PI3K/AKT confers intrinsic and acquired resistance to pirtobrutinib in chronic lymphocytic leukemia.

PURPOSE: Pirtobrutinib, a non-covalent Bruton's tyrosine kinase (BTK) inhibitor, has been approved as the first agent to overcome resistance to covalent BTK inhibitors (such as ibrutinib, acalabrutinib, and zanubrutinib). However, the mechanisms of pirtobrutinib resistance in chronic lymphocytic leukemia (CLL) remain poorly understood. METHODS: To investigate pirtobrutinib resistance, we established resistant cell models using BTK knock-out via CRISPR-Cas9 or chronic exposure to pirtobrutinib in MEC-1 cells. These models mimicked intrinsic or acquired resistance, respectively. We then analyzed differential protein expression between wild-type (WT) and resistant MEC-1 cells using Revers Phase Protein microArray (RPPA) and confirmed the findings through Western Blot. Additionally, we evaluated potential drugs to overcome pirtobrutinib resistance by conducting cell proliferation assays, apoptosis studies, and animal experiments using both sensitive and resistant cells. RESULTS: MEC-1 cells developed resistance to pirtobrutinib either through BTK knock-out or prolonged drug exposure over three months. RPPA analysis revealed significant activation of proteins related to the PI3K/AKT pathway, including AKT and S6, in the resistant cells. Western Blot confirmed increased phosphorylation of AKT and S6 in pirtobrutinib-resistant MEC-1 cells. Notably, both the PI3K inhibitor (CAL101) and the AKT inhibitor (MK2206) effectively reduced cell proliferation and induced apoptosis in the resistant cells. The anti-tumor efficacy of these drugs was mediated by inhibiting the PI3K/AKT pathway. In vivo animal studies further supported the potential of targeting PI3K/AKT to overcome both intrinsic and acquired resistance to pirtobrutinib. CONCLUSION: The PI3K/AKT pathway plays a crucial role in both intrinsic and acquired resistance to pirtobrutinib in CLL. Therapeutically targeting this pathway may offer a promising strategy to overcome pirtobrutinib resistance.

Quantification of binding capacity of natural products to target proteins by sensors integrating SERS labeling and photocrosslinked molecular probes.

Natural products-based screening of active ingredients and their interactions with target proteins is an important ways to discover new drugs. Assessing the binding capacity of target proteins, particularly when multiple components are involved, presents a significant challenge for sensors. As far as we know, there is currently no sensor that can accomplish high-throughput quantitative analysis of natural product-target protein binding capacity based on Raman spectroscopy. In this study, a novel sensor model has been developed for the quantitative analysis of binding capacity based on Surface-Enhanced Raman Spectroscopy (SERS) and Photocrosslinked Molecular Probe (PCMP) technology. This sensor, named SERS-PCMP, leverages the high throughput of molecular probe technology to investigate the active ingredients in natural products, along with the application of SERS labelling technology for target proteins. Thus it significantly improves the efficiency and accuracy of target protein identification. Based on the novel strategy, quantitative analysis of the binding capacity of 20 components from Shenqi Jiangtang Granules (SJG) to α-Glucosidase were completed. Ultimately, the binding capacity of these active ingredients was ranked based on the detected Raman Intensity. The compounds with higher binding capacity were Astragaloside IV (Intensity, 138.17), Ginsenoside Rh2 (Intensity, 87.46), Ginsenoside Rg3 (Intensity, 73.92) and Ginsenoside Rh1 (Intensity, 64.37), which all exceeded the binding capacity of the positive drug Acarbose (Intensity, 28.75). Furthermore, this strategy also performed a high detection sensitivity. The limit of detection for the enzyme using 0.1 mg of molecular probe magnetic nanoparticles (MP MNPs) was determined to be no less than 0.375 µg/mL. SERS-PCMP sensor integrating SERS labeling and photocrosslinked molecular probes which offers a fresh perspective for future drug discovery studies. Such as high-throughput drug screening and the exploration of small molecule-target protein interactions in vitro.

