68Ga labeled EphA2-targeted cyclic peptide: a novel positron imaging tracer for triple-negative breast cancer?

The absence of better biomarkers currently limits early diagnosis and treatment of triple-negative breast cancer (TNBC). Our previously published study reported that the cyclic-peptide SD01 exhibited specific binding to EphA2 (Ephrin type-A receptor 2) on TNBC. To develop a novel PET imaging agent, we prepared gallium-68 (68Ga) labeled-DOTA-SD01 and evaluated its specificity and effectiveness through micro PET/CT imaging in a TNBC-bearing mouse model. SD01 and a control linear peptide YSA were conjugated to DOTA and subsequently labeled with 68Ga, obtaining 68Ga-DOTA-SD01 and 68Ga-DOTA-YSA. Both showed high radiochemical purity, stability, good hydrophilicity, and high binding affinity to 4T1 cells. Micro PET/CT imaging showed high radioactivity accumulation in tumors; SUVmean (mean standardized uptake value) of tumors in the group of 68Ga-DOTA-SD01 was 3.34 ± 0.25 and 2.65 ± 0.32 in the group of 68Ga-DOTA-YSA; T/NT ratios (target to non-target, SUVmean ratios of tumor to muscle) were 3.12 ± 0.06 and 2.77 ± 0.11 at 30 min, respectively (p < 0.05). The biodistribution study showed that tumor uptake % ID per g (percentage of injected dose per gram of tissue) in the group of 68Ga-DOTA-SD01 was 2.73 ± 0.34, and 1.77 ± 0.38 in the group of 68Ga-DOTA-YSA; T/NT ratios (radioactivity of tumor to muscle) were 3.55 ± 0.12 and 3.05 ± 0.10 for both groups at 30 min, respectively (p < 0.05). All these suggest that 68Ga-DOTA-SD01 may act as a better novel PET imaging agent for EphA2 positive tumors, such as TNBC.

Effectiveness of Low-frequency Pulse Electrical Stimulation Combined with Dexamethasone in Treating Facial Nerve Paralysis and Its Impact on Facial Nerve Function and Electromyography.

Objective: This study aimed to evaluate the efficacy of adjunct low-frequency pulse electrical stimulation alongside dexamethasone in the treatment of facial nerve paralysis and its subsequent effects on facial nerve function and electromyographic parameters. With the aim of addressing a knowledge gap in the field, this research provides valuable insights into the potential benefits of combining these treatments and their impact on clinical outcomes, facial nerve functionality, and electromyographic dynamics. Methods: A cohort of 66 patients with facial nerve paralysis treated at our institution between April 2018 and November 2021 were randomly assigned to either an observation (n=33) or an experimental group (n=33). The observation group received standard pharmacotherapy, including Western medications and Daqinjiao decoction, along with dexamethasone. The experimental group was administered low-frequency pulse electrical stimulation in addition to the observation group's regimen. Outcomes assessed were clinical efficacy, facial nerve paralysis scoring, facial nerve functional scoring and indices, electromyographic latency, amplitude ratios between affected and unaffected sides, as well as any adverse events. Results: The experimental group demonstrated a significant improvement over the observation group in clinical treatment outcomes, facial nerve paralysis scores, and facial nerve function scores (P < .05 for all). Furthermore, electromyographic analysis revealed shorter latency periods and greater amplitude ratios in the experimental group's facial muscles post-treatment (P < .05). No significant difference was observed in the incidence of adverse reactions between the two groups (P > .05). Conclusion: The integration of low-frequency pulse electrical stimulation with dexamethasone therapy significantly ameliorates the severity of facial nerve paralysis, enhances facial nerve function, and improves electromyographic signals in facial muscles without increasing adverse effects. These findings support the clinical value and safety of this combined treatment approach for facial nerve paralysis, suggesting its suitability for broader clinical application. These results suggest that this combined treatment approach holds promise for broader clinical application, potentially providing a more effective and safer therapeutic option for patients with facial nerve paralysis. Implementing this approach in clinical practice may lead to improved treatment outcomes, better functional recovery, and enhanced quality of life for affected individuals.

Macrophage hitchhiking for systematic suppression in postablative multifocal hepatocellular carcinoma.

