Body Composition and Energy Expenditure in Youth With Spina Bifida: Protocol for a Multisite, Cross-Sectional Study.

BACKGROUND: Obesity prevalence in youth with spina bifida is higher than in their typically developing peers. Obesity is associated with lifelong medical, psychological, and economic burdens. Successful prevention or treatment of obesity in individuals with spina bifida is compromised by (1) the lack of valid and reliable methods to identify body fat in a clinical setting and (2) limited data on energy expenditure that are necessary to provide daily caloric recommendations. OBJECTIVE: The objectives of this study will be to develop 2 algorithms for use in youth with spina bifida in a clinical setting, one to model body fat and one to predict total daily energy expenditure. In addition, physical activity and dietary intake will be described for the sample. METHODS: This multisite, prospective, national clinical study will enroll 232 youth with myelomeningocele aged 5 to 18 years (stratified by age and mobility). Participants will be enrolled for 1 week. Data obtained include 4 measures of body composition, up to 5 height measures, a ramped activity protocol, and a nutrition and physical activity screener. Participants will wear an accelerometer for the week. On the final study day, 2 samples of urine or saliva, which complete the doubly labeled water protocol, will be obtained. The analysis will include descriptive statistics, Bland-Altman plots, concordance correlation, and regression analysis. RESULTS: The study received extramural federal funding in July 2019. Data collection was initiated in March 2020. As of April 2024, a total of 143 (female participants: n=76, 53.1%; male participants: n=67, 46.9%) out of 232 participants have been enrolled. Data collection is expected to continue throughout 2024. A no-cost extension until November 2025 will be requested for data analysis and dissemination of findings. CONCLUSIONS: This study furthers previous pilot work that confirmed the acceptability and feasibility of obtaining alternate height, body composition, and energy expenditure measures. The findings from this study will enhance screening, prevention, and treatment of abnormal weight status by facilitating the accurate identification of youths' weight status category and recommendations of daily caloric needs for this population that is at higher risk of obesity. Furthermore, the findings have the potential to impact outcomes for youth diagnosed with disabilities other than spina bifida who experience similar challenges related to alterations in body composition or fat distribution or measurement challenges secondary to mobility issues or musculoskeletal problems. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/52779.

Pen2/ErbB4 signaling regulates stemness of pancreatic ductal carcinoma.

Cancer stem cells (CSCs) are critical for progression, invasion, metastasis, and chemotherapy resistance of pancreatic ductal adenocarcinoma (PDAC). Presenilin enhancer 2 (Pen2), a vital component of the gamma-secretase complex, is overexpressed in various cancers and plays a significant role in carcinogenesis. Here, we investigated the association between Pen2 expression and the stem-like properties of PDAC cells. We analyzed Pen2 and its downstream target, Erb-B2 Receptor Tyrosine Kinase 4 (ErbB4), using public databases. The expression of Pen2 in CSC populations, marked by CD133+, CD44+, or epithelial cell adhesion molecule (EpCAM)+, was evaluated. Pen2-positive cells were sorted from Pen2-negative ones in PDAC cells transduced with a vector designed to express green fluorescent protein (GFP) under the Pen2 promoter. Stemness was examined in vitro and in vivo in Pen2-positive versus Pen2-negative cells. Our results showed that Pen2 was significantly upregulated, while ErbB4 was significantly downregulated in PDAC tissues compared to adjacent non-tumorous tissues, with an inverse relationship between Pen2 and Erbb4 levels. PDACs with high Pen2 expression are associated with considerably poorer patient survival. The CSC populations identified by CD133+, CD44+, and EpCAM+ markers displayed significantly higher Pen2 and lower EpCAM levels. Compared to Pen2-negative PDAC cells, Pen2-positive cells formed more tumor spheres, were more invasive and migratory, and showed significantly increased resistance to chemotherapy-induced apoptosis. Altering Pen2 levels reversed these oncogenic effects. In vivo, Pen2-positive cells formed larger tumors in immunodeficient mice. Overall, our findings suggest that Pen2 is highly expressed in CSCs within PDAC cells, being a novel therapeutic target.

An Organophosphorescence Probe with Ultralong Lifetime and Intrinsic Tissue Selectivity for Specific Tumor Imaging and Guided Tumor Surgery.

