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Harnessing a noncanonical vestibular input in the head-direction network to rectify age-related navigational deficits
No full textNavigational decline is a metric distinct from aging-related cognitive degradation, yet the affected circuits and synaptic changes remain elusive. This study identified a long-range excitatory projection from parvalbumin (PV) neurons in the brainstem medial vestibular nucleus (MVN) of mice that monosynaptically innervates the midbrain dorsal tegmental nucleus (DTN). This PVMVN→DTN projection exhibits high neuronal excitability and synaptic plasticity as electrophysiological traits. In vivo chemogenetic inhibition of the PVMVN→DTN projection impaired the navigational performance of adult mice. Navigational deficits in aged mice linked to both diminished innervation and synaptic drive of the PVMVN→DTN pathway were pinpointed as hallmarks of the aging process. Strikingly, targeted activation of this pathway mitigated navigational impairments in older mice. In sum, our results revealed an excitatory PVMVN→DTN pathway that impacts navigation. Rescue from aging-related navigational decline by activation of a spared projection pathway further highlights the potential for targeted therapies.</p
A Qualitative Exploration of Hong Kong Medical Educators' Perspectives on Factors Influencing Their Resilience
No full textIntroduction: Globally, alarming trends of psychological distress among physicians and medical students threaten patient care and professionalism. The resilience and well-being of medical educators have been recognised as key influences on learners. However, relevant research is limited, especially in Asian contexts. Using the National Academy of Medicine (NAM) model as a lens, this study explores what external and individual factors impact the resilience of Hong Kong (HK)-based medical educators. Methods: HK-based medical educators, who taught medical students and physicians, were recruited using purposive sampling. They participated in semi-structured online interviews from 06/2021 to 04/2022. Anonymous sociodemographic information was collected through an online survey, and video recordings were transcribed anonymously. Guided by the NAM model, a hybrid deductive and inductive thematic analysis was conducted. Results: Twenty medical educators participated. They identified factors capturing all seven NAM model domains as influencing their resilience. Of those, "organisational factors" (institutional expectations, recognition, and rewards) and "personal factors" (social support from family, friends, and colleagues, and a sense of purpose in their roles) were perceived as influencing their resilience to a similar extent, suggesting that both organisational support and individual connections can bolster medical educators' resilience. Discussion: This study, the first of its kind in Asia, examined the applicability and contextual suitability of the NAM model for use among HK-based medical educators. They perceived organisational and individual factors as complementary in influencing their resilience. Our findings highlighted the importance of considering both system- and individual-level aspects when designing strategies for promoting resilience in this population
PKR modulates sterile systemic inflammation-triggered neuroinflammation and brain glucose metabolism disturbances
Get PDFSterile systemic inflammation may contribute to neuroinflammation and accelerate the progression of neurodegenerative diseases. The double-stranded RNA-dependent protein kinase (PKR) is a key signaling molecule that regulates immune responses by regulating macrophage activation, various inflammatory pathways, and inflammasome formation. This study aims to study the role of PKR in regulating sterile systemic inflammation-triggered neuroinflammation and cognitive dysfunctions. Here, the laparotomy mouse model was used to study neuroimmune responses triggered by sterile systemic inflammation. Our study revealed that genetic deletion of PKR in mice potently attenuated the laparotomy-induced peripheral and neural inflammation and cognitive deficits. Furthermore, intracerebroventricular injection of rAAV-DIO-PKR-K296R to inhibit PKR in cholinergic neurons of ChAT-IRES-Cre-eGFP mice rescued the laparotomy-induced changes in key metabolites of brain glucose metabolism, particularly the changes in phosphoenolpyruvate and succinate levels, and cognitive impairment in short-term and spatial working memory. Our results demonstrated the critical role of PKR in regulating neuroinflammation, brain glucose metabolism and cognitive dysfunctions in a peripheral inflammation model. PKR could be a novel pharmacological target for treating systemic inflammation-induced neuroinflammation and cognitive dysfunctions.published_or_final_versio
Effect of lecture-related journal articles on medical students’ motivation to learn biomedical sciences
No full textFinerenone Alleviates Over-Activation of Complement C5a-C5aR1 Axis of Macrophages by Regulating G Protein Subunit Alpha i2 to Improve Diabetic Nephropathy
No full textDiabetic nephropathy (DN), one of the most common complications of diabetes mellitus (DM), accounts for a major cause of chronic kidney disease (CKD) worldwide, with a complicated pathogenesis and limited effective strategies nowadays. The mineralocorticoid receptor (MR) is a classical ligand-activated nuclear transcription factor. It is expressed in the renal intrinsic and immune cells, especially macrophages. Over-activation of the MR was observed in patients with DN and was associated with DN prognosis. The renoprotective role of a new generation of non-steroidal selective mineralocorticoid receptor antagonist (MRA), finerenone, has been confirmed in DM and CKD patients. However, the mechanism by which finerenone improves renal inflammation in DN has yet to be completely understood. It was found in this research that the oral administration of finerenone attenuated the kidney injuries in established DN in db/db mice, and particularly improved the pathological changes in the renal tubulointerstitia. Specifically, finerenone inhibited the over-activation of the MR in macrophages, thereby reducing the expression of G protein subunit alpha i2 (GNAI2, Gnαi2), a key downstream component of the C5aR1 pathway. Animal experiments demonstrated that C5aR1 knockout alleviated renal injuries, confirming the critical pathogenic role of C5aR1 in DN. Moreover, finerenone mitigated inflammatory and chemotaxis responses by downregulating Gnαi2 in macrophages. These effects were reflected by reduced expressions of the pro-inflammatory chemokines CXCL15 and CCL2, the regulation of macrophage polarization and improvements in apoptosis. This study intends to understand the protective role of finerenone in DN, which is conducive to revealing the pathophysiological mechanism of DN and further optimizing the treatment of DN patients
