The iAAA-mitochondrial protease YME1L1 regulates the degradation of the short-lived mitochondrial transporter SLC25A38.

Mitochondrial transporters facilitate the exchange of diverse metabolic intermediates across the inner mitochondrial membrane, ensuring an adequate supply of substrates and cofactors to support redox and biosynthetic reactions within the mitochondrial matrix. However, the regulatory mechanisms governing the abundance of these transporters, crucial for maintaining metabolic compartmentalization and mitochondrial functions, remain poorly defined. Through analysis of protein half-life data and mRNA-protein correlations, we identified SLC25A38, a mitochondrial glycine transporter, as a short- lived protein with a half-life of 4 hours under steady-state conditions. Pharmacological inhibition and genetic depletion of various cellular proteolytic systems revealed that SLC25A38 is rapidly degraded by the iAAA-mitochondrial protease YME1L1. Depolarization of the mitochondrial membrane potential induced by the mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrozone prevented the degradation of SLC25A38. This dual regulation of SLC25A38 abundance by YME1L1 and mitochondrial membrane potential suggests a link between SLC25A38 turnover, the integrity of the inner mitochondrial membrane, and electron transport chain function. These findings open avenues for investigating whether mitochondrial glycine import coordinates with mitochondrial bioenergetics.

Designing Chinese hospital emergency departments to leverage artificial intelligence-a systematic literature review on the challenges and opportunities.

Artificial intelligence (AI) has witnessed rapid advances in the healthcare domain in recent years, especially in the emergency field, where AI is likely to radically reshape medical service delivery. Although AI has substantial potential to enhance diagnostic accuracy and operational efficiency in hospitals, research on its applications in Emergency Department building design remains relatively scarce. Therefore, this study aims to investigate Emergency Department facility design by identifying the challenges and opportunities of using AI. Two systematic literature reviews are combined, one in AI and the other in sensors, to explore their potential application to support decision-making, resource optimisation and patient monitoring. These reviews have then informed a discussion on integrating AI sensors in contemporary Emergency Department designs for use in China to support the evidence base on resuscitation units, emergency operating rooms and Emergency Department Intensive Care Unit (ED-ICU) design. We hope to inform the strategic implementation of AI sensors and how they might transform Emergency Department design to support medical staff and enhance the patient experience.

A Serum Pharmacochemistry and Network Pharmacology-based Approach to Study the Anti-depressant Effect of Chaihu-Shugan San.

AIMS: The aim of this study is to explore the anti-depressant mechanism of Chaihu- Shugan San based on serum medicinal chemistry and network pharmacology methods. BACKGROUND: Depression lacks effective treatments, with current anti-depressants ineffective in 40% of patients. Chaihu-Shugan San (CHSGS) is a well-known traditional Chinese medicine compound to treat depression. However, the chemical components and the underlying mechanisms targeting the liver and brain in the anti-depressant effects of CHSGS need to be elucidated. METHODS: The chemical components of CHSGS in most current network pharmacology studies are screened from TCMSP and TCMID databases. In this study, we investigated the mechanism and material basis of soothing the liver and relieving depression in the treatment of depression by CHSGS based on serum pharmacochemistry. The anti-depressant mechanism of CHSGS was further verified by proteomics and high-throughput data. RESULTS: Through serum medicinal chemistry, we obtained 9 bioactive substances of CHSGS. These ingredients have good human oral bioavailability and are non-toxic. Based on liver ChIPseq data, CHSGS acts on 8 targets specifically localized in the liver, such as FGA, FGB, and FGG. The main contributors to CHSGS soothing the liver qi targets are hesperetin, nobiletin, ferulic acid, naringin and albiflorin. In addition, network pharmacology analysis identified 9 blood components of CHSGS that corresponded to 63 anti-depressant targets in the brain. Among them, nobiletin has the largest number of anti-depressant targets, followed by glycyrrhizic acid, ferulic acid, albiflorin and hesperetin. We also validated the anti-depressant mechanism of CHSGS based on hippocampal proteomics. CHSGS exerts anti-depressant effects on synaptic structure and neuronal function by targeting multiple synapse related proteins. CONCLUSION: This study not only provides a theoretical basis for further expanding the clinical application of CHSGS, but also provides a series of potential lead compounds for the development of depression drugs.

