The complex effects of miR-146a in the pathogenesis of Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive dysfunction and behavioral abnormalities. Neuroinflammatory plaques formed through the extracellular deposition of amyloid-ß proteins, as well as neurofibrillary tangles formed by the intracellular deposition of hyperphosphorylated tau proteins, comprise two typical pathological features of Alzheimer's disease. Besides symptomatic treatment, there are no effective therapies for delaying Alzheimer's disease progression. MicroRNAs (miR) are small, non-coding RNAs that negatively regulate gene expression at the transcriptional and translational levels and play important roles in multiple physiological and pathological processes. Indeed, miR-146a, a NF-κB-regulated gene, has been extensively implicated in the development of Alzheimer's disease through several pathways. Research has demonstrated substantial dysregulation of miR-146a both during the initial phases and throughout the progression of this disorder. MiR-146a is believed to reduce amyloid-ß deposition and tau protein hyperphosphorylation through the TLR/IRAK1/TRAF6 pathway; however, there is also evidence supporting that it can promote these processes through many other pathways, thus exacerbating the pathological manifestations of Alzheimer's disease. It has been widely reported that miR-146a mediates synaptic dysfunction, mitochondrial dysfunction, and neuronal death by targeting mRNAs encoding synaptic-related proteins, mitochondrial-related proteins, and membrane proteins, as well as other mRNAs. Regarding the impact on glial cells, miR-146a also exhibits differential effects. On one hand, it causes widespread and sustained inflammation through certain pathways, while on the other hand, it can reverse the polarization of astrocytes and microglia, alleviate neuroinflammation, and promote oligodendrocyte progenitor cell differentiation, thus maintaining the normal function of the myelin sheath and exerting a protective effect on neurons. In this review, we provide a comprehensive analysis of the involvement of miR-146a in the pathogenesis of Alzheimer's disease. We aim to elucidate the relationship between miR-146a and the key pathological manifestations of Alzheimer's disease, such as amyloid-ß deposition, tau protein hyperphosphorylation, neuronal death, mitochondrial dysfunction, synaptic dysfunction, and glial cell dysfunction, as well as summarize recent relevant studies that have highlighted the potential of miR-146a as a clinical diagnostic marker and therapeutic target for Alzheimer's disease.

Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis.

JOURNAL/nrgr/04.03/01300535-202504000-00027/figure1/v/2024-07-06T104127Z/r/image-tiff Cardiac arrest can lead to severe neurological impairment as a result of inflammation, mitochondrial dysfunction, and post-cardiopulmonary resuscitation neurological damage. Hypoxic preconditioning has been shown to improve migration and survival of bone marrow-derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest, but the specific mechanisms by which hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown. To this end, we established an in vitro co-culture model of bone marrow-derived mesenchymal stem cells and oxygen-glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis, possibly through inhibition of the MAPK and nuclear factor κB pathways. Subsequently, we transplanted hypoxia-preconditioned bone marrow-derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia. The results showed that hypoxia-preconditioned bone marrow-derived mesenchymal stem cells significantly reduced cardiac arrest-induced neuronal pyroptosis, oxidative stress, and mitochondrial damage, whereas knockdown of the liver isoform of phosphofructokinase in bone marrow-derived mesenchymal stem cells inhibited these effects. To conclude, hypoxia-preconditioned bone marrow-derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest, and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

Varied clinical presentations of RP1L1 variants in Chinese patients: a study of occult macular dystrophy and vitelliform macular dystrophy.

