Nontraditional Roles of Magnesium Ions in Modulating Sav2152: Insight from a Haloacid Dehalogenase-like Superfamily Phosphatase from Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has rapidly spread through various routes. A genomic analysis of clinical MRSA samples revealed an unknown protein, Sav2152, predicted to be a haloacid dehalogenase (HAD)-like hydrolase, making it a potential candidate for a novel drug target. In this study, we determined the crystal structure of Sav2152, which consists of a C2-type cap domain and a core domain. The core domain contains four motifs involved in phosphatase activity that depend on the presence of Mg2+ ions. Specifically, residues D10, D12, and D233, which closely correspond to key residues in structurally homolog proteins, are responsible for binding to the metal ion and are known to play critical roles in phosphatase activity. Our findings indicate that the Mg2+ ion known to stabilize local regions surrounding it, however, paradoxically, destabilizes the local region. Through mutant screening, we identified D10 and D12 as crucial residues for metal binding and maintaining structural stability via various uncharacterized intra-protein interactions, respectively. Substituting D10 with Ala effectively prevents the interaction with Mg2+ ions. The mutation of D12 disrupts important structural associations mediated by D12, leading to a decrease in the stability of Sav2152 and an enhancement in binding affinity to Mg2+ ions. Additionally, our study revealed that D237 can replace D12 and retain phosphatase activity. In summary, our work uncovers the novel role of metal ions in HAD-like phosphatase activity.

Differential diagnosis of cemento-osseous dysplasia and periapical cyst using texture analysis of CBCT.

BACKGROUND: Radiolucencies found at the root apex in patients with cemento-osseous dysplasia (COD) may be mistaken for periapical cysts (PC) of endodontic origin. The purpose of this study was to examine the utility of quantitative texture analysis using cone-beam computed tomography (CBCT) to differentiate between COD and PC. METHODS: Patients who underwent CBCT at Wonkwang University Daejeon Dental Hospital between January 2019 and December 2022 and were diagnosed with COD and PC by clinical, radiologic, and, if necessary, histopathologic examination were included. Twenty-five patients each were retrospectively enrolled in the COD and PC group. All lesions observed on axial CBCT images were manually segmented using the open-access software MaZda version 4.6 to establish the regions of interest, which were then subjected to texture analysis. Among the 279 texture features obtained, 10 texture features with the highest Fisher coefficients were selected. Statistical analysis was performed using the Mann-Whitney U-test, Welch's t-test, or Student's t-test. Texture features that showed significant differences were subjected to receiver operating characteristics (ROC) curve analysis to evaluate the differential diagnostic ability of COD and PC. RESULTS: The COD group consisted of 22 men and 3 women, while the PC group consisted of 14 men and 11 women, showing a significant difference between the two groups in terms of sex (p=0.003). The 10 selected texture features belonged to the gray level co-occurrence matrix and included the sum of average, sum of entropy, entropy, and difference of entropy. All 10 selected texture features showed statistically significant differences (p<0.05) when comparing patients with COD (n=25) versus those with PC (n=25), osteolytic-stage COD (n=11) versus PC (n=25), and osteolytic-stage COD (n=11) versus cementoblastic-stage COD (n=14). ROC curve analysis to determine the ability to differentiate between COD and PC showed a high area under the curve ranging from 0.96 to 0.98. CONCLUSION: Texture analysis of CBCT images has shown good diagnostic value in the differential diagnosis of COD and PC, which can help prevent unnecessary endodontic treatment, invasive biopsy, or surgical intervention associated with increased risk of infection.

Biotransformation of 2-keto-4-hydroxybutyrate via aldol condensation using an efficient and thermostable carboligase from Deinococcus radiodurans.