Dual Pathways in Catalytic Ammonia Oxidation by a Ruthenium Complex Bearing a Tetradentate Bipyridine-Bipyrazole Ligand: Isolation of a Diruthenium Intermediate with a µ-Hexazene Derivative.

We report herein chemical and electrochemical ammonia oxidation (AO) catalyzed by a Ru complex, [RuII(H2L)(pic)2]2+ [1, H2L = 6,6'-di(1H-pyrazol-3-yl)-2,2'-bipyridine, pic = 4-picoline], where H2L is a tetradentate ligand with a bipyridyl unit connected to two pyrazoles. 1 functions as an efficient electrocatalyst for the oxidation of NH3 to N2, with a low overpotential of 0.51 V vs Fc+/0 and a Faradaic efficiency of 96%. 1 also undergoes catalytic chemical AO using (4-BrPh)3N•+ as an oxidant, with a turnover number for N2 reaching 41. A novel binuclear complex, [RuIII(L)(pic)2(N2)RuIII(L)(pic)2]4+ (2), was isolated and structurally characterized in the catalytic chemical AO by 1. Complex 2 possesses a zigzag dianionic µ-hexazene unit where the N2 derived from ammonia oxidation is bonded to the pyrazoles, with an NN2-NN2 bond length of 1.3091(70) Å. 2 readily releases N2 upon treating with NH3. Based on experimental and DFT studies, in chemical AO the formation of an N-N bond is proposed to occur via bimolecular coupling of a ruthenium pyrazole imido intermediate to give 2; while in electrochemical AO the N-N bond is formed by nucleophilic attack of NH3 on the intermediate.

Kidney targeting and modulating macrophage polarization through AMPK signaling: Therapeutic mechanism of berberine in uric acid nephropathy.

Uric acid nephropathy (UAN), caused by a common metabolic disorder resulting from hyperuricemia (HUA), has an increasing incidence. Previous studies have shown that berberine (BBR) has clear urate-lowering and anti-inflammatory effects in UAN mice, but its mechanism needs to be further clarified. Therefore, Potassium Oxonate (PO) combined with hypoxanthine (HX) induced UAN mice model and MSU induced THP-1 cells polarization model were adopted to investigate the mechanism of BBR on UAN in terms of tissue distribution and molecular pharmacology. Study unveiled that BBR was first found to bind to red blood cells (RBCs), which were recognized and phagocytosed by monocytes, then recruited by the injured kidney. Subsequently, BBR was enriched and functional in damaged kidney. The results of in vivo experiments revealed that, BBR reduced UA, BUN, CRE levels as well as the release of TNF-α, IL-1ß, IL-18 and IL-6, and alleviated renal injury in UAN mice, as consistent with previous studies. Additionally, BBR decreased MCP-1 expression, while diminishing macrophage infiltration and decreasing M1 proportion as determined by RT-qPCR. In vitro experiments, demonstrated that MSU promoted inflammatory polarization of THP-1 cells, while BBR reduced synthesis of inflammatory factors and inhibited MSU-induced inflammatory polarization. These effects of BBR were dependent on AMPK activation along with indirect inhibition of NF-κB signaling pathway mediated. However, the anti-inflammatory and macrophage polarization regulation effects of BBR were completely reversed upon administration of Compound C, an AMPK inhibitor. Therefore, BBR ameliorated kidney injury via regulating macrophage polarization through AMPK, which has therapeutic potential for UAN patients.

