Identification and characterization of a marine bacterium extract from Mameliella sp. M20D2D8 with antiviral effects against influenza A and B viruses.

Despite significant improvements in vaccines and chemotherapeutic drugs, pathogenic RNA viruses continue to have a profound impact on the global economy and pose a serious threat to animal and human health through emerging and re-emerging outbreaks of diseases. To overcome the challenge of viral adaptation and evolution, increased vigilance is required. Particularly, antiviral drugs derived from new, natural sources provide an attractive strategy for controlling problematic viral diseases. In this antiviral study, we discovered a previously unknown bacterium, Mameliella sp. M20D2D8, by conducting an antiviral screening of marine microorganisms. An extract from M20D2D8 exhibited antiviral activity with low cytotoxicity and was found to be effective in vitro against multiple influenza virus strains: A/PR8 (IC50 = 2.93 µg/mL, SI = 294.85), A/Phil82 (IC50 = 1.42 µg/mL, SI = 608.38), and B/Yamagata (IC50 = 1.59 µg/mL, SI = 543.33). The antiviral action was found to occur in the post-entry stages of viral replication and to suppress viral replication by inducing apoptosis in infected cells. Moreover, it efficiently suppressed viral genome replication, protein synthesis, and infectivity in MDCK and A549 cells. Our findings highlight the antiviral capabilities of a novel marine bacterium, which could potentially be useful in the development of drugs for controlling viral diseases.

Understanding the Korean Dialysis Cohort for Mineral, Vascular Calcification, and Fracture (ORCHESTRA) Study: Design, Method, and Baseline Characteristics.

INTRODUCTION: End-stage renal disease (ESRD) is a growing disease worldwide, including Korea. This is an important condition that affects patient outcome. To provide optimal management for mineral disturbance, vascular calcification, and bone disease in ESRD patients, the Korean dialysis cohort for mineral, vascular calcification, and fracture (ORCHESTRA) study was conducted by enrolling Korean dialysis patients. METHODS: Sixteen university-affiliated hospitals and one Veterans' Health Service Medical Center participated in this study. This prospective cohort study enrolled approximately 900 consecutive patients on dialysis between May 2019 and January 2021. Enrolled subjects were evaluated at baseline for demographic information, laboratory tests, radiologic imaging, and bone mineral densitometry (BMD) scans. After enrollment, regular assessments of the patients were performed, and their biospecimens were collected according to the study protocol. The primary outcomes were the occurrence of major adverse cardiovascular events, invasive treatment for peripheral artery disease, and osteoporotic fractures. The secondary outcomes were hospitalization for cerebrovascular disease or progression of abdominal aortic calcification. Participants will be assessed for up to 3 years to determine whether primary or secondary outcomes occur. RESULTS: Between May 2019 and January 2021, all participating centers recruited 900 consecutive dialysis patients, including 786 undergoing hemodialysis (HD) and 114 undergoing peritoneal dialysis (PD). The mean age of the subjects was 60.4 ± 12.3 years. Males accounted for 57.7% of the total population. The mean dialysis vintage was 6.1 ± 6.0 years. The HD group was significantly older, had a longer dialysis vintage, and more comorbidities. Overall, the severity of vascular calcification was higher and the level of BMD was lower in the HD group than in the PD group. CONCLUSION: This nationwide, multicenter, prospective cohort study focused on chronic kidney disease-mineral and bone disorder and aimed to provide clinical evidence to establish optimal treatment guidelines for Asian dialysis patients.

Establishment of canine mammary gland tumor cell lines harboring PI3K/Akt activation as a therapeutic target.

