Filgotinib Improves Experimental Pulmonary Fibrosis by Modulating JAK1/STAT3/SOCS3/IL-17A Signalling.

Background: Regulatory agencies in Europe and Japan have approved filgotinib, a selective JAK1 inhibitor, for use in treating rheumatoid arthritis, but its effect and mechanism of action in treating pulmonary fibrosis remain unclear.

Methods: We performed an in vivo investigation in rats on filgotinib's effect on pulmonary fibrosis resulting from the intratracheal infusion of bleomycin (BLM). Then, we focused on the mechanisms by which filgotinib inhibits experimentally induced pulmonary fibrosis in vitro by determining its effect on TGF-β1-induced proliferation of mouse lung fibroblasts.

GT1 and ZmHB13/VRL1 regulate flower sexual differentiation by modulating jasmonate biosynthesis and signaling in maize.

As a typical monoecious plant, maize (Zea mays L.) produces unisexual male and female flowers comprising tassels and ears, respectively. However, the molecular mechanisms underlying unisexual flower development remain largely unclear.

Glutamine transporter inhibitor enhances the sensitivity of NSCLC to trametinib through GSDME-dependent pyroptosis.

Trametinib, an inhibitor of mitogen-activated extracellular signal-regulated kinases 1/2 (MEK1/2), is used to treat BRAF melanoma and non-small-cell lung cancer (NSCLC). Mutant Kirsten rat sarcoma viral oncogene homolog (KRAS) promotes glutamine utilization, therefore, in the present study we investigated the anti-cancer effects of trametinib in combination with V-9302, a glutamine transporter inhibitor, in NSCLC with KRAS mutations. Trametinib in combination with V-9302 exhibited a potent synergistic antitumor effect, inducing cell cycle arrest and pyroptosis.

LG1 promotes preligule band formation through directly activating ZmPIN1 genes in maize.

Increasing plant density is an effective strategy for enhancing crop yield per unit land area. A key architectural trait for crops adapting to high planting density is a smaller leaf angle (LA). Previous studies have demonstrated that LG1, a SQUAMOSA BINDING PROTEIN (SBP) transcription factor, plays a critical role in LA establishment.

Overcoming drug resistance through extracellular vesicle-based drug delivery system in cancer treatment.

Drug resistance is a major challenge in cancer therapy that often leads to treatment failure and disease relapse. Despite advancements in chemotherapeutic agents and targeted therapies, cancers often develop drug resistance, making these treatments ineffective. Extracellular vesicles (EVs) have gained attention for their potential applications in drug delivery because of their natural origin, biocompatibility, and ability to cross biological barriers.

Dual inhibition of HERs and PD-1 counteract resistance in KRAS-mutant head and neck cancer.

Background: Basket clinical trials targeting the KRAS-mutation in solid tumors have shown initial promise, including in orphan KRAS head and neck cancer (HNC). However, development of resistance to KRAS-mutant-specific inhibitors (KRASi) remains a major obstacle. Here, we investigated the intrinsic (tumor-cell autonomus) and tumor-microenvironment (TME) mechanisms of resistance to the KRASi-MRTX849 and AMG510 in a unique syngenic murine KRAS-mutated HNC cell line.

Time-Dependent Comparison of the Structural Variations of Natural Products and Synthetic Compounds.

The identification of natural products (NPs) has played a pivotal role in drug discovery and shaped the evolution of synthetic compounds (SCs). However, the extent to which NPs have historically influenced the structural characteristics of SCs remains unclear. In this study, we conducted a comprehensive, time-dependent chemoinformatic analysis to investigate the impact of NPs on the structural evolution of SCs.

Yes-associated protein indispensably mediates hirsutine-induced inhibition on cell growth and Wnt/β-catenin signaling in colorectal cancer.

Background And Purpose: Targeting Wnt/β-catenin signaling emerges as one of the promising strategies for colorectal cancer (CRC) treatment, as this signaling is highly activated in CRC progression. Despite reports on the cytotoxic effects of hirsutine (HT), an indole alkaloid found in herbal medicines from the genus Uncaria, its therapeutic potential for CRC and the involved mechanisms are poorly understood. This study investigates the anticancer efficacy and the probable mechanisms of HT against CRC.

Benzophenone-4 inhibition in marine diatoms: Physiological and molecular perspectives.

Benzophenone-4 (BP-4), a widely utilized organic ultraviolet (UV) filter, is recognized as a pseudo-persistent contaminant in aquatic environments. To elucidate the effects and mechanisms of BP-4 on marine diatoms, an investigation was conducted on the growth rate, photosynthetic pigment content, photosynthetic parameters, antioxidant enzyme activity, malondialdehyde (MDA) levels, cellular structure, and transcriptome profile of the model species, Phaeodactylum tricornutum. The results showed a pronounced inhibition of algal growth upon exposure to BP-4, with a 144 h-EC value of 201 mg·L.

SLC13A3 is a major effector downstream of activated β-catenin in liver cancer pathogenesis.

Activated Wnt/β-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of β-catenin in liver cancer.

ZmSPL10, ZmSPL14 and ZmSPL26 act together to promote stigmatic papilla formation in maize through regulating auxin signaling and ZmWOX3A expression.

