Spontaneous cerebrospinal fluid rhinorrhea associated with an incidental pituitary adenoma.

Spontaneous cerebrospinal fluid (CSF) rhinorrhea presenting as the sole symptom of untreated pituitary adenoma is rare, with only 15 cases having been reported in the English literature. All these untreated pituitary adenoma contributing to spontaneous CSF rhinorrhea were diagnosed by the preoperative neuroimaging. Herein, we described an extraordinary rare patient with a pituitary microadenoma, presenting with spontaneous CSF rhinorrhea as the sole symptom. However, this pituitary microadenoma was only found incidentally at surgery, not preoperatively. To the best knowledge of us, this is the first reported case of spontaneous CSF rhinorrhea associated with an untreated pituitary adenoma diagnosed at surgery.

Advances in targeted therapy in non-small cell lung cancer with actionable mutations and leptomeningeal metastasis.

WHAT IS KNOWN AND OBJECTIVE?: Leptomeningeal metastasis (LM) is a serious complication of advanced non-small cell lung cancer (NSCLC) that is diagnosed in approximately 3%-5% of patients. LM occurs more frequently in patients with NSCLC harbouring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements and is usually accompanied by a poor prognosis, with a median overall survival (OS) of several months if patients receive conventional treatments. However, tyrosine kinase inhibitor (TKI) therapy after LM diagnosis is an independent predictive factor for extended survival. Here, we aim to summarize the latest advances in targeted therapy for LM and provide patients with better treatment options. METHODS: By reviewing the recent progress of targeted therapy in NSCLC with LM, especially the efficacy of newer generation TKIs, we aim to provide clinicians with a reference to further optimize patient treatment plans. RESULTS AND DISCUSSION: Osimertinib was confirmed to have a several-fold higher CNS permeability than other EGFR-TKIs and was recommended as the preferred choice for patients with EGFR-positive LM whether or not they harboured the T790M mutation. Second-generation ALK-TKIs have a higher rate of intracranial response and can be positioned as front-line drugs in NSCLC with LM. However, the sequence in which ALK-TKIs are administered for effective disease control requires further evaluation. In addition, targeted therapy revealed a potential choice in patients with LM and rare mutations, such as ROS1 and BRAF. WHAT IS NEW AND CONCLUSIONS?: The development of therapeutic agents with greater CNS penetration is vital for the management of CNS metastasis from NSCLC, particularly in the EGFR-mutant and ALK-rearranged subtypes. Systemic therapy with newer generation TKIs is preferred as the initial intervention. This is because newer generation TKIs are designed to penetrate the blood-brain barrier and possess significantly higher intracranial activities. However, their further effectiveness is limited by inadequate blood-brain barrier penetration and acquired drug resistance. Further studies are needed to further understand the mechanisms underlying resistance to treatment.

Batch production of uniform graphene films via controlling gas-phase dynamics in confined space.

Batch production of continuous and uniform graphene films is critical for the application of graphene. Chemical vapor deposition (CVD) has shown great promise for mass producing high-quality graphene films. However, the critical factors affected the uniformity of graphene films during the batch production need to be further studied. Herein, we propose a method for batch production of uniform graphene films by controlling the gaseous carbon source to be uniformly distributed near the substrate surface. By designing the growth space of graphene into a rectangular channel structure, we adjusted the velocity of feedstock gas flow to be uniformly distributed in the channel, which is critical for uniform graphene growth. The monolayer graphene film grown inside the rectangular channel structure shows high uniformity with average sheet resistance of 345 Ω sq-1 without doping. The experimental and simulation results show that the placement of the substrates during batch growth of graphene films will greatly affect the distribution of gas-phase dynamics near the substrate surface and the growth process of graphene. Uniform graphene films with large-scale can be prepared in batches by adjusting the distribution of gas-phase dynamics.

C2-Symmetric 1,2-Diphenylethane-1,2-diamine-Derived Primary-Tertiary Diamine-Catalyzed Asymmetric Mannich Addition of Cyclic N-Sulfonyl Trifluoromethylated Ketimines.

A simple chiral primary-tertiary diamine derived from C2-symmetric 1,2-diphenylethane-1,2-diamine as the organocatalyst in combination with the trifluoroacetic acid additive for the asymmetric Mannich reaction of cyclic N-sulfonyl trifluoromethylated ketimines and methyl ketones afforded the desired product with high enantioselectivity (73-96% ee). The reactions proceeded well for a variety of different substituted cyclic N-sulfonyl trifluoromethyl ketimines and various alkyl methyl ketones, providing access to diverse enantioenriched benzo-fused cyclic sulfamidate N-heterocycles bearing a trifluoromethylated α-tetrasubstituted carbon stereocenter. This study also investigated the diastereoselective reduction of the carbonyl group and ring cleavage reduction of the sulfamidate group of the corresponding Mannich product.

