Activity Of Complexes Research Articles

Host-Guest Complexation of Itraconazole with Cyclodextrins for Bioavailability Enhancement.

Itraconazole is an antifungal agent included in the triazole pharmacological classification that belongs to the BCS class II, characterized by a low solubility in an aqueous medium (of 1 ng/mL, at neutral pH), which is frequently translated in a low oral bioavailability but with a high permeability. In this sense, it is necessary to find solutions to increase/improve the solubility of itraconazole in the aqueous environment. The main purpose of this study is the preparation and analysis of five different guest-host inclusion complexes containing intraconazole. Initially, a blind docking process was carried out to determine the interactions between itraconazole and the selected cyclodextrins. The second step of the study was to find out if the active pharmaceutical ingredient was entrapped in the cavity of the cyclodextrin, by using spectroscopic and thermal techniques. Also, the antifungal activity of the inclusion complexes was studied to examine if the entrapment of itraconazole influences the therapeutic effect. The results showed that the active substance was entrapped in the cavity of the cyclodextrins, with a molar ratio of 1:3 (itraconazole-cyclodextrin), and that the therapeutic effect was not influenced by the entrapment.

Specific NOX4 Inhibition Preserves Mitochondrial Function and Dampens Kidney Dysfunction Following Ischemia-Reperfusion-Induced Kidney Injury.

Background: Acute kidney injury (AKI) is a sudden episode of kidney failure which is frequently observed at intensive care units and related to high morbidity/mortality. Although AKI can have many different causes, ischemia-reperfusion (IR) injury is the main cause of AKI. Mechanistically, NADPH oxidases (NOXs) are involved in the pathophysiology contributing to oxidative stress following IR. Previous reports have indicated that knockout of NOX4 may offer protection in cardiac and brain IR, but there is currently less knowledge about how this could be exploited therapeutically and whether this could have significant protection in IR-induced AKI. Aim: To investigate the hypothesis that a novel and specific NOX4 inhibitor (GLX7013114) may have therapeutic potential on kidney and mitochondrial function in a mouse model of IR-induced AKI. Methods: Kidneys of male C57BL/6J mice were clamped for 20 min, and the NOX4 inhibitor (GLX7013114) was administered via osmotic minipump during reperfusion. Following 3 days of reperfusion, kidney function (i.e., glomerular filtration rate, GFR) was calculated from FITC-inulin clearance and mitochondrial function was assessed by high-resolution respirometry. Renal histopathological evaluations (i.e., hematoxylin-eosin) and TUNEL staining were performed for apoptotic evaluation. Results: NOX4 inhibition during reperfusion significantly improved kidney function, as evidenced by a better-maintained GFR (p < 0.05) and lower levels of blood urea nitrogen (p < 0.05) compared to untreated IR animals. Moreover, IR caused significant tubular injuries that were attenuated by simultaneous NOX4 inhibition (p < 0.01). In addition, the level of renal apoptosis was significantly reduced in IR animals with NOX4 inhibition (p < 0.05). These favorable effects of the NOX4 inhibitor were accompanied by enhanced Nrf2 Ser40 phosphorylation and conserved mitochondrial function, as evidenced by the better-preserved activity of all mitochondrial complexes. Conclusion: Specific NOX4 inhibition, at the time of reperfusion, significantly preserves mitochondrial and kidney function. These novel findings may have clinical implications for future treatments aimed at preventing AKI and related adverse events, especially in high-risk hospitalized patients.

