Risk factors for anxiety and its impacts on acute exacerbation in older patients with chronic obstructive pulmonary disease.

Background: Anxiety is common in patients with chronic obstructive pulmonary disease (COPD), especially in older patients with the definition of age over 60 years old. Few studies have focused on anxiety in older COPD patients. This study aimed to analyze the risk factors of anxiety in older COPD patients and the impacts of anxiety on future acute exacerbation. Methods: The general information, questionnaire data, previous acute exacerbation and pulmonary function were collected. Hamilton Anxiety Rating Scale (HAMA) was used to evaluate the anxiety of older COPD patients. The patients were followed up for one year, the number and the degrees of acute exacerbations of COPD were recorded. Results: A total of 424 older COPD patients were included in the analysis. 19.81% (N = 84) had anxiety symptoms, and 80.19% (N = 340) had no anxiety symptoms. There were increased pack-years, more comorbidities, and more previous acute exacerbations in older COPD patients with anxiety compared to those without anxiety (P < 0.05). Meanwhile, a higher modified Medical Research Council (mMRC), a higher COPD assessment test (CAT) score and a shorter six-minute walking distance (6MWD) were found in older COPD patients with anxiety (P < 0.05). The BODE index, mMRC, CAT score, comorbidities and acute exacerbations were associated with anxiety. Eventually, anxiety will increase the risk of future acute exacerbation in older COPD patients (OR = 4.250, 95% CI: 2.369-7.626). Conclusion: Older COPD patients with anxiety had worsening symptoms, more comorbidities and frequent acute exacerbation. Meanwhile, anxiety may increase the risk of acute exacerbation in the future. Therefore, interventions should be provided to reduce the risk of anxiety in older COPD patients at an early stage.

The role of mir96 in predicting CTC status and prognostic evaluation in gastric cancer patients.

In this study, 20 patients clinically diagnosed with advanced gastric cancer were selected as subjects. Circulating tumor cells (CTCs) in the peripheral blood of gastric cancer patients were detected and counted by collecting peripheral blood samples at Ningbo No. 2 Hospital and using the Cell Rich TM system combined with a negative enrichment strategy. In addition, routine pathological examination and immunohistochemical staining were performed on surgical specimens, including HER2, EBER, E-cadherin, and vimentin indicators. These indicators were correlated and analyzed with CTC counts and routine clinical tests. At the same time, miRNA groups were performed to explore the miRNAs with or without correlation with CTC and to try to construct a predictive model for CTC status. Tumor tissue from patients whose CTC counts did not match the results of the miRNA prediction model was subjected to second-generation gene sequencing to analyze indicators such as tumor heterogeneity and immune microenvironment. The results of the study showed that CTCs were detected in the peripheral blood of 50% (10/20) of gastric cancer patients using the Cell Rich TM system, serum fibrinogen was negatively correlated with CTC counts, whereas TNM staging elements, HER2 receptor and p53 were not correlated with CTC counts. miRNA assays showed that the expression levels of miR218, miR1207, miR96, miR409, miR149, miR148a, miR155, miR370 and miR223 were significantly different between the two groups of CTC≥2 and CTC<2. Among them, miR-96 showed good efficacy as an indicator for predicting CTC status and assisting in determining the prognosis of gastric cancer. In conclusion, the present study demonstrated that the Cell Rich TM system combined with the negative enrichment strategy can effectively detect CTCs in the peripheral blood of gastric cancer patients and that the expression of miR-96 can be used as an effective indicator to predict CTC status and assist in determining the prognosis of gastric cancer. These findings have important implications for the diagnosis and treatment of gastric cancer and provide new clues for the further study of the tumor immune microenvironment and tumor heterogeneity.

Genome-Wide Analysis of R2R3-MYB Genes and Functional Characterization of SmMYB75 in Eggplant Fruit Implications for Crop Improvement and Nutritional Enhancement.

