Development of FK506-loaded maleimide-functionalized cationic niosomes for prolonged retention and therapeutic efficacy in dry eye disease.

Tacrolimus (FK506) is widely used in ocular diseases such as corneal transplantation-host disease, uveitis, conjunctivitis, and dry eye disease (DED). However, its low aqueous solubility and poor ocular retention pose challenges for its application in the eye diseases. This study developed a novel FK506-loaded maleimide-functionalized cationic niosomes (FK506 M-CNS), aiming to prolong the retention time of FK506 in the eye and enhance its therapeutic efficacy. FK506 M-CNS had a particle size of 87.69 ± 1.05 nm and zeta potential of 22.06 ± 1.01 mV. Results of histological evaluation through H&E staining and in vitro cytotoxicity of human corneal epithelial cells consistently revealed the excellent biocompatibility of FK506 M-CNS. FK506 M-CNS exhibited superior ocular retention compared to the market product Talymus®. FK506 M-CNS significantly alleviated the symptoms of DED and promoted the recovery of corneal epithelia. FK506 M-CNS group had the lowest expression levels of inflammatory factors associated with DED. These superiorities might be due to the electrostatic interaction between cationic niosomes and negatively charged mucin in the eye, and the covalent binding of maleimide with the thiol group in the mucin. The maleimide group improved the ocular retention and efficacy of FK506, but did not increase the toxicity. Results indicated that FK506 M-CNS had great potential as a nanopharmaceutical in the treatment of ocular diseases, and M-CNS could be a promising drug carrier for ophthalmic drug delivery systems.

Association of outdoor artificial light at night with myopia among Chinese adolescents: a representative cross-sectional study.

Background: The association between the rapid increase in myopia among adolescents and the amount of outdoor artificial light at night (ALAN) remains unclear. The aim of this study was to investigate the association between outdoor ALAN and myopia in adolescents. Methods: Stratified cluster random sampling was used to obtain a sample of 33,160 students (age range: 9-18 years; mean: 13.51 years) with complete data from 120 primary and secondary schools across the Ningxia region in China in 2021. Myopia was defined as a spherical equivalent (SE) ≤-0.5 diopters (D) in at least one eye, determined by automated refractometers without cycloplegia. Outdoor ALAN data were obtained from satellite data and the two-year average outdoor ALAN exposure for each participant was determined by matching it to their school address (home addresses were not available). The association between ALAN and myopia was assessed using multiple logistic regression models and restricted cubic spline (RCS) regression. Stratified analyses were performed by age, sex, residence, school level, and outdoor exercise time. Results: The myopia group had higher outdoor ALAN levels than the non-myopia group [median (interquartile spacing): 14.44 (3.88-26.56) vs. 6.95 (1.21-21.74) nanoWatts/cm2/sr]. After adjusting for covariates identified through stepwise regression, it was observed that the prevalence of myopia increased by 4% for every 10-unit change [95% confidence interval (CI): 1.02-1.07]. Compared to the first quantile (Q1) of outdoor ALAN exposure, the odds ratio (OR) of myopia was 1.20 (95% CI: 1.08-1.34) in the fourth quantile. RCS further showed a positive nonlinear relationship between outdoor ALAN exposure and myopia (p for nonlinear <0.001). Stronger effects were not found in subgroup analyses. Conclusion: Outdoor ALAN exposure is positively and nonlinearly associated with the prevalence of myopia in adolescents. Controlling outdoor light pollution may constitute a potential strategy to reduce the incidence of myopia in adolescents.

AI Prediction of Structural Stability of Nanoproteins Based on Structures and Residue Properties by Mean Pooled Dual Graph Convolutional Network.

