Microfluidic post-insertion of polyethylene glycol lipids and KK or RGD high functionality and quality lipids in milk-derived extracellular vesicles.

To achieve the desired delivery effect, extracellular vesicles (EVs) must bypass rapid clearance from circulation and exhibit affinity for target cells; however, it is difficult to simultaneously incorporate two materials into EVs. Post-insertion is a general modification method that can be performed by simply mixing different solutions. Previously, we have developed a microfluidic post-insertion method that supported fast and upscaled modification of EVs using KK-modified high-functionality and -quality (HFQ) lipids.

Synthesis of a novel adapter lipid using Fc-region mediated antibody modification for post-insert preparation of transferrin receptor targeted messenger RNA-loaded lipid nanoparticles.

Lipid nanoparticles (LNPs) are promising delivery systems with the ability to deliver small interfering RNA (siRNA) and messenger RNA (mRNA) in diseased tissues and intracellular sites of action. However, delivery to non-hepatic tissues via systemic administration remains challenging. Antibody modification of LNPs is a hopeful approach for improving their selectivity to target tissues.

BOD1L mediates chromatin binding and non-canonical function of H3K4 methyltransferase SETD1A.

The H3K4 methyltransferase SETD1A plays an essential role in both development and cancer. However, essential components involved in SETD1A chromatin binding remain unclear. Here, we discovered that BOD1L exhibits the highest correlated SETD1A co-dependency in human cancer cell lines.

Integrated enhancer regulatory network by enhancer-promoter looping in gastric cancer.

Enhancer -regulatory elements play critical roles in gene regulation at many stages of cell growth. Enhancers in cancer cells also regulate the transcription of oncogenes. In this study, we performed a comprehensive analysis of long-range chromatin interactions, histone modifications, chromatin accessibility and expression in two gastric cancer (GC) cell lines compared to normal gastric epithelial cells.

Two cases of strangulated bowel obstruction due to exposed vessel and nerve after laparoscopic and robot-assisted lateral lymph node dissection (LLND) for rectal cancer.

Background: The majority of small bowel obstructions (SBO) are caused by adhesion due to abdominal surgery. Internal hernias, a very rare cause of SBO, can arise from exposed blood vessels and nerves during pelvic lymphadenectomy (PL). In this report, we present two cases of SBO following laparoscopic and robot-assisted lateral lymph node dissection (LLND) for rectal cancer, one case each, of which obstructions were attributed to the exposure of blood vessels and nerves during the procedures.

Correction: Investigation of the new non-invasive semi-quantitative method of 123I-IMP pediatric cerebral perfusion SPECT.

[This corrects the article DOI: 10.1371/journal.pone.

SETD1A function in leukemia is mediated through interaction with mitotic regulators BuGZ/BUB3.

The H3K4 methyltransferase SETD1A plays a crucial role in leukemia cell survival through its noncatalytic FLOS domain-mediated recruitment of cyclin K and regulation of DNA damage response genes. In this study, we identify a functional nuclear localization signal in and interaction partners of the FLOS domain. Our screen for FLOS domain-binding partners reveals that the SETD1A FLOS domain binds mitosis-associated proteins BuGZ/BUB3.

Determination of Arsenic Species in Edible Insects by LC-ICP-MS.

Background: Edible insects may contain arsenic. Analysis of arsenic species is necessary in order to accurately assess arsenic exposure.

Objective: An analytical method was validated and used to determine and quantitate arsenic species in edible insects.

Development of an apolipoprotein E mimetic peptide-lipid conjugate for efficient brain delivery of liposomes.

Liposomes are versatile carriers that can encapsulate various drugs; however, for delivery to the brain, they must be modified with a targeting ligand or other modifications to provide blood-brain barrier (BBB) permeability, while avoiding rapid clearance by reticuloendothelial systems through polyethylene glycol (PEG) modification. BBB-penetrating peptides act as brain-targeting ligands. In this study, to achieve efficient brain delivery of liposomes, we screened the functionality of eight BBB-penetrating peptides reported previously, based on high-throughput quantitative evaluation methods with BBB permeability evaluation system using Transwell, brain perfusion system, and others.

Effect of Cholesterol Content of Lipid Composition in mRNA-LNPs on the Protein Expression in the Injected Site and Liver After Local Administration in Mice.

Delivery of messenger RNA (mRNA) using lipid nanoparticles (LNPs) is expected to be applied to various diseases following the successful clinical use of the mRNA COVID-19 vaccines. This study aimed to evaluate the effect of the cholesterol molar percentage of mRNA-LNPs on protein expression in hepatocellular carcinoma-derived cells and in the liver after intramuscular or subcutaneous administration of mRNA-LNPs in mice. For mRNA-LNPs with cholesterol molar percentages reduced to 10 mol% and 20 mol%, we formulated neutral charge particles with a diameter of approximately 100 nm and polydispersity index (PDI) <0.

Stability Study of mRNA-Lipid Nanoparticles Exposed to Various Conditions Based on the Evaluation between Physicochemical Properties and Their Relation with Protein Expression Ability.

Lipid nanoparticles (LNPs) are currently in the spotlight as delivery systems for mRNA therapeutics and have been used in the Pfizer/BioNTech and Moderna COVID-19 vaccines. mRNA-LNP formulations have been indicated to require strict control, including maintenance at fairly low temperatures during their transport and storage. Since it is a new pharmaceutical modality, there is a lack of information on the systematic investigation of how storage and handling conditions affect the physicochemical properties of mRNA-LNPs and their protein expression ability.

