Reactive oxygen species switcher via MnO-coated Prussian blue loaded hyaluronic acid methacrylate hydrogel microspheres for local anti-tumor treatment.

ROS-induced therapy can eradicate breast tumors when combined with thermal ablation, but excessive ROS also threatens peritumoral tissue with inflammation. To eradicate tumors and avoid inflammatory sequela, it is necessary to generate ROS in treatment stage and scavenge ROS in prognostic stage. However, it is a great challenge to reverse ROS in different stages.

Local glycolysis-modulating hydrogel microspheres for a combined anti-tumor and anti-metastasis strategy through metabolic trapping strategy.

Anti-glycolysis is well-recognized for inhibition of tumor proliferation. However, tumor metabolic heterogeneity confers great challenges in the therapeutic efficacy of glycolysis inhibitors. Here, a metabolic trapping strategy was employed to avoid metabolism heterogeneity in tumors.

Fabrication of Biomimetic Hybrid Liposomes via Microfluidic Technology: Homotypic Targeting and Antitumor Efficacy Studies in Glioma Cells.

Introduction: The treatment of glioblastoma is hindered by the blood-brain barrier (BBB) and rapid drug clearance by the immune system. To address these challenges, we propose a novel drug delivery system using liposomes modified with cell membrane fragments. These modified liposomes can evade the immune system, cross the BBB, and accumulate in tumor tissue through homotypic targeting, thereby delivering drugs like paclitaxel and carboplatin more effectively.

Ventral frontostriatal circuitry mediates the computation of reinforcement from symbolic gains and losses.

Reinforcement learning (RL), particularly in primates, is often driven by symbolic outcomes. However, it is usually studied with primary reinforcers. To examine the neural mechanisms underlying learning from symbolic outcomes, we trained monkeys on a task in which they learned to choose options that led to gains of tokens and avoid choosing options that led to losses of tokens.

Implantable Patch of Oxidized Nanofibrillated Cellulose and Lysozyme Amyloid Nanofibrils for the Regeneration of Infarcted Myocardium Tissue and Local Delivery of RNA-Loaded Nanoparticles.

Biopolymeric implantable patches are popular scaffolds for myocardial regeneration applications. Besides being biocompatible, they can be tailored to have required properties and functionalities for this application. Recently, fibrillar biobased nanostructures prove to be valuable in the development of functional biomaterials for tissue regeneration applications.

Quantum Sensing of Free Radical Generation in Mitochondria of Single Heart Muscle Cells during Hypoxia and Reoxygenation.

Cells are damaged during hypoxia (blood supply deprivation) and reoxygenation (oxygen return). This damage occurs in conditions such as cardiovascular diseases, cancer, and organ transplantation, potentially harming the tissue and organs. The role of free radicals in cellular metabolic reprogramming under hypoxia is under debate, but their measurement is challenging due to their short lifespan and limited diffusion range.

Injectable Nanocomposite Hydrogels of Gelatin-Hyaluronic Acid Reinforced with Hybrid Lysozyme Nanofibrils-Gold Nanoparticles for the Regeneration of Damaged Myocardium.

Biopolymeric injectable hydrogels are promising biomaterials for myocardial regeneration applications. Besides being biocompatible, they adjust themselves, perfectly fitting the surrounding tissue. However, due to their nature, biopolymeric hydrogels usually lack desirable functionalities, such as antioxidant activity and electrical conductivity, and in some cases, mechanical performance.

Resolving ecosystem complexity in ecological risk assessment for mine site rehabilitation.

Context: Ecological Risk Assessments (ERAs) are important tools for supporting evidence-based decision making. However, most ERA frameworks rarely consider complex ecological feedbacks, which limit their capacity to evaluate risks at community and ecosystem levels of organisation.

Method: We used qualitative mathematical modelling to add additional perspectives to previously conducted ERAs for the rehabilitation of the Ranger uranium mine (Northern Territory, Australia) and support an assessment of the cumulative risks from the mine site.

Inference as a fundamental process in behavior.

In the real world, uncertainty is omnipresent due to incomplete or noisy information. This makes inferring the state-of-the-world difficult. Furthermore, the state-of-the-world often changes over time, though with some regularity.

Biomimetic platelet membrane-coated nanoparticles for targeted therapy.

The development of cell membrane-modified biomimetic nanoparticles has extensively increased during the past years due to their exceptional biocompatibility, evasion from the immune system, and targeting ability. Known as a cutting-edge area of research in nanomedicine, such novel nanoplatforms can mimic different functions of the primary cells, while successfully delivering their cargos to the defect site with the aim of enhancing the therapeutic responses and reducing the side effects. Platelet is a key factor for haemostasis and a major player in wound healing, inflammation, and many other biological functions and pathological conditions.

SFPQ-ABL1 and BCR-ABL1 use different signaling networks to drive B-cell acute lymphoblastic leukemia.

Philadelphia-like (Ph-like) acute lymphoblastic leukemia (ALL) is a high-risk subtype of B-cell ALL characterized by a gene expression profile resembling Philadelphia chromosome-positive ALL (Ph+ ALL) in the absence of BCR-ABL1. Tyrosine kinase-activating fusions, some involving ABL1, are recurrent drivers of Ph-like ALL and are targetable with tyrosine kinase inhibitors (TKIs). We identified a rare instance of SFPQ-ABL1 in a child with Ph-like ALL.

Differential coding of goals and actions in ventral and dorsal corticostriatal circuits during goal-directed behavior.

