Combustion aerosols and suspended dust with controlled processes in Lhasa: Elemental analysis and size distribution characteristics.

To explore air contamination resulting from special biomass combustion and suspended dust in Lhasa, the present study focused on the size distribution and chemical characteristics of particulate matter (PM) emission resulting from 7 types of non-fossil pollution sources. We investigated the concentration and size distribution of trace elements from 7 pollution sources collected in Lhasa. Combining Lhasa's atmospheric particulate matter data, enrichment factors (EFs) have been calculated to examine the potential impact of those pollution sources on the atmosphere quality of Lhasa. The highest mass concentration of total elements of biomass combustion appeared at PM0.4, and the second highest concentration existed in the size fraction 0.4-1 µm; the higher proportion (12 %) of toxic metals was produced by biomass combustion. The elemental composition of suspended dust and atmospheric particulate matter was close (except for As and Cd); the highest concentration of elements was all noted in PM2.5-10 (PM3-10). Potassium was found to be one of the main biomass markers. The proportion of Cu in suspended dust is significantly lower than that of atmospheric particulate matter (0.53 % and 3.75 %), which indicates that there are other anthropogenic sources. The EFs analysis showed that the Cr, Cu, Zn, and Pb produced by biomass combustion were highly enriched (EFs > 100) in all particle sizes. The EFs of most trace elements increased with decreasing particle size, indicating the greater influence of humanfactors on smaller particles.

Phagosome Isolation with Magnetic Beads and Purification of Toll-Like Receptor (TLR) Complexes in Phagosomes.

Phagocytosis is a central process by which macrophage cells internalize and eliminate microbes as well as apoptotic cells. The nascent phagosome undergoes a complex maturation process involving sequential fusion with endosomal compartments. The endosomal TLRs, including TLR3, -7, -8, and -9, play a critical role in innate immunity by sensing bacterial or viral nucleic acids and are preferentially transported to the phagosomal membrane of innate immune cells upon activation. Therefore, phagosome isolation is helpful for studies on pathogenic invasion and the functions of phagosome proteins, including endosomal TLRs.

Arsenic exposure and oxidative damage to lipid, DNA, and protein among general Chinese adults: A repeated-measures cross-sectional and longitudinal study.

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (ß: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners.

Encapsulation of Lactiplantibacillus plantarum with casein-gellan gum emulsions to enhance its storage, pasteurization, and gastrointestinal survival.

Probiotics serve a very important role in human health. However, probiotics have poor stability during processing, storage, and gastrointestinal digestion. The gellan gum (GG) is less susceptible to enzymatic degradation and resistant to thermal and acidic environments. This study investigated the effect of casein (CS)-GG emulsions to encapsulate Lactiplantibacillus plantarum CICC 6002 (L. plantarum CICC 6002) on its storage stability, thermal stability, and gastrointestinal digestion. L. plantarum CICC 6002 was suspended in palm oil and emulsions were prepared using CS or CS-GG complexes. We found the CS-GG emulsions improved the viability of L. plantarum CICC 6002 after storage, pasteurization, and digestion compared to the CS emulsions. In addition, we investigated the influence of the gellan gum concentration on emulsion stability, and the optimal stability was observed in the emulsion prepared by CS-0.8% GG complex. This study provided a new strategy for the protection of probiotics based on CS-GG delivery system.

Correlation analysis and modeling application from objective indicators to subjective evaluation of scented tea: A case study of rose tea.

Different scented teas provide various choices for consumers from appearance, aroma, flavor and others. Aiming to define advantages and market positions of different scented teas and promote optimization of market structure, characteristics for scented tea favored by consumers and outstanding attributes of different scented teas should be clarified. Rose tea was taken as study object. Sensory evaluation and consumer acceptance were investigated. GC-MS and HPLC fingerprints were established. Physicochemical characteristics were determined. RGB integration analysis was inventively proposed for correlation analysis. The volatile compounds with spicy, green or herbal odor as camphene, ß-phenethyl acetate, eugenol, and physicochemical parameters as antioxidant capacity, reducing sugar content, pH showed positive correlation with popular sensory properties. Six models for consumer preference by objective description were built through GA-SVR (accuracy = 1), and APP was developed. The research mode of scented tea has been successfully established to study multiple subjective characteristics with measurable objective parameters.