Canine mammary gland tumors (MGT) have a poor prognosis in intact female canines, posing a clinical challenge. This study aimed to establish novel canine mammary cancer cell lines from primary tumors and characterize their cellular and molecular features to find potential therapeutic drugs. The MGT cell lines demonstrated rapid cell proliferation and colony formation in an anchorage-independent manner. Vimentin and α-SMA levels were significantly elevated in MGT cell lines compared to normal canine kidney (MDCK) cells, while CDH1 expression was either significantly lower or not detected at all, based on quantitative real-time PCR (qRT-PCR) analysis. Functional annotation and enrichment analysis revealed that epithelial-mesenchymal transition (EMT) phenotypes and tumor-associated pathways, particularly the PI3K/Akt signaling pathway, were upregulated in MGT cells. BYL719 (Alpelisib), a PI3K inhibitor, was also examined for cytotoxicity on the MGT cell lines. The results show that BYL719 can significantly inhibit the proliferation of MGT cell lines in vitro. Overall, our findings suggest that the MGT cell lines may be valuable for future studies on the development, progression, metastasis, and management of tumors.

The phase angle before transplantation can predict the status of low muscle mass after kidney transplantation.

BACKGROUND: This study aimed to evaluate the association between phase angle, muscle strength, and muscle mass in patients undergoing kidney transplantation. METHODS: Patients whose pre- and follow-up phase angles were measured after kidney transplantation were enrolled. Phase angle and body composition were measured using a multi-frequency bioimpedance analysis device before and at 7 and 14 days and 3, 6, and 12 months after transplantation. Muscle strength was evaluated using handgrip strength (HGS). Low HGS was defined as < 28 kg in males and < 18 kg in females. Low muscle mass was defined as an appendicular lean mass index of < 7.0 kg/m2 in males and < 5.7 kg/m2 in females. RESULTS: Eighty-eight patients (mean age 52.3 ± 10.1 years) were analyzed. The mean phase angle of pre-transplantation was 5.0 ± 1.0°. Body fat percentage was significantly higher at 6 and 12 months after transplantation than pre-transplantation (P < 0.0001). Twelve months after kidney transplantation, the prevalence of low HGS decreased (pre-transplantation vs. 12 months post-transplantation: 28.4% vs. 17.0%), and the prevalence of low muscle mass (pre-transplantation vs. 12 months post-transplantation: 21.6% vs. 28.4%) increased. The pre-transplantation phase angle was significantly associated with low muscle mass at 12 months after kidney transplantation (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.16-0.72; P = 0.005). The pre-transplantation phase angle was not significantly associated with low HGS (OR: 0.37; 95% CI 0.12-1.17; P = 0.090) 12 months after kidney transplantation. CONCLUSIONS: Pre-transplantation phase angle can predict muscle mass status 12 months after kidney transplantation.

An update of the severe trauma scoring system using the Korean National Emergency Department Information System (NEDIS) database.

BACKGROUND: Various scoring systems are utilized to assess severe trauma patients, with one of the most commonly used tools being the International Classification of Diseases Injury Severity Score (ICISS) criteria derived from the Survival Risk Ratio (SRR) calculated using diagnostic codes. This study aimed to redefine the severe trauma scoring system in Korea based on the SRR for diagnostic codes, and subsequently evaluate its performance in predicting survival outcomes for trauma patients. METHODS: This study included trauma patients who visited Level 1 and 2 emergency departments (EDs) between January 2016 and December 2019, utilizing the Korean National Emergency Department Information System (NEDIS) database. The primary outcome of this study was in-hospital mortality. The new SRR-2020 value was calculated for each of the 865 trauma diagnosis codes (Korean Standard Classification of Diseases [KCD-7] codes, 4-digit format), and the patient-specific ICISS-2020 value was derived by multiplying the corresponding SRR-2020 value based on patient diagnosis. We compared the predictive performance for in-hospital mortality between severe trauma patients with an ICISS <0.9 based on the newly developed ICISS-2020 version and those defined by the previously used ICISS-2015 version. RESULTS: A total of 3,841,122 patients were enrolled, with an in-hospital mortality rate of 0.5 %. Severe trauma patients with ICISS-2020 < 0.9 accounted for 5.3 % (204,897 cases) that was lower than ICISS-2015 < 0.9 accounting for 15.3 % (587,801 cases). Among the 20,619 in-hospital mortality cases, 81.4 % had ICISS-2020 < 0.9, and 88.6 % had ICISS-2015 < 0.9. When comparing predictive performance for in-hospital mortality between the two ICISS versions, ICISS-2020 showed higher accuracy (0.95), specificity (0.95), positive predictive value (PPV) (0.08), positive likelihood ratio (LR+) (16.53), and area under the receiver operating characteristic curve (AUROC) (0.96) than ICISS-2015 for accuracy (0.85), sensitivity (0.88), specificity (0.85), PPV (0.03), LR+ (5.94), and AUROC (0.94). However, regarding sensitivity, ICISS-2020 < 0.9 showed a lower value of 0.81 compared to ICISS-2015 < 0.9, which was 0.88. The negative predictive value (NPV) was 1.00 for both versions. CONCLUSIONS: The newly developed ICISS-2020, utilizing a nationwide emergency patient database, demonstrated relatively good performance (accuracy, specificity, PPV, LR+, and AUROC) in predicting survival outcomes for patients with trauma.

