3-Eth­oxy-2-hy­droxy­benzaldehyde 2,4-di­nitro­phenylhydrazone N,N-di­methyl­formamide monosolvate

The Schiff base of the title compound, C15H14N4O6·C3H7NO, was obtained from the condensation reaction of 3-eth­oxy-2-hy­droxy­benzaldehyde and 2,4-dinitro­phenyl­hydrazine. The dihedral angle between the benzene rings is 3.05 (10)° and intra­molecular N—H⋯O and O—H⋯O hydrogen bonds generate S(6) and S(5) ring motifs, respectively. In the crystal, the Schiff base and dimethyl­formamide solvent mol­ecules are linked by an O—H⋯O hydrogen bond

A Real-World Disproportionality Analysis of Everolimus: Data Mining of the Public Version of FDA Adverse Event Reporting System

Background: Everolimus is an inhibitor of the mammalian target of rapamycin and is used to treat various tumors. The presented study aimed to evaluate the Everolimus-associated adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The AE records were selected by searching the FDA Adverse Event Reporting System database from the first quarter of 2009 to the first quarter of 2022. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio the proportional reporting ratio the Bayesian confidence propagation neural network and the empirical Bayes geometric mean and MedDRA was used to systematically classify the results. Results: A total of 24,575 AE reports of Everolimus were obtained using data from the FAERS database, and Everolimus-induced AEs occurrence targeted 24 system organ classes after conforming to the four algorithms simultaneously. The common significant SOCs were identified, included benign, malignant and unspecified neoplasms, reproductive system and breast disorders, etc. The significant AEs were then mapped to preferred terms such as stomatitis, pneumonitis and impaired insulin secretion, which have emerged in the study usually reported in patients with Everolimus. Of note, unexpected significant AEs, including biliary ischaemia, angiofibroma, and tuberous sclerosis complex were uncovered in the label. Conclusion: This study provided novel insights into the monitoring, surveillance, and management of adverse drug reaction associated with Everolimus. The outcome of serious adverse events and the corresponding detection signals, as well as the unexpected significant adverse events signals are worthy of attention in order to improving clinical medication safety during treatment of Everolimus

2-Hydroxy-3-methoxybenzaldehyde 2,4-dinitrophenylhydrazone pyridine monosolvate

The Schiff base molecule of the title compound, C14H12N4O6·C5H5N, was obtained from the condensation reaction of 2-hy­droxy-3-meth­oxy­benzaldehyde and 2,4-dinitro­phenyl­hydrazine. The C=N bond of the Schiff base has a trans arrangement and the dihedral angle between the two benzene rings is 3.49 (10)°. An intra­molecular N—H⋯O hydrogen bond generates an S(6) ring. In the crystal, O—H⋯O hydrogen bonds link the Schiff base mol­ecules

Gray Matter Atrophy in Parkinson’s Disease and the Parkinsonian Variant of Multiple System Atrophy: A Combined ROI- and Voxel-Based Morphometric Study

OBJECTIVES: Parkinson’s disease (PD) and the parkinsonian variant of multiple system atrophy (MSA-P) are distinct neurodegenerative disorders that share similar clinical features of parkinsonism. The morphological alterations of these diseases have yet to be understood. The purpose of this study was to evaluate gray matter atrophy in PD and MSA-P using regions of interest (ROI)-based measurements and voxel-based morphometry (VBM). METHODS: We studied 41 patients with PD, 20 patients with MSA-P, and 39 controls matched for age, sex, and handedness using an improved T1-weighted sequence that eased gray matter segmentation. The gray matter volumes were measured using ROI and VBM. RESULTS: ROI volumetric measurements showed significantly reduced bilateral putamen volumes in MSA-P patients compared with those in PD patients and controls (po0.05), and the volumes of the bilateral caudate nucleus were significantly reduced in both MSA-P and PD patients compared with those in the controls (po0.05). VBM analysis revealed multifocal cortical and subcortical atrophy in both MSA-P and PD patients, and the volumes of the cerebellum and temporal lobes were remarkably reduced in MSA-P patients compared with the volumes in PD patients (po0.05). CONCLUSIONS: Both PD and MSA-P are associated with gray matter atrophy, which mainly involves the bilateral putamen, caudate nucleus, cerebellum, and temporal lobes. ROI and VBM can be used to identify these morphological alterations, and VBM is more sensitive and repeatable and less time-consuming, which may have potential diagnostic value

