Analysis of Priority Conservation Areas Using Habitat Quality Models and MaxEnt Models.

This study investigated core habitat areas for yellow-throated martens (Martes flavigula) and leopard cats (Prionailurus bengalensis), two endangered forest species sensitive to habitat fragmentation in Korea. Overlaying the InVEST-HQ and MaxEnt models, priority conservation areas were identified by analyzing gaps in currently protected areas. The InVEST-HQ model showed that habitat quality ranged from 0 to 0.86 on a scale from 0 to 1, and the majority of the most suitable areas on the Environmental Conservation Value Assessment Map, designated as grade 1, were derived correctly. The MaxEnt model analysis accurately captured the ecological characteristics of the yellow-throated marten and the leopard cat and identified probable regions of occurrence. We analyzed the most suitable yellow-throated marten and leopard cat habitats by superimposing the two results. Gap analysis determined gaps in existing protected areas and identified priority conservation areas. The core area (14.7%) was mainly distributed in forests such as the Baekdudaegan Mountains Reserve in regions such as Gyeongbuk, Gyeongnam, and Gangwon; 12.9% was outside protected areas, and only 1.8% was protected. The overlap results between protected and non-protected areas were compared with different land use types. Conservation priority areas were identified as those with more than 95% forest cover, offering an appropriate habitat for the two species. These findings can be used to identify priority conservation areas through objective habitat analysis and as a basis for protected area designation and assessment of endangered species habitat conservation, thereby contributing to biodiversity and ecosystem conservation.

Model-based development of cell voltage control system for modified bio-electro-Fenton process.

A modified bio-electro-Fenton (M-BEF) process with a cell voltage control system that improves the efficiency of organic removal and energy savings is demonstrated. The M-BEF process can accomplish bioelectricity generation, H2O2 production, and the Fenton reaction in a continuous-flow reactor. During synthetic wastewater treatment containing biodegradable (glucose) and recalcitrant (biphenyl) organic matter, the effluent chemical oxygen demand (COD) concentration was maintained between 2 and 6 mg L-1. To investigate the impact of different operating schemes on energy usage, model-based design (MBD) modeling and simulations were performed, which showed that COD removal efficiency without an external voltage supply was unstable at < 70 %. The automatic cell voltage control system saved 90 % of the power compared to the continuous cell voltage supply system. Further testing on more environmental samples and pollutants will enable real-time optimization of supplied power and wastewater treatment using the cell voltage control system.

Clinical presentation, viral shedding, and neutralizing antibody responses of mpox cases in South Korea: Single center experience.

BACKGROUND: A global mpox outbreak occurred in 2022, and a domestic outbreak started in South Korea in April 2023. This study aimed to evaluate the clinical characteristics, viral shedding, and immune response of mpox in South Korea. METHODS: Patients hospitalized with mpox in the National Medical Center between September 2022 and June 2023 were included in this study. Oropharyngeal (OP), anogenital lesion (AL), and skin lesion (SL) swabs and blood samples were collected, and monkeypox virus (MPXV) DNA using real-time polymerase chain reaction (RT-PCR) and culture assays were performed. Neutralizing antibodies (NAbs) against MPXV A.2.1, B.1.1, and B.1.3 were detected using plaque reduction neutralization tests. RESULTS: Eighteen patients were enrolled, of whom 17 (94.4 %) were male, with a median (IQR) age of 32.5 (24-51) years. While nine (50 %) were HIV-infected individuals, none of them revealed CD4+ counts less than 200 cells/µL. MPXV DNA was detected in 87.3 % and 82.7 % of patient's ALs and SLs, respectively, until 2 weeks after symptom onset. While MPXV was isolated for up to 15 days in all three sample types, the culture positivity decreased to 53.8 % and 42.9 % in ALs and SLs after 10 days, respectively, and 28.6 % and 22.2 %, respectively, after 2 weeks from symptom onset. The NAb titers against MPXV A.2.1 were significantly lower than those against B.1.1 and B.1.3. CONCLUSIONS: Infectious MPXV was isolated from various anatomical sites up to 15 days after symptom onset. The MPXV NAb response was varied among different lineages, and this implies limited cross-lineage protection.

Severe mpox requiring colostomy in a patient with advanced HIV disease: A case report and literature review.