Organic phosphorescent materials are excellent candidates for use in tumor imaging. However, a systematic comparison of the effects of the intensity, lifetime, and wavelength of phosphorescent emissions on bioimaging performance has not yet been undertaken. This study addresses these gaps and reveals that longer lifetimes effectively increase the signal intensity, whereas longer wavelengths enhance the penetration depth. Conversely, a strong emission intensity with a short lifetime does not necessarily yield robust imaging signals. Building upon these findings, an organo-phosphorescent material with a lifetime of 0.94 s was designed for tumor imaging. Remarkably, the phosphorescent signals of various organic nanoparticles are nearly extinguished in blood-rich organs because of the quenching effect of iron ions. Moreover, for the first time, we demonstrated that iron ions universally quench the phosphorescence of organic room-temperature phosphorescent materials, which is an inherent property of such substances. Leveraging this property, both the normal liver and hepatitis tissues exhibit negligible phosphorescent signals, whereas liver tumors display intense phosphorescence. Therefore, phosphorescent materials, unlike chemiluminescent or fluorescent materials, can exploit this unique inherent property to selectively distinguish liver tumor tissues from normal tissues without additional modifications or treatments.

Self-Adaptive Photodynamic-to-Photothermal Switch for Smart Antitumor Photoimmunotherapy.

Photodynamic therapy (PDT) and photothermal therapy (PTT) possess different merits in cancer phototherapy, but the tumor microenvironment becomes unfavorable during the phototheranostic progress. Herein, we report a self-adaptive cyanine derivative Cy5-TPA with the PDT-dominated state to PTT-dominated state autoswitch feature for enhanced photoimmunotherapy. The incorporation of rotatable triphenylamine (TPA) moiety renders Cy5-TPA with the temperature or intramolecular-motion regulated photoactivities, which shows preferable reactive oxygen species (ROS) generation at lower temperature while stronger photothermal conversion at higher ones. Such a promising feature permits the in situ switch from PDT-dominated state to PTT-dominated state along with intratumoral temperature increase during laser irradiation, which also works in line with the concurrently reduced intratumoral oxygen level, exhibiting a self-adaptive phototherapeutic behavior to maximize the phototherapeutic antitumor outcome. Most importantly, the self-adaptive PDT-dominated state to PTT-dominated state switch also facilitates the sequential generation and release of damage-associated molecular patterns during immunogenic cell death (ICD). Hence, Cy5-TPA demonstrates excellent photoimmunotherapy performance in ICD induction, dendritic cell maturation, and T cell activation for tumor eradication and metastasis inhibition.

Probiotics Armed with In Situ Mineralized Nanocatalysts and Targeted Biocoatings for Multipronged Treatment of Inflammatory Bowel Disease.

While oral probiotics show promise in treating inflammatory bowel disease, the primary challenge lies in sustaining their activity and retention within the inflamed gastrointestinal environment. In this work, we develop an engineered probiotic platform that is armed with biocatalytic and inflamed colon-targeting nanocoatings for multipronged management of IBD. Notably, we achieve the in situ growth of artificial nanocatalysts on probiotics through a bioinspired mineralization strategy. The resulting ferrihydrite nanostructures anchored on bacteria exhibit robust catalase-like activity across a broad pH range, effectively scavenging ROS to alleviate inflammation. The further envelopment with fucoidan-based shields confers probiotics with additional inflamed colon-targeting functions. Upon oral administration, the engineered probiotics display markedly improved viability and colonization within the inflamed intestine, and they further elicit boosted prophylactic and therapeutic efficacy against colitis through the synergistic interplay of nanocatalysis-based immunomodulation and probiotics-mediated microbiota reshaping. The robust and multifunctional probiotic platforms offer great potential for the comprehensive management of gastrointestinal disorders.

Regulation of Root Exudation in Wheat Plants in Response to Alkali Stress.

