Cuproptosis-Related lncRNA Predict Prognosis and Immune Response of LUAD.

Background: Lung cancer is the leading cause of cancer deaths worldwide, primarily due to lung adenocarcinoma (LUAD). However, the heterogeneity of programmed cell death results in varied prognostic and predictive outcomes. This study aimed to develop an LUAD evaluation marker based on cuproptosis-related lncRNAs. Methods: First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate, LASSO, and multivariate Cox regression analyses were conducted to construct cuproptosis-associated lncRNA models. LUAD patients were categorized into high-risk and low-risk groups using prognostic risk values. Kaplan-Meier analysis, PCA, GSEA, and nomograms were employed to evaluate and validate the results. Results: 7 cuproptosis-related lncRNAs were identified, and a risk model was created. High-risk tumors exhibited cuproptosis-related gene alterations in 95.54% of cases, while low-risk tumors showed alterations in 85.65% of cases, mainly involving TP53. The risk value outperformed other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival. The cuproptosis-related lncRNA-based risk model demonstrated high validity for LUAD evaluation, potentially influencing individualized treatment approaches. Expression analysis of four candidate cuproptosis-related lncRNAs (AL606834.1, AL161431.1, AC007613.1, and LINC02835) in LUAD tissues and adjacent normal tissues revealed significantly higher expression levels of AL606834.1 and AL161431.1 in LUAD tissues, positively correlating with tumor stage, lymph node metastasis, and histopathological grade. Conversely, AC007613.1 and LINC02835 exhibited lower expression levels, negatively correlating with these factors. High expression of AL606834.1 and AL161431.1 indicated poor prognosis, while low expression of AC007613.1 and LINC02835 was associated with unfavorable outcomes. Univariate and multivariate analyses confirmed these lncRNAs as independent risk factors for LUAD prognosis. Conclusion: The 4 cuproptosis-related (lncRNAsAL606834.1, AL161431.1, AC007613.1, and LINC02835) can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.

The efficacy and safety of bilateral synchronous transcutaneous auricular vagus nerve stimulation for prolonged disorders of consciousness: a multicenter, double-blind, stratified, randomized controlled trial protocol.

Background: Treatment of disorders of consciousness (DOC) poses a huge challenge for clinical medicine. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation method, which shows potential in improving recovery of DOC. However, the evidence came from single-center, small-sample randomized controlled trial, which is insufficient to form a conclusion. Thereby, we propose a prospective, multicenter, double-blind, stratified, two-arm randomized controlled trial protocol to investigate the efficacy and safety of bilateral synchronous taVNS for treatment of DOC. Methods: We aim to recruit 382 patients with prolonged DOC, and divide them into an active stimulation group and a sham stimulation group. The patients in the active stimulation group will receive bilateral synchronous taVNS with a 200 µs pulse width, 20 Hz frequency, and personal adjusted intensity. The sham stimulation group will wear the same stimulator but without current output. Both groups will receive treatment for 30 min per session, twice per day, 6 days per week lasting for 4 weeks. The clinical assessment including Coma Recovery Scale-Revised (CRS-R), Full Outline of Unresponsiveness (FOUR), Glasgow Coma Scale (GCS), and Extended Glasgow Outcome Scale (GOS-E) will be conducted to evaluate its efficacy. Heart rate variability (HRV), blood pressure, and adverse events will be recorded to evaluate its safety. Discussion: These results will enable us to investigate the efficacy and safety of taVNS for DOC. This protocol will provide multicenter, large-sample, high-quality Class II evidence to support bilateral synchronous taVNS for DOC, and will advance the field of treatment options for DOC.Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=221851, ChiCTR2400081978.

Acute Effects of Local High-Frequency Percussive Massage on Deep Fascial and Muscular Stiffness and Joint Range of Motion in Young Adult Men.