This severe monkeypox case described a 23-year-old male with advanced HIV-1 disease presenting perirectal abscess, extensive anal ulcerative lesions requiring colostomy, and tecovirimat resistance. Radiologically non-liquefied perirectal abscess presented diagnostic challenges highlighting the complexity of aggressive monkeypox manifestations in immunocompromised individuals.

Polarization-independent edge detection based on the spin-orbit interaction of light.

In previous edge detection schemes based on the spin-orbit interaction of light, the direction and intensity of the edge-enhanced images are influenced by the incident polarization state. In this study, we develop an edge detection strategy that is insensitive to changes in both the incident polarization and the incident angle. The output intensity and transfer function remain entirely impervious to changes in incident polarization, being explicitly formulated as functions of the incident angle, specifically in terms of cot 2⁡θ i and cot⁡θ i , respectively. This behavior is attributed to the opposing nature of the polarization components E~r H-H and E~r V-V in the x-direction after undergoing mapping through the Glan polarizer, while the sum of polarization components E~r H-V and E~r V-H in the y-direction can be simplified to terms independent of incident polarization. Furthermore, we propose a metasurface design to achieve the required optical properties in order to realize the derived edge detection scheme.

Genomic Analysis of Monkeypox Virus During the 2023 Epidemic in Korea.

We aimed to characterize the genomes of monkeypox virus isolates from the Far East, providing insights into viral transmission and evolution. Genomic analysis was conducted on 8 isolates obtained from patients with monkeypox virus disease in the Republic of Korea between May 2022 and early 2023. These isolates were classified into Clade IIb. Distinct lineages, including B.1.1, A.2.1, and B.1.3, were observed in 2022 and 2023 isolates, with only the B.1.3 lineage detected in six isolates of 2023. These genetic features were specific to Far East isolates (the Republic of Korea, Japan, and Taiwan), distinguishing them from the diverse lineages found in the Americas, Europe, Africa, and Oceania. In early 2023, the prevalence of the B.1.3 lineage of monkeypox virus identified in six patients with no overseas travel history is considered as an indicator of the potential initiation of local transmission in the Republic of Korea.

Sustainable control of Microcystis aeruginosa, a harmful cyanobacterium, using Selaginella tamariscina extracts.

Eco-friendly reagents derived from plants represent a promising strategy to mitigate the occurrence of toxic cyanobacterial blooms. The use of an amentoflavone-containing Selaginella tamariscina extract (STE) markedly decreased the number of Microcystis aeruginosa cells, thus demonstrating significant anti-cyanobacterial activity. In particular, the Microcystis-killing fraction obtained from pulverized S. tamariscina using hot-water-based extraction at temperatures of 40 °C induced cell disruption in both axenic and xenic M. aeruginosa. Liquid chromatographic analysis was also conducted to measure the concentration of amentoflavone in the STE, thus supporting the potential M. aeruginosa-specific killing effects of STE. Bacterial community analysis revealed that STE treatment led to a reduction in the relative abundance of Microcystis species while also increasing the 16S rRNA gene copy number in both xenic M. aeruginosa NIBR18 and cyanobacterial bloom samples isolated from a freshwater environment. Subsequent testing on bacteria, cyanobacteria, and algae isolated from freshwater revealed that STE was not toxic for other taxa. Furthermore, ecotoxicology assessment involving Aliivibrio fischeri, Daphnia magna, and Danio rerio found that high STE doses immobilized D. magna but did not impact the other organisms, while there was no change in the water quality. Overall, due to its effective Microcystis-killing capability and low ecotoxicity, aqueous STE represents a promising practical alternative for the management of Microcystis blooms.

Antidepressant and anxiolytic potential of Citrus reticulata Blanco essential oil: a network pharmacology and animal model study.