Peripheral tear of the triangular fibrocartilage complex: diagnostic accuracy of magnetic resonance imaging and diagnostic performance of the primary and secondary signs.

OBJECTIVE: This study is to assess the diagnostic performance of magnetic resonance imaging (MRI) findings for type 1B triangular fibrocartilage complex (TFCC) tear of the wrist. MATERIALS AND METHODS: This study retrospectively enrolled 78 patients to examine the diagnostic performance of preoperative MRI examinations in patients with type 1B TFCC tears. Thirty-nine participants had confirmed type 1B TFCC tear. The control group included 39 patients who were randomly selected from 1157 patients who underwent MRI for wrist pain. Both groups underwent a review of 19 MRI findings by two independent radiologists, and the correlation between each diagnostic finding and type 1B TFCC tear was assessed using the chi-squared test. The 19 MRI findings comprised eight primary signs of abnormalities in the distal or proximal lamina, in conjunction with 11 secondary signs suggestive of abnormalities in the surrounding structures. RESULTS: The TFCC tear group demonstrated a significantly higher incidence of two primary MRI signs, i.e., fiber discontinuity and signal alteration in the distal lamina, as observed by both readers (R1, 74.4% vs. 38.5%, p = 0.003, and 87.2% vs. 43.6%, p < 0.001; R2, 74.4% vs. 35.9%, p = 0.001, and 87.2% vs. 53.8%, p < 0.003, respectively). Reader 2 identified a higher prevalence of two additional primary MRI signs: fiber discontinuity and signal alteration in the proximal lamina (all p < 0.05). None of the 11 secondary MRI signs demonstrated statistically significant associations with type 1B TFCC. CONCLUSION: MRI manifestations of fiber discontinuity and signal alteration in the distal lamina may provide predictive markers for type 1B TFCC wrist tear.

Cerebrospinal fluid flow artifact reduction with deep learning to optimize the evaluation of spinal canal stenosis on spine MRI.

PURPOSE: The aim of study was to employ the Cycle Generative Adversarial Network (CycleGAN) deep learning model to diminish the cerebrospinal fluid (CSF) flow artifacts in cervical spine MRI. We also evaluate the agreement in quantifying spinal canal stenosis. METHODS: For training model, we collected 9633 axial MR image pairs from 399 subjects. Then, additional 104 image pairs from 19 subjects were gathered for the test set. The deep learning model was developed using CycleGAN to reduce CSF flow artifacts, where T2 TSE images served as input, and T2 FFE images, known for fewer CSF flow artifacts. Post training, CycleGAN-generated images were subjected to both quantitative and qualitative evaluations for CSF artifacts. For assessing the agreement of spinal canal stenosis, four raters utilized an additional 104 pairs of original and CycleGAN-generated images, with inter-rater agreement evaluated using a weighted kappa value. RESULTS: CSF flow artifacts were reduced in the CycleGAN-generated images compared to the T2 TSE and FFE images in both quantitative and qualitative analysis. All raters concordantly displayed satisfactory estimation results when assessing spinal canal stenosis using the CycleGAN-generated images with T2 TSE images (kappa = 0.61-0.75) compared to the original FFE with T2 TSE images (kappa = 0.48-0.71). CONCLUSIONS: CycleGAN demonstrated the capability to produce images with diminished CSF flow artifacts. When paired with T2 TSE images, the CycleGAN-generated images allowed for more consistent assessment of spinal canal stenosis and exhibited agreement levels that were comparable to the combination of T2 TSE and FFE images.

