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BACKGROUND Digital health technologies are becoming increasingly available to children and young people and their families. However, there are no scoping reviews that provide both an overview of the characteristics of digital interventions for children and young people and potential challenges to be considered when developing and implementing them. OBJECTIVE This study aimed to systematically review scientific publications to identify the current characteristics and potential complications of digital interventions for children and young people. METHODS This scoping review was conducted using the framework of Arksey and O’Malley and adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for scoping reviews. A search of 5 databases (PubMed, Scopus, Embase, MEDLINE, and CINAHL) and Google Scholar was performed for eligible clinical trials published between January 1, 2018, and August 19, 2022. RESULTS The initial search of the 5 databases yielded 3775 citations; duplicates and those not meeting the inclusion criteria were eliminated. In total, 34 articles were included in the final review and relevant information, such as the descriptive characteristics and potential challenges, were classified. Mental health (26/34, 76%) was the most common target for the digital intervention for children and young people, exceeding physical health (8/34, 24%) by more than 3 times. In addition, a substantial number of digital interventions were dedicated solely to children and young people. Digital interventions for children and young people were more likely to be delivered via computers (17/34, 50%) rather than smartphones (13/34, 38%). More than one-third of the studies (13/34, 38%) applied cognitive behavioral theory as the theory of digital interventions. The duration of the digital intervention for children and young people was more likely to vary depending on the target user rather than the target disease. Intervention components were classified into 5 categories: guidance, task and activity, reminder and monitoring, supportive feedback, and reward system. Potential challenges were subcategorized into ethical, interpersonal, and societal challenges. For ethical challenges, the consent of children and young people or caregivers, potential risk of adverse events, and data privacy issues were considered. For interpersonal challenges, the engagement of children and young people was affected by the preference or barrier of caregivers to participate in studies. For societal challenges, restricted ethnicity in recruitment, limited availability of digital technology, differences in internet use patterns between girls and boys, unified clinical settings, and language barriers were described. CONCLUSIONS We identified potential challenges and provided suggestions about ethical, interpersonal, and societal aspects to consider when developing and deploying digital-based interventions for children and young people. Our findings provide a thorough overview of the published literature and may serve as a comprehensive, informative foundation for the development and implementation of digital-based interventions for children and young people.

Oxygen, which is necessary for sustaining energy metabolism, is consumed in many biochemical reactions in eukaryotes. When the oxygen supply is insufficient for maintaining multiple homeostatic states at the cellular level, cells are subjected to hypoxic stress. Hypoxia induces adaptive cellular responses mainly through hypoxia-inducible factors (HIFs), which are stabilized and modulate the transcription of various hypoxia-related genes. In addition, many epigenetic regulators, such as DNA methylation, histone modification, histone variants, and adenosine triphosphate-dependent chromatin remodeling factors, play key roles in gene expression. In particular, hypoxic stress influences the activity and gene expression of histone-modifying enzymes, which controls the posttranslational modification of HIFs and histones. This review covers how histone methylation and histone acetylation enzymes modify histone and nonhistone proteins under hypoxic conditions and surveys the impact of epigenetic modifications on gene expression. In addition, future directions in this area are discussed.

Hemophilia is a hereditary disease that remains incurable. Although innovative treatments such as gene therapy or bispecific antibody therapy have been introduced, substantial unmet needs still exist with respect to achieving long-lasting therapeutic effects and treatment options for inhibitor patients. Antithrombin (AT), an endogenous negative regulator of thrombin generation, is a potent genome editing target for sustainable treatment of patients with hemophilia A and B. In this study, we developed and optimized lipid nanoparticles (LNPs) to deliver Cas9 mRNA along with single guide RNA that targeted AT in the mouse liver. The LNP-mediated CRISPR-Cas9 delivery resulted in the inhibition of AT that led to improvement in thrombin generation. Bleeding-associated phenotypes were recovered in both hemophilia A and B mice. No active off-targets, liver-induced toxicity, and substantial anti-Cas9 immune responses were detected, indicating that the LNP-mediated CRISPR-Cas9 delivery was a safe and efficient approach for hemophilia therapy., Description, We showed that lipid nanoparticle–packed CRISPR- mediated antithrombin gene editing offers a sustainable and safe hemophilia therapy.

