Core Complex Research Articles

Chloride Gradient Is Involved in Ammonium Influx in Human Erythrocytes.

The ammonia/ammonium (NH3/NH4+, AM) concentration in human erythrocytes (RBCs) is significantly higher than in plasma. Two main possible mechanisms for AM transport, including simple and facilitated diffusion, are described; however, the driving force for AM transport is not yet fully characterized. Since the erythroid ammonium channel RhAG forms a structural unit with anion exchanger 1 (eAE1) within the ankyrin core complex, we hypothesized the involvement of eAE1 in AM transport. To evaluate the functional interaction between eAE1 and RhAG, we used a unique feature of RBCs to swell and lyse in isotonic NH4+ buffer. The kinetics of cell swelling and lysis were analyzed by flow cytometry and an original laser diffraction method, adapted for accurate volume sensing. The eAE1 role was revealed according to (i) the changes in cell swelling and lysis kinetics, and (ii) changes in intracellular pH, triggered by eAE1 inhibition or the modulation of eAE1 main ligand concentrations (Cl- and HCO3-). Additionally, the AM import kinetics was analyzed enzymatically and colorimetrically. In NH4+ buffer, RBCs concentration-dependently swelled and lysed when [NH4+] exceeded 100 mM. Cell swelling and hemolysis were tightly regulated by chloride concentration. The complete substitution of chloride with glutamate prevented NH4+-induced cell swelling and hemolysis, and the restoration of [Cl-] dose-dependently amplified the rates of RBC swelling and lysis and the percentage of hemolyzed cells. Similarly, eAE1 inhibition impeded cell swelling and completely prevented hemolysis. Accordingly, eAE1 inhibition, or a lack of chloride anions in the buffer, significantly decreased NH4+ import. Our data indicate that the eAE1-mediated chloride gradient is required for AM transport. Taken together, our data reveal a new player in AM transport in RBCs.

Characterization of the complete chloroplast genome of Rhodiola sachalinensis and comparative analysis with its congeneric plants.

Rhodiola, belonging to the Crassulaceae family, is a perennial herbaceous plant genus. There are about 90 Rhodiola species worldwide, some of which have been reported to have medicinal properties. Rhodiola sachalinensis is a perennial medicinal herb within this genus and, in the present study, its chloroplast genome was sequenced, assembled, annotated and compared with 24 other Rhodiola species. The results obtained show that the chloroplast genome of R. sachalinensis is 151 595 bp long and has a CG content of 37.7%. The inverted repeats (IR) region of the Rhodiola chloroplast genome is the most conserved region, with the main differences being observed in the ycf1 and ndhF genes at the IRb-small single copy boundary, and rps19 and trnH genes at the IRa-large single copy boundary. Phylogenetic analysis showed that Rhodiola species form two major clades, and species with recorded medicinal properties, clustered together in one branch except for R. dumulosa. Within the genus, R. sachalinensis is most closely related to Rhodiola rosea, although comparative analyses showed that only R. sachalinensis and Rhodiola subopposita contained the psbZ gene, which encodes a highly conserved protein subunit of the Photosystem II core complex. Overall, the present study contributes to the understanding of the chloroplast genome of Rhodiola species, and provides a theoretical basis for the study of their genetic diversity and possible use as medicinal plants.

From nappe stacking to strike-slip deformation: Alpine structural overprints refined by cave and karst geology in the Danubian thin-skinned units (Southern Carpathians, Romania)

