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Abstract Background Pulp canal occlusion (PCO) increases the difficulty of root canal treatment as well as tooth preservation and restoration. This is the first case report of successful localization of a calcified root canal under the guidance of a dynamic navigation system (DNS) for complete root canal retreatment and aesthetic restoration after a failed attempt to locate the calcified root canal with a traditional dental operating microscope (DOM). Case presentation The patient was scheduled for root canal treatment for a labially inclined maxillary central incisor and post-core crown restoration with resin veneers in another hospital, but the calcified root canal could not be located with a microscope, so the patient was referred to our department. Root canal retreatment was planned for tooth #8, and the calcified root canal of tooth #9 was planned to be located and dredged under the guidance of a DNS. We used a DNS for successful positioning and to complete the root canal retreatment operation in the following 4 steps: preoperative CBCT imaging, preoperative plan design, calibration and registration, and real-time dynamic navigation. Three months later, teeth #8 and #9 presented no clinical symptoms, after which the fiber post-cores and zirconia all-ceramic crown restorations were completed. At the 12-month follow-up visit, the patient continued to be symptom­free, and satisfied with the final aesthetic restoration. Conclusions This case report suggests that DNS may be a promising technique with high accuracy and effectiveness to reduce the risk of iatrogenic errors and provide maximal preservation of dentin, when the traditional treatment of calcified root canals approaches failure (lateral perforation).

Aquatic ecosystems can harbour more than one non-native fish species and this can represent a threat due to trophic interactions with native fishes. However, research on interactions amongst multiple co-occurring native and non-native fish remains scarce. In this study, 551 organisms from 44 native fish, 11 non-native fish, 35 macroinvertebrates (of which one was non-native), together with 162 samples of basal resources were collected from six rivers of the Lower Pearl River Basin of China. Nitrogen and carbon stable isotope analysis was used to calculate community-wide trophic metrics and the degree of trophic overlap between native and non-native fish at both the community and functional feeding group level, together with diet composition. At the community level, there was a high degree of trophic niche overlap between native and non-native fish as a result of similarities in trophic characteristics. At the functional feeding group level, both native and non-native functional feeding groups demonstrated the capacity to occupy the niche space of each other. A significant trophic niche overlap, exceeding 50%, was found between non-native detritivorous and omnivorous fish, suggesting competition. The difference in diet composition between some native and non-native fish depended on the category of diet source across the rivers, suggesting dietary segregation. Albeit limited, the present findings suggest that trophic interaction between native and non-native fish is likely to reach a dynamic equilibrium status in the community owing to trophic segregation of fish species and the antagonistic effects amongst non-native fish.

Abstract LiInSe2 crystals are promising semiconductor materials for neutron detectors due to the large neutron capture cross-sectional area of the specific isotopes (6Li) and high charge transport properties. However, the optoelectronic performance fails to reach the expected level due to the difficulty of controlling the crystal defects. Herein, we modulate the stoichiometric ratio to control the type of defects in single LiInSe2 crystals grown by the vertical Bridgman method. The UV‒vis–NIR transmission results indicate that the band gap of the yellow colored Li1.01In1Se2 sample is close to ~ 2.83 eV at room temperature, and this value is consistent with the theoretical band gap of LiInSe2 (~ 2.86 eV). Photoluminescence (PL) spectroscopy was used to analyze the defect concentration. The results indicate that the defect types in the yellow Li1.01In1Se2 single crystal are VSe + and LiIn 2−; these result from the introduction of excess Li and the suppression of the adverse defects in InLi 2+ and VLi −. These results demonstrate a feasible route for obtaining high-quality yellow 6LiInSe2 crystals and promote the application of 6LiInSe2 neutron detectors.

Abstract Congenital long QT syndrome (LQTS) is a genetic heart disorder, which may lead to life-threatening arrhythmias, especially in children. Here, we reported two children who were initially misdiagnosed with epilepsy and experienced Torsades de Pointes (TdP) cardiac electrical storm (ES). Through whole exome sequencing (WES), we identified two Potassium voltage-gated channel subfamily H member 2 (KCHN2) mutations (c.1841 C > T and c.1838 C > T) respectively in a 6-year-old boy and a 13-year-old girl. Clinical data indicated that the QT interval was significantly prolonged, the T-wave pattern of chest V5-V6 leads and limb leads were inverted. Our study suggests that patients with epilepsy, especially those refractory epilepsy with atypical features, need comprehensive evaluation of cardiovascular function. KCNH2 mutation in pore region, QT interval prolongation and T wave inversion are high risk factors for ES. For LQT2 patients with ES, Nadolol and left cardiac sympathetic denervation are indicated, sometimes with an ICD.

