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The gamma-ray-induced random mutagenesis of an engineered β-carotene-producing Escherichia coli XL1-Blue resulted in the variant Ajou 45, which exhibits significantly enhanced β-carotene production. The whole-genome sequencing of Ajou 45 identified 55 mutations, notably including a reduction in the copy number of cyaA , encoding adenylate cyclase, a key enzyme regulating intracellular cyclic AMP (cAMP) levels. While the parental XL1-Blue strain harbors two copies of cyaA , Ajou 45 retains only one, potentially leading to reduced intracellular cAMP concentrations. This reduction may alleviate catabolite repression and redirect metabolic flux toward the β-carotene biosynthesis pathway. To validate this mechanistic insight, a targeted cyaA knockout was engineered in XL1-Blue, and its β-carotene production and growth phenotypes were compared with those of Ajou 45 and XL1-Blue. The findings demonstrated that a reduced cyaA copy number substantially enhances β-carotene biosynthesis by modulating cAMP-mediated regulatory networks. This study highlights the efficacy of integrating random mutagenesis with integrative genomic analysis for microbial strain engineering and presents a novel strategy for enhancing carotenoid production in E. coli .

Parrots play a crucial role in the ecosystem by performing various roles, such as consuming the reproductive structures of plants and dispersing plant seeds. However, most are threatened because of habitat loss and commercial trade. Amazon parrots are one of the most traded and illegally traded parrots. Therefore, monitoring their wild populations and global trade is crucial for their conservation. However, monitoring wild populations is becoming more challenging because the manual analysis of large-scale datasets of images obtained from camera trap methods is labor-intensive and time consuming. Monitoring the wildlife trade is difficult because of the large quantities of wildlife trade. Amazon parrots can be difficult to identify because of their morphological similarity. Object detection models have been widely used for automatic and accurate species classification. In this study, to classify 26 Amazon parrot species, 8 Single Shot MultiBox Detector models were assessed. Among the eight models, the DenseNet121 model showed the highest mean average precision at 88.9%. This model classified the 26 Amazon parrot species at 90.7% on average. Continuous improvement of deep learning models classifying Amazon parrots may support monitoring wild populations and the global trade of these species., Competing Interests: The authors declare no conflicts of interest.

Streptococcus pyogenes , or group A Streptococcus (GAS), a gram-positive bacterium, is implicated in a wide range of clinical manifestations and life-threatening diseases. One of the key virulence factors of GAS is streptopain, a C10 family cysteine peptidase. Since its discovery, various homologs of streptopain have been reported from other bacterial species. With the increased affordability of sequencing, a significant increase in the number of potential C10 family-like sequences in the public databases is anticipated, posing a challenge in classifying such sequences. Sequence-similarity-based tools are the methods of choice to identify such streptopain-like sequences. However, these methods depend on some level of sequence similarity between the existing C10 family and the target sequences. Therefore, in this work, we propose a novel predictor, C10Pred, for the prediction of C10 peptidases using sequence-derived optimal features. C10Pred is a support vector machine (SVM) based model which is efficient in predicting C10 enzymes with an overall accuracy of 92.7% and Matthews' correlation coefficient (MCC) value of 0.855 when tested on an independent dataset. We anticipate that C10Pred will serve as a handy tool to classify novel streptopain-like proteins belonging to the C10 family and offer essential information.

For products such as smartphones, the technology gap between companies is gradually narrowing with the advancements in technology. Therefore, product design can be a visible strategy for differentiation. However, it is difficult to apply automated production and defect detection processes to the various designs that are being developed. This study proposes a high-speed circular measurement method for correcting the alignment of round parts, which is difficult in an automated process. For analyzing the performance of the proposed method, its processing speed and accuracy are compared with those of the existing methods. The results of the analysis indicate that the overall performance of the proposed method is better than those of the existing methods.