Stable laminar shear stress induces G1 cell cycle arrest and autophagy in urothelial carcinoma by a torque sensor-coupled cone-and-plate device.

The microenvironments of urinary systems play crucial roles in the development and metastasis of cancers due to their generation of complex temporal and spatial fluidic profiles. Because of their versatility in creating desired biomimetic flow, cone-and-plate bioreactors offer great potential for bladder cancer research. In this study, we construct a biocompatible cone-and-plate device coupled with a torque sensor, enabling the application and real-time monitoring of stable shear stress up to 50 dyne/cm². Under a stable shear stress stimulation at 12 dyne/cm2, bladder cancer cell BFTC-905 is arrested at the G1 phase with decreased cell proliferation after 24-hour treatment. This effect is associated with increased cyclin-dependent kinase inhibitors p21 and p27, inhibiting cyclin D1/CDK4 complex with dephosphorylation of serine 608 on the retinoblastoma protein. Consequently, an increase in cyclin D3 and decreases in cyclin A2 and cyclin E2 are observed. Moreover, we demonstrate that the shear stress stimulation upregulates the expression of autophagy-related proteins Beclin-1, LC3B-I and LC3B-II, while caspase cleavages are not activated under the same condition. The design of this system and its application shed new light on flow-induced phenomena in the study of urothelial carcinomas.

The Association Between Physical Activity and risk for breast cancer in US female adults: A cross-sectional study based on NHANES 2011-2020.

BACKGROUND: Breast cancer poses a significant threat to women's health worldwide. This study aimed to evaluate the association between various levels of physical activity and the incidence of breast cancer. METHODS: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES), spanning 2011 to 2020. The study included female participants aged 20 years or older, who provided detailed data on breast cancer incidence, physical activity levels, and other pertinent variables. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using multivariate logistic regression analyses, alongside subgroup and sensitivity analyses. RESULTS: After adjusting for potential confounders, multivariate logistic regression analyses indicated that compared to individuals with low physical activity (<600 METs min/week), light physical activity (600 to < 1800 METs min/week), moderate physical activity (1800 to < 3000 METs min/week) and high physical activity (≥3000 METs min/week) were associated with breast cancer with adjusted ORs of 0.95 (95 % CI 0.68-1.34, P = 0.787), 0.92 (95 % CI 0.57-1.49, P = 0.747), and 0.56 (95 % CI 0.37-0.86, P = 0.009) respectively. These results were consistent across sensitivity and subgroup analyses. CONCLUSION: High-intensity physical activity may decrease the risk of breast cancer, highlighting the importance of proactively implementing healthy lifestyle interventions to protect the health of adult women.

Red/near-infrared (NIR) difluoroboron ß-diketonate derivatives with reversible mechanochromism for cellular imaging.