The structural stability of proteins is an important topic in various fields such as biotechnology, pharmaceuticals, and enzymology. Specifically, understanding the structural stability of protein is crucial for protein design. Artificial design, while pursuing high thermodynamic stability and rigidity of proteins, inevitably sacrifices biological functions closely related to protein flexibility. The thermodynamic stability of proteins is not always optimal when they are highest to perfectly perform their biological functions. Extensive theoretical and experimental screening is often required to obtain stable protein structures. Thus, it becomes critically important to develop a stability prediction model based on the balance between protein stability and bioactivity. To design protein drugs with better functionality in a broader structural space, a novel protein structural stability predictor called PSSP has been developed in this study. PSSP is a mean pooled dual graph convolutional network (GCN) model based on sequence characteristics and secondary structure, distance matrix, graph, and residue properties of a nanoprotein to provide rapid prediction and judgment. This model exhibits excellent robustness in predicting the structural stability of nanoproteins. Comparing with previous artificial intelligence algorithms, the results indicate this model can provide a rapid and accurate assessment of the structural stability of artificially designed proteins, which shows the great promises for promoting the robust development of protein design.

Drug Repurposing: Research Progress of Niclosamide and Its Derivatives on Antibacterial Activity.

The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.

Runoff variation alters estuarine sediment microbiome and nitrogen removal processes by affecting salinity.

Runoff variations shape the dynamics of the estuarine environmental factors, profoundly influencing the nitrogen cycle in estuarine sediments. However, our understanding of how these changes regulate microbially-mediated nitrogen removal processes remains limited. In this study, the impacts of changes in environmental factors caused by normal and low runoffs on denitrification and anammox in sediments of the Liao River Estuary in China, were investigated, using continuous-flow experiments combined with 15N tracing techniques and molecular methods. Results indicated that denitrification was the main nitrogen removal process in estuarine sediments under both runoff conditions. Elevated salinity under low runoff condition increased the abundance of nitrifying bacteria (Nitrospina, Nitrosomonas and Nitrosomonadaceae), thereby promoting the coupled nitrification-denitrification nitrogen removal process. Furthermore, seawater intrusion under low runoff contributed to dilute nitrite concentrations, resulting in decreased denitrification rates in sediments. Overall, this study highlighted the impacts of runoff variations on biological nitrogen removal process through affecting environmental factors, gene abundance and microbial community in the estuary.

SpliceTransformer predicts tissue-specific splicing linked to human diseases.

We present SpliceTransformer (SpTransformer), a deep-learning framework that predicts tissue-specific RNA splicing alterations linked to human diseases based on genomic sequence. SpTransformer outperforms all previous methods on splicing prediction. Application to approximately 1.3 million genetic variants in the ClinVar database reveals that splicing alterations account for 60% of intronic and synonymous pathogenic mutations, and occur at different frequencies across tissue types. Importantly, tissue-specific splicing alterations match their clinical manifestations independent of gene expression variation. We validate the enrichment in three brain disease datasets involving over 164,000 individuals. Additionally, we identify single nucleotide variations that cause brain-specific splicing alterations, and find disease-associated genes harboring these single nucleotide variations with distinct expression patterns involved in diverse biological processes. Finally, SpTransformer analysis of whole exon sequencing data from blood samples of patients with diabetic nephropathy predicts kidney-specific RNA splicing alterations with 83% accuracy, demonstrating the potential to infer disease-causing tissue-specific splicing events. SpTransformer provides a powerful tool to guide biological and clinical interpretations of human diseases.

3DSTarPred: A Web Server for Target Prediction of Bioactive Small Molecules Based on 3D Shape Similarity.

Target identification plays a critical role in preclinical drug development. The in silico approach has been developed and widely applied to assist medicinal chemists and pharmacologists in drug target identification. There are many target prediction web servers available today that have revealed both advantages and shortcomings in practical applications. Here, we present 3DSTarPred, a web server for three-dimensional (3D) shape similarity-based target prediction of small molecules. A benchmark study showed that 3DSTarPred achieved a target prediction success rate of 76.27%, which was higher than that of existing target prediction web servers. In addition, the performance of 3DSTarPred in the target prediction of diverse substructures/superstructures was also better than that of the existing target prediction web servers. In case studies, 3DSTarPred was used to identify the potential targets of two small molecules, one being kaempferol, a natural lead compound for the treatment of Alzheimer's disease (AD), and the other being sildenafil, a candidate for drug repurposing in AD. The case studies further demonstrated the reliability and success of 3DSTarPred in practice. The 3DSTarPred server is freely available at http://3dstarpred.pumc.wecomput.com.

