High-speed generation of non-Rayleigh speckle.

Speckle with non-Rayleigh amplitude distribution has significant research value in imaging and measurement using structured illumination. However, existing speckle customizing schemes have been limited in generation speed due to the refresh rate of spatial light modulators (SLMs). In this work, we proposed a method to rapidly generate non-Rayleigh distributed speckle fields using a digital micro-mirror device (DMD). In contrast to SLMs that allow for gray-scale phase modulation, DMD is limited to binary amplitude control. To solve this limitation, we design a Gerchberg-Saxton-like algorithm based on super-pixel method, this algorithm enables the customization of non-Rayleigh speckle with arbitrary intensity probability density function. Statistical analyses of experimental results have demonstrated that the customized speckles exhibit excellent stability in their lateral statistical properties, while also maintaining consistent propagation characteristics with Rayleigh speckle in the longitudinal direction. This method provides a new approach for high-speed and arbitrary intensity speckle customization, holding potential applications in imaging, measurement, and encryption fields.

HO-1 upregulation promotes mitophagy-dependent ferroptosis in PM2.5-exposed hippocampal neurons.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

Peripheral blood indicators and COVID-19: an observational and bidirectional Mendelian randomization study.

Blood is critical for health, supporting key functions like immunity and oxygen transport. While studies have found links between common blood clinical indicators and COVID-19, they cannot provide causal inference due to residual confounding and reverse causality. To identify indicators affecting COVID-19, we analyzed clinical data (n = 2,293, aged 18-65 years) from Guangzhou Medical University's first affiliated hospital (2022-present), identifying 34 significant indicators differentiating COVID-19 patients from healthy controls. Utilizing bidirectional Mendelian randomization analyses, integrating data from over 2.46 million participants from various large-scale studies, we established causal links for six blood indicators with COVID-19 risk, five of which is consistent with our observational findings. Specifically, elevated Troponin I and Platelet Distribution Width levels are linked with increased COVID-19 susceptibility, whereas higher Hematocrit, Hemoglobin, and Neutrophil counts confer a protective effect. Reverse MR analysis confirmed four blood biomarkers influenced by COVID-19, aligning with our observational data for three of them. Notably, COVID-19 exhibited a positive causal relationship with Troponin I (Tnl) and Serum Amyloid Protein A, while a negative association was observed with Plateletcrit. These findings may help identify high-risk individuals and provide further direction on the management of COVID-19.

The Changing and Predicted Trends in Chronic Obstructive Pulmonary Disease Burden in China, the United States, and India from 1990 to 2030.

Background: This study analyzed the burden of chronic obstructive pulmonary disease (COPD) in China, the United States, and India from 1990 to 2019 and projected the trends for the next decade. Methods: This study utilized the GBD 2019 to compare the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life years (DALYs) rate, and the proportion attributed to different risk factors in China, the United States, and India. Joinpoint models and autoregressive integrated moving average (ARIMA) models were employed to capture the changing trends in disease burden and forecast outcomes. Results: From 1990 to 2019, China's age-standardized COPD incidence and mortality rates decreased by 29% and 70%, respectively. In the same period, India's rates decreased by 8% and 33%, while the United States saw an increase of 9% in COPD incidence and a 22% rise in mortality rates. Smoking and ambient particulate matter pollution are the two most significant risk factors for COPD, while household air pollution from solid fuels and low temperatures are the least impactful factors in the United States and India, respectively. The proportion of risk from household air pollution from solid fuels is higher in India than in China and the United States. Predictions for 2030 suggest that the age-standardized DALY rates, ASIR, and ASMR in the United States and India are expected to remain stable or decrease, while China's age-standardized incidence rate is projected to rise. Conclusion: Over the past three decades, the incidence of COPD has been decreasing in China and India, while showing a slight increase in the United States. Smoking and ambient particulate matter pollution are the primary risk factors for men and women, respectively. The risk of household air pollution from solid fuels in India needs attention.

Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways.

BACKGROUND: The rapid emergence and global dissemination of the Omicron variant of SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores the urgent need for an enhanced understanding of Omicron's pathophysiological mechanisms to guide clinical management and shape public health strategies. Our study is aimed at deciphering the intricate molecular mechanisms underlying Omicron infections, particularly focusing on the identification of specific biomarkers. METHODS: This investigation employed a robust and systematic approach, initially encompassing 15 Omicron-infected patients and an equal number of healthy controls, followed by a validation cohort of 20 individuals per group. The study's methodological framework included a comprehensive multi-omics analysis that integrated proteomics and metabolomics, augmented by extensive bioinformatics. Proteomic exploration was conducted via an advanced Ultra-High-Performance Liquid Chromatography (UHPLC) system linked with mass spectrometry. Concurrently, metabolomic profiling was executed using an Ultra-Performance Liquid Chromatography (UPLC) system. The bioinformatics component, fundamental to this research, entailed an exhaustive analysis of protein-protein interactions, pathway enrichment, and metabolic network dynamics, utilizing state-of-the-art tools such as the STRING database and Cytoscape software, ensuring a holistic interpretation of the data. RESULTS: Our proteomic inquiry identified eight notably dysregulated proteins (THBS1, ACTN1, ACTC1, POTEF, ACTB, TPM4, VCL, ICAM1) in individuals infected with the Omicron variant. These proteins play critical roles in essential physiological processes, especially within the coagulation cascade and hemostatic mechanisms, suggesting their significant involvement in the pathogenesis of Omicron infection. Complementing these proteomic insights, metabolomic analysis discerned 146 differentially expressed metabolites, intricately associated with pivotal metabolic pathways such as tryptophan metabolism, retinol metabolism, and steroid hormone biosynthesis. This comprehensive metabolic profiling sheds light on the systemic implications of Omicron infection, underscoring profound alterations in metabolic equilibrium. CONCLUSIONS: This study substantially enriches our comprehension of the physiological ramifications induced by the Omicron variant, with a particular emphasis on the pivotal roles of coagulation and platelet pathways in disease pathogenesis. The discovery of these specific biomarkers illuminates their potential as critical targets for diagnostic and therapeutic strategies, providing invaluable insights for the development of tailored treatments and enhancing patient care in the dynamic context of the ongoing pandemic.

Association between Atopic Dermatitis and Colorectal Cancer: TET2 as a Shared Gene Signature and Prognostic Biomarker.

Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.

Identification of rBlo t 41 with a chitin-binding type-2 domain: A novel major allergen from Blomia tropicalis.

BACKGROUND: Blomia tropicalis (B. tropicalis) has been reported to impose an increased risk of allergic diseases. However, few characteristics of the unknown allergen components responsible for B. tropicalis allergy and clinical relevance have been fully identified. METHODS: We synthesized and characterized the physicochemical properties and cross-reactivity of the newly discovered recombinant B. tropicalis group 41 allergen (rBlo t 41). Subsequently, sera were collected from 107 B. tropicalis allergic subjects to evaluate the prevalence of the rBlo t 41. Lastly, its allergenicity was tested in humans by basophil activation assays, and in mice by a model of allergic asthma. RESULTS: The mature protein of rBlo t 41 was described as 104 amino acids long and 15.8 kDa, and its limited cross-reactivity was observed between allergens of house dust mites (HDM). Sensitization rate of rBlo t 41 (56.07 %) was lower than rBlo t 2 (76.29 %) and rBlo t 5 (69.07 %) in our study. Besides, rBlo t 41 elicited CD63 upregulation in basophils, whereas rBlo t 41-sensitized mice generated rBlo t 41-IgE and developed allergic airway inflammation after allergen exposure. Of note, component-based tests showed a high area under curve value (AUC = 0.75) of rBlo t 41, displaying its favorable diagnostic potential in B. tropicalis allergy. CONCLUSIONS: rBlo t 41 was identified as a candidate novel major allergen with good diagnostic potential in B. tropicalis sensitization. Additionally, we provided strong evidence about rBlo t 41 on the clinically relevant manifestations in B. tropicalis allergies, conducive to facilitating the development of component-resolved diagnosis.

Decoding acute myocarditis in patients with COVID-19: Early detection through machine learning and hematological indices.

During the persistent COVID-19 pandemic, the swift progression of acute myocarditis has emerged as a profound concern due to its augmented mortality, underscoring the urgency of prompt diagnosis. This study analyzed blood samples from 5,230 COVID-19 individuals, identifying key blood and myocardial markers that illuminate the relationship between COVID-19 severity and myocarditis. A predictive model, applying Bayesian and random forest methodologies, was constructed for myocarditis' early identification, unveiling a balanced gender distribution in myocarditis cases contrary to a male predominance in COVID-19 occurrences. Particularly, older men exhibited heightened vulnerability to severe COVID-19 strains. The analysis revealed myocarditis was notably prevalent in younger demographics, and two subvariants COVID-19 progression paths were identified, characterized by symptom intensity and specific blood indicators. The enhanced myocardial marker model displayed remarkable diagnostic accuracy, advocating its valuable application in future myocarditis detection and treatment strategies amidst the COVID-19 crisis.

Multicenter study of seasonal and regional airborne allergens in Chinese preschoolers with allergic rhinitis.

This study is nationwide multicenter epidemiological research, aimed at investigating the distribution changes and seasonal patterns of various airborne allergens among preschool children with allergic rhinitis (AR) in different regions of China, and analyzing the clinical correlation between sensitization to various airborne allergens and AR symptoms in children. Information on children was collected through standard questionnaires, and total IgE (tIgE) and specific IgE (sIgE) for 11 inhalant allergens were tested. The results showed that dust mites are the primary allergens for preschool AR children (39%). Among pollen allergens, Amb a had the highest positivity rate (8.1%), followed by Art v (7.8%). The sensitization rates for two mites peaked in May (46.9% and 40.6%). Art v peaked in August (21.5%), while Amb a had peaks in May (12.7%) and August (17.8%). The sensitization peaks for various tree pollens mainly occurred in August. In the Eastern monsoon region, the sensitization rate to mites was significantly higher than in the Northwest arid and semi-arid regions; whereas, for pollen allergens, the sensitization rates to Amb a, Pla a, Pin a, Pop d, and Bet v were significantly higher in the Northwest arid and semi-arid regions than in the Eastern monsoon region. The correlation among various tree pollens, specifically between Pla a, Pin r, Pop d, and Bet v was strong (0.63 ~ 0.79), with a cross-overlapping percentage of 53.9%. Children with multiple pollen sensitizations had higher cumulative nasal symptom scores than those negative for pollen (P < 0.01). Children with only pollen sensitization had higher cumulative rhinitis symptom scores than the all-negative group (P < 0.0001) and the mite-only sensitization group [P < 0.05], while the mite-only sensitization group also had higher scores than the all-negative group [P < 0.05], and the group sensitized to both pollen and mites had lower scores than the pollen-only group [P < 0.05]. This study indicates that sensitization to mites and grass pollens exhibits significant regional differences, with grass pollen allergies primarily occurring in autumn, sensitization to pollens in general exhibits a pronounced seasonal pattern. Moreover, pollen sensitization aggravates nasal and ocular symptoms in AR children.

Gastroesophageal reflux disease with 6 neurodegenerative and psychiatric disorders: Genetic correlations, causality, and potential molecular mechanisms.

The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.

The genetic etiology of body fluids on chronic obstructive airways disease.

BACKGROUND: Numerous studies have documented significant alterations in the bodily fluids of Chronic Obstructive Pulmonary Disease (COPD) patients. However, existing literature lacks causal inference due to residual confounding and reverse causality. METHODS: Summary-level data for COPD were obtained from two national biobanks: the UK Biobank, comprising 1,605 cases and 461,328 controls, and FinnGen, with 6,915 cases and 186,723 controls. We also validated our findings using clinical data from 2,690 COPD patients and 3,357 healthy controls from the First Affiliated Hospital of Guangzhou Medical University. A total of 44 bodily fluid biomarkers were selected as candidate risk factors. Mendelian randomization (MR) and meta-analyses were used to evaluate the causal effects of these bodily fluids on COPD and lung function (FEV1/FVC). RESULTS: Mendelian randomization (MR) and meta-analyses, by integrating data from the UK Biobank and FinnGen cohort, found that 3 bodily fluids indicators (HDLC, EOS, and TP) were causally associated with the risk of COPD, two (EOS and TP) of which is consistent with our observational findings. Moreover, we noticed EOS and TP were causally associated with the risk of lung function (FEV1/FVC). CONCLUSIONS: The MR findings and clinical data highlight the independent and significant roles of EOS and TP in the development of COPD and lung function (FEV1/FVC), which might provide a deeper insight into COPD risk factors and supply potential preventative strategies.

Study of Allergy and Sensitization Relationship in Children and Parents in Southern China.

INTRODUCTION: The incidence of allergic diseases has increased globally, with genetics playing an essential role in these conditions' development. However, there is still a gap in understanding of how parental allergy status affects children's allergies. METHODS: An electronic questionnaire was used to assess allergy-related symptoms in kindergarten children and their parents, with a clinical diagnosis and concurrent serum allergen-specific immunoglobulin E (IgE), total IgE, and blood cell counts obtained. RESULTS: 88 family groups were enrolled, with allergy prevalence of 85.2% in children, 50% in fathers, and 42% in mothers. Allergic rhinoconjunctivitis was the most common allergic disease. When the mother had an allergy, the children's allergy diagnosis rate was 91.3%; 86.67% when the father had an allergy; and 85.71% when both parents had allergies. The child sensitization rate was 78.26% when the father had sensitization, 59.09% just as the mother had sensitization, and 84.21% when both parents had sensitization. Paternal allergies affected children's quality of life due to allergic rhinitis but not their rhinitis symptoms. Maternal allergies or sensitization did not significantly affect children's symptoms or quality-of-life scores. CONCLUSION: The study found a positive correlation between childhood and parental allergies, and further studies are needed to confirm the findings.

Developing and validating clinical models to identify candidates for allergic rhinitis pre-exposure prophylaxis.

PURPOSE: Few risk-forecasting models of allergic rhinitis (AR) exist that may aid AR pre-exposure prophylaxis (PrEP) in clinical practice. Therefore, this study aimed to develop and validate an effective clinical model for identifying candidates for AR PrEP using a routine medical questionnaire. METHODS: This study was conducted in 10 Chinese provinces with 13 medical centers (n = 877) between 2019 and 2021. Clinical characteristics and exposure history were collected via face-to-face interviews. Well-trained physicians diagnosed patients with AR based on skin prick test results and clinical performance. The least absolute shrinkage and selection operator model was used to identify potential risk factors for AR, and the logistic regression model was used to construct the risk-forecasting model. Predictive power and model reliability were assessed using area under the receiver operating characteristic curve and calibration curves, respectively. RESULTS: This study diagnosed 625 patients with AR who had positive responses to at least one indoor or outdoor allergen and 460 to at least one outdoor pollen allergen. Two nomograms were established to identify two types of AR with various sensitization patterns. Both models had an area under curve of approximately 0.7 in the development and internal validation datasets. Additionally, our findings found good agreement for the calibration curves of both models. CONCLUSION: Early identification of candidates for AR PrEP using routine medical information may improve the deployment of limited resources and effective health management. Our models showed good performance in predicting AR; therefore, they can serve as potential automatic screening tools to identify AR PrEP candidates.

Body mass index affects spirometry indices in patients with chronic obstructive pulmonary disease and asthma.

Background: Body mass index (BMI) is known to affect the outcomes of spirometry indices. However, its association with spirometry indices in COPD and asthma is less studied. We aimed to explore the impact of BMI on these patients. Methods: Patients with COPD or asthma who completed bronchodilator tests (BDTs) between 2017 and 2021 were reviewed. Spirometry indices were compared among patients with COPD or asthma that were subclassified as underweight (BMI< 18.5 kg/m2), normal weight (≥18.5 to < 25), overweight (≥ 25 to < 30), and obesity (≥ 30). Results. Results: Analysis was conducted on 3891 COPD patients (age:66.5 ± 7.8 years) and 1208 asthma patients (age:59.7 ± 7.5 years). COPD patients classified as underweight demonstrated significantly lower values of pre-and post FEV1 (L, %), pre-and post FVC (L, %), and pre- and post-FEV1/FVC (all p < 0.05). In contrast, COPD patients who were overweight or obese exhibited higher values for pre-and post FEV1 (L, %), and pre and post FEV1/FVC (all p < 0.05). Within the cohort of asthma patients, those underweight had lower pre-and post FEV1 (L, %), pre and post FVC (L, %), pre and post FEV1/FVC %. Obese asthma patients displayed higher pre and post FEV1/FVC (all p < 0.05). Conclusion: Significant BMI category differences in spirometry indices can be seen in patients with COPD or asthma. Both underweight and obesity could affect the diagnosis and severity of these diseases. Recognizing these effects is essential to better management and diagnosis of these patients.

Comparative analysis of cysteine proteases reveals gene family evolution of the group 1 allergens in astigmatic mites.

BACKGROUND: Astigmatic mites contain potent allergens that can trigger IgE-mediated immune responses, leading to allergic diseases such as asthma, allergic rhinitis and atopic dermatitis. In house dust mites Dermatophagoides pteronyssinus and Dermatophagoides farinae, group 1 allergens (Der p 1 and Der f 1), characterized as papain-like cysteine proteases, have been defined as the major allergens that have high prevalence and potency. Previous studies of mite group 1 allergens mainly focused on identification, comparison of sequence and structure, as well as the investigation of cross-reactivity. To achieve a comprehensive view of mite group 1 allergens, we performed a comparative genomic analysis of all the cysteine proteases in six astigmatic mite species to elucidate the evolutionary relationships of group 1 allergens. METHODS: Based on the high-quality and annotated genomes, all the cysteine proteases in six astigmatic mite species were identified by sequence homology search. The phylogenetic relationships, gene synteny and expression levels were revealed by bioinformatic tools. The allergenicity of recombinant cysteine proteases was evaluated by enzyme-linked immunosorbent assay. RESULTS: Tandem duplication was revealed as the major feature of cysteine protease gene evolution in astigmatic mites. The high IgE-binding capacity and the significant expression level of the cysteine protease DP_007902.01 suggested its potential as a novel group 1 allergen of D. pteronyssinus. In addition, gene decay events were identified in the skin-burrowing parasitic mite Sarcoptes scabiei. CONCLUSION: This comprehensive analysis provided insights into the evolution of cysteine proteases, as well as the component-resolved diagnosis of mite allergies.

Impact of ultra-low temperature storage on serum sIgE detection and allergic disease biobank feasibility.

Research has shown that the concentration and composition of biological samples may change after long-term ultra-low temperature storage. Consequently, this study examined the effect of ultra-low temperature storage on serum sIgE detection by comparing sIgE concentrations at various durations from the time of sample storage to subsequent testing. We selected 40 serum samples from the Guangzhou Medical University Affiliated First Hospital Biobank, which had been tested for house dust mites, dog hair, tobacco mold, cockroaches, and cow milk allergen sIgE. Samples were categorized by storage duration: 14 samples stored for 10 years, 12 for 5 years, and 14 for 3 years. They were also classified by sIgE positive levels: 15 samples at levels 1-2, 15 at levels 3-4, and 10 at levels 5-6. The allergen sIgE of these samples was retested using the same technology. Regardless of the type of allergen or the level of positivity, the majority of sIgE concentrations measured at the time of storage were higher than the current measurements, but the difference was not statistically significant. The correlation between the sIgE results at the time of storage and the current results was high for samples stored for 10 years (rs = 0.991, P < 0.001) and 5 years (rs = 0.964, P < 0.001). Serum allergen sIgE is stable when stored under ultra-low temperature conditions, making the construction of a biological sample bank for allergic diseases feasible. This will facilitate researchers in quickly obtaining samples, conducting technical research, and translating findings, thereby promoting the development of the field of allergy through integration of industry, academia, and research.

Correlation between immune-related Tryptophan-Kynurenine pathway and severity of severe pneumonia and inflammation-related polyunsaturated fatty acids.

BACKGROUND: Immune dysfunction and oxidative stress caused by severe pneumonia can lead to multiple organ dysfunction and even death, causing a significant impact on health and the economy. Currently, great progress has been made in the diagnosis and treatment of this disease, but the mortality rate remains high (approximately 50%). Therefore, there is still potential for further exploration of the immune response mechanisms against severe pneumonia. OBJECTIVE: This study analyzed the difference in serum metabolic profiles between patients with severe pneumonia and health individuals through metabolomics, aiming to uncover the correlation between the Tryptophan-Kynurenine pathway and the severity of severe pneumonia, as well as N-3/N-6 polyunsaturated fatty acids (PUFAs). METHODS: In this study, 44 patients with severe pneumonia and 37 health controls were selected. According to the changes in the disease symptoms within the 7 days of admission, the patients were divided into aggravation (n = 22) and remission (n = 22) groups. Targeted metabolomics techniques were performed to quantify serum metabolites and analyze changes between groups. RESULTS: Metabolomics analysis showed that serum kynurenine and kynurenine/tryptophan (K/T) were significantly increased and tryptophan was significantly decreased in patients with severe pneumonia; HETE and HEPE in lipids increased significantly, while eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA), α-linolenic acid (linolenic acid, α-LNA), arachidonic acid (ARA), Dihomo-γ-linolenic acid (DGLA), and 13(s)-hydroperoxylinoleic acid (HPODE) decreased significantly. Additionally, the longitudinal comparison revealed that Linolenic acid, DPA, and Tryptophan increased significantly in the remission group, while and kynurenine and K/T decreased significantly. In the aggravation group, Kynurenine and K/T increased significantly, while ARA, 8(S)-hydroxyeicosatetraenoic acid (HETE), 11(S)-HETE, and Tryptophan decreased significantly. The correlation analysis matrix demonstrated that Tryptophan was positively correlated with DGLA, 12(S)-hydroxyeicosapentaenoic acid (HEPE), ARA, EPA, α-LNA, DHA, and DPA. Kynurenine was positively correlated with 8(S)-HETE and negatively correlated with DHA. Additionally, K/T was negatively correlated with DGLA, ARA, EPA, α-LNA, DHA, and DPA. CONCLUSION: This study revealed that during severe pneumonia, the Tryptophan-Kynurenine pathway was activated and was positively correlated with the disease progression. On the other hand, the activation of the Tryptophan-Kynurenine pathway was negatively correlated with N-3/N-6 PUFAs.

MIRS: An AI scoring system for predicting the prognosis and therapy of breast cancer.

Tumor-infiltrating immune cells (TIICs) and metastasis are crucial characteristics for tumorigenesis. However, the potential role of their combination in breast cancer (BRCA) remains elusive. Herein, on the basis of quantifying TIICs and tumor metastasis together, we established a precise prognostic scoring system named metastatic and immunogenomic risk score (MIRS) using a neural network model. MIRS showed better performance when compared with other published signatures. MIRS stratifies patients into a high risk subtype (MIRShigh) and a low risk subtype (MIRSlow). The MIRShigh patients exhibit significantly lower survival rate compared with MIRSlow patients (P<0.0001), higher response to chemotherapy, but lower response to immunotherapy. Conversely, higher infiltration level of TIICs and significantly prolonged survival (P=0.029) are observed in MIRSlow patients, indicating sensitive response in immunotherapy. This work presents a promising indicator to guide treatment options of the BRCA population and provides a predicted webtool that is almost universally applicable to BRCA patients.