Background: Citrus reticulata Blanco essential oil (CBEO) has attracted increasing attention as a potential treatment for depression and anxiety in recent years. However, there is limited evidence regarding the active compounds responsible for its therapeutic effects. In addition, substantial amounts of CBEO and prolonged therapy are often required. This study aims to investigate the rapid acting antidepressant and anxiolytic effects of CBEO, identify the underlying composition as well as optimize its dosage and duration. Methods: CBEO composition was determined using gas chromatography-mass spectrometry (GC-MS), and the corresponding targets were obtained from the SwissTargetPrediction database. Depression-related targets were collected from DisGeNET, GeneCards, Therapeutic Target Database, and Online Mendelian Inheritance in Man. Subsequently, the overlap between CBEO and depression targets was utilized to build a network diagram depicting the relationship between the active ingredients and targets using Cytoscape software. The STRING database facilitated the construction of a protein-protein interaction network, and the Ma'ayan Laboratory Enrichment tool was employed for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Wiki pathway analyses. Molecular docking was conducted using AutoDock Vina and Discovery Studio Visualizer. Topological analysis predicted the main antidepressant active ingredients in CBEO. A mixture of these compounds was prepared based on their relative GC-MS ratios. Tail suspension test, elevated plus maze, corticosterone-induced PC12 cells, and lipopolysaccharide (LPS)-induced BV2 cells were used to validate the antidepressant and anxiolytic potential of CBEO and CBEO's main bioactive constituents. Results: CBEO contains 18 components that target 121 proteins. We identified 595 targets associated with depression; among them, 29 targets were located between essential oils and depression. Topological results revealed that linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol were the major active compounds of CBEO in the management of depression. GO analysis identified G protein-coupled opioid receptor activity, phospholipase C-activating G protein-coupled receptor, and neuron projections that were mostly related to molecular functions, cellular components, and biological processes. Neuroactive ligand-receptor interactions, chemical carcinogenesis, and calcium signaling pathways were the major pathways identified in KEGG analysis. Molecular docking showed that the main bioactive ingredients of CBEO had favorable binding affinities for Protein-Protein Interaction's hub proteins, including OPRM1, PTGS2, ESR1, SLC6A4, DRD2, and NR3C1. These five compounds were then mixed at 0.8:5:0.6:2:1 (w/w) ratio to form a CBEO antidepressant active compound mixture. An acute intranasal treatment of CBEO (25 mg/kg) only demonstrated an antidepressant effect, whereas the main bioactive compounds combination (12.5 mg/kg) illustrated both antidepressant and anxiolytic effects in mice. Linalool, p-cymene, and terpinene-4-ol exhibited neuroprotective and anti-neuroinflammation in the in vitro study, while these effects were not observed for α-terpinene and α-terpineol. Conclusion: Linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol cymene might be mainly contributing to CBEO's antidepressant effect by regulating neuroactive ligand-receptor interaction, neuron projection, and receptor signaling pathway. A mixture of these compounds showed rapid antidepressant potential via intranasal administration, which was comparable to that of CBEO. The mixture also exhibited an anxiolytic effect while not seen in CBEO.

Adverse Reactions After Intradermal Vaccination With JYNNEOS for Mpox in Korea.

In response to the Mpox domestic epidemic, South Korea initiated a nationwide vaccination program in May 2023, administering a 0.1 mL intradermal dose of JYNNEOS (Modified Vaccinia Ankara vaccine, Bavarian Nordic) to a high-risk group. To investigate the adverse reactions after intradermal JYNNEOS vaccination, an anonymous online survey was conducted at the National Medical Center from May 22 to July 31, 2023. Overall, 142 individuals responded. Over 80% of the respondents reported local reactions of predominantly mild severity. The predominant local reactions were pruritus, redness, and swelling; their incidence rates after the first dose were 66.2%, 48.1%, and 49.4%, respectively; the corresponding rates after the second dose were 69.2%, 60.6%, and 53.8%. Fewer respondents reported systemic symptoms. The most common systemic symptom was fatigue, the incidence rates of which after the first and second doses were 37.7% and 24.6%, respectively. Overall, the intradermally administered JYNNEOS vaccine appeared well tolerated.

Brain network hypersensitivity underlies pain crises in sickle cell disease.