Abstract Grape seed proanthocyanidin extract (GSPE) is a natural polyphenolic compound, which plays an important role in anti-inflammatory and antioxidant. The present study aimed to investigate the effects of GSPE supplementation on the cholesterol metabolism and antioxidant status of finishing pigs. In longissimus dorse (LD) muscle, the data showed that GSPE significantly decreased the contents of total cholesterol (T-CHO) and triglyceride (TG), and decreased the mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) and Fatty acid synthase (FAS), while increased the mRNA expression of carnitine palmitoyl transferase-1b (CPT1b), peroxisome proliferator-activated receptors (PPARα) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). GSPE also reduced the enzyme activities of HMG-CoAR and FAS, and meanwhile amplified the activity of CPT1b in LD muscle of finishing pigs. Furthermore, dietary GSPE supplementation increased the serum catalase (CAT) and total antioxidant capacity (T-AOC), serum and liver total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) levels, while reduced serum and liver malondialdehyde (MDA) level in finishing pigs. In the liver, Superoxide Dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase 1 (GPX1), Nuclear Factor erythroid 2-Related Factor 2 (NRF2) mRNA levels were increased by GSPE. In conclusion, this study showed that GSPE might be an effective dietary supplement for improving cholesterol metabolism and antioxidant status in finishing pigs.

Abstract Objective This study was to investigate the carcinogenic capacity of circYARS in laryngeal squamous cell carcinoma (LSCC) and to reveal its potential mechanism as a competitive endogenous RNA. Methods The differentially expressed circRNA and mRNA in LSCC were detected by RT-qPCR. Dual luciferase reporter assay and RIP were conducted to test the interaction between circYARS, miR-29a-3p, and IREB2. The functional effects of these molecules were investigated by CCK-8, flow cytometry, colony formation assay, Transwell, Western blot, and xenotransplantation mouse models. Results In LSCC tissues and cell lines, circYARS and IREB2 levels were enhanced, while miR-29a-3p level was lowered. Depleting circYARS led to decreased IREB2 by promoting miR-29a-3p expression. As a result of miR-29a-3p enhancement or circYARS silence, the proliferative, migratory, and invasion of cancer cells were suppressed and apoptosis was stimulated. Conclusion circYARS is involved in the tumorigenicity and progression of LSCC through the miR-29a-3p/IREB2 axis, providing strategies and targets for therapeutic intervention of LSCC.

Background Undergraduates, as the backbone of the youth group and highly educated members of the family and society, had a strong radiating function on the health of the whole population. Undergraduates have good health awareness but poor health behaviors, and the realization of proactive health among undergraduates faces a series of challenges that require conceptual change and action support. Objective To study the influencing factors of proactive health of undergraduates and provide suggestions for health education in colleges and universities. Methods A total of 4 036 undergraduates from 6 universities in Shandong Province were selected by stratified cluster sampling method to conduct a questionnaire survey on proactive health by using self-designed questionnaires (including general information questionnaires and proactive health scales). Pearson correlation analysis and multiple linear regression analysis were used for the analysis of factors affecting proactive health, and the importance of influencing factors was analyzed using random forest metrics. Results The proactive health score of undergraduates was 24.61±4.65 score. Females had higher active health scores than males, while lower grade undergraduates had higher proactive health scores than higher grade (P

Traditional encrypted communication technologies have been easily detected and have struggled to meet the needs of secure communication. Steganography, capable of hiding information by modifying the carrier, has been utilized to realize covert communication. However, the potential for steganography to be employed in illegal acts has directed increasing attention towards steganalysis for the detection of steganography, thereby bestowing great research significance upon it. Deep learning has yielded numerous research achievements in fields such as computer vision, pattern recognition, and natural language processing, introducing new opportunities and challenges to steganalysis. These advancements have propelled the generation of new ideas and methods in steganalysis. Currently, color images constitute the mainstream carrier in the process of internet transmission. Nevertheless, existing steganalysis features for color images primarily rely on manual design and often treat the color image as three independent grayscale images, without fully considering the internal relationships between the three color channels, thus necessitating an improvement in detection capabilities for encrypted images. The application of deep learning in the field of color image steganalysis remains in its preliminary stage. The concepts, classifications, and research significance of steganography and steganalysis were introduced, along with an outline of their current research status. Several key techniques for the steganalysis of color images were introduced, compared, summarized, and their development trends were analyzed.