Chaetoglobosin G inhibits proliferation, autophagy and cell cycle of lung cancer cells through EGFR/MEK/ERK signaling pathway.

Chaetoglobosin G (CG) is a fungal secondary metabolite and shows anti-tumor effects. However, the mechanisms behind the anti-tumor effect is still unclear. In this study, we evaluated the anti-proliferation effect of CG on human NSCLC A549 cells and explored the underlying mechanisms. The anti-proliferation effect of CG on A549 cells was evaluated by MTT. The targets of CG were screened through transcriptome sequencing. A flow cytometer was used to detect cell cycle and apoptosis. Western blotting was used to analyze apoptosis, cell cycle and autophagy related protein expression. Our results showed that CG had a dose-dependent inhibitory effect on proliferation of A549 cells. Transcriptome sequencing analysis found that CG obviously induced cell cycle arrest. Flow cytometry analysis and western blot showed that CG induced G2/M arrest with p21 protein upregulation and cyclinB1 protein downregulation. Western blot analysis also indicated that p-EGFR, EGFR, p-MEk and p-ERK protein expressions decreased and autophagy protein LC3II expression increased, indicating that CG can promote autophagy through EGFR/MEK/ERK/LC3 pathway. Moreover, CG can induce apoptosis with bcl-2 protein decrease. In conclusion, this study indicated that CG obviously inhibited A549 cell proliferation, and its mechanism may induce autophagy of A549 cells through EGFR/MEK/ERK/LC3 pathway to upregulate the expression of P21, thus lead to G2/M phase arrest to exert an anti-tumor role.

Microwave plasma assisted reduction synthesis of hexagonal cobalt nanosheets with enhanced electromagnetic performances.

In this study, we employed a microwave plasma assisted reduction (MPAR) method to prepare metallic nanoparticles with desirable morphology. Compared with the hydrogen thermal reduction technique, the MPAR technique could greatly maintain the original morphology of self-sacrificing precursors, as well as proving to be highly efficient, energy-saving and pollution-free. Taking ferromagnetic metallic Co as a forerunner, Co nanosheets with inerratic hexagonal morphology were successfully synthesized on a large scale uniformly. The lateral dimension of the achieved Co nanosheets is in the range of 3∼5 µm with tens of nanometers in thickness. The intact hexagonal flaky shape of Co nanosheets is beneficial for improving dielectric loss by increasing electric channels and interfacial polarization. Consequently, the minimum reflection loss could reach up to -71 dB at a thin thickness of 1.2 mm. Furthermore, the effective bandwidth (RL < -10 dB) could be achieved in a wide range of 2.8∼18 GHz by integrating the thickness from 5.0∼1.0 mm, which provides the possibility for applications in electromagnetic shielding and radar stealth fields. It is believed that the MPAR technique is suitable for designing and preparing novel microwave absorbers on the basis of appropriate precursors, providing new opportunities to acquire high-performance microwave absorbers in the future.

Ultrathin Bimetal Color Filter Based on Plasmonic Nanostructure.

Plasmonic subtractive color filters through a nanostructured ultrathin Ag film have attracted intensive attention due to their good durability, high color tunability and high transmission. However, Ag film suffers from discontinuity when the thickness is below 15 nm, which limits the further increasement of transmission efficiency. Herein a bimetal ultrathin (~10 nm) subtractive color filter with one dimensional nanogratings was demonstrated and fabricated. By adding an embedded Al layer to suppress the formation of Ag islands, a smooth, continuous and reliable bimetal film was obtained. At the same time, the blue shift of transmission minimum was beneficial to overcome difficulty in nanostructure fabrication. This method also provided a new approach to tune the color by simply varying the thickness of Al layer. A broad palette of colors, including cyan, magenta and yellow, was attained in bimetal color filter with high transmission beyond 80%.

Basal Ganglionic Germinoma With Syncytiotrophoblastic Giant Cells Mimicking a Growing Hematoma.

Basal ganglionic germinoma (BGG) with syncytiotrophoblastic giant cells (STGC) is a rare type of ectopic germ cell tumors with mild elevation of human chorionic gonadotropin level. Intratumoral hemorrhage is not uncommon for BGG, but presenting with repeated hemorrhage is very rare. Herein, we described an extremely rare case of BGG with STGC mimicking a growing hematoma. Furthermore, the characteristics, treatment, and prognosis of BGG with STGC were investigated and reviewed.

