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Abstract Little is known about the papillomacular bundle defect (PMBD) in glaucoma. As such, we investigated the frequency of PMBD in glaucoma patients with high myopia, and its risk factors. In this retrospective, cross-sectional study, retinal nerve fiber layer (RNFL) defect was analyzed in 92 glaucomatous eyes with high myopia (axial length of 26.0 mm or more or an average spherical value of − 6.0 diopters or less). After dividing them into two groups with and without PMBD, the clinical characteristics of the groups were compared and analyzed. The mean age of the patients was 52.1 ± 10.5 years, and there were 53 males and 39 females. PMBD were observed in 55 eyes (59.8%). There was no significant intergroup difference in baseline or follow-up intraocular pressure (IOP). Parapapillary atrophy (PPA)-to-disc-area ratio (OR 3.83, CI: 1.58–10.27, p = 0.010), lamina cribrosa defect (LCD; OR 2.92, CI: 1.14–8.13, p = 0.031) and central visual field defect (CVFD; OR 3.56, CI: 1.38–9.58, p = 0.010) were significantly associated with the PMBD. .

Abstract This study aimed to analyze the duration and causes of persistent subretinal fluid (PSF) after scleral buckle (SB) surgery in patients with macula-involving rhegmatogenous retinal detachment (RRD). Sixty-one eyes of 61 patients with macula-involving RRD who underwent SB surgery between 2016 and 2022 were reviewed retrospectively. PSF was confirmed on optical coherence tomography. The PSF duration after surgery and the analysis of relevant ocular and systemic factors were conducted according to the PSF duration. The mean duration of PSF was 5.9 ± 4.6 months in all eyes and 8.1 ± 5.0 months in eyes not treated with external subretinal fluid (SRF) drainage, which was significantly longer than 4.5 ± 3.7 months in those subjected to external SRF drainage. The mean best-corrected visual acuity improved significantly 3 months after surgery. There were significant visual improvements in the external SRF drainage group compared to the non-drainage group during all follow-up periods. Longstanding shallow RRD was significantly associated with longer PSF duration after SB surgery. External SRF drainage during SB surgery can effectively reduce SRF, shorten the duration of PSF, and accelerate visual improvement.

Abstract Background Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. Methods We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. Results Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. Conclusions We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. Trial registration NCT05338931; Date: 2022–04-01.

Abstract Genetic, environment, and behaviour factors have a role in causing sudden cardiac arrest (SCA). We aimed to determine the strength of the association between various risk factors and SCA incidence. We conducted a multicentre case-control study at 17 hospitals in Korea from September 2017 to December 2020. The cases included out-of-hospital cardiac arrest aged 19–79 years with presumed cardiac aetiology. Community-based controls were recruited at a 1:1 ratio after matching for age, sex, and urban residence level. Multivariable conditional logistic regression analysis was conducted. Among the 1016 cases and 1731 controls, 948 cases and 948 controls were analysed. A parental history of SCA, low educational level, own heart disease, current smoking, and non-regular exercise were associated with SCA incidence (Adjusted odds ratio [95% confidence interval]: 2.51 [1.48–4.28] for parental history of SCA, 1.37 [1.38–2.25] for low edication level, 3.77 [2.38–5.90] for non-coronary artery heart disease, 4.47 [2.84–7.03] for coronary artery disease, 1.39 [1.08–1.79] for current smoking, and 4.06 [3.29–5.02] for non-regular exercise). Various risk factors related to genetics, environment, and behaviour were independently associated with the incidence of SCA. Establishing individualised SCA prevention strategies in addition to general prevention strategies is warranted.

This study aimed to evaluate the enhancement of A. gossypii control by A. colemani when Z. elegans was planted as a companion crop in cucumber greenhouses. The density and spatial distribution of A. gossypii and parasitized mummies were investigated across three treatment plots: (1) the simultaneous application of A. colemani and cultivation of Z. elegans (parasitoid-zinnia plot); (2) the application of A. colemani alone (parasitoid plot); and (3) a control plot (no application of both). A. gossypii maintained low densities in the parasitoid–zinnia plots, while its densities in the parasitoid plots initially decreased but rapidly increased thereafter. The spatial distribution patterns of A. gossypii and parasitized mummies showed similar trends across treatments. However, the parasitism rate of A. gossypii exhibited random distribution in parasitoid and control plots, while showing uniform distribution in the parasitoid–zinnia treatment. These results supported the idea that cultivating Z. elegans alongside cucumber could enhance the effectiveness of A. colemani as a biocontrol agent against A. gossypii, highlighting the importance of such companion planting in pest management strategies.

Waterborne polyurethane (WPU) often suffers from poor water resistance and mechanical properties due to hydrophilic emulsifiers. To address these issues, this study introduces glycidyl carbamate (GC) as a crosslinker to improve WPU performance. Three types of GC were synthesized using aliphatic, cycloaliphatic, and aromatic isocyanates, respectively. The crosslinked network was established through a reaction between the epoxide group of GC and the carboxylic acid and amine groups of WPU. Among these, the WPU film utilizing aromatic isocyanate-based GC exhibited the highest crosslink density, modulus, hardness, and water resistance, due to the rigidity of the aromatic molecular structure. However, the film displayed excessive brittleness, resulting in reduced tensile strength, along with yellowing typically associated with aromatic compounds. The WPU crosslinked with cycloaliphatic GC demonstrated the next best mechanical properties and water resistance, with a 2.7-fold increase in tensile strength, a 1.5-fold increase in hardness, and a 66% reduction in the water swelling ratio compared to neat WPU. This study presents a novel and effective strategy to enhance the water resistance and mechanical properties of WPU films, making them suitable for advanced coating applications.

