Local Changes Research Articles

SCN as a local probe of protein structural dynamics.

The dynamics of lysozyme is probed by attaching -SCN to all alanine residues. The one-dimensional infrared spectra exhibit frequency shifts in the position of the maximum absorption of 4 cm-1, which is consistent with experiments in different solvents and indicates moderately strong interactions of the vibrational probe with its environment. Isotopic substitution 12C → 13C leads to a redshift by -47 cm-1, which agrees quantitatively with experiments for CN-substituted copper complexes in solution. The low-frequency, far-infrared part of the protein spectra contains label-specific information in the difference spectra when compared with the wild type protein. Depending on the position of the labels, local structural changes are observed. For example, introducing the -SCN label at Ala129 leads to breaking of the α-helical structure with concomitant change in the far-infrared spectrum. Finally, changes in the local hydration of SCN-labeled alanine residues as a function of time can be related to the reorientation of the label. It is concluded that -SCN is potentially useful for probing protein dynamics, both in the high-frequency part (CN-stretch) and in the far-infrared part of the spectrum.

GGNBP2 regulates histone ubiquitination and methylation in spermatogenesis

ABSTRACT Gametogenetin binding protein 2 (GGNBP2) was indispensable in normal spermatids for transformation into mature spermatozoa in mice, and when Gametogenetin binding protein 2 is bound to BRCC36 and RAD51, the complex participates in repairing DNA double-strand breaks (DSB) during the meiotic progression of spermatocytes. Ggnbp2 knockout resulted in the up-regulation of H2AK119ubi and down-regulation of H2BK120ubi in GC-2 cells (mouse spermatogonia-derived cell line) and postnatal day 18 testis lysate. Our results also demonstrated that Gametogenetin binding protein 2 inducedASXL1 to activate the deubiquitinating enzyme BAP1 in deubiquitinating H2A, while Gametogenetin binding protein 2 knockout disrupted the interaction between ASXL1 and BAP1, resulting in BAP1 localization change. Furthermore, the Gametogenetin binding protein 2 deletion reduced H2B ubiquitination by affecting E2 enzymes and E3 ligase binding. Gametogenetin binding protein 2 regulated H2A and H2B ubiquitination levels and controlled H3K27 and H3K79 methylation by PRC2 subunits and histone H3K79 methyltransferase. Altogether, our results suggest that Ggnbp2 knockout increased DNA damage response by promoting H2A ubiquitination and H3K27trimethylation (H3K27me3) and reduced nucleosome stability by decreasing H2B ubiquitination and H3K79 dimethylation (H3K79me2), revealing new mechanisms of epigenetic phenomenon during spermatogenesis. Gametogenetin binding protein 2 seems critical in regulating histone modification and chromatin structure in spermatogenesis.

GC Insights: Communicating long-term changes in local climate risk using a physically plausible causal chain

Abstract. Directly linking greenhouse gas emissions or global warming to experiences of local climatic changes is a potentially important communication tool. Using observations, we develop a physically plausible “causal chain” visualisation to demonstrate the connections between global carbon dioxide emissions and local climate events. We highlight how increased flood risk in one river basin in the UK could be discussed with people directly affected by recent floods.

Morphological Measurement and Clinical Significance of Abnormal Development of Distal Femur with Hemophilia Knee Arthritis: A Consideration on the Renewal of Total Knee Prosthesis.

