Clinical and prognostic significance analysis of glycolysis-related genes in HNSCC.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents one of the most malignant cancers worldwide, with poor survival. Experimental evidence implies that glycolysis/hypoxia is associated with HNSCC. In this study, we aimed to construct a novel glycolysis-/hypoxia-related gene (GHRG) signature for survival prediction of HNSCC. METHODS: A multistage screening strategy was used to establish the GHRG prognostic model by univariate/least absolute shrinkage and selection operator (LASSO)/step multivariate Cox regressions from The Cancer Genome Atlas cohort. A nomogram was constructed to quantify the survival probability. Correlations between risk score and immune infiltration and chemotherapy sensitivity were explored. RESULTS: We established a 12-GHRG mRNA signature to predict the prognosis in HNSCC patients. Patients in the high-risk score group had a much worse prognosis. The predictive power of the model was validated by external HNSCC cohorts, and the model was identified as an independent factor for survival prediction. Immune infiltration analysis showed that the high-risk score group had an immunosuppressive microenvironment. Finally, the model was effective in predicting chemotherapeutic sensitivity. CONCLUSIONS: Our study demonstrated that the GHRG model is a robust prognostic tool for survival prediction of HNSCC. Findings of this work provide novel insights for immune infiltration and chemotherapy of HNSCC, and may be applied clinically to guide therapeutic strategies.

IR808@MnO nano-near infrared fluorescent dye's diagnostic value for malignant pleural effusion.

BACKGROUND: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion. RESEARCH QUESTION: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions. STUDY DESIGN AND METHODS: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language. RESULTS: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 µl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 µl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652-0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%. INTERPRETATION: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption.

Molecular Mechanism of Phosphorylation-Mediated Impacts on the Conformation Dynamics of GTP-Bound KRAS Probed by GaMD Trajectory-Based Deep Learning.

The phosphorylation of different sites produces a significant effect on the conformational dynamics of KRAS. Gaussian accelerated molecular dynamics (GaMD) simulations were combined with deep learning (DL) to explore the molecular mechanism of the phosphorylation-mediated effect on conformational dynamics of the GTP-bound KRAS. The DL finds that the switch domains are involved in obvious differences in conformation contacts and suggests that the switch domains play a key role in the function of KRAS. The analyses of free energy landscapes (FELs) reveal that the phosphorylation of pY32, pY64, and pY137 leads to more disordered states of the switch domains than the wild-type (WT) KRAS and induces conformational transformations between the closed and open states. The results from principal component analysis (PCA) indicate that principal motions PC1 and PC2 are responsible for the closed and open states of the phosphorylated KRAS. Interaction networks were analyzed and the results verify that the phosphorylation alters interactions of GTP and magnesium ion Mg2+ with the switch domains. It is concluded that the phosphorylation pY32, pY64, and pY137 tune the activity of KRAS through changing conformational dynamics and interactions of the switch domains. We anticipated that this work could provide theoretical aids for deeply understanding the function of KRAS.

Binding Mechanism of Inhibitors to BRD4 and BRD9 Decoded by Multiple Independent Molecular Dynamics Simulations and Deep Learning.

Bromodomain 4 and 9 (BRD4 and BRD9) have been regarded as important targets of drug designs in regard to the treatment of multiple diseases. In our current study, molecular dynamics (MD) simulations, deep learning (DL) and binding free energy calculations are integrated to probe the binding modes of three inhibitors (H1B, JQ1 and TVU) to BRD4 and BRD9. The MD trajectory-based DL successfully identify significant functional function domains, such as BC-loop and ZA-loop. The information from the post-processing analysis of MD simulations indicates that inhibitor binding highly influences the structural flexibility and dynamic behavior of BRD4 and BRD9. The results of the MM-GBSA calculations not only suggest that the binding ability of H1B, JQ1 and TVU to BRD9 are stronger than to BRD4, but they also verify that van der Walls interactions are the primary forces responsible for inhibitor binding. The hot spots of BRD4 and BRD9 revealed by residue-based free energy estimation provide target sites of drug design in regard to BRD4 and BRD9. This work is anticipated to provide useful theoretical aids for the development of selective inhibitors over BRD family members.

Unveiling Conformational States of CDK6 Caused by Binding of Vcyclin Protein and Inhibitor by Combining Gaussian Accelerated Molecular Dynamics and Deep Learning.

