Rhein-based Pickering emulsion for hepatocellular carcinoma:Shaping the metabolic signaling and immunoactivation in transarterial chemoembolization

The efficacy of transarterial chemoembolization(TACE)has been limited by insufficient embolization and a high incidence of tumor recurrence.Herein,we iden-tified that aberrant metabolic reprogramming and immunosuppression contribute to TACE refractoriness and Rhein,as a potential glycolytic metabolism inhibitor and immunoactivation inducer,was optimized to sensitize tumors to TACE therapy.To achieve efficient embolization,we developed an oil-in-water lipiodol embolic emulsion by stabilizing the self-assembled Rhein nanogel.The assembled Rhein exhibited a nanofiber network,and its integration enhanced the mechanical stability and viscoelasticity of the lipiodol embolic agent.With the synergistic advantages of solid and liquid embolic agents,this carrier-free Pickering emulsion exhibits effi-cient embolization and sustained drug release in models of unilateral renal artery embolization,rabbit ear tumor embolization,rabbit orthotopic liver cancer,and rat orthotopic liver cancer.Compared to conventional three-way catheter mixing meth-ods,multimodal imaging corroborates a marked enhancement in local drug retention and tumor suppression.Importantly,the incorporation of Rhein-mediated syner-gistic immunoembolization in this strategy achieved efficient embolization while robustly activating anti-tumor immune responses,including inducing immunogenic cell death,dendritic cell activation,and major histocompatibility complex class I pre-sentation to CD8+T cells for tumor killing.Together,thesefindings reveal a novel strategy for the application of self-assembled Rhein nanofiber-stabilized lipiodol emulsion to control metabolic signaling and immunoactivation in TACE.

Oxygen permeability and CO_2-tolerance of Ce_(0.8)Gd_(0.2)O_(2-δ)-Ln BaCo_2O_(5+δ) dual-phase membranes

A series of oxygen permeable dual-phase composite oxides 60 wt% Ce0.8Gd0.2O2-δ-40 wt% LnBaCo2O5＋δ （CGO-LBCO, Ln = La, Pr, Nd, Sin, Gd and Y） were synthesized through a sol-gel route and effects of the Ln3＋ cations on their phase structure, oxygen permeability and chemical stability against CO2 were investigated systemically by XRD, SEM, TG-DSC and oxygen permeation experiments. XRD patterns reveal that the larger Ln3＋ cations （La3＋, Pr3＋ and Nd3＋） successfully stabilized the double-layered perovskite structure of sintered LBCO, while the smaller ones （Sm3＋, Gd3＋, and Y3＋） resulted in the partial decomposition of LBCO with some impurities formed. CGO-PBCO yields the highest oxygen permeation flux, reaching 2.8× 10^-7 mol.s-1.cm-2 at 925 ℃ with 1 mm thickness under air/He gradient. The TG-DSC profiles in 20 mol% CO2/N2 and oxygen permeability experiments with CO2 as sweep gas show that CGO-YBCO demonstrates the best chemical stability against CO2, possibly due to its minimum basicity. The stable oxygen permeation flux of CGO-YBCO under CO2 atmosphere reveals its potential application in the oxy-fuel combustion route for CO2 capture.

Connecting Calcium-Based Nanomaterials and Cancer:From Diagnosis to Therapy

As the indispensable second cellular messenger,calcium signaling is involved in the regulation of almost all physiological processes by activating specific target proteins.The importance of calcium ions(Ca^(2+))makes its“Janus nature”strictly regulated by its concentration.Abnormal regulation of calcium signals may cause some diseases;however,artificial regulation of calcium homeostasis in local lesions may also play a therapeutic role.“Calcium overload,”for example,is characterized by excessive enrichment of intracellular Ca^(2+),which irreversibly switches calcium signaling from“positive regulation”to“reverse destruction,”leading to cell death.However,this undesirable death could be defined as“calcicoptosis”to offer a novel approach for cancer treatment.Indeed,Ca^(2+)is involved in various cancer diagnostic and therapeutic events,including calcium overload-induced calcium homeostasis disorder,calcium channels dysregulation,mitochondrial dysfunction,calcium-associated immunoregulation,cell/vascular/tumor calcification,and calcification-mediated CT imaging.In paral-lel,the development of multifunctional calcium-based nanomaterials(e.g.,calcium phosphate,calcium carbonate,calcium peroxide,and hydroxyapatite)is becoming abundantly available.This review will highlight the latest insights of the calcium-based nanomaterials,explain their application,and provide novel perspective.Identifying and characterizing new patterns of calcium-dependent signaling and exploiting the disease element linkage offer additional translational opportunities for cancer theranostics.

