Excimer laser coronary angioplasty combined with drug-coated balloon in the treatment of in-stent restenosis.

OBJECTIVES: The aim of this study is to investigate the safety and efficacy of excimer laser coronary angioplasty (ELCA) combined with drug-coated balloons (DCBs) in the treatment of in-stent restenosis (ISR), and to explore whether the contrast injection technique would improve the neointimal tissue ablation of ELCA. METHODS: We studied patients diagnosed with ISR between January 2019 and October 2022 at two medical centers. These patients underwent DCB angioplasty guided by optical coherence tomography (OCT). Based on whether ELCA was performed before DCB treatment, patients were categorized into two groups: the ELCA + DCB group and the DCB group. All patients underwent clinical follow-up 1 year after the procedure. The primary endpoint was the 1-year rate of target lesion revascularization (TLR), which was defined as any repeat percutaneous intervention or bypass surgery on the target vessel conducted to address restenosis or other complications related to the target lesion. The secondary endpoints including immediate luminal gain (ΔMLA, defined as the difference in minimum lumen area before and after the intervention). RESULTS: A total of 85 lesions in 75 patients were included. The mean age of the study population was 64.2 ± 12.0 years, with 81.3% male. Baseline clinical characteristics were well-balanced, and procedural success was 100% in both groups. The ELCA + DCB group (n = 24) exhibited a greater ΔMLA compared to the DCB group (n = 61) (3.57 ± 0.79 mm² vs. 2.50 ± 1.06 mm², [95% confidence interval, CI: 0.57-1.69], p < 0.001), The reduction in 1-year TLR was more frequently observed in patients from the ELCA + DCB group compared to the DCB group (hazard ratio 0.33 [95% CI: 0.11-0.99]; log-rank p = 0.048). The exploratory analysis showed that ELCA with contrast infusion is associated with greater acute lumen gain compared to ELCA with saline infusion (p < 0.001). CONCLUSIONS: The combination of ELCA and DCB is a safe and effective treatment strategy for in-stent stenosis. Additionally, compared with saline injection, ELCA with contrast injection is associated with greater acute lumen gain. However, the optimal contrast agent concentration and long-term outcome of the contrast injection technique need confirmation through larger sample sizes and prospective studies.

Cinnamic Acid: A Low-Toxicity Natural Bidentate Ligand for Uranium Decorporation.

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C9H7O2)2·UO2 (denoted as UO2-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.

Investigation of Additive-Manufactured Carbon Fiber-Reinforced Polyethylene Terephthalate Honeycomb for Application as Non-Pneumatic Tire Support Structure.

A non-pneumatic tire (NPT) overcomes the shortcomings of a traditional pneumatic tire such as wear, punctures and blowouts. In this respect, it shows great potential in improving driving safety, and has received great attention in recent years. In this paper, a carbon fiber-reinforced polyethylene terephthalate (PET/CF) honeycomb is proposed as a support structure for NPTs, which can be easily prepared using 3D printing technology. The experimental results showed that the PET/CF has high strength and modulus and provides excellent mechanical properties. Then, a finite element (FE) model was established to predict the compression performance of auxetic honeycombs. Good agreement was achieved between the experimental data and FE analysis. The influence of the cell parameters on the compressive performance of the support structure were further analyzed. Both the wall thickness and the vertically inclined angle could modulate the mechanical performance of the NPT. Finally, the application of vertical force is used to analyze the static load of the structure. The PET/CF honeycomb as the support structure of the NPT showed outstanding bearing capacity and stiffness in contrast with elastomer counterparts. Consequently, this study broadens the material selection for NPTs and proposes a strategy for manufacturing a prototype, which provides a reference for the design and development of non-pneumatic tires.

Toward Improving the Generation Quality of Autoregressive Slot VAEs.

Unconditional scene inference and generation are challenging to learn jointly with a single compositional model. Despite encouraging progress on models that extract object-centric representations ("slots") from images, unconditional generation of scenes from slots has received less attention. This is primarily because learning the multiobject relations necessary to imagine coherent scenes is difficult. We hypothesize that most existing slot-based models have a limited ability to learn object correlations. We propose two improvements that strengthen object correlation learning. The first is to condition the slots on a global, scene-level variable that captures higher-order correlations between slots. Second, we address the fundamental lack of a canonical order for objects in images by proposing to learn a consistent order to use for the autoregressive generation of scene objects. Specifically, we train an autoregressive slot prior to sequentially generate scene objects following a learned order. Ordered slot inference entails first estimating a randomly ordered set of slots using existing approaches for extracting slots from images, then aligning those slots to ordered slots generated autoregressively with the slot prior. Our experiments across three multiobject environments demonstrate clear gains in unconditional scene generation quality. Detailed ablation studies are also provided that validate the two proposed improvements.

