Browse Articles

Mitochondrial-cytochrome c oxidase II promotes glutaminolysis to sustain tumor cell survival upon glucose deprivation

AbstractGlucose deprivation, a hallmark of the tumor microenvironment, compels tumor cells to seek alternative energy sources for survival and growth. Here, we show that glucose deprivation upregulates the expression of mitochondrial-cytochrome c oxidase II (MT-CO2), a subunit essential for the respiratory chain complex IV, in facilitating glutaminolysis and sustaining tumor cell survival. Mechanistically, glucose deprivation activates Ras signaling to enhance MT-CO2 transcription and inhibits IGF2BP3, an RNA-binding protein, to stabilize MT-CO2 mRNA. Elevated MT-CO2 increases flavin adenosine dinucleotide (FAD) levels in activating lysine-specific demethylase 1 (LSD1) to epigenetically upregulate JUN transcription, consequently promoting glutaminase-1 (GLS1) and glutaminolysis for tumor cell survival. Furthermore, MT-CO2 is indispensable for oncogenic Ras-induced glutaminolysis and tumor growth, and elevated expression of MT-CO2 is associated with poor prognosis in lung cancer patients. Together, these findings reveal a role for MT-CO2 in adapting to metabolic stress and highlight MT-CO2 as a putative therapeutic target for Ras-driven cancers.

When Diversity Goals Meet Multiregional Trials

DNA promoter task-oriented dictionary mining and prediction model based on natural language technology

The usefulness of automated high frequency ultrasound image analysis in atopic dermatitis staging

Machine learning-based technique for gain prediction of mm-wave miniaturized 5G MIMO slotted antenna array with high isolation characteristics

Interfacial coupling effects in two-dimensional ordered arrays for microwave attenuation

NEJM at ESC — Asundexian versus Apixaban in Patients with Atrial Fibrillation

Biochemical properties and substrate specificity of GOB-38 in Elizabethkingia anophelis

Layer dependent thermal transport properties of one- to three-layer magnetic Fe:MoS2

Raiding nature’s genetic toolbox for UV-C resistance by functional metagenomics

AbstractAs we assess the habitability of other worlds, we are limited by being able to only study terrestrial life adapted to terrestrial conditions. The environments found on Earth, though tremendously diverse, do not approach the multitude of potentially habitable environments beyond Earth, and so limited terrestrial adaptive capabilities tell us little about the fundamental biochemical boundaries of life. One approach to this problem is to use experimental laboratory evolution to adapt microbes to these novel environmental conditions. This approach can be dramatically improved through functional metagenomics, large-scale introduction of foreign genetic material to screen for phenotypes in a new host organism. This takes advantage of Earth’s immense biological diversity with high-throughput screening for genetic tools that can facilitate adaptation. We address a key gap in functional metagenomics work by exploring the impact of the experimental parameters chosen for functional metagenomics libraries. Experimental design dictates both fragment size and copy number, and we show that both can have outsized effects on the resultant phenotypes in non-intuitive ways. These results highlight the potential of functional metagenomics for adapting life rapidly to challenging new environments, with important implications in both astrobiology and bioindustry, while also emphasizing the impacts of decisions in experimental design.

Universal, untargeted detection of bacteria in tissues using metabolomics workflows

Abstract Fast and reliable identification of bacteria directly in clinical samples is a critical factor in clinical microbiological diagnostics. Current approaches require time-consuming bacterial isolation and enrichment procedures, delaying stratified treatment. Here, we describe a biomarker-based strategy that utilises bacterial small molecular metabolites and lipids for direct detection of bacteria in complex samples using mass spectrometry (MS). A spectral metabolic library of 233 bacterial species is mined for markers showing specificity at different phylogenetic levels. Using a univariate statistical analysis method, we determine 359 so-called taxon-specific markers (TSMs). We apply these TSMs to the in situ detection of bacteria using healthy and cancerous gastrointestinal tissues as well as faecal samples. To demonstrate the MS method-agnostic nature, samples are analysed using spatial metabolomics and traditional bulk-based metabolomics approaches. In this work, TSMs are found in >90% of samples, suggesting the general applicability of this workflow to detect bacterial presence with standard MS-based analytical methods.

Transitional Justice — A Politico-Legal Approach to Health Equity

Employing a low-code machine learning approach to predict in-hospital mortality and length of stay in patients with community-acquired pneumonia

Quantitative analysis of choroidal vascular structures and anatomical changes in pachychoroid spectrum diseases using ultra-widefield SS-OCTA

Learning to hear again with alternating cochlear frequency allocations

Superselective embolic particle guidance in vessel networks via shape-adaptive acoustic manipulation

Interleaved quartic high gain DC–DC converter

Abstract This research paper presents a high-gain DC–DC converter with ultra-step-up voltage gain capability. The proposed converter is synthesized from a two-phase interleaved boost converter (IBC), and its voltage gain is doubled by adopting a voltage lift capacitor. To enhance its voltage gain capability, a floating capacitor-based gain extension cell is adopted subsequently. This cell yields a voltage gain that is cubed times the output voltage obtained from a classical boost converter (CBC). By cascading the two stages, the voltage gain of the proposed converter is enhanced to quartic times (4th power) that of the CBC. The proposed gain extension concept is validated by conducting practical experiments on a 16 V to 400 V, 150 W prototype version. Practically, the prototype converter delivers 150 W to the load and operates at a full-load efficiency of 92.7% when its switches are operated at safe duty ratio values. Under dynamic conditions, the proposed converter regulates the output voltage to 400 V quickly over a wide range of input voltage and load current variations; the overshoots and undershoots are also negligible. The maximum voltage gain of the proposed converter momentarily increases to 37 when the input voltage is drastically reduced to 10.8 V while the switches are still operated at safe duty ratio values. The voltage stress on the semiconductor devices is only a fraction of the output voltage due to the hybrid voltage gain extension technique. The input current is also ripple-free as the switches in the IBC structure are always operated at a duty ratio of 50%, and only the third switch is controlled to meet the required voltage gain. The salient features of the proposed converter are clearly highlighted by comparing it with several converters that possess quadratic, cubic, and quartic voltage gain functions. The common-ground connection between the source and the load in the proposed converter is an added preferable feature for PV applications.

Removal of microplastics by algal biomass from aqueous solutions: performance, optimization, and modeling

Association of body mass index with clinicopathological features among patients with clear cell renal cell carcinoma treated with surgery: a retrospective study

Structural and electronic features enabling delocalized charge-carriers in CuSbSe2

AbstractInorganic semiconductors based on heavy pnictogen cations (Sb3+ and Bi3+) have gained significant attention as potential nontoxic and stable alternatives to lead-halide perovskites for solar cell applications. A limitation of these novel materials, which is being increasingly commonly found, is carrier localization, which substantially reduces mobilities and diffusion lengths. Herein, CuSbSe2 is investigated and discovered to have delocalized free carriers, as shown through optical pump terahertz probe spectroscopy and temperature-dependent mobility measurements. Using a combination of theory and experiment, the critical enabling factors are found to be: 1) having a layered structure, which allows distortions to the unit cell during the propagation of an acoustic wave to be relaxed in the interlayer gaps, with minimal changes in bond length, thus limiting deformation potentials; 2) favourable quasi-bonding interactions across the interlayer gap giving rise to higher electronic dimensionality; 3) Born effective charges not being anomalously high, which, combined with the small bandgap ($$\le$$ ≤ 1.2 eV), result in a low ionic contribution to the dielectric constant compared to the electronic contribution, thus reducing the strength of Fröhlich coupling. These insights can drive forward the rational discovery of perovskite-inspired materials that can avoid carrier localization.