Comparative of OCT and OCTA parameters in patients with early chronic angle-closure glaucoma and early pituitary adenoma.

Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) have the potential application in evaluating pathological structural change of the optic nerve. We aimed to evaluate the value of the OCT and OCTA parameters of the optic disk and macular in differentiating early chronic primary angle-closure glaucoma (CPACG) and early pituitary adenoma (PA) in case of mild visual field defects (the mean defect (MD) > 6 dB). The results showed that regarding OCTA parameters, CPACG patients had lower retinal blood flow density of most layers of the optic disk and macular than PA patients. Regarding OCT parameters, CPACG patients had thinner circumpapillary retinal nerve fiber layer (CP-RNFL) in all quadrants and average CP-RNFL, ganglion cell layer (GCL) and macular ganglion cell complex (GCC) in each quadrant of macular inner and outer rings, and inner plexus layer (IPL) of macular inner ring, superior-outer ring and temporal-outer ring than PA patients. The Z test indicated that OCTA parameters and OCT parameters had similar value in the diagnosis of disease. In conclusion, in the case of similar visual field damage, early CPACG patients have smaller blood flow density and thinner optic disk and macular than early PA. OCTA has similar performance to OCT in diagnosing CPACG and PA.

Assessment of diagnostic value of ultrasound and multi-slice spiral computed tomography in acute appendicitis: a retrospective study.

PURPOSE: Ultrasound and multi-slice spiral computed tomography (CT) are frequently used to assist the diagnosis of acute appendicitis (AA), and the examination results may vary among different demographics. This study aimed to compare the diagnostic accuracy of ultrasound and CT for AA. METHODS: We performed a retrospective analysis of patients diagnosed with AA who underwent emergency surgery at our hospital from March 2021 to August 2023, with postoperative pathological results as the gold standard. Differences in the diagnostic accuracy of ultrasound and CT for different types of AA, age groups, and body mass index (BMI) values were then analyzed. RESULTS: The overall sample comprised 279 confirmed cases of AA, with 64 cases of simple appendicitis, 127 cases of suppurative appendicitis, and 88 cases of gangrenous appendicitis. For these three pathological classifications, the diagnostic accuracy of ultrasound was 68.75% (44/64), 73.22% (93/127), and 81.81% (72/88), respectively, while the diagnostic accuracy of CT was 71.87% (46/64), 82.67% (105/127), and 90.90% (80/88), respectively. There was no statistically significant difference in the overall diagnostic accuracy between the two methods (P > 0.05). Subgroup analysis showed no difference in diagnostic accuracy between the two methods for patients with normal BMI (P > 0.05). However, for overweight, obese, and elderly patients, CT provided significantly better diagnostic accuracy than ultrasound (P < 0.05). CONCLUSION: While ultrasound and CT have similar diagnostic accuracy for different pathological types of AA, CT is more accurate for overweight, obese, and elderly patients.

Association of diaphragmatic dysfunction with duration of mechanical ventilation in patients in the pediatric intensive care unit: a prospective cohort study.

