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Abstract Macro‐encapsulation systems for delivery of cellular therapeutics in diabetes treatment offer major advantages such as device retrievability and high cell packing density. However, microtissue aggregation and absence of vasculature have been implicated in the inadequate transfer of nutrients and oxygen to the transplanted cellular grafts. Herein, we develop a hydrogel‐based macrodevice to encapsulate therapeutic microtissues positioned in homogeneous spatial distribution to mitigate their aggregation while concurrently supporting an organized intra‐device network of vascular‐inductive cells. Termed Waffle‐inspired Interlocking Macro‐encapsulation (WIM) device, this platform comprises two modules with complementary topography features that fit together in a lock‐and‐key configuration. The waffle‐inspired grid‐like micropattern of the “lock” component effectively entraps insulin‐secreting microtissues in controlled locations while the interlocking design places them in a co‐planar spatial arrangement with close proximity to vascular‐inductive cells. The WIM device co‐laden with INS‐1E microtissues and human umbilical vascular endothelial cells (HUVECs) maintains desirable cellular viability in vitro with the encapsulated microtissues retaining their glucose‐responsive insulin secretion while embedded HUVECs express pro‐angiogenic markers. Furthermore, a subcutaneously implanted alginate‐coated WIM device encapsulating primary rat islets achieves blood glucose control for 2 weeks in chemically induced diabetic mice. Overall, this macrodevice design lays foundation for a cell delivery platform, which has the potential to facilitate nutrients and oxygen transport to therapeutic grafts and thereby might lead to improved disease management outcome.

Background and Aim: Reproductive disorders in swine herds pose significant challenges to pig breeding due to both infectious and non-infectious factors. In large-scale pig farming, coinfections are increasingly common, affecting sow health and herd productivity. This study aimed to determine occurrence and coinfection patterns of Mycoplasma suis and porcine circovirus type 3 in Vietnamese pig farms and to evaluate their association with reproductive disorders and clinical signs in affected herds. Materials and Methods: We collected 291 samples from 15 farms, composed of whole blood and various tissues from fetuses and weak-born piglets. Molecular biological testing was conducted to detect key pathogens of interest. Consistently, porcine circovirus type 3 (PCV3) and porcine Hemoplasma were detected and sequenced for the whole genome and partial 16S rRNA, respectively. The genetic diversity of PCV3 and Mycoplasma suis was analyzed. Results: Various clinical signs, including abortion, stillborn, mummified, and weak-born piglets, and dermatitis, were recorded. M. suis was detected in 252/291 (86.59%) samples from all 15 surveyed farms, with an occurrence of 100%. PCV3 was detected in 35.05% (102/291) samples and 73.3% (11/15) of farms. PCV3 and M. suis coinfections were observed in 29.21% of the positive samples. It should be noted that most PCV3 Ct-values were above 30, indicating the existence of PCV3 in the herd but with insufficient data to confirm its pathogenic potential. The complete genomes of 10 PCV3 strains identified in this study exhibited high sequence homology, with >97% nucleotide identity. In addition, the eight partial 16S rRNA porcine Hemoplasma sequences shared absolute identity with M. suis isolates from pigs in China and Germany. Conclusion: This report on the occurrence of M. suis and PCV3 in pigs from farms with reproductive failure provides important insights into the expanding global distribution of these pathogens. Our findings warrant further investigations of the pathogenic potential and economic implications of M. suis and PCV3 in pigs with reproductive failure in Vietnam.

Reproductive disorders in sows pose significant economic challenges to the swine industry worldwide. In this study, we investigated the presence of porcine circovirus type 3 (PCV3) and Mycoplasma suis (M. suis) in cases of reproductive failure at a breeding sow farm in Vietnam. PCR and RT-PCR assays were performed to detect related pathogens on samples collected from sows with reproductive disorders, and phylogenetic analysis was conducted to characterize the PCV3 strains. Additionally, the incidence and shedding patterns of PCV3 were assessed. Results revealed a high frequency of PCV3 and M. suis infections in sows with reproductive disorders (54.5% and 45.4% respectively), while other pathogens were not detected. Phylogenetic analysis showed that the PCV3 strains belonged to the PCV3b subtype. The findings suggest that PCV3 may play a significant role in causing reproductive problems in sows and highlight the potential impact of early PCV3 infection on piglets during later production stages.

The graphene oxide-silver nanocomposites (AgNPs@GO) have attracted much attention due to their targeted effect and nontoxicity against normal cells. The toxic factors, including the chemical reagents during the synthesis of AgNPs@GO, must be considered and minimized for the cancer treatment application. This study aims to apply the response surface methodology (RSM) with central composite design (CCD) for investigating independent factors, including mass ratio Ag+/GO, temperature, and reaction time, to find the optimal conditions for graphene oxide-silver nanocomposite (AgNPs@GO) synthesis. The green tea leaves extract was used as an alternative reducing agent for the green synthesis of AgNPs@GO. The maximum absorption wavelength of AgNPs, highly dependent on silver nanoparticles' size and shape, was utilized as the target function. The results show optimal conditions for the green synthesis of AgNPs@GO with the mass ratio of Ag+/GO is 2:1 at 30 °C for 40 minutes. The average maximum absorption wavelength of the synthesized AgNPs@GO at the optimal condition of 416.78 nm, with silver nanoparticles on the GO sheet having an average size of 21.2 ± 5.61 nm, the round shape and distributed on the GO sheets uniformly, without aggregation. In addition, the synthesized AgNPs@GO was against HepG2, MDA231, and MDA453, with the IC₅₀ of 152.582, 152.428, and 199.844 μg/mL, respectively.

The Improvac® vaccine has been shown to improve growth performance, meat quality, and sexual behavior in swine herds in several countries. This study initially investigated the ability of this vaccine to control sex hormones and the development of reproductive organs in Vietnamese crossbred pigs (Yorkshire – Landrace x Duroc). A total of 45 male piglets were randomly divided into three groups: vaccinated at 12 and 18 weeks old, surgically castrated males at 7 days old, and entire males. Meanwhile, 40 female piglets were randomly assigned to one of two groups: those vaccinated at 12 and 16 weeks of age or entire females. Serum from experimental pigs was collected monthly before and after vaccination until slaughter (25 weeks of age). At the time of slaughter, reproductive organs were obtained to assess changes at the macroscopic and microscopic features. Anti-GnRH antibodies in the immunized male and female pigs increased dramatically and remained for several weeks following a booster shot, while serum levels of sex hormones were significantly lower than in the entire group (P

Human breastmilk is an invaluable nutritional and pharmacological resource with a highly diverse metabolite profile, which can directly affect the metabolism of infants. Application of metabolomics can discriminate the complex relationship between such nutrients and infant health. As the most common biological fluid in metabolomic study, infant urinary metabolomics may provide the physiological impacts of different nutritional resources, namely human breastmilk and formulated milk. In this study, we aimed to identify possible differences in the urine metabolome of 30 infants (1–14 days after birth) fed with breast milk (n = 15) or formulated milk (n = 15). From metabolomic analysis with gas chromatography-mass spectrometry, 163 metabolites from single mass spectrometry (GC-MS), and 383 metabolites from tandem mass spectrometry (GC-MS/MS) were confirmed in urinary samples. Various multivariate statistical analysis were performed to discriminate the differences originating from physiological/nutritional variables, including human breastmilk/formulate milk feeding, sex, and duration of feeding. Both unsupervised and supervised discriminant analyses indicated that feeding resources (human breastmilk/formulated milk) gave marginal but significant differences in urinary metabolomes, while other factors (sex, duration of feeding) did not show notable discrimination between groups. According to the biomarker analyses, several organic acid and amino acids showed statistically significant differences between different feeding resources, such as 2-hydroxyhippurate.

