Search

Abstract Lipid droplets (LDs) are dynamic cellular organelles that play an essential role in lipid metabolism and storage. LD dysregulation has been implicated in various diseases. However, investigations into the cellular LD dynamics under disease conditions have been rarely reported, possibly due to the absence of high performing LD imaging agents. Here a novel fluorogenic probe, AM‐QTPA, is reported for specific LD imaging. AM‐QTPA demonstrates viscosity sensitivity and aggregation‐induced emission enhancement characteristics. It is live cell permeable and can specifically light up LDs in cells, with low background noise and superior signals that can be quantified. After validation in cell model with LD accumulation induced by oleic acid treatment, AM‐QTPA is applied in a small proof‐of‐concept number of human fibroblast samples derived from people diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a complex and debilitating disease with unknown cause. The results indicate the presence of larger but fewer LDs in ME/CFS fibroblasts compared to the healthy counterparts, accompanying with frequent LD‐mitochondria contacts, suggesting potential upregulation of lipolysis in ME/CFS connective tissue like fibroblasts. Overall, AM‐QTPA provides new understanding of the anomalous LD dynamics in disease status, which, potentially, will facilitate in‐depth investigation of the pathogenesis of ME/CFS.

Multi-drug resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are a global health threat. The severity of the problem lies in its impact on mortality, therapeutic limitations, the threat to public health, and the costs associated with managing infections caused by these resistant strains. Effectively addressing this challenge requires innovative approaches to research, the development of new antimicrobials, and more responsible antibiotic use practices globally. Antimicrobial peptides (AMPs) are a part of the innate immune system of all higher organisms. They are short, cationic and amphipathic molecules with broad-spectrum activity. AMPs interact with the negatively charged bacterial membrane. In recent years, AMPs have attracted considerable interest as potential antibiotics. However, AMPs have low bioavailability and short half-lives, which may be circumvented by chemical modification. This review presents recent in vitro and in silico strategies for the modification of AMPs to improve their stability and application in preclinical experiments.

Autophagy is a degradative recycling process central to the maintenance of homeostasis in all eukaryotes. By ensuring the degradation of damaged mitochondria, it plays a key role in maintaining mitochondrial health and function. Of the highly conserved autophagy proteins, autophagy-related protein 1 (Atg1) is essential to the process. The involvement of these proteins in intracellular signalling pathways, including those involving mitochondrial function, are still being elucidated. Here the role of Atg1 was investigated in the simple model organism Dictyostelium discoideum using an atg1 null mutant and mutants overexpressing or antisense-inhibiting atg1. When evaluated against the well-characterised outcomes of mitochondrial dysfunction in this model, altered atg1 expression resulted in an unconventional set of phenotypic outcomes in growth, endocytosis, multicellular development, and mitochondrial homeostasis. The findings here show that Atg1 is involved in a tightly regulated signal transduction pathway coordinating energy-consuming processes such as cell growth and multicellular development, along with nutrient status and energy production. Furthermore, Atg1’s effects on energy homeostasis indicate a peripheral ancillary role in the mitochondrial signalling network, with effects on energy balance rather than direct effects on electron transport chain function. Further research is required to tease out these complex networks. Nevertheless, this study adds further evidence to the theory that autophagy and mitochondrial signalling are not opposing but rather linked, yet strictly controlled, homeostatic mechanisms.

The article develops a concept of “secular religiosity” to characterize “post-traditional” Jewish affiliation as an individual and private matter, which the sociologist Peter Berger casts as a “heretical imperative” to make autonomous, individual choices. The waning of the heteronomous authority of rabbinic Judaism, yielded theological and hermeneutic strategies to address the “secular religiosity” of individuals who sought to affirm distinctive Jewish spiritual and devotional practices. The article concludes by adumbrating two contrasting paradigmatic strategies exemplified by Franz Rosenzweig and Martin Buber respectively.

This study investigates the integration of quantum circuits with classical neural networks for enhancing credit scoring for small- and medium-sized enterprises (SMEs). We introduce a hybrid quantum–classical model, focusing on the synergy between quantum and classical rather than comparing the performance of separate quantum and classical models. Our model incorporates a quantum layer into a traditional neural network, achieving notable reductions in training time. We apply this innovative framework to a binary classification task with a proprietary real-world classical credit default dataset for SMEs in Singapore. The results indicate that our hybrid model achieves efficient training, requiring significantly fewer epochs (350) compared to its classical counterpart (3500) for a similar predictive accuracy. However, we observed a decrease in performance when expanding the model beyond 12 qubits or when adding additional quantum classifier blocks. This paper also considers practical challenges faced when deploying such models on quantum simulators and actual quantum computers. Overall, our quantum–classical hybrid model for credit scoring reveals its potential in industry, despite encountering certain scalability limitations and practical challenges.

