Technologies for Decoding Cancer Metabolism with Spatial Resolution.

It is increasingly appreciated that cancer cells adapt their metabolic pathways to support rapid growth and proliferation as well as survival, often even under the poor nutrient conditions that characterize some tumors. Cancer cells can also rewire their metabolism to circumvent chemotherapeutics that inhibit core metabolic pathways, such as nucleotide synthesis. A critical approach to the study of cancer metabolism is metabolite profiling (metabolomics), the set of technologies, usually based on mass spectrometry, that allow for the detection and quantification of metabolites in cancer cells and their environments.

Consensus statement on the management of hyperkalaemia-An Asia-Pacific perspective.

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors.

The views of teenagers with obesity, their caregivers, and doctors: a plain language summary of the ACTION Teens global survey.

What Is This Summary About?: This is a summary of a research survey called ACTION Teens. In our survey, 12,987 people from 10 countries answered questions about obesity. They were: 5275 teenagers with obesity, 5389 caregivers of teenagers with obesity, and 2323 doctors who provide medical care for teenagers with obesity.

The Length Change Ratio of Ground Granulated Blast Furnace Slag-Based Geopolymer Blended with Magnesium Oxide Cured in Various Environments.

Geopolymer (GP) has been considered a potential material to replace ordinary Portland cement (OPC) because of its excellent mechanical properties and environmentally friendly process. However, the promotion of GP is limited due to the large shrinkage and the different operating procedures compared to cement. This study aims to reduce the shrinkage of ground granulated blast furnace slag (GGBFS) based GP by the hydration expansion properties of activated magnesium oxide (MgO).

Misalignment among adolescents living with obesity, caregivers, and healthcare professionals: ACTION Teens global survey study.

Background: There is limited evidence regarding the experiences, challenges, and needs of adolescents living with obesity (ALwO), their caregivers, and healthcare professionals (HCPs).

Objectives: The cross-sectional, survey-based global ACTION Teens study aimed to identify perceptions, attitudes, behaviours, and barriers to effective obesity care among ALwO, caregivers of ALwO, and HCPs.

Methods: ALwO (aged 12 to <18 years; N = 5275), caregivers (N = 5389), and HCPs treating ALwO (N = 2323) from 10 countries completed an online survey (August-December 2021).

Letter to the editor regarding Li et al. (2022) Identifying ecosystem service bundles and the spatiotemporal characteristics of trade-offs and synergies in coal mining areas with a high groundwater table, Liu et al. (2021) Ecosystem service multifunctionality assessment and coupling coordination analysis with land use and land cover change in China's coastal zones, and Zhang et al. (2021) Spatial relationships between ecosystem services and socioecological drivers across a large-scale region: A case study in the Yellow River Basin.

Three studies used empirical equations to calculate the rainfall erosivity factor R, and all three equations appeared to be incorrect. All of the studies were published in the journal Science of the Total Environment, and none of them accurately cited the sources of the incorrect equations that were used in them. We were able to track down the original equation as well as the source of the equation.

The utility of flow cytometric platelet forward scatter as an alternative to mean platelet volume.

The use of mean platelet diameter (MPD) to classify inherited thrombocytopenia (IT) has been demonstrated in several studies. Alternatively, the mean platelet volume (MPV) may be used, but in macrothrombocytopenia this may not be available. We hypothesized that platelet forward scatter (FSC) measurements using flow cytometry may be used for the size-based classification of IT.

Endoloop-Assisted Polypectomy for a Symptomatic Giant Colonic Polyp in a Pediatric Patient.

Colonic polyps are a common cause of persistent bloody stools in pediatric patients. Such polyps are easily diagnosed by a barium study of the lower gastrointestinal tract or by colonoscopy. Polypectomies utilizing electric ligators are generally performed on pediatric patients, and such patients can be easily operated on.

Building platelet phenotypes: Diaphanous-related formin 1 (DIAPH1)-related disorder.

Variants of the Diaphanous-Related Formin 1 () gene have recently been reported causing inherited macrothrombocytopenia. The essential/"diagnostic" characteristics associated with the disorder are emerging; however, robust and complete criteria are not established. Here, we report the first cases of -related disorder in Australia caused by the autosomal dominant gain-of-function DIAPH1 R1213X variant formed by truncation of the protein within the diaphanous auto-regulatory domain (DAD) with loss of regulatory motifs responsible for autoinhibitory interactions within the DIAPH1 protein.

Soil erosion modelling: A bibliometric analysis.

Soil erosion can present a major threat to agriculture due to loss of soil, nutrients, and organic carbon. Therefore, soil erosion modelling is one of the steps used to plan suitable soil protection measures and detect erosion hotspots. A bibliometric analysis of this topic can reveal research patterns and soil erosion modelling characteristics that can help identify steps needed to enhance the research conducted in this field.

MFSD7C switches mitochondrial ATP synthesis to thermogenesis in response to heme.

