Regeneration Effect of a New Bio-Based Warm-Mix Rejuvenator on Performance and Micro-Morphology of Aged Asphalt.

The use of warm-mix recycling technology can reduce the mixing temperature and the secondary aging of binders in reclaimed asphalt pavement (RAP), which is one of the effective ways to recycle high-content RAP. In this study, the penetration, softening point, ductility, and viscosity were used to characterize the conventional physical properties of aged asphalt after regenerating, while a dynamic shear rheometer (DSR), force ductility tester (FDT), and atomic force microscope (AFM) were used to evaluate the rheological performance and micro-morphology of aged asphalt incorporating a new bio-based warm-mix rejuvenator (BWR) and a commercial warm-mix rejuvenator (ZJ-WR). The regeneration mechanism of warm-mix rejuvenators on aged asphalt was analyzed by Fourier transform infrared spectroscopy (FTIR). The results show that the new bio-based warm-mix rejuvenator can restore the conventional physical properties, low-temperature performance, and micro-morphology of aged asphalt with an appropriate dosage, but it has a negative effect on high-temperature performance. In comparison with 2D area parameters, 3D roughness parameters were more accurate in evaluating the variation in micro-morphology of aged asphalt after regeneration. The FTIR analysis results indicate that both the new bio-based warm-mix rejuvenator and the commercial warm-mix rejuvenator regenerate aged asphalt by physical action, and AS=O and AC-H values are more reasonable than the AC=O value for the restoration evaluation of aged asphalt. And the new bio-based warm-mix rejuvenator has a better regeneration effect on the performance and micro-morphology of aged asphalt than the commercial warm-mix rejuvenator.

Cellulose nanofiber-mediated manifold dynamic synergy enabling adhesive and photo-detachable hydrogel for self-powered E-skin.

Self-powered skin attachable and detachable electronics are under intense development to enable the internet of everything and everyone in new and useful ways. Existing on-demand separation strategies rely on complicated pretreatments and physical properties of the adherends, achieving detachable-on-demand in a facile, rapid, and universal way remains challenging. To overcome this challenge, an ingenious cellulose nanofiber-mediated manifold dynamic synergy strategy is developed to construct a supramolecular hydrogel with both reversible tough adhesion and easy photodetachment. The cellulose nanofiber-reinforced network and the coordination between Fe ions and polymer chains endow the dynamic reconfiguration of supramolecular networks and the adhesion behavior of the hydrogel. This strategy enables the simple and rapid fabrication of strong yet reversible hydrogels with tunable toughness ((Valuemax-Valuemin)/Valuemax of up to 86%), on-demand adhesion energy ((Valuemax-Valuemin)/Valuemax of up to 93%), and stable conductivity up to 12 mS cm-1. We further extend this strategy to fabricate different cellulose nanofiber/Fe3+-based hydrogels from various biomacromolecules and petroleum polymers, and shed light on exploration of fundamental dynamic supramolecular network reconfiguration. Simultaneously, we prepare an adhesive-detachable triboelectric nanogenerator as a human-machine interface for a self-powered wireless monitoring system based on this strategy, which can acquire the real-time, self-powered monitoring, and wireless whole-body movement signal, opening up possibilities for diversifying potential applications in electronic skins and intelligent devices.

Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.

Progress in the design and synthesis of nanostructured self-assembling systems has facilitated the realization of numerous nanoscale geometries, including fibers, ribbons, and sheets. A key challenge has been achieving control across multiple length scales and creating macroscopic structures with nanoscale organization. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical macrostructures. Further, we demonstrate the ability to tune the nanostructure of macroscopic hydrogels through modulating phosphate buffer concentration during peptide self-assembly. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an extracellular matrix-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to decouple nanostructure from macrostructure and generate a gradient of anisotropic nanofibrous hydrogels. We anticipate that control of architecture at multiple length scales will be critical for a variety of applications, including the bottom-up tissue engineering explored here.

Clinical Features Post Anterior Cruciate Ligament Reconstruction Associated with Structural Alterations in Corticospinal Tract.