The knee joint of hemophiliacs may face the result of local morphological changes due to long-term irritation of synovitis. This study aims to elucidate the morphological characteristics of distal femur in hemophilic arthritis (HA) and compare the compatibility of three types of prostheses with the anteroposterior (AP) and mediolateral (ML) dimensions of the femoral osteotomy surface. This study retrospectively and randomly selected 50 patients with HA registered for treatment at our hospital from June 2016 to August 2022 as the study subjects, with an equal number of male osteoarthritis (OA) patients and healthy male individuals set as the control group. This study used medical digitalization software to simulate osteotomies on the distal femur during total knee arthroplasties (TKA) for 50 patients with HA, OA patients, and the healthy population, respectively, and measure the morphological parameters to compare with three commonly used femoral components of TKA in clinical practice. The differences between the femur resection of anteroposterior and mediolateral (FRAP, FRML) osteotomy surface and the prosthesis's BOX-AP/ML were compared in three prostheses. One-way ANOVA and multiple Kruskal-Wallis H test were used for the normal or non-normal distribution data, and pairwise comparisons between groups were conducted using the Bonferroni method, and the linear correlation analysis was utilized to assess the relationship between section femoral morphological data and prosthesis parameters. In HA patients, the morphological characteristics of the distal femur were shown as shorter than femur AP (FAP), medial and lateral condyle anterior-posterior dimension (FMCAP, FLCAP), notch width (NW), posterolateral condyle height (PLCH), posteromedial condyle width (PMCW), and posterior condylar axis length (PCAL) dimension. They had comparatively smaller femur section aspect ratios (p < 0.005). They showed longer posterolateral condyle width (PLCW), anterior condyle mediolateral dimension (FRACML), anterolateral condyle height (ALCH), and femur resection anterior condylar mediolateral (FRACML) dimension (p < 0.005). They showed larger distal femur aspect ratio and resection aspect ratio (FAR, FRAR, p < 0.005). All selected prostheses showed ML undercoverage under similar AP dimensions, and ML undersizing of Attune systems was more obvious in three femoral prostheses. The distal femur morphological change of HA patient is shown as smaller AP dimension, narrow posterior condyle spacing, lower and shallower trochlear, thinner anterior condyle, wider and lower intercondylar notch and higher posterior-lateral condyle. The selected prostheses showed ML undercoverage under similar AP dimensions. This typical morphological tendency of the distal femur seems to warrant consideration in the process of knee joint prosthesis upgrading.

Wind-Sea and Swell Climate in the Black and Azov Seas, Based on 42-Year Spectral Wave Hindcast

Long-term wave climates of the Black and Azov Seas are widely assessed based on the bulk wave parameters of the mixed sea. However, studies based on spectral wave partitions are rarely documented. Assessment of the wave climate based on the individual wave systems provides a more reliable description of the sea states' characteristics and the variability in the long-term wave climate. For instance, the wind-sea climate may reflect a real change in the local climate. However, local change in swell characteristics may not necessarily reflect a change in the local climate, and it can locally influence the mixed sea climate variability. This study assessed the spatial distributions of the long-term averages and maxima of mixed seas, wind-sea, and swell partitions at annual and seasonal scales. The contributions of wind-sea and swell partitions to the mixed-sea were computed, and their spatial and temporal variability was also assessed for overall and extreme sea state conditions. Finally, the occurrence in main wave systems' directions and occurrence of crossing, opposing, and following wind-sea and swell interactions were computed. The wind-sea contribution to the mixed-sea exceeds 70 % in all Black Sea and >95 % in the Azov Sea. The swells are more dominant on the Northeastern and Northwestern Black Sea basins. Thus, the results show spatial and temporal variability in the wind-sea climate close to the mixed sea but largely different compared to the swell climate. The inter-annual trends in the swell partitions and wind-sea are inversed at some locations.

An Optimal Weighted Ensemble Machine Learning Approach to Accurate Estimate the Coastal Boundary Layer Height Using ERA5 Multi‐Variables

AbstractThe coastal boundary layer height (CBLH/Coastal‐BLH) is critical in determining the exchange of heat, momentum, and materials between the land and ocean, thereby regulating the local climate and weather change. However, due to the complexity of geographical characteristics and meteorological conditions, accurate estimation of the CBLH remains challenging. Herein, based on continuous high‐resolution measurements of CBL performed from November 2019 to April 2020 in coastal Ningbo city in eastern China, an optimal weighted ensemble model (OWEM) integrating multi‐meteorological variables of the ERA5 reanalysis data sets is constructed and validated to estimate the CBLH. The mean absolute percentage error of the derived CBLH by OWEM is as low as 3%–5%, significantly lower than that of 36%–65% of the ERA5 CBLH products. Furthermore, three categories of different weather scenarios, that is, sunny, cloudy, and rainy, are separately discussed, and OWEM shows greater performance and higher accuracies in comparison with the traditional Least Absolute Shrinkage and Selection Operator, Random Forest, Adaboost, LightGBM, and ensemble model, among which, OWEM under fair weather days behave best, with a robust R2 of 0.97 and a minimum mean absolute error (MAE) of 23 m. Further training results based on wind flow classification, that is, land breeze, sea breeze, and parallel wind, also indicate the outperformance of OWEM than other models, with a relatively large error in parallel wind of 50 m. Subsequent analysis of the Shapley Additive Explanations method strongly correlated with model feature importance, both reveal that thermodynamic factors such as temperature (T2m) and wind velocity (10 m U) are the major factors positively related to estimation accuracy during sunny days. Nevertheless, Relative Humidity dominates on rainy and cloudy days, TP on land breeze days, and dynamic variables like 10 m U and 10 m V on entire types of wind flow weather. In conclusion, the accurate estimation of CBLH from OWEM serves as a feasible and innovative approach, providing technical support for marine meteorology and related engineering applications, for example, onshore wind power, coastal ecological protection, etc.