Metal-organic frameworks (MOFs) are promising materials for a myriad of applications because of their easy synthesis and large variability through the organic linker. For open-environment applications, the organic content can, however, give rise to fouling, that is, biofilm formation. Biofilms can destroy the MOF and reduce the sorption capacity. Therefore, it is necessary to formulate MOFs for open-environment application to avoid the growth of microorganisms. Chitosan is a polysaccharide biopolymer, obtained from chitin shells of shrimps by alkaline deacetylation, and has known fungistatic properties. Here, chitosan is used as a matrix for MOF@chitosan composites with different aluminum-based MOFs to implement the fungistatic effect of chitosan to MOFs. The obtained composites with the highest possible MOF loadings of up to 90% were tested according to DIN EN ISO 846 to examine the fungistatic material properties against the fungi Chaetomium globosum and Aspergillus falconensis.

Quantum error correction (QEC) for generic errors is challenging due to the demanding threshold and resource requirements. Interestingly, when physical noise is biased, we can tailor our QEC schemes to the noise to improve performance. Here we study a family of codes having XZZX-type stabilizer generators, including a set of cyclic codes generalized from the five-qubit code and a set of topological codes that we call generalized toric codes (GTCs). We show that these XZZX codes are highly qubit efficient if tailored to biased noise. To characterize the code performance, we use the notion of effective distance, which generalizes code distance to the case of biased noise and constitutes a proxy for the logical failure rate. We find that the XZZX codes can achieve a favorable resource scaling by this metric under biased noise. We also show that the XZZX codes have remarkably high thresholds that reach what is achievable by random codes, and furthermore they can be efficiently decoded using matching decoders. Finally, by adding only one flag qubit, the XZZX codes can realize fault-tolerant QEC while preserving their large effective distance. In combination, our results show that tailored XZZX codes give a resource-efficient scheme for fault-tolerant QEC against biased noise.

Introduction: Antithrombotic agents are the basic therapeutic option for patients with arterial thrombosis who underwent percutaneous coronary intervention (PCI). In Bangladesh, aspirin and clopidogrel are frequently prescribed as antithrombotics or platelet inhibitors. Studies reported the genetic polymorphisms of CYP2C19*2, CYP2C19*17, and ITGB3 cause an alteration of the pharmacodynamic and pharmacokinetic profile of aspirin and clopidogrel. Therefore, we aimed to assess the prevalence of CYP2C19*2, CYP2C19*17, and ITGB3 polymorphisms among Bangladeshi patients with cardiovascular disease (CVD) who underwent PCI. Methods: Here we assessed a total of 1,000 CVD patients (male 782 and female 218) who underwent PCI and were treated with clopidogrel and/or aspirin. We performed genotyping of patients treated with clopidogrel and aspirin by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) methods. The PCR products of clopidogrel-treated patients were screened with agarose gel electrophoresis and then digested with SmaI and NsiI-HF for CYP2C19*2 and CYP2C19*17, respectively. We genotyped aspirin-treated patients with T-ARMS-PCR for missense rs5918 (PlA1/A1) polymorphism of the ITGB3 gene. Then we ran the digested PCR products on 2% agarose gel electrophoresis to detect the mentioned polymorphisms. Results: Among the clopidogrel-treated patients, we observed 64.1% polymorphism (hetero + mutant) of CYP2C19*2 (loss-of-function allele) and 22.7% (hetero + mutant) of CYP2C19*17 (gain-of-function allele). On the other hand, among the aspirin-treated patients, polymorphisms of ITGB3 were 84.1% homozygous (PlA1/A1), 15.6% heterozygous (PlA1/A2), and 0.3% mutant homozygous. Conclusion: In the present study, we observed a high prevalence of genetic polymorphisms of CYP2C19 and ITGB3 genes. Therefore, we recommend genotyping of CVD patients before prescribing clopidogrel or aspirin to prevent coagulation. Based on the genotyping study, the adjustment of doses or alternative generics might require to avoid therapeutic failure or toxicity in some cases.