BACKGROUND: Occult Macular Dystrophy (OMD), primarily caused by retinitis pigmentosa 1-like 1 (RP1L1) variants, is a complex retinal disease characterised by progressive vision loss and a normal fundus appearance. This study aims to investigate the diverse phenotypic expressions and genotypic correlations of OMD in Chinese patients, including a rare case of Vitelliform Macular Dystrophy (VMD) associated with RP1L1. METHODS: We analysed seven OMD patients and one VMD patient, all with heterozygous pathogenic RP1L1 variants. Clinical assessments included Best Corrected Visual Acuity (BCVA), visual field testing, Spectral Domain Optical Coherence Tomography (SD-OCT), multifocal Electroretinograms (mfERGs), and microperimetry. Next-generation sequencing was utilised for genetic analysis. RESULTS: The OMD patients displayed a range of phenotypic variability. Most (5 out of 7) had the RP1L1 variant c.133 C > T; p.R45W, associated with central vision loss and specific patterns in SD-OCT and mfERG. Two patients exhibited different RP1L1 variants (c.3599G > T; p.G1200V and c.2880G > C; p.W960C), presenting milder phenotypes. SD-OCT revealed photoreceptor layer changes, with most patients showing decreased mfERG responses in the central rings. Interestingly, a unique case of VMD linked to the RP1L1 variant was observed, distinct from traditional OMD presentations. CONCLUSIONS: This study highlights the phenotypic diversity within OMD and the broader spectrum of RP1L1-associated macular dystrophies, including a novel association with VMD. The findings emphasise the complexity of RP1L1 variants in determining clinical manifestations, underscoring the need for comprehensive genetic and clinical evaluations in macular dystrophies.

Association of lifestyle with sleep health in general population in China: a cross-sectional study.

The concept of a healthy lifestyle is receiving increasing attention. This study sought to identify an optimal healthy lifestyle profile associated with sleep health in general population of China. An online cross-sectional survey was conducted from June to July 2022. Six healthy lifestyle factors were assessed: healthy diet, regular physical exercise, never smoking, never drinking alcohol, low sedentary behavior, and normal weight. Participants were categorized into the healthy lifestyle (5-6 factors), average (3-4 factors), and unhealthy lifestyle groups (0-2 factors). The study's primary outcome was sleep health, which included sleep quality, duration, pattern, and the presence of any sleep disorder or disturbance, including insomnia, excessive daytime sleepiness, obstructive apnea syndrome, and narcolepsy. Multivariable logistic regression analysis was applied to explore lifestyles associated with the selected sleep health outcomes. 41,061 individuals were included, forming 18.8% healthy, 63.8% average, and 17.4% unhealthy lifestyle groups. After adjusting for covariates, participants with healthy lifestyle were associated with a higher likelihood of good sleep quality (OR = 1.56, 95% CI = 1.46-1.68), normal sleep duration (OR = 1.60, 95% CI = 1.49-1.72), healthy sleep pattern (OR = 2.15, 95% CI = 2.00-2.31), and lower risks of insomnia (OR = 0.66, 95% CI = 0.61-0.71), excessive daytime sleepiness (OR = 0.66, 95% CI = 0.60-0.73), and obstructive apnea syndrome (OR = 0.40, 95% CI = 0.37-0.43), but not narcolepsy (OR = 0.92, 95% CI = 0.83-1.03), compared to those with unhealthy lifestyle. This large cross-sectional study is the first to our knowledge to quantify the associations of a healthy lifestyle with specific aspects of sleep health. The findings offer support for efforts to improve sleep health by modulating lifestyle.

Alendronate sodium induces G1 phase arrest and apoptosis in human umbilical vein endothelial cells by inhibiting ROS-mediated ERK1/2 signaling.

Bisphosphonates are potent bone resorption inhibitors, among which alendronate sodium (ALN) is commonly prescribed for most osteoporosis patients, but long-term application of ALN can cause bisphosphonate-related osteonecrosis of jaw (BRONJ), the pathogenesis of which remains unclear. Previous studies have suggested that bisphosphonates cause jaw ischemia by affecting the biological behavior of vascular endothelial cells, leading to BRONJ. However, the impacts of ALN on vascular endothelial cells and its mechanism remain unclear. The purpose of this work is to assess the influence of ALN on human umbilical vein endothelial cells (HUVECs) and clarify the molecular pathways involved. We found that high concentration of ALN induced G1 phase arrest in HUVECs, demonstrated by downregulation of Cyclin D1 and Cyclin D3. Moreover, high concentration of ALN treatment showed pro-apoptotic effect on HUVECs, demonstrated by increased levels of the cleaved caspase-3, the cleaved PARP and Bax, along with decreased levels of anti-apoptotic protein Bcl-2. Further experiments showed that ERK1/2 phosphorylation was decreased. Additionally, ALN provoked the build-up of reactive oxygen species (ROS) in HUVECs, leading to ERK1/2 pathway suppression. N-acetyl-L-cysteine (NAC), a ROS scavenger, efficiently promoted the ERK1/2 phosphorylation and mitigated the G1 phase arrest and apoptosis triggered by ALN in HUVECs. PD0325901, an inhibitor of ERK1/2 that diminishes the ERK1/2 phosphorylation enhanced the ALN-induced G1 phase arrest and apoptosis in HUVECs. These findings show that ALN induces G1 phase arrest and apoptosis through ROS-mediated ERK1/2 pathway inhibition in HUVECs, providing novel insights into the pathogenic process, prevention and treatment of BRONJ in individuals receiving extended use of ALN.