Caves are ideal environments for preserving quantifiable deformational indicators in orogenic areas, as they are conditioned by regional tectonics. The caves and karst of Isverna, developed in the Barremian-Aptian limestones of the Danubian sedimentary nappes (Southern Carpathians, SW Romania), expose formerly undetected evidence of compressional tectonics, overlapping older structures related to décollement and deformation of the underlying Turonian-Senonian tectonic mélange. The Danubian domain (the distal part of the Moesian Platform) was incorporated into the Carpathian Orogen during the Late Cretaceous subduction of the Ceahlău–Severin Ocean and collision with the continental Dacia mega-unit. Subsequent Eocene–Oligocene orogen–parallel extension led to the development of a metamorphic core complex and detachment faults, constructing a complicated arcuate fault system around the Moesian Platform during the Late Miocene strike-slip deformation. The integrated analysis of structural, kinematic, and geomorphological data indicates a connection between the strike-slip deformation and the subsequent shortening, exhumation and surface exposure of Cerna Nappe within the Isverna shear zone. Four main evolutionary stages of the Danubian thin-skinned units in the central Mehedinți Mountains were distinguished from cave and karst geology, and illustrated in a detailed 3D model: i) Initial décollement and mélange deformation during the Alpine nappe stacking; ii) Extensional décollement toward SE; iii) Dextral shearing and WNW-ESE contraction; iv) Karstification and cave development. Most structural and kinematic markers recorded within the limestones of the Cerna Nappe date from stage (iii), whereas older structures were better preserved in the tectonic mélange of the Lainici Nappe. The resulting model could be further integrated into the polyphase tectonic evolution of the Southern Carpathians and their relation with the Moesian Platform. This study demonstrates the utility of caves and karst for constraining the chronology of tectonic deformations in complex structural systems and for reconstructing more refined conceptual 3D models.

Tectono‐sedimentary evolution of high‐displacement crustal‐scale normal faults and basement highs on rifted margins: Klakk Fault Complex and Frøya High, Mid‐Norwegian Margin

AbstractCrustal‐scale high‐displacement (>10 km) normal faults are not captured in existing tectono‐sedimentary models of rift basins. We used 2D and 3D seismic reflection and well data to perform a structural and source‐to‐sink analysis of the southern part of the Klakk Fault Complex and the western part of the Vingleia Fault Complex, Mid‐Norwegian rifted margin. The north–south trending Klakk Fault Complex has a zig‐zag to sinuous plan‐view geometry, forming a series of structural recesses and salients along strike. In cross‐section, the fault complex has a listric to convex‐up or low‐angle planar geometry with displacements above 20 km. This fault complex exhumed basement highs, the Frøya High and Sklinna Ridge, in its footwall and created a series of supradetachment basins, for example, the Rås Basin, in its hanging wall. In contrast, the northeast‐southwest trending Vingleia Fault Complex has a zig‐zag geometry in plan view and planar to listric geometry in cross‐section and displacement of up to 5 km. This fault has the Frøya High in its footwall and the southern Halten Terrace in its hanging wall. Restoration of selected structural cross‐sections shows a prominent fault‐parallel ridge, up to 15 km east of the Klakk Fault Complex interpreted as a palaeodrainage divide. This divide separates steep drainages developed along the west‐dipping footwall scarp to the Klakk Fault Complex, from broader, gentler east‐dipping drainages up to ca. 10 km long developed on a back‐tilted dip slopes along the eastern side of the Frøya High and Sklinna Ridge. Progressive headward erosion of active flank catchments was enhanced around topographically elevated structural salients to the point of capturing previous dip‐slope‐directed drainages during the earliest Cretaceous. A network of submarine canyons develop down‐dip of the drainage catchments along the Klakk Fault Complex scarp, whose geometries and length are controlled by their location with respect to the structural salients or recesses, and the presence of fault terraces. The middle Jurassic‐earliest Cretaceous synrift deposits form two seismic sequences that are filled with five distinctive seismic facies that record the evolution from a linked normal fault during rift climax to a high‐displacement stage. During the high displacement stage, exhumed local continental core complexes formed structural salients, separated along strike by structural recesses at the heads of supradetachment basins. Key elements of the high‐displacement fault stage include (i) the development of structural salients at sites of rift climax displacement maxima, (ii) development of supradetachment basins in rift climax displacement minima and (iii) migration of major depocentres away from the centre of rift climax fault segments. We synthesise these observations into a generic tectono‐sedimentary model for high‐displacement faults.

Sulfoquinovosyl diacylglycerol is required for dimerisation of the Rhodobacter sphaeroides reaction centre-light harvesting 1 core complex.