June Hong Ahn, Jin Hong Chung, Kyeong-Cheol Shin, Eun Young Choi, Hyun Jung Jin, Mi Suk Lee, Mi Jeong Nam, Kwan Ho Lee Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Yeungnam University, Daegu, South KoreaCorrespondence: Kwan Ho LeeDivision of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, 170 Hyunchung-Ro, Nam-Gu, Daegu 42415, South KoreaEmail ghlee@med.yu.ac.krObjective: Chronic obstructive pulmonary disease (COPD) acute exacerbations are significant causes of morbidity and mortality. “Frequent exacerbator” phenotypes are considered a distinct subgroup and this phenotype has a negative effect on lung function, quality of life, activity, hospital admission, and mortality. We assess inhaler handling technique and adherence, and evaluate risk factors associated with frequent exacerbations in COPD patients.Methods: This study was a cross-sectional, case-control study. We prospectively enrolled 189 COPD patients from Yeungnam University Hospital from January 2018 to November 2018. Subjects were tested regarding their inhaler technique in face-to-face interviews with an advanced practice nurse of inhaler upon study entry. Frequency of moderate to severe COPD exacerbations were reviewed via electronic medical records during 12 months prior to study entry. Frequent exacerbations were defined as ≥2 moderate to severe exacerbations in the prior 12 months. Multivariate logistic regression was performed to identify risk factors for frequent exacerbations.Results: Among 189 COPD patients, 50 (26.5%) were frequent exacerbators. Based on univariate analyses, body mass index (BMI) < 25 kg/m2, lower forced expiratory volume in 1 s (FEV1), higher mMRC, lower feeling of satisfaction with the inhaler, and any critical errors were potential risk factors for frequent exacerbations. Multivariate logistic regression analyses revealed that BMI < 25 kg/m2 (OR, 2.855, 95% CI, 1.247–6.534; p=0.013), higher mMRC (OR, 1.625, 95% CI, 1.072–2.463; p=0.022), and any critical error (OR, 2.020, 95% CI, 1.021–3.999; p=0.044) were risk factors.Conclusion: Any critical error, BMI < 25 kg/m2 and high mMRC are independent risk factors for frequent exacerbations in COPD patients. Careful monitoring and education around inhaler devices, particularly in frequent exacerbators, are important components of COPD treatment.Keywords: COPD, inhalation therapy, drug use error, disease exacerbation

Jong Geol Jang,1 Jee Seon Kim,2 Jin Hong Chung,1 Kyeong Cheol Shin,1 June Hong Ahn,1 Mi Sook Lee,3 So Hee Bang,3 Da Yeong Park,3 Mee Jung Nam,3 Hyun Jung Jin,1,* Kwan Ho Lee1,* 1Division of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University Medical Center, College of Medicine, Daegu, Republic of Korea; 2Department of Internal Medicine, Semyeong Christianity Hospital, Pohang, Republic of Korea; 3Department of Education and Management Services, Yeungnam University Medical Center,College of Medicine, Daegu, Republic of Korea*These authors contributed equally to this workCorrespondence: Hyun Jung JinDivision of Pulmonology and Allergy, Department of Internal Medicine, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 42415, Republic of KoreaTel +82-53-640-6578Fax +82-53-640-6449Email jhj0619@yu.ac.krBackground: Despite the increasing prevalence of chronic obstructive pulmonary disease (COPD) worldwide, knowledge and awareness of COPD remain extremely low. This prospective study aimed to demonstrate the effectiveness of organized educational intervention.Patients and methods: The study participants included patients diagnosed with COPD and receiving inhaler treatment. In this prospective study, the patients made three sequential visits to the hospital (baseline, 1 month, 3 months). On their first and second visits, patients received systematic education about COPD. On their first and third visits, each patient was evaluated using a COPD Assessment Test, COPD Knowledge Questionnaire, Hospital Anxiety and Depression Scale, and Rosenberg Self-Esteem Scale.Results: Fifty-five participants were enrolled in the study. The mean COPD knowledge score before and after education was 12.51±3.19 and 17.89±1.37, respectively, indicating a significant increase in the score post-education (P

