Rapid analysis and characterization of compounds by mass spectrometry may overlook trace compounds, although targeted analysis methods can significantly improve detection sensitivity, it is difficult to discover novel scaffold compounds. This study developed a strategy for discovering trace compounds in the aging process of traditional Chinese medicine based on MS fragmentation and known metabolic pathway. Specifically, we found that the characteristic component of C. reticulata 'Chachi', methyl N-methylanthranilate (MMA), fragmented in ESI-CID to produce rearrangement ion 3-hydroxyindole, which has been proven to exist in trace amounts in C. reticulata 'Chachi' comparing with the reference substance by LC-MS/MS. By combining the known metabolic pathways of 3-hydroxyindole and the possible methylation reactions that may occur during aging, 10 possible indole derivatives were untargeted predicted. These compounds were confirmed to originate from MMA by purchasing or synthesizing reference substances and all of them were detected in C. reticulata 'Chachi' through LC-MS/MS analysis, achieving trace compound analysis from untargeted to targeted. It may contribute to explain the aging mechanism of C. reticulata 'Chachi' and the strategy of CID-induced special rearrangement ion binding metabolic pathway has potential application value in discovering trace compounds.

Early stable deep molecular response (DMR) of nilotinib is associated with goal of treatment-free remission (TFR) for patients with chronic-phase chronic myeloid leukemia (CML-CP). It is significant to early distinguish patients who can obtain DMR and fit for TFR. We performed a multicenter study to explore early cumulative MR4.5 rate by 18 months with nilotinib in patients with newly diagnosed CML-CP (ND-CML-CP) in China. From 29 institutes, 106 ND-CML-CP patients received nilotinib (300mg BID). The cumulative MR4.5 rate of nilotinib by 18 months was 69.8% (74/106). The cumulative MMR and MR4.0 rates of nilotinib by 18 months were 94.3% (100/106) and 84.9% (90/106), respectively. Patients with ultra-early molecular response (u-EMR) at 6 weeks were not significantly different to obtain DMR or MMR by 24 months compared to those without u-EMR (P=0.7584, P=0.9543, respectively). Our study demonstrated that treatment with nilotinib in patients with ND-CML-CP contributed to obtain high early MR4.5.

Fibrosis is the end result of persistent inflammatory responses induced by a variety of stimuli, including chronic infections, autoimmune reactions, and tissue injury. Fibrotic diseases affect all vital organs and are characterized by a high rate of morbidity and mortality in the developed world, although currently there are no approved antifibrotic therapies. In recent years, high levels of interleukin-17 (IL-17) have been associated with chronic inflammatory diseases with fibrotic complications, that culminate in organ failure. In this review, we provide an update on the role of IL-17 in fibrotic diseases, with particular attention to the most recent lines of research in the therapeutic field represented by the epigenetic mechanisms that control IL-17 levels in fibrosis. A better knowledge of the IL-17 signalling pathway implications in fibrosis could design new strategies for therapeutic benefits.

The thionamide antithyroid drugs were discovered largely following serendipitous observations by numerous researchers in the 1940s who found that sulfhydryl-containing compounds were goitrogenic in animals. Prof. Edwin B. Astwood was the first to use these compounds to treat hyperthyroidism. In this review, we summarize the history of the development of these drugs and the coordination possibility of 2-thiouracil and its derivatives, as well as the biological activities of some of its complexes. Some of them are used as agents for the treatment of tuberculosis, and arthritis, others have bactericidal and fungicidal activity, the third cytotoxic properties, and could be used to treat various types of cancer.

Zinc nanoparticles (ZnNPs) open new opportunities for biomedical applications as a strategy against microbes and dye removal in an efficient way. The composite ZnNPs using Rhododendron arboreum (R. arboreum) stem bark were synthesized and characterized for UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The synthesized nanoparticles showed zones of inhibition of 23±0.09, 18±0.1 and 16±0.05 mm, against the Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli strains. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against K. pneumoniae, S. aureus, and E. coli were found to be 34±0.21 and 72.71±0.47, 47±0.11 and 94.86±0.84 and 94±0.18 and 185.43±0.16 µg/mL, respectively. The biosynthesized ZnNPs resulted in significant eradication of the outer and inner membranes of the bacterial cells. Likewise, the synthesized ZnNPs showed time-dependent photocatalytic degradation activity and revealed 65% methyl orange dye degradation with an irradiation period of 6 hours. The findings of this study suggest the suitability of the novel R. arboreum stem bark-based ZnNPs as an effective ameliorant against bactericidal activities and photocatalysts for the removal of hazardous water contaminants.

