Precise HER2 Protein Degradation via Peptide-Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy.

Breast cancer, the most prevalent malignancy among women, frequently exhibits high HER2 expression, making HER2 a critical therapeutic target. Traditional treatments combining the anti-HER2 antibody trastuzumab with immunotherapy face limitations due to toxicity and tumor microenvironment immunosuppression. This study introduces an innovative strategy combining HER2-targeting peptides with the photosensitizer (PSs) pyropheophorbide-a (Pha) via a gelatinase-cleavable linker, forming self-assembling nanoparticles.

CalTrig: A GUI-based Machine Learning Approach for Decoding Neuronal Calcium Transients in Freely Moving Rodents.

Advances in imaging using miniature microscopes have enabled researchers to study single-neuron activity in freely-moving animals. Tools such as MiniAN and CalmAn have been developed to convert isual signals umerical data, collectively referred to as CalV2N. However, substantial challenges remain in analyzing the large datasets generated by CalV2N, particularly in integrating data streams, evaluating CalV2N output quality, and reliably and efficiently identifying transients.

Decoding the Role of Secondary Motor Cortex Neuronal Ensembles during Cocaine Self-Administration: Insights from Longitudinal Calcium Imaging via Miniscopes.

Recent findings in our lab demonstrated that the risk of cocaine relapse is closely linked to the hyperexcitability of cortical pyramidal neurons in the secondary motor cortex (M2), noticeable 45 days after cocaine intravenous self-administration (IVSA). The present study was designed to explore the underlying mechanisms of neuronal alterations in M2. Our hypothesis was that M2 neurons were affected directly by cocaine taking behaviors.

Clinical efficacy of Femoral Neck System for treatment of unstable femoral neck fractures in young adults.

Objective: This study was performed to evaluate the mid-term clinical efficacy of the Femoral Neck System (FNS) (DePuy Synthes, Zuchwil, Switzerland) in treating young patients with unstable Pauwels type III femoral neck fractures.

Methods: We performed a retrospective observational analysis of 21 young adults treated with the FNS. Clinical outcomes were assessed based on fracture reduction quality, Harris hip scores, and postoperative complication rates.

Sex-Specific Impact of Fkbp5 on Hippocampal Response to Acute Alcohol Injection: Involvement in Alterations of Metabolism-Related Pathways.

High levels of alcohol intake alter brain gene expression and can produce long-lasting effects. FK506-binding protein 51 (FKBP51) encoded by is a physical and cellular stress response gene and has been associated with alcohol consumption and withdrawal severity. has been previously linked to neurite outgrowth and hippocampal morphology, sex differences in stress response, and epigenetic modification.

Recent advances in aptamer-based targeted drug delivery systems for cancer therapy.

The past decade has become an important strategy in precision medicine for the targeted therapy of many diseases, expecially various types of cancer. As a promising targeted element, nucleic acid aptamers are single-stranded functional oligonucleotides which have specific abilities to bind with various target molecules ranging from small molecules to entire organisms. They are often named 'chemical antibody' and have aroused extensive interest in diverse clinical studies on account of their advantages, such as considerable biostability, versatile chemical modification, low immunogenicity and quick tissue penetration.

Amyloid-β oligomers in the nucleus accumbens decrease motivation via insertion of calcium-permeable AMPA receptors.

It is essential to identify the neuronal mechanisms of Alzheimer's Disease (AD)-associated neuropsychiatric symptoms, e.g., apathy, before improving the life quality of AD patients.

Calcium Permeable-AMPA Receptors and Excitotoxicity in Neurological Disorders.

Excitotoxicity is one of the primary mechanisms of cell loss in a variety of diseases of the central and peripheral nervous systems. Other than the previously established signaling pathways of excitotoxicity, which depend on the excessive release of glutamate from axon terminals or over-activation of NMDA receptors (NMDARs), Ca influx-triggered excitotoxicity through Ca-permeable (CP)-AMPA receptors (AMPARs) is detected in multiple disease models. In this review, both acute brain insults (e.

Limited versus extended cocaine intravenous self-administration: Behavioral effects and electrophysiological changes in insular cortex.

Aims: Limited vs extended drug exposure has been proposed as one of the key factors in determining the risk of relapse, which is the primary characteristic of addiction behaviors. The current studies were designed to explore the related behavioral effects and neuronal alterations in the insular cortex (IC), an important brain region involved in addiction.

Methods: Experiments started with rats at the age of 35 days, a typical adolescent stage when initial drug exposure occurs often in humans.

Contrasting effects of adolescent and early-adult ethanol exposure on prelimbic cortical pyramidal neurons.

Background: Adolescence and early-adulthood are vulnerable developmental periods during which binge drinking can have long-lasting effects on brain function. However, little is known about the effects of binge drinking on the pyramidal cells of the prelimbic cortex (PrL) during early and protracted withdrawal periods.

Methods: In the present study, we performed whole-cell patch clamp recordings and dendritic spine staining to examine the intrinsic excitability, spontaneous excitatory post-synaptic currents (sEPSCs), and spine morphology of pyramidal cells in the PrL from rats exposed to chronic intermittent ethanol (CIE) during adolescence or early-adulthood.

Prenatal alcohol exposure reduces posterior dorsomedial striatum excitability and motivation in a sex- and age-dependent fashion.

Prenatal alcohol exposure (PAE)-induced clinical symptoms have been widely reported but effective treatments are not yet available due to our limited knowledge of the neuronal mechanisms underlying behavioral outputs. Operant behaviors, including both goal-directed and habitual actions, are essential for everyday life. The dorsomedial striatum (DMS) and the dorsolateral striatum (DLS) have been identified as mediating each type of instrumental behavior, respectively.

Design, synthesis and biological evaluation of novel 3-hexyloxy chlorin e-based 15- or 13-amino acid derivatives as potent photosensitizers for photodynamic therapy.

This study aimed to improve the biological effectiveness and pharmacokinetic properties of chlorin e, a second-generation photosensitizer (PS), for tumor photodynamic therapy (PDT). Herein, the novel 3-hexyloxy chlorin e-based 15- or 13-amino acid derivatives 3a, 3b, 3c and 8 were synthesized and their photophysical properties and in vitro bioactivities such as phototoxicity against A549, HeLa and melanoma B16-F10 cells, reactive oxygen species (ROS) production and subcellular localization were evaluated. In addition, preferred target compounds were also investigated for their in vivo pharmacokinetic in SD rats and in vivo antitumor efficacies in C57BL/6 mice bearing melanoma B16-F10 cells.

Gelated Vorinostat with inner-lysosome triggered release for tumor-targeting chemotherapy.

Histonedeacetylase inhibitor (HDACi) has great potential in targeted antitumor therapy by inhibiting tumor migration, invasion, and metastasis. As one of the typical HDACis, vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) was approved as a therapeutic agent for cancer therapy, however, challenges remain due to their poor solubility, short half-life and low efficiency in cellular penetration. Considering the disadvantages of usual drug carriers, folate and vorinostat bound BSA nanogel (FVBN)was fabricated to implement higher solubility, stability, cellular uptake, and lipase-responsive release.

Folate-mediated and pH-responsive chidamide-bound micelles encapsulating photosensitizers for tumor-targeting photodynamic therapy.

 Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic. In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol--poly(aspartic acid) (PEG--PAsp) grafted folate (FA-PEG--PAsp) to obtain the block polymer folate polyethylene glycol--poly(asparaginyl-chidamide) (FA-PEG--PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice.  Model photosensitizer pyropheophorbide- (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol--poly(asparaginyl-chidamide) micelles encapsulating Pha].

Accurate Pelvis and Femur Segmentation in Hip CT With a Novel Patch-Based Refinement.

Due to bone deformation and joint space narrowing in diseased hips, accurate segmentation for pelvis, and femur from hip computed tomography (CT) images remains a challenging task. Therefore, the paper presents a fully automatic segmentation framework for the pelvis and femur in both of healthy and diseased hips. The framework involves three steps: preprocessing, coarse segmentation, and refinement.

Shape-intensity prior level set combining probabilistic atlas and probability map constrains for automatic liver segmentation from abdominal CT images.

Purpose: Propose a fully automatic 3D segmentation framework to segment liver on challenging cases that contain the low contrast of adjacent organs and the presence of pathologies from abdominal CT images.

Methods: First, all of the atlases are weighted in the selected training datasets by calculating the similarities between the atlases and the test image to dynamically generate a subject-specific probabilistic atlas for the test image. The most likely liver region of the test image is further determined based on the generated atlas.

Cementless arthroplasty with a distal femoral shortening for the treatment of Crowe type IV developmental hip dysplasia.