9-Hydroxy-8-oxypalmatine, a novel liver-mediated oxymetabolite of palmatine, alleviates hyperuricemia and kidney inflammation in hyperuricemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Palmatine is a main bioactive alkaloid of Cortex Phellodendri, which has been commonly prescribed for the treatment of hyperuricemia (HUA) in China. The metabolites of palmatine were crucial to its prominent biological activity. 9-Hydroxy-8-oxypalmatine (9-OPAL) is a novel liver-mediated secondary oxymetabolite of palmatine. AIM OF THE STUDY: The current study was to assess the efficacy of 9-OPAL, a novel liver-mediated secondary oxymetabolite of palmatine derived from Cortex Phellodendri, in experimental HUA mouse model and further explore its underlying mechanism. MATERIALS AND METHODS: An in vitro metabolic experiment with oxypalmatine was carried out using liver samples. We separated and identified a novel liver metabolite, and investigated its anti-HUA effect in mice. HUA mice were induced by potassium oxonate and hypoxanthine daily for one week. After 1 h of modeling, mice were orally administered with different doses of 9-OPAL (5, 10 and 20 mg/kg). The pathological changes of the kidneys were evaluated using hematoxylin-eosin staining (H&E). The acute toxicity of 9-OPAL was assessed. The effects of 9-OPAL on serum levels of uric acid (UA), adenosine deaminase (ADA), xanthine oxidase (XOD), creatinine (CRE), blood urea nitrogen (BUN) and inflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA) or biochemical method. Furthermore, Western blot, quantitative real-time PCR (qRT-PCR) and molecular docking were used to investigate the effect of 9-OPAL on the expression of renal urate transporters and NLRP3 signaling pathway in HUA mice. RESULTS: 9-OPAL had been discovered to be a novel liver-mediated oxymetabolite of palmatine for the first time. Treatment with 9-OPAL significantly reduced the UA, CRE as well as BUN levels, and also effectively attenuated abnormal renal histopathological deterioration with favorable safety profile. Besides, 9-OPAL significantly decreased the serum and hepatic activities of XOD and ADA, dramatically inhibited the up-regulation of UA transporter protein 1 (URAT1) and glucose transporter protein 9 (GLUT9), and reversed the down-regulation of organic anion transporter protein 1 (OAT1). Additionally, 9-OPAL effectively mitigated the renal inflammatory markers (TNF-α, IL-1ß, IL-6 and IL-18), and downregulated the transcriptional and translational expressions of renal Nod-like receptor family pyrin domain containing 3 (NLRP3), caspase-1, apoptosis-associated speck-like (ASC) and IL-1ß in HUA mice. Molecular docking results revealed 9-OPAL bound firmly with XOD, OAT1, GLUT9, URAT1, NLRP3, caspase-1, ASC and IL-1ß. CONCLUSIONS: 9-OPAL was found to be a novel liver-mediated secondary metabolite of palmatine with favorable safety profile. 9-OPAL had eminent anti-hyperuricemic and renal-protective effects, and the mechanisms might be intimately associated with repressing XOD activities, modulating renal urate transporter expression and suppressing the NLRP3 inflammasome activation. Our investigation might also provide further experimental evidence for the traditional application of Cortex Phellodendri in the treatment of HUA.

Identification of potential shared gene signatures between gastric cancer and type 2 diabetes: a data-driven analysis.

Background: Gastric cancer (GC) and type 2 diabetes (T2D) contribute to each other, but the interaction mechanisms remain undiscovered. The goal of this research was to explore shared genes as well as crosstalk mechanisms between GC and T2D. Methods: The Gene Expression Omnibus (GEO) database served as the source of the GC and T2D datasets. The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify representative genes. In addition, overlapping genes between the representative genes of the two diseases were used for functional enrichment analysis and protein-protein interaction (PPI) network. Next, hub genes were filtered through two machine learning algorithms. Finally, external validation was undertaken with data from the Cancer Genome Atlas (TCGA) database. Results: A total of 292 and 541 DEGs were obtained from the GC (GSE29272) and T2D (GSE164416) datasets, respectively. In addition, 2,704 and 336 module genes were identified in GC and T2D. Following their intersection, 104 crosstalk genes were identified. Enrichment analysis indicated that "ECM-receptor interaction," "AGE-RAGE signaling pathway in diabetic complications," "aging," and "cellular response to copper ion" were mutual pathways. Through the PPI network, 10 genes were identified as candidate hub genes. Machine learning further selected BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 as hub genes. Conclusion: "ECM-receptor interaction," "AGE-RAGE signaling pathway in diabetic complications," "aging," and "cellular response to copper ion" were revealed as possible crosstalk mechanisms. BGN, VCAN, FN1, FBLN1, COL4A5, COL1A1, and COL6A3 were identified as shared genes and potential therapeutic targets for people suffering from GC and T2D.