Oxygen permeation and phase structure properties of partially A-site substituted BaCo_(0.7)Fe_(0.225)Ta_(0.075)O_(3-δ) perovskites

Ba0.9R0.1Co0.TFe0.225Ta0.07503-δ （BRCFT, R = Ca, La or Sr） membranes were synthesized by a solid-state reaction. Metal cation Ca2＋, La3＋ or Sr2＋ doping on A-site partially substituted Ba2＋ in BaCoo.TFe0.225Ta0.07503-δ oxides, and its subsequent effects on phase structure stability, oxygen permeability and oxygen desorption were systematically investigated by XRD, TG-DSC, Hz-TPR, O2-TPD techniques and oxygen permeation experiments. The partial substitution with Ca2＋, La3＋ or Sr2＋, whose ionic radii are smaller than that of Ba2＋, succeeded in stabilizing the cubic perovskite structure without formation of impurity phases, as revealed by XRD analysis. Oxygen-involving experi- ments showed that BRCFT with A-site fully occupied by Ba2＋ exhibited good oxygen permeation flux under He flow, reaching about 2.3 mL.min-l .cm-2 at 900 with I mm thickness. Of all the membranes, BLCFT membrane showed better chemical stability in CO2, owing to the reduction in alkalinity of the mixed conductor oxide by La doping. In addition, we also found the stability of the perovskite structure under reducing atmospheres was strengthened by increasing the size of A-site cation （Ba2＋〉La3＋〉SrZ＋〉Ca2＋）.

Hydrogen production from simulated hot coke oven gas by catalytic reforming over Ni/Mg(Al)O catalysts

Hydrogen production by catalytic reforming of simulated hot coke oven gas （HCOG） with toluene as a model tar compound was investigated in a fixed bed reactor over Ni/Mg（Al）O catalysts. The catalysts were prepared by a homogeneous precipitation method using urea hydrolysis and characterized by ICE BET, XRD, TPR, TEM and TG. XRD showed that the hydrotalcite type precursor after calcination formed （Ni, Mg）Al2O4 spinel and Ni-Mg-O solid solution structure. TPR results suggested that the increase in Ni/Mg molar ratio gave rise to the decrease in the reduction temperature of Ni^2＋ to Ni^0 on Ni/Mg（Al）O catalysts. The reaction results indicated that toluene and CH4 could completely be converted to H2 and CO in the catalytic reforming of the simulated HCOG under atmospheric pressure and the amount of H2 in the reaction effluent gas was about 4 times more than that in original HCOG. The catalysts with lower Ni/Mg molar ratio showed better catalytic activity and resistance to coking, which may become promising catalysts in the catalytic reforming of HCOG.

Next generation patient-derived prostate cancer xenograft models

There is a critical need for more effective therapeutic approaches for prostate cancer. Research in this area, however, has been seriously hampered by a lack of clinically relevant, experimental in vivo models of the disease. This review particularly focuses on the development of prostate cancer xenograft models based on subrenal capsule grafting of patients＇ tumor tissue into nonobese diabetic/ severe combined immunodeficient （NOD/ SCID） mice. This technique allows successful development of transplantable, patient-derived cancer tissue xenograft lines not only from aggressive metastatic, but also from localized prostate cancer tissues. The xenografts have been found to retain key biological properties of the original malignancies, including histopathological and molecular characteristics, tumor heterogeneity, response to androgen ablation and metastatic ability. As such, they are highly clinically relevant and provide valuable tools for studies of prostate cancer progression at cellular and molecular levels, drug screening for personalized cancer therapy and preclinical drug efficacy testing; especially when a panel of models is used to cover a broader spectrum of the disease. These xenograft models could therefore be viewed as next-generation models of prostate cancer.

