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Niemann-Pick type C (NP-C) disease is a neurodegenerative lysosomal storage disorder primarily caused by mutations in NPC1 . However, its pathogenesis remains poorly understood. While mounting evidence has demonstrated the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of neurodegenerative disorders, the lncRNA expression profile in NP-C has not been determined. Here, we used RNA-seq analysis to determine lncRNA and mRNA expression profiles of the cerebella of NPC1 −/− mice. We found that 272 lncRNAs and 856 mRNAs were significantly dysregulated in NPC1 −/− mice relative to controls (≥ 2.0-fold, p  < 0.05). Quantitative real-time PCR (qRT‐PCR) was utilized to validate the expression of selected lncRNAs and mRNAs. Next, a lncRNA-mRNA coexpression network was employed to examine the potential roles of the differentially expressed (DE) lncRNAs. Functional analysis revealed that mRNAs coexpressed with lncRNAs are mainly linked to immune system–related processes and neuroinflammation. Moreover, knockdown of the lncRNA H19 ameliorated changes in ROS levels and cell viability and suppressed the lipopolysaccharide (LPS)–induced inflammatory response in vitro. Our findings indicate that dysregulated lncRNA expression patterns are associated with NP-C pathogenesis and offer insight into the development of novel therapeutics based on lncRNAs.

Background Vector control using Lysinibacillus sphaericus is an effective strategy for preventing the transmission of mosquito-borne diseases. Our previous study demonstrated that exposure to L. sphaericus during the larval stage of Anopheles dirus significantly reduced the fecundity of surviving adult mosquitoes. However, the underlying mechanisms driving this reduction remain unclear. Sublethal doses of L. sphaericus , often resulting from insufficient or delayed application, can still impact mosquito populations. Therefore, this study aimed to investigate how sublethal doses of L. sphaericus inhibit the reproductive capacity of An. dirus mosquitoes. Methods First, the staining method was used to detect L. sphaericus in surviving adult mosquitoes that had been exposed to sublethal doses during the larval stage. Second, adult mosquitoes were fed a sucrose solution containing L. sphaericus , and the effects on the reproductive capacity were observed. Third, transcriptome sequencing and qPCR were employed to identify and validate genes associated with oviposition suppression in An. dirus following treatment with sublethal doses of L. sphaericus . Finally, we assessed the effects of sublethal doses and direct feeding of L. sphaericus on vitellogenin ( Vg ) expression and activation of the target of rapamycin (TOR) signaling pathway using qPCR and Western blotting. Results Our findings demonstrated that L. sphaericus persists in adult An . dirus mosquitoes that survived larval exposure to sublethal doses. Additionally, feeding adult female mosquitoes with L. sphaericus significantly suppressed their oviposition ability. Transcriptome analysis revealed substantial alterations in gene expression profiles among surviving mosquitoes exposed to sublethal doses of L. sphaericus . Notably, L. sphaericus inhibit lysosomal function and lipid metabolism, which are critical for mosquito physiology. Furthermore, L. sphaericus significantly downregulated the Akt-TOR signaling pathway and Vg expression in adult mosquitoes. Conclusions Exposure An. dirus larvae to L. sphaericus resulted in the persistence of L. sphaericus in surviving adult mosquitoes and significantly suppressed female oviposition by downregulating Vg expression via inhibition of lysosomal function and the TOR signaling pathway. This study offers novel insights into the interaction between L. sphaericus and its mosquito host and identifies potential molecular targets for controlling mosquito population density by modulating oviposition behavior. Graphical Abstract

Background: Niemann-Pick disease type C1 (NP-C1) is a rare, autosomal-recessive neurodegenerative disorder with no United States Food and Drug Administration (FDA)-approved drug. Lithium has been shown to have considerable neuroprotective effects for neurological disorders such as bipolar disorder, Alzheimer’s disease and stroke and has been tested in many clinical trials. However, the pharmacological effect of lithium on NP-C1 neurodegenerative processes has not been investigated. The aim of this study was to provide an initial evaluation of the safety and feasibility of lithium carbonate in patients with NP-C1. Methods: A total of 13 patients diagnosed with NP-C1 who met the inclusion criteria received lithium orally at doses of 300, 600, 900, or 1,200 mg daily. The dose was reduced based on tolerance or safety observations. Plasma 7-ketocholesterol (7-KC), an emerging biomarker of NP-C1, was the primary endpoint. Secondary endpoints included NPC Neurological Severity Scores (NNSS) and safety. Results: Of the 13 patients with NP-C1 (12–33 years) enrolled, three withdrew (discontinuation of follow-up outpatient visits). The last observed post-treatment values of 7-KC concentrations (128 ng/ml, SEM 20) were significantly lower than pretreatment baselines values (185 ng/ml, SEM 29; p = 0.001). The mean NNSS was improved after lithium treatment at 12 months ( p = 0.005). Improvement in swallowing capacity was observed in treated patients ( p = 0.014). No serious adverse events were recorded in the patients receiving lithium. Conclusion: Lithium is a potential therapeutic option for NP-C1 patients. Larger randomized and double-blind clinical trials are needed to further support this finding. Clinical Trial Registration: ClinicalTrials.gov , NCT03201627.

