Prediction of the n-Octanol/Water Partition Coefficients of Basic Compounds Using Multi-Parameter QSRR Models Based on IS-RPLC Retention Behavior in a Wide pH Range.

The n-octanol-water partition coefficient (logP) is an important physicochemical parameter which describes the behavior of organic compounds. In this work, the apparent n-octanol/water partition coefficients (logD) of basic compounds were determined using ion-suppression reversed-phase liquid chromatography (IS-RPLC) on a silica-based C18 column. The quantitative structure-retention relationship (QSRR) models between logD and logkw (logarithm of retention factor corresponding to 100% aqueous fraction of mobile phase) were established at pH 7.0-10.0. It was found that logD had a poor linear correlation with logkw at pH 7.0 and pH 8.0 when strongly ionized compounds were included in the model compounds. However, the linearity of the QSRR model was significantly improved, especially at pH 7.0, when molecular structure parameters such as electrostatic charge ne and hydrogen bonding parameters A and B were introduced. External validation experiments further confirmed that the multi-parameter models could accurately predict the logD value of basic compounds not only under strong alkaline conditions, but also under weak alkaline and even neutral conditions. The logD values of basic sample compounds were predicted based on the multi-parameter QSRR models. Compared with previous work, the findings of this study extended the pH range for the determination of the logD values of basic compounds, providing an optional mild pH for IS-RPLC experiments.

Efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia. / å„¿ç«¥è½»åº¦ç¼ºé“æ€§è´«è¡€é—´æ­‡è¡¥é“ç–—æ³•çš„æœ‰æ•ˆæ€§ç ”ç©¶.

OBJECTIVES: To study the efficacy of intermittent iron supplementation in children with mild iron-deficiency anemia. METHODS: A total of 147 children with mild iron-deficiency anemia were enrolled in this prospective study. They were divided into an intermittent iron supplementation group (n=83) and a conventional iron supplementation group (n=64). The levels of hemoglobin were measured before treatment and after 1 and 3 months of treatment. The treat response rate and the incidence rate of adverse drug reactions were compared between the two groups. RESULTS: Both groups had a significant increase in the level of hemoglobin after iron supplementation (P<0.05). After 1 month of treatment, the conventional iron supplementation group had a significantly higher treatment response rate than the intermittent iron supplementation group (61% vs 42%, P<0.05). After 3 months of treatment, there was no significant difference in the treatment response between the two groups (86% vs 78%, P>0.05). The incidence rate of adverse drug reactions in the conventional iron supplementation group was significantly higher than that in the intermittent iron supplementation group (25% vs 8%, P<0.05). CONCLUSIONS: For children with mild iron-deficiency anemia, although intermittent iron supplementation is inferior to conventional iron supplementation in the short-term efficacy, there is no significant difference in the long-term efficacy between the two methods, and compared with conventional iron supplementation, intermittent iron supplementation can reduce the incidence of adverse drug reactions, alleviate family financial burdens, and improve treatment compliance of children, thus holding promise for clinical application.

Solvent-Driven Reversible Phase Transition of a Pillared Metal-Organic Framework.

Over the last decade, the controllable reversible phase transition of functional materials has received growing interest as it shows unique suitability for various technological applications. Although many metal-organic frameworks (MOFs) possess a lamellar structure, the reversible structural transformation of MOFs between their three-dimensional (3D) phase and two-dimensional (2D) phase remains a largely unexplored area. Herein, we report for the first time a europium MOF with unprecedented reversible morphology in different solvents at room temperature. This europium MOF displayed a 3D nanorod morphology in organic solvent and a 2D nanobelt architecture in water. As a proof of concept for potential applications of this reversible-phase-transition MOF, we were able to use a delamination recovery method to load dye molecules that previously could not be loaded into europium MOFs.

Three Silver Coordination Polymers with Diverse Architectures Constructed from Pyridine Carboxylic Hydrazide Ligands.

