Browse Articles

Horizontally oriented compact colloidal quantum well films enable efficient and stable electroluminescent diodes

Fully environmental approach to design advanced optical polymer composites with high optoelectronic performance using green synthesized nickel metal complexes

Targeting the ECM in melanoma

MCL1 modulates mTORC1 signaling to promote bioenergetics and tumorigenesis

Abstract Myeloid cell leukemia-1 (MCL1) is among the most overexpressed proteins in tumors. MCL1 contributes to tumorigenesis by antagonizing apoptosis. However, apoptosis-unrelated functions are emerging. Screening an array of signaling switches identifies mTORC1 to be modulated by MCL1 but not by the anti-apoptotic Bcl-2 or Bcl-xL. mTORC1 is a central metabolic regulator. MCL1 impacts metabolism via modulating the expression of hexokinase 2 (HK2) in an mTORC1-dependent manner, which ultimately contributes to the tumor-promoting effects of MCL1. MCL1 inhibitors suppress mTORC1 in tumor cells but are associated with cardiotoxicity due to mTORC1 inhibition in the heart. Dietary leucine supplementation rescues mTORC1 signaling in the hearts of humanized Mcl-1 mice and greatly ameliorates the cardiotoxicity of MCL1 inhibitors. Taken together, here we describe tumor-promoting roles for MCL1 in regulating mTORC1 signaling and subsequently in bioenergetics, besides its role in antagonizing apoptosis, identifying MCL1 as a hinge of cell bioenergetics and survival.

Human researchers are superior to large language models in writing a medical systematic review in a comparative multitask assessment

Abstract The capability of Large Language Models (LLMs) to support and facilitate research activities has sparked growing interest in their integration into scientific workflows. This paper aims to evaluate and compare against human researchers the performance of 6 different LLMs in conducting the various tasks necessary to produce a systematic literature review. The evaluation of the 6 LLMs was split into 3 tasks: literature search, article screening and selection (task 1); data extraction and analysis (task 2); final paper drafting (task 3). Their results were compared with a human-produced systematic review on the same topic, serving as reference standard. The evaluation was repeated on two rounds to evaluate between-version changes and improvements of LLMs over time. Out of the 18 scientific articles to be extracted from the literature for task 1, the best LLM managed to identify 13. Data extraction and analysis for task 2 was only partially accurate and cumbersome. The full papers generated by LLMs for task 3 were short and uninspiring, often not fully adhering to the standard PRISMA 2020 template for a systematic review. Currently, LLMs are not capable of conducting a scientific systematic review in the medical domain without prompt-engineering strategies. However, their capabilities are advancing rapidly, and, with an appropriate supervision they can provide valuable support throughout the review process.

Designing insulin receptor agonists

Acquisition of ampliconic sequences marks a selfish mouse t-haplotype

The role of subjective interoception in autobiographical deficits in aphantasia

Abstract Autobiographical memory deficits are well-documented in aphantasia, yet the underlying mechanisms remain unclear. Emerging models suggest that interoception plays a crucial role in mental imagery, a key component of memory retrieval. In this study, we investigate the relationship between self-reported interoception, mental imagery, and autobiographical memory, with a specific focus on aphantasia. First, we examined whether interoceptive awareness and autobiographical memory differ between individuals with core aphantasia ( n  = 69), hypophantasia ( n  = 266) and typical imagers ( n  = 133). Our findings reveal that aphantasics report significantly lower autobiographical memory as well as subjective interoceptive awareness across key subscales, including emotional awareness and noticing. Secondly, a mediation analysis reveals that mental imagery mediates the relationship between the emotional awareness subscale of the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire and autobiographical memory, suggesting that subjective interoception may contribute to memory recall indirectly through its influence on imagery. These findings provide novel empirical support for the idea that interoception is linked to both mental imagery and memory retrieval. The reduced interoceptive awareness observed in aphantasia may contribute to their known deficits in autobiographical memory, positioning aphantasia as a condition that extends beyond a lack of mental imagery to include altered interoceptive processing.

