Genetic improvement of low-lignin poplars: a new strategy based on molecular recognition, chemical reactions and empirical breeding.

As an important source of pollution in the papermaking process, the presence of lignin in poplar can seriously affect the quality and process of pulping. During lignin synthesis, Caffeoyl-CoA-O methyltransferase (CCoAOMT), as a specialized catalytic transferase, can effectively regulate the methylation of caffeoyl-coenzyme A (CCoA) to feruloyl-coenzyme A. Targeting CCoAOMT, this study investigated the substrate recognition mechanism and the possible reaction mechanism, the key residues of lignin binding were mutated and the lignin content was validated by deep convolutional neural-network model based on genome-wide prediction (DCNGP).

Atopic dermatitis: pathogenesis and therapeutic intervention.

The skin serves as the first protective barrier for nonspecific immunity and encompasses a vast network of skin-associated immune cells. Atopic dermatitis (AD) is a prevalent inflammatory skin disease that affects individuals of all ages and races, with a complex pathogenesis intricately linked to genetic, environmental factors, skin barrier dysfunction as well as immune dysfunction. Individuals diagnosed with AD frequently exhibit genetic predispositions, characterized by mutations that impact the structural integrity of the skin barrier.

Identification of core therapeutic targets for Monkeypox virus and repurposing potential of drugs: A WEB prediction approach.

A new round of monkeypox virus has emerged in the United Kingdom since July 2022 and rapidly swept the world. Currently, despite numerous research groups are studying this virus and seeking effective treatments, the information on the open reading frame, inhibitors, and potential targets of monkeypox has not been updated in time, and the comprehension of monkeypox target ligand interactions remains a key challenge. Here, we first summarized and improved the open reading frame information of monkeypox, constructed the monkeypox inhibitor library and potential targets library by database research as well as literature search, combined with advanced protein modeling technologies (Sequence-based and AI algorithms-based homology modeling).

BRD4 Degradation Enhanced Glioma Sensitivity to Temozolomide by Regulating Notch1 via Glu-Modified GSH-Responsive Nanoparticles.

Temozolomide (TMZ) serves as the principal chemotherapeutic agent for glioma; nonetheless, its therapeutic efficacy is compromised by the rapid emergence of drug resistance, the inadequate targeting of glioma cells, and significant systemic toxicity. ARV-825 may play a role in modulating drug resistance by degrading the BRD4 protein, thereby exerting anti-glioma effects. Therefore, to surmount TMZ resistance and achieve efficient and specific drug delivery