A series of silver coordination polymers (CPs) have been synthesized through self-assembly of three pyridinecarboxylic acid hydrazide (p-, m-, o-position) ligands with silver clusters (named Ag1-iah, Ag2-iah, and Ag3-iah). These silver CPs show different one- and two-dimensional topologies including cross-helical chains, planar network, and parallel helical chains for Ag1-iah, Ag2-iah, and Ag3-iah, respectively. The combination of experimental and computational results reveals the critical role in the space distribution of the coordination site of silver clusters and ligands in controlling the silver CPs' dimensionality and packing arrangement and modulating the optical properties and stability. Luminescent investigations reveal that Ag3-iah can selectively detect dichloromethane or trichloromethane in tetrachloromethane. These silver CPs provide a good model to study the influence of the space distribution of the coordination site of ligands on their packing arrangement and properties.

[Research progress on effect factors of secondary metabolites content in callus].

Secondary metabolites are the result of that plant interaction with biological and non-biological factors in the long-term evolution process, and play an important role in plant growth, development and physiology. The effective components of medicinal plant are usually the secondary metabolites in plant cells, and the synthesis of them are affected by a variety of factors, such as environmental impact. Acquirement of the secondary metabolites via callus culture has the advantage of low cost and less environmental impact. The synthesis and accumulation of medicinal plant secondary metabolites are not only controlled by light, temperature and pH, but also infected by germplasm, plant growth regulator and elicitor. This article presents a review of the influencing factors, and provides a basis for further study and development.

Epigenetic control of circadian clocks by environmental signals.

Circadian clocks have evolved to enable organisms to respond to daily environmental changes. Maintaining a robust circadian rhythm under various perturbations and stresses is essential for the fitness of an organism. In the core circadian oscillator conserved in eukaryotes (from fungi to mammals), a negative feedback loop based on both transcription and translation drives circadian rhythms. The expression of circadian clock genes depends both on the binding of transcription activators at the promoter and on the chromatin state of the clock genes, and epigenetic modifications of chromatin are crucial for transcriptional regulation of circadian clock genes. Herein we review current knowledge of epigenetic regulation of circadian clock mechanisms and discuss how environmental cues can control clock gene expression by affecting chromatin states.

[Analysis of Plasma Metabolic Profile in Children with Transfusion-Dependent Thalassemia].

OBJECTIVE: To explore the plasma metabolomic characteristics of children with transfusion-dependent thalassemia (TDT), and reveal the changes of metabolic pattern in children with TDT. METHODS: 23 children with TDT who received regular blood transfusion in Ganzhou Women and Children's Health Care Hospital in 2021 were selected, and 11 healthy children who underwent physical examination during the same period were selected as the control group. The routine indexes between children with TDT and the control group were compared, and then the metabolic composition of plasma samples from children with TDT and the control group was detected by liquid chromatography-mass spectrometry. An OPLS-DA model was established to perform differential analysis on the detected metabolites, and the differential metabolic pathways between the two groups were analyzed based on the differential metabolites. RESULTS: The results of routine testing showed that the indexes of ferritin, bilirubin, total bile acid, glucose and triglycerides in children with TDT were significantly higher than those in healthy controls, while hemoglobin and total cholesterol were significantly lower (all P <0.05). However there was no significant difference in lactate dehydrogenase between the two groups (P >0.05). Compared with the control group, 190 differential metabolites (VIP>1) were identified in TDT children. Among them, 168 compounds such as arginine, proline and glycocholic acid were significantly increased, while the other 22 compounds such as myristic acid, eleostearic acid, palmitic acid and linoleic acid were significantly decreased. The metabolic pathway analysis showed that the metabolic impact of TDT on children mainly focused on the upregulation of amino acid metabolism and downregulation of lipid metabolism. CONCLUSION: The amino acid and lipid metabolism in children with TDT were significantly changed compared with the healthy control group. This finding is helpful to optimize the treatment choice for children with TDT, and provides a new idea for clinical treatment.

Comparison of CT-guided thoracic sympathetic nerve block and radiofrequency in the treatment of primary palmar hyperhidrosis.