Sickle cell disease (SCD) is a genetic disorder causing painful and unpredictable Vaso-occlusive crises (VOCs) through blood vessel blockages. In this study, we propose explosive synchronization (ES) as a novel approach to comprehend the hypersensitivity and occurrence of VOCs in the SCD brain network. We hypothesized that the accumulated disruptions in the brain network induced by SCD might lead to strengthened ES and hypersensitivity. We explored ES's relationship with patient reported outcome measures (PROMs) as well as VOCs by analyzing EEG data from 25 SCD patients and 18 matched controls. SCD patients exhibited lower alpha frequency than controls. SCD patients showed correlation between frequency disassortativity (FDA), an ES condition, and three important PROMs. Furthermore, stronger FDA was observed in SCD patients with a higher frequency of VOCs and EEG recording near VOC. We also conducted computational modeling on SCD brain network to study FDA's role in network sensitivity. Our model demonstrated that a stronger FDA could be linked to increased sensitivity and frequency of VOCs. This study establishes connections between SCD pain and the universal network mechanism, ES, offering a strong theoretical foundation. This understanding will aid predicting VOCs and refining pain management for SCD patients.

The composition of the bacterial communities collected from the PM10 samples inside the Seoul subway and railway station.

Health implications of indoor air quality (IAQ) have drawn more attention since the COVID epidemic. There are many different kinds of studies done on how IAQ affects people's well-being. There hasn't been much research that looks at the microbiological composition of the aerosol in subway transit systems. In this work, for the first time, we examined the aerosol bacterial abundance, diversity, and composition in the microbiome of the Seoul subway and train stations using DNA isolated from the PM10 samples from each station (three subway and two KTX stations). The average PM10 mass concentration collected on the respective platform was 41.862 µg/m3, with the highest average value of 45.95 µg/m3 and the lowest of 39.25 µg/m3. The bacterial microbiomes mainly constituted bacterial species of soil and environmental origin (e.g., Acinetobacter, Brevundimonas, Lysinibacillus, Clostridiodes) with fewer from human sources (Flaviflexus, Staphylococcus). This study highlights the relationship between microbiome diversity and PM10 mass concentration contributed by outdoor air and commuters in South Korea's subway and train stations. This study gives insights into the microbiome diversity, the source, and the susceptibility of public transports in disease spreading.

Risk factors for critical COVID-19 illness during Delta- and Omicron-predominant period in Korea; using K-COV-N cohort in the National health insurance service.

BACKGROUND: This study evaluated the clinical characteristics of patients with COVID-19 in Korea, and examined the relationship between severe COVID-19 cases and underlying health conditions during the Delta (September 20, 2021 to December 4, 2021) and the Omicron (February 20, 2022 to March 31, 2022) predominant period. METHODS: This study assessed the association between critical COVID-19 illness and various risk factors, including a variety of underlying health conditions, using multiple logistic regression models based on the K-COV-N cohort, a nationwide data of confirmed COVID-19 cases linked with COVID-19 vaccination status and the National Health Insurance claim information. RESULTS: We analyzed 137,532 and 8,294,249 cases of COVID-19 infection during the Delta and the Omicron variant dominant periods, respectively. During the Delta as well as the Omicron period, old age (≥80 years) showed the largest effect size among risk factors for critical COVID-19 illness (aOR = 18.08; 95% confidence interval [CI] = 14.71-22.23 for the Delta; aOR = 24.07; 95% CI = 19.03-30.44 for the Omicron period). We found that patients with solid organ transplant (SOT) recipients, unvaccinated, and interstitial lung disease had more than a two-fold increased risk of critical COVID-19 outcomes between the Delta and Omicron periods. However, risk factors such as urban residence, underweight, and underlying medical conditions, including chronic cardiac diseases, immunodeficiency, and mental disorders, had different effects on the development of critical COVID-19 illness between the Delta and Omicron periods. CONCLUSION: We found that the severity of COVID-19 infection was much higher for the Delta variant than for the Omicron. Although the Delta and the Omicron variant shared many risk factors for critical illness, several risk factors were found to have different effects on the development of critical COVID-19 illness between those two variants. Close monitoring of a wide range of risk factors for critical illness is warranted as new variants continue to emerge during the pandemic.

Prediction accuracy of genomic estimated breeding values for fruit traits in cultivated tomato (Solanum lycopersicum L.).