The bioconversion of 4-hydroxy-2-keto acid derivatives via aldol condensation of formaldehyde and pyruvate has received substantial attention as potential source of chemicals for production of amino acids, hydroxy carboxylic acids, and chiral aldehydes. We developed an environmentally friendly biocatalyst consisting of a novel thermostable class II pyruvate aldolase from Deinococcus radiodurans with maltose-binding protein (MBP-DrADL), which has specific activity of 46.3 µmol min-1 mg-1. Surprisingly, MBP-DrADL maintained over 60% of enzyme activity for 4 days at 50 to 65 °C, we used MBP-DrADL as the best candidate enzyme to produce 2-keto-4-hydroxybutyrate (2-KHB) from formaldehyde and pyruvate via aldol condensation. The optimum reaction conditions for 2-KHB production were 50 °C, pH 8.0, 5 mM Mg2+, 100 mM formaldehyde, and 200 mM pyruvate. Under these optimized conditions, MBP-DrADL produced 76.5 mM (8.94 g L-1) 2-KHB over 60 min with a volumetric productivity of 8.94 g L-1 h-1 and a specific productivity of 357.6 mg mg-enzyme-1 h-1. Furthermore, 2-KHB production was improved by continuous addition of substrates, which produced approximately 124.8 mM (14.6 g L-1) of 2-KHB over 60 min with a volumetric productivity and specific productivity of 14.6 g L-1 h-1 and 583.4 mg mg-enzyme-1 h-1, respectively. MBP-DrADL showed the highest specific productivity for 2-KHB production yet reported. Our study provides a highly efficient biocatalyst for the synthesis of 2-KHB and lays the foundation for large-scale production and application of high-value compounds from formaldehyde.

Metastatic Osteosarcoma of the Distal Femur in a Korean Water Deer (Hydropotes inermis argyropus).

A free-living female Korean water deer (Hydropotes inermis argyropus) was found with swelling in the left femur. Radiographic and histopathologic examination confirmed distal femoral osteosarcoma with metastases to the inguinal lymph node and the lungs; there are no previous reports of osteosarcoma in water deer.

Comedones and epidermal cysts on the abdominal skin of a dog occurring after a laparotomy.

An 8-year-old neutered male shih tzu dog underwent laparotomy for cystolithectomy. Ten days later, multiple various-sized cystic nodules were observed on the suture line and surrounding abdominal skin, although the surgical incision had healed well. Microscopically, various-sized cysts lined with thin walls of stratified squamous epithelium in the dermis were dilated and filled with keratin. Adnexal differentiation from the wall was not seen. Thus, the abdominal lesions were diagnosed as comedones and epidermal cysts. Herein, we describe the case of a dog with comedones and epidermal cysts on the abdominal skin after a laparotomy. Key clinical message: Multiple various-sized cystic lesions of the follicles are described. The implantation of epidermal fragments into the dermis by surgery may induce epidermal cysts and comedones in the skin of hyperadrenocorticism-affected dogs.

Comédons et kystes épidermiques sur la peau abdominale d'un chien survenant après une laparotomie. Un chien shih tzu mâle castré de 8 ans a subi une laparotomie pour cystolithectomie. Dix jours plus tard, de multiples nodules kystiques de différentes tailles ont été observés sur la ligne de suture et sur la peau abdominale environnante, bien que l'incision chirurgicale ait bien cicatrisé. Au microscope, des kystes de différentes tailles bordés de fines parois d'épithélium pavimenteux stratifié dans le derme étaient dilatés et remplis de kératine. Aucune différenciation annexielle par rapport à la paroi n'a été observée. Ainsi, les lésions abdominales ont été diagnostiquées comme des comédons et des kystes épidermiques. Nous décrivons ici le cas d'un chien présentant des comédons et des kystes épidermiques sur la peau abdominale après une laparotomie.Message clinique clé:De multiples lésions kystiques des follicules, de différentes tailles, sont décrites. L'implantation chirurgicale de fragments d'épiderme dans le derme peut provoquer des kystes épidermiques et des comédons dans la peau des chiens atteints d'hypercorticisme.(Traduit par Dr Serge Messier).

Pulmonary-vein-to-pulmonary-artery ratio can be utilized to evaluate myxomatous mitral valve disease progression in dogs.