Background: Primary palmar hyperhidrosis (PPH) is a condition marked by an overactive secretion of the hand's exocrine glands and is frequently hereditary. The profuse sweating associated with this condition can significantly impair the patient's daily activities and quality of life. Objective: The objective of this study was to compared the benefits and drawbacks of thoracic sympathetic block and thoracic sympathetic radiofrequency in the treatment of PPH. Methods: A retrospective analysis was conducted on 69 patients. They were divided into groups A and B according to their treatment. Group A (34 cases) received CT-guided percutaneous thoracic sympathetic nerve chain anhydrous alcohol chemical damage block, and group B (35 cases) received CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency thermocoagulation. Results: Palmar sweating disappeared immediately after the operation. The recurrence rates at 1, 3, 6, 12, 24, and 36 months were 5.88% vs. 2.86% (P > 0.05), 20.59% vs. 5.71% (P > 0.05), 32.35% vs. 11.43% (P < 0.05),32.35% vs. 11.43% (P < 0.05), 25% vs. 14.71% (P < 0.05), and 68.75% vs. 20.59% (P < 0.05), respectively. The incidence of intercostal neuralgia and compensatory hyperhidrosis was higher in group A compared with of group B (52.94% vs. 22.86%, P < 0.05; 55.88% vs. 22.86%, P < 0.05). Conclusion: Both methods were found to be effective in treating PPH, but thoracic sympathetic radiofrequency had a longer-term effect, a lower recurrence rate, and a lower incidence of intercostal neuralgia and compensatory hyperhidrosis than a thoracic sympathetic block.

[Response of Organic Carbon Loss to Soil Erosion and Its Drivers: A Meta-analysis].

Soil erosion is the main driving force of soil organic carbon (SOC) loss and plays an important role in the global carbon cycle. It is helpful to understand the mechanism of SOC loss under soil erosion by evaluating the main driving factors of SOC loss under soil erosion and their influence degree. Therefore, based on 24 cases published in domestic and foreign journals from 2007 to 2021, this study investigated the effects of soil erosion on SOC loss in China under different climatic factors (climate types, rainfall, and rainfall intensity) and soil factors (soil types, bulk density, and aggregate size) by using Meta-analysis. The results showed that:① compared with that under no erosion disturbance, the SOC content under erosion decreased significantly (overall decreased 16.0%), showing obvious negative response characteristics. ② Under the erosion background, the negative response degree of SOC to different factors was as follows:rainfall intensity (65.0%)>mean annual rainfall (24.3%)>soil types (21.4%)>bulk density (20.2%)>aggregate size (16.5%)>climate types (9.1%). ③ Principal component analysis showed that climate was the dominant factor affecting SOC loss, and rainfall intensity was again shown to be the key factor. In this study, the characteristics and influencing factors of SOC loss under soil erosion in China were analyzed, which provided theoretical reference for the systematic understanding of the role of soil erosion in the carbon cycle.

[Clinical Characteristics and Correlation with Prognosis of DLBCL with Bone Marrow Involvement and Chromosomal Abnormalities].

OBJECTIVE: To investigate the clinical characteristics of diffuse large B-cell lymphoma(DLBCL) patients with bone marrow involvement and chromosome abnormalities, and further analyze the correlation between the degree of chromosome abnormality and prognosis. METHODS: The clinical data of 88 patients diagnosed with DLBCL with bone marrow involvement and complete chromosomal findings in Shanxi Province Cancer Hospital were retrospectively analyzed. The χ2 test was used to analyze their clinical characteristics, and the Kaplan-Meier method was used in PFS and OS, and log-rank method in comparison. RESULTS: Chromosome abnormalities were detected in 31 of the 88 patients(35.2%), 15 of whom had complex karyotype(17.0%). The positive rate of BCL-2, BCL-6, C-MYC and Ki-67≥80% was high in patients with complex karyotype, and most of them are double expressor lymphoma. Survival analysis showed that patients with complex karyotype of DLBCL had poorer PFS and OS compared to those with normal karyotype and 1-2 chromosomal abnormalities. CONCLUSION: In DLBCL patients with bone marrow involvement and chromosome abnormalities, patients with complex karyotype have a shorter survival time.

Functional map of the macroglomerular complex of male Helicoverpa armigera.