Herb-Nanoparticle Hybrid System for Improved Oral Delivery Efficiency to Alleviate Breast Cancer Lung Metastasis.

Background: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging. Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb-nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum-Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid-polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC-Orbitrap-MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated. Results: The HNS reduced particle-mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer's patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-ß1, which altered the TME in 4T1 tumor-bearing mice. Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.

Sphingosine-1 phosphate receptor 1 (S1PR1) expression maintains stemness of acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) arises from leukemia stem cells (LSCs) and is maintained by cells which have acquired features of stemness. We compared transcription profiles of AML cells with/without stem cell features defined as in vitro clonogenicity and serial engraftment in immune-deficient mice xenograft model. We used multi-parameter flow cytometry (MPFC) to separate CD34+ bone marrow-derived leukemia cells into sphingosine-1 phosphate receptor 1 (S1PR1)+ and S1PR1- fractions. Cells in the S1PR1+ fraction demonstrated significantly higher clonogenicity and higher engraftment potential compared with those in the S1PR1- fraction. In contrast, CD34+ bone marrow cells from normal samples showed reduced clonogenicity in the S1PR1+ fraction compared with the S1PR1- fraction. Inhibition of S1PR1 expression in an AML cell line reduced the colony-forming potential of KG1 cells. Transcriptomic analyses and rescue experiments indicated PI3K/AKT pathway and MYBL2 are downstream mediators of S1PR1-associated stemness. These findings implicate S1PR1 as a functional biomarker of LSCs and suggest its potential as a therapeutic target in AML treatment.

Explainable spatio-temporal graph evolution learning with applications to dynamic brain network analysis during development.

Modeling dynamic interactions among network components is crucial to uncovering the evolution mechanisms of complex networks. Recently, spatio-temporal graph learning methods have achieved noteworthy results in characterizing the dynamic changes of inter-node relations (INRs). However, challenges remain: The spatial neighborhood of an INR is underexploited, and the spatio-temporal dependencies in INRs' dynamic changes are overlooked, ignoring the influence of historical states and local information. In addition, the model's explainability has been understudied. To address these issues, we propose an explainable spatio-temporal graph evolution learning (ESTGEL) model to model the dynamic evolution of INRs. Specifically, an edge attention module is proposed to utilize the spatial neighborhood of an INR at multi-level, i.e., a hierarchy of nested subgraphs derived from decomposing the initial node-relation graph. Subsequently, a dynamic relation learning module is proposed to capture the spatio-temporal dependencies of INRs. The INRs are then used as adjacent information to improve the node representation, resulting in comprehensive delineation of dynamic evolution of the network. Finally, the approach is validated with real data on brain development study. Experimental results on dynamic brain networks analysis reveal that brain functional networks transition from dispersed to more convergent and modular structures throughout development. Significant changes are observed in the dynamic functional connectivity (dFC) associated with functions including emotional control, decision-making, and language processing.

Effects of regulating gut microbiota by electroacupuncture in the chronic unpredictable mild stress rat model.

