Activity Of Complexes Research Articles

Activity recognition based on spatio-temporal features with transfer learning

<span lang="EN-US">Human action recognition (HAR) has gathered significant attention recently due to its high demand in various application domains. We explore different CNN architectures for extracting Spatio-Temporal features. In addition to spatial correlation in 2D images, video actions also own the temporal domain attributes. Many research attempts addressed simple activity recognition, but complex activity recognition is still challenging. In the proposed work, the concept of transfer learning consists of two pre-trained networks, ResNet50 and VGG16, which are used to extract Spatiotemporal features and are later fused using the averaging method. Pre-processed frames are considered for the pre-trained network, the pre-processing consists of frame extraction, resizing, and contrast enhancement. The fused features are trained using a multiclass non-linear SVM classifier that achieved an accuracy of 89.71% on the UCF-101 database.</span>

Synthesis of Cd (II), Fe (III), Cu (II), and Cr (VI) complexes of Schiff bases and their antibacterial activities

Schiff base and the metal derivatives have been utilized in numerous areas of the economy. Synthesis and antibacterial activities of Cd (II), Cr (VI), Cu (II), and Fe (III) complexes of Schiff bases were evaluated in this work. Complexes synthesized were Bis(1-phenyl-3-methyl-4-Phenyl acetyl 5-pyrazolone)Cadmium (II) (Cd(HPMPP)2), Tris(1-phenyl-3-methyl-4-benzoyl-5-pyrazolone)Iron(III)(Fe(HPMBP)3), Bis(1-phenyl-3-methyl-4-phenylacetyl-5-pyrazolone)Copper (II) (Cu(HPMPP)2), Hexakis(1-phenyl-3-methyl-4-palmitoyl-5-pyrazolone)Chromium (VI) (Cr(HPMPP)6), and Tris(1-phenyl-3-methyl-4- palmitoyl-5-pyrazolone)Iron (III) (Fe(HPMPP)3). The physical state, colour, and melting point of these complexes were determined using appropriate analytical techniques. Results showed that all the complexes were crystalline in nature; their colours were variable, while their melting points were sharp. The solubility of these complexes in deionized water, acetone, methanol, and ethanol was also carried out. The outcome revealed that all the metal complexes were insoluble in deionized water, Cr(HPMPP)6 was soluble in acetone, methanol, and ethanol. However, the solubility of other metal complexes in the organic solvents used was variable. The antibacterial activities of these metal complexes at different concentrations were also tested against distilled water, E. coli, S. aureus, B. subtillus, and S. typhi. The results showed that, antimicrobial activity of these complexes against distilled water was negative whereas, the bacterial growth of all the bacteria was inhibited by the complexes though at different rates. The inhibition rate of microorganisms was inversely proportional to the concentration of the complexes. The antibacterial activities of Cd(HPMPP)2 and Cr(HPMPP)6 were outstanding against the growth of all the bacteria. Thus, a proper processing of these complexes might result in excellent antibacterial drugs. However, more studies on the mode of action of these complexes against microorganisms and their toxicity should be done in order to establish their potentials for pharmaceutical applications.

Curcumin protects against aging-related stress and dysfunction through autophagy activation in rat brain.

Curcumin (Curcuma longa) is a well-known medicinal plant that induces autophagy in various model species, helping maintain cellular homeostasis. Its role as a caloric restriction mimetic (CRM) is being investigated. This study explores the potential of curcumin (CUR), as a CRM, to provide neuroprotection in D galactose induced accelerated senescence model of rats through modulation of autophagy. For six weeks, male rats received simultaneous supplementation of D-gal (300mg/kg b.w., subcutaneously) and CUR (200mg/kg b.w., oral). The oxidative stress indices, antioxidants, and electron transport chain complexes in brain tissues were measured using standard methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) gene expression analysis was used to evaluate the expression of autophagy, neuroprotection, and aging marker genes. Our results show that curcumin significantly (p ≤ 0.05) enhanced the level of antioxidants and considerably lowered the level of oxidative stress markers. Supplementing with CUR also increased the activity of electron transport chain complexes in the mitochondria of aged brain tissue, demonstrating the antioxidant potential of CUR at the mitochondrial level. CUR was found to upregulate the expression of the aging marker gene (SIRT-1) and the genes associated with autophagy (Beclin-1 and ULK-1), as well as neuroprotection (NSE) in the brain. The expression of IL-6 and TNF-α was downregulated. Our findings demonstrate that CUR suppresses oxidative damage brought on by aging by modulating autophagy. These findings imply that curcumin might be beneficial for neuroprotection in aging and age-related disorders.