In vitro antibacterial activity of OPS-2071 against Gram-positive and Gram-negative enteropathogenic bacteria.

Background: Enteric infections are a major public health issue in developing countries. Antimicrobial resistance is also a problem for enteric infection. OPS-2071 is a novel quinolone antibiotic with low oral absorption and potent antibacterial activity against Clostridioides difficile.

Antibacterial and Immunosuppressive Effects of OPS-2071, a Candidate Therapy for Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Although many types of drug are used, clinical outcomes are still unsatisfactory. Previous studies have suggested that intestinal bacteria are involved in the pathogenesis of IBD.

[An Evaluation of Radiation Dose for Wide Volume Scan during Chest CT].

Purpose: A volume scan can cover a range of 160 mm with a single gantry rotation. It can be performed sequentially (a wide volume [WV] scan) to cover more than 160 mm, and volume Xact+ (Xact+) can be used when volume scan is done to extend the reconstruction area. The purpose of this study was to investigate the dose distribution and organ doses for a WV scan during chest CT.

and Antibacterial Activities of a Novel Quinolone Compound, OPS-2071, against Clostridioides difficile.

OPS-2071 is a novel quinolone antibacterial agent characterized by low oral absorption that reduces the risk of adverse events typical of fluoroquinolone class antibiotics. The and antibacterial activities of OPS-2071 against were evaluated in comparison to vancomycin and fidaxomicin. OPS-2071 exhibited potent antibacterial activity against 54 clinically isolated strains with a MIC of 0.

Cumulative Fraction of Response for Once- and Twice-Daily Delamanid in Patients with Pulmonary Multidrug-Resistant Tuberculosis.

Pharmacokinetic (PK) and pharmacodynamic (PD) analyses were conducted to determine the cumulative fraction of response (CFR) for 100 mg twice-daily (BID) and 200 mg once-daily (QD) delamanid in patients with multidrug-resistant tuberculosis (MDR-TB), using a pharmacodynamic target (PDT) that achieves 80% of maximum efficacy. First, in the mouse model of chronic TB, the PK/PD index for delamanid efficacy was determined to be area under the drug concentration-time curve over 24 h divided by MIC (AUC/MIC), with a PDT of 252. Second, in the hollow-fiber system model of tuberculosis, plasma-equivalent PDTs were identified as an AUC/MIC of 195 in log-phase bacteria and 201 in pH 5.

OPC-167832, a Novel Carbostyril Derivative with Potent Antituberculosis Activity as a DprE1 Inhibitor.

There is an urgent need for new, potent antituberculosis (anti-TB) drugs with novel mechanisms of action that can be included in new regimens to shorten the treatment period for TB. After screening a library of carbostyrils, we optimized 3,4-dihydrocarbostyril derivatives and identified OPC-167832 as having potent antituberculosis activity. The MICs of the compound for ranged from 0.

Adduct Formation of Delamanid with NAD in Mycobacteria.

Delamanid (DLM), a nitro-dihydroimidazooxazole derivative currently approved for pulmonary multidrug-resistant tuberculosis (TB) therapy, is a prodrug activated by mycobacterial 7,8-didemethyl-8-hydroxy 5-deazaflavin electron transfer coenzyme (F)-dependent nitroreductase (Ddn). Despite inhibiting the biosynthesis of a subclass of mycolic acids, the active DLM metabolite remained unknown. Comparative liquid chromatography-mass spectrometry (LC-MS) analysis of DLM metabolites revealed covalent binding of reduced DLM with a nicotinamide ring of NAD derivatives (oxidized form) in DLM-treated var.

Diaryliodonium Salt-Mediated Intramolecular C-N Bond Formation Using Boron-Masking -Hydroxyamides.

Intramolecular aromatic C-N bond formation reactions using electron-rich aromatic tethered boron-masking -hydroxyamide as substrate were realized. These new C-N bond formation reactions involve the in situ generation of a diaryliodonium salt by treatment with hypervalent iodine, deborylation by base treatment, spontaneous N → O acyl migration, cyclization, reductive elimination, elimination of benzoic acid, and tautomerization to indole formation. Hereby, we obtained highly functionalized electron-rich indoles and quinoline in practical yields.

Investigation of the relation between administered dose and image quality for pediatric Tc-DMSA renal scintigraphy: clinical study applying the JSNM (Japanese Society of Nuclear Medicine) pediatric dosage card : The Japanese Society of Nuclear Medicine Technology (JSNMT), the Optimization of Imaging Technique Committee for Pediatric Nuclear Medicine Studies.

Purpose: In 2013, the Japanese Society of Nuclear Medicine (JSNM) announced consensus guidelines for pediatric nuclear medicine. These JSNM guidelines proposed use of lower administered doses compared with traditionally determined doses, which were estimated from age, weight or body surface area (BSA) based on the administered dose for adults in Japan. When the JSNM guidelines are used, the relationship between this recommended administered dose and image quality remains unclear.

Delamanid: From discovery to its use for pulmonary multidrug-resistant tuberculosis (MDR-TB).

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is the leading cause of death from an infectious disease globally. The widespread and ever-increasing resistance to TB drugs is reducing the effectiveness of treatment and jeopardizing TB control. New effective drugs with acceptable safety profiles are needed to turn the tide.