Near-infrared (NIR) fluorophores have promoted the development of materials for bioimaging, but traditional NIR dyes usually suffer from aggregation-caused quenching (ACQ), impeding their applications. Herein, we propose two difluoroboron ß-diketonate complexes TBO and TBS, consisting a donor-acceptor (D-A) structure with triphenylamine (TPA) moiety as an electron donors and difluoroboron as well as furan or thiophene building block as an electron acceptor. The theoretical calculation and optical data shows that both of them have intramolecular charge transfer (ICT) characteristics. Such ICT characteristics endow them with both solvatochromism and dual-state emission (DSE) properties. In the solvent CH2Cl2, the emission wavelength of TBO ranges from 550 nm to 750 nm, with a low fluorescence quantum yield (Φ = 7.0 %). However, in the less polar solvent hexane, the emission wavelength blue-shifts, with an increased Φ reaching up to 18 %. Moreover, TBO and TBS exhibit mechanochromic characteristics and rare multi-channel fluorescence emission phenomena at solid-state. Their solid-state samples can emit fluorescence in four spectral bands with maximum emission wavelengths at 300 nm, 400 nm, 600 nm, and 770 nm under excitation at 240 nm. These unique optical properties are expected to be utilized for detecting polarity of system and deformation. Moreover, according to the results of cell imaging and flow cytometry, TBO molecular were easily internalized into Hela cells and distributed in the cytoplasm with strong red fluorescence. Therefore, this research inspires more insight into development of NIR luminogens for biomedical imaging.

Reaction-Driven Migration Dynamics of Nano-Metal Particles Unraveled by Quantitative Electron Microscopies.

The stability of supported nano-metal catalysts holds significant importance in both scientific and economic practice, beyond the long pursuit of enhanced activity. While previous efforts have concentrated on augmenting the interaction between nano-metals and carriers, in the thermodynamic macro-perspective, to achieve optimized repression upon particle migration coalescence and Ostwald ripening, nevertheless, the microscale kinetics of migrating catalyst particles driven by the reaction remains unknown. In this work, the migration of nano-copper particles is investigated during hydrogen oxidation reaction by utilizing high spatiotemporal resolution of environmental transmission electron microscopy. It is shown that there exists a delicate correlation between the migration dynamics of nano-copper particles and the evolution of asymmetrically distributed Cu and Cu2O phases over the particle surface. It is found that the interplay of reduction and oxidation near the surface areas filled with Cu and Cu2O phases can facilitate the pressure gradient, which drives the migration of nano-particles. A driving force model is therefore established which is capable of qualitatively explaining the influences of reaction conditions such as temperature and hydrogen-to-oxygen ratio on the reaction-driven particle migration. This work adds a potential yet critical perspective to understanding particle migration and thus the nano-metal catalyst particle sintering in heterogeneous catalysis.

Changes in Skeletal Muscle Mass in the First 3 Months Following Gastrointestinal Cancer Surgery: A Prospective Study.

BACKGROUND: Surgical resection is the primary treatment for gastrointestinal (GI) cancers, but postoperative skeletal muscle loss (SML) is common and linked to poor prognosis. This study aims to identify patterns of muscle change, examine its association with quality of life (QoL), and explore predictors of SML in the first 3 months. PATIENTS AND METHODS: A prospective cohort study was conducted on patients newly diagnosed with GI cancer and undergoing surgery in China between September 2021 and May 2022. Skeletal muscle mass (SMM) and QoL were assessed at admission, 7 days, 1 month, and 3 months post-surgery. Demographic, clinical data, and biomarkers were collected. Missing data were imputed using multiple imputation. Data were analyzed using growth mixture modelling, bivariate analyses, and logistic regression. RESULTS: A total of 483 patients completed baseline assessment. Of the 242 patients with complete muscle assessments, 92% experienced SML. Three distinct patterns of muscle change were identified: 57% had normal preoperative SMM with mild postoperative SML, 16% had low preoperative SMM with moderate SML, and 27% had normal preoperative mass but severe postoperative SML. Moderate/severe SML was associated with more postoperative complications, poorer health, and higher symptom burden. Independent predictors included advanced age, preoperative sarcopenia, advanced cancer stage, and low prognostic nutrition index (PNI ≤ 45). The results did not change when using imputed values. CONCLUSIONS: Although SML is prevalent, patterns of muscle change are heterogeneous among patients. Advanced age, preoperative sarcopenia, advanced cancer stage, and cancer-related inflammation are predictors for moderate/severe SML, highlighting the need for early detection and management.

Astragaloside I Promotes Lipophagy and Mitochondrial Biogenesis to Improve Hyperlipidemia by Regulating Akt/mTOR/TFEB Pathway.