Planning for the Implementation of Fine Motor Work Therapy Activities for Special Needs Pupils

Occupational therapy activities can assist pupils with special needs in resolving some of their fine motor issues. Teachers should increase special needs pupils' pre-writing preparation with planned and structured activities that are methodical and have increasing qualities. This study aimed to observe how far Special Education teachers could go in planning appropriate activities based on their pupils' abilities by selecting occupational therapy activities and then sharing the potential impact expectations of fine motor ability of special needs pupils, particularly pupils with learning difficulties. This is a qualitative study that employs the hands-on method, observation, discussion, and interviews with 41 teachers and 17 pupil management assistants who participated in a continuous professional development course, which the researcher conducted at the Institute of Teacher Education Campus level and were able to produce a planning of activities that has the learned characteristics of advanced tolerance, focus, adaptability, and choosing the simplest to most complex occupational therapy activities. Furthermore, teachers can share the outcomes of activity planning and group discussion, as well as set expectations for the potential of the targeted pupils. Finally, this study suggests that special education teachers should collaborate and receive professionalism training on an ongoing basis to foster the proliferation of ideas and skills in planning appropriate activities to improve the fine motor skills of pupils with special needs.

Productive dynamics of Sugarcane (Saccharum officinarum l.) in the Brejo Paraibano Microregion, Brazil

The academic article analyzed the productive dynamics of sugarcane in the Brejo Paraibano Microregion from 2017 to 2022. The objective was to understand the factors influencing the performance of this agricultural culture, emphasizing the importance of efficient management of cultural practices and fertilization for the quality of sugarcane fields. The study methodologically involved data analysis and systematic review of specialized literature. The results indicated variations in planted area, quantity produced, and productivity, influenced by climatic conditions and agricultural practices. In summary, it was possible to conclude that sugarcane agricultural production is a complex and dynamic activity, with strategies and innovations linked to sustainability present in this context, aiming at the economic and social development of the Brejo Paraibano region. Sugarcane activity is a complex and dynamic activity in agricultural production, and it is possible to highlight the importance of an integrated and holistic approach to understanding and improving the sector's performance in the specific context of the Brejo Paraibano region. Keywords: Sugarcane Agriculture, Agricultural Management, Economic Sustainability.

Explainable AI for myocardial infarction using the vectorcardiogram

Abstract Background and purpose Myocardial infarction (MI), a widespread cardiovascular ailment, often lacks immediate patient awareness being early and accurate MI diagnosis crucial for lifesaving interventions. In artificial intelligence studies, ECG signals are extensively explored, while fewer examine the potential of vectorcardiogram (VCG) which offers a three-dimensional cardiac dipole representation. Traditional Machine Learning methods manually extract features; some studies advocate VCG features. Deep Learning, especially Convolutional Neural Networks (CNN), automates feature extraction. Although ECG contains redundant information from the VCG's 12 projections, no studies directly apply CNNs to VCG, nor assess the impact of redundancy on predictive ability. This study aims to bridge this gap by investigating CNNs' diagnostic capabilities with VCG inputs, specifically focusing on improving MI classification. Methods The PTB-XL database was used for this study, containing 10-seconds ECG data from various pathologies, including MI. The database encompasses 9,481 records from healthy patients and 4,129 records from patients with MI. Data was divided into 80% for training and 20% for testing. Consequently, the dataset was expanded to have 52% representing MI and 48% representing healthy cases. We designed a 1D-CNN classifier (Figure 1.A) with three convolutional layers. The network was trained using both ECG and VCG reconstruction through the Inverse Dower Transform. Results The trained model achieved accuracy values of 0.895 and 0.914 for the test set when utilizing ECG and VCG, respectively. These results underscore how the information condensation in the VCG contributes to an enhanced predictive capacity of the model. In a qualitative analysis, activation maps extracted from the CNN illustrate heightened activation in the QRS complex when the disease is present, contrasting with diminished activation in its absence. These maps depict the weight assigned to each signal segment, enabling the classification of signals into healthy and diseased categories. The presented figure exemplifies a notable activation in the QRS loop in the case of myocardial infarction (MI), aligning with the observed alteration in the cardiac signal associated with this pathology (Figure 1.B). Conclusion In this study, an interpretable CNN has been designed for MI detection, with the VCG yielding better results than the ECG for this task due to information compression. This provides a new insight for enhancing classification capability in Deep Learning models, allowing for advancements in the MI detection.

