PCW-A1001, AI-assisted design approach to design a selective inhibitor for FLT-3(D835Y) in acute myeloid leukemia.

Treating acute myeloid leukemia (AML) by targeting FMS-like tyrosine kinase 3 (FLT-3) is considered an effective treatment strategy. By using AI-assisted hit optimization, we discovered a novel and highly selective compound with desired drug-like properties with which to target the FLT-3 (D835Y) mutant. In the current study, we applied an AI-assisted design approach to identify a novel inhibitor of FLT-3 (D835Y).

Indolin-2-one Nitroimidazole Antibiotics Exhibit an Unexpected Dual Mode of Action.

Nitroimidazoles such as metronidazole are used as anti-infective drugs against anaerobic bacteria. Upon reduction of the nitro group, reactive radicals damage DNA and proteins in the absence of oxygen. Unexpectedly, a recent study of nitroimidazoles linked to an indolin-2-one substituent revealed potent activities against aerobic bacteria.

PCW-1001, a Novel Pyrazole Derivative, Exerts Antitumor and Radio-Sensitizing Activities in Breast Cancer.

As pyrazole and its derivatives have a wide range of biological activities, including anticancer activity, the design of novel pyrazole derivatives has emerged as an important research field. This study describes a novel pyrazole derivative that exerts antitumor and radiosensitizing activities in breast cancer both and . We synthesized a novel pyrazole compound N,N-dimethyl-N'-(3-(1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)phenyl)azanesulfonamide (PCW-1001) and showed that it inhibited several oncogenic properties of breast cancer both and .

Electrochemical Synthesis of Glycine from Oxalic Acid and Nitrate.

In manufacturing C-N bond-containing compounds, it is an important challenge to alternate the conventional methodologies that utilize reactive substrates, toxic reagents, and organic solvents. In this study, we developed an electrochemical method to synthesize a C-N bond-containing molecule avoiding the use of cyanides and amines by harnessing nitrate (NO ) as a nitrogen source in an aqueous electrolyte. In addition, we utilized oxalic acid as a carbon source, which can be obtained from electrochemical conversion of CO Thus, our approach can provide a route for the utilization of anthropogenic CO and nitrate wastes, which cause serious environmental problems including global warming and eutrophication.

Synthesis and Structure-Activity Relationships of Aristoyagonine Derivatives as Brd4 Bromodomain Inhibitors with X-ray Co-Crystal Research.

Epigenetic regulation is known to play a key role in progression of anti-cancer therapeutics. Lysine acetylation is an important mechanism in controlling gene expression. There has been increasing interest in bromodomain owing to its ability to modulate transcription of various genes as an epigenetic 'reader.

Degrasyn exhibits antibiotic activity against multi-resistant Staphylococcus aureus by modifying several essential cysteines.

Degrasyn inhibits deubiquitination enzymes and has anti-cancer activity. We here show that it also exhibits antimicrobial activity against multi-resistant Staphylococcus aureus. Structure activity relationship studies demonstrate an important role of the electrophilic α-cyanoacrylamide moiety as a Michael acceptor.

Minimally Invasive Single-Site Cholecystectomy in Obese Patients: Laparoscopic vs. Robotic.

Purpose: Laparoscopic cholecystectomy is treatment method for management of benign gallbladder diseases. Further attempts are made to operate single-port laparoscopic cholecystectomy. However, single-port laparoscopic cholecystectomy, the procedure remains technically difficult, especially in obese patient.

Bronchoscopic management of solitary bronchial myelolipoma: a case report.

Background: Myelolipoma is a rare benign tumor composed of mature adipose and hematopoietic tissues. Most myelolipomas are found in the adrenal glands, whereas intrathoracic myelolipoma is extremely rare. In particular, bronchial myelolipoma without the involvement of lung parenchyma has never been reported.

Clinical outcomes of radial probe endobronchial ultrasound using a guide sheath for diagnosis of peripheral lung lesions in patients with pulmonary emphysema.

Background: Generally, structural destruction of lung parenchyma, such as pulmonary emphysema, is considered to be related to the low diagnostic yields and high complication rates of lung biopsies of peripheral lung lesions. Currently, little is known about the clinical outcomes of using endobronchial ultrasound with a guide sheath (EBUS-GS) to diagnose peripheral lesions in patients with emphysema.

Methods: This retrospective study was performed to identify the clinical outcomes of EBUS-GS in patients with pulmonary emphysema.

Time to appropriate treatment in patients with multidrug-resistant tuberculosis in South Korea: Are we still in 2010?

Background: This study investigated the time to appropriate treatment and factors affecting late treatment initiation in patients with multidrug-resistant tuberculosis (MDR-TB) in South Korea.

Methods: Data from patients with culture-confirmed pulmonary MDR-TB who received treatment at Pusan National University Hospital (PNUH) between January 2010 and July 2018 were reviewed retrospectively. Patients were divided into two groups according to the first institution they visited [patients who were transferred to PNUH after diagnosis of MDR-TB (Group A) and patients who were initially diagnosed with TB at PNUH (Group B)].

Regression-Based Network Estimation for High-Dimensional Genetic Data.