CONTEXT: Structural evidence for corticospinal tract (CST) abnormality between patients with ACLR and healthy controls, and the relationships between CST structure and clinical features of the patients (e.g., objective sensorimotor outcomes, postoperative duration) are lacking. OBJECTIVES: To investigate whether the structural features of CST 1) differ between patients with ACLR and healthy controls, and 2) were associated with clinical features in patients following ACLR. DESIGN: Cross-sectional study. SETTING: Sports medicine laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-six patients who had undergone ACLR and twenty-six healthy controls were enrolled in this cross-sectional investigation. MAIN OUTCOME MEASURE(S): Using the CST as the region of interest, we performed diffusion tensor imaging to measure the microstructure of white matter tracts. Between-group comparisons and correlation analyses with clinical features in patients with ACLR were performed. RESULTS: The patients with ACLR showed significant, moderate lower fractional anisotropy (FA, Cohen's d = -0.666, 95% CIs -1.221 to -0.104), lower axial diffusivity (AD, Cohen's d = -0.526, 95% CIs -1.077 to 0.030), and higher radial diffusivity (RD, Cohen's d = 0.514, 95% CIs -0.042 to 1.064) when compared to that of healthy controls, with the RD values being significantly correlated with the postoperative duration (r = 0.623, p < 0.001) after controlling the age, sex, and BMI in patients with ACLR. CONCLUSIONS: This study revealed that patients with ACLR have impaired integrity (lower FA values and higher RD values) in the CST contralateral to the ACLR injured limb in comparison with healthy controls. Decreased integrity (higher RD) of the CST in patients was significantly associated with longer postoperative duration, which hinted that impaired structural integrity of the CST may be a maladaptive process of neuroplasticity in ACLR.

Mapping annual 10-m soybean cropland with spatiotemporal sample migration.

China, as the world's biggest soybean importer and fourth-largest producer, needs accurate mapping of its planting areas for global food supply stability. The challenge lies in gathering and collating ground survey data for different crops. We proposed a spatiotemporal migration method leveraging vegetation indices' temporal characteristics. This method uses a feature space of six integrals from the crops' phenological curves and a concavity-convexity index to distinguish soybean and non-soybean samples in cropland. Using a limited number of actual samples and our method, we extracted features from optical time-series images throughout the soybean growing season. The cloud and rain-affected data were supplemented with SAR data. We then used the random forest algorithm for classification. Consequently, we developed the 10-meter resolution ChinaSoybean10 maps for the ten primary soybean-producing provinces from 2019 to 2022. The map showed an overall accuracy of about 93%, aligning significantly with the statistical yearbook data, confirming its reliability. This research aids soybean growth monitoring, yield estimation, strategy development, resource management, and food scarcity mitigation, and promotes sustainable agriculture.

Explore the shared molecular mechanism between dermatomyositis and nasopharyngeal cancer by bioinformatic analysis.

BACKGROUND: Dermatomyositis (DM) is prone to nasopharyngeal carcinoma (NPC), but the mechanism is unclear. This study aimed to explore the potential pathogenesis of DM and NPC. METHODS: The datasets GSE46239, GSE142807, GSE12452, and GSE53819 were downloaded from the GEO dataset. The disease co-expression module was obtained by R-package WGCNA. We built PPI networks for the key modules. ClueGO was used to analyze functional enrichment for the key modules. DEG analysis was performed with the R-package "limma". R-package "pROC" was applied to assess the diagnostic performance of hub genes. MiRNA-mRNA networks were constructed using MiRTarBase and miRWalk databases. RESULTS: The key modules that positively correlated with NPC and DM were found. Its intersecting genes were enriched in the negative regulation of viral gene replication pathway. Similarly, overlapping down-regulated DEGs in DM and NPC were also enriched in negatively regulated viral gene replication. Finally, we identified 10 hub genes that primarily regulate viral biological processes and type I interferon responses. Four key genes (GBP1, IFIH1, IFIT3, BST2) showed strong diagnostic performance, with AUC>0.8. In both DM and NPC, the expression of key genes was correlated with macrophage infiltration level. Based on hub genes' miRNA-mRNA network, hsa-miR-146a plays a vital role in DM-associated NPC. CONCLUSIONS: Our research discovered pivot genes between DM and NPC. Viral gene replication and response to type I interferon may be the crucial bridge between DM and NPC. By regulating hub genes, MiR-146a will provide new strategies for diagnosis and treatment in DM complicated by NPC patients. For individuals with persistent viral replication in DM, screening for nasopharyngeal cancer is necessary.

