Development of a FRET aptasensor based on MoS2-doped Zn-MOF as luminophore for selective detection of cadmium in aqueous solutions.

A robust "on-off" fluorescent aptasensor was developed using nanohybrids of molybdenum sulfide (MoS2) quantum dot (QD)-doped zinc metal-organic frameworks (Zn-MOF) for selective and sensitive detection of cadmium ions (Cd2+) in water. This nanohybrid (MoS2@Zn-MOF), synthesized via "bottle around the ship" methodology, exhibited a high-intensity fluorescence emission centered at 430 nm (λEm) (blue) on excitation at 320 nm (λEx). Further, the conjugation of this fluorophore to phosphate-modified cadmium aptamer (Cd-2-2) was achieved through carbodiimide reaction. The hybridization of prepared sensing probe (MoS2@Zn-MOF/Cd-2-2 aptamer) was done with dabcyl-conjugated complementary DNA (cDNA), acting as energy donor-acceptor pair in the fluorescence resonance energy transfer (FRET) system. This hybridization causes the fluorescence quenching of the nanohybrid. In the presence of Cd2+, the aptamer from the fabricated nano-biosensing probe binds to these ions, resulting in release of dabcyl-cDNA oligomer. This release of dabcyl-cDNA oligomer from the sensing probes restores the fluorescence of the nanohybrid. Under optimized conditions (sensing probe/dabcyl-cDNA ratio 1/7, pH 7.4, and temp 28 °C), the sensing probe showed a fast response time of 1 min. The fluorescence intensity of the nanohybrid can be utilized to determine the concentration of Cd2+. The proposed aptasensor achieved highly sensitive detection of Cd2+ with a limit of detection (LOD) of 0.24 ppb over the range of 1 × 10-9 to 1 × 10-4 M along with minimal effects of interferences (e.g., Hg2+, Pb2+, and Zn2+) and good reproducibility. The designed aptasensor based on MoS2@Zn-MOF nanofluorophore offers a highly sensitive and selective approach for rapid screening of metal ions in aqueous environments.

The effects of metal-oxide content in MnO2-activated carbon composites on reactive adsorption and catalytic oxidation of formaldehyde and toluene in air.

The deterioration in air quality caused by volatile organic compounds (VOCs) has become an important environmental issue. Here, activated carbon (AC) composites with manganese oxide (MnO2: 1 % to 50 %) are synthesized as MAC for the removal of formaldehyde (FA) and toluene in air through a combination of reactive adsorption and catalytic oxidation (RACO) at room temperature (RT). The best-performing composite (MAC-20: 20 % of MnO2) exhibits a 10 % breakthrough volume (BTV10%) of FA and toluene at 41.2 and 377 L g-1, respectively while realizing complete oxidation of FA and toluene into carbon dioxide (CO2) at 100 °C and 275 °C, respectively. The reaction kinetic rates (r) for 10 % removal efficiency of FA and toluene (XFA or T) at RT are estimated as 9.82E-02 and 3.20E-02 mmol g-1 h-1, respectively. The high performance of MAC-20 can be attributed to its enriched adsorption capacity of oxygen vacancy (OV) and the presence of adsorbed oxygen (OA), as shown by an Mn3+/Mn4+ ratio of 0.729 and an OA/lattice­oxygen (OL) ratio of 1.50. The results of this study highlight the interactive roles of oxygen abundance and temperature in the generation of distinctive oxidation patterns for FA in reference to toluene. This study is expected to offer practical guidance for the implementation of RACO against diverse VOCs for efficient management of air quality.

The practical utility of ternary nickel-cobalt-manganese oxide-supported platinum catalysts for room-temperature oxidative removal of formaldehyde from the air.