BACKGROUND: Local high-frequency percussive (HFP) massage has recently found widespread application in physical therapy. Although HFP massage reportedly improves range of motion (ROM), the mechanism underlying its action has not yet been proven. This study aimed to clarify whether a 5-minute percussive massage regimen affects muscular or connective tissues, such as the deep fascia and deep intermuscular fascia and the change in joint ROM. METHOD: The study sample was calculated using G*Power analysis program, and this study enrolled 15 healthy men who underwent 5-minute HFP massage to the medial gastrocnemius muscle. Shear-wave elastography was used to measure tissue stiffness in the deep fascia, muscle, and deep intermuscular fascia through shear-wave velocity as well as the ROM of the volunteers' ankle joint dorsiflexion before and after the HFP massage. A value of P < .05 was used to declare statistical significance, and post hoc was used to calculate the effect size using G*Power. RESULTS: Shear-wave velocity revealed a significant change in the deep fascia (P = .003; shear-wave velocity: -0.7 m/s) and significant increase in ROM of ankle dorsiflexion (P = .002; increase in ROM: 3.0°) after 5 minutes of HFP massage. However, the muscle and deep intermuscular fascia did not exhibit any significant changes. CONCLUSIONS: HFP massage for 5 minutes modified the stiffness of the deep fascia and concurrently improved the ankle joint-dorsiflexion ROM. This method can be used as an intervention to decrease stiffness of the deep fascia and increase the ROM efficiently.

BnPLP1 Positively Regulates Flowering Time, Plant Height, and Main Inflorescence Length in Brassica napus.

Protein prenylation mediated by the Arabidopsis thaliana PLURIPETALA (AtPLP) gene plays a crucial role in plant growth, development, and environmental response by adding a 15-carbon farnesyl group or one to two 20-carbon geranylgeranyl groups onto one to two cysteine residues at the C-terminus of the target protein. However, the homologous genes and their functions of AtPLP in rapeseed are unclear. In this study, bioinformatics analysis and gene cloning demonstrated the existence of two homologous genes of AtPLP in the Brassica napus L. genome, namely, BnPLP1 and BnPLP2. Evolutionary analysis revealed that BnPLP1 originated from the B. rapa L. genome, while BnPLP2 originated from the B. oleracea L. genome. Genetic transformation analysis revealed that the overexpression of BnPLP1 in Arabidopsis plants exhibited earlier flowering initiation, a prolonged flowering period, increased plant height, and longer main inflorescence length compared to the wild type. Contrarily, the downregulation of BnPLP1 expression in B. napus plants led to delayed flowering initiation, shortened flowering period, decreased plant height, and reduced main inflorescence length compared to the wild type. These findings indicate that the BnPLP1 gene positively regulates flowering time, plant height, and main inflorescence length. This provides a new gene for the genetic improvement of flowering time and plant architecture in rapeseed.

A prediction model for acute respiratory distress syndrome in immunocompetent adults with adenovirus-associated Pneumonia: a multicenter retrospective analysis.

BACKGROUND: In recent years, the number of human adenovirus (HAdV)-related pneumonia cases has increased in immunocompetent adults. Acute respiratory distress syndrome (ARDS) in these patients is the predominant cause of HADV-associated fatality rates. This study aimed to identify early risk factors to predict early HAdV-related ARDS. METHODS: Data from immunocompetent adults with HAdV pneumonia between June 2018 and May 2022 in ten tertiary general hospitals in central China was analyzed retrospectively. Patients were categorized into the ARDS group based on the Berlin definition. The prediction model of HAdV-related ARDS was developed using multivariate stepwise logistic regression and visualized using a nomogram. RESULTS: Of 102 patients with adenovirus pneumonia, 41 (40.2%) developed ARDS. Overall, most patients were male (94.1%), the median age was 38.0 years. Multivariate logistic regression showed that dyspnea, SOFA (Sequential Organ Failure Assessment) score, lactate dehydrogenase (LDH) and mechanical ventilation status were independent risk factors for this development, which has a high mortality rate (41.5%). Incorporating these factors, we established a nomogram with good concordance statistics of 0.904 (95% CI 0.844-0.963) which may help to predict early HAdV-related ARDS. CONCLUSION: A nomogram with good accuracy in the early prediction of ARDS in patients with HAdV-associated pneumonia may could contribute to the early management and effective treatment of severe HAdV infection.

