Advances in Understanding Drought Stress Responses in Rice: Molecular Mechanisms of ABA Signaling and Breeding Prospects.

Drought stress is a pivotal environmental factor impacting rice production and presents a significant challenge to sustainable agriculture worldwide. This review synthesizes the latest research advancements in the regulatory mechanisms and signaling pathways that rice employs in response to drought stress. It elaborates on the adaptive changes and molecular regulatory mechanisms that occur in rice under drought conditions.

The regulatory role of KIAA1429 in epithelial-mesenchymal transition in cervical cancer via mediating m6A modification of BTG2.

Unlabelled: Cervical cancer (CC) represents one of the important cancers affecting global female population worldwide. We sought to elucidate the roles and mechanisms of KIAA1429 in the malignant properties of CC cells and the epithelial-mesenchymal transition (EMT) process. KIAA1429 was predicted to be abnormally expressed in CC and correlate with shortened survival of CC patients by GEPIA2 and GSCA databases.

Hormone therapy enhances anti-PD1 efficacy in premenopausal estrogen receptor-positive and HER2-negative advanced breast cancer.

The efficacy of immunotherapy for estrogen receptor-positive/HER2-negative (ER+/HER2-) metastatic breast cancer (MBC) has not been proven. We conduct a phase 1b/2 trial to assess the efficacy of combining pembrolizumab (anti-PD1 antibody), exemestane (nonsteroidal aromatase inhibitor), and leuprolide (gonadotropin-releasing hormone agonist) for 15 patients with premenopausal ER+/HER2- MBC who had failed one to two lines of hormone therapy (HT) without chemotherapy. The primary endpoint of progression-free survival rate at 8 months (i.

Correction: FragGen: towards 3D geometry reliable fragment-based molecular generation.

[This corrects the article DOI: 10.1039/D4SC04620J.].

Inflammasomes: potential therapeutic targets in hematopoietic stem cell transplantation.

The realm of hematopoietic stem cell transplantation (HSCT) has witnessed remarkable advancements in elevating the cure and survival rates for patients with both malignant and non-malignant hematologic diseases. Nevertheless, a considerable number of patients continue to face challenges, including transplant-related complications, infection, graft failure, and mortality. Inflammasomes, the multi-protein complexes of the innate immune system, respond to various danger signals by releasing inflammatory cytokines and even mediating cell death.

3DSMILES-GPT: 3D molecular pocket-based generation with token-only large language model.

The generation of three-dimensional (3D) molecules based on target structures represents a cutting-edge challenge in drug discovery. Many existing approaches often produce molecules with invalid configurations, unphysical conformations, suboptimal drug-like qualities, limited synthesizability, and require extensive generation times. To address these challenges, we present 3DSMILES-GPT, a fully language-model-driven framework for 3D molecular generation that utilizes tokens exclusively.

Ecological distribution of ammonia oxidizers in Yellow River sediments and their influencing factors.

Ammonia oxidation, the first and rate-limiting step of nitrification, is a crucial step in nitrogen cycling. The distribution patterns of key ammonia oxidizers, including ammonia-oxidizing archaea (AOA) and bacteria (AOB), and comammox (complete ammonia oxidation) Nitrospira, provide vital insights for nitrogen cycling in natural ecosystems. Currently, the distribution and contribution of AOA, AOB and comammox Nitrospira in freshwater ecosystems remain largely underexplored.

A new pathway for ferroptosis regulation: The PRMTs.

Protein arginine methyltransferases (PRMTs) play an essential role in the regulation of ferroptosis, a form of programmed cell death characterized by abnormal iron ion metabolism, lipid peroxidation, and DNA damage. Through methylation, PRMTs modify specific proteins, thereby altering their activity, localizations, or interactions with other molecules to control the ferroptosis process. This study was conducted to provide a comprehensive overview of the relationship between PRMTs and ferroptosis, with a focus on the mechanisms by which PRMTs regulate ferroptosis and their effect on this cell death pathway.

ClickGen: Directed exploration of synthesizable chemical space via modular reactions and reinforcement learning.

Despite the significant potential of generative models, low synthesizability of many generated molecules limits their real-world applications. In response to this issue, we develop ClickGen, a deep learning model that utilizes modular reactions like click chemistry to assemble molecules and incorporates reinforcement learning along with inpainting technique to ensure that the proposed molecules display high diversity, novelty and strong binding tendency. ClickGen demonstrates superior performance over the other reaction-based generative models in terms of novelty, synthesizability, and docking conformation similarity for existing binders targeting the three proteins.