Enantioselective organocatalytic Michael additions of N,N'-dialkylbarbituric acids to enones.

N,N'-Dialkylbarbituric acids as cyclic malonamide donors were successfully used in the enantioselective Michael addition reaction of enones. Using cinchona alkaloid-based bifunctional squaramide as an organocatalyst, this Michael reaction of N,N'-di-tert-butylbarbituric acid with various enones features a highly enantioselective (91-99% ee) production of the corresponding optically active 5-substituted barbituric acid derivatives. The transformations of the Michael product for the barbituric acid structural unit were realized in two ways, deprotection to remove the N-tert-butyl group and alkylation to produce 5,5-disubstituted barbituric acid derivatives.

Synthesis, Photoluminescence and Bio-Targeting Applications of Blue Graphene Quantum Dots.

Chemical derived graphene oxide, an atomically thin sheet of graphite with two-dimensional construction, offers interesting physical, electronic, thermal, chemical, and mechanical properties that are currently being explored for advanced physics electronics, membranes, and composites. Herein, we study graphene quantum dots (GQD) with the blue photoluminescence under various parameters. The GQD samples were prepared at different temperatures, and the blue photoluminescence intensity of the solution improved radically as the heating temperatures increased. Concerning PL peak and intensity of the quantum dots, the results demonstrated dependence on time under heating, temperature of heating, and pH adjusted by the addition of sodium hydroxide. After hydrothermal synthesis routes, the functional groups of graphene oxide were altered the morphology showed the stacking configuration, and self-assembled structure of the graphene sheets with obvious wrinkles appeared at the edge structures. In addition, absorption, PL, and PLE spectra of the graphene quantum dots increase with different quantities of sodium hydroxide added. Finally, using GQD to target PNTIA cells was carried out successfully. High uptake efficiency and no cytotoxic effects indicate graphene quantum dots can be suitable for bio-targeting.

Brain Abscess Following Intracerebral Hemorrhage in a Patient With Pneumonia.

Brain abscess is a rare but potentially lethal infection of brain parenchyma, requiring prompt surgical intervention and high-dose antibiotic therapy. Brain abscess is a known complication of surgically treated intracerebral hemorrhage (ICH), but it is exceptionally rare that it occurs at the same site of a nonoperated ICH. Such cases may result from hematogenous spread from distant foci (pneumonia, infectious endocarditis) or contiguous sites. Herein, the authors report a case of 75-year-old woman presenting with a brain abscess 6 weeks after a nonoperated ICH. As the patient suffered from pneumonia during the course of ICH, the authors suspected that the brain abscess might originate from the pneumonia via hematogenous spread. The awareness of brain abscess formation at the site of ICH is of great importance for early diagnosis and prompt treatment.

A highly enantioselective and regioselective organocatalytic direct Mannich reaction of methyl alkyl ketones with cyclic imines benzo[e][1,2,3]oxathiazine 2,2-dioxides.

A highly enantioselective direct Mannich reaction of methyl alkyl ketones with cyclic imines benzo[e][1,2,3]oxathiazine 2,2-dioxides, catalyzed by the combination of cinchona alkaloid derived primary amine and TFA, is disclosed. For unsymmetrical methyl alkyl ketones, it is favoured that specific regioselective addition to the imine substrates occurs at the less-substituted methyl group by steric control.

Graphene nanowalls in photodetectors.

Graphene nanowalls (GNWs) have emerged as a promising material in the field of photodetection, thanks to their exceptional optical, electrical, mechanical, and thermodynamic properties. However, the lack of a comprehensive review in this domain hinders the understanding of GNWs' development and potential applications. This review aims to provide a systematic summary and analysis of the current research status and challenges in GNW-based photodetectors. We begin by outlining the growth mechanisms and methods of GNWs, followed by a discussion on their physical properties. Next, we categorize and analyze the latest research progress in GNW photodetectors, focusing on photovoltaic, photoconductive, and photothermal detectors. Lastly, we offer a summary and outlook, identifying potential challenges and outlining industry development directions. This review serves as a valuable reference for researchers and industry professionals in understanding and exploring the opportunities of GNW materials in photodetection.

Integrative analysis of DNA methylation and gene expression data for the diagnosis and underlying mechanism of Parkinson's disease.

