Influence of elevated liver enzyme level on 30-day mortality rates in patients undergoing nonemergency orthopedic surgery.

BACKGROUND: The effect of elevated preoperative liver enzyme levels on postoperative outcomes is a topic of concern to clinicians. This study explored the association between elevated preoperative liver enzyme levels and surgical outcomes in patients undergoing orthopedic surgery. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we obtained data on adult patients who received nonemergency orthopedic surgery under general anesthesia between 2011 and 2021. RESULTS: We evaluated the data of 477,524 patients, of whom 6.1% (24 197 patients) had elevated preoperative serum glutamic oxaloacetic transaminase (SGOT) levels. An elevated SGOT level was significantly associated with 30-day postoperative mortality (adjusted hazard ratio, 1.62; 95% confidence interval, 1.39 to 1.90). We determined that the mortality rate rose with SGOT levels. The results remained unchanged after propensity score matching. CONCLUSION: Elevated preoperative SGOT levels constitute an independent risk factor for 30-day postoperative mortality and are proportionately associated with the risk of 30-day postoperative mortality.

Does Focal Kyphotic Deformity at Non-responsible Levels Affect the Outcomes of Anterior Cervical Decompression and Fusion?

OBJECTIVE: Focal cervical kyphotic deformity (FCK) without neurologic compression is not uncommon in patients with cervical spondylotic myelopathy (CSM) who underwent anterior cervical decompression and fusion (ACDF) surgery. It remains unclear whether FCK at non-responsible levels needs to be treated simultaneously. This study aims to investigate whether FCK at non-responsible levels is the prognostic factor for CSM and elucidate the surgical indication for FCK. METHODS: Patients with CSM who underwent ACDF between January 2016 and April 2021 were included. Patients were divided into two groups according to the presence of FCK and two classifications according to global cervical sagittal alignment. Clinical outcomes were compared using Japanese Orthopaedic Association (JOA) scores and recovery rate (RR) of neurologic function. Univariate and multivariate analysis based on RR assessed the relationship between various possible prognostic factors and clinical outcomes. The receiver operating characteristic curve (ROC) was used to determine the optimal cutoff value of the focal Cobb angle to predict poor clinical outcomes. RESULTS: A total of 94 patients were included, 41 with FCK and 53 without. Overall, the RR of neurologic function was significantly lower in the FCK than in the non-FCK group. Further analysis showed that the RR difference between the two groups was only observed in hypo-lordosis classification (kyphotic and sigmoid alignment), but not in the lordosis classification. Multivariate analysis showed that the preoperative focal Cobb angle in the FCK level (OR = 0.42; 95% CI = 0.18-0.97) was independently associated with clinical outcomes in the hypo-lordosis classification. The optimal cutoff point of the preoperative focal kyphotic Cobb angle was calculated at 4.05°. CONCLUSION: For CSM with hypo-lordosis, FCK was a risk factor for poor postoperative outcomes. Surgeons may consider treating the FCK simultaneously if the focal kyphotic Cobb angle of FCK is greater than 4.05° and is accompanied by cervical global kyphotic or sigmoid deformity.

Alterations in the gut mycobiome with coronary artery disease severity.

BACKGROUND: Coronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. METHODS: In this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FINDINGS: Based on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. INTERPRETATION: In conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FUNDING: This work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202417, Ggyfz202308), the Beijing Natural Science Foundation (No. 7222068); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).

Association of the external environmental exposome and obesity: A comprehensive nationwide study in 2019 among Chinese children and adolescents.

