Enhancing Flow Mediated Dilation Analysis by Optimizing an Open-Source Software with Automated Edge Detection.

Flow mediated dilation (FMD) is a common measure of endothelial function and an indicator of vascular health. Automated software methods exist to improve the speed and accuracy of FMD analysis. Compared to commercial software, open-source software offers similar capabilities at a much lower cost while allowing for increased customization specific to users' needs. We introduced modifications to an existing open-source software, FloWave.us to better meet FMD analysis needs. The purpose of this study was to compare the repeatability and reliability of the modified FloWave.us software to the original software and to manual measurements. To assess these outcomes, Duplex ultrasound imaging data from the popliteal artery in older adults were analyzed. The average percent FMD for the modified software was 6.98±3.68% and 7.27±3.81% for Observer 1 and 2 respectively, compared to 9.17±4.91% and 10.70±4.47% with manual measurements and 5.07±31.79% with the original software for Observer 1. The modified software and manual methods demonstrated higher intra-observer intraclass correlation coefficients (ICCs) for repeated measures for baseline diameter, peak diameter, and percent FMD compared to the original software. For percent FMD, the inter-observer ICC was 0.593 for manual measurements and 0.723 for the modified software. With the modified method an average of 97.7±2.4% of FMD videos frames were read, compared to only 17.9±15.0% frames read with the original method when analyzed by the same observer. Overall, this work further establishes open-source software as a robust and viable tool for FMD analysis and demonstrates improved reliability compared to the original software.

HIV-Negative Case of Talaromyces marneffei Pulmonary Infection with Liver Cirrhosis in China: A Case Report and Literature Review.

Background: Talaromyces marneffei (TM) is the third most prevalent opportunistic infection in HIV-positive patients after tuberculosis and cryptococcosis. However, such infection of non-HIV individuals has rarely been reported. Case Presentation: We describe a very rare case of a 52-year-old male who presented with a single space-occupying lesion on the right lung and was eventually diagnosed with pulmonary TM infection. The patient was HIV-negative and had liver cirrhosis with portal vein thrombosis. Lung tissue next-generation sequencing (NGS) revealed TM infection. We successfully treated the patient with voriconazole for 8 weeks and observed lesion absorption via subsequent CT. The patient consumed wild bamboo rats two months before admission. Mutations related to congenital immune deficiency were not detected by whole-exome sequencing. Conclusion: Early and timely diagnosis is critical for improving patient prognosis. NGS plays a vital role in the diagnosis of pulmonary TM infection in patients. To our knowledge, this is the first published case of pulmonary TM infection in an HIV-negative patient with liver cirrhosis.

De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression.

p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in approximately 50% of all human cancers. In its canonical role, p16 inhibits the G1-S-phase cell cycle progression through suppression of cyclin-dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. However, the broader impact of p16/CDKN2A loss on other nucleotide metabolic pathways and potential therapeutic targets remains unexplored. Using CRISPR knockout libraries in isogenic human and mouse melanoma cell lines, we determined several nucleotide metabolism genes essential for the survival of cells with loss of p16/CDKN2A. Consistently, many of these genes are upregulated in melanoma cells with p16 knockdown or endogenously low CDKN2A expression. We determined that cells with low p16/CDKN2A expression are sensitive to multiple inhibitors of de novo purine synthesis, including antifolates. Finally, tumors with p16 knockdown were more sensitive to the antifolate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2Alow tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents. SIGNIFICANCE: Antimetabolites were the first chemotherapies, yet many have failed in the clinic due to toxicity and poor patient selection. Our data suggest that p16 loss provides a therapeutic window to kill cancer cells with widely-used antifolates with relatively little toxicity.

Coordination Self-Assembled AuTPyP-Cu Metal-Organic Framework Nanosheets with pH/Ultrasound Dual-Responsiveness for Synergistically Triggering Cuproptosis-Augmented Chemotherapy.