Is pulmonary vascular remodeling an intermediate link between hyperglycemia and adverse outcomes in patients with idiopathic pulmonary arterial hypertension? Insights from a multi-center cohort study.

BACKGROUND: Hyperglycemia upon admission is associated with poor prognosis of many cardiovascular diseases. However, the relationship of stress hyperglycemia ratio (SHR), admission blood glucose (ABG), and hemoglobin A1c (HbA1c) with pulmonary hypertension has not been reported. This study aimed to explore the association of hyperglycemia indices with disease severity and long-term adverse outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS: This multi-center cohort study included 625 consecutive patients diagnosed with or treated for IPAH between January 2015 and June 2023. SHR was calculated using the followings: ABG (mmol/L)/(1.59 × HbA1c [%] - 2.59). The primary endpoint was defined as clinical worsening events. Multivariable Cox regression and restricted cubic spline analyses were employed to evaluate the association of SHR, ABG, and HbA1c with endpoint events. The mediating effect of pulmonary hemodynamics was evaluated to investigate the potential mechanism between hyperglycemia and clinical outcomes. RESULTS: During a mean follow-up period of 3.8 years, 219 (35.0%) patients experienced all-cause death or clinical worsening events. Hyperglycemia indices correlated with well-validated variables that reflected the severity of IPAH, such as the World Health Organization functional class, 6-min walk distance, and N-terminal pro-brain natriuretic peptide levels. Multivariable Cox regression analyses indicated that SHR (hazard ratio [HR] 1.328, 95% confidence intervals [CI]: 1.185, 1.489 per 0.1-unit increment, P < 0.001) and ABG (HR 1.317, 95% CI: 1.134, 1.529 per 1.0-unit increment, P < 0.001) were independent predictors of primary endpoint events. Mediation analysis indicated that pulmonary vascular resistance mediated 5.65% and 14.62% of the associations between SHR and ABG and clinical worsening events, respectively. The addition of SHR significantly improved reclassification, discrimination ability, and model fit beyond the clinical risk prediction model. CONCLUSIONS: SHR is positively associated with clinical worsening in patients with IPAH. The association appeared to be partially mediated through the pathway of pulmonary vascular remodeling, indicating that SHR may serve as a valuable indicator for providing additional risk information.

Development of a small molecule-based two-photon photosensitizer for targeting cancer cells.

Photodynamic therapy (PDT) employing two-photon (TP) excitation is increasingly recognized to induce cell damage selectively in targeted areas, underscoring the importance of developing TP photosensitizers (TP-PSs). In this study, we developed BSe-B, a novel PS that combines a selenium containing dye with biotin, a cancer-selective ligand, and is optimized for TP excitation. BSe-B demonstrated enhanced cancer selectivity, efficient generation of type-I based reactive oxygen species (ROS), low dark toxicity, and excellent cell-staining capability. Evaluation across diverse cell lines (HeLa, A549, OVCAR-3, WI-38, and L-929) demonstrated that BSe-B differentiated and targeted cancer cells while sparing normal cells. BSe-B displayed excellent in vivo biocompatibility. In cancer models such as three-dimensional spheroids and actual colon cancer tissues, BSe-B selectively induced ROS production and cell death under TP irradiation, demonstrating precise spatial control. These findings highlight the potential of BSe-B for imaging-guided PDT and its capability for micro treatment within tissues. Thus, BSe-B demonstrates robust TP-PDT capabilities, making it a promising dual-purpose tool for cancer diagnosis and treatment.

Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease.