Soil alkalization is an important environmental factor limiting crop production. Despite the importance of root secretion in the response of plants to alkali stress, the regulatory mechanism is unclear. In this study, we applied a widely targeted metabolomics approach using a local MS/MS data library constructed with authentic standards to identify and quantify root exudates of wheat under salt and alkali stresses. The regulatory mechanism of root secretion in alkali-stressed wheat plants was analyzed by determining transcriptional and metabolic responses. Our primary focus was alkali stress-induced secreted metabolites (AISMs) that showed a higher secretion rate in alkali-stressed plants than in control and salt-stressed plants. This secretion was mainly induced by high-pH stress. We discovered 55 AISMs containing -COOH groups, including 23 fatty acids, 4 amino acids, 1 amino acid derivative, 7 dipeptides, 5 organic acids, 9 phenolic acids, and 6 others. In the roots, we also discovered 29 metabolites with higher levels under alkali stress than under control and salt stress conditions, including 2 fatty acids, 3 amino acid derivatives, 1 dipeptide, 2 organic acids, and 11 phenolic acids. These alkali stress-induced accumulated carboxylic acids may support continuous root secretion during the response of wheat plants to alkali stress. In the roots, RNAseq analysis indicated that 5 6-phosphofructokinase (glycolysis rate-limiting enzyme) genes, 16 key fatty acid synthesis genes, and 122 phenolic acid synthesis genes have higher expression levels under alkali stress than under control and salt stress conditions. We propose that the secretion of multiple types of metabolites with a -COOH group is an important pH regulation strategy for alkali-stressed wheat plants. Enhanced glycolysis, fatty acid synthesis, and phenolic acid synthesis will provide more energy and substrates for root secretion during the response of wheat to alkali stress.

Fluorinated Organic Polymers for Cancer Drug Delivery.

In the realm of cancer therapy, the spotlight is on nanoscale pharmaceutical delivery systems, especially polymer-based nanoparticles, for their enhanced drug dissolution, extended presence in the bloodstream, and precision targeting achieved via surface engineering. Leveraging the amplified permeation and retention phenomenon, these systems concentrate therapeutic agents within tumor tissues. Nonetheless, the hurdles of systemic toxicity, biological barriers, and compatibility with living systems persist. Fluorinated polymers, distinguished by their chemical idiosyncrasies, are poised for extensive biomedical applications, notably in stabilizing drug metabolism, augmenting lipophilicity, and optimizing bioavailability. Material science heralds the advent of fluorinated polymers that, by integrating fluorine atoms, unveil a suite of drug delivery merits: the hydrophobic traits of fluorinated alkyl chains ward off lipid or protein disruption, the carbon-fluorine bond's stability extends the drug's lifecycle in the system, and a lower alkalinity coupled with a diminished ionic charge bolsters the drug's ability to traverse cellular membranes. This comprehensive review delves into the utilization of fluorinated polymers for oncological pharmacotherapy, elucidating their molecular architecture, synthetic pathways, and functional attributes, alongside an exploration of their empirical strengths and the quandaries they encounter in both experimental and clinical settings.

Carboxylic acid accumulation and secretion contribute to the alkali-stress tolerance of halophyte Leymus chinensis.

Leymus chinensis is a dominant halophytic grass in alkalized grasslands of Northeast China. To explore the alkali-tolerance mechanism of L. chinensis, we applied a widely targeted metabolomic approach to analyze metabolic responses of its root exudates, root tissues and leaves under alkali-stress conditions. L. chinensis extensively secreted organic acids, phenolic acids, free fatty acids and other substances having -COOH or phosphate groups when grown under alkali-stress conditions. The buffering capacity of these secreted substances promoted pH regulation in the rhizosphere during responses to alkali stress. L. chinensis leaves exhibited enhanced accumulations of free fatty acids, lipids, amino acids, organic acids, phenolic acids and alkaloids, which play important roles in maintaining cell membrane stability, regulating osmotic pressure and providing substrates for the alkali-stress responses of roots. The accumulations of numerous flavonoids, saccharides and alcohols were extensively enhanced in the roots of L. chinensis, but rarely enhanced in the leaves, under alkali-stress conditions. Enhanced accumulations of flavonoids, saccharides and alcohols increased the removal of reactive oxygen species and alleviated oxygen damage caused by alkali stress. In this study, we revealed the metabolic response mechanisms of L. chinensis under alkali-stress conditions, emphasizing important roles for the accumulation and secretion of organic acids, amino acids, fatty acids and other substances in alkali tolerance.

Preparation of AIEgen-based near-infrared afterglow luminescence nanoprobes for tumor imaging and image-guided tumor resection.

