Incidence of Tuberculosis Among Immigrants in Korea Who Participated in a Latent Tuberculosis Infection Screening Program.

BACKGROUND: With a rapid decrease in tuberculosis (TB) incidence, the significance of latent tuberculosis infection (LTBI) has been underscored in South Korea. Although South Korea does not have a high proportion of immigrants compared to other countries, there is a growing argument that it should actively embrace immigrants as a solution to address issues of low birth rates and population aging. This study aimed to assess TB incidence among immigrants who participated a pilot LTBI screening program in South Korea. METHODS: Records of immigrants participated in a pilot LTBI screening program in South Korea between 2018 and 2019 were linked with Korean National TB Surveillance System to determine TB development. Participants underwent interferon-gamma release assay (IGRA) and chest X-rays. Standardized incidence ratios (SIRs) stratified by age, country of origin's TB burden was calculated with a reference group of general South Korean population. RESULTS: Of a total of 9,517 participants, 14 TB cases were identified. Participants with positive IGRA results who did not initiate LTBI treatment showed TB incidence of 312.5 per 100,000 person-years, whereas those with negative results showed TB incidence of 34.4 per 100,000 person-years, resulting in an incidence rate ratio of 9.08 (95% confidence interval [CI], 2.50-32.99). SIR of TB among total participants including those with negative IGRA results was 2.60 (95% CI, 1.54-4.38; P < 0.001), whereas SIR among those with positive IGRA results was 5.86 (95% CI, 3.15-10.89; P < 0.001). In the calculation of SIR among participants with positive IGRA results, those aged under 35 from high TB-burden countries or intermediate TB-burden countries showed a high SIR (18.08; 95% CI, 2.55-128.37; P = 0.004), and 11.30 (95% CI, 2.82-45.16; P < 0.001), respectively). Contrary to previous reports that suggest the majority of elderly population with a positive IGRA result were due to remote infection and had a lower TB risk compared to younger ages, SIR among those aged 65 or over from intermediate TB-burden countries was 6.15 (95% CI, 0.87-43.69; P = 0.069), which was comparable to that in younger participants aged between 35 and 49 (SIR, 4.87; 95% CI, 1.22-19.49; P = 0.025) or those aged between 50 and 64 (SIR, 4.62; 95% CI, 1.73-12.31; P = 0.002). CONCLUSION: Young immigrants with positive IGRA results from countries with high or intermediate TB burden showed a relatively high TB risk compared to a general South Korea population. In addition, unexpected high TB risk was observed among elderly immigrants with positive IGRA results. In establishing future policies for LTBI in immigrants in South Korea, screenings should primarily focus on younger age group (who aged under 35). Additionally, further research is needed on the high TB risk observed in elderly immigrants.

A unified computational view of DNA duplex, triplex, quadruplex and their donor-acceptor interactions.

DNA can assume various structures as a result of interactions at atomic and molecular levels (e.g., hydrogen bonds, π-π stacking interactions, and electrostatic potentials), so understanding of the consequences of these interactions could guide development of ways to produce elaborate programmable DNA for applications in bio- and nanotechnology. We conducted advanced ab initio calculations to investigate nucleobase model structures by componentizing their donor-acceptor interactions. By unifying computational conditions, we compared the independent interactions of DNA duplexes, triplexes, and quadruplexes, which led us to evaluate a stability trend among Watson-Crick and Hoogsteen base pairing, stacking, and even ion binding. For a realistic solution-like environment, the influence of water molecules was carefully considered, and the potassium-ion preference of G-quadruplex was first analyzed at an ab initio level by considering both base-base and ion-water interactions. We devised new structure factors including hydrogen bond length, glycosidic vector angle, and twist angle, which were highly effective for comparison between computationally-predicted and experimentally-determined structures; we clarified the function of phosphate backbone during nucleobase ordering. The simulated tendency of net interaction energies agreed well with that of real world, and this agreement validates the potential of ab initio study to guide programming of complicated DNA constructs.

Comparison of the standardized incidence ratio of tuberculosis among workers at medical and educational institutions: a nationwide LTBI observational cohort study.

BACKGROUND: The objective of this study was to determine the incidence of tuberculosis (TB) among workers at medical institutions based on interferon-gamma release assay (IGRA) and compare it with that of workers at educational institutions and the general population. METHODS: From March 2017 to December 2020, we used a cohort of workers from medical and educational institutions in Korea, who underwent IGRA as part of a national screening program for latent tuberculosis infection (LTBI). After connecting to the National Health Insurance Service (NHIS) database to detect for any actual cases of active TB, we estimated standardized incidence ratio (SIR) and the expected number of cases to compare the incidence of TB with that of the general population. RESULTS: Significant disparities in TB incidence were revealed among workers in medical and educational institutions, based on IGRA results, age, and occupation. Individuals positive for IGRA in medical institutions displayed substantially higher SIR for TB, 7.19 (6.15-8.41), compared to counterparts in educational institutions, 3.69 (3.02-4.51). Comparing by age group, we see that the SIRs are higher in younger age groups compared to older ones, with 37.30 (28.11-49.50) and 11.89 (7.28-19.41) for IGRA-positive medical and education workers under 30 years of age, respectively. In the results by occupation within the medical institutions, nurses had the highest SIR at 14.17 (11.14-18.04). CONCLUSIONS: Healthcare workers in medical institutions are more likely to develop actual TB after a positive result of LTBI screening in Korea. Intensive management and surveillance programs should be reinforced.