[Research Progress in the Effect of Exercise Intervention on Sleep Disorders and the Mechanisms Involved]. / è¿åŠ¨å¹²é¢„å¯¹ç¡çœ éšœç¢çš„å½±å“åŠä½œç”¨æœºåˆ¶ç ”ç©¶è¿›å±•.

Sleep disorders, a common concern in modern society, seriously affect people's physical and mental health. Reported findings suggest that both acute exercise intervention and long-term regular exercise intervention can improve the disrupted sleep structure and normalize the duration and proportion of the different phases of sleep. Moreover, exercise intervention has a positive effect on the endocrine functions, the metabolic functions, the immune response, the autonomic nervous system, and cardiac functions during sleep. It is a non-medicative therapeutic strategy for improving sleep disorders. The specific type of exercise intervention (aerobic exercise, resistance exercise, or meditative movement) adopted is one of the moderating variables of exercise intervention programs. Different types of exercise improve sleep disorders by way of different mechanisms. Exercise volume and intensity are another moderating variable of exercise intervention programs. The optimal amount and intensity of exercise for different individuals to improve sleep disorders may vary. Exercise interventions implemented at the different times throughout a day can also have varying degrees of impact on sleep disorders and there is no consensus on the optimal exercise time for improving sleep quality at present. Herein, we summarized the mechanisms by which exercise intervention improves sleep disorders from four perspectives, including epigenetics, hyperarousal, human circadian rhythm, and body temperature regulation. In addition, we discussed the current gaps and prospects of research in this field, aiming to provide a theoretical basis for the development of exercise prescriptions for sleep disorders.

The hippocampal FTO-BDNF-TrkB pathway is required for novel object recognition memory reconsolidation in mice.

Memory reconsolidation refers to the process by which the consolidated memory was restored after reactivation (RA). Memory trace becomes labile after reactivation and inhibition of memory reconsolidation may disrupt or update the original memory trace, which provided a new strategy for the treatment of several psychiatric diseases, such as drug addiction and post-traumatic stress disorder. Fat mass and obesity-associated gene (FTO) is a novel demethylase of N6-methyladenosine (m6A) and it has been intensively involved in learning and memory. However, the role of FTO in memory reconsolidation has not been determined. In the present study, the function of FTO in memory reconsolidation was investigated in the novel object recognition (NOR) model in mice. The results showed that RA of NOR memory increased hippocampal FTO expression in a time-dependent manner, while FTO inhibitor meclofenamic acid (MA) injected immediately, but not 6 h after RA disrupted NOR memory reconsolidation. MA downregulated BDNF expression during NOR memory reconsolidation in the hippocampus, while the TrkB agonist 7,8-Dihydroxyflavone (7,8-DHF) reversed the disruptive effects of MA on NOR memory reconsolidation. Furthermore, overexpression of FTO increased BDNF expression via decreasing mRNA m6A in HT22 cells. Taken together, these results indicate that FTO may up-regulate the BDNF-TrkB pathway to promote NOR memory reconsolidation through m6A modification.

Presence of IgG antibodies is not a reliable marker of Toxoplasma gondii infection in feral mice.

The single-celled parasite Toxoplasma gondii uses mice as a vector to reach its definitive host, the cat, where it can accomplish its sexual reproduction and produce oocysts, which will contaminate the environment. In this study, we have captured 103 feral house mice (Mus musculus) on Kangaroo Island, Australia. We have measured the level of exposure to T.gondii serologically with the Modified Agglutination Test and conjointly with a T.gondii B1 gene PCR. We have included stringent quality control steps in the molecular analysis to reduce the risk of false positivity and false negativity. Our results indicated a low seroprevalence of 0.97%, 95%CI [-0.36; 0.58] associated with the detection of T.gondii genetic material in 51.46%, 95%CI [41.93, 60.88] of mice brains. Neither sex nor mice body weight had an effect on the PCR outcome. We postulate that both the transmission route, horizontal or vertical, and natural selection processes could lead to this discordance which has been observed elsewhere in wild mice. The question of the biological mechanisms allowing the chronic infection of wild mice in the absence of a measurable humoral immune response remains. Our findings indicate that serological studies should not be used to measure the level of exposure to T.gondii in feral house mice.

Impaired episodic-like memory in a mouse model of Alzheimer's disease is associated with hyperactivity in prefrontal-hippocampal regions.

Alzheimer's disease (AD) is a degenerative brain disorder with a long prodromal period. An APPNL-G-F knock-in mouse model is a preclinical model to study incipient pathologies during the early stages of AD. Despite behavioral tests revealing broad cognitive deficits in APPNL-G-F mice, detecting these impairments at the early disease phase has been challenging. In a cognitively demanding task that assessed episodic-like memory, 3-month-old wild-type mice could incidentally form and retrieve 'what-where-when' episodic associations of their past encounters. However, 3-month-old APPNL-G-F mice, corresponding to an early disease stage without prominent amyloid plaque pathology, displayed impairment in recalling 'what-where' information of past episodes. Episodic-like memory is also sensitive to the effect of age. Eight-month-old wild-type mice failed to retrieve conjunctive 'what-where-when' memories. This deficit was also observed in 8-month-old APPNL-G-F mice. c-Fos expression revealed that impaired memory retrieval in APPNL-G-F mice was accompanied by abnormal neuronal hyperactivity in the medial prefrontal cortex and CA1 dorsal hippocampus. These observations can be used for risk stratification during preclinical AD to detect and delay the progression into dementia.

The role and mechanism of tryptophan - kynurenine metabolic pathway in depression.

Major depressive disorder (MDD) is a common mental illness characterized by persistent low mood and anhedonia, normally accompanied with cognitive impairment. Due to its rising incidence and high rate of recurrence and disability, MDD poses a substantial threat to patients' physical and mental health, as well as a significant economic cost to society. However, the etiology and pathogenesis of MDD are still unclear. Chronic inflammation may cause indoleamine-2,3-dioxygenase (IDO) to become overactive throughout the body and brain, resulting in excess quinolinic acid (QUIN) and less kynuric acid (KYNA) in the brain. QUIN's neurotoxicity damages glial cells and neurons, accelerates neuronal apoptosis, hinders neuroplasticity, and causes depression due to inflammation. Therefore, abnormal TRP-KYN metabolic pathway and its metabolites have been closely related to MDD, suggesting changes in the TRP-KYN metabolic pathway might contribute to MDD. In addition, targeting TRP-KYN with traditional Chinese medicine showed promising treatment effects for MDD. This review summarizes the recent studies on the TRP-KYN metabolic pathway and its metabolites in depression, which would provide a theoretical basis for exploring the etiology and pathogenesis of depression.

Establishment of an intervention model for adolescent obesity based on component isochronous substitution method / 中国学校卫生

Objective@#To explore the relationship between isochronous substitution and BMI, waist circumference (WC), and body fat rate (FAT) among physical activity (PA), sedentary (SB), and sleep (SLP), so as to provide effective measures for obesity control in adolescents.@*Methods@#A total of 193 adolescents aged 12-15 (90 males and 103 females) was randomly selected, and their height, weight, and BMI were measured using routine testing methods from May to August 2022. The PA, SB and SLP of the participants were measured using a 3D accelerometer (ActiGraph GT3X+).@*Results@#The arithmetic mean value overestimated SLP (40.8%) and SB (39.6%) to some extent, and underestimated LPA (16.1%) and MVPA (3.5%) to some extent. Based on the ISM at 15 min, MVPA was substituted for other activity, BMI Z decreased by 0.17-0.22 units, WC Z decreased by 0.16-0.20 units, and FAT Z decreased by 0.17-0.22 units. The substitution between MVPA and for other activity exhibited significant asymmetry. The effects of MVPA substitutions for SB was the largest, followed by the effects of MVPA substitutions for SLP, and the effects of MVPA substitutions for LPA was the lowest. As MVPA substitutions for other behaviors, it reached its maximum (0.06-0.08 units ) when the MVPA time increased by 5 minutes.@*Conclusions@#MVPA plays an irreplaceable role in the control of adolescent obesity . While reducing SB time, MVPA duration should be increased to ensure that the daily MVPA duration is not less than 55 minutes in order to effectively control obesity.