Fluorescence imaging represents a vital tool in modern biology, oncology and biomedical applications. Afterglow luminescence (AGL), which circumvents the light scattering and tissue autofluorescence interference associated with real-time excitation source, shows remarkably increased imaging sensitivity and depth. Here we present a protocol for the design and synthesis of AGL nanoprobes with an aggregation-induced emission (AIE) effect to simultaneously red shift and amplify the afterglow signal for tumor imaging and image-guided tumor resection. The nanoprobe (AGL AIE dot) is composed of an enol ether format of Schaap's agent and a near-infrared AIE fluorogen (AIEgen) (tetraphenylethylene-phenyl-dicyanomethylene-4H-chromene, TPE-Ph-DCM) to suppress the nonradiative dissipation pathway. Pre-irradiating AGL AIE dots with white light could generate singlet oxygen to convert Schaap's agent to its 1,2-dioxetane format, thus initializing the AGL process. With the aid of AIEgen, the AGL shows simultaneously red shifted emission maximum (from ~540 nm to ~625 nm) and enhanced intensity (by 3.2-fold), facilitating better signal-to-background ratio, imaging sensitivity and depth. Intriguingly, the activated AGL can last for over 10 days. Compared with conventional approaches, our method provides a new solution to concurrently red shift and amplify afterglow signals for better in vivo imaging outcomes. The preparation of AGL AIE dots takes ~2 days, the in vitro characterization takes ~10 days (less than 1 day if not involving afterglow kinetic profile study) and the tumor imaging and image-guided tumor resection takes ~7 days. These procedures can be easily reproduced and amended after standard laboratory training in chemical synthesis and animal handling.

Exploring Control Authority Preferences in Robotic Arm Assistance for Power Wheelchair Users.

This paper uses mixed methods to explore the preliminary design of control authority preferences for an Assistive Robotic Manipulator (ARM). To familiarize users with an intelligent robotic arm, we perform two kitchen task iterations: one with user-initiated software autonomy (predefined autonomous actions) and one with manual control. Then, we introduce a third scenario, enabling users to choose between manual control and system delegation throughout the task. Results showed that, while manually switching modes and controlling the arm via joystick had a higher mental workload, participants still preferred full joystick control. Thematic analysis indicates manual control offered greater freedom and sense of accomplishment. Participants reacted positively to the idea of an interactive assistive system. Users did not want to ask the system to only assist, by taking over for certain actions, but also asked for situational feedback (e.g., 'How close am I (the gripper)?', 'Is the lid centered over the jug?'). This speaks to a future assistive system that ensures the user feels like they drive the system for the entirety of the task and provides action collaboration in addition to more granular situational awareness feedback.

Co-targeting CD47 and VEGF elicited potent anti-tumor effects in gastric cancer.

BACKGROUND: CD47, serving as an intrinsic immune checkpoint, has demonstrated efficacy as an anti-tumor target in hematologic malignancies. Nevertheless, the clinical relevance of CD47 in gastric cancer and its potential as a therapeutic target remains unclear. METHODS: The expression of CD47 in clinical gastric cancer tissues was assessed using immunohistochemistry and Western blot. Patient-derived cells were obtained from gastric cancer tissues and co-cultured with macrophages derived from human peripheral blood mononuclear cells. Flow cytometry analyses were employed to evaluate the rate of phagocytosis. Humanized patient-derived xenografts (Hu-PDXs) models were established to assess the efficacy of anti-CD47 immunotherapy or the combination of anti-CD47 and anti-VEGF therapy in treating gastric cancer. The infiltrated immune cells in the xenograft were analyzed by immunohistochemistry. RESULTS: In this study, we have substantiated the high expression of CD47 in gastric cancer tissues, establishing a strong association with unfavorable prognosis. Through the utilization of SIRPα-Fc to target CD47, we have effectively enhanced macrophage phagocytosis of PDCs in vitro and impeded the growth of Hu-PDXs. It is noteworthy that anti-CD47 immunotherapy has been observed to sustain tumor angiogenic vasculature, with a positive correlation between the expression of VEGF and CD47 in gastric cancer. Furthermore, the successful implementation of anti-angiogenic treatment has further augmented the anti-tumor efficacy of anti-CD47 therapy. In addition, the potent suppression of tumor growth, prevention of cancer recurrence after surgery, and significant prolongation of overall survival in Hu-PDX models can be achieved through the simultaneous targeting of CD47 and VEGF using the bispecific fusion protein SIRPα-VEGFR1 or by combining the two single-targeted agents. CONCLUSIONS: Our preclinical studies collectively offer substantiation that CD47 holds promise as a prospective target for gastric cancer, while also highlighting the potential of anti-angiogenic therapy to enhance tumor responsiveness to anti-CD47 immunotherapy.

