Pharmacokinetics, pharmacodynamics, and safety of GS-3583, a FLT3 agonist Fc fusion protein, from single-ascending-dose phase I study in healthy participants.

Conventional dendritic cells subtype 1 (cDC1) play a vital role in the priming and expansion of tumor-specific CD8+ T cells and their recruitment to tumor microenvironment. However, cDC1s are often underrepresented in the microenvironment. Systemic administration of Fms-like tyrosine kinase 3 ligand, a hematopoietic growth factor that binds to FLT3 on myeloid and lymphoid progenitor cells, leads to cDC1 expansion in the periphery and recruitment into the microenvironment.

Efficacy and Safety of Sacituzumab Govitecan in Patients With Advanced Solid Tumors (TROPiCS-03): Analysis in Patients With Advanced Endometrial Cancer.

Purpose: Patients with advanced endometrial cancer (EC) who progress on or after platinum-based therapy and immunotherapy have poor prognosis. We report efficacy and safety of sacituzumab govitecan (SG), a trophoblast cell-surface antigen 2 (Trop-2)-directed antibody-drug conjugate, in patients with advanced EC.

Methods: TROPiCS-03 (ClinicalTrials.

Targeting TRPV1 signaling: Galangin improves ethanol-induced gastric mucosal injury.

Ethnopharmacological Relevance: Galangin, a bioactive compound extracted from Alpinia officinarum Hance (Zingiberaceae), a plant with significant ethnopharmacological importance, has been used for thousands of years as a spice, condiment, and medicinal agent for various conditions, including gastrointestinal disorders. Although there is evidence suggesting its potential to improve gastric ulcers, the molecular mechanisms underlying its anti-ulcer properties are not fully understood.

Objective: of the Study: This study aimed to investigate the effects of galangin on ethanol-induced acute gastric mucosal injury (AGMI) in mice and elucidate its molecular mechanisms.

Hydrogel Extinguishants.

The exploitation of clean and efficient fire extinguishing materials has substantial implications for improving disaster prevention, mitigation, and relief capabilities, maintaining public safety, and protecting people's lives and property as well as the natural environment. Natural polymer hydrogel with high water containment, excellent film formation, high heat insulation, ecofriendliness, and degradability has huge potential in achieving new breakthroughs for developing clean and efficient fire extinguishing materials and products. In recent years, the exploitation of hydrogel extinguishing materials and the fabrication of products has attracted great attention, gradually replacing traditional fire extinguishing products.

Oral PD-L1 inhibitor GS-4224 selectively engages PD-L1 high cells and elicits pharmacodynamic responses in patients with advanced solid tumors.

Background: Checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) pathway are effective therapies in a range of immunogenic cancer types. Blocking this pathway with an oral therapy could benefit patients through greater convenience, particularly in combination regimens, and allow flexible management of immune-mediated toxicities.

Methods: PD-L1 binding activity was assessed in engineered dimerization and primary cell target occupancy assays.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation.

Background: Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear.

Methods: Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg).

Phase I Study of GS-3583, an FMS-like Tyrosine Kinase 3 Agonist Fc Fusion Protein, in Patients with Advanced Solid Tumors.

Purpose: GS-3583, an FMS-like tyrosine kinase 3 (FLT3) agonist Fc fusion protein, expanded conventional dendritic cells (cDC) in the periphery of healthy volunteers, suggesting potential for GS-3583 to increase cDCs in the tumor microenvironment and promote T cell-mediated antitumor activity in cancer patients. This phase Ib open-label study assessed GS-3583 in adults with advanced solid tumors.

Patients And Methods: Multiple escalating doses of GS-3583 (standard 3+3 design) were administered intravenously on days 1 and 15 of cycle 1 and day 1 of each subsequent 28-day cycle for up to 52 weeks.

Impacted spike frequency adaptation associated with reduction of KCNQ2/3 exacerbates seizure activity in temporal lobe epilepsy.

Numerous epilepsy-related genes have been identified in recent decades by unbiased genome-wide screens. However, the available druggable targets for temporal lobe epilepsy (TLE) remain limited. Furthermore, a substantial pool of candidate genes potentially applicable to TLE therapy awaits further validation.

Components study on gastroprotective effect and holistic mechanism of the herbal pair Alpinia officinarum - Cyperus rotundus based on spectrum-effect relationship and integrated transcriptome and metabolome analyses.