Habituation of Central and Electrodermal Responses to an Auditory Two-Stimulus Oddball Paradigm

The orienting reaction (OR) towards a new stimulus is subject to habituation, i.e., progressively attenuates with stimulus repetition. The skin conductance responses (SCRs) are known to represent a reliable measure of OR at the peripheral level. Yet, it is still a matter of debate which of the P3 subcomponents is the most likely to represent the central counterpart of the OR. The aim of the present work was to study habituation, recovery, and dishabituation phenomena intrinsic to a two-stimulus auditory oddball paradigm, one of the most-used paradigms both in research and clinic, by simultaneously recording SCRs and P3 in twenty healthy volunteers. Our findings show that the target stimulus was capable of triggering a more marked OR, as indexed by both SCRs and P3, compared to the standard stimulus, that could be due to its affective saliency and relevance for task completion; the application of temporal principal components analysis (PCA) to the P3 complex allowed us to identify several subcomponents including both early and late P3a (eP3a; lP3a), P3b, novelty P3 (nP3), and both a positive and a negative Slow Wave (+SW; −SW). Particularly, lP3a and P3b subcomponents showed a similar behavior to that observed for SCRs , suggesting them as central counterparts of OR. Finally, the P3 evoked by the first standard stimulus after the target showed a significant dishabituation phenomenon which could represent a sign of the local stimulus change. However, it did not reach a sufficient level to trigger an SCR/OR since it did not represent a salient event in the context of the task.

Chromatin and gene regulation in archaea.

The chromatinisation of DNA by nucleoid-associated proteins (NAPs) in archaea 'formats' the genome structure in profound ways, revealing both striking differences and analogies to eukaryotic chromatin. However, the extent to which archaeal NAPs actively regulate gene expression remains poorly understood. The dawn of quantitative chromatin mapping techniques and first NAP-specific occupancy profiles in different archaea promise a more accurate view. A picture emerges where in diverse archaea with very different NAP repertoires chromatin maintains access to regulatory motifs including the gene promoter independently of transcription activity. Our re-analysis of genome-wide occupancy data of the crenarchaeal NAP Cren7 shows that these chromatin-free regions are flanked by increased Cren7 binding across the transcription start site. While bacterial NAPs often form heterochromatin-like regions across islands with xenogeneic genes that are transcriptionally silenced, there is little evidence for similar structures in archaea and data from Haloferax show that the promoters of xenogeneic genes remain accessible. Local changes in chromatinisation causing wide-ranging effects on transcription restricted to one chromosomal interaction domain (CID) in Saccharolobus islandicus hint at a higher-order level of organisation between chromatin and transcription. The emerging challenge is to integrate results obtained at microscale and macroscale, reconciling molecular structure and function with dynamic genome-wide chromatin landscapes.

Changed Seasonality and Forcings of Peak Annual Flows in Ephemeral Channels at Flagstaff, Northern Arizona, USA