Prognostic correlation between specialized capillary endothelial cells and lung adenocarcinoma.

Background: In-depth analysis of the functional changes occurring in endothelial cells (ECs) involved in capillary formation can help to elucidate the mechanism of tumour vascular growth. Methods: Appropriate datasets were retrieved from the GEO database to obtain single-cell data on LUAD samples and adjacent normal tissue samples. ECs were selected by an automatic annotation program in R and further subdivided based on reported EC marker genes. Functional changes in different types of capillary ECs were then visualized, and the concrete expression was classified by genetic data in the TCGA. Finally, a prognostic model was constructed to predict immunoinfiltration status, survival and drug therapy effects. Results: The LUAD data contained in the GSE183219 dataset were suitable for our analysis. After dimensionality reduction analysis and cell annotation, EC general capillary and EC aerocyte subsets as capillary specialized phenotypes showed a series of functional changes in tumour samples, with a total of 108 genes found to undergo functional changes. Use of CellPhoneDB revealed a close interaction of activity between ECs. After integration of TCGA, GSE68465 and GSE11969 datasets, the genes obtained were analysed by cluster analysis and risk model construction, identifying 8 genes. Drug sensitivity, immune cell and molecular differences can be accurately predicted. Conclusions: EC general capillary and EC aerocyte subsets are recognized capillary ECs in the tumour microenvironment, and the functional changes between them are relevant to the prognosis and treatment of LUAD patients and have the potential to be used in target therapy.

Fused Azulenyl Squaraine Derivatives Improve Phototheranostics in the Second Near-Infrared Window by Concentrating Excited State Energy on Non-Radiative Decay Pathways.

The second near-infrared (NIR-II) theranostics offer new opportunities for precise disease phototheranostic due to the enhanced tissue penetration and higher maximum permissible exposure of NIR-II light. However, traditional regimens lacking effective NIR-II absorption and uncontrollable excited-state energy decay pathways often result in insufficient theranostic outcomes. Herein a phototheranostic nano-agent (PS-1 NPs) based on azulenyl squaraine derivatives with a strong NIR-II absorption band centered at 1092 nm is reported, allowing almost all absorbed excitation energy to dissipate through non-radiative decay pathways, leading to high photothermal conversion efficiency (90.98 %) and strong photoacoustic response. Both in vitro and in vivo photoacoustic/photothermal therapy results demonstrate enhanced deep tissue cancer theranostic performance of PS-1 NPs. Even in the 5 mm deep-seated tumor model, PS-1 NPs demonstrated a satisfactory anti-tumor effect in photoacoustic imaging-guided photothermal therapy. Moreover, for the human extracted tooth root canal infection model, the synergistic outcomes of the photothermal effect of PS-1 NPs and 0.5 % NaClO solution resulted in therapeutic efficacy comparable to the clinical gold standard irrigation agent 5.25 % NaClO, opening up possibilities for the expansion of NIR-II theranostic agents in oral medicine.

Azulene-Containing Bis(squaraine) Dyes: Design, Synthesis and Aggregation Behaviors.

The relationship among chemical structure, physicochemical property and aggregation behavior of organic functional material is an important research topic. Here, we designed and synthesized three bis(squaraine) dyes BSQ1, BSQ2 and BSQ3 through the combination of two kinds of unsymmetrical azulenyl squaraine monomers. Their physicochemical properties were investigated in both molecular and aggregate states. Generally, BSQ1 displayed different assembly behaviors from BSQ2 and BSQ3. Upon fabrication into nanoparticles, BSQ1 tend to form J-aggregates while BSQ2 and BSQ3 tend to form H-aggregates in aqueous medium. When in the form of thin films, three bis(squaraine) dyes all adopted J-aggregation packing modes while only BSQ1 presented the most significant rearrangement of aggregate structures as well as the improvement in the carrier mobilities upon thermal annealing. Our research highlights the discrepancy of aggregation behaviors originating from the molecular structure and surrounding circumstances, providing guidance for the molecular design and functional applications of squaraines.

Rehabilitation clinicians' use of mainstream wireless technologies in practice: a scoping review.