The reaction centre-light harvesting 1 (RC-LH1) core complex is indispensable for anoxygenic photosynthesis. In the purple bacterium Rhodobacter (Rba.) sphaeroides RC-LH1 is produced both as a monomer, in which 14 LH1 subunits form a C-shaped antenna around 1 RC, and as a dimer, where 28 LH1 subunits form an S-shaped antenna surrounding 2 RCs. Alongside the five RC and LH1 subunits, an additional polypeptide known as PufX provides an interface for dimerisation and also prevents LH1 ring closure, introducing a channel for quinone exchange that is essential for photoheterotrophic growth. Structures of Rba. sphaeroides RC-LH1 complexes revealed several new components; protein-Y, which helps to form the quinone channel; protein-Z, of unknown function and seemingly unique to dimers; and a tightly bound sulfoquinovosyl diacylglycerol (SQDG) lipid that interacts with two PufX arginine residues. This lipid lies at the dimer interface alongside weak density for a second molecule, previously proposed to be an ornithine lipid. In this work we have generated strains of Rba. sphaeroides lacking protein-Y, protein-Z, SQDG or ornithine lipids to assess the roles of these previously unknown components in the assembly and activity of RC-LH1. We show that whilst the removal of either protein-Y, protein-Z or ornithine lipids has only subtle effects, SQDG is essential for the formation of RC-LH1 dimers but its absence has no functional effect on the monomeric complex.

Addition of diazonium salts to the coordinatively unsaturated core of a dinuclear organoruthenium complex

Abstract The reaction of [Ru2(CO)4(µ-H)(µ-PtBu2)(µ-Ph2PCH2PPh2)] (1) with the diazonium salts [PhN2]BF4 and [p-BrC6H4N2]BF4 in dichloromethane at T = 273 K was investigated. The oxidative addition afforded the products [Ru2(CO)4(µ-H)(µ-PtBu2)(µ-Ph2PCH2PPh2)(µ-N2Ph)]BF4 (2a) and [Ru2(CO)4(µ-H)(µ-PtBu2)(µ-Ph2PCH2PPh2)(µ-N2C6H4-p-Br)]BF4 (2b) in good yields. The products have been characterized by NMR and IR spectroscopy and mass spectrometry and the molecular structure of 2a has been determined by a single-crystal X-ray diffraction analysis (monoclinic, space group P21/m, Z = 2).

Urban resilience governance mechanism: Insights from COVID‐19 prevention and control in 30 Chinese cities

AbstractDue to the pervasive uncertainty in human society, super large and megacities are increasingly prone to becoming high‐risk areas. However, the construction of urban resilience in this new era lacks sufficient research on the core conditions and complex interactive mechanisms governing it. Hence, this study proposes a specialized event‐oriented framework for governing urban resilience in China based on the pressure‐state‐response (PSR) theory. We examined COVID‐19 cases in 30 cities across China and analyzed the distribution of prevention and control achievements between high‐level and non‐high‐level conditions. Our findings reveal the following key points: (1) High‐level achievements in COVID‐19 prevention and control rely on three condition configurations: non‐pressure‐responsive type, pressure‐state type, and pressure‐responsive type. (2) High economic resilience may indicate a robust state of urban systems amid demographic pressures. In cities experiencing fewer event pressure factors, the application of digital technology plays a crucial role in daily urban management. (3) The implementation of flexible policies proves beneficial in mitigating the impact of objective pressure conditions, such as environmental factors, on urban resilience.

TauP301L disengages from the proteosome core complex and neurogranin coincident with enhanced neuronal network excitability

Tauopathies are characterised by the pathological accumulation of misfolded tau. The emerging view is that toxic tau species drive synaptic dysfunction and potentially tau propagation before measurable neurodegeneration is evident, but the underlying molecular events are not well defined. Human non-mutated 0N4R tau (tauWT) and P301L mutant 0N4R tau (tauP301L) were expressed in mouse primary cortical neurons using adeno-associated viruses to monitor early molecular changes and synaptic function before the onset of neuronal loss. In this model tauP301L was differentially phosphorylated relative to tauwt with a notable increase in phosphorylation at ser262. Affinity purification - mass spectrometry combined with tandem mass tagging was used to quantitatively compare the tauWT and tauP301L interactomes. This revealed an enrichment of tauP301L with ribosomal proteins but a decreased interaction with the proteasome core complex and reduced tauP301L degradation. Differences in the interaction of tauP301L with members of a key synaptic calcium-calmodulin signalling pathway were also identified, most notably, increased association with CaMKII but reduced association with calcineurin and the candidate AD biomarker neurogranin. Decreased association of neurogranin to tauP301L corresponded with the appearance of enhanced levels of extracellular neurogranin suggestive of potential release or leakage from synapses. Finally, analysis of neuronal network activity using micro-electrode arrays showed that overexpression of tauP301L promoted basal hyperexcitability coincident with these changes in the tau interactome and implicating tau in specific early alterations in synaptic function.

Crafting Stable Antibiotic Nanoparticles via Complex Coacervation of Colistin with Block Copolymers.

To combat the ever-growing increase of multidrug-resistant (MDR) bacteria, action must be taken in the development of antibiotic formulations. Colistin, an effective antibiotic, was found to be nephrotoxic and neurotoxic, consequently leading to a ban on its use in the 1980s. A decade later, colistin use was revived and nowadays used as a last-resort treatment against Gram-negative bacterial infections, although highly regulated. If cytotoxicity issues can be resolved, colistin could be an effective option to combat MDR bacteria. Herein, we investigate the complexation of colistin with poly(ethylene oxide)-b-poly(methacrylic acid) (PEO-b-PMAA) block copolymers to form complex coacervate core micelles (C3Ms) to ultimately improve colistin use in therapeutics while maintaining its effectiveness. We show that well-defined and stable micelles can be formed in which the cationic colistin and anionic PMAA form the core while PEO forms a protecting shell. The resulting C3Ms are in a kinetically arrested and stable state, yet they can be made reproducibly using an appropriate experimental protocol. By characterization through dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS), we found that the best C3M formulation, based on long-term stability and complexation efficiency, is at charge-matching conditions. This nanoparticle formulation was compared to noncomplexed colistin on its antimicrobial properties, enzymatic degradation, serum protein binding, and cytotoxicity. The studies indicate that the antimicrobial properties and cytotoxicity of the colistin-C3Ms were maintained while protein binding was limited, and enzymatic degradation decreased after complexation. Since colistin-C3Ms were found to have an equal effectivity but with increased cargo protection, such nanoparticles are promising components for the antibiotic formulation toolbox.

Archaeological research on the Kanka fortress city: between nomads and farmers

The settlement of Kanka is one of the largest urban centres on the right bank of the Syrdarya. It comprises a citadel, three shakhristans, each surrounded on three sides by defensive walls, and a suburb of rabad. The fourth side of the settlement bordered the riverbank, along which a wall also ran. A significant object, discovered during the excavations of Shakhristan 1 was the city temple, which was a large monumental structure. The core of the temple complex was a square hall surrounded by bypass corridors. The walls of the temple were decorated with paintings and relief moldings. New research in the settlement was conducted on the eastern part of the city temple, the supposed entrance part site of the temple complex. The archaeological excavations at the Kanka monument have yielded insights into the lifestyle of an outpost city situated at the border of the territories of nomads, pastoralists, and farmers in ancient Central Asia. The findings indicate that ancient nomadic populations likely played a significant role in the dissemination of scientific progress. Through their extensive migrations and cultural interactions, they could have served as conduits for exchanging knowledge and technological innovations among disparate regions.

The Ottawa River Gneiss Complex revisited: definition of the metamorphic core and detachment zone of a large Grenvillian metamorphic core complex

Using new and published data, we synthesize the tectonic evolution of the Ottawa River Gneiss Complex (ORGC), the metamorphic core and detachment zone of a large mid- to late-Ottawan metamorphic core complex in the western Grenville Province. Field and petrologic data indicative of retrogression and exhumation, combined with maps and schematic crustal-scale sections, are used to document spatial and temporal relationships of multi-scale structures developed during its formation, of which the largest, termed mega-cross-folds and megaboudins, occur within and define the detachment zone. Mega-cross-folds, orogen-normal structures up to 70 km in length with coaxial constrictional fabrics in their hinge-lines, formed in a single phase of deformation during retrogression and exhumation. A cluster of asymmetric megaboudins, individually from 10–50 km long with granulite-facies cores and high-strain amphibolite-facies rims, similarly formed during syntectonic retrogression and exhumation of granulite-facies precursors. We argue the mega-cross-folds developed in a regime of regional transtension, whereas the megaboudin cluster formed by extensional inversion of an anastomosing early-Ottawan thrust system, with the strain patterns of both suggesting the detachment zone was the site of intense ductile flow between the stronger metamorphic core and cover. Comparison of these results with generic numerical models of extensional collapse of overthickened continental crust suggests the first-order tectonometamorphic features of the ORGC developed during necking of the upper crust and associated large-scale extensional flow of the mid and lower crust into the domiform necked region during collapse of the early-Ottawan thrust stack.

Palladium-Catalyzed Amino-Sulfonylation of Aryl Iodide Derivatives via the Insertion of Sulfur Dioxide: One-Pot Synthesis of Aryl Primary Sulfonamides with Thiourea Dioxides

AbstractA palladium-catalyzed one-pot amino-sulfonylation of aryl iodide derivatives with thiourea dioxide, PdCl2dppf, and one-pot added hydroxylamine-O-sulfonic acid is presented. This amino-sulfonylation gave structure diversity to aryl primary sulfonamides and features good functional group compatibility, mild reaction conditions, excellent regioselectivity, and moderate to good yields. The robustness and potential of this method have also been successfully demonstrated by late-stage elaboration and gram-scale reaction. This approach achieves the divergent construction of the complex core structures that are prevalent in highly valuable natural products such as Sulpiride, Venetoclax, and Furosemide­.

Teacher and Teaching-related Practices Student Teachers May Have Difficulty Believing They Can Enact/Engage in While in Field Practice: Perspectives from Student Teachers and Teachers in Field-practice Schools

Field practice is pivotal in teacher education, serving both as a bridge connecting the theoretical and practical dimensions of the teaching profession in real-world schools, and as a place for acquiring the complex core skills of the profession in their own right. While prior work has mainly explored general teacher self-efficacy, or broad student-related concerns in field practice, there is surprisingly little knowledge of the specific teacher and teaching-related practices that might challenge student teachers during field practice. This study aims to address this gap by exploring the issue both from the student teacher and the field-practice teacher perspective. Utilizing focus groups and individual interviews with students and field-practice teachers, the study employs content analysis, and an innovative agreement circle to identify which practices students may doubt they can enact/engage in while in field practice. The findings highlight four main areas of concern stemming from both students and field practice teachers: adaptability in teaching; balancing subject knowledge with pedagogical competence; classroom leadership; and teaching independently. The study also uncovers discrepancies between student teachers, who are preoccupied with their teaching performance, and field-practice teachers, who also emphasize the importance of collaborative practices with, for example, parents. The study opens a new field of inquiry and is the first step towards a theory of practice self-efficacy in education. Future research could focus on creating measurement tools to evaluate student teacher efficacy in field practice within the four identified areas, thereby enabling identification of early challenges, assessment of field-practice effectiveness, and the provision of tailored field-practice preparation.

RhoG facilitates a conformational transition in the guanine nucleotide exchange factor complex DOCK5/ELMO1 to an open state