Ethnopharmacological Relevance: The herbal pair Alpinia officinarum-Cyperus rotundus (HPAC) has an extended history of use in the treatment of gastric ulcers, and its curative effect is definite.

Aim Of The Study: To explore the material basis and holistic mechanism of HPAC on ethanol-induced gastric ulcers.

Materials And Methods: Three chemometrics, GRA, OPLS, and BCA, were used to construct the spectrum-effect relationship between the HPLC fingerprints of HPAC extracts and the bioactivity indices (cell viability; the levels of TNF-α, IL-6, COX-2, and PGE2; and wound healing rate) against GES-1 cell damage to screen the bioactive ingredients.

Cytotoxic Indole Diterpenoids from a -Derived Fungus sp. PQJ-1.

Two new indole diterpene derivatives, 5-hydroxy--aflatrem () and 14-hydroxy--aflatrem (), along with one known analogue, 14-(,-dimethl--valyloxy)paspalinine (), were isolated from the fermentation broth of the fungus sp. PQJ-1 derived from . The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses.

Engineering of a GSH activatable photosensitizer for enhanced photodynamic therapy through disrupting redox homeostasis.

Although disrupted redox homeostasis has emerged as a promising approach for tumor therapy, most existing photosensitizers are not able to simultaneously improve the reactive oxygen species level and reduce the glutathione (GSH) level. Therefore, designing photosensitizers that can achieve these two aspects of this goal is still urgent and challenging. In this work, an organic activatable near-infrared (NIR) photosensitizer, CyI-S-diCF, is developed for GSH depletion-assisted enhanced photodynamic therapy.

Isoindigo-Thiophene D-A-D-Type Conjugated Polymers: Electrosynthesis and Electrochromic Performances.

Four novel isoindigo-thiophene D-A-D-type precursors are synthesized by Stille coupling and electrosynthesized to yield corresponding hybrid polymers with favorable electrochemical and electrochromic performances. Intrinsic structure-property relationships of precursors and corresponding polymers, including surface morphology, band gaps, electrochemical properties, and electrochromic behaviors, are systematically investigated. The resultant isoindigo-thiophene D-A-D-type polymer combines the merits of isoindigo and polythiophene, including the excellent stability of isoindigo-based polymers and the extraordinary electrochromic stability of polythiophene.

Large-fused-ring-based D-A type electrochromic polymer with magenta/yellowish green/cyan three-color transitions.

Large-fused-ring-based conjugated polymers possess wide application prospects in optoelectronic devices due to their high charge transport and wide optical absorption. In this paper, three low-bandgap donor-acceptor (D-A) type polymers PBIT- ( = 1, 2, 3) based on alkylated benzodithiophene and tris(thienothiophene) as donors and thiadiazol-quinoxaline as an acceptor were synthesized Stille coupling polymerization at different (donor/acceptor) D/A molar feed ratios. The band gaps of PBIT-1, PBIT-2, PBIT-3 were 1.

Toward High-Performance Electrochromic Conjugated Polymers: Influence of Local Chemical Environment and Side-Chain Engineering.

Three homologous electrochromic conjugated polymers, each containing an asymmetric building block but decorated with distinct alkyl chains, were designed and synthesized using electrochemical polymerization in this study. The corresponding monomers, namely T610FBTT810, DT6FBT, and DT48FBT, comprise the same backbone structure, i.e.

Truxene-Centered Electron Acceptors for Non-Fullerene Solar Cells: Alkyl Chain and Branched Arm Engineering.

A series of symmetrical truxene-centered and 3-ethylrhodanine end-capped electron acceptors with high absorption coefficient, namely Tr(Hex)-3RD, Tr(Dec)-3RD, and Tr(Hex)-6RD, were prepared and constructed for non-fullerene solar cells. To satisfy solution-processability, multiple energy levels, and suitable morphology, these three acceptors were comparatively studied through alkyl chain (hexyl/decyl) and branched-arm engineering (three/six branched arms). The six-bladed propeller acceptor of Tr(Hex)-6RD recorded the power conversion efficiency (PCE) of 1.

Midkine-Notch2 Pathway Mediates Excessive Proliferation of Airway Smooth Muscle Cells in Chronic Obstructive Lung Disease.