Prediction of the success of electrical cardioversion in patients with atrial fibrillation using parameters obtained by spectral and vectorcardiographic analysis of the ECG

Abstract Introduction Electrical cardioversion (ECV) still presents a treatment option for atrial fibrillation (AF). Despite the great success rate in the acute setting, its long-term success rate is low. The aim of the study was to find predictors of SR maintenance after ECV using spectral and vectorcardiographic (VCG) analysis of the ECG curve. Methods Consecutive patients with AF referred for elective ECV were prospectively enrolled. The digital ECG recording obtained before the ECV was analyzed using spectral and VCG analysis. All patients had Holter monitoring and clinical follow-up three months after cardioversion to assess SR maintenance. Atrial fibrillation activity was analyzed by spectral analysis, determining the dominant frequency (DF), RI (regularity index) and OI (organization index). QRS complexes were analyzed by vectorcardiography and dXmean, dYmean and dZmean (derivation of VCG signals) parameters were determined. Using logistic regression (LR) with backward parameter reduction, separate and combined predictive models of SR maintenance were calculated based on both the analysis from the VCG data and the spectral analysis data. Additional models with a forward selection of clinical variables were also calculated. The efficiency of the models was evaluated on a separate test subset of the data (N=32). Results A total of 80 patients were enrolled (age 70+10 years, 48 (64%) men, CHADSVASc 3.17+1.5, BMI 29.75kg/m2). At the 3-month follow-up, AF recurrence was present in 36 patients (45%). Using only vectorcardiographic parameters, dXmean (OR 3.07, 95 %CI 1.14- 8.63), p=0.001) and dYmean (OR 0.26, 95% CI 0.09-0.72), p <0.001) best predicted the SR maintenance (AUC of 0.72). Using only spectral analysis parameters, the best predictor was DF (OR 3.07, 95%CI 1.14-8.63), p=0.012) with AUC of 0.66. By combining the results of spectral analysis and vectorcardiography, an AUC of 0.78 was achieved. Among the clinical parameters, the most significant predictors were insufficiently controlled arterial hypertension and previous history of stroke. Conclusion Digital analysis of ECG curves using deeper mathematical models provides a better predictive model than classical clinical and echocardiographic models. The combination of spectral analysis of fibrillation atrial activity and vectorocardiographic analysis of QRS complexes revealed more accurate predictive information compared to both analyses alone.

#2528 Comparing patient-reported and performance-based physical function assessments in hemodialysis: insights from the CONVINCE trial

Abstract Background and Aims Physical function is a crucial outcome in nephrology. In alignment with the Patient-Reported Outcomes Measurement Information System (PROMIS) Initiative, physical function is characterized as the ability to execute activities involving physical actions, ranging from self-care to more complex activities, such as social activities. This definition of physical function spans various domains of the International Classification of Functioning, Health, and Disability (ICF). The assessment of physical function commonly employs two distinct approaches, patient-reported outcomes (PRO) and observed performance outcomes (PerfO). PRO and PerfO assessments have distinct advantages and limitations and were found to correlate only moderately, adding complexity to cross-instrument outcome comparisons and interpretation. Despite this, there is limited understanding of the factors contributing to the discordance between PRO and PerfO assessments in patients with kidney disease. In this study, we applied a previously established common T-score metric for patient-reported and performance-based physical function to compare patterns of associations with potential laboratory-based, psychosocial, sociodemographic, and health-related determinants in hemodialysis patients. Method Cross-sectional data from the baseline assessment of the CONVINCE trial (N = 1,132), a multinational randomized controlled trial comparing high-dose hemodiafiltration with high-flux hemodialysis, were analysed. To investigate the relationships between potential determinants and performance-based versus patient-reported physical function, we performed multiple linear regression analysis. Dependent variables were standardized T-scores derived from the PROMIS physical function short-form 4a (PRO) and the Physical Performance Test (PerfO). Both measures assess a generic concept of physical function. We compared the effect sizes of each potential determinant in the multiple regression model using partial f2 values, with thresholds of 0.02, 0.15, and 0.35 denoting small, medium, and large effects. Results Both, PerfO and PRO exhibited significant associations with a laboratory marker-based indicator of muscle mass (simplified creatinine index), albeit with relatively small effects (partial f² of 0.04 and 0.05, respectively). None of the other laboratory measures investigated in this study showed any relevant associations with physical functioning. Age demonstrated a negative association with physical function, with a larger effect size observed for performance-based (partial f² = 0.11) compared to patient-reported physical function (partial f² = 0.04). In contrast to performance-based physical function, patient-reported physical function displayed a stronger association with self-reported health domains, particularly pain interference and fatigue. Exploring the differences between patient-reported and performance-based T-scores at the individual level, we found that younger age and more cognitive/emotional fatigue were associated with lower patient-reported compared to performance-based physical function (small effect sizes). Conclusion PRO and PerfO assessments of physical function in hemodialysis patients had similar associations with the simplified creatinine index, suggesting comparable links to objective physical impairment. However, PRO-based physical function exhibited a notably stronger association with other patient-reported variables, suggesting that patient-reported constructs of physical function might represent more than just capability, but ‘capability free from symptomatic constraints’. This distinction should be taken into account when directly comparing or aggregating PRO and PerfO scores. A noteworthy aspect of our study is the utilization of a common T-score metric for both PRO and PerfO measures. This method enhances interpretability of results and facilitates comparisons across diverse assessment types, thereby offering valuable insights into the determinants of physical function in patients undergoing hemodialysis.