The isochronous substitution effect of 24 hour activity behavior on physical health of college students / 中国学校卫生

Objective@#An isochronous substitution model was established to explore the association and substitution effect between college students 24 hour activity behavior and physical health, so as to provide specific activity behavior suggestions for college students to improve their physical health.@*Methods@#A stratified random cluster sampling method was used to conduct physical fitness tests and 24 hour activity behavior surveys among 2 794 college students in 12 colleges and universities in Tianjin.Time spent on sedentary behavior(SB), light intensity physical activity(LPA), moderate to vigorous physical activity(MVPA) and sleep(SLP) time. The isochronous method of components was used to explore the relationship between 24 h activity behavior and physical health.@*Results@#Except for 50 m running, MVPA was negatively correlated with BMI Z ( β =-0.62, P <0.05), but positively correlated with other physical fitness indexes ( β =0.34~274.23, P <0.05). LPA was not associated with lung capacity, sitting forward flexion and 50 m running, and negatively correlated with other physical fitness indexes ( β =-14.30- -0.19, P <0.05). SB was negatively correlated with most physical fitness indexes ( β =-11.57- -0.33, P <0.05), but positively correlated with BMI Z ( β =0.45, P < 0.05 ). In addition to lung capacity, SLP was positively correlated with BMI Z , total physical fitness score,1 minute sit-ups, pull ups, 800/1 000 m running, sitting forward flexion, and 50 m running ( β =0.27-11.21, P <0.05), but negatively correlated with long jump ( β =-0.10, P <0.05）. Isochronous substitution showed that the adverse effects of 30 min/d SB and LPA substitution of MVPA were much greater than the beneficial effects of MVPA substitution for corresponding behaviors (total physical score: SB, -0.58 vs 0.47 points; LPA, -0.50 vs 0.38 points).@*Conclusion@#MVPA and SLP have been found to have a positive effect on physical fitness among college students. Therefore, in the process of improving the physical health of college students, ensuring adequate sleep, improving MVPA and reducing SB as much as possible may be one of the effective methods.

Emerging Roles of FTO in Neuropsychiatric Disorders.

FTO (fat mass and obesity associated) is a recently discovered gene related to obesity and expressed in various tissues of the human body, especially with high expression in the brain. Earlier studies have found that FTO is involved in several biological processes, including brain development and function. In particular, recent studies have found that FTO is a demethylase of N6-methyladenosine (m6A) and it can affect neurological function through the m6A modification of mRNA. At present, a number of studies have shown that FTO is associated with many neuropsychiatric disorders. This paper reviews the discovery, structure, function, and tissue expression of FTO followed by discussing the relationship between FTO and neuropsychiatric diseases. In addition, the potential roles of FTO gene in drug addiction, major depression (MDD), and schizophrenia (SCZ) through regulating m6A modification of dopamine related genes were also highlighted.

Deep Brain Stimulation in Drug Addiction Treatment: Research Progress and Perspective.

Drug addiction is a chronic psychiatric disorder characterized by compulsive drug-seeking and drug-using behavior, and a tremendous socioeconomic burden to society. Current pharmacological and psychosocial methods have shown limited treatment effects for substance abuse. Deep Brain Stimulation (DBS) is a novel treatment for psychiatric disease and has gradually gained popularity in the treatment of addiction. Addiction is characterized by neuroplastic changes in the nucleus accumbens (NAc), a key structure in the brain reward system, and DBS in this region has shown promising treatment effects. In this paper, the research progress on DBS for drug addiction has been reviewed. Specifically, we discuss the mechanism of NAc DBS for addiction treatment and summarize the results of clinical trials on DBS treatment for addiction to psychoactive substances such as nicotine, alcohol, cocaine, opioids and methamphetamine/amphetamine. In addition, the treatment effects of DBS in other brain regions, such as the substantia nigra pars reticulata (SNr) and insula are discussed.

