Disruption of G-quadruplex dynamicity by BRCA2 abrogation instigates phase separation and break-induced replication at telomeres.

Dynamic interaction between BRCA2 and telomeric G-quadruplexes (G4) is crucial for maintaining telomere replication homeostasis. Cells lacking BRCA2 display telomeric damage with a subset of these cells bypassing senescence to initiate break-induced replication (BIR) for telomere synthesis. Here we show that the abnormal stabilization of telomeric G4 following BRCA2 depletion leads to telomeric repeat-containing RNA (TERRA)-R-loop accumulation, triggering liquid-liquid phase separation (LLPS) and the assembly of Alternative Lengthening of Telomeres (ALT)-associated promyelocytic leukemia (PML) bodies (APBs). Disruption of R-loops abolishes LLPS and impairs telomere synthesis. Artificial engineering of telomeric LLPS restores telomere synthesis, underscoring the critical role of LLPS in ALT. TERRA-R-loops also recruit Polycomb Repressive Complex 2 (PRC2), leading to tri-methylation of Lys27 on histone H3 (H3K27me3) at telomeres. Half of paraffin-embedded tissue sections from human breast cancers exhibit APBs and telomere length heterogeneity, suggesting that BRCA2 mutations can predispose individuals to ALT-type tumorigenesis. Overall, BRCA2 abrogation disrupts the dynamicity of telomeric G4, producing TERRA-R-loops, finally leading to the assembly of telomeric liquid condensates crucial for ALT. We propose that modulating the dynamicity of telomeric G4 and targeting TERRA-R-loops in telomeric LLPS maintenance may represent effective therapeutic strategies for treating ALT-like cancers with APBs, including those with BRCA2 disruptions.

Establishment of a patient-specific avatar organoid model derived from endoscopic ultrasonography-guided fine needle biopsy for timely clinical application in pancreatic ductal adenocarcinoma.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma (PDAC) has the worst survival rate among tumors. At the time of diagnosis, more than 80% of PDACs are considered to be surgically unresectable, and there is an unmet need for treatment options in these inoperable PDACs. This study aimed to establish a patient-derived organoid (PDO) platform from endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) collected at diagnosis and to determine its clinical applicability for the timely treatment of unresectable PDAC. METHODS: Patients with suspected PDAC were prospectively enrolled at the Samsung Medical Center from 2015 to 2019. PDAC tissues were acquired by means of EUS-FNB to establish PDAC PDOs, which were comprehensively analyzed for histology, genomic sequencing, and high-throughput screening (HTS) drug sensitivity test. RESULTS: PDAC PDOs were established with a success rate of 83.2% (94/113). It took approximately 3 weeks from acquiring minimal EUS-FNB specimens to generating sufficient PDAC PDOs for the simultaneous HTS drug sensitivity test and genomic sequencing. The high concordance between PDAC tissues and matched PDOs was confirmed, and whole-exome sequencing revealed the increased detection of genetic alterations in PDOs compared with EUS-FNB tissues. The HTS drug sensitivity test showed clinical correlation between the ex vivo PDO response and the actual chemotherapeutic response of the study patients in the real world (13 out of 15 cases). In addition, whole-transcriptome sequencing identified candidate genes associated with nab-paclitaxel resistance, such as ITGB7, ANPEP, and ST3GAL1. CONCLUSIONS: This PDAC PDO platform allows several therapeutic drugs to be tested within a short time window and opens the possibility for timely personalized medicine as a "patient avatar model" in clinical practice.

Use of a combined antibacterial synergy approach and the ANNOgesic tool to identify novel targets within the gene networks of multidrug-resistant Klebsiella pneumoniae.