Research on ageing‐associated genes is important for investigating ageing and anti‐ageing strategies. Here, we firstly reported that the human positive cofactor 4 (PC4), a multifunctional and highly conserved nucleoprotein, is accumulated and activated during ageing and causes global accelerated ageing process by disrupting proteostasis. Mechanistically, PC4 interacts with Sin3‐HDAC complex and inhibits its deacetylated activity, leads to hyper‐acetylation of the histones at the promoters of mTOR‐related genes and causes mTOR signalling activation. Accordingly, mTOR activation causes excessive protein synthesis, resulting in impaired proteostasis and accelerated senescence. These results reveal a new biological function of PC4 in vivo, recognizes PC4 as a new ageing‐associated gene and provides a genetically engineered mouse model to simulate natural ageing. More importantly, our findings also indicate that PC4 is involved in histone acetylation and serves as a potential target to improve proteostasis and delay ageing. Proposed hypothesis for PC4 accelerating ageing process by activating mTOR signalling through promoting histone acetylation. PC4 is increased with age and inhibits the deacetylation activity of sin3a‐HDAC complexes, causing the transcriptional activation of the mTOR‐related genes and promoting the protein synthesis while the protein folding and the degradation of misfolding protein decreases with age, resulting in impaired proteostasis and cellular senescence.

Pain imposes a significant urden on patients, affecting them physically, psychologically, and economically. Despite numerous studies on the pathogenesis of pain, its clinical management remains suboptimal, leading to the under-treatment of many pain patients. Recently, research on the role of macrophages in pain processes has been increasing, offering potential for novel therapeutic approaches. Macrophages, being indispensable immune cells in the innate immune system, exhibit remarkable diversity and plasticity. However, the majority of research has primarily focused on the contributions of M1 macrophages in promoting pain. During the late stage of tissue damage or inflammatory invasion, M1 macrophages typically transition into M2 macrophages. In recent years, growing evidence has highlighted the role of M2 macrophages in pain relief. In this review, we summarize the mechanisms involved in M2 macrophage polarization and discuss their emerging roles in pain relief. Notably, M2 macrophages appear to be key players in multiple endogenous pathways that promote pain relief. We further analyze potential pathways through which M2 macrophages may alleviate pain.

Calibration is a critical step for the phase measuring deflectometry system. Existing calibration methods are mainly optimizing the calibration parameters with respect to the 2D re-projection error criterion. However, such a procedure cannot reduce metric errors in the practical application. Therefore, an accurate and practical calibration method is proposed. In which, conventional calibration means is first applied for the primary calibration. Then, a precise square planar mirror is used for the optimization of system calibration parameters. All the intrinsic and extrinsic parameters are considered as a global multi-objective optimization problem. Three metric error criteria are introduced to evaluate the 3D reconstruction accuracy of the reference mirror. Compared with classical calibration means, which apply the parameter optimization in 2D image space to minimize the re-projection errors, the proposed optimization approach is executed in 3D space directly. An experiment and comparison are conducted to verify that the proposed optimal calibration approach can effectively reduce the system deviation and to improve the system measurement accuracy.

With the rapid development of satellite remote sensing technology, carbon-cycle research, as a key focus of global climate change, has also been widely developed in terms of carbon source/sink-research methods. The internationally recognized “top-down” approach, which is based on satellite observations, is an important means to verify greenhouse gas-emission inventories. This article reviews the principles, categories, and development of satellite detection payloads for greenhouse gases and introduces inversion algorithms and datasets for satellite remote sensing of XCO2. It emphasizes inversion methods based on machine learning and assimilation algorithms. Additionally, it presents the technology and achievements of carbon-assimilation systems used to estimate carbon fluxes. Finally, the article summarizes and prospects the future development of carbon-assimilation inversion to improve the accuracy of estimating and monitoring Earth’s carbon-cycle processes.