The chirality of a chemical differentiates it from its mirror-image counterpart. This unique property has significant implications in chemistry, biology, and drug discovery, where chiral chemicals display high selectivity and activity in achieving target specificity and reducing attrition rates in drug development. Stress granules (SGs) are dynamic assemblies of proteins and RNA that form in the cytoplasm of cells under stress conditions. Modulating their formation or disassembly could offer a novel approach to treating a wide range of diseases. This has led to significant interest in SGs as potential therapeutic targets. This study examined the NTF2-like domain of G3BP1 as a possible target for SG modulation. Molecular docking was used to simulate the interactions of compounds with the domain, and a potential candidate with a chiral structure was identified. The experiments showed that the compound induced the formation of SG-like granules. Importantly, the ability of this compound to modulate SG offers valuable insights into a new mechanism underlying the dynamics and promoting the assembly of SGs, and this new mechanism, in turn, holds potential for the development of drugs with diverse mechanisms of action and potentially synergistic effects.

One of the major challenges in QLED research is improving the stability of the devices. In this study, we fabricated all inorganic quantum-dot light emitting diodes (QLEDs) using hafnium oxide (HfOx) as the hole transport layer (HTL), a material commonly used for insulator. Oxygen vacancies in HfOx create defect states below the Fermi level, providing a pathway for hole injection. The concentration of these oxygen vacancies can be controlled by the annealing temperature. We optimized the all-inorganic QLEDs with HfOx as the HTL by changing the annealing temperature. The optimized QLEDs with HfOx as the HTL showed a maximum luminance and current efficiency of 66,258 cd/m2 and 9.7 cd/A, respectively. The fabricated all-inorganic QLEDs exhibited remarkable stability, particularly when compared to devices using organic materials for the HTL. Under extended storage in ambient conditions, the all-inorganic device demonstrated a significantly enhanced operating lifetime (T50) of 5.5 h, which is 11 times longer than that of QLEDs using an organic HTL. These results indicate that the all-inorganic QLEDs structure, with ITO/MoO3/HfOx/QDs/ZnMgO/Al, exhibits superior stability compared to organic-inorganic hybrid QLEDs.

Heavy metals have serious negative effects on various aquatic organisms, and therefore rapid and accurate ecotoxicological assessments of heavy metals are necessary. Fish-derived cells sensitive to heavy metals have been used as valuable tools for ecotoxicological assessments. However, this method requires a minimum toxicity treatment time of 96 h, which limits its use when rapid ecotoxicological assessments are required or ecotoxicological assessments of a large number of toxicants are performed. In this study, these limitations were overcome by adjusting parameters including the concentration of fetal bovine serum (FBS) in the medium and the treatment time of the toxicant. Specifically, we found that the maximum time for fish cells to remain unstarved was 6 h when using a medium containing 1% FBS. We applied both parameters to the ecotoxicological assessment (using a medium containing 1% FBS for the toxicity assessment and treating the toxicant for only 6 h). Surprisingly, these adjusted parameters allowed us to obtain faster and more accurate data than the traditional assessment. This improvement was due to the new assessment conditions that minimized the possibility that the growth-inducing effects of nutrients present in excess in the medium could interfere with the cellular response to the toxicant. The accuracy of this assessment was not limited to measuring the toxicity of heavy metals. In conclusion, we have established an ecotoxicity assessment that can generate rapid and accurate data on heavy metals. This new platform will become the cornerstone of rapid and accurate ecotoxicity assessments of heavy metals.

Natural products with high antioxidant activity are considered as innovative prevention strategies to effectively prevent age-related macular degeneration (AMD) in the early stage because the generation of reactive oxygen species (ROS) leading to the development of drusen is reported as an important cause of this disease. To investigate the prevention effects of the methanol extracts of Euphorbia heterophylla L. (MEE) on AMD, its effects on the antioxidant activity, inflammatory response, apoptosis pathway, neovascularization, and retinal tissue degeneration were analyzed in N-retinylidene-N-retinylethanolamine (A2E)-landed spontaneously arising retinal pigment epithelia (ARPE)-19 cells and BALB/c mice after exposure to blue light (BL). The MEE contained 10 active components and showed high free radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and nitric oxide (NO) radicals. The pretreatments of high-dose MEE remarkably suppressed the production of intracellular ROS (88.2%) and NO (25.2%) and enhanced (SOD) activity (84%) and the phosphorylation of nuclear factor erythroid 2–related factor 2 (Nrf2) in A2E + BL-treated ARPE-19 cells compared to Vehicle-treated group. The activation of the inducible nitric oxide synthase (iNOS)-induced cyclooxygenase-2 (COX-2) mediated pathway, inflammasome activation, and expression of inflammatory cytokines was significantly inhibited in A2E + BL-treated ARPE-19 cells after the MEE pretreatment. The activation of the apoptosis pathway and increased expression of neovascular proteins (36% for matrix metalloproteinase (MMP)-9) were inhibited in the MEE pretreated groups compared to the Vehicle-treated group. Furthermore, the thickness of the whole retina (31%), outer nuclear layer (ONL), inner nuclear layer (INL), and photoreceptor layer (PL) were significantly increased by the MEE pretreatment of BALB/c mice with BL-induced retinal degeneration. Therefore, these results suggest that the MEE, with its high antioxidative activity, protects against BL-induced retinal degeneration through the regulation of the antioxidative system, inflammatory response, apoptosis, and neovascularization in the AMD mouse model.

Hemp seed protein (HSP), a by-product of hemp oil processing, was converted into a functional protein ingredient enriched with γ-aminobutyric acid (GABA) and peptides through a two-step microbial fermentation process. To enhance peptide and free amino acid production from HSP, it was hydrolyzed using alkaline protease produced by Bacillus subtilis HA. The HSP was hydrolyzed at a degree of 40% at 55 °C for 24 h, yielding a pH of 6.55, an acidity of 1.22%, and 205.45 mg% tyrosine equivalents. This process resulted in the production of low molecular-weight peptides. (Lb. plantarum KS2020. This serial co-fermentation process, combining proteolysis and lactic acid fermentation, not only increased the peptide content but also promoted GABA accumulation, positioning HSP hydrolysate as a promising candidate for functional foods with potential health benefits.