BACKGROUND: Genomic selection (GS) is an efficient breeding strategy to improve quantitative traits. It is necessary to calculate genomic estimated breeding values (GEBVs) for GS. This study investigated the prediction accuracy of GEBVs for five fruit traits including fruit weight, fruit width, fruit height, pericarp thickness, and Brix. Two tomato germplasm collections (TGC1 and TGC2) were used as training populations, consisting of 162 and 191 accessions, respectively. RESULTS: Large phenotypic variations for the fruit traits were found in these collections and the 51K Axiom™ SNP array generated confident 31,142 SNPs. Prediction accuracy was evaluated using different cross-validation methods, GS models, and marker sets in three training populations (TGC1, TGC2, and combined). For cross-validation, LOOCV was effective as k-fold across traits and training populations. The parametric (RR-BLUP, Bayes A, and Bayesian LASSO) and non-parametric (RKHS, SVM, and random forest) models showed different prediction accuracies (0.594-0.870) between traits and training populations. Of these, random forest was the best model for fruit weight (0.780-0.835), fruit width (0.791-0.865), and pericarp thickness (0.643-0.866). The effect of marker density was trait-dependent and reached a plateau for each trait with 768-12,288 SNPs. Two additional sets of 192 and 96 SNPs from GWAS revealed higher prediction accuracies for the fruit traits compared to the 31,142 SNPs and eight subsets. CONCLUSION: Our study explored several factors to increase the prediction accuracy of GEBVs for fruit traits in tomato. The results can facilitate development of advanced GS strategies with cost-effective marker sets for improving fruit traits as well as other traits. Consequently, GS will be successfully applied to accelerate the tomato breeding process for developing elite cultivars.

Treatment of a Large Tibial Non-Union Bone Defect in a Cat Using Xenograft with Canine-Derived Cancellous Bone, Demineralized Bone Matrix, and Autograft.

A 17-month-old domestic short-hair cat was referred due to a non-union in the left tibia. The initial repair, conducted 3 months prior at another animal hospital, involved an intramedullary (IM) pin and wire to address a comminuted fracture. Unfortunately, the wire knot caused a skin tract, resulting in osteomyelitis. Although the wire knot was removed at that hospital, the draining tract persisted, continuously discharging exudate. Upon evaluation, the first surgery was reassessed and revised, involving the removal of the IM pin and the application of external skeletal fixation alongside an antibiotic susceptibility test. After 118 days post-revision surgery, while some cortical continuity was observed, a significant bone defect persisted, posing a substantial risk of refracture should the implant be removed. A second revision surgery was performed, utilizing a bone plate combined with cancellous bone autograft, recombinant human bone morphogenetic protein-2, and xenograft featuring a canine-derived cancellous chip mixed with demineralized bone matrix. Remarkably, the bone completed its healing within 105 days following the subsequent surgery. Radiography demonstrated successful management of the large bone defect up to the 2-year postoperative check-up. During telephone follow-ups for 3.5 years after surgery, no complications were identified, and the subject maintained a favorable gait.

[Factors Influencing the Intention for Continual Fertility Treatments by the Women Undergoing Assisted Reproductive Technology Procedures: A Cross-Sectional Study].

PURPOSE: This cross-sectional study aimed to identify factors influencing the intention for continual fertility treatments among women undergoing assisted reproductive technology (ART). METHODS: A total of 197 women were recruited through convenience sample from fertility hospitals in Gyeonggi-do and Busan, South Korea. Data were collected using a self-report questionnaire incorporating measures of uncertainty; Depression Anxiety Stress Scales; Fatigue Severity Scale; Coping Scale for Infertility-Women; spousal support; treatment environment; and intention for continual fertility treatment. Descriptive statistics, chi-square tests, t-tests, and logistic regression analysis were conducted using IBM SPSS 26.0. RESULTS: As many as 70.6% of the participants expressed an intention for continual fertility treatments. Logistic regression analysis revealed that factors such as uncertainty (odds ratio [OR] = 0.44, 95% confidence interval [CI] 0.20~0.95), active coping (OR = 4.04, 95% CI 1.11~14.71), treatment environment (OR = 2.77, 95% CI 1.26~6.07), and the duration of marriage (OR = 2.61, 95% CI 1.24~5.49) were significantly related with this intention. CONCLUSION: These findings underscore the significance of uncertainty management, having proactive coping strategies, having supportive treatment environments, and considering the duration of marriage concerning women's intention for continual fertility treatment in the context of ART. The implications of these results extend to the development of nursing intervention programs aimed at providing crucial support for women undergoing ART and seeking to continue their infertility treatment.