Full-spectral genome analysis of natural killer/T cell lymphoma highlights impacts of genome instability in driving its progression.

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is a clinically and genetically heterogeneous disease with poor prognosis. Genome sequencing and mutation characterization provides a powerful approach for patient stratification, treatment target discovery, and etiology identification. However, previous studies mostly concentrated on base-level mutations in primary NKTCL, whereas the large-scale genomic alterations in NKTCL and the mutational landscapes in relapsed/refractory NKTCL remain largely unexplored. METHODS: Here, we assembled whole-genome sequencing and whole-exome sequencing data from 163 patients with primary or relapsed/refractory NKTCL and compared their somatic mutational landscapes at both nucleotide and structure levels. RESULTS: Our study not only confirmed previously reported common NKTCL mutational targets like STAT3, TP53, and DDX3X but also unveiled several novel high-frequency mutational targets such as PRDM9, DST, and RBMX. In terms of the overall mutational landscape, we observed striking differences between primary and relapsed/refractory NKTCL patient groups, with the latter exhibits higher levels of tumor mutation burden, copy number variants (CNVs), and structural variants (SVs), indicating a strong signal of genomic instability. Complex structural rearrangements such as chromothripsis and focal amplification are also significantly enriched in relapsed/refractory NKTCL patients, exerting a substantial impact on prognosis. Accordingly, we devised a novel molecular subtyping system (i.e., C0-C4) with distinct prognosis by integrating potential driver mutations at both nucleotide and structural levels, which further provides an informative guidance for novel treatments that target these specific driver mutations and genome instability as a whole. CONCLUSIONS: The striking differences underlying the mutational landscapes between the primary and relapsed/refractory NKTCL patients highlight the importance of genomic instability in driving the progression of NKTCL. Our newly proposed molecular subtyping system is valuable in assisting patient stratification and novel treatment design towards a better prognosis in the age of precision medicine.

Propofol Alleviates Anxiety-Like Behaviors Associated with Pain by Inhibiting the Hyperactivity of PVNCRH Neurons via GABAA Receptor ß3 Subunits.

Pain, a comorbidity of anxiety disorders, causes substantial clinical, social, and economic burdens. Emerging evidence suggests that propofol, the most commonly used general anesthetic, may regulate psychological disorders; however, its role in pain-associated anxiety is not yet described. This study investigates the therapeutic potential of a single dose of propofol (100 mg kg-1) in alleviating pain-associated anxiety and examines the underlying neural mechanisms. In acute and chronic pain models, propofol decreased anxiety-like behaviors in the elevated plus maze (EPM) and open field (OF) tests. Propofol also reduced the serum levels of stress-related hormones including corticosterone, corticotropin-releasing hormone (CRH), and norepinephrine. Fiber photometry recordings indicated that the calcium signaling activity of CRH neurons in the paraventricular nucleus (PVNCRH) is reduced after propofol treatment. Interestingly, artificially activating PVNCRH neurons through chemogenetics interfered with the anxiety-reducing effects of propofol. Electrophysiological recordings indicated that propofol decreases the activity of PVNCRH neurons by increasing spontaneous inhibitory postsynaptic currents (sIPSCs). Further, reducing the levels of γ-aminobutyric acid type A receptor ß3 (GABAAß3) subunits in PVNCRH neurons diminished the anxiety-relieving effects of propofol. In conclusion, this study provides a mechanistic and preclinical rationale to treat pain-associated anxiety-like behaviors using a single dose of propofol.

Effects of the Pituitary-targeted Gland Axes on Hepatic Lipid Homeostasis in Endocrine-associated Fatty Liver Disease-A Concept Worth Revisiting.

Hepatic lipid homeostasis is not only essential for maintaining normal cellular and systemic metabolic function but is also closely related to the steatosis of the liver. The controversy over the nomenclature of non-alcoholic fatty liver disease (NAFLD) in the past three years has once again sparked in-depth discussions on the pathogenesis of this disease and its impact on systemic metabolism. Pituitary-targeted gland axes (PTGA), an important hormone-regulating system, are indispensable in lipid homeostasis. This review focuses on the roles of thyroid hormones, adrenal hormones, sex hormones, and their receptors in hepatic lipid homeostasis, and summarizes recent research on pituitary target gland axes-related drugs regulating hepatic lipid metabolism. It also calls on researchers and clinicians to recognize the concept of endocrine-associated fatty liver disease (EAFLD) and to re-examine human lipid metabolism from the macroscopic perspective of homeostatic balance.