Fused Deposition Modeling of Isotactic Polypropylene/Graphene Nanoplatelets Composites: Achieving Enhanced Thermal Conductivity through Filler Orientation.

High-performance thermally conductive composites are increasingly vital due to the accelerated advancements in communication and electronics, driving the demand for efficient thermal management in electronic packaging, light-emitting diodes (LEDs), and energy storage applications. Controlling the orderly arrangement of fillers within a polymer matrix is acknowledged as an essential strategy for developing thermal conductive composites. In this study, isotactic polypropylene/GNP (iPP/GNP) composite filament tailored for fused deposition modeling (FDM) was achieved by combining ball milling with melt extrusion processing. The rheological properties of the composites were thoroughly studied. The shear field and pressure field distributions during the FDM extrusion process were simulated and examined using Polyflow, focusing on the influence of the 3D printing processing flow field on the orientation of GNP within the iPP matrix. Exploiting the unique capabilities of FDM and through strategic printing path design, thermally conductive composites with GNPs oriented in the through-plane direction were 3D printed. At a GNP content of 5 wt%, the as-printed sample demonstrated a thermal conductivity of 0.64 W/m · K, which was 1.5 times the in-plane thermal conductivity for 0.42 W/m · K and triple pure iPP for 0.22 W/m · K. Effective medium theory (EMT) model fitting results indicated a significantly reduced interface thermal resistance in the through-plane direction compared to the in-plane direction. This work shed brilliant light on developing PP-based thermal conductive composites with arbitrarily-customized structures.

Health burden from food systems is highly unequal across income groups.

Food consumption contributes to the degradation of air quality in regions where food is produced, creating a contrast between the health burden caused by a specific population through its food consumption and that faced by this same population as a consequence of food production activities. Here we explore this inequality within China's food system by linking air-pollution-related health burden from production to consumption, at high levels of spatial and sectorial granularity. We find that low-income groups bear a 70% higher air-pollution-related health burden from food production than from food consumption, while high-income groups benefit from a 29% lower health burden relative to their food consumption. This discrepancy largely stems from a concentration of low-income residents in food production areas, exposed to higher emissions from agriculture. Comprehensive interventions targeting both production and consumption sides can effectively reduce health damages and concurrently mitigate associated inequalities, while singular interventions exhibit limited efficacy.

A Bioengineered Nanovesicle Vaccine Boosts T-B cell Interaction for Immunotherapy of Echinococcus multilocularis.

Alveolar echinococcosis (AE) is a zoonotic parasitic disease, resulting from being infected with the metacestode larvae of the tapeworm Echinococcus multilocularis (E. multilocularis). Novel prophylactic and therapeutic interventions are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. Bioengineered nano cellular membrane vesicles are widely used for displaying the native conformational epitope peptides because of their unique structure and biocompatibility. In this study, four T-cells and four B-cells dominant epitope peptides of E. multilocularis with high immunogenicity were engineered into the Vero cell surface to construct a membrane vesicle nanovaccine for the treatment of AE. The results showed that the nanovesicle vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit E. multilocularis infection. This study presents for the first time a nanovaccine strategy that can completely eliminate the burden of E. multilocularis.

Health-environment efficiency of diets shows nonlinear trends over 1990-2011.

Understanding the impacts of diets on health and the environment, as well as their association with socio-economic development, is key to operationalize and monitor food systems shifts. Here we propose a health-environment efficiency indicator defined as a ratio of health benefits and four key food-related environmental impacts (greenhouse gas emissions, scarcity-weighted water withdrawal, acidifying and eutrophying emissions) to assess how diets have performed in supporting healthy lives in relation to environmental pollution and resource consumption across 195 countries from 1990 to 2011. We find that the health-environment efficiency of each environmental input follows a nonlinear path along the Socio-Demographic Index gradient representing different development levels. Health-environment efficiency first increases thanks to the elimination of child and maternal malnutrition through greater food supply, then decreases driven by additional environmental impacts from a shift to animal products, and finally shows a slow growth in some developed countries again as they shift towards healthier diets.

Longitudinal association between e-cigarette use and respiratory symptoms among US adults: Findings from the Population Assessment of Tobacco and Health Study Waves 4-5.