Alcohol consumption can increase the risk of chronic diseases, such as myocardial infarction, coronary artery disease, hyperlipidemia, and hypertension. We aimed to assess the association between genotype, DNA methylation patterns, alcohol consumption, and chronic diseases in Korean population. We analyzed 8840 subjects for genotypes and 446 for DNA methylation among the 9351 subjects from the Korean Genome and Epidemiology Study (KoGES). We further divided both groups into two sub-groups according to the presence/absence of chronic diseases. We selected genes whose methylation varied significantly with alcohol consumption, and visualized genotype and DNA methylation patterns specific to each group. Genome-wide association study (GWAS) revealed single nucleotide polymorphisms (SNPs) rs2074356 and rs11066280 in HECT domain E3 ubiquitin protein ligase 4 ( HECTD4 ) to be significantly associated with alcohol consumption in both the presence. The rs12229654 genotype also displayed significantly different patterns with alcohol consumption. Furthermore, we retrieved differentially methylated regions (DMRs) from four groups based on sex and chronic diseases and compared them by drinking status. In genotype analysis, cardiovascular diseases (CVDs) showed a higher proportion in drinker than in non-drinker, but not in DMR analysis. Additionally, we analyzed the enriched Gene Ontology terms and Kyoto Gene and Genome Encyclopedia (KEGG) pathways and visualized the network, heatmap, and upset plot. We show that the pattern of DNA methylation associated with CVD is strongly influenced by alcoholism. Overall, this study identified genetic and epigenetic variants influenced by alcohol consumption and chronic diseases.

This study investigated the effects of partial replacement of dietary fat with krill oil (KO) or coconut oil (CO) on dyslipidemia and lipid metabolism in rats fed with a high-fat diet (HFD). Sprague Dawley rats were divided into three groups as follows: HFD, HFD + KO, and HFD + CO. The rats were fed each diet for 10 weeks and then intraperitoneally injected with phosphate-buffered saline (PBS) or lipopolysaccharide (LPS) (1 mg/kg). The KO- and CO-fed rats exhibited lower levels of serum lipids and aspartate aminotransferases than those of the HFD-fed rats. Rats fed with HFD + KO displayed significantly lower hepatic histological scores and hepatic triglyceride (TG) content than rats fed with HFD. The KO supplementation also downregulated the adipogenic gene expression in the liver. When treated with LPS, the HFD + KO and HFD + CO groups reduced the adipocyte size in the epididymal white adipose tissues (EAT) relative to the HFD group. These results suggest that KO and CO could improve lipid metabolism dysfunction.

Chemotherapy response and metastasis prediction play important roles in the treatment of pediatric osteosarcoma, which is prone to metastasis and has a high mortality rate. This study aimed to estimate the prediction model using gene expression and image texture features. 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) images of 52 pediatric osteosarcoma patients were used to estimate the machine learning algorithm. An appropriate algorithm was selected by estimating the machine learning accuracy. 18 F-FDG PET/CT images of 21 patients were selected for prediction model development based on simultaneous KI67 and EZRIN expression. The prediction model for chemotherapy response and metastasis was estimated using area under the curve (AUC) maximum image texture features (AUC_max) and gene expression. The machine learning algorithm with the highest test accuracy in chemotherapy response and metastasis was selected using the random forest algorithm. The chemotherapy response and metastasis test accuracy with image texture features was 0.83 and 0.76, respectively. The highest test accuracy and AUC of chemotherapy response with AUC_max, KI67 , and EZRIN were estimated to be 0.85 and 0.89, respectively. The highest test accuracy and AUC of metastasis with AUC_max, KI67 , and EZRIN were estimated to be 0.85 and 0.8, respectively. The metastasis prediction accuracy increased by 10% using radiogenomics data.

Lingula anatina is a brachiopod widely distributed in the western Pacific region. Even though L. anatina has been targeted for a number of biological studies, there is still limited information on intraspecific genetic variations of L. anatina . In this study, L. anatina specimens were collected from Korea and Vietnam, and complete mitochondrial genome (mitogenome) sequences were analyzed and compared with previous records. The total mitogenomes of L. anatina were 24,875 bp and 25,305 bp in size for Korean and Vietnamese specimens, respectively. Those mitogenomes are extraordinarily longer than the typical mitogenome size for an animal but shorter than the previous record from Yanagawa (Japan) for this species. The gene orders and the sizes of the protein-coding genes are also different from those for the Japanese specimen. Furthermore, the nonsynonymous (Ka) and synonymous (Ks) substitution rates in protein-coding genes (PCGs) were calculated to test the idea of evolutionary rate differences in mitochondrial genomes. The analyses showed relatively low Ka and Ks for the complete mitogenomes from Buan (Korea), Doson (Vietnam) and Yanagawa (Japan). The Ka/Ks ratio was less than 1 in comparisons of three localities, indicating the existence of purifying selection in this species. The phylogenetic analyses showed that L. anatina diverged among localities in the western Pacific region.

Cacatua alba , Cacatua galerita, and Cacatua goffiniana are parrots of the family Cacatuidae. Wild populations of these species are declining with C. alba listed by the International Union for the Conservation of Nature and Natural Resources (IUCN) as Endangered. In this study, complete mitogenomes were sequenced for a comparative analysis among the Cacatua species, and a detailed analysis of the control region. Mitogenome lengths of C. alba, C. galerita, and C. goffiniana were 18,894, 18,900, and 19,084 bp, respectively. They included 13 protein coding genes, two ribosomal RNA genes, 24 transfer RNA genes, three degenerated genes, and two control regions. Ten conserved motifs were found in three domains within each of the two control regions. For an evolution of duplicated control regions of Cacatua , domain I and the 3' end of domain III experienced an independent evolution, while domain II and most of the regions of domain III was subjected to a concerted evolution. Based on a phylogenetic analysis of 37 mitochondrial genes, the genus Cacatua formed a well-supported, monophyletic, crown group within the Cacatuidae. Molecular dating results showed that Cacatua diverged from other genera of Cacatuinae in the middle of Miocene.

The purpose of this study was to apply multicriteria decision making and an analytic hierarchy process (AHP) model for assessing sustainable management of hypertension and diabetes. Perception of two alternative health care priorities was also investigated. One priority was improving treatment compliance of patients with hypertension and diabetes. The other priority was strengthening the healthcare system for continuous care. Our study design to evaluate community-based intervention programs for hypertension and diabetes was developed using brainstorming, Delphi techniques, and content analysis along with literature review. We finally proposed a hierarchical structure of the AHP model with 50 third sub-criteria in six levels. By surveying this AHP questionnaire to a total of 185 community health practitioners in Korea, we found that improving treatment compliance of patients with chronic diseases should be relatively more important than strengthening the healthcare system. Further research is needed to expand survey subjects to primary care physicians and even policymakers of central government for the appropriate application of this AHP model.

Chinese mitten crab (CMC) or Eriocheir sinensis is a strong osmoregulator that can keep rigorous cellular homeostasis. CMC can flourish in freshwater, as well as seawater, habitats and represents the most important species for freshwater aquaculture. Salt stress can have direct effects on several stages (e.g., reproduction, molting, growth, etc.) of the CMC life cycle. To get a better overview of the genes involved in the gills of CMC under different salinity conditions, we conducted an RNA-Seq meta-analysis on the transcriptomes of four publicly available datasets. The meta-analysis identified 405 differentially expressed transcripts (DETs), of which 40% were classified into various transporter classes, including accessory factors and primary active transporters as the major transport classes. A network analysis of the DETs revealed that adaptation to salinity is a highly regulated mechanism in which different functional modules play essential roles. To the best of our knowledge, this study is the first to conduct a transcriptome meta-analysis of gills from crab RNA-Seq datasets under salinity. Additionally, this study is also the first to focus on the differential expression of diverse transporters and channels (transportome) in CMC. Our meta-analysis opens new avenues for a better understanding of the osmoregulation mechanism and the selection of potential transporters associated with salinity change.

