Methylococcus mesophilus sp. nov., the first non-thermotolerant methanotroph of the genus Methylococcus, from a rice field.

Strain 16-5T, a mesophilic methanotroph of the genus Methylococcus, was isolated from rice field soil sampled in Chungcheong Province, Republic of Korea. Strain 16-5T had both particulate and soluble methane monooxygenases and could only grow on methane and methanol as electron donors. Strain 16-5 T cells are Gram-negative, white to light tan in color, non-motile, non-flagellated, diplococcoid to cocci, and have the typical type I intracytoplasmic membrane system. Strain 16-5T grew at 18-38 °C (optimum, 27 °C) and at pH 5.0-8.0 (optimum, pH 6.5-7.0). C16 : 1 ω7c (38.8%), C16 : 1 ω5c (18.8%), C16 : 1 ω6c (16.8%) and C16 : 0 (16.9%) were the major fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified phospholipid were the major polar lipids. The main respiratory quinone was methylene-ubiquinone-8. Strain 16-5T displayed the highest 16S rRNA gene sequence similarities to other taxonomically recognized members of the genus Methylococcus, i.e. Methylococcus capsulatus TexasT (98.62%) and Methylococcus geothermalis IM1T (98.49 %), which were its closest relatives. It did, however, differ from all other taxonomically described Methylococcus species due to some phenotypic differences, most notably its inability to grow at temperatures above 38 °C, where other Methylococcus species thrive. Its 4.34 Mbp-sized genome has a DNA G+C content of 62.47 mol%, and multiple genome-based properties such as average nucleotide identity and digital DNA-DNA hybridization value distanced it from its closest relatives. Based on the data presented above, this strain represents the first non-thermotolerant species of the genus Methylococcus. The name Methylococcus mesophilus sp. nov. is proposed, and 16-5T (=JCM 35359T=KCTC 82050T) is the type strain.

Metabolomic and transcriptomic changes in mungbean (Vigna radiata (L.) R. Wilczek) sprouts under salinity stress.

Mungbean (Vigna radiata) sprouts are consumed globally as a healthy food with high nutritional values, having antioxidant and anticancer capacity. Under mild salinity stress, plants accumulate more secondary metabolites to alleviate oxidative stress. In this study, metabolomic and transcriptomic changes in mungbean sprouts were identified using a reference cultivar, sunhwa, to understand the regulatory mechanisms of secondary metabolites in response to salinity stress. Under salinity conditions, the contents of phenylpropanoid-derived metabolites, including catechin, chlorogenic acid, isovitexin, p-coumaric acid, syringic acid, ferulic acid, and vitexin, significantly increased. Through RNA sequencing, 728 differentially expressed genes (DEGs) were identified and 20 DEGs were detected in phenylpropanoid and flavonoid biosynthetic pathways. Among them, 11 DEGs encoding key enzymes involved in the biosynthesis of the secondary metabolites that increased after NaCl treatment were significantly upregulated, including dihydroflavonol 4-reductase (log2FC 1.46), caffeoyl-CoA O-methyltransferase (1.38), chalcone synthase (1.15), and chalcone isomerase (1.19). Transcription factor families, such as MYB, WRKY, and bHLH, were also identified as upregulated DEGs, which play a crucial role in stress responses in plants. Furthermore, this study showed that mild salinity stress can increase the contents of phenylpropanoids and flavonoids in mungbean sprouts through transcriptional regulation of the key enzymes involved in the biosynthetic pathways. Overall, these findings will provide valuable information for molecular breeders and scientists interested in improving the nutritional quality of sprout vegetables.

Adjuvant Chemotherapy vs. Surgery Alone for pT3N0M0 Gastric Cancer.

BACKGROUND: As both the role and clinical application of adjuvant chemotherapy (CTx) for pT3N0M0 gastric cancer after curative gastrectomy have fluctuated chronologically, the oncological benefit of adjuvant CTx in patients should be elucidated. METHODS: Between 2000 and 2018, 1083 patients underwent radical gastrectomy for pT3N0M0 gastric cancer and were subsequently divided into two groups: the surgery-alone group (n = 471) and the adjuvant CTx group (n = 612). Chronological changes in adjuvant CTx and various chemotherapeutic regimens were evaluated and disease-free survival was compared between the two groups. Risk factors for tumor recurrence were also analyzed. RESULTS: The proportion of patients in the surgery-alone group was more than 60% until 2001, whereas in the CTx group this increased to over 80%, especially after publication of the American Joint Committee on Cancer (AJCC) 7th edition staging manual. The main chemotherapeutic agents were tegafur-uracil (UFT) and 5-fluorouracil with leucovorin until 2008, whereas tegafur/gimeracil/oteracil (TS-1) has been the main agent since 2009. The 5-year disease-free survival was 89.2% in the surgery-alone group and 89.9% in the CTx group, which was not significantly different (p = 0.694). In multivariate analysis, larger tumor size (≥ 4.5 cm) and venous invasion were significant risk factors for tumor recurrence. In addition, adjuvant CTx did not improve the oncological outcome, even in the large tumor size group (p = 0.760) and the venous invasion group (p = 0.753). CONCLUSIONS: As adjuvant CTx did not show any oncological benefit in pT3N0M0 gastric cancer in this large-scale study, it might be unnecessary for these patients after curative gastrectomy.