Blocking tick-borne encephalitis

Publisher Correction: Anomalous photoelectrochemical etching of undoped semiconductor surfaces

Microplastic-induced alterations in water flow and solute transport dynamics in soil

Abstract The growing use of plastic-based practices in agriculture has led to a significant accumulation of plastic waste in soil. Microplastics (MPs) increasingly threaten soil health and fertility by disrupting its physical and chemical environment, and impairing essential ecological functions. We conducted laboratory column measurements combined with microfluidic experiments to assess the effects of MPs on water flow and solute transport in soil, key processes for sustaining soil water and nutrient availability and thus crop growth and yield. Changes in hydraulic conductivity and solute breakthrough curves in sandy soils were investigated in the presence of varying concentrations of polyethylene (PE) and polyvinylchloride (PVC) microplastics. Alterations in pore structure and clogging of pore throats by MPs, as further evidenced through confocal and fluorescence microscopy of synthesized porous media, led to 39% and 74% reductions in hydraulic conductivity of sand samples containing 5% PVC and 5% PE, respectively. Solute transport experiments using a brine tracer revealed broader breakthrough curves in the presence of MPs. Overall, the enhancement of pore-scale flow heterogeneity driven by the development of preferential flow paths and the formation of low-permeability zones increased hydrodynamic dispersion and resulted in both early breakthrough and delayed transport of the tracer within the soil column.

PROTAC for p300/CBP in prostate cancer

Host range expansion of asexual parasite can be explained by loss of adaptions in Muller’s Ratchet

The circRNA circKNSTRN promotes breast cancer progression by modulating the miR-320a-3p/SPAG5 axis

Lectin-based bispecific targets tumour-associated glycans

An RNA interference therapeutic potentially achieves functional cure of chronic hepatitis B virus infection

Mitochondrial glutathione transporter SLC25A40 regulates macrophage cytokine production

Abstract Mitochondrial glutathione (mtGSH) supports iron-sulfur cluster (ISC) stability in the electron transport chain (ETC). Here we have investigated the role of the mtGSH transporter SLC25A40 in macrophage activation. SLC25A40 is present in both murine and human macrophages and its expression was increased by LPS treatment. Reducing SLC25A40 expression using siRNA destabilized ISC-rich ETC proteins and elevated mitochondrial and cellular reactive oxygen species (ROS). It also induced expression of the genes Gclc and Gclm , which are involved in GSH biosynthesis. SLC25A40 deficiency also diminished IL-1β and IL-10 production at the transcriptional level in response to LPS. As a result, the production of mature IL-1β was decreased following activation of NLRP3 by nigericin or ATP, with no effect on pyroptosis. Depleting mtGSH with mitochondrially-targeted CDNB phenocopied these defects, whereas supplementation with a cell-permeable GSH ester partially restored pro-IL-1β production. Together, these data identify SLC25A40 as a key regulator that sustains ETC integrity to promote cytokine production, revealing a previously unrecognized role for the SLC25A40-mtGSH axis in coupling mitochondrial redox control to macrophage activation.

Designing error-free prime editors

Targeting leukemic stem cell biomechanics suppresses stemness and enhances NK cell-mediated immunotherapy

Africa’s booming rice cultivation is fueling regional warming

Abstract The significant increase of surface air temperature in Africa during the recent industrial period has been previously attributed to emissions from rapidly growing urbanization and industrial emissions. This study highlights the rapid growth of rice cultivation as another major influencing factor. We estimate that a 436% (14 million hectares) surge in rice cultivation area during the industrial period (1960-2018) in the sub-Saharan African region is associated with an increase of 603 million tons of agricultural methane emissions, making it the largest source of methane among all sectoral contributors, including energy, industrial processes, waste, land-use change, and forestry. These changes are further associated with an increase in the total surface air temperature anomaly to 1.3 $$^\circ$$ C, with greenhouse gas (GHG) forcing alone accounting for a rise from 0.47 $$^\circ$$ C to 0.92 $$^\circ$$ C throughout the industrial era compared to pre-industrial baseline (1850–1900), as estimated using the Regular Optimal Fingerprinting (ROF) method. Continued rice cultivation expansion to feed Africa’s rapidly growing population holds the potential for further intensifying current and future warming conditions. However, adopting more sustainable rice farming practices can help to reduce emissions and mitigate these effects.