Spotted leaf mutants which produce necrotic lesions spontaneously are important sources to study programmed cell death in plant defense responses. A novel white-spotted leaf (wspl) mutant was induced from Ilpum, Korean japonica rice cultivar by the treatment of ethyl methane sulfonate (EMS). The phenotype of wspl mutant differed from that of other spotted leaf mutants in that not only brown spots but also white lesion mimic spots were observed on the tip of the leaves from the vegetative stage. Strong nitro blue tetrazolium (NBT) and 3, 3′-diaminobenzidine (DAB) staining were observed on the older leaf of wspl mutant in microscopic reactive oxygen species (ROS) assay, and the chlorophyll content of wspl mutant maintained longer than wild-type in the old leaves. Genetic analysis revealed that the wspl mutant trait was controlled by a single recessive gene and the locus of wspl gene was mapped on the long arm of chromosome 5 between the flanking markers S05100 and S05112 (4.1 Mb). Through the combination of the genetic mapping and SNP analysis, two candidate genes for white-spotted leaf were identified in the genic region. A novel phenotype of white-spotted leaf mutant has not yet been reported, thus further study of the wspl mutant will contribute to understanding of the molecular mechanisms involved in lesion mimic phenotype in rice.

본 연구는 대부분의 정상인들이 자연스럽게 경험할 수도 있는 우울경험인 ‘일상우울’과 임상적 수준의 ‘우울증’을 구별하고, 일상우울이 임상적 우울의 발생에 선행한다는 새로운 구조 모형의 타당성을 검증하기 위해 진행되었다. 이를 위해 제주도를 제외한 전국의 성인 남녀 440명을 대상으로 설문조사를 실시하였다. 일상우울의 예측요인으로 예상되는 스트레스지각, 사회경제적 지위, 사회적지지가 일상우울을 매개해 임상수준의 우울을 예측하는 관계모형을 검증한 결과, 우울 유발 변인이 일상우울을 설명하고 이것이 임상적 우울을 예측한다는 모형의 전반적인 적합도가 높게 나타났다. 이는 우울 유발 변인인 스트레스, 사회경제적 지위, 사회적지지가 일상우울을 예측한다는 본 연구의 가설과 일치하였다. 본 연구결과를 통해 일상우울이 역학적 우울의 발생을 예측하는 새로운 개념이 될 수 있다는 가능성이 확인되었으며, 이러한 일상우울 개념의 도입은 우울증 환자들에 대한 사회의 인식을 개선하는 데에도 기여할 수 있을 것으로 보인다. 또한 심리학자의 시각에서 정신병리를 바라본 드문 시도라는 점에서 그 의의가 있다.

우울증은 만성적이고 재발적인 경과뿐 아니라 자살의 영향력과 관련하여 중요한 사회적 문제로 간주되고 있다. 전 세계의 여러 연구자들은 우울증의 심각성을 인식하고, 다양한 치료의 개발과 그 효과 검증에 관심을 집중하고 있다. 본 연구에서는 그동안의 연구를 통해 우울증 치료에 있어서 그 효과가 강력하게 지지된 인지치료, 행동활성화치료, 대인관계치료, 문제해결치료의 치료 요인과 과정, 국내 치료효능연구를 개관하였다. 또한 국내 우울증의 심리치료 결과를 요약하여, 이를 바탕으로 우울증에 대한 근거기반치료의 권고안을 제시하였다. 본 연구에서는 국내 연구결과를 기반으로 인지행동치료와 수용전념치료, 마음챙김에 기반한 인지치료를 효과가 있음직한 치료로 제안하였다. 이를 통해 향후 심리치료 연구에 대한 제언을 하였으며, 국내의 근거기반 우울증 치료의 연구 및 보급을 촉진하고자 하였다.

