Prediction of Pathologic Response in Unresectable Hepatocellular Carcinoma After Downstaging with Locoregional and Systemic Combination Therapy.

Background: The combination of locoregional and systemic therapy may achieve remarkable tumor response for unresectable hepatocellular carcinoma (HCC).

Objective: We aimed to investigate the correlation between radiologic and pathologic responses following combination therapy, evaluate their prognostic values, and to establish a non-invasive prediction system for pathologic response.

Methods: This single-center retrospective study included 112 consecutive patients with HCC who underwent locoregional and systemic combination therapy followed by liver resection or transplantation.

Prognostic Implications of MRI-assessed Intratumoral Fat in Hepatocellular Carcinoma: An Asian and European Cohort Study.

Background The clinicopathologic-radiologic and prognostic characteristics of intratumoral fat in hepatocellular carcinoma (HCC) are critical for personalized treatment but remain understudied. Purpose To investigate the clinicopathologic-radiologic associations and prognostic implications of MRI-assessed intratumoral fat in HCCs. Materials and Methods This retrospective cohort study included consecutive adult patients who underwent resection for solitary HCCs and preoperative contrast-enhanced MRI from two tertiary-care hospitals in East Asia (March 2011 to December 2021) and Western Europe (September 2012 to December 2019).

MRI-based prediction of the need for wide resection margins in patients with single hepatocellular carcinoma.

Objectives: To develop an MRI-based score that enables individualized predictions of the survival benefit of wide over narrow resection margins.

Materials And Methods: This single-center retrospective study (December 2011 to May 2022) included consecutive patients who underwent curative-intent resection for single Barcelona Clinic Liver Cancer (BCLC) 0/A HCC and preoperative contrast-enhanced MRI. In patients with narrow resection margins, preoperative demographic, laboratory, and MRI variables independently associated with early recurrence-free survival (RFS) were identified using Cox regression analyses, which were employed to develop a predictive score (named "MARGIN").

Utility of protein-protein binding surfaces composed of anti-parallel alpha-helices and beta-sheets selected by phage display.

Over the past 3 decades, a diverse collection of small protein domains have been used as scaffolds to generate general purpose protein-binding reagents using a variety of protein display and enrichment technologies. To expand the repertoire of scaffolds and protein surfaces that might serve this purpose, we have explored the utility of (i) a pair of anti-parallel alpha-helices in a small highly disulfide-bonded 4-helix bundle, the CC4 domain from reversion-inducing Cysteine-rich Protein with Kazal Motifs and (ii) a concave beta-sheet surface and two adjacent loops in the human FN3 domain, the scaffold for the widely used monobody platform. Using M13 phage display and next generation sequencing, we observe that, in both systems, libraries of ∼30 million variants contain binding proteins with affinities in the low μM range for baits corresponding to the extracellular domains of multiple mammalian proteins.

Prediction of late recurrence after curative-intent resection using MRI-measured spleen volume in patients with hepatocellular carcinoma and cirrhosis.

Background: Late recurrence of hepatocellular carcinoma (HCC) after liver resection is regarded as a de novo tumor primarily related to the severity of underlying liver disease. We aimed to investigate risk factors, especially spleen volume, associated with late recurrence in patients with HCC and cirrhosis.

Methods: We retrospectively analyzed 301 patients with HCC and cirrhosis who received curative resection and preoperative MRI.

Preoperative MRI-based multiparametric model for survival prediction in hepatocellular carcinoma patients with portal vein tumor thrombus following hepatectomy.

Purpose: To develop a predictive model integrating clinical and MRI features for postoperative survival in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT).

Method: Between January 2008 and May 2021, consecutive HCC patients with PVTT who underwent preoperative contrast-enhanced MRI and surgical resection at a tertiary hospital were retrospectively enrolled. The MR images were independently reviewed by two blinded radiologists.

A self-cascaded unimolecular prodrug for pH-responsive chemotherapy and tumor-detained photodynamic-immunotherapy of triple-negative breast cancer.

Despite the success of immune checkpoint blockade (ICB) therapy in cancer management, ICB-based immunotherapy of triple-negative breast cancer (TNBC) still suffers from immunosuppressive tumor microenvironment (ITM). To break through the bottleneck of TNBC immunotherapy, a self-cascaded unimolecular prodrug consisting of an acidic pH-activatable doxorubicin and an aggregation-induced emission luminogen (AIEgen) photosensitizer coupled to a caspase-3-responsive peptide was engineered. The generated prodrug, could not only release doxorubicin initiatively in acidic tumor microenvironment, but also activate apoptosis-related caspase-3.