Mitochondria-related lncRNAs: predicting prognosis, tumor microenvironment and treatment response in lung adenocarcinoma.

Lung cancer is the most common type of malignant tumor that affects people in China and even across the globe, as it exhibits the highest rates of morbidity and mortality. Lung adenocarcinoma (LUAD) is a type of lung cancer with a very high incidence. The purpose of this study was to identify potential biomarkers that could be used to forecast the prognosis and improve the existing therapy options for treating LUAD. Clinical and RNA sequencing data of LUAD patients were retrieved from the TCGA database, while the mitochondria-associated gene sets were acquired from the MITOMAP database. Thereafter, Pearson correlation analysis was carried out to screen mitochondria-associated lncRNAs. Furthermore, univariate Cox and Lasso regression analyses were used for the initial screening of the target lncRNAs for prognostic lncRNAs before they could be incorporated into a multivariate Cox Hazard ratio model. Then, the clinical data, concordance index, Kaplan-Meier (K-M) curves, and the clinically-relevant subjects that were approved by the Characteristic Curves (ROC) were employed for assessing the model's predictive value. Additionally, the differences in immune-related functions and biological pathway enrichment between high- and low-risk LUAD groups were examined. Nomograms were developed to anticipate the OS rates of the patients within 1-, 3-, and 5 years, and the differences in drug sensitivity and immunological checkpoints were compared. In this study, 2175 mitochondria-associated lncRNAs were screened. Univariate, multivariate, and Lasso Cox regression analyses were carried out to select 13 lncRNAs with an independent prognostic significance, and a prognostic model was developed. The OS analysis of the established prognostic prediction model revealed significant variations between the high- and low-risk patients. The AUC-ROC values after 1, 3, and 5 years were seen to be 0.746, 0.692, and 0.726, respectively. The results suggested that the prognostic model riskscore could be used as an independent prognostic factor that differed from the other clinical characteristics. After analyzing the findings of the study, it was noted that both the risk groups showed significant differences in their immune functioning, immunological checkpoint genes, and drug sensitivity. The prognosis of patients with LUAD could be accurately and independently predicted using a risk prediction model that included 13 mitochondria-associated lncRNAs.

A case of acute severe cryptogenic organic pneumonia with secondary hemophilia. / 继发嗜血现象的重症急进型隐源性机化性肺炎1例.

Cryptogenic organic pneumonia (COP) refers to organic pneumonia that has not been identified a clear cause by current medical methods. A small proportion of COP can exhibit severe and progressive characteristics, while severe COP can cause systemic inflammatory storms and can be secondary to hemophilia. This article reported a case of acute severe COP secondary to hemophilia. A 67-year-old male patient was admitted to the hospital due to cough, shortness of breath, and fever. At first, he was misdiagnosed as severe pneumonia, but failed to receive anti infection treatments. Sputum pathogenetic examination and Macrogene testing of alveolar lavage fluid were performed, and no etiology was found to explain the patient's condition. The condition was gradually worsened and hemophilia occurred to explain, suggesting that acute severe COP was relevant. After receiving hormone treatment, the condition gradually relieved and the absorption of lung lesions improved. Hemophilia secondary to COP is rare, and the specific mechanism needs further study.

METTL14 Regulates PLAGL2/ß-Catenin Signaling Axis to Promote the Development of Nonsmall Cell Lung Cancer.