All-dielectric polarization-sensitive metasurface for terahertz polarimetric imaging.

Terahertz polarimetric imaging, capable of capturing not only intensity profiles but also the polarization states of the incident pattern, is an essential technique with promising applications such as security scans and medical diagnoses. Recently, a novel approach for terahertz imaging has been proposed using a metasurface absorber that converts terahertz light into a temperature profile. However, polarization remains indistinguishable in the imaging process due to the isotropic geometry of the metasurface. To address this issue, this study introduces an all-dielectric, polarization-sensitive metasurface absorber and showcases its suitability for terahertz polarimetric imaging. Optical and thermal simulations confirm that the polarization dependence of our metasurface is translated into the thermal domain, allowing us to distinguish both intensity and polarization states in the incoming image. Additionally, we demonstrate that polarimetric imaging under general, elliptical polarization is attainable. This metasurface facilitates terahertz polarimetric imaging, eliminating the need for complex setups or bulky components, thereby reducing the form factor and enabling widespread use.

Intranasal delivery of herbal medicine for disease treatment: A systematic review.

BACKGROUND: Intranasal administration has been adopted in traditional medicine to facilitate access to the bloodstream and central nervous system (CNS). In modern medicine, nasal drug delivery systems are valuable for disease treatment because of their noninvasiveness, good absorption, and fast-acting effects. OBJECTIVE: This study aimed to systematically organize preclinical and clinical studies on intranasal herbal medicines to highlight their potential in drug development. METHODS: A comprehensive search for literature until February 2023 was conducted on PubMed and the Web of Science. From the selected publications, we extracted key information, including the types of herbal materials, target diseases, intranasal conditions, methods of toxicity evaluation, main outcomes, and mechanisms of action, and performed quality assessments for each study. RESULTS: Of the 45 studies, 13 were clinical and 32 were preclinical; 28 studies used herbal extracts, 9 used prescriptions, and 8 used natural compounds. The target diseases were rhinosinusitis, influenza, fever, stroke, migraine, insomnia, depression, memory disorders, and lung cancer. The common intranasal volumes were 8-50 µl in mice, 20-100 µl in rats, and 100-500 µl in rabbits. Peppermint oil, Ribes nigrum folium, Melia azedarach L., Elaeocarpus sylvestris, Radix Bupleuri, Da Chuan Xiong Fang, Xingnaojing microemulsion, and Ginsenoside Rb1 emerged as potential candidates for rapid intranasal therapy. The in vivo toxicity assessments were based on mortality, body weight, behavioral changes, mucociliary activity, histopathology, and blood tests. Most intranasal treatments were safe, except for Cyclamen europaeum, Jasminum sambac, Punica granatum L., and violet oil, which caused mild adverse effects. At lower doses, intranasal herbal treatments often show greater effects than oral administration. The actions of intranasal herbal medicine mainly involve regulating inflammation and neurotransmission, with the olfactory bulb and anterior cingulate cortex to be relevant brain regions. CONCLUSION: Intranasal delivery of herbal materials holds promise for enhancing drug delivery efficacy and reducing treatment duration, offering a potential future perspective for developing intranasal therapies for various diseases.

Intranasal Delivery of Anti-Apoptotic siRNA Complexed with Fas-Signaling Blocking Peptides Attenuates Cellular Apoptosis in Brain Ischemia.

Ischemic stroke-induced neuronal cell death leads to the permanent impairment of brain function. The Fas-mediating extrinsic apoptosis pathway and the cytochrome c-mediating intrinsic apoptosis pathway are two major molecular mechanisms contributing to neuronal injury in ischemic stroke. In this study, we employed a Fas-blocking peptide (FBP) coupled with a positively charged nona-arginine peptide (9R) to form a complex with negatively charged siRNA targeting Bax (FBP9R/siBax). This complex is specifically designed to deliver siRNA to Fas-expressing ischemic brain cells. This complex enables the targeted inhibition of Fas-mediating extrinsic apoptosis pathways and cytochrome c-mediating intrinsic apoptosis pathways. Specifically, the FBP targets the Fas/Fas ligand signaling, while siBax targets Bax involved in mitochondria disruption in the intrinsic pathway. The FBP9R carrier system enables the delivery of functional siRNA to hypoxic cells expressing the Fas receptor on their surface-a finding validated through qPCR and confocal microscopy analyses. Through intranasal (IN) administration of FBP9R/siCy5 to middle cerebral artery occlusion (MCAO) ischemic rat models, brain imaging revealed the complex specifically localized to the Fas-expressing infarcted region but did not localize in the non-infarcted region of the brain. A single IN administration of FBP9R/siBax demonstrated a significant reduction in neuronal cell death by effectively inhibiting Fas signaling and preventing the release of cytochrome c. The targeted delivery of FBP9R/siBax represents a promising alternative strategy for the treatment of brain ischemia.