Formaldehyde (FA), a carcinogenic oxygenated volatile organic compound, is present ubiquitously in indoor air. As such, it is generally regarded as a critical target for air quality management. The oxidative removal of FA under dark and room-temperature (RT) conditions is of practical significance. A series of ternary nickel-cobalt-manganese oxide-supported platinum catalysts (Pt/NiCoMnO4) have been synthesized for FA oxidative removal at RT in the dark. Their RT conversion values for 50 ppm FA (XFA) at 5,964 h-1 gas hourly space velocity (GHSV) decrease in the following order: 1 wt% Pt/NiCoMnO4 (100 %) > 0.5 wt% Pt/NiCoMnO4 (25 %) > 0.05 wt% Pt/NiCoMnO4 (14 %) > NiCoMnO4 (6 %). The catalytic performance of 1 wt% Pt/NiCoMnO4 has been examined further under the control of various process variables (e.g., catalyst mass, flow rate, relative humidity, FA concentration, time on stream, and molecular oxygen content). The catalytic oxidation of FA at low temperatures (e.g., RT and 60 °C) is accounted for by Langmuir-Hinshelwood mechanism (single-site competitive-adsorption), while Mars van Krevelen kinetics is prevalent at higher temperatures. In situ diffuse-reflectance infrared Fourier-transform spectroscopy reveals that FA oxidation proceeds through a series of reaction intermediates such as DOM, HCOO-, and CO32-. Based on the density functional theory simulations, the unique electronic structures of the nearest surface atoms (platinum and nickel) are suggested to be responsible for the superior catalytic activity of Pt/NiCoMnO4.

Endoscopic ultrasound-guided tissue sampling induced pancreatic duct leak resolved by the placement of a pancreatic stent: A case report.

BACKGROUND: Pancreatic ductal leaks complicated by endoscopic ultrasonography-guided tissue sampling (EUS-TS) can manifest as acute pancreatitis. CASE SUMMARY: A 63-year-old man presented with persistent abdominal pain and weight loss. Diagnosis: Laboratory findings revealed elevated carbohydrate antigen 19-9 (5920 U/mL) and carcinoembryonic antigen (23.7 ng/mL) levels. Magnetic resonance imaging of the pancreas revealed an approximately 3 cm ill-defined space-occupying lesion in the inferior aspect of the head, with severe encasement of the superior mesenteric artery. Pancreatic ductal adenocarcinoma was confirmed after pathological examination of specimens obtained by EUS-TS using the fanning method. Interventions and outcomes: The following day, the patient experienced severe abdominal pain with high amylase (265 U/L) and lipase (1173 U/L) levels. Computed tomography of the abdomen revealed edematous wall thickening of the second portion of the duodenum with adjacent fluid collections and a suspicious leak from either the distal common bile duct or the main pancreatic duct in the head. Endoscopic retrograde cholangiopancreatography revealed dye leakage in the head of the main pancreatic duct. Therefore, a 5F 7 cm linear plastic stent was deployed into the pancreatic duct to divert the pancreatic juice. The patient's abdominal pain improved immediately after pancreatic stent insertion, and amylase and lipase levels normalized within a week. Neoadjuvant chemotherapy was then initiated. CONCLUSION: Using the fanning method in EUS-TS can inadvertently cause damage to the pancreatic duct and may lead to clinically significant pancreatitis. Placing a pancreatic stent may immediately resolve acute pancreatitis and shorten the waiting time for curative therapy. When using the fanning method during EUS-TS, ductal structures should be excluded to prevent pancreatic ductal leakage.

Evaluation of Esthetic Results after Mass Removal with Elliptical Skin Excision Using Ultrasonography to Measure Skin Thickness.

Background: The growth of benign cutaneous masses causes the overlaying skin to expand and become thinner, especially at the central, most projected point. In this retrospective study, a surgical technique comprising an elliptical skin excision was employed to account for these skin changes. Methods: This retrospective study enrolled 980 patients with benign masses. Preoperatively, all patients underwent ultrasonography to evaluate the mass depth and thickness of the attached skin, and mass excision was performed using the elliptical skin-excision method. The operative time was recorded, and complications and esthetic outcomes were assessed using the Cutometer® and the modified Vancouver Scar Scale (mVSS) during 1- and 3-month follow-up visits. Results: The mean operative time (17.48 ± 3.46 min) was significantly shorter than that of conventional methods (p < 0.05). Cutometer parameters showed no significant differences from those of intact skin. The average mVSS scores were 5.21 ± 1.42 and 3.50 ± 1.79 at 1- and 3-month follow-ups, respectively. Conclusions: Mass excision with an elliptical skin attachment resulted in improved esthetic results and easy removal. The attached skin enabled convenient handling without damaging the capsule or other adjacent structures, leaving a thick dermis on both wound edges. Thus, this technique resulted in minimal scarring.

Sporosarcina jeotgali sp. nov., Sporosarcina oncorhynchi sp. nov., and Sporosarcina trichiuri sp. nov., Isolated from Jeotgal, a Traditional Korean Fermented Seafood.

Three novel, Gram-stain-positive, obligate aerobic, catalase- and oxidase-positive bacterial strains, designated B2O-1T, T2O-4T, and 0.2-SM1T-5T, were isolated from jeotgal, a traditional Korean fermented seafood. Strains B2O-1T, T2O-4T, and 0.2-SM1T-5T exhibited distinct colony colors, characterized by pink, yellow, and red opaque circular colonies, respectively. Phylogenetic analysis revealed that three strains formed a paraphyletic clade within the genus Sporosarcina and shared < 99.0% similarity with Sporosarcina aquimarina KCTC 3840T and Sporosarcina saromensis KCTC 13119T in their 16S rRNA gene sequences. The three strains exhibiting Orthologous Average Nucleotide Identity values < 79.3% and digital DNA-DNA hybridization values < 23.1% within the genus Sporosarcina affirmed their distinctiveness. Strains B2O-1T, T2O-4T, and 0.2-SM1T-5T contained MK-7 as a sole respiratory menaquinone and A4α type peptidoglycan based on lysine with alanine, glutamic acid, and aspartic acid. The common polar lipids include diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. Strain T2O-4T contained one unidentified phospholipid, whereas strain 0.2-SM1T-5T contained two unidentified phospholipids. Cellular fatty acid profiles, with C15:0 anteiso as the major fatty acid, supported the affiliation of the three strains to the genus Sporosarcina. Based on the polyphasic characteristics, strains B2O-1T (= KCTC 43506T = JCM 36032T), T2O-4T (= KCTC 43489T = JCM 36031T), and 0.2-SM1T-5T (= KCTC 43519T = JCM 36034T) represent three novel species within the genus Sporosarcina, named Sporosarcina jeotgali sp. nov., Sporosarcina oncorhynchi sp. nov., and Sporosarcina trichiuri sp. nov., respectively.

Anti-competitive adsorption of gaseous benzene on hydrophilic microporous carbon in humid conditions.

The adsorption capture of ambient volatile organic compounds (VOCs) is of practical importance for air quality management. Herein, unique anti-competitive adsorption behavior of benzene on a hydrophilic activated carbon (Procarb-900 (P900)) is evidenced in the presence of competing components (e.g., formaldehyde (FA) and/or moisture). Contrary to general expectations, the adsorption capacity of 10 Pa benzene (QB) onto P900 (30 mg) at the 99 % breakthrough level improves from 144.8 to 187 mg g-1 as the relative humidity (RH) increases from 0 to 25 %. Such pattern is maintained at 183.9 mg g-1 even at the relatively high RH of 50 %. Furthermore, QB exhibits a remarkable increase of 56.1 % (to 226.0 mg g-1) in the binary phase (100 ppm benzene plus 50 ppm FA) relative to its single phase (144.8 mg g-1). The kinetic studies confirm the occurrence of anti-competitive adsorption of benzene under humid conditions with the unusual decrease in rate constants at the elevated RHs (i.e., 25 and 50 %). The thermodynamic studies suggest the exothermic nature of benzene adsorption onto P900. The hydrophilicity of P900's outer surface promotes the preferential adsorption of polar FA and water vapor over non-polar benzene, which deforms the activated carbon texture and lowers the pore size distribution (PSD). The narrow PSD enhances benzene uptake in the complex systems due to the confinement effect. Overall, this study offers insights into the unique anti-competitive adsorption of non-polar VOCs (e.g., benzene) on hydrophilic microporous adsorbents in the presence of potential interferences such as polar water vapor and FA. These findings offer a guideline for the practical implementation of adsorption techniques for gaseous VOCs in humid conditions.

Characterization of Chemical Interactions between Clinical Drugs and the Oral Bacterium, Corynebacterium matruchotii, via Bioactivity-HiTES.