Mechanisms for managing investment activities in the agro-industrial complex

The relevance of the study of investment management mechanisms in the agro-industrial complex is explained by the fact that only those subjects of the agro-industrial complex that carry out active investment activities have prospects for successful functioning. However, the pace of their development is largely determined not only by the volume of investments, but also by the efficiency of their use. At the same time, the concept of «investment» reflects a complex and significant economic category. On the one hand, investments make it possible to carry out the process of agricultural production itself, and on the other, the results of the production process affect savings, that is, the possibilities of further investment. At the same time, the conducted study of the indicators of measurement and evaluation of investment projects allowed us to more fully reveal their content, objective relationships between them. At the same time, the prerequisite for calculating performance indicators was the justification of approaches that take into account objective economic laws

High-nitrogen fertilizer alleviated adverse effects of drought stress on the growth and photosynthetic characteristics of Hosta ‘Guacamole’

BackgroundSeveral plants are facing drought stress due to climate change in recent years. In this study, we aimed to explore the effect of varying watering frequency on the growth and photosynthetic characteristics of Hosta ‘Guacamole’. Moreover, we investigated the effect of high-nitrogen and -potassium fertilizers on alleviating the impacts of drought stress on the morphology, photosynthetic characteristics, chlorophyll fluorescence, fast chlorophyll a fluorescence transient, JIP-test parameters, and enzymatic and non-enzymatic scavenging system for reactive oxygen species (ROS) in this species.ResultsLeaf senescence, decreased chlorophyll contents, limited leaf area, and reduced photosynthetic characteristics and oxygen-evolving complex (OEC) activity were observed in Hosta ‘Guacamole’ under drought stress. However, high-nitrogen fertilizer (30-10-10) could efficiently alleviate and prevent the adverse effects of drought stress. High-nitrogen fertilizer significantly increased chlorophyll contents, which was higher by 106% than drought stress. Additionally, high-nitrogen fertilizer significantly improved net photosynthetic rate and water use efficiency, which were higher by 467% and 2900% than those under drought stress. It attributes that high-nitrogen fertilizer could reduce transpiration rate of leaf cells and stomatal opening size in drought stress. On the other hand, high-nitrogen fertilizer enhanced actual photochemical efficiency of PS II and photochemical quenching coefficient, and actual photochemical efficiency of PS II significantly higher by 177% than that under drought stress. Furthermore, high-nitrogen fertilizer significantly activated OEC and ascorbate peroxidase activities, and enhanced the performance of photosystem II and photosynthetic capacity compared with high-potassium fertilizers (15-10-30).ConclusionsHigh-nitrogen fertilizer (30-10-10) could efficiently alleviate the adverse effects of drought stress in Hosta ‘Guacamole’ via enhancing OEC activity and photosynthetic performance and stimulating enzymatic ROS scavenging system.

Regulation of Mertk Surface Expression via ADAM17 and γ-Secretase Proteolytic Processing.

Mertk, a type I receptor tyrosine kinase and member of the TAM family of receptors, has important functions in promoting efferocytosis and resolving inflammation under physiological conditions. In recent years, Mertk has also been linked to pathophysiological roles in cancer, whereby, in several cancer types, including solid cancers and leukemia/lymphomas. Mertk contributes to oncogenic features of proliferation and cell survival as an oncogenic tyrosine kinase. In addition, Mertk expressed on macrophages, including tumor-associated macrophages, promotes immune evasion in cancer and is suggested to act akin to a myeloid checkpoint inhibitor that skews macrophages towards inhibitory phenotypes that suppress host T-cell anti-tumor immunity. In the present study, to better understand the post-translational regulation mechanisms controlling Mertk expression in monocytes/macrophages, we used a PMA-differentiated THP-1 cell model to interrogate the regulation of Mertk expression and developed a novel Mertk reporter cell line to study the intracellular trafficking of Mertk. We show that PMA treatment potently up-regulates Mertk as well as components of the ectodomain proteolytic processing platform ADAM17, whereas PMA differentially regulates the canonical Mertk ligands Gas6 and Pros1 (Gas6 is down-regulated and Pros1 is up-regulated). Under non-stimulated homeostatic conditions, Mertk in PMA-differentiated THP1 cells shows active constitutive proteolytic cleavage by the sequential activities of ADAM17 and the Presenilin/γ-secretase complex, indicating that Mertk is cleaved homeostatically by the combined sequential action of ADAM17 and γ-secretase, after which the cleaved intracellular fragment of Mertk is degraded in a proteasome-dependent mechanism. Using chimeric Flag-Mertk-EGFP-Myc reporter receptors, we confirm that inhibitors of γ-secretase and MG132, which inhibits the 26S proteasome, stabilize the intracellular fragment of Mertk without evidence of nuclear translocation. Finally, the treatment of cells with active γ-carboxylated Gas6, but not inactive Warfarin-treated non-γ-carboxylated Gas6, regulates a distinct proteolytic itinerary-involved receptor clearance and lysosomal proteolysis. Together, these results indicate that pleotropic and complex proteolytic activities regulate Mertk ectodomain cleavage as a homeostatic negative regulatory event to safeguard against the overactivation of Mertk.

A systematic review on the biochemical threshold of mitochondrial genetic variants.

Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, P = 0.01, n = 13); however, no correlation was observed in fibroblasts (P = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.

Structure-Guided Design of Ferritin-Platinum Prodrugs for Targeted Therapy of Esophageal Squamous Cell Carcinoma.

Due to its intrinsic tumor-targeting attribute, limited immunogenicity, and cage architecture, ferritin emerges as a highly promising nanocarrier for targeted drug delivery. In the effort to develop ferritin cage-encapsulated cisplatin (CDDP) as a therapeutic agent, we found unexpectedly that the encapsulation led to inactivation of the drug. Guided by the structural information, we deciphered the interactions between ferritin cages and CDDP, and we proposed a potential mechanism responsible for attenuating the antitumor efficacy of CDDP encapsulated within the cage. Six platinum prodrugs were then designed to avoid the inactivation. The antitumor activities of these ferritin-platinum prodrug complexes were then evaluated in cells of esophageal squamous cell carcinoma (ESCC). Compared with free CDDP, the complexes were more effective in delivering and retaining platinum in the cells, leading to increased DNA damage and enhanced cytotoxic action. They also exhibited improved pharmacokinetics and stronger antitumor activities in mice bearing ESCC cell-derived xenografts as well as patient-derived xenografts. The successful encapsulation also illustrates the critical significance of comprehending the interactions between small molecular drugs and ferritin cages for the development of precision-engineered nanocarriers.

Far-gate synaptic transistors utilizing ion-charge dual-transfer mechanism for neurotransmitter-multiplexing temporal coding

The ability of artificial synapses to replicate multiplexed-transmission is a significant advancement in emulating complex brain activities. However, it generally required more stringent material requirements of intrinsic-ambipolarity and more complex structures of P/N dual-channel. Here, we proposed a far-gate synaptic transistor (FGST) just using a single-channel composed of a common unipolar semiconductor to emulate the cooperation and competition between two excitatory neurotransmitters. FGST exhibits a unique ion-charge dual-transfer mechanism, enabling distinct behavioral regulation modes with switchable synaptic plasticity: ion-dominant potentiation-depression with short-term plasticity and hole-dominant potentiation with enhanced memory. Moreover, FGST with dual-excitatory enhancement can be used for temporal contrast encoding, dividing currents into multiple memory states based on a fixed threshold; by comparing the variations in postsynaptic currents with different thresholds, it offers a method for further expanding the number of temporal states in the device. This work is a step toward constructing multifunctional artificial intelligent systems.

Driving Towards Sustainable Future Through EV Health Monitoring System

Driving is a complex activity performed in a continually varying and stimulating environment. The coordination and execution of various skills like cognitive, sensory, psychomotor and physical are extremely necessary to drive safe. Most of the studies related to driving highlighted that 75% of traffic accidents occurs due to human factors including driver’s fatigue, deprived health condition, attention loss, bad emotional state, and lack of skills. Most of the developed country is ageing. Hence, the drivers above 60 years is also increasing. Ageing results are weakening in cognitive function and threaten driver safety. The aged drivers (age above 60 years) have a comparatively more significant risk of accident due to medical emergency than other factors like bad emotional state and lack of skills. The wellness of drivers’ is considered as a key factor of traffic accidents. Heart failure and non-traumatic disease (i.e., stroke) are the main risk factors for drivers’ death. Many of the victims have no prior knowledge of the presence of the condition. Stroke is a disease caused due to the disturbance in blood supply to the parts of the brain. After experiencing stroke, a driver’s ability to drive is generally affected by the visual, perceptual, motor, and cognitive deficits. Stroke leads to arm weakness, facing dropping, blurred vision, dizziness, coordination issue and speech difficulties of victims which are essential for driving. It is necessary to protect the driver’s those are possibly be the victims for stroke. Since, stroke onset during driving lead a serious threat to the other drivers and the general public. Now-a-days, there are lots of automotive industry competing not only to provide better performance in terms of the vehicle but also to provide the driver with better comfort even in long rides. Automakers are developing vehicle that could provide health monitoring service with Internet of Things (IoT). In IoT, an automobile or vehicle-treated as a “thing”. IoT plays an important role in connected vehicles development. It provide us cloud connectivity, health monitoring, safety and security. Automakers are developing vehicles with IoT enabled including healthcare, accident prevention, vehicle safety, driver safety, driver and passenger comfort, vehicle monitoring, etc. The paper aimed on summarizing the current developments in driver’s health and comfort monitoring through IoT.

Structural investigation, molecular docking, X‐ray studies, and in vitro biological activities of new transition metal complexes based isoleucine‐pyridyl hybrid Schiff base

One significant class of chemotherapeutic medicines with the ability to overcome drug resistance is metal‐based medications. The creation of novel therapeutic medications with distinct modes of action is required due to the rise in drug resistance, treatment failures, and the scarcity of available treatments. The amino acid isoleucine interacts with the arylidene (synthesized from isatin and 2,6‐diamino‐pyridine) forming the HL Schiff base ligand, which then interacts with some transition metal ions to form the metal complexes. Thermal analysis, spectroscopy (1H‐NMR, IR, mass, and ultraviolet–visible), solid reflectance, magnetic moment, molar conductivity, and elemental analyses were employed for examining the synthesized HL and resultant complexes. Mass spectra besides elemental analyses studies verified the formulae of the Schiff base ligand and metal complexes. All the complexes, except for the Fe(III) complex which is non‐electrolyte, exhibited electrolytic behavior as indicated by their molar conductivity values. The obtained complexes exhibited octahedral geometrical shapes, except for the complexes of Co(II), Ni(II), and Zn(II), which displayed tetrahedral geometry. Thermal analysis showed that the complexes consistently release organic ligands and anionic components following the initial loss of water molecules of hydration. The conducted X‐ray diffraction patterns elucidated their lattice dynamics and not only confirmed the purity of the samples, but also demonstrated that the ligand and complexes of Cr(III), Fe(III), Mn(II), Cu(II), Zn(II), and Cd(II) have a crystalline structure in addition to determination of average size of the crystallites. Scanning electron microscope (SEM) was investigated for Schiff base ligand and Co(II) complex. The complexes demonstrated superior efficacy than HL towards fungal and bacteria organisms against Aspergillus fumigatus and Candida albicans, Salmonella Sp., Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. The MCF‐7 cancer cell was subjected to investigation by synthesized complexes and IC50 values ranged from 12 to 23.1 μg/ml. Molecular docking studies define and anticipate the inhibitory potential and binding mode of the generated ligand with the 1GS4, 2HQ6, 3DJD, and 5JPE receptors.

Bowel function and inflammation: Is motility the other side of the coin?

Digestion and intestinal absorption allow the body to sustain itself and are the emblematic functions of the bowel. On the flip side, functions also arise from its role as an interface with the environment. Indeed, the gut houses microorganisms, collectively known as the gut microbiota, which interact with the host, and is the site of complex immune activities. Its role in human pathology is complex and scientific evidence is progressively elucidating the functions of the gut, especially regarding the pathogenesis of chronic intestinal diseases and inflammatory conditions affecting various organs and systems. This editorial aims to highlight and relate the factors involved in the pathogenesis of intestinal and systemic inflammation.