N6-methyladenosine (m6A) is an abundant eukaryotic mRNA modification involved in regulating the formation and metastasis of nonsmall cell lung cancer (NSCLC). We collected clinical NSCLC tissue and paracarcinoma tissue. Then methyltransferase-like 14 (METTL14), pleomorphic adenoma gene like-2 (PLAGL2), and ß-catenin expressions were assessed using quantitative real-time PCR and western blot. PLAGL2, and ß-catenin (nuclear) expressions were increased in NSCLC tissues. Cell proliferation, migration, invasion, and death were examined. PLAGL2 could activate ß-catenin signaling to affect cell proliferation and migration abilities. RNA immunoprecipitation assay was operated to identify m6A modification levels of PLAGL2 after knockdown and overexpression of METTL14. PLAGL2 was regulated by METTL14-mediated m6A modification. Knockdown of METTL14 repressed cell proliferation, migration, and invasion, and promoted cell death. Interestingly, these effects were reversed when PLAGL2 was overexpressed. Finally, tumor formation in nude mice was performed to verify the role of the METTL14/PLAGL2/ß-catenin signaling axis. Tumor formation in nude mice demonstrated METTL14/PLAGL2/ß-catenin axis promoted NSCLC development in vivo. In brief, METTL14 promoted NSCLC development by increasing m6A methylation of PLAGL2 to activate ß-catenin signaling. Our research provided essential clues for in-depth comprehension of the mechanism of NSCLC occurrence and development and also provided the basis for NSCLC treatment.

Establishment and validation of a predictive model of preeclampsia based on transcriptional signatures of 43 genes in decidua basalis and peripheral blood.

Preeclampsia (PE) has an increasing incidence worldwide, and there is no gold standard for prediction. Recent progress has shown that abnormal decidualization and impaired vascular remodeling are essential to PE pathogenesis. Therefore, it is of great significance to analyze the decidua basalis and blood changes of PE to explore new methods. Here, we performed weighted gene co-expression network analysis based on 9553 differentially expressed genes of decidua basalis data (GSE60438 includes 25 cases of PE and 23 non-cases) from Gene Expression Omnibus to screen relevant module-eigengenes (MEs). Among them, MEblue and MEgrey are the most correlated with PE, which contains 371 core genes. Subsequently, we applied the logistic least absolute shrinkage and selection operator regression, screened 43 genes most relevant to prediction from the intersections of the 371 genes and training set (GSE48424 includes 18 cases of PE and 18 non-cases) genes, and built a predictive model. The specificity and sensitivity are illustrated by receiver operating characteristic curves, and the stability was verified by two validation sets (GSE86200 includes 12 cases of PE and 48 non-cases, and GSE85307 includes 47 cases of PE and 110 non-cases). The results demonstrated that our predictive model shows good predictions, with an area under the curve of 0.991 for the training set, 0.874 and 0.986 for the validation sets. Finally, we found the 43 key marker genes in the model are closely associated with the clinically accepted predictive molecules, including FLT1, PIGF, ENG and VEGF. Therefore, this predictive model provides a potential approach for PE diagnosis and treatment.

Evolving an Ultra-Sensitive Near-Infrared ß-Galactosidase Fluorescent Probe for Breast Cancer Imaging and Surgical Resection Navigation.

Early diagnosis and therapy are clinically crucial in decreasing mortality from breast carcinoma. However, the existing probes have difficulty in accurately identifying the margins and contours of breast carcinoma due to poor sensitivity and specificity. There is an urgent need to develop high-sensitive fluorescent probes for the diagnosis of breast carcinoma and for differentiating tumors from normal tissues during surgery. ß-Galactosidase is a significant biomarker, whose overexpression is closely associated with the progression of breast tumors. Herein, we have constructed a ß-galactosidase-activated fluorescent probe NIR-ßgal-2 through rational design and molecular docking engineering simulations. The probe displayed superior sensitivity (detection limit = 2.0 × 10-3 U/mL), great affinity (Km = 1.84 µM), and catalytic efficiency (kcat/Km = 0.24 µM-1 s-1) for ß-galactosidase. Leveraging this probe, we demonstrated the differentiation of cancer cells overexpressing ß-galactosidase from normal cells and then applied the probe for intraoperative guided excision of breast tumors. Moreover, we exhibited the application of NIR-ßgal-2 for the successful resection of orthotopic breast tumors by "in situ spraying" and monitored a good prognostic recovery. This work may promote the application of enzyme-activated near-infrared fluorescent probes for the development of carcinoma diagnosis and image-guided surgery.

DCAF13 is essential for the pathogenesis of preeclampsia through its involvement in endometrial decidualization.