OBJECTIVE: Children and adolescents are particularly vulnerable to the effects of various environmental factors, which could disrupt growth processes and potentially lead to obesity. Currently, comprehensive and systematic assessments of these environmental exposures during developmental periods are lacking. Therefore, this study aims to evaluate the association between external environmental exposures and the incidence of obesity in children and adolescents. METHODS: Data was collected from the 2019 Chinese National Survey on Students' Constitution and Health, including 214,659 Han children aged 7 to 19. Body Mass Index (BMI) and BMI-for-age z-score (zBMI) were the metrics used to assess overweight and obesity prevalence. The study assessed 18 environmental factors, including air pollutants, natural space, land cover, meteorological conditions, built environment, road conditions, and artificial light at night. Exposome-wide association study (ExWAS) to analyze individual exposures' associations with health outcomes, and Weighted Quantile Sum (WQS) to assess cumulative exposure effects. RESULTS: Among the children and adolescents, there were 24.2 % participants classified as overweight or obesity. Notably, 17 out of 18 environmental factors exhibited significant associations with zBMI and overweight/obesity. Seven air pollutants, road conditions, and built density were positively correlated with higher zBMI and obesity risk, while NDVI, forests, and meteorological factors showed negative correlations. Co-exposure analysis highlighted that SO2, ALAN, PM10, and trunk road density significantly increased zBMI, whereas rainfall, grassland, and forest exposure reduced it. Theoretically reduction in the number and prevalence of cases was calculated, indicating potential reductions in prevalence of up to 4.51 % for positive exposures and 5.09 % for negative exposures. Notably, substantial reductions were observed in regions with high pollution levels. CONCLUSION: This large-scale investigation, encompassing various environmental exposures in schools, highlights the significant impact of air pollution, road characteristics, rainfall, and forest coverage on childhood obesity.

Long-term variations of urban-Rural disparities in infectious disease burden of over 8.44 million children, adolescents, and youth in China from 2013 to 2021: An observational study.

BACKGROUND: An accelerated epidemiological transition, spurred by economic development and urbanization, has led to a rapid transformation of the disease spectrum. However, this transition has resulted in a divergent change in the burden of infectious diseases between urban and rural areas. The objective of our study was to evaluate the long-term urban-rural disparities in infectious diseases among children, adolescents, and youths in China, while also examining the specific diseases driving these disparities. METHODS AND FINDINGS: This observational study examined data on 43 notifiable infectious diseases from 8,442,956 cases from individuals aged 4 to 24 years, with 4,487,043 cases in urban areas and 3,955,913 in rural areas. The data from 2013 to 2021 were obtained from China's Notifiable Infectious Disease Surveillance System. The 43 infectious diseases were categorized into 7 categories: vaccine-preventable, bacterial, gastrointestinal and enterovirus, sexually transmitted and bloodborne, vectorborne, zoonotic, and quarantinable diseases. The calculation of infectious disease incidence was stratified by urban and rural areas. We used the index of incidence rate ratio (IRR), calculated by dividing the urban incidence rate by the rural incidence rate for each disease category, to assess the urban-rural disparity. During the nine-year study period, most notifiable infectious diseases in both urban and rural areas exhibited either a decreased or stable pattern. However, a significant and progressively widening urban-rural disparity in notifiable infectious diseases was observed. Children, adolescents, and youths in urban areas experienced a higher average yearly incidence compared to their rural counterparts, with rates of 439 per 100,000 compared to 211 per 100,000, respectively (IRR: 2.078, 95% CI [2.075, 2.081]; p < 0.001). From 2013 to 2021, this disparity was primarily driven by higher incidences of pertussis (IRR: 1.782, 95% CI [1.705, 1.862]; p < 0.001) and seasonal influenza (IRR: 3.213, 95% CI [3.205, 3.220]; p < 0.001) among vaccine-preventable diseases, tuberculosis (IRR: 1.011, 95% CI [1.006, 1.015]; p < 0.001), and scarlet fever (IRR: 2.942, 95% CI [2.918, 2.966]; p < 0.001) among bacterial diseases, infectious diarrhea (IRR: 1.932, 95% CI [1.924, 1.939]; p < 0.001), and hand, foot, and mouth disease (IRR: 2.501, 95% CI [2.491, 2.510]; p < 0.001) among gastrointestinal and enterovirus diseases, dengue (IRR: 11.952, 95% CI [11.313, 12.628]; p < 0.001) among vectorborne diseases, and 4 sexually transmitted and bloodborne diseases (syphilis: IRR 1.743, 95% CI [1.731, 1.755], p < 0.001; gonorrhea: IRR 2.658, 95% CI [2.635, 2.682], p < 0.001; HIV/AIDS: IRR 2.269, 95% CI [2.239, 2.299], p < 0.001; hepatitis C: IRR 1.540, 95% CI [1.506, 1.575], p < 0.001), but was partially offset by lower incidences of most zoonotic and quarantinable diseases in urban areas (for example, brucellosis among zoonotic: IRR 0.516, 95% CI [0.498, 0.534], p < 0.001; hemorrhagic fever among quarantinable: IRR 0.930, 95% CI [0.881, 0.981], p = 0.008). Additionally, the overall urban-rural disparity was particularly pronounced in the middle (IRR: 1.704, 95% CI [1.699, 1.708]; p < 0.001) and northeastern regions (IRR: 1.713, 95% CI [1.700, 1.726]; p < 0.001) of China. A primary limitation of our study is that the incidence was calculated based on annual average population data without accounting for population mobility. CONCLUSIONS: A significant urban-rural disparity in notifiable infectious diseases among children, adolescents, and youths was evident from our study. The burden in urban areas exceeded that in rural areas by more than 2-fold, and this gap appears to be widening, particularly influenced by tuberculosis, scarlet fever, infectious diarrhea, and typhus. These findings underscore the urgent need for interventions to mitigate infectious diseases and address the growing urban-rural disparity.