In Korea, typhoid fever is a rare disease due to improved living standards. However, this disease remains a major burden in developing countries and regions, such as India and Southeast Asia, In this study, we isolated Salmonella Typhi (S. Typhi) from eight typhoid patients, travelers returning from India. Isolated strains characterized with antimicrobial susceptibility profile and whole genome sequencing (WGS) analysis.All strains were resistant to nalidixic acid and azithromycin. Among them, four isolates were highly resistant to ciprofloxacin (MIC ≥32 μg/ml) and never confirmed in Korea PulseNet DB. On the basis of the WGS, we found that the ciprofloxacin-resistant strain belonged to global dominant multi-drug resistant (MDR) genotype, haplotype H58 (SNP glpA C1047T, SptP protein Q185* (premature stop codon)) not harbour MDR plasmid. They have H58-associated SNPs in membranes and metabolism genes, including yhdA, yajI, hyaE, tryE, rlpB and metH. Also, Phylogenetic analysis showed that H58 strains were assigned sublineage II, and the non-H58 strains were closely related to haplotype H50.High-level ciprofloxacin-resistant S. Typhi haplotype H58 in Korea was first confirmed as influx from overseas by travelers. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.Author summaryTyphoid fever is a systemic human disease including gastroenteritis, fever, and severe diarrhea, caused by Salmonella enterica serotype typhi (S. Typhi), and requires prompt antibiotic treatment. Due to improved living standards, it has become a rare disease but still prevalent in developing countries such as India and Southeast Asia. Most of the reported case were related with travelers or immigrants from these regions. There is global health problem that emergence of antimicrobial resistant strain associated with fluoroquinolones and third-generation cephalosporins because of leading to treatment failure, serious morbidity, and as well as economic loss. Of antimicrobial resistant S. Typhi, haplotype H58 is a dominant multi-drug resistant lineage and has reported in endemic region over past two decades. We identified fluoroquinolones resistance in S. Typhi infected after travel to India. Among them, some strains highly resistant to ciprofloxacin were confirmed to have characteristics of haplotype H58. In Korea, S. Typhi haplotype H58 from traveller has not been confirmed before. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.

Macrophage colony-stimulating factor (M-CSF) is a hematopoietic growth factor that stimulates the proliferation and differentiation of mononuclear phagocytes. To be biologically active, M-CSF must form a homodimer linked by disulfide bridges. However, the refolding step of recombinant M-CSF is not only extremely laborious but also rate-limiting. Here, we describe an efficient and simplified method for refolding and purifying M-CSF from Escherichia coli. A truncated M-CSF (amino acids 36–181) was tagged with histidine, expressed, and then purified using nickel affinity columns under denaturing conditions. Our redox refolding buffer containing a mixture of reduced and oxidized glutathione and arginine correctly refolded M-CSF. Chromatography on Q-sepharose columns selectively purified the M-CSF dimer from the monomeric form. The dimeric nature of the purified M-CSF was confirmed using multi angle light scattering combined with high performance liquid chromatography. Moreover, cell proliferation and osteoclast differentiation assays using bone marrow-derived macrophages demonstrated that the recombinant M-CSF was biologically active ex vivo.

Preclinical studies using genetically engineered mouse models (GEMM) have the potential to expedite the development of effective new therapies; however, they are not routinely integrated into drug development pipelines. GEMMs may be particularly valuable for investigating treatments for less common cancers, which frequently lack alternative faithful models. Here, we describe a multicenter cooperative group that has successfully leveraged the expertise and resources from philanthropic foundations, academia, and industry to advance therapeutic discovery and translation using GEMMs as a preclinical platform. This effort, known as the Neurofibromatosis Preclinical Consortium (NFPC), was established to accelerate new treatments for tumors associated with neurofibromatosis type 1 (NF1). At its inception, there were no effective treatments for NF1 and few promising approaches on the horizon. Since 2008, participating laboratories have conducted 95 preclinical trials of 38 drugs or combinations through collaborations with 18 pharmaceutical companies. Importantly, these studies have identified 13 therapeutic targets, which have inspired 16 clinical trials. This review outlines the opportunities and challenges of building this type of consortium and highlights how it can accelerate clinical translation. We believe that this strategy of foundation–academic–industry partnering is generally applicable to many diseases and has the potential to markedly improve the success of therapeutic development. Cancer Res; 77(21); 5706–11. ©2017 AACR.

Obesity is a major public health concern. Despite its multi-factorial etiology, alterations in intestinal microbiota and the immune system are frequently observed. We investigated the effect of Duolac Gold (DG), a probiotic formulation containing 2 Lactobacillus strains (L. acidophilus LA1 and L. rharmnosus LR5), 3 Bifidobacterium (B. bifidum BF3, B. lactis BL3, and B. longum BG7), and Streptococcus thermophilus ST3, on morphometric and metabolic parameters, intestinal microbiota, and intestinal immune responses in a high-fat diet (HFD)-induced obese rat model. Rats received either a conventional balanced diet or HFD with or without water containing DG for 8 weeks. HFD-induced adiposity, intestinal microbiota, and changes in inflammatory cytokine, chemokine, and metabolite levels in serum were evaluated. DG administration effectively decreased HFD-induced body weight and modulated morphometric and metabolic parameters. Quantitative analysis of fecal microbiota showed that obese rats given DG exhibited significantly increased levels of Bacteroidetes, Lactobacillus, and Bifidobacterium, with significant decreases in the level of Firmicutes. Serum levels of the inflammatory cytokines and the chemokine were also altered. Serum metabolite analysis revealed that DG administration modulated HFD-induced changes in serum metabolites, including fatty acids (FA), lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylcholine (PC), and triacylglycerol (TAG). DG administration appears to have the potential to alleviate HDF-induced obesity through the modulation of intestinal microbiota, immune responses, and host metabolism, which supports the use of probiotics to treat obesity.

Bone tissue is continuously remodeled by the coordinated action of osteoclasts and osteoblasts. Nuclear factor-activated T cells c1 (NFATc1) is a well-known transcription factor for osteoclastogenesis and transcriptionally activated by the c-Fos and nuclear factor-kappa B (NF-&kappa, B) signaling pathways in response to receptor activation of NF-&kappa, B ligand (RANKL). Since excessive RANKL signaling causes an increase of osteoclast formation and bone resorption, inhibition of RANKL or its signaling pathway is an attractive therapeutic approach to the treatment of pathologic bone loss. In this study, we show that an ethyl acetate fraction (LEA) from the shiitake mushroom, Lentinula edodes, inhibited RANKL-induced osteoclast differentiation by blocking the NFATc1 signaling pathway. We found that the water extract and its subsequent ethyl acetate fraction of L. edodes significantly suppressed osteoclast formation. Comparative transcriptome analysis revealed that LEA specifically downregulated a set of RANKL target genes, including Nfatc1. Next, we found that LEA suppresses Nfatc1 expression mainly through the inhibition of the transactivity of p65 and NFATc1. Moreover, treatment of LEA rescued an osteoporotic phenotype in a zebrafish model of glucocorticoid-induced osteoporosis. Collectively, our findings define an undocumented role of the shiitake mushroom extract in regulating bone development.

The bone tissue is a dynamic complex that constitutes of several interdependent systems and is continuously remodeled through the concerted actions of bone cells. Osteoblasts are mononucleated cells, derived from mesenchymal stem cells, responsible for bone formation. Osteoclasts are large multinucleated cells that differentiate from hematopoietic progenitors of the myeloid lineage and are responsible for bone resorption. The lineage-specific differentiation of bone cells requires an epigenetic regulation of gene expressions involving chromatin dynamics. The key step for understanding gene regulatory networks during bone cell development lies in characterizing the chromatin modifying enzymes responsible for reorganizing and potentiating particular chromatin structure. This review covers the histone-modifying enzymes involved in bone development, discusses the impact of enzymes on gene expression, and provides future directions and clinical significance in this area.

The purposes of this study were to analyze mothers" eating, cooking, and exercise habits based on their demographic characteristics and to examine the relationship between those habits and their late school-aged children"s Broca index. A total of 393 questionnaires were mailed to the mothers of late school-aged children who registered at four elementary schools in the Seoul area, of which 159 participants (40.0%) completed questionnaires. Statistical data analyses were performed using SPSS/Win 21.0 for descriptive statistics, t-test ANOVA, and Pearson"s regression coefficient. There was a statistically significant difference in mothers" cooking habit (F=3.920, P=0.022) and exercise habit (F=3.211, P=0.043) according to their educational level. Interestingly, 82.4% of mothers had a Broca index of less than 90% of normal body mass level. A significant positive correlation of Broca index between mothers and their late school-aged children (r=0.345, P

Global health competency is an essential capacity for nursing students. This study evaluated the effect of a global outreach program on global health competency and cultural self-efficacy in nursing students and examined the students' experiences with the program. Participants included thirty-one undergraduate nursing students at a university in Seoul, Republic of Korea, who participated in a global outreach program in 2015 and 2016. Quantitative data were collected before and after program participation using questionnaires evaluating global health competency and cultural self-efficacy, and were analyzed using descriptive statistics and paired t-tests. Both global health competency and cultural self-efficacy increased significantly after the global outreach program. Qualitative data were collected via focus group interviews and reflective journals, and were analyzed using conventional content analysis and thematic analysis, respectively. The results of the content and thematic analyses were compared, and two themes and eight-sub-themes were finally extracted through the data analysis. The program was effective in improving nursing students' global health competency and cultural self-efficacy.