ATP synthesis and thermogenesis are two critical outputs of mitochondrial respiration. How these outputs are regulated to balance the cellular requirement for energy and heat is largely unknown. Here we show that major facilitator superfamily domain containing 7C (MFSD7C) uncouples mitochondrial respiration to switch ATP synthesis to thermogenesis in response to heme.

A PEROXO-Tag Enables Rapid Isolation of Peroxisomes from Human Cells.

Peroxisomes are metabolic organelles that perform a diverse array of critical functions in human physiology. Traditional isolation methods for peroxisomes can take more than 1 h to complete and can be laborious to implement. To address this, we have now extended our prior work on rapid organellar isolation to peroxisomes via the development of a peroxisomally localized 3XHA epitope tag ("PEROXO-Tag") and associated immunoprecipitation ("PEROXO-IP") workflow.

An integrated approach to inherited platelet disorders: results from a research collaborative, the Sydney Platelet Group.

Inherited disorders of platelet function (IPFD) and/or number (IPND) are heterogeneous conditions that result in variable mucocutaneous bleeding symptoms as a result of deranged primary haemostasis caused by platelet dysfunction or thrombocytopenia. Diagnosis is important to guide post-operative bleeding prophylactic strategies, to avoid treatment with inappropriate medications, and inform prognosis. Achieving an accurate diagnosis has traditionally been hampered by the requirement of multiple, often complex, laboratory tests that are not always available at single centres.

Extended dual antiplatelet therapy for Asian patients with acute coronary syndrome: expert recommendations.

Background: Recently, new evidence from large scale trials and updated guidelines have emerged on the risks and benefits of extended dual antiplatelet therapy (DAPT) for patients with acute coronary syndrome (ACS).

Aims: To discuss, clarify and advise on the application of the evidences and guidelines on individual patient selection for extended DAPT, with regard to balancing risk factors, particularly in Asian populations.

Methods: A total of 14 local cardiologists from Hong Kong with extensive experience in cardiology and cardiac interventions convened in a series of 3 advisory board meetings from October 2016 to September 2017, which included reviews of new evidence in the literature and discussions of the latest clinical trends, using an anonymous, electronic voting system for arriving at consensuses.

MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo.

Mitochondria are metabolic organelles that are essential for mammalian life, but the dynamics of mitochondrial metabolism within mammalian tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful for studying metabolism in vivo, such an approach lacks resolution at the cellular and subcellular level. In vivo methods for interrogating organellar metabolites in specific cell types within mammalian tissues have been limited.

Rapid immunopurification of mitochondria for metabolite profiling and absolute quantification of matrix metabolites.

Mitochondria carry out numerous metabolic reactions that are critical to cellular homeostasis. Here we present a protocol for interrogating mitochondrial metabolites and measuring their matrix concentrations. Our workflow uses high-affinity magnetic immunocapture to rapidly purify HA-tagged mitochondria from homogenized mammalian cells in ∼12 min.

mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient.

The mTORC1 kinase is a master growth regulator that senses many environmental cues, including amino acids. Activation of mTORC1 by arginine requires SLC38A9, a poorly understood lysosomal membrane protein with homology to amino acid transporters. Here, we validate that SLC38A9 is an arginine sensor for the mTORC1 pathway, and we uncover an unexpectedly central role for SLC38A9 in amino acid homeostasis.

Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras.

The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines.

Absolute Quantification of Matrix Metabolites Reveals the Dynamics of Mitochondrial Metabolism.

Mitochondria house metabolic pathways that impact most aspects of cellular physiology. While metabolite profiling by mass spectrometry is widely applied at the whole-cell level, it is not routinely possible to measure the concentrations of small molecules in mammalian organelles. We describe a method for the rapid and specific isolation of mitochondria and use it in tandem with a database of predicted mitochondrial metabolites ("MITObolome") to measure the matrix concentrations of more than 100 metabolites across various states of respiratory chain (RC) function.

A PHGDH inhibitor reveals coordination of serine synthesis and one-carbon unit fate.

Serine is both a proteinogenic amino acid and the source of one-carbon units essential for de novo purine and deoxythymidine synthesis. In the canonical pathway of glucose-derived serine synthesis, Homo sapiens phosphoglycerate dehydrogenase (PHGDH) catalyzes the first, rate-limiting step. Genetic loss of PHGDH is toxic toward PHGDH-overexpressing breast cancer cell lines even in the presence of exogenous serine.

An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis.

The mitochondrial electron transport chain (ETC) enables many metabolic processes, but why its inhibition suppresses cell proliferation is unclear. It is also not well understood why pyruvate supplementation allows cells lacking ETC function to proliferate. We used a CRISPR-based genetic screen to identify genes whose loss sensitizes human cells to phenformin, a complex I inhibitor.

SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance.

Cancer cells adapt their metabolic processes to support rapid proliferation, but less is known about how cancer cells alter metabolism to promote cell survival in a poorly vascularized tumour microenvironment. Here we identify a key role for serine and glycine metabolism in the survival of brain cancer cells within the ischaemic zones of gliomas. In human glioblastoma multiforme, mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci.