Events In Process Research Articles

Search for Crucial Events in Physiological Processes

Search for Crucial Events in Physiological Processes

Phytochemical Profiling of Ethanolic Extracts from the Bark and Tuber of Colocasia Esculenta (L) Schott, Identification and Quantification of Compounds Present in Kenya

Bacterial infections are the major cause of morbidity and mortality, with high financial impacts among human beings globally. Antibiotics are used in the treatment of bacterial infections. They eliminate or prevent bacteria from reproducing and spreading. Since they do so at different rates, some bacteria may mutate with an under-dose and resist antibiotic treatment through natural selection. The bacteria develop acquired antimicrobial resistance to several drugs due to increased use and misuse of antibiotics. This has resulted in increased interest in the use of medicinal plants in the treatment of bacterial infections. The plants serve as resistance modifying agents from the metabolites that they produce. Previous studies show that metabolites such as tannins, alkaloids and polyphenols may have antimicrobial and resistance-modifying properties. They destroy the microorganisms and interfere with the crucial events in the pathogenic process, reducing the bacteria's ability to develop resistance to botanicals.
 Colocasia esculenta (L) Schott leaves were previously tested against Pseudomonas aeruginosa and the extracts showed higher activity against bacterial infections compared to the use of the antibiotic drug Clarithromycin. Leaves of aqueous and ethanolic extracts of Colocasia esculenta in previous studies were found to contain steroids, Flavonoids, saponins, terpenoids, Anthroquinones and Alkaloids. The extracts were found to have anti-diabetic activity and anti-helminthic activity compared to the standard drug, Piperazine citrate. This study determined phytochemicals present in ethanolic extracts of the bark and tuber of Colocasia esculenta (L) Schott in Kenya. A qualitative research design was adopted in this study. Colocasia esculenta plant samples used in this study were purposely obtained from Kaimosi Friends University farm in Vihiga County. They were taken to the laboratory of Botany at Maseno University, where they were washed with sterile distilled water, separated into bark and tuber, dried, crushed into powder, packed separately in airtight plastic containers, labelled and stored for later use. Plant ethanolic extracts were prepared separately (from powders) in triplicate for use in experiments. Screening for the presence of phytochemicals was done using standard methods. Qualitative analysis of the plant samples was used to check for the presence of flavonoids, saponins, steroids, tannins, alkaloids, glycosides, phenolic compounds and anthraquinones. Data were collected and then analyzed. Results were presented in the form of a table as the presence or absence of the specific phytochemicals. Results showed that Saponins, steroids, tannins, alkaloids, glycosides and phenolic compounds were present in both the tuber and bark ethanolic extracts of Colocasia esculenta. Interestingly, the bark extract had more saponins and tannins than the tuber extract. The results of this study can be used to further determine the antibacterial activity of the extracts on selected sidearm bacteria. The findings could be of commercial interest to both the Kenya Ministry of Health and pharmaceutical companies in the world in the production of new antibacterial drugs. Policymakers may help reduce the increasing mortality due to bacterial infections by using results from this study. The results can also support Kenya's Vision 2030 of ensuring adequate health care for all by integrating traditional healthcare practices into the national healthcare system for the realization of universal health coverage.

Interpreting Negative IOD Events Based on the Transfer Routes of Wave Energy in the Upper Ocean

Abstract The present study adopts an energy-based approach to interpret the negative phase of Indian Ocean dipole (IOD) events. This is accomplished by diagnosing the output of hindcast experiments from 1958 to 2018 based on a linear ocean model. The authors have performed a composite analysis for a set of negative IOD (nIOD) events, distinguishing between independent nIOD events and concurrent nIOD events with El Niño–Southern Oscillation (ENSO). The focus is on investigating the mechanism of nIOD events in terms of wave energy transfer, employing a linear wave theory that considers the group velocity. The proposed diagnostic scheme offers a unified framework for studying the interaction between equatorial and off-equatorial waves. Both the first and third baroclinic modes exhibit interannual variations characterized by a distinct packet of eastward energy flux associated with equatorial Kelvin waves. During October–December, westerly wind anomalies induce the propagation of eastward-moving equatorial waves, leading to thermocline deepening in the central-eastern equatorial Indian Ocean, a feature absent during neutral IOD years. The development of wave energy demonstrates different patterns during nIOD events of various types. In concurrent nIOD–ENSO years, characterized by strong westerly winds, the intense eastward transfer of wave energy becomes prominent as early as October. This differs significantly from the situation manifested in independent nIOD years. The intensity of the energy-flux streamfunction/potential reaches its peak around November and then rapidly diminishes in December during both types of nIOD years. Significance Statement The present study provides an interpretation of wave energy transfer episodes in the upper ocean during the negative phase of the Indian Ocean dipole (IOD) based on the diagnosis of hindcast experiments. The results suggest that the reflection of Kelvin and Rossby waves at the eastern and western boundaries of the Indian Ocean (IO), respectively, accompanied by variations in thermocline depth, plays a crucial role in the development process of IOD events. Specifically, during the negative phase of the IOD, the tropical IO exhibits positive signals of energy-flux streamfunction in the Northern Hemisphere, along with positive signals of energy-flux potential associated with westerly wind anomalies occurring in October–December. These findings highlight the significance of these factors in shaping the characteristics of negative IOD events.