The mechanism of sex pheromone reception in the male cotton bollworm Helicoverpa armigera has been extensively studied because it has become an important model system for understanding insect olfaction. However, the pathways of pheromone processing from the antenna to the primary olfactory center in H. armigera have not yet been clarified. Here, the physiology and morphology of male H. armigera olfactory sensory neurons (OSNs) were studied using single sensillum recording along with anterograde filling and intracellular recording with retrograde filling. OSNs localized in type A sensilla responded to the major pheromone component cis-11-hexadecenal, and the axonal terminals projected to the cumulus (Cu) of the macroglomerular complex (MGC). The OSNs in type B sensilla responded to the behavioral antagonist cis-9-tetradecenal, and the axonal terminals projected to the dorsomedial anterior (DMA) unit of the MGC. In type C sensilla, there were 2 OSNs: one that responded to cis-9-tetradecenal and cis-11-hexadecenol with the axonal terminals projecting to the DMA, and another that responded to the secondary pheromone components cis-9-hexadecenal and cis-9-tetradecenal with the axonal terminals projecting to the dorsomedial posterior (DMP) unit of the MGC. Type A and type B sensilla also housed the secondary OSNs, which were silent neurons with axonal terminals projected to the glomerulus G49 and DMP. Overall, the neural pathways that carry information on attractiveness and aversiveness in response to female pheromone components in H. armigera exhibit distinct projections to the MGC units.

The nutrient-sensing GCN2 signaling pathway is essential for circadian clock function by regulating histone acetylation under amino acid starvation.

Circadian clocks are evolved to adapt to the daily environmental changes under different conditions. The ability to maintain circadian clock functions in response to various stresses and perturbations is important for organismal fitness. Here, we show that the nutrient-sensing GCN2 signaling pathway is required for robust circadian clock function under amino acid starvation in Neurospora. The deletion of GCN2 pathway components disrupts rhythmic transcription of clock gene frq by suppressing WC complex binding at the frq promoter due to its reduced histone H3 acetylation levels. Under amino acid starvation, the activation of GCN2 kinase and its downstream transcription factor CPC-1 establish a proper chromatin state at the frq promoter by recruiting the histone acetyltransferase GCN-5. The arrhythmic phenotype of the GCN2 kinase mutants under amino acid starvation can be rescued by inhibiting histone deacetylation. Finally, genome-wide transcriptional analysis indicates that the GCN2 signaling pathway maintains robust rhythmic expression of metabolic genes under amino acid starvation. Together, these results uncover an essential role of the GCN2 signaling pathway in maintaining the robust circadian clock function in response to amino acid starvation, and demonstrate the importance of histone acetylation at the frq locus in rhythmic gene expression.

Conjugation of the glutelin hydrolysates-glucosamine by transglutaminase and functional properties and antioxidant activity of the products.

A novel mixture of glycopeptides was prepared from corn glutelin and glucosamine (GlcN). The functional properties and antioxidative activities of this mixture were investigated. Corn glutelin was limited hydrolyzed by Alcalase, and then its hydrolysates were glycosylated with GlcN by transglutaminase (TGase) to modify its main and side chain, respectively. Under the optimized conditions, the content of GlcN conjugated to peptides was 81.98 ± 1.98 mg/g glutelin peptides. According to electrospray ionization mass spectrometry (ESI-MS) analysis, there are two types of glycopeptides in the mixture, TGase and non-enzymatic glycated counterparts. Compared with original glutelin, the glycosylated glutelin hydrolysates exhibited better solubility in the pH range of 2-11 and other functional properties except foaming stability. Meanwhile, it is more easily digested by pepsin and trypsin, and possessed excellent antioxidative activities. It also exhibited cytoprotective effects and intracellular ROS scavenging activities in LO2 cells subjected to oxidative stress by oxidation with ethanol solution.

Neuronal architecture and functional mapping of the taste center of larval Helicoverpa armigera (Lepidoptera: Noctuidae).