The activation of LBH-CRYAB signaling promotes cardiac protection against I/R injury by inhibiting apoptosis and ferroptosis.

Myocardial ischemia-reperfusion (I/R) injury stands out among cardiovascular diseases, and current treatments are considered unsatisfactory. For cardiomyocytes (CMs) in ischemic tissues, the upregulation of Limb-bud and Heart (LBH) and αB-crystallin (CRYAB) and their subsequent downregulation in the context of cardiac fibrosis have been verified in our previous research. Here, we focused on the effects and mechanisms of activated LBH-CRYAB signaling on damaged CMs during I/R injury, and confirmed the occurrence of mitochondrial apoptosis and ferroptosis during I/R injury. The application of inhibitors, ectopic expression vectors, and knockout mouse models uniformly verified the role of LBH in alleviating both apoptosis and ferroptosis of CMs. p53 was identified as a mutual downstream effector for both LBH-CRYAB-modulated apoptosis and ferroptosis inhibition. In mouse models, LBH overexpression was confirmed to exert enhanced cardiac protection against I/R-induced apoptosis and ferroptosis, suggesting that LBH could serve as a promising target for the development of I/R therapy.

Exosomal CircRNAs in Circulation Serve as Diagnostic Biomarkers for Acute Myocardial Infarction.

BACKGROUND: The diagnostic potential of circular RNAs (circRNAs) in circulating exosomes for acute myocardial infarction (AMI) is not well understood, despite existing research indicating their role in cardiovascular diseases. This study aimed to clarify the significance of exosomal circular RNAs as indicators for AMI. METHODS: We examined 120 individuals diagnosed with AMI and 83 individuals with non-cardiogenic chest pain (NCCP), all previously enrolled in a conducted study. High-throughput sequencing to identify differentially expressed circRNAs in the circulating exosomes of AMI patients. To validate, we employed Real-Time polymerase chain reaction (RT-PCR) targeting five circRNAs that exhibited notable increase. RESULTS: The sequencing identified 893 exosomal circRNAs with altered expression in AMI patients, including 118 up-regulated and 775 down-regulated circRNAs. Genes linked to these circRNAs were enriched in crucial Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, highlighting their direct relevance to AMI pathophysiology. Three exosomal circRNAs (hsa_circ_0001558, hsa_circ_0001535, and hsa_circ_0000972) showed significant up-regulation in AMI patients during the initial validation cohort. The corresponding area under the curve (AUC) values were 0.79, 0.685, and 0.683, respectively. Further validation of hsa_circ_0001558 in a second cohort showed a 4.45-fold increase in AMI patients, with AUC = 0.793. The rise was particularly noticeable in patients with non-ST-elevation myocardial infarction (NSTEMI) (2.80 times, AUC = 0.72) and patients with ST-elevation myocardial infarction (STEMI) (5.27 times, AUC = 0.831) compared to patients with NCCP. CONCLUSIONS: Our findings demonstrate significant differences in the expression patterns of circRNAs in plasma exosomes between AMI patients and NCCP patients. Specifically, hsa_circ_0001558 appears as a promising indicator for AMI diagnosis. Further research is necessary to fully evaluate the diagnostic potential of exosomal circRNAs in the context of AMI, emphasizing the importance of these findings.

Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant tumor associated with Epstein-Barr virus (EBV) infection. Chemoradiotherapy is the mainstream treatment for locally advanced NPC, and chemotherapeutic drugs are an indispensable part of NPC treatment. However, the toxic side-effects of chemotherapy drugs limit their therapeutic value, and new chemotherapy drugs are urgently needed for NPC. Silvestrol, an emerging natural plant anticancer molecule, has shown promising antitumor activity in breast cancer, melanoma, liver cancer, and other tumor types by promoting apoptosis in cancer cells to a greater extent than in normal cells. However, the effects of silvestrol on NPC and its possible molecular mechanisms have yet to be fully explored. METHODS: Cell counting kit-8 (CCK-8), cell scratch, flow cytometry, 5-ethynyl-2'-deoxyuridine (EdU), and Western blot (WB) assays were used to evaluate the effects of silvestrol on the cell viability, cell cycle, apoptosis, and migration of NPC cells. RNA sequencing (RNA-Seq) was used to study the effect of extracellular signal-regulated kinase (ERK) inhibitors on the cell transcriptome, and immunohistochemistry (IHC) to assess protein expression levels in patient specimens. RESULTS: Silvestrol inhibited cell migration and DNA replication of NPC cells, while promoting the expression of cleaved caspase-3, apoptosis, and cell cycle arrest. Furthermore, silvestrol altered the level of ERK phosphorylation. The ERK-targeted inhibitor LY3214996 attenuated silvestrol-mediated inhibition of NPC cell proliferation but not migration. Analysis of RNA-Seq data and WB were used to identify and validate the downstream regulatory targets of silvestrol. Expression of GADD45A, RAP1A, and hexokinase-II (HK2) proteins was inhibited by silvestrol and LY3214996. Finally, IHC revealed that GADD45A, RAP1A, and HK2 protein expression was more abundant in cancer tissues than in non-tumor tissues. CONCLUSIONS: Silvestrol inhibits the proliferation of NPC cells by targeting ERK phosphorylation. However, the inhibition of NPC cell migration by silvestrol was independent of the Raf-MEK-ERK pathway. RAP1A, HK2, and GADD45A may be potential targets for the action of silvestrol.

Differentiated impacts of short-term exposure to fine particulate constituents on infectious diseases in 507 cities of Chinese children and adolescents: A nationwide time-stratified case-crossover study from 2008 to 2021.

