored framework, which is flexible but can achieve an optimal shield effect with minimal physicochemical influence on the cell. The chemical framework completely obstructed the RhD antigens on the cell surface, and the assessments of both blood transfusion in a mouse model and immunostimulation with human RhD-positive RBCs in a rabbit model confirmed the RhD-epitope stealth characteristics of the engineered RBCs. This work provides an efficient methodology for improving the cell surface for universal blood transfusion and generally indicates the potential of rationally designed cell surface engineering for transfusion and transplantation medicine.

Arginine-Rich Manganese Silicate Nanobubbles as a Ferroptosis-Inducing Agent for Tumor-Targeted Theranostics.

Ferroptosis, an iron-based cell-death pathway, has recently attracted great attention owing to its effectiveness in killing cancer cells. Previous investigations focused on the development of iron-based nanomaterials to induce ferroptosis in cancer cells by the up-regulation of reactive oxygen species (ROS) generated by the well-known Fenton reaction. Herein, we report a ferroptosis-inducing agent based on arginine-rich manganese silicate nanobubbles (AMSNs) that possess highly efficient glutathione (GSH) depletion ability and thereby induce ferroptosis by the inactivation of glutathione-dependent peroxidases 4 (GPX4). The AMSNs were synthesized via a one-pot reaction with arginine (Arg) as the surface ligand for tumor homing. Subsequently, a significant tumor suppression effect can be achieved by GSH depletion-induced ferroptosis. Moreover, the degradation of AMSNs during the GSH depletion contributed to T1-weighted magnetic resonance imaging (MRI) enhancement as well as on-demand chemotherapeutic drug release for synergistic cancer therapy. We anticipate that the GSH-depletion-induced ferroptosis strategy by using manganese-based nanomaterials would provide insights in designing nanomedicines for tumor-targeted theranostics.

Exploring the Steric and Electronic Factors Governing the Regio- and Enantioselectivity of the Pd-Catalyzed Decarboxylative Generation and Allylation of 2-Azaallyl Anions.

The impact of the steric and electronic factors in both the para-substituted benzaldimine and 2,2-diarylglycine components on the regioselectivity and enantioselectivity of the palladium-catalyzed decarboxylative allylation of allyl 2,2-diarylglycinate aryl imines was explored. These studies revealed that using 2,2-di(2-methoxyphenyl)glycine as the amino acid linchpin allowed for the exclusive synthesis of the desired homoallylic benzophenone imine regioisomers, independent of the nature of the imine moiety, in typically high yields. The resulting enantiomeric ratios, however, are slightly decreased in comparison to the transformations involving the corresponding allyl 2,2-diphenylglycinate imines, but this is more than balanced out by the increases in yield and regioselectivity. Overall, these studies suggest a general strategy for the highly regioselective functionalization of 2-azaallyl anions.

Renal-Clearable Hollow Bismuth Subcarbonate Nanotubes for Tumor Targeted Computed Tomography Imaging and Chemoradiotherapy.

Although metallic nanomaterials with high X-ray attenuation coefficients have been widely used as X-ray computed tomography (CT) contrast agents, their intrinsically poor biodegradability requires them to be cleared from the body to avoid any potential toxicity. On the other hand, extremely small-sized nanomaterials with outstanding renal clearance properties are not much effective for tumor targeting because of their too rapid clearance in vivo. To overcome this dilemma, here we report on the hollow bismuth subcarbonate nanotubes (BNTs) assembled from renal-clearable ultrasmall bismuth subcarbonate nanoclusters for tumor-targeted imaging and chemoradiotherapy. The BNTs could be targeted to tumors with high efficiency and exhibit a high CT contrast effect. Moreover, simultaneous radio- and chemotherapy using drug-loaded BNTs could significantly suppress tumor volumes, highlighting their potential application in CT imaging-guided therapy. Importantly, the elongated nanotubes could be disassembled into isolated small nanoclusters in the acidic tumor microenvironment, accelerating the payload release and kidney excretion. Such body clearable CT contrast agent with high imaging performance and multiple therapeutic functions shall have a substantial potential for biomedical applications.

Ceria nanocrystals decorated mesoporous silica nanoparticle based ROS-scavenging tissue adhesive for highly efficient regenerative wound healing.

Restoration of tissue integrity and tissue function of wounded skin are both essential for wound repair and regeneration, while synergistic promotion of the two remains elusive. Since elevated reactive oxygen species (ROS) production in the injured site has been implicated in triggering a set of deleterious effects such as cellular senescence, fibrotic scarring, and inflammation, it is speculated that alleviating oxidative stress in the microenvironment of injured site would be beneficial to promote regenerative wound healing. In this study, a highly versatile ROS-scavenging tissue adhesive nanocomposite is synthesized by immobilizing ultrasmall ceria nanocrystals onto the surface of uniform mesoporous silica nanoparticles (MSN). The ceria nanocrystals decorated MSN (MSN-Ceria) not only has strong tissue adhesion strength, but also significantly restricts ROS exacerbation mediated deleterious effects, which efficiently accelerates the wound healing process, and more importantly, the wound area exhibits an unexpected regenerative healing characteristic featured by marked skin appendage morphogenesis and limited scar formation. This strategy can also be adapted to other wound repair where both ROS-scavenging activity and tissue adhesive ability matter.

pH-Sensitive Pt Nanocluster Assembly Overcomes Cisplatin Resistance and Heterogeneous Stemness of Hepatocellular Carcinoma.

Response rates to conventional chemotherapeutics remain unsatisfactory for hepatocellular carcinoma (HCC) due to the high rates of chemoresistance and recurrence. Tumor-initiating cancer stem-like cells (CSLCs) are refractory to chemotherapy, and their enrichment leads to subsequent development of chemoresistance and recurrence. To overcome the chemoresistance and stemness in HCC, we synthesized a Pt nanocluster assembly (Pt-NA) composed of assembled Pt nanoclusters incorporating a pH-sensitive polymer and HCC-targeting peptide. Pt-NA is latent in peripheral blood, readily targets disseminated HCC CSLCs, and disassembles into small Pt nanoclusters in acidic subcellular compartments, eventually inducing damage to DNA. Furthermore, treatment with Pt-NA downregulates a multitude of genes that are vital for the proliferation of HCC. Importantly, CD24+ side population (SP) CSLCs that are resistant to cisplatin are sensitive to Pt-NA, demonstrating the immense potential of Pt-NA for treating chemoresistant HCC.

Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents.

Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.