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Alzheimer’s disease is characterized by progressive amyloid deposition and cognitive decline, yet the pathological mechanisms and treatments remain elusive. Here we report the therapeutic potential of low-intensity 40 hertz blue light exposure in a 5xFAD mouse model of Alzheimer’s disease. Our findings reveal that light treatment prevents memory decline in 4-month-old 5xFAD mice and motivation loss in 14-month-old 5xFAD mice, accompanied by restoration of glial water channel aquaporin-4 polarity, improved brain drainage efficiency, and a reduction in hippocampal lipid accumulation. We further demonstrate the beneficial effects of 40 hertz blue light are mediated through the activation of the vLGN/IGL-Re visual circuit. Notably, concomitant use of anti-Aβ antibody with 40 hertz blue light demonstrates improved soluble Aβ clearance and cognitive performance in 5xFAD mice. These findings offer functional evidence on the therapeutic effects of 40 hertz blue light in Aβ-related pathologies and suggest its potential as a supplementary strategy to augment the efficacy of antibody-based therapy. Treatments for Alzheimer’s disease (AD) remain limited. Here, the authors show that 40 hertz blue light activates a visual circuit to boost glymphatic drainage, and enhances memory, motivation, and anti-Aβ therapy efficacy in a mouse model of AD.

Chronic vascular inflammation and immune cell infiltration are key pathogenic features of intracranial aneurysms (IAs). Although phenotypic switching of vascular smooth muscle cells (VSMCs) and macrophage M1 polarization have both been observed in IAs, the intercellular communication mechanisms linking these two processes remain incompletely understood. This study aimed to explore the potential role of the THBS1-CD47 axis in mediating crosstalk between VSMCs and macrophages within the IA microenvironment. We analyzed bulk transcriptomic (GSE54083) and single-cell RNA-sequencing (GSE193533) datasets to characterize the cellular landscape of IAs. Weighted gene co-expression network analysis (WGCNA) and the CellChat algorithm were applied to predict key ligand-receptor interactions. To validate these predictions , human aortic VSMCs (HA-VSMCs) were induced toward a secretory phenotype and co-cultured with THP-1-derived macrophages. shRNA-mediated THBS1 knockdown, CD47-neutralizing antibodies, and NF-κB inhibitors were used to investigate the underlying mechanisms. Bioinformatic analyses suggested enrichment of M1-like macrophages and phenotypically switched VSMCs in IA tissues compared with controls. CellChat analysis identified THBS1-CD47 as a potential key ligand-receptor pair linking secretory VSMCs and macrophages. Consistent with these predictions, experiments showed that secretory VSMCs released elevated levels of THBS1, which correlated with increased expression of M1 markers (CD86, iNOS) and pro-inflammatory cytokines in co-cultured macrophages. Mechanistic studies suggested that VSMC-derived THBS1 may promote this inflammatory response by activating the CD47/NF-κB signaling axis, as blockade of this pathway markedly attenuated macrophage M1 polarization. Collectively, our findings support a model in where secretory VSMCs may actively regulate the immune microenvironment of IAs through paracrine secretion of THBS1. This signaling appears to drive macrophage M1 polarization via the CD47/NF-κB axis. Targeting the THBS1-CD47 interaction may represent a promising therapeutic strategy to alleviate vascular inflammation in IAs.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with high prevalence rate among the elderly population. A large number of clinical studies have suggested repetitive transcranial magnetic stimulation (rTMS) as a promising non-invasive treatment for patients with mild to moderate AD. However, the underlying cellular and molecular mechanisms remain largely uninvestigated. In the current study, we examined the effect of high frequency rTMS treatment on the cognitive functions and pathological changes in the brains of 4- to 5-month old 5xFAD mice, an early pathological stage with pronounced amyloidopathy and cognitive deficit. Our results showed that rTMS treatment effectively prevented the decline of long-term memories of the 5xFAD mice for novel objects and locations. Importantly, rTMS treatment significantly increased the drainage efficiency of brain clearance pathways, including the glymphatic system in brain parenchyma and the meningeal lymphatics, in the 5xFAD mouse model. Significant reduction of Aβ deposits, suppression of microglia and astrocyte activation, and prevention of decline of neuronal activity as indicated by the elevated c-FOS expression, were observed in the prefrontal cortex and hippocampus of the rTMS-treated 5xFAD mice. Collectively, these findings provide a novel mechanistic insight of rTMS in regulating brain drainage system and β-amyloid clearance in the 5xFAD mouse model, and suggest the potential use of the clearance rate of contrast tracer in cerebrospinal fluid as a prognostic biomarker for the effectiveness of rTMS treatment in AD patients.