This study assesses the association of short-term exposure to PM2.5 (particles ≤2.5 µm) on infectious diseases among Chinese children and adolescents. Analyzing data from 507 cities (2008-2021) on 42 diseases, it focuses on PM2.5 components (black carbon (BC), ammonium (NH4+), inorganic nitrate (NO3-), organic matter (OM), and sulfate (SO42-)). PM2.5 constituents significantly associated with incidence. Sulfate showed the most substantial effect, increasing all-cause infectious disease risk by 2.72 % per interquartile range (IQR) increase. It was followed by BC (2.04 % increase), OM (1.70 %), NO3- (1.67 %), and NH4+ (0.79 %). Specifically, sulfate and BC had pronounced impacts on respiratory diseases, with sulfate linked to a 10.73 % increase in seasonal influenza risk and NO3- to a 16.39 % rise in tuberculosis. Exposure to PM2.5 also marginally increased risks for gastrointestinal, enterovirus, and vectorborne diseases like dengue (7.46 % increase with SO42-). Sexually transmitted and bloodborne diseases saw an approximate 6.26 % increase in incidence, with specific constituents linked to diseases like hepatitis C and syphilis. The study concludes that managing PM2.5 levels could substantially reduce infectious disease incidence, particularly in China's middle-northern regions. It highlights the necessity of stringent air quality standards and targeted disease prevention, aligning PM2.5 management with international guidelines for public health protection.

Radiologic Evaluation of Uncinate Processes of the Cervical Spine and the Relationship Between the Uncinate Process and Vertebral Artery: Implication in Anterior Cervical Spine Surgery.

OBJECTIVE: To determine the relationship between the uncinate process (UP) and vertebral artery (VA) from a radiologic view and to confirm the surgical safety margin to minimize the risk of VA injury during anterior cervical approaches. METHODS: We retrospectively reviewed computed tomography angiography of 205 patients by using a contrast-enhanced computed tomography angiography protocol of the VA. Four kinds of images were simultaneously reconstructed to measure all the parameters associated with VA and UP of cervical spine. RESULTS: The shortest distance from the UP's tip to the VA's medial border (P < 0.001) was at the C-6 level (2.9 ± 0.9 mm on the left and 3.2 ± 1.3 mm on the right), and the longest distance (P < 0.001) was at the C-3 level on both sides. The distance between UP's tip and the medial border of the ipsilateral VA was statistically significantly different at each cervical level, and the right distance was larger than the left (P < 0.05). We found the height of UP gradually increased from C-3 to C5-level and then decreased from C-5 to C-7 level for both sides. The mean distance between the medial borders of left UP and left VA was on average 7.5 ± 1.4 mm. The diameter of VA was on average 3.4 ± 0.6 mm on the left side and 3.2 ± 0.7 mm on the right. The diameter of the VA was statistically significantly different on both sides, and the left side was larger than the right (P < 0.05). CONCLUSIONS: Detailed radiologic anatomy of VA and UP was reviewed in this study. A deep understanding of the correlation between the UP and VA is essential to perform anterior cervical spine surgery safely and ensure adequate spinal canal decompression.

Prevalence, trends, and characteristics of metabolic dysfunction-associated steatotic liver disease among the US population aged 12-79 years.

BACKGROUND AND AIMS: Clinical observation revealed an increase in metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence among adults and adolescents and young adults (AYA). However, its prevalence trend in specific subgroups and its characteristics are unclear. APPROACH AND RESULTS: This cross-sectional study included adults and AYA aged 20-79 and 12-19 years, respectively, from the National Health and Nutrition Examination Survey from 1999 to 2018. MASLD was defined as US Fatty Liver Index ≥30 in adults and alanine amino transaminase elevation and obesity in AYA. Joinpoint and logistic regression were used to evaluate the MASLD prevalence trend and its associated characteristics. MASLD was diagnosed in 17 156 892 of 51 109 914 (33.6%) adults and 1 705 586 of 29 278 666 AYA (5.8%). During the study period, MASLD prevalence significantly increased from 30.8% to 37.7% ( P  < 0.01) in adults and in subgroups of female participants, individuals aged 20-45 and 61-79 years, and non-Hispanic white individuals. Conversely, MASLD prevalence did not significantly change in AYA (from 5.1% to 5.2%, P  = 0.139), except in the subgroup of Mexican Americans (from 8.2% to 10.8%, P  = 0.01). Among adults, high MASLD prevalence was associated with male sex, Mexican American ethnicity, age >50 years, being unmarried, poverty income ratio <130, poor or fair health condition, obesity or overweight, and chronic conditions. Among AYA, high MASLD prevalence was associated with male sex, poverty income ratio <130, and education. CONCLUSION: Accordingly, we concluded that health care providers should prevent and treat conditions associated with MASLD by raising awareness of the increasing trend of MASLD.

