Hydroxylation of Aryl Sulfonium Salts for Phenol Synthesis under Mild Reaction Conditions.

Hydroxylation of aryl sulfonium salts could be realized by utilizing acetohydroxamic acid and oxime as hydroxylative agents in the presence of cesium carbonate as a base, leading to a variety of structurally diverse hydroxylated arenes in 47-95% yields. In addition, the reaction exhibited broad functionality tolerance, and a range of important functional groups (e.g., cyano, nitro, sulfonyl, formyl, keto, and ester) could be well amenable to the mild reaction conditions.

Harmonics of Parton Saturation in Lepton-Jet Correlations at the Electron-Ion Collider.

Parton saturation is one of the most intriguing phenomena in the high energy nuclear physics research frontier, especially in the upcoming era of the Electron-Ion Collider (EIC). The lepton-jet correlation in deep inelastic scattering provides us with a new gateway to the parton saturation at the EIC. In particular, we demonstrate that azimuthal angle anisotropies of the lepton-jet correlation are sensitive to the strength of the saturation momentum in the EIC kinematic region. In contrast to the predictions based on the collinear framework calculation, significant nuclear modification of the anisotropies is observed when we compare the saturation physics results in e+p and e+Au scatterings. By measuring these harmonic coefficients at the EIC, one can conduct quantitative analyses in different collisional systems and unveil compelling evidence for saturation effects.

Effects of Compound Trace Minerals on the Growth Performance, Carcass Characteristics and Meat Quality of Fattening Pigs.

The objective of this study was to evaluate the effects of supplemental levels of compound minerals (CM), which was formulated from a mixture of 300 mg calcium, 150 mg magnesium, 25 mg zinc, 15 mg iron, 4 mg manganese, and 2 mg copper per gram, on the growth performance and feed conversion ratio of Duroc × (Landrace × Yorkshire) fattening pigs. A total of 53 female pigs and 45 male pigs at 35 days of age were individually notched and randomly allocated to three treatments, including0 (basal diet), 0.5 (basal diet with 0.5 mg CM/kg feed), and 1 (basal diet with 1 mg CM/kg feed). There were three replicates for each of the three treatments with 28, 34, and 36 pigs in the first, second, and third treatments, respectively. The experiment was divided into two phases, the growing stage, and the finishing stage. Supplementation of compound minerals in the diet led to an increased average daily weight gain and improved feed conversion ratio and meat quality without effects on the lean meat percentage. An addition of 1 mg of compound minerals per 1 kg of feed is the recommended dose to improve the production performance of fattening pigs. These results suggest that the use of compound minerals could improve the growth traits of fattening pigs under tropical environmental conditions.

Synthesis and Anti-Proliferation Activity Evaluation of Novel 2-Chloroquinazoline as Potential EGFR-TK Inhibitors.

A novel series of 2-chloroquinazoline derivatives had been synthesized and their anti-proliferation activities against the four EGFR high-expressing cells A549, NCI-H1975, AGS and HepG2 cell lines were evaluated. The preliminary SAR study of the scaffold of new compounds showed that the compounds with a chlorine substituent on R3 had a better anti-proliferation activity than those substituted by hydrogen atom or vinyl group. Among them, 2-chloro-N-[2-chloro-4-(3-chloro-4-fluoroanilino)quinazolin-6-yl]acetamide (10b) had the best activity, and the corresponding IC50 were 3.68, 10.06, 1.73 and 2.04 µM, respectively. And compound 10b had better or equivalent activity against four cell lines than Gefitinib. The activity of the compound 10b on the EGFR enzyme was subsequently tested. The Wound Healing of A549, AGS and HepG2 cells by this compound showed that the compound can inhibit the migration of cancer cells. Finally, the action channel of the compound 10b was supported by western blotting experiments. It provides useful information for the design of EGFR-TK inhibitors.

Novel human monoclonal antibodies targeting the F subunit of leukocidins reduce disease progression and mortality caused by Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is a leading cause of Gram-positive bacterial infections worldwide; however, the treatment of S. aureus infection has become increasingly difficult due to the prevalence of methicillin-resistant S. aureus strains, highlighting the urgent need for the development of novel strategies. The complexity of S. aureus pathogenesis relies on virulence factors. Recent studies have demonstrated that leukocidins expressed by the majority of clinical isolates play important roles in the pathogenesis of S. aureus. RESULTS: In this study, we developed three human monoclonal antibodies against all F-components of leukocidins HlgABC, LukSF, and LukED with high affinity. These antibodies were found to be capable of blocking leukocidin-mediated cell lysis in vitro. Furthermore, the antibodies dramatically reduced disease progression and mortality after S. aureus infection in vivo. CONCLUSIONS: Our findings revealed that neutralizing bicomponent leukocidins may be a promising strategy to combat infections caused by S. aureus.

Phospholipase A2 enzymes PLA2G2A and PLA2G12B as potential diagnostic and prognostic biomarkers in cholangiocarcinoma.

BACKGROUND: Phospholipase A2 (PLA2) enzymes are pivotal in various biological processes, such as lipid mediator production, membrane remodeling, bioenergetics, and maintaining the body surface barrier. Notably, these enzymes play a significant role in the development of diverse tumors. AIM: To systematically and comprehensively explore the expression of the PLA2 family genes and their potential implications in cholangiocarcinoma (CCA). METHODS: We conducted an analysis of five CCA datasets from The Cancer Genome Atlas and the Gene Expression Omnibus. The study identified differentially expressed genes between tumor tissues and adjacent normal tissues, with a focus on PLA2G2A and PLA2G12B. Gene Set Enrichment Analysis was utilized to pinpoint associated pathways. Moreover, relevant hub genes and microRNAs for PLA2G2A and PLA2G12B were predicted, and their correlation with the prognosis of CCA was evaluated. RESULTS: PLA2G2A and PLA2G12B were discerned as differentially expressed in CCA, manifesting significant variations in expression levels in urine and serum between CCA patients and healthy individuals. Elevated expression of PLA2G2A was correlated with poorer overall survival in CCA patients. Additionally, the study delineated pathways and miRNAs associated with these genes. CONCLUSION: Our findings suggest that PLA2G2A and PLA2G12B may serve as novel potential diagnostic and prognostic markers for CCA. The increased levels of these genes in biological fluids could be employed as non-invasive markers for CCA, and their expression levels are indicative of prognosis, underscoring their potential utility in clinical settings.

Complete mitochondrial genome of Belligobio pengxianensis (Cypriniformes: Gobionidae).

Belligobio pengxianensis is a small fish endemic to the upper Yangtze River of China. In this study, the complete mitochondrial genome of B. pengxianensis is determined for the first time, and it should become a reference sequence to aid in species identification, biodiversity monitoring and conservation. The mitogenome has overall length of 16,610 bp and AT content of 55.23%, including 13 protein-coding genes, two ribosomal RNAs, 22 transfer RNAs, and one non-coding control region. The results of phylogenetic analyses show that B. pengxianensis is nested within the genus Hemibarbus.

Nickel-Catalyzed Direct Cross-Coupling of Aryl Thioether with Aryl Bromide.

A straightforward cross-coupling of aryl thioether with aryl bromide with the aid of nickel salt, magnesium, and lithium chloride in tetrahydrofuran at ambient temperature was accomplished. The one-pot reactions proceeded efficiently via C-S bond cleavage to produce the desired biaryls in modest to good yields, avoiding the use of pregenerated or commercial organometallic reagents.

Non-invasive Assessment of Axillary Lymph Node Metastasis Risk in Early Invasive Breast Cancer Adopting Automated Breast Volume Scanning-Based Radiomics Nomogram: A Multicenter Study.

OBJECTIVE: The aim of the work described here was to develop a non-invasive tool based on the radiomics and ultrasound features of automated breast volume scanning (ABVS), clinicopathological factors and serological indicators to evaluate axillary lymph node metastasis (ALNM) in patients with early invasive breast cancer (EIBC). METHODS: We retrospectively analyzed 179 ABVS images of patients with EIBC at a single center from January 2016 to April 2022 and divided the patients into training and validation sets (ratio 8:2). Additionally, 97 ABVS images of patients with EIBC from a second center were enrolled as the test set. The radiomics signature was established with the least absolute shrinkage and selection operator. Significant ALNM predictors were screened using univariate logistic regression analysis and further combined to construct a nomogram using the multivariate logistic regression model. The receiver operating characteristic curve assessed the nomogram's predictive performance. DISCUSSION: The constructed radiomics nomogram model, including ABVS radiomics signature, ultrasound assessment of axillary lymph node (ALN) status, convergence sign and erythrocyte distribution width (standard deviation), achieved moderate predictive performance for risk probability evaluation of ALNs in patients with EIBC. Compared with ultrasound, the nomogram model was able to provide a risk probability evaluation tool not only for the ALNs with positive ultrasound features but also for micrometastatic ALNs (generally without positive ultrasound features), which benefited from the radiomics analysis of multi-sourced data of patients with EIBC. CONCLUSION: This ABVS-based radiomics nomogram model is a pre-operative, non-invasive and visualized tool that can help clinicians choose rational diagnostic and therapeutic protocols for ALNM.

Antibodies Against Pseudomonas aeruginosa Alkaline Protease Directly Enhance Disruption of Neutrophil Extracellular Traps Mediated by This Enzyme.

Extracellular traps released by neutrophils (NETs) are essential for the clearance of Pseudomonas aeruginosa. Alkaline protease (AprA) secreted by P. aeruginosa negatively correlates with clinical improvement. Moreover, anti-AprA in patients with cystic fibrosis (CF) can help identify patients with aggressive forms of chronic infection. However, the mechanism underlying the clinical outcomes remains unclear. We demonstrated that aprA deficiency in P. aeruginosa decreased the bacterial burden and reduced lung infection. AprA degraded NET components in vitro and in vivo but did not affect NET formation. Importantly, antibodies induced by AprA acted as an agonist and directly enhanced the degrading activities of AprA. Moreover, antisera from patients with P. aeruginosa infection exhibited antibody-dependent enhancement (ADE) similar to that of the antibodies we prepared. Our further investigations showed that the interaction between AprA and the specific antibodies might make the enzyme active sites better exposed, and subsequently enhance the recognition of substrates and accelerate the degradation. Our findings revealed that AprA secreted by P. aeruginosa may aggravate infection by destroying formed NETs, an effect that was further enhanced by its antibodies.

Hierarchical supramolecular ordering with biaxial orientation of a combined main-chain/side-chain liquid-crystalline polymer obtained from radical polymerization of 2-vinylterephthalate.

The liquid-crystalline (LC) phase structures and transitions of a combined main-chain/side-chain LC polymer (MCSCLCP) 1 obtained from radical polymerization of a 2-vinylterephthalate, poly(2,5-bis{[6-(4-butoxy-4'-oxybiphenyl) hexyl]oxycarbonyl}styrene), were studied using differential scanning calorimetry, one- and two-dimensional wide-angle X-ray diffraction (1D and 2D WAXD), and polarized light microscopy. We have found that 1 with sufficiently high molecular weight can self-assemble into a hierarchical structure with double orderings on the nanometer and subnanometer scales at low temperatures. The main chains of 1, which are rodlike as a result of the "jacketing" effect generated by the central rigid portion of the side chains laterally attached to every second carbon atom along the polyethylene backbone, form a 2D centered rectangular scaffold. The biphenyl-containing side chains fill the space between the main chains, forming a smectic E (SmE)-like structure with the side-chain axis perpendicular to that of the main chain. This biaxial orientation of 1 was confirmed by our 2D WAXD experiments through three orthogonal directions. The main-chain scaffold remains when the SmE-like packing is melted at elevated temperatures. Further heating leads to a normal smectic A (SmA) structure followed by the isotropic state. We found that when an external electric field was applied, the main-chain scaffold greatly inhibited the motion of the biphenyls. While the main chains gain a sufficiently high mobility in the SmA phase, macroscopic orientation of 1 can be achieved using a rather weak electric field, implying that the main and side chains with orthogonal directions can move cooperatively. Our work demonstrates that when two separate components, one offering the "jacketing" effect to the normally flexible backbone and the other with mesogens that form surrounding LC phases, are introduced simultaneously into the side chains, the polymer obtained can be described as an MCSCLCP with a fascinating hierarchically ordered structure.

[Primary culture of human malignant meningioma cells and its intracranial orthotopic transplantation in nude mice].

OBJECTIVE: To obtain stable primary cultures of human malignant meningioma cells and establish an intracranial in-situ tumor model in nude mice. METHODS: Ten surgical specimens of highly suspected malignant meningioma were obtained with postoperative pathological confirmation. Primary malignant meningioma cells were cultured from the tissues using a modified method and passaged. After identification with cell immunofluorescence, the cultured cells were inoculated into the right parietal lobe of 6 nude mice using stereotaxic apparatus and also transplanted subcutaneously in another 6 nude mice. The nude mice were executed after 6 weeks, and HE staining and immunohistochmistry were used to detect tumor growth and the invasion of the adjacent brain tissues. RESULTS: The primary malignant meningioma cells were cultured successfully, and postoperative pathology reported anaplastic malignant meningioma. Cell immunofluorescence revealed positivity for vimentin and EMA in the cells, which showed a S-shaped growth curve in culture. Flow cytometry revealed a cell percentage in the Q3 area of (95.99∓2.58)%. Six weeks after transplantation, tumor nodules occurred in the subcutaneous tumor group, and the nude mice bearing the in situ tumor showed obvious body weight loss. The xenografts in both groups contained a mean of (36∓5.35)% cells expressing Ki-67, and the intracranial in situ tumor showed obvious invasion of the adjacent peripheral brain tissues. CONCLUSION: We obtained stable primary cultures of malignant meningioma cells and successfully established a nude mouse model bearing in situ human malignant meningioma.

Differential expression of serum proteins in rats subchronically exposed to arsenic identified by iTRAQ-based proteomic technology-14-3-3 ζ protein to serve as a potential biomarker.

Arsenic is a multi-system toxicant. However, the mechanism of arsenic toxicity is not fully clarified and few effective protein biomarkers could be used for arsenic poisoning. This study was to investigate the differentially expressed proteins in the serum of rats subchronically exposed to arsenic. Sixty male rats were randomly divided into four groups, and the dose of sodium arsenite in drinking water for each group was 0, 2, 10, and 50 mg L-1, respectively. The exposure lasted for 12 weeks. An Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach was used to identify the differentially expressed proteins in serum between control and 50 mg L-1 groups. A total of 201 serum proteins were identified by iTRAQ, of which 12 were significantly changed by arsenic exposure with two up-regulated and ten down-regulated proteins. One down-regulated protein 14-3-3 ζ, an abundant protein expressed in the brain, was verified by ELISA using serum samples and by immunohistochemical, real time PCR, and western blot methods using brain tissues in four groups. Our work provided valuable insight into the serum protein changes in rats exposed to arsenic, and indicated that 14-3-3 ζ may serve as a useful biomarker for nervous damage caused by arsenic poisoning.

Release of nitric oxide by N-nitropyrazoles in rabbit lacrimal gland cell culture.

PURPOSE: In order to prove the effects of N-nitropyrazoles to increase ocular blood flow and to facilitate retinal function after ischemia are due to nitric oxide (NO) release, eleven N-nitropyrazoles which are known NO donors were used to test their ability to produce NO in rabbit lacrimal gland (RLG) cell cultures. METHODS: Nitropyrazoles (0.3-3 microg/ml) were added into RLG cell culture and the NO produced was determined with nitrate-nitrite colorimetric assay. RESULTS: All nitropyrazoles (11 compounds) tested produced NO in various degrees with the highest degree by 13 fold over control (DN-5) and the lowest level by only 2.8 fold over control (DN-7). CONCLUSION: The results indicated that NO is involved in ocular blood flow increase and retinal function recovery after ischemia by N-nitropyrazoles. However, there is no potency relationship between in vitro data and in vivo data, which is understandable because the experimental environments are different.

Relationship between nitric oxide production and choroidal blood flow.

PURPOSE: To invent a drug which can specifically facilitate choroid blood flow via increase of nitric oxide (NO). METHOD: Cell culture was used for in vitro experiments to determine the production of NO by NO donors and colored microsphere technique was used for in vivo experiments to determine the blood flow in various tissues of rabbit eyes. RESULTS: ZX-5 and ZX-4 are two geographic isomers with ZX-5 as trans-form and ZX-4 as cis-form. (1-phenyl-3-[3-methoxy-2-propoxy-5-[4-(3,4,5-trimethoxy-phenyl)-1,3-d lane-2-yl]phenyl]thiourea). It was found that ZX-5 released significant amount of NO at 3, 10, 30 microg/ml concentrations and increased choroid blood flow at 1%, 50 microl instillation into eyes. It was not effective on the blood flow of iris or ciliary body. The corresponding ZX-4 was not effective on ocular blood flow nor it released NO. CONCLUSION: ZX-5 can specifically increase the choroidal blood flow which could be useful to suppress the choroidal neovascularization in age-related macular degeneration (AMD). It is hoped that ZX-5 type of compounds could be used for the treatment/prevention of AMD in the elderly.

Effects of C-nitropyrazoles and C-nitroazoles on ocular blood flow and retinal function recovery after ischemic insult.

AIM: Effects of C-nitropyrazoles and C-nitroazoles on ocular blood flow and retinal function recovery after ischemia have been studied. METHODS: The compounds were tested on ocular blood flow of ocular hypertensive (40 mmHg) rabbit eyes with colored microsphere technique. They were also tested on the retinal function recovery after ischemia of rat eyes with electroretinography. RESULTS: All compounds (DC-1 through DC-17) showed significant increase in retinal function recovery after ischemia in the range of 26 % to 120 % (P<0.05). Among five compounds (DC-1 through DC-5) studied, four compounds (DC-2 through DC-5) increased the blood flow in choroid, iris, and ciliary body, but not in retina. DC-1 did not show significant increase of blood flow in any of these ocular tissues. CONCLUSION: C-Nitropyrazoles can facilitate significant retinal function recovery after ischemic insult through the increase of ocular blood flow. Since rabbit's retina is scarce in vasculature, it did not show significant change in blood flow by C-nitropyrazoles as expected. Among all 17 compounds, DC-5 seems to be the most potent compound.