Abstract Red swamp crayfish, Procambarus clarkii, is the most cultured freshwater crayfish species. It attracts significant research attention due to its considerable economic importance. However, the limited availability of genome information has impeded further genetic studies and breeding programs. By utilizing Illumina, PacBio, and Hi-C sequencing technologies, we present a more comprehensive and continuous chromosome-level assembly for P. clarkii than the published one. The final genome size is 4.03 Gb, consisting of 2,358 scaffolds with a N50 of 42.87 Mb. Notably, 3.68 Gb, corresponding to 91.42% of the genome, was anchored to 94 chromosomes. The assembly comprises 70.64% repetitive sequences, including 5.21% tandem repeats and 65.40% transposable elements. Additionally, a total of 4,456 non-coding RNAs and 28,852 protein-coding genes were predicted in the P. clarkii genome, with 96.26% of the genes were annotated. This high-quality genome assembly not only represents a significant improvement for the genome of P. clarkii and provides insights into the unique genome evolution, but also offers valuable information for developing freshwater aquaculture and accelerating genetic breeding.

Abstract Background Sjögren’s Syndrome (SS) is a rare chronic autoimmune disorder primarily affecting adult females, characterized by chronic inflammation and salivary and lacrimal gland dysfunction. It is often associated with systemic lupus erythematosus, rheumatoid arthritis and kidney disease, which can lead to increased mortality. Early diagnosis is critical, but traditional methods for diagnosing SS, mainly through histopathological evaluation of salivary gland tissue, have limitations. Methods The study used 100 labial gland biopsy, creating whole-slide images (WSIs) for analysis. The proposed model, named Cell-tissue-graph-based pathological image analysis model (CTG-PAM) and based on graph theory, characterizes single-cell feature, cell-cell feature, and cell-tissue feature. Building upon these features, CTG-PAM achieves cellular-level classification, enabling lymphocyte recognition. Furthermore, it leverages connected component analysis techniques in the cell graph structure to perform SS diagnosis based on lymphocyte counts. Findings CTG-PAM outperforms traditional deep learning methods in diagnosing SS. Its area under the receiver operating characteristic curve (AUC) is 1.0 for the internal validation dataset and 0.8035 for the external test dataset. This indicates high accuracy. The sensitivity of CTG-PAM for the external dataset is 98.21%, while the accuracy is 93.75%. In comparison, the sensitivity and accuracy for traditional deep learning methods (ResNet-50) are lower. The study also shows that CTG-PAM’s diagnostic accuracy is closer to skilled pathologists compared to beginners. Interpretation Our findings indicate that CTG-PAM is a reliable method for diagnosing SS. Additionally, CTG-PAM shows promise in enhancing the prognosis of SS patients and holds significant potential for the differential diagnosis of both non-neoplastic and neoplastic diseases. The AI model potentially extends its application to diagnosing immune cells in tumor microenvironments.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis that is a rare complication of ovarian teratoma. The primary treatment is surgical resection of the tumor combined with immunotherapy, however, the pathogenesis of ovarian teratoma associated anti-NMDAR encephalitis is still unclear. In addition, the patients present with various clinical manifestations, with neurological manifestations predominating, which is easy to be misdiagnosed and overlooked, requiring joint diagnosis and treatment by gynecologists and neurologists. This article briefly describes the structure and function of NMDAR, reviews the previous research results on ovarian teratoma associated anti-NMDAR encephalitis, and summarizes the research progress on its pathogenesis, early diagnosis, differential diagnosis, treatment, prognosis and recurrence, aiming to provide theoretical basis and ideas for better diagnosis and treatment of ovarian teratoma associated anti-NMDAR encephalitis.

In this study, we consider the introduction of new mobility services and technologies into the megacity of Beijing, China, as per developed strategy and action plans, in order to investigate their potential contribution to sustainable mobility. This includes population relocation (decentralization), the construction of new rail lines, the introduction of shared bike services as a feeder to subway stations, the electrification of passenger vehicles and the adoption of automated and shared vehicles. The well-established, system dynamics-based MARS model is adapted to Beijing and further improved via the inclusion of these new services, technologies and policies. We find that decentralization can have a profound effect on overall sustainability if not considered in conjunction with other policies and that new rail lines and shared bikes may only have benefits in specific zones. Shared and automated vehicles could increase VKT by 60% and reduce active and public transport trips by a quarter. As such, nuanced integrated policy approaches will be required that are similar to those currently in place, such as imposed car shedding and taxi fleet control.

Abstract Background Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS). Methods The SCCS is a prospective cohort of primarily low-income adults aged 40–79, enrolled from the southeastern United States during 2002–2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants. Results Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P

Carbon mitigation technologies lead to air quality improvement and health co-benefits, while the practical effects of the technologies are dependent on the energy composition, technological advancements, and economic development. In China, mitigation technologies such as end-of-pipe treatment, renewable energy adoption, carbon capture and storage (CCS), and sector electrification demonstrate significant promise in meeting carbon reduction targets. However, the optimization of these technologies for maximum co-benefits remains unclear. Here, we employ an integrated assessment model (AIM/enduse, CAM-chem, IMED|HEL) to analyze air quality shifts and their corresponding health and economic impacts at the provincial level in China within the two-degree target. Our findings reveal that a combination of end-of-pipe technology, renewable energy utilization, and electrification yields the most promising results in air quality improvement, with a reduction of fine particulate matter (PM2.5) by −34.6 μg m−3 and ozone by −18.3 ppb in 2050 compared to the reference scenario. In contrast, CCS technology demonstrates comparatively modest improvements in air quality (−9.4 μg m−3 for PM2.5 and −2.4 ppb for ozone) and cumulative premature deaths reduction (−3.4 million from 2010 to 2050) compared to the end-of-pipe scenario. Notably, densely populated regions such as Henan, Hebei, Shandong, and Sichuan experience the most health and economic benefits. This study aims to project effective future mitigation technologies and climate policies on air quality improvement and carbon mitigation. Furthermore, it seeks to delineate detailed provincial-level air pollution control strategies, offering valuable guidance for policymakers and stakeholders in pursuing sustainable and health-conscious environmental management.

Bronchopulmonary dysplasia (BPD) is a severe lung disease in preterm infants, the abnormal proliferate and differentiate ability of type II epithelial cells (AEC II) is the key to the pathological basis of BPD. Mechanisms regarding abnormal AEC II in BPD remain unclear. The present work investigated the role and mechanisms of invariant natural killer T (iNKT) cells in lung disorder in BPD using public datasets, clinical samples, a hyperoxia-induced BPD mouse model and AEC II-iNKT cells transwell co-culture system. Firstly, we found that the NKT cells development factor IL-15 increased over time in patients with BPD in public databases, and clinically collected peripheral blood NKT cells in patients with BPD were increased. Subsequently, the percentage of iNKT cells increased in hyperoxia group compared with normoxia group, with the highest at P7, accompanied by increased activation with abnormal lung development. The administration of anti-CD1d neutralizing antibody to inhibit iNKT cells could alleviate the abnormal lung development of hyperoxia group mice, while α-GalCer administration could aggravate lung injury in hyperoxia group mice, and adoptive transfer of iNKT cells could aggravate the abnormal lung development in hyperoxia group mice. In addition, to further verify the role of iNKT cells on AEC II, AEC II-iNKT cells co-culture system was established. The presence of iNKT cells could aggravate the abnormal expression of SP-C and T1α under hyperoxia. Meanwhile, RNA-seq analysis showed that ferroptosis-related genes were highly expressed in AEC II co-cultured with iNKT cells under hyperoxia. We further validated the effect of the presence of iNKT cells under hyperoxia environment on AEC II ferroptosis levels, suggested that iNKT cells promote AEC II ferroptosis under hyperoxia, accompanied by decreased expression of SP-C and T1α. Our study found that the recruitment of iNKT cells in the lung may be an important cause of alveolarization disorder in BPD.

Abstract Gut microbiota is related to host fitness, and influenced by geographical locations and habitats. Pomacea canaliculata is a malignant invasive alien snail that threatens agricultural production and ecosystem functions worldwide. Clarifying the general rules of the gut microbial community structure and function of the snails in different geographical locations and habitats is of great significance for understanding their invasion at different spatial scales. This study used high‐throughput sequencing technology to compare and analyze the differences in community structure and function of gut microbiota in P. canaliculata from five geographical locations (Liuzhou, Yulin, Nanning, Wuzhou, and Hezhou) and three different habitats (pond, paddy field, and ditch) in Guangxi Province. The results showed that intestinal microbial alpha diversity of P. canaliculata was higher in Liuzhou, Yulin, lower in Nanning, Wuzhou, Hezhou, and higher in ponds compared with paddy fields and ditches. The dominant phyla of gut microbiota in snails were Firmicutes, Cyanobacteria, Proteobacteria, Fusobacteriota, Bacteroidota, and the dominant genus was Lactococcus. The community structure of gut microbiota in snails varied significantly across different geographical locations and habitats, and the phyla Firmicutes, Cyanobacteria had significantly higher relative abundance in snails collected from Nanning and Yulin, respectively. Moreover, the relative abundance of gut functional microbiota associated with human disease in P. canaliculata was significantly affected by geographical locations and habitats, and with the highest abundance in ponds. However, the relative abundance of functional microbiota related to metabolism, genetic information processing, organizational system, environmental information processing, and cellular processes were only significantly affected by geographical locations. Collectively, geographical locations and habitats had significantly different effects on the community structure and function of gut microbiota in P. canaliculata, and the greater differences were caused by geographical locations rather than by habitats.

