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Abstract Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.

Objectives The incidence of treatment failures following standard triple therapy (STT) for Helicobacter pylori eradication (HPE) has reached an unacceptable level. Sequential therapy (SQ) has emerged as a promising approach to counteract the escalation of antibiotic resistance. In this study, we used a chronological cohort dataset to conduct a comparative analysis of the eradication rates, compliance, and adverse events associated with the 7-day STT and SQ. Methods A total of 789 patients underwent HPE treatment at Asan Medical Center between July 2013 and August 2017. Among them, 378 received a 7-day STT and 411 received a 10-day SQ. Baseline clinical data and treatment parameters were compared between the two treatment groups. Results SQ demonstrated an eradication rate of 84.7% (348/411), which was superior to that of the 7-day STT (74.1%; p

Background/Aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p

Nonalcoholic fatty liver is involved in the development of nonalcoholic steatohepatitis and chronic liver injury. Impairment of hepatic transsulfuration reactions is suggested to be critically linked with alcoholic liver injury, but its role in nonalcoholic fatty liver remains unknown. We examined the early changes in sulfur-amino acid metabolism and their implication in nonalcoholic fatty liver disease (NAFLD). Male rats were provided with a standard liquid diet or a high-fat liquid diet (HF) for 3 wk. An additional group of rats received the HF diet supplemented with betaine (1%). HF diet intake elevated hepatic triglyceride and serum tumor necrosis factor-[alpha] (TNF[alpha]) concentrations. Antioxidant capacity of liver cytosol against hydroxyl and peroxyl radicals was reduced significantly. Hepatic S-adenosylmethionine (SAM) and glutathione (GSH) decreased, but hypotaurine and taurine concentrations increased. Methionine adenosyltransferase (MAT) activity, not its concentration, was depressed, whereas both activity and concentration of cysteine dioxygenase and GSH S-transferase were elevated. Betaine supplementation of the HF diet inhibited hepatic fat accumulation and serum TNF[alpha] elevation. The decrease in cytosolic antioxidant capacity was also prevented. MAT activity and its concentration were induced significantly. Hepatic SAM and GSH increased and elevation of hypotaurine and taurine was depressed. The results indicate that the metabolism of S-containing substances is significantly disturbed by the HF diet, suggesting a causal role of impairment of hepatic transsulfuration reactions in NAFLD. Betaine supplementation protects the liver from nonalcoholic steatosis and oxidative stress most probably via its effects on the transsulfuration reactions.

Author(s): Hee K. Chae [1, 4]; Diana Y. Siberio-Pérez [1, 2]; Jaheon Kim [1]; YongBok Go [1]; Mohamed Eddaoudi [1]; Adam J. Matzger [1, 2]; Michael O'Keeffe (corresponding author) [3, [...]

The atomic force microscopy (AFM) is used to study the photocatalytic decomposition of octadecyltrichlorosilane (OTS) based self-assembled monolayer formed on TiO2. The reactive oxidizing species attack the alkyl radicals on the TiO2 surface producing alkoxy radicals and carbonyls.

Author(s): Omar M. Yaghi (corresponding author) [1, 2]; Michael O'Keeffe [1, 3]; Nathan W. Ockwig [1, 2]; Hee K. Chae [1, 2, 4]; Mohamed Eddaoudi [1, 2]; Jaheon Kim [1, [...]

Abstract Objective KINDLE‐Korea is part of a real‐world KINDLE study that aimed to characterize the treatment patterns and clinical outcomes of patients with stage III non‐small cell lung cancer (NSCLC). Materials and Methods The KINDLE was an international real‐world study that explores patient and disease characteristics, treatment patterns, and survival outcomes. The KINDLE‐Korea included stage III NSCLC patients diagnosed between January 2013 and December 2017. Results A total of 461 patients were enrolled. The median age was 66 years (range: 24–87). Most patients were men (75.7%) with a history of smoking (74.0%), stage IIIA NSCLC (69.2%), and unresectable disease (52.9%). A total of 24.3% had activating EGFR mutation and 62.2% were positive for PDL1 expression. Broadly categorized, 44.6% of the patients received chemoradiation (CRT)‐based therapy, 35.1% underwent surgery, and 20.3% received palliative therapies as initial treatment. The most commonly adopted approaches for patients with stage IIIA and IIIB disease were surgery and CRT, respectively. The median PFS was 15.2 months and OS was 66.7 months. Age >65 years, adenocarcinoma histology, and surgery as the initial treatment were significantly associated with longer OS. Conclusion This study revealed the heterogeneity of treatment patterns and survival outcomes in patients with stage III NSCLC before durvalumab consolidation came into clinical practice. There is an unmet need for patients who are not eligible for surgery as an initial therapy. Novel therapeutic approaches are highly warranted to improve clinical outcomes.