Background: Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder and the leading cause of disability in the daily activities. In the management of PD, accurate and specific biomarkers in blood for the early diagnosis of PD are urgently needed. DNA methylation is one of the main epigenetic mechanisms and associated with the gene expression and disease initiation of PD. We aimed to construct a methylation signature for the diagnosis of PD patients, and explore the potential value of DNA methylation in therapeutic options. Materials and methods: Whole blood DNA methylation and gene expression data of PD patients as well as healthy controls were extracted from Gene Expression Omnibus database. Next, differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between PD patients and healthy controls were identified. Least absolute shrinkage and selection operator cox regression analysis was carried out to construct a diagnostic signature based on the overlapped genes. And, the receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) was used to assess the diagnostic performance of the signature in both the training and testing datasets. Finally, gene ontology and gene set enrichment analysis were subsequently carried out to explore the underlying mechanisms. Results: We obtained a total of 9,596 DMGs, 1,058 DEGs, and 237 overlapped genes in the whole blood between PD patients and healthy controls. Eight methylation-driven genes (HIST1H4L, CDC42EP3, KIT, GNLY, SLC22A1, GCM1, INO80B, and ARHGAP26) were identified to construct the gene expression signature. The AUCs in predicting PD patients were 0.84 and 0.76 in training dataset and testing dataset, respectively. Additionally, eight methylation-altered CpGs were also identified to construct the CpGs signature which showed a similarly robust diagnostic capability, with AUCs of 0.8 and 0.73 in training dataset and testing dataset, respectively. Conclusion: We conducted an integrated analysis of the gene expression and DNA methylation data, and constructed a methylation-driven genes signature and a methylation-altered CpGs signature to distinguish the patients with PD from healthy controls. Both of them had a robust prediction power and provide a new insight into personalized diagnostic and therapeutic strategies for PD.

Rho GTPase Activating Protein 9 (ARHGAP9) in Human Cancers.

BACKGROUND: In recent years, targeted therapy combined with traditional chemoradiotherapy and surgery has brought new opportunities for cancer treatment. However, the complex characteristics of cancer, such as heterogeneity and diversity, limit the clinical success of targeted drugs. Discovering of new cancer targets and deepening the understanding of their functional mechanisms will bring additional promising application prospects for the research and development of personalized cancer-targeted drugs. OBJECTIVES: This study aimed to summarize the role of the Rho GTPase activating protein 9 (ARHGAP9) gene in tumorigenesis and development to discover therapeutic targets for cancer in the future. METHODS: For this review, we collected patents from the databases of Espacenet and WIPO and articles from PubMed that were related to the ARHGAP9 gene. RESULTS: Genetic/epigenetic variations and abnormal expression of the ARHGAP9 gene are closely associated with a variety of diseases, including cancer. ARHGAP9 can inactivate Rho GTPases by hydrolyzing GTP into GDP and regulate cancer cellular events, including proliferation, differentiation, apoptosis, migration and invasion, by inhibiting JNK/ERK/p38 and PI3K/AKT signaling pathways. In addition to reviewing these mechanisms, we assessed various patents on ARHGAP9 to determine whether ARHGAP9 might be used as a predictive biomarker for diagnosis/prognosis evaluation and a druggable target for cancer treatment. CONCLUSION: In this review, the current knowledge of ARHGAP9 in cancer is summarized with an emphasis on its molecular function, regulatory mechanism and disease implications. Its characterization is crucial to understanding its important roles during different stages of cancer progression and therapy as a predictive biomarker and/or target.

Cross-Linking of Centrifugally Spun Starch/Polyvinyl Alcohol (ST/PVA) Composite Ultrafine Fibers and Antibacterial Activity Loaded with Ag Nanoparticles.

In this research, centrifugally spun ultrafine composite starch/polyvinyl alcohol (ST/PVA) fibers with high water stability were prepared by cross-linking with a mixture of glutaraldehyde and formic acid in the form of vapor phase. The effect of cross-linking temperature combined with time on the water stability, crystal structure, and thermal properties of fibers was investigated to obtain the optimum parameters. On this basis, we further prepared Ag-loaded ST/PVA fibers with different contents of nano silver. The structure and properties of Ag-loaded fibers, which cross-linked under the optimum parameters, were analyzed. As a result, the Ag-loaded fibers exhibited excellent water stability and mechanical properties and possessed inhibition zone diameters of 3 and 2 mm to Escherichia coli and Staphylococcus. aureus, respectively. The antibacterial property of the Ag-loaded ST/PVA fibers provided a new route for developing less costly antibacterial fiber materials in the future.

The Effect of Ethanol on Abnormal Grain Growth in Copper Foils.