CDK6 plays a key role in the regulation of the cell cycle and is considered a crucial target for cancer therapy. In this work, conformational transitions of CDK6 were identified by using Gaussian accelerated molecular dynamics (GaMD), deep learning (DL), and free energy landscapes (FELs). DL finds that the binding pocket as well as the T-loop binding to the Vcyclin protein are involved in obvious differences of conformation contacts. This result suggests that the binding pocket of inhibitors (LQQ and AP9) and the binding interface of CDK6 to the Vcyclin protein play a key role in the function of CDK6. The analyses of FELs reveal that the binding pocket and the T-loop of CDK6 have disordered states. The results from principal component analysis (PCA) indicate that the binding of the Vcyclin protein affects the fluctuation behavior of the T-loop in CDK6. Our QM/MM-GBSA calculations suggest that the binding ability of LQQ to CDK6 is stronger than AP9 with or without the binding of the Vcyclin protein. Interaction networks of inhibitors with CDK6 were analyzed and the results reveal that LQQ contributes more hydrogen binding interactions (HBIs) and hot interaction spots with CDK6. In addition, the binding pocket endures flexibility changes from opening to closing states and the Vcyclin protein plays an important role in the stabilizing conformation of the T-loop. We anticipate that this work could provide useful information for further understanding the function of CDK6 and developing new promising inhibitors targeting CDK6.

GDE3 regulates oligodendrocyte precursor proliferation via release of soluble CNTFRα.

Oligodendrocyte development is tightly controlled by extrinsic signals; however, mechanisms that modulate cellular responses to these factors remain unclear. Six-transmembrane glycerophosphodiester phosphodiesterases (GDEs) are emerging as central regulators of cellular differentiation via their ability to shed glycosylphosphatidylinositol (GPI)-anchored proteins from the cell surface. We show here that GDE3 controls the pace of oligodendrocyte generation by negatively regulating oligodendrocyte precursor cell (OPC) proliferation. GDE3 inhibits OPC proliferation by stimulating ciliary neurotrophic factor (CNTF)-mediated signaling through release of CNTFRα, the ligand-binding component of the CNTF-receptor multiprotein complex, which can function as a soluble factor to activate CNTF signaling. GDE3 releases soluble CNTFRα by GPI-anchor cleavage from the plasma membrane and from extracellular vesicles (EVs) after co-recruitment of CNTFRα in EVs. These studies uncover new physiological roles for GDE3 in gliogenesis and identify GDE3 as a key regulator of CNTF-dependent regulation of OPC proliferation through release of CNTFRα.

Atrial Fibrillation (AFIB) in the ICU: Incidence, Risk Factors, and Outcomes: The International AFIB-ICU Cohort Study.

OBJECTIVES: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. DESIGN: Multicenter, prospective, inception cohort study. SETTING: Forty-four ICUs in 12 countries in four geographical regions. SUBJECTS: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8-17.6), of which newly developed AF was 13.3% (11.5-15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16-23), magnesium 16% (13-20), potassium 15% (12-19), amiodarone 51% (47-55), beta-1 selective blockers 34% (30-38), calcium channel blockers 4% (2-6), digoxin 16% (12-19), and direct current cardioversion in 4% (2-6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95-1.99). CONCLUSIONS: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

Identification and bioinformatic analysis of CircRNAs in the plasma of patients with very severe chronic obstructive pulmonary disease.

BACKGROUND: The differential expression of circular RNAs (circRNAs) in individuals with very severe chronic obstructive pulmonary disease (COPD) and healthy individuals was screened using microarray technology. The related functions and mechanisms were analyzed using bioinformatic methods to explore the potential of target circRNAs as biomarkers of COPD and provide insights for future pathogenesis. PATIENTS AND METHODS: Thirty patients with very severe COPD and thirty healthy controls were diagnosed at The Second People's Hospital of Hefei from September 2021 to September 2022. The differential expression of circRNAs was compared and analyzed using a gene microarray and verified using quantitative real-time polymerase chain reaction (qRT-PCR) technology. RESULTS: A total of 90 upregulated and 29 downregulated circRNAs were screened in patients with very severe COPD and compared with those in healthy controls. qRT-PCR analysis showed that hsa_circ_0062683 of patients with very severe COPD was significantly upregulated, and hsa_circ_0089763 and hsa_circ_0008882 were significantly downregulated. By constructing the circRNA-miRNA interaction network, it was found that hsa-miR-612, hsa-miR-593-5p, hsa-miR-765, and hsa-miR-103a-2-5p are the miRNAs regulated by more differentially expressed circRNAs (DEcircRNAs). DEcircRNAs may participate in the development of COPD through hypoxia or regulation of various immune cells. CONCLUSION: Plasma circRNAs may play a helpful role in the diagnosis and assessment of COPD and be valuable disease biomarkers.