Reactive oxygen species (ROS) mediated tumor cell death is a powerful anticancer strategy. Cuproptosis is a copper-dependent and ROS-mediated prospective tumor therapy strategy. However, the complex tumor microenvironment (TME), low tumor specificity, poor therapy efficiency, and lack of imaging capability impair the therapy output of current cuproptosis drugs. Herein, we designed a dual-responsive two-dimensional metal-organic framework (2D MOF) nanotheranostic via a coordination self-assembly strategy using Au(III) tetra-(4-pyridyl) porphine (AuTPyP) as the ligand and copper ions (Cu2+) as nodes. The dual-stimulus combined with the protonation of the pyridyl group in AuTPyP and deep-penetration ultrasound (US) together triggered the controlled release in an acidic TME. The ultrathin structure (3.0 nm) of nanotheranostics promoted the release process. The released Cu2+ was reduced to Cu+ by depleting the overexpressed glutathione (GSH) in the tumor, which not only activated the Ferredoxin 1 (FDX1)-mediated cuproptosis but also catalyzed the overexpressed hydrogen peroxide (H2O2) in the tumor into reactive oxygen species via Fenton-like reaction. Simultaneously, the released AuTPyP could specifically bind with thioredoxin reductase and activate the redox imbalance of tumor cells. These together selectively induced significant mitochondrial vacuoles and prominent tumor cell death but did not damage the normal cells. The fluorescence and magnetic resonance imaging (MRI) results verified this nanotheranostic could target the HeLa tumor to greatly promote the self-enhanced effect of chemotherapy/cuproptosis and tumor inhibition efficiency. The work helped to elucidate the controlled assembly of multiresponsive nanotheranostics and the high-specificity ROS regulation for application in anticancer therapy.

A one-two punch targeting reactive oxygen species and fibril for rescuing Alzheimer's disease.

Toxic amyloid-beta (Aß) plaque and harmful inflammation are two leading symptoms of Alzheimer's disease (AD). However, precise AD therapy is unrealizable due to the lack of dual-targeting therapy function, poor BBB penetration, and low imaging sensitivity. Here, we design a near-infrared-II aggregation-induced emission (AIE) nanotheranostic for precise AD therapy. The anti-quenching emission at 1350 nm accurately monitors the in vivo BBB penetration and specifically binding of nanotheranostic with plaques. Triggered by reactive oxygen species (ROS), two encapsulated therapeutic-type AIE molecules are controllably released to activate a self-enhanced therapy program. One specifically inhibits the Aß fibrils formation, degrades Aß fibrils, and prevents the reaggregation via multi-competitive interactions that are verified by computational analysis, which further alleviates the inflammation. Another effectively scavenges ROS and inflammation to remodel the cerebral redox balance and enhances the therapy effect, together reversing the neurotoxicity and achieving effective behavioral and cognitive improvements in the female AD mice model.

A Giant Heterometallic Polyoxometalate Nanocluster for Enhanced Brain-Targeted Glioma Therapy.

Giant heterometallic polyoxometalate (POM) clusters with precise atom structures, flexibly adjustable and abundant active sites are promising for constructing functional nanodrugs. However, current POM drugs are almost vacant in orthotopic brain tumor therapy due to the inability to effectively penetrate the blood-brain barrier (BBB) and low drug activity. Here, we designed the largest (3.0 nm × 6.0 nm) transition-metal-lanthanide co-encapsulated POM cluster {[Ce10 Ag6 (DMEA)(H2 O)27 W22 O70 ][B-α-TeW9 O33 ]9 }2 88- featuring 238 metal centers via synergistic coordination between two geometry-unrestricted Ce3+ and Ag+ linkers with tungsten-oxo cluster fragments. This POM was combined with brain-targeted peptide to prepare a brain-targeted nanodrug that could efficiently traverse BBB and target glioma cells. The Ag+ active centers in the nanodrug specifically activate reactive oxygen species to regulate the apoptosis pathway of glioma cells with a low half-maximal inhibitory concentration (5.66 µM). As the first brain-targeted POM drug, it efficiently prolongs the survival of orthotopic glioma-bearing mice.

Alfosbuvir plus Daclatasvir for Treatment of Chronic Hepatitis C Virus Infection in China.