Household consumption has become an important field of carbon dioxide emissions. Urban–rural disparity in the household carbon emissions (HCEs) of residents and their influencing factors are relevant to HCE reduction. Taking Fujian as the study area, the LMDI and SDA models were used to analyze the effects of influencing factors for the direct household carbon emissions (DHCEs) and indirect carbon emissions (IHCEs) of urban and rural residents from 2006 to 2018. The HCEs continue to rise, approximately 65% from the IHCEs in 2017, and urban areas occupied 67% in 2018. The gap between urban and rural per capita HCEs is narrowing. In 2017, approximately 75% of urban per capita HCEs came from the IHCEs, while the per capita DHCEs’ occupation exceeded the IHCEs in rural areas. Per capita consumption expenditure has the largest positive effect on the DHCEs and IHCEs in urban and rural areas. With the urbanization process, the inhibition effect of rural DHCEs is larger than the positive effect of the urban DHCEs, while the positive impact on urban areas is more substantial than on rural areas in the IHCEs. Combined with regional differences, urban and rural areas should take “common but differentiated” emission reduction responsibilities.

Major depressive disorder is one of the most common mental health conditions. Meningeal lymphatics are essential for drainage of molecules in the cerebrospinal fluid to the peripheral immune system. Their potential role in depression-like behaviour has not been investigated. Here, we show in mice, sub-chronic variable stress as a model of depression-like behaviour impairs meningeal lymphatics in females but not in males. Manipulations of meningeal lymphatics regulate the sex difference in the susceptibility to stress-induced depression- and anxiety-like behaviors in mice, as well as alterations of the medial prefrontal cortex and the ventral tegmental area, brain regions critical for emotional regulation. Together, our findings suggest meningeal lymphatic impairment contributes to susceptibility to stress in mice, and that restoration of the meningeal lymphatics might have potential for modulation of depression-like behaviour. The mechanisms underlying sex differences in response to stress are unclear. Here, the authors show that meningeal lymphatics dysfunction modulates the sex difference in the stress susceptibility to depression- and anxiety-like behaviours in mice.

ObjectivesWe evaluated the feasibility of using a precise oral glucose loading combined with subcutaneous insulin administration protocol for 18F-FDG PET myocardial metabolic imaging in patients with coronary artery disease (CAD) complicated by diabetes mellitus (DM).Methods179 consecutive CAD patients complicated by DM were enrolled. Oral glucose was given at variable doses based on baseline blood glucose, and subcutaneous insulin was injected at adjusted doses according to post-load glucose levels before FDG injection. SPECT myocardial perfusion imaging and PET myocardial metabolic imaging were performed using a one-day protocol. The image quality and adverse reaction data were analyzed.ResultsAmong 179 patients, FDG image quality was scored as excellent in 57.5%, very good in 31.8%, good in 7.8%, fair in 1.7% and non-diagnostic in 1.1%. When patients were stratified by blood glucose level at time of FDG injection >7.77 mmol/L, 5.55–7.77 mmol/L and <5.55 mmol/L, the image quality were excellent in 43.1, 60.4 and 74.1%, very good in 43.1, 30.7 and 14.8%, good in 9.8, 5.9 and 11.1%, fair in 3.9, 1.0% and 0, and non-diagnostic in 0, 2.0% and 0, respectively. Patients were divided into insulin therapy group and oral medication group, the image quality were excellent in 50.7 and 62.5%, very good in 33.3 and 30.8%, good in 10.7 and 5.8%, fair in 2.7 and 1.0%, and non-diagnostic in 2.7% and 0, respectively. Patients with blood glucose at time of FDG injection >7.77 mmol/L had significantly lower odds of excellent image quality ( p = 0.021) than those with 5.55–7.77 mmol/L or <5.55 mmol/L, while no significant difference was observed between the latter two groups ( p = 0.262). 47 patients (26.3%) exhibited completely viable myocardium, 89 patients (49.7%) had partially viable myocardium, and 43 patients (24.0%) showed nonviable myocardium. None of the patients had severe adverse reactions.ConclusionThe precise oral glucose loading protocol prior to 18F-FDG injection is feasible for clinical application.

Background Premature ovarian insufficiency (POI) is a rare hypergonadotropic disorder in adolescents, with an incidence under 0.01 % before age 20. Case presentation A 14-year-old Han Chinese girl presented with secondary amenorrhea within 1 year of menarche. After comprehensive examination, she was diagnosed with idiopathic POI, complicating by metabolic dysfunction of insulin resistance (elevated fasting insulin) and dyslipidemia. Treated with cyclic hormone therapy, calcium, and vitamin D 3 , she achieved regular withdrawal bleeding and metabolic improvement. Conclusion Although the occurrence of POI shortly after menarche was extremely rare, POI should be considered in adolescents with secondary amenorrhea, even shortly post-menarche. Multidisciplinary management of reproductive and metabolic health for patients with POI was vital importance.