Cigarettes smoking and e-cigarettes using among university students: a cross-section survey in Guangzhou, China, 2021.

BACKGROUND: There is an increase in the use of cigarettes and e-cigarettes worldwide, and the similar trends may be observed in young adults. Since 2014, e-cigarettes have become the most commonly used nicotine products among young adults (Sun et al., JAMA Netw Open 4:e2118788, 2021). With the increase in e-cigarette use and the decrease in use of cigarettes and other tobacco products, however, there is limited information about Chinese smokers, e-cigarettes users and trends in cigarettes and e-cigarettes use among university students. Therefore, our objective was to investigate the using status of cigarettes, e-cigarettes and smoking behavior among the students from 7 universities in Guangzhou, China. METHODS: Students at 7 different universities in Guangzhou were investigated online in 2021 through a cross-sectional survey. A total of 10,008 students were recruited and after screening, 9361 participants were adopted in our statistics. Descriptive analysis, Chi-square analysis, and multiple logistic regression analysis were used to explore the smoking status and influencing factors. RESULTS: The average age of the 9361 university students was 22.4 years (SD = 3.6). 58.3% of participants were male. 29.8% of the participants smoked or used e-cigarettes. Among the smokers and users of e-cigarettes, 16.7% were e-cigarettes only users, 35.0% were cigarettes only users, and 48.3% were dual users. Males were more likely to smoke or use e-cigarettes. Medical students, students from prestigious Chinese universities, and students with higher levels of education were less likely. Students with unhealthy lifestyles (e.g., drinking alcohol frequently, playing video games excessively, staying up late frequently) were more likely to smoke or use e-cigarettes. Emotion can have significant impacts on both cigarettes and e-cigarettes dual users when choosing cigarettes or e-cigarettes to use. More than half of dual users said they would choose cigarettes when they were depressed and e-cigarettes when they were happy. CONCLUSION: We identified factors influencing the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Gender, education level background, specialization, lifestyle habits and emotion all influenced the use of cigarettes and e-cigarettes among university students in Guangzhou, China. Male, low education level, from non-prestigious Chinese universities or vocational schools, non-medical specialization, and presence of unhealthy lifestyles were influencing factors for the use of cigarettes and e-cigarettes among university students in Guangzhou and students with these factors were more likely to smoke or use e-cigarettes. Besides, emotions can influence dual users' choice of products. This study provides more information to better understand young people's preferences for cigarettes and e-cigarettes by elucidating the characteristics of cigarettes and e-cigarettes use, as well as related influencing factors, among university students in Guangzhou. Further research involving more variables connected to the use of cigarettes and e-cigarettes will be required in our future study.

Combined biological effects and lung proteomics analysis in mice reveal different toxic impacts of electronic cigarette aerosol and combustible cigarette smoke on the respiratory system.

Combustible cigarettes produce many toxic substances that have been linked to diseases, such as lung cancer and chronic obstructive pulmonary disease. For those smokers unable or unwilling to quit, electronic cigarettes (e-cigarettes) could be used as an alternative to cigarettes. However, the effects and mechanisms of e-cigarette aerosol (ECA) on respiratory function have not been fully elucidated, and in vivo studies of its safety are limited compared to cigarette smoke (CS). In this article, we chose nicotine levels as dosing references and C57BL/6 mice for a 10-week subchronic inhalation toxicity study. A comprehensive set of toxicological endpoints was used to study the effect of exposure. Both CS (6 mg/kg) and ECA (6 or 12 mg/kg) inhalation had decreased the animal's lung function and increased levels of inflammation markers, along with pathological changes in the airways and lungs, with ECA displaying a relatively small effect at the same dose. Proteomic analysis of lung tissue showed greater overall protein changes by CS than that of ECA, with more severe inflammatory network perturbations. Compared with ECA, KEGG analysis of CS revealed upregulation of more inflammatory and virus-related pathways. Protein-protein interactions (PPI) showed that both ECA and CS significantly changed ribosome and complement system-related proteins in mouse lung tissue. The results support that e-cigarette aerosol is less harmful to the respiratory system than cigarette smoke at the same dose using this animal model, thus providing additional evidence for the relative safety of e-cigarettes.