The simultaneous enhancement of lipophagy and mitochondrial biogenesis has emerged as a promising strategy for lipid lowering. The transcription factor EB (TFEB) exhibits a dual role, whereby it facilitates the degradation of lipid droplets (LDs) through the process of lipophagy while simultaneously stimulating mitochondrial biogenesis to support the utilization of lipophagy products. The purpose of this study was to explore the effect of astragaloside I (AS I) on hyperlipidemia and elucidate its underlying mechanism. AS I improved serum total cholesterol and triglyceride levels and reduced hepatic steatosis and lipid accumulation in db/db mice. AS I enhanced the fluorescence colocalization of LDs and autophagosomes and promoted the proteins and genes related to the autolysosome. Moreover, AS I increased the expression of mitochondrial biogenesis-related proteins and genes, indicating that AS I promoted lipophagy and mitochondrial biogenesis. Mechanistically, AS I inhibits the protein level of p-TFEB (ser211) expression and promotes TFEB nuclear translocation. The activation of TFEB by AS I was impeded upon the introduction of the mammalian target of rapamycin (mTOR) agonist MHY1485. The inhibition of p-mTOR by AS I and the activation of TFEB were no longer observed after administration of the Akt agonist SC-79, which indicated that AS I activated TFEB to promote lipophagy-dependent on the Akt/mTOR pathway and may be a potentially effective pharmaceutical and food additive for the treatment of hyperlipidemia.

Mechanisms of a mindfulness psyCho-behAvioRal intErvention (MCARE) on depression and anxiety symptoms in patients with acute coronary syndrome: A longitudinal mediation analysis.

OBJECTIVE: This study aimed to explore the mediating roles of mindfulness and illness perception in the effects of a social media-based Mindfulness psyCho-behAvioRal intErvention (MCARE) on depressive and anxiety symptoms among patients with ACS. METHODS: This study conducted a secondary longitudinal mediation analysis using data from a randomized controlled trial of the MCARE grogram in patients with ACS. Participants were recruited at two tertiary hospitals in Jinan, China. The MCARE program consisted of six weekly sessions addressing mindfulness training and disease management to facilitate understanding and management of emotions and illness. The analytical sample included participants who completed measures of the primary outcomes, i.e., depression (PHQ-9) and anxiety (GAD-7) and potential mediators, i.e., mindfulness (CAMS-R) and illness perception (Brief-IPQ) at baseline (T0), immediate post-intervention (T1), and 12-week after the commencement of the intervention (T2). RESULTS: This study included 146 participants (mean age 58.9 years (SD = 8.9), 69.2 % male), including both intervention and control groups. The mediation analysis revealed a significant mediating effect of T1 mindfulness in the relationship between the group and T2 depression symptoms (indirect effect: -0.109, 95 % CI: -0.191, -0.041; P = 0.004), accounting for 26 % of the effect. For T2 anxiety symptoms, T1 illness perception exhibited a significant mediating effect (indirect effect: -0.055, 95 % CI: -0.110, -0.005; P = 0.035), accounting for 22 % of the effect. CONCLUSIONS: This study found that mindfulness and illness perception played a mediating role in the effects of the MCARE program on depressive and anxiety symptoms among patients with ACS.

Establishment and validation of a predictive model for spontaneous preterm birth in singleton pregnant women.