The dedicator of cytokinesis (DOCK)/engulfment and cell motility (ELMO) complex serves as a guanine nucleotide exchange factor (GEF) for the GTPase Rac. RhoG, another GTPase, activates the ELMO-DOCK-Rac pathway during engulfment and migration. Recent cryo-EM structures of the DOCK2/ELMO1 and DOCK2/ELMO1/Rac1 complexes have identified closed and open conformations that are key to understanding the autoinhibition mechanism. Nevertheless, the structural details of RhoG-mediated activation of the DOCK/ELMO complex remain elusive. Herein, we present cryo-EM structures of DOCK5/ELMO1 alone and in complex with RhoG and Rac1. The DOCK5/ELMO1 structure exhibits a closed conformation similar to that of DOCK2/ELMO1, suggesting a shared regulatory mechanism of the autoinhibitory state across DOCK-A/B subfamilies (DOCK1−5). Conversely, the RhoG/DOCK5/ELMO1/Rac1 complex adopts an open conformation that differs from that of the DOCK2/ELMO1/Rac1 complex, with RhoG binding to both ELMO1 and DOCK5. The alignment of the DOCK5 PIP3 binding site with the RhoG C-terminal lipidation site suggests simultaneous binding of RhoG and DOCK5/ELMO1 to the plasma membrane. Structural comparison of the apo and RhoG-bound states revealed that RhoG facilitates a closed-to-open state conformational change of DOCK5/ELMO1. Biochemical and surface plasmon resonance (SPR) assays confirm that RhoG enhances the Rac GEF activity of DOCK5/ELMO1 and increases its binding affinity for Rac1. Further analysis of structural variability underscored the conformational flexibility of the DOCK5/ELMO1/Rac1 complex core, potentially facilitating the proximity of the DOCK5 GEF domain to the plasma membrane. These findings elucidate the structural mechanism underlying the RhoG-induced allosteric activation and membrane binding of the DOCK/ELMO complex.

The expanding clinical and genetic spectrum of DYNC1H1-related disorders

Abstract Intracellular trafficking involves an intricate machinery of motor complexes including the dynein complex to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains as well as cytoplasmic light and intermediate chains have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy-chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders, and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies, and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross-River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of NDD manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging, and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients.

Effect of Red Emissive Ligand Number on Dendronized Solution‐Processable Iridium(III) Complexes for Organic Light‐Emitting Diodes

AbstractTris‐bidentate iridium(III) complexes used in organic light‐emitting diodes (OLEDs) are typically homoleptic or heteroleptic with three or two identical emissive ligands, respectively. Herein red phosphorescence emitting dendrimers composed of first generation biphenyl dendrons, 2‐ethylhexyloxy surface groups and an iridium(III) complex core with three, two or one emissive [4‐phenyl]−2‐[thiophen‐2‐yl]quinoline ligands are reported. The dendrimers have similar photoluminescence quantum yields (PLQYs) in solution (84–88%), neat film (23–25%) and when blended with tris(4‐carbazoyl‐9‐ylphenyl)amine (72–73%), enabling the effect of the number of emissive ligands on OLED performance to be determined. The external quantum efficiency (EQE) of OLEDs composed of neat dendrimer films increased with decreasing number of emissive ligands, with the device composed of the dendrimer having a single emissive ligand having an EQE of 9.2%, which is almost double that expected from a bottom emitting device and a film PLQY of 25 ± 3.6%. The emission is Lambertian and the higher‐than‐expected EQE is ascribed to alignment of the single emissive ligand being optimal for light‐outcoupling. The EQE of OLEDs containing the blend film also increased with decreasing emissive number of ligands (maximum EQE = 15.4%).

ARRB1 inhibits extracellular matrix degradation and apoptosis of nucleus pulposus cells by promoting autophagy and attenuates intervertebral disc degeneration

ObjectiveIntervertebral disc degeneration (IVDD) is the leading cause of lower back pain (LBP). β-arrestin 1 (ARRB1) is a multifunctional protein that regulates numerous pathological processes. The aim of this study was to investigate the role of ARRB1 in IVDD. MethodsThe expression of ARRB1 in nucleus pulposus (NP) of rats with IVDD was assayed. Next, rat nucleus pulposus cells (NPCs) were infected with lentiviruses containing shArrb1 (LV-shArrb1) and overexpressing Arrb1 (LV-oeArrb1). The roles of Arrb1 in serum-deprived NPCs were investigated by measuring apoptosis, extracellular matrix degradation, and autophagic flux. For experiments in vivo, LV-oeArrb1 lentivirus was injected into the NP tissues of IVDD rats to evaluate the effects of Arrb1 overexpression on NP. ResultsIn the NP tissues of IVDD rats, ARRB1 and cleaved caspase-3 expression increased, and the ratio of LC3II/LC3I protein expression was upregulated. Arrb1 knockdown aggravated extracellular matrix degradation, cellular apoptosis, and impairment of autophagic flux in rat NPCs under serum-deprived conditions, whereas Arrb1 overexpression significantly reversed these effects. ARRB1 interacted with Beclin 1, and Arrb1 knockdown suppressed the formation of the Beclin1-PIK3C3 core complex. The autophagy inhibitor 3-methyladenine (3-MA) offset the protective effects of Arrb1 overexpression in serum-deprived NPCs. Furthermore, Arrb1 overexpression inhibited apoptosis and extracellular matrix degradation, promoted autophagy in NP, and delayed the development of IVDD in rats. ConclusionARRB1 prevents extracellular matrix degradation and apoptosis of NPCs by upregulating autophagy and ameliorating IVDD progression, presenting an innovative strategy for the treatment of IVDD.