Extraventricular site indicates higher grade but better prognosis in adult supratentorial ependymomas: a 14-year single-center retrospective cohort.

Supratentorial extraventricular ependymoma (STEE) and supratentorial intraventricular ependymoma (STIE) are two subsets of supratentorial ependymoma (SE). These two subsets have similar gene features and only differ in original sites: STEE occurs in the brain parenchyma, and STIE is located in ventricles and surrounded by cerebral spinal fluid. The present study aims to depict the diversities of these two subsets and elucidate the potential effects of the anatomic site on the tumor with the same type, grade, and molecular features. Sixty-six consecutive adult SE patients from 2008 to 2021 were enrolled in our study. Clinical data, pathological features, and long-term outcomes were analyzed retrospectively. Results demonstrated that adult STEE presented with a higher proportion of WHO grade 3 (P = .028) and higher Ki-67 index (≥10%) (P = .019) compared to adult STIE. Survival analysis demonstrated that patients of grade 3 STEE exhibited a significantly longer overall survival (OS) than patients of grade 3 STIE (median OS, 24.4 months vs. 13.0 months; P = .004). Grade 2 (hazard ratio (HR) = 0.217; P < .001) and gross total resection (GTR) (HR = 0.156; P < .001) were identified as favorable prognostic factors for all adult SE. The STEE was also associated with a lesser hazard of death for patients of grade 3 on multivariate analysis (HR = 0.263; P = .047). These findings suggested that the extraventricular site was an indicator for higher grade and better prognosis in adult supratentorial ependymoma.

Inhibition of mitochondrial carrier homolog 2 (MTCH2) suppresses tumor invasion and enhances sensitivity to temozolomide in malignant glioma.

BACKGROUND: Malignant glioma exerts a metabolic shift from oxidative phosphorylation (OXPHOs) to aerobic glycolysis, with suppressed mitochondrial functions. This phenomenon offers a proliferation advantage to tumor cells and decrease mitochondria-dependent cell death. However, the underlying mechanism for mitochondrial dysfunction in glioma is not well elucidated. MTCH2 is a mitochondrial outer membrane protein that regulates mitochondrial metabolism and related cell death. This study aims to clarify the role of MTCH2 in glioma. METHODS: Bioinformatic analysis from TCGA and CGGA databases were used to investigate the association of MTCH2 with glioma malignancy and clinical significance. The expression of MTCH2 was verified from clinical specimens using real-time PCR and western blots in our cohorts. siRNA-mediated MTCH2 knockdown were used to assess the biological functions of MTCH2 in glioma progression, including cell invasion and temozolomide-induced cell death. Biochemical investigations of mitochondrial and cellular signaling alternations were performed to detect the mechanism by which MTCH2 regulates glioma malignancy. RESULTS: Bioinformatic data from public database and our cohort showed that MTCH2 expression was closely associated with glioma malignancy and poor patient survival. Silencing of MTCH2 expression impaired cell migration/invasion and enhanced temozolomide sensitivity of human glioma cells. Mechanistically, MTCH2 knockdown may increase mitochondrial OXPHOs and thus oxidative damage, decreased migration/invasion pathways, and repressed pro-survival AKT signaling. CONCLUSION: Our work establishes the relationship between MTCH2 expression and glioma malignancy, and provides a potential target for future interventions.

A COVID-19 Young Male Patient with Pneumonia and Liver Injury.

BACKGROUND: COVID-19 caused by SARS-CoV-2 has been inducing an ongoing global health and economic emergency. Although viral pneumonia is the most striking presentation for COVID-19 patients, it has been noticed that some patients may also be accompanied with an abnormal liver function. METHODS: CT was performed in both lungs, and routine bloodwork and the blood metabolic panel were measured. RESULTS: Here, we report on a young male patient without any history of live diseases who suffered simultaneously both SARS-CoV-2 caused pneumonia and hepatitis as evidenced by increased serum bilirubin together with increased serum transaminases. CONCLUSIONS: Studies on mechanisms whereby SARS-CoV-2 causing liver damages might provide more information about the pathogenesis of COVID-19 and help management of this global health emergency.