BACKGROUND: Mechanical ventilation (MV) can cause diaphragmatic injury and ventilator induced diaphragmatic dysfunction (VIDD). Diaphragm ultrasonography (DU) is increasingly used to assess diaphragmatic anatomy, function and pathology of patients receiving MV in the pediatric intensive care unit (PICU). We report the poor contractile ability of diaphragm during ventilation of critically ill patients in our PICU and the association to prolonged length of MV and PICU stay. METHODS: Patients who received MV within 24 h of admission to the PICU, expected to undergo continuous MV for more than 48 h and succeeded to extubate were included in the study. DU monitoring was performed daily after the initiation of MV until extubation. Diaphragm thickening fraction (DTF) measured by DU was used as an indicator of diaphragmatic contractile activity. Patients with bilateral DTF = 0% during DU assessment were allocated into the severe VIDD group (n = 26) and the rest were into non-severe VIDD group (n = 29). The association of severe VIDD with individual length of MV, hospitalization and PICU stay were analyzed. RESULTS: With daily DU assessment, severe VIDD occurred on 2.9 ± 1.2 days after the initiation of MV, and lasted for 1.9 ± 1.7 days. Values of DTF of all patients recovered to > 10% before extubation. The severe VIDD group had a significantly longer duration (days) of MV [12.0 (8.0-19.3) vs. 5.0 (3.5-7.5), p < 0.001] and PICU stay (days) [30.5 (14.9-44.5) vs. 13.0 (7.0-24.5), p < 0.001]. The occurrence of severe VIDD, first day of severe VIDD and length of severe VIDD were significantly positively associated with the duration of MV and PICU stay. The occurrence of severe VIDD on the second and third days after initiation of MV significantly associated to longer PICU stay (days) [43.0 (9.0-70.0) vs. 13.0 (3.0-40.0), p = 0.009; 36.0 (17.0-208.0) vs. 13.0 (3.0-40.0), p = 0.005, respectively], and the length of MV (days) was significantly longer in those with severe VIDD on the third day after initiation of MV [16.5 (7.0-29.0) vs. 5.0 (2.0-22.0), p = 0.003]. CONCLUSIONS: Daily monitoring of diaphragmatic function with bedside ultrasonography after initiation of MV is necessary in critically ill patients in PICU and the influences and risk factors of severe VIDD need to be further studied. (355 words).

Complex structure and activation mechanism of arginine kinase McsB by McsA.

Protein phosphorylation is a pivotal post-translational modification modulating various cellular processes. In Gram-positive bacteria, the protein arginine kinase McsB, along with its activator McsA, has a key role in labeling misfolded and damaged proteins during stress. However, the activation mechanism of McsB by McsA remains elusive. Here we report the cryo-electron microscopy structure of a tetrameric McsA-McsB complex at 3.41 Å resolution. Biochemical analysis indicates that the homotetrameric assembly is essential for McsB's kinase activity. The conserved C-terminal zinc finger of McsA interacts with an extended loop in McsB, optimally orienting a critical catalytic cysteine residue. In addition, McsA binding decreases the CtsR's affinity for McsB, enhancing McsB's kinase activity and accelerating the turnover rate of CtsR phosphorylation. Furthermore, McsA binding also increases McsB's thermostability, ensuring its activity under heat stress. These findings elucidate the structural basis and activation mechanism of McsB in stress response.

RST31 controls salt tolerance in rice (Oryza sativa) by regulating the cytokinin pathway.

Salt stress affects the growth of rice, which reduces grain yield. However, the mechanism of the rice response to salt stress is not fully understood. The rice salt tolerance 31 (rst31) mutant exhibits longer shoots and greater dry weight than wild type (WT) plants under salt stress conditions. Through map-based cloning and genetic complementation methods, we determined that RST31 encodes a half-size ABCG transporter protein, ABCG18. We showed that mutation of RST31 reduces DNA damage under salt stress, with less accumulation of reactive oxygen species (ROS). The deficiency of RST31 suppressed the root-to-shoot transport of cytokinin, which resulted in a decrease in cytokinin content in the shoot and an increase in cytokinin content in the root. ROS accumulated abundantly in WT and rst31 mutant plants after exogenous treatment with trans-zeatin, reducing rst31 tolerance of salt stress. Collectively, our results suggest that high cytokinin level in shoots leads to an increase in ROS content and severe DNA damage under salt stress, which lead to sensitivity to salt stress. These findings enhance our understanding of plant responses to salt stress through cytokinin pathways.

Relationship between cognitive function and sleep quality in middle-aged and older adults for minimizing disparities and achieving equity in health: Evidence from multiple nationwide cohorts.