Enhanced Root and Stem Growth and Physiological Changes in Pinus bungeana Zucc. Seedlings by Microbial Inoculant Application

Background and Objectives: As an extensively used tree species in landscaping and afforestation in China, lacebark pine (Pinus bungeana Zucc.) seedlings are in high demand. However, the small number of fine roots and the low growth rate of lacebark pine seedlings increase the risks encountered during transplant and extend the nursery time for outplanting. We aimed to find out whether a microbial inoculant would promote root growth and accordingly, shorten the nursery cultivation time. Materials and Methods: One-year-old lacebark pine seedlings were treated with the inoculant Bacillus subtilis 8–32 six times from June to September. At each application time, five treatments of undiluted microbial inoculants (UM), 30 times diluted microbial inoculants (30 DM), 40 times diluted microbial inoculants (40 DM), 50 times diluted microbial inoculants (50 DM), and distilled water as a control (CTRL) were administered to the seedlings. In the end, all the seedlings were harvested to measure the root growth, aboveground growth, and the physiological indices. Results: Root and stem growth was enhanced by the inoculants in terms of the increased number of root tips, the length and surface area of the roots, the biomass of the roots and stems, as well as the increase in height and basal stem diameter. The chlorophyll a/b of the needles was increased, in spite of the fact that the total chlorophyll content was decreased by the microbial inoculant treatments at the end of the growth phase. Meanwhile, the maximum photochemical efficiency (Fv/Fm) of the needles was increased by the inoculant treatments. The soluble sugar content was additionally translocated into the stems in the UM treatment, suggesting the change in carbon allocation. The content of available potassium, phosphorus, and ammonium nitrogen in the potting soil was increased in the 30 DM group, and the content of soil organic matter was increased in all the inoculant treatments. Conclusions: The microbial inoculant Bacillus subtilis 8–32, in appropriate concentrations, could be applied to promote root and shoot growth and improve the seedling quality of the lacebark pine during cultivation

The Mechanism of Downregulated Interstitial Fluid Drainage Following Neuronal Excitation.

The drainage of brain interstitial fluid (ISF) has been observed to slow down following neuronal excitation, although the mechanism underlying this phenomenon is yet to be elucidated. In searching for the changes in the brain extracellular space (ECS) induced by electrical pain stimuli in the rat thalamus, significantly decreased effective diffusion coefficient (DECS) and volume fraction (α) of the brain ECS were shown, accompanied by the slowdown of ISF drainage. The morphological basis for structural changes in the brain ECS was local spatial deformation of astrocyte foot processes following neuronal excitation. We further studied aquaporin-4 gene (APQ4) knockout rats in which the changes of the brain ECS structure were reversed and found that the slowed DECS and ISF drainage persisted, confirming that the down-regulation of ISF drainage following neuronal excitation was mainly attributable to the release of neurotransmitters rather than to structural changes of the brain ECS. Meanwhile, the dynamic changes in the DECS were synchronized with the release and elimination processes of neurotransmitters following neuronal excitation. In conclusion, the downregulation of ISF drainage following neuronal excitation was found to be caused by the restricted diffusion in the brain ECS, and DECS mapping may be used to track the neuronal activity in the deep brain

TGFβƒ1 Promotes Gemcitabine Resistance Through Regulating the LncRNA-LET/NF90/miR-145 Signaling Axis in Bladder Cancer