R2R3-MYB represents a substantial gene family that plays diverse roles in plant development. In this study, 102 SmR2R3-MYB genes were identified from eggplant fruit and classified into 31 subfamilies. Analysis indicated that segmental duplication events played a pivotal role in the expansion of the SmR2R3-MYB gene family. Furthermore, the prediction of miRNAs targeting SmR2R3-MYB genes revealed that 60 SmR2R3-MYBs are targeted by 57 miRNAs, with specific miRNAs displaying varying numbers of target genes, providing valuable insights into the regulatory functions of miRNAs in plant growth, development, and responses to stress conditions. Through expression profile analysis under various treatment conditions, including low temperature (4 °C), plant hormone (ABA, Abscisic acid), and drought stress (PEG, Polyethylene glycol), diverse and complex regulatory mechanisms governing SmR2R3-MYB gene expression were elucidated. Notably, EGP21875.1 and EGP21874.1 exhibited upregulation in expression under all treatment conditions. Transcriptome and metabolome analyses demonstrated that, apart from anthocyanins (delphinidin-3-O-glucoside, cyanidin-3-O-(6-O-p-coumaroyl)-glucoside, and malvidin-3-O-(6-O-p-coumaroyl)-glucoside), overexpression of SmMYB75 could also elevate the content of various beneficial compounds, such as flavonoids, phenolic acids, and terpenes, in eggplant pulp. This comprehensive study enhances our understanding of SmR2R3-MYB gene functions and provides a strong basis for further research on their roles in regulating anthocyanin synthesis and improving eggplant fruit quality.

Single-cell transcriptomic analysis reveals a systemic immune dysregulation in COVID-19-associated pediatric encephalopathy.

Unraveling the molecular mechanisms for COVID-19-associated encephalopathy and its immunopathology is crucial for developing effective treatments. Here, we utilized single-cell transcriptomic analysis and integrated clinical observations and laboratory examination to dissect the host immune responses and reveal pathological mechanisms in COVID-19-associated pediatric encephalopathy. We found that lymphopenia was a prominent characteristic of immune perturbation in COVID-19 patients with encephalopathy, especially those with acute necrotizing encephalopathy (AE). This was characterized a marked reduction of various lymphocytes (e.g., CD8+ T and CD4+ T cells) and significant increases in other inflammatory cells (e.g., monocytes). Further analysis revealed activation of multiple cell apoptosis pathways (e.g., granzyme/perforin-, FAS- and TNF-induced apoptosis) may be responsible for lymphopenia. A systemic S100A12 upregulation, primarily from classical monocytes, may have contributed to cytokine storms in patients with AE. A dysregulated type I interferon (IFN) response was observed which may have further exacerbated the S100A12-driven inflammation in patients with AE. In COVID-19 patients with AE, myeloid cells (e.g., monocytic myeloid-derived suppressor cells) were the likely contributors to immune paralysis. Finally, the immune landscape in COVID-19 patients with encephalopathy, especially for AE, were also characterized by NK and T cells with widespread exhaustion, higher cytotoxic scores and inflammatory response as well as a dysregulated B cell-mediated humoral immune response. Taken together, this comprehensive data provides a detailed resource for elucidating immunopathogenesis and will aid development of effective COVID-19-associated pediatric encephalopathy treatments, especially for those with AE.

Injectable hydrogel nanoarchitectonics with near-infrared controlled drug delivery for in situ photothermal/endocrine synergistic endometriosis therapy.

BACKGROUND: Endometriosis is a common gynecological disease in women of childbearing age. Commonly used treatment methods, such as endocrine and surgical therapies, display poor therapeutic effects with a high relapse probability. Thus, novel treatments for endometriosis are required. METHODS: In our study, polydopamine (PDA), letrozole (LTZ), and agarose (AG) hydrogels were combined to construct an injectable hydrogel with near-infrared controlled drug delivery named LTZ-PDA@AG hydrogel for endometriosis treatment. The release of letrozole can be accurately controlled by the near-infrared light intensity, exposure duration, polydopamine concentration, and hydrogel composition. Meanwhile, we isolated endometrial stromal cells from endometrium in patients with endometriosis, and constructed the rats' model of endometriosis to verify the biological effects of LTZ-PDA@AG hydrogel. RESULTS: Owing to the sufficiently deep penetration of near-infrared light, the LTZ-PDA@AG hydrogel displayed a high temperature increase for efficient photothermal therapy. In addition, high local temperatures can further enhance the diffusion and penetration of letrozole, thereby achieving excellent therapeutic effect in vivo. Importantly, the in vivo and vitro test demonstrated the capacity of the nanocomposite hydrogel for endocrine-photothermal synergistic therapy and the biocompatibility. CONCLUSION: Our work proposes a novel concept for precision endometriosis therapy by photothermal-enhanced endocrine therapy for endometriosis, which is proposed for the first time for the treatment of endometriosis and demonstrates excellent potential for further clinical translation. TRIAL REGISTRATION: Not applicable. LTZ-PDA@AG hydrogels were synthesized and displayed a high temperature increase for efficient photothermal therapy under NIR. The present study shows the capacity of the nanocomposite hydrogel for endocrine-photothermal synergistic therapy and the biocompatibility.

Fabrication and Investigation of the Microwave Absorption of Nonwovens Modified by Carbon Nanotubes and Graphene Flakes.

This study aims to investigate the influences of carbon nanotubes (CNTs) and graphene flakes (GFs) on the microwave absorption performance of nonwovens. Nonwovens were modified with CNTs and GFs through an impregnation method, creating a series of absorption samples with different carbon nanomaterial contents. Then the absorption performance of the samples was tested on both sides in the X-band (8.2~12.4 GHz) and the Ku-band (12~18 GHz) using the arch method. The experimental results showed that the absorption performance of GF-impregnated nonwovens was superior to that of CNT-impregnated nonwovens, and the overall absorption performance in the Ku-band was better than in the X-band. At a CNT content of 5 wt.%, the reflection loss of the impregnated nonwovens on the backside reached a minimum of -14.06 dB and remained below -10 dB in the 17.42~17.88 GHz frequency range. The sample fabricated with 4 wt.% GFs in the impregnation solution exhibited the best absorption performance, with minimum reflection losses of -15.33 dB and -33.18 GHz in the X-band and Ku-band, respectively. When the GFs were at 3 wt.%, the absorption bandwidth below -10 dB reached 4.16 GHz. In contrast to CNT-impregnated nonwovens, the frontside of GF-impregnated nonwovens demonstrated better absorption performance in the Ku-band. The results of this work provide experimental data support for the fabrication and application of microwave absorption materials.

Changes of Serum C-Reactive Protein Level in Patients With Depressive Disorders After Treatment With Agomelatine Combined With Aerobic Exercise and Its Significance.

OBJECTIVE: Depressive disorders constitute a series of debilitating diseases. This study investigated the therapeutic effect of agomelatine (AG) combined with aerobic exercise (AE) on patients with moderate-severe depression (MSD) and the changes of the serum C-reactive protein (CRP) level in patients after treatment as well as its significance. METHODS: A total of 178 MSD patients were randomly assigned to the AG group (N = 90) and AG + AE group (N = 88). The severity of depressive disorders and anhedonia was assessed using the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores. The serum CRP level in MSD patients was detected by turbidity assay. Patients were defined as remitters, responders, and nonresponders according to the HAM-D 17 score, and the treatment efficacy was analyzed, followed by evaluation of the serum CRP level in patients with different treatment responses. Finally, the adverse reactions of patients during treatment were statistically analyzed. RESULTS: After treatment, the HAM-D, Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores and the serum CRP level of the 2 groups were reduced, and changes in the AG + AE group was more significant than that in the AG group. The clinical efficacy of the AG + AE group was better than that of the AG group. After treatment, the serum levels of CRP in remitters and responders were reduced, but not significantly in nonresponders. The incidence of adverse events in the AG + AE group was lower than that in the AG group. CONCLUSION: AG + AE reduced the serum level of CRP in MSD patients and had good therapeutic effects on MSD patients.

Apoptosis inhibitor of macrophage (AIM)/CD5L is involved in the pathogenesis of COPD.

BACKGROUND: Alveolar macrophages (AMs) and AM-produced matrix metalloprotease (MMP)-12 are known to play critical roles in the pathogenesis of chronic obstructive pulmonary disease (COPD). The apoptosis inhibitor of the macrophages (AIM)/CD5 molecule-like (CD5L) is a multifunctional protein secreted by the macrophages that mainly exists in the blood in a combined form with the immunoglobulin (Ig)M pentamer. Although AIM has both facilitative and suppressive roles in various diseases, its role in COPD remains unclear. METHODS: We investigated the role of AIM in COPD pathogenesis using porcine pancreas elastase (PPE)-induced and cigarette smoke-induced emphysema mouse models and an in vitro model using AMs. We also analyzed the differences in the blood AIM/IgM ratio among nonsmokers, healthy smokers, and patients with COPD and investigated the association between the blood AIM/IgM ratio and COPD exacerbations and mortality in patients with COPD. RESULTS: Emphysema formation, inflammation, and cell death in the lungs were attenuated in AIM-/- mice compared with wild-type (WT) mice in both PPE- and cigarette smoke-induced emphysema models. The PPE-induced increase in MMP-12 was attenuated in AIM-/- mice at both the mRNA and protein levels. According to in vitro experiments using AMs stimulated with cigarette smoke extract, the MMP-12 level was decreased in AIM-/- mice compared with WT mice. This decrease was reversed by the addition of recombinant AIM. Furthermore, an analysis of clinical samples showed that patients with COPD had a higher blood AIM/IgM ratio than healthy smokers. Additionally, the blood AIM/IgM ratio was positively associated with disease severity in patients with COPD. A higher AIM/IgM ratio was also associated with a shorter time to the first COPD exacerbation and higher all-cause and respiratory mortality. CONCLUSIONS: AIM facilitates the development of COPD by upregulating MMP-12. Additionally, a higher blood AIM/IgM ratio was associated with poor prognosis in patients with COPD. TRIAL REGISTRATION: This clinical study, which included nonsmokers, healthy smokers, and smokers with COPD, was approved by the Ethics Committee of the Hokkaido University Hospital (012-0075, date of registration: September 5, 2012). The Hokkaido COPD cohort study was approved by the Ethics Committee of the Hokkaido University School of Medicine (med02-001, date of registration: December 25, 2002).

Structural features on quantitative chest computed tomography of patients with maximal mid-expiratory flow impairment in a normal lung function population.

BACKGROUND: Maximal mid-expiratory flow (MMEF) is an earlier predictor of chronic obstructive pulmonary disease (COPD) development than forced expiratory volume in 1 s (FEV1). Changes of lung structure in patients with MMEF impairment only is still not clear. Therefore, this study aimed to investigate the structural features of patients with decreased MMEF by quantitative computed tomography (QCT) and develop a predictive model for predicting patients with reduced MMEF in normal lung function population. METHODS: In this study, 131 patients with normal spirometry results and available volumetric chest CT images were enrolled and divided into the reduced MMEF group (FEV1/forced expiratory vital capacity (FEV1/FVC) > 0.7, FEV1% predictive values (FEV1%pred) > 80%, MMEF%pred < 80%, n = 52) and the normal MMEF group (FEV1/FVC > 0.7, FEV1%pred > 80%, MMEF%pred ≥ 80%, n = 79). The emphysema, small airway disease and medium-size airway parameters were measured by a commercial software. The differences were investigated in clinical features, spirometrical parameters and QCT parameters between the two groups. A nomogram model was constructed based on the results of the multivariable logistic regression model. Spearman's correlation coefficients were calculated between QCT measurements and spirometrical parameters. RESULTS: There were more males in reduced MMEF group than normal group (P < 0.05). Lung parenchyma parameter (PRMEmph) and airway-related parameters (functional small airway disease (PRMfSAD), luminal area of fifth- and sixth- generation airway (LA5, LA6) were significantly different between the reduced MMEF group and the normal group (20.2 ± 17.4 vs 9.4 ± 6.7, 3.4 ± 3.5 vs 1.9 ± 2.0, 12.2 ± 2.5 vs 13.7 ± 3.4, 7.7 ± 2.4 vs 8.9 ± 2.8, respectively, all P < 0.01). After multivariable logistical regression, only sex (odds ratio [OR]: 2.777; 95% confidence interval [CI]:1.123-3.867), PRMfSAD (OR:1.102, 95%CI:1.045-1.162) and LA6 (OR:0.650, 95%CI:0.528-0.799) had significant differences between the two groups (P < 0.05) and a model incorporating with the three indicators was constructed (area under curve, 0.836). Correlation analysis showed MMEF%pred had mild to moderate correlation with airway-related measurements. CONCLUSION: In normal lung function population, patients with reduced MMEF have potential medium-size and small airway changes, and MMEF%pred is significantly associated with airway-related CT parameters. The nomogram incorporating with sex, PRMfSAD and LA6 has good predictive value and offers more objective evidences in a group with reduced MMEF.

Serum-integrated omics reveal the host response landscape for severe pediatric community-acquired pneumonia.

OBJECTIVE: Community-acquired pneumonia (CAP) is the primary cause of death for children under five years of age globally. Hence, it is essential to investigate new early biomarkers and potential mechanisms involved in disease severity. METHODS: Proteomics combined with metabolomics was performed to identify biomarkers suitable for early diagnosis of severe CAP. In the training cohort, proteomics and metabolomics were performed on serum samples obtained from 20 severe CAPs (S-CAPs), 15 non-severe CAPs (NS-CAPs) and 15 healthy controls (CONs). In the verification cohort, selected biomarkers and their combinations were validated using ELISA and metabolomics in an independent cohort of 129 subjects. Finally, a combined proteomics and metabolomics analysis was performed to understand the major pathological features and reasons for severity of CAP. RESULTS: The proteomic and metabolic signature was markedly different between S-CAPs, NS-CAPs and CONs. A new serum biomarker panel including 2 proteins [C-reactive protein (CRP), lipopolysaccharide (LBP)] and 3 metabolites [Fasciculol C, PE (14:0/16:1(19Z)), PS (20:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, 19Z))] was developed to identify CAP and to distinguish severe pneumonia. Pathway analysis of changes revealed activation of the cell death pathway, a dysregulated complement system, coagulation cascade and platelet function, and the inflammatory responses as contributors to tissue damage in children with CAP. Additionally, activation of glycolysis and higher levels of nucleotides led to imbalanced deoxyribonucleotide pools contributing to the development of severe CAP. Finally, dysregulated lipid metabolism was also identified as a potential pathological mechanism for severe progression of CAP. CONCLUSION: The integrated analysis of the proteome and metabolome might open up new ways in diagnosing and uncovering the complexity of severity of CAP.

Comparative transcriptomic analysis of early fruit development in eggplant (Solanum melongena L.) and functional characterization of SmOVATE5.

KEY MESSAGE: Comparative transcriptome analysis of early fruits of long and round eggplants, SmOVATE5, is involved in regulating fruit development. Eggplant, a solanaceous crop that has undergone a long period of domestication, is one of the most important vegetables worldwide. The shape of its fruit is an important agronomic trait and consumers in different regions have different preferences. However, a limited understanding of the molecular mechanisms regulating fruit development and shape has hindered eggplant breeding. In this study, we performed morphological observations and transcriptome analysis of long- and round-fruited eggplant genotypes to understand the molecular regulation during the early development of different fruit shapes. Morphological studies revealed that the two varieties already exhibited distinctly different phenotypes at the initial stage of fruit development before flowering, with rapid fruit enlargement beginning on the sixth day after flowering. Comparative transcriptome analysis identified phytohormone-related genes that were significantly upregulated on the day of flowering, indicating they may be involved in regulating the initial stages of fruit development. Notably, SmARF1 showed a sustained upregulation pattern in both varieties, suggesting that it may promote eggplant fruit growth. In addition, several differentially expressed genes of the SUN, YABBY, and OVATE families are potentially involved in the regulation of fruit development or fruit shape. We demonstrated that the SmOVATE5 gene has a negative regulatory function suppressing plant growth and development. In conclusion, this study provides new insights into the molecular regulatory mechanisms of eggplant fruit development, and the genes identified may provide valuable references for different fruit shape breeding programs.

Prognostic prediction of lung adenocarcinoma by integrative analysis of RHOH expression and methylation.

BACKGROUND AND OBJECTIVE: The development of epigenetics holds great promise for diagnosis and treatment of lung adenocarcinoma (LUAD). The purpose of this work was to analyze the correlation between Ras Homolog Gene Family Member H (RHOH) expression and methylation in patients with LUAD and its association with survival. METHODS: Data related to gene expression, DNA methylation, and clinical features of LUAD from The Cancer Genome Atlas (TCGA) database were analyzed. A total of 50 patients were included in verification group. The methylation level of RHOH in verification group was detected by bisulfite amplicon sequencing. RESULTS: The RHOH methylation level in TCGA cohort was significantly and negatively correlated with its expression level (Cor = -0.5, p = 2.687e-33). Patients with hypermethylation and low expression of RHOH had significantly worse prognosis than patients with hypomethylation and low expression of RHOH (TCGA: p = 0.004; validation cohort: p = 0.006, HR: 4.740, 95% CI: 1.567-14.340). CONCLUSION: Our research revealed that RHOH may prove to be a new potential prognostic predictor for LUAD patients.

Primary malignant melanoma of the bladder collides with high-grade non-invasive urothelial papillary carcinoma: A case report.

The present study reported a case of primary malignant melanoma of the bladder colliding with high-grade non-invasive urothelial papillary carcinoma with clinical, pathologic and immunohistochemical analysis, and reviewed the relevant literature. A 74-year-old male presented with hematuria; B ultrasound and computed tomography revealed a solid mass in the bladder and transurethral resection of the bladder lesion was performed. Microscopically, the tumors were composed of morphologically diverse malignant melanomas (95%) and high-grade non-invasive urothelial papillary carcinoma (5%), with no closely related or transitional regions. Immunohistochemistry indicated that malignant melanoma cells expressed HMB45, Melan-A and S-100, whereas they did not express any epithelial markers. The urothelial carcinomas expressed broad-spectrum cytokeratin and GATA3, and were negative for melanoma markers. The diagnosis of collision tumor between primary malignant melanoma of bladder and high-grade non-invasive urothelial papillary carcinoma depends on clinical and pathological examinations; this pathology is prone to recurrence and metastasis and has a poor prognosis.

Subtyping preserved ratio impaired spirometry (PRISm) by using quantitative HRCT imaging characteristics.

BACKGROUND: Preserved Ratio Impaired Spirometry (PRISm) is defined as FEV1/FVC ≥ 70% and FEV1 < 80%pred by pulmonary function test (PFT). It has highly prevalence and is associated with increased respiratory symptoms, systemic inflammation, and mortality. However, there are few radiological studies related to PRISm. The purpose of this study was to investigate the quantitative high-resolution computed tomography (HRCT) characteristics of PRISm and to evaluate the correlation between quantitative HRCT parameters and pulmonary function parameters, with the goal of establishing a nomogram model for predicting PRISm based on quantitative HRCT. METHODS: A prospective and continuous study was performed in 488 respiratory outpatients from February 2020 to February 2021. All patients underwent both deep inspiratory and expiratory CT examinations, and received pulmonary function test (PFT) within 1 month. According to the exclusion criteria and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification standard, 94 cases of normal pulmonary function, 51 cases of PRISm and 48 cases of mild to moderate chronic obstructive lung disease (COPD) were included in the study. The lung parenchyma, parametric response mapping (PRM), airway and vessel parameters were measured by automatic segmentation software (Aview). One-way analysis of variance (ANOVA) was used to compare the differences in clinical features, pulmonary function parameters and quantitative CT parameters. Spearman rank correlation analysis was used to evaluate the correlation between CT quantitative index and pulmonary function parameters. The predictors were obtained by binary logistics regression analysis respectively in normal and PRISm as well as PRISm and mild to moderate COPD, and the nomogram model was established. RESULTS: There were significant differences in pulmonary function parameters among the three groups (P < 0.001). The differences in pulmonary parenchyma parameters such as emphysema index (EI), pixel indices-1 (PI-1) and PI-15 were mainly between mild to moderate COPD and the other two groups. The differences of airway parameters and pulmonary vascular parameters were mainly between normal and the other two groups, but were not found between PRISm and mild to moderate COPD. Especially there were significant differences in mean lung density (MLD) and the percent of normal in PRM (PRMNormal) among the three groups. Most of the pulmonary quantitative CT parameters had mild to moderate correlation with pulmonary function parameters. The predictors of the nomogram model using binary logistics regression analysis to distinguish normal from PRISm were smoking, MLD, the percent of functional small airways disease (fSAD) in PRM (PRMfSAD) and Lumen area. It had a good goodness of fit (χ2 = 0.31, P < 0.001) with the area under curve (AUC) value of 0.786. The predictor of distinguishing PRISm from mild to moderate COPD were PRMEmph (P < 0.001, AUC = 0.852). CONCLUSIONS: PRISm was significantly different from subjects with normal pulmonary function in small airway and vessel lesions, which was more inclined to mild to moderate COPD, but there was no increase in pulmonary parenchymal attenuation. The nomogram based on quantitative HRCT parameters has good predictive value and provide more objective evidence for the early screening of PRISm.

Extrarenal Wilms tumor with hypertension and dilated cardiomyopathy in an infant: A report of an unusual case.

While Wilms tumors are the most frequently detected kidney cancer type in children, extrarenal Wilms tumors (ERWTs) remain rare. This report is the first to describe hypertension and dilated cardiomyopathy in a patient with an ERWT. A 6-month-old male infant presented with an abdominal mass and paroxysmal hypertension; echocardiography revealed dilated cardiomyopathy with an ejection fraction of 34%, as well as substantially increased plasma renin activity. Pathology yielded a definitive diagnosis of ERWT. Cardiac function and blood pressure gradually returned to normal after tumorectomy. The early diagnosis of such a tumor together with efficient oncologic treatment are vital to optimal patient outcomes.

Comparative genomic investigation of TCP gene family in eggplant (Solanum melongena L.) and expression analysis under divergent treatments.

KEY MESSAGE: The putative TCP genes and their responses to abiotic stress in eggplant were comprehensively characterized, and SmTCP genes (Smechr0202855.1 and Smechr0602431.1) may be involved in anthocyanin synthesis. The Teosinte branched1/Cycloidea/Proliferating cell factors (TCPs), a family of plant-specific transcription factors, plays paramount roles in a plethora of developmental and physiological processes. We here systematically characterized putative TCP genes and their response to abiotic stress in eggplant. In total, 30 SmTCP genes were categorized into two subfamilies based on the classical TCP conserved domains. Chromosomal location analysis illustrated the random distribution of putative SmTCP genes along 12 eggplant chromosomes. Cis-acting elements and miRNA target prediction suggested that versatile and complicated regulatory mechanisms that control SmTCPs gene expression, and 3 miRNAs (miR319a, miR319b, and miR319c-3p) might act as major regulators targeting SmTCPs. Tissue expression profiles indicated divergent spatiotemporal expression patterns of SmTCPs. qRT-PCR assays demonstrated different expression profiles of SmTCP under 4 °C, drought and ABA treatment conditions, suggesting the possible participation of SmTCP genes in multiple signaling pathways. Furthermore, RNA-seq data of eggplant anthocyanin synthesis coupled with yeast one-hybrid and dual-luciferase assays suggested the involvement of SmTCP genes (Smechr0202855.1 and Smechr0602431.1) in the mediation of anthocyanin synthesis. Our study will facilitate further investigation on the putative functional characterization of eggplant TCP genes and lay a solid foundation for the in-depth study of the involvement of SmTCP genes in the regulation of anthocyanin synthesis.

Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis.

Autophagy participates in the regulation of pulmonary arterial hypertension (PAH). However, the role of autophagy-related genes (ARGs) in the pathogenesis of the PAH is still unclear. This study aimed to identify the ARGs in PAH via bioinformatics analysis. A microarray dataset (GSE113439) was downloaded from the Gene Expression Omnibus database to identify differentially expressed ARGs (DEARGs). Protein-protein interactions network, gene ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to screen hub genes and the underlying molecular mechanisms of PAH. Finally, the mRNA expression of the hub genes was validated using the GSE53408 dataset. Twenty-six DEARGs were identified, all of which were upregulated. Enrichment analyses revealed that these DEARGs were mainly enriched in the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway, PI3K-Akt signaling pathway, response to hypoxia, response to nutrient levels, and autophagy. Among these hub genes, the mRNA expression levels of HSP90AA1, HIF1A, MET, IGF1, LRRK2, CLTC, DNM1L, MDM2, RICTOR, and ROCK2 were significantly upregulated in PAH patients than in healthy individuals. Ten hub DEARGs were identified and may participate in the pathogenesis of the PAH via the regulation of autophagy. The present study may provide novel therapeutic targets for PAH prevention and treatment and expand our understanding of PAH.

The Combined Value of Type2 Inflammatory Markers in Chronic Obstructive Pulmonary Disease.

The roles of type2 inflammatory markers in chronic airway diseases have been assessed in previous studies. However, the relationship between the combined value of these biomarkers and chronic obstructive pulmonary disease (COPD) has not been fully elucidated. We aimed to investigate the roles of the combined value of the fraction of exhaled nitric oxide (FeNO) level and blood eosinophil count in COPD and the predictive capability of these biomarkers. In total, 266 patients were included in our analysis. When the two type2 biomarkers were assessed separately, there were limited correlations between either increased FeNO level or blood eosinophil count and decreased incidence of total exacerbation or frequency of mild exacerbation. Combining these two biomarkers strengthened their association with both incidence and frequency of acute exacerbation. In addition, during further assessment, simultaneously increased FeNO level and blood eosinophil count were associated with both mild and moderate acute exacerbation. Among the subjects included in this analysis, although the predictive capability was improved when these two biomarkers were combined, the improvement was not statistically significant, indicating the need to increase the sample size. The combination of FeNO level and blood eosinophil count exhibited strong and independent additive value in the assessment of acute exacerbation in COPD; simultaneously increased FeNO level and blood eosinophil count played a protective role in progression of COPD.

Cytosolic peptides encoding CaV1 C-termini downregulate the calcium channel activity-neuritogenesis coupling.

L-type Ca2+ (CaV1) channels transduce channel activities into nuclear signals critical to neuritogenesis. Also, standalone peptides encoded by CaV1 DCT (distal carboxyl-terminus) act as nuclear transcription factors reportedly promoting neuritogenesis. Here, by focusing on exemplary CaV1.3 and cortical neurons under basal conditions, we discover that cytosolic DCT peptides downregulate neurite outgrowth by the interactions with CaV1's apo-calmodulin binding motif. Distinct from nuclear DCT, various cytosolic peptides exert a gradient of inhibitory effects on Ca2+ influx via CaV1 channels and neurite extension and arborization, and also the intermediate events including CREB activation and c-Fos expression. The inhibition efficacies of DCT are quantitatively correlated with its binding affinities. Meanwhile, cytosolic inhibition tends to facilitate neuritogenesis indirectly by favoring Ca2+-sensitive nuclear retention of DCT. In summary, DCT peptides as a class of CaV1 inhibitors specifically regulate the channel activity-neuritogenesis coupling in a variant-, affinity-, and localization-dependent manner.