Pyroptosis inhibitors MCC950 and VX-765 mitigate myocardial injury by alleviating oxidative stress, inflammation, and apoptosis in acute myocardial hypoxia.

Acute myocardial infarction (AMI) is a prevalent cardiovascular disease with high morbidity and mortality rates worldwide. Pyroptosis is an inflammatory form of programmed cell death that has been linked to various pathological conditions. However, its exact contribution to the onset and progression of heart injury in AMI has not yet fully elucidated. Herein, we established mouse AMI model by ligating the left anterior descending artery and performed transcriptome analysis during the early phase of AMI. Mouse HL-1 and human AC-16 cardiomyocytes were subjected to hypoxia to simulate ischemic injury in vitro. Our results revealed a significant activation of the inflammatory response at 3 h post-ligation, as confirmed by RNA sequencing. We identified the occurrence of NLRP3 inflammasome-mediated pyroptosis in the cardiac tissues of human cases with AMI, as well as in mouse models of AMI and hypoxia-induced cardiomyocytes, using immunohistochemistry staining and Western blotting assays. Concurrently, pharmacological inhibition of NLRP3 inflammasome-mediated pyroptosis with MCC950 and VX-765 effectively decreased hypoxia-induced cardiomyocytes injury, while mitigating myocardial oxidative stress, apoptosis and inflammation caused by hypoxia. Moreover, the circulating levels of gasdermin D (GSDMD), the pyroptosis executor, were remarkably elevated in the plasma of mice with early AMI and in the supernatant of hypoxia-exposed cardiomyocytes in a time-dependent manner using ELISA and Western blotting. Furthermore, the change in circulating GSDMD positively correlated with Creatine Kinase-MB (CK-MB) in the plasma of early-stage AMI mouse. In summary, these findings indicated a critical role for NLRP3 inflammasome-mediated pyroptosis in the progression of AMI, the administration of MCC950 and VX-765 may be attractive candidate therapeutic approaches for cardiac injury caused by acute hypoxia or even AMI. Additionally, the circulating GSDMD exhibits potential as a newly diagnostic biomarker for AMI.

Empowering caregivers of children with bronchiolitis obliterans: The effectiveness of an internet-based follow-up platform.

OBJECTIVE: Limited evidence on home care and need for long-term individualized follow-up highlight the importance of developing an Internet-based follow-up platform to support caregivers of children with Bronchiolitis Obliterans (BO). This Study aims to explore and test the potential benefits of this platform by comparing family management, medication compliance and clinical systems. STUDY DESIGN AND METHODS: A two-arm, single-blind randomized controlled trial was conducted on 168 children with BO and their families from January 2022 to October 2022. Families were randomly divided into Internet-based follow-up group and conventional follow-up group with a ratio of 1:1. Scores of family management measures (FaMM), 8-item of Morisky Medication Adherence (8-MMAS) and BO clinical symptoms of both groups were collected at three points of time: the day of discharge (T1), 3 months after discharge (T2), and 6 months after discharge (T3). The changes of each group due to intervention were compared by repeated-measures ANOVA. RESULTS: 90 families completed the trial, including 48 in the Internet-based follow-up group and 42 in the conventional follow-up group. The results showed a significant difference in the group-by-time interaction on the scores of Child's Daily Life, Condition Management Ability and Parental Mutuality (p < 0.05). No group-by-time effect was found on the scores of View of Condition Impact and Family Life Difficulty. Scores of BO clinical symptoms and MMAS-8 showed intra-group, inter-group, and group-by-time effects. CONCLUSIONS: The Internet-based follow-up platform can empower caregivers in enhancing effective family management, improving medication compliance in children with BO, and relieving patients' clinical symptoms. TRIAL REGISTRATION: Chinese Clinical Trials Registry of ChiCTR2200065121 (04/28/2022).

A simulation training of family management for parents of children with epilepsy: a randomized clinical trial.