Assessing visibility and bone changes of spinal metastases in CT scans: a comprehensive analysis across diverse cancer types.

OBJECTIVES: To analyze the characteristics of spinal metastasis in CT scans across diverse cancers for effective diagnosis and treatment, using MRI as the gold standard. METHODS: A retrospective study of 309 patients from four centers, who underwent concurrent CT and spinal MRI, revealing spinal metastasis, was conducted. Data on metastasis including total number, volume, visibility on CT (visible, indeterminate, or invisible), and type of bone change were collected. Through chi-square and Mann-Whitney U tests, we characterized the metastasis across diverse cancers and investigated the variation in the intra-individual ratio representing the percentage of lesions within each category for each patient. RESULTS: Out of 3333 spinal metastases from 309 patients, 55% were visible, 21% indeterminate, and 24% invisible. Sclerotic and lytic lesions made up 47% and 43% of the visible and indeterminate categories, respectively. Renal cell carcinoma (RCC), prostate cancer, and hepatocellular carcinoma (HCC) had the highest visibility at 86%, 73%, and 67% (p < 0.0001, p < 0.0001, and p = 0.003), while pancreatic cancer was lowest at 29% (p < 0.0001). RCC and HCC had significantly high lytic metastasis ratios (interquartile range (IQR) 0.96-1.0 and 0.31-1.0, p < 0.001 and p = 0.005). Prostate cancer exhibited a high sclerotic lesion ratio (IQR 0.52-0.97, p < 0.001). About 39% of individuals had invisible or indeterminate lesions, even with a single visible lesion on CT. The intra-individual ratio for indeterminate and invisible metastases surpassed 18%, regardless of the maximal size of the visible metastasis. CONCLUSIONS: This study highlights the variability in characteristics of spinal metastasis based on the primary cancer type through unique lesion-centric analysis.

Profiling of endogenous metabolites and changes in intestinal microbiota distribution after GEN-001 (Lactococcus lactis) administration.

This study aimed to identify metabolic biomarkers and investigate changes in intestinal microbiota in the feces of healthy participants following administration of Lactococcus lactis GEN-001. GEN-001 is a single-strain L. lactis strain isolated from the gut of a healthy human volunteer. The study was conducted as a parallel, randomized, phase 1, open design trial. Twenty healthy Korean males were divided into five groups according to the GEN-001 dosage and dietary control. Groups A, B, C, and D1 received 1, 3, 6, and 9 GEN-001 capsules (1 × 1011 colony forming units), respectively, without dietary adjustment, whereas group D2 received 9 GEN-001 capsules with dietary adjustment. All groups received a single dose. Fecal samples were collected 2 days before GEN-001 administration to 7 days after for untargeted metabolomics and gut microbial metagenomic analyses; blood samples were collected simultaneously for immunogenicity analysis. Levels of phenylalanine, tyrosine, cholic acid, deoxycholic acid, and tryptophan were significantly increased at 5-6 days after GEN-001 administration when compared with predose levels. Compared with predose, the relative abundance (%) of Parabacteroides and Alistipes significantly decreased, whereas that of Lactobacillus and Lactococcus increased; Lactobacillus and tryptophan levels were negatively correlated. A single administration of GEN-001 shifted the gut microbiota in healthy volunteers to a more balanced state as evidenced by an increased abundance of beneficial bacteria, including Lactobacillus, and higher levels of the metabolites that have immunogenic properties.

Toll-like receptor 4 (TLR4): new insight immune and aging.