BACKGROUND AIMS: Hepatocellular carcinoma (HCC), particularly the multifocal HCC, features aggressive invasion and dismal prognosis. Locoregional treatments were often refractory to eliminate tumor tissue, resulting in residual tumor cells persisting and subsequent progression. Owing to problematic delivery to the tumor tissue, systemic therapies, such as lenvatinib (LEN) therapy, show limited clinical benefit in preventing residual tumor progression. Therefore, more advanced strategies for postablative multifocal HCC are urgently needed. APPROACH RESULTS: Motivated by the chemotaxis in tumor penetration of macrophages, we report a strategy named microinvasive ablation-guided macrophage hitchhiking (MAMH) for the targeted therapy toward HCC. In this study, the strategy leverages the natural inflammatory gradient induced by ablation to guide LEN-loaded macrophages toward tumor targeting, which increased by ~10-fold the delivery efficiency of LEN in postablative HCC in vivo. MAMH has demonstrated significant antitumor activity in various HCC models, including the hydrodynamic tail vein injection multifocal HCC mouse model and the orthotopic xenograft HCC rabbit model, systematically inhibiting residual tumor progression after ablation and prolonging the median survival of tumor-bearing mice. The potential antitumor mechanism was explored using techniques such as flow cytometry, enzyme-linked immunosorbent assay, and immunohistochemistry. We found that the strategy significantly suppressed tumor cell proliferation and neovascularization, and such enhanced delivery of LEN stimulated systemic immune responses and induced durable immune memory. CONCLUSIONS: The macrophage hitchhiking strategy demonstrates exceptional therapeutic efficacy and biosafety across various species, offering promising prospects for clinical translation in controlling residual tumor progression and improving outcomes following HCC ablation.

Secukinumab in patients with moderate to severe hidradenitis suppurativa based on prior biologic exposure: An efficacy and safety analysis from the SUNSHINE and SUNRISE phase III trials.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease associated with a substantial disease burden. Secukinumab has previously been reported to have sustained efficacy with a favourable safety profile in patients with moderate to severe HS. It is unknown if prior biologic exposure impacts the efficacy and safety of secukinumab. OBJECTIVES: To investigate the efficacy and safety of secukinumab in patients with moderate to severe HS based on prior exposure to biologics. METHODS: This was an analysis of the SUNSHINE and SUNRISE phase III trials of secukinumab in patients with moderate to severe HS. Patients were randomized at baseline to receive secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W), or placebo for 16 weeks. After week 16, patients receiving SECQ2W and SECQ4W remained on the same treatment regimen, while patients randomized to placebo were switched to either SECQ2W or SECQ4W up to week 52. Assessments based on prior exposure to biologics included HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flare rates, HS-related pain (numeric rating scale [NRS]) 30], international HS severity scoring system (IHS4), dermatology life quality index, European quality of life five-dimension, and safety. RESULTS: Overall, 1084 patients were randomized in the SUNSHINE and SUNRISE trials and included in this analysis, with 255 (23.5%) patients being biologic experienced (SECQ2W [N=80]; SECQ4W [N=81]; placebo [N=94]) and 829 (76.5%) being biologic-naïve (SECQ2W [N=281]; SECQ4W [N=279]; placebo [N=269]). At week 16, responses were more efficacious for secukinumab compared with placebo for HiSCR in patients who were biologic-experienced (SECQ2W, 37.0% [odds ratio (OR): 1.60; 95% confidence interval (CI): 0.83, 3.08]; SECQ4W, 38.8% [OR: 1.67; 95% CI: 0.86, 3.22; placebo, 27.3%) and biologic-naive (SECQ2W, 45.6% [OR: 1.64; 95% CI: 1.15, 2.33]; SECQ4W, 45.4% [OR: 1.61; 95% CI: 1.13, 2.29]; placebo, 34.2%). Similar results were observed for AN count, NRS30, and IHS4-55. The higher response seen at week 16 with secukinumab was sustained, with a trend for improvement over time, through week 52 in both subgroups. Additional efficacy was observed for quality-of-life assessments, and no differences in safety between subgroups were observed. CONCLUSIONS: Regardless of prior biologic exposure, secukinumab was efficacious in improving signs and symptoms of HS. This finding positions secukinumab as the first option in patients who are biologic-naïve, as well as in patients who have previously been treated with other biologic therapy, based on individual patient needs. TRIAL REGISTRATION: SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).