BACKGROUND: In the EMPA-KIDNEY trial, empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, had positive cardiorenal effects in patients with chronic kidney disease who were at risk for disease progression. Post-trial follow-up was designed to assess how the effects of empagliflozin would evolve after the discontinuation of the trial drug. METHODS: In the active trial, patients with chronic kidney disease were randomly assigned to receive either empagliflozin (10 mg once daily) or matching placebo and were followed for a median of 2 years. All the patients had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area or an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Subsequently, surviving patients who consented were observed for 2 additional years. No trial empagliflozin or placebo was administered during the post-trial period, but local practitioners could prescribe open-label SGLT2 inhibitors, including open-label empagliflozin. The primary composite outcome was kidney disease progression or cardiovascular death as assessed from the start of the active-trial period to the end of the post-trial period. RESULTS: Of the 6609 patients who had undergone randomization in the active trial, 4891 (74%) were enrolled in the post-trial period. During this period, the use of open-label SGLT2 inhibitors was similar in the two groups (43% in the empagliflozin group and 40% in the placebo group). During the combined active- and post-trial periods, a primary-outcome event occurred in 865 of 3304 patients (26.2%) in the empagliflozin group and in 1001 of 3305 patients (30.3%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.72 to 0.87). During the post-trial period only, the hazard ratio for a primary-outcome event was 0.87 (95% CI, 0.76 to 0.99). During the combined periods, the risk of kidney disease progression was 23.5% in the empagliflozin group and 27.1% in the placebo group; the risk of the composite of death or end-stage kidney disease was 16.9% and 19.6%, respectively; and the risk of cardiovascular death was 3.8% and 4.9%, respectively. There was no effect of empagliflozin on death from noncardiovascular causes (5.3% in both groups). CONCLUSIONS: In a broad range of patients with chronic kidney disease at risk for progression, empagliflozin continued to have additional cardiorenal benefits for up to 12 months after it was discontinued. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EuDRACT number, 2017-002971-24.).

Self-Adaptive Activation of DNAzyme Nanoassembly for Synergistically Combined Gene Therapy.

DNAzymes represents a promising toolbox for gene silencing but face challenges related to poor substrate accessibility in specific cells. Herein, a compact DNA nanoassembly, incorporating multimeric therapeutic DNAzyme, was prepared for selective delivery of gene-silencing DNAzyme with requisite cofactors and auxiliary chemo-drugs. By virtue of the sequence-conservative duplex-specific nuclease, the endogenous miRNA catalyzes the successive and site-specific cleavage of DNA nanoassembly substrate (nominated as the localized RNA walking machine) and thus ensures the liberation/activation of therapeutic agents with high accuracy and efficacy. The miR-10b-stimulated DNAzyme was designed to downregulate the TWIST transcription factor, an upstream promotor of miR-10b, thus acquiring the self-sufficient downregulation of TWIST/miR-10b signaling nodes (self-adaptive negative feedback loop) for abrogating tumor metastasis and chemo-resistance issues.

IPNA clinical practice recommendations for the diagnosis and management of children with IgA nephropathy and IgA vasculitis nephritis.

IgA nephropathy and IgA vasculitis with nephritis, albeit rare, represent two relatively frequent glomerular conditions in childhood. Compared to adults, pediatric IgA nephropathy has a more acute presentation, most frequently with synpharyngitic macrohematuria and histologically with more intense inflammation and less intense chronic damage. Management of these conditions is controversial and supported by little high-quality evidence. The paucity of evidence is due to the disease heterogeneity, its inter-ethnic variability, and the difficulty of extrapolating data from adult studies due to the peculiarities of the condition in children. IgA vasculitis with nephritis is a kidney manifestation of a systemic disorder, typical of the pediatric age, in which both the diagnosis of kidney involvement and its management are poorly defined, and an interdisciplinary approach is crucial. Both conditions can have a profound and long-lasting impact on kidney function and the global health of affected children. The International Pediatric Nephrology Association has therefore convened a diverse international group of experts from different disciplines to provide guidance on the recommended management of these conditions in children and to establish common definitions and define priorities for future high-quality, evidence-based collaborative studies for the benefit of children.

Active Left Atrial Ejection Fraction as a Non-Invasive Marker in Pulmonary Hypertension Secondary to Heart Failure.

