Browse Articles

Geometry optimization of broadband, planar, spiral inductors via continuous trace width modulation

Metal–Organic Frameworks with Enhanced Electret Capability for Selective Electrostatic Separation

Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models

Abstract Targeted therapies in cancer are limited by cells exhibiting drug tolerance. We aimed to target drug tolerance in order to delay the development of acquired resistance. In melanoma, tolerance to MAPK pathway inhibitors is associated with loss of SOX10 and an enhanced TEAD transcriptional program. We show that loss of SOX10 is sufficient to up-regulate TEAD targets with dependence on the co-activator, TAZ. Active TAZ is sufficient to mediate tolerance to BRAF inhibitors and MEK inhibitors. We develop two covalent inhibitors, OPN-9643 and OPN-9652, designed to target the central palmitate binding pocket of TEADs. In SOX10-deficient cells, OPN-9643 and OPN-9652 reduce TEAD-dependent reporter activity and expression of TEAD targets, CTGF and CYR61. OPN-9643 and OPN-9652 treatment enhances the inhibitory effects of MAPK-targeted therapies in 2D and 3D growth assays in SOX10 knockout cells and reverses tolerance mediated by active TAZ. In vivo, OPN-9652 delays the onset of acquired resistance to BRAF inhibitors and MEK inhibitors from minimal residual disease. Thus, TAZ-TEAD activity plays an important role in melanoma drug tolerance and the development of acquired resistance.

Seasonal and spatial variations of physicochemical parameters and heavy metals in surface water of interconnected Nigeria lagoons experiencing distinct anthropogenic disturbances

Mining Solid-State Electrolytes from Metal–Organic Framework Databases through Large Language Models and Representation Clustering

A rapidly closing window for coral persistence under global warming

Association of maternal pre-pregnancy body mass index with neonatal respiratory outcomes: a nationwide population-based cohort study

Regulating Lithium Intercalation/Plating Competition To Enhance Low-Temperature Performance of Li-Ion Batteries

Neuronal type-specific modulation of cognition and AP-1 signaling by early-life rearing conditions

Association between mobile social networks usage and mental health and social behaviours in medical students in southern Iran

Turn-On Conductivity with Proton-Coupled Electron Transport in Metal–Organic Frameworks

Boosting Electrochemical CO ₂ Reduction to Formate over La-Doped SnO ₂ via Pinning Effect and Water Activation

A catalyst-free bioorthogonal reaction for malononitrile addition to azodicarboxylates

Development and validation of a risk prediction model for re-tear after arthroscopic rotator cuff repair

User-Friendly, Living Coordination–Insertion Polymerizations with Broad Functional Group Tolerance

Olaparib, durvalumab, and cyclophosphamide, and a prognostic blood signature in platinum-sensitive ovarian cancer: the randomized phase 2 SOLACE2 trial

Abstract SOLACE2 (ACTRN12618000686202) investigates whether 12-weeks of olaparib, or cyclophosphamide-olaparib priming, improves subsequent durvalumab-olaparib progression-free survival (PFS), and is superior to olaparib monotherapy without any priming, in platinum-sensitive recurrent ovarian cancer (n = 114). We also evaluate the utility of CUP-CC assay, an immune signature of C-C chemokine receptor type 4 up-regulation, chemokines, and cytokines. Priming with olaparib, or cyclophosphamide-olaparib, followed by durvalumab-olaparib, are both associated with longer PFS compared to olaparib monotherapy, but do not reach the pre-specified primary endpoint of 36-week trial threshold (PFS36). PFS36 rates are 47.4% (95% CI, 31.0-62.1; olaparib priming then olaparib-durvalumab), 48.7% (32.5-63.2; olaparib-cyclophosphamide then olaparib-durvalumab) and 35.1% (20.4-50.3; olaparib monotherapy). PFS is significantly longer for the homologous recombination deficient (N = 71) as compared to the proficient (HRP) (N = 29) subgroups (Hazard Ratio (HR) 0.55, 0.35-0.87). CUP-CC+ subgroup (N = 58) has a significantly longer PFS (HR 0.31, 0.19-0.49) than CUP-CC- (N = 46). Future studies should investigate whether CUP-CC has the potential to personalize poly (ADP-ribose) polymerase inhibitor therapies for patients who are BRCA wild-type, including HRP patients.

Study of phase separation process in multi-component mixtures using analytical methods and decomposition variational iteration method for the fourth-order Cahn–Hilliard equation

Revealing Recombination and Ultrafast Relaxation Mechanisms in Atomically Precise Titania Nanoclusters

Tracking business opportunities for climate solutions using AI in regulated accounting reports

Abstract The transition to a low-carbon economy offers substantial business opportunities, yet most research focuses on risks. This study develops a metric to identify firms advancing “climate solutions” by applying large language models to 39,710 10-K filings from 4,483 U.S. firms (2005-2022). The metric reveals a rising emphasis on climate solutions, validated by its responsiveness to policy shocks (e.g., Inflation Reduction Act) and correlation with green revenues and innovation indicators. We apply the measure to three inquiries: (i) firms engaged in climate solutions experience higher revenue growth, especially in sectors with strong intellectual property protection and technologies with high abatement potential; (ii) a modest political divide exists, with firms located in states with predominantly Republican voting patterns exhibiting lower climate solutions—a gap that narrows for low-cost technologies; and (iii) seemingly unrelated industries converge around shared technologies, reflected in higher stock return synchronicity. These results illustrate the value of AI-based analysis of regulatory filings for uncovering climate-related business opportunities.

Prenatal methamphetamine exposure induces oxidative stress and apoptosis in the ovaries of rat offspring

Abstract Methamphetamine abuse among women of reproductive age is a growing concern, necessitating investigation of its intrauterine effects on offspring. In this study, we examined the induction of oxidative stress and apoptosis in the ovaries of rat offspring following maternal methamphetamine exposure. Pregnant Wistar rats received methamphetamine (2 mg/kg or 5 mg/kg) from gestational day 10 until delivery. Control rats received 0.9% saline (1 mL/kg) on the same schedule. Female offspring were raised to puberty and their ovaries were examined, compared to controls. Protein expression levels of FASL and TRAIL were assessed by immunohistochemistry, and antioxidant enzyme levels (superoxide dismutase, SOD) and oxidative stress marker levels (malondialdehyde, MDA) were evaluated by ELISA 1 . Histological examination of the ovaries was performed using H&E staining. Maternal methamphetamine treatment significantly increased ovarian FASL and TRAIL protein expression in the pubertal offspring ( p ≤ 0.001). In utero methamphetamine exposure led to a dose-dependent increase in ovarian MDA levels and a corresponding decrease in SOD activity ( p ≤ 0.05). Histologically, exposed offspring showed a reduction in the number of primordial, primary, secondary, and Graafian follicles, as well as a reduction in corpora lutea, compared to controls ( p < 0.05). Conversely, the number of atretic follicles increased significantly in a dose-dependent manner ( p < 0.05). Prenatal methamphetamine exposure induces oxidative stress and promotes apoptosis in the ovaries of offspring, leading to reduced ovarian follicle reserves. These findings raise concerns that methamphetamine use during pregnancy may impair female reproductive health in offspring.