INTRODUCTION: A pan-genotypic and effective treatment regimen for patients with chronic hepatitis C virus (HCV) infection remains an unmet medical need in China. Alfosbuvir is a novel potent HCV NS5B polymerase inhibitor in development for the treatment of chronic HCV infection. We conducted a phase 3 study to evaluate the efficacy and safety of alfosbuvir in combination with daclatasvir in Chinese patients with HCV infection. METHODS: All patients received 600 mg alfosbuvir tablets plus 60 mg daclatasvir tablets once daily for 12 weeks. The primary endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). A follow-up visit was done at week 4 and 12, and those who achieved SVR12 were followed up at post-treatment week 24. RESULTS: Of the 326 patients who received at least one dose of the study drug, 320 (98.2% [95% confidence interval (CI): 96.5%-99.5%]) achieved sustained virological response at post-treatment week 12 (SVR12), which was superior to the historical SVR12 rate of 88% (p < 0.0001). The SVR12 rates were similar regardless of most baseline characteristics. The most common adverse event (AE) (≥ 10%) was hypercholesterolemia. Serious adverse events (SAEs) were reported in 25 (7.7%) patients, none of which was judged to be related to the study drug. The majority of AEs were mild to moderate in severity. CONCLUSIONS: Alfosbuvir plus daclatasvir for 12 weeks was highly effective and safe in Chinese patients infected with HCV genotype 1, 2, 3, or 6, suggesting that this regimen could be a promising option for HCV treatment in China irrespective of genotype. TRIAL REGISTRATION: ClinicalTrial.gov identifier, NCT04070235.

Comparison of Hospital Online Price and Telephone Price for Shoppable Services.

Importance: US hospitals are required to publicly post their prices for specified shoppable services online. However, the extent to which a hospital's prices posted online correlate with the prices they give to a telephone caller is unknown. Objective: To compare hospitals' online cash prices for vaginal childbirth and brain magnetic resonance imaging (MRI) with prices offered to secret shopper callers requesting price estimates by telephone. Design, Setting, and Participants: This cross-sectional study included cash online prices from each hospital's website for vaginal childbirth and brain MRI collected from representative US hospitals between August and October 2022. Thereafter, again between August and October 2022, simulated secret shopper patients called each hospital requesting their lowest cash price for these procedures. Main Outcomes and Measures: We calculated the difference between each hospital's online and phone prices for vaginal childbirth and brain MRI, and the Pearson correlation coefficient (r) between the online and phone prices for each procedure, among hospitals able to provide both prices. Results: A total of 60 representative US hospitals (20 top-ranked, 20 safety-net, and 20 non-top-ranked, non-safety-net hospitals) were included in the analysis. For vaginal childbirth, 63% (12 of 19) of top-ranked hospitals, 30% (6 of 20) of safety-net hospitals, and 21% (4 of 19) of non-top-ranked, non-safety-net hospitals provided both online and telephone prices. For brain MRI, 85% (17 of 20) of top-ranked hospitals, 50% (10 of 20) of safety-net hospitals, and 100% (20 of 20) of non-top-ranked, non-safety-net hospitals provided prices both online and via telephone. Online prices and telephone prices for both procedures varied widely. For example, online prices for vaginal childbirth posted by top-ranked hospitals ranged from $0 to $55 221 (mean, $23 040), from $4361 to $14 377 (mean $10 925) for safety-net hospitals, and from $1183 to $30 299 (mean $15 861) for non-top-ranked, non-safety-net hospitals. Among the 22 hospitals providing prices both online and by telephone for vaginal childbirth, prices were within 25% of each other for 45% (10) of hospitals, while 41% (9) of hospitals had differences of 50% or more (Pearson r = 0.118). Among the 47 hospitals providing both online and phone prices for brain MRI, prices were within 25% of each other for 66% (31) of hospitals), while 26% (n = 12) had differences of 50% or more (Pearson r = -0.169). Among hospitals that provided prices both online and via telephone, there was a complete match between the online and telephone prices for vaginal childbirth in 14% (3 of 22) of hospitals and for brain MRI in 19% (9 of 47) of hospitals. Conclusions and Relevance: Findings of this cross-sectional study suggest that there was poor correlation between hospitals' self-posted online prices and prices they offered by telephone to secret shoppers. These results demonstrate hospitals' continued problems in knowing and communicating their prices for specific services. The findings also highlight the continued challenges for uninsured patients and others who attempt to comparison shop for health care.