Impact of Plant-Based Foods and Nutraceuticals on Toxoplasma gondii Cysts: Nutritional Therapy as a Viable Approach for Managing Chronic Brain Toxoplasmosis.

Toxoplasma gondii is an obligate intracellular parasite that mainly infects warm-blooded animals including humans. T. gondii can encyst and persist chronically in the brain, leading to a broad spectrum of neurological sequelae. Despite the associated health threats, no clinical drug is currently available to eliminate T. gondii cysts. In a continuous effort to uncover novel therapeutic agents for these cysts, the potential of nutritional products has been explored. Herein, we describe findings from in vitro and in vivo studies that support the efficacy of plant-based foods and nutraceuticals against brain cyst burden and cerebral pathologies associated with chronic toxoplasmosis. Finally, we discuss strategies to increase the translatability of preclinical studies and nutritional products to address whether nutritional therapy can be beneficial for coping with chronic T. gondii infections in humans.

Identification of Biomarkers Related to CD8+ T Cell Infiltration With Gene Co-expression Network in Lung Squamous Cell Carcinoma.

Lung squamous cell carcinoma (LSCC) is one of the most common types of lung cancer in adults worldwide. With the development of modern medicine, cancer treatment that harnesses the power of the immune system might be particularly effective for treating LSCC. In this research, LSCC expression data, which quantify the cellular composition of immune cells, were analyzed by weighted gene coexpression network analysis (WGCNA) and a deconvolution algorithm based on the Gene Expression Omnibus (GEO) database, and the results indicated a close relationship between LSCC and CD8+ T cells. Six hub genes (SYT3, METTL8, HSPB3, GFM1, ERLIN2, and CLCN2) were verified by gene-gene network and protein-protein interaction (PPI) network analyses. We found that the six hub genes were increased in cancer tissues and were closely correlated with cancer development and progression. After immune correlation analysis, METTL8 was selected as a prognostic biomarker. Finally, we found that the METTL8 levels were increased in multiple lung cancer cell lines and LSCC tissues. METTL8 inhibition could clearly induce G1 cell cycle arrest and suppress proliferation. Therefore, METTL8, which is related to CD8+ T cell infiltration, might be identified as a potential biomarker and gene therapy target in LSCC.

P2X7 Receptor as a Potential Target for Major Depressive Disorder.

Major depressive disorder (MDD) is a common mental disorder. Although the genetic, biochemical, and psychological factors have been related to the development of MDD, it is generally believed that a series of pathological changes in the brain caused by chronic stress is the main cause of MDD. However, the specific mechanisms underlying chronic stress-induced MDD are largely undermined. Recent investigations have found that increased pro-inflammatory cytokines and changes in the inflammatory pathway in the microglia cells in the brain are the potential pathophysiological mechanism of MDD. P2X7 receptor (P2X7R) and its mediated signaling pathway play a key role in microglia activation. The present review aimed to present and discuss the accumulating data on the role of P2X7R in MDD. Firstly, we summarized the research progress in the correlation between P2X7R and MDD. Subsequently, we presented the P2X7R mediated microglia activation in MDD and the role of P2X7R in increased blood-brain barrier (BBB) permeability caused by chronic stress. Lastly, we also discussed the potential mechanism underlying-P2X7R expression changes after chronic stress. In conclusion, P2X7R is a key molecule regulating the activation of microglia. Chronic stress activates microglia in the hippocampus by secreting interleukin- 1ß (IL-1ß) and other inflammatory cytokines, and increasing the BBB permeability, thus promoting the occurrence and development of MDD, which indicated that P2X7R might be a promising therapeutic target for MDD.