Measurement of auricle parameters for planning and post-operative evaluation presents substantial challenges due to the complex 3D structure of the human auricle. Traditional measurement methods rely on manual techniques, resulting in limited precision. This study introduces a novel automated surface-based three-dimensional measurement method for quantifying human auricle parameters. The method was applied to virtual auricles reconstructed from Computed Tomography (CT) scans of a cadaver head and subsequent measurement of important clinically relevant aesthetical auricular parameters (length, width, protrusion, position, auriculocephalic angle, and inclination angle). Reference measurements were done manually (using a caliper and using a 3D landmarking method) and measurement precision was compared to the automated method. The CT scans were performed using both a contemporary high-end and a low-end CT scanner. Scans were conducted at a standard scanning dose, and at half the dose. The automatic method demonstrated significantly higher precision in measuring auricle parameters compared to manual methods. Compared to traditional manual measurements, precision improved for auricle length (9×), width (5×), protrusion (5×), Auriculocephalic Angle (5–54×) and posteroanterior position (23×). Concerning parameters without comparison with a manual method, the precision level of supero-inferior position was 0.489 mm; and the precisions of the inclination angle measurements were 1.365 mm and 0.237 mm for the two automated methods investigated. Improved precision of measuring auricle parameters was associated with using the high-end scanner. A higher dose was only associated with a higher precision for the left auricle length. The findings of this study emphasize the advantage of automated surface-based auricle measurements, showcasing improved precision compared to traditional methods. This novel algorithm has the potential to enhance auricle reconstruction and other applications in plastic surgery, offering a promising avenue for future research and clinical application.

Background Patients who undergo tracheostomy often experience respiratory muscle dysfunction and reduced airway clearance capacity, leading to reduced quality of life. While inspiratory muscle training (IMT) is effective at improving respiratory outcomes among mechanically ventilated patients, evidence about its clinical utility and safety, especially in tracheostomized populations, is limited. Moreover, the optimal IMT protocol for this patient cohort remains undefined. The aim of this study is to evaluate the effects of high-intensity interval inspiratory muscle training (HI-IMT) on diaphragmatic function, airway clearance capacity, anxiety levels, decannulation rates, quality of life, and safety outcomes among tracheostomy patients. Methods This is a single-center, single-blind, randomized controlled trial. Seventy tracheostomized patients (aged 40–70 years, with tracheostomy for 1–3 months) will be randomly assigned to either the HI-IMT group or the control group. The HI-IMT group will receive IMT at 50% of the maximal inspiratory pressure (MIP), 30 breaths/day, 5 days/week for 2 weeks. The control group will receive sham training, which will involve performing the same breathing cycles without any applied resistance. Both groups will receive standard care, including pharmacological therapy, rehabilitative nursing, and basic rehabilitation exercises. Diaphragmatic function, airway clearance ability, anxiety levels, and quality of life will be assessed using the MIP% predicted (primary outcome) and peak inspiratory flow (PIF), the Semi-Quantitative Cough Strength Score (SCSS), the standardized Zung Self-Rating Anxiety Scale (SAS), and the Tracheostomy-Specific Quality of Life (TQOL) scale. Additionally, decannulation rates and adverse events will be systematically recorded throughout the study period. Data will be analyzed using parametric or non-parametric tests for unadjusted between-group comparisons. All analyses will adhere to the intention-to-treat principle, with a p -value < 0.05 set for statistical significance. Discussion This study is expected to provide valuable evidence about the efficacy and safety of HI-IMT in improving diaphragmatic function and overall outcomes among tracheostomized patients. These findings may contribute to the development of standardized respiratory rehabilitation protocols tailored to this patient population. Trial registration Chinese Clinical Trial, ChiCTR2500099091. Registered on 18 March 2025. https://www.chictr.org.cn/bin/project/edit?pid=265948 .

Background Homozygous or compound heterozygous variants in the KLHL40 gene cause nemaline myopathy 8 (NEM8), a severe autosomal recessive muscle disorder characterized by prenatal polyhydramnios, fetal akinesia or hypokinesia, joint contractures, fractures, respiratory failure and dysphagia. Currently, 46 individuals with NEM8 have been described in the literature, and 30 variants in KLHL40 have been identified. Results Here, we reported five individuals from four unrelated Chinese families who presented common features of nemaline myopathy and infrequent clinical characteristics. Whole-exome sequencing (WES) was used to identify the causative gene. WES identified a recurrent missense variant c.1516A>C (p.Thr506Pro) and a novel frameshift variant c.543del (p.Ser182Profs*17) in KLHL40 in patient 1, a nonsense variant c.602G>A (p.Trp201*) and a missense variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 2, and homozygous variant c.1516A>C (p.Thr506Pro) in KLHL40 in patient 3 and both siblings (patients 4 and 5), all of which were confirmed by Sanger sequencing. Next, we estimated the incidence of this disorder in the southern and northern Chinese population to be 4.59/10 6 and 2.95/10 6 , respectively, based on the cumulative allele frequency of pathogenic variants in internal database. Conclusion The results of our study expand the mutation spectrum of KLHL40 and enrich our understanding of the clinical characteristics of NEM8. Genetic counseling was provided for the four families involved in this study. Given the severity and the relatively high incidence of this condition, we strongly suggest that KLHL40 be incorporated into a carrier screening panel for the Chinese population.