In the field of natural product research, the rediscovery of already-known compounds is one of the significant issues hindering new drug development. Recently, an innovative approach called bioactivity-HiTES has been developed to overcome this limitation, and several new bioactive metabolites have been successfully characterized by this method. In this study, we applied bioactivity-HiTES to Corynebacterium matruchotii, the human oral bacterium, with 3120 clinical drugs as potential elicitors. As a result, we identified two cryptic metabolites, methylindole-3-acetate (MIAA) and indole-3-acetic acid (IAA), elicited by imidafenacin, a urinary antispasmodic drug approved by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). MIAA showed weak antibacterial activity against a pulmonary disease-causing Mycobacterium conceptionense with an IC50 value of 185.7 µM. Unexpectedly, we also found that C. matruchotii metabolized fludarabine phosphate, a USFDA-approved anticancer drug, to 2-fluoroadenine which displayed moderate antibacterial activity against both Bacillus subtilis and Escherichia coli, with IC50 values of 8.9 and 20.1 µM, respectively. Finally, acelarin, a prodrug of the anticancer drug gemcitabine, was found to exhibit unreported antibacterial activity against B. subtilis with an IC50 value of 33.6 µM through the bioactivity-HiTES method as well. These results indicate that bioactivity-HiTES can also be applied to discover biotransformed products in addition to finding cryptic metabolites in microbes.

Comparative Analysis of Temperature-Responsive Hydrogel (PF 72) for Postoperative Pain After Bimaxillary Surgery: A Retro-spective Study.

Bimaxillary surgery is a painful invasive procedure in plastic surgery. Pain control is typically achieved using intravenous analgesics. We aimed to investigate the efficacy of a novel temperature-responsive hydrogel, PF72, mixed with ropivacaine, as a local pain management solution when applied directly to the surgical site following orthognathic surgery. The study was conducted from October 2022 to July 2023 and included a cohort of 40 candidates for orthognathic surgery, encompassing LeFort I maxillary ostectomy and sagittal split ramus osteotomy. The participants were divided into an Injection group (n = 20), where PF72 was administered at the surgical site before the orthognathic surgery, and a Control group (n = 20), which relied solely on intravenous analgesics. Pain was evaluated at 3, 6, 24, 48, and 72 h after surgery using a numerical rating scale (NRS). The mean NRS scores at 24 h were 6.35 and 4 for the Control and Injection groups, respectively. The mean NRS scores at 72 h were 3.4 and 2.55 for the Control and Injection groups, respectively. Patients who received PF72 experienced less pain than those who received intravenous analgesics. These findings underscore the potential of PF72 as an effective alternative for enhancing pain management in patients undergoing orthognathic surgery.Level of Evidence III Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reduced and modified graphene oxide with Ag/V2O5 as a ternary composite visible light photocatalyst against dyes and pesticides.

Water pollution by dyes and pesticides poses significant threats to our ecosystem. In this research, a visible-light ternary composite photocatalytic system was fabricated using graphene oxide (GO) by reducing with N2H4, modifying with KOH, and decorating with Ag/V2O5. The fabricated photocatalysts were characterized through FTIR, SEM, XRD, BET, PL, EDX, ESR, UV-vis spectroscopy, TGA, ESI-MS, and Raman spectroscopy. The point zero charge of the reduced and modified GO (RMGO/Ag/V2O5) was measured to be 6.7 by the pH drift method. This ternary composite was able to achieve complete removal of methyl orange (MO) and chlorpyrifos (CP) in solutions in 80 min under the optimum operation conditions (e.g., in terms of pollutant/catalyst concentrations, pH effects, and contact time). The role of active species responsible for photocatalytic activity was confirmed by scavenger analysis and ESR investigations. The potential mechanism for photocatalytic activity was studied through a fragmentation process carried out by MS analysis. Through nonlinear fitting of the experimental data, MO and CP exhibited the best fit results with the pseudo 1st-order kinetics (quantum yields of 1.07 × 10-3 and 2.16 × 10-3 molecules photon-1 and space-time yields of 1.53 × 10-5 and 2.7 × 10-5 molecules photon-1 mg-1, respectively). The structure of the nanomaterials remained mostly intact to support increased stability and reusability of the prepared photocatalysts even after 10 successive regeneration cycles.