Natural hydrogel dressings in wound care: Design, advances, and perspectives

Natural hydrogels have emerged as a pivotal innovation in wound care,offering a unique combination of high absorbency,biocompatibility,and versatility.However,due to the complexity of wound healing,the physiological state of the wound varies dynamically,and the mechanism of natural hydrogels that boost wound healing is still unclear.In this review,we firstly provide a comprehensive introduction to the bio-logical process of wound healing,emphasizing the critical stages and factors affecting healing.This work concludes the composition and properties of natural hydrogels,including collagen,gelatin,hyaluronic acid,chitosan,alginates,cellulose,and fibroin,highlighting their biocompatibility and biodegradability.The focus shifts to the various crosslinking strategies employed to enhance the structural integrity and functionality of natural hydrogels.This review further investigates the biological effects of natural hydro-gels in wound healing,detailing their antibacterial,antioxidant,anti-inflammatory,adhesive,and hemo-static functions.Furthermore,we propose the challenges and future perspectives of natural hydrogels in practical applications.This review offers a comprehensive overview of the current state and poten-tial future advancements in natural hydrogel dressings for wound care,highlighting their critical role in addressing complex and hard-to-heal wounds.

Recent Advances in Interventional Fluorescence Imaging: Toward the Precise Visualization of Transarterial Mini-Invasive Delivery Systems

CONSPECTUS:Interventional fluorescence imaging has gradually developed into a promising imaging strategy for the diagnosis of diseases in clinic.This strategy could benefit interventional targeted treatment because of the clear display of microstructures at the margins and boundaries.There are some stranded crucial issues in clinical application:(i)fast clearance of fluorescence probes;(ii)light instability and photobleaching;and(iii)residual and microsatellite lesions.The development of superstable homoge-neous intermixed formulation technology(SHIFT)can solve the aforementioned clinical problems for precision hepatectomy.Interventional fluorescence imaging based on SHIFT-prepared product has some advantages such as(i)strong stability,(ii)greatly extending imageable time window,and(iii)precisely visualizing microsatellite lesions.In this Account,we overview our current progress in interventional fluorescence imaging based on SHIFT method for surgical resection following long-lasting embolization conversion.To greatly realize interventional fluorescence imaging,we summarize clinical and preclinical application of interventional fluorescence imaging in a transarterial delivery system.Indeed,compared with conventional fluorescence imaging,interventional fluorescence imaging possesses non-negligible strengths on improved intensity in target location and step-down systemic toxicity.Unfortunately,a challenging issue is that immobile fluorescence performance is difficult to maintain after long-time embolization,resulting in a failed hepatectomy.On this basis,associated with our previous research,SHIFT was proposed and developed.Thus,we detailedly introduce and account the development and preponderance of SHIFT on interventional fluorescence imaging.Predictably,after lengthy embolization,its lightful fluorescence was still observable in tumor targets of a clinical trial.To regulate the fluorescence rendering of microsatellite lesion,SHIFT combining with pure nanoprobes(nanoICG)occurs,namely SHIFT nanoICG,and we dwell on its performance in transarterial invasive surgical navigation and its clinical application under interventional fluorescence imaging compared with conventional indocyanine green(ICG)formulations.Amazingly,the SHIFT nanoICG brings us an extraordinary imaging consequence for deep-seated tumor tissues and imperceptible microsatellite lesions.Finally,we offer perspectives on the future tendency of interventional imaging-guided SHIFT products in clinical translation such as chemoembolization,radioembolization,and immunotherapy.Actually,these directions have been underway for some time,and even relative products are already applied for clinical trials,exhibiting effective therapeutic outcomes.Our green high-performance SHIFT products are concentrated on meeting clinical needs and solving clinical problems,breaking through the cure limitations of patients with advanced diseases.Thus,the discovery offers insight into the development and superiority of SHIFT products under interventional fluorescence imaging and simultaneously provides a new view on the development of clinically pragmatic products.