Radiotherapy using high linear energy transfer (LET) radiation results in effectively killing tumor cells while minimizing dose (biological effective) to normal tissues to block toxicity. It is well known that high LET radiation leads to lower cell survival per absorbed dose than low LET radiation. High-linear energy transfer (LET) neutron treatment induces autophagy in tumor cells, but its precise mechanisms in osteosarcoma are unknown. Here, we investigated this mechanism and the underlying signaling pathways. Autophagy induction was examined in gamma-ray-treated KHOS/NP and MG63 osteosarcoma cells along with exposure to high-LET neutrons. The relationship between radiosensitivity and autophagy was assessed by plotting the cell surviving fractions against autophagy levels. Neutron treatment increased autophagy rates in irradiated KHOS/NP and MG63 cells; neutrons with high-LETs showed more effective inhibition than those with lower LET gamma-rays. To determine whether the unfolded protein response and Akt-mTOR pathways triggered autophagy, phosphorylated eIF2α and JNK levels, and phospho-Akt, phosphor-mTOR, and phospho-p70S6 levels were, respectively, investigated. High-LET neutron exposure inhibited Akt phosphorylation and increased Beclin 1 expression during the unfolded protein response, thereby enhancing autophagy. The therapeutic efficacy of high-LET neutron radiation was also assessed in vivo using an orthotopic mouse model. Neutron-irradiated mice showed reduced tumor growth without toxicity relative to gamma-ray-treated mice. The effect of high-LET neutron exposure on the expression of signaling proteins LC3, p-elF2a, and p-JNK was investigated by immunohistochemistry. Tumors in high-LET-neutron radiation-treated mice showed higher apoptosis rates, and neutron exposure significantly elevated LC3 expression, and increased p-elF2a and p-JNK expression levels. Overall, these results demonstrate that autophagy is important in radiosensitivity, cell survival, and cellular resistance against high-LET neutron radiation. This correlation between cellular radiosensitivity and autophagy may be used to predict radiosensitivity in osteosarcoma., Competing Interests: The authors declare no conflicts of interest.

Osteosarcoma (OS) originates from osteoid bone tissues and is prone to metastasis, resulting in a high mortality rate. Although several treatments are available for OS, an effective cure does not exist for most patients with advanced OS. Zoledronic acid (ZOL) is a third-generation bisphosphonate that inhibits osteoclast-mediated bone resorption and has shown efficacy in treating bone metastases in patients with various types of solid tumors. Here, we sought to clarify the mechanisms through which ZOL inhibits OS cell proliferation. ZOL treatment inhibited OS cell proliferation, viability, and colony formation. Autophagy inhibition by RNA interference against Beclin-1 or ATG5 inhibited ZOL-induced OS cell death. ZOL induced autophagy by repressing the protein kinase B/mammalian target of rapamycin/p70S6 kinase pathway and extracellular signal-regulated kinase signaling-dependent autophagy in OS cell lines and patient-derived OS cells. Microarrays of miRNA showed that ZOL increased the levels of miR-212-3p, which is known to play an important role in autophagy, in OS in vitro and in vivo systems. Collectively, our data provided mechanistic insight into how increased miR-212-3p through ZOL treatment induces autophagy synergistically in OS cells, providing a preclinical rationale for conducting a broad-scale clinical evaluation of ZOL + miR-212-3p in treating OS.

In a cable-driven parallel robot (CDPR), force sensors are utilized at each winch motor to measure the cable tension in order to obtain the force distribution at the robot end-effector. However, because of the effects of friction in the pulleys and the unmodeled cable properties of the robot, the measured cable tensions are often inaccurate, which causes force-control difficulties. To overcome this issue, this paper presents an artificial neural network (ANN)-based indirect end-effector force-estimation method, and its application to CDPR force control. The pulley friction and other unmodeled effects are considered as black-box uncertainties, and the tension at the end-effector is estimated by compensating for these uncertainties using an ANN that is developed using the training datasets from CDPR experiments. The estimated cable tensions at the end-effector are used to design a P-controller to track the desired force. The performance of the proposed ANN model is verified through comparisons with the forces measured directly at the end-effector. Furthermore, cable force control is implemented based on the compensated tensions to evaluate the performance of the CDPR in wrench space. The experimental results show that the proposed friction-compensation method is suitable for application in CDPRs to control the cable force., Competing Interests: The authors declare no conflicts of interest.