Efficacy and Safety of Conversion Surgery for Advanced Hepatocellular Carcinoma After Hepatic Arterial Infusion Chemotherapy.

The aim of this study was to investigate the efficacy and safety of conversion surgery for advanced hepatocellular carcinoma (HCC) after hepatic arterial infusion chemotherapy (HAIC). Data from 172 HCC patients treated at Sun Yat-sen University Cancer Center between January 2016 and June 2021 with effective assessment of HAIC treatment response were retrospectively analyzed. Clinical pathological data, treatment process, survival, and occurrence of adverse events were recorded. Patients were grouped according to whether they achieved imaging remission after HAIC, underwent conversion surgery, and met the surgical resection criteria. Efficacy and safety were analyzed. The median progression-free survival (PFS) and overall survival (OS) in the imaging remission group were 8.6 months and 26.3 months, respectively, which were longer than the 4.6 months (P<0.05) and 15.6 months (P<0.05) in the nonremission group. Compared with 6.7 months and 18.9 months in the HAIC maintenance group, the median PFS and median OS in the conversion surgery group were 16.5 months (P<0.05) and 45.0 months (P<0.05), but there was a higher risk of treatment-related hemoglobin decrease, alanine aminotransferase increase, aspartate aminotransferase increase, and total bilirubin increase (P<0.05). The risk of biliary fistula, abdominal hemorrhage and ascites in the HAIC conversion surgery group was higher than that of the single surgery group (P<0.05). Compared with the conversion surgery group, the median PFS and median OS of patients in the HAIC maintenance group who met the resection criteria were shorter: 7.1 months (P<0.05) and 21.7 months (P<0.05), respectively. All adverse events during the study were less than moderate, and no toxicity-related deaths occurred during follow-up. HAIC-based conversion therapy had acceptable toxic effects and could effectively stabilize intrahepatic lesions in advanced HCC, improve the survival benefit of patients, and provide some patients with the opportunity for conversion surgery to further improve prognosis.

Advances in free-electron-laser based scattering techniques and spectroscopic methods