This study focuses on the carbon emissions of key industries in Henan Province, employing techniques of seasonal adjustment, frequency transformation, and statistical modeling to construct an industry-level “Electricity–Energy–Carbon” model to aid in the high-frequency monitoring of carbon emissions in the province’s industries. Based on relevant data, this research performs high-frequency calculations of carbon emissions from energy consumption in 34 typical industries and from the production processes of 53 typical sub-categories in the industrial sector of Henan. The findings reveal the following: Firstly, industrial energy consumption in Henan accounts for over half of the total provincial energy consumption, with most months seeing proportions around 60%. Industries such as energy, non-ferrous metals, building materials, steel, chemicals, petrochemicals, and paper making contribute to over 80% of the industrial energy consumption’s carbon emissions, often nearing 90% in most months. Secondly, among the major industries, such as non-ferrous metals, chemicals, building materials, and steel, there is a dual challenge of being restricted under the “high energy consumption and high emissions” project while also being required to build key industrial bases, leading to fluctuating trends in historical annual carbon emissions data. Thirdly, six sub-categories, namely plastic products, cement, flat glass, steel, ten types of non-ferrous metals, and alumina, have significant carbon emissions in their production processes, accounting for about 72.3% of the total production-related emissions.

Background Several individuals with depressive symptoms either do not seek help or delay treatment. This study elucidates the effects of various interventions on help-seeking behaviours, key intermediate indicators of behaviour (intentions, attitudes, subjective norms, and perceived behavioural control), and stigma. Methods Six databases were searched from their inception to January 2024. Two researchers independently conducted study selection, data extraction, and quality appraisal. Data were analysed using Review Manager 5.4 software and STATA 18.0 software. Results Thirteen studies were included, encompassing seven types of interventions: positive emotion infusion, information support intervention, mental contrasting with implementation intentions, self-perspective interventions, telephone care management, health information feedback, and depression follow-up monitoring. Existing interventions did not improve help-seeking behaviour in individuals with depressive symptoms (OR = 1.67, 95% CI: 1.05, 2.94, P  = .05) but improved help-seeking intentions immediately after the intervention (SMD = 0.64, 95% CI: 0.20, 1.08, P  < .001). Subgroup analyses showed that mental contrasting with implementation intentions (SMD = 0.62, 95% CI: 0.37, 0.88) was more effective than positive emotion infusion (SMD = 0.20, 95% CI: 0.06, 0.34) in enhancing help-seeking intentions. Additionally, mental contrasting with implementation intentions improved help-seeking intentions 2 weeks after the intervention (MD = 4.44, 95% CI: 2.60, 6.28, P  < .001). Providing information support positively affected attitudes toward help-seeking (MD = 0.36, 95% CI: 0.16, 0.57, P  < .001). No study measured subjective norms and perceived behavioural control. Moreover, available research was insufficient to provide reliable results concerning help-seeking stigma. Conclusion Existing interventions improved help-seeking intentions in individuals with depressive symptoms but did not affect help-seeking behaviour, warranting further research. Additionally, researchers should explore the role of interventions on subjective norms, perceived behavioural control, and stigma. Future studies should consider long-term follow-up of improved help-seeking behaviour and compare the effects of different interventions. Registration number PROSPERO CRD42024496771.

The lung-brain axis represents a complex bidirectional communication network that is pivotal in the crosstalk between respiratory and neurological functions. This review summarizes the current understanding of the mechanisms and protein markers that mediate the effects of lung diseases on brain health. In this review, we explore the mechanisms linking lung injury to neurocognitive impairments, focusing on neural pathways, immune regulation and inflammatory responses, microorganism pathways, and hypoxemia. Specifically, we highlight the role of the vagus nerve in modulating the central nervous system response to pulmonary stimuli; Additionally, the regulatory function of the immune system is underscored, with evidence suggesting that lung-derived immune mediators can traverse the blood-brain barrier, induce neuroinflammation and cognitive decline; Furthermore, we discuss the potential of lung microbiota to influence brain diseases through microbial translocation and immune activation; Finally, the impact of hypoxemia is examined, with findings indicating that it can exacerbate cerebral injury via oxidative stress and impaired perfusion. Moreover, we analyze how pulmonary conditions, such as pneumonia, ALI/ARDS, and asthma, contribute to neurological dysfunction. Prolonged mechanical ventilation can also contribute to cognitive impairment. Conversely, brain diseases (e.g., stroke, traumatic brain injury) can lead to acute respiratory complications. In addition, protein markers such as TLR4, ACE2, A-SAA, HMGB1, and TREM2 are crucial to the lung-brain axis and correlate with disease severity. We also discuss emerging therapeutic strategies targeting this axis, including immunomodulation and microbiome engineering. Overall, understanding the lung-brain interplay is crucial for developing integrated treatment strategies and improving patient outcomes. Further research is needed to elucidate the molecular mechanisms and foster interdisciplinary collaboration.