Roles of Lipids in Cancer

The term ‘lipids’ refers to a class of biological molecules primarily composed of hydrocarbons such as fatty acids, glycerolipids, sphingolipids and sterol lipids. Lipids take part in a variety of physiological functions and have specific roles depending on their chemical structure and localisation within or outside cells. For example, glycerolipids (e.g. triglycerides) are often used as energy stores, sterol lipids (e.g. cholesterol) and glycerophospholipids as structural components of cell membranes (e.g. the lipid bilayer), and sphingolipids as part of a signalling cascade. Since lipids are a source of energy and basic building block of all living cells, it is not surprising that development of cancer (i.e. uncontrolled proliferation of cells) is closely tied to the metabolism of lipids. This notion is supported by studies into the reprogrammed metabolic machinery in cancer cells, and also cell and animal model experiments showing that cancer growth and metastasis can be induced or inhibited by the exogenous addition of lipids. Here, we review how cancer cells can alter their lipid metabolism to meet their metabolic requirements, and the potential tumorigenic and tumour-suppressive mechanisms in which lipids are involved

Fine-tuning Large Language Model (LLM) Artificial Intelligence Chatbots in Ophthalmology and LLM-based evaluation using GPT-4

Purpose: To assess the alignment of GPT-4-based evaluation to human clinician experts, for the evaluation of responses to ophthalmology-related patient queries generated by fine-tuned LLM chatbots. Methods: 400 ophthalmology questions and paired answers were created by ophthalmologists to represent commonly asked patient questions, divided into fine-tuning (368; 92%), and testing (40; 8%). We find-tuned 5 different LLMs, including LLAMA2-7b, LLAMA2-7b-Chat, LLAMA2-13b, and LLAMA2-13b-Chat. For the testing dataset, additional 8 glaucoma QnA pairs were included. 200 responses to the testing dataset were generated by 5 fine-tuned LLMs for evaluation. A customized clinical evaluation rubric was used to guide GPT-4 evaluation, grounded on clinical accuracy, relevance, patient safety, and ease of understanding. GPT-4 evaluation was then compared against ranking by 5 clinicians for clinical alignment. Results: Among all fine-tuned LLMs, GPT-3.5 scored the highest (87.1%), followed by LLAMA2-13b (80.9%), LLAMA2-13b-chat (75.5%), LLAMA2-7b-Chat (70%) and LLAMA2-7b (68.8%) based on the GPT-4 evaluation. GPT-4 evaluation demonstrated significant agreement with human clinician rankings, with Spearman and Kendall Tau correlation coefficients of 0.90 and 0.80 respectively; while correlation based on Cohen Kappa was more modest at 0.50. Notably, qualitative analysis and the glaucoma sub-analysis revealed clinical inaccuracies in the LLM-generated responses, which were appropriately identified by the GPT-4 evaluation. Conclusion: The notable clinical alignment of GPT-4 evaluation highlighted its potential to streamline the clinical evaluation of LLM chatbot responses to healthcare-related queries. By complementing the existing clinician-dependent manual grading, this efficient and automated evaluation could assist the validation of future developments in LLM applications for healthcare.Comment: 13 Pages, 1 Figure, 8 Table

Preliminary Findings of the High Quantity of Microplastics in Faeces of Hong Kong Residents

Microplastics are recognised as a ubiquitous and hazardous pollutant worldwide. These small-sized particles have been detected in human faeces collected from a number of cities, providing evidence of human ingestion of microplastics and their presence in the gastrointestinal tract. Here, using Raman spectroscopy, we identified an average of 50 particles g−1 (20.4–138.9 particles g−1 wet weight) in faeces collected from a healthy cohort in Hong Kong. This quantity was about five times higher than the values reported in other places in Asia and Europe. Polystyrene was the most abundant polymer type found in the faeces, followed by polypropylene and polyethylene. These particles were primarily fragments, but about two-thirds of the detected polyethylene terephthalate were fibres. More than 88% of the microplastics were smaller than 300 µm in size. Our study provides the first data on the faecal level, and thus the extent of ingestion, of microplastics in Hong Kong’s population. This timely assessment is crucial and supports the recently estimated ingestion rate of microplastics by Hong Kong residents through seafood consumption, which is one of the highest worldwide. These findings may be applicable to other coastal populations in South China with similar eating habits