Background On May 19, 2017, the cluster of 6 acute respiratory infections due to adenovirus in the swimming department of a physical education school (School J) was reported to Korea Centers for Disease Control and Prevention. An epidemiological investigation was conducted to identify the transmission route of the infection and to control the outbreak. Materials and methods A retrospective cohort study (Study 1) was conducted on students and teachers of the athletic departments using the swimming pool, and a prospective surveillance (Study 2) was conducted on all students and teachers of the School J. A case was defined as any student and school personnel who developed more than two of the following symptoms from April 10 to July 2, 2017: fever, sore throat, cough, rhinorrhea, or headache. Relative risks (RRs) were calculated to compare the attack rates according to potential risk factors. Multivariable logistic regression was performed to identify the risk factors for infection in the outbreak. Results 47 cases were identified: 33 (55.9%) cases occurred among 59 students and teachers in Study 1 and 14 (3.9%) among 362 students and school personnel in Study 2. There were 18 laboratory confirmed adenovirus infection cases. The common symptoms were headache (71.7%), fever (69.6%), rhinorrhea (63.0%), sputum (56.5%), and sore throat (54.3%). 23.9% of the cases were accompanied with diarrhea and 19.6% with eye congestion. None of the cases developed pneumonia. 32.6% of the cases were hospitalized. In Study 1, attack rate in the swimming department was higher than that in others (RR: 1.90; 95% confidence interval [CI]: 1.01-3.60). In Study 2, being a member of the shooting department (RR: 20.70; 95% CI: 4.90-87.47) and being a first year high school student (RR: 10.95; 95% CI: 2.90-41.33) were identified as risk factors for the infections. Genetic analyses of the adenoviruses showed 100% identical sequence in homology and confirmed the human adenovirus B55 (HAdV-B55). No adenovirus was detected at examining the water and environment of the swimming pool and dormitory. Conclusion The outbreak is inferred to be occurred via propagated transmission among the students in the same athletic department, while the students with symptoms of respiratory infection continued performing school activities without any restrictions. Infection control measures such as early detection of symptoms of respiratory infection and restriction of group activity are necessary to prevent respiratory infection outbreak in the communal living setting.

β2-Adrenergic receptor (β2-AR) is implicated in muscle metabolic activities such as glycogen metabolism, glucose uptake, lipolysis and muscle growth. However, the functional role of β2-AR in the differentiation of skeletal muscle is largely unknown. Here, we examined the functional role of β2-AR in L6 myoblast differentiation using the long-term-acting β2-AR-specific agonist formoterol. We observed that formoterol treatment strongly suppressed L6 myoblast differentiation and the expression of myosin heavy chain (MHC) in a dose- and time-dependent manner. Showing that both long-acting agonist (formoterol) and short-acting agonist (terbutaline) inhibited the induction of MHC protein, whereas β2-AR antagonist (ICI-118,551) upregulated MHC expression, we clearly demonstrated that β2-AR is involved in L6 myoblast differentiation. Furthermore, our pharmacological inhibition study revealed that the PI3K–AKT pathway is the main signaling pathway for myotube formation. Formoterol inhibited the activation of PI3K–AKT signaling, but not that of ERK signaling. Moreover, formoterol selectively inhibited AKT activation by IGF-I, but not by insulin. Collectively, our findings reveal a previously undocumented role of β2-AR activation in modulating the differentiation of L6 myoblasts.

Highlight An integrated approach of metabolomics and transcriptomics was applied to understand regulatory networks associated with biosynthesis of anthocyanins that are differentially regulated in light-red- and dark-purple-colored potato cultivars., To gain insights into the regulatory networks related to anthocyanin biosynthesis and identify key regulatory genes, we performed an integrated analysis of the transcriptome and metabolome in sprouts germinated from three colored potato cultivars: light-red Hongyoung, dark-purple Jayoung, and white Atlantic. We investigated transcriptional and metabolic changes using statistical analyses and gene–metabolite correlation networks. Transcript and metabolite profiles were generated through high-throughput RNA-sequencing data analysis and ultraperformance liquid chromatography quadrupole time-of-flight tandem mass spectrometry, respectively. The identification and quantification of changes in anthocyanin were performed using molecular formula-based mass accuracy and specific features of their MS2 spectra. Correlation tests of anthocyanin contents and transcriptional changes showed 823 strong correlations (correlation coefficient, R 2>0.9) between 22 compounds and 119 transcripts categorized into flavonoid metabolism, hormones, transcriptional regulation, and signaling. The connection network of anthocyanins and genes showed a regulatory system involved in the pigmentation of light-red Hongyoung and dark-purple Jayoung potatoes, suggesting that this systemic approach is powerful for investigations into novel genes that are potential targets for the breeding of new valuable potato cultivars.