Since the 1980s, the development of new drug classes for the treatment of multidrug-resistant Klebsiella pneumoniae has become limited, highlighting the urgent need for novel antibiotics. To address this challenge, this study aimed to explore the synergistic interactions between chemical compounds and representative antibiotics, such as carbapenem and colistin. The primary objective of this study was not only to mitigate the adverse impact of multidrug-resistant K. pneumoniae on public health but also to establish a sustainable balance among humans, animals, and the environment. Phenotypical measurements were conducted using the broth microdilution technique to determine the drug sensitivity of bacterial strains. Additionally, a genotypical approach was employed, involving traditional RNA sequencing analysis to identify differentially expressed genes and the computational ANNOgesic tool to detect noncoding RNAs. This study revealed the existence of various pathways and regulatory RNA elements that form a functional network. These pathways, characterized by the expression of specific genes, contribute to the combined treatment effect and bacterial survival strategies. The connections between pathways are facilitated by regulatory RNA elements that respond to environmental changes. These findings suggest an adaptive response of bacteria to harsh environmental conditions.IMPORTANCENoncoding RNAs were identified as key players in post-transcriptional regulation. Moreover, this study predicted the presence of novel small regulatory RNAs that interact with target genes, as well as the involvement of riboswitches and RNA thermometers in conjunction with associated genes. These findings will contribute to the discovery of potential antimicrobial therapeutic candidates. Overall, this study offers valuable insights into the synergistic effects of chemical compounds and antibiotics, highlighting the role of regulatory RNA elements in bacterial response, and survival strategies. The identification of novel noncoding RNAs and their interactions with target genes, riboswitches, and RNA thermometers holds promise for the development of antimicrobial therapies.

Quantitative and qualitative mutational impact of ionizing radiation on normal cells.

The comprehensive genomic impact of ionizing radiation (IR), a carcinogen, on healthy somatic cells remains unclear. Using large-scale whole-genome sequencing (WGS) of clones expanded from irradiated murine and human single cells, we revealed that IR induces a characteristic spectrum of short insertions or deletions (indels) and structural variations (SVs), including balanced inversions, translocations, composite SVs (deletion-insertion, deletion-inversion, and deletion-translocation composites), and complex genomic rearrangements (CGRs), including chromoplexy, chromothripsis, and SV by breakage-fusion-bridge cycles. Our findings suggest that 1 Gy IR exposure causes an average of 2.33 mutational events per Gb genome, comprising 2.15 indels, 0.17 SVs, and 0.01 CGRs, despite a high level of inter-cellular stochasticity. The mutational burden was dependent on total irradiation dose, regardless of dose rate or cell type. The findings were further validated in IR-induced secondary cancers and single cells without clonalization. Overall, our study highlights a comprehensive and clear picture of IR effects on normal mammalian genomes.

Revealing the Substrate Constraint Effect on the Thermodynamic Behaviour of the Pd-H through Capacitive-Based Hydrogen-Sorption Measurement.

Mechanical constraints imposed on the Pd-H system can induce significant strain upon hydrogenation-induced expansion, potentially leading to changes in the thermodynamic behavior, such as the phase-transition pressure. However, the investigation of the constraint effect is often tricky due to the lack of simple experimental techniques for measuring hydrogenation-induced expansion. In this study, a capacitive-based measurement system is developed to monitor hydrogenation-induced areal expansion, which allows us to control and evaluate the magnitude of the substrate constraint. By using the measurement technique, the influence of substrate constraint intensity on the thermodynamic behavior of the Pd-H system is investigated. Through experiments with different constraint intensities, it is found that the diffefrence in the constraint intensity minimally affects the phase-transition pressure when the Pd-H system allows the release of constraint stress through plastic deformation. These experiments can improve the understanding of the substrate constraint behaviours of Pd-H systems allowing plastic deformation while demonstrating the potential of capacitive-based measurement systems to study the mechanical-thermodynamic coupling of M-H systems.

Effectiveness of breath acetone monitoring in reducing body fat and improving body composition: a randomized controlled study.