BACKGROUND: We assessed longitudinal effects of e-cigarette use on respiratory symptoms in a nationally representative sample of US adults by combustible tobacco smoking status. METHODS: We analyzed Waves 4-5 public-use data from the Population Assessment of Tobacco and Health Study. Study sample included adult respondents who reported no diagnosis of respiratory diseases at Wave 4, and completed Waves 4-5 surveys with no missing data on analytic variables (N = 15,291). Outcome was a validated index of functionally important respiratory symptoms based on 7 wheezing/cough questions (range 0-9). An index score of ≥2 was defined as having important respiratory symptoms. Weighted lagged logistic regression models were performed to examine the association between e-cigarette use status at Wave 4 (former/current vs. never use) and important respiratory symptoms at Wave 5 by combustible tobacco smoking status (i.e., never/former/current smokers), adjusting for Wave 4 respiratory symptom index, sociodemographic characteristics, secondhand smoke exposure, body mass index, and chronic disease. RESULTS: Among current combustible tobacco smokers, e-cigarette use was associated with increased odds of reporting important respiratory symptoms (former e-cigarette use: adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI]: 1.07-1.81; current e-cigarette use: AOR = 1.55, 95% CI: 1.17-2.06). Among former combustible tobacco smokers, former e-cigarette use (AOR = 1.51, 95% CI: 1.06-2.15)-but not current e-cigarette use (AOR = 1.59, 95% CI: 0.91-2.78)-was associated with increased odds of important respiratory symptoms. Among never combustible tobacco smokers, no significant association was detected between e-cigarette use and important respiratory symptoms (former e-cigarette use: AOR = 1.62, 95% CI: 0.76-3.46; current e-cigarette use: AOR = 0.82, 95% CI: 0.27-2.56). CONCLUSIONS: The association between e-cigarette use and respiratory symptoms varied by combustible tobacco smoking status. Current combustible tobacco smokers who use e-cigarettes have an elevated risk of respiratory impairments.

Bioinspired Tumor Calcification-Guided Early Diagnosis and Eradication of Hepatocellular Carcinoma.

Tumor calcification is found to be associated with the benign prognostic, and which shows considerable promise as a somewhat predictive index of the tumor response clinically. However, calcification is still a missing area in clinical cancer treatment. A specific strategy is proposed for inducing tumor calcification through the synergy of calcium peroxide (CaO2)-based microspheres and transcatheter arterial embolization for the treatment of hepatocellular carcinoma (HCC). The persistent calcium stress in situ specifically leads to powerful tumor calcioptosis, resulting in diffuse calcification and a high-density shadow on computed tomography that enables clear localization of the in vivo tumor site and partial delineation of tumor margins in an orthotopic HCC rabbit model. This osmotic calcification can facilitate tumor clinical diagnosis, which is of great significance in differentiating tumor response during early follow-up periods. Proteome and phosphoproteome analysis identify that calreticulin (CALR) is a crucial target protein involved in tumor calcioptosis. Further fluorescence molecular imaging analysis also indicates that CALR can be used as a prodromal marker of calcification to predict tumor response at an earlier stage in different preclinical rodent models. These findings suggest that upregulated CALR in association with tumor calcification, which may be broadly useful for quick visualization of tumor response.

Generation and characterization of nanobodies targeting human pepsinogens.

Human pepsinogens (mainly pepsinogen I and pepsinogen II) are the major inactive precursor forms of the digestive enzyme pepsin which play a crucial role in protein digestion. The levels and ratios of human pepsinogens have demonstrated potential as diagnostic biomarkers for gastrointestinal diseases, particularly gastric cancer. Nanobodies are promising tools for the treatment and diagnosis of diseases, owing to their unique recognition properties. In this study, recombinant human pepsinogens proteins were expressed and purified as immunized antigens. We constructed a VHH phage library and identified several nanobodies via phage display bio-panning. We determined the binding potency and cross-reactivity of these nanobodies. Our study provides technical support for developing immunodiagnostic reagents targeting human pepsinogens.

Recent advances in sulfur dioxide releasing nanoplatforms for cancer therapy.

Sulfur dioxide (SO2), long considered to be a harmful atmospheric pollutant, has recently been posited as the fourth gasotransmitter, as it is produced endogenously in mammals and has important pathophysiological effects. The field of tumor therapy has witnessed a paradigm shift with the emergence of SO2-based gas therapy. This has been possible because SO2 is a potent glutathione consumer that can promote the production of reactive oxygen species, eventually leading to oxidative-stress-induced cancer cell death. Nevertheless, this therapeutic gas cannot be directly administrated in gaseous form. Thus, various nano formulations incorporating SO2 donors or prodrugs capable of storing and releasing SO2 have been developed in an attempt to achieve active/passive intratumoral accumulation and SO2 release in the tumor microenvironment. In this review article, the advances over the past decade in nanoplatforms incorporating sulfur SO2 prodrugs to provide controlled release of SO2 for cancer therapy are summarized. We first describe the synthesis of polypeptide SO2 prodrugs to overcome multiple drug resistance that was pioneered by our group, followed by other macromolecular SO2 prodrug structures that self-assemble into nanoparticles for tumor therapy. Second, we describe nanoplatforms composed of various small-molecule SO2 donors with endogenous or exogenous stimuli responsiveness, including thiol activated, acid-sensitive, and ultraviolet or near-infrared light-responsive SO2 donors, which have been used for tumor inhibition. Combinations of SO2 gas therapy with photodynamic therapy, chemotherapy, photothermal therapy, sonodynamic therapy, and nanocatalytic tumor therapy are also presented. Finally, we discuss the current limitations and challenges and the future outlook for SO2-based gas therapy. STATEMENT OF SIGNIFICANCE: Gas therapy is attracting increasing attention in the scientific community because it is a highly promising strategy against cancer owing to its inherent biosafety and avoidance of drug resistance. Sulfur dioxide (SO2) is recently found to be produced endogenously in mammals with important pathophysiological effects. This review summarizes recent advances in SO2 releasing nanosystems for cancer therapy, including polymeric prodrugs, endogenous or exogenous stimulus-activated SO2 donors delivered by nanoplatform and combination therapy strategies.

A Novel Polyamino Acid Sulfur Dioxide Prodrug Synergistically Elevates ROS with ß-Lapachone in Cancer Treatment.

Due to the distorted redox balance, cancer cells are considered more vulnerable to excessive reactive oxygen species (ROS). In a variety of oxidative stress-related therapies, gas therapy has emerged as a new therapeutic strategy owing to its efficacy and biosafety. Herein, a newly-discovered gasotransmitter sulfur dioxide (SO2) and a tumor specific ROS generation agent ß-lapachone (Lapa) were firstly combined for anticancer therapy. Firstly, amphiphilic glutathione (GSH) responsive polypeptide SO2 prodrug PEG-b-poly(Lys-DNs) was synthesized by ring opening polymerization of SO2-containing N-carboxyanhydride. Then, Lapa was encapsulated into the polymeric micelles with loading content of 8.6 % and loading efficiency of 51.6 %. The obtained drug-loaded nanoparticles (NPs(Lapa)) exhibited a fast release of Lapa and SO2 in the stimuli of 10 mM GSH in PBS. Subsequently, in vitro experiment showed that NPs(Lapa) exhibited obvious cytotoxicity towards 4 T1 cancer cells at a concentration of 2.0 µg/mL, which may be attributed to the depletion of intracellular GSH and upregulation of ROS level both by SO2 release and by the ROS generation from lapachone transformation. In vivo fluorescence imaging showed that the NPs were gradually enriched in tumor tissues in 24 h, probably due to the enhanced permeability and retention effect of NPs. Finally, NPs(Lapa) showed the best anticancer effect in 4 T1 tumor bearing mice with a tumor inhibiting rate (IRT) of 61 %, whereas IRT for free Lapa group was only 23.6 %. This work may be a new attempt to combine SO2 gas therapy with ROS inducer for anticancer therapy through oxidative stress.

A Novel Cu(II) Loaded Polypeptide SO2 Prodrug Nanoformulation Combining Chemodynamic and Gas Anticancer Therapies.

Sulfur dioxide (SO2)-based gas therapy and chemodynamic therapyare both reactive oxygen species (ROS)-mediated anticancer strategies, but there are few reports of their combined application. To this end, a novel graft-type copolymeric SO2 prodrug, PLG-g-mPEG-DNs, is designed and synthesized in this work. The amphiphilic polypeptides can self-assemble into nanoparticles (NPs) and encapsulated Cu(II) ions by metal-carboxyl coordination. In vitro release results showed that the obtained NPs-Cu can respond to the acidic pH and high glutathione levels typical of a tumor microenvironment to release Cu(II) and SO2 simultaneously. Both a Cu(II)-triggered Fenton-like reaction and the SO2 gas would promote ROS production and upregulate the oxidative stress in tumor cells, leading to an enhanced killing effect towards 4T1 cancer cells compared to either Cu(II) or the NPs alone. Furthermore, the in vitro hemolysis of NPs-Cu is less than 1.0% at a high concentration of 8 mg/mL, indicating good blood compatibility and the potential for in vivo tumor inhibition application.

Large Nonlinear Transverse Conductivity and Berry Curvature in KTaO3 Based Two-Dimensional Electron Gas.

Two-dimensional electron gas (2DEG) at oxide interfaces exhibits various exotic properties stemming from interfacial inversion and symmetry breaking. In this work, we report large nonlinear transverse conductivities in the LaAlO3/KTaO3 interface 2DEG under zero magnetic field. Skew scattering was identified as the dominant origin based on the cubic scaling of nonlinear transverse conductivity with linear longitudinal conductivity and 3-fold symmetry. Moreover, gate-tunable nonlinear transport with pronounced peak and dip was observed and reproduced by our theoretical calculation. These results indicate the presence of Berry curvature hotspots and thus a large Berry curvature triplet at the oxide interface. Our theoretical calculations confirm the existence of large Berry curvatures from the avoided crossing of multiple 5d-orbit bands, orders of magnitude larger than that in transition-metal dichalcogenides. Nonlinear transport offers a new pathway to probe the Berry curvature at oxide interfaces and facilitates new applications in oxide nonlinear electronics.

Trade-offs between cold protection and air pollution-induced mortality of China's heating policy.

The winter heating policy in northern China was designed to safeguard households from the harsh subfreezing temperatures. However, it has inadvertently resulted in seasonal spikes in air pollution levels because of the reliance on coal as an energy source. While the loss of life years attributable to mortality from air pollution caused by winter heating has been estimated, the beneficial effect of protection from cold temperatures has not been assessed, primarily due to a lack of individual-level data linking these variables. Our study aims to address this research gap. We provide individual-level empirical evidence that quantifies the impact of protection from cold temperatures and air pollution on mortality, studying 5,334 older adults living around the Huai River during the period between 2000 and 2018. Our adjusted Cox-proportional hazard models show that winter heating was associated with a 22% lower mortality rate (95% CI: 16-28%). Individuals residing in areas without access to winter heating are subjected to heightened mortality risks during periods of cold temperatures. The protective effect is offset by a 27.8% rise attributed to elevated PM2.5 levels. Our results imply that the equilibrium between the effects of these two factors is achieved when PM2.5 concentration exceeds 24.3 µg/m3 (95% CI: 18.4-30.2). Our research suggests that while the existing winter heating policy significantly mitigates winter mortality by lessening the detrimental effects of cold temperatures, future air pollution reduction could provide further health benefits.

Carbon footprint and embodied nutrition evaluation of 388 recipes.

Food consumption, which delivers fundamental energy and essential nutrients to human beings, is crucial for achieving a series of sustainable goals. Alongside rising population growth and living standards, there has been a significant increase in food cultivation demands, supply chain complexities, and waste management. Therefore, to protect human health and the environment, promoting sustainable food systems and the uptake of sustainable dietary habits are vital. Yet, information on the environmental and health impact of dietary choices remains inconsistent across multiple evaluation methods, which fail to deliver essential ideas to consumers. In this study, we formulate an integrated approach using Environmentally Extended Input-Output analysis, covering the food supply chain from production to the distribution phase, complemented with a hybrid Life Cycle Assessment for cooking and disposal processes, to quantify the carbon footprint of specific recipes. Our dataset also includes the distinct nutritional values of each recipe. This dataset not only informs the food industry and recipe platforms, enabling more sustainable choices, but also helps individuals balance nutritional value with environmental impact, leading to more informed and sustainable dietary decisions.

Danggui Shaoyao San ameliorates the lipid metabolism via the PPAR signaling pathway in a Danio rerio (zebrafish) model of hyperlipidemia.

The escalating prevalence of hyperlipidemia has a profound impact on individuals' daily physiological well-being. The traditional Chinese medicine (TCM) prescription Danggui Shaoyao San (DSS) has demonstrated significant clinical efficacy and promising prospects for clinical application. Leveraging network pharmacology and bioinformatics, we hypothesize that DSS can ameliorate lipid metabolic disorders in hyperlipidemia by modulating the PPAR signaling pathway. In this study, we employed a zebrafish model to investigate the impact of DSS on lipid metabolism in hyperlipidemia. Body weight alterations were monitored by pre- and postmodeling weight measurements. Behavioral assessments and quantification of liver biochemical markers were conducted using relevant assay kits. Pathways associated with lipid metabolism were identified through network pharmacology and GEO analysis, while PCR was utilized to assess genes linked to lipid metabolism. Western blotting was employed to analyze protein expression levels, and liver tissue underwent Oil Red O and immunofluorescence staining to evaluate liver lipid deposition. Our findings demonstrate that DSS effectively impedes weight gain and reduces liver lipid accumulation in zebrafish models with elevated lipid levels. The therapeutic effects of DSS on lipid metabolism are mediated through its modulation of the PPAR signaling pathway, resulting in a significant reduction in lipid accumulation within the body and alleviation of certain hyperlipidemia-associated symptoms.