PURPOSE: This scoping review was conducted to understand the barriers, facilitators, and education and training needs of rehabilitation clinicians in their use of mainstream wireless technologies (MWT) to support people with disabilities and older adults. It was also conducted to understand the functional skills of clients that were targeted with MWT use. MATERIALS AND METHODS: This scoping review was reported using PRISMA-ScR (Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews) and the Population (or Participants)/Concept/Context) framework. We searched PubMed; ProQuest to access APA PsycINFO; Web of Science Core Collection; and EBSCOhost to access Cumulated Index to Nursing and Allied Health Literature (CINAHL), Ovid MEDLINE ALL, and Education Resources Information Center (ERIC). Articles published between 2015-2022 were retrieved. RESULTS: A total of 90 articles were included. Most interventions were apps, smartphones, and tablets; were geared toward adults; and targeted motor, cognitive and speech skills. An infographic on barriers and facilitators was generated as a decision support tool for clinicians when implementing MWT. The topic, format, timing, and source of information clinicians need are also delineated. CONCLUSION: MWT such as apps, smartphones and tablets are being used by rehabilitation clinicians to address motor, cognitive, and speech skills, most commonly in adults. Clinicians voice a need for more education and training. Barriers and facilitators exist at the clinician-, technology-, client-, institution-, and policy levels.Implications For RehabilitationA total of 90 articles from 2015-2022 were included in this scoping reviewMost interventions were apps, smartphones, and tablets; were geared toward adults; and targeted motor, cognitive and speech skills.An infographic was generated as a decision support tool for clinicians when implementing mainstream wireless technologies in clinical practice.Clinicians' education and training needs with regard to mainstream wireless technologies are broad. Materials on a variety of topics, in different formats, from multiple sources are needed.This review also discusses implications of findings on policy, technology development, and future research.

Ion-imprinted chitosan prepared without cross-linking agent for efficient selective adsorption of Al(III) from rare earth solution.

In the aqueous phase, ion-imprinted materials exhibit excellent selective adsorption properties for specific ions, but their complicated preparation process and large amount of crosslinker consumption limit their application. In this study, ion-imprinted chitosan (IIP-CS) was prepared by a simple one-step hydrothermal method without a cross-linking agent for the efficient adsorption of trace amounts of Al(III) from a rare earth solution. The structures and morphology of IIP-CS were analyzed by FT-IR, SEM, and XRD. The Al(III) adsorption characteristics of IIP-CS were investigated under various preparation processes and adsorption conditions. It was found that the optimum mass ratio of IIP-CS is 3 : 1 and pH is 3 and the adsorption capacity reaches up to 40.36 mg g-1. In addition, three different isothermal models-Temkin, Freundlich, and Langmuir-were used to analyze the equilibrium adsorption of IIP-CS in aqueous solution. The results obtained are consistent with the Langmuir model. The adsorption process of Al(III) on IIP-CS follows a pseudo-secondary kinetic model, suggesting that electron sharing or exchange between IIP-CS and Al(III) is a key factor affecting its adsorption rate. IIP-CS shows high selectivity coefficients for Al(III) in mixtures of La(III), Y(III), and Gd(III), which are 792.50, 163.26, and 55.16, respectively. The mechanism of action is the formation of a complex via amidation between Al(III) and IIP-CS. IIP-CS is an adsorbent with excellent regeneration and selective adsorption performance in aqueous solution.

Transformable Supramolecular Self-Assembled Peptides for Cascade Self-Enhanced Ferroptosis Primed Cancer Immunotherapy.

Immunotherapy has received widespread attention for its effective and long-term tumor-eliminating ability. However, for immunogenic "cold" tumors, such as prostate cancer (PCa), the low immunogenicity of the tumor itself is a serious obstacle to efficacy. Here, this work reports a strategy to enhance PCa immunogenicity by triggering cascade self-enhanced ferroptosis in tumor cells, turning the tumor from "cold" to "hot". This work develops a transformable self-assembled peptide TEP-FFG-CRApY with alkaline phosphatase (ALP) responsiveness and glutathione peroxidase 4 (GPX4) protein targeting. TEP-FFG-CRApY self-assembles into nanoparticles under aqueous conditions and transforms into nanofibers in response to ALP during endosome/lysosome uptake into tumor cells, promoting lysosomal membrane permeabilization (LMP). On the one hand, the released TEP-FFG-CRAY nanofibers target GPX4 and selectively degrade the GPX4 protein under the light irradiation, inducing ferroptosis; on the other hand, the large amount of leaked Fe2+ further cascade to amplify the ferroptosis through the Fenton reaction. TEP-FFG-CRApY-induced immunogenic ferroptosis improves tumor cell immunogenicity by promoting the maturation of dendritic cells (DCs) and increasing intratumor T-cell infiltration. More importantly, recovered T cells further enhance ferroptosis by secreting large amounts of interferon-gamma (IFN-γ). This work provides a novel strategy for the molecular design of synergistic molecularly targeted therapy for immunogenic "cold" tumors.