Given the continuous advancement in genome sequencing technology, large volumes of gene expression data can be easily obtained. However, the corresponding increase in genetic information necessitates adoption of a new approach for network estimation. Data dimensions increase with the progress in genome sequencing technology, thereby making it difficult to estimate gene networks by causing multicollinearity.

Discovery of Novel Pyruvate Dehydrogenase Kinase 4 Inhibitors for Potential Oral Treatment of Metabolic Diseases.

Pyruvate dehydrogenase kinase 4 (PDK4) activation is associated with metabolic diseases including hyperglycemia, insulin resistance, allergies, and cancer. Structural modifications of hit anthraquinone led to the identification of a new series of allosteric PDK4 inhibitors. Among this series, compound 8c showed promising in vitro activity with an IC value of 84 nM.

The use of bedaquiline to treat patients with multidrug-resistant tuberculosis and end-stage renal disease: A case report.

The use of bedaquiline to treat patients with multidrug-resistant tuberculosis (MDR-TB) and end-stage renal disease (ESRD) may raise safety concerns. Currently, no clinical information is available on the use of bedaquiline to treat MDR-TB patients with ESRD. We report the use of bedaquiline to treat two patients with MDR-TB and ESRD.

A Chemical Disruptor of the ClpX Chaperone Complex Attenuates the Virulence of Multidrug-Resistant Staphylococcus aureus.

The Staphylococcus aureus ClpXP protease is an important regulator of cell homeostasis and virulence. We utilized a high-throughput screen against the ClpXP complex and identified a specific inhibitor of the ClpX chaperone that disrupts its oligomeric state. Synthesis of 34 derivatives revealed that the molecular scaffold is restrictive for diversification, with only minor changes tolerated.

Design, synthesis, and biological evaluation of aryl N-methoxyamide derivatives as GPR119 agonists.

A series of N-methoxyamide derivatives was identified and evaluated as GPR119 agonists. Several N-methoxyamides with thienopyrimidine and pyridine scaffolds showed potent GPR119 agonistic activities. Among them, compound 9c displayed good in vitro activity and potency.

Evaluation of Verigene Blood Culture Test Systems for Rapid Identification of Positive Blood Cultures.

The performance of molecular tests using the Verigene Gram-Positive and Gram-Negative Blood Culture nucleic acid tests (BC-GP and BC-GN, resp.; Naosphere, Northbrook, IL, USA) was evaluated for the identification of microorganisms detected from blood cultures. Ninety-nine blood cultures containing Gram-positive bacteria and 150 containing Gram-negative bacteria were analyzed using the BC-GP and BC-GN assays, respectively.

The Natural Course of Endobronchial Inflammatory Polyps as a Complication after Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration.

We presented a case of unusual endobronchial inflammatory polyps as a complication following endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in a patient with tuberculous lymphadenitis. EBUS-TBNA of the right hilar lymph node was performed in a 29-year-old, previously healthy man. The patient was confirmed with tuberculous lymphadenitis and received antituberculosis medication over the course of 6 months.

Clonal and horizontal spread of the blaOXA-232 gene among Enterobacteriaceae in a Korean hospital.

All 16 Klebsiella pneumoniae isolates and both Escherichia coli isolates harbored the bla(OXA-232) and bla(CTX-M-15) genes. Furthermore, all 16 K. pneumoniae isolates belonged to a unique pulsed-field gel electrophoresis clone and were assigned to an identical sequence type (ST14).

Analysis of rotavirus genotypes in Korea during 2013: an increase in the G2P[4] genotype after the introduction of rotavirus vaccines.

Background: Group A rotavirus is the leading cause of acute gastroenteritis in children worldwide. We investigated G and P genotypes of group A rotavirus strains isolated from patients during 2013 and investigated which genotypes were identified from vaccinated patients.

Methods: From January to December 2013, 2235 fecal specimens were tested for rotavirus antigen, of which 374 specimens (16.

Changes in the incidence of Streptococcus pneumoniae bacteremia and its serotypes over 10 years in one hospital in South Korea.

Here, we examined the distribution of pneumococcal serotypes and the antibiotic susceptibility of Streptococcus pneumoniae in clinical blood isolates. The serotypes of 91 S. pneumoniae blood isolates, collected from January 2003 to March 2014, were identified by multiplex PCR and sequencing.

Synthesis and biological evaluation of thienopyrimidine derivatives as GPR119 agonists.

A series of thienopyrimidine derivatives was synthesized and evaluated for their GPR119 agonistic ability. Several thienopyrimidine derivatives containing R(1) and R(2) substituents displayed potent GPR119 agonistic activity. Among them, compound 5d, which is a prototype, showed good in vitro activity with an EC50 value of 3 nM and human and rat liver microsomal stability.

Analysis of reporting time for identification of methicillin-resistant Staphylococcus aureus carriers using ChromID MRSA.

We assessed the reporting times for identification of nasal methicillin-resistant Staphylococcus aureus (MRSA) carriers in 2011 in a university-affiliated hospital using surveillance cultures incubated for 1 and 2 days with ChromID MRSA (bioMérieux, France). Of 2,732 nasal swabs tested, MRSA was detected in 829 (85.6%) and 140 (14.