Molecular Insights into Female Hybrid Sterility in Interspecific Crosses between Drosophila melanogaster and Drosophila simulans

Species of the genus Drosophila have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are under-investigated. Here, we performed an analysis of hybrid female sterility by crossing Drosophila melanogaster females and Drosophila simulans males. Using transcriptomic data analysis and molecular, cellular, and genetic approaches, we analyzed differential gene expression, transposable element (TE) activity, piRNA biogenesis, and functional defects of oogenesis in hybrids. Premature germline stem cell loss was the most prominent defect of oogenesis in hybrid ovaries. Because of the differential expression of genes encoding piRNA pathway components, rhino and deadlock, the functional RDCmel complex in hybrid ovaries was not assembled. However, the activity of the RDCsim complex was maintained in hybrids independent of the genomic origin of piRNA clusters. Despite the identification of a cohort of overexpressed TEs in hybrid ovaries, we found no evidence that their activity can be considered the main cause of hybrid sterility. We revealed a complicated pattern of Vasa protein expression in the hybrid germline, including partial AT-chX piRNA targeting of the vasasim allele and a significant zygotic delay in vasamel expression. We arrived at the conclusion that the hybrid sterility phenotype was caused by intricate multi-locus differences between the species.

The OGT-c-Myc-PDK2 axis rewires the TCA cycle and promotes colorectal tumor growth.

Deregulated glucose metabolism termed the "Warburg effect" is a fundamental feature of cancers, including the colorectal cancer. This is typically characterized with an increased rate of glycolysis, and a concomitant reduced rate of the tricarboxylic acid (TCA) cycle metabolism as compared to the normal cells. How the TCA cycle is manipulated in cancer cells remains unknown. Here, we show that O-linked N-acetylglucosamine (O-GlcNAc) regulates the TCA cycle in colorectal cancer cells. Depletion of OGT, the sole transferase of O-GlcNAc, significantly increases the TCA cycle metabolism in colorectal cancer cells. Mechanistically, OGT-catalyzed O-GlcNAc modification of c-Myc at serine 415 (S415) increases c-Myc stability, which transcriptionally upregulates the expression of pyruvate dehydrogenase kinase 2 (PDK2). PDK2 phosphorylates pyruvate dehydrogenase (PDH) to inhibit the activity of mitochondrial pyruvate dehydrogenase complex, which reduces mitochondrial pyruvate metabolism, suppresses reactive oxygen species production, and promotes xenograft tumor growth. Furthermore, c-Myc S415 glycosylation levels positively correlate with PDK2 expression levels in clinical colorectal tumor tissues. This study highlights the OGT-c-Myc-PDK2 axis as a key mechanism linking oncoprotein activation with deregulated glucose metabolism in colorectal cancer.