Dual-Site Förster Resonance Energy Transfer Route of Upconversion Nanoparticles-Based Brain-Targeted Nanotheranostic Boosts the Near-Infrared Phototherapy of Glioma.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor with low survival, primarily due to the blood-brain barrier (BBB) and high infiltration. Upconversion nanoparticles (UCNPs)-based near-infrared (NIR) phototherapy with deep penetration is a promising therapy method against glioma but faces low photoenergy utilization that is induced by spectral mismatch and single-site Förster resonance energy transfer (FRET). Herein, we designed a brain-targeting NIR theranostic system with a dual-site FRET route and superior spectral matching to maximize energy utilization for synergistic photodynamic and photothermal therapy of glioma. The system was fabricated by Tm-doped UCNPs, zinc tetraphenylporphyrin (ZnTPP), and copper sulfide (CuS) nanoparticles under multioptimized modulation. First, the Tm-doping ratio was precisely adjusted to improve the relative emission intensity at 475 nm of UCNPs (11.5-fold). Moreover, the J-aggregate of ZnTPP increased the absorption at 475 nm (163.5-fold) of monomer; both together optimize the FRET matching between UCNPs and porphyrin for effective NIR photodynamic therapy. Simultaneously, the emission at 800 nm was utilized to magnify the photothermal effect of CuS nanoparticles for photothermal therapy via the second FRET route. After being modified by a brain-targeted peptide, the system efficiently triggers the synergistic phototherapy ablation of glioma cells and significantly prolongs the survival of orthotopic glioma-bearing mice after traversing the BBB and targeting glioma. This success of advanced spectral modulation and dual-site FRET strategy may inspire more strategies to maximize the photoenergy utilization of UCNPs for brain diseases.

Healthcare Utilization in Patients with Chronic Obstructive Pulmonary Disease Discharged from Coronavirus 2019 Hospitalization.

Rationale: There is concern that patients with chronic obstructive pulmonary disease (COPD) are at greater risk of increased healthcare utilization (HCU) following Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-COV-2) infection. Objective: To assess whether COPD is an independent risk factor for increased post-discharge HCU. Methods: We conducted a retrospective cohort study of patients with COPD discharged home from a hospitalization due to Coronavirus Disease 2019 (COVID-19) between April 1, 2020, and March 31, 2021, using Optum's de-identified Clinformatics® Data Mart Database (CDM). COVID-19 was identified by an International Classification of Diseases, tenth revision, clinical modification (ICD-10-CM) diagnosis code of U07.1. The primary outcome was HCU (ie, emergency department (ED) visits, readmissions, rehabilitation/skilled nursing facility (SNF) visits, outpatient office visits, and telemedicine visits) nine months post-discharge after COVID-19 hospitalization (from here on "post-discharge") in patients with COPD compared to HCU of patients without COPD. Poisson regression modeling was used to calculate relative risk (RR) and confidence interval (CI) for COPD, adjusted for the other covariates. Results: We identified a cohort of 160,913 patients hospitalized with COVID-19, with 57,756 discharged home and 14,622 (25.3%) diagnosed with COPD. Patients with COPD had a mean age of 75.48 years (±9.49); 55.5% were female and 70.9% were White. Patients with COPD had an increased risk of HCU in the nine months post-discharge after adjusting for the other covariates. Risk of ED visits, readmissions, length of stay during readmission, rehabilitation/SNF visits, outpatient office visits, and telemedicine visits were increased by 57% (RR 1.57; 95% CI 1.53-1.60), 50% (RR 1.50; 95% CI 1.46-1.54), 55% (RR 1.55; 95% CI 1.53-1.56), 18% (RR 1.18; 95% CI 1.14-1.22), 16% (RR 1.16; 95% CI 1.16-1.17), and 28% (RR 1.28; 95% CI 1.24-1.31), respectively. Younger patients (ages 18 to 65 years), women, and Hispanic patients with COPD showed an increased risk for post-discharge HCU. Conclusion: Patients with COPD hospitalized with COVID-19 experienced increased HCU post-discharge compared to patients without COPD.

De novo purine metabolism is a metabolic vulnerability of cancers with low p16 expression.

p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in ~50% of all human cancers. In its canonical role, p16 inhibits the G1-S phase cell cycle progression through suppression of cyclin dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. Whether other nucleotide metabolic genes and pathways are affected by p16/CDKN2A loss and if these can be specifically targeted in p16/CDKN2A-low tumors has not been previously explored. Using CRISPR KO libraries in multiple isogenic human and mouse melanoma cell lines, we determined that many nucleotide metabolism genes are negatively enriched in p16/CDKN2A knockdown cells compared to controls. Indeed, many of the genes that are required for survival in the context of low p16/CDKN2A expression based on our CRISPR screens are upregulated in p16 knockdown melanoma cells and those with endogenously low CDKN2A expression. We determined that cells with low p16/Cdkn2a expression are sensitive to multiple inhibitors of de novo purine synthesis, including anti-folates. Tumors with p16 knockdown were more sensitive to the anti-folate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2A-low tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents.