Background: Severe developmental dysplasia of the hip is a surgical challenge. The purpose of this study is to describe the cementless arthroplasty with a distal femoral shortening osteotomy for Crowe type IV developmental hip dysplasia and to report the results of this technique.

Materials And Methods: 12 patients (2 male and 10 female) of Crowe type IV developmental hip dysplasia operated between January 2005 and December 2010 were included in the study.

Bidirectional modulation of incubation of cocaine craving by silent synapse-based remodeling of prefrontal cortex to accumbens projections.

Glutamatergic projections from the medial prefrontal cortex (mPFC) to nucleus accumbens (NAc) contribute to cocaine relapse. Here we show that silent synapse-based remodeling of the two major mPFC-to-NAc projections differentially regulated the progressive increase in cue-induced cocaine seeking after withdrawal (incubation of cocaine craving). Specifically, cocaine self-administration in rats generated AMPA receptor-silent glutamatergic synapses within both infralimbic (IL) and prelimbic mPFC (PrL) to NAc projections, measured after 1 day of withdrawal.

Maturation of silent synapses in amygdala-accumbens projection contributes to incubation of cocaine craving.

In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after withdrawal from the drug. This 'incubation of cocaine craving' is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens (NAc). However, the circuit-level adaptations mediating this plasticity remain elusive.

Accuracy limits for the thickness measurement of the hip joint cartilage in 3-D MR images: simulation and validation.

This paper describes a theoretical simulation method for ascertaining the inherent limits on the accuracy of thickness measurement of hip joint cartilage in 3-D MR images. This method can specify where and how thickness can be measured with sufficient accuracy under the certain MR imaging conditions. In the numerical simulation, we present a mathematical model for two adjacent sheet structures separated by a small distance, which simulated the femoral and acetabular cartilage and the joint space width in the hip joint; moreover, we perform the numerical simulation of MR imaging and postprocessing for thickness measurement.

Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells.

New therapies for late stage and castration resistant prostate cancer (CRPC) depend on defining unique properties and pathways of cell sub-populations capable of sustaining the net growth of the cancer. One of the best enrichment schemes for isolating the putative stem/progenitor cell from the murine prostate gland is Lin(-);Sca1(+);CD49f(hi) (LSC(hi)), which results in a more than 10-fold enrichment for in vitro sphere-forming activity. We have shown previously that the LSC(hi) subpopulation is both necessary and sufficient for cancer initiation in the Pten-null prostate cancer model.

Isolation and characterization of human prostate stem/progenitor cells.

Isolation of prostate epithelial cells with stem/progenitor characteristics may enable further evaluation of the hierarchy of prostate glandular development and malignant transformation. Prostate epithelial cells capable of sphere formation in semisolid cultures possess stem/progenitor cell characteristics. This is demonstrated by self-renewal (via indefinite passaging) and in vivo differentiation into prostate tubules with discreet basal and luminal layers.

A technique for visualization and mapping of local cartilage thickness changes in MR images of osteoarthritic knee.

Purpose: The aim of this paper is to describe a technique for the visualization and mapping of focal, local cartilage thickness changes over time in magnetic resonance images of osteoarthritic knee.

Methods: Magnetic resonance imaging was performed in 25 fresh frozen pig knee joints and 15 knees of patients with borderline to mild osteoarthritis (51.2±6.

Epcam, CD44, and CD49f distinguish sphere-forming human prostate basal cells from a subpopulation with predominant tubule initiation capability.

Background: Human prostate basal cells expressing alpha-6 integrin (CD49f(Hi)) and/or CD44 form prostaspheres in vitro. This functional trait is often correlated with stem/progenitor (S/P) activity, including the ability to self-renew and induce differentiated tubules in vivo. Antigenic profiles that distinguish tubule-initiating prostate stem cells (SCs) from progenitor cells (PCs) and mature luminal cells (LCs) with less regenerative potential are unknown.

An analysis algorithm for accurate determination of articular cartilage thickness of hip joint from MR images.

Purpose: To test the accuracy of the most widely used technique based on edge detection for thickness measurement of the hip joint cartilage in MR images, and to improve the measurement accuracy by developing a new measurement method based on a model of the MRI process.

Materials And Methods: MRI was performed in 3 normal cadaver hips, 25 hips of normal volunteers, and 25 hips of patients with osteoarthritis. In general, thickness was defined as the distance between the two sides of the hip cartilage along the normal directions of the cartilage surfaces.