Lightweight reinforced wood beams through compression of its surface layers combined with the removal of lignin and hemicellulose.

When wood is used as a stressed component of building materials, the parts most prone to failure are the upper and lower surfaces which can be called the weak structure. In a hydrothermal environment, lignin and hemicellulose in wood readily soften and dissolve, thus leading to their designation as the weak structure. The weak structures results in the wood having a low strength. In this paper, the sandwich beam material can be obtained by two steps from the skin self-reinforcement method, whereby the weak structure of the wood surface was removed by the delignification, and then the wood surface was densified. The authenticity of the sandwich structure is proved by a scanning electron microscope (SEM) and density profile analysis. When the moisture content (MC) is 10 %-12 % and the mass loss ratio is 23.04 %, the optimal resilience of the sandwich beam is only 1 %, the maximum modulus of rupture (MOR) and modulus of elasticity (MOE) are 1.42 and 2.1 times greater than those of natural wood, respectively. This finding shows that our method strengthens the weak structure of natural wood, which has good flexural performance and springback ratio.

Strong, Lightweight, and Shape-Memory Bamboo-Derived All-Cellulose Aerogels for Versatile Scaffolds of Sustainable Multifunctional Materials.

Strong, lightweight, and shape-memory cellulose aerogels have great potential in multifunctional applications. However, achieving the integration of these features into a cellulose aerogel without harsh chemical modifications and the addition of mechanical enhancers remains challenging. In this study, a strong, lightweight, and water-stimulated shape-memory all-cellulose aerogel (ACA) is created using a combination strategy of partial dissolution and unidirectional freezing from bamboo. Benefiting from the firm architecture of cellulose microfibers bridging cellulose nanofibers /regenerated cellulose aggregated layers and the bonding of different cellulose crystal components (cellulose Iß and cellulose II), the ACA, with low density (60.74 mg cm-3 ), possesses high compressive modulus (radial section: 1.2 MPa, axial section: 0.96 MPa). Additionally, when stimulated with water, the ACA exhibits excellent shape-memory features, including highly reversible compression-resilience and instantaneous fold-expansion behaviors. As a versatile scaffold, ACA can be integrated with hydroxyapatite, carboxyl carbon nanotubes, and LiCl, respectively, via a simple impregnation method to yield functionalized cellulose composites for applications in thermal insulation, electromagnetic interference shielding, and piezoresistive sensors. This study provides inspiration and a reliable strategy for the elaborately structural design of functional cellulose aerogels endows application prospects in various multifunction opportunities.

Assessment of the glymphatic function in children with attention-deficit/hyperactivity disorder.

OBJECTIVES: Whether the alternation of the glymphatic system exists in neurodevelopmental disease still remains unclear. In this study, we investigated structural and functional changes in the glymphatic system in the treatment-naïve attention-deficit/hyperactivity disorder (ADHD) children by quantitatively measuring the Virchow-Robin spaces (VRS) volume and diffusion tensor image-analysis along the perivascular space (DTI-ALPS). METHODS: Forty-seven pediatric ADHD patients and 52 age- and gender-matched typically developing (TD) children were recruited in this prospective study. The VRS volume was calculated using a semi-automated approach in axial T2-weighted images. Diffusivities along the x-, y-, and z-axes in the projection, association, and subcortical neural fiber areas were measured. The ALPS index, a ratio that accentuated water diffusion along the perivascular space, was calculated. The Mann-Whitney U test was used to compare the quantitative parameters; Pearson's correlation was used to analyze the correlation with clinical symptoms. RESULTS: The cerebral VRS volume (mean, 15.514 mL vs. 11.702 mL) and the VRS volume ratio in the ADHD group were larger than those in the TD group (all p < 0.001). The diffusivity along the x-axis in association fiber area and ALPS index were significantly smaller in the ADHD group vs. TD group (mean, 1.40 vs.1.59, p < 0.05 after false discovery rate adjustment). Besides, the ALPS index was related to inattention symptoms of ADHD (r = - 0.323, p < 0.05). CONCLUSIONS: Our study suggests that the glymphatic system alternation may participate in the pathogenesis of ADHD, which may be a new research direction for exploring the mechanisms of psycho-behavioral developmental disorders. Moreover, the VRS volume and ALPS index could be used as the metrics for diagnosing ADHD. CLINICAL RELEVANCE STATEMENT: Considering the potential relevance of the glymphatic system for exploring the mechanisms of attention deficit/hyperactivity, the Virchow-Robin spaces volume and the analysis along the perivascular space index could be used as additional metrics for diagnosing the disorder. KEY POINTS: • Increased Virchow-Robin space volume and decreased analysis along the perivascular space index were found in the treatment-naïve attention-deficit/hyperactivity disorder children. • The results of this study indicate that the glymphatic system alternation may have a valuable role in the pathogenesis of attention-deficit/hyperactivity disorder. • The analysis along the perivascular space index is correlated with inattention symptoms of attention-deficit/hyperactivity disorder children.