TLR4, a transmembrane receptor, plays a central role in the innate immune response. TLR4 not only engages with exogenous ligands at the cellular membrane's surface but also interacts with intracellular ligands, initiating intricate intracellular signaling cascades. Through MyD88, an adaptor protein, TLR4 activates transcription factors NF-κB and AP-1, thereby facilitating the upregulation of pro-inflammatory cytokines. Another adapter protein linked to TLR4, known as TRIF, autonomously propagates signaling pathways, resulting in heightened interferon expression. Recently, TLR4 has garnered attention as a significant factor in the regulation of symptoms in aging-related disorders. The persistent inflammatory response triggered by TLR4 contributes to the onset and exacerbation of these disorders. In addition, alterations in TLR4 expression levels play a pivotal role in modifying the manifestations of age-related diseases. In this review, we aim to consolidate the impact of TLR4 on cellular senescence and aging-related ailments, highlighting the potential of TLR4 as a novel therapeutic target that extends beyond immune responses.

The mediating effects of parenting style on the relationship between parental stress and behavioral problems in girls with precocious puberty in Korea: a cross-sectional study.

BACKGROUND: This study aimed to examine the mediating effects of parenting style on the relationship between parental stress and behavioral problems of girls with precocious puberty. METHODS: This cross-sectional study analyzed a convenience sample of 200 mothers of girls with precocious puberty at a university hospital located in a metropolitan area. The Parental Stress measurement, Parents as Social Context Questionnaire, and Korean version Child Behavior Checklist (K-CBCL) 6-18 were measured via self-report questionnaires. Descriptive, t-test, Pearson correlation, and bootstrapping analyses were used to analyze the data. RESULTS: Negative parenting styles had a full mediating effect on the relationship between parental stress and internalizing and externalizing behavioral problems. CONCLUSIONS: Care plans for parents of girls with precocious puberty should be designed and applied in health care settings to reduce internalizing and externalizing behavioral problems by decreasing negative parenting styles.

Dual-layer spectral detector CT arthrography of the shoulder: assessment of image quality and value in differentiating calcium from iodine.

BACKGROUND: Dual-layer spectral detector computed tomography (DLCT) may potentially improve CT arthrography through enhanced image quality and analysis of the chemical composition of tissue. PURPOSE: To evaluate the image quality of monoenergetic reconstructions from DLCT arthrography of the shoulder and assess the additional diagnostic value in differentiating calcium from iodine. MATERIAL AND METHODS: Images from consecutive shoulder DLCT arthrography examinations performed between December 2016 and February 2018 were retrospectively reviewed for hyperattenuating lesions within the labrum and tendons. The mean attenuation of the target lesion, noise, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR) of the virtual monoenergetic images obtained at 40-200 keV were compared with conventional 140-kVp images. Two evaluators independently classified each target lesion as contrast media or calcification, without and with DLCT spectral data. Receiver operating curve (ROC) analysis was performed to assess the diagnostic performance of shoulder DLCT arthrography, without and with the aid of spectral data. RESULTS: The study included 20 target lesions (18 DLCT arthrography examinations of 17 patients). The SNRs of the monoenergetic images at 40-60 keV were significantly higher than those of conventional images (P < 0.05). The CNRs of the monoenergetic images at 40-70 keV were significantly higher than those of conventional images (P < 0.001). The ability to differentiate calcium from iodine, without and with DLCT spectral data, did not significantly differ (P = 0.441 and P = 0.257 for reviewers 1 and 2, respectively). CONCLUSION: DLCT had no additive value in differentiating calcium from iodine in small, hyperattenuating lesions in the labrum and tendons.

The Multifunctional Protein Syntenin-1: Regulator of Exosome Biogenesis, Cellular Function, and Tumor Progression.