Neuroprotection effects of kynurenic acid-loaded micelles for the Parkinson’s disease models

Anti-glutamatergic agents may have neuroprotective effects against excitotoxicity that is known to be involved in the pathogenesis of Parkinson’s disease (PD). One of these agents is kynurenic acid (KYNA), a tryptophan metabolite, which is an endogenous N-methyl-D-aspartic acid (NMDA) receptor antagonist. However, its pharmacological properties of poor water solubility and limited blood–brain barrier (BBB) permeability rules out its systemic administration in disorders affecting the central nervous system. Our aim in the present study was to investigate the neuroprotective effects of KYNA-loaded micelles (KYNA-MICs) against PD in vitro and in vivo. Lipid-based micelles (MICs) in conjunction with KYNA drug delivery have the potential to enhance the penetration of therapeutic drugs into a diseased brain without BBB obstacles. KYNA-MICs were characterized by particle size (105.8 ± 12.1 nm), loading efficiency (78.3 ± 4.23%), and in vitro drug release (approximately 30% at 24 h). The in vitro experiments showed that KYNA-MICs effectively reduced 2-fold protein aggregation. The in vivo studies revealed that KYNA was successfully delivered by 5-fold increase in neurotoxin-induced PD brains. The results showed significant enhancement of KYNA delivery into brain. We also found that the KYNA-MICs exhibited several therapeutic effects. The KYNA-MICs reduced protein aggregation of an in vitro PD model, ameliorated motor functions, and prevented loss of the striatal neurons in a PD animal model. The beneficial effects of KYNA-MICs are probably explained by the anti-excitotoxic activity of the treatment’s complex. As the KYNA-MICs did not induce any appreciable side-effects at the protective dose applied to a chronic PD mouse model, our results demonstrate that KYNA provides neuroprotection and attenuates PD pathology.

The impact of personality and self-efficacy on domain modeling productivity in graphical and textual notations

ContextSoftware development is a complex and human-intensive activity, where human factors can have a significant impact on productivity and quality of results. To address the complexity of software, domain modeling has gained much importance, mainly due to software methodologies such as Model-Driven Engineering and Domain-Driven Design. In particular, domain modeling is an essential task that allows developers to understand and effectively represent the problem domain. However, domain modeling productivity can be affected by several human factors, including developers' personality and self-efficacy. ObjectiveThe study aims to explore the influence of human factors, specifically developers' personality and self-efficacy, on domain modeling productivity in graphical and textual notations. MethodAn empirical controlled study was conducted with 134 third-year computer science students from the University of Alicante, guided by the definition of a theoretical model based on previous studies. The participants were tasked with creating domain models in both graphical and textual notations. The order in which the notations were used was randomized, and the participants were given different system specifications to model. After modeling, 98 participants completed questionnaires assessing their personality, self-efficacy, and notation satisfaction. The design and evaluation of the experiment employed the Goal, Question, and Metrics framework. Data analysis was performed using a stepwise selection method to select the most appropriate regression model. ResultsThe study indicates that personality and self-efficacy have a significant impact on the performance of junior domain model developers. Specifically, it was discovered that while neuroticism had a negative impact on efficiency in both notations, developers' ability belief and use of graphical notation had a positive influence on effectiveness and efficiency in creating domain models. ConclusionsThese findings highlight the importance of considering human factors and notation choice in software development. Developers' personality and self-efficacy emerge as critical considerations for enhancing both productivity and quality in domain modeling.

Abstract IA022: AI in bladder cancer pathology and research: What can we expect and what not?

Abstract Artificial intelligence (AI) applications are rapidly evolving, disruptive technologies that recently attracted tremendous public awareness including euphoria, bull runs at stock exchanges but also criticism and skepticism. Pathology, a crucial clinical diagnostic discipline, faces significant challenges despite its critical role and broad scope. A notable issue is the declining interest among medical graduates in pursuing further training in Surgical Pathology and Molecular Pathology. This disinterest is compounded by a trend towards part-time work and the aging demographic in Western industrial nations, which increases the demand for precise cancer diagnoses, molecular pathology and advanced oncological treatments. As the need for skilled pathologists grows, the availability of these professionals is steadily decreasing. Furthermore, political policies in heavily regulated healthcare systems (e.g., Germany) are exacerbating the shortage by limiting residency and specialist training positions despite the growing need. Adding to the reluctance among medical graduates to consider pathology as discipline is the looming “threat”” of replacing the field with Artificial Intelligence (AI) technologies. However, historical precedents suggest that necessity often spurs significant innovation. AI's role in pathology is expanding, reshaping the field with new technological advancements. AI, broadly encompassing various computational algorithms designed to perform tasks typically requiring human intelligence such as learning, reasoning, and pattern recognition, is now being applied extensively across different domains including medical diagnostics. Recent implementations in pathology include AI-driven algorithms that automate processes such as the Gleason grading of prostate biopsies, lymph node metastasis detection, detection of molecular bladder cancer subtypes or grading of kidney cancer showing high accuracy levels, speed and reproducibility in delivering results. These tools, while they do not replace pathologists, significantly reduce their workload by automating routine tasks, thus freeing up time for more complex diagnostic activities or simply dealing with the increasing workload. Despite the exciting possibilities, the use of AI in predicting molecular alterations, such as FGFR3 mutations in bladder cancer, faces limitations due to insufficient sensitivity and specificity, indicating that such technologies are not yet suitable for screening purposes. In conclusion, AI is increasingly vital in addressing the challenges of modern pathology, particularly in compensating for the shortage of pathologists. As technology advances, its integration into clinical practice offers promising solutions to enhance diagnostic accuracy and efficiency in uropathology, paving the way for more personalized and effective patient care. Citation Format: Markus Eckstein. AI in bladder cancer pathology and research: What can we expect and what not? [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr IA022.