When attempts to lose body fat mass frequently fail, breath acetone (BA) monitoring may assist fat mass loss during a low-carbohydrate diet as it can provide real-time body fat oxidation levels. This randomized controlled study aimed to evaluate the effectiveness of monitoring BA levels and providing feedback on fat oxidation during a three-week low-carbohydrate diet intervention. Forty-seven participants (mean age = 27.8 ± 4.4 years, 53.3% females, body mass index = 24.1 ± 3.4 kg m-2) were randomly assigned to three groups (1:1:1 ratio): daily BA assessment with a low-carbohydrate diet, body weight assessment (body scale (BS)) with a low-carbohydrate diet, and low-carbohydrate diet only. Primary outcome was the change in fat mass and secondary outcomes were the changes in body weight and body composition. Forty-five participants completed the study (compliance rate: 95.7%). Fat mass was significantly reduced in all three groups (allP< 0.05); however, the greatest reduction in fat mass was observed in the BA group compared to the BS (differences in changes in fat mass, -1.1 kg; 95% confidence interval: -2.3, -0.2;P= 0.040) and control (differences in changes in fat mass, -1.3 kg; 95% confidence interval: -2.1, -0.4;P= 0.013) groups. The BA group showed significantly greater reductions in body weight and visceral fat mass than the BS and control groups (allP< 0.05). In addition, the percent body fat and skeletal muscle mass were significantly reduced in both BA and BS groups (allP< 0.05). However, no significant differences were found in changes in body fat percentage and skeletal muscle mass between the study groups. Monitoring BA levels, which could have motivated participants to adhere more closely to the low-carbohydrate diet, to assess body fat oxidation rates may be an effective intervention for reducing body fat mass (compared to body weight assessment or control conditions). This approach could be beneficial for individuals seeking to manage body fat and prevent obesity.

Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. METHODS: The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. RESULTS: The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10-3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. CONCLUSIONS: Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.

Trends and Meta-Analysis of Research on the Operation of Programs for Bereaved Families in South Korea.

Purpose: This study aimed to analyze interventions for bereaved families and evaluate their effectiveness, with the ultimate goal of supporting evidence-based nursing for bereaved families. Methods: Research trends were identified based on a search of domestic databases from January 2000 to December 2022, and a meta-analysis was conducted on interventions for bereaved families. Forty-five papers were selected, and information was extracted on participants, research design, and interventions. A meta-analysis of seven papers was performed, and the effect size was calculated. Results: Fourteen papers dealt with interventions for middle-aged women who had lost their spouses, 20 used qualitative research methods, and 20 were on art therapy programs. Thirty studies had fewer than 10 participants, and most interventions had 60~120 minutes per session and 9~16 sessions in total. There were seven randomized controlled trials, and all studies included in the quality evaluation showed a low risk of bias. Four papers measured grief as an outcome, and the effect size was -1.9577 (95% CI -2.9206 to -0.9947), indicating that the treatment significantly decreased grief (P<0.001). Six papers measured depression as an outcome, and the effect size was -1.6775 (95% CI -2.1835 to -1.1716), showing that the treatment significantly decreased depression (P<0.001). Conclusion: Intervention programs for bereaved families were shown to be effective in relieving grief and depression. However, programs should be developed that target middle-aged men who have lost their spouses and children who have lost their parents. Randomized controlled trials should also be conducted on interventions to reduce grief and depression.

The Lived Self-Care Experiences of Patients Undergoing Long-Term Haemodialysis: A Phenomenological Study.

The study aims to understand the lived self-care experiences of patients who have undergone long-term haemodialysis. The study adopts a qualitative phenomenological design. Data were collected for six months, from 1 July to 31 December 2020. Out of 90 outpatients in a haemodialysis clinic at a university hospital in Seoul, Korea, 11 patients who had received haemodialysis for more than 10 years were purposefully selected, and 9 of them took part in in-depth interviews. The main research question was, 'What was the experience of surviving long-term haemodialysis?' The study revealed four main themes surrounding the topic of self-care: (A) the desire to keep living despite challenges, (B) creating one's own dietary principles, (C) moving one's body with the remaining strength, and (D) moving toward independence. In the long-term self-care of haemodialysis patients, they shared personal observations on their disease and treatment process and their struggles to try to manage their own physical and emotional self-care. By exploring the experience of long-term haemodialysis, it is possible to gain a deeper understanding of their perceptions, emotions, and motivations. With this information, healthcare professionals can develop interventions and support strategies that are tailored to the specific needs of haemodialysis patients.

Factors Affecting Inpatients' Mortality through Intentional Self-Harm at In-Hospitals in South Korea.