Human breast milk (HBM) contains many bioactive components that protect infants from various microorganisms. Pattern recognition receptors on phagocytic cells recognize microbial pathogens and promote the innate immune system. This study aimed to evaluate the effect of HBM on the expression of pattern recognition receptors and innate cytokines in the monocytic cell line THP-1 and the phagocytic activity of RAW264.7 macrophages. Expression levels of specific mRNAs in THP-1 cells were quantitated using reverse transcription-polymerase chain reaction. Phagocytic activity was measured by fluorescence microscopy to detect the uptake of fluorescent dye-labeled carboxylate-modified polystyrene latex beads in RAW264.7 macrophages. HBM stimulated the phagocytic activity of RAW264.7 macrophages. HBM increased mRNA expression of pattern recognition receptors, including the cluster of differentiation 14 and toll-like receptor 2 and 4, and various innate cytokines, including tumor necrosis factor α, interleukin-1β, C-X-C motif chemokine 8, and C-C motif chemokine ligand 2, in THP-1 monocytic cells. Furthermore, milk oligosaccharides in HBM, such as lacto- N -fucopentaose I, enhanced the expression of pattern recognition receptors and various innate cytokines. HBM is able to modulate the innate immune response by upregulating the expression of pattern recognition receptors and various innate cytokines in monocytes/macrophages.

Polycaprolactone (PCL) is a versatile biomaterial with a wide range of medical applications, but its use in blood-contacting devices is hampered due to insufficient hemocompatibility. In this work, electrospun polycaprolactone (PCL) membranes were chemically grafted with conjugated linoleic acid (CLA) to prevent induced blood coagulation. The density of grafted CLA and its effects on the morphology and wettability of the membranes were examined. The study also investigated how the membrane interacted with human whole blood and platelets to determine its antithrombotic properties. As the results suggested, the grafting caused a negligible effect on the physical properties of the membrane but greatly improved its compatibility with blood, showing that the approach can be investigated further for blood-contacting applications.

A dual phase steel has been produced directly from the liquid under conditions that simulate direct strip casting and thin slab casting. The kinetics of polygonal ferrite formation during the inter-critical anneal were quantified using the JMAK approach, and this revealed significantly retarded transformation kinetics in the strip cast samples compared to the commercial steel that was processed through the conventional hot rolling approach. The transformation rate in the strip cast samples were as much as three orders of magnitude slower compared to the commercial steel. It was found that the kinetics of the ferrite formation were retarded principally by the large prior austenite grain size in the strip cast samples, and this hypothesis was tested experimentally by both coarsening of the prior austenite grain size, and by refinement of the prior austenite grain size. However, even after grain size normalization, small differences in transformation kinetics between the direct strip cast and commercial steel specimens were observed. These differences were explained by investigation of MnS precipitation in the steels. It was found that the transformation rate is high when the solutes are in solid solution, and that the rate of transformation slows significantly when precipitation of nano-precipitates occurs.

PURPOSE: To develop Korean Menstrual Symptom Scale (KMSS) for university students and test its reliability and validity. METHODS: The scale was developed by intensive literature review, development of preliminary items, verification of content validity, development of secondary items, verification of construct validity, and extraction of final items. Thirty-nine items were constructed. Data for validity and reliability testing were collected with a questionnaire survey from 391 university students. Data were analyzed with descriptive statistics, factor analysis, and reliability coefficients (Cronbach's α) with the SPSS program. RESULTS: There were 37 final items which were sorted into six factors: ‘negative affection (8 items)’, ‘change of activity level (7 items)’, ‘physical symptom (9 items)’, ‘mood change (9 items)’, ‘change in concentration level (4 items)’, and ‘body water retention (5 items)’. The cumulative percent of variance was 63.3%. Regarding the reliability of the scale, its Cronbach's α was 0.96. Cronbach's α values for these factors ranged from 0.75 to 0.91. CONCLUSION: The KMSS demonstrated acceptable validity and reliability. Repeated research is needed to measure menstrual symptom experienced by women of variable ages.

Microwave heating of Ag+ in polyvinyl alcohol (PVA) is an effective method to synthesize silver nanoparticles (AgNPs), a broad-range antibacterial agent. However, the microwave may cause PVA solution to dry out and degrade. This study is aimed at investigating the effect of microwave irradiation on different concentrations of PVA in PVA/Ag+ solution in short periods of exposure. Fourier-transform infrared (FTIR) spectroscopy was employed to evaluate chemical changes of samples with different exposure times and PVA concentration. The results confirm the redox reaction of Ag+ with PVA. In addition, Ag+ reduces the rate of hydrolysis of PVA, and the ether bridges are limited by the spatial structure.