Autophagy is a degradative recycling process central to the maintenance of homeostasis in all eukaryotes. By ensuring the degradation of damaged mitochondria, it plays a key role in maintaining mitochondrial health and function. Of the highly conserved autophagy proteins, autophagy-related protein 1 (Atg1) is essential to the process. The involvement of these proteins in intracellular signalling pathways, including those involving mitochondrial function, are still being elucidated. Here the role of Atg1 was investigated in the simple model organism Dictyostelium discoideum using an atg1 null mutant and mutants overexpressing or antisense-inhibiting atg1. When evaluated against the well-characterised outcomes of mitochondrial dysfunction in this model, altered atg1 expression resulted in an unconventional set of phenotypic outcomes in growth, endocytosis, multicellular development, and mitochondrial homeostasis. The findings here show that Atg1 is involved in a tightly regulated signal transduction pathway coordinating energy-consuming processes such as cell growth and multicellular development, along with nutrient status and energy production. Furthermore, Atg1's effects on energy homeostasis indicate a peripheral ancillary role in the mitochondrial signalling network, with effects on energy balance rather than direct effects on electron transport chain function. Further research is required to tease out these complex networks. Nevertheless, this study adds further evidence to the theory that autophagy and mitochondrial signalling are not opposing but rather linked, yet strictly controlled, homeostatic mechanisms. [ABSTRACT FROM AUTHOR]

Background Older people with human immunodeficiency virus (HIV, PWH) are prone to using multiple medications due to higher rates of medical comorbidities and the use of antiretroviral therapy (ART). We assessed the prevalence and clinical impact of polypharmacy among PWH. Methods We leveraged clinical data from the AIDS Clinical Trials Group A5322 study "Long-Term Follow-up of Older HIV-infected Adults: Addressing Issues of Aging, HIV Infection and Inflammation" (HAILO). We included PWH aged ≥40 years with plasma HIV RNA levels <200 copies/µL. We assessed the relationship between polypharmacy (defined as the use of 5 or more prescription medications, excluding ART) and hyperpolypharmacy (defined as the use of 10 or more prescription medications, excluding ART) with slow gait speed (less than 1 meter/second) and falls, including recurrent falls. Results Excluding ART, 24% of study participants had polypharmacy and 4% had hyperpolypharmacy. Polypharmacy was more common in women (30%) than men (23%). Participants with polypharmacy had a higher risk of slow gait speed (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.27–2.50) and increased risk of recurrent falls (OR = 2.12; 95% CI = 1.06–4.23). The risk for recurrent falls was further increased in those with hyperpolypharmacy compared with those without polypharmacy (OR = 3.46; 95% CI = 1.32–9.12). Conclusions In this large, mixed-sex cohort of PWH aged ≥40 years, polypharmacy was associated with slow gait speed and recurrent falls, even after accounting for medical comorbidities, alcohol use, substance use, and other factors. These results highlight the need for increased focus on identifying and managing polypharmacy and hyperpolypharmacy in PWH. [ABSTRACT FROM AUTHOR]

The article develops a concept of "secular religiosity" to characterize "post-traditional" Jewish affiliation as an individual and private matter, which the sociologist Peter Berger casts as a "heretical imperative" to make autonomous, individual choices. The waning of the heteronomous authority of rabbinic Judaism, yielded theological and hermeneutic strategies to address the "secular religiosity" of individuals who sought to affirm distinctive Jewish spiritual and devotional practices. The article concludes by adumbrating two contrasting paradigmatic strategies exemplified by Franz Rosenzweig and Martin Buber respectively. [ABSTRACT FROM AUTHOR]

This study investigates the integration of quantum circuits with classical neural networks for enhancing credit scoring for small- and medium-sized enterprises (SMEs). We introduce a hybrid quantum–classical model, focusing on the synergy between quantum and classical rather than comparing the performance of separate quantum and classical models. Our model incorporates a quantum layer into a traditional neural network, achieving notable reductions in training time. We apply this innovative framework to a binary classification task with a proprietary real-world classical credit default dataset for SMEs in Singapore. The results indicate that our hybrid model achieves efficient training, requiring significantly fewer epochs (350) compared to its classical counterpart (3500) for a similar predictive accuracy. However, we observed a decrease in performance when expanding the model beyond 12 qubits or when adding additional quantum classifier blocks. This paper also considers practical challenges faced when deploying such models on quantum simulators and actual quantum computers. Overall, our quantum–classical hybrid model for credit scoring reveals its potential in industry, despite encountering certain scalability limitations and practical challenges. [ABSTRACT FROM AUTHOR]