Preeclampsia (PE) is a syndrome that occurs during pregnancy and affects more than 8 million mother-infant pairs each year. Most previous studies on the pathogenesis of PE have focused on the placenta. However, decidualization is the basis for placentation and subsequent development. The CRL4 (Cullin 4-RING E3 ubiquitin ligase) complex ubiquitinates and degrades substrates, while DCAF13 (DDB1 and CUL4-associated factor 13) is a component and substrate receptor of this complex, which recognizes and recruits the complex different substrates. DCAF13 plays a major role in the maintenance of follicles and the development of oocytes. However, its role in subsequent pregnancies remains unclear. In the present study, we first investigated DCAF13 levels in the decidua of PE patients and found that it is significantly lower than that of normal pregnant women. Second, we found that DCAF13 expression increases during decidualization, and reducing expression of DCAF13 by siRNA prevents decidualization. Third, in vivo experiments in mice further revealed that Dcaf13 expression increases with decidualization. Finally, we generated and found that uteri of pseudopregnant conditional Dcaf13 knockout mice fails to undergo decidualization. Therefore, we propose that DCAF13 plays a key role in decidualization. Abnormal expression of DCAF13 affects the decidualization process, which is likely involved in the occurrence and development of PE.

Enhancing the Release Efficiency of a Molecular Chemotherapeutic Prodrug by Photodynamic Therapy.

Tumor-specific, hypoxia-activated prodrugs have been developed to alleviate the side effects of chemotherapy drugs. However, the release efficiency of hypoxia-activated prodrugs is restricted by the degree of tumor hypoxia, which further leads to poor cancer treatment effects. On the other hand, oxygen is consumed gradually in photodynamic therapy (PDT), which aggravates hypoxia at the tumor site. In this study, we combined hypoxia-activated prodrugs with PDT agents to promote the prodrugs release, thereby improving their bioavailability and therapeutic effects. As a proof of concept, a mitochondria-targeted molecular prodrug, CS-P, was designed and synthesized. It can be selectively activated by tumor hypoxia to release chemotherapeutic drugs and photosensitizers, and then further discharge drugs after light irradiation. The design strategy proposed in this paper provides a new idea for enhancing hypoxia-activated prodrug release and real-time monitoring prodrug release.

Advances in Optical Imaging of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), emerging as one of the most common chronic liver diseases including simple steatosis and non-alcoholic steatohepatitis (NASH), is likely to progress to liver fibrosis and hepatic carcinoma if not treated in time. Therefore, early diagnosis and treatment of NAFLD are necessary. Currently, liver biopsy, as the gold standard for clinical diagnosis of NAFLD, is not widely accepted by patients due to its invasiveness. However, other non-invasive methods that had been reported for NAFLD (such as magnetic resonance imaging, positron emission tomography, and ultrasound) still suffer from low resolution and sensitivity, which are available as a guide for liver biopsy sometimes. As a non-invasive modality with high spatiotemporal resolution and superior sensitivity, optical imaging methods have been widely favored in recent years, mainly including fluorescence imaging, photoacoustic imaging, and bioluminescence imaging. With these optical imaging approaches, a series of optical probes based on optical and molecular-specific design have been developed for the biomarker diagnosis and research of diseases. In this review, we summarize the existing non-invasive optical imaging probes for the detection of biomarkers in NAFLD, including microenvironment (viscosity, polarity), ROS, RSS, ions, proteins, and nucleic acids. Design strategies for optical imaging probes and their applications in NAFLD bioimaging are discussed and focused on. We also highlight the potential challenges and prospects of designing new generations of optical imaging probes in NAFLD studies, which will further enhance the diversity, practicality, and clinical feasibility of NAFLD research.

Cofilin-1 promotes fibrocyte differentiation and contributes to pulmonary fibrosis.