MARCH5 promotes aerobic glycolysis to facilitate ovarian cancer progression via ubiquitinating MPC1.

MARCH5 is a ring-finger E3 ubiquitin ligase located in the outer membrane of mitochondria. A previous study has reported that MARCH5 was up-regulated and contributed to the migration and invasion of OC cells by serving as a competing endogenous RNA. However, as a mitochondrial localized E3 ubiquitin ligase, the function of MARCH5 in mitochondrial-associated metabolism reprogramming in human cancers remains largely unexplored, including OC. We first assessed the glycolysis effect of MARCH5 in OC both in vitro and in vivo. Then we analyzed the effect of MARCH5 knockdown or overexpression on respiratory activity by evaluating oxygen consumption rate, activities of OXPHOS complexes and production of ATP in OC cells with MARCH5. Co-immunoprecipitation, western-blot, and in vitro and vivo experiments were performed to investigate the molecular mechanisms underlying MARCH5-enhanced aerobic glycolysis s in OC. In this study, we demonstrate that the abnormal upregulation of MARCH5 is accompanied by significantly increased aerobic glycolysis in OC. Mechanistically, MARCH5 promotes aerobic glycolysis via ubiquitinating and degrading mitochondrial pyruvate carrier 1 (MPC1), which mediates the transport of cytosolic pyruvate into mitochondria by localizing on mitochondria outer membrane. In line with this, MPC1 expression is significantly decreased and its downregulation is closely correlated with unfavorable survival. Furthermore, in vitro and in vivo assays revealed that MARCH5 upregulation-enhanced aerobic glycolysis played a critical role in the proliferation and metastasis of OC cells. Taken together, we identify a MARCH5-regulated aerobic glycolysis mechanism by degradation of MPC1, and provide a rationale for therapeutic targeting of aerobic glycolysis via MARCH5-MPC1 axis inhibition.

Identification of calcium chelating peptides from peanut protein hydrolysate and absorption activity of peptide-calcium complex.

Peanut peptides have good chelating ability with metal ions. However, there are few studies on the chelation mechanism of peanut peptides with calcium and absorption properties of peptide-calcium complex. Peptides with high calcium chelating rate were isolated and purified from peanut protein hydrolysate (PPH), and the chelation rate of component F21 was higher (81.4 ± 0.8%). Six peptides were identified from component F21 by liquid chromatography-tandem mass spectrometry, and the frequency of acidic amino acids and arginine in the amino acid sequence was higher in all six peptides. Peanut peptide-calcium complex (PPH21-Ca) was prepared by selecting component F21 (PPH21). Ultraviolet analysis indicated that the chelate reaction occurred between peanut peptide and calcium ions. Fourier transform infrared analysis showed that the chelating sites were carboxyl and amino groups on the amino acid residues of peptides. Scanning electron microscopy revealed that the surface of peanut peptide had a smooth block structure, but the surface of the complex had a granular morphology. Caco-2 cell model tests revealed that the bioavailability of PPH21-Ca was 58.4 ± 0.5%, which was significantly higher than that of inorganic calcium at 37.0 ± 0.4%. Peanut peptides can chelate calcium ions by carboxyl and amino groups, and the peptide-calcium complex had higher bioavailability. This study provides a theoretical basis for the development of new calcium supplement products that are absorbed easily. © 2024 Society of Chemical Industry.

Perceptions of College of Teacher Education Faculty and Students on the Academic Support Facilities of Central Philippines State University-san Carlos

Teaching is a complex human activity that encompasses various aspects such as planning, strategies, interactions, organizational arrangements, and material resources within the teaching-learning process. This study seeks to assess the perceptions of instructors and education students regarding the challenges faced at Central Philippines State University, San Carlos City Campus, during the 2023-2024 academic year. Using a descriptive research design, the study aims to characterize the population or phenomenon under study, focusing on what, where, when, and how of these challenges. The respondents include 13 regular instructors, 18 contractual instructors, and 221 students. Purposive sampling is employed to select specific individuals or units for analysis. Proper statistical treatment of data is essential for utilizing the data effectively. The frequency statistical procedure is used to analyze the data collected from the respondents to address the second research question. The findings indicate a positive perception among both faculty members and students, with a significant correlation between them. Academic support services, such as workshops on time management, effective communication, and stress management, play a crucial role in students' overall growth and development by enhancing essential life skills.