BACKGROUND: Cognitive decline, a heavy burden on middle-aged and older adults as global aging is aggravated, was found to be associated with sleep quality. However, the country-between heterogeneity of the association prevented us from quantifying underlying relationship and identifying potential effect modifiers for vulnerable populations and targeted interventions. METHODS: We collected data from 79,922 eligible adults in five nationwide cohorts, examined the respective relationships between cognitive function and sleep quality, synthesized underlying average relationships by meta-analysis, and explored effect modifiers by meta-regressions. Additionally, we conducted subgroup and interaction analyses to identify vulnerable populations and to determine their disparities in vulnerability. RESULTS: Although country-between disparities exist, cognitive function is robustly associated with sleep quality in middle-aged and older adults worldwide, with an effect (ß) of 0.015 [0.003, 0.027]. Executive function is the subdomain most relevant to sleep quality. Disparities in the effects of sleep quality on subdomains exist in populations with different sexes (orientation: ßfemale/ßmale = 1.615, P = 0.020), marital statuses (orientation: ßunmarried/ßmarried = 2.074, P < 0.001), education levels (orientation:ßuneducated/ßeducated = 2.074, P < 0.001) and chronic disease statuses (memory: ßunhealthy/ßhealthy = 1.560, P = 0.005). CONCLUSIONS: Cognitive function decreases with worsening sleep quality in middle-aged and older adults. Vulnerability to poor sleep generally persists in singles, females, the uneducated and people with chronic diseases. To minimize disparities and achieve health equity, we advocate for targeted interventions, i.e., encouraging socialization in singles, confirming effectiveness of hormone replacement therapy in females, employing compulsory education in middle-aged and older adults.

Solamargine acts as an antiviral by interacting to MZF1 and targeting the core promoter of the hepatitis B virus gene.

BACKGROUND: Hepatitis B virus (HBV) infection is still a serious threat to global health and can lead to a variety of liver diseases, including acute and chronic hepatitis, liver cirrhosis, liver failure, hepatocellular carcinoma (HCC), and so on. At present, there are mainly two kinds of drugs for the treatment of hepatitis B at home and abroad: interferon (IFN) and nucleoside/nucleotide analogs (NAs). In recent years, natural compounds have been considered an important source for the development of new anti-HBV drugs due to their complex structure, diverse components, high efficiency, and low toxicity. Many studies have demonstrated that Solamargine has significant anticancer activity, but the antiviral effect is rarely studied. This study aimed to verify the anti-HBV effect of Solamargine and to explore the specific mechanism. METHOD: The relative expression of HBV pregenomic RNA (pgRNA) was detected by reverse transcription real-time fluorescence quantitative PCR (RT-qPCR). Northern blot and western blot were used to detect the relative expression of HBV pgRNA and target protein. PCR was used in the construction of HBV pg-promoter, ENII/BCP, and a series of gene deletion mutant fluorescent reporter vectors. The fluorescence relative expression of each mutant was detected by Renilla luciferase assay. RESULTS: By binding to MZF1 (Myeloid zinc finger protein 1, MZF1), Solamargine inhibits HBV core promoter activity, reduces pregenomic RNA level, and inhibits HBV, achieving antiviral effects.

Hsa-miR-181a-2-3p inhibits the oncogenicity of colon cancer by directly targeting STING.