Mеsozoic Tectonothermal Evolution of the Zagan Metamorphic Core Complex in Western Transbaikalia: 40Ar/39Ar and FTA Dating

Mеsozoic Tectonothermal Evolution of the Zagan Metamorphic Core Complex in Western Transbaikalia: 40Ar/39Ar and FTA Dating

Mеsozoic Tectonothermal Evolution of the Zagan Metamorphic Core Complex in Western Transbaikalia: 40Ar/39Ar and FTA Dating

Abstract A model of tectonothermal evolution of the Zagan metamorphic core complex (MCC) based on the new data from 40Ar/39Ar dating of amphibole, mica, and apatite fission-track dating is discussed. A relationship with the long-range impact of processes from the collision of the North China (Amurian–North China) block with the Siberian continent in the Mesozoic era is proposed. The Zagan MСС was formed in the Cretaceous period on the southern flank of a high mountain uplift of Western Transbaikalia, composed of late Paleozoic granitoids of the Angara–Vitim batholith. According to 40Ar/39Ar dating of amphiboles and micas from the mylonite zone, the active development time of the Zagan MCC corresponds to the early Cretaceous epoch (131, 114 Ma). The tectonic exposure of the core from about 15 km to the depths of about 10 km occurred at a rate of tectonic erosion of 0.4–0.3 mm/year as a result of post-collisional extension of the Mongol–Okhotsk orogen. Apatite fission-track dating shows that further exhumation and cooling of the rocks to about 3 km occurred in the lower-upper Cretaceous epoch (112, 87 Ma). The erosional denudation rate was about 0.3 mm/year.MCC- metamorphic core complexes, AFT- apatite fission-track

Encapsulation of three different types of polyphenols in casein using a customized pH-driven method: Preparation and characterization

Phenolic compounds represent natural compounds endowed with diverse biological functionalities. However, their inherent limitations, characterized by poor water solubility and low oral bioavailability, limit their broader applications. Encapsulation delivery systems are emerging as a remedy, able to ameliorate these limitations by enhancing the stability and solubility of phenolic compounds. In this study, a novel, customized pH-driven approach was developed by determining the optimal deprotonation and protonation points of three different types of polyphenols: ferulic acid, resveratrol, and rhein. The polyphenols were successfully encapsulated in a casein carrier. The solubility, stability, LogD, and LogS curves of the three polyphenols at different pH values were analyzed to identify the optimal deprotonation points for ferulic acid (pH 9), resveratrol (pH 11), and rhein (pH 10). Based on these findings, three different nanoparticles were prepared. The encapsulation efficiencies of the three phenolic compounds were 95.86%, 94.62%, and 94.18%, respectively, and the casein nanoparticles remained stable at room temperature for seven days. FTIR spectroscopy, fluorescence spectroscopy, and molecular docking study substantiated the encapsulation of phenolic compounds within the hydrophobic core of casein-based complexes, facilitated by hydrogen bonding interactions and hydrophobic interactions. Furthermore, the analysis of antioxidant activity elucidated that casein nanoparticles heightened both the water solubility and antioxidant efficacy of the phenolic compounds. This customized encapsulation technique, by establishing a transitional pH value, resolves the challenges of chemical instability and facile degradation of polyphenols under alkaline conditions in the application process of pH-driven methods. It presents novel insights for the application of polyphenols in the domains of food and biomedical fields.