Explore the vast range of titles available.

Calcium and vitamin D deficiencies have been ongoing problems in Koreans due to a lack of food sources of calcium and vitamin D. Postmenopausal women aged 50 to 64 years (n = 25) were randomly assigned to consume three home meal replacements (HMRs)/week with (treatment) and without (control) eggshell powder and vitamin D for 6 months. Additionally, subjects who agreed to continue the study consumed the same three HMRs/week for an additional 6 months in this randomized double-blind study. We confirmed the high compliance of the study participants by analyzing carotenoids, the bioactive substances of HMRs, in the blood. The treatment group consumed an additional 261 mg/d of calcium and 10.3 μg/d of vitamin D from the HMRs, thus meeting the recommended intakes of calcium and vitamin D for Koreans. As a result of consuming fortified HMRs for 6 months, the decline in femoral neck bone density was significantly reduced in the treatment group (p = 0.035). This study indicates that inexpensive eggshell powder may be a good source of calcium for populations with low consumption of milk and dairy products. Additionally, functional HMRs fortified with eggshell powder and vitamin D can be a good dietary strategy for bone health.

Backgrounds. Recent studies suggest that diarrhea-predominant irritable bowel syndrome (IBS) is associated with intestinal bacterial microflora, colonic inflammation, and small intestinal bacterial overgrowth (SIBO). The purpose of this study was to evaluate the effect of a multistrain probiotic intake on these associated factors in patients with diarrhea-predominant IBS. Methods. The recruited volunteers were adults who were diagnosed with diarrhea-predominant IBS according to the Rome III criteria. After 8 weeks of probiotic ingestion, changes in gastrointestinal symptoms, fecal microbiome, SIBO, and fecal calprotectin were determined. Results. There was an increase in beneficial bacteria (41.2 ± 16.8% vs. 53.7 ± 15.3%, P=0.018) and a decrease in harmful bacteria (13.0 ± 13.9% vs. 4.7 ± 4.0%, P=0.010) in the microbial stool analysis. The SIBO prevalence also decreased at the end of treatment. However, the average levels of fecal calprotectin showed a decreasing tendency, without reaching statistical significance (364.4 ± 729.1 mg/kg vs. 200.9 ± 347.6 mg/kg, P=0.375). Conclusion. Treatment with a multistrain probiotic for 8 weeks led to significant increases in beneficial bacteria in the gut as well as the improvement of gastrointestinal symptoms. This study is registered at the Clinical Research Information Service (KCT0002906).

RNA-binding proteins (RBPs) provide a critical post-transcriptional regulatory layer in determining RNA fate. Currently, UV crosslinking followed by oligo-dT pull-down is the gold standard in identifying the RBP repertoire of poly-adenylated RNAs, but such method is ineffective in capturing RBPs that recognize double-stranded RNAs (dsRNAs). Here, we utilize anti-dsRNA K1 antibody immunoprecipitation followed by quantitative mass spectrometry to comprehensively identify RBPs bound to cellular dsRNAs without external stimulus. Notably, our dsRNA interactome contains proteins involved in sensing N 6 -methyladenosine RNAs and stress granule components. We further perform targeted CRISPR-Cas9 knockout functional screening and discover proteins that can regulate the interferon (IFN) response during exogenous RNA sensing. Interestingly, most dsRBPs promote IFN-β secretion in response to dsRNA stimulation and act as antiviral factors during HCoV-OC43 infection. Our dsRNA interactome capture provides an unbiased and comprehensive characterization of putative dsRBPs and will facilitate our understanding of dsRNA sensing in physiological and pathological contexts. Exploration of dsRNA interactome using the K1 antibody and functional studies using CRISPR-Cas9 knockout screening of these dsRBP candidates elucidate the role of dsRNA interactome in immune responses and their importance in viral infection.

When used to edit genomes, Cas9 nucleases produce targeted double-strand breaks in DNA. Subsequent DNA-repair pathways can induce large genomic deletions (larger than 100 bp), which constrains the applicability of genome editing. Here we show that Cas9-mediated double-strand breaks induce large deletions at varying frequencies in cancer cell lines, human embryonic stem cells and human primary T cells, and that most deletions are produced by two repair pathways: end resection and DNA-polymerase theta-mediated end joining. These findings required the optimization of long-range amplicon sequencing, the development of a k -mer alignment algorithm for the simultaneous analysis of large DNA deletions and small DNA alterations, and the use of CRISPR-interference screening. Despite leveraging mutated Cas9 nickases that produce single-strand breaks, base editors and prime editors also generated large deletions, yet at approximately 20-fold lower frequency than Cas9. We provide strategies for the mitigation of such deletions. DNA repair after Cas9-mediated double-strand breaks induces large DNA deletions at frequencies 20-fold higher than elicited by base editors and prime editors leveraging Cas9 nickases producing single-strand breaks.

A sub-Å resolution analysis of a Si crystal structure was performed successfully using a phase extension technique that combined the high-voltage electron microscopy (HVEM) and energy-filtered precession electron diffraction (EF-PED) methods. The high resolution electron microscopy (HREM) image of Si [211] was obtained with a spatial resolution of 0.12 nm using HVEM. The electron diffraction of Si [211] was acquired with a spatial resolution of 0.06 nm by employing the EF-PED method. The phase information of Si [211] was extracted from a deconvoluted image by applying instrumental parameters. Its amplitude information with higher spatial resolution was quasi-kinematically extracted from EF-PED data. Finally, it was revealed that Si atoms were clearly separated with a resolution of 0.78 Å in the enhanced resolution image. Therefore, it is expected that the combination of the HVEM and EF-PED methods will be a useful and powerful tool for the quantitative characterization of nanostructured materials.