A novel MT-ATP6 variant associated with complicated ataxia in two unrelated Italian patients: case report and functional studies

BackgroundMT-ATP6 is a mitochondrial gene which encodes for the intramembrane subunit 6 (or A) of the mitochondrial ATP synthase, also known asl complex V, which is involved in the last step of oxidative phosphorylation to produce cellular ATP through aerobic metabolism. Although classically associated with the NARP syndrome, recent evidence highlights an important role of MT-ATP6 pathogenic variants in complicated adult-onset ataxias.MethodsWe describe two unrelated patients with adult-onset cerebellar ataxia associated with severe optic atrophy and mild cognitive impairment. Whole mitochondrial DNA sequencing was performed in both patients. We employed patients’ primary fibroblasts and cytoplasmic hybrids (cybrids), generated from patients-derived cells, to assess the activity of respiratory chain complexes, oxygen consumption rate (OCR), ATP production and mitochondrial membrane potential.ResultsIn both patients, we identified the same novel m.8777 T > C variant in MT-ATP6 with variable heteroplasmy level in different tissues. We identifed an additional heteroplasmic novel variant in MT-ATP6, m.8879G > T, in the patients with the most severe phenotype. A significant reduction in complex V activity, OCR and ATP production was observed in cybrid clones homoplasmic for the m.8777 T > C variant, while no functional defect was detected in m.8879G > T homoplasmic clones. In addition, fibroblasts with high heteroplasmic levelsof m.8777 T > C variant showed hyperpolarization of mitochondrial membranes.ConclusionsWe describe a novel pathogenic mtDNA variant in MT-ATP6 associated with adult-onset ataxia, reinforcing the value of mtDNA screening within the diagnostic workflow of selected patients with late onset ataxias.

Synthesis, characterization, and biological activity of cationic ruthenium-arene complexes with sulfur ligands.

Five cationic ruthenium-arene complexes with the generic formula [Ru(SAc)(S2C·NHC)(p-cymene)](PF6) (5a-e) were prepared in almost quantitative yields using a straightforward one-pot, two-step experimental procedure starting from [RuCl2(p-cymene)]2, an imidazol(in)ium-2-dithiocarboxylate (NHC·CS2) zwitterion, KSAc, and KPF6. These half-sandwich compounds were fully characterized by various analytical techniques and the molecular structures of two of them were solved by X-ray diffraction analysis, which revealed the existence of an intramolecular chalcogen bond between the oxygen atom of the thioacetate ligand and a proximal sulfur atom of the dithiocarboxylate unit. DFT calculations showed that the C=S…O charge transfer amounted to 2.4kcalmol-1. The dissolution of [Ru(SAc)(S2C·IMes)(p-cymene)](PF6) (5a) in moist DMSO-d6 at room temperature did not cause the dissociation of its sulfur ligands. Instead, p-cymene was slowly released to afford the 12-electron [Ru(SAc)(S2C·IMes)]+ cation that could be detected by mass spectrometry. Monitoring the solvolysis process by 1H NMR spectroscopy showed that more than 22days were needed to fully decompose the starting ruthenium-arene complex. Compounds 5a-e exhibited a high antiproliferative activity against human glioma Hs683 and human lung carcinoma A549 cancer cells. In particular, the IMes derivative (5a) was the most potent compound of the series, achieving toxicities similar to those displayed by marketed platinum drugs.

