Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats.

Allogeneic modified bone marrow-derived human mesenchymal stromal/stem cells (hMSC-SB623 cells) are in clinical development for the treatment of chronic motor deficits after traumatic brain injury and cerebral ischemic stroke. However, their exact mechanisms of action remain unclear. Here, we investigated the effects of this cell therapy on cortical network excitability, brain tissue, and peripheral blood at a chronic stage after ischemic stroke in a rat model.

Discovery of ZLC491 as a Potent, Selective, and Orally Bioavailable CDK12/13 PROTAC Degrader.

Selective degradation of cyclin-dependent kinases 12 and 13 (CDK12/13) emerges as a new potential therapeutic approach for triple-negative breast cancer (TNBC) and other human cancers. While several proteolysis-targeting chimera (PROTAC) degraders of CDK12/13 were reported, none are orally bioavailable. Here, we report the discovery of as a potent, selective, and orally bioavailable CDK12/13 PROTAC degrader.

ABBV-319: a CD19-targeting glucocorticoid receptor modulator antibody-drug conjugate therapy for B-cell malignancies.

Glucocorticoids are key components of the standard-of-care treatment regimens for B-cell malignancy. However, systemic glucocorticoid treatment is associated with several adverse events. ABBV-319 is a CD19-targeting antibody-drug conjugate engineered to reduce glucocorticoid-associated toxicities while possessing 3 distinct mechanisms of action (MOA) to increase therapeutic efficacy: (1) antibody-mediated delivery of a glucocorticoid receptor modulator (GRM) payload to activate apoptosis, (2) inhibition of CD19 signaling, and (3) enhanced fragment crystallizable (Fc)-mediated effector function via afucosylation of the antibody backbone.

Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS.

Proteomic Associations of NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) in Heart Failure With Preserved Ejection Fraction.

Background: NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels are variably elevated in heart failure with preserved ejection fraction (HFpEF), even in the presence of increased left ventricular filling pressures. NT-proBNP levels are prognostic in HFpEF and have been used as an inclusion criterion for several recent randomized clinical trials. However, the underlying biologic differences between HFpEF participants with high and low NT-proBNP levels remain to be fully understood.

Ptpn23 Controls Cardiac T-Tubule Patterning by Promoting the Assembly of Dystrophin-Glycoprotein Complex.

Background: Cardiac transverse tubules (T-tubules) are anchored to sarcomeric Z-discs by costameres to establish a regular spaced pattern. One of the major components of costameres is the dystrophin-glycoprotein complex (DGC). Nevertheless, how the assembly of the DGC coordinates with the formation and maintenance of T-tubules under physiological and pathological conditions remains unclear.

Hollow Bowl NiS @polyaniline Conductive Linker/Graphene Conductive Network: A Triple Composite for High-Performance Supercapacitor Applications.

The achievement of the outstanding theoretical capacitance of nickel sulfide (NiS ) is challenging due to its low conductivity, slow electrochemical kinetics, and poor structural stability. In this study, we utilize polyaniline (PANI) as a linker to anchor the NiS with a hollow bowl-like structure, uniformly dispersed at the surface of graphene oxide (GO)(NiS @15PG). The presence of PANI provides growth sites, resulting in a uniform and dense arrangement of NiS .

Ethical Considerations and Fairness in the Use of Artificial Intelligence for Neuroradiology.

In this review, concepts of algorithmic bias and fairness are defined qualitatively and mathematically. Illustrative examples are given of what can go wrong when unintended bias or unfairness in algorithmic development occurs. The importance of explainability, accountability, and transparency with respect to artificial intelligence algorithm development and clinical deployment is discussed.

Identifying Proliferative Hepatocellular Carcinoma at Pretreatment CT: Implications for Therapeutic Outcomes after Transarterial Chemoembolization.

Background Hepatocellular carcinomas (HCCs) can be divided into proliferative and nonproliferative types, which may have implications for outcomes after conventional transarterial chemoembolization (cTACE). Biopsy to identify proliferative HCC is not routinely performed before cTACE. Purpose To develop and validate a predictive model for identifying proliferative HCCs using CT imaging features and to compare therapeutic outcomes between predicted proliferative and nonproliferative HCCs after cTACE according to this model.

Hypertension-Driven Regulatory T-Cell Perturbations Accelerate Myocardial Ischemia-Reperfusion Injury.

Background: Patients with a history of hypertension have elevated inflammation and a worse prognosis after acute myocardial infarction (AMI). Regulatory T cells (Tregs) are reported to lose their immunosuppressive capacity under pathological conditions. However, whether hypertension leads to Treg dysfunction, thus accelerating myocardial ischemia-reperfusion injury, is still unknown.

Live motile sperm sorting device for enhanced sperm-fertilization competency: comparative analysis with density-gradient centrifugation and microfluidic sperm sorting.