Flood variability associated with urbanization, ecological change, and climatic change is of increasing economic and social concern in and around Flagstaff, Arizona, where flood hydrology is influenced by a biannual precipitation regime and the relatively unique geologic setting at the edge of the San Francisco Volcanic Field on the southern edge of the Colorado Plateau. There has been limited long-term gauging of the ephemeral channels draining the developed lands and dry coniferous forests of the region, resulting in a spaciotemporal gap in observation-based assessments of large-scale flooding patterns. We present new data from over 10 years of flood monitoring using a crest stage gauge network, combined with other channel monitoring records from multiple agency sources, to assess inter-decadal patterns of flood change in the area, with a specific emphasis on examining how various controls and disturbances have altered the character and seasonality of peak annual flows. Methods of analysis included the following: using Fisher’s Exact Test to compare the seasonality of flooding between historic data spanning the 1970s and contemporary data obtained since 2010; summarizing GIS-based spatial data and meteorological timeseries to characterize study catchment conditions and changes between flood study periods; and relating spatiotemporal patterns of flood seasonality and occurrences of notably large floods with catchment characteristics and environmental changes. Our results show systematic patterns and changes in Flagstaff-area flood regimes that relate to geologic and topographic controls of the varied catchment systems, and in response to records of climate variations and local catchment disturbances, including urbanization and, especially, high-severity wildfire. For most catchments there has been a shift from predominantly late winter to spring snowmelt floods, or mixed seasonal flood regimes, towards monsoon-dominated flooding, patterns which may relate to observed local warming and precipitation changes. Post-wildfire flooding has produced extreme flood discharges which have likely exceeded historical estimates of flood magnitude over decade-long monitoring periods by one to two orders of magnitude. We advocate for continued monitoring and the expansion of local stream gauge networks to enable seasonal, magnitude-frequency trend analyses, improved climate and environmental change attribution, and to better inform the many planned and ongoing flood mitigation projects being undertaken in the increasingly developed Flagstaff region.

Structural, morphological, and optical investigations of Mn-doped LaAlO3 perovskite obtained by microwave-assisted combustion and rapid calcination at low temperature

In this work, LaAlO3 perovskite was doped with 1, 2, 3, 5, 8, and 13 mol% of Mn using the microwave-assisted combustion method. The powders produced were heat treated at 700 °C and 900 °C for 10 min in an adapted microwave oven and then characterized by Thermogravimetric analysis (TG/DTG) and Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD) and Rietveld refinement, X-ray Photoelectron Spectroscopy (XPS), Fourier Transform Infrared Spectroscopy (FTIR), Raman, Ultraviolet–Visible Reflectance (UV–Vis), Field Emission Scanning Electron Microscopy (FE-SEM) and Energy Dispersive X-ray Spectroscopy (EDS). The materials produced doped with the highest concentration of Mn (13 %) showed a single-phase reduced crystallite size compared to the pure sample. The unit cell volumes increased compared to the pure material, while the oxidation state of the dopant was mainly Mn3+. The refinement data for the volume of the different polyhedral that comprise the LaAlO3 unit cell revealed a local change at both sites, which may also indicate Mn substitution at the A site. The heat treatment temperature did not change significantly, demonstrating the method's efficiency in producing perovskites at temperatures and times below those reported in the literature. The morphology observed was porous and irregular agglomerates, and the bandgap was 2.90 eV.

Probing charge redistribution at the interface of self-assembled cyclo-P5 pentamers on Ag(111)

Phosphorus pentamers (cyclo-P5) are unstable in nature but can be synthesized at the Ag(111) surface. Unlike monolayer black phosphorous, little is known about their electronic properties when in contact with metal electrodes, although this is crucial for future applications. Here, we characterize the atomic structure of cyclo-P5 assembled on Ag(111) using atomic force microscopy with functionalized tips and density functional theory. Combining force and tunneling spectroscopy, we find that a strong charge transfer induces an inward dipole moment at the cyclo-P5/Ag interface as well as the formation of an interface state. We probe the image potential states by field-effect resonant tunneling and quantify the increase of the local change of work function of 0.46 eV at the cyclo-P5 assembly. Our experimental approach suggest that the cyclo-P5/Ag interface has the characteristic ingredients of a p-type semiconductor-metal Schottky junction with potential applications in field-effect transistors, diodes, or solar cells.

Linking local climate scenarios to global warming levels: applicability, prospects and uncertainties

Abstract Global warming levels (GWLs) are increasingly becoming a central concept in climate change studies. In recent years, their integrative quality for climate change impact analysis has been demonstrated, and methodological advancements have helped to compensate for some inherent shortfalls of the concept. However, their applicability at the regional level is debatable, and no study to date has examined the possibility of linking local climate scenarios to GWLs. For the case of Austria, we have evaluated the relation between global and local warming patterns, and whether version changes of global climate models could be incorporated into local climate scenarios by means of the GWL concept, without updating the actual data. We applied the time sampling approach, where GWLs are determined as periods when global mean temperature anomalies cross a certain threshold. GWL periods were sampled both from the global models in the background of the local climate scenarios (CMIP5), and from an equivalent ensemble of newer-generation climate models (CMIP6). Uncertainties resulting from sampling GWLs from different global climate model ensembles were examined, and prospects for local climate change impact assessments were discussed. Accounting for updated global climate model versions might be useful when the changes at certain GWLs are related to fixed reference periods, but temperature increments between GWLs remained relatively constant across model versions, even on the local level. The study bridges a significant gap to link regional and local climate projections to GWLs. Climate change impacts assessments that build on those datasets can benefit from the integrative character of GWLs, making studies comparable across multiple disciplines and model versions, and thus fostering a way to communicate local climate change impacts more comprehensible.