Signaling Pathways in Neurovascular Development.

During development, the central nervous system (CNS) vasculature grows to precisely meet the metabolic demands of neurons and glia. In addition, the vast majority of the CNS vasculature acquires a unique set of molecular and cellular properties-collectively referred to as the blood-brain barrier-that minimize passive diffusion of molecules between the blood and the CNS parenchyma. Both of these processes are controlled by signals emanating from neurons and glia.

The WNT7A/WNT7B/GPR124/RECK signaling module plays an essential role in mammalian limb development.

In central nervous system vascular endothelial cells, signaling via the partially redundant ligands WNT7A and WNT7B requires two co-activator proteins, GPR124 and RECK. WNT7A and RECK have been shown previously to play a role in limb development, but the mechanism of RECK action in this context is unknown. The roles of WNT7B and GPR124 in limb development have not been investigated.

Substituent, Solvent, and Dispersion Effects on the Zwitterionic Character and Dimerization Thermochemistry of the Group 6 Fulvene Metal Tricarbonyl Complexes.

Dimerizations of fulvene metal tricarbonyl complexes of the type (CHCRR')M(CO) (R, R' = MeO, Me, H; M = Cr, Mo, W) to form a metal-metal bond and a new carbon-carbon bond, thereby giving binuclear cyclopentadienyl metal carbonyl derivatives, are predicted to be thermochemically favored but to have significant activation energies ranging from Δ = 19 to 42 kcal/mol. However, the introduction of dimethylamino but not methoxy substituents onto the exocyclic carbon atom changes the situation drastically so that the monomers [CHCH(NMe)]M(CO) and [CHC(NMe)]M(CO) become strongly thermochemically favored, lying Δ = 43 kcal/mol (M = W) to 63 kcal/mol (M = Cr) below their corresponding dimers. In such dimethylamino-substituted (fulvene)M(CO) derivatives, the M-C distance to the exocyclic fulvene carbon is lengthened beyond the bonding distance to give a zwitterionic structure with a pentahapto fulvene ligand.

Fibronectin-Targeting and Cathepsin B-Activatable Theranostic Nanoprobe for MR/Fluorescence Imaging and Enhanced Photodynamic Therapy for Triple Negative Breast Cancer.

Because of the lack of specific targets, the highly aggressive triple negative breast cancer (TNBC) is unable to benefit from endocrine therapy or conventional targeting therapy. Even worse, current diagnostic and therapeutic approaches have limited value for TNBC. Therefore, developing TNBC-specific theranostic probes for accurate diagnosis and further selective therapy will build a powerful toolbox for TNBC management.

A mouse model for kinesin family member 11 (Kif11)-associated familial exudative vitreoretinopathy.

During mitosis, Kif11, a kinesin motor protein, promotes bipolar spindle formation and chromosome movement, and during interphase, Kif11 mediates diverse trafficking processes in the cytoplasm. In humans, inactivating mutations in KIF11 are associated with (1) retinal hypovascularization with or without microcephaly and (2) multi-organ syndromes characterized by variable combinations of lymphedema, chorioretinal dysplasia, microcephaly and/or mental retardation. To explore the pathogenic basis of KIF11-associated retinal vascular disease, we generated a Kif11 conditional knockout (CKO) mouse and investigated the consequences of early postnatal inactivation of Kif11 in vascular endothelial cells (ECs).

Molecular Engineered Squaraine Nanoprobe for NIR-II/Photoacoustic Imaging and Photothermal Therapy of Metastatic Breast Cancer.

Various squaraine dyes have been developed for biological imaging. Nevertheless, squaraine dyes with emission in the second window (NIR-II, 1000-1700 nm) have few reports largely due to the short of a simple and universal design strategy. In this contribution, molecular engineering strategy is explored to develop squaraine dyes with NIR-II emission.

F-labeled magnetic nanoparticles for monitoring anti-angiogenic therapeutic effects in breast cancer xenografts.

Purpose: To develop a novel fluorine-18 (F)-labeled arginine-glycine-aspartic acid (RGD)-coupled ultra-small iron oxide nanoparticle (USPIO) (hereafter, referred to as F-RGD@USPIO) and conduct an in-depth investigation to monitor the anti-angiogenic therapeutic effects by using a novel dual-modality PET/MRI probe.

Methods: The RGD peptide and F were coupled onto USPIO by click chemistry. In vitro experiments including determination of stability, cytotoxicity, cell binding of the obtained F-RGD@USPIO were carried out, and the targeting kinetics and bio-distribution were tested on an MDA-MB-231 tumor model.