A rare case of ciliated muconodular papillary tumor accompanied with adenocarcinoma in situ.

BACKGROUND: Ciliated muconodular papillary tumor (CMPT) is an incredibly rare pulmonary tumor. Currently, little is known about CMPT, and it has not yet been classified by the World Health Organization. The clinical manifestation of CMPT is nonspecific and the diagnosis is only based on pathology. CMPT has been documented in limited reports as a benign tumor, thus the treatment is typically with surgical excision if a solid tumor is identifiable. The prognosis of CMPT is very positive, as no recurrence has been reported in the limited literature available. However, CMPT accompanied with adenocarcinoma in situ has not been reported previously in the literature. CASE PRESENTATION: In this report, we presented a case of a 53-year-old male smoker with CMPT associated with adenocarcinoma in situ. This diagnosis was confirmed by pathological examination, including immunohistostaining. No solid resectable lesion was identified on CT scan; therefore, no surgery was performed. The patient's adenocarcinoma in situ was disseminated in both lungs, thus chemotherapeutic treatment with cisplatin and pemetrexed was given. The patient will be continually followed up closely on a wait-and-watch basis. CONCLUSIONS: In summary, our report reveals a unique case of CMPT in conjunction with adenocarcinoma in situ, potentially revealing an association between CMPT and malignancy which has not been previously reported. More similar case studies will be beneficial to determine the authentic relationship between CMPT and adenocarcinoma in situ.

Tooth discoloration and the effects of internal bleaching on the novel endodontic filling material SavDen® MTA.

BACKGROUND/PURPOSE: Mineral trioxide aggregate (MTA) was widely used in endodontic therapy as bioceramic material. Although MTA has high biocompatibility, it may lead to tooth discoloration. The aim of this study was to investigate the discoloration of two different bioceramic materials and the effects of internal bleaching. METHODS: Thirty single-canal mandibular premolars were extracted and randomly assigned to three groups (n = 10), white ProRoot® MTA, SavDen® MTA and a control group. Endodontic access opening, cleaning and shaping were performed, then the teeth were obturated using the two bioceramic materials. Tooth color was recorded at baseline, day 1, and 1, 2, 4, 6, 8, 12, 16, and 24 weeks after treatment. At the end of 24 weeks, sodium perborate was used to perform internal bleaching. Tooth color was recorded at 1, 2, and 6 weeks subsequently. Teeth were measured using a DeguDent® spectrophotometer, and data were transformed into Commission Internationale de l'Eclairage (CIE) L∗a∗b∗ system. RESULTS: Teeth treated with white ProRoot® MTA showed significant color change and decrease in L∗ value. Internal bleaching leaded to decrease of the ΔE∗ value for all three groups and increase in the L∗ value. There was no difference in tooth discoloration between SavDen® MTA and the control group after obturation and internal bleaching. CONCLUSION: In terms of visual perception, white ProRoot® MTA tends to cause black and blue discoloration. SavDen® MTA, formulated with calcium lactate gluconate, could be used to reduce tooth discoloration in endodontic treatment.

Engrailed 2 (EN2) acts as a glioma suppressor by inhibiting tumor proliferation/invasion and enhancing sensitivity to temozolomide.

BACKGROUND: Glioma is one of the most malignant brain tumors and accounts for the majority of brain cancer related death. Despite progress on mechanistic studies, current understandings of the initiation and progression of glioma are still incomplete. Previous studies demonstrate that Engrailed-2 (EN2), a homeobox-containing transcription factor, is associated with tumorigenesis in a range of cancers heterogeneously, however, the profiles of EN2 expression and its potential functions in gliomas remain unclear. METHODS: Real-time PCR was used to identify the expression of EN2 in glioma tissues. To study the biological function of EN2 in glioma, we compared the cell viability and proliferation profiles between EN2 overexpressed and control cells using cell counting kit-8 (CCK8) assay, EdU incorporation assay and colony formation assay. Flow cytometry and Hoechst staining assays were performed to investigate the role of EN2 on glioma cell death. Finally, wound healing and transwell assays were carried out to investigate the role of EN2 on glioma cell invasion. RESULTS: We identified that EN2 was downregulated in human gliomas compared with paired adjacent normal tissues and negatively associated with glioma malignancy. Elevated EN2 expression inhibits cell proliferation, enhances glioma sensitivity to temozolomide and inhibits migration/invasion of glioma cells. CONCLUSIONS: Our data identify a novel function of EN2 in glioma suppression and provide potential therapeutic targets for glioma therapy.