Fibrocytes originate from the bone marrow monocyte lineage and participate in the pathogenesis of pulmonary fibrosis. Research providing a comprehensive picture of fibrocytes is still limited. Cofilin-1 (CFL-1) is an important protein that regulates cell proliferation, migration and differentiation. Whether CFL-1 can induce monocyte differentiation into fibrocytes and promote the process of pulmonary fibrosis is unknown. Compared with that of healthy controls, the expression of CFL-1 was significantly increased in the plasma and peripheral blood mononuclear cells (PBMCs) from idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD) patients (P < 0.05). The percentages of peripheral blood fibrocytes in the IPF group (4.2550 ± 0.3483%) and CTD-ILD group (4.7100 ± 0.4811%) were higher than that in the control group (1.6340 ± 0.2549%) (both P < 0.05). In vitro, PBMCs transfected with siRNA-CFL-1 showed lower expression of CFL-1, and the percentage of fibrocytes was lower than that of the control (P < 0.05). PBMCs transfected with Lv-CFL-1 to increase the expression of CFL-1 showed a higher percentage of fibrocytes than the control (P < 0.05). In mice with bleomycin-induced pulmonary fibrosis, the relative expression of CFL-1 was increased, and the percentage of fibrocytes was higher than that in the saline group (P < 0.05). In bleomycin-induced mice, interference with Lv-CFL-1 decreased the expression of CFL-1, the percentage of fibrocytes was lower, and the lung tissue showed less fibrosis (P < 0.05). The overexpression of CFL-1 is associated with pulmonary fibrogenesis. CFL-1 could promote the differentiation of fibrocytes from monocyte peripheral blood mononuclear cells and promote pulmonary fibrosis.

[Primary mediastinal choriocarcinoma: A case report and literature review].

Primary mediastinal choriocarcinoma in male is not a very common disease, with nonspecific clinical manifestations. Gynecomastia and testicular atrophy are present in some cases. The levels of serum human chorionic gonadotropin are often significantly increased. Giant lump in the mediastinum and bilateral lungs multiple metastases can be seen on the computed tomography for lung. The diagnosis for it depends on pathological biopsy. Current treatment method is a comprehensive, consisting of chemotherapy, radiotherapy and surgery. This paper reported a case of primary mediastinal choriocarcinoma in male, who were diagnosed and treated in the Second Xiangya Hospital of Central South University. He was admitted for cough and hemoptysis, and finally diagnosed by biopsy. The prognosis is very poor. Therefore, it is important to take physical examination regularly because it can be detected and diagnosed early.

[A case of pulmonary alternariosis complicated with aspergillosis].

A 61-year-old woman with pulmonary alternariosis and aspergillosis was reported. The patient presented with recurrent hemoptysis and cough for 3 years. Alternaria was identified by fungal culture. Biopsy specimen showed pulmonary aspergillosis. The patient had been treated with voriconazole at 400 mg/d through intravenous guttae for 7 days, and then switched amphotericin B at 25 mg/d through intravenous guttae for 11 days. The patient was treated with voriconazole at 400 mg through oral when she was discharged from hospital. After the treatment, the clinical symptoms of hemoptysis and cough were recovered, and the lung CT examinations showed normal.

[Secondary infection of traumatic pulmonary cyst misdiagnosed as cholesterol encapsulated pleural effusion: a rare case and review of literature].

Pulmonary cyst is a relatively common benign lesion. It is easy to be misdiagnosed when the cyst complicated with infection. This paper reported a case of a giant traumatic pulmonary cyst (diameter 10 cm) combined with chronic infection. Firstly, the patient was diagnosed as cholesterol pleurisy after undergoing thoracoscopic biopsy. With repeated pleural effusion, the patient was scheduled for right anterolateral thoracotomy, which showed a thin-walled cyst (10 cm in diameter) attached to parietal and diaphragm, with the stem of cavity originated from the right lower lobe after the cyst cavity was dissociated. Pathological examination revealed that it was apseudocyst, which could be diagnosed as traumatic pulmonary cyst combined with chronic infection according to history of trauma. After undergoing right lower lobectomy and stripping of fiberboard, the prognosis was good. Traumatic pulmonary cyst, which was discovered interval 10 years after chest trauma, was rare. Traumatic pulmonary cyst combined with cholesterol cystic fluid was very rare. Huge pulmonary cyst complicated with infection was easily misdiagnosed as loculated pleural effusion. Therefore, to be correct diagnosis and treatment, clinician must carefully ask medical history. In addition, early image examination should be considered in those patients with chest trauma whether there are clinical symptoms or not.