The sense of taste plays a crucial role in herbivorous insects by discriminating nutrients from complex plant metabolic compounds. The peripheral coding of taste has been thoroughly studied in many insect species, but the central gustatory pathways are poorly described. In the present study, we characterized single neurons in the gnathal ganglion of Helicoverpa armigera larvae using the intracellular recording/staining technique. We identified different types of neurons, including sensory neurons, interneurons, and motor neurons. The morphologies of these neurons were largely diverse and their arborizations seemingly covered the whole gnathal ganglion. The representation of the single neurons responding to the relevant stimuli of sweet and bitter cues showed no distinct patterns in the gnathal ganglion. We postulate that taste signals may be processed in a manner consistent with the principle of population coding in the gnathal ganglion of H. armigera larvae.

The role of technetium-99m methoxyisobutyl isonitrile scintigraphy in predicting the therapeutic effect of chemotherapy against nasopharyngeal carcinoma.

BACKGROUND: The authors prospectively evaluated the correlation between technetium-99m methoxyisobutyl isonitrile ((99m) Tc-MIBI) accumulation in tumors and response to induction chemotherapy in patients with nasopharyngeal carcinoma (NPC). METHODS: Eighty-six patients with locally advanced NPC underwent single-photon emission computed tomography 15 minutes after an intravenous injection of 740 megabecquerels (20 mCi) (99m) Tc-MIBI before chemotherapy. The tumor uptake ratio (TUR) was calculated. Two weeks after the second cycle of combined chemotherapy with 5-fluorouracil (5-FU) and cisplatin (DDP), the tumor response rate was evaluated. The correlation between (99m) Tc-MIBI accumulation in tumors and response to chemotherapy with 5-FU/DDP was examined. RESULTS: Positive accumulation of (99m) Tc-MIBI in tumors was observed in 76 patients (88.4%). The tumor response was a complete response (CR) in 8 patients, a partial response (PR) in 68 patients, stable disease (SD) in 9 patients, and progressive disease (PD) in 1 patient. The response rate (CR and PR) to 5-FU/DDP chemotherapy in patients who had positive (99m) Tc-MIBI accumulation (tumor uptake ratio [TUR] >1.1) was higher than that in patients who had negative (99m) Tc-MIBI accumulation (TUR ≤ 1.1; 98.7% vs 10%; P < .001). CONCLUSIONS: Patients with negative (99m) Tc-MIBI accumulation were resistant to 5-FU/DDP chemotherapy. (99m) Tc-MIBI imaging in patients with NPC was capable of predicting tumor response to chemotherapy with 5-FU/DDP and can help in the selection of patients for induction chemotherapy.

Glycosylated zein as a novel nanodelivery vehicle for lutein.

Glucosamine-glycosylated zein (GLZ) generated by transglutaminase was developed as a novel delivery vehicle to prepare lutein-loaded glycosylated zein nanoparticles (GLZ-LUT). GLZ-LUT exhibited a polydispersed spherical microstructure, lutein was embedded into GLZ to form nanocomplexes via self-assembly, they had a lower zeta potential and an average particle size of less than 200 nm. Compared to lutein-loaded zein nanoparticles (Zein-LUT), the lutein entrapment efficiency of GLZ-LUT was increased from 81.55% to 89.60%. Infrared spectroscopy (FTIR) analysis results confirmed that zein was successfully modified and that lutein was encapsulated by hydrophobic zein and GLZ. Moreover, GLZ showed significantly higher solubilization of lutein than Zein-LUT and significantly improved the in vitro release of lutein in the simulated gastrointestinal tract. The in vitro antioxidant activity of lutein was also enhanced by the encapsulation of zein and glycosylated zein. These findings indicated that GLZ represent a potentially efficient and promising nanodelivery carrier for lutein compounds.

Astragaloside­IV modulates NGF­induced osteoblast differentiation via the GSK3β/β­catenin signalling pathway.

Astragaloside (AST) is derived from the Chinese herb Astragalus membranaceus, and studies have demonstrated that it promotes differentiation of bone marrow­derived mesenchymal stem cells (BMSCs). To the best of our knowledge, however, the functions of the component AST­IV in osteogenesis have not previously been elucidated. The present study aimed to verify the effects of AST­IV in osteogenesis. First, the proliferation and differentiation status of human BMSCs incubated with AST­IV were analysed and compared with a control (no AST­IV treatment). In order to determine the involvement of the glycogen synthase kinase (GSK)3ß signalling pathway in AST­IV, overexpression and inhibition of GSK3ß was induced during incubation of BMSCs with AST­IV. In order to investigate how neuronal growth factor (NGF) contributes to BMSCs differentiation, BMSCs were co­incubated with an anti­NGF antibody and AST IV, and then levels of osteogenesis markers were assessed. The results demonstrated for the first time that AST­IV contributed to BMSCs differentiation. Furthermore, the GSK3ß/ß­catenin signalling pathway was revealed to be involved in AST­IV­induced osteogenesis; moreover, AST­IV accelerated differentiation by enhancing the expression levels of NGF. In summary, the present study demonstrated that AST­IV promotes BMSCs differentiation, thus providing a potential target for the treatment of osteoporosis.

Fluacrypyrim, a novel STAT3 activation inhibitor, induces cell cycle arrest and apoptosis in cancer cells harboring constitutively-active STAT3.

STAT3 protein has an important role in oncogenesis and is a promising anticancer target. Herein, we demonstrate that a novel small molecule fluacrypyrim (FAPM) inhibits the growth of leukemia cells by a predominant G1 arrest with significant decrease of the protein and mRNA levels of cyclin D1. As cyclin D1 is transcriptionally regulated by STAT3, FAPM is then shown to markedly inhibit the STAT3 phosphorylation with marginal effect on the other signal transducers and activators of transcription, and without effect on phosphoinositide-3-kinase and mitogen-activated protein kinase pathways. Further analysis shows that FAPM significantly increases the protein tyrosine phosphatases (PTPs) activity in a dose-dependent manner, and the inhibition of PTP activation by sodium pervanadate reverses FAPM-induced suppression of STAT3 tyrosine phosphorylation, indicating an important role of PTP in the action of FAPM. Finally, FAPM treatment results in selective suppression of STAT3-mediated transcriptional activity and its downstream effectors, and subsequent induction of growth arrest and apoptosis in STAT3-dependent cancer cell lines. This study therefore identifies FAPM as a potent STAT3 activation inhibitor with possible therapeutic potential against malignancies with constitutive STAT3 activation.

1,3-Dithian-2-one azine.

In an asymmetric unit of the title compound, C(8)H(12)N(2)S(4), there are two crystallographically independent half mol-ecules lying on inversion centers. One of the mol-ecules is disordered over two positions with relative occupancies of 82.0 (2) and 18.0 (2) for the major and minor components. In the crystal structure, mol-ecules are linked into a three-dimensional framework via inter-molecular C-H⋯N hydrogen-bonding inter-actions.

Astragalus saponin IV promotes osteogenic differentiation of bone marrow mesenchymal stem cells via miR-21/NGF/BMP2/Runx2 pathway.

BACKGROUND: Astragalus saponin IV(AS- IV) extracted from tranditional Chinese medicine Radix Astragali Mongolici, which had been reported to have medicinal properties in treating several types of diseases. This study aimed at investigating the biological functions of AS-IV on bone marrow mesenchymal cells(BMSCs) differentiation, therefore, seeking for a better application of AS-IV on fracture or other orthopedic disorders. METHODS: AS-IV was co-incubated with BMSCs in vitro to testify whether it can influence the proliferation and differentiation of BMSCs. Cell proliferation activity was detected by Cell Counting Kit-8 (CCK-8), while its differentiation promoting capibility was obtained by alkaline phosphatase (ALP) activity assay and Alizarin red S staining. Besides, differentiation protein markers of preosteoblast was detected by western blots. Neuron growth factor antagonists (NGFA) and microRNA-21 (miR-21) inhibitors were co incubated with AS-IV to search the regulatory pathways it activated in BMSCs. RESULTS: AS-IV incubation boosted the proliferation of BMSCs, and accelerated the differentiating direction into preosteoblasts. Runx2, OPN, BMP2, OCN proteins were up regulated after AS- IV treatment. MiR-21/NGF/BMP2/Runx2 pathway can participate the biological effects of AS- IV on BMSCs. CONCLUSION: AS- IV might be used as a therapeutic agent for bone fracture or other orthopedic disorders.