Complement component 3 (C3) deficiency has recently been reported as one of the novel causes of constipation. To identify a unique gene specific to constipation caused by C3 deficiency, the total RNA extracted from the mid colon of C3 knockout (C3 KO) mice was hybridized to oligonucleotide microarrays, and the function of the candidate gene was verified in in vitro and in vivo models. C3 KO mice used for microarrays showed definite phenotypes of constipation. Overall, compared to the wild type (WT), 1237 genes were upregulated, and 1292 genes were downregulated in the C3 KO mice. Of these, the major genes included were lysine (K)-specific demethylase 5D (KDM5D), olfactory receptor 870 (Olfr870), pancreatic lipase (PNLIP), and alkaline phosphatase intestinal (ALPI). Specifically, the ALPI gene was selected as a novel gene candidate based on alterations during loperamide (Lop)-induced constipation and intestinal bowel disease (IBD). The upregulation of ALPI expression treated with acetate recovered the expression level of mucin-related genes in primary epithelial cells of C3 KO mice as well as most phenotypes of constipation in C3 KO mice. These results indicate that ALPI plays an important role as the novel gene associated with C3 deficiency-induced constipation.

As cellular senescence, reactive oxygen species (ROS) accumulate excessively, causing cellular damage. Flavonoids derived from natural products are known for their antioxidant effects and their ability to delay cellular senescence. Previous studies have attempted to mitigate cellular senescence using flavonoids from natural sources. However, the detailed mechanisms and regulatory targets of some flavonoids exhibiting antioxidant effects have not been fully elucidated. Therefore, we screened a library of flavonoids for antioxidant properties. Isoschaftoside, a glycosidic flavonoid, significantly reduced ROS levels in senescent cells. It was found that mitochondrial function was restored, and dependence on glycolysis was reduced in senescent cells treated with isoschaftoside. Additionally, we identified that isoschaftoside suppresses ROS by reducing the expression of RAC2 and LINC00294 in senescent cells. Taken together, this study establishes a novel mechanism for ROS inhibition and the regulation of cellular senescence by isoschaftoside. Our findings contribute important insights to antioxidant and anti-senescence research.

Abstract A method for patterning single‐layer graphene (SLG) and single‐layer oxidized graphene (SOG) within a continuous atomic layer to form lateral heterojunctions is presented. Raman spectroscopy is employed to investigate the evolution of defect‐related Raman peaks during excimer‐UV irradiation, facilitating the identification of structural changes and defect formation processes. Electrical transport measurements reveal that SOG‐patterned field‐effect transistors (FETs) exhibit varying characteristics depending on the degree of oxidation, thus offering the potential to tailor the electrical properties of graphene devices for specific requirements. Scanning Kelvin probe microscopy measurements reveal the surface potential and work function of the SOG regions compared with those of SLG. The effective functionality of the SOG pattern to operate as a resistor, allowing control of the electrical conductivity in the SOG‐patterned SLG channels, is demonstrated. This capability restricts the current flow while preserving the pristine electrical properties of the graphene channel. Moreover, the SOG pattern can serve as a potential barrier to constructing SLG‐SOG‐patterned integrated circuits, providing exciting opportunities for engineering advanced electronic components. This breakthrough in graphene devices simplifies the fabrication process of graphene‐based FETs and provides the foundation for developing atomically thin integrated circuits for a wide range of applications.

Objectives: Little is known about the disparities in underweight prevalence among the general population in high-income countries. We investigated the trends in underweight prevalence and disparities across sociodemographic groups among Korean adults and older adults. Setting and participants: A series of cross-sectional data on Korean national health checkups for adults aged ≥20 years were analyzed from 2005 to 2016. Measurements: Based on body mass index (kg/m2), underweight was graded as mild (17.0–18.49), moderate (16.0–16.9), and severe (

Cognitive aging widely varies among individuals due to different stress experiences throughout the lifespan and vulnerability of neurocognitive mechanisms. To understand the heterogeneity of cognitive aging, we investigated the effect of early adulthood stress (EAS) on three different hippocampus-dependent memory tasks: the novel object recognition test (assessing recognition memory: RM), the paired association test (assessing episodic-like memory: EM), and trace fear conditioning (assessing trace memory: TM). Two-month-old rats were exposed to chronic mild stress for 6 weeks and underwent behavioral testing either 2 weeks or 20 months later. The results show that stress and aging impaired different types of memory tasks to varying degrees. RM is affected by combined effect of stress and aging. EM became less precise in EAS animals. TM, especially the contextual memory, showed impairment in aging although EAS attenuated the aging effect, perhaps due to its engagement in emotional memory systems. To further explore the neural underpinnings of these multi-faceted effects, we measured long-term potentiation (LTP), neural density, and synaptic density in the dentate gyrus (DG). Both stress and aging reduced LTP. Additionally, the synaptic density per neuron showed a further reduction in the stress aged group. In summary, EAS modulates different forms of memory functions perhaps due to their substantial or partial dependence on the functional integrity of the hippocampus. The current results suggest that lasting alterations in hippocampal circuits following EAS could potentially generate remote effects on individual variability in cognitive aging, as demonstrated by performance in multiple types of memory.

Alzheimer’s disease (AD) is characterized by the presence of two critical pathogenic factors: amyloid-β (Aβ) and tau. Aβ and tau become neurotoxic aggregates via self-assembly, and these aggregates contribute to the pathogenesis of AD. Therefore, there has been growing interest in therapeutic strategies that simultaneously target Aβ and tau aggregates. Although neferine has attracted attention as a suitable candidate agent for alleviating AD pathology, there has been no study investigating whether neferine affects the modulation of Aβ or tau aggregation/dissociation. Herein, we investigated the dual regulatory effects of neferine on Aβ and tau aggregation/dissociation. We predicted the binding characteristics of neferine to Aβ and tau using molecular docking simulations. Next, thioflavin T and atomic force microscope analyses were used to evaluate the effects of neferine on the aggregation or dissociation of Aβ42 and tau K18. We verified the effect of neferine on Aβ fibril degradation using a microfluidic device. In addition, molecular dynamics simulation was used to predict a conformational change in the Aβ42-neferine complex. Moreover, we examined the neuroprotective effect of neferine against neurotoxicity induced by Aβ and tau and their fibrils in HT22 cells. Finally, we foresaw the pharmacokinetic properties of neferine. These results demonstrated that neferine, which has attracted attention as a potential treatment for AD, can directly affect Aβ and tau pathology.

Background: The Korean out-of-hospital cardiac arrest registry (KOHCAR) serves as the basis for a chain of survival monitoring and quality improvement programs for out-of-hospital cardiac arrest (OHCA). This study describes the development history and current status of KOHCAR. Methods/design: The KOHCAR, initiated in 2008, is a population-based OHCA registry that captures all emergency medical service (EMS)-assessed OHCA cases, regardless of etiology. The KOHCAR represents complete nationwide data and aligns with South Korea's comprehensive plan for cardiovascular disease, which has a legal basis. The KOHCAR is a collaboration between the National Fire Agency (NFA) and the Korea Disease Control and Prevention Agency (KDCA). The NFA identifies OHCA patients and provides prehospital information after integrating various EMS records, whereas the KDCA collects hospital information and clinical outcomes through a medical record review. Comprehensive Utstein variables, including patient and arrest characteristics, prehospital and hospital management, and survival outcomes, were collected. Discussion: The KOHCAR has significantly contributed to improving OHCA survival rates in South Korea; however, the COVID-19 pandemic has posed challenge. To address the post-pandemic survival rate decline, there is a need to enhance data utilization, expand data sources, and tailor communication with diverse stakeholders.

Abstract Post-infectious irritable bowel syndrome (PI-IBS) occurs in about 10% of cases following gastroenteritis. The incidence of IBS is higher in females. However, it is not clear whether this is due to biological or psychosocial factors. We aimed to investigate the influence of gender roles on the incidence of PI-IBS, alongside traditional risk factors. Our study included 231 patients diagnosed with gastroenteritis who were hospitalized and treated with antibiotics between 2018 and 2021. The Korean Sex Role Inventory-Short Form (KSRI-SF), based on the Bem Sex Role Inventory (BSRI) was used to categorize patients (androgynous, masculine, feminine, and undifferentiated types). Six months after treatment, we conducted a telephone survey to confirm the presence of PI-IBS using the ROME IV criteria. Among the patients, 43.3% were female, and the mean age was 43.67 ± 16.09 years. After 6 months, 34 patients developed PI-IBS. Univariate analysis revealed that younger age, female sex, KSRI-SF undifferentiated type, and longer duration of antibiotic use independently influenced the occurrence of PI-IBS. Multivariate analysis showed that PI-IBS was associated with the KSRI-SF undifferentiated type and higher C-reactive protein (CRP) levels. Our study showed that the KSRI-SF undifferentiated type and high CRP levels at initial infection were associated with PI-IBS.

Abstract The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and the vast dynamic range of the plasma proteome. Here we address these challenges with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves the sensitivity of traditional proximity ligation assays by ~10,000-fold to attomolar level, by suppressing assay background via a dual capture and release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification of both low- and high-abundance proteins spanning a wide dynamic range is achieved by attenuating signals from abundant targets with unconjugated antibodies and next-generation sequencing of barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines and chemokines and other proteins demonstrates superior sensitivity to a proximity extension assay in detecting biologically important low-abundance biomarkers in patients with autoimmune diseases and COVID-19. Fully automated NULISA makes broad and in-depth proteomic analysis easily accessible for research and diagnostic applications.

Highlights Fundamental mechanisms in terms of driving force, material design, and exsolution processes are outlined, and novel behaviors of socketing and shape-shifting throughout the interaction with the oxide support are discussed. This review examines the key control factors, encompassing external conditions and intrinsic properties that affect the surface exsolution of metallic nanoparticles. The extraordinary nature of exsolution particles and their effect on various applications are discussed, along with the latest strategies for improving exsolution behavior.

PURPOSE With the widespread of mitochondrial function, the need to accurately quantify and comprehend mitochondrial O2 respiration has gained prominence within the physiological and pathological spheres. Various in situ, in vitro, and in vivo approaches have been available to investigate numerous aspects of mitochondrial O2 consumption. This review aims to provide a specific method for researchers to consider in examining mitochondrial O2 respiration using permeabilized or homogenized tissues. These techniques allow direct access to mitochondrial O2 respiration, facilitating an exploration of mitochondrial bioenergetics under well-defined substrate conditions. METHODS Here, we present a method for measuring mitochondrial O2 consumption in permeabilized or homogenized tissues using high-resolution respirometry (Oroboros Oxygraph-2K, Oroboros Instrument). RESULTS A high-resolution respirometry provides the most direct way to assess mitochondrial O2 respiration with interpretations based on specific modeling approaches. CONCLUSIONS As many diseases are closely associated with mitochondrial dysfunction, ongoing advancements in this methodology may provide researchers with exciting and novel opportunities for finding the potential role of mitochondria in the etiology and treatment of various diseases.

Abstract Little is known about the diagnostic utility of three-dimensional neuroretinal rim thickness (3D-NRRT) for differentiating patients with superior segmental optic nerve hypoplasia (SSOH) from normal-tension glaucoma (NTG). Since SSOH is defined by characteristic optic nerve head features, investigation of diagnostic usefulness of 3D-NRRT is necessary. In this cross-sectional study, 49 SSOH eyes, 52 NTG eyes, and 41 normal eyes were enrolled. Retinal nerve fiber layer thickness (RNFLT) and 3D-NRRT values, as obtained in the right-eye orientation by optical coherence tomography (OCT), were recorded. On RNFLT clock-hour comparison, the 11–3 clock-hour sectors were significantly thinner for SSOH than for NTG (all P

Abstract Malignant melanoma is a fatal disease with an increasing global incidence. Despite numerous studies focused on anti-cancer drugs, a variety of side effects of cancer treatment remain challenging. Thus, there is a pressing need to identify novel anti-cancer agents with minimal cytotoxicity and side effects. DB3 (1,3,7,9-tetrahydroxy-2,8-dimethyl-4,6-di[ethanoyl]dibenzofuran) is a member of the dibenzofuran family and is extracted from Ramalina terebrata (Antarctic lichen). We investigated if DB3 exerted an antitumor effect on B16F10 melanoma cells. The results revealed that DB3 exerted time- and dose-dependent reduction of cell viability by inducing apoptosis and significantly suppressing cell proliferation through cell cycle arrest in the G0/G1 phase in B16F10 melanoma cells. Additionally, DB3 impeded the migration and invasiveness of B16F10 cells. Subsequently, we observed that DB3 decreased the expression levels of Cdk4/Cyclin D1 and the phosphorylation of p38, JNK, ERK, and AKT. Furthermore, DB3 decreased melanoma tumor growth in a mouse tumor syngraft model. Based on these findings, we propose that DB3 possesses potential for use as an anti-cancer agent for melanoma treatment.

Abstract Background The gut–brain axis (GBA) in Parkinson's disease (PD) has only been investigated in limited mice models despite dysbiosis of the gut microbiota being considered one of the major treatment targets for neurodegenerative disease. Therefore, this study examined the compositional changes of fecal microbiota in novel transgenic (Tg) mice overexpressing human α-synuclein (hαSyn) proteins under the neuron-specific enolase (NSE) to analyze the potential as GBA model. Results The expression level of the αSyn proteins was significantly higher in the substantia nigra and striatum of NSE-hαSyn Tg mice than the Non-Tg mice, while those of tyrosine hydroxylase (TH) were decreased in the same group. In addition, a decrease of 72.7% in the fall times and a 3.8-fold increase in the fall number was detected in NSE-hαSyn Tg mice. The villus thickness and crypt length on the histological structure of the gastrointestinal (GI) tract decreased in NSE-hαSyn Tg mice. Furthermore, the NSE-hαSyn Tg mice exhibited a significant increase in 11 genera, including Scatolibacter, Clostridium, Feifania, Lachnoclostridium, and Acetatifactor population, and a decrease in only two genera in Ligilactobacillus and Sangeribacter population during enhancement of microbiota richness and diversity. Conclusions The motor coordination and balance dysfunction of NSE-hαSyn Tg mice may be associated with compositional changes in gut microbiota. In addition, these mice have potential as a GBA model.

Abstract The purpose of this study was to investigate the correlation between glycated hemoglobin (HbA1c) levels and hearing loss (HL) using data from a tertiary hospital. Our hypothesis regarding the relationship between HL and HbA1c levels was that elevated HbA1c levels are associated with an increased risk of HL. We retrospectively reviewed the medical charts of patients diagnosed with sensorineural HL or diabetes between 2006 and 2021 at the Catholic Medical Center (CMC). Data were collected from the CMC’s Clinical Data Warehouse. Participants were selected from patients who were prescribed pure-tone audiometry and an HbA1c blood test. The survey was completed for 5287 participants. The better ear pure-tone audiometry (PTA) for air conduction thresholds at 500, 1000, 2000, and 4000 Hz was calculated. Sensorineural HL was defined as a better ear PTA of 25 dB or higher. We used the HbA1c level as a diagnostic criterion for diabetes. The following criteria were used to define the HbA1c level: normal, HbA1c level below 5.6%; prediabetes, level between 5.6 and 6.4%; and diabetes, level of 6.5% or more. Among 5287 participants, 1129 were categorized as normal, 2119 as prediabetic, and 2039 as diabetic. The diabetic group was significantly older (p 25 dB) and control group (PTA ≤ 25 dB), based on their PTA threshold of four frequencies. After adjusting for age and sex, we found no significant odds ratio (OR) of HL between the prediabetes group and the normal group. Notably, the OR of HL was significantly higher in the diabetes group with each PTA threshold and frequency. The 6.3% HbA1c level cutoff value was determined by analyzing the receiver operating characteristic curve for predicting hearing impairment > 25 dB. Diabetes was associated with hearing loss in all frequency ranges, particularly at high frequencies. Screening for HL is strongly recommended for patients with elevated HbA1c levels.

Abstract Background To evaluate the chemosensitivity to doxorubicin (DOX) in two primary cells derived from a tumor of FVB/N-Trp53tm1Hw1 knockout (KO) mice with TALEN-mediated Trp53 mutant gene, we evaluated the cell survivability, cell cycle distribution, apoptotic cell numbers and apoptotic protein expression in solid tumor cells and ascetic tumor cells treated with DOX. Results The primary tumor cells showed a significant (P

Abstract Background Several significant associations between air pollution and thyroid function have been reported, but few studies have identified whether these associations differ by obesity, particularly its regional distribution. We assessed the relationship between ambient air pollution and thyroid hormone, and whether this relationship is modified by abdominal adiposity, as indicated by the waist circumference, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and visceral-to-subcutaneous fat ratio (VSR) in Korean men. Methods We included 2440 male adults in the final analysis and used each person’s annual average exposure to four air pollutants: particulate matter with an aerodynamic diameter ≤ 10 μm (PM10), nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). Abdominal fat deposition was quantified by computed tomography. Serum thyrotropin (TSH) and free thyroxine (FT4) concentrations were measured for thyroid hormone. To evaluate the relationship between air pollution and thyroid hormone according to adiposity, we performed multiple linear regression analysis on the two subgroups stratified by abdominal fat level. Results Abdominal adiposity was significantly related to FT4 concentration. The exposures to air pollutants were associated with increased TSH and decreased FT4 concentrations. In stratified analysis using abdominal fat traits, ambient air pollution except for SO2 was significantly related to increased TSH and decreased FT4 concentrations in the high adiposity group (all p

Abstract Due to its additional frequency response, dual-frequency ultrasound has advantages over conventional ultrasound, which operates at a specific frequency band. Moreover, a tunable frequency from a single transducer enables sonographers to achieve ultrasound images with a large detection area and high resolution. This facilitates the availability of more advanced techniques that simultaneously require low- and high-frequency ultrasounds, such as harmonic imaging and image-guided therapy. In this study, we present a novel method for dual-frequency ultrasound generation from a ferroelectric piezoelectric micromachined ultrasound transducer (PMUT). Uniformly designed transducer arrays can be used for both deep low-resolution imaging and shallow high-resolution imaging. To switch the ultrasound frequency, the only requirement is to tune a DC bias to control the polarization state of the ferroelectric film. Flextensional vibration of the PMUT membrane strongly depends on the polarization state, producing low- and high-frequency ultrasounds from a single excitation frequency. This strategy for dual-frequency ultrasounds meets the requirement for either multielectrode configurations or heterodesigned elements, which are integrated into an array. Consequently, this technique significantly reduces the design complexity of transducer arrays and their associated driving circuits.

Background/Aims: Tegoprazan, a new, fast, and strong potassium-competitive acid blocker, has been approved for the treatment of gastric acid-related diseases in Korea. However, real-world clinical data regarding this drug are scarce. We aimed to compare the Helicobacter pylori eradication rates of tegoprazan- and rabeprazole-based triple therapy.Methods: We retrospectively reviewed data from patients who received first-line treatment for H. pylori infection using tegoprazan- or rabeprazole-based triple therapy for 2 weeks (50 mg tegoprazan or 20 mg rabeprazole+1,000 mg amoxicillin+500 mg clarithromycin twice daily). The primary endpoint was the eradication rate as determined by intention-to-treat analysis.Results: Of the 677 patients included in our study, 344 and 333 received tegoprazan-based and rabeprazole-based triple therapy, respectively. The eradication rate from intention-to-treat analysis was 76.7% (95% confidence interval [CI], 72.1% to 81.0%) for tegoprazan-based triple therapy and 75.4% (95% CI, 70.5% to 79.8%) for rabeprazole-based triple therapy. There was no significant difference in the eradication rates between the two groups (p>0.999). Per-protocol analysis also revealed no significant difference between the eradication rates of the two groups (tegoprazan 83.4% [95% CI, 79.0% to 87.2%] vs rabeprazole 83.5% [79.0% to 87.4%], p>0.999). Furthermore, there was no significant difference in adverse event rates between the two groups (tegoprazan, 27.6%; rabeprazole, 25.8%; p=0.604).Conclusions: The eradication rate of tegoprazan-based triple therapy was similar to that of rabeprazole-based triple therapy. Further studies on the dose-escalation effect of tegoprazan for H. pylori eradication and the efficacy of tegoprazan in regimens other than conventional triple therapy are needed.

Abstract The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL‐C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL‐C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: −7.08%, 95% CI: −11.79 to −2.38, p = .0034, per‐protocol analysis set [PPS]: −6.97%, 95% CI: −11.76 to −2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL‐C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: −10.13%, 95% CI: −15.41 to −4.84, p = .0002, PPS: −10.96%, 95% CI: −15.98 to −5.93, p

Abstract In the absence of available data, we evaluated the effects of delayed hospitalization (symptom-to-door time [SDT] ≥ 24 h) on major clinical outcomes after new-generation drug-eluting stent implantation in patients with non-ST-segment elevation myocardial infarction (NSTEMI) and complex lesions. In total, 4373 patients with NSTEMI were divided into complex (n = 2106) and non-complex (n = 2267) groups. The primary outcome was the 3-year rate of major adverse cardiac events (MACE), defined as all-cause death, recurrent MI, and any repeat revascularization. Secondary outcomes included the individual MACE components. In the complex group, all-cause death (adjusted hazard ratio [aHR], 1.752; p = 0.004) and cardiac death (aHR, 1.966; p = 0.010) rates were significantly higher for patients with SDT ≥ 24 h than for those with SDT

Abstract Ticagrelor-based dual antiplatelet therapy (DAPT) provides potent antiplatelet inhibition but may increase the bleeding risk in Asian populations. We investigated the influence of early ticagrelor dose reduction (120 mg) on clinical outcomes in Korean patients undergoing percutaneous coronary intervention (PCI). A multicenter prospective clinical cohort study was conducted with patients who received standard-dose ticagrelor-based DAPT (180 mg) after PCI for complex lesions. Major adverse cardiovascular event (MACE: a composite of cardiovascular death, myocardial infarction, stroke, and repeat revascularization), bleeding, and net adverse clinical events (NACE: a composite of MACE and bleeding) were assessed. Among the 772 patients on standard-dose ticagrelor-based DAPT, 115 (14.8%) switched to low-dose ticagrelor-based DAPT (120 mg) within 6 months. Common reasons for the regimen changes were switching as planned (38.8%), dyspnea (25.5%), and bleeding (23.6%). A multivariable Cox proportional hazard model (CPH) showed that the risks of MACE, bleeding, and NACE were not different between the low-dose and standard-dose groups throughout the entire follow-up period and the period beyond 6 months post-PCI. Time-varying multivariable CPH models of the ticagrelor dose reduction yielded similar results. A reduction of the ticagrelor dose within 6 months after PCI is feasible and safe even in patients with complex lesions harboring a high ischemic event risk.

Abstract Background Oncologic impact of genetic alteration across synchronous colorectal cancer (CRC) still remains unclear. This study aimed to compare the oncologic relevance according to genetic alteration between synchronous and solitary CRC with performing systematic review. Methods Multicenter retrospective analysis was performed for CRC patients with curative resection. Genetic profiling was consisted of microsatellite instability (MSI) testing, RAS (K-ras, and N-ras), and BRAF (v-Raf murine sarcoma viral oncogene homolog B1) V600E mutation. Multivariate analyses were conducted using logistic regression for synchronicity, and Cox proportional hazard model with stage-adjusting for overall survival (OS) and disease-free survival (DFS). Results It was identified synchronous (n = 36) and solitary (n = 579) CRC with similar base line characteristics. RAS mutation was associated to synchronous CRC with no relations of MSI and BRAF. During median follow up of 77.8 month, Kaplan–meier curves showed significant differences according to MSI-high for OS, and in RAS, and BRAF mutation for DFS, respectively. In multivariable analyses, RAS and BRAF mutation were independent factors (RAS, HR = 1.808, 95% CI = 1.18–2.77, p = 0.007; BRAF, HR = 2.417, 95% CI = 1.32–4.41, p = 0.004). Old age was independent factor for OS (HR = 3.626, 95% CI = 1.09–12.00, p = 0.035). Conclusion This study showed that oncologic outcomes might differ according to mutation burden characterized by RAS, BRAF, and MSI between synchronous CRC and solitary CRC. In addition, our systematic review highlighted a lack of data and much heterogeneity in genetic characteristics and survival outcomes of synchronous CRC relative to that of solitary CRC.

CRISPR–Cas systems are known to be part of the bacterial adaptive immune system that provides resistance against intruders such as viruses, phages and other mobile genetic elements. To combat this bacterial defense mechanism, phages encode inhibitors called Acrs (anti-CRISPR proteins) that can suppress them. AcrIC9 is the most recently identified member of the AcrIC family that inhibits the type IC CRISPR–Cas system. Here, the crystal structure of AcrIC9 from Rhodobacter capsulatus is reported, which comprises a novel fold made of three central antiparallel β-strands surrounded by three α-helixes, a structure that has not been detected before. It is also shown that AcrIC9 can form a dimer via disulfide bonds generated by the Cys69 residue. Finally, it is revealed that AcrIC9 directly binds to the type IC cascade. Analysis and comparison of its structure with structural homologs indicate that AcrIC9 belongs to DNA-mimic Acrs that directly bind to the cascade complex and hinder the target DNA from binding to the cascade.

Abstract Background Muscle synergies, computationally identified intermuscular coordination patterns, have been utilized to characterize neuromuscular control and learning in humans. However, it is unclear whether it is possible to alter the existing muscle synergies or develop new ones in an intended way through a relatively short-term motor exercise in adulthood. This study aimed to test the feasibility of expanding the repertoire of intermuscular coordination patterns through an isometric, electromyographic (EMG) signal-guided exercise in the upper extremity (UE) of neurologically intact individuals. Methods 10 participants were trained for six weeks to induce independent control of activating a pair of elbow flexor muscles that tended to be naturally co-activated in force generation. An untrained isometric force generation task was performed to assess the effect of the training on the intermuscular coordination of the trained UE. We applied a non-negative matrix factorization on the EMG signals recorded from 12 major UE muscles during the assessment to identify the muscle synergies. In addition, the performance of training tasks and the characteristics of individual muscles’ activity in both time and frequency domains were quantified as the training outcomes. Results Typically, in two weeks of the training, participants could use newly developed muscle synergies when requested to perform new, untrained motor tasks by activating their UE muscles in the trained way. Meanwhile, their habitually expressed muscle synergies, the synergistic muscle activation groups that were used before the training, were conserved throughout the entire training period. The number of muscle synergies activated for the task performance remained the same. As the new muscle synergies were developed, the neuromotor control of the trained muscles reflected in the metrics, such as the ratio between the targeted muscles, number of matched targets, and task completion time, was improved. Conclusion These findings suggest that our protocol can increase the repertoire of readily available muscle synergies and improve motor control by developing the activation of new muscle coordination patterns in healthy adults within a relatively short period. Furthermore, the study shows the potential of the isometric EMG-guided protocol as a neurorehabilitation tool for aiming motor deficits induced by abnormal intermuscular coordination after neurological disorders. Trial registration This study was registered at the Clinical Research Information Service (CRiS) of the Korea National Institute of Health (KCT0005803) on 1/22/2021.

Abstract Background Basic fibroblast growth factor (bFGF) is one of the critical components accelerating angiogenesis and tissue regeneration by promoting the migration of dermal fibroblasts and endothelial cells associated with matrix formation and remodeling in wound healing process. However, clinical applications of bFGF are substantially limited by its unstable nature due to rapid decomposition under physiological microenvironment. Results In this study, we present the bFGF-loaded human serum albumin nanoparticles (HSA-bFGF NPs) as a means of enhanced stability and sustained release platform during tissue regeneration. Spherical shape of the HSA-bFGF NPs with uniform size distribution (polydispersity index

Additive manufacturing (AM) is not necessarily a new process but an advanced method for manufacturing complex three-dimensional (3D) parts. Among the several advantages of AM are the affordable cost, capability of building objects with complex structures for small-batch production, and raw material versatility. There are several sub-categories of AM, among which is fused filament fabrication (FFF), also commonly known as fused deposition modeling (FDM). FFF has been one of the most widely used additive manufacturing techniques due to its cost-efficiency, simplicity, and widespread availability. The FFF process is mainly used to create 3D parts made of thermoplastic polymers, and complex physical phenomena such as melt flow, heat transfer, solidification, crystallization, etc. are involved in the FFF process. Different techniques have been developed and employed to analyze these phenomena, including experimental, analytical, numerical, and finite element analysis (FEA). This study specifically aims to provide a comprehensive review of the developed numerical models and simulation tools used to analyze melt flow behavior, heat transfer, crystallization and solidification kinetics, structural analysis, and the material characterization of polymeric components in the FFF process. The strengths and weaknesses of these numerical models are discussed, simplifications and assumptions are highlighted, and an outlook on future work in the numerical modeling and FE simulation of FFF is provided.

The effects of aging on the healing capacity of maxillofacial bone defects have not been studied. The aim of this study was to evaluate the effects of aging on the regeneration of round bony defects in the mandible. We created a round-shaped bony defect in the mandibular angle area in rats of different ages (2-[2 M], 10-[10 M], and 20-month-old [20 M]) and evaluated new bone regeneration in these groups. Changes in bone turnover markers such as alkaline phosphatase, procollagen type I N-terminal propeptide (PINP), cross-linked C-telopeptide of type I collagen, and tartrate-resistant acid phosphatase 5B (TRAP5b) were investigated. The bone volume/total volume and bone mineral density of the 20 M group were significantly higher than those of the 2 M group (p = 0.029, 0.019). A low level of the bone formation marker PINP was observed in the 20 M group, and a high level of the bone resorption marker TRAP5b was observed in the 10 M and 20 M groups. Micro-computed tomography (µ-CT) results showed that older rats had significantly higher bone formation than younger rats, with lower serum levels of PINP and higher levels of TRAP5b. The local environment of the old rat bone defects, surrounded by thickened bone, may have affected the results of our study. In conclusion, old rats showed greater new bone regeneration and healing capacity for round mandibular bone defects. This result was related to the fact that the bone defects in the 20 M rat group provided more favorable conditions for new bone regeneration.

As engine monitoring data has become more complex with an increasing number of sensors, fault prediction based on artificial intelligence (AI) has emerged. Existing fault prediction models using AI significantly improve the accuracy of predictions by effectively handling such complex data, but at the same time, the problem arises that the AI-based models cannot explain the rationale of their predictions to users. To address this issue, we propose a time-series explanatory fault prediction framework to provide an explainability even when using AI-based fault prediction models. It consists of a data feature reduction process, a fault prediction model training process using long short-term memory, and an interpretation process of the fault prediction model via an explainable AI method. In particular, the proposed framework can explain a fault prediction based on time-series data. Therefore, it indicates which part of the data was significant for the fault prediction not only in terms of sensor type but also in terms of time. Through extensive experiments, we evaluate the proposed framework using various fault data by comparing the prediction performance of fault prediction and by assessing how well the main pre-symptoms of the fault are extracted when predicting a fault.

Sarcopenia, the age-related decline in muscle mass and function, poses a significant health challenge as the global population ages. Mitochondrial dysfunction is a key factor in sarcopenia, as evidenced by the role of mitochondrial reactive oxygen species (mtROS) in mitochondrial biogenesis and dynamics, as well as mitophagy. Resistance exercise training (RET) is a well-established intervention for sarcopenia; however, its effects on the mitochondria in aging skeletal muscles remain unclear. This review aims to elucidate the relationship between mitochondrial dynamics and sarcopenia, with a specific focus on the implications of RET. Although aerobic exercise training (AET) has traditionally been viewed as more effective for mitochondrial enhancement, emerging evidence suggests that RET may also confer beneficial effects. Here, we highlight the potential of RET to modulate mtROS, drive mitochondrial biogenesis, optimize mitochondrial dynamics, and promote mitophagy in aging skeletal muscles. Understanding this interplay offers insights for combating sarcopenia and preserving skeletal muscle health in aging individuals.

In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.

Objectives: This study aimed to analyze the association between alcohol use disorder (AUD) and suicidal ideation (SI) in the general Korean population. Methods: The 2022 Mental Health Awareness Survey was collected from the Chungcheongnam-do Mental Health Welfare Center (CHMHC). Before Propensity Score Matching (PSM), 823 participants were included in this study. After 1:4 PSM, the 255 participants were analyzed using the chi-square test and matched conditional logistic regression. Results: The AUD group had higher odds of experiencing SI than the non-AUD (adjusted odds ratio [AOR]: 2.40, 95% confidence intervals [CI]: 1.10–5.22). Stratified matched conditional logistic regression showed that, among the female, Conclusions: Through this study, we found a strong association between the AUD group and SI. This association was particularly strong among female,

Actin, which plays a crucial role in cellular structure and function, interacts with various binding proteins, notably myosin. In mammals, actin is composed of six isoforms that exhibit high levels of sequence conservation and structural similarity overall. As a result, the selection of actin isoforms was considered unimportant in structural studies of their binding with myosin. However, recent high-resolution structural research discovered subtle structural differences in the N-terminus of actin isoforms, suggesting the possibility that each actin isoform may engage in specific interactions with myosin isoforms. In this study, we aimed to explore this possibility, particularly by understanding the influence of different actin isoforms on the interaction with myosin 7A. First, we compared the reported actomyosin structures utilizing the same type of actin isoforms as the high-resolution filamentous skeletal α-actin (3.5 Å) structure elucidated using cryo-EM. Through this comparison, we confirmed that the diversity of myosin isoforms leads to differences in interaction with the actin N-terminus, and that loop 2 of the myosin actin-binding sites directly interacts with the actin N-terminus. Subsequently, with the aid of multiple sequence alignment, we observed significant variations in the length of loop 2 across different myosin isoforms. We predicted that these length differences in loop 2 would likely result in structural variations that would affect the interaction with the actin N-terminus. For myosin 7A, loop 2 was found to be very short, and protein complex predictions using skeletal α-actin confirmed an interaction between loop 2 and the actin N-terminus. The prediction indicated that the positively charged residues present in loop 2 electrostatically interact with the acidic patch residues D24 and D25 of actin subdomain 1, whereas interaction with the actin N-terminus beyond this was not observed. Additionally, analyses of the actomyosin-7A prediction models generated using various actin isoforms consistently yielded the same results regardless of the type of actin isoform employed. The results of this study suggest that the subtle structural differences in the N-terminus of actin isoforms are unlikely to influence the binding structure with short loop 2 myosin 7A. Our findings are expected to provide a deeper understanding for future high-resolution structural binding studies of actin and myosin.

Methods and means of remote control of the ecological state of the atmosphere are constantly improving. Lidar sensing allows obtaining up-to-date information about natural and technogenic sources of atmospheric pollution. There is a wide range of problems in ecological control, where the deployment of an inexpensive mobile lidar network is required. For this purpose, it is suggested to use Q-switch and MOPA fiber lasers in lidars. Q-switch fiber lasers have a simpler design and are more practical to use. However, pulses from Q-switch lasers have long full-pulse durations. In the present work, a lidar signal inversion method (LSIM) is proposed for solving this problem. Verification and outdoor experimentation of the LSIM was carried out with the reference signal method (RSM). The advantage of the proposed RSM is the minimum number of controllable parameters necessary for LSIM verification and approbation. As a result, the accuracy of the obtained results increased. Thus, the possibility of application of the Q-switch fiber lasers for lidar sensing is shown both theoretically and experimentally.