&lt;sec&gt;In 2005, the FLASH soft X-ray free-electron laser (FEL) in Hamburg, Germany, achieved its first lasing, which began an intensive phase of global FEL construction. Subsequently, the United States, Japan, South Korea, China, Italy, and Switzerland all began building such photon facilities. Recently, the new generation of FEL has started to utilize superconducting acceleration technology to achieve high-repetition-rate pulse output, thereby improving experimental efficiency. Currently completed facility is the European XFEL, ongoing constructions are the LCLS-II in the United States and the SHINE facility in Shanghai, and the facility in preparation is the Shenzhen superconducting soft X-ray free-electron laser (S&lt;sup&gt;3&lt;/sup&gt;FEL).&lt;/sec&gt;&lt;sec&gt;These FEL facilities generate coherent and tunable ultrashort pulses ranging from the extreme ultraviolet to hard X-ray spectrum, which advances the FEL-based scattering techniques such as ultrafast X-ray scattering, spectroscopy, and X-ray nonlinear optics, thereby transforming the way we study correlated quantum materials on an ultrafast timescale.&lt;/sec&gt;&lt;sec&gt;The self-amplified spontaneous emission (SASE) process in FEL leads to timing jitter between FEL pulses and the synchronized pump laser, influencing the accuracy of ultrafast time-resolved measurements. To address this issue, timing tools have been developed to measure these jitters and reindexed each pump-probe signal after measurement. This success enables ultrafast X-ray diffraction (UXRD) to be first realized, and a systematic study of Peierls distorted materials is demonstrated. In addition, the high flux of FEL pulses enables Fourier transform inelastic X-ray scattering (FT-IXS) method, which can extract the phonon dispersion curve of the entire Brillouin zone by performing the Fourier transform on the measured momentum dependent coherent phonon scattering signals, even when the system is in a non-equilibrium state.&lt;/sec&gt;&lt;sec&gt;The UXRD is typically used to study ultrafast lattice dynamics, which requires hard X-ray wavelengths. In contrast, time resolved resonant elastic X-ray scattering (tr-REXS) in the soft X-ray regime has become a standard method of investigating nano-sized charge and spin orders in correlated quantum materials on an ultrafast time scale.&lt;/sec&gt;&lt;sec&gt;In correlated quantum materials, the interplay between electron dynamics and lattice dynamics represents another important research direction. In addition to Zhi-Xun Shen's successful demonstration of the combined tr-ARPES and UXRD method at SLAC, this paper also reports the attempts to integrate UXRD with resonant X-ray emission spectroscopy (RXES) for the simultaneous measurement of electronic and lattice dynamics.&lt;/sec&gt;&lt;sec&gt;Resonant inelastic X-ray scattering (RIXS) is a powerful tool for studying elementary and collective excitations in correlated quantum materials. However, in FEL-based soft X-ray spectroscopy, the wavefront tilt introduced by the widely used grating monochromators inevitably stretches the FEL pulses, which degrades the time resolution. Therefore, the new design at FEL beamlines adopts low line density gratings with long exit arms to reduce pulse stretch and achieve relatively high energy resolution. For example, the Heisenberg-RIXS instrument at the European XFEL achieves an energy resolution of 92 meV at the Cu &lt;i&gt;L&lt;/i&gt;&lt;sub&gt;3&lt;/sub&gt; edge and approximately 150 fs time resolution.&lt;/sec&gt;&lt;sec&gt;In recent years, scientists at SwissFEL’s Furka station have drawn inspiration from femtosecond optical covariance spectroscopy to propose a new method of generating two-dimensional time-resolved resonant inelastic X-ray scattering (2D tr-RIXS) spectra. This method involves real-time detection of single-shot FEL incident and scattered spectra, followed by deconvolution calculation to avoid photon waste and wavefront tilt caused by monochromator slits. The SQS experimental station at European XFEL, built in 2023, features a 1D-XUV spectrometer that utilizes subtle variations in photon energy absorption across the sample to induce spatial energy dispersion. Using Wolter mirrors, it directly images spatially resolved fluorescence emission from the sample onto the detector to generate 2D tr-RIXS spectra without the need for deconvolution. However, this design is limited to specific samples. Currently, the S&lt;sup&gt;3&lt;/sup&gt;FEL under designing has a novel 2D tr-RIXS instrument that uses an upstream low line density grating monochromator to generate spatial dispersion of the beam spot, allowing the full bandwidth of SASE to project spatially dispersed photon energy onto the sample. Subsequently, an optical design similar to the 1D-XUV spectrometer will be employed to achieve 2D tr-RIXS spectra, thereby expanding the applicability beyond specific liquid samples. These new instruments are designed to minimize pulse elongation by fully utilizing SASE’s full bandwidth, approaching Fourier-transform-limited RIXS spectra in both time and energy resolution.&lt;/sec&gt;&lt;sec&gt;Nonlinear X-ray optical techniques, such as sum-frequency generation (SFG) and second-harmonic generation, are adapting to X-ray wavelengths and opening up new avenues for detecting elementary excitations. The X-ray transient grating spectroscopy extends its capabilities to studying charge transport and spin dynamics on an ultrafast timescale. The future development of these scattering methods provides unique opportunities for detecting dynamical events in various systems, including surface and interface processes, chirality, nanoscale transport, and so-called multidimensional core-level spectroscopy.&lt;/sec&gt;

Effect of Electromagnetic Field on Proliferation and Migration of Fibroblasts and Keratinocytes: Implications in Wound Healing and Regeneration.

Proliferation and migration of fibroblasts, keratinocytes, and endothelial cells are key events in the physiological process of wound healing. This process includes different but overlapping stages: hemostasis, inflammatory phase, the proliferative phase, and the remodeling phase. Traumatic brain injury (TBI) is defined as a mechanical insult to the brain from external mechanical force (primary injury), usually followed by the secondary injury including edema, inflammation, excitotoxicity, oxidative stress, or mitochondrial dysfunction. The process of tissue repair following TBI is based on the neuronal-glial interactions, where phagocytosis by microglia plays a crucial role. Low-frequency electromagnetic field (LF-EMF) has been shown to enhance tissue repair after TBI, however, there are limited studies investigating the effects of LF-EMF on the proliferation and migration of keratinocytes, fibroblasts, VSMCs, and endothelial cells in the context of wound healing and on neuronal cells and microglia in relation to healing after TBI. Better understanding of the effects of LF-EMF on the proliferation, migration, and differentiation of these cells is important to enhance tissue healing after injury. This review article comprehensively discussed the effect of EMF/LF-EMF on these cells. Results published by different authors are hardly comparable due to different methodological approach and experimental settings. EMF promotes migration and proliferation of fibroblasts, keratinocytes and endothelial cells (EC), and thus could improve wound healing. The pilot study preformed on a large animal model of TBI suggests anti-inflammatory effects of EMF stimulation following TBI. Therefore, EMF is recognized as a potential therapeutic option to accelerate the wound healing and improve cellular recovery and function after TBI. Nonetheless, future studies are needed to define the optimal parameters of EMF stimulation in terms of frequency or duration of exposure.

In situ generation and reaction of a sub-picosecond electron pulse: ultrafast broadband spectroscopy.

A sub-picosecond resolved broadband transient absorption spectrometer for in situ generation and study of ultrafast reaction of short pulse electrons in water has been reported. A femtosecond near infrared (NIR) laser driven multiphoton ionization of water was used for the in situ generation of an ultra-short electron pulse in aqueous media. The dynamics of such electrons have been investigated using a broadband pump-probe spectrometer with a temporal resolution of sub-picosecond. The formation of the pre-hydrated electron having absorption in the NIR region and its subsequent solvation process leading to the formation of the hydrated electron has been monitored in real time using pump-probe spectroscopy. As a proof of concept, a reaction of pre-hydrated electrons and hydrated electrons with a highly oxidizing agent, methyl viologen, has been carried out. The competition of the reaction with methyl viologen and solvent relaxation of the pre-hydrated electron has been demonstrated by broadband ultrafast spectroscopy. Our results show that the reactivity of pre-hydrated electrons with methyl viologen is almost two orders of magnitude higher as compared to the hydrated electrons. Unlike complicated laser driven accelerators, the present table-top setup for the generation of an in situ ultrashort electron pulse and its reaction with different classes of molecules, especially biomolecules, will help us understand the early events of radiation-induced processes under reductive stress.

Synthesis and relaxivity of gadolinium-based DOTAGA conjugated 3-phosphoglycerate.

The synthesis and characterization of a gadolinium-based contrast agent conjugated to 3-phosphoglycerate (Gd-3PG) are reported. The synthetic steps are optimized to incorporate a selective deprotection strategy for a primary tert-butyl dimethyl silyl (TBS) hydroxyl over a secondary one. The relaxivity of Gd-3PG shows characteristic improvement, likely due to secondary sphere effects and/or an increase in molecular weight (5.39 ± 0.14 mM-1 s-1 at 1.4 T and 37 °C). Michaelis-Menten enzymatic kinetics was measured on the modified 3PG-arm and it showed similar activity to the native 3PG metabolite, Km = 240 ± 30 μM. This agent and future versions of this type of GBCA, which are conjugated to glycolytic metabolites, were designed to monitor in vivo allosteric regulatory events in glycolytic processes.

Heterobimetallic 3d-4f complexes supported by a Schiff-base tripodal ligand.

Complexes featuring multiple metal centres are of growing interest regarding metal-metal cooperation and its tuneability. Here the synthesis and characterisation of heterobimetallic complexes of a 3d metal (4: Mn, 5: Co) and lanthanum supported by a (1,1,1-tris[(3-methoxysalicylideneamino)methyl]ethane) ligand is reported, as well as discussion of their electronic structure via electron paramagnetic resonance (EPR) spectroscopy, electrochemical experiments and computational studies. Competitive binding experiments of the ligand and various metal salts unequivocally demonstrate that in these heterobimetallic complexes the 3d metal (Mn, Co) selectively occupies the κ6-N3O3 binding site of the ligand, whilst La occupies the κ6-O6 metal binding site in line with their relative oxophilicities. EPR spectroscopy supported by density functional theory analysis indicates that the 3d metal is high spin in both cases (S = 5/2 (Mn), 3/2 (Co)). Cyclic voltammetry studies on the Mn/La and Co/La bimetallic complexes revealed a quasi-reversible Mn2+/3+ redox process and poorly-defined irreversible oxidation events respectively.

Keypoints in Cells and Atherogenesis

Endothelial dysfunction is the initial event in the atherogenic process, resulting from several events, such as expression of leukocyte binding sites, production of growth factors, chemotactic and vasoreactive molecules, ability to oxidize low-density lipoprotein (LDL) and respond to oxidized lipoproteins, ability to express procoagulant activity, and modulation of vascular permeability. Thus, the endothelium, when subjected to different conditions and factors, plays an active role in the development of atherosclerotic plaque. The expression of several adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1), E-selectin, vascular cell adhesion molecule-1 (VCAM-1), P-selectin in atherosclerotic plaques, mediating the interaction between endothelial cells and leukocytes, has been described. The modification of LDLs, in conjunction with other chemotactic factors produced by injured endothelial cells, recruit circulating monocytes into the subendothelial space, where they become macrophages. The proliferation of smooth muscle cells is an important event in the progression of arterial injury, occurring in 3 stages: smooth muscle cell replication still within the media layer; migration from the middle layer to the intima and proliferation within the intima. Apoptotic cells were evidenced in the atherosclerotic lesion, suggesting that apoptosis is part of the normal vascular healing process. The final stage of atherosclerotic lesion development is conversion of the fibrotic lesion to an advanced lesion, a lesion in which a thrombus forms as a result of plaque ulceration or intraplaque hemorrhage.

Life Insurance Aggregate Claims Distribution Model Estimation

Risk is a hazard or consequence that can occur in an ongoing process or future events. As the party responsible for assuming and managing risks, the insurance company must be prepared to provide compensation in the event of claims; otherwise, they may face bankruptcy. Hence, it is important to understand the characteristics of risks handled by the insurance company. The risk's characteristics can be analyzed through the distribution model of previous-period claims. The sum of aggregate claims over several periods forms the aggregate claims distribution. The aggregate claims distribution used to determine the amount of pure premium and gross premium that must be obtained by the insurance company. In this research, the determination of distribution model estimation was examined for data cases on aggregate claims of life insurance in Indonesia 2016-2020. The result of this research conduct that the appropriate distribution model is the inverse Gaussian 3P distribution (three parameters).

Dysfunkcja gruczołów Meiboma jako przyczyna stanów zapalnych powierzchni oka

Meibomian glands dysfunction is described as one of the most common ophthalmic diseases in the world. Meibomian glands dysfunction is the most common cause of posterior blepharitis. Meibomian glands are the only ones responsible for the production of the tear film lipid layer. There are many diseases which induce Meibomian glands dysfunction, even leading to their disappearance. It is concluded that Meibomian glands dysfunction can both cause and result from dry eye syndrome through a process of events involving inflammation of the ocular surface. Accurate diagnosis becomes a great challenge, and it is of key importance in selecting the optimal form of treatment. This article provides an overview of the current understanding of Meibomian gland dysfunction and its therapeutic outlook.

Complex Spatio-Temporal Interplay of Distinct Immune and Bone Cell Subsets during Bone Fracture Healing.

The healing of a bone injury is a highly complex process involving a multitude of different tissue and cell types, including immune cells, which play a major role in the initiation and progression of bone regeneration. We histologically analyzed the spatio-temporal occurrence of cells of the innate immune system (macrophages), the adaptive immune system (B and T lymphocytes), and bone cells (osteoblasts and osteoclasts) in the fracture area of a femoral osteotomy over the healing time. This study was performed in a bone osteotomy gap mouse model. We also investigated two key challenges of successful bone regeneration: hypoxia and revascularization. Macrophages were present in and around the fracture gap throughout the entire healing period. The switch from initially pro-inflammatory M1 macrophages to the anti-inflammatory M2 phenotype coincided with the revascularization as well as the appearance of osteoblasts in the fracture area. This indicates that M2 macrophages are necessary for the restoration of vessels and that they also play an orchestrating role in osteoblastogenesis during bone healing. The presence of adaptive immune cells throughout the healing process emphasizes their essential role for regenerative processes that exceeds a mere pathogen defense. B and T cells co-localize consistently with bone cells throughout the healing process, consolidating their crucial role in guiding bone formation. These histological data provide, for the first time, comprehensive information about the complex interrelationships of the cellular network during the entire bone healing process in one standardized set up. With this, an overall picture of the spatio-temporal interplay of cellular key players in a bone healing scenario has been created. A spatio-temporal distribution of immune cells, bone cells, and factors driving bone healing at time points that are decisive for this process-especially during the initial steps of inflammation and revascularization, as well as the soft and hard callus phases-has been visualized. The results show that the bone healing cascade does not consist of five distinct, consecutive phases but is a rather complex interrelated and continuous process of events, especially at the onset of healing.

Identification, evolution, and expression of GDSL-type Esterase/Lipase (GELP) gene family in three cotton species: a bioinformatic analysis

BackgroundGDSL esterase/lipases (GELPs) play important roles in plant growth, development, and response to biotic and abiotic stresses. Presently, an extensive and in-depth analysis of GELP family genes in cotton is still not clear enough, which greatly limits the further understanding of cotton GELP function and regulatory mechanism.ResultsA total of 389 GELP family genes were identified in three cotton species of Gossypium hirsutum (193), G. arboreum (97), and G. raimondii (99). These GELPs could be classified into three groups and eight subgroups, with the GELPs in same group to have similar gene structures and conserved motifs. Evolutionary event analysis showed that the GELP family genes tend to be diversified at the spatial dimension and certain conservative at the time dimension, with a trend of potential continuous expansion in the future. The orthologous or paralogous GELPs among different genomes/subgenomes indicated the inheritance from genome-wide duplication during polyploidization, and the paralogous GELPs were derived from chromosomal segment duplication or tandem replication. GELP genes in the A/D subgenome underwent at least three large-scale replication events in the evolutionary process during the period of 0.6—3.2 MYA, with two large-scale evolutionary events between 0.6—1.8 MYA that were associated with tetraploidization, and the large-scale duplication between 2.6—9.1 MYA that occurred during diploidization. The cotton GELPs indicated diverse expression patterns in tissue development, ovule and fiber growth, and in response to biotic and abiotic stresses, combining the existing cis-elements in the promoter regions, suggesting the GELPs involvements of functions to be diversification and of the mechanisms to be a hormone-mediated manner.ConclusionsOur results provide a systematic and comprehensive understanding the function and regulatory mechanism of cotton GELP family, and offer an effective reference for in-depth genetic improvement utilization of cotton GELPs.

Screening biomarkers for spinal cord injury using weighted gene co-expression network analysis and machine learning.

JOURNAL/nrgr/04.03/01300535-202412000-00028/figure1/v/2024-04-08T165401Z/r/image-tiff Immune changes and inflammatory responses have been identified as central events in the pathological process of spinal cord injury. They can greatly affect nerve regeneration and functional recovery. However, there is still limited understanding of the peripheral immune inflammatory response in spinal cord injury. In this study, we obtained microRNA expression profiles from the peripheral blood of patients with spinal cord injury using high-throughput sequencing. We also obtained the mRNA expression profile of spinal cord injury patients from the Gene Expression Omnibus (GEO) database (GSE151371). We identified 54 differentially expressed microRNAs and 1656 differentially expressed genes using bioinformatics approaches. Functional enrichment analysis revealed that various common immune and inflammation-related signaling pathways, such as neutrophil extracellular trap formation pathway, T cell receptor signaling pathway, and nuclear factor-κB signal pathway, were abnormally activated or inhibited in spinal cord injury patient samples. We applied an integrated strategy that combines weighted gene co-expression network analysis, LASSO logistic regression, and SVM-RFE algorithm and identified three biomarkers associated with spinal cord injury: ANO10, BST1, and ZFP36L2. We verified the expression levels and diagnostic performance of these three genes in the original training dataset and clinical samples through the receiver operating characteristic curve. Quantitative polymerase chain reaction results showed that ANO10 and BST1 mRNA levels were increased and ZFP36L2 mRNA was decreased in the peripheral blood of spinal cord injury patients. We also constructed a small RNA-mRNA interaction network using Cytoscape. Additionally, we evaluated the proportion of 22 types of immune cells in the peripheral blood of spinal cord injury patients using the CIBERSORT tool. The proportions of naïve B cells, plasma cells, monocytes, and neutrophils were increased while the proportions of memory B cells, CD8+ T cells, resting natural killer cells, resting dendritic cells, and eosinophils were markedly decreased in spinal cord injury patients increased compared with healthy subjects, and ANO10, BST1 and ZFP26L2 were closely related to the proportion of certain immune cell types. The findings from this study provide new directions for the development of treatment strategies related to immune inflammation in spinal cord injury and suggest that ANO10, BST1, and ZFP36L2 are potential biomarkers for spinal cord injury. The study was registered in the Chinese Clinical Trial Registry (registration No. ChiCTR2200066985, December 12, 2022).

Inter-Institutional Communication Model for Online Learning for Elementary School Students

This study seeks to understand various communication events in the learning process holistically. The communication events in this paper include communication from the interpersonal level, computer-mediated communication, to organizational communication. This study explains the communication process from the human aspect (non-technical) and human relations with learning media technology (technical). This study seeks to answer how daily communication and communication media technology is vital in implementing online education for elementary school students. This study aims to offer an inter-institutional communication model that can be used to provide online education for students in elementary schools during disaster emergencies such as the Covid-19 pandemic. This study uses a focus group discussion (FGD) methodology with data collection techniques in interviews, field observations, and literature studies. This study uses data analysis in three-stage coding: open, axial, and selective. The subjects in this study were providers of elementary school (Sekolah Dasar) in Subdistrict (Kelurahan) Teluk Pucung, Kota Bekasi. This study finds that there is a need for intensification of communication from the daily level involving local stakeholders to resolve non-technical problems. The government needs to improve the communication media technology infrastructure and innovation in learning media technology for students who take online learning at the elementary level.

Age-Induced Accumulation of Succinate Promotes Cardiac Fibrogenesis.

Age-related cardiac fibrosis is a risk factor for heart failure and a marker for heart aging. However, the mechanisms underlying age-related cardiac fibrosis remain unclear. Ischemia and hypoxia are inevitable events in the aging process, which are direct causes of mitochondrial dysfunction and metabolic alterations. In this study, we identified metabolic changes and determined the mechanisms by which succinate (a tricarboxylic acid cycle intermediate) accumulation promotes fibroblast activation and apoptosis resistance in the aging heart. We also assessed its significance in relation to cardiac fibrosis and diastolic dysfunction. We first investigated how aging promotes persistent cardiac fibrosis. Following this, the metabolic alterations of the aging heart were identified by untargeted metabolomics, and the succinate level was verified via quantitative analysis. Furthermore, the correlations between succinate and fibrosis or diastolic dysfunction in older mice/people were assessed. We also described the role of succinate and its receptor SUCNR1/GPR91 in establishing a fibrosis network during diastolic dysfunction with age using SUCNR1-/- mouse model and an AAV9-based approach. We further identified the specific mechanisms involved in PKM2 dimerization, which regulate fibroblast activation and apoptosis resistance. We demonstrated that aging promotes fibrogenesis and diastolic dysfunction, which are linked to fibroblast activation and apoptosis resistance in the heart. Succinate levels were correlated with diastolic dysfunction and cardiac fibrosis in older mice and people. Functionally, succinate promoted fibroblast activation and apoptosis resistance, which aggravate cardiac fibrosis formation in both young and old mice. This was attributed to the ability of succinate to stimulate PKM2 dimerization via succinate receptor SUCNR1. Furthermore, dimeric PKM2 translocated to the nucleus and mitochondria, where it promoted fibroblast activation and apoptosis resistance, respectively. Accumulated PKM2 in the nucleus interacted with HIF-1α, increasing the DNA binding of HIF-1α and the expression of fibrogenic genes, resulting in fibroblast activation. In the mitochondria, accumulated PKM2 phosphorylated VDAC1 at T93 and increased VDAC1 degradation by promoting SYVN1-based E3 ligase binding to VDAC1, which is associated with increased apoptosis resistance and fibrosis persistence. We found that targeting succinate accumulation by metformin can inhibit fibroblast activation and apoptosis resistance in mice, which is a potential strategy to control age-related cardiac fibrosis and diastolic dysfunction. Our findings indicate that targeting metabolic dysregulation has significant implications for the treatment of age-related cardiac fibrosis and diastolic dysfunction. We further demonstrate a novel mechanism by which succinate induces fibroblast activation and apoptosis resistance by promoting PKM2 dimerization. Hence, inhibiting succinate generation or blocking its downstream effects is potentially a promising new strategy for slowing the heart aging.

Fitting latent non-Gaussian models using variational Bayes and Laplace approximations

–Latent Gaussian models (LGMs) are perhaps the most commonly used class of models in statistical applications. Nevertheless, in areas ranging from longitudinal studies in biostatistics to geostatistics, it is easy to find datasets that contain inherently non-Gaussian features, such as sudden jumps or spikes, that adversely affect the inferences and predictions made using an LGM. These datasets require more general latent non-Gaussian models (LnGMs) that can handle automatically these non-Gaussian features. However, fast implementation and easy-to-use software are lacking, preventing the broad applicability of LnGMs. In this paper, we derive variational Bayes algorithms for fast and scalable inference of LnGMs. The approximation leads to an LGM that downweights extreme events in the latent process, reducing their influence and leading to more robust inferences. It can be applied to a wide range of models, such as autoregressive processes for time series, simultaneous autoregressive models for areal data, and spatial Matérn models. To facilitate Bayesian inference, we introduce the ngvb package, where LGMs implemented in R-INLA can be easily extended to LnGMs by adding a single line of code.

Application of PAT Probes in Aluminum Phosphate Adjuvant Manufacturing.

This study is focused on monitoring process parameters and quality attributes of aluminum phosphate (AlPO4) using multiple in-line probes incorporated into an industrial-scale adjuvant suspension manufacturing unit. The manufacturing of aluminum adjuvant suspension was monitored at manufacturing scale using conductivity, turbidity, infrared, and particle sizing and count probes to follow the continuous evolution of particle formation and size distribution, and the reaction kinetics during the synthesis of AlPO4. The data showed that AlPO4 forms large particles at the early stages of mixing, followed by a decrease in size and then stabilization towards the later stages of mixing and pH adjustment. The results provided a complementary view of process events and assisted in optimizing several parameters, e.g., flow rate of reactants AlCl3 and Na3PO4 solutions, mixing rate, pH, and conductivity of AlPO4, as well as adjuvant quality attribute such as particle size, thus streamlining and shortening the process development stage. The results of this study showed the usefulness of the in-line probes to automate continuous assessment of AlPO4 batch-to-batch consistency during in-house adjuvant production at the industrial scale.

Ultrastructure of neuron-glia interaction in the norm and experimental pathology

Long-term experience was gained in analyzing synapses and their glial surroundings in normal, natural, and experimental models of functional plasticity and brain pathology development. However, most studies in this area rely on electrophysiological techniques combined with fluorescent imaging. Notably, fine synapse structure and astrocytic processes cannot be resolved using light or some electron microscopy techniques. Studies on experimental brain pathology using volume electron microscopy methods [1] were previously restricted due to their high labor intensity. However, automated methods for sample preparation and analysis, using machine vision and artificial intelligence, significantly simplified this task. Using transmission electron microscopy methods and 3D reconstructions, this study examined the Str. radiatum CA1 hippocampal region of rat brains in a chronic lithium-pilocarpine model of epilepsy. The results indicate a decrease in synaptic number along with an increase in their size and a reduction in astrocytic isolation of the active zones. A decrease in glial ensheathment of enlarged active zones and facilitation of neurotransmitter diffusion to active synapses may have a multiplicative effect on epileptiform activity growth and excitotoxicity. The simplification of the astrocytes meshwork in the somatosensory cortex’s layer 2/3 is comparable to that of layer 1. This decrease in layer 1’s inhibitory action enables pyramidal neurons in layer 2/3 to potentially exhibit epileptiform activity. Thus, the superficial cortical layers’ structural-functional aspects can be used as a natural cellular model in epilepsy development studies. Reduction of Ca2+ events in astrocyte processes in lithium-pilocarpine induced epilepsy may result from the low buffer capacity of Ca2+ ions in the smooth endoplasmic reticulum (sER) and/or impaired Ca2+ wave transmission through the gap junctions between astrocytic processes. High resolution is necessary to analyze the gap junctions, and special methods are required for sER visualization in perisynaptic astrocytic processes. We developed original sER staining methods [2] to quantitatively evaluate gap junctions and sER cisternae within astrocytic meshworks in layers 1 and 2/3 of the somatosensory cortex. In layer 1, the area of gap junctions in relation to the volume of an astrocyte was twice as high as in layer 2/3. The proportion of sER volume differed between layer 1 and layer 2/3 tissues. Specifically, the total sER cisternae volume in layer 2/3 was twice as high as in layer 1, relative to the volume of astrocytic processes [3]. Additionally, a doubling of single astrocytic gap junction area concomitant with decreased calcium events was observed. The results suggest a normal balance between Ca2+ stores (sER) and gap junctions, whose disruption may contribute to the development of seizures.