OBJECTIVE: This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats. METHODS: A total of 40 male Sprague Dawley rats were divided into three groups: normal control, chronic unpredictable mild stress (CUMS), and EA (CUMS + EA). The rats in CUMS and EA groups underwent chronic stress for 10 weeks, and EA group rats received EA treatment for 4 weeks starting from week 7. Body weight and behavioral tests, including the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were monitored. Gut microbiota composition was assessed via 16S rDNA sequencing, and lipid metabolism was analyzed by using UPLC-Q-TOF/MS technology. RESULTS: In comparison to CUMS group, EA could improve the behavior including bodyweight, immovability time, sucrose preference index, crossing piece index and rearing times index. After 4 weeks of EA treatment, 5-HT in hippocampus, serum and colon of depressive rats were simultaneously increased, indicating a potential alleviation of depression-like behaviors. In future studies revealed that EA could regulate the distribution and functions of gut microbiota, and improve the intestinal barrier function of CUMS rats. The regulation of intestinal microbial homeostasis by EA may further affect lipid metabolism in CUMS rats, and thus play an antidepressant role. CONCLUSION: This study suggested that EA has potential antidepressant effects by regulating gut microbiota composition and abundance, subsequently affecting lipid metabolism.

Clinical research progress of telomerase targeted cancer immunotherapy: a literature review.

Background and Objective: Telomerase is activated or overexpressed in 85-90% of tumors, which maintains the length of telomere and has become an important anti-cancer target. Increasing clinical and preclinical data suggest that telomerase-targeted cancer immunotherapy could achieve effective killing of tumor cells in vivo. This article reviews the research progress of telomerase targeted cancer immunotherapy in clinical and pre-clinical trials, aiming to provide a reference for further clinical research and treatment of cancers. Methods: We investigated the research progress of telomerase immunotherapy in the last 20 years from four electronic databases. Key Content and Findings: Telomerase-targeted immunotherapies have been developed with the arising of a new era in immuno-oncology, including peptide vaccines, DNA vaccines, dendritic cells (DCs), adoptive cell transfer (ACT) therapies, antibodies, etc. Some of them have been approved for undergoing clinical trials by the Food and Drug Administration (FDA) for the treatment of various cancers, such as pancreatic cancer, non-small cell lung cancer, melanoma, leukaemia. Of all the treatment modalities, vaccines are the primary treatment methods, some of which have been even entered into phase III clinical trials. The main clinical application direction of telomerase vaccine is the combination with other drugs and treatment modalities, including combination with other vaccines targeting human telomerase reverse transcriptase (hTERT), traditional chemotherapy drugs and immunosuppressors. We also summarized the recent findings of immunotherapy targeting hTERT, focusing on various vaccines and the current status of associated clinical trials. We further discussed the advantages, disadvantages and potential developmental directions of various telomerase-targeted immunotherapies. Conclusions: Telomerase-targeted cancer immunotherapy has promising prospects in improving patient survival expectancy. This review may provide data support and design ideas for all researchers and pharmaceutical enterprises in this field.

Bulk photovoltaic effect in ferroelectric nematic liquid crystals.

The bulk photovoltaic (BPV) effect in ferroelectric liquid crystals is of increasing scientific interest owing to its great potential for light-energy conversion. The ferroelectric nematic phase exhibits a huge spontaneous polarization that can be aligned to a preferred direction. In this Letter, we investigate the tensorial properties of the BPV effect in the planarly aligned ferroelectric nematic phase of the liquid crystalline material RM734. A steady-state short-circuit photocurrent of ~160 pA and an open-circuit photovoltage of ~50 mV were observed in a cell with a thickness of 5.5 µm under the illumination of ultraviolet light without any bias voltage. Based on the photocurrent measurements in different electrode configurations, the non-zero elements of the BPV tensor were obtained. The BPV effect is attributed to the combination of the spontaneous polarization and the asymmetric distribution of photoinduced charge carriers. This study not only provides an understanding of the bulk PV mechanism in soft ferroelectrics but also promises a wide range of unprecedented, to the best of our knowledge, benefits for light harvesting to engineer marketable photovoltaic devices.

Characterizing human spontaneous thoughts and its application in major depressive disorder.