Safety and efficacy of an herbal formula, Gwakhyangjeonggi-san on atopic dermatitis with gastrointestinal symptoms: Protocol for a randomized controlled trial.

INTRODUCTION: Gwakhyangjeonggi-san (GJS) is an herbal formula with anti-inflammatory and anti-allergic properties that is broadly used to treat a wide range of diseases including gastrointestinal disorders and allergic diseases. There have been several clinical studies conducted on its effects on atopic dermatitis (AD). So far, no randomized controlled trials have been conducted. Here, we describe the protocol for a randomized controlled study designed to investigate the efficacy and safety of GJS for treating patients with AD that have gastrointestinal symptoms. METHODS AND ANALYSIS: A randomized, double-blind, placebo-controlled, parallel-group, clinical trial has been designed to investigate the clinical efficacy and safety of GJS on patients with AD that have gastrointestinal symptoms. A total of 58 participants with AD will be recruited and randomly allocated to the GJS or placebo group in a 1:1 ratio. The participants will be administered GJS or placebo granules 3 times a day for 8 weeks. Data will be collected from the participants at baseline and after 4 and 8 weeks. The primary outcome measure will be the mean change in the SCORing of Atopic Dermatitis (SCORAD) index from baseline to 8 weeks. The secondary outcomes will include the eczema area and severity index (EASI), dermatology life quality index (DLQI), EuroQoL 5 dimensions 5 levels (EQ-5D-5L), and immunological factors. The Korean Gastrointestinal Symptom Rating Scale (KGSRS), Nepean Dyspepsia Index will also be obtained for assessing the gastrointestinal status. DISCUSSION: The findings of this study are expected to provide evidence on the safety and effectiveness of GJS and for treating patients with AD that have gastrointestinal symptoms. Additionally, the study will explore the mechanism of GJS action via gut microbiome. This study will provide new perspectives on approaching treatment for AD. ETHICS AND DISSEMINATION: The study protocol was approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital at Gangdong (KHNMCOH2019-06-002-001). TRIAL REGISTRATION NUMBER: This study has been registered at the Korean National Clinical Trial Registry, Clinical Research Information Service (KCT0004299).

Delayed recovery of pediatric sudden sensorineural hearing loss treated with acupuncture: A case report.

RATIONALE: The rate of spontaneous recovery of sudden sensorineural hearing loss (SSNHL) has been reported to be as high as 32% to 65%. Although the majority of spontaneous recoveries occur within 2 weeks, treatment of refractory SSNHL failing conventional therapy is difficult. In particular, it is more difficult to treat children-who have a worse prognosis than adults-with SSNHL refractory to conventional therapy. No studies reported delayed recovery of pediatric SSNHL later than 3 months after onset, or delayed recovery treated with acupuncture. PATIENT CONCERNS: A 15-year-old girl experienced hearing loss after acquiring a cold. DIAGNOSIS: She did not undergo audiometry and only took medicine for a common cold after diagnosis by an internal medicine doctor. Ninety-three days after onset, she visited an otorhinolaryngology clinic and was diagnosed with SSNHL. Seven rounds of intratympanic steroid (ITS) treatment were performed 93 to 135 days after onset; audiogram at 149 days did not demonstrate improvement. INTERVENTIONS: Two-hundred sixty-six days after onset, she visited to TKM hospital and was admitted for 21 days and received outpatient treatment for 1 month after discharge. She was treated acupuncture, transcutaneous electrical nerve stimulation, and moxibustion. OUTCOMES: She experienced improvement in experienced improvement in pure tone average, speech recognition threshold, and word recognition scores after acupuncture treatment. Delayed ITS treatment at 93 to 135 days after onset did not improve the patient's hearing loss. However, slight recovery was achieved at the conclusion of treatment. LESSONS: Acupuncture may be a therapeutic option for individuals who do not experience improvement after the use of steroids or miss early treatment.

Discovery of novel 2-hydroxydiarylamide derivatives as TMPRSS4 inhibitors.

TMPRSS4 is a novel type II transmembrane serine protease that has been implicated in the invasion and metastasis of colon cancer cells. In this study, a novel series of 2-hydroxydiarylamide derivatives were synthesized and evaluated for inhibiting TMPRSS4 serine protease activity and suppressing cancer cell invasion. These derivatives demonstrated good inhibitory activity against TMPRSS4 serine protease, which correlated with the promising anti-invasive activity of colon cancer cells overexpressing TMPRSS4.

Structure-activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling.

A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics.