Recent Progress in Polyion Complex Nanoparticles with Enhanced Stability for Drug Delivery.

Polyion complex (PIC) nanoparticles, including PIC micelles and PICsomes, are typically composed of poly(ethylene glycol) block copolymers coupled with oppositely charged polyelectrolytes or therapeutic agents via electrostatic interaction. Due to a simple and rapid preparation process with high drug-loading efficiency, PIC nanoparticles are beneficial to maintaining the chemical integrity and high biological activity of the loaded drugs. However, the stability of PIC nanoparticles can be disrupted in high-ionic-strength solutions because electrostatic interaction is the DRIVING force; these disruptions can thus impair drug delivery. Herein, we summarize the advances in the use of PIC nanoparticles for delivery of charged drugs, focusing on the different chemical and physical strategies employed to enhance their stability, including enhancing the charge density, crosslinking, increasing hydrophobic interactions, forming hydrogen bonds, and the development of PIC-based gels. In particular, we describe the use of PIC nanoparticles to load peptide antibiotics targeting antibiotic-resistant and biofilm-related diseases and the use of nanoparticles that load chemotherapeutics and gaseous donors for cancer treatment. Furthermore, the application of PIC nanoparticles as magnetic resonance imaging contrast agents is summarized for the first time. Therefore, this review is of great significance for advances in the use of polymeric nanoparticles for functional drug delivery.

Third-order nonlinear Hall effect in a quantum Hall system.

In two-dimensional systems, perpendicular magnetic fields can induce a bulk band gap and chiral edge states, which gives rise to the quantum Hall effect. The quantum Hall effect is characterized by zero longitudinal resistance (Rxx) and Hall resistance (Rxy) plateaus quantized to h/(υe2) in the linear response regime, where υ is the Landau level filling factor, e is the elementary charge and h is Planck's constant. Here we explore the nonlinear response of monolayer graphene when tuned to a quantum Hall state. We observe a third-order Hall effect that exhibits a nonzero voltage plateau scaling cubically with the probe current. By contrast, the third-order longitudinal voltage remains zero. The magnitude of the third-order response is insensitive to variations in magnetic field (down to ~5 T) and in temperature (up to ~60 K). Moreover, the third-order response emerges in graphene devices with a variety of geometries, different substrates and stacking configurations. We term the effect third-order nonlinear response of the quantum Hall state and propose that electron-electron interaction between the quantum Hall edge states is the origin of the nonlinear response of the quantum Hall state.

Climate adaptation through crop migration requires a nexus perspective for environmental sustainability in the North China Plain.

Crop migration can moderate the impacts of global warming on crop production, but its feedback on the climate and environment remains unknown. Here we develop an integrated framework to capture the climate impacts and the feedback of adaptation behaviours with the land-water-energy-carbon nexus perspective and identify opportunities to achieve the synergies between climate adaptation and environmental sustainability. We apply the framework to assess wheat and maize migration in the North China Plain and show that adaptation through wheat migration could increase crop production by ~18.5% in the 2050s, but at the cost of disproportional increment in land use (~19.2%), water use (~20.2%), energy use (~19.5%) and carbon emissions (~19.9%). Irrigation and fertilization management are critical mitigation opportunities in the framework, through which wheat migration can be optimized to reduce the climatic and environmental impacts and avoid potential carbon leakage. Our work highlights the sustainable climate adaptation to mitigate negative environmental externalities.

The Hemodynamic Changes Induced by Lung Recruitment Maneuver to Predict Fluid Responsiveness in Children during One Lung Ventilation-A Prospective Observational Study.

BACKGROUND: The prediction of fluid responsiveness in critical patients helps clinicians in decision making to avoid either under- or overloading of fluid. This study was designed to determine whether lung recruitment maneuver (LRM) would have an effect on the predictability of fluid responsiveness by the changes of hemodynamic parameters in pediatric patients who were receiving lung-protective ventilation and one-lung ventilation (OLV). METHODS: A total of 34 children, aged 1-6 years old, scheduled for heart surgeries via right thoracotomy were enrolled. Patients were anesthetized and OLV with lung-protection ventilation settings was established, and then, positioned on left lateral decubitus. LRM and volume expansion (VE) were performed in sequence. Heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP) diastolic arterial pressure (DAP), stroke volume (SV), stroke volume variation (SVV), and pulse pressure variation (PPV) were recorded via an A-line based monitor system at the following time points: before and after LRM (T1 and T2) and before and after VE (T3 and T4). An increase in stroke volume (SV) or mean arterial pressure (MAP) of ≥10% following fluid loading identified fluid responders. The predictability of fluid responsiveness by the changes of SV (ΔSVLRM) and MAP (ΔMAPLRM) after LRM and VE were statistically evaluated by receiver operating characteristic curves [area under the curves (AUC)]. RESULTS: SVs in all patients were significantly decreased after LRM (p < 0.01) and then, increased and returned to baseline after VE (p < 0.01). In total, 16 out of 34 patients who were fluid responders had significantly lower SV after LRM compared to that in fluid non-responders. The area under the receiver operating characteristic curves for ΔSVLRM was 0.828 (95% confidence interval [CI], 0.660 to 0.935; p < 0.001) and it indicated that ΔSVLRM was able to predict the fluid responsiveness of pediatric patients. MAPs in all patients were also decreased significantly after LRM, and 12 of them fell into the category of fluid responders after VE. Statistically, ΔMAPLRM did not predict fluid responsiveness when LRM was considered as an influential factor (p = 0.07). CONCLUSIONS: ΔSVLRM, but not ΔMAPLRM, showed great reliability in the prediction of the fluid responsiveness following VE in children during one-lung ventilation with lung-protective settings. TRIAL REGISTRATION: ChiCTR2300070690.

Multistage feature fusion knowledge distillation.

Generally, the recognition performance of lightweight models is often lower than that of large models. Knowledge distillation, by teaching a student model using a teacher model, can further enhance the recognition accuracy of lightweight models. In this paper, we approach knowledge distillation from the perspective of intermediate feature-level knowledge distillation. We combine a cross-stage feature fusion symmetric framework, an attention mechanism to enhance the fused features, and a contrastive loss function for teacher and student models at the same stage to comprehensively implement a multistage feature fusion knowledge distillation method. This approach addresses the problem of significant differences in the intermediate feature distributions between teacher and student models, making it difficult to effectively learn implicit knowledge and thus improving the recognition accuracy of the student model. Compared to existing knowledge distillation methods, our method performs at a superior level. On the CIFAR100 dataset, it boosts the recognition accuracy of ResNet20 from 69.06% to 71.34%, and on the TinyImagenet dataset, it increases the recognition accuracy of ResNet18 from 66.54% to 68.03%, demonstrating the effectiveness and generalizability of our approach. Furthermore, there is room for further optimization of the overall distillation structure and feature extraction methods in this approach, which requires further research and exploration.

Repurposing indocyanine green: exploring the potential of an old drug in modern medicine.

The repurposing of existing drugs, referred to as theranostics, has made profound impacts on precision medicine. Indocyanine green (ICG), a well-established and clinical dye, has continued to be a star agent, described as a multifunctional molecule with concurrent photo- or sono-sensitiveness capabilities and co-delivery accessibility, showing remarkable potential in the area of unimodal or multimodal imaging-guided therapy of various diseases, leading to the extensive consideration of immediate clinical translations. In this review, we strive to bring the understanding of repurposing performance assessment for ICG into practice by clarifying the relationships between its features and applicability. Specifically, we address the obstacles encountered in the process of developing an ICG repurposing strategy, as well as the noteworthy advancements made in the field of ICG repurposing. We also go into detail about the structure-function correlations of drugs containing ICG and how different structural groups significantly affect the physicochemical properties.

Multiple pulmonary sclerosing pneumocytoma, based on a study of 36 cases worldwide.

To analyze the clinical characteristics and to improve clinicians' understanding of multiple pulmonary sclerosing pneumocytoma (PSP) patients. A total of 36 PSP patients with multiple tumor characteristics were identified from the literature search. They were compared with 43 solitary PSP patients diagnosed and treated in our hospital in the past 5 years. Thus, the pathogenesis, clinical symptoms, diagnosis methods, treatment strategies, and prognosis of pulmonary sclerosing pneumocytoma (PSP) patients with multiple tumors were explored. Patients with multiple PSP are mostly distributed in Asia (88.89%) and are females (83.33%). PSP can be located in any one lobe (19.44%), or grow across ipsilateral lobes (44.44%), or even, bilateral lobes (36.11%). It can be accompanied by metastasis (9.09%) and is prone to misdiagnosis (27.78%). Compared with solitary PSP, the occurrence age of multiple PSP was younger (mean ± standard deviation [SD]: 40.36 ± 18.12: 51.28 ± 12.74 years), but there was no significant difference in sex, tumor size (mean ± SD: 43.54 ± 46.18: 30.56 ± 17.62 mm), or symptoms. Individualized surgical resection is required for treatment, including pneumonectomy (17.65%), lobectomy (23.53%), subpulmonary lobectomy (38.24%), or combined lobectomy (5.88%). Multiple PSP is relatively rare. Surgical resection within a limited time should be the main treatment for such patients. The prognosis of patients with multiple PSP is generally good, but inappropriate diagnosis and treatment plans may lead to poor prognosis.

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.

A "turn-on" fluorescent sensor for herbicide quizalofop-p-ethyl based on cyanostilbene-pyridine macrocycle.

Quizalofop-p-ethyl is a widely used herbicide that also poses a risk to human health and environmental safety. However, there is still a lack of simple and in-situ detecting method for quizalofop-p-ethyl so far. In this work, the fluorescent sensor was firstly developed on detection of quizalofop-p-ethyl based on cyanostilbene-pyridine macrocycle (CPM). CPM was prepared by the "1 + 1" condensation of pyridine-substituted cyanostilbene derivative with 4,4'-Bis(chloromethyl)biphenyl in 68 % yield. The weak fluorescence of CPM in aqueous media transferred to strong orange fluorescence after sensing quizalofop-p-ethyl. This sensing behavior exhibited high selectivity among 28 kinds of herbicides and ions. The limitation of detection (LOD) was 2.98 × 10-8 M and the limitation of quantification (LOQ) was 9.94 × 10-8 M (λex = 390 nm, λem = the maximum emission between 512 nm and 535 nm) with a dynamic range of 0.01-0.9 eq. The binding constant (Ka) of quizalofop-p-ethyl to the sensor CPM was 3.2 × 106 M-1. The 1:1 sensing mechanism was confirmed as that quizalofop-p-ethyl was located in the cavity of CPM, which enhanced aggregating effect and reduced the intramolecular rotation of aromatic groups for better AIE effect. The sensing ability of CPM for quizalofop-p-ethyl had been efficiently applied in test paper experiments, agricultural product tests and real water samples, revealing that CPM has good application prospect for simple and in-situ detection of quizalofop-p-ethyl in real environment.

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.

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.

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.

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.

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.

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.

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.

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.