Low-temperature oxidative removal of benzene from the air using titanium carbide (MXene)-Supported platinum catalysts.

MXenes are an emerging class of two-dimensional (2D) inorganic materials with great potential for versatile applications such as adsorption and catalysis. Here, we describe the synthesis of a platinized titanium carbide MXene (Pt@Ti3C2) catalyst with varying amounts of platinum (0.1%-2 wt.%) for the low-temperature oxidation of benzene, an aromatic volatile organic compound often found in industrial flue gas. A 1% formulation of Pt@Ti3C2-R allowed near-complete (97%) oxidation of benzene to CO2 at 225 °C with a steady-state reaction rate (r) of 0.119 mol g-1·h-1. This low-temperature catalytic oxidation reaction was promoted by an increase in the lattice oxygen (O*)/Pt2+ species (active sites) of 1%Pt@Ti3C2-R from 45.3/34.6% to 71.0/61.1% through pre-thermal reduction under H2 flow, as revealed by X-ray photoelectron spectroscopy, temperature-programmed reduction, and in situ diffuse reflectance infrared Fourier transform spectroscopy analyses. The cataltyic activity of 1% Pt@Ti3C2-R against benzene was assessed under the control of the key process variables (e.g., catalyst mass, flow rate, benzene concentration, relative humidity, and time-on-stream) to help optimize the oxidation reaction process. The results provide new insights into the use of platinum-based 2D MXene catalysts for low-temperature oxidative removal of benzene from the air.

Comparison between the mesenteric fixation method (MEFIX) and conventional methods at preventing the occurrence of Petersen's hernia: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. METHODS: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy. DISCUSSION: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

Comparison of Eastern and Western patients undergoing bariatric surgery at two US and Korean institutions: a retrospective analysis of differing bariatric patient populations.

BACKGROUND: Currently, there are differences in both demographics and indications for bariatric surgery between Eastern and Western countries. We compared postoperative outcomes between Korean and American bariatric programs in order to assess how bariatric surgery differently affects these populations. METHODS: We enrolled 540 patients who underwent bariatric surgery at University of California, Los Angeles (UCLA) and 85 patients who underwent surgery at Kosin University Gospel Hospital (KUGH) between January 2019 and December 2020. We compared demographics, complications, weight loss, and metabolic parameters between these groups. RESULTS: There was a difference in age between the UCLA and KUGH patient groups (44.3 years vs 37.6 years, P < 0.01). Frequencies of T2DM and OSA were also different (4.2% vs 50.6%, 34.1% vs 85.9% P < 0.01. Length of hospital stay varied (1.55 days vs 6.68 days, P < 0.01), but there was no difference in operating time and complications. There was no difference in percent of excess weight loss between the two groups at 6 months (29.7 vs 33.8, P = 0.13). Hepatic steatosis index (HSI) was higher in the UCLA group both before (54.2 vs 51.5, P < 0.01) and after (44.4 vs 40.0, P = 0.02) surgery. LSG was the most frequently performed operation, and robotic surgery and revisions were performed only in the UCLA program. CONCLUSION: There were differences in age, BMI, length of stay, and choice of operation between Korean and American bariatric patients. Also, there were differences in the degree of fatty liver disease using HSI and liver enzymes before and after surgery. There was no significant differences in operation time and complications. These findings suggest differences in bariatric practices and reactions to bariatric surgery in Eastern and Western settings.

1,8-Dihydroxy-3-methoxy-anthraquinone inhibits tumor angiogenesis through HIF-1α downregulation.