Glymphatic Imaging in Pediatrics.

The glymphatic system, which facilitates cerebrospinal fluid (CSF) flow through the brain parenchyma, is important for brain development and waste clearance. Advances in imaging techniques, particularly magnetic resonance imaging, have make it possible to evaluate glymphatic structures and functions in vivo. Recently, several studies have focused on the development and alterations of the glymphatic system in pediatric disorders. This review discusses the development of the glymphatic system, advances of imaging techniques and their applications in pediatric disorders. First, the results of the reviewed studies indicate that the development of the glymphatic system is a long-lasting process that continues into adulthood. Second, there is a need for improved glymphatic imaging techniques that are non-invasive and fast to improve suitability for pediatric applications, as some of existing methods use contrast injection and are susceptible to motion artifacts from long scanning times. Several novel techniques are potentially feasible for pediatric patients and may be used in the future. Third, the glymphatic dysfunction is associated with a large number of pediatric disorders, although only a few have recently been investigated. In conclusion, research on the pediatric glymphatic system remains an emerging field. The preliminary applications of glymphatic imaging techniques have provided unique insight into the pathological mechanism of pediatric diseases, but mainly limited in visualization of enlarged perivascular spaces and morphological measurements on CSF volumes. More in-depth studies on glymphatic functions are required to improve our understanding of the mechanisms underlying brain development and pediatric diseases. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Impaired glymphatic system revealed by DTI-ALPS in cerebral palsy due to periventricular leukomalacia: relation with brain lesion burden and hand dysfunction.

PURPOSE: Preterm children with cerebral palsy (CP) often have varying hand dysfunction, while the specific brain injury with periventricular leukomalacia (PVL) cannot quite explain its mechanism. We aimed to investigate glymphatic activity using diffusion tensor image analysis along the perivascular space (DTI-ALPS) method and evaluate its association with brain lesion burden and hand dysfunction in children with CP secondary to PVL. METHODS: We retrospectively enrolled 18 children with bilateral spastic CP due to PVL and 29 age- and sex-matched typically developing controls. The Manual Ability Classification System (MACS) was used to assess severity of hand dysfunction in CP. A mediation model was performed to explore the relationship among the DTI-ALPS index, brain lesion burden, and the MACS level in children with CP. RESULTS: There were significant differences in the DTI-ALPS index between children with CP and their typically developing peers. The DTI-ALPS index of the children with CP was lower than that of the controls (1.448 vs. 1.625, P = 0.003). The mediation analysis showed that the DTI-ALPS index fully mediated the relationship between brain lesion burden and the MACS level (c' = 0.061, P = 0.665), explaining 80% of the effect. CONCLUSION: This study provides new insights into the neural basis of hand dysfunction in children with CP, demonstrating an important role of glymphatic impairment in such patients. These results suggest that PVL might affect hand function in children with CP by disrupting glymphatic drainage.

Infusing phytate-based biomass flame retardants into the cellulose lumens of Chinese fir wood attains superior flame retardant efficacy.

To be suitable for certain construction and furniture applications, wood must be treated with a flame retardant and impregnating flame retardants into the cellulose lumens of wood is an effective flame retardant method. Phytic acid, the main storage form of phosphorus in various plant tissues, is an inexpensive, and non-toxic biomaterial that shows potential applications as an environmentally friendly bio-based flame retardant. In this study, phytic acid and zinc phytate were used to impregnate delignified wood under vacuum and pressure, which greatly enhanced the flame retardancy and smoke suppression properties of Chinese fir, while still maintaining its original texture. Phytic acid and zinc phytate were hydrogen-bonded to cellulose in wood. Phytic acid and zinc phytate were hydrogen-bonded to cellulose in wood. The results showed that the total heat release (THR) of Chinese fir treated with zinc phytate decreased from 55.66 MJ/m2 to 5.90 MJ/m2, and a compact carbonized protective layer was quickly formed on the surface of Chinese fir after ignition. Thermogravimetric analysis (TGA) showed that the char yield of Chinese fir treated by the flame retardant was 177.6 % higher than that of untreated wood. This study provides an efficient, sustainable, and economical method to prepare Chinese fir with excellent flame retardancy and thermal insulation performance.