ELAVL2 loss promotes aggressive mesenchymal transition in glioblastoma.

Glioblastoma (GBM), the most lethal primary brain cancer, exhibits intratumoral heterogeneity and molecular plasticity, posing challenges for effective treatment. Despite this, the regulatory mechanisms underlying such plasticity, particularly mesenchymal (MES) transition, remain poorly understood. In this study, we elucidate the role of the RNA-binding protein ELAVL2 in regulating aggressive MES transformation in GBM. We found that ELAVL2 is most frequently deleted in GBM compared to other cancers and associated with distinct clinical and molecular features. Transcriptomic analysis revealed that ELAVL2-mediated alterations correspond to specific GBM subtype signatures. Notably, ELAVL2 expression negatively correlated with epithelial-to-mesenchymal transition (EMT)-related genes, and its loss promoted MES process and chemo-resistance in GBM cells, whereas ELAVL2 overexpression exerted the opposite effect. Further investigation via tissue microarray analysis demonstrated that high ELAVL2 protein expression confers a favorable survival outcome in GBM patients. Mechanistically, ELAVL2 was shown to directly bind to the transcripts of EMT-inhibitory molecules, SH3GL3 and DNM3, modulating their mRNA stability, potentially through an m6A-dependent mechanism. In summary, our findings identify ELAVL2 as a critical tumor suppressor and mRNA stabilizer that regulates MES transition in GBM, underscoring its role in transcriptomic plasticity and glioma progression.

Moisture-Induced Degradation of Quantum-Sized Semiconductor Nanocrystals through Amorphous Intermediates.

Elucidating the water-induced degradation mechanism of quantum-sized semiconductor nanocrystals is an important prerequisite for their practical application because they are vulnerable to moisture compared to their bulk counterparts. In-situ liquid-phase transmission electron microscopy is a desired method for studying nanocrystal degradation, and it has recently gained technical advancement. Herein, the moisture-induced degradation of semiconductor nanocrystals is investigated using graphene double-liquid-layer cells that can control the initiation of reactions. Crystalline and noncrystalline domains of quantum-sized CdS nanorods are clearly distinguished during their decomposition with atomic-scale imaging capability of the developed liquid cells. The results reveal that the decomposition process is mediated by the involvement of the amorphous-phase formation, which is different from conventional nanocrystal etching. The reaction can proceed without the electron beam, suggesting that the amorphous-phase-mediated decomposition is induced by water. Our study discloses unexplored aspects of moisture-induced deformation pathways of semiconductor nanocrystals, involving amorphous intermediates.

Noncovalent minimal assembly of exogenous histamine with hemin cofactor as a peroxidase-mimicking cooperative catalyst.

By mimicking the synergistic interplay of primary and secondary coordination spheres within native peroxidases, we demonstrate a scaffold-free, yet highly effective molecular-level cooperation between an iron(III)-containing hemin cofactor and exogenous histamine in accelerating a peroxidase-like reaction. Density functional theory computations predict that, among structurally similar molecules, the histamine is the most interactive partner of hemin to elicit a spontaneous peroxidation by electrostatically attracting the proton of hydrogen peroxide to its own imidazole and thermodynamically stabilizing a transition-state intermediate. Although the molecular weight of hemin-histamine pair is 763, 1.7% of the horseradish peroxidase, cooperative catalysis of two natural molecules exhibits 17.3 times greater catalytic efficiency (17.93 M-1s-1) and 57.8 times larger specific activity (36.45 µmol/min·mg) than the hemin alone (1.04 M-1s-1 and 0.63 µmol/min·mg). Despite no scaffold or covalent linkage, the self-assembly with hemin is highly histamine-specific in complex environments, leading rapid color changes by substrate oxidation within 10 s.

Chain flexibility of medicinal lipids determines their selective partitioning into lipid droplets.