Superstable homogeneous lipiodol-ICG formulation:initial feasibility and first-in-human clinical application for ruptured hepatocellular carcinoma

The most common treatment of spontaneous tumor rupture hemorrhage(STRH)is transcatheter arterial embolization(TAE)followed by liver resection,and surgical navigation using near-infrared fluorescence is effective method for detecting hidden lesions and ill-defined tumor boundaries.However,due to the blockage of the tumor-supplying artery after effective TAE treatment,it is difficult to deliver sufficient fluorescent probes to the tumor region.In this study,we report on the successful application of superstable homogeneous intermixed formulation technology(SHIFT)in precise conversion hepatectomy for ruptured hepatocellular carcinoma(HCC).A homogeneous lipiodol-ICG formulation obtained by SHIFT(SHIFT-ICG)was developed for clinical practice for STRH.A ruptured HCC patient received the combined protocol for embolization and fluorescence surgical navigation and exhibited excellent hemostatic effect.Lipiodol and ICG were both effectively deposited in the primary lesion,including a small metastatic lesion.In follow-up laparoscopic hepatectomy,SHIFT-ICG could clearly and precisely image the full tumor regions and boundaries in real time,and even indistinguishable satellite lesions still expressed a remarkable fluorescence intensity.In conclusion,the simple and green SHIFT-ICG formulation can be effectively used in emergency embolization hemostasis and later precise fluorescence navigation hepatectomy in patients with ruptured HCC bleeding and has high clinical application value.

3D bioprinting of tumor models and potential applications

Cancer is the most common cause of human mortality and has created an unbridgeable health gap due to its unrestrained aberrant proliferation,rapid growth,metastasis,and high heterogeneity.Conventional two-dimensional cell culture and animal models for tumor diagnostic and therapeutic studies have extremely low clinical translation rates due to their intrinsic limitations.Appropriate tumor models are therefore required for cancer research.Engineered human three-dimensional(3D)cancer models stand out for their ability to better replicate the spatial organization,cellular resources,and microenvironmental features(e.g.,hypoxia,necrosis,and delayed proliferation)of actual human tumors.Further,the fabrication of these models can be achieved by an emerging technology known as 3D bioprinting,which allows for the fabrication of living structures by precisely regulating the spatial distribution of cells,biomolecules,and matrix components.The aim of this paper is to review the current technologies and bioinks associated with 3D bioprinted cancer models for glioma,breast,liver,intestinal,cervical,ovarian,and neuroblastoma,as well as,advances in the applications of 3D bioprinted-based tumor models in the fields of tumor microenvironment,tumor vascularization,tumor stem cells,tumor resistance and therapeutic drug screening,tumorimmunotherapy,and precision medicine.

Strong biosynthesis and weak catabolism of theanine in new shoots contribute to the high theanine accumulation in Albino/etiolated tea plant(Camellia sinensis)

Tea processed from albino/etiolated tea shoots is favored by consumers because of its high theanine accumulation.To explore why theanine accumulates highly in new shoots of albino/etiolated tea cultivars,we compared theanine content in shoots and roots of albino/etiolated and common green tea cultivars.Results suggested that high theanine accumulation in albino/etiolated tea shoots was likely not caused by higher theanine biosynthesis in roots.Further analyses suggested that CsAlaDC-catalyzed ethylamine biosynthesis and CsGOGAT1-catalyzed glutamate biosynthesis were more active,and CsGGT2-catalyzed theanine catabolism was weaker in new shoots of these albino/etiolated tea plant cultivars.Therefore,the high theanine accumulation in albino/etiolated shoots is probably contributed by the strong theanine biosynthesis and weak catabolism in new shoots.These findings provided more comprehensive insights into the high accumulation of theanine in new shoots of albino/etiolated tea cultivars,and the knowledge can be used in plant breeding for new cultivars with higher theanine accumulation.