A Brain-Targeting NIR-II Ferroptosis System: Effective Visualization and Oncotherapy for Orthotopic Glioblastoma.

Near-infrared-II (NIR-II) ferroptosis activators offer promising potentials in in vivo theranostics of deep tumors, such as glioma. However, most cases are nonvisual iron-based systems that are blind for in vivo precise theranostic study. Additionally, the iron species and their associated nonspecific activations might trigger undesired detrimental effects on normal cells. Considering gold (Au) is an essential cofactor for life and it can specifically bind to tumor cells, Au(I)-based NIR-II ferroptosis nanoparticles (TBTP-Au NPs) for brain-targeted orthotopic glioblastoma theranostics are innovatively constructed. It achieves the real-time visual monitoring of both the BBB penetration and the glioblastoma targeting processes. Moreover, it is first validated that the released TBTP-Au specifically activates the effective heme oxygenase-1-regulated ferroptosis of glioma cells to greatly extend the survival time of glioma-bearing mice. This new ferroptosis mechanism based on Au(I) may open a new way for the fabrication of advanced and high-specificity visual anticancer drugs for clinical trials.

Melanoma-associated repair-like Schwann cells suppress anti-tumor T-cells via 12/15-LOX/COX2-associated eicosanoid production.

Peripheral glia, specifically the Schwann cells (SCs), have been implicated in the formation of the tumor microenvironment (TME) and in cancer progression. However, in vivo and ex vivo analyses of how cancers reprogram SC functions in different organs of tumor-bearing mice are lacking. We generated Plp1-CreERT/tdTomato mice which harbor fluorescently labeled myelinated and non-myelin forming SCs. We show that this model enables the isolation of the SCs with high purity from the skin and multiple other organs. We used this model to study phenotypic and functional reprogramming of the SCs in the skin adjacent to melanoma tumors. Transcriptomic analyses of the peritumoral skin SCs versus skin SCs from tumor-free mice revealed that the former existed in a repair-like state typically activated during nerve and tissue injury. Peritumoral skin SCs also downregulated pro-inflammatory genes and pathways related to protective anti-tumor responses. In vivo and ex vivo functional assays confirmed immunosuppressive activities of the peritumoral skin SCs. Specifically, melanoma-reprogrammed SCs upregulated 12/15-lipoxygenase (12/15-LOX) and cyclooxygenase (COX)-2, and increased production of anti-inflammatory polyunsaturated fatty acid (PUFA) metabolites prostaglandin E2 (PGE2) and lipoxins A4/B4. Inhibition of 12/15-LOX or COX2 in SCs, or EP4 receptor on lymphocytes reversed SC-dependent suppression of anti-tumor T-cell activation. Therefore, SCs within the skin adjacent to melanoma tumors demonstrate functional switching to repair-like immunosuppressive cells with dysregulated lipid oxidation. Our study suggests the involvement of the melanoma-associated repair-like peritumoral SCs in the modulation of locoregional and systemic anti-tumor immune responses.

Synergy of Cd Doping and S Vacancies in CdxZn1-xIn2S4 Hierarchical Nanotubes for Highly Improved Visible-Light-Driven H2 Evolution.

Photocatalytic water splitting over semiconductors is believed as a promising avenue to obtain H2 fuel from renewable solar energy. However, developing highly active and non-noble-metal photocatalysts for H2 evolution is still quite challenging to date. In this work, by constructing nanosheet-based nanotubes with Cd-doping and S vacancies, a highly improved visible-light-driven H2 production for ZnIn2S4 is achieved. Unlike nanoflowers aggregated with nanosheets, the nanosheet-assembled hierarchical nanotubes allow multiple scattering and reflection of incident light within the interior space, leading to an enhanced light-harvesting efficiency. Together with the benefits from Cd doping and S-vacancy engineering, including narrowed band gaps, efficient transmission and separation of charge carriers, abundant catalytically active sites, heightened photo-stability and photo-electron reduction capacity, as well as a strong electrostatic attraction to protons, the synthesized S-deficient CdxZn1-xIn2S4 hierarchical nanotubes exhibit an extraordinary photocatalytic H2 evolution capability under visible-light irradiation, delivering an outstanding H2-generation activity of 28.99 mmol·g-1·h-1 (corresponding to an apparent quantum yield of 37.1% at 400 nm), which is much superior to that of CdxZn1-xIn2S4 nanoflowers, Pt-loaded ZnIn2S4 nanotubes, and most ever reported ZnIn2S4-based photocatalysts. Our study could inspire the development of low-cost and high-performance photocatalysts via rational structural design and optimization.