Syntenin acts as an adaptor and scaffold protein through its two PSD-95, Dlg, and ZO-1 (PDZ) domains, participating in multiple signaling pathways and modulating cellular physiology. It has been identified as an oncogene, promoting cancer development, metastasis, and angiogenesis in various carcinomas. Syntenin-1 is also associated with the production and release of exosomes, small extracellular vesicles that play a significant role in intercellular communication by containing bioactive molecules such as proteins, lipids, and nucleic acids. The trafficking of exosomes involves a complex interplay of various regulatory proteins, including syntenin-1, which interacts with its binding partners, syndecan and activated leukocyte cell adhesion molecule (ALIX). Exosomal transfer of microRNAs, a key cargo, can regulate the expression of various cancer-related genes, including syntenin-1. Targeting the mechanism involving the regulation of exosomes by syntenin-1 and microRNAs may provide a novel treatment strategy for cancer. This review highlights the current understanding of syntenin-1's role in regulating exosome trafficking and its associated cellular signaling pathways.

Relationship between parental stress and post-traumatic stress disorder: The moderating effect of visitation restrictions in paediatric intensive care units during COVID-19.

BACKGROUND: Visitation restrictions due to COVID-19 kept parents from being with their children who were hospitalized in the PICU and from meeting with professional staff. AIM: This study examined the moderating effect of COVID-19-induced visitation restrictions on the relationship between stress and post-traumatic stress disorder in parents of children admitted to the paediatric intensive care unit. STUDY DESIGN: We conducted a descriptive, exploratory study involving 93 parents of children hospitalized in the paediatric intensive care unit using the Korean version of the Parental Stressor Scale: Paediatric Intensive Care Unit and the Revised Impact of Events Scale. Descriptive, Pearson's correlation, and logistic regression analyses were used to investigate the data. Self-reported survey questionnaires were provided for parents to complete in a separate area of the outpatient clinic when they visited for follow-up care after their children were discharged from the paediatric intensive care unit. RESULTS: Mothers showed significantly higher post-traumatic stress disorder scores than fathers. The relationship between all the sub-domains of perceived stress and post-traumatic stress disorder was statistically significant. Visitation restrictions because of the COVID-19 pandemic had significant moderating effects on the relationship between perceived parental stress and post-traumatic stress disorder. Moreover, the moderating effects of COVID-19 were exhibited when the two sub-domains-hyperarousal and intrusion-were investigated. CONCLUSIONS: Paediatric intensive care unit visitation may be an important intervention for parental post-traumatic stress disorder. Parental visitation should be enabled, and alternative interventions should be developed in situations where visitation is prohibited. RELEVANCE TO CLINICAL PRACTICE: It is necessary to develop and apply various and effective alternatives visitation that can prepare hospitals for visiting restrictions during pandemic situations which could emerge in the future.

Monitored Anesthesia Care in Minimally Invasive Spine Surgery-A Retrospective Case Series Study.

Background and Objectives: Minimally invasive spine surgery (MISS) under monitored anesthesia care (MAC) has emerged as a treatment modality for spinal radiculopathy. It is essential to secure the airway and guarantee spontaneous respiration without endotracheal intubation during MISS in a prone position. Materials and Methods: To evaluate the feasibility and safety of MAC with dexmedetomidine during MISS, we retrospectively reviewed clinical cases. A retrospective review of medical records was conducted between September 2015 and June 2016. A total of 17 patients undergoing MISS were included. Vital signs were analyzed every 15 min. The depth of sedation was assessed using the bispectral index (BIS) and the frequency of rescue sedatives. Adverse events during anesthesia, including bradycardia, hypotension, respiratory depression, postoperative nausea, and vomiting, were evaluated. Results: All cases were completed without the occurrence of airway-related complications. None of the patients needed conversion to general anesthesia. The median maintenance dosage of dexmedetomidine for adequate sedation was 0.40 (IQR 0.40-0.60) mcg/kg/hr with a median loading dose of 0.70 (IQR 0.67-0.82) mcg/kg. The mean BIS during the main procedure was 76.46 ± 10.75. Rescue sedatives were administered in four cases (23.6%) with a mean of 1.5 mg intravenous midazolam. After dexmedetomidine administration, hypotension and bradycardia developed in six (35.3%) and three (17.6%) of the seventeen patients, respectively. Conclusions: MAC using dexmedetomidine is a feasible anesthetic method for MISS in a prone position. Hypotension and bradycardia should be monitored carefully during dexmedetomidine administration.