NIa-Pro of sugarcane mosaic virus targets Corn Cysteine Protease 1 (CCP1) to undermine salicylic acid-mediated defense in maize.

Papain-like cysteine proteases (PLCPs) play pivotal roles in plant defense against pathogen invasions. While pathogens can secrete effectors to target and inhibit PLCP activities, the roles of PLCPs in plant-virus interactions and the mechanisms through which viruses neutralize PLCP activities remain largely uncharted. Here, we demonstrate that the expression and activity of a maize PLCP CCP1 (Corn Cysteine Protease), is upregulated following sugarcane mosaic virus (SCMV) infection. Transient silencing of CCP1 led to a reduction in PLCP activities, thereby promoting SCMV infection in maize. Furthermore, the knockdown of CCP1 resulted in diminished salicylic acid (SA) levels and suppressed expression of SA-responsive pathogenesis-related genes. This suggests that CCP1 plays a role in modulating the SA signaling pathway. Interestingly, NIa-Pro, the primary protease of SCMV, was found to interact with CCP1, subsequently inhibiting its protease activity. A specific motif within NIa-Pro termed the inhibitor motif was identified as essential for its interaction with CCP1 and the suppression of its activity. We have also discovered that the key amino acids responsible for the interaction between NIa-Pro and CCP1 are crucial for the virulence of SCMV. In conclusion, our findings offer compelling evidence that SCMV undermines maize defense mechanisms through the interaction of NIa-Pro with CCP1. Together, these findings shed a new light on the mechanism(s) controlling the arms races between virus and plant.

Hsa_circ_0004872 alleviates meningioma progression by sponging miR-190a-3p/PTEN signaling.

BACKGROUND: Meningioma, the most prevalent intracranial tumor, possesses a significant propensity for malignant transformation. Circular RNAs (circ-RNAs), a class of non-coding RNAs, have emerged as crucial players in tumorigenesis. This study explores the functional relevance of hsa_circ_0004872, a specific circ-RNA, in the context of meningioma. METHODS: Molecular structure and stability of hsa_circ_0004872 were elucidated through PCR identification. Meningioma cell proliferation and apoptosis were assessed using the CCK-8 assay and flow cytometry, respectively. Gene and protein expression were analyzed via qRT-PCR and western blot. Molecular interactions were confirmed through dual-luciferase reporter gene and RIP assays. RESULTS: Hsa_circ_0004872, derived from exons 2 to 4 of the host gene MAPK1, demonstrated enhanced stability compared to its host MAPK1. Clinical data described that hsa_circ_0004872 was reduced in meningioma tissues and cell lines, and negatively correlated to poor survival rate of meningioma patients. Overexpression of hsa_circ_0004872 exhibited inhibitory effects on cell proliferation and promotion of apoptosis in vitro. Subsequent investigations unveiled a direct interaction between hsa_circ_0004872 and miR-190a-3p, leading to the activation of the PI3K/AKT signaling pathway through targeting PTEN. Notably, miR-190a-3p silence accelerated the apoptosis and proliferation inhibition of meningioma cells by inactivating PTEN/PI3K/AKT signaling, while miR-190a-3p overexpression showed an opposite effect, which greatly reversed the anti-tumor effects of hsa_circ_0004872 overexpression. CONCLUSION: In summary, our findings highlighted the intricate role of hsa_circ_0004872 in meningioma, shedding light on the regulatory mechanisms involving circ-RNAs in tumor progression. This positions hsa_circ_0004872 as a potential key regulatory factor in meningioma with implications for future therapeutic interventions.

Causal effects from nonalcoholic fatty liver disease on cholelithiasis: A mendelian randomization study.

Background and Aims: Both nonalcoholic fatty liver disease (NAFLD) and cholelithiasis are highly prevalent hepatobiliary diseases with risk of progression into severe outcomes. Considering the close relationship between liver and gallbladder in anatomy and physiology, a potential causal relationship between NAFLD and cholelithiasis has been speculated. Methods: Mendelian randomization (MR) was employed using genome-wide association study (GWAS) summary statistics in Million Veteran Program (MVP) for NAFLD, and statistics in UK biobank for cholelithiasis. Results: Our results demonstrate that NAFLD has a causal effect on cholelithiasis risk (OR, 1.003; 95%CI, 1.000-1.006; p = 0.03). We also performed the sensitivity analysis and heterogeneity test to ensure the accuracy of outcome and avoid the reverse causality. Conclusion: NAFLD should be regarded as a potential pathogenic factor in pathogenesis study of cholelithiasis, and be considered in assessment and treatment of cholelithiasis.

Comparative Study of the Orientation and Order Effects on the Thermoelectric Performance of 2D and 3D Perovskites.

Calcium titanium oxide has emerged as a highly promising material for optoelectronic devices, with recent studies suggesting its potential for favorable thermoelectric properties. However, current experimental observations indicate a low thermoelectric performance, with a significant gap between these observations and theoretical predictions. Therefore, this study employs a combined approach of experiments and simulations to thoroughly investigate the impact of structural and directional differences on the thermoelectric properties of two-dimensional (2D) and three-dimensional (3D) metal halide perovskites. Two-dimensional (2D) and three-dimensional (3D) metal halide perovskites constitute the focus of examination in this study, where an in-depth exploration of their thermoelectric properties is conducted via a comprehensive methodology incorporating simulations and experimental analyses. The non-equilibrium molecular dynamics simulation (NEMD) was utilized to calculate the thermal conductivity of the perovskite material. Thermal conductivities along both in-plane and out-plane directions of 2D perovskite were computed. The NEMD simulation results show that the thermal conductivity of the 3D perovskite is approximately 0.443 W/mK, while the thermal conductivities of the parallel and vertical oriented 2D perovskites increase with n and range from 0.158 W/mK to 0.215 W/mK and 0.289 W/mK to 0.309 W/mK, respectively. Hence, the thermal conductivity of the 2D perovskites is noticeably lower than the 3D ones. Furthermore, the parallel oriented 2D perovskites exhibit more effective blocking of heat transfer behavior than the perpendicular oriented ones. The experimental results reveal that the Seebeck coefficient of the 2D perovskites reaches 3.79 × 102 µV/K. However, the electrical conductivity of the 2D perovskites is only 4.55 × 10-5 S/cm, which is one order of magnitude lower than that of the 3D perovskites. Consequently, the calculated thermoelectric figure of merit for the 2D perovskites is approximately 1.41 × 10-7, slightly lower than that of the 3D perovskites.

Maresin 1 Activates LGR6 to Alleviate Neuroinflammation via the CREB/JMJD3/IRF4 Pathway in a Rat Model of Subarachnoid Hemorrhage.