BackgroundsGastric cancer (GC) remains a global health threat due to frequent treatment failures caused by primary or acquired resistance. Although cancer-associated fibroblasts (CAFs) have been implicated in this process, it is still unclear which specific subtype(s) of CAFs hinder T-cell infiltration and promote resistance to immunotherapy.MethodsWe analyzed the GC fibroblast atlas in detail by combining 63,955 single cells from 14 scRNA-seq datasets. We also performed RNA-seq data in a local GC cohort and examined 13 bulk RNA-seq datasets to understand the biological and clinical roles of different CAF subsets. Additionally, we conducted in vitro experiments to study the role of specific proteins in GC development.ResultsWe identified a total of 17 fibroblast subsets in gastric cancer, nine of which did not fit into the existing CAFs classification. These subsets exhibited significant heterogeneity in distribution and biological characteristics (metabolism, cell-cell interactions, differentiation state), as well as clinical functions such as prognosis and response to immunotherapy. In particular, cluster 6 stood out for its high expression of MFAP5, CFD, and PI16; it was found to be negatively associated with both overall survival and response to immunotherapy in GC. This association was linked to an immunosuppressive microenvironment characterized by an increase in M2 macrophages but higher levels of T cell dysfunction and exclusion—a feature shared by tumors expressing MFAP5. Furthermore, the addition of human recombinant MFAP5 promoted proliferation and migration of HGC-27 cells by inducing the MFAP5/NOTCH1/HEY1 signaling pathway.ConclusionWe introduce a high-resolution GC fibroblast atlas. The 17 identified fibroblast clusters provide valuable opportunities for gaining deeper biological insights into the relationship between fibroblasts and GC development. Particularly, cluster 6 and its specific marker MFAP5 could serve as prognostic factors in GC and form a foundation for personalized therapeutic combinations to address primary resistance to ICIs.

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1–101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

[Introduction] In recent years, as the installed capacity of the fusion device has been increasing, the power supply system of the device requires high-amplitude and long-pulse power output, which causes a strong power impact on the grid, and even power supply disconnection in severe cases to pose a serious threat to the safety of the fusion device. Additionally, the high-amplitude pulses also result in a lot of redundancy in the power supply system design. [Method] To solve these problems, this paper proposed a novel fusion power supply topology with energy storage, that is, the power supply system was designed with energy storage to mitigate the impact of pulse power on the grid. During the operation of the power supply, the grid provided steady-state power while the energy storage device delivered pulse power, effectively reducing the cost of the power supply. [Result] According to the experience in industrial power supply and distribution, this paper presents the calculation formulas for the selection of key components in different topologies and conducts a cost analysis and comparison for different power supply topologies based on simulation data. [Conclusion] The experimental results show that the new power supply topology not only reduces the power impact on the grid and improves the energy utilization of the power supply system, but also reduces transformer capacity, thus it is cost-efficient.