Maize silk is a specialized type of stigma, covered with numerous papillae for pollen grain capture. However, the developmental process of stigmatic papillae and the underlying regulatory mechanisms have remained largely unknown. Here, we combined the cytological, genetic and molecular studies to demonstrate that three homologous genes ZmSPL10, ZmSPL14 and ZmSPL26 play a central role in promoting stigmatic papilla formation in maize.

Micellar-type aggregates of HP-β-CD/GML inclusion complex: Increased water-solubility and effective antibacterial capabilities.

The inclusion complex (IC) was successfully obtained by encapsulating glycerol monolaurate (GML) into the cavity of hydroxypropyl-β-cyclodextrin (HP-β-CD). Compared with solubility of pure GML <80 μg/mL in water, and the water-solubility of encapsulated GML was significantly improved and reached to 270,000 μg/mL. IC can form nanoparticles by self-assembly, probably assigned to its strong capability to form micellar-type aggregates.

Sequential Inhibition of PARP and BET as a Rational Therapeutic Strategy for Glioblastoma.

PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair.

Lansoprazole (LPZ) reverses multidrug resistance (MDR) in cancer through impeding ATP-binding cassette (ABC) transporter-mediated chemotherapeutic drug efflux and lysosomal sequestration.

Aims: Lansoprazole is one of the many proton pump inhibitors (PPIs) that acts more strongly with ABCB1 and ABCG2. The present study is to investigate the potential of lansoprazole on reversal of ABCB1/G2-mediated MDR in cancer, in vitro and in vivo.

Methods: Reversal studies and combination evaluation were conducted to determine the synergistic anti-MDR effects on lansoprazole.

Functions of Basic Helix-Loop-Helix (bHLH) Proteins in the Regulation of Plant Responses to Cold, Drought, Salt, and Iron Deficiency: A Comprehensive Review.

Abiotic stresses including cold, drought, salt, and iron deficiency severely impair plant development, crop productivity, and geographic distribution. Several bodies of research have shed light on the pleiotropic functions of BASIC HELIX-LOOP-HELIX (bHLH) proteins in plant responses to these abiotic stresses. In this review, we mention the regulatory roles of bHLH TFs in response to stresses such as cold, drought, salt resistance, and iron deficiency, as well as in enhancing grain yield in plants, especially crops.

A novel pan-PI3K inhibitor KTC1101 synergizes with anti-PD-1 therapy by targeting tumor suppression and immune activation.

Background: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed.

A Biomimetic Upconversion Nanobait-Based Near Infrared Light Guided Photodynamic Therapy Alleviates Alzheimer's Disease by Inhibiting β-Amyloid Aggregation.

Aberrant β-amyloid (Aβ) fibrillation is the key event in Alzheimer's disease (AD), the inhibition and degradation of which are recognized as a promising therapeutic strategy to alleviate the nerve damage of AD. Photodynamic therapy (PDT) holds great potential for modulation of Aβ self-assembly, which is nevertheless limited by the inefficient utilization of reactive oxygen species (ROS). Herein, an erythrocyte membrane (EM)-modified core-shell upconversion nanoparticle (UCNP/Cur@EM) is designed and fabricated as a biomimetic nanobait to improve the PDT efficiency in AD.

A single immunization with H5N1 virus-like particle vaccine protects chickens against divergent H5N1 influenza viruses and vaccine efficacy is determined by adjuvant and dosage.

The H5N1 subtype highly pathogenic avian influenza virus (HPAIV) reveals high variability and threatens poultry production and public health. To prevent the spread of H5N1 HPAIV, we developed an H5N1 virus-like particle (VLP) vaccine based on the insect cell-baculovirus expression system. Single immunization of the H5N1 VLP vaccines induced high levels of HI antibody titres and provided effective protection against homologous virus challenge comparable to the commercial inactivated vaccine.

Developing a Two-Photon "AND" Logic Probe and Its Application in Alzheimer's Disease Differentiation.

In Alzheimer's disease, hypochlorous acid involved in the clearance of invading bacteria or pathogens and butyrylcholinesterase engaged in the hydrolysis of the neurotransmitter acetylcholine are relatively significantly altered. However, there are few dual detection probes for hypochlorous acid and butyrylcholinesterase. In addition, single-response probes suffer from serious off-target effects and near-infrared probes do not easily penetrate the blood-brain barrier due to their excessive molecular weight.

ZmELF3.1 integrates the RA2-TSH4 module to repress maize tassel branching.

Tassel branch number (TBN) is a key agronomic trait for adapting to high-density planting and grain yield in maize. However, the molecular regulatory mechanisms underlying tassel branching are still largely unknown. Here, we used molecular and genetic studies together to show that ZmELF3.

Discovery of a Novel Ubenimex Derivative as a First-in-Class Dual CD13/Proteasome Inhibitor for the Treatment of Cancer.

The CD13 inhibitor ubenimex is used as an adjuvant drug with chemotherapy for the treatment of cancer due to its function as an immunoenhancer, but it has limitations in its cytotoxic efficacy. The proteasome inhibitor ixazomib is a landmark drug in the treatment of multiple myeloma with a high anti-cancer activity. Herein, we conjugated the pharmacophore of ubenimex and the boric acid of ixazomib to obtain a dual CD13 and proteasome inhibitor ().