INTRODUCTION: In the current study, we screened for highly sensitive and specific predictors of premature birth, with the aim to establish an sPTB prediction model that is suitable for women in China and easy to operate and popularize, as well as to establish a sPTB prediction scoring system for early, intuitive, and effective assessment of premature birth risk. METHODS: A total of 685 pregnant women with a single pregnancy during the second trimester (16-26 weeks) were divided into premature and non-premature delivery groups based on their delivery outcomes. Clinical and ultrasound information were collected for both groups, and risk factors that could lead to sPTB in pregnant women were screened and analyzed using a cut-off value. A nomogram was developed to establish a prediction model and scoring system for sPTB. In addition, 119 pregnant women who met the inclusion criteria for the modeling cohort were included in the external validation of the model. The accuracy and consistency of the model were evaluated using the area under the receiver operating characteristic (ROC) and C-calibration curves. RESULTS: Multivariate logistic regression analysis showed a significant correlation (P < 0.05) between the number of miscarriages in pregnant women, history of miscarriages in the first week of pregnancy, history of preterm birth, CL of pregnant women, open and continuous cervical opening, and the occurrence of sPTB in pregnant women. We drew a nomogram column chart based on the six risk factors mentioned above, obtained a predictive model for sPTB, and established a scoring system to divide premature birth into three risk groups: low, medium, and high. After validating the model, the Hosmer Lemeshow test indicated a good fit (p = 0.997). The modeling queue C calibration curve was close to diagonal (C index = 0.856), confirming that the queue C calibration curve was also close to diagonal (C index = 0.854). The AUCs of the modeling and validation queues were 0.850 and 0.881, respectively. CONCLUSION: Our predictive model is consistent with China's national conditions, as well as being intuitive and easy to operate, with wide applicability, thus representing a helpful tool to assist with early detection of sPTB in clinical practice, as well as for clinical management in assessing low, medium, and high risks of sPTB.

Efficacy of ozonated autohemotherapy for improvement of myocardial injury following traumatic brain injury.

BACKGROUND: Traumatic brain injury is a kind of injury caused by external violence on the head. Its danger is not limited to life rescue in the early stage of the disease. Moreover, the subsequent inflammatory reaction and the change in its oxidative stress level will cause secondary myocardial injury. The purpose of this study is to explore the myocardial protective effect of ozone autohemotherapy (OA) in the progression of acute traumatic brain injury (TBI). METHODS: Forty patients with acute TBI were recruited and divided into The treatment group (Group OA, n = 18) and the Control group (Group C, n = 19). Patients in Group OA received OA before surgery and on the 1st and 2nd postoperative days, while patients in Group C underwent autologous blood transfusion. Venous blood was collected from all patients before (T0) and after 7 days (T1) days of surgery for measurement of cardiac troponin T (cTnT) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP). At T0 and T1, transthoracic cardiac ultrasound was performed to measure left ventricular ejection fraction (LVEF), tricuspid annular plane systolic excursion (TAPSE), and venous blood was sampled to determine the contents of superoxide dismutase (SOD) and malondialdehyde (MDA). NIH Stroke Scale (NIHSS) and Glasgow Coma Scale (GCS) scores were calculated, and other clinical indexes were recorded. RESULTS: (1) The levels of cTnT at T1 were significantly higher as compared with that at T0 in both groups (p < 0.01). Compared with Group C, a remarkable decline in the content of NT-proBNP was found in Group OA at T1 (p = 0.021). (2) The LVEF (p = 0.002) and serum SOD (p = 0.015) at T1 were significantly increased in Group OA as compared with those in Group C. (3) The length of Intensive Care Unit and hospitalization time for patients in Group OA was distinctly shorter than that for patients in Group C (p = 0.021, p = 0.015, respectively). CONCLUSION: Perioperative OA treatment can alleviate the secondary myocardial injury during the disease course of TBI, which might be associated with its myocardial protective effect against oxidative stress. TRIAL REGISTRATION: This study was approved by the Ethical Committee of Changzhou NO.2 People's Hospital. The protocol was registered prospectively with the Chinese Clinical Trial Registry (ChiCTR2000029612) on February 02, 2020.

Stapokibart (CM310) targets IL-4Rα for the treatment of type 2 inflammation.