Preparation Optimization of Enhanced Poplar Wood by Organic-Inorganic Hybrid Treatment via Response Surface Methodology.

In this work, a strategy for hybrid treatment was proposed, aiming to present a hybrid impregnation agent including lignin-derived resin (LR) and surface-modified montmorillonite (GMMT) to treat fast-growing poplar wood. The treating agents could penetrate the wood, fill the cavities of the wood interior, and strengthen the cell wall structure. The optimal WPG of 36.2% was obtained upon the response surface methodology (RSM) at the conditions of 34% LR, 1.8% GMMT, 1.2 MPa impregnation pressure, and 99 min impregnation time. The density, water uptake (WU), modulus of rupture (MOR), modulus of elasticity (MOE), and compressive strength (CS) of the samples were tested to evaluate the enhancement of the physical and mechanical properties. In addition, these samples were investigated via cone calorimeter (CONE), Fourier Transform Infrared spectrometer (FTIR), and X-ray diffraction (XRD). The results showed that the density of the treated samples increased significantly up to 0.72 g/cm3. Compared with 134.8% of the control, the WU of the treated wood sample could decrease to 60.3%. In addition, the MOR and MOE of the resulting samples reached up to 131.8 MPa and 18.14 GPa, respectively, which were 62.3% and 77.7% higher than the control. Notably, the CS was 84.7 MPa with an increase of up to 94.7%. Moreover, the peak heat release rate (HRR) of the treated sample was obviously reduced to 231.33 kW/m2, a decrease of 17.5% compared to the control (271.71 kW/m2).

A preoperative CT-based deep learning radiomics model in predicting the stage, size, grade and necrosis score and outcome in localized clear cell renal cell carcinoma: A multicenter study.

BACKGROUND AND PURPOSE: The Stage, Size, Grade and Necrosis (SSIGN) score is the most commonly used prognostic model in clear cell renal cell carcinoma (ccRCC) patients. It is a great challenge to preoperatively predict SSIGN score and outcome of ccRCC patients. The aim of this study was to develop and validate a CT-based deep learning radiomics model (DLRM) for predicting SSIGN score and outcome in localized ccRCC. METHODS: A multicenter 784 (training cohort/ test 1 cohort / test 2 cohort, 475/204/105) localized ccRCC patients were enrolled. Radiomics signature (RS), deep learning signature (DLS), and DLRM incorporating radiomics and deep learning features were developed for predicting SSIGN score. Model performance was evaluated with area under the receiver operating characteristic curve (AUC). Kaplan-Meier survival analysis was used to assess the association of the model-predicted SSIGN with cancer-specific survival (CSS). Harrell's concordance index (C-index) was calculated to assess the CSS predictive accuracy of these models. RESULTS: The DLRM achieved higher micro-average/macro-average AUCs (0.913/0.850, and 0.969/0.942, respectively in test 1 cohort and test 2 cohort) than the RS and DLS did for the prediction of SSIGN score. The CSS showed significant differences among the DLRM-predicted risk groups. The DLRM achieved higher C-indices (0.827 and 0.824, respectively in test 1 cohort and test 2 cohort) than the RS and DLS did in predicting CSS for localized ccRCC patients. CONCLUSION: The DLRM can accurately predict the SSIGN score and outcome in localized ccRCC.

Enhanced Preservative Performance of Pine Wood through Nano-Xylan Treatment Assisted by High-Temperature Steam and Vacuum Impregnation.