Dual activities of a silencing information regulator complex in yeast transcriptional regulation and DNA‐damage response

AbstractThe Saccharomyces cerevisiae silencing information regulator (SIR) complex contains up to four proteins, namely Sir1, Sir2, Sir3, and Sir4. While Sir2 encodes a NAD‐dependent histone deacetylase, other SIR proteins mainly function as structural and scaffold components through physical interaction with various proteins. The SIR complex displays different conformation and composition, including Sir2 homotrimer, Sir1‐4 heterotetramer, Sir2‐4 heterotrimer, and their derivatives, which recycle and relocate to different chromosomal regions. Major activities of the SIR complex are transcriptional silencing through chromosomal remodeling and modulation of DNA double‐strand‐break repair pathways. These activities allow the SIR complex to be involved in mating‐type maintenance and switching, telomere and subtelomere gene silencing, promotion of nonhomologous end joining, and inhibition of homologous recombination, as well as control of cell aging. This review explores the potential link between epigenetic regulation and DNA damage response conferred by the SIR complex under various conditions aiming at understanding its roles in balancing cell survival and genomic stability in response to internal and environmental stresses. As core activities of the SIR complex are highly conserved in eukaryotes from yeast to humans, knowledge obtained in the yeast may apply to mammalian Sirtuin homologs and related diseases.

Acupuncture modulates the AMPK/PGC-1 signaling pathway to facilitate mitochondrial biogenesis and neural recovery in ischemic stroke rats

AimsThe main objective of this study was to investigate the role and mechanism of acupuncture on anti-nerve injury in the acute phase by regulating mitochondrial energy metabolism via monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) axis in rat ischemic stroke.Main methodsMiddle cerebral artery occlusion (MCAO) was established by middle cerebral artery occlusion/reperfusion. One-week of acupuncture was performed during the acute phase of ischemic stroke. The neurological function and brain tissue integrity were evaluated. Mitochondrial function (intracellular ATP level and the activity of mitochondrial respiratory chain complex I) and the level of NADH oxidase (NOX) were detected by enzymatic chemistry. Next, the potential molecular mechanisms were explored by western blotting, fluorescence quantitative PCR and immunohistochemistry method.Key findings(1) Acupuncture treatment for MCAO/R rats showed a significant improvement in the infarcted tissue accompanied by functional recovery in Zea-Longa score and balance beam score outcomes, motor function performances. (2) Acupuncture increased the levels of ATP and mitochondrial respiratory chain complex I, decreased the NOX levels in cerebral ischemia established by suture-occluded method. (3) Acupuncture reduced the necrosis dissolution of neuronal cells and meningeal edema, while promoting angiogenesis. (4) Quantitative immunohistochemical staining results showed acupuncture can increase the expression of AMPK, p-AMPK and the mitochondrial transcription factor PGC-1α, NRF2, TFAM and uncoupling protein 2 (UCP2). Meanwhile, acupuncture treatment up-regulated the expression of the corresponding protein. (5) Subsequently, acupuncture enhanced AMPK phosphorylation as well as the expression of PGC-1α, NRF2, TFAM and UCP2, implicated in mitochondrial synthesis and cellular apoptosis. (6) Finally, injections of AMPK antagonists and activators confirmed AMPK as a therapeutic target for the anti-nerve damage effects of acupuncture.SignificanceAcupuncture intervention relieved ischemic stroke progression in MCAO rats by promoting energy metabolism and mitochondrial biogenesis in the brain and alleviating neuronal apoptosis, which was mediated by eliciting AMPK/PGC-1α axis, among them AMPK is a therapeutic target.

Search for new biologically active compounds: in vitro studies of antitumor and antimicrobial activity of dirhodium(II,II) paddlewheel complexes.