Tunable Magnetic Properties in Sr2_2FeReO6_6 Double-Perovskite

Double-perovskite oxides have attracted recent attention due to their attractive functionalities and application potential. In this paper, we demonstrate the effect of dual controls, i.e., the deposition pressure of oxygen (P$_O2$) and lattice mismatch ($\epsilon$), on tuning magnetic properties in epitaxial double-perovskite Sr$_2$FeReO$_6$ films. In a nearly-lattice-matched Sr$_2$FeReO$_6$/SrTiO$_3$ film, the ferrimagnetic-to-paramagnetic phase transition occurs when P$_O2$ is reduced to 30 mTorr, probably due to the formation of Re$^{4+}$ ions that replace the stoichiometric Re$^{5+}$ to cause disorders of $B$-site ions. On the other hand, a large compressive strain or tensile strain shifts this critical P$_O2$ to below 1 mTorr or above 40 mTorr, respectively. The observations could be attributed to the modulation of $B$-site ordering by epitaxial strain through affecting elemental valence. Our results provide a feasible way to expand the functional tunability of magnetic double-perovskite oxides that hold great promise for spintronic devices.Comment: Main text 18 pages, 5 figures; Supplementary information 8 pages, 4 figure

Neuropeptides Modulate Local Astrocytes to Regulate Adult Hippocampal Neural Stem Cells

Neural stem cells (NSCs) in the dentate gyrus (DG) reside in a specialized local niche that supports their neurogenic proliferation to produce adult-born neurons throughout life. How local niche cells interact at the circuit level to ensure continuous neurogenesis from NSCs remains unknown. Here we report the role of endogenous neuropeptide cholecystokinin (CCK), released from dentate CCK interneurons, in regulating neurogenic niche cells and NSCs. Specifically, stimulating CCK release supports neurogenic proliferation of NSCs through a dominant astrocyte-mediated glutamatergic signaling cascade. In contrast, reducing dentate CCK induces reactive astrocytes, which correlates with decreased neurogenic proliferation of NSCs and upregulation of genes involved in immune processes. Our findings provide novel circuit-based information on how CCK acts on local astrocytes to regulate the key behavior of adult NSCs

One Decade of Development and Evolution of MicroRNA Target Prediction Algorithms

Nearly two decades have passed since the publication of the first study reporting the discovery of microRNAs (miRNAs). The key role of miRNAs in post-transcriptional gene regulation led to the performance of an increasing number of studies focusing on origins, mechanisms of action and functionality of miRNAs. In order to associate each miRNA to a specific functionality it is essential to unveil the rules that govern miRNA action. Despite the fact that there has been significant improvement exposing structural characteristics of the miRNA-mRNA interaction, the entire physical mechanism is not yet fully understood. In this respect, the development of computational algorithms for miRNA target prediction becomes increasingly important. This manuscript summarizes the research done on miRNA target prediction. It describes the experimental data currently available and used in the field and presents three lines of computational approaches for target prediction. Finally, the authors put forward a number of considerations regarding current challenges and future direction

Electrooxidation of glucose by binder-free bimetallic Pd1Ptx/graphene aerogel/nickel foam composite electrodes with low metal loading in basic medium

Many 2D graphene-based catalysts for electrooxidation of glucose involved the use of binders and toxic reducing agents in the preparation of the electrodes, which potentially causes the masking of original activity of the electrocatalysts. In this study, a green method was developed to prepare binder-free 3D graphene aerogel/nickel foam electrodes in which bimetallic Pd-Pt NP alloy with different at% ratios were loaded on 3D graphene aerogel. The influence of Pd/Pt ratio (at%: 1:2.9, 1:1.31, 1:1.03), glucose concentration (30 mM, 75 mM, 300 mM, 500 mM) and NaOH concentration (0.1 M, 1 M) on electrooxidation of glucose were investigated. The catalytic activity of the electrodes was enhanced with increasing the Pd/Pt ratio from 1:2.9 to 1:1.03, and changing the NaOH/glucose concentration from 75 mM glucose/0.1 M NaOH to 300 mM glucose/1 M NaOH. The Pd1Pt1.03/GA/NF electrode achieved a high current density of 388.59 A g−1 under the 300 mM glucose/1 M NaOH condition. The stability of the electrodes was also evaluated over 1000 cycles. This study demonstrated that the Pd1Pt1.03/GA/NF electrode could be used as an anodic electrode in glucose-based fuel cells