Goal-directed behavior requires identifying objects in the environment that can satisfy internal needs and executing actions to obtain those objects. The current study examines ventral and dorsal corticostriatal circuits that support complementary aspects of goal-directed behavior. We analyze activity from the amygdala, ventral striatum, orbitofrontal cortex, and lateral prefrontal cortex (LPFC) while monkeys perform a three-armed bandit task.

Novel missense mutations affecting the structure of the conserved fibrinogen Bβ C-terminal domain cause congenital hypofibrinogenemia.

This study describes the identification of two new mutations of the fibrinogen beta-chain in patients with inherited fibrinogen deficiency. Modelling of the impact of the mutations predict that these single amino acid substitutions are sufficient to abolish secretion of the mutant chains into the circulation, resulting in low fibrinogen levels in the patients. In addition, whole exome sequencing identified genetic modifiers for both patients which could contribute to the patients' global hemostatic function.

A convolutional neural network for estimating synaptic connectivity from spike trains.

The recent increase in reliable, simultaneous high channel count extracellular recordings is exciting for physiologists and theoreticians because it offers the possibility of reconstructing the underlying neuronal circuits. We recently presented a method of inferring this circuit connectivity from neuronal spike trains by applying the generalized linear model to cross-correlograms. Although the algorithm can do a good job of circuit reconstruction, the parameters need to be carefully tuned for each individual dataset.

Reward-related choices determine information timing and flow across macaque lateral prefrontal cortex.

Prefrontal cortex is critical for cognition. Although much is known about the representation of cognitive variables in the prefrontal cortex, much less is known about the spatio-temporal neural dynamics that underlie cognitive operations. In the present study, we examined information timing and flow across the lateral prefrontal cortex (LPFC), while monkeys carried out a two-armed bandit reinforcement learning task in which they had to learn to select rewarding actions or rewarding objects.

Biohybrid Nanosystems for Cancer Treatment: Merging the Best of Two Worlds.

During the last 20+ years, research into the biomedical application of nanotechnology has helped in reshaping cancer treatment. The clinical use of several passively targeted nanosystems resulted in improved quality of care for patients. However, the therapeutic efficacy of these systems is not superior to the original drugs.

Cotargeting BCL-2 and MCL-1 in high-risk B-ALL.

Improving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has a poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab and chimeric antigen receptor T cells. Targeting aberrant cell survival pathways with selective small molecule BH3-mimetic inhibitors of BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is an emerging therapeutic option.

ACL reconstruction with lateral extra-articular tenodesis using a continuous graft: 10-year outcomes of 50 cases.

Background: Persistence of pivot shift is the main problem after isolated intra-articular anterior cruciate ligament (ACL) reconstruction. Adding lateral extra-articular tenodesis (LET) to the ACL procedure increases the knee's stability by controlling rotational laxity. The aim of this study was to evaluate the long-term clinical and radiological outcomes of combined ACL reconstruction with LET using a continuous hamstring graft as a first-line procedure.

Dimensionality, information and learning in prefrontal cortex.

Learning leads to changes in population patterns of neural activity. In this study we wanted to examine how these changes in patterns of activity affect the dimensionality of neural responses and information about choices. We addressed these questions by carrying out high channel count recordings in dorsal-lateral prefrontal cortex (dlPFC; 768 electrodes) while monkeys performed a two-armed bandit reinforcement learning task.

Prefrontal Cortex Predicts State Switches during Reversal Learning.

Reinforcement learning allows organisms to predict future outcomes and to update their beliefs about value in the world. The dorsal-lateral prefrontal cortex (dlPFC) integrates information carried by reward circuits, which can be used to infer the current state of the world under uncertainty. Here, we explored the dlPFC computations related to updating current beliefs during stochastic reversal learning.

Incursions of Candida auris into Australia, 2018.

Candida auris is an emerging global healthcare-associated pathogen. During July-December 2018, four patients with C. auris were identified in Victoria, Australia, all with previous overseas hospitalization.

The application of RNA sequencing for the diagnosis and genomic classification of pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and implementation of risk-adapted therapy has been instrumental in the dramatic improvements in clinical outcomes. A key to risk-adapted therapies includes the identification of genomic features of individual tumors, including chromosome number (for hyper- and hypodiploidy) and gene fusions, notably ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1 in B-cell ALL (B-ALL). RNA-sequencing (RNA-seq) of large ALL cohorts has expanded the number of recurrent gene fusions recognized as drivers in ALL, and identification of these new entities will contribute to refining ALL risk stratification.

Information-Limiting Correlations in Large Neural Populations.

Understanding the neural code requires understanding how populations of neurons code information. Theoretical models predict that information may be limited by correlated noise in large neural populations. Nevertheless, analyses based on tens of neurons have failed to find evidence of saturation.

Reactive oxygen species responsive nanoplatforms as smart drug delivery systems for gastrointestinal tract targeting.

The pharmacological therapy for gastrointestinal (GI) diseases, such as inflammatory bowel diseases, continues to present challenges in targeting efficacy. The need for maximal local drug exposure at the inflamed regions of the GI tract has led research to focus on a disease-targeted drug delivery approach. Smart nanomaterials responsive to the reactive oxygen species (ROS) concentrated in the inflamed areas, can be formulated into nanoplatforms to selectively release the active compounds, avoiding unspecific drug delivery to healthy tissues and limiting systemic absorption.

Targeted therapy and disease monitoring in CNTRL-FGFR1-driven leukaemia.

We report two patients with leukaemia driven by the rare CNTRL-FGFR1 fusion oncogene. This fusion arises from a t(8;9)(p12;q33) translocation, and is a rare driver of biphenotypic leukaemia in children. We used RNA sequencing to report novel features of expressed CNTRL-FGFR1, including CNTRL-FGFR1 fusion alternative splicing.