Lanthanide furoate complexes as promising systems with double effects – From suppression of mycobacteria to potential bioimaging

Several ternary complexes of rare earth ions (Gd3+, Eu3+, Sm3+) with 3-furoic (H3fur) / 5-nitro-2-furoic (Hnfur) acids and 1,10-phenanthroline (phen) have been synthesized. According to the X-ray data the resulting complexes can be divided into two groups − heterocarboxylate [Ln2(3fur)4(OAc)2(phen)2]·L and homocarboxylate complexes [Ln2(nfur)6(phen)2]·L (LnIII = Gd (1, 2), Eu (3, 4), Sm (5, 6, 7); L = 4EtOH (1–4), 4MeOH (5), H2O (7)). The stability of the complexes 1–6 in solutions was studied by recording electronic absorption spectra for two days. Optical properties of the complexes 1–6 were studied by recording absorption, excitation and luminescence spectra. The study of antibacterial properties 1–7 showed high activity of complexes in vitro against non-pathogenic Mycolicibacterium smegmatis. For the most active 3, antibacterial activity against the reference strain Mycobacterium tuberculosis H37Rv was determined (minimum inhibitory concentration (MIC) up to 12.5 μg/mL)..

Exploration of the Tungsten(VI) complex of hydroxamic acid's RNA binding affinity, histone deacetylase inhibitory activity, and antioxidant activity

Ribonucleic acid (RNA) is a versatile molecule, thus the opportunity to target RNA is abundant. Hence, the current exploration deals with the interaction of a metal complex of hydroxamic acid with t-RNA, along with HDAC8 inhibition activity and antioxidant activity. Binding characteristics of complex 1, Bis(N-phenylbenzohydroxamato)Tungsten(VI), which is represented as [N-PBHA-W(VI)] with Torula yeast RNA (t-RNA) were investigated by using several types of spectroscopic techniques, measurements of viscosity, and computational study through molecular docking. The intrinsic binding constant, Kb was evaluated for complex 1 which shows changes in the shift of absorption spectra, and the intensity of spectra also varies. From fluorescence measurement, the binding constant of complex 1 towards t-RNA is 6.64 ± 0.05 × 105 M−1. Stern-Volmer quenching constant was calculated. Two displacement method sare performed by using the fluorescence spectroscopic technique which discloses a groove mode of binding. The groove mode of binding is also uncovered by viscosity measurement, which was observed by increasing the complex 1 concentration. An electrochemical investigation was carried out by using cyclic voltammetry. A circular dichroism study was also employed, which further suggests a strong binding occurred between the metal complex used and t-RNA. The docked postures of t-RNA with complex 1 expose the strong interactions which suggest a minor groove mode of binding. All the experimental evidence indicates that the interaction of complex 1 with t-RNA is a minor groove mode of binding which complements the molecular docking results. In-silico studies of HDAC8 inhibition activity of complex 1 reveal that the inhibition takes place mainly by hydrophobic interaction. DPPH–radical scavenging method employed for the antioxidant activity.