BACKGROUND: Patients with pulmonary hypertension (PH) secondary to left heart failure (HF) exhibit a complex pathophysiological profile and poor prognosis. Left atrial function is pivotal in the progression of this disease, yet its predictive significance remains exclusive. This study aimed to explore the predictive capability of LA metrics in this population and compare them with other common predictors. METHODS: In this retrospective study, consecutive patients with PH secondary to HF who underwent cardiac magnetic resonance (CMR) imaging between December 2010 and December 2021 were enrolled. The composite endpoint was defined as all-cause death, heart-lung transplantation, or left ventricular assist device implantation. Survival analyses were performed using Kaplan-Meier curves and Cox regression analyses. RESULTS: A total of 174 patients with PH secondary to HF, with a mean age of 53.2 ± 14.9 years, including 90 men, were included in the final analysis. During a median follow-up of 31.9 months, 58 patients (33.3%) with PH reached the endpoints. There was a fair correlation between active left atrial ejection fraction (LAEF) and pulmonary artery wedge pressure (r = -0.397, p = 0.044). Active LAEF had a strong correlation with oxygen consumption at anaerobic threshold (r = 0.769, p < 0.001) and peak oxygen consumption (r = 0.754, p < 0.001). Active LAEF demonstrated comparable prognostic performance to other variables measured by echocardiography or CMR. After adjusting for clinical variables and left ventricular ejection fraction, active LAEF was still an independent predictor for adverse events (C-statistic: 0.784). Subgroup analysis among HF patients with preserved ejection fraction demonstrated that those with active LAEF ≤ 8.6% had a 7.05-fold higher risk of experiencing the composite endpoint compared to those with active LAEF > 8.6%. CONCLUSION: Although active LAEF does not demonstrate statistical improvement in outcome discrimination compared to established metrics, it may still merit consideration for assessing disease severity and prognosis in patients with PH secondary to HF. The integration of active LAEF and HF subtypes may stratify individuals at different levels of risk.

Identification of Key Proteins Related to Cashmere Fiber Diameter by Integrated Proteomics and Bioinformatic Analyses in the Alpas and Alxa Goat Breeds.

BACKGROUND: Goats (Capra hircus) have always been a source of fiber for human use and hold an important place in international high-end textiles. Fiber diameter is the most concerning economic indicator for producers. Understanding the formation mechanism of fiber diameter and its related key proteins can help optimize and control the production of cashmere. METHODS: Cashmere goats (n = 36) of the Alpas (n = 18) and Alxa (n = 18) breeds, with a similar age (2 years old) and live weight (25-26 kg), were selected from the Yiwei White Cashmere Goat Breeding Farm, Erdos, Inner Mongolia. Using phenotypic indicators, we evaluated the diameter of the cashmere fibers in Alxa and Alpas goats. We also used electron microscopy to examine the cashmere fiber's structure and label-free liquid chromatography-tandem mass spectrometry to determine the protein content of the two cashmere fibers. The proteins affecting fiber diameter were identified and analyzed by Western blot, Co-Immunoprecipitation, and bioinformatics analysis. RESULTS: The average diameter of the Alxa breed was smaller (p < 0.05) than that of the Alpas breed (Alxa's cashmere vs. Alpas' cashmere). Proteomics technology enabled the highly confident detection of 171 proteins. A total of 68 differentially expressed proteins were identified in the two types of cashmere; 131 proteins were specifically expressed in Alpas goats, and 40 proteins were specifically expressed in Alxa goats. A key protein group that could cause variations in fiber diameter was found using the protein-protein interaction network. To ascertain the reason for the variation in fiber diameter, a structural study of the major protein groups was carried out. CONCLUSIONS: KRT10, KRT14, KRT17, and KRT82 are the main proteins impacting the diameter difference, and they have a substantial effect on the average fiber diameter.

Titanium boride nanosheets with photo-enhanced sonodynamic efficiency for glioblastoma treatment.

