Orthohantaviruses, etiological agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a critical public health threat worldwide. Hantaan orthohantavirus ...(HTNV) outbreaks are particularly endemic in Gyeonggi Province in northern area of the Republic of Korea (ROK). Small mammals were collected from three regions in the Gyeonggi Province during 2017 and 2018. Serological and molecular prevalence of HTNV was 25/201 (12.4%) and 10/25 (40%), respectively. A novel nanopore‐based diagnostic assay using a cost‐efficient Flongle chip was developed to rapidly and sensitively detect HTNV infection in rodent specimens within 3 h. A rapid phylogeographical surveillance of HTNV at high‐resolution phylogeny was established using the amplicon‐based Flongle sequencing. In total, seven whole‐genome sequences of HTNV were newly obtained from wild rodents collected in Paju‐si (Gaekhyeon‐ri) and Yeoncheon‐gun (Hyeonga‐ri and Wangnim‐ri), Gyeonggi Province. Phylogenetic analyses revealed well‐supported evolutionary divergence and genetic diversity, enhancing the resolution of the phylogeographic map of orthohantaviruses in the ROK. Incongruences in phylogenetic patterns were identified among HTNV tripartite genomes, suggesting differential evolution for each segment. These findings provide crucial insights into on‐site diagnostics, genome‐based surveillance, and the evolutionary dynamics of orthohantaviruses to mitigate hantaviral outbreaks in HFRS‐endemic areas in the ROK.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
To utilize human heat energy as a permanent power source, we demonstrate, for the first time, an intrinsically highly foldable and stretchable thermoelectric generator that is based upon chemically ...exfoliated 1T-transition metal dichalcogenide (TMDC) nanosheets (NSs) for self-powered wearable electronics. The power factors of WS sub(2) (n-type) and NbSe sub(2) (p-type) NS films were evaluated to be 5-7 mu K super(-2) m super(-1) and 26-34 mu W K super(-2) m super(-1), respectively, near room temperature. With these films, parallel-connected thermoelectric generators that were fabricated were able to constantly produce up to 38 nW of output power at Delta 60 K. The thermoelectric device stably sustained its performance, even after 100 bending cycles and after 100 stretching cycles (50% strain). By direct observation, we found that the film is highly stretched by partial tearing and folding but still maintains an electrical percolation pathway. The morphology then is quickly recovered by a plug-in contact between the torn parts as the external strain is released. Finally, we demonstrate the electric power generation from a prototype wearable thermoelectric generator that was woven into a wristband fitted on a real human body.
Heme, a porphyrin ring complexed with iron, is a metalloprosthetic group of numerous proteins involved in diverse metabolic and respiratory processes across all domains of life, and is thus ...considered essential for respiring organisms. Several microbial groups are known to lack the de novo heme biosynthetic pathway and therefore require exogenous heme from the environment. These heme auxotroph groups are largely limited to pathogens, symbionts, or microorganisms living in nutrient-replete conditions, whereas the complete absence of heme biosynthesis is extremely rare in free-living organisms. Here, we show that the acI lineage, a predominant and ubiquitous free-living bacterial group in freshwater habitats, is auxotrophic for heme, based on the experimental or genomic evidence. We found that two recently cultivated acI isolates require exogenous heme for their growth. One of the cultured acI isolates also exhibited auxotrophy for riboflavin. According to whole-genome analyses, all (
= 20) isolated acI strains lacked essential enzymes necessary for heme biosynthesis, indicating that heme auxotrophy is a conserved trait in this lineage. Analyses of >24,000 representative genomes for species clusters of the Genome Taxonomy Database revealed that heme auxotrophy is widespread across abundant but not-yet-cultivated microbial groups, including
,
(SAR406),
(OM1), and Marine groups IIb and III of
Our findings indicate that heme auxotrophy is a more common phenomenon than previously thought, and may lead to use of heme as a growth factor to increase the cultured microbial diversity.
The purpose of this study is to identify the crack initiation and damage stress thresholds of granite from the Korea atomic energy research institute’s Underground Research Tunnel (KURT). From this, ...a quantitative damage evolution was inferred using various methods, including the crack volumetric strain,
b
value, the damage parameter from the moment tensor, and the acoustic emission (AE) energy. Uniaxial compression tests were conducted, during which both the stress–strain and AE activity were recorded simultaneously. The crack initiation threshold was found at a stress level of 0.42–0.53
σ
c
, and the crack damage threshold was identified at 0.62–0.84
σ
c
. The normalized integrity of KURT granite was inferred at each stress level from the damage parameter by assuming that the damage is accumulated beyond the crack initiation stress threshold. The maximum deviation between the crack volumetric strain and the AE method was 16.0 %, which was noted at a stress level of 0.84
σ
c
. The damage parameters of KURT granite derived from a mechanically measured stress–strain relationship (crack volumetric strain) were successfully related and compared to those derived from physically detected acoustic emission waves. From a comprehensive comparison of damage identification and quantification methods, it was finally suggested that damage estimations using the AE energy method are preferred from the perspectives of practical field applicability and the reliability of the obtained damage values.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The demands for higher energy density of rechargeable batteries have been continuously increasing recently, and cationic redox based current cathodes have little scope to further increase energy ...density since they already exhibit near‐theoretical specific capacities. In this regard, oxygen redox (OR) reactions have emerged as a promising breakthrough for sodium‐ion battery (SIB) cathodes. Most OR‐based layered oxides suffer from drastic hysteretic‐oxygen capacities upon discharging after the first charging. In contrast, stable and nonhysteretic oxygen capacities are herein enabled via Al3+ incorporation into Li‐excess Na layered oxide (NLMO). By combining experimental work and first‐principles calculations, it is found that there is an additional stable phase during the oxygen redox for Al incorporated NLMO in comparison with bare NLMO, which is a critical factor in extending and stabilizing the discharge capacity in thermodynamics. In addition, the additional redox‐inactive Al3+ leads to heterogeneous oxygen redox rather than homogeneous, which results in stabilization of the oxide framework with sensitively control of the oxygen participation upon cycling.
The substitution of Al3+ in a Li‐excess Na layered oxide enables stable and nonhysteretic oxygen capacities. The presence of an additional stable phase during the oxygen redox is a critical factor in extending and stabilizing the discharge capacity. In addition, redox‐inactive Al3+ causes heterogeneous oxygen redox, which stabilizes the oxide framework under sensitively controlled oxygen participation upon cycling.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Paramyxoviruses, negative-sense single-stranded RNA viruses, pose a critical threat to human public health. Currently, 78 species, 17 genera, and 4 subfamilies of paramyxoviruses are harbored by ...multiple natural reservoirs, including rodents, bats, birds, reptiles, and fish. Henipaviruses are critical zoonotic pathogens that cause severe acute respiratory distress and neurological diseases in humans. Using reverse transcription-polymerase chain reaction, 115
species individuals were examined for the prevalence of paramyxovirus infections. Paramyxovirus RNA was observed in 26 (22.6%) shrews collected at five trapping sites, Republic of Korea. Herein, we report two genetically distinct novel paramyxoviruses (genus:
): Gamak virus (GAKV) and Daeryong virus (DARV) isolated from
and
, respectively. Two GAKVs and one DARV were nearly completely sequenced using next-generation sequencing. GAKV and DARV contain six genes (3'-N-P-M-F-G-L-5') with genome sizes of 18,460 nucleotides and 19,471 nucleotides, respectively. The phylogenetic inference demonstrated that GAKV and DARV form independent genetic lineages of
in
species. GAKV-infected human lung epithelial cells elicited the induction of type I/III interferons, interferon-stimulated genes, and proinflammatory cytokines. In conclusion, this study contributes further understandings of the molecular prevalence, genetic characteristics and diversity, and zoonotic potential of novel paramyxoviruses in shrews.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by chronic pelvic pain related to the bladder with no effective treatment options.