How Should a Medical-Legal Partnership Address Unique Needs of People With Criminal Legal System Involvement?

Medical-legal partnerships (MLPs) are well suited to address health-harming legal needs associated with the collateral consequences of mass incarceration in the United States, such as those that limit access to food, housing, employment, and family reunification postrelease. MLP innovations seek to expand the current model to address patients' criminal, as well as postrelease, civil legal needs by including community health workers and some patients as legal partners and creating coalitions to promote local and state policy change. Overall, this article explains how these MLP innovations can support rights of people returning to communities after incarceration and can be leveraged to mitigate criminal legal system involvement.

Triple-function carbon-based Ca2+ ion-selective pH ring microelectrode to study real-time bacteria-mediated hydroxyapatite corrosion

BackgroundThe local pH change mediated by the pathogenic bacterial species Streptococcus mutans plays a significant role in the corrosion of hydroxyapatite (HA) present in the tooth in the dynamic oral cavity. The acid produced by the bacteria decreases the local pH and releases Ca2+ ions from the HA. We studied the bacteria-mediated demineralization of HA by scanning electrochemical microscopy (SECM) after growing S. mutans biofilm on HA for 7 days. ResultsWe notably developed a triple-function SECM-compatible tip that could be positioned above the biofilm. It can also measure the pH and [Ca2+] change simultaneously above the biofilm-HA substrate. The triple-function SECM tip is a combination of a potentiometric pH sensor deposited with iridium oxide and a dual-function carbon-based Ca2+ ion-selective membrane electrode with a slope of 67 mV/pH and 34.3 mV/log [Ca2+], respectively. The distance-controlled triple-function SECM tip monitored real-time pH and [Ca2+] changes 30 μm above the S. mutans biofilm. The high temporal resolution pH data demonstrated that after approximately 20 min of sucrose addition, S. mutans started to produce acid to titrate the solution buffer, causing a pH change from 7.2 to 6.5 for HA and from 7.2 to 5 for the glass substrate. We observed that, after 30 min of acid production, ∼300 μM of Ca2+ ions were increased at pH 6.5 above the biofilm surface as a result of the pH change in the local microenvironment. After the release of Ca2+ from HA, the pH environment again shifted toward the neutral side, from 6.5 to 7.2. Therefore, precipitation of Ca2+ happens at the top of the biofilm, thus corroding the HA from underneath. For a glass substrate, in contrast, no Ca2+ ions were released, and the pH did not change back to 7.2. We were able to observe the dynamics of the HA demineralization–remineralization process simultaneously with our newly developed triple-function SECM tip or microprobe. SignificanceThis technique could notably advance the study of similar complex processes, such as bacteria-mediated corrosion in biomedical and environmental contexts.

FORENSIC-MEDICAL FEATURES OF THE HEART IN CASES OF ACUTE CORONARY INSUFFICIENCY WITH SUDDEN CARDIAC DEATH

The article provides an assessment of changes in the endocardium of the atria and ventricles of the heart in cases of sudden cardiac death due to acute coronary insufficiency. In cases of sudden death due to acute coronary insufficiency, distinct focal pathological changes were observed in the connective tissue of the endocardium of the left atrium and ventricle, manifested by loss of fibrillar structures and fragmentation of its non-cellular elements. This corresponded to local contractile changes in the cardiomyocytes, localised in the subendocardial space of the affected parts of the heart, leading to local fragmentation and an increase in the thickness of the endocardial folds. In addition, the loss of their characteristic waviness and the acquisition of linearity were observed. These changes are considered to be manifestations of morpho-functional disorders of the endocardium of the specified heart segments. The aim of the study was to determine the characteristics of endocardial changes in the atria and ventricles in cases of sudden death due to acute ischaemic heart disease. Materials and Methods. The study material included 12 hearts from young and middle-aged individuals without cardiovascular disease (control group) and 12 hearts from working-age individuals who died suddenly of acute ischaemic heart disease. Conclusions: At the time of death from acute ischaemic heart disease, there were pronounced focal pathological changes in cellular and non-cellular components in the connective tissue of the endocardium of the left atrium and ventricle. These changes caused focal contractile changes in cardiomyocytes localised in the subendocardial layer of the myocardium of the left ventricle. The identified changes in the subendocardial layer of the myocardium caused focal thickening, fragmentation, and increased thickness of the endocardial folds, their undulation, which can be considered as manifestations of morpho-functional disorders of the endocardium.