Neuroinflammation is an early event of brain injury after subarachnoid hemorrhage (SAH). Whether the macrophage mediators in resolving inflammation 1 (MaR1) is involved in SAH pathogenesis is unknown. In this study, 205 male Sprague-Dawley rats were subjected to SAH via endovascular perforation in the experimental and control groups. MaR1 was dosed intranasally at 1 h after SAH, with LGR6 siRNA and KG-501, GSK-J4 administered to determine the signaling pathway. Neurobehavioral, histological and biochemical data were obtained from the animal groups with designated treatments. The results showed: (i) The leucine-rich repeat containing G protein-coupled receptor 6 (LGR6) was decreased after SAH and reached to the lowest level at 24 h after SAH. Jumonji d3 (JMJD3) protein levels tended to increase and peaked at 24 h after SAH. LGR6 and JMJD3 expression were co-localized with microglia. (ii) MaR1 administration mitigated short-term neurological deficits, brain edema and long-term neurobehavioral performance after SAH, and attenuated microglial activation and neutrophil infiltration. (iii) Knockdown of LGR6, inhibition of CREB phosphorylation or JMJD3 activity abolished the anti-neuroinflammatory effect of MaR1 on the expression of CREB, CBP, JMJD3, IRF4, IRF5, IL-1ß, IL-6 and IL-10, thus prevented microglial activation and neutrophil infiltration. Together, the results show that MaR1 can activate LGR6 and affect CREB/JMJD3/IRF4 signaling to attenuate neuroinflammation after SAH, pointing to a potential pharmacological utility in this disorder.

Anatomically realistic aortic dissection simulator as a potential training tool for point-of-care ultrasound.

Aim: Simulators for aortic dissection diagnosis are limited by complex anatomy influencing the accuracy of point-of-care ultrasound for diagnosing aortic dissection. Therefore, this study aimed to create a healthy ascending aorta and class DeBakey, type II aortic dissection simulator as a potential point-of-care ultrasound training model. Material and methods: 3D mould simulators were created based on computed tomography images of one healthy and one DeBakey type II aortic dissection patient. In the next step, two polyvinyl alcohol-based and two silicone-based simulators were synthesised. Results: The results of the scanning electron microscope assessment showed an aortic dissection simulator's surface with disorganised surface texture and higher root mean square (RMS or Rq) value than the healthy model of polyvinyl alcohol (RqAD = 20.28 > RqAAo = 10.26) and silicone (RqAD = 33.8 > RqAAo = 23.07). The ultrasound assessment of diameter aortic dissection showed higher than the healthy ascending aorta in polyvinyl alcohol (dAD = 28.2 mm > dAAo = 20.2 mm) and Si (dAD = 31.0 mm > dAAo = 22.4 mm), while the wall thickness of aortic dissection showed thinner than the healthy aorta in polyvinyl alcohol, which is comparable with the actual aorta measurement. The intimal flap of aortic dissection was able to replicate and showed a false lumen in the ultrasound images. The flap was measured quantitatively, indicating that the intimal flap was hyperechoic. Conclusions: The simulators were able to replicate the surface morphology and echogenicity of the intimal flap, which is a linear hyperechoic area representing the separation of the aorta wall.

Gut Fungal Microbiota Alterations in Pulmonary Arterial Hypertensive Rats.

The gut microbiome's imbalance has been implicated in the pathogenesis of pulmonary arterial hypertension (PAH), yet the contribution of the gut mycobiome remains largely unclear. This study delineates the gut mycobiome profile in PAH and examines its interplay with the bacterial microbiome alterations. Fecal samples from monocrotaline-induced PAH rats and matched controls were subjected to internal transcribed spacer 1 (ITS1) sequencing for fungal community assessment and 16S ribosomal RNA (rRNA) gene sequencing for bacterial community characterization. Comparative analysis revealed no significant disparities in the overall mycobiome diversity between the PAH and control groups. However, taxonomic profiling identified differential mycobiome compositions, with the PAH group exhibiting a significant enrichment of genera such as Wallemia, unidentified_Branch02, Postia, Malassezia, Epicoccum, Cercospora, and Alternaria. Conversely, genera Xeromyces, unidentified_Plectosphaerellaceae, and Monilia were more abundant in the controls. Correlations of Malassezia and Wallemia abundance with hemodynamic parameters were observed. Indications of bidirectional fungal-bacterial community interactions were also noted. This investigation reveals distinct gut mycobiome alterations in PAH, which are intricately associated with concurrent bacterial microbiome changes, suggesting a possible contributory role of gut fungi in PAH pathophysiology. These findings underscore the potential for novel gut mycobiome-targeted therapeutic interventions in PAH management.