OBJECTIVE: To evaluate the diagnostic value of pulmonary-vein-to-pulmonary-artery ratio (PV:PA) in dogs with myxomatous mitral valve degeneration (MMVD), classified according to the American College of Veterinary Internal Medicine (ACVIM) consensus guidelines. ANIMALS: 80 client-owned dogs with either MMVD (n = 65) or no cardiovascular disease (control group; n = 15) between August 5, 2020, and July 19, 2023. METHODS: This is a retrospective study. Dogs with MMVD were classified according to ACVIM consensus guidelines. Echocardiograms, thoracic radiographs, and other measurements needed in this study were reviewed in all dogs. Spearman correlation was used to determine the correlation between the PV:PA and the following variables: vertebral heart size, vertebral left atrial size, left-atrium-to-aorta ratio, normalized left ventricular internal diameter, and peak transmitral early diastolic velocity. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of PV:PA in distinguishing between stages B1 and B2 and stages B2 and C. RESULTS: All conventional indices showed correlations with PV:PA. The area under the ROC curve (AUC) for stages B1 and B2 was 0.83, and the cutoff value for differentiating stage B2 was 1.52. The AUC for stages B2 and C was 0.81, and the cutoff value for differentiating stage C was 2.09. CLINICAL RELEVANCE: PV:PA was significantly different between control and the stage B1 group, stage B1 and B2 group, and stage B2 and C group. PV:PA can be an index that can be used in evaluating MMVD dogs.

A wireless, implantable bioelectronic system for monitoring urinary bladder function following surgical recovery.

Partial cystectomy procedures for urinary bladder-related dysfunction involve long recovery periods, during which urodynamic studies (UDS) intermittently assess lower urinary tract function. However, UDS are not patient-friendly, they exhibit user-to-user variability, and they amount to snapshots in time, limiting the ability to collect continuous, longitudinal data. These procedures also pose the risk of catheter-associated urinary tract infections, which can progress to ascending pyelonephritis due to prolonged lower tract manipulation in high-risk patients. Here, we introduce a fully bladder-implantable platform that allows for continuous, real-time measurements of changes in mechanical strain associated with bladder filling and emptying via wireless telemetry, including a wireless bioresorbable strain gauge validated in a benchtop partial cystectomy model. We demonstrate that this system can reproducibly measure real-time changes in a rodent model up to 30 d postimplantation with minimal foreign body response. Studies in a nonhuman primate partial cystectomy model demonstrate concordance of pressure measurements up to 8 wk compared with traditional UDS. These results suggest that our system can be used as a suitable alternative to UDS for long-term postoperative bladder recovery monitoring.

Packaged WGM MBR sensor for high-performance temperature measurement using CNN-based multimode barcode images.

The whispering gallery mode (WGM) optical microresonator sensors are emerging as a promising platform for precise temperature measurements, driven by their excellent sensitivity, resolution and integration. Nevertheless, challenges endure regarding stability, single resonant mode tracking, and real-time monitoring. Here, we demonstrate a temperature measurement approach based on convolutional neural network (CNN), leveraging the recognition of multimode barcode images acquired from a WGM microbottle resonator (MBR) sensor with robust packaged microresonator-taper coupling structure (packaged-MTCS). Our work ensures not only a high sensitivity of -14.28 pm/℃ and remarkable resolution of 3.5 × 10-4 ℃ across a broad dynamic range of 96 ℃ but also fulfills the demands for real-time temperature measurement with an average detection accuracy of 96.85% and a speed of 0.68s per image. These results highlight the potential of high-performance WGM MBR sensors in various fields and lay the groundwork for stable soliton microcomb excitation through thermal tuning.

Brain structural correlates of subjective sleepiness and insomnia symptoms in shift workers.

Background: Studies on the brain structures of shift workers are limited; thus, this cross-sectional study aimed to compare the brain structures and the brain structural correlates of subjective sleepiness and insomnia symptoms between shift workers and non-shift workers. Methods: Shift workers (n = 63) and non-shift workers (n = 58) completed questionnaires assessing subjective sleepiness and insomnia symptoms. Cortical thickness, cortical surface area, and subcortical volumes were measured by magnetic resonance imaging. The brain morphometric measures were compared between the groups, and interaction analyses using the brain morphometric measures as the dependent variable were performed to test the interactions between the study group and measures of sleep disturbance (i.e., subjective sleepiness and insomnia symptoms). Results: No differences in cortical thickness, cortical surface area, or subcortical volumes were detected between shift workers and non-shift workers. A single cluster in the left motor cortex showed a significant interaction between the study group and subjective sleepiness in the cortical surface area. The correlation between the left motor cortex surface area and the subjective sleepiness level was negative in shift workers and positive in non-shift workers. Significant interaction between the study group and insomnia symptoms was present for the left/right putamen volumes. The correlation between the left/right putamen volumes and insomnia symptom levels was positive in shift workers and negative in non-shift workers. Conclusion: Left motor cortex surface area and bilateral putamen volumes were unique structural correlates of subjective sleepiness and insomnia symptoms in shift workers, respectively.

Demonstration of Two-Dimensional Exciton Complex Palette.

Exciton complexes in two-dimensional semiconductors, encompassing bright and dark excitons, biexcitons, and defect-bound excitons, have shown significant potential across a wide range of research areas. These applications range from exploring quantum many-body phenomena to developing nonclassical light sources and quantum transport devices. To fully leverage their dynamic and interactive properties and extend the capabilities of excitonic devices, realizing systematic engineering and mixing of the exciton complexes are crucial. Unlike conventional material methods, which often lead to undesired changes in the electronic band structure and binding energy, optical methods provide a means to manipulate the radiative decay dynamics of individual exciton complexes in a purely environmental manner. Here, we employ a specialized photonic platform, analogous to an artist's palette, to arrange and mix exciton complexes on an identical two-dimensional transition metal dichalcogenide medium. Essentially, a gradient thickness mirror (GTM) continuously tunes the local distribution of optical vacuum field interference. The GTM platform enables us to create and examine five distinct compositions of the exciton complexes of the WSe2 monolayer and their contributions to the photoluminescence spectrum. Moreover, the exciton complex palette facilitates the observation of dark and defect-bound excitons, even at high temperatures of 70 K, and its performance can be further managed by simple postprocessing manipulations.

Hyperband electro-optic modulator based on a two-pulley coupled lithium niobate racetrack resonator.

Integrated optical modulators (IOMs) are crucial components of on-chip photonic circuits. However, most conventional IOMs are restricted to specific spectral bands. Here, we leveraged the wide transparency window of lithium niobate in conjunction with the two-pulley coupled resonator method. This approach led to the development of a hyperband electro-optic (EO) modulator that operates over an expansive spectral range from 775 to 1550 nm on a single device. The demonstrated EO modulator exhibits half-wave voltage-length products of 0.25, 0.93, and 0.68 V·cm at wavelengths of 1539.50, 969.70, and 775.17 nm, respectively.

Toxic dinoflagellate Centrodinium punctatum (Cleve) F.J.R. Taylor: An examination on the responses in growth and toxin contents to drastic changes of temperature and salinity.

To understand environmental effects affecting paralytic shellfish toxin production of Centrodinium punctatum, this study examined the growth responses, and toxin contents and profiles of a C. punctatum culture exposed to drastic changes of temperature (5-30 °C) and salinity (15-40). C. punctatum grew over a temperature range of 15-25 °C, with an optimum of 20 °C., and over a salinity range of 25-40, with optimum salinities of 30-35. This suggests that C. punctatum prefers relatively warm waters and an oceanic habitat for its growth and can adapt to significant changes of salinity levels. When C. punctatum was cultivated at different temperature and salinity levels, the PST profile included four major analogs (STX, neoSTX, GTX1 and GTX4, constituted >80 % of the profile), while low amounts of doSTX and traces of dc-STX and dc-GTX2 were also observed. Interestingly, though overall toxin contents did not change significantly with temperature, increases in the proportion of STX, and decreases in proportions in GTX1 and GTX4 were observed with higher temperatures. Salinity did not affect either toxin contents or profile from 25 to 35. However, the total toxin content dropped to approximately half at salinity 40, suggesting this salinity may induce metabolic changes in C. punctatum.