Photorhabdus luminescens is a gram-negative bioluminescent bacterium known as an intestinal bacterium that coexists in the digestive tract of insect-pathogenic nematodes. As part of our ongoing exploration to identify bioactive compounds from diverse natural resources, the chemical analysis of the cultures of P. luminescens KACC 12254 via LC/MS and TLC-based analyses enabled the isolation and identification of a major fluorescent compound. Its chemical structure was elucidated as 1,8-dihydroxy-3-methoxyanthraquinone (DMA) using HR-ESI-MS and NMR analysis. In this study, we conducted comprehensive investigations utilizing human colorectal cancer HCT116 cells, human umbilical cord vascular endothelial cells (HUVECs), and zebrafish embryos to assess the potential benefits of DMA in suppressing tumor angiogenesis. Our results convincingly demonstrate that DMA effectively suppresses the stability of hypoxia-inducible factor-1α (HIF-1α) protein and its target genes without inducing any cytotoxic effects. Furthermore, DMA demonstrates the ability to inhibit HIF-1α transcriptional activation and mitigate the production of reactive oxygen species (ROS). In our in vitro experiments, DMA exhibits notable inhibitory effects on VEGF-mediated tube formation, migration, and invasion in HUVECs. Additionally, in vivo investigations using zebrafish embryos confirm the antiangiogenic properties of DMA. Notably, DMA does not exhibit any adverse developmental or cardiotoxic effects in the in vivo setting. Moreover, we observe DMA's capability to restrain tumor growth through the downregulation of PI3K/AKT and c-RAF/ERK pathway. Collectively, these compelling findings underscore DMA's potential as a promising therapeutic candidate for targeted intervention against HIF-1α and angiogenesis in cancer treatment.

Thermocatalytic oxidation of a binary mixture of formaldehyde and toluene at ambient levels by a titanium dioxide supported platinum catalyst.

The thermocatalytic oxidative potential of various supported noble metal catalysts (SNMCs) is well-known for hazardous volatile organic compounds (VOCs), e.g., formaldehyde (FA) and toluene. However, little is known about SNMC performance against ambient VOC pollution with low concentration (subppm levels) relative to industrial effuluents with high concentrations (several hundred ppm). Here, the thermocatalytic oxidation performance of a titanium dioxide (TiO2)-supported platinum catalyst (Pt/TiO2) has been evaluated for a low-concentration binary mixture of FA and toluene at low temperatures and in the dark. A sample of TiO2 containing 1 wt% Pt with thermal reduction pre-treatment under hydrogen achieved 100 % conversion of FA (500 ppb) and toluene (100 ppb) at 130 °C and a gas hourly velocity of 59,701 h-1. Its catalytic activity was lowered by either a decrease in catalyst mass or an increase in VOC concentration, relative humidity, or flow rate. In situ diffuse reflectance infrared Fourier transform spectroscopy, density functional theory simulations, and molecular oxygen (O2) temperature-programmed desorption experiments were used to identify possible VOC oxidation pathways, reaction mechanisms, and associated surface phenomena. The present work is expected to offer insights into the utility of metal oxide-supported Pt catalysts for the low-temperature oxidative removal of gaseous VOCs in the dark, primarily for indoor air quality management.

Global Natural Products Social (GNPS)-Based Molecular-Networking-Guided Isolation of Phenolic Compounds from Ginkgo biloba Fruits and the Identification of Estrogenic Phenolic Glycosides.

Ginkgo biloba L. stands as one of the oldest living tree species, exhibiting a diverse range of biological activities, including antioxidant, neuroprotective, anti-inflammatory, and cardiovascular activities. As part of our ongoing discovery of novel bioactive components from natural sources, we directed our focus toward the investigation of potential bioactive compounds from G. biloba fruit. The profiles of its chemical compounds were examined using a Global Natural Products Social (GNPS)-based molecular networking analysis. Guided by this, we successfully isolated and characterized 11 compounds from G. biloba fruit, including (E)-coniferin (1), syringin (2), 4-hydroxybenzoic acid 4-O-ß-D-glucopyranoside (3), vanillic acid 4-O-ß-D-glucopyranoside (4), syringic acid 4-O-ß-D-glucopyranoside (5), (E)-ferulic acid 4-O-ß-D-glucoside (6), (E)-sinapic acid 4-O-ß-D-glucopyranoside (7), (1'R,2'S,5'R,8'S,2'Z,4'E)-dihydrophaseic acid 3'-O-ß-D-glucopyranoside (8), eucomic acid (9), rutin (10), and laricitrin 3-rutinoside (11). The structural identification was validated through a comprehensive analysis involving nuclear magnetic resonance (NMR) spectroscopic data and LC/MS analyses. All isolated compounds were evaluated using an E-screen assay for their estrogen-like effects in MCF-7 cells. As a result, compounds 2, 3, 4, 8, and 9 promoted cell proliferation in MCF-7 cells, and these effects were mitigated by the ER antagonist, ICI 182,780. In particular, cell proliferation increased most significantly to 140.9 ± 6.5% after treatment with 100 µM of compound 2. The mechanism underlying the estrogen-like effect of syringin (2) was evaluated using a Western blot analysis to determine the expression of estrogen receptor α (ERα). We found that syringin (2) induced an increase in the phosphorylation of ERα. Overall, these experimental results suggest that syringin (2) can potentially aid the control of estrogenic activity during menopause.