Native T1 mapping compared to ultrasound elastography for staging and monitoring liver fibrosis: an animal study of repeatability, reproducibility, and accuracy.

Objectives: To investigate the repeatability, reproducibility, and staging and monitoring of the performance of native T1 mapping for noninvasively assessing liver fibrosis in comparison with acoustic radiation force impulse (ARFI) elastography.

Methods: The repeatability and reproducibility were explored in 8 male Sprague-Dawley rats with intraclass correlation coefficient (ICC). Different degrees of fibrosis were induced in 52 rats by carbon-tetrachloride (CCl4) insult.

Hypothalamic sydrome as an initial presentation of Wernicke encephalopathy: A case report.

Rationale: Wernicke encephalopathy (WE) is a syndrome characterized by an acute or subacute onset of ataxia, ophthalmoplegia, and mental status changes. To our knowledge, hypothalamic syndrome is rare in WE.

Patient Concerns: A 73-year-old female patient with acute cerebral infarct, who showed initial symptoms of vomiting, nausea, ataxia, and subsequent anorexia, was treated with parenteral nutritional supplement for 20 days.

Molecular determinants in Frizzled, Reck, and Wnt7a for ligand-specific signaling in neurovascular development.

The molecular basis of Wnt-Frizzled specificity is a central question in developmental biology. Reck, a multi-domain and multi-functional glycosylphosphatidylinositol-anchored protein, specifically enhances beta-catenin signaling by Wnt7a and Wnt7b in cooperation with the 7-transmembrane protein Gpr124. Among amino acids that distinguish Wnt7a and Wnt7b from other Wnts, two clusters are essential for signaling in a Reck- and Gpr124-dependent manner.

Dlg1 activates beta-catenin signaling to regulate retinal angiogenesis and the blood-retina and blood-brain barriers.

Beta-catenin (i.e., canonical Wnt) signaling controls CNS angiogenesis and the blood-brain and blood-retina barriers.

Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures.

The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in circumventricular organs (CVOs), small midline brain structures that are supplied by high permeability capillaries. In the eye and brain, high permeability capillaries are also present in the choriocapillaris, which supplies the retinal pigment epithelium and photoreceptors, and the ciliary body and choroid plexus, the sources of aqueous humor and cerebrospinal fluid, respectively.

An ALP-activatable and mitochondria-targeted probe for prostate cancer-specific bimodal imaging and aggregation-enhanced photothermal therapy.

Tumor-derived alkaline phosphatase (ALP) is over-expressed in metastatic prostate cancer. The development of selective probes for ALP detection is therefore critical for early diagnosis and therapy of metastatic prostate cancer. Herein, we develop a mitochondria-targeted near-infrared activatable fluorescent/photoacoustic (NIR FL/PA) probe for the selective detection of prostate cancer-derived ALP and aggregation-enhanced photothermal therapy.

Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance.

β-Catenin signaling controls the development and maintenance of the blood-brain barrier (BBB) and the blood-retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand-receptor systems-the Norrin and Wnt7a/Wnt7b systems-are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB maintenance in mice that shows striking threshold and partial redundancy effects. In particular, the combined loss of Wnt7a and Norrin or Wnt7a and Frizzled4 (Fz4) leads to anatomically localized BBB defects that are far more severe than observed with loss of Wnt7a, Norrin, or Fz4 alone.

Blue Te Nanoneedles with Strong NIR Photothermal and Laser-Enhanced Anticancer Effects as "All-in-One" Nanoagents for Synergistic Thermo-Chemotherapy of Tumors.

The conventional blue Te nanostructures exhibit strong photoabsorption in the near-infrared (NIR) region but have ultralong lengths (tenths of micrometers), while purple Te nanostructures with short lengths (such as nanodots and nanorods) show extremely low intensity of the NIR band. These Te nanostructures cannot achieve simultaneously both the suitable size and high NIR absorption, undoubtedly hindering their bioapplication. Herein, blue Te nanoneedles are prepared through a facile one-pot reduction route for the first time, and they have strong NIR absorbance while maintaining the shortened length (<500 nm).

Enzyme-triggered self-assembly of gold nanoparticles for enhanced retention effects and photothermal therapy of prostate cancer.

A peptide-modified gold nanoparticle was developed for tumour-targeted therapy. Triggered by alkaline phosphatase, the CREKA-YPFFK(Nph) peptide can self-assemble and further result in accumulation of gold nanoparticles in tumour cells. The large-sized gold nanoparticle aggregates cannot escape from the tumour tissue, therefore realizing the goal of tumour-specific targeting, enhanced retention and photothermal effects.