Helical motifs form the important structure of proteins, nucleic acids and oligosaccharides. The construction of these helical motifs contributes to the development of molecular based materials such as sensors, molecular switches and intercalatodproteinsrs.

Smart molecular helical springs were investigated as tunable receptors.

Astragalus membranaceus and Cinnamomum cassia are used as spices and flavorful ingredients, or medicinal herbs with pharmacological effects. In this study, the hair-growth-promoting effects of the YH complex, a newly developed formula consisting of membranaceus and C. cassia, are investigated with the prediction of its molecular mechanism. The target gene of the YH complex was about 74.8% overlapped with the gene set of ‘Hair growth’ on the GO Biological Process database. The oral administration of the YH complex promoted hair regrowth and increased hair-shaft thickness in depilated hair loss mice. In addition, the anagen/telogen hair follicle ratio was significantly increased by the YH complex. The growth factors affecting the growth of hair follicles were dose-dependently increased by treatment with the YH complex. The Wnt/β-catenin signaling pathway expressions in skin tissues were apparently increased by the administration of the YH complex. In conclusion, the YH complex consisting of A. membranaceus and C. cassia induced hair follicle differentiation and preserved the growing-anagen phase by increasing growth factors and the Wnt/β-catenin signaling pathway, leading to the restoration of hair loss. The YH complex can be a remedy for hair loss diseases, such as alopecia areata, androgenetic alopecia, telogen effluvium, and chemotherapy-induced alopecia.

Background This study evaluated the diagnostic yield and positive predictive factors of post-percutaneous core needle biopsy (PCNB) sputum cytology in diagnosing malignancy. Methods This retrospective study included patients who underwent PCNB at a single center from January 2014 to March 2022. Patient demographics, lung lesion characteristics on computed tomography, underlying lung disease, post-PCNB complications, histopathologic results of PCNB, post-PCNB sputum specimens, and final diagnoses were reviewed. The diagnostic yields and related factors were analyzed. Results Overall, 177 consecutive patients with sputum specimens obtained after PCNB for intrapulmonary lesions were enrolled. Among them, 152 patients had a final diagnosis of malignancy. Diagnostic sputum specimens with atypical or malignant cells were obtained in 12 patients. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of sputum cytology were 7.89%, 100%, 20.90%, 100%, and 15.15%, respectively. Lesion size, air-bronchogram, lesion multiplicity, and the cell type of squamous cell and adenocarcinoma differed significantly between the groups with diagnostic versus non-diagnostic sputum (p

Background/Aims The treatment for gastric mucosa-associated lymphoid tissue lymphoma (MALToma) generally involves eradication of Helicobacter pylori. However, MALToma lesions may recur even without H. pylori re-infection. Furthermore, the remission rate of H. pylori-negative MALToma after eradication is low. Therefore, herein, we report on endoscopic submucosal dissection (ESD) as a treatment strategy for gastric MALToma. Methods We retrospectively reviewed the data of all patients of gastric MALToma who underwent endoscopic resection at our institution between January 2000 and December 2021. Clinical remission was defined as complete histological remission or probable minimal residual disease according to the GELA grading system for post-treatment evaluation of gastric MALToma. Results Six patients with gastric MALToma underwent ESD. Two patients were diagnosed with gastric MALToma, which improved after eradication treatment and relapsed approximately 36 and 41 months later, respectively. These patients had singular lesions localized to the mucosa and did not experience H. pylori re-infection. The lesions were successfully removed via ESD. The remaining four patients had H. pylori-negative gastric MALToma. These patients also had single, localized lesions that were removed via ESD. All the patients remained in clinical remission until the final follow-up. Conclusions ESD is a safe and effective intervention for H. pylori-negative gastric MALToma when the lesion is single and confined to the mucosal layer.

The stomach has become the most commonly used site for grafts to replace the esophagus in esophageal cancer surgery because of its good blood supply and ability to enable single-reconstruction anastomosis. However, anastomotic failure is a serious complication after esophageal cancer surgery. Unlike anastomotic leakage due to local ischemia, gastric tube necrosis is a life-threatening condition with a high mortality rate. Gastric tube necrosis involves extensive ischemia due to a decreased blood supply, and an urgent operation is mandatory in most cases. Endoscopic vacuum therapy (EVT) has been used for anastomotic leakage after esophageal surgery. In recent years, it has been successfully used for more extensive disease, including large esophageal perforation as an indication for reoperation. Hence, we report a case of extensive gastric tube necrosis treated by EVT after an Ivor Lewis operation.

Research has been conducted on the trinucleating ligands. The preparation of these ligands from the hexachlorocyclotriphosphazene reaction with 3,3'-dihydroxy-2,2'-bipyridine is examined.