In competitive economic environments, a service-quality improvement program (SQIP) should focus on customer satisfaction and should differentiate a company's service from its competitors' service. In this paper, current and competitive service quality (SQ) levels are considered for improving competitive SQ using current SQ levels measured by the SERVQUAL model with a ratio-score scale. Second, competitive SQ is analyzed by customer assessment relative to each service attribute. Subsequently, the entropy method is used to quantify competitiveness. The value of each attribute's entropy indicates the relative importance of the attribute for SQIP. Third, the final priorities are determined by the combination of current SQ level and entropy value. Empirical testing on a fast-food case study identifies the importance of considering the current SQ level and competitive performance indices simultaneously within a SQIP model.

Adenine base editors (ABEs) catalyze specific A-to-G conversions at genomic sites of interest. However, ABEs also induce cytosine deamination at the target site. To reduce the cytosine editing activity, we engineered a commonly used adenosine deaminase, TadA7.10, and found that ABE7.10 with a D108Q mutation in TadA7.10 exhibited tenfold reduced cytosine deamination activity. The D108Q mutation also reduces cytosine deamination activity in two recently developed high-activity versions of ABE, ABE8e and ABE8s, and is compatible with V106W, a mutation that reduces off-target RNA editing. ABE7.10 containing a P48R mutation displayed increased cytosine deamination activity and a substantially reduced adenine editing rate, yielding a TC-specific base editing tool for TC-to-TT or TC-to-TG conversions that broadens the utility of base editors. Engineered variants of adenine base editors have reduced cytosine base editing or a specific C-to-G base editing activity.

To evaluate the prevalence of deltoid ligament and distal tibiofibular syndesmosis injury on 3T magnetic resonance imaging (MRI) in patients with chronic lateral ankle instability (CLAI). Fifty patients (mean age, 35 years) who had undergone preoperative 3T MRI and surgical treatment for CLAI were enrolled. The prevalence of deltoid ligament and syndesmosis injury were assessed. The complexity of lateral collateral ligament complex (LCLC) injury was correlated with prevalence of deltoid or syndesmosis injuries. The diagnostic accuracy of ankle ligament imaging at 3T MRI was analyzed using arthroscopy as a reference standard. On MRI, deltoid ligament injury was identified in 18 (36%) patients as follows: superficial ligament alone, 9 (50%); deep ligament alone 2 (11%); and both ligaments 7 (39%). Syndesmosis abnormality was found in 21 (42%) patients as follows: anterior inferior tibiofibular ligament (AITFL) alone, 19 (90%); and AITFL and interosseous ligament, 2 (10%). There was no correlation between LCLC injury complexity and the prevalence of an accompanying deltoid or syndesmosis injury on both MRI and arthroscopic findings. MRI sensitivity and specificity for detection of deltoid ligament injury were 84% and 93.5%, and those for detection of syndesmosis injury were 91% and 100%, respectively. Deltoid ligament or syndesmosis injuries were common in patients undergoing surgery for CLAI, regardless of the LCLC injury complexity. 3T MRI is helpful for the detection of all types of ankle ligament injury. Therefore, careful interpretation of pre-operative MRI is essential.

CRISPR-Cas9 nucleases are versatile tools for genetic engineering cells and function by producing targeted double-strand breaks (DSBs) in the DNA sequence. However, the unintended production of large deletions (>100 bp) represents a challenge to the effective application of this genome-editing system. We optimized a long-range amplicon sequencing system and developed a k-mer sequence-alignment algorithm to simultaneously detect small DNA alteration events and large DNA deletions. With this workflow, we determined that CRISPR-Cas9 induced large deletions at varying frequencies in cancer cell lines, stem cells, and primary T cells. With CRISPR interference screening, we determined that end resection and the subsequent TMEJ [DNA polymerase theta-mediated end joining] repair process produce most large deletions. Furthermore, base editors and prime editors also generated large deletions despite employing mutated Cas9 nickases that produce single-strand breaks. Our findings reveal an important limitation of current genome-editing tools and identify strategies for mitigating unwanted large deletion events.Competing Interest StatementThe authors have declared no competing interest.

A sub-Aa resolution analysis of a Si crystal structure was performed successfully using a phase extension technique that combined the high-voltage electron microscopy (HVEM) and energy-filtered precession electron diffraction (EF-PED) methods. The high resolution electron microscopy (HREM) image of Si [211] was obtained with a spatial resolution of 0.12 nm using HVEM. The electron diffraction of Si [211] was acquired with a spatial resolution of 0.06 nm by employing the EF-PED method. The phase information of Si [211] was extracted from a deconvoluted image by applying instrumental parameters. Its amplitude information with higher spatial resolution was quasi-kinematically extracted from EF-PED data. Finally, it was revealed that Si atoms were clearly separated with a resolution of 0.78 Aa in the enhanced resolution image. Therefore, it is expected that the combination of the HVEM and EF-PED methods will be a useful and powerful tool for the quantitative characterization of nanostructured materials.