Single-crystal Cu not only has high electrical and thermal conductivity, but can also be used as a promising platform for the epitaxial growth of two-dimensional materials. Preparing large-area single-crystal Cu foils from polycrystalline foils has emerged as the most promising technique in terms of its simplicity and effectiveness. However, the studies on transforming polycrystalline foil into large-area single-crystal foil mainly focus on the influence of annealing temperature and strain energy on the recrystallization process of copper foil, while studies on the effect of annealing atmosphere on abnormal grain growth behavior are relatively rare. It is necessary to carry out more studies on the effect of annealing atmosphere on grain growth behavior to understand the recrystallization mechanism of metal. Here, we found that introduction of ethanol in pure argon annealing atmosphere will cause the abnormal grain growth of copper foil. Moreover, the number of abnormally grown grains can be controlled by the concentration of ethanol in the annealing atmosphere. Using this technology, the number of abnormally grown grains on the copper foil can be controlled to single one. This abnormally grown grain will grow rapidly to decimeter-size by consuming the surrounding small grains. This work provides a new perspective for the understanding of the recrystallization of metals, and a new method for the preparation of large-area single-crystal copper foils.

Identification of m6A-Related lncRNAs Associated With Prognoses and Immune Responses in Acute Myeloid Leukemia.

Background: Acute myeloid leukemia (AML) remains the most common type of hematopoietic malignancy in adults and has an unfavorable outcome. Herein, we aimed to construct an N6-methylandenosine (m6A)-related long noncoding RNAs (lncRNAs) signature to accurately predict the prognosis of patients with AML using the data downloaded from The Cancer Genome Atlas (TCGA) database. Methods: The RNA-seq and clinical data were obtained from the TCGA AML cohort. First, Pearson correlation analysis was performed to identify the m6A-related lncRNAs. Next, univariate Cox regression analysis was used to determine the candidate lncRNAs with prognostic value. Then, feature selection was carried out by Least absolute shrinkage and selection operator (LASSO) analysis, and seven eligible m6A-related lncRNAs were included to construct the prognostic risk signature. Kaplan-Meier and receiver operating characteristic (ROC) curve analyses were performed to evaluate the predictive capacity of the risk signature both in the training and testing datasets. A nomogram was used to predict 1-year, 2-year, and 3-year overall survival (OS) of AML patients. Next, the expression levels of lncRNAs in the signature were validated in AML samples by qRT-PCR. Functional enrichment analyses were carried out to identify probable biological processes and cellular pathways. The ceRNA network was developed to explore the downstream targets and mechanisms of m6A-related lncRNAs in AML. Results: Seven m6A-related lncRNAs were identified as a prognostic signature. The low-risk group hold significantly prolonged OS. The nomogram showed excellent accuracy of the signature for predicting 1-year, 2-year and 3-year OS (AUC = 0.769, 0.820, and 0.800, respectively). Moreover, the risk scores were significantly correlated with enrichment in cancer hallmark- and malignancy-related pathways and immunotherapy response in AML patients. Conclusion: We developed and validated a novel risk signature with m6A-related lncRNAs which could predict prognosis accurately and reflect the immunotherapy response in AML patients.

Design, synthesis, and biological evaluation of 1,5-diaryl-1,2,4-triazole derivatives as selective cyclooxygenase-2 inhibitors.

A series of 1,5-diaryl-1,2,4-triazole derivatives were synthesized and evaluated as cyclooxygenase-2 (COX-2) inhibitors. The results of the preliminary biological assays in vivo showed that eight compounds 5b, 6b, 6c, 7c, 8b, 8d, 9c, and 9d have potent anti-inflammatory activity (P < 0.01), while compounds 6b, 6c, and 9c exhibit marked potency. Compound 6c was then selected for further investigation. In the COX inhibition assay in vitro, compound 6c was identified as a potent and selective inhibitor of COX-2 (COX-2 IC(50) = 0.37 µM; SI = 0.018), being equipotent to celecoxib (COX-2 IC(50) = 0.26 µM; SI = 0.015). In a rat carrageenan-induced paw edema assay, 6c exhibited moderate anti-inflammatory activity (35% inhibition of inflammation) at 2 h after administration of 15 mg/kg as an oral dose. A docking study also revealed that compound 6c binds in the active site of COX-2 in a similar mode to that of the known selective COX-2 inhibitor SC-558.

Enantioselective (3+2) cycloaddition via N-heterocyclic carbene-catalyzed addition of homoenolates to cyclic N-sulfonyl trifluoromethylated ketimines: synthesis of fused N-heterocycle γ-lactams.

An enantioselective (3+2) cycloaddition of enals and cyclic N-sulfonyl trifluoromethyl ketimines via N-heterocyclic carbene-catalyzed homoenolate addition is described. This reaction can efficiently construct fused N-heterocycle γ-lactams bearing two adjacent chiral centers with >20 : 1 dr and 94-99% ee, with one chiral center as a trifluoromethylated α-tetrasubstituted carbon stereocenter.