“山因云晦明,云共山高下”:超稳定均相碘油配方技术的临床应用

近年来,相比于化疗、放疗和肝脏移植等治疗方法,直接手术切除依旧是最为常用和有效的肝癌治疗手段[1].晚期肝癌患者因为肿瘤体积较大,肝硬化并发症以及具有术中潜在大出血风险而不适宜直接肿瘤切除治疗[2].为了提高晚期肝癌患者的可切除性,经导管动脉栓塞术(transcatheter arterial embolization,TAE)降期后手术切除应运而生,其原理是将栓塞制剂直接注射进入病灶部位促使患者肿瘤变小再进行切除[3].

The blooming intersection of transcatheter hepatic artery chemoembolization and nanomedicine

Transcatheter hepatic artery chemoembolization(TACE)is a universal treatment for patients with hepatocellular carcinoma(HCC)that inhibits tumor growth by cutting off the blood supply and provides chemotherapeutics locally to the tumor.The strategy of combining TACE formulation with image-guided ablation holds tremendous potential,but patient tolerance and undesired toxicity/immunosuppression remains a challenge.The application of nanotechnology in TACE opens new doors for the treatment of HCC.Strikingly,nanomaterials or nano-drugs dispersed in the TACE formulation can effectively improve the delivery efficiency of drugs by achieving both controlled and continuous release.In addition,the utilization of multifunctional nanoparticles can provide guidance and monitoring for various advanced imaging methods for TACE treatment,and can realize the combination therapy of thermal ablation,microwave ablation,in situ radiotherapy,and other therapies,greatly expanding the therapeutic strategies available for HCC treatment.Here,the current exploration of nanotechnology in TACE of HCC is briefly summarized and the challenges of TACE with nanoformulations for clinical translation are comprehensively discussed.

Superstable homogeneous iodinated formulation technology:revolutionizing transcatheter arterial chemoembolization

Hepatocellular carcinoma(HCC)is a common malignant tumor with a high mortality rate,especially in Asian countries[1].Currently,lipiodol-based transcatheter arterial embolization(TAE)has been extensively applied for patients with intermediate or advanced stages,which significantly prolongs survival[2].

Oxygen Permeation and Stability of Ce_(0.8)Gd_(0.2)O_(2-δ)-PrBaCo_(2-x)FexO_(5+δ) Dual-phase Composite Membranes

Dual-phase membranes of 60 wt% Ce0.8Gd0.2O2-δ-40 wt% Pr Ba Co2exFexO3 d（0 x 2） were prepared by a combined citrate and ethylene diamine tetraacetic acid（EDTA） complexing method. X-ray diffraction（XRD）results revealed the good chemical compatibility between ion-conducting phase CGO and electron-conducting phases PBC2 xFxO after sintering in air. The Fe ionic dopant had a significant effect on the phase structure stability and oxygen permeability under CO2 atmosphere, which was confirmed by XRD, thermogravimetrye differential scanning calorimetry（TGeD SC）, scanning electron microscopy（SEM） and oxygen permeation experiments. CGOeP BC0.5F1.5O dual-phase membrane demonstrated a stable oxygen permeation flux of2.71x10-7mol cm 2s 1with 50 mol% He/CO2 as the sweep gas at 925 C, and this value was much higher than that of perovskite-type membranes. The rate-limiting step in the oxygen permeation process changed from the bulk diffusion to the surface oxygen exchange when the CGOeP BC0.5F1.5O membrane thickness decreased to 0.8 mm or less. Due to the high oxygen permeation fluxes and the excellent structural stability under CO2 atmosphere, the CGOeP BC0.5F1.5O membrane is a great potential candidate material for separating oxygen from air in the oxy-fuel combustion techniques.

Facile one-step synthesis of Cu_2O@Cu sub-microspheres composites as anode materials for lithium ion batteries

Cu2O@Cu sub-microspheres composites with a narrow particle size distribution from 300 to 500 nm was successfully fabricated by one-step synthesis through the direct thermal decomposition of copper nitrate （Cu（NO3）2） in octadecylamine （ODA） solvent. As anode materials for lithium ion batteries, the Cu2O@Cu composites obviously possess high specific capacity, excellent cyclic stability and rate capability. The coulombic efficiency is about 84% in the 1 st cycle and increases significantly up to 97.8% during successive cycles at various current densities. Even under a high current density of 500 mA g^-l, the discharge capacity of Cu2O@Cu composites remains up to 200 mAh g^-1. The excellent electrochemical properties are ascribed to the synergistic effect between high electronic conductivity and volume-buffering capacity of metallic copper composited with Cu2O.2017 Published by Elsevier Ltd on behalf of The editorial office of Journal of Materials Science ＆ Technology.

Molecular diagnosis and treatment of meningiomas:an expert consensus(2022)

Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations.The fifth edition of the WHO Classification of Tumors of the Central Nervous System(WHO CNS5),published in 2021,introduces major changes that advance the role of molecular diagnostics in meningiomas.To follow the revision of WHO CNS5,this expert consensus statement was formed jointly by the Group of Neuro-Oncology,Society of Neurosurgery,Chinese Medical Association together with neuropathologists and evidence-based experts.The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients.

Conversion therapy of intermediate and advanced hepatocellular carcinoma using superstable homogeneous iodinated formulation technology

Interventional embolization is one of the most common treatment strategies in the clinical cancer treatment,especially in liver cancer(Sieghart et al.,2015).However,unstable dispersion and rapid drug release are the bottlenecks in clinical practice.The superstable homogeneous iodinated formulation technology(SHIFT)in interventional embolization treatment has achieved homogeneous dispersion of drugs in lipiodol embolic agent,showing promising clinical translation prospects(Chen et al.,2020 a;He et al.,2022 a.

Advanced radionuclides in diagnosis and therapy for hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common primary malignant tumor of the liver,but early diagnosis and effective treatment are still difficult.With the development of radionuclide applications in medicine,nuclear medicine is playing an increasingly important role in the diagnosis and treatment of HCC.Radionuclide-based positron emission tomography-computed tomography and single-photon emission computed tomography-computed tomography molecular imaging are indispensable for assessing progression,staging,differentiation,preoperative planning,postoperative prediction,and evaluation of HCC in clinical applications.Moreover,radionuclide-based endoradiotherapy provides an objective therapeutic strategy for patients with unresectable advanced HCC.This review highlights the application and development of radionuclides in the diagnosis and treatment of HCC.More efforts are warranted for the development of advanced radionuclides to make significant contributions in the treatment of HCC.

Antigen self-presenting nanovaccine for cancer immunotherapy

Cancer immunotherapy has made breakthroughs in clinical application and has become the fourth most prevalent tumor treatment method after surgical resection,chemotherapy,and radiotherapy.It mainly enhances the anti-tumor immunity of the tumor microenvironment by stimulating or mobilizing the immune system to control and kill tumor cells[1].T lymphocytes are an important component of the body’s immune system,which indirectly or directly affects the occurrence and development of tumors,and emerging advances in T lymphocyte-based tumor immunotherapy also attract much more attention.It is a common knowledge that the activation,proliferation,and differentiation of antigen-specific lymphocytes are the key to the successful establishment of anti-tumor immunity,and this process largely depends on the interaction between T cells and antigen-presenting cells(APCs)[1].Activation of CD8+cytotoxic T lymphocytes(CTLs)has proved to be an important role in cancer immunotherapy.Tumor antigens are presented to T cells through major histocompatibility complex class I(MHC-I)molecules on the surface of APCs,thereby stimulating the activation and proliferation of CD8+T cells,and finally producing a strong,sustained,and effective CTL response[2].Therefore,fully mobilizing the function of T lymphocytes is essential for tumor immunotherapy.