Noble Metal Nanoparticle-Loaded Porphyrin Hexagonal Submicrowires Composites (M-HW): Photocatalytic Synthesis and Enhanced Photocatalytic Activity.

Surface plasmon resonance (SPR) photocatalysts have attracted considerable attention because of their strong absorption capacity of visible light and enhanced photogenic carrier separation efficiency. However, the separate production of metal nanoparticles (NPs) and semiconductors limits the photogenic charge transfer. As one of the most promising organic photocatalysts, porphyrin self-assemblies with a long-range ordered structure-enhance electron transfer. In this study, plasmonic noble metal-based porphyrin hexagonal submicrowires composites (M-HW) loaded with platinum (Pt), silver (Ag), gold (Au), and palladium (Pd) NPs were synthesized through a simple in situ photocatalytic method. Homogeneous and uniformly distributed metal particles on the M-HW composites enhanced the catalytic or chemical properties of the organic functional nanostructures. Under the same loading of metal NPs, the methyl orange photocatalytic degradation efficiency of Ag-HW [kAg-HW (0.043 min-1)] composite was three times higher than that of HW, followed by Pt-HW [kPt-HW (0.0417 min-1)], Au-HW [kAu-HW (0.0312 min-1)], and Pd-HW [kPd-HW (0.0198 min-1)]. However, the rhodamine B (RhB) and eosin B photocatalytic degradations of Pt-HW were 4 times and 2.6 times those of HW, respectively. Finally, the SPR-induced electron injection, trapping, and recombination processes of the M-HW system were investigated. These results showed that M-HW plasmonic photocatalysts exhibited excellent photocatalytic performances, making them promising materials for photodegrading organic pollutants.

Synthesis of the ZnTPyP/WO3 nanorod-on-nanorod heterojunction direct Z-scheme with spatial charge separation ability for enhanced photocatalytic hydrogen generation.

The direct Z-scheme photocatalytic system can effectively improve the separation efficiency of photogenerated carriers through the photosynthesis-based photocarrier transport model. In this study, zinc porphyrin-assembled nanorods (ZnTPyP) and WO3 nanorods' nanorod-on-nanorod heterojunctions (ZnTPyP/WO3) were successfully prepared through a simple modified acid-base neutralization micelle-confined assembly method using WO3 nanorods as the nucleation template and ZnTPyP as building blocks. ZnTPyP achieved a controllable assembly onto WO3 nanorods through N-W coordination. ZnTPyP/WO3 nanorod-on-nanorod heterojunctions exhibited a structure-dependent photocatalytic performance for hydrogen production. The ZnTPyP/WO3 nanorod-on-nanorod heterojunctions exhibited a optimal hydrogen production rate (74.53 mmol g-1 h-1) using Pt as the co-catalyst, which was 2.64 times that of the ZnTPyP self-assembled nanorods. The improvement in the photocatalytic hydrogen production efficiency could be mainly attributed to the direct Z-scheme electron-transfer mechanism from WO3 to ZnTPyP. This is the first report of an approach using porphyrin-assembled nanostructures to construct organic-inorganic Z-scheme photocatalysts. This study offers valuable information for preparing new efficient photocatalysts based on organic supramolecular orderly aggregate materials.

Near-Infrared Aggregation-Induced Emission Luminogens for In Vivo Theranostics of Alzheimer's Disease.

Optimized theranostic strategies for Alzheimer's disease (AD) remain almost absent from bench to clinic. Current probes and drugs attempting to prevent ß-amyloid (Aß) fibrosis encounter failures due to the blood-brain barrier (BBB) penetration challenge and blind intervention time window. Herein, we design a near-infrared (NIR) aggregation-induced emission (AIE) probe, DNTPH, via balanced hydrophobicity-hydrophilicity strategy. DNTPH binds selectively to Aß fibrils with a high signal-to-noise ratio. In vivo imaging revealed its excellent BBB permeability and long-term tracking ability with high-performance AD diagnosis. Remarkably, DNTPH exhibits a strong inhibitory effect on Aß fibrosis and promotes fibril disassembly, thereby attenuating Aß-induced neurotoxicity. DNTPH treatment significantly reduced Aß plaques and rescued learning deficits in AD mice. Thus, DNTPH serves as the first AIE in vivo theranostic agent for real-time NIR imaging of Aß plaques and AD therapy simultaneously.