Long-read transcriptome sequencing provides insight into lignan biosynthesis during fruit development in Schisandra chinensis.

BACKGROUND: Schisandra chinensis, an ancient member of the most basal angiosperm lineage which is known as the ANITA, is a fruit-bearing vine with the pharmacological effects of a multidrug system, such as antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anti-osteoporosis effects. Its major bioactive compound is represented by lignans such as schisandrin. Molecular characterization of lignan biosynthesis in S. chinensis is of great importance for improving the production of this class of active compound. However, the biosynthetic mechanism of schisandrin remains largely unknown. RESULTS: To understand the potential key catalytic steps and their regulation of schisandrin biosynthesis, we generated genome-wide transcriptome data from three different tissues of S. chinensis cultivar Cheongsoon, including leaf, root, and fruit, via long- and short-read sequencing technologies. A total of 132,856 assembled transcripts were generated with an average length of 1.9 kb and high assembly completeness. Overall, our data presented effective, accurate gene annotation in the prediction of functional pathways. In particular, the annotation revealed the abundance of transcripts related to phenylpropanoid biosynthesis. Remarkably, transcriptome profiling during fruit development of S. chinensis cultivar Cheongsoon revealed that the phenylpropanoid biosynthetic pathway, specific to coniferyl alcohol biosynthesis, showed a tendency to be upregulated at the postfruit development stage. Further the analysis also revealed that the pathway forms a transcriptional network with fruit ripening-related genes, especially the ABA signaling-related pathway. Finally, candidate unigenes homologous to isoeugenol synthase 1 (IGS1) and dirigent-like protein (DIR), which are subsequently activated by phenylpropanoid biosynthesis and thus catalyze key upstream steps in schisandrin biosynthesis, were identified. Their expression was increased at the postfruit development stage, suggesting that they may be involved in the regulation of schisandrin biosynthesis in S. chinensis. CONCLUSIONS: Our results provide new insights into the production and accumulation of schisandrin in S. chinensis berries and will be utilized as a valuable transcriptomic resource for improving the schisandrin content.

T cell-intrinsic miR-155 is required for Th2 and Th17-biased responses in acute and chronic airway inflammation by targeting several different transcription factors.

Asthmatic airway inflammation is divided into two typical endotypes: Th2-mediated eosinophilic and Th1- or Th17-mediated neutrophilic airway inflammation. The miRNA miR-155 has well-documented roles in the regulation of adaptive T-cell responses and innate immunity. However, no specific cell-intrinsic role has yet been elucidated for miR-155 in T cells in the course of Th2-eosinophilic and Th17-neutrophilic airway inflammation using actual in vivo asthma models. Here, using conditional KO (miR155ΔCD4 cKO) mice that have the specific deficiency of miR-155 in T cells, we found that the specific deficiency of miR-155 in T cells resulted in fully suppressed Th2-type eosinophilic airway inflammation following acute allergen exposure, as well as greatly attenuated the Th17-type neutrophilic airway inflammation induced by repeated allergen exposure. Furthermore, miR-155 in T cells appeared to regulate the expression of several different target genes in the functional activation of CD4+ Th2 and Th17 cells. To be more precise, the deficiency of miR-155 in T cells enhanced the expression of c-Maf, SOCS1, Fosl2 and Jarid2 in the course of CD4+ Th2 cell activation, while C/EBPß was highly enhanced in CD4+ Th17 cell activation in the absence of miR-155 expression. Conclusively, our data revealed that miR-155 could promote Th2 and Th17-mediated airway inflammation via the regulation of several different target genes, depending on the context of asthmatic diseases. Therefore, these results provide valuable insights into actual understanding of specific cell-intrinsic role of miR-155 in eosinophilic and neutrophilic airway inflammation for the development of fine-tune therapeutic strategies.