Lineage-specific evolution of Aquibium, a close relative of Mesorhizobium, during habitat adaptation.

The novel genus Aquibium that lacks nitrogenase was recently reclassified from the Mesorhizobium genus. The genomes of Aquibium species isolated from water were smaller and had higher GC contents than those of Mesorhizobium species. Six Mesorhizobium species lacking nitrogenase were found to exhibit low similarity in the average nucleotide identity values to the other 24 Mesorhizobium species. Therefore, they were classified as the non-N2-fixing Mesorhizobium lineage (N-ML), an evolutionary intermediate species. The results of our phylogenomic analyses and the loss of Rhizobiales-specific fur/mur indicated that Mesorhizobium species may have evolved from Aquibium species through an ecological transition. Halotolerant and alkali-resistant Aquibium and Mesorhizobium microcysteis belonging to N-ML possessed many tripartite ATP-independent periplasmic transporter and sodium/proton antiporter subunits composed of seven genes (mrpABCDEFG). These genes were not present in the N2-fixing Mesorhizobium lineage (ML), suggesting that genes acquired for adaptation to highly saline and alkaline environments were lost during the evolution of ML as the habitat changed to soil. Land-to-water habitat changes in Aquibium species, close relatives of Mesorhizobium species, could have influenced their genomic evolution by the gain and loss of genes. Our study indicated that lineage-specific evolution could have played a significant role in shaping their genome architecture and conferring their ability to thrive in different habitats.IMPORTANCEPhylogenetic analyses revealed that the Aquibium lineage (AL) and non-N2-fixing Mesorhizobium lineage (N-ML) were monophyletically grouped into distinct clusters separate from the N2-fixing Mesorhizobium lineage (ML). The N-ML, an evolutionary intermediate species having characteristics of both ancestral and descendant species, could provide a genomic snapshot of the genetic changes that occur during adaptation. Genomic analyses of AL, N-ML, and ML revealed that changes in the levels of genes related to transporters, chemotaxis, and nitrogen fixation likely reflect adaptations to different environmental conditions. Our study sheds light on the complex and dynamic nature of the evolution of rhizobia in response to changes in their environment and highlights the crucial role of genomic analysis in understanding these processes.

Systemic Treatment with Fas-Blocking Peptide Attenuates Apoptosis in Brain Ischemia.

Apoptosis plays a crucial role in neuronal injury, with substantial evidence implicating Fas-mediated cell death as a key factor in ischemic strokes. To address this, inhibition of Fas-signaling has emerged as a promising strategy in preventing neuronal cell death and alleviating brain ischemia. However, the challenge of overcoming the blood-brain barrier (BBB) hampers the effective delivery of therapeutic drugs to the central nervous system (CNS). In this study, we employed a 30 amino acid-long leptin peptide to facilitate BBB penetration. By conjugating the leptin peptide with a Fas-blocking peptide (FBP) using polyethylene glycol (PEG), we achieved specific accumulation in the Fas-expressing infarction region of the brain following systemic administration. Notably, administration in leptin receptor-deficient db/db mice demonstrated that leptin facilitated the delivery of FBP peptide. We found that the systemic administration of leptin-PEG-FBP effectively inhibited Fas-mediated apoptosis in the ischemic region, resulting in a significant reduction of neuronal cell death, decreased infarct volumes, and accelerated recovery. Importantly, neither leptin nor PEG-FBP influenced apoptotic signaling in brain ischemia. Here, we demonstrate that the systemic delivery of leptin-PEG-FBP presents a promising and viable strategy for treating cerebral ischemic stroke. Our approach not only highlights the therapeutic potential but also emphasizes the importance of overcoming BBB challenges to advance treatments for neurological disorders.