The soft channels of policy diffusion: Insights from local climate change adaptation policy

AbstractDiffusion has become both an important concept for studying policy spread and a popular governance approach, particularly where direct coercion is unavailable or undesirable. However, the prevailing mechanism‐centered concept is difficult to measure and poorly captures the governance potential of policy diffusion. To address these issues, this article presents a new channel‐centered framework that distinguishes between six soft policy diffusion channels: autonomous, collaborative, exemplary, persuasive, organized, and funded diffusion. The framework is probed by studying local climate change adaptation policy using original survey data collected from the administrations of 190 municipalities located in the central German state of Hessen. The regression results indicate that the local institutionalization of adaptation in Hessen is associated with several interventions by higher levels of government, including the provision of a policy model, a municipal climate network, and grant programs. However, the density of concrete adaptation measures is associated with noninstitutionalized exchanges between municipalities. External grants are also found to be more effective in institutionalizing adaptation in larger municipalities. These results demonstrate the usefulness of the framework for distinguishing and comparing different diffusion channels and suggest that different types of interventions may be required to effectively support adaptation policy development at the local level.

Retrosynthesis prediction with an iterative string editing model

Retrosynthesis is a crucial task in drug discovery and organic synthesis, where artificial intelligence (AI) is increasingly employed to expedite the process. However, existing approaches employ token-by-token decoding methods to translate target molecule strings into corresponding precursors, exhibiting unsatisfactory performance and limited diversity. As chemical reactions typically induce local molecular changes, reactants and products often overlap significantly. Inspired by this fact, we propose reframing single-step retrosynthesis prediction as a molecular string editing task, iteratively refining target molecule strings to generate precursor compounds. Our proposed approach involves a fragment-based generative editing model that uses explicit sequence editing operations. Additionally, we design an inference module with reposition sampling and sequence augmentation to enhance both prediction accuracy and diversity. Extensive experiments demonstrate that our model generates high-quality and diverse results, achieving superior performance with a promising top-1 accuracy of 60.8% on the standard benchmark dataset USPTO-50 K.

Ion Dynamics in Nanocrystalline Li2S‐LiI – on the Influence of Local Disorder on Short‐Range Hopping and Long‐Range Ion Transport

The enormous interest in developing powerful Li‐based batteries leads to a boost in materials research. Though Li–sulfur batteries offer very high energy densities, the nature of Li‐ion dynamics in the final discharge product has not been fully understood yet. While nanocrystalline shows enhanced ion dynamics compared to its coarse‐grained counterpart, the interaction of with another binary such as LiI seems to be rather unexplored. Herein, an equimolar mixture of and LiI is treated in a high‐energy ball mill, and both the overall and local structural changes are studied by X‐ray powder diffraction and nuclear magnetic resonance (NMR), respectively . Besides the formation of amorphous regions, evidences are found for the generation of anion‐mixed sites that give rise to facile Li exchange on the 2D exchange NMR timescale. Compared to a coarse‐grained reference sample, the overall (bulk) ionic conductivity of nanocrystalline ‐LiI increases by two orders of magnitude. Besides the anion‐mixing effect, this increase benefits from nanosize effects that include the formation of defect‐rich interfacial regions. NMR relaxation measurements fully support this result and reveal heterogeneous dynamics with lower activation energies for both the localized hopping processes and long‐range ion transport in nm‐sized ‐LiI.

Buyang huanwu decoction improves synaptic plasticity of ischemic stroke by regulating the cAMP/PKA/CREB pathway

Ethnopharmacological relevanceIschemic stroke is an acute central nervous system disease that poses a threat to human health. It induces a series of severe pathological mechanisms, ultimately leading to neuronal cell death in the brain due to local ischemia and hypoxia. Buyang Huanwu decoction (BYHWD), as a representative formula for treating ischemic stroke, has shown good therapeutic effects in stroke patients. Aim of the studyThis study aimed to explore the mechanism of BYHWD in promoting neural remodeling after ischemic stroke from the perspective of neuronal synaptic plasticity, based on the cAMP/PKA/CREB signaling pathway. Materials and methodsA modified suture technique was employed to establish a rat model of MCAO. The rats were divided into sham, model, and BYHWD (20 g/kg) groups. After the corresponding intervention, rat brains from each group were collected. TMT quantitative proteomics technology was employed for the research. Following proteomics studies, we investigated the mechanism of BYHWD in the intervention of ischemic stroke through animal experiments and cell experiments. The experimental animals were divided into sham, model, and BYHWD (5 g/kg, 10 g/kg, and 20 g/kg) groups. Infarct volume and severity of brain injury were measured by TTC staining. HE staining was utilized to evaluate alterations in tissue morphology. The Golgi staining was used to observe changes in cell body, dendrites, and dendritic spines. Transmission electron microscopy was used to observe the ultrastructure of synapses in the cortex and hippocampus. TUNEL staining was conducted to identify apoptotic neurons. Meanwhile, a stable and reliable (OGD/R) SH-SY5Y cell model was established. The effect of BYHWD-containing serum on SH-SY5Y cell viability was measured by CCK-8 kit. The apoptosis situation of SH-SY5Y cells was determined by Annexin V-FITC/PI. Immunofluorescence was employed to measure the fluorescence intensity of synaptic-related factors Syt1, Psd95, and Syn1. Synaptic plasticity pathways were assessed by using RT-qPCR and Western blot to determine the expression levels of cAMP, Psd95, Prkacb, Creb1/p-Creb1, BDNF, Shank2, Syn1, Syt1, Bcl-2, Bcl-2/Bax mRNA and proteins. ResultsAfter treatment with BYHWD, notable alterations were detected in the signaling pathways linked to synaptic plasticity and the cAMP signaling pathway-related targets among the intervention targets. This trend of change was also reflected in other bioinformatics analyses, indicating the important role of synaptic plasticity changes before and after modeling and drug intervention. The results of vivo and vitro experiments showed that BYHWD improved local pathological changes, and reduced cerebral infarct volume, and neurological function scores in MCAO rats. It increased dendritic spine density, improved synaptic structural plasticity, and had a certain neuroprotective effect. BYHWD increased the postsynaptic membrane thickness, synaptic interface curvature, and synaptic quantity. 10% BYHWD-containing serum was determined as the optimal concentration for treatment. 10% BYHWD-containing serum significantly reduced the overall apoptotic rate of (OGD/R) SH-SY5Y cells. Immunofluorescence experiments demonstrated that 10% BYHWD-containing serum could improve synaptic plasticity and increase the relative expression levels of synaptic-related proteins Syt1, Psd95, and Syn1. BYHWD and decoction-containing serum upregulated the mRNA and protein expression levels in (OGD/R) SH-SY5Y cells and MCAO rats, suggesting its ability to improve damaged neuronal synaptic plasticity and enhance transmission efficiency, which might be achieved through the regulation of the cAMP/PKA/CREB pathway. ConclusionsThis study may provide a basis for clinical medication by elucidating the underlying experimental evidence for the promotion of neural plasticity after ischemic stroke by BYHWD.

Electronic structure evolution upon lithiation: A Li K-edge study of silicon oxide anode through X-ray Raman spectroscopy

The comprehensive understanding of the local structural changes surrounding lithium in lithium silicate (LixSiOy) and silicide (LixSi) within Li/SiOx batteries during the reversible structural transformations has been hindered by the limitations of current methodologies. In this work, the evolution of electronic structure at various lithiation stages has been addressed well by examining the Li K-edge spectra through X-ray Raman spectroscopy (XRS). The features observed in the Li K-edge XRS spectra provide insights into the development and alteration of LixSiOy, which emerges in the initial phases and may be accompanied by a reduction in the ionicity of Li–O bonding during lithiation. These features also agree well with the accompanying FDMNES code simulation. The correlation between electrochemical mechanisms and spectral characteristics is further explored by applying pseudo-Voigt peaks and cumulative pseudo-Voigt functions for fitting purposes. The absence of a significant edge shift indicates a similarity in the electronic structure of LixSi throughout lithiation, and no evidence of Li2O formation has also been observed. The Li K-edge XRS spectra exhibit strong agreement with the electrochemical behavior, establishing it as a valuable tool for investigating the evolution of electronic structure in Li/SiOx batteries.