Abstract Background Influenza A viruses (IAV) are extremely common respiratory viruses for the acute exacerbation of chronic obstructive pulmonary disease (AECOPD), in which IAV infection may further evoke abnormal macrophage polarization, amplify cytokine storms. Melatonin exerts potential effects of anti-inflammation and anti-IAV infection, while its effects on IAV infection-induced AECOPD are poorly understood. Methods COPD mice models were established through cigarette smoke exposure for consecutive 24 weeks, evaluated by the detection of lung function. AECOPD mice models were established through the intratracheal atomization of influenza A/H3N2 stocks in COPD mice, and were injected intraperitoneally with melatonin (Mel). Then, The polarization of alveolar macrophages (AMs) was assayed by flow cytometry of bronchoalveolar lavage (BAL) cells. In vitro, the effects of melatonin on macrophage polarization were analyzed in IAV-infected Cigarette smoking extract (CSE)-stimulated Raw264.7 macrophages. Moreover, the roles of the melatonin receptors (MTs) in regulating macrophage polarization and apoptosis were determined using MTs antagonist luzindole. Results The present results demonstrated that IAV/H3N2 infection deteriorated lung function (reduced FEV20,50/FVC), exacerbated lung damages in COPD mice with higher dual polarization of AMs. Melatonin therapy improved airflow limitation and lung damages of AECOPD mice by decreasing IAV nucleoprotein (IAV-NP) protein levels and the M1 polarization of pulmonary macrophages. Furthermore, in CSE-stimulated Raw264.7 cells, IAV infection further promoted the dual polarization of macrophages accompanied with decreased MT1 expression. Melatonin decreased STAT1 phosphorylation, the levels of M1 markers and IAV-NP via MTs reflected by the addition of luzindole. Recombinant IL-1β attenuated the inhibitory effects of melatonin on IAV infection and STAT1-driven M1 polarization, while its converting enzyme inhibitor VX765 potentiated the inhibitory effects of melatonin on them. Moreover, melatonin inhibited IAV infection-induced apoptosis by suppressing IL-1β/STAT1 signaling via MTs. Conclusions These findings suggested that melatonin inhibited IAV infection, improved lung function and lung damages of AECOPD via suppressing IL-1β/STAT1-driven macrophage M1 polarization and apoptosis in a MTs-dependent manner. Melatonin may be considered as a potential therapeutic agent for influenza virus infection-induced AECOPD. Graphical Abstract Schematic mechanisms underlying the regulatory effects of melatonin on macrophage polarization and apoptosis in IAV infection plus cigarette stimulation-induced AECOPD model.

Abstract The regulation of thymocyte development by RNA-binding proteins (RBPs) is largely unexplored. We identify 642 RBPs in the thymus and focus on Arpp21, which shows selective and dynamic expression in early thymocytes. Arpp21 is downregulated in response to T cell receptor (TCR) and Ca2+ signals. Downregulation requires Stim1/Stim2 and CaMK4 expression and involves Arpp21 protein phosphorylation, polyubiquitination and proteasomal degradation. Arpp21 directly binds RNA through its R3H domain, with a preference for uridine-rich motifs, promoting the expression of target mRNAs. Analysis of the Arpp21–bound transcriptome reveals strong interactions with the Rag1 3′-UTR. Arpp21–deficient thymocytes show reduced Rag1 expression, delayed TCR rearrangement and a less diverse TCR repertoire. This phenotype is recapitulated in Rag1 3′-UTR mutant mice harboring a deletion of the Arpp21 response region. These findings show how thymocyte-specific Arpp21 promotes Rag1 expression to enable TCR repertoire diversity until signals from the TCR terminate Arpp21 and Rag1 activities.

Abstract The telomere repeat-containing RNA (TERRA) forms R-loops to promote homology-directed DNA synthesis in the alternative lengthening of telomere (ALT) pathway. Here we report that TERRA contributes to ALT via interacting with the lysine-specific demethylase 1A (LSD1 or KDM1A). We show that LSD1 localizes to ALT telomeres in a TERRA dependent manner and LSD1 function in ALT is largely independent of its demethylase activity. Instead, LSD1 promotes TERRA recruitment to ALT telomeres via RNA binding. In addition, LSD1 and TERRA undergo phase separation, driven by interactions between the RNA binding properties of LSD1 and the G-quadruplex structure of TERRA. Importantly, the formation of TERRA-LSD1 condensates enriches the R-loop stimulating protein Rad51AP1 and increases TERRA-containing R-loops at telomeres. Our findings suggest that LSD1-TERRA phase separation enhances the function of R-loop regulatory molecules for ALT telomere maintenance, providing a mechanism for how the biophysical properties of histone modification enzyme-RNA interactions impact chromatin function.

ABSTRACT: Lutein is an antioxidant that can indicate the oxidative status of organisms through its coloration and may be involved in the development process of chicken skeletal muscle. In this study, after feeding Nanhai Yellow Chickens with lutein-containing feed for 21 d, the lutein group significantly increased the muscle fiber diameter and decreased the fiber density in the chicken's leg muscles compared to the control group. To elucidate the potential regulatory mechanisms by which lutein is involved in muscle development, RNA-seq was used to detect changes in gene expression in chicken leg muscle tissue. After data analysis, a total of 249 significantly differentially expressed genes (DEG) were identified, including TGF-β superfamily (MSTN and TGFB1) and nonreceptor tyrosine kinase c-Src (SRC). Results from GO and KEGG analysis showed that the DEGs were enriched in GO terms such as positive regulation of the ERK1/ERK2 cascade and negative regulation of myoblast differentiation, as well as signaling pathways including the Toll-like receptor signaling pathway and the MAPK signaling pathway. These significantly enriched GO terms and pathways are closely related to muscle development, suggesting that lutein may play an important role in the process of chicken muscle development. This study provides insights into the regulatory mechanisms of dietary lutein on chicken muscle development.