Antioxidant and Antimelanogenic Activities of Lactobacillus kunkeei NCHBL-003 Isolated from Honeybees.

Excessive reactive oxygen species production can detrimentally impact skin cell physiology, resulting in cell growth arrest, melanogenesis, and aging. Recent clinical studies have found that lactic acid bacteria have a special effect directly or indirectly on skin organs, but the exact mechanism has not been elucidated. In this study, we investigated the mechanisms underlying the antioxidant protective effect and the inhibitory effect on melanin synthesis of Lactobacillus kunkeei culture supernatant (CSK), isolated from Apis mellifera Linnaeus (the Western honeybee). CSK exhibited notable efficacy in promoting cell migration and wound healing under oxidative stress, surpassing the performance of other strains. CSK pretreatment significantly upregulated the expression of Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/heme oxygenase-1), a key player in cellular defenses against oxidative stress, relative to the control H2O2-treated cells. The DCF-DA (dichloro-dihydro-fluorescein diacetate) assay results confirmed that CSK's ability to enhance Nrf2 and HO-1 expression aligns with its robust ability to remove H2O2-induced reactive oxygen species. Furthermore, CSK upregulated MAPK (mitogen-activated protein kinase) phosphorylation, an upstream signal for HO-1 expression, and MAPK inhibitors compromised the wound-healing effect of CSK. Additionally, CSK exhibited inhibitory effects on melanin synthesis, downregulating melanogenesis-related genes in B16F10 cells. Thus, the present study demonstrated that CSK exhibited antioxidant effects by activating the Nrf2/HO-1 pathway through MAPK phosphorylation, thereby restoring cell migration and demonstrating inhibitory effects on melanin production. These findings emphasize the antioxidant and antimelanogenic potential of CSK, suggesting its potential use as a therapeutic agent, promoting wound healing, and as an active ingredient in skin-lightening cosmetics.

Serping1 associated with α-synuclein increase in colonic smooth muscles of MPTP-induced Parkinson's disease mice.

Patients with Parkinson's disease (PD) have gastrointestinal motility disorders, which are common non-motor symptoms. However, the reasons for these motility disorders remain unclear. Increased alpha-synuclein (α-syn) is considered an important factor in peristalsis dysfunction in colonic smooth muscles in patients with PD. In this study, the morphological changes and association between serping1 and α-syn were investigated in the colon of the 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced chronic PD model. Increased serping1 and α-syn were noted in the colon of the PD model, and decreased serping1 also induced a decrease in α-syn in C2C12 cells. Serping1 is a major regulator of physiological processes in the kallikrein-kinin system, controlling processes including inflammation and vasodilation. The kinin system also comprises bradykinin and bradykinin receptor 1. The factors related to the kallikrein-kinin system, bradykinin, and bradykinin receptor 1 were regulated by serping1 in C2C12 cells. The expression levels of bradykinin and bradykinin receptor 1, modulated by serping1 also increased in the colon of the PD model. These results suggest that the regulation of increased serping1 could alleviate Lewy-type α-synucleinopathy, a characteristic of PD. Furthermore, this study could have a positive effect on the early stages of PD progression because of the perception that α-syn in colonic tissues is present prior to the development of PD motor symptoms.

Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.