Microplastics are detected in human gallstones and have the ability to form large cholesterol-microplastic heteroaggregates.

Ubiquitous pollution due to microplastics through the food chain is a major cause of various deleterious effects on the human health. The aim of this study was to determine the existence of microplastics and the internal mechanism of microplastics as accelerators of cholelithiasis. Gallstones were collected from 16 patients after cholecystectomy, and microplastics in the gallstones were detected through laser direct infrared and pyrolysis gas chromatographymass spectrometry examinations. Mice model of gallstone were constructed with or without different diameters of microplastic (0.5, 5 and 50 µm). The affinity between microplastic and cholesterol or bilirubin was tested by co-culturing and qualified using molecular dynamics simulations. Finally, altered gut microbiota among the groups were identified using 16 s rRNA sequencing. The presence of microplastics in the gallstones of all the patients were confirmed. Microplastic content was significantly higher in younger chololithiasis patients (age<50 years). Mice fed a high-cholesterol diet with microplastic drinks showed more severe chololithiasis. In terms of the mechanism, microplastics showed a higher affinity for cholesterol than for bilirubin. Significant alterations in the gut microbiota have also been identified after microplastic intake in mice. Our study revealed the presence of microplastics in human gallstones, showcasing their potential to aggravate chololithiasis by forming large cholesterol-microplastic heteroaggregates and altering the gut microbiota.

Preparation of chitosan mesoporous membrane/halloysite composite for efficiently selective adsorption of Al(III) from rare earth ions solution through constructing pore structure on substrate.

The removal of impurity Al(III) from rare earth ion solution by selective adsorption method was one of the challenging tasks. Herein, calcination and acid dissolution treatment were used to construct the pore structure for the halloysite substrate (Hal-650-H) and provide conditions for the formation of the chitosan mesoporous membrane to prepare composite (Hal-H-2CS). The selective adsorption properties and mechanism of the Hal-H-2CS for Al(III) in the rare earth ion solution were studied. The results showed that the formation of mesoporous structures for chitosan provided abundant sites for the adsorption of Al(III). Hal-H-2CS showed remarkable selective adsorption properties for Al(III) in a wide pH range and the binary mixtures with high content of Al(III) or La(III). The maximum adsorption capacity of Al(III) was 106 mg/g, while the adsorption capacity of La(III) was only 1.41 mg/g at pH 4.0. In addition, the Hal-H-2CS exhibited excellent regeneration and structural stability. The remarkable selective properties of Hal-H-2CS was achieved by the synergistic effect between chitosan mesoporous membrane and Hal-650-H, the main adsorption sites were the OH, NH2, CONH2 of chitosan and the oxygen sites of the Hal-650-H. This work provides a new strategy for the design and preparation of outstanding selective adsorbent for Al(III).

π-π Interaction-Induced Organic Long-wavelength Room-Temperature Phosphorescence for In Vivo Atherosclerotic Plaque Imaging.

Room-temperature phosphorescent (RTP) materials have great potential for in vivo imaging because they can circumvent the autofluorescence of biological tissues. In this study, a class of organic-doped long-wavelength (≈600 nm) RTP materials with benzo[c][1,2,5] thiadiazole as a guest was constructed. Both host and guest molecules have simple structures and can be directly purchased commercially at a low cost. Owing to the long phosphorescence wavelength of the doping system, it exhibited good tissue penetration (10 mm). Notably, these RTP nanoparticles were successfully used to image atherosclerotic plaques, with a signal-to-background ratio (SBR) of 44.52. This study provides a new approach for constructing inexpensive red organic phosphorescent materials and a new method for imaging cardiovascular diseases using these materials.