Abstract Background The rice roots are highly salt-sensitive organ and primary root growth is rapidly suppressed by salt stress. Sucrose nonfermenting 1-related protein kinase2 (SnRK2) family is one of the key regulator of hyper-osmotic stress signalling in various plant cells. To understand early salt response of rice roots and identify SnRK2 signaling components, proteome changes of transgenic rice roots over-expressing OSRK1, a rice SnRK2 kinase were investigated. Results Proteomes were analyzed by two-dimensional electrophoresis and protein spots were identified by LC-MS/MS from wild type and OSRK1 transgenic rice roots exposed to 150 mM NaCl for either 3 h or 7 h. Fifty two early salt -responsive protein spots were identified from wild type rice roots. The major up-regulated proteins were enzymes related to energy regulation, amino acid metabolism, methylglyoxal detoxification, redox regulation and protein turnover. It is noted that enzymes known to be involved in GA-induced root growth such as fructose bisphosphate aldolase and methylmalonate semialdehyde dehydrogenase were clearly down-regulated. In contrast to wild type rice roots, only a few proteins were changed by salt stress in OSRK1 transgenic rice roots. A comparative quantitative analysis of the proteome level indicated that forty three early salt-responsive proteins were magnified in transgenic rice roots at unstressed condition. These proteins contain single or multiple potential SnRK2 recognition motives. In vitro kinase assay revealed that one of the identified proteome, calreticulin is a good substrate of OSRK1. Conclusions Our present data implicate that rice roots rapidly changed broad spectrum of energy metabolism upon challenging salt stress, and suppression of GA signaling by salt stress may be responsible for the rapid arrest of root growth and development. The broad spectrum of functional categories of proteins affected by over-expression of OSRK1 indicates that OSRK1 is an upstream regulator of stress signaling in rice roots. Enzymes involved in glycolysis, branched amino acid catabolism, dnaK-type molecular chaperone, calcium binding protein, Sal T and glyoxalase are potential targets of OSRK1 in rice roots under salt stress that need to be further investigated.

Abstract Background To investigate the molecular and cellular pathogenesis underlying myocarditis, we used an experimental autoimmune myocarditis (EAM)-induced heart failure rat model that represents T cell mediated postinflammatory heart disorders. Results By performing unbiased 2-dimensional electrophoresis of protein extracts from control rat heart tissues and EAM rat heart tissues, followed by nano-HPLC-ESI-QIT-MS, 67 proteins were identified from 71 spots that exhibited significantly altered expression levels. The majority of up-regulated proteins were confidently associated with unfolded protein responses (UPR), while the majority of down-regulated proteins were involved with the generation of precursor metabolites and energy metabolism in mitochondria. Although there was no difference in AKT signaling between EAM rat heart tissues and control rat heart tissues, the amounts and activities of extracellular signal-regulated kinase (ERK)-1/2 and ribosomal protein S6 (rpS6) were significantly increased. By comparing our data with the previously reported myocardial proteome of the Coxsackie viruses of group B (CVB)-mediated myocarditis model, we found that UPR-related proteins were commonly up-regulated in two murine myocarditis models. Even though only two out of 29 down-regulated proteins in EAM rat heart tissues were also dysregulated in CVB-infected rat heart tissues, other proteins known to be involved with the generation of precursor metabolites and energy metabolism in mitochondria were also dysregulated in CVB-mediated myocarditis rat heart tissues, suggesting that impairment of mitochondrial functions may be a common underlying mechanism of the two murine myocarditis models. Conclusions UPR, ERK-1/2 and S6RP signaling were activated in both EAM- and CVB-induced myocarditis murine models. Thus, the conserved components of signaling pathways in two murine models of acute myocarditis could be targets for developing new therapeutic drugs or methods aimed at treating enigmatic myocarditis.