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.

Management of post-liver transplantation biliary stricture inaccessible by endoscopic retrograde cholangiopancreatography: A case report.

BACKGROUND: One challenging scenario in the treatment of biliary stricture is that post-liver transplantation (LT) biliary strictures cannot be accessed using endoscopic retrograde cholangiopancreatography (ERCP). Here, we report such a case that was successfully treated using a novel endoscopic technique. CASE SUMMARY: A 60-year-old man presented with obstructive jaundice caused by a post-LT biliary stricture. He underwent LT for compensated alcoholic liver cirrhosis and hepatocellular carcinoma. Laboratory investigations unveiled a cholestatic pattern of abnormalities in liver function and a total bilirubin level of 16 mg/dL. Magnetic resonance cholangiopancreatography revealed a stricture extending from the right intrahepatic bile duct into the common hepatic duct. Severe postoperative deformities made accessing the ampulla of Vater with a side-viewing duodenoscope impossible. Percutaneous transhepatic biliary drainage (PTBD) was performed to treat biliary obstruction. Moreover, to resolve the stricture completely, a fully covered self-expandable metal stent (FC-SEMS) with a novel proximal retrievable string was deployed into the post-LT biliary stricture through the PTBD tract. Before inserting the stent through the PTBD tract, the stent with the distal string was manually inverted to ensure that the distal part with the string became the proximal part for later endoscopic removal. After 6 mo, the FC-SEMS was successfully removed without complications, as the string was pulled out using a forward-viewing gastroscope. CONCLUSION: Deployment and endoscopic removal of an FC-SEMS with a novel proximal string through the PTBD tract may be a viable option for treating post-LT biliary strictures that are inaccessible by ERCP.

6-Pentyl-α-Pyrone from Trichoderma gamsii Exert Antioxidant and Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Mouse Macrophages.

Filamentous fungi produce several beneficial secondary metabolites, including bioactive compounds, food additives, and biofuels. Trichoderma, which is a teleomorphic Hypocrea that falls under the taxonomic groups Ascomycota and Dikarya, is an extensively studied fungal genus. In an ongoing study that seeks to discover bioactive natural products, we investigated potential bioactive metabolites from the methanolic extract of cultured Trichoderma gamsii. Using liquid chromatography-mass spectrometry (LC-MS), one major compound was isolated and structurally identified as 6-pentyl-α-pyrone (6PP) based on nuclear magnetic resonance data and LC-MS analysis. To determine its antioxidant and anti-inflammatory activity, as well as the underlying mechanisms, we treated lipopolysaccharide (LPS)-stimulated Raw264.7 mouse macrophages with 6PP. We found that 6PP suppresses LPS-induced increase in the levels of nitric oxide, a mediator of oxidative stress and inflammation, and restores LPS-mediated depletion of total glutathione by stabilizing nuclear factor erythroid 2-related factor 2 (Nrf2), an antioxidative factor, and elevating heme oxygenase-1 levels. Furthermore, 6PP inhibited LPS-induced production of proinflammatory cytokines, which are, at least in part, regulated by heme oxygenase-1 (HO-1). 6PP suppressed proinflammatory responses by inhibiting the nuclear localization of nuclear factor kappa B (NF-κB), as well as by dephosphorylating the mitogen-activated protein kinases (MAPKs). These results indicate that 6PP can protect macrophages against oxidative stress and LPS-induced excessive inflammatory responses by activating the Nrf2/HO-1 pathway while inhibiting the proinflammatory, NF-κB, and MAPK pathways.