This study used environmentally friendly nano-xylan to enhance the drug loading and preservative performance (especially against white-rot fungi) of pine wood (Pinus massoniana Lamb), determine the best pretreatment, nano-xylan modification process, and analyze the antibacterial mechanism of nano-xylan. High-temperature, high-pressure steam pretreatment-assisted vacuum impregnation was applied to enhance the nano-xylan loading. The nano-xylan loading generally increased upon increasing the steam pressure and temperature, heat-treatment time, vacuum degree, and vacuum time. The optimal loading of 14.83% was achieved at a steam pressure and temperature of 0.8 MPa and 170 °C, heat treatment time of 50 min, vacuum degree of 0.08 MPa, and vacuum impregnation time of 50 min. Modification with nano-xylan prohibited the formation of hyphae clusters inside the wood cells. The degradation of integrity and mechanical performance were improved. Compared with the untreated sample, the mass loss rate of the sample treated with 10% nano-xylan decreased from 38 to 22%. The treatment with high-temperature, high-pressure steam significantly enhanced the crystallinity of wood.

177 Lu-DOTATATE Therapy in a Case of Castrate-Resistant Prostate Cancer With Neuroendocrine Differentiation.

ABSTRACT: An 84-year-old man with prostate cancer with neuroendocrine differentiation underwent PET/CT for staging. 68 Ga-prostate-specific membrane antigen PET/CT did not show significant abnormal tracer accumulation, whereas 18 F-OC ( 18 F-AlF-NOTA-octreotide) PET/CT showed elevated tracer uptake at multiple sites throughout the body. Therefore, the patient opted to receive 1 cycle of 177 Lu-DOTATATE peptide receptor radionuclide therapy with a dose of 200 mCi. Encouragingly, radiographic tumor remission and improvement of clinical symptoms were observed after only 1 cycle of treatment.

A 3D stacked corrugated pore structure composed of CoNiO2 and polyaniline within the tracheids of wood-derived carbon for high-performance asymmetric supercapacitors.

A novel 3D stacked corrugated pore structure of polyaniline (PANI)/CoNiO2@activated wood-derived carbon (AWC) has been successfully constructed to prepare high-performance electrode materials for supercapacitors. AWC functions as a supporting framework that provides ample attachment sites for the loaded active materials. The CoNiO2 nanowire substrate, consisting of 3D stacked pores, not only serves as a template for subsequent PANI loading, but also acts as an effective buffer to mitigate the volume expansion of the PANI during ionic intercalation. The distinctive corrugated pore structure of PANI/CoNiO2@AWC facilitates electrolyte contact and significantly enhances the electrode material properties. The PANI/CoNiO2@AWC composite materials exhibit excellent performance (14.31F cm-2 at 5 mA cm-2) and superior capacitance retention (80% from 5 to 30 mA cm-2), owing to the synergistic effect among their components. Finally, PANI/CoNiO2@ AWC//reduced graphene oxide (rGO)@AWC asymmetric supercapacitor is assembled, which has a wide operating voltage (0 âˆ¼ 1.8 V), high energy density (4.95 mWh cm-3 at 26.44 mW cm-3) and cycling stability (90.96% after 7000 cycles).

Fabrication and Process Optimization of Chinese Fir-Derived SiC Ceramic with High-Performance Friction Properties.

In this study, a novel friction material with biomass-ceramic (SiC) dual matrixes was fabricated using Chinese fir pyrocarbon via the liquid-phase silicon infiltration and in situ growth method. SiC can be grown in situ on the surface of a carbonized wood cell wall by mixing and calcination of wood and Si powder. The samples were characterized using XRD, SEM, and SEM-EDS analysis. Meanwhile, their friction coefficients and wear rates were tested to study their frictional properties. To explore the influence of crucial factors on friction performance, response surface analysis was also conducted to optimize the preparation process. The results showed that longitudinally crossed and disordered SiC nanowhiskers were grown on the carbonized wood cell wall, which could enhance the strength of SiC. The designed biomass-ceramic material had satisfying friction coefficients and low wear rates. The response surface analysis results indicate that the optimal process could be determined (carbon to silicon ratio of 3:7, reaction temperature of 1600 °C, and 5% adhesive dosage). Biomass-ceramic materials utilizing Chinese fir pyrocarbon could display great promise to potentially replace the current iron-copper-based alloy materials used in brake systems.

A CT-based deep learning radiomics nomogram outperforms the existing prognostic models for outcome prediction in clear cell renal cell carcinoma: a multicenter study.