BACKGROUND: Spontaneous thought is a universal, complex, and heterogeneous cognitive activity that significantly impacts mental activity and strongly correlates with mental disorders. METHODS: Utilizing the think-aloud method, we captured spontaneous thoughts during rest from 38 diagnosed with depression, alongside 36 healthy controls and 137 healthy individuals. Through a comprehensive assessment of various dimensions of thought content, we compared thought content between individuals with depression and healthy controls, and between healthy women and men. Finally, we employed natural language processing (NLP) to develop regression models for multidimensional content assessment and a classification model to differentiate between individuals with and without depression. RESULTS: Compared to healthy controls, individuals with depression had more internally oriented and less externally oriented spontaneous thoughts. They focused more on themselves and negative things, and less on positive things, experiencing higher levels of negative emotions and lower levels of positive emotions. Besides, we found that compared to healthy men, healthy women's spontaneous thoughts focus more on interoception, the self, past events, and negative events, and they experience higher levels of negative emotions. Meanwhile, we identified the potential application of the think-aloud method to collect spontaneous thoughts and integrate NLP in the field of depression. CONCLUSIONS: This study offers direct insights into the stream of thought during individuals' resting state, revealing differences between individuals with depression and healthy controls, as well as sex differences in the content of spontaneous thoughts. It enhances our understanding of spontaneous thought and offers a new perspective for preventing, diagnosing, and treating depression.

Rising atmospheric carbon dioxide concentrations increase gaps of rice yields between low- and middle-to-high-income countries.

The rising carbon dioxide concentrations are expected to increase future rice yields. However, variations in the CO2 fertilization effect (CFE) between rice subspecies and the influence of concurrent global warming introduce uncertainty in future global rice yield projections. Here we conducted a meta-analysis of rising carbon dioxide field experiments and employed crop modelling to assess future global rice yields for the top 14 rice producing countries. We found a robust parabolic relationship between rice CFE and temperature, with significant variations between rice subspecies. Our projections indicate that global rice production in the 2050s is expected to increase by 50.32 million tonnes (7.6%) due to CFE compared with historical production. Because low-income countries will experience higher temperatures, the gaps (difference of Δyield) between middle-to-high-income and low-income countries are projected to widen from the 2030s to the 2090s under elevated carbon dioxide. These findings underscore the critical role of CFE and emphasize the necessity to increase investments in research and technology for rice producing systems in low-income countries.

Elderly patients with dysphagia in the intensive care unit: Association between malnutrition and delirium.

BACKGROUND: Dysphagia, as a geriatric syndrome, is prevalent in the intensive care unit (ICU). Malnutrition resulting from swallowing disorders is likely to correlate with adverse ICU outcomes, including delirium, thereby escalating the costs of care and hospitalization. However, malnutrition has not received the attention it deserves in ICU clinical nursing practice. As two preventable and correctable conditions-malnutrition and delirium-the advantages of early identification and intervention are substantial. Exploring the relationship between malnutrition and delirium, starting from the high-risk group of elderly patients with swallowing difficulties in the ICU, will aid us in managing patients promptly and effectively. AIM: To investigate the relationship between malnutrition and the incidence of delirium in elderly patients with dysphagia in the ICU. SUDY DESIGN: This is a retrospective study. Data for this study were obtained from the Medical Information Mart for Intensive Care-IV. All 2273 patients included were dysphagia older patients over 65 years of age admitted to the ICU, and logistic regression was used to explore the relationship between malnutrition and delirium. We also used propensity score matching (PSM) for sensitivity analysis. RESULTS: Among the included patients with swallowing difficulties, 13% individuals (297/2273) exhibited malnutrition, with a delirium incidence rate of 55.9% (166/297). In the non-malnutrition group (1976/2273), the delirium incidence rate is 35.6% (704/1976). After adjusting for 31 covariates, multifactorial logistic regression showed that malnutrition was significantly positively associated with the incidence of delirium in elderly dysphagic patients in the ICU (adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) = 1.47-2.62). The results remained stable after analysis by PSM. CONCLUSION: Malnutrition was significantly positively associated with the incidence of delirium in elderly dysphagic patients in the ICU. Malnutrition should be given adequate attention in the ICU. RELEVANCE TO CLINICAL PRACTICE: ICU nurses should pay particular attention to malnutrition, especially among the high-prevalence group of patients with dysphagia. Early identification and nutritional intervention for these patients may help reduce the costs of care and health care expenditures.