OBJECTIVE: Colon cancer is a common malignant tumor of the gastrointestinal system, which is characterized by high morbidity and mortality. The purpose of this study was to analyze the expression and biological role of miR-181a-2-3p in colon cancer and to investigate the molecular mechanism of its regulatory effect on colon cancer through stimulator of interferon genes (STING). METHODS: Real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect the expression of miR-181a-2-3p in colon cancer cell lines and normal intestinal epithelial cells. After overexpression of miR-181a-2-3p in colon cancer cell lines SW480 and HT29, cells were examined by CCK8, Transwell, and flow cytometry assays for alterations in proliferation, migration, apoptosis, and cell cycle. Target genes of miR-181a-2-3p were predicted by bioinformatics and validated by dual luciferase assays. Rescue experiments were performed to explore the role of STING in the effect of miR-181a-2-3p. The effect of miR-181a-2-3p on colon cancer proliferation in vivo was validated by nude mouse tumorigenicity assay. RESULTS: miR-181a-2-3p was lowly expressed in both colon cancer tissues and cell lines. Overexpression of miR-181a-2-3p led to reduced proliferation and migration, increased apoptosis, and altered cell cycle in colon cancer cell lines SW480 and HT29. STING was a target gene of miR-181a-2-3p. Increased STING expression partially counteracted the effect of overexpression of miR-181a-2-3p on colon cancer cell lines. miR-181a-2-3p also suppressed colon cancer proliferation in vivo. CONCLUSION: miR-181a-2-3p inhibits the proliferation and oncogenicity of colon cancer, and its molecular mechanism could be inhibited by STING.

Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma.

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571-158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

Unveiling the overlooked small-sized microbiome in river ecosystems.

Enriching microorganisms using a 0.22-µm pore size is a general pretreatment procedure in river microbiome research. However, it remains unclear the extent to which this method loses microbiome information. Here, we conducted a comparative metagenomics-based study on microbiomes with sizes over 0.22 µm (large-sized) and between 0.22 µm and 0.1 µm (small-sized) in a subtropical river. Although the absolute concentration of small-sized microbiome was about two orders of magnitude lower than that of large-sized microbiome, sequencing only large-sized microbiome resulted in a significant loss of microbiome diversity. Specifically, the microbial community was different between two sizes, and 347 genera were only detected in small-sized microbiome. Small-sized microbiome had much more diverse viral community than large-sized fraction. The viruses had abundant ecological functions and were hosted by 825 species of 169 families, including pathogen-related families. Small-sized microbiome had distinct antimicrobial resistance risks from large-sized microbiome, showing an enrichment of eight antibiotic resistance gene (ARG) types as well as the detection of 140 unique ARG subtypes and five enriched risk rank I ARGs. Draft genomes of five major resistant pathogens having diverse ecological and pollutant-degrading functions were only assembled in small-sized microbiome. These findings provide novel insights into river ecosystems, and highlight the overlooked small-sized microbiome in the environment.

Effects of the Amylose/Amylopectin Ratio of Starch on Borax-Crosslinked Hydrogels.

Herein, we simultaneously prepared borax-crosslinked starch-based hydrogels with enhanced mechanical properties and self-healing ability via a simple one-pot method. The focus of this work is to study the effects of the amylose/amylopectin ratio of starch on the grafting reactions and the performance of the resulting borax-crosslinked hydrogels. An increase in the amylose/ amylopectin ratio increased the gel fraction and grafting ratio but decreased the swelling ratio and pore diameter. Compared with hydrogels prepared from low-amylose starches, hydrogels prepared from high-amylose starches showed pronouncedly increased network strength, and the maximum storage modulus increased by 8.54 times because unbranched amylose offered more hydroxyl groups to form dynamic borate ester bonds with borate ions and intermolecular hydrogen bonds, leading to an enhanced crosslink density. In addition, all the hydrogels exhibited a uniformly interconnected network structure. Furthermore, owing to the dynamic borate ester bonds and hydrogen bonds, the hydrogel exhibited excellent recovery behavior under continuous step strain, and it also showed thermal responsiveness.

Association between depressive duration and cognitive decline in middle-aged and older adults: Evidence from the Health and Retirement Study 2010-2018.

BACKGROUND: Depression has been found to be associated with cognitive decline, but whether longer depressive durations lead to more severe cognitive declines has not been investigated. We aimed to estimate the association between depressive duration and cognitive decline in middle-aged and older Americans based on a large-scale representative population study. METHODS: We included 27,886 participants from the Health and Retirement Study (HRS) in 2010-2018. Four datasets with 2-, 4-, 6-, and 8-year consecutive interviews were further derived which involving persistent depressed and persistent depression-free individuals. Multiple linear regressions were constructed to estimate the effects of each depressive duration on the decline in global cognition, memory and mental status. Meta-regressions were performed to test the linear trends and to explore the heterogeneity between sex, age and baseline cognitive function along with subgroup analyses. RESULTS: Depressive durations of 2, 4, 6, and 8 years were associated with reductions in global cognitive scores of 0.62 points (95% CI: 0.51-0.73), 0.77 points (95% CI: 0.60-0.94), 0.83 points (95% CI: 0.55-1.10), and 1.09 points (95% CI: 0.63-1.55), respectively, indicating a linear trend (P = 0.016). More pronounced associations were observed in middle-aged adults and females. Similar patterns were found in the associations between depressive duration and two subdomains, i.e., memory and mental health. LIMITATIONS: This study is essentially a cross-sectional study and therefore cannot provide causal associations. CONCLUSIONS: Longer depressive durations were linearly related to more severe cognitive declines. Timely intervention for depression targeted middle-aged adults can more effectively alleviate cognition-related burdens.

The clinical impacts of lung microbiome in bronchiectasis with fixed airflow obstruction: a prospective cohort study.

BACKGROUND: Airflow obstruction is a hallmark of disease severity and prognosis in bronchiectasis. The relationship between lung microbiota, airway inflammation, and outcomes in bronchiectasis with fixed airflow obstruction (FAO) remains unclear. This study explores these interactions in bronchiectasis patients, with and without FAO, and compares them to those diagnosed with chronic obstructive pulmonary disease (COPD). METHODS: This prospective observational study in Taiwan enrolled patients with either bronchiectasis or COPD. To analyze the lung microbiome and assess inflammatory markers, bronchoalveolar lavage (BAL) samples were collected for 16S rRNA gene sequencing. The study cohort comprised 181 patients: 86 with COPD, 46 with bronchiectasis, and 49 with bronchiectasis and FAO, as confirmed by spirometry. RESULTS: Patients with bronchiectasis, with or without FAO, had similar microbiome profiles characterized by reduced alpha diversity and a predominance of Proteobacteria, distinctly different from COPD patients who exhibited more Firmicutes, greater diversity, and more commensal taxa. Furthermore, compared to COPD and bronchiectasis without FAO, bronchiectasis with FAO showed more severe disease and a higher risk of exacerbations. A significant correlation was found between the presence of Pseudomonas aeruginosa and increased airway neutrophilic inflammation such as Interleukin [IL]-1ß, IL-8, and tumor necrosis factor-alpha [TNF]-α, as well as with higher bronchiectasis severity, which might contribute to an increased risk of exacerbations. Moreover, in bronchiectasis patients with FAO, the ROSE (Radiology, Obstruction, Symptoms, and Exposure) criteria were employed to classify individuals as either ROSE (+) or ROSE (-), based on smoking history. This classification highlighted differences in clinical features, inflammatory profiles, and slight microbiome variations between ROSE (-) and ROSE (+) patients, suggesting diverse endotypes within the bronchiectasis with FAO group. CONCLUSION: Bronchiectasis patients with FAO may exhibit two distinct endotypes, as defined by ROSE criteria, characterized by greater disease severity and a lung microbiome more similar to bronchiectasis without FAO than to COPD. The significant correlation between Pseudomonas aeruginosa colonization and increased airway neutrophilic inflammation, as well as disease severity, underscores the clinical relevance of microbial patterns. This finding reinforces the potential role of these patterns in the progression and exacerbations of bronchiectasis with FAO.

Neutrophils Recruited by NKX2-1 Suppression via Activation of CXCLs/CXCR2 Axis Promote Lung Adenocarcinoma Progression.

NK2 Homeobox 1 (NKX2-1) is a well-characterized pathological marker that delineates lung adenocarcinoma (LUAD) progression. The advancement of LUAD is influenced by the immune tumor microenvironment through paracrine signaling. However, the involvement of NKX2-1 in modeling the tumor immune microenvironment is still unclear. Here, the downregulation of NKX2-1 is observed in high-grade LUAD. Meanwhile, single-cell RNA sequencing and Visium in situ capturing profiling revealed the recruitment and infiltration of neutrophils in orthotopic syngeneic tumors exhibiting strong cell-cell communication through the activation of CXCLs/CXCR2 signaling. The depletion of NKX2-1 triggered the expression and secretion of CXCL1, CXCL2, CXCL3, and CXCL5 in LUAD cells. Chemokine secretion is analyzed by chemokine array and validated by qRT-PCR. ATAC-seq revealed the restrictive regulation of NKX2-1 on the promoters of CXCL1, CXCL2, and CXCL5 genes. This phenomenon led to increased tumor growth, and conversely, tumor growth decreased when inhibited by the CXCR2 antagonist SB225002. This study unveils how NKX2-1 modulates the infiltration of tumor-promoting neutrophils by inhibiting CXCLs/CXCR2-dependent mechanisms. Hence, targeting CXCR2 in NKX2-1-low tumors is a potential antitumor therapy that may improve LUAD patient outcomes.

Pyrrole as a multi-functional additive to concurrently stabilize Zn anode and cathode via interphase regulation towards advanced aqueous zinc-ion battery.

The advancement of aqueous zinc-ion batteries (AZIBs) is impeded by challenges encompassing cathodic and anodic aspects, such as limited capacity and dendrite formation, constraining their broader utilization. Herein, pyrrole, an economically viable and readily accessible compound, is proposed as a versatile electrolyte additive to address these challenges. Experiments and DFT calculations reveal that pyrrole and its derivatives preferentially adsorb onto zinc foil, facilitating the formation of a pyrrole-based solid electrolyte interphase (SEI), which effectively guides uniform Zn2+ deposition through strong attraction force and suppresses hydrogen evolution reactions and parasitic reactions. On the cathode side, the additive promotes the formation of a durable cathode electrolyte interphase (CEI) enriched with poly-pyrrole (Ppy) analogues. Such layer significantly contributes to extra capacity of both polyaniline (PANI) and MnO2 cathodes by leveraging the electrochemical reactivity of Ppy towards Zn2+ and improves their cyclic stability. Consequently, a dendrite-free Zn anode is realized with an extended cyclic lifespan surpassing 6000 h in Zn//Zn cell, coupled with an average Coulombic efficiency of 99.7 % in Cu//Zn cell. Moreover, the PANI//Zn and MnO2//Zn full cells demonstrate enhanced capacities along with improved cycling stability. This work provides a new additive strategy towards concurrent stabilization of cathode and Zn anode in AZIBs.

18 F-FDG PET/CT of Benign Tracheal Schwannoma.

ABSTRACT: Schwannoma is a benign tumor originating from Schwann cells. It commonly occurs in the head, neck, and extremities, but rarely occurs in the trachea. Tracheal schwannoma is usually asymptomatic. We reported the 18 F-FDG PET/CT findings of a 61-year-old man with bronchoscopically biopsy-proven schwannoma, which presented challenges in differentiation from certain benign tumors and low-grade malignancies in the trachea.

Characterizing the distribution pattern of traffic-related air pollutants in near-road neighborhoods.

In near-road neighborhoods, residents are more frequently exposed to traffic-related air pollution (TRAP), and they are increasingly aware of pollution levels. Given this consideration, this study adopted portable air pollutant sensors to conduct a mobile monitoring campaign in two near-road neighborhoods, one in an urban area and one in a suburban area of Shanghai, China. The campaign characterized spatiotemporal distributions of fine particulate matter (PM2.5) and black carbon (BC) to help identify appropriate mitigation measures in these near-road micro-environments. The study identified higher mean TRAP concentrations (up to 4.7-fold and 1.7-fold higher for PM2.5 and BC, respectively), lower spatial variability, and a stronger inter-pollutant correlation in winter compared to summer. The temporal variations of TRAP between peak hour and off-peak hour were also investigated. It was identified that district-level PM2.5 increments occurred from off-peak to peak hours, with BC concentrations attributed more to traffic emissions. In addition, the spatiotemporal distribution of TRAP inside neighborhoods revealed that PM2.5 concentrations presented great temporal variability but almost remained invariant in space, while the BC concentrations showed notable spatiotemporal variability. These findings provide valuable insights into the unique spatiotemporal distributions of TRAP in different near-road neighborhoods, highlighting the important role of hyperlocal monitoring in urban micro-environments to support tailored designing and implementing appropriate mitigation measures.

Type 2 Biomarkers and Their Clinical Implications in Bronchiectasis: A Prospective Cohort Study.

PURPOSE: Bronchiectasis is predominantly marked by neutrophilic inflammation. The relevance of type 2 biomarkers in disease severity and exacerbation risk is poorly understood. This study explores the clinical significance of these biomarkers in bronchiectasis patients. METHODS: In a cross-sectional cohort study, bronchiectasis patients, excluding those with asthma or allergic bronchopulmonary aspergillosis, underwent clinical and radiological evaluations. Bronchoalveolar lavage samples were analyzed for cytokines and microbiology. Blood eosinophil count (BEC), serum total immunoglobulin E (IgE), and fractional exhaled nitric oxide (FeNO) were measured during stable disease states. Positive type 2 biomarkers were defined by established thresholds for BEC, total IgE, and FeNO. RESULTS: Among 130 patients, 15.3% demonstrated BEC ≥ 300 cells/µL, 26.1% showed elevated FeNO ≥ 25 ppb, and 36.9% had high serum total IgE ≥ 75 kU/L. Approximately 60% had at least one positive type 2 biomarker. The impact on clinical characteristics and disease severity was variable, highlighting BEC and FeNO as reflective of different facets of disease severity and exacerbation risk. The combination of low BEC with high FeNO appeared to indicate a lower risk of exacerbation. However, Pseudomonas aeruginosa colonization and a high neutrophil-to-lymphocyte ratio (NLR ≥ 3.0) were identified as more significant predictors of exacerbation frequency, independent of type 2 biomarker presence. CONCLUSIONS: Our study underscores the distinct roles of type 2 biomarkers, highlighting BEC and FeNO, in bronchiectasis for assessing disease severity and predicting exacerbation risk. It advocates for a multi-biomarker strategy, incorporating these with microbiological and clinical assessments, for comprehensive patient management.

A novel signature based on twelve programmed cell death patterns to predict the prognosis of lung adenocarcinoma.

Programmed cell death (PCD) plays a pivotal role in tumor initiation and progression. However, the prognostic value and clinical characteristics of PCD-related genes (PRGs) remain unclear. We collected and analyzed genes associated with twelve PCD patterns, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, netotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, and oxeiptosis to construct a gene signature. Our analysis identified 215 differentially expressed PRGs out of 1254 in lung adenocarcinoma (LUAD) and normal lung tissues. Subsequently, we performed univariate Cox regression analysis and identified 58 prognostic PRGs. Based on LASSO Cox regression analysis, we constructed a risk score using the expression levels of seven genes: DAPK2, DDIT4, E2F2, GAPDH, MET, PIM2, and FOXF1. Patients with lower risk scores showed earlier stages of cancer, longer survival times, and better immune infiltrations and functions. Notably, we found that knockdown of DDIT4 significantly increased apoptosis and impaired the proliferation of human LUAD cell lines. Our study proposes a PRG-based prognostic signature that sheds light on the potential role of PCD-related genes in LUAD and provides valuable insights into future therapeutic strategies.