Improvement in the Adaptation and Resilience of the Green Areas of Yerevan City to Climate–Ecological Challenges

The services provided by green infrastructures may lead to a decrease in climate-related ecological, social, and health risks, especially in the urban environment. Consequently, the best guarantee to make this environment as safe as possible is to increase the extent of green areas, taking into consideration the functional importance, and climatic–ecological peculiarities of the area. These are also issues for the Republic of Armenia’s (RA) capital Yerevan. There the current conditions of the green areas of Yerevan city do not meet the expected requirements of the climatic–ecological development of urban areas. The green area per capita is 8 m2, which is unevenly distributed within 12 different administrative districts of Yerevan city. The aim of this research was to study the natural climatic and ecological conditions of Yerevan city and the status of the green areas of the city. The eco-biological indicators of the trees and shrubs growing in Yerevan green areas have been assessed, and the more resilient plant species have been singled out. All 12 administrative districts of Yerevan have been mapped and the green area per capita for each administrative district has been calculated. The received data have been combined with health indicators and suggestions have been made to add green areas in Yerevan according to the functional significance and sustainability of shrubby species and to their decorative and phyto-filtration properties. The city has unfavorable climatic conditions. It is located in the northern section of the subtropical climatic zone and has a distinct dry continental climate. Temperatures above +40 °C are typical, while winter is rather cold and sometimes temperatures may drop below −20 °C (in January 2008, it dropped to −27.6 °C). The amount of atmospheric precipitation has reduced by 9%. The city is counted as one of the driest urban areas of the South Caucasus. The other unfavorable ecological conditions are heavy traffic, the city’s open landfill, the concentration of industrial enterprises, large-scale construction works, etc. The atmospheric concentrations of particulate matter (PM), gases and heavy metals have been detected to exceed the permitted limits. In terms of health care, the death cases due to various diseases (acute respiratory, vascular, and cancer) have increased, which requires complex activities to reduce environmental pollution and to improve the microclimate.

Complex activity and short-term plasticity of human cerebral organoids reciprocally connected with axons

An inter-regional cortical tract is one of the most fundamental architectural motifs that integrates neural circuits to orchestrate and generate complex functions of the human brain. To understand the mechanistic significance of inter-regional projections on development of neural circuits, we investigated an in vitro neural tissue model for inter-regional connections, in which two cerebral organoids are connected with a bundle of reciprocally extended axons. The connected organoids produced more complex and intense oscillatory activity than conventional or directly fused cerebral organoids, suggesting the inter-organoid axonal connections enhance and support the complex network activity. In addition, optogenetic stimulation of the inter-organoid axon bundles could entrain the activity of the organoids and induce robust short-term plasticity of the macroscopic circuit. These results demonstrated that the projection axons could serve as a structural hub that boosts functionality of the organoid-circuits. This model could contribute to further investigation on development and functions of macroscopic neuronal circuits in vitro.

Synthesis and Alkyne Metathesis Activity of Pincer Rhenium Carbyne Complexes

Synthesis and Alkyne Metathesis Activity of Pincer Rhenium Carbyne Complexes

Integrated proteomics reveals autophagy landscape and an autophagy receptor controlling PKA-RI complex homeostasis in neurons

Autophagy is a conserved, catabolic process essential for maintaining cellular homeostasis. Malfunctional autophagy contributes to neurodevelopmental and neurodegenerative diseases. However, the exact role and targets of autophagy in human neurons remain elusive. Here we report a systematic investigation of neuronal autophagy targets through integrated proteomics. Deep proteomic profiling of multiple autophagy-deficient lines of human induced neurons, mouse brains, and brain LC3-interactome reveals roles of neuronal autophagy in targeting proteins of multiple cellular organelles/pathways, including endoplasmic reticulum (ER), mitochondria, endosome, Golgi apparatus, synaptic vesicle (SV) for degradation. By combining phosphoproteomics and functional analysis in human and mouse neurons, we uncovered a function of neuronal autophagy in controlling cAMP-PKA and c-FOS-mediated neuronal activity through selective degradation of the protein kinase A - cAMP-binding regulatory (R)-subunit I (PKA-RI) complex. Lack of AKAP11 causes accumulation of the PKA-RI complex in the soma and neurites, demonstrating a constant clearance of PKA-RI complex through AKAP11-mediated degradation in neurons. Our study thus reveals the landscape of autophagy degradation in human neurons and identifies a physiological function of autophagy in controlling homeostasis of PKA-RI complex and specific PKA activity in neurons.