MgAl oxide coatings containing MgO and MgAl2O4 phases were doped with CeO2 particles using plasma electrolytic oxidation (PEO) of AZ31 magnesium alloy in 5 g/L NaAlO2 water solution, with CeO2 particles added at concentrations up to 8 g/L. They underwent extensive inve-stigation into their morphology, chemical and phase compositions, and most importantly, photoluminescent (PL) properties and photocatalytic-activity (PA) in photodegradation of methyl orange (10 cm3 of 8 mg/L). The concentration of CeO2 particles in the aluminate electrolyte influences the amount of CeO2 particles incorporated into MgAl oxide coatings, but CeO2 particles have no signi-ficant effect on the surface morphology, thickness, or phase structure of the coatings. The PL emi- ssion spectrum of MgAl oxide coating is divided into two bands: one in the 350-600 nm range related to structural defects in MgO, and another much more intense in the 600-775 nm range attributed to F+ centres in MgAl2O4. Incorporated CeO2 particles do not have a significant effect on the PL intensity of the band in the red spectral region, but the PL intensity of the first band increases with the concentration of CeO2 particles. PA of MgAl/CeO2 oxide coatings is higher than that of pure MgAl oxide coatings. The highest PA was observed for MgAl/CeO2 oxide coatings formed in aluminate electrolytes with the addition of 2 g/L of CeO2 particles. The MgAl/CeO2 oxide coatings remained chemically and physically stable across multiple cycles, indicating their potential for applications.

Shear dynamics simulation under extreme pressure was used to optimise the composition of ester-based lubricant base oil and extreme pressure additives. As a result, the ester-based lubricant in the weak-gel drilling fluid achieves reduction and increases the efficiency in drilling construction, and the field operation efficiency improves. The results of base oil lubrication simulation show that three base oils, namely, methyl oleate, ethyl oleate and butyl oleate, can be stably adsorbed on the surface layer of the shear surface. Methyl oleate has the lowest system temperature after shear stabilisation and has a high load-bearing capacity. The shear stress of methyl oleate decreases by changing the initial shear temperature and speed. It increases by 6.36 MPa when the speed increases from 10 m/s to 30 m/s. At this time, the shear stress of butyl oleate increases by 10.11 MPa. The results of the four-ball friction experiments show that the radius of the abrasion spot of methyl oleate is 179.83 μm, which is smaller than that of the other two base oils. Moreover, the friction coefficient of methyl oleate is 0.0018, which is approximately 1/3 of that of butyl oleate. Methyl oleate has better lubrication efficiency. The shear simulation results are consistent with the experimental results. The simulation can be used for the molecular design of lubricant materials. The oleic acid amide–containing amine group and the glyceride oleic–containing hydroxyl group were selected as the extreme pressure functional components for shear simulation. Results show that the shear stress of oleic acid amide is much lower than that of oleic acid glyceride when the initial shear temperature and speed change. The extreme pressure lubrication component–containing amine group is better than the extreme pressure lubrication material–containing hydroxyl group. The effects of different oleamide contents in the two-component mixtures on the lubricating properties were investigated through shear simulation, with methyl oleate as the base oil and oleamide as the extreme pressure functional component. The simulation results show that the lubricant has the optimal shear stress when 10% oleamide is added to the lubricant. The base properties of the lubricant were tested using a mixture of 90% methyl oleate and 10% oleamide, formulated as a lubricant. Results show that the friction coefficient can be reduced to 0.03 when 0.5% of the lubricant is added to the base mud. Moreover, the lubricant film formed shows high strength. Then, 1% lubricant was added to the weak-gel drilling fluid to evaluate the effect of the lubricant on the gel structure of the drilling fluid. Results show that adding lubricant does not affect the rheological properties of the drilling fluid. The gel structure of the system also remains stable even after 7 days of continuous ageing. The results of the field experiments in Hua3-01 well show that adding 1% ester-based lubricant to the field drilling fluid reduces the drilling friction by 33%. Thus, the efficiency of directional side drilling can be effectively improved, complicated accidents, such as poor starting and stopping of drilling and stuck jamming, can be avoided, and the goals of reducing quantity and increasing efficiency can be completed.

Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer’s disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infec-tion, underscoring the importance of cellular cholesterol levels not only in the viral entry pro-cess but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellu-lar accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.

High-power laser facilities necessitate predicting incremental damage to final optics to identify evolving damage trends. In this study, we propose a surface damage detection method utilizing image segmentation employing ResNet-18, and a damage area estimation network employing U-Net++. Paired sets of online and offline images of optics obtained from a large laser facility is used to train the network. The trends of varying damage could be identified by incorporating additional experimental parameters. A key advantage of the proposed method is that the network can be trained end-to-end on small samples, eliminating the need for manual labeling or feature extraction. The software developed based on these models can facilitate the daily inspection and maintenance of optics in large laser facilities.

Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival related genes (SRBs) using the gene expression dataset of Cavalli et al. (2017) and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was HMGA1 (high mobility group AT-hook 1), which is a known oncogene and a histone H1 competitor. High expression of HMGA1 was associated with worse survival, primarily in the Group 3γ subtype. The high expression of HMGA1 was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype with 93% deletion of 17p and 98% copy gain of 17q. Pathway analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provide a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that HMGA1, along with other SRGs on chromosome 6 and 17 warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.

Background/Objectives: Although the role of F-18 FDG PET/CT imaging is well established in oncology, its diagnostic value in routine monitoring for recurrent colorectal cancer (CRC) is still controversial. The aim was to evaluate the diagnostic value of FDG PET/CT in detecting recurrent CRC in correlation with CEA, CA 19-9 levels, and conventional imaging modalities (CIM). Methods: Between 2009 and 2023, we retrospectively studied 134 CRC patients referred for FDG PET/CT imaging on the suspicion of recurrence based on elevated CEA and/or CA 19-9, and/or equivocal radiological findings. According to the Institutional Tumor Board CRC protocol, after initial treatment which was dependent on TNM stage (neoadjuvant therapy, primary resection or adjuvant treatment), patients underwent a standard 5-year surveillance including CEA and CA 19-9 measurements, CIM, and colonoscopy every 6 months. The statistics including univariate and multivariable analyses were conducted using the IBM SPSS 20.0 statistical software. P-values <0.05 were considered statistically significant. Results: Recurrent CRC was confirmed in 54/134 (40.3%) patients with elevated tumor markers. FDG PET/CT shows high diagnostic performance in detecting recurrent CRC with sensitivity, specificity, PPV, NPV, and accuracy of 94.4%, 82.5%, 78.5%, 95.7%, and 87.3%, respectively. The CEA shows a high sensitivity of 98.1%, but both low specificity and accuracy of 15% and 48.5%, respectively. The sensitivity, specificity, and accuracy, for CA 19-9 and CIM for the correct diagnosis in CRC patients were: 44.4%, 67.5%, 58.2%, and 51.9%, 98.8%, 79.9%, respectively. The AUC for FDG PET/CT, elevated CEA levels, CIM, and elevated CA 19-9 levels was 0.885 (95% CI: 0.824-0.946; p<0.001), 0.844 (95% CI: 0.772-0.916; p<0.001), 0.753 (95% CI: 0.612-0.844; p<0.001); and 0.547 (95% CI: 0.442-0.652; p=0.358). Univariate analysis shows that both FDG PET/CT- and CIM-positive results were highly associated with CRC recurrence (p<0.001 and p<0.001, respectively), while gender, mucinous tumor type, presence of initial lymph node metastasis (N+), and presence of initial distant metastasis (M+) have no significance (p=0.211, p=0.158, p=0.583, and p=0.201, respectively). Our multivariate analysis shows that independent predictors for CRC recurrence are: positive FDG PET/CT scans (p<0.001), positive CIM results (p=0.001) and elevated CA19-9 levels (p=0.023). Although CA 19-9 was not detected as a statistically significant predictor in the univariate analysis (p=0.358), in a multivariate analysis it was recognized as a significant predicting factor in detecting CRC recurrence (p=0.023). Conclusions: FDG PET/CT shows a high diagnostic efficacy in CRC recurrence detection, in correlation with CEA levels, CA 19-9 levels, and CIM. This imaging modality should be routinely integrated into the postoperative follow-op in patients with elevated tumor markers.