A subset of brain regions within adult functional connectivity networks demonstrate high reliability across early development.

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized as functional networks. These areas show stronger internal and weaker external functional connectivity (FC) and exhibit similar FC profiles within rather than between networks. Previous studies have demonstrated the development of these networks from nascent forms present before birth to their mature, adult-like topography in childhood. However, analyses often still use definitions based on adult functional networks. We aim to assess how this might lead to the misidentification of functional networks and explore potential consequences and solutions. Our findings suggest that even though adult networks provide only a marginally better than-chance description of the infant FC organization, misidentification was largely driven by specific areas. By restricting functional networks to areas showing adult-like network clustering, we observed consistent within-network FC both within and across scans and throughout development. Additionally, these areas were spatially closer to locations with low variability in network identity among adults. Our analysis aids in understanding the potential consequences of using adult networks "as is" and provides guidance for future research on selecting and utilizing functional network models based on the research question and scenario.

Genomic epidemiology reveals 2022 mpox epidemic in New York City governed by heavy-tailed sexual contact networks.

The global mpox epidemic in 2022 was likely caused by transmission of mpox virus (MPXV) through sexual contact networks, with New York City (NYC) experiencing the first and largest outbreak in the United States. By performing a phylogeographic and epidemiological analysis of MPXV, we identify at least 200 introductions of MPXV into NYC and 84 leading to onward transmission. Through a comparative analysis with human immunodeficiency virus (HIV) in NYC, we find that both MPXV and HIV genomic cluster sizes are best fit by scale-free distributions and that people in MPXV clusters are more likely to have previously received an HIV diagnosis (odds ratio=1.58; p=0.012) and be a member of a recently growing HIV transmission cluster, indicating overlapping sexual contact networks. We then model the transmission of MPXV through sexual contact networks and show that highly connected individuals would be disproportionately infected at the start of an epidemic, thereby likely resulting in the exhaustion of the most densely connected parts of the sexual network. This dynamic explains the rapid expansion and decline of the NYC outbreak, as well as the estimated cumulative incidence of less than 2% within high-risk populations. By synthesizing the genomic epidemiology of MPXV and HIV with epidemic modeling, we demonstrate that MPXV transmission dynamics can be understood by general principles of sexually transmitted pathogens.

Association of healthy lifestyle factors and genetic liability with bipolar disorder: Findings from the UK Biobank.

BACKGROUND: The interplay between genetic and lifestyle factors in the development of bipolar disorder (BD) remains unclear. METHODS: A cohort study was carried out on 365,517 participants from the UK Biobank. Lifestyle scores, based on smoking, physical activity, diet, alcohol consumption, sedentary behavior, sleep duration, and social contact, were grouped as favorable (scores 6-7), intermediate (scores 4-5), or unfavorable (scores 0-3). The BD polygenic risk score (PRS) was also categorized into high, intermediate, and low-risk groups using PRS tertiles. Cox regression models determined hazard ratios (HRs) and 95 % confidence intervals (CIs) for BD. RESULTS: During the 12.9-year follow-up, 529 individuals developed BD. Comparing those with favorable lifestyles to those with unfavorable participants, the HR of developing BD was 3.28 (95 % CI, 2.76-3.89). Similarly, individuals with a high PRS had a risk of 3.20 (95 % CI, 2.83-3.63) compared to those with a low PRS. Notably, individuals with both a high PRS and an unfavorable lifestyle had a significantly higher risk of BD (HR = 6.31, 95 % CI, 4.14-9.63) compared to those with a low PRS and a favorable lifestyle. Additionally, the interaction between PRS and lifestyle contributed an additional risk, with a relative excess risk of 1.74 (95 % CI, 0.40-3.07) and an attributable proportion due to the interaction of 0.37 (95 % CI, 0.16-0.58). CONCLUSIONS: Our findings suggest that genetic liability for BD, measured as PRS, and lifestyle have an additive effect on the risk of developing BD. A favorable lifestyle was associated with a reduced risk of developing BD.