In guiding lipid droplets (LDs) to serve as storage vessels that insulate high-value lipophilic compounds in cells, we demonstrate that chain flexibility of lipids determines their selective migration in intracellular LDs. Focusing on commercially important medicinal lipids with biogenetic similarity but structural dissimilarity, we computationally and experimentally validate that LD remodeling should be differentiated between overproduction of structurally flexible squalene and that of rigid zeaxanthin and ß-carotene. In molecular dynamics simulations, worm-like flexible squalene is readily deformed to move through intertwined chains of triacylglycerols in the LD core, whereas rod-like rigid zeaxanthin is trapped on the LD surface due to a high free energy barrier in diffusion. By designing yeast cells with either much larger LDs or with a greater number of LDs, we observe that intracellular storage of squalene significantly increases with LD volume expansion, but that of zeaxanthin and ß-carotene is enhanced through LD surface broadening; as visually evidenced, the outcomes represent internal penetration of squalene and surface localization of zeaxanthin and ß-carotene. Our study shows the computational and experimental validation of selective lipid migration into a phase-separated organelle and reveals LD dynamics and functionalization.

Metabolite trafficking enables membrane-impermeable-terpene secretion by yeast.

Metabolites are often unable to permeate cell membranes and are thus accumulated inside cells. We investigate whether engineered microbes can exclusively secrete intracellular metabolites because sustainable metabolite secretion holds a great potential for mass-production of high-value chemicals in an efficient and continuous manner. In this study, we demonstrate a synthetic pathway for a metabolite trafficking system that enables lipophilic terpene secretion by yeast cells. When metabolite-binding proteins are tagged with signal peptides, metabolite trafficking is highly achievable; loaded metabolites can be precisely delivered to a desired location within or outside the cell. As a proof of concept, we systematically couple a terpene-binding protein with an export signal peptide and subsequently demonstrate efficient, yet selective terpene secretion by yeast (~225 mg/L for squalene and ~1.6 mg/L for ß-carotene). Other carrier proteins can also be readily fused with desired signal peptides, thereby tailoring different metabolite trafficking pathways in different microbes. To the best of our knowledge, this is the most efficient cognate pathway for metabolite secretion by microorganisms.

Ultrahigh-resolution full-color perovskite nanocrystal patterning for ultrathin skin-attachable displays.

High-definition red/green/blue (RGB) pixels and deformable form factors are essential for the next-generation advanced displays. Here, we present ultrahigh-resolution full-color perovskite nanocrystal (PeNC) patterning for ultrathin wearable displays. Double-layer transfer printing of the PeNC and organic charge transport layers is developed, which prevents internal cracking of the PeNC film during the transfer printing process. This results in RGB pixelated PeNC patterns of 2550 pixels per inch (PPI) and monochromic patterns of 33,000 line pairs per inch with 100% transfer yield. The perovskite light-emitting diodes (PeLEDs) with transfer-printed active layers exhibit outstanding electroluminescence characteristics with remarkable external quantum efficiencies (15.3, 14.8, and 2.5% for red, green, and blue, respectively), which are high compared to the printed PeLEDs reported to date. Furthermore, double-layer transfer printing enables the fabrication of ultrathin multicolor PeLEDs that can operate on curvilinear surfaces, including human skin, under various mechanical deformations. These results highlight that PeLEDs are promising for high-definition full-color wearable displays.

Contrast-enhanced ultrasonography for the evaluation of liver fibrosis after biliary obstruction.

AIM: To investigate perfusion change in contrast-enhanced ultrasonography (CEUS) to evaluate liver fibrosis based on biliary obstruction using an animal model. METHODS: New Zealand white rabbits (3-4 kg) underwent bile duct ligation to form a biliary obstruction model. We performed liver CEUS and laboratory tests on the day before the operation (day 0) and every 7 postoperative days until the rabbits were sacrificed. After CEUS, signal intensity of liver parenchyma with a time-intensity curve was analyzed. Perfusion parameters were automatically calculated from region-of-interests, including peak signal intensity, mean transit time, area under the curve and time to peak. Histological grades of liver fibrosis were assessed according to the Metavir score system immediately after sacrifice. Generalized estimating equations were used to analyze the association between liver fibrosis grades and perfusion parameters for statistical analysis. The perfusion parameters were measured on the last day and the difference between day 0 and the last day were evaluated. RESULTS: From the nine rabbits, histological grades of liver fibrosis were grade 1 in one rabbit, grade 2 and 3 in three rabbits each, and grade 4 in two rabbits. Among the four CEUS parameters, only the peak signal intensity measured on the last day demonstrated a significant association with liver fibrosis grades (OR = 1.392, 95%CI: 1.114-1.741, P = 0.004). The difference in peak signal intensity between day 0 and the last day also demonstrated an association with liver fibrosis (OR = 1.191, 95%CI: 0.999-1.419, P = 0.051). The other parameters tested, including mean transit time, area under the curve, and time to peak, showed no significant correlation with liver fibrosis grades. CONCLUSION: This animal study demonstrates that CEUS can be used to evaluate liver fibrosis from biliary obstruction using peak signal intensity as a parameter.