Measuring Zak phase in room-temperature atoms.

Cold atoms provide a flexible platform for synthesizing and characterizing topological matter, where geometric phases play a central role. However, cold atoms are intrinsically prone to thermal noise, which can overwhelm the topological response and hamper promised applications. On the other hand, geometric phases also determine the energy spectra of particles subjected to a static force, based on the polarization relation between Wannier-Stark ladders and geometric Zak phases. By exploiting this relation, we develop a method to extract geometric phases from energy spectra of room-temperature superradiance lattices, which are momentum-space lattices of timed Dicke states. In such momentum-space lattices the thermal motion of atoms, instead of being a source of noise, provides effective forces which lead to spectroscopic signatures of the Zak phases. We measure Zak phases directly from the anti-crossings between Wannier-Stark ladders in the Doppler-broadened absorption spectra of superradiance lattices. Our approach paves the way of measuring topological invariants and developing their applications in room-temperature atoms.

Biomimetic Dp44mT-nanoparticles selectively induce apoptosis in Cu-loaded glioblastoma resulting in potent growth inhibition.

Selective targeting of elevated copper (Cu) in cancer cells by chelators to induce tumor-toxic reactive oxygen species (ROS) may be a promising approach in the treatment of glioblastoma multiforme (GBM). Previously, the Cu chelator di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) attracted much interest due to its potent anti-tumor activity mediated by the formation of a highly redox-active Cu-Dp44mT complex. However, its translational potential was limited by the development of toxicity in murine models of cancer reflecting poor selectivity. Here, we overcame the limitations of Dp44mT by incorporating it in new biomimetic nanoparticles (NPs) optimized for GBM therapy. Biomimetic design elements enhancing selectivity included angiopeptide-2 functionalized red blood cell membrane (Ang-M) camouflaging of the NPs carrier. Co-loading Dp44mT with regadenoson (Reg), that transiently opens the blood-brain-barrier (BBB), yielded biomimetic Ang-MNPs@(Dp44mT/Reg) NPs that actively targeted and traversed the BBB delivering Dp44mT specifically to GBM cells. To further improve selectivity, we innovatively pre-loaded GBM tumors with Cu. Oral dosing of U87MG-Luc tumor bearing mice with diacetyl-bis(4-methylthiosemicarbazonato)-copperII (Cu(II)-ATSM), significantly enhanced Cu-level in GBM tumor. Subsequent treatment of mice bearing Cu-enriched orthotopic U87MG-Luc GBM with Ang-MNPs@(Dp44mT/Reg) substantially prevented orthotopic GBM growth and led to maximal increases in median survival time. These results highlighted the importance of both angiopeptide-2 functionalization and tumor Cu-loading required for greater selective cytotoxicity. Targeting Ang-MNPs@(Dp44mT/Reg) NPs also down-regulated antiapoptotic Bcl-2, but up-regulated pro-apoptotic Bax and cleaved-caspase-3, demonstrating the involvement of the apoptotic pathway in GBM suppression. Notably, Ang-MNPs@(Dp44mT/Reg) showed negligible systemic drug toxicity in mice, further indicating therapeutic potential that could be adapted for other central nervous system disorders.

Tourism Information Management System Using Neural Networks Driven by Particle Swarm Model.

Based on the concept of "smart tourism," this paper designs and implements a tourism management information system based on PSO-optimized NN. The foreground tourism web page of the system adopts DIV + CSS mode for page planning and layout, PHP as the client script language, and SQL server as the database to store and analyze user information. At the same time, the system adds personalized components to the user's search ranking results, so that the routes and scenic spots presented in front of users in the result interface are more in line with users' consumption habits. In order to verify the performance of the model and algorithm constructed in this paper, several experiments were carried out in this paper. Experimental results show that the prediction accuracy of this algorithm is 94.67% and the recall rate is 96.11%. This algorithm can overcome the disadvantages of traditional algorithms and provide some effective suggestions for tourism management. At the same time, this paper applies the concept of "smart tourism" to specific tourism informatization, which can promote the transformation and upgrading of tourism industry structure and further enhance the overall development level of tourism industry.