Epidemiological features and temporal trends of the co-infection between HIV and tuberculosis, 1990-2021: findings from the Global Burden of Disease Study 2021.

BACKGROUND: The co-infection of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and tuberculosis (TB) poses a significant clinical challenge and is a major global public health issue. This study aims to elucidate the disease burden of HIV-TB co-infection in global, regions and countries, providing critical information for policy decisions to curb the HIV-TB epidemic. METHODS: The ecological time-series study used data from the Global Burden of Disease (GBD) Study 2021. The data encompass the numbers of incidence, prevalence, mortality, and disability-adjusted life year (DALY), as well as age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and DALY rate for HIV-infected drug-susceptible tuberculosis (HIV-DS-TB), HIV-infected multidrug-resistant tuberculosis (HIV-MDR-TB), and HIV-infected extensively drug-resistant tuberculosis (HIV-XDR-TB) from 1990 to 2021. from 1990 to 2021. The estimated annual percentage change (EAPC) of rates, with 95% confidence intervals (CIs), was calculated. RESULTS: In 2021, the global ASIR for HIV-DS-TB was 11.59 per 100,000 population (95% UI: 0.37-13.05 per 100,000 population), 0.55 per 100,000 population (95% UI: 0.38-0.81 per 100,000 population), for HIV-MDR-TB, and 0.02 per 100,000 population (95% UI: 0.01-0.03 per 100,000 population) for HIV-XDR-TB. The EAPC for the ASIR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.71 (95% CI: 1.92-7.59) and 13.63 (95% CI: 9.44-18.01), respectively. The global ASMR for HIV-DS-TB was 2.22 per 100,000 population (95% UI: 1.73-2.74 per 100,000 population), 0.21 per 100,000 population (95% UI: 0.09-0.39 per 100,000 population) for HIV-MDR-TB, and 0.01 per 100,000 population (95% UI: 0.00-0.03 per 100,000 population) for HIV-XDR-TB in 2021. The EAPC for the ASMR of HIV-MDR-TB and HIV-XDR-TB from 1990 to 2021 were 4.78 (95% CI: 1.32-8.32) and 10.00 (95% CI: 6.09-14.05), respectively. CONCLUSIONS: The findings indicate that enhancing diagnostic and treatment strategies, strengthening healthcare infrastructure, increasing access to quality medical care, and improving public health education are essential to combat HIV-TB co-infection.

Novel insight into astrocyte-mediated gliotransmission modulates the synaptic plasticity in major depressive disorder.

Major depressive disorder (MDD) is a form of glial cell-based synaptic dysfunction disease in which glial cells interact closely with neuronal synapses and perform synaptic information processing. Glial cells, particularly astrocytes, are active components of the brain and are responsible for synaptic activity through the release gliotransmitters. A reduced density of astrocytes and astrocyte dysfunction have both been identified the brains of patients with MDD. Furthermore, gliotransmission, i.e., active information transfer mediated by gliotransmitters between astrocytes and neurons, is thought to be involved in the pathogenesis of MDD. However, the mechanism by which astrocyte-mediated gliotransmission contributes to depression remains unknown. This review therefore summarizes the alterations in astrocytes in MDD, including astrocyte marker, connexin 43 (Cx43) expression, Cx43 gap junctions, and Cx43 hemichannels, and describes the regulatory mechanisms of astrocytes involved in synaptic plasticity. Additionally, we investigate the mechanisms acting of the glutamatergic, gamma-aminobutyric acidergic, and purinergic systems that modulate synaptic function and the antidepressant mechanisms of the related receptor antagonists. Further, we summarize the roles of glutamate, gamma-aminobutyric acid, d-serine, and adenosine triphosphate in depression, providing a basis for the identification of diagnostic and therapeutic targets for MDD.