Superenhancer-driven circRNA Myst4 involves in pulmonary artery smooth muscle cell ferroptosis in pulmonary hypertension.

The abnormal expression of circular RNAs (circRNAs) is emerging as a critical cause in regulation of pathological changes of hypoxic pulmonary hypertension (PH), in which ferroptosis is a new pathological change reported recently. However, how circRNAs regulate ferroptosis remains unclear. Here, we proved a significant decrease in circMyst4 expression in hypoxia. In vitro assays revealed that circMyst4 alleviated hypoxic pulmonary artery smooth muscle cell (PASMC) ferroptosis through directly combing with DDX5 in the nucleus to promote GPX4 mRNA processing and inhibiting the formation of the Eef1a1/ACSL4 complex in the cytoplasm. Additionally, superenhancer (SE) was verified to drive the generation of circMyst4. In vivo assays revealed that circMyst4 inhibited the progression of hypoxic PH. Overall, SE-driven circMyst4 may be a new potential therapeutic target for mediating PASMC ferroptosis through promoting DDX5-regulated GPX4 mRNA processing and inhibiting the binding between Eef1a1 and ACSL4.

Restriction of salt, alcohol and coffee intake and Ménière's disease: insight from Mendelian randomization study.

Background: Restricting salt, caffeine, and alcohol intake is commonly recommended as a first-line treatment for patients with Ménière's disease (MD). However, it remains unclear whether these interventions effectively improve symptoms of MD. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the relationship between these dietary modifications and MD. Methods: Summary statistics for salt added to food, alcohol consumption, coffee consumption, and MD were sourced from the United Kingdom Biobank, GSCAN, and the FinnGen study, involving up to 941,280 participants. The main analyses were performed using the random-effects inverse-variance weighted (IVW) approach and were complemented by four additional methods. Multiple sensitivity analyses were performed to validate the findings, and both forward and reverse MR analyses were employed to address potential reverse causality bias. Results: The primary MR results using the IVW method revealed that salt added to food (OR = 0.719, 95% CI: 0.429-1.206; p = 0.211), alcohol consumption (OR = 0.834, 95% CI: 0.427-1.628; p = 0.595), and coffee consumption (OR = 0.852, 95% CI: 0.555-1.306; p = 0.461) were not significantly correlated with MD. In reverse analysis, no evidence of significant effect was found from MD to salt added to food (OR = 1.000, 95% CI: 0.993-1.007; p = 0.957), alcohol consumption (OR = 0.998, 95% CI: 0.987-1.008; p = 0.682), and coffee consumption (OR = 0.998, 95% CI: 0.985-1.011; p = 0.72). Conclusion: This MR analysis did not identify convincing evidence to support the idea that restricting salt, caffeine, and alcohol intake is beneficial for the treatment of MD.

CircSSR1 regulates pyroptosis of pulmonary artery smooth muscle cells through parental protein SSR1 mediating endoplasmic reticulum stress.

INTRODUCTION: Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. METHODS: RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. RESULTS: CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. CONCLUSION: Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.

Polyethylene Glycol-Enzyme Nanocomplexes as Carrier-free Biocatalyst for Pickering Interfacial Catalysis.

PEG-enzyme nanocomplexes are prepared and stabilized in an oil-in-water-type emulsion for Pickering interfacial biocatalysis, and these nanocomplexes function as catalysts and emulsifiers at the emulsion interface. The nanocomplexes are self-assembled by cross-linking mPEG-ALD with lipase, without complicated synthesis steps, toxic chemical reagents, and external carriers. Moreover, the mild cross-linking process preserves the original structure of the enzyme, the retention rate of enzyme activity is 82.1%, and the nanocomplexes are used to emulsify biphasic aqueous-organic solution into Pickering emulsion. The system exhibits excellent reusability, with enzyme activity remaining at 86.05% after five cycles, providing a desirable eco-friendly platform for carrier-free Pickering interfacial biocatalysis.

Mass Spectrometry Analysis of Neurotransmitter Shifting during Neurogenesis and Neurodegeneration of PC12 Cells.

Parkinson's disease (PD) affects movement; however, most patients with PD also develop nonmotor symptoms, such as hyposmia, sleep disorder, and depression. Dopamine levels in the brain have a critical influence on movement control, but other neurotransmitters are also involved in the progression of PD. This study analyzed the fluctuation of neurotransmitters in PC12 cells during neurogenesis and neurodegeneration by performing mass spectrometry. We found that the dopaminergic metabolism pathway of PC12 cells developed vigorously during the neuron differentiation process and that the neurotransmitters were metabolized into 3-methoxytyramine, which was released from the cells. The regulation of the intracellular and extracellular concentrations of adenosine indicated that adenine nucleotides were actively utilized in neural differentiation. Moreover, we exposed the differentiated PC12 cells to rotenone, which is a suitable material for modeling PD. The cells exposed to rotenone in the early stage of differentiation exhibited stimulated serotoninergic metabolism, and the contents of the serotoninergic neurotransmitters returned to their normal levels in the late stage of differentiation. Interestingly, the nondifferentiated cells can resist the toxicant rotenone and produce normal dopaminergic metabolites. However, when differentiated neuron cells were exposed to rotenone, they were seriously damaged, leading to a failure to produce dopaminergic neurotransmitters. In the low-dosage damage process, the amino acids that functioned as dopaminergic pathway precursors could not be absorbed by the cells, and dopamine and L-dopa were secreted and unable to be reuptaken to trigger the cell damage.

Association of diabetic retinopathy with plasma atherosclerotic index, visceral obesity index, and lipid accumulation products: NHANES 2005-2008.

BACKGROUND: Abdominal obesity, a significant risk factor for the progression of diabetic retinopathy (DR), may lead to improved visual outcomes through early assessment. This study aims to evaluate any potential associations between DR and novel lipid metabolism markers, including the Atherogenic Index of Plasma (AIP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP). METHODS: This study aimed to elucidate the association between various lipid markers and DR by screening the National Health and Nutrition Examination Survey (NHANES) database in the United States from 2005 to 2008. To examine the correlation, multifactor logistic regression analysis, subgroup analysis, threshold effect analysis, interaction test, and smooth curve fitting were used. RESULTS: Among the 2591 participants included, the incidence of DR was 13.6% and the mean age was 59.55 ± 12.26 years. After adjusting for important confounding covariates, logistic regression studies suggested a possible positive association between LAP, VAI, AIP, and DR occurrence (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.002, 1.006; P < 0.0001; [OR] = 1.090; 95% [CI]: 1.037, 1.146; P = 0.0007; [OR] = 1.802; 95% [CI]: 1.240, 2.618; P = 0.0020). The nonlinear association between LAP and DR was further illustrated using an S-shaped curve by smoothing curve fitting, with the inflection point of the curve located at 63.4. Subgroup analyses and interaction tests were performed with full variable adjustment (P > 0.05 for all interactions). CONCLUSION: Studies have shown that elevated levels of LAP, VAI, and AIP increase the likelihood of DR, suggesting that they have the potential to be predictive markers of DR, emphasizing their potential utility in risk assessment and prevention strategies, and advocating for early intervention to mitigate the likelihood of DR.

Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish.

The ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-ß family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-ß signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/NO.

The associations between modifiable risk factors and constipation: a comprehensive mendelian randomization study.