This study aimed to identify the patient characteristics, comorbidities, risk factors, and means of the self-harm of patients who attempt self-harm in and outside of a hospital, and to determine the characteristics of death by suicide among survival and death patient groups in South Korea. This study used data from the Korean National Hospital Discharge In-depth Injury Survey conducted from 2007 to 2019. In total, 7192 outpatient participants and 43 inpatient participants performed self-harm. Frequency analysis, chi-square tests, Fisher's exact test, and logistic regression analysis were performed using STATA, version 15.0 (StataCorp), and statistical significance was set at 5%. Thirty-one inpatients who performed self-harm survived, and 12 died. Among male inpatients, the older they were, the higher the rates of self-harm and mortality rates due to falls and poisoning if they had comorbidities and financial problems. In addition, the rate of self-harm attempts within a short period after hospitalization was high. Our evidence of the characteristics of patients who performed self-harm in the hospital and the influencing factors of self-harm can be used as primary data for predicting patients at a high risk of self-harm and for creating preventative policies to reduce the risk of self-harm among inpatients in South Korea.

Projections from LIM homeobox 6 (Lhx6) + zona incerta neurons to the cholinergic or monoaminergic nuclei of the rat.

A recent report suggested that LIM homeobox 6 (Lhx6) + GABA-releasing neurons of the ventral zona incerta (VZI) promote sleep, particularly paradoxical sleep (PS). While their potential involvement in sleep still needs to be firmly confirmed, little is known about their specific input/output connections with widespread brain regions, including those involved in sleep. Thus, the present study was designed to examine whether Lhx6-expressing neurons (in parallel to intermingled MCH-expressing ones) may send efferent projections to cholinergic and/or monoaminergic nuclei from basal forebrain (BF) to brainstem (BS). Based on the present observations, the proportions of Lhx6+ neuronal projection to the BF and BS cholinergic nuclei over the total number of Lhx6+ VZI cells were approximately 5.9% and 6.9%, respectively. Likewise, the proportions of Lhx6+ neuronal projection to the dorsal raphe and locus coeruleus over the total number of Lhx6+ VZI cells were about 4.3% and 3.9%, respectively. In addition, Lhx6+ cells projecting to the cholinergic or monoaminergic nuclei were scattered along the entire dorsal-to-ventral extent of the VZI. Based on the present as well as our previous observations, it is suggested that Lhx6+ VZI neurons might play an important role in the regulation of PS, partly via the neural network involving the cholinergic as well as monoaminergic nuclei of the rat.

Flow Characteristics of the Conjugate of Anti-CD3 Monoclonal Antibodies and Magnetic Nanoparticle in PBS and Blood Vessels.

Previously, anti-CD3 antibodies delivered intravenously have been known for their negative side effects. The experimental conditions for optimal liquid production are derived from the Fc-directed conjugation of anti-CD3 foralumab antibodies and magnetic nanoparticles (Ab-MNPs). The anti-CD3 antibodies are prepared for conjugation with MNPs using SiteClick antibody labelling kits. The successful conjugation of the Ab-MNPs is confirmed using a transmission electron microscopy (TEM) image and an energy dispersive spectroscopy (EDS) analysis. The average values ​​of the moving speed of MNPs and Ab-MNPs in phosphate buffer saline (PBS) were + 3.16 pix/frame and + 6.70 pix/frame in the x-axis, respectively. This implies that MNPs with CD3 antibodies attached to the surface through biocompatible ligand functional groups has better fluidity in PBS. Afterwards, a non-clinical animal testing for the flow characteristics of Ab-MNPs inside a blood vessel is carried out to observe the effects of Ab-MNP delivery through intravenous injection.

Characterization of Domestication Loci Associated with Awn Development in Rice.

Rice (Oryza sativa L.) is a widely studied domesticated model plant. Seed awning is an unfavorable trait during rice harvesting and processing. Hence, loss of awn was one of the target characters selected during domestication. However, the genetic mechanisms underlying awn development in rice are not well understood. In this study, we analyzed and characterized the genes for awn development using a mapping population derived from a cross between the Korean indica cultivar 'Milyang23' and a near-isogenic line NIL4/9 derived from a cross between 'Hwaseong' and Oryza minuta. Two quantitative trait loci (QTLs), qAwn4 and qAwn9, mapped on chromosomes 4 and 9, respectively, increased awn length in an additive manner. Through comparative sequencing analyses of the parental lines, LABA1 was determined as the causal gene underlying qAwn4. qAwn9 was mapped to a 199-kb physical region between markers RM24663 and RM24679. Within this interval, 27 annotated genes were identified, and five genes, including a basic leucine zipper transcription factor 76 (OsbZIP76), were considered as candidate genes for qAwn9 based on their functional annotations and sequence variations. Haplotype analysis using the candidate gene revealed tropical-japonica specific sequence variants in the qAwn9 region, which partly explains the non-detection of qAwn9 in previous studies that used progenies from interspecific crosses. This provides further evidence that OsbZIP76 is possibly a causal gene for qAwn9. The O. minuta qAwn9 allele was identified as a major QTL, providing an important molecular target for understanding the genetic control of awn development in rice. Our results lay the foundation for further cloning of the awn gene underlying qAwn9.