BACKGROUND: Epilepsy is a chronic neurological disorder that is more likely to be diagnosed in children. The main treatment involves long-term use of anti-epileptic drugs and above all, home care is of great importance. As there has not been a widely accepted home care protocols, simulating a home care environment is necessary for caregivers to develop skills of proper home care. This study aims to evaluate the effectiveness of a simulation training of family management style (STOFMS) for parents of children with epilepsy in China. METHODS: A randomized controlled trial was conducted on 463 children with epilepsy and their families. They were recruited from March 2020 to November 2022 and randomly assigned to the STOFMS group or the conventional group in a 1:1 ratio. Scores of family management measures, 8-item of Morisky Medication Adherence and epilepsy clinical symptom of both groups were collected at three points of time: within 24 h after admission (T0), 3 months after discharge (T1), and 6 months after discharge (T2). Changes due to intervention were compared across groups by repeated-measures ANOVA. The study report followed the CONSORT 2010 checklist. RESULTS: There were statistically significant differences between the two groups at T2. A considerable increase over the baseline was observed in the total management level score and subscale scores in the STOFMS group at T1, compared with essentially no change in the control group. In terms of medication adherence, the STOFMS group performance improved greatly at T1 and T2 compared with the control group. The same result was also found in clinical efficacy at T2 (p < 0.05). CONCLUSION: STOFMS is an effective intervention to improve family management level, treatment adherence and clinical efficacy for children with epilepsy. TRIAL REGISTRATION: The registration number is ChiCTR2200065128. Registered at 18 October 2022, http://www.medresman.org.cn.

Discovery of drug targets based on traditional Chinese medicine microspheres (TCM-MPs) fishing strategy combined with bio-layer interferometry (BLI) technology.

Target discovery of natural products is a key step in the development of new drugs, and it is also a difficult speed-limiting step. In this study, a traditional Chinese medicine microspheres (TCM-MPs) target fishing strategy was developed to discover the key drug targets from complex system. The microspheres are composed of Fe3O4 magnetic nanolayer, oleic acid modified layer, the photoaffinity group (4- [3-(Trifluoromethyl)-3H-diazirin-3-yl] benzoic acid, TAD) layer and active small molecule layer from inside to outside. TAD produces highly reactive carbene under ultraviolet light, which can realize the self-assembly and fixation of drug active small molecules with non-selective properties. Here, taking Shenqi Jiangtang Granules (SJG) as an example, the constructed TCM-MPs was used to fish the related proteins of human glomerular mesangial cells (HMCs) lysate. 28 differential proteins were screened. According to the target analysis based on bioinformatics, GNAS was selected as the key target, which participated in insulin secretion and cAMP signaling pathway. To further verify the interaction effect of GNAS and small molecules, a reverse fishing technique was established based on bio-layer interferometry (BLI) coupled with UHPLC-Q/TOF-MS/MS. The results displayed that 26 small molecules may potentially interact with GNAS, and 7 of them were found to have strong binding activity. In vitro experiments for HMCs have shown that 7 active compounds can significantly activate the cAMP pathway by binding to GNAS. The developed TCM-MPs target fishing strategy combined with BLI reverse fishing technology to screen out key proteins that directly interact with active ingredients from complex target protein systems is significant for the discovery of drug targets for complex systems of TCM.

Reliability and validity assessment of the Chinese version of the Intrahospital Transport Safety Scale (IHTSS) in intensive care units.

BACKGROUND: Intrahospital transport of critically ill patients is a common practice in intensive care units (ICUs), where patients' safety is constantly challenged in high-intensity and dynamic environments. While Intrahospital Transport Safety Scale (IHTSS) is widely used internationally to evaluate the intrahospital transport safety, it has not been introduced in China. OBJECTIVES: This study aimed to assess the reliability and validity of the Chinese version of the IHTSS scale among critical care nurses in China. METHODS: A cross-sectional study was conducted using a cluster sampling method. A total of 544 critical care nurses from 25 ICUs in 10 tertiary hospitals were recruited. We employed exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to examine the questionnaire's underlying factor structure, ensuring construct validity. Additionally, internal consistency was assessed using Cronbach's alpha coefficient, test-retest reliability, and corrected item-total correlation. RESULTS: The Chinese version of the scale displayed robust psychometric properties, with a Cronbach's α coefficient of 0.976, a split-half reliability of 0.906, and a test-retest reliability of 0.856. EFA revealed a robust four-factor model that accounted for 75.970% of the variance, with the factor loadings of the items ranging from 0.433 to 0.951. CFA indicated a strong model fit, with a chi-square to degrees of freedom ratio (CMIN/DF) of 2.765, comparative fit index (CFI) of 0.943, incremental fit index (IFI) of 0.943, and goodness-of-fit index (GFI) of 0.845, supporting the efficacy of the four-factor model in assessing intrahospital transport safety for critically ill patients. CONCLUSION: The Chinese version of the IHTSS demonstrated favourable reliability and validity among critical care nurses in China, making it a suitable tool for measuring the level of intrahospital transport safety for critically ill patients.