OBJECTIVES: To develop and validate a CT-based deep learning radiomics nomogram (DLRN) for outcome prediction in clear cell renal cell carcinoma (ccRCC), and its performance was compared with the Stage, Size, Grade, and Necrosis (SSIGN) score, the University of California, Los Angeles, Integrated Staging System (UISS), the Memorial Sloan-Kettering Cancer Center (MSKCC), and the International Metastatic Renal Cell Database Consortium (IMDC). METHODS: A multicenter of 799 localized (training/ test cohort, 558/241) and 45 metastatic ccRCC patients were studied. A DLRN was developed for predicting recurrence-free survival (RFS) in localized ccRCC patients, and another DLRN was developed for predicting overall survival (OS) in metastatic ccRCC patients. The performance of the two DLRNs was compared with that of the SSIGN, UISS, MSKCC, and IMDC. Model performance was assessed with Kaplan-Meier curves, time-dependent area under the curve (time-AUC), Harrell's concordance index (C-index), and decision curve analysis (DCA). RESULTS: In the test cohort, the DLRN achieved higher time-AUCs (0.921, 0.911, and 0.900 for 1, 3, and 5 years, respectively), C-index (0.883), and net benefit than SSIGN and UISS in predicting RFS for localized ccRCC patients. The DLRN provided higher time-AUCs (0.594, 0.649, and 0.754 for 1, 3, and 5 years, respectively) than MSKCC and IMDC in predicting OS for metastatic ccRCC patients. CONCLUSIONS: The DLRN can accurately predict outcomes and outperformed the existing prognostic models in ccRCC patients. CLINICAL RELEVANCE STATEMENT: This deep learning radiomics nomogram may facilitate individualized treatment, surveillance, and adjuvant trial design for patients with clear cell renal cell carcinoma. KEY POINTS: • SSIGN, UISS, MSKCC, and IMDC may be insufficient for outcome prediction in ccRCC patients. • Radiomics and deep learning allow for the characterization of tumor heterogeneity. • The CT-based deep learning radiomics nomogram outperforms the existing prognostic models in ccRCC outcome prediction.

Construction of nano-drug delivery and antitumor system of stimuli-responsive polypeptides.

The size of the nanoparticles is moderate and the dispersion is well, which will not be recognized nonspecifically and clearance by the endothelial reticular system. In this study, stimuli-responsive polypeptides nano-delivery system has been constructed, which can realize the response to various stimuli in the tumor microenvironment. Tertiary amine groups are grafted to the side chain of polypeptides as the point of charge reversal and particle expansion. In addition, a new kind of liquid crystal monomer was prepared by substituting cholesterol-cysteamine, which can promote polymers to realize the transformation of spatial conformation by adjusting the ordered arrangement of macromolecules. The introduction of hydrophobic elements greatly enhanced the self-assembly performance of polypeptides, which could effectively improve the drug loading and encapsulation rate of nanoparticles. Nanoparticles could achieve targeted aggregation in tumor tissues, and there were no toxicity and side effects on normal bodies during treatment, with good safety in vivo.

Genetically Programmable Vesicles for Enhancing CAR-T Therapy against Solid Tumors.

Chimeric antigen receptor-T (CAR-T) cell therapy has shown remarkable success in eradicating hematologic malignancies; however, its efficacy in treating solid tumors has always been limited due to the presence of an immune-suppressive tumor microenvironment (TME). Here, genetically programmable cellular vesicles expressing high-affinity anti-programmed death-ligand 1 single chain variable fragment (anti-PD-L1 scFv) loaded with glutamine antagonist (D@aPD-L1 NVs) are developed to metabolically dismantle the immunosuppressive TME and enhance the efficiency of anti-mesothelin CAR-T cells in orthotopic lung cancer. As anti-PD-L1 scFv can specifically bind to the programmed death-ligand 1 (PD-L1) on tumor cells, D@aPD-L1 NVs enable the targeted delivery of glutamine antagonists to the tumor site and address the upregulation of PD-L1 on tumor cells, which prevents the premature exhaustion of CAR-T cells. More importantly, D@aPD-L1 NVs effectively reduce the number of immunosuppressive cells and promote the recruitment of inflammatory cells and the secretion of inflammatory cytokines in tumor tissues. These unique features of D@aPD-L1 NVs improve the infiltration and effector functions of CAR-T cells, which ultimately enhance the anti-tumor ability and long-term memory immunity of CAR-T cells. The findings support that D@aPD-L1 NVs act as a promising drug to strengthen the effectiveness of CAR-T cells against solid tumors.