Stapokibart (CM310) is a humanized IL-4Rα monoclonal antibody currently undergoing phase 3 trials for type 2 inflammatory diseases. In contrast to dupilumab, which bound exclusively to human IL-4Rα, stapokibart demonstrated cross-species reactivity to IL-4Rα from human, cynomolgus monkey, and rat. Stapokibart exhibited comparable blocking activity to dupilumab. Epitope mapping revealed that stapokibart bound to distinct sites on IL-4Rα compared to dupilumab. In vitro assays showed that stapokibart was comparable or numerically superior in blocking IL-4Rα-mediated signaling compared to dupilumab. In vivo studies further demonstrated that stapokibart effectively inhibited the progression of type 2 inflammation. Pharmacokinetic studies revealed a circulating half-life of approximately 298-351 h in cynomolgus monkeys and 55-142 h in rats for stapokibart. Toxicity studies indicated a favorable safety profile in cynomolgus monkeys and rats. The preclinical evaluation of stapokibart supports its clinical development.

CDT1, transcriptionally regulated by E2F2, promotes lung adenocarcinoma progression.

CDT1, a gene that shows excessive expression in various malignancies, functions as a pivotal regulator of replication licensing. In this study, we observed a positive correlation in expression between CDT1 and E2F2 among patients with lung adenocarcinoma (LUAD). Our findings substantiated that E2F2 directly interacted with the promoter region of CDT1, as confirmed by ChIP-qPCR assays, and depletion of E2F2 resulted in a downregulation of CDT1 expression in LUAD cell lines by gene interference technology. Furthermore, we identified an upregulation of CDT1 mRNA level in Chinese LUAD samples. Notably, in the loss-of-function assays, depletion of CDT1 in LUAD cell lines inhibited cell proliferation, migration, and invasion. Concurrently, it promoted cell apoptosis and induced G0/G1 phase arrest using MTT, flow cytometry, and Transwell assays, reinforcing its role as an oncogene.Furthermore, enhanced tumor ablation was determined in a CDT1-downregulated LUAD tumor-bearing nude mouse model. Collectively, our results strongly suggest that E2F2 positively regulates CDT1 expression and actively participates in the progression of lung adenocarcinoma, thereby providing valuable insights into identifying novel therapeutic targets for LUAD treatment.

Evaluation of the Curative Effects of Surgical Intervention in Cases of Congenital Malformation of the Ossicular Chain in Children.

Purpose: Congenital malformation of the ossicular chain results in challenges with hearing and language development in children. We aimed to analyze the clinical characteristics, prognosis, and surgical treatments of different types of congenital ossicular chain malformations in children. Methods: Eight cases (10 ears) treated between October 2019 and February 2022 were analyzed retrospectively. Patients were divided according to the location of the ossicular chain malformation and whether it was complicated by external ear malformation. Imaging, audiological examination, intraoperative exploration of the middle ear, and postoperative outcomes were recorded. Results: Group 1 incudostapedial joint deformity): 6 ears/60%; Group 2 (simple incus deformity): 2 ears/20%; Group 3 (simple malleus deformity): 2 ears/20%; Group A (with external ear malformations): 4 ears/40%; Group B (without external ear malformations): 6 ears/60%. The average hearing threshold before and after the operation was 51.25 ± 12.88 and 31.94 ± 12.96 dB, respectively. There were differences in the intervention effects of different malformed sites (Group 1: t = 5.139, P = .004; Group 2: t = 13.500, P = .047; Group 3: t = 15.000, P = .042). The effect of the intervention in cases of malformation with mobile stapes footplates was better than that with immobile stapes footplates (t = 4.082, P = .027). The effect of the intervention without external ear malformations was better than that with external ear malformations (t = 7.706, P = .001). Conclusions: The intervention yielded superior results in cases of malformation with mobile stapes footplates compared to those with immobile stapes footplates. Different intervention strategies should be determined through precise deformity assessments, with the degree of stapes mobility serving as a crucial factor in improving the prognosis.

Exploring the relationship between the interleukin family and lung adenocarcinoma through Mendelian randomization and RNA sequencing analysis.