Valosin-containing protein (VCP)/p97, an AAA+ ATPase critical for maintaining proteostasis, emerges as a promising target for cancer therapy. This study reveals that targeting VCP selectively eliminates breast cancer cells while sparing non-transformed cells by inducing paraptosis, a non-apoptotic cell death mechanism characterized by endoplasmic reticulum and mitochondria dilation. Intriguingly, oncogenic HRas sensitizes non-transformed cells to VCP inhibition-mediated paraptosis. The susceptibility of cancer cells to VCP inhibition is attributed to the non-attenuation and recovery of protein synthesis under proteotoxic stress. Mechanistically, mTORC2/Akt activation and eIF3d-dependent translation contribute to translational rebound and amplification of proteotoxic stress. Furthermore, the ATF4/DDIT4 axis augments VCP inhibition-mediated paraptosis by activating Akt. Given that hyperactive Akt counteracts chemotherapeutic-induced apoptosis, VCP inhibition presents a promising therapeutic avenue to exploit Akt-associated vulnerabilities in cancer cells by triggering paraptosis while safeguarding normal cells.

Longevous Cycling of Rechargeable Zn-Air Battery Enabled by "Raisin-Bread" Cobalt Oxynitride/Porous Carbon Hybrid Electrocatalysts.

Developing commercially viable electrocatalyst lies at the research hotspot of rechargeable Zn-air batteries, but it is still challenging to meet the requirements of energy efficiency and durability in realistic applications. Strategic material design is critical to addressing its drawbacks in terms of sluggish kinetics of oxygen reactions and limited battery lifespan. Herein, a "raisin-bread" architecture is designed for a hybrid catalyst constituting cobalt nitride as the core nanoparticle with thin oxidized coverings, which is further deposited within porous carbon aerogel. Based on synchrotron-based characterizations, this hybrid provides oxygen vacancies and Co-Nx -C sites as the active sites, resulting from a strong coupling between CoOx Ny nanoparticles and 3D conductive carbon scaffolds. Compared to the oxide reference, it performs enhanced stability in harsh electrocatalytic environments, highlighting the benefits of the oxynitride. Furthermore, the 3D conductive scaffolds improve charge/mass transportation and boost durability of these active sites. Density functional theory calculations reveal that the introduced N species into hybrid can synergistically tune the d-band center of cobalt and improve its bifunctional activity. As a result, the obtained air cathode exhibits bifunctional overpotential of 0.65 V and a battery lifetime exceeding 1350 h, which sets a new record for rechargeable Zn-air battery reported so far.

Enhanced Dural Repair Using Biodegradable Sealants Based on Photocurable Hyaluronic Acid.

Cerebrospinal fluid (CSF) leakage is a common complication of intradural surgery or incidental durotomy in neurosurgery. Dural suturing is a common method for durotomy repair, but this technique requires a long operation time and includes the risk of CSF leakage by incomplete sealing. Glue-type sealants are effective for watertight dural closure. However, unresolved shortcomings include insufficient sealing performance, poor biocompatibility, and excessive swelling. Here, a dural sealant using light-activated hyaluronic acid (HA) with multi-networks (HA photosealant) that provides fast sealing performance and high biocompatibility is reported. The HA photosealants form a watertight hydrogel barrier with multilength networks under low-energy visible light exposure (405 nm, <1 J cm-2) for 5 s and allow firm tissue adhesion on the wet dural surface. In a rabbit model of craniectomy and durotomy, HA photosealants exhibit the faster sealing performance of dural tears and enhance dural repair with accelerated bone formation compared to commercial surgical glues, with no degenerative changes, such as inflammation or necrosis, in histopathological evaluation. This biocompatible HA photosealant can be applied in a variety of clinical settings that require fast wound closure as a promising potential.

The First Case of Cutaneous Acanthamoebiasis Caused by Acanthamoeba triangularis in Korea.

A 62-year-old man with multiple myeloma visited our clinic with multiple painful erythematous to purpuric nodules on his whole body. He received a skin biopsy which showed septal and lobular inflammation with vasculitis, and multiple amoebic organisms were found. Polymerase chain reaction and culture were performed and an Acanthamoeba triangularis infection was diagnosed. This is the first report on cutaneous acanthamoebiasis caused by A. triangularis, suggesting that A. triangularis should be regarded as a clinical pathogen that can cause ocular as well as disseminated infection.