Characterizing identity by descent segments in Chinese interpopulation unrelated individual pairs.

Identity by descent (IBD) segments, uninterrupted DNA segments derived from the same ancestral chromosomes, are widely used as indicators of relationships in genetics. A great deal of research focuses on IBD segments between related pairs, while the statistical analyses of segments in irrelevant individuals are rare. In this study, we investigated the basic informative features of IBD segments in unrelated pairs in Chinese populations from the 1000 Genome Project. A total of 5922 IBD segments in Chinese interpopulation unrelated individual pairs were detected via IBIS and the average length of IBD was 3.71 Mb in length. It was found that 17.86% of unrelated pairs shared at least one IBD segment in the Chinese cohort. Furthermore, a total of 49 chromosomal regions where IBD segments clustered in high abundance were identified, which might be sharing hotspots in the human genome. Such regions could also be observed in other ancestry populations, which implies that similar IBD backgrounds also exist. Altogether, these results demonstrated the distribution of common background IBD segments, which helps improve the accuracy in pedigree studies based on IBD analysis.

4 mC site recognition algorithm based on pruned pre-trained DNABert-Pruning model and fused artificial feature encoding.

DNA 4 mC plays a crucial role in the genetic expression process of organisms. However, existing deep learning algorithms have shortcomings in the ability to represent DNA sequence features. In this paper, we propose a 4 mC site identification algorithm, DNABert-4mC, based on a fusion of the pruned pre-training DNABert-Pruning model and artificial feature encoding to identify 4 mC sites. The algorithm prunes and compresses the DNABert model, resulting in the pruned pre-training model DNABert-Pruning. This model reduces the number of parameters and removes redundancy from output features, yielding more precise feature representations while upholding accuracy.Simultaneously, the algorithm constructs an artificial feature encoding module to assist the DNABert-Pruning model in feature representation, effectively supplementing the information that is missing from the pre-trained features. The algorithm also introduces the AFF-4mC fusion strategy, which combines artificial feature encoding with the DNABert-Pruning model, to improve the feature representation capability of DNA sequences in multi-semantic spaces and better extract 4 mC sites and the distribution of nucleotide importance within the sequence. In experiments on six independent test sets, the DNABert-4mC algorithm achieved an average AUC value of 93.81%, outperforming seven other advanced algorithms with improvements of 2.05%, 5.02%, 11.32%, 5.90%, 12.02%, 2.42% and 2.34%, respectively.

Improving the geographical origin classification of Radix glycyrrhizae (licorice) through hyperspectral imaging assisted by U-Net fine structure recognition.

Radix glycyrrhizae (licorice) is extensively employed in traditional Chinese medicine, and serves as a crucial raw material in industries such as food and cosmetics. The quality of licorice from different origins varies greatly, so classification of its geographical origin is particularly important. This study proposes a technique for fine structure recognition and segmentation of hyperspectral images of licorice using deep learning U-Net neural networks to segment the tissue structure patterns (phloem, xylem, and pith). Firstly, the three partitions were separately labeled using the Labelme tool, which was utilized to train the U-Net model. Secondly, the obtained optimal U-Net model was applied to predict three partitions of all samples. Lastly, various machine learning models (LDA, SVM, and PLS-DA) were trained based on segmented hyperspectral data. In addition, a threshold method and a circumcircle method were applied to segment licorice hyperspectral images for comparison. The results revealed that compared with the threshold segmentation method (which yielded SVM classifier accuracies of 99.17%, 91.15%, and 92.50% on the training set, validation set, and test set, respectively), the U-Net segmentation method significantly enhanced the accuracy of origin classification (99.06%, 94.72% and 96.07%). Conversely, the circumcircle segmentation method did not effectively improve the accuracy of origin classification (99.65%, 91.16% and 92.13%). By integrating Raman imaging of licorice, it can be inferred that the U-Net model, designed for region segmentation based on the inherent tissue structure of licorice, can effectively improve the accuracy origin classification, which has positive significance in the development of intelligence and information technology of Chinese medicine quality control.

