The structures and absolute configurations of two organic compounds, excoecoumarin A and excoecoumarin B, were studied by recording their electronic circular dichroism (ECD) spectra and performing ...quantum‐chemistry computations. The optical rotations and the nuclear magnetic resonance (NMR), ECD, vibrational circular dichroism (VCD), and ultraviolet (UV) spectra of candidate structures were computed using the B3LYP approach of the density functional theory. The structures and absolute configurations of excoecoumarins A and B are inferred from the agreement between the experimental and theoretical NMR, ECD, and UV spectra. Although a specific configuration can be assigned to excoecoumarin A, three structures are possible for excoecoumarin B. The computations indicated that the absolute configuration of excoecoumarin B can be further identified by acquiring the VCD spectra. In any case, the present study indicated that the structures reported previously should be revised.
The structures and absolute configurations of two organic molecules, excoecoumarins A and B, were studied by acquiring the electronic circular dichroism (ECD) spectra and performing the NMR and ECD computations. Based on the agreement between experiment and theory, the absolute configuration of A has been inferred out of 64 possibilities. Although three structures are possible for B, we predict that the absolute configuration of B can be identified by acquiring its vibrational circular dichroism spectra.
Auxin is well known to stimulate coleoptile elongation and rapid seedling growth in the air. However, its role in regulating rice germination and seedling establishment under submergence is largely ...unknown. Previous studies revealed that excessive levels of indole‐3‐acetic acid(IAA) frequently cause the inhibition of plant growth and development. In this study, the high‐level accumulation of endogenous IAA is observed under dark submergence, stimulating rice coleoptile elongation but limiting the root and primary leaf growth during anaerobic germination (AG). We found that oxygen and light can reduce IAA levels, promote the seedling establishment and enhance rice AG tolerance. miRNA microarray profiling and RNA gel blot analysis results show that the expression of miR167 is negatively regulated by submergence; it subsequently modulates the accumulation of free IAA through the miR167‐ARF‐GH3 pathway. The OsGH3‐8 encodes an IAA‐amido synthetase that functions to prevent free IAA accumulation. Reduced miR167 levels or overexpressing OsGH3‐8 increase auxin metabolism, reduce endogenous levels of free IAA and enhance rice AG tolerance. Our studies reveal that poor seed germination and seedling growth inhibition resulting from excessive IAA accumulation would cause intolerance to submergence in rice, suggesting that a certain threshold level of auxin is essential for rice AG tolerance.
Summary statement
Excessive auxin accumulation negatively affects rice AG. Conversely, oxygen and light significantly reduce IAA levels, promote the seedling establishment during AG, and submergence‐repressed miR167 reduces IAA levels through miR167‐ARF‐GH3 pathway and enhances AG tolerance.
Although mass spectrometry-based plasma proteomics enables sensitive and large-scale discovery and validation of biomarkers for various diseases, its integrative application to hepatocellular ...carcinoma (HCC) and cholangiocarcinoma (CCA) is not well investigated. Therefore, we analyzed albumin- and immunoglobulin G-depleted plasma samples from 148 and 60 patients with HCC and CCA, respectively, using liquid chromatography-tandem mass spectrometry. The algorithm used to measure the content of each protein was the percentage of exponentially modified protein abundance index. From 5320 proteins assayed in plasma, 53 and 25 biomarker candidates were identified for HCC and CCA, respectively. The abundance of six and two HCC markers particularly protruded in stage II and III, respectively, whereas plasma serine protease inhibitor was the sole marker the level of which steadily decreased with CCA progression. From a prognostic facet, we showed candidate markers and their cutoff levels for evaluating probability of tumor recurrence and patient survival period. Combination Kaplan-Meier models showed that HCC stage III or IV and both the content of alpha-2-HS-glycoprotein and apolipoprotein CIII 0.2% exhibited the poorest post-surgical recurrence-free and overall survivals. Furthermore, the content of afamin greater than or equal to0.2% played a significant role on the poor prognosis in patients with CCA. Our findings, taken together, characterized novel plasma biomarker signatures in dissecting tumor stages and post-surgical outcomes of HCC and CCA.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are widely recommended for health promotion. Over the last decade, prescription omega-3 fatty acid products (RxOME3FAs) ...have been approved for medical indications. Nonetheless, there is no comprehensive analysis of safety and tolerability of RxOME3FAs so far.
A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FA products were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity.
Among the 21 included RCTs (total 24,460 participants; 12,750 from RxOME3FA treatment cohort and 11,710 from control cohort), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (fishy taste; p = 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements elevated fasting blood sugar (p = 0.005); elevated alanine transaminase (p = 0.022); elevated blood urea nitrogen (p = 0.047); decreased hemoglobin (p = 0.002); decreased hematocrit (p = 0.009). Subgroup analysis revealed that EPA/DHA combination products were associated with more treatment-related gastrointestinal adverse events eructation (belching; p = 0.010); nausea (p = 0.044) and low-density lipoprotein cholesterol elevation (p = 0.009; difference in means = 4.106mg/dL).
RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs.
•Among the 21 included RCTs, there was no definite evidence of any RxOME3FA-emerging serious adverse event.•RxOME3FAs were associated with mild adverse events and minor changes upon laboratory measurements.•The two subgroups of RxOME3FAs,EPA/DHA combinations and EPA-only products, may have slightly different adverse-effect profiles.