Disseminated Nocardia Infection in an Old Male Patient with Nephrotic Syndrome.

BACKGROUND: Nocardia infection is a very rare bacterial infection caused by Gram-positive, aerobic nocardia species. However, in recent years, it has become a serious infection in immunocompromised patients. Earlier diagnosis plays a pivotal in the effective treatment of nocardia infection. METHODS: In this study, we reported a 65-year-old male patient with nephrotic syndrome who had disseminated abscesses in the lungs, right lower limb, and right cheek. RESULTS: Bacterial culture from these lesions confirmed the presence of nocardia. Timely administration of sensitive antibiotics resulted in a quick recovery for this patient. CONCLUSIONS: Nocardia infection should be considered in the differential diagnosis of infectious lesions, especially when a patient has multiple abscesses and an underlying disorder in which the immune function of the patient may be compromised.

Optimal geometry parameter for plasmonic sensitivities of individual Au nanopoarticle sensors.

The shape, aspect ratio and size are key parameters governing the plasmon sensitivities of individual Au nanoparticle bio/chemical sensors. It is crucial to unveil the general geometry parameters to optimize their corresponding sensitivity applications. In this work, the geometry-dependent refractive-index sensitivity factor (S) and figure of merit (FOM) of individual Au nanoparticle sensors (including a nanodisc, nanorod, nanoellipsoid and hexagonal nanoplate) are numerically investigated by discrete dipole approximation (DDA). S is revealed to increase quadratically/linearly with aspect ratio, while FOM reaches a maximum at an optimized aspect ratio of about 3.0/8.0 for the studied prolate/oblate nanoparticles, respectively, reflecting their shapes and aspect ratios and, hence, their size effects. However, their responses to shape factors are shown to follow nearly the same trend regardless of their different detailed geometries, demonstrating that their shape factors provide the general geometry parameters governing the plasmon sensitivities of the concerned individual Au nanoparticle sensors. This can be analytically explained well under dipolar localized surface plasmon resonance (LSPR) conditions. Their optimal FOM is predicted to be about 12.5 RIU-1 at a shape factor of 10.5; the underlying reason for this is analytically discussed as well. The obtained results in this work are believed to hold great promise for choosing appropriate nanoparticle geometry parameters for individual Au nanoparticle LSPR-based bio/chemical sensor design and applications as well as to access the corresponding optimal geometry parameters and FOM simultaneously.

Genetic deletion of Rheb1 in the brain reduces food intake and causes hypoglycemia with altered peripheral metabolism.

Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals.

A Diagnostic Nomogram for Predicting Hypercapnic Respiratory Failure in Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

Purpose: To develop and validate a nomogram for assessing the risk of developing hypercapnic respiratory failure (HRF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: From January 2019 to August 2023, a total of 334 AECOPD patients were enrolled in this research. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression to determine independent predictors and develop a nomogram. This nomogram was appraised by the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow goodness-of-fit test (HL test), decision curve analysis (DCA), and clinical impact curve (CIC). The enhanced bootstrap method was used for internal validation. Results: Sex, prognostic nutritional index (PNI), hematocrit (HCT), and activities of daily living (ADL) were independent predictors of HRF in AECOPD patients. The developed nomogram based on the above predictors showed good performance. The AUCs for the training, internal, and external validation cohorts were 0.841, 0.884, and 0.852, respectively. The calibration curves and HL test showed excellent concordance. The DCA and CIC showed excellent clinical usefulness. Finally, a dynamic nomogram was developed (https://a18895635453.shinyapps.io/dynnomapp/). Conclusion: This nomogram based on sex, PNI, HCT, and ADL demonstrated high accuracy and clinical value in predicting HRF. It is a less expensive and more accessible approach to assess the risk of developing HRF in AECOPD patients, which is more suitable for primary hospitals, especially in developing countries with high COPD-related morbidity and mortality.