The chronic disease management program, a community-based intervention including patient education, recall and remind service, and reduction of out-of-pocket payment, was implemented in 2005 in Korea to improve patients' adherence for antihypertensive medications. This study aimed to assess the effect of a community-based hypertension intervention intended to enhance patient adherence to prescribed medications. This study applied a non-equivalent control group design using the Korean National Health Insurance Big Data. Hongcheon County has been continuously implementing the intervention program since 2012. This study involved a cohort of patients with hypertension aged >65 and <85 years, among residents who lived in the study area for five years (between 2010 and 2014). The final number of subjects was 2685 in both the intervention and control region. The indirect indicators were analyzed as patients' adherence and level of continuous treatment using the difference-in-difference regression. The proportion of hypertensive patients who continuously received insurance benefits for >240 days in 2014 was 81.0% in the intervention region and 79.7% in the control region. The number of dispensations per prescription and the dispensation days per hypertensive patient in the intervention region increased by approximately 10.88% and 2.2 days on average by month, respectively, compared to those in the control region. The intervention program encouraged elderly patients with hypertension to receive continuous care. Another research is needed to determine whether further improvement in the continuity of comprehensive care will prevent the progression of cardiovascular diseases.

The crustacean Daphnia pulex is one of the best model organisms for studying inducible defense mechanisms due to their inducible morphology in response to the predator Chaoborus larvae. In this study, multiple developmental stages of D. pulex were exposed to C. flavicans larvae and transcriptome profiles of samples from late embryo to fifth instar were sequenced by the RNA-seq technique to investigate the genetic background underlying inducible defenses. In comparison, differentially expressed genes between defensive and normal morphs were identified, including 908 genes in late embryo, 1383 genes in the first-third (1⁻3) instar, and 1042 genes in fourth-fifth (4⁻5) instar. Gene ontology enrichment analysis showed that structural constituents of the cuticle and structural molecule activity genes were prominent up-regulated genes in late embryos. Down-regulated genes in late embryos and 1⁻3 instar comprised metabolic process, hydrolase activity, and peptidase activity gene classes. Pathway analysis indicated that small molecule neurotransmitter pathways were potentially involved in the development of inducible defenses. The characterization of genes and pathways in multiple developmental stages can improve our understanding of inducible defense responses of D. pulex to predation at the molecular level.

In this paper, we report on a confocal thermoreflectance imaging system that can examine the thermal characteristics of microelectronic devices by penetrating the backside of a device through the substrate. In this system, the local reflectivity variations due to heat generation in the device are measured point by point by a laser scanning confocal microscope capable of eliminating out-of-focus reflections and the thermoreflectance is extracted via Fourier-domain signal processing. In comparison to the conventional widefield thermoreflectance microscope, the proposed laser scanning confocal thermoreflectance microscope improves the thermoreflectance sensitivity by ~23 times and the spatial resolution by ~25% in backside thermoreflectance measurements., Competing Interests: The authors declare no conflict of interest.

Self-perceived health is a health measure with well-established links with mortality, healthcare services utilization, and future health. Various components of self-perceived health have been identified in different populations. In this study, we aimed to investigate the components of self-perceived health in a Nepali population. This was a cross-sectional survey conducted in the Kailali district of Nepal in 2014. The sample was initially consisted of 309 households, representative of the population of one municipality and one village; however, 304 participants were included in the analyses. Information on socio-demographic characteristics, health condition, satisfaction with healthcare services, psychological factors, and health behaviors was extracted. Logistic regression analyses were carried out to identify putative components of self-perceived health. Among the 304 respondents, 244 (80.3%) and 60 (19.7%) perceived their health as good and poor, respectively. Middle age and lower satisfaction with healthcare services were associated with worse self-perceived health, accounting for 10.3% of variance. No regular exercise, drinking, smoking, and being unhappy were also related with worse self-perceived health, after adjustment for age and satisfaction level. In the final model, however, drinking status did not significantly contribute. Our findings support previous findings that individuals with positive health behaviors and psychological wellbeing are more likely to perceive their health better. This study may direct public health policies toward more targeted interventions.