OBJECTIVE: Early identification of modifiable risk factors is crucial for the prevention of constipation. This study systematically investigated the relationship between genetically predicted modifiable risk factors and constipation. METHODS: The inverse variance weighting (IVW) method was employed as the primary analytical approach. For similar exposure indicators, the multivariate Mendelian randomization (MVMR) method was used to adjust for potential biases in univariate MR analysis. The robustness of the results was further evaluated using the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis. Bonferroni correction was applied to reduce the false positive rate in the results. RESULTS: The IVW analysis indicated a significant causal association between genetically predicted gastroesophageal reflux disease [OR (95% CI) = 1.192 (1.079-1.315), P = 0.0005], atorvastatin use [OR (95% CI) = 16.995 (3.327-86.816), P = 0.0007], and constipation. Additionally, there was a potential causal association between education level [OR (95% CI) = 0.859 (0.767-0.964), P = 0.009], major depressive disorder [OR (95% CI) = 1.206 (1.041-1.399), P = 0.013], hypothyroidism [OR (95% CI) = 2.299 (1.327-3.985), P = 0.003], and aspirin use [OR (95% CI) = 4.872 (1.174-20.221), P = 0.029] with constipation. No causal associations were found for the other included indicators. Sensitivity analysis demonstrated the absence of evidence for heterogeneity and pleiotropy in any positive results. CONCLUSION: This study identified several risk factors that could be targeted for the prevention of constipation, offering valuable insights for public health policies.

Assessing the Predictive Utility of the C-Reactive Protein-to-Lymphocyte Ratio for Mortality in Isolated Traumatic Brain Injury: A Single-Center Retrospective Analysis.

Introduction: Early identification of high-risk traumatic brain injury (TBI) patients is crucial for optimizing treatment strategies and improving outcomes. The C-reactive protein-to-lymphocyte ratio (CLR) reflects systemic immunology and inflammation function and serves as a new biomarker for patient stratification. This study aimed to assess the predictive value of the CLR for mortality in patients with isolated moderate to severe TBI. Methods: A retrospective analysis of trauma registry data from 2009 to 2022 was conducted, including 1641 adult patients with isolated moderate to severe TBI. Patient demographics, the CLR, injury characteristics, and outcomes were compared between deceased and surviving patients. Univariate and multivariate analyses were performed to identify mortality risk factors. The optimal CLR cut-off value for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis. Results: The CLR was significantly higher in deceased patients compared to survivors (60.1 vs. 33.9, p < 0.001). The optimal CLR cut-off value for predicting mortality was 54.5, with a sensitivity of 0.328 and a specificity of 0.812. The area under the ROC curve was 0.566, indicating poor discriminative ability. In the multivariate analysis, the CLR was not a significant independent predictor of mortality (OR 1.03, p = 0.051). After propensity score matching to attenuate the difference in baseline characteristics, including sex, age, comorbidities, conscious level, and injury severity, the high-CLR group (CLR ≥ 54.5) did not have significantly higher mortality compared to the low-CLR group (CLR < 54.5). Conclusion: While the CLR was associated with mortality in TBI patients, it demonstrated poor discriminative ability as a standalone predictor. The association between a high CLR and worse outcomes may be primarily due to other baseline patient and injury characteristics, rather than the CLR itself.

Perceived stress and prenatal depression symptoms among couples with gestational diabetes mellitus: The mediating role of dyadic coping.

PROBLEM: No studies have been conducted to examine the relationships between perceived stress, positive/negative dyadic coping, and prenatal depression symptoms in Chinese couples with gestational diabetes mellitus (GDM). BACKGROUND: GDM is a stressful event for pregnant women and their partners, which may result in clinically significant prenatal depression symptoms in couples. AIM: This study aims to examine the relationships and differences in perceived stress, positive/negative dyadic coping, and prenatal depression symptoms between Chinese pregnant women with GDM and their partners and to explore the mediating role of positive/negative dyadic coping. METHODS: A cross-sectional study was conducted in Guangzhou, China, from January to October 2021. 402 pairs of GDM couples completed the questionnaires, including the Edinburgh Postnatal Depression Scale, the Chinese version of the Dyadic Coping Inventory, and the Perceived Stress Scale. Dyadic data was analyzed using the actor-partner interdependence mediation model. FINDINGS: 37.6 % of pregnant women with GDM and 24.6 % of their partners experienced clinically significant prenatal depression symptoms. Depression symptoms in couples mutually influence each other. Perceived stress was directly or indirectly related to their and partners' prenatal depression symptoms in GDM couples, with negative dyadic coping acting as a mediator. Maternal negative dyadic coping was also a partner-mediator. DISCUSSION: The findings of the present study may provide healthcare professionals with a better understanding of the effect of the interpersonal interaction between the couples as a dyad on prenatal depression symptoms in Chinese context. CONCLUSION: There were intrapersonal and interpersonal associations among perceived stress, negative dyadic coping, and prenatal depression symptoms in pregnant women with GDM and their partners. It suggests a need for screening clinically significant prenatal depression symptoms and decreasing perceived stress and negative dyadic coping among couples with GDM with a focus on pregnant women with GDM.

Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis.

BACKGROUND: Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown. AIM: To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease (NAFLD) risk. METHODS: Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study (GWAS) conducted by the Blood Cell Consortium. Summary-level data for liver enzymes were obtained from the United Kingdom Biobank. NAFLD data were obtained from a GWAS meta-analysis (8434 cases and 770180 controls, discovery dataset) and the Fingen GWAS (2275 cases and 372727 controls, replication dataset). This analysis was conducted using the inverse-variance weighted method, followed by various sensitivity analyses. RESULTS: One SD increase in the genetically predicted haemoglobin concentration (HGB) was associated with a ß of 0.0078 (95%CI: 0.0059-0.0096), 0.0108 (95%CI: 0.0080-0.0136), 0.0361 (95%CI: 0.0156-0.0567), and 0.0083 (95%CI: 00046-0.0121) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transferase, respectively. Genetically predicted haematocrit was associated with ALP (ß = 0.0078, 95%CI: 0.0052-0.0104) and ALT (ß = 0.0057, 95%CI: 0.0039-0.0075). Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD [odds ratio (OR) = 1.199, 95%CI: 1.087-1.322] and (OR = 1.157, 95%CI: 1.071-1.250). The results of the sensitivity analyses remained significant. CONCLUSION: Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis, which may facilitate the diagnosis and prevention of NAFLD.

Lemairamin (Wgx-50) Attenuates DSS-Induced Intestinal Inflammation in Zebrafish.

Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.

Evaluating the Impact of Nutritional Risk on Stress-Induced Hyperglycemia and Trauma Patient Outcomes.

INTRODUCTION: Stress-induced hyperglycemia (SIH) and malnutrition are common in trauma patients and are linked to worse outcomes. This study examined the influence of nutritional status, determined by the Geriatric Nutritional Risk Index (GNRI), on the incidence of SIH in trauma patients. METHODS: A retrospective analysis was conducted on adult trauma patients admitted to a Level I trauma center from 1 January 2009 to December 31, 2021. Patients were categorized into four groups: SIH, diabetic hyperglycemia (DH), diabetic normoglycemia (DN), and non-diabetic normoglycemia (NDN). Nutritional status was assessed using GNRI: high risk (GNRI < 82), moderate risk (82 ≤ GNRI < 92), low risk (92 ≤ GNRI ≤ 98), and no risk (GNRI > 98). Incidence of SIH and outcomes were analyzed across GNRI groups. RESULTS: SIH was associated with higher mortality across all GNRI groups compared to NDN, with the highest rate (45.7%) in the high-risk group. Mortality decreased as GNRI increased in all glucose groups. NDN patients had the lowest mortality rates across GNRI groups. There was no correlation between GNRI and SIH incidence (p = 0.259). CONCLUSION: SIH significantly influenced mortality across all nutritional status groups, with the highest impact in malnourished patients. Although malnutrition did not affect SIH incidence, both SIH and poor nutritional status independently contributed to worse trauma outcomes. Targeted management of hyperglycemia and nutritional deficiencies is crucial for improving survival.

Association between sleep regularity and arterial stiffness among middle-age adults in Southwestern China.