Sonodynamic therapy (SDT) has garnered significant attention in cancer treatment, however, the low-yield reactive oxygen species (ROS) generation from sonosensitizers remains a major challenge. In this study, titanium boride nanosheets (TiB2 NSs) with photo-enhanced sonodynamic efficiency was fabricated for SDT of glioblastoma (GBM). Compared with commonly-used TiO2 nanoparticles, the obtained TiB2 NSs exhibited much higher ROS generation efficiency under ultrasound (US) irradiation due to their narrower band gap (2.50 eV). Importantly, TiB2 NSs displayed strong localized surface plasmon resonance (LSPR) effect in the second near-infrared (NIR II) window, which facilitated charge transfer rate and improved the separation efficiency of US-triggered electron-hole pairs, leading to photo-enhanced ROS generation efficiency. Furthermore, TiB2 NSs were encapsulated with macrophage cell membranes (CM) and then modified with RGD peptide to construct biomimetic nanoagents (TiB2@CM-RGD) for efficient blood-brain barrier (BBB) penetrating and GBM targeting. After intravenous injection into the tumor-bearing mouse, TiB2@CM-RGD can efficiently cross BBB and accumulate in the tumor sites. The tumor growth was significantly inhibited under simultaneous NIR II laser and US irradiation without causing appreciable long-term toxicity. Our work highlighted a new type of multifunctional titanium-based sonosensitizer with photo-enhanced sonodynamic efficiency for GBM treatment. STATEMENT OF SIGNIFICANCE: Titanium boride nanosheets (TiB2 NSs) with photo-enhanced sonodynamic efficiency was fabricated for SDT of glioblastoma (GBM). The obtained TiB2 NSs displayed strong localized surface plasmon resonance (LSPR) effect in the second near-infrared (NIR II) window, which facilitated charge transfer rate and improved the separation efficiency of US-triggered electron-hole pairs, leading to photo-enhanced ROS generation efficiency. Furthermore, TiB2 NSs were encapsulated with macrophage cell membranes (CM) and then modified with RGD peptide to construct biomimetic nanoagents (TiB2@CM-RGD) for efficient blood-brain barrier (BBB) penetrating and GBM targeting. After intravenous injection into the tumor-bearing mouse, TiB2@CM-RGD can efficiently cross BBB and accumulate in the tumor sites. The tumor growth was significantly inhibited under simultaneous NIR II laser and US irradiation without causing appreciable long-term toxicity.

Distribution and diversity of ticks determined by environmental factors in Ningxia, China.

Ticks are important vectors of zoonotic pathogens, and represent an increasing threat for human and animal health. Considering the complex natural environments of Ningxia Hui Autonomous Region, China, we expect the diverse tick species in this region. Here, we conduct a field survey on parasitic and host-seeking ticks. A total of 10,419 ticks were collected, which belonged to nine species of four genera. There were significant differences in terms of vegetation index, altitude, and seven climatic factors among the four tick genera -Hyalomma, Dermacentor, Haemaphysalis, and Ixodes, except between Haemaphysalis and Ixodes, where no significant differences were observed in these factors. The ecological niche modelling revealed that the suitable habitats for Hyalomma asiaticum was in the northwest Ningxia, with annual ground surface temperature as the most important factor. The suitable area for Dermacentor nuttalli was in the southwest and eastern regions of Ningxia with elevation as the highest contribution. D. silvarum was best suited to the southern Ningxia also with elevation as the most important factor. The four tick species including Haemaphysalis longicornis, Hae. qinghaiensis, Hae. japonica, and Ixodes persulcatus were best suited to the southernmost Ningxia with annual precipitation as the main factors for Hae. longicornis and elevation for the other three ticks. The results of predicted potential distribution of different tick species provide a scientific basis for the prevention and control of ticks and tick-borne diseases in the region. Furthermore, the subsequent impacts of the Greening Program to regain forests and grasslands from former agricultural lands in Ningxia on tick population dynamics deserve further investigation.

Zingerone attenuates concanavalin A-induced acute liver injury by restricting inflammatory responses.

Autoimmune hepatitis (AIH), an immune-mediated liver injury, plays an important role in the development and pathogenesis of several liver diseases. However, therapeutic alternatives for the treatment of AIH remain limited. Zingerone (ZIN) is a natural non-toxic phenolic compound extracted from ginger that possesses various pharmacological activities. Thus, this study aimed to investigate the effect of ZIN on AIH using a mouse model of acute liver injury induced by concanavalin A (Con A). To establish liver injury, C57BL/6J mice were intraperitoneally administered ZIN, followed by 20 mg/kg Con A after 3 h. Thereafter, the liver and serum were collected for analysis. The results revealed that ZIN pretreatment significantly suppressed the elevation of liver injury markers induced by Con A exposure and improved the survival of mice. Additionally, ZIN significantly ameliorated liver histopathological injury, hepatocyte apoptosis, and oxidative stress. Notably, ZIN inhibited hepatic M1 macrophage polarization and decreased the expression of M1 macrophage-associated pro-inflammatory genes and cytokines, including interleukin-1ß (IL-1ß), IL-12, IL-6, and tumor necrosis factor-α (TNF-α). Western blotting analysis indicated that ZIN inhibited the phosphorylation of extracellular receptor kin, c-Jun N-terminal kinase, and p65 in vitro. Taken together, these results suggest that ZIN exerts a protective effect in the Con A-induced acute liver injury model by inhibiting M1 macrophage polarization and suppressing NF-κB, mitogen-activated protein kinase, and interferon regulatory factor signaling pathways. This highlights the possibility of using ZIN as a safe drug for the treatment of liver injury and provides a novel therapeutic direction for clinical studies on liver diseases.