To evaluate the efficacy ...and safety of transurethral resection (TUR) and transurethral coagulation (TUC) as treatments for Hunner lesion (HL) in IC/BPS.
A single-center, prospective, randomized controlled trial involving 126 patients with HL in IC/BPS.
TUR or TUC.
Primary outcome was recurrence-free time after surgery. Secondary outcomes included change of the number of frequency, nocturia, urgency episodes in voiding diaries, O’Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Interstitial Cystitis Problem Index (ICPI), pelvic pain and urgency/frequency (PUF) symptom scale, and visual analog scale (VAS) for pain and risk factors for recurrence.
There were no differences in the recurrence-free time between treatment groups, a difference of 12.2 mo (95% confidence interval CI, 11.1–17.6) for TUR, and a difference of 11.5 mo (95% CI, 9.03–16.1; p=0.735) for TUC. No difference was found in decreased mean daytime frequency, nocturia, urgency episodes, ICSI, ICPI, PUF symptom scale, and VAS for pain between both groups over 12 mo. Regardless of treatment types, there were significant improvements in all symptom questionnaires and pain compared with baseline (all, p < 0.05). Treatment type (TUR or TUC), age, sex, previous history of hydrodistension, and number of HLs did not affect recurrence. Incidence of bladder injury was higher in the TUR group (7.9%) than in the TUC group (3.4%).
There was no difference in the recurrence-free time and effect on urinary symptoms, including pain between TUC and TUR, for HL. Taking into account procedure-related complications, the surgeon can choose the method with which he/she is most familiar and comfortable.
In patients with bladder pain syndrome with Hunner lesions, both endoscopic resection and coagulation of the lesions are effective treatments.
In interstitial cystitis/bladder pain syndrome patients with Hunner lesion, either transurethral resection (TUR) or transurethral coagulation (TUC) of Hunner lesion is a definite treatment in terms of symptom improvement and quality of life. However, TUR of Hunner lesion is not superior in recurrence-free time to TUC, but may have a higher chance to develop bladder injury. Therefore, surgeons prefer a surgical method that they are familiar with, but less experienced surgeons may use TUC to reduce surgical complications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Fabry disease is an X-linked lysosomal storage disease caused by a mutation in the galactosidase alpha (GLA) gene. Despite advances in therapeutic technologies, the lack of humanized experimental ...models of Fabry disease has limited the development of new therapies to cure the disease. Herein, we modeled Fabry disease using human inducible pluripotent stem cell (iPSC)-derived kidney organoids and the CRISPR-Cas9 genome-editing system. GLA-mutant human kidney organoids revealed deformed podocytes and tubular cells with accumulation of globotriaosylceramide (Gb3). Ultrastructural analysis showed abundant electron-dense granular deposits and electron-dense lamellate lipid-like deposits that formed concentric bodies (zebra bodies) in the cytoplasm of podocytes and tubules. The oxidative stress level was increased in GLA-mutant kidney organoids, and the increase was accompanied by apoptosis. Enzyme replacement treatment (ERT) with recombinant human α-Gal A decreased the Gb3 accumulation and oxidative stress, which resulted in amelioration of the deformed cellular structure of the GLA-mutant kidney organoids. Transcription profile analyses showed decreased glutathione (GSH) metabolism in GLA-mutant kidney organoids. GSH replacement treatment decreased oxidative stress and attenuated the structural deformity of the GLA-mutant kidney organoids. GSH treatment also increased the expression of podocyte and tubular markers and decreased apoptosis. In conclusion, GLA-mutant kidney organoids derived from human iPSCs are valuable tools for studying the mechanisms and developing novel therapeutic alternatives for Fabry disease.
Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality ...and morbidity, effective antiviral therapeutics or vaccines for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK).
We collected small mammals on Jeju Island during 2018-2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mice harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analyses identified a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence.
Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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