High tumor recurrence is frequently observed in patients with urinary bladder cancers (UBCs), with the need for biomarkers of prognosis and drug response. Chemoresistance and subsequent recurrence of cancers are driven by a subpopulation of tumor initiating cells, namely cancer stem-like cells (CSCs). However, the underlying molecular mechanism in chemotherapy-induced CSCs enrichment remains largely unclear. In this study, we found that during gemcitabine treatment lncRNA-Low Expression in Tumor (lncRNA-LET) was downregulated in chemoresistant UBC, accompanied with the enrichment of CSC population. Knockdown of lncRNA-LET increased UBC cell stemness, whereas forced expression of lncRNA-LET delayed gemcitabine-induced tumor recurrence. Furthermore, lncRNA-LET was directly repressed by gemcitabine treatment-induced overactivation of TGFβ/SMAD signaling through SMAD binding element (SBE) in the lncRNA-LET promoter. Consequently, reduced lncRNA-LET increased the NF90 protein stability, which in turn repressed biogenesis of miR-145 and subsequently resulted in accumulation of CSCs evidenced by the elevated levels of stemness markers HMGA2 and KLF4. Treatment of gemcitabine resistant xenografts with LY2157299, a clinically relevant specific inhibitor of TGFβRI, sensitized them to gemcitabine and significantly reduced tumorigenecity in vivo. Notably, overexpression of TGFβ1, combined with decreased levels of lncRNA-LET and miR-145 predicted poor prognosis in UBC patients. Collectively, we proved that the dysregulated lncRNA-LET/NF90/miR-145 axis by gemcitabine-induced TGFβ1 promotes UBC chemoresistance through enhancing cancer cell stemness. The combined changes in TGFβ1/lncRNA-LET/miR-145 provide novel molecular prognostic markers in UBC outcome. Therefore, targeting this axis could be a promising therapeutic approach in treating UBC patients

Advances in bioorganic molecules inspired degradation and surface modifications on Mg and its alloys

Mg alloys possess biodegradability, suitable mechanical properties, and biocompatibility, which make them possible to be used as biodegradable implants. However, the uncontrollable degradation of Mg alloys limits their general applications. In addition to the factors from the metallic materials themselves, like alloy compositions, heat treatment process and microstructure, some external factors, relating to the test/service environment, also affect the degradation rate of Mg alloys, such as inorganic salts, bioorganic small molecules, bioorganic macromolecules. The influence of bioorganic molecules on Mg corrosion and its protection has attracted more and more attentions. In this work, the cutting-edge advances in the influence of bioorganic molecules (i.e., protein, glucose, amino acids, vitamins and polypeptide) and their coupling effect on Mg degradation and the formation of protection coatings were reviewed. The research orientations of biomedical Mg alloys in exploring degradation mechanisms in vitro were proposed, and the impact of bioorganic molecules on the protective approaches were also explored

Can integration reduce inequity in healthcare utilization?: evidence and hurdles in China

Background: Integration of medical insurance schemes has been prioritized as one of the key strategies to address inequity in China's health system. The first pilot attempt to integrate started in 2003 and later expanded nationwide. This study aims to assess its intended impact on inequity in inpatient service utilization and identify the main determinants contributing to ieffectiveness. Methods: A total of 49,365 respondents in the pilot integrated area and 77,165 respondents in the non-integration area were extracted from the Fifth National Health Services Survey. A comparative analysis was conducted between two types of areas. We calculate a concentration index (CI) and horizontal inequity index (HI) in inpatient service utilization and decompose the two indices. Results: Insurance integration played a positive role in reducing inequality in inpatient service utilization to some extent. A 13.23% lower in HI, a decrease in unmet inpatient care and financial barriers to inpatient care in the pilot integrated area compared with the non-integration area; decomposition analysis showed that the Urban-Rural Residents Basic Medical Insurance, a type of integrated insurance, contributed 37.49% to reducing inequality in inpatient service utilization. However, it still could not offset the strong negative effect of income and other insurance schemes that have increased inequality. Conclusions: The earlier pilot attempt for integrating medical insurance was not enough to counteract the influence of factors which increased the inequality in inpatient service utilization. Further efforts to address the inequality should focus on widening access to financing, upgrading the risk pool, reducing gaps within and between insurance schemes, and providing broader chronic disease benefit packages. Social policies that target the needs of the poor with coordinated efforts from various levels and agencies of the government are urgently needed