Sex disparities of clinical manifestations in acute pulmonary embolism and predictive value for in-hospital mortality: Insights from CURES.

BACKGROUND: Pulmonary embolism (PE) is a common and potentially fatal disease, with differences in mortality rates among PE patients of different sexes. This study aims to investigate the disparities in clinical manifestations and in-hospital mortality rates between sexes in PE patients, as well as the association of clinical symptoms with in-hospital mortality. METHODS: We analyzed data from the China pUlmonary thromboembolism REgistry Study (CURES), a nationwide, multicenter, prospective registry focusing on patients with acute PE. Using propensity score matching (PSM) to pair male and female patients with PE, we explored the correlation between clinical symptoms and in-hospital mortality through multivariable regression analysis. RESULTS: A total of 15,203 patients with acute PE were enrolled, and 380 died during hospitalization. The incidence of chest pain, hemoptysis, and palpitations was significantly higher in males compared to females. The incidence of dyspnea, fever, and syncope was higher in females. Hemoptysis and dyspnea were associated with increased in-hospital mortality in males, whereas dyspnea, fever, and palpitations were linked to higher mortality in females. Overall, males exhibited a higher in-hospital mortality than females (2.9 % vs. 2.1 %, p = 0.002). After matching 13,130 patients using the PSM method, the mortality rate of males remained higher than that of females (2.7 % vs. 2.1 %, p = 0.020). CONCLUSIONS: Our study demonstrates that male patients with PE have a higher risk of in-hospital mortality than females. Significant differences in clinical symptoms between sexes are associated with increased mortality risk, emphasizing the need for clinical awareness.

Distribution of habitat suitability for Suaeda salsa in the Liaohe River Estuary and its relationship with carbon storage.

Suaeda salsa acts as a natural barrier between land and sea in estuarine wetlands while also serving as a significant source of carbon storage. Understanding the synergistic relationship between the spatial distribution of Suaeda salsa habitat suitability and its carbon storage capabilities is essential for guiding ecological restoration and bolstering the carbon sequestration potential of wetlands. Drawing on field survey data from the Liaohe River Estuary wetlands collected in 2021 and 2022, we applied the Maxent model to delineate the spatial distribution of Suaeda salsa habitat suitability. The findings indicate that the principal environmental determinants for the Suaeda salsa community are elevation, soil phosphorus, and sand and soil salt content. Habitats can be divided from into four classes with increasing suitability index: I, II, III, and IV. As the most favorable habitat, class IV spanned 33.07 km2 and constituted 22.37 % of the area. By integrating remote sensing and ground survey data, a carbon storage evaluation model for Suaeda salsa was developed. This model revealed that the carbon storage within the Liaohe River Estuary reached 8238.18 and 16,194.08 tons in 2021 and 2022, respectively. Finally, the spatial overlay analysis of habitat suitability distribution and carbon storage revealed that an increase in habitat suitability led to an increase in carbon storage in Suaeda salsa, which was also influenced by the surrounding land use types. This work demonstrates a significant positive correlation between habitat suitability and carbon sequestration capacity. In the future, we suggest that ecological restoration projects in the Liaohe Estuary region focus on areas with higher habitat suitability. This study supports the sustainable management of the Suaeda salsa community and provides a theoretical basis for enhancing the carbon sequestration capacity of estuarine wetlands.