BACKGROUND: Sleep regularity has been linked to a risk of arterial stiffness (AS). However, the association between sleep regularity indicators, which reflect 24-hour sleep variability, and AS has not yet been examined. METHODS: We analyzed data from 516 adults, aged 40-65 years (the median age of 51 years), from the 'Follow-up Study of Sleep Characteristics and Chronic Diseases in the Middle-aged and Elderly Population in Guizhou Province'. Participants underwent assessments of AS (OMRON HBP-8000, baPWV ≥ 1400 cm/s) and sleep (wrist smart band (Honor band 5i) for ≥ 7 days). Logistic regression was utilized to evaluate the odds ratio (OR) and 95% confidence interval (CI) of the association between sleep regularity and AS. RESULTS: A total of 516 people were included in this study, of which 279 (54.07%) were in the AS group. The univariate results showed that the AS group (Median 71.18) had lower SRI compared to the No-AS group (Median 75.00) (p < 0.001). The multifactorial results showed participants with higher SRI scores were more likely to have a lower risk of AS compared to those with lower SRI scores (ORQ4 VS. Q1=0.46, 95%CI: 0.25-0.85, p = 0.013). The SRI effect was more pronounced in male (ORQ4 VS. Q1=0.28, 95%CI: 0.12-0.69, p = 0.005), snoring populations (ORQ4 VS. Q1=0.13, 95%CI: 0.04-0.48, p = 0.002), and non-retired populations (ORQ4 VS. Q1=0.45, 95%CI: 0.22-0.92, p = 0.028). CONCLUSIONS: The present findings indicated that the effect between SRI and AS may be more sensitive than the standard deviation of sleep duration as well as the standard deviation of sleep onset.

Modified Standard Total en bloc Spondylectomy for Solitary Thoracic or Lumbar Spinal Metastasis: A 1-Stage Posterior Approach Under Direct Visualization.

BACKGROUND: Solitary spinal metastasis (SM) is one of the indications for total en bloc spondylectomy (TES). Conventional TES carries the risk of damage to the great vessels anterior to the vertebral column, mainly because of a lack of visualization of the anterior structures. In this study, we devised a modified standard TES technique to achieve direct visualization in a 1-stage posterior approach. METHODS: Included in this study were patients ≥18 years old with solitary thoracic or lumbar SM who underwent the modified standard TES at our institution between January 2017 and October 2022. Patient data were retrospectively sourced from medical records, and patients had a minimum of 3 months of postoperative follow-up. RESULTS: This study involved 71 East Asian patients (median age, 57 years; 34 males), comprising 38 patients with thoracic SM and 33 with lumbar SM. Lung cancer was the most common tumor histology. Fourteen patients (19.7%) experienced intraoperative complications; pleural rupture was the predominant complication, and there were no cases of injury to the spinal cord or great vessels. The median operative time was 305 minutes (range, 203 to 660 minutes). The median intraoperative blood loss was 1,000 mL (range, 400 to 4,000 mL). The median perioperative blood transfusion was 4 units (range, 0 to 12 units), and the median hospitalization duration was 17 days (range, 14 to 29 days). Additionally, 27 patients (38.0%) had acute (perioperative) complications. Seven patients were lost to follow-up. Significant clinical improvement was achieved 3 months postoperatively. Postoperative early and late complications were observed in 5 patients. Of the 64 patients with completed follow-up, 47 (73.4%) had negative surgical margins, and none received postoperative radiation therapy. Revision surgery for local tumor recurrence was performed in 4.7% of patients. The median follow-up was 31.5 months (range, 3 to 81 months). CONCLUSIONS: Our modified standard TES was demonstrated to be a safe and effective surgical technique for solitary thoracolumbar SM. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Targeting Rap1b signaling cascades with CDNF: Mitigating platelet activation, plasma oxylipins and reperfusion injury in stroke.