Mechanisms of COVID‐19‐associated olfactory dysfunction Chang, Koping; Zaikos, Thomas; Kilner‐Pontone, Nicholas ...
Neuropathology and applied neurobiology,
April 2024, 2024-Apr, 2024-04-00, 20240401, Letnik:
50, Številka:
2
Journal Article
Recenzirano
Olfactory dysfunction is one of the most common symptoms of COVID‐19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the ...emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID‐19‐associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID‐19‐associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long‐term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID‐19‐associated olfactory dysfunction.
This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations, and current understanding of the mechanisms of COVID‐19‐associated olfactory dysfunction. The pathogenic mechanisms underlying COVID‐19‐associated olfactory dysfunction are complex and likely multifactorial. Infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, whereas olfactory receptor neuron dysfunction, olfactory bulb injury, and alterations in the olfactory cortex may lead to persistent, long‐term olfactory dysfunction.
Objective
A C‐to‐T single‐nucleotide polymorphism (SNP) located at position 1858 of human protein tyrosine phosphatase PTPN22 complementary DNA carries the highest risk of rheumatoid arthritis (RA) ...among all non‐HLA genetic variants. This C1858T SNP converts an arginine (R620) to a tryptophan (W620), but it is unclear why it has such a strong impact on RA, a disease characterized by anti–citrullinated protein antibodies. The aim of this study was to test the hypothesis that PTPN22 regulates protein citrullination.
Methods
The level of citrullinated proteins in immune cells was quantified by Western blotting. The physical interaction between PTPN22 and peptidyl arginine deiminase type 4 (PAD‐4), which is one of the enzymes that catalyzes protein citrullination, was examined by coimmunoprecipitation. Neutrophils were collected from healthy donors carrying the C1858T SNP and healthy donors not carrying this SNP. The formation of neutrophil extracellular traps (NETs) was examined by immunocytochemistry.
Results
PTPN22 physically interacted with PAD‐4, and a deficiency in PTPN22 enhanced protein citrullination. This abnormality was reversed by exogenous wild‐type PTPN22 or catalytically dead mutant PTPN22. The R‐to‐W conversion rendered PTPN22 unable to interact with PAD‐4 and suppress citrullination. The C1858T SNP was associated with hypercitrullination in peripheral blood mononuclear cells and a heightened propensity for spontaneous formation of NETs, which is a PAD‐4–dependent process.
Conclusion
PTPN22 is an inhibitor of PAD‐4 and protein citrullination. This function of PTPN22 is independent of its phosphatase activity but requires R620. Our data not only establish a molecular link between PTPN22 and PAD‐4, but also suggest that the C1858T SNP increases the risk of RA by enhancing protein citrullination and spontaneous formation of NETs.
Cinnamomum plants (Lauraceae) are a woody species native to South and Southeast Asia forests, and are widely used as food flavors and traditional medicines. This study aims to evaluate the chemical ...constituents of Cinnamomum osmophloeum ct. linalool leaf oil, and its antidepressant and motor coordination activities and the other behavioral evaluations in a rodent animal model. The major component of leaf oil is linalool, confirmed by GC-MS analysis. Leaf oil would not induce the extra body weight gain compared to the control mice at the examined doses after 6 weeks of oral administration. The present results provide the first evidence for motor coordination and antidepressant effects present in leaf oil. According to hypnotic, locomotor behavioral, and motor coordination evaluations, leaf oil would not cause side effects, including weight gain, drowsiness and a diminishment in the motor functions, at the examined doses. In summary, these results revealed C. osmophloeum ct. linalool leaf essential oil is of high potential as a therapeutic supplement for minor/medium depressive syndromes.
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•High-speed electrodeposition technology for efficient Cu pillar adhesion.•Current density dominated the Cu microstructure, pillar morphology and its adhesion.•Finite element analysis ...of high-speed electrodeposition.•Enhancement of electrolyte circulation can greatly facilitate electrodeposition.
The fabrication of Cu pillars has recently attracted much attention from the microelectronic/communication industry because pillars can act as thermal dissipation devices and electrical interconnections among different packaging levels, providing efficient utilization of space in microelectronic packaging applications. This study was conducted to investigate the fabrication of Cu pillars through a high-speed electrodeposition method and their adhesion to an Ajinomoto build-up film (ABF). The morphological, crystallographic, electrical, and mechanical characteristics of the Cu pillars electroplated with various current densities (j = 2, 5, 7.5, and 10 A/dm2) were systematically investigated through a scanning electron microscope (SEM) combined with electron backscatter diffraction (EBSD) analysis system, field-emission transmission electron microscope (FE-TEM), an ohm meter, and a nanoindenter. Additionally, the adhesion of the Cu pillars to an ABF substrate after high-temperature storage was evaluated via a shear test. Finally, a finite element analysis (FEA) method (COMSOL-Multiphysics) was employed to simulate the current density and electrolyte distributions in a via structure upon high-speed Cu electrodeposition to characterize the morphological/crystallographic/mechanical transitions induced by increasing j. This valuable information advances our understanding of electrochemical metal deposition and would be helpful in the development of high-speed Cu electrodeposition technology.
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