Checkpoint Kinase 1 (CHK1) Functions as Both a Diagnostic Marker and a Regulator of Epithelial-to-Mesenchymal Transition (EMT) in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is more difficult to treat and has a higher mortality rate than other subtypes. Although hormone receptor-targeted therapy is an effective treatment to increase survival rate in breast cancer patients, it is not suitable for TNBC patients. To address the issues, differentially expressed genes (DEGs) in TNBC patients from the Gene Expression Omnibus (GEO) database were analyzed. A total of 170 genes were obtained from three Genomic Spatial Events (GSEs) using the intersection of each GSE dataset and 61 DEGs were identified after validation with the gene enrichment analysis. We combined this with the degree scores from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network, of which 7 genes were correlated with survival rate. Finally, a proteomics database revealed that only the CHK1 protein level was differently expressed in basal-like compared with other subtypes. We demonstrated that CHK1 expression was higher in TNBC cell lines compared with non-TNBC cell lines, and CHK1 promotes epithelial to mesenchymal transition (EMT) as well as migration and invasion ability. Our study provides new insight into the TNBC subnetwork that may be useful in the prognosis and treatment of TNBC patients.

Comparison between Antegrade versus Retrograde Ureteral Stent Placement for Malignant Ureteral Obstruction.

PURPOSE: To compare the technical success of antegrade uteral stent (AUS) and retrograde ureteral stent (RUS) placements in patients with malignant ureteral obstruction (MUO) and to determine the predictors of technical failure of RUS. MATERIALS AND METHODS: This study retrospectively included 61 AUS placements (44 patients) performed under fluoroscopic guidance and 76 RUS placements (55 patients) performed under cystoscopic guidance in patients with MUO from January 2019 to December 2020. Technical success rates of the 2 techniques were compared using inverse probability of treatment weighting (IPTW) analysis. Logistic regression was used to identify predictive factors for technical failures. RESULTS: Technical success was achieved in 98.4% of the AUS group and 47.4% of the RUS group. After stabilized IPTW, the technical success rate was higher in the AUS group than in the RUS group (adjusted risk difference, 49.4%; 95% confidence interval [CI], 35.4%-63.1%). The independent predictors for technical failure of the RUS procedure were age of ≥65 years (odds ratio [OR], 5.56; 95% CI, 1.73-21.27), ureteral orifice invasion (OR, 4.21; 95% CI, 1.46-13.46), and extrinsic cancer (OR, 15.58; 95% CI, 2.92-111.81). CONCLUSIONS: The technical success rate of AUS placement was higher than that of RUS placement in patients with MUO. RUS failure was associated with age of ≥65 years, cancer with ureteral orifice invasion, and extrinsic ureteral obstruction.

Discovery of donor age markers from bloodstain by LC-MS/MS using a metabolic approach.

Bloodstains are frequently encountered at crime scenes and they provide important evidence about the incident, such as information about the victim or suspect and the time of death or other events. Efforts have been made to identify the age of the bloodstain's donor through genomic approaches, but there are some limitations, such as the availability of databases and the quality dependence of DNA. There is a need for the development of a tool that can obtain information at once from a small blood sample. The aim of this study is to identify bloodstain metabolite candidates that can be used to determine donor age. We prepared bloodstain samples and analyzed metabolites using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Eighteen molecular features (MFs) were selected as candidates using volcano plots and multivariate analysis. Based on the MS/MS spectrum of the MFs, the following nine metabolites were identified from the METaboliteLINk database: Δ2-cis eicosenoic acid, ergothioneine, adenosine 5'-monophosphate, benzaldehyde, phenacylamine, myristic acid ethyl ester, p-coumaric acid, niacinamide, and N-arachidonoyl-L-alanine. These nine age markers at high or low abundances could be used to estimate the age of a bloodstain's donor. This study was the first to develop metabolite age markers that can be used to analyze crime scene bloodstains.