C-H Bond Activation by a Seven-Coordinate Bipyridine-Bipyrazole Ruthenium(IV) Oxo Complex.

Ruthenium-oxo species with high coordination numbers have long been proposed as active intermediates in catalytic oxidation chemistry. By employing a tetradentate bipyridine-bipyrazole ligand, we herein reported the synthesis of a seven-coordinate (CN7) ruthenium(IV) oxo complex, [RuIV(tpz)(pic)2(O)]2+ (RuIVO) (tpz = 6,6'-di(1H-pyrazol-1-yl)-2,2'-bipyridine, pic = 4-picoline), which exhibits high activity toward the oxidation of alkylaromatic hydrocarbons. The large kinetic isotope effects (KIE) for the oxidation of DHA/DHA-d4 (KIE = 10.3 ± 0.1) and xanthene/xanthene-d2 (KIE = 17.2 ± 0.1), as well as the linear relationship between log (rate constants) and bond dissociation energies of alkylaromatics, confirmed a mechanism of hydrogen atom abstraction.

Analysis of related factors of behavioral problems in children with congenital pseudarthrosis of tibia

SUMMARY OBJECTIVE: This study aimed to investigate the factors associated with behavioral problems in children with congenital pseudarthrosis of the tibia. METHODS: Random sampling is utilized to obtain a sample of 90 patients. The behavioral problems of the patients are detected by Achenbach Children's Behavior Scale. Parental emotional problems are investigated by the Self-Rating Depression Scale and Self-Rating Anxiety Scale. RESULTS: The results demonstrate that the detection rate of behavioral problems in children with congenital pseudarthrosis of the tibia is 53.3% (48/90). Among these behavioral problems, an abnormal rate is higher in the four dimensions: thinking, violation of discipline, social interaction, and aggression. The anxiety and depression scores of caregivers are statistically higher in the abnormal group than in the normal group. The results of the multivariate analysis show that the anxiety degree of the parents had a significant impact on the behavior of the children. CONCLUSIONS: Children with congenital pseudarthrosis of the tibia are facing the issues of high rates of behavioral problems. Parents of children with congenital pseudarthrosis of the tibia had higher levels of anxiety and depression than parents of normal children. The anxiety and depressive state of mind of parents or caregivers had a significant impact on the behavior of children with congenital pseudarthrosis of the tibia.

Induction of defense-related enzymes in patchouli inoculated with virulent Ralstonia solanacearum

Background: Defense-related anti-oxidative response is a vital defense mechanism of plants against pathogen invasion. Ralstonia solanacearum is an important phytopathogen. Bacterial wilt caused by R. solanacearum is the most destructive disease and causes severe losses in patchouli, an important aromatic and medicinal plant in Southeast Asia. The present study evaluated the defense response of patchouli inoculated with virulent R. solanacearum. Results: Results showed that the basic enzymatic activities differed not only between the leaves and stems but also between the upper and lower parts of the same organ of patchouli. POD, SOD, PPO, and PAL enzymatic activities were significantly elevated in leaves and stems from patchouli inoculated with R. solanacearum compared to those in control. The variation magnitude and rate of POD, PPO, and PAL activities were more obvious than those of SOD in patchouli inoculated with R. solanacearum. PAGE isoenzymatic analysis showed that there were one new POD band and two new SOD bands elicited, and at least two isoformic POD bands and two SOD bands were observably intensified compared to the corresponding control. Conclusion: Our results suggest that not only defense-related enzymatic activities were elevated but also the new isoenzymatic isoforms were induced in patchouli inoculated with R. solanacearum.