BackgroundGlaucoma, a leading cause of global blindness, is characterized by optic nerve damage and visual field loss. Previous studies have suggested a potential association between glaucoma and anxiety disorders. However, the causal relationship between these two conditions remains unclear.MethodsIn this study, we conducted a Mendelian Randomization analysis to investigate the causal relationship between glaucoma and anxiety disorders. We sourced Genome-Wide Association Study (GWAS) datasets for glaucoma and anxiety with the largest sample sizes from the Integrative Epidemiology Unit OpenGWAS (IEU OpenGWAS) project website. Instrumental variables were selected based on specific criteria, and statistical analyses were performed using the R programming language.ResultsAfter filtering and merging the datasets, a total of 60 Single Nucleotide Polymorphisms (SNPs) were obtained for analysis. Regression models were applied to assess the causal relationship between glaucoma and anxiety disorders. The results from all four methods indicated that glaucoma does not cause anxiety disorders (p > 0.05).ConclusionThrough rigorous Mendelian Randomization analysis, our findings indicate that glaucoma is not a causative factor for anxiety, with minimal influence from confounding factors in this study. These findings enhance our understanding of the relationship between glaucoma and anxiety.

Ultraviolet B (UVB) light exposure accelerates skin photoaging. Human adipose-derived stem cell exosomes (hADSC-Exos) and some antioxidants may have anti-photoaging effects. However, it is unknown whether the combination of hADSC-Exos and antioxidants plays a synergistic role in anti-photoaging. In cellular and 3D skin models, we showed that vitamin E (VE) and hADSC-Exos were optimal anti-photoaging combinations. In vivo, VE and hADSC-Exos increased skin tightening and elasticity in UVB-induced photoaging mice Combined treatment with VE and hADSC-Exos inhibited SIRT1/NF-κB pathway. These findings contribute to the understanding of hADSC-Exos in conjunction with other antioxidants, thereby providing valuable insights for the future pharmaceutical and cosmetic industries.

Objective To develop a nomogram for predicting occurrence of secondary pulmonary infection in patients with critically traumatic brain injury (TBI) during their stay in the intensive care unit, to further optimise personalised treatment for patients and support the development of effective, evidence-based prevention and intervention strategies.Data source This study used patient data from the publicly available MIMIC-IV (Medical Information Mart for Intensive Care IV) database.Design A population-based retrospective cohort study.Methods In this retrospective cohort study, 1780 patients with TBI were included and randomly divided into a training set (n=1246) and a development set (n=534). The impact of pulmonary infection on survival was analysed using Kaplan-Meier curves. A univariate logistic regression model was built in training set to identify potential factors for pulmonary infection, and independent risk factors were determined in a multivariate logistic regression model to build nomogram model. Nomogram performance was assessed with receiver operating characteristic (ROC) curves, calibration curves and Hosmer-Lemeshow test, and predictive value was assessed by decision curve analysis (DCA).Result This study included a total of 1780 patients with TBI, of which 186 patients (approximately 10%) developed secondary lung infections, and 21 patients died during hospitalisation. Among the 1594 patients who did not develop lung infections, only 85 patients died (accounting for 5.3%). The survival curves indicated a significant survival disadvantage for patients with TBI with pulmonary infection at 7 and 14 days after intensive care unit admission (p1, p

Summary: Cleaner heating policies aim to reduce air pollution and may bring about health benefits to individuals. Based on a fixed-effect model focusing on Beijing, this study found that after the onset of air pollution, daily clinic visits, hospitalization days, and hospitalization expenses increased several days after the occurrence of air pollution. These hospitalization changes were observed in males and females and three different age groups. A difference-in-differences (DID) model was constructed to identify the influences of cleaner heating policies on health consequences. The study revealed that the policy positively affects health outcomes, with an average decrease of 3.28 thousand clinic visits for all diseases. The total hospitalization days and expenses tend to decrease by 0.22 thousand days and 0.34 million CNY (Chinese Yuan), respectively. Furthermore, implementing the policy significantly reduced the number of daily clinic visits for respiratory diseases, asthma, stroke, diabetes, and chronic obstructive pulmonary diseases (COPDs).

IntroductionMild cognitive impairment (MCI) is an important stage in Alzheimer’s disease (AD) research, focusing on early pathogenic factors and mechanisms. Examining MCI patient subtypes and identifying their cognitive and neuropathological patterns as the disease progresses can enhance our understanding of the heterogeneous disease progression in the early stages of AD. However, few studies have thoroughly analyzed the subtypes of MCI, such as the cortical atrophy, and disease development characteristics of each subtype.MethodsIn this study, 396 individuals with MCI, 228 cognitive normal (CN) participants, and 192 AD patients were selected from ADNI database, and a semi-supervised mixture expert algorithm (MOE) with multiple classification boundaries was constructed to define AD subtypes. Moreover, the subtypes of MCI were obtained by using the multivariate linear boundary mapping of support vector machine (SVM). Then, the gray matter atrophy regions and severity of each MCI subtype were analyzed and the features of each subtype in demography, pathology, cognition, and disease progression were explored combining the longitudinal data collected for 2 years and analyzed important factors that cause conversion of MCI were analyzed.ResultsThree MCI subtypes were defined by MOE algorithm, and the three subtypes exhibited their own features in cortical atrophy. Nearly one-third of patients diagnosed with MCI have almost no significant difference in cerebral cortex from the normal aging population, and their conversion rate to AD are the lowest. The subtype characterized by severe atrophy in temporal lobe and frontal lobe have a faster decline rate in many cognitive manifestations than the subtype featured with diffuse atrophy in the whole cortex. APOE ε4 is an important factor that cause the conversion of MCI to AD.ConclusionIt was proved through the data-driven method that MCI collected by ADNI baseline presented different subtype features. The characteristics and disease development trajectories among subtypes can help to improve the prediction of clinical progress in the future and also provide necessary clues to solve the classification accuracy of MCI.

Huangqi Guizhi Wuwu Decoction (HQGZWWD) has shown promising potential in treating various cardiovascular diseases. This study aimed to elucidate the molecular basis and therapeutic role of HQGZWWD in the treatment of doxorubicin (DOX)-induced myocardial injury. The HPLC fingerprint of HQGZWWD was used to analyze the active components. A DOX-induced myocardial damage rat model was developed, and the therapeutic effects of HQGZWWD were evaluated using echocardiography, myocardial enzyme levels, and hematoxylin and eosin staining. Network pharmacology was used to screen treatment targets, and western blotting and immunohistochemistry were performed to assess cellular pyroptosis levels. Oxidative stress levels were measured using assay kits, and mitochondrial damage was examined using transmission electron microscopy. An in vitro model of DOX-induced cell damage was established, and treatment was administered using serum containing HQGZWWD and N-acetylcysteine (NAC). Oxidative stress levels were detected using assay kits and DCFH-DA, whereas cellular pyroptosis levels were assessed through WB, immunofluorescence, and ELISA assays. HQGZWWD ameliorated DOX-induced myocardial injury. Network pharmacology identified IL-1β and IL-18 as crucial targets. HQGZWWD downregulated the protein levels of the inflammatory factors IL-1β and IL-18, inhibited the expression of GSDMD-NT, and simultaneously suppressed the synthesis of Caspase-1, ASC, NLRP3, and Caspase-11. Additionally, HQGZWWD inhibited oxidative stress, and the use of NAC as an oxidative stress inhibitor resulted in significant inhibition of the GSDMD-NT protein in H9C2 cells. These findings highlight the myocardial protective effects of HQGZWWD by inhibiting oxidative stress and suppressing both canonical and non-canonical pyroptotic pathways.

Summary: Ambitious action plans have been launched to address climate change and air pollution. Through coupling the IMED|CGE, GAINS, and IMED|HEL models, this study investigate the impacts of implementing carbon neutrality and clean air policies on the energy-environment-health-economy chain in the Beijing-Tianjin-Hebei-Henan-Shandong-Shanxi region of China. Results show that Shandong holds the largest reduction in energy consumption and carbon emissions toward the 1.5°C target. Shandong, Henan, and Hebei are of particularly prominent pollutant reduction potential. Synergistic effects of carbon reduction on decreasing PM2.5 concentration will increase in the future, specifically in energy-intensive regions. Co-deployment of carbon reduction and end-of-pipe technologies are beneficial to decrease PM2.5-related mortalities and economic loss by 4.7–12.9% in 2050. Provincial carbon reduction cost will be higher than monetary health benefits after 2030, indicating that more zero-carbon technologies should be developed. Our findings provide scientific enlightenment on policymaking toward achieving carbon reduction and pollution mitigation from multiple perspectives.