Background In November 2015, reuse of needles and syringes in conjunction with an increase in cases of HCV at a clinic in Korea was reported and investigated by public health authorities. Patients who received injections at the clinic from the first time this infection control breach may have occurred in 2008 through 2015 when the practice was stopped were offered screening for HCV and other blood-borne pathogens such as HIV, HTLV, HBV, syphilis, and malaria. Objectives The aim of this study was to assess whether an outbreak of hepatitis C had occurred among the potentially exposed clinic patients due to this infection control breach. Study Design We performed hepatitis C viral RNA load tests and genotyping using plasma from hepatitis C antibody-positive individuals who had visited the clinic between May 2008 and November 2015. We analyzed the core-E2 and NS5B regions of the virus from RNA-positive samples by constructing a phylogenetic tree based on maximum likelihood analysis. To identify transmission risk factors and epidemiological relationships among the patients, we reviewed their medical records, assessed staff infection control practices and performed environmental inspection of the clinic. Environmental samples from medication room surfaces and medication vial contents were tested for HCV RNA. Results and Conclusions Among the 1721 patients tested, 96 were IgG-positive and 70 were viral RNA-positive. Among the 61 patients whose viral loads were greater than the detection limit, 41 (67.2%) were classified as genotype 1a, 1 (1.6%) as genotype 1b, 18 (29.5%) as genotype 1, and one (1.6%) as genotype 2. After sequencing, 12 genotype 1 cases were further classified as genotype 1a (11) or 1b (1). The sequences of the core-E2 and NS5B regions of 45 patients formed a monophyletic cluster distinct from genotype 1a. The hepatitis C virus sequences from patients and environmental specimens were well-matched in the partial E1 gene region. We detected genotype 1a RNA in environmental specimens, indicating a healthcare-associated outbreak caused by reuse of syringes and contaminated multi-dose vials. Our molecular epidemiological investigation of hepatitis C genotype 1a, rare in Korea, will aid investigations of infection sources during future pathogen outbreaks.

Osteoporosis is a common disorder of bone remodeling, caused by the imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Recently, we reported that matrix metalloproteinase-9 (MMP-9)-dependent histone H3 proteolysis is a key event for proficient osteoclast formation. Although it has been reported that several MMP-9 inhibitors, such as tetracycline and its derivatives, show an inhibitory effect on osteoclastogenesis, the molecular mechanisms for this are not fully understood. Here we show that tetracycline analogs, especially tigecycline and minocycline, inhibit osteoclast formation by blocking MMP-9-mediated histone H3 tail cleavage. Our molecular docking approach found that tigecycline and minocycline are the most potent inhibitors of MMP-9. We also observed that both inhibitors significantly inhibited H3 tail cleavage by MMP-9 in vitro. These compounds inhibited receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast formation by blocking the NFATc1 signaling pathway. Furthermore, MMP-9-mediated H3 tail cleavage during osteoclast differentiation was selectively blocked by these compounds. Treatment with both tigecycline and minocycline rescued the osteoporotic phenotype induced by prednisolone in a zebrafish osteoporosis model. Our findings demonstrate that the tetracycline analogs suppress osteoclastogenesis via MMP-9-mediated H3 tail cleavage, and suggest that MMP-9 inhibition could offer a new strategy for the treatment of glucocorticoid-induced osteoporosis.

Silicon stripixel sensors utilizing a novel design of comb-type pixels intertwining with one other are capable of two-dimensional position detection of charged particles. We have designed and fabricated the stripixel sensors with 128 X and 128 Y strips in an active area of about 6 cm × 6 cm. Each strip in our design, in turn, consists of 128 comb-type basic units. X and Y basic units are intertwined in such a fashion that a pair of X and Y units forms a pixel in a stripixel sensor, and the pixel is sensitive to a charged particle passing through it. We present the design, device simulation, and fabrication of the silicon stripixel sensors. We also present the electrical characteristics of the sensors.