Cerebral reperfusion injury in stroke, stemming from interconnected thrombotic and inflammatory signatures, often involves platelet activation, aggregation and its interaction with various immune cells, contributing to microvascular dysfunction. However, the regulatory mechanisms behind this platelet activation and the resulting inflammation are not well understood, complicating the development of effective stroke therapies. Utilizing animal models and platelets from hemorrhagic stroke patients, our research demonstrates that human cerebral dopamine neurotrophic factor (CDNF) acts as an endogenous antagonist, mitigating platelet aggregation and associated neuroinflammation. CDNF moderates mitochondrial membrane potential, reactive oxygen species production, and intracellular calcium in activated platelets by interfering with GTP binding to Rap1b, thereby reducing Rap1b activation and downregulating the Rap1b-MAPK-PLA2 signaling pathway, which decreases release of the pro-inflammatory mediator thromboxane A2. In addition, CDNF reduces the inflammatory response in BV2 microglial cells co-cultured with activated platelets. Consistent with ex vivo findings, subcutaneous administration of CDNF in a rat model of ischemic stroke significantly reduces platelet activation, aggregation, lipid mediator production, infarct volume, and neurological deficits. In summary, our study highlights CDNF as a promising therapeutic target for mitigating platelet-induced inflammation and enhancing recovery in stroke. Harnessing the CDNF pathway may offer a novel therapeutic strategy for stroke intervention.

Convergent evolution of monocyte differentiation in adult skin instructs Langerhans cell identity.

Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identity. Using ablation of embryo-derived LCs in the murine adult skin and tracking differentiation of incoming monocyte-derived replacements, we found intrinsic intraepidermal heterogeneity. We observed that ontogenically distinct monocytes give rise to LCs. Within the epidermis, Jagged-dependent activation of Notch signaling, likely within the hair follicle niche, provided an initial site of LC commitment before metabolic adaptation and survival of monocyte-derived LCs. In the human skin, embryo-derived LCs in newborns retained transcriptional evidence of their macrophage origin, but this was superseded by DC-like immune modules after postnatal expansion. Thus, adaptation to adult skin niches replicates conditioning of LC at birth, permitting repair of the embryo-derived LC network.

Comprehensive assessment of three crayfish culture modes: From production performance to environmental sustainability.

Integrated agriculture-aquaculture has emerged as a promising ecological development model. Crayfish, a popular aquaculture species, are traditionally reared either in monoculture ponds (mono-C) or in rice-crayfish polyculture system (poly-RC). In this study, we introduced a novel polyculture system by combining fruit tree with crayfish (poly-FC), aiming to compare these three crayfish culture modes in terms of production performance and ecological sustainability. The results indicated that crayfish reared in the two polyculture modes exhibited significantly higher specific growth rate and condition factor compared to those in mono-C. Crayfish cultured in poly-FC also showed better muscle quality and higher levels of crude fat and flavor or essential amino acids. Isotope mixing model showed that feed and benthic animals were the primary food sources of crayfish in mono-C, whereas aquatic plants, fruit litter or rice contributed more to those in polyculture modes. For greenhouse gas emissions, poly-FC mode emitted almost no CO2 and N2O even favored negative CH4 emission, while poly-RC and mono-C modes showed positive emissions of CH4 and CO2, respectively. Supported by metagenomics, the sink of CH4 in poly-FC was probably due to the lower mcr abundance but the higher pmo abundance in water. The low production and emission of N2O in poly-FC might result from the low-abundant Nitrospirae_bacterium and its coding gene norC in sediment, consistent with the lower denitrification rate but the higher NO3- concentration than mono-C. Overall, our findings reveal the superiority of polyculture of fruit tree with crayfish in terms of production performance and greenhouse gas emissions in the system.

Distributed Identity Authentication with Lenstra-Lenstra-Lovász Algorithm-Ciphertext Policy Attribute-Based Encryption from Lattices: An Efficient Approach Based on Ring Learning with Errors Problem.

In recent years, research on attribute-based encryption (ABE) has expanded into the quantum domain. Because a traditional single authority can cause the potential single point of failure, an improved lattice-based quantum-resistant identity authentication and policy attribute encryption scheme is proposed, in which the generation of random values is optimized by adjusting parameters in the Gaussian sampling algorithm to improve overall performance. Additionally, in the key generation phase, attributes are processed according to their shared nature, which reduces the computational overhead of the authorization authority. In the decryption phase, the basis transformation of the Lenstra-Lenstra-Lovász (LLL) lattice reduction algorithm is utilized to rapidly convert shared matrices into the shortest vector form, which can reduce the computational cost of linear space checks. The experimental results demonstrate that the proposed method not only improves efficiency but also enhances security compared with related schemes.