BACKGROUND: Lung adenocarcinoma (LUAD) is still one of the most prevalent malignancies. Interleukin factors are closely associated with the initiation and progression of cancer. However, the relationship between interleukin factors and LUAD has not been fully elucidated. This study aimed to use Mendelian randomization (MR) and RNA sequencing (RNA-seq) analyses to identify the interleukin factors associated with the onset and progression of LUAD. METHODS: Exposure-related instrumental variables were selected from interleukin factor summary datasets. The LUAD summary dataset from FINGENE served as the outcome. MR and sensitivity analyses were conducted to screen for interleukin factors associated with LUAD occurrence. Transcriptome analyses revealed the role of interleukin factors in lung tissues. The results were validated through Western blotting and further confirmed with driver gene-negative patients from multiple centers. Potential mechanisms influencing LUAD occurrence and development were explored using bulk RNA-seq and single-cell RNA-seq data. RESULTS: MR analysis indicated that elevated plasma levels of IL6RB, IL27RA, IL22RA1, and IL16 are causally associated with increased LUAD risk, while IL18R1 and IL11RA exhibit the opposite effect. Transcriptome analyses revealed that IL11RA, IL18R1, and IL16 were downregulated in tumor tissues compared with normal lung tissue, but only higher expression of IL11RA correlated with improved prognosis in patients with LUAD from different centers and persisted even in driver-gene negative patients. The IL11RA protein level was lower in various LUAD cell lines than in human bronchial epithelial cells. The genes co-expressed with IL11RA were enriched in the Ras signaling pathway and glycosylation processes. Fibroblasts were the primary IL11RA-expressing cell population, with IL11RA+fibroblasts exhibiting a more immature state. The genes differentially expressed between IL11RA+and IL11RA- fibroblasts were involved in the PI3K-Akt/TNF signaling pathway. CONCLUSION: According to the MR and transcriptome analyses, the downregulation of IL11RA was closely related to the occurrence and development of LUAD.

Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell-Inner Plexiform Layer Parameters and Their Associated Factors in Cynomolgus Macaques.

Purpose: The purpose of this study was to define the normal range of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer (mGCL), and macular inner plexiform layer (mIPL) thickness in cynomolgus macaques, and explore their inter-relationship and correlation with age, refractive errors, and axial length (AL). Methods: In this cross-sectional study, we measured biometric and refractive parameters, and pRNFL/mGCL/mIPL thickness in 357 healthy cynomolgus macaques. Monkeys were divided into groups by age and spherical equivalent (SE). Correlation and regression analyses were used to explore the relationship between pRNFL and mGCL/mIPL thickness, and their correlation with the above parameters. Results: The mean age, SE, and AL were 14.46 ± 6.70 years, -0.96 ± 3.23 diopters (D), and 18.39 ± 1.02 mm, respectively. The mean global pRNFL thickness was 95.06 ± 9.42 µm (range = 54-116 µm), with highest values in the inferior quadrant, followed by the superior, temporal, and nasal quadrants (P < 0.001). Temporal pRNFL thickness correlated positively with age (r = 0.218, P < 0.001) and AL (r = 0.364, P < 0.001), and negatively with SE (r = -0.270, P < 0.001). In other quadrants, pRNFL thickness correlated negatively with age and AL, but positively with SE. In the multivariable linear regression model, adjusted for sex and AL, age (ß = -0.350, P < 0.001), and SE (ß = 0.206, P < 0.001) showed significant associations with global pRNFL thickness. After adjusting for age, sex, SE, and AL, pRNFL thickness positively correlated with mGCL (ß = 0.433, P < 0.001) and mIPL thickness (ß = 0.465, P < 0.001). Conclusions: The pRNFL/mGCL/mIPL thickness distribution and relationship with age, AL, and SE in cynomolgus macaques were highly comparable to those in humans, suggesting that cynomolgus monkeys are valuable animal models in ophthalmic research.