A Phase Separation-Assisted Pre-Enrichment Method for Ultrasensitive Respiratory Virus Detection
Get PDFEnriching trace biomarkers (e.g., proteins, nucleic acids) is critical for biomedical applications; yet conventional methods often lack versatility, limiting their effectiveness to specific biomarker types. To address this, the phase separation-assisted pre-enrichment (PSAP) technology is presented that exploits differential polymer-polymer partitioning to achieve 47-fold antigen and 44-fold RNA enrichment simultaneously. Through systematic optimization of interfacial chemistry, including pH modulation, polymer hydrophilicity, mass fraction, and molecular weights, the protocol is refined to enable direct integration with commercial diagnostics. PSAP-boosted rapid antigen ests (RATs) detected SARS-CoV-2 and Influenza viruses at tenfold and fivefold lower limits, respectively. In clinical validation, 53 clinical specimens (containing PCR undetectable samples as controls) are analyzed. The PSAP method significantly enhanced detection accuracy for both viral antigens and RNA, particularly improving positivity rates in low viral load specimens (27 < Ct < 31) compared to conventional approaches while maintaining specificity in high-Ct and negative controls. With its universality and tunability, PSAP demonstrates universal applicability across respiratory pathogens and lays the foundation for next-generation point-of-care diagnostics.published_or_final_versio
The 2024 APLAR Consensus on the Management of Lupus Nephritis
No full textThe APLAR has published a set of recommendations on the management of systemic lupus erythematosus (SLE) in 2021. The current consensus paper supplements and updates specifically the treatment of lupus nephritis (LN) according to two rounds of Delphi exercise from members of the APLAR SLE special interest group, invited nephrologists, histopathologists, and lupus nephritis patients. For initial treatment of LN, we recommend a combination of glucocorticoids (GCs) with cyclophosphamide (CYC), mycophenolate mofetil (MMF), or the calcineurin inhibitors (CNIs) as first-line options. An upfront combination of immunosuppressive drugs and the biological agents may be considered in patients at significant risk of disease progression and renal function deterioration. Switching or “add-on” among different immunosuppressive agents, including biological agents, may be considered for refractory disease. Subsequent/maintenance therapy of LN should continue for at least 3 years to reduce the risk of renal flares. Lower dose MMF and azathioprine are options, but MMF maintenance should follow induction by the same drug. Prednisolone or equivalent should be maintained at a dose of 5 mg/day or less. The APLAR consensus for the management of LN includes recommendations for adjunctive therapies, monitoring and treatment of LN-related co-morbidities, and renal replacement therapies. It is hoped that this consensus paper can provide an evidence-based and pragmatic approach to the management of LN, taking into account the evidence level of therapies in Asian patients, cost-effectiveness, and differences in health care resources and reimbursement policies in the Asia-Pacific region.</p
Edge Computing-Enabled Peer-to-Peer Energy Trading in a Local Energy Community
No full textLocal energy communities establish a platform for prosumers and consumers to share surplus generation via peerto-peer (P2P) energy trading. Traditional optimization techniques for energy management problems necessitate precise models and accurate predictions. In contrast, reinforcement learning has gained widespread attention as it can handle system uncertainties without relying on models. However, multi-agent reinforcement learning (MARL) approaches for P2P energy trading involve a large volume of communications and computations, hindering the practical deployment of decision-making algorithms on edge devices whose communication and computation resources are very limited. To this end, this paper proposes an efficient and privacy-preserving MARL approach for edge computing-enabled P2P energy trading. Specifically, we design an information interaction framework that shares representations rather than sensitive observations to protect the privacy of various agents. In addition, we develop an event-triggered communication approach that controls the frequency of interactions through a gating mechanism to reduce communication overhead among agents. To save the memory footprint of each agent, we investigate an evolutionary training method that updates the networks using perturbation without backward gradient computation. Case studies on a real-world dataset demonstrate that our proposed method yields significant efficiency improvements while maintaining high decision-making performance
Generation of programmable GHz burst-mode ultrashort pulses using free-space angular-chirp-enhanced delay
No full textIn this work, we propose a method for generating programmable GHz burst-mode ultrashort pulses from existing pulse sources with kHz-MHz fundamental repetition rates. It enables flexibly controlling the pulse number and intensity pattern of GHz pulse burst, as well as the repetition rate of the intra-pulses and physical time delay of the pulse. This method leverages an acousto-optic deflector (AOD) with radio-frequency encoded programmability in conjunction with a pair of long non-parallel mirrors, known as free-space angular-chirp-enhanced delay (FACED). The AOD enables real-time programming of the angular difference for aligning with the discrete angular reflection condition of FACED, facilitating the programmable splitting of a single pulse into burst-mode pulses with a GHz repetition rate. The versatility of this burst-mode GHz ultrashort pulses generation technique makes it well-suited for various applications, including material processing and nonlinear imaging.</p