Gel polymer electrolytes for rechargeable batteries toward wide-temperature applications.

Rechargeable batteries, typically represented by lithium-ion batteries, have taken a huge leap in energy density over the last two decades. However, they still face material/chemical challenges in ensuring safety and long service life at temperatures beyond the optimum range, primarily due to the chemical/electrochemical instabilities of conventional liquid electrolytes against aggressive electrode reactions and temperature variation. In this regard, a gel polymer electrolyte (GPE) with its liquid components immobilized and stabilized by a solid matrix, capable of retaining almost all the advantageous natures of the liquid electrolytes and circumventing the interfacial issues that exist in the all-solid-state electrolytes, is of great significance to realize rechargeable batteries with extended working temperature range. We begin this review with the main challenges faced in the development of GPEs, based on extensive literature research and our practical experience. Then, a significant section is dedicated to the requirements and design principles of GPEs for wide-temperature applications, with special attention paid to the feasibility, cost, and environmental impact. Next, the research progress of GPEs is thoroughly reviewed according to the strategies applied. In the end, we outline some prospects of GPEs related to innovations in material sciences, advanced characterizations, artificial intelligence, and environmental impact analysis, hoping to spark new research activities that ultimately bring us a step closer to realizing wide-temperature rechargeable batteries.

A Rare Instance of Spinal Cord Cavernous Malformation With Adjacent Intramedullary Microhemorrhage.

The natural history of spinal cord cavernous malformation (SCM) may be characterized by recurrent episodes of hemorrhage resulting in a range of neurologic deficits, most of which are microhemorrhage and subsequent gliosis that can lead to progressive myelopathy. Macrohemorrhage with acute onset of symptoms is extremely rare and leads to irreversible neurologic deficits. In this article, we present an unusual case of ruptured cavernous malformation (CM) in the cervical spinal cord with large extralesional hemorrhage. The patient underwent an operation of posterior longitudinal myelotomy and had a good neurologic recovery. A histologic examination revealed the typical features of cavernous angioma.

Development and validation of a novel prognostic nomogram for advanced diffuse large B cell lymphoma.

Advanced diffuse large B cell lymphoma (DLBCL) is a common malignant tumor with aggressive clinical features and poor prognosis. At present, there is lack of effective prognostic tool for patients with advanced (stage III/IV) DLBCL. The aim of this study is to identify prognostic indicators that affect survival and response and establish the first survival prediction nomogram for advanced DLBCL. A total of 402 patients with advanced DLBCL were enrolled in this study. COX multivariate analysis was used to obtain independent prognostic factors. The independent prognostic factors were included in the nomogram, and the nomogram to predict the performance of the model was established by R rms package, C-index (consistency index), AUC curve and calibration curve. The training and validation cohorts included 281 and 121 patients. In the training cohort, multivariate analysis showed that Ki-67 (70% (high expression) vs ≤ 70% (low expression), p < 0.001), LDH (lactate dehydrogenase) (elevated vs normal, p = 0.05), FER (ferritin) (elevated vs normal, p < 0.001), and ß2-microglobulin (elevated vs normal, p < 0.001) were independent predictors and the nomogram was constructed. The nomogram showed that there was a significant difference in OS among the low-risk, intermediate-risk and high-risk groups, with 5-year survival rates of 81.6%, 44% and 6%, respectively. The C-index of the nomogram in the training group was 0.76. The internal validation of the training group showed good consistency. In the internal validation cohort of the training group, the AUC was 0.828, and similar results were obtained in the validation group, with a C-index of 0.74 and an AUC of 0.803. The proposed nomogram provided a valuable individualized risk assessment of OS in advanced DLBCL patients.

Organic Fluorophores with Large Stokes Shift for the Visualization of Rapid Protein and Nucleic Acid Assays.

Organic small-molecule fluorophores, characterized by flexible chemical structure and adjustable optical performance, have shown tremendous potential in biosensing. However, classical organic fluorophore motifs feature large overlap between excitation and emission spectra, leading to the requirement of advanced optical set up to filter desired signal, which limits their application in scenarios with simple settings. Here, a series of wavelength-tunable small-molecule fluorescent dyes (PTs) bearing simple organic moieties have been developed, which exhibit Stokes shift up to 262 nm, molar extinction coefficients ranged 30,000-100,000 M-1 cm-1, with quantum yields up to 54.8 %. Furthermore, these dyes were formulated into fluorescent nanoparticles (PT-NPs), and applied in lateral flow assay (LFA). Consequently, limit of detection for SARS-CoV-2 nucleocapsid protein reached 20 fM with naked eye, a 100-fold improvement in sensitivity compared to the pM detection level for colloidal gold-based LFA. Besides, combined with loop-mediated isothermal amplification (LAMP), the LFA system achieved the visualization of single copy level nucleic acid detection for monkeypox (Mpox).

Research on WSN reliable ranging and positioning algorithm for forest environment.

Wireless sensor network (WSN) location is a significant research area. In complex environments like forests, inaccurate signal intensity ranging is a major challenge. To address this issue, this paper presents a reliable WSN distance measurement-positioning algorithm for forest environments. The algorithm divides the positioning area into several sub-regions based on the discrete coefficient of the collected signal strength. Then, using the fitting method based on the signal intensity value of each sub-region, the algorithm derives the reference points of the logarithmic distance path loss model and path loss index. Finally, the algorithm locates target nodes using anchor nodes in different regions. Additionally, to enhance the positioning accuracy, weight values are assigned to the positioning result based on the discrete coefficient of the signal intensity in each sub-region. Experimental results demonstrate that the proposed WSN algorithm has high precision in forest environments.

Developing the E. coli platform for efficient production of UMP-derived chemicals.

5-Methyluridine (5-MU) is a prominent intermediate for industrial synthesis of several antiviral-drugs, however, its availability over the past decades has overwhelmingly relied on chemical and enzymatic strategies. Here, we have realized efficient production of 5-MU in E. coli, for the first time, via a designer artificial pathway consisting of a two-enzyme cascade (UMP 5-methylase and phosphatase). More importantly, we have engineered the E. coli cell factory to boost 5-MU production by systematic evaluation of multiple strategies, and as a proof of concept, we have further developed an antibiotic-free fermentation strategy to realize 5-MU production (10.71 g/L) in E. coli MB229 (a ΔthyA strain). Remarkably, we have also established a versatile and robust platform with exploitation of the engineered E. coli for efficient production of diversified UMP-derived chemicals. This study paves the way for future engineering of E. coli as a synthetic biology platform for acceleratively accessing UMP-derived chemical diversities.

Revisiting the impact of public spaces on the mental health of rural migrants in Wuhan: an integrated multi-source data analysis.

Current research on public spaces and mental health often focuses on the independent relationship of one or more social mediators, neglecting the nuanced implications and serial mechanisms inherent in the progressive social process. Using Wuhan city, China, as a study case with multi-source data, this research applies Multilevel Generalized Structural Equation Modeling and deep learning techniques to explore the differential effects of public spaces with varying degrees of publicness (i.e., typical, semi-, and privately owned) on rural migrants' mental health. Crucially, this study scrutinizes both explicit (social interaction) and implicit (perceived integration) social mechanisms to revisit the relationships. The findings reveal that not all public spaces equally influence mental health, with typical and privately owned public spaces conferring profound benefits. Notably, public spaces impact mental health chiefly through perceived integration instead of through direct social interaction. Social interaction improves mental health primarily by enhancing perceived integration, suggesting that meaningful connections beyond superficial encounters are critical. In particular, we observed significant social effects in typical and privately owned public spaces but limited social functionality in semi-public spaces. This evidence contributes to the knowledge required to create supportive social environments within public spaces, integral to nurturing inclusive urban development.

Gradient Hydrogels Spatially Trapped Optical Cell Profiling for Quantitative Blood Cellular Osmotic Analysis.

The quantitative exploration of cellular osmotic responses and a thorough analysis of osmotic pressure-responsive cellular behaviors are poised to offer novel clinical insights into current research. This underscores a paradigm shift in the long-standing approach of colorimetric measurements triggered by red cell lysis. In this study, we engineered a purpose-driven optofluidic platform to facilitate the goal. Specifically, creating photocurable hydrogel traps surmounts a persistent challenge─optical signal interference from fluid disturbances. This achievement ensures a stable spatial phase of cells and the acquisition of optical signals for accurate osmotic response analysis at the single-cell level. Leveraging a multigradient microfluidic system, we constructed gradient osmotic hydrogel traps and developed an imaging recognition algorithm, empowering comprehensive analysis of cellular behaviors. Notably, this system has successfully and precisely analyzed individual and clustered cellular responses within the osmotic dimension. Prospective clinical testing has further substantiated its feasibility and performance in that it demonstrates an accuracy of 92% in discriminating complete hemolysis values (n = 25) and 100% in identifying initial hemolysis values (n = 25). Foreseeably, this strategy should promise to advance osmotic pressure-related cellular response analysis, benefiting further investigation and diagnosis of related blood diseases, blood quality, drug development, etc.

Tunable Macroscopic Alignment of Self-Assembling Peptide Nanofibers.

Fibrous proteins that comprise the extracellular matrix (ECM) guide cellular growth and tissue organization. A lack of synthetic strategies able to generate aligned, ECM-mimetic biomaterials has hampered bottom-up tissue engineering of anisotropic tissues and led to a limited understanding of cell-matrix interactions. Here, we present a facile extrusion-based fabrication method to produce anisotropic, nanofibrous hydrogels using self-assembling peptides. The application of shear force coinciding with ion-triggered gelation is used to kinetically trap supramolecular nanofibers into aligned, hierarchical structures. We establish how modest changes in phosphate buffer concentration during peptide self-assembly can be used to tune their alignment and packing. In addition, increases in the nanostructural anisotropy of fabricated hydrogels are found to enhance their strength and stiffness under hydrated conditions. To demonstrate their utility as an ECM-mimetic biomaterial, aligned nanofibrous hydrogels are used to guide directional spreading of multiple cell types, but strikingly, increased matrix alignment is not always correlated with increased cellular alignment. Nanoscale observations reveal differences in cell-matrix interactions between variably aligned scaffolds and implicate the need for mechanical coupling for cells to understand nanofibrous alignment cues. In total, innovations in the supramolecular engineering of self-assembling peptides allow us to generate a gradient of anisotropic nanofibrous hydrogels, which are used to better understand directed cell growth.

Perception of strigolactones and the coordinated phytohormonal regulation on rice (Oryza sativa) tillering is affected by endogenous ascorbic acid.

Phytohormones play a key role in regulating tiller number. Ascorbic acid (Asc)-phytohormone interaction plays a pivotal role in the regulation of senescence. We analysed the relationship between Asc and the enzyme concentrations and gene transcript abundances related to the signal perception of strigolactones (SLs), the contents of four phytohormones (abscisic acid, ABA; jasmonic acid, JA; indole acetic acid, IAA; cytokinin, CTK), the enzyme concentrations and gene transcript abundances related to the synthesis or transportation of these four phytohormones. Our results showed that Asc deficiency leads to the upregulation of enzyme concentrations, gene transcript abundances related to the SL signal perception, ABA synthesis and IAA transport. The altered level of Asc also leads to a change in the contents of ABA, JA, IAA and CTK. These findings support the conclusion that Asc or Asc/DHA play an important role in the signal perception and transduction of SLs, and Asc may affect the coordinated regulation of SL, IAA and CTK on rice (Oryza sativa ) tillering.

The combination of IL-2 nanoparticles and Palbociclib enhances the anti-tumor immune response for colon cancer therapy.

Immunotherapy of tumors plays a pivotal role in the current treatment of cancer. While interleukin 2 (IL-2) demonstrated its efficacy as an immunotherapeutic drug in the early days, its short blood circulation time poses challenges in maintaining effective therapeutic concentrations. Additionally, IL-2's activation of regulatory T cells can counteract its anti-cancer effects. Therefore, the primary goal of this study was to formulate IL-2-carrying nanoparticles via boron-nitrogen coordination between methoxy poly (ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide]phenylboronic acid (mPEG-b-PHEA-PBA, P-PBA) and poly (L-lysine) (PLL). These nanoparticles are intended to be used in combination with CDK4/6 inhibitors to address the short blood circulation time of IL-2, reduce its immunosuppressive effects, and enhance the overall immune response. The envisaged outcome is a sustained and potent therapeutic effect, offering a novel and promising combination therapy strategy for tumor immunotherapy.