Inflammation-induced proliferation of airway smooth muscle cells (ASMCs) and subsequent airway remodeling is a hallmark of chronic obstructive lung disease (COPD). The role of midkine (MK) in COPD is unclear. In this work, we explored the role of MK-Notch2 signaling in COPD by inhibiting the expression of MK using lentivirus shRNA in ASMCs and instillation of AAV9-MK in the airway of a COPD rat model .

Self-Healing Silver Nanowires and Reduced Graphene Oxide/Polyurethane Composite Film Based on the Diels-Alder Reaction under Infrared Radiation.

The hybrid composite of silver nanowires (AgNWs) and reduced graphene oxide (RGO) was synthesized in situ by an improved polyol-thermal method. The AgNWs-RGO with mass contents of 5-37 wt% was added into the thermo-reversible Diels-Alder reaction polyurethane (DA-PU) matrix with the AgNWs as the main conductor and the RGO as the auxiliary conductor to prepare self-healing composite conductive films. Further, the electrical conductivity, thermal conductivity, mechanical properties, infrared thermal response, and self-healing property of the composite film under infrared light irradiation were studied.

Near-Infrared-Light-Assisted Self-Healing Graphene-Thermopolyurethane Composite Films.

Graphene-thermopolyurethane (G-TPU) composite films were fabricated and the effects of the TPU initial concentration, characteristics of TPU, and graphene loading on the electrical, mechanical, thermal, infrared thermal response and near-infrared-light-assisted self-healing properties of the composite films were investigated in detail. The experimental results demonstrate that the comprehensive performances of the composite film are related to the initial concentration of the TPU solution and the characteristics of the TPU and the graphene loading. The composite film prepared from TPU solution with low initial concentration can have conductivity under the condition of low graphene content.

Inkjet-Printed Silver Nanowire Ink for Flexible Transparent Conductive Film Applications.

The development of flexible transparent conductive electrodes has been considered as a key issue in realizing flexible functional electronics. Inkjet printing provides a new opportunity for the manufacture of FFE due to simple process, cost-effective, environmental friendliness, and digital method to circuit pattern. However, obtaining high concentration of inkjet- printed silver nanowires (AgNWs) conductive ink is a great challenge because the high aspect ratio of AgNWs makes it easy to block the jetting nozzle.

Randomized, open-label, phase 2 study of andecaliximab plus nivolumab versus nivolumab alone in advanced gastric cancer identifies biomarkers associated with survival.

Background: Matrix metalloproteinase-9 (MMP9) selectively cleaves extracellular matrix proteins contributing to tumor growth and an immunosuppressive microenvironment. This study evaluated andecaliximab (ADX), an inhibitor of MMP9, in combination with nivolumab (NIVO), for the treatment of advanced gastric cancer.

Methods: Phase 2, open-label, randomized multicenter study evaluating the efficacy, safety, and pharmacodynamics of ADX+NIVO versus NIVO in patients with pretreated metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Chemical Constituents and Anti-Gastric Ulcer Activity of Essential Oils of Alpinia officinarum (Zingiberaceae), Cyperus rotundus (Cyperaceae), and Their Herbal Pair.

The essential oil (EO) of the herbal pair (HP), Alpinia officinarum-Cyperus rotundus (HP G-X) has been conventionally used in traditional Chinese medicine (TCM) for 'warming the stomach' and relieving pain. However, its pharmacologically active compounds, as well as the mechanism of its anti-gastric ulcer properties remain unclear. In this study, the EOs obtained from HP G-X and its corresponding single herbs were analyzed using GC/MS.

Novel Insights into Inkjet Printed Silver Nanowires Flexible Transparent Conductive Films.

Silver nanowire (AgNWs) inks for inkjet printing were prepared and the effects of the solvent system, wetting agent, AgNWs suspension on the viscosity, surface tension, contact angle between ink droplet and poly(ethylene) terephthalate (PET) surface, and pH value of AgNWs ink were discussed. Further, AgNWs flexible transparent conductive films were fabricated by using inkjet printing process on the PET substrate, and the effects of the number printing layer, heat treatment temperature, drop frequency, and number of nozzle on the microstructures and photoelectric properties of AgNWs films were investigated in detail. The experimental results demonstrated that the 14-layer AgNWs printed film heated at 60 °C and 70 °C had an average sheet resistance of 13 Ω∙sq and 23 Ω∙sq and average transparency of 81.