Application of sixminute walk test in the evaluation of children and adolescents cardiorespiratory endurance / 中国学校卫生

Abstract@#Cardiopulmonary endurance is an important indicator of the physical health of children and adolescents. The 6 Minute Walk Test(6MWT) is an emerging method used to assess the cardiorespiratory endurance of children and adolescents, and has been applied in many countries and regions. This study aims to review the application of 6MWT in the assessment of cardiopulmonary endurance in children and adolescents, analyze the application prospects and precautions of 6MWT, and provide references for the application and promotion of 6MWT in the assessment of cardiopulmonary endurance in children and adolescents, as well as the formulation of related evaluation standards.

BDNF and nicotine dependence: associations and potential mechanisms.

Smoking is the leading preventable cause of death worldwide and tobacco addiction has become a serious public health problem. Nicotine is the main addictive component of tobacco, and the majority of people that smoke regularly develop nicotine dependence. Nicotine addiction is deemed to be a chronic mental disorder. Although it is well known that nicotine binds to the nicotinic acetylcholine receptors (nAChRs) and activates the mesolimbic dopaminergic system (MDS) to generate the pleasant and rewarding effects, the molecular mechanisms of nicotine addiction are not fully understood. Brain-derived neurotrophic factor (BDNF) is the most prevalent growth factor in the brain, which regulates neuron survival, differentiation, and synaptic plasticity, mainly through binding to the high affinity receptor tyrosine kinase receptor B (TrkB). BDNF gene polymorphisms are associated with nicotine dependence and blood BDNF levels are altered in smokers. In this review, we discussed the effects of nicotine on BDNF expression in the brain and summarized the underlying signaling pathways, which further indicated BDNF as a key regulator in nicotine dependence. Further studies that aim to understand the neurobiological mechanism of BDNF in nicotine addcition would provide a valuable reference for quitting smoking and developing the treatment of other addictive substances.

IL-37 As a Potential Biotherapeutics of Inflammatory Diseases.

Interleukin-37 (IL-37) was discovered as a new member of pro-inflammatory IL-1 superfamily. However, further studies suggested that IL-37 plays a critical anti-inflammatory role in innate and adaptive immunity. IL-37 may suppress the inflammatory process via intracellular SMAD family member 3 (SMAD3) and extracellular IL-18 Receptor alpha (IL-18Rα) signaling pathway, respectively. Meanwhile, the abnormal expression of IL-37 was observed in immune-mediated inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, atherosclerosis, systemic lupus erythematosus, asthma, and multiple sclerosis, which suggest IL-37 is a potential therapeutic target for these diseases. In this review, we summarize the anti-inflammatory mechanism of IL-37 and discuss the critical roles of IL-37 in the pathogenesis of these diseases. Further studies are required to confirm the effectiveness of IL-37 as a novel target for these inflammatory diseases.

Urolithin-A attenuates neurotoxoplasmosis and alters innate response towards predator odor.

Neurotoxoplasmosis, also known as cerebral toxoplasmosis, is an opportunistic chronic infection caused by the persistence of parasite Toxoplasma gondii cysts in the brain. In wild animals, chronic infection is associated with behavioral manipulation evident by an altered risk perception towards predators. In humans, reactivation of cysts and conversion of quiescent parasites into highly invasive tachyzoites is a significant cause of mortality in immunocompromised patients. However, the current standard therapy for toxoplasmosis is not well tolerated and is ineffective against the parasite cysts. In recent years, the concept of dietary supplementation with natural products derived from plants has gained popularity as a natural remedy for brain disorders. Notably, urolithin-A, a metabolite produced in the gut following consumption of ellagitannins-enriched food such as pomegranate, is reported to be blood-brain barrier permeable and exhibits neuroprotective effects in-vivo. In this study, we investigated the potential of pomegranate extract and urolithin-A as anti-neurotoxoplasmosis agents in-vitro and in-vivo. Treatment with pomegranate extract and urolithin-A reduced the parasite tachyzoite load and interfered with cyst development in differentiated human neural culture. Administration of urolithin-A also resulted in the formation of smaller brain cysts in chronically infected mice. Interestingly, this phenomenon was mirrored by an enhanced risk perception of the UA-treated infected mice towards predatory cues. Together, our findings demonstrate the potential of dietary supplementation with urolithin-A-enriched food as a novel natural remedy for the treatment of acute and chronic neurotoxoplasmosis.