A methodology has been developed to assess the presence and dissipation of herbicides of wide range of polarities in soil using in-tube solid phase microextraction (IT-SPME) coupled on-line to capillary liquid chromatography (capLC). The compounds investigated were tritosulfuron (TRT), triflusulfuron-methyl (TRF), aclonifen (ACL) and bifenox (BF), with log octanol-water partition coefficients (log Kow) ranging from 0.62 to 4.48. The linearity, recoveries, intra and interday precision, limits of detection (LODs) and quantification (LOQs), and accuracy of the method were established. The proposed approach was successfully applied assess the degradation of the tested herbicides in different types of soil (agricultural, urban and forest) after being exposed to different laboratory and outdoor conditions. The results obtained showed a greater persistence of the most apolar compounds ACL and BF, regardless of the soil characteristics, whereas a significant degradation of highly polar herbicides TRT and TRF was observed in soils with lowest organic matter even after a few days of exposure. Those results indicate that the proposed approach can be considered an effective tool for a better understanding of soil pollution.

A recent study showed the potential of DA Perten 7200 NIR Spectrometer in detecting chlorpyrifos-methyl pesticide residue in rough, brown, and milled rice. However, this instrument is still lab-based and generally suited for point-of-sale testing in many countries. To provide a field deployable version of this technique, an existing light emitting diode (LED)-based instrument which provide discrete NIR wavelength illumination and reflectance spectra over the range of 850-1550 nm was tested. Spectra were collected from rough, brown, and milled rice at different pesticide concentrations and analysed for quantitative and qualitative measurement using partial least squares regression (PLS) and discriminant analysis (DA). Simulations for LED-based instruments were also evaluated using segments of spectra from the DA7200 to represent LED illumination. For the simulation of the existing LED-based instrument (LEDPrototype1) using their wavelengths range yielded 70.4% to 100% correct classification. Simulation of a second LED instrument, LEDPrototype2, with spectral segments selected based on significant wavelength regions from PLS regressions coefficients obtained from the DA7200 showed improved performance with R2 of 0.59 to 0.82 and correct classifications of 71.3 to 100%. An actual LED based instrument with this capability could provide a quick screening tool to determine if MRLs are exceeded.

Yellow pitahaya is a tropical fruit that has gained popularity in recent years. Natural elicitors are compounds that can stimulate the resistance and quality of fruits. The objective of this study was to evaluate the effects of natural elicitors: methyl salicylate (MeSa), methyl jasmonate (JaMe), salicylic acid (SA) and oxalic acid (OA) at concentrations of 0.1 mM (SaMe and JaMe) and 5 mM (SA and OA), applied to the yellow pitahaya fruits, under greenhouse conditions. After full blossom, 4 applications were made with a frequency of 15 days. At time of harvest and after storage, the following variables were evaluated: firmness (whole fruit), total soluble solids (TSS), total acidity (TA), phenolics and carotenoids (in the pulp), while phenolics, carotenoids, macronutrients and micronutrients were determined in the peel. The results showed that JaMe presented a delay of the ripening process, according to TSS, TA, firmness, and total phenolic compounds results, while MeSa advanced the fruit maturation. Regarding the alternative use of the peel as by-product, the application of natural elicitors significantly increased the content of polyphenols, carotenoids, macronutrients and micronutrients in the peel, which can be used as a bioactive compound in the food industry. In conclusion, the results indicate that natural elicitors can be an alternative to improve the quality and shelf life of yellow pitahaya fruits.