Brassinosteroid biosynthesis gene OsD2 is associated with low-temperature germinability in rice.

In rice, low-temperature germinability (LTG) is essential for stable stand establishment using the direct seeding method in temperate and high-altitude areas. Previously, we reported that the quantitative trait locus qLTG1 is associated with LTG. qLTG1 is also associated with tolerance to several abiotic stresses, such as salt and osmotic conditions. In this study, map-based cloning and sequence analysis indicated that qLTG1 is allelic to DWARF2 (OsD2), which encodes cytochrome P450 D2 (LOC_Os01g10040) involved in brassinosteroid (BR) biosynthesis. Sequence comparison of the two parental lines, Hwaseong and Oryza rufipogon (IRGC 105491), revealed five single nucleotide polymorphisms (SNPs) in the coding region. Three of these SNPs led to missense mutations in OsD2, whereas the other two SNPs were synonymous. We evaluated two T-DNA insertion mutants, viz., overexpression (OsD2-OE) and knockdown (OsD2-KD) mutants of OsD2, with the Dongjin genetic background. OsD2-KD plants showed a decrease in LTG and grain size. In contrast, OsD2-OE plants showed an increase in grain size and LTG. We also examined the expression levels of several BR signaling and biosynthetic genes using the T-DNA insertion mutants. Gene expression analysis and BR application experiments demonstrated that BR enhanced the seed germination rate under low-temperature conditions. These results suggest that OsD2 is associated with the regulation of LTG and improving grain size. Thus, OsD2 may be a suitable target for rice breeding programs to improve rice yield and LTG.

Interaction of starch branching enzyme 3 and granule-bound starch synthase 1 alleles increases amylose content and alters physico-chemical properties in japonica rice (Oryza sativa L.).

Four near-isogenic lines (NILs) with different allele combinations of the starch branching enzyme 3 (SBE3) and granule-bound starch synthase 1 (GBSS1) were developed by crossing the japonica rice cultivars "Dodamssal" and "Hwayeong." The associations between sequence variations in SBE3 and GBSS1, and starch-related traits were investigated. These sequence variations led to changes in seed morphology, starch structure, starch crystallinity, amylopectin chain length distribution, digestibility, apparent amylose content (AAC), and resistant starch content (RS). SBE3 and GBSS1 showed genetic interaction in regulating AAC and RS. Gene expression profiling of panicle tissues revealed significant differences in expression levels of GBSS1, SBE3, and other starch-related genes among the four NILs, indicating that variations in GBSS1 and SBE3 changed the expression level of starch-related genes. These variations contributed to the changes observed in AAC, RS, and physico-chemical characteristics of the rice starch from the NILs.

Dynamic interaction of BRCA2 with telomeric G-quadruplexes underlies telomere replication homeostasis.

BRCA2-deficient cells precipitate telomere shortening upon collapse of stalled replication forks. Here, we report that the dynamic interaction between BRCA2 and telomeric G-quadruplex (G4), the non-canonical four-stranded secondary structure, underlies telomere replication homeostasis. We find that the OB-folds of BRCA2 binds to telomeric G4, which can be an obstacle during replication. We further demonstrate that BRCA2 associates with G-triplex (G3)-derived intermediates, which are likely to form during direct interconversion between parallel and non-parallel G4. Intriguingly, BRCA2 binding to G3 intermediates promoted RAD51 recruitment to the telomere G4. Furthermore, MRE11 resected G4-telomere, which was inhibited by BRCA2. Pathogenic mutations at the OB-folds abrogated the binding with telomere G4, indicating that the way BRCA2 associates with telomere is innate to its tumor suppressor activity. Collectively, we propose that BRCA2 binding to telomeric G4 remodels it and allows RAD51-mediated restart of the G4-driven replication fork stalling, simultaneously preventing MRE11-mediated breakdown of telomere.

Physicochemical analysis of non-fermented probiotic milk with probiotic Lactobacillus plantarum Ln1 isolated from Korea traditional fermented food.

The objective of this study was to develop a non-fermented probiotic milk that maintains its physicochemical properties, microbial properties, antioxidant activity, and sensory properties during storage (0, 7, and 14 days). During storage, pH and viable cell counts decreased; however, titratable acidity increased. In addition, the composition and sensory characteristics of the non-fermented probiotic milk showed no significant differences between samples (MLN; milk with Lactobacillus plantarum Ln1, MGG; milk with Lactobacillus rhamnosus GG, and milk control). The antioxidant activities of MLN determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, ABTS+ radical scavenging, and reducing power assay were higher during the examined storage periods when compared with those of the other samples. Overall, the physicochemical properties, microbial properties, and sensory factors of MLN showed no significant differences. However, high antioxidant activity was observed. Thus, we present a new functional dairy product with antioxidant activity.

Mesenchymal Stem Cells Potentiate the Vasculogenic Capacity of Endothelial Colony-Forming Cells under Hyperglycemic Conditions.

Many studies have demonstrated a reduced number and vasculogenic capacity of endothelial colony-forming cells (ECFCs) in diabetic patients. However, whether the vasculogenic capacity of ECFCs is recovered or not when combined with pericyte precursors, mesenchymal stem cells (MSCs), under hyperglycemic conditions has not been studied. Thus, we investigated the role of MSCs in ECFC-mediated vascular formation under high-glucose conditions. The ECFCs and MSCs were treated with normal glucose (5 mM; NG) or high glucose (30 mM; HG) for 7 days. The cell viability, proliferation, migration, and tube formation of ECFCs were reduced in HG compared to NG. Interestingly, the ECFC+MSC combination after HG treatment formed tubular structures similar to NG-treated ECFCs+MSCs. An in vivo study using a diabetic mouse model revealed that the number of perfused vessels formed by HG-treated ECFCs+MSCs in diabetic mice was comparable with that of NG-treated ECFCs+MSCs in normal mice. Electron microscopy revealed that the ECFCs+MSCs formed pericyte-covered perfused blood vessels, while the ECFCs alone did not form perfused vessels when injected into the mice. Taken together, MSCs potentiate the vasculogenic capacity of ECFCs under hyperglycemic conditions, suggesting that the combined delivery of ECFCs+MSCs can be a promising strategy to build a functional microvascular network to repair vascular defects in diabetic ischemic regions.

Highly Sensitive and Selective Detection of Hydrogen Using Pd-Coated SnO2 Nanorod Arrays for Breath-Analyzer Applications.

We report a breath hydrogen analyzer based on Pd-coated SnO2 nanorods (Pd-SnO2 NRs) sensor integrated into a miniaturized gas chromatography (GC) column. The device can measure a wide range of hydrogen (1-100 ppm), within 100 s, using a small volume of human breath (1 mL) without pre-concentration. Especially, the mini-GC integrated with Pd-SnO2 NRs can detect 1 ppm of H2, as a lower detection limit, at a low operating temperature of 152 °C. Furthermore, when the breath hydrogen analyzer was exposed to a mixture of interfering gases, such as carbon dioxide, nitrogen, methane, and acetone, it was found to be capable of selectively detecting only H2. We found that the Pd-SnO2 NRs were superior to other semiconducting metal oxides that lack selectivity in H2 detection. Our study reveals that the Pd-SnO2 NRs integrated into the mini-GC device can be utilized in breath hydrogen analyzers to rapidly and accurately detect hydrogen due to its high selectivity and sensitivity.

Correction: Characterization of Brassica rapa metallothionein and phytochelatin synthase genes potentially involved in heavy metal detoxification.

[This corrects the article DOI: 10.1371/journal.pone.0252899.].