FragGen: towards 3D geometry reliable fragment-based molecular generation.

3D structure-based molecular generation is a successful application of generative AI in drug discovery. Most earlier models follow an atom-wise paradigm, generating molecules with good docking scores but poor molecular properties (like synthesizability and drugability). In contrast, fragment-wise generation offers a promising alternative by assembling chemically viable fragments.

Efficacy of Tocilizumab in Refractory Graves Orbitopathy From Real-World Clinical Practice: An Observational Study.

Context: The efficacy of tocilizumab (TCZ) in treating Graves orbitopathy (GO) remains uncertain due to the small sample sizes of earlier studies, and there is a lack of research on the drug for juvenile GO.

Objective: To evaluate the effectiveness of TCZ in treating GO that is resistant to conventional therapy.

Design: This observational study at a tertiary care center included 79 Chinese GO patients, 15 of whom were pediatric patients, with 52 of these patients having moderate to severe active GO (all adult patients having steroid-resistant GO).

Intraocular Pressure Changes After Combined Orbital Decompression and Glucocorticoid Treatment for Graves Orbitopathy.

Objective: To evaluate the change in the intraocular pressure (IOP) in subjects with Graves orbitopathy (GO) after orbital decompression (OD) with glucocorticoids (GCs).

Methods: Ninety-nine orbits of 76 patients with GO were retrospectively reviewed, with either OD (Group A), OD with intravenous glucocorticoids (i.v.

CovalentInDB 2.0: an updated comprehensive database for structure-based and ligand-based covalent inhibitor design and screening.

The rational design of targeted covalent inhibitors (TCIs) has emerged as a powerful strategy in drug discovery, known for its ability to achieve strong binding affinity and prolonged target engagement. However, the development of covalent drugs is often challenged by the need to optimize both covalent warhead and non-covalent interactions, alongside the limitations of existing compound libraries. To address these challenges, we present CovalentInDB 2.

Porcine reproductive and respiratory syndrome virus activates lipid synthesis through a ROS-dependent AKT/PCK1/INSIG/SREBPs axis.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen in pigs. This study aimed to investigate the impact of PRRSV infection on cellular metabolism, particularly focusing on lipid metabolism to understand its role in promoting viral replication. We conducted a metabolic analysis on MARC-145 cells before and after PRRSV infection.

A transcription-independent role for HIF-1α in modulating microprocessor assembly.

Microprocessor is an essential nuclear complex responsible for the initial RNase-mediated cleavage of primary miRNA, which is a tightly controlled maturation process that requires the proper assembly of Drosha and DGCR8. Unlike previously identified mechanisms directly targeting the enzymatic subunit Drosha, current knowledge about the biological ways of controlling miRNA nuclear maturation through DGCR8 is less addressed. In this study, we unveiled that the microprocessor assembly is governed by a master gene regulator HIF-1α irrespective of its canonical transcriptional activity.

PCAF acetylates AIB1 to form a transcriptional coactivator complex to promote glycolysis in endometrial cancer.

Introduction: Despite rapid advances in molecular biology, personalized molecular therapy remains a clinical challenge for endometrial cancer due to its complex and heterogeneous tumor microenvironment.Based on clinical findings, AIB1 is a marker molecule for poor prognosis in endometrial cancer and may serve as a potential therapeutic target. Moreover, it is well known that aerobic glycolysis plays an important role in tumour energy metabolism.

Role of Doppler Trasonography in Predicting Recovery From Early Allograft Dysfunction in Liver Postoperative Patients.

Objective: The aim of this study was to observe the recovery of liver function in patients with early allograft dysfunction (EAD) at one month postoperatively and explore whether early postoperative ultrasonic hemodynamic parameters can predict this outcome.

Methods: Patients with EAD postoperatively, who underwent orthotopic liver transplantation (OLT) in our hospital from December 2012 to June 2021, were retrospectively collected. Based on the recovery of liver function within one month, patients were divided into two groups: the recovery group (FR-1M) and the non-recovery group (Non-FR-1M).

Physiological and transcriptomic profiles reveal key regulatory pathways involved in cold resistance in sunflower seedlings.

During sunflower growth, cold waves often occur and impede plant growth. Therefore, it is crucial to study the underlying mechanism of cold resistance in sunflowers. In this study, physiological analysis revealed that as cold stress increased, the levels of ROS, malondialdehyde, ascorbic acid, and dehydroascorbic acid and the activities of antioxidant enzymes increased.