Purpose: A live motile sperm sorting device (LensHooke CA0) developed to prevent the deleterious effects of centrifugation was evaluated comparatively with conventional density-gradient centrifugation (DGC) and microfluidic-based device (Zymot) in sperm selection.

Methods: Semen samples from 239 men were collected. CA0 under different incubation intervals (5, 10, 30, and 60 min) and temperatures (20, 25, and 37℃) was conducted.

Mast cell tolerance in the skin microenvironment to commensal bacteria is controlled by fibroblasts.

Activation and degranulation of mast cells (MCs) is an essential aspect of innate and adaptive immunity. Skin MCs, the most exposed to the external environment, are at risk of quickly degranulating with potentially severe consequences. Here, we define how MCs assume a tolerant phenotype via crosstalk with dermal fibroblasts (dFBs) and how this phenotype reduces unnecessary inflammation when in contact with beneficial commensal bacteria.

Longitudinal Analysis of Ocular Manifestation and Interleukin During Intravitreal Treatment of Vitreoretinal Lymphoma With Methotrexate.

Purpose: To explore the trend of ocular manifestations and interleukin (IL) during the treatment of vitreoretinal lymphoma (VRL) and to evaluate the potential effects of different intravitreal administration schedules on the therapeutic response.

Design: Interventional comparative nonrandomized clinical study.

Methods: Patients diagnosed with VRL between January 2011 and January 2022 were included.

Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma.

Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B cell lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the tumor microenvironment (TME) of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 phase 2 trial.

3D-organoid culture supports differentiation of human CAR iPSCs into highly functional CAR T cells.

Unlimited generation of chimeric antigen receptor (CAR) T cells from human-induced pluripotent stem cells (iPSCs) is an attractive approach for "off-the-shelf" CAR T cell immunotherapy. Approaches to efficiently differentiate iPSCs into canonical αβ T cell lineages, while maintaining CAR expression and functionality, however, have been challenging. We report that iPSCs reprogramed from CD62L naive and memory T cells followed by CD19-CAR engineering and 3D-organoid system differentiation confers products with conventional CD8αβ-positive CAR T cell characteristics.

Genome-wide landscape of mRNAs, microRNAs, lncRNAs, and circRNAs in hemorrhagic shock-induced ALI/ARDS in rats.

Background: Hemorrhagic shock (HS) can develop into multiple organ dysfunction syndrome, among which acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) usually lead to poor outcomes. The underlying molecular mechanisms of HS-induced ALI/ARDS remain unclear. This study sought to investigate gene expression profiles and predict competing endogenous RNA (ceRNA) regulatory networks in an HS-induced ALI/ARDS preclinical model.

Multi-organ proteomic landscape of COVID-19 autopsies.

The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls.

DNA scaffolds enable efficient and tunable functionalization of biomaterials for immune cell modulation.

Biomaterials can improve the safety and presentation of therapeutic agents for effective immunotherapy, and a high level of control over surface functionalization is essential for immune cell modulation. Here, we developed biocompatible immune cell-engaging particles (ICEp) that use synthetic short DNA as scaffolds for efficient and tunable protein loading. To improve the safety of chimeric antigen receptor (CAR) T cell therapies, micrometre-sized ICEp were injected intratumorally to present a priming signal for systemically administered AND-gate CAR-T cells.

Somatic Mutations in Aldosterone-Producing Adenoma Are Associated With a Worse Baseline Status and Better Recovery of Left Ventricular Remodeling and Diastolic Function.

Primary aldosteronism is the most common secondary endocrine form of hypertension and causes many cardiovascular injuries. somatic mutations have recently been identified in aldosterone-producing adenoma. However, their impacts on left ventricular remodeling precluding the interference of age, sex, and blood pressure are still uncertain.

Depletion of senescent-like neuronal cells alleviates cisplatin-induced peripheral neuropathy in mice.

Chemotherapy-induced peripheral neuropathy is among the most common dose-limiting adverse effects of cancer treatment, leading to dose reduction and discontinuation of life-saving chemotherapy and a permanently impaired quality of life for patients. Currently, no effective treatment or prevention is available. Senescence induced during cancer treatment has been shown to promote the adverse effects.

Myelin Imaging in Human Brain Using a Short Repetition Time Adiabatic Inversion Recovery Prepared Ultrashort Echo Time (STAIR-UTE) MRI Sequence in Multiple Sclerosis.

Background Water signal contamination is a major challenge for direct ultrashort echo time (UTE) imaging of myelin in vivo because water contributes most of the signals detected in white matter. Purpose To validate a new short repetition time (TR) adiabatic inversion recovery (STAIR) prepared UTE (STAIR-UTE) sequence designed to suppress water signals and to allow imaging of ultrashort T2 protons of myelin in white matter using a clinical 3-T scanner. Materials and Methods In this prospective study, an optimization framework was used to obtain the optimal inversion time for nulling water signals using STAIR-UTE imaging at different TRs.