Four neutral Rh1-Rh4 complexes of the general formula [Rh2(CH3COO)4L2], where L is an N-alkylimidazole ligand, were synthesized and characterized using various spectroscopic techniques, and in the case of Rh4 the crystal structure was confirmed. Investigation of the interactions of these complexes with HSA by fluorescence spectroscopy revealed that the binding constants Kb are moderately strong (∼104 M-1), and site-marker competition experiments showed that the complexes bind to Heme site III (subdomain IB). Competitive binding studies for CT DNA using EB and HOE showed that the complexes bind to the minor groove, which was also confirmed by viscosity experiments. Molecular docking confirmed the experimental data for HSA and CT DNA. Antimicrobial tests showed that the Rh2-Rh4 complexes exerted a strong inhibitory effect on G+ bacteria B. cereus and G- bacteria V. parahaemolyticus as well as on the yeast C. tropicalis, which showed a higher sensitivity compared to fluconazole. The cytotoxic activity of Rh1-Rh4 complexes tested on three cancer cell lines (HeLa, HCT116 and MDA-MB-231) and on healthy MRC-5 cells showed that all investigated complexes elicited more efficient cytotoxicity on all tested tumor cells than on control cells. Investigation of the mechanism of action revealed that the Rh1-Rh4 complexes inhibit cell proliferation via different mechanisms of action, namely apoptosis (increase in expression of the pro-apoptotic Bax protein and caspase-3 protein in HeLa and HCT116 cells; changes in mitochondrial potential and mitochondrial damage; release of cytochrome c from the mitochondria; cell cycle arrest in G2/M phase in both HeLa and HCT116 cells together with a decrease in the expression of cyclin A and cyclin B) and autophagy (reduction in the expression of the protein p62 in HeLa and HCT116 cells).

Sepsis compromises post-ischemic stroke neurological recovery and is associated with sex differences

AimsInfection is a complication after stroke and outcomes vary by sex. Thus, we investigated if sepsis affects brain from ischemic stroke and sex involvement. Main methodsMale and female Wistar rats, were submitted to middle cerebral artery occlusion (MCAO) and after 7 days sepsis to cecal ligation and perforation (CLP). Infarct size, neuroinflammation, oxidative stress, and mitochondrial activity were quantified 24 h after CLP in the prefrontal cortex and hippocampus. Survival and neurological score were assessed up to 15 days after MCAO or 8 days after CLP (starting at 2 h after MCAO) and memory at the end. Key findingsCLP decreased survival, increased neurological impairments in MCAO females. Early, in male sepsis following MCAO led to increased glial activation in the brain structures, and increased TNF-α and IL-1β in the hippocampus. All groups had higher IL-6 in both tissues, but the hippocampus had lower IL-10. CLP potentiated myeloperoxidase (MPO) in the prefrontal cortex of MCAO male and female. In MCAO+CLP, only male increased MPO and nitrite/nitrate in hippocampus. Males in all groups had protein oxidation in the prefrontal cortex, but only MCAO+CLP in the hippocampus. Catalase decreased in the prefrontal cortex and hippocampus of all males and females, and MCAO+CLP only increased this activity in males. Female MCAO+CLP had higher prefrontal cortex complex activity than males. In MCAO+CLP-induced long-term memory impairment only in females. SignificanceThe parameters evaluated for early sepsis after ischemic stroke show a worse outcome for males, while females are affected during long-term follow-up.

Hydrothermal preparation, crystal structure, Hirshfeld surface analysis, photophysical properties and antifungal activity of a series of complexes assembled by 5-bromo-2-(carboxymethoxy)benzoic acid ligands

Five complexes [Co(BCBA)(H2O)3]n (1), [Co(BCBA)(4,4′-Bipy)2·(H2O)]n (2), [Cu(BCBA)(H2O)]n (3), [Zn(BCBA)(H2O)]n (4) and [Cd(BCBA)(2,2′-Bipy)(H2O)·(H2O)]n (5) (H2BCBA= 5‑bromo-2-(carboxymethoxy)benzoic acid, 4,4′-Bipy = 4,4′-bipyridine and 2,2′-Bipy = 2,2′-bipyridine) have been synthesized with H2BCBA ligand by solvothermal condition. All the complexes have been structurally characterized by infrared spectra (IR), elemental analyses and single-crystal X-ray diffraction analyses. Complex 1 is a zero-dimensional structure, and complexes 2–5 are one-dimensional chain structure. Furthermore, thermogravimetric analyses (TGA), Hirshfeld surface analysis, photo-luminescence properties, Solid-state UV–Vis diffuse reflectance spectroscopy and antifungal activity for complexes 1–5 were investigated. The reciprocal H···O/H/Br/C contacts dominate over 86 % of total Hirshfeld surface. Complexes 1–5 have certain inhibitory effects on 8 pathogenic fungi. Among them, complex 5 has the strongest antibacterial activity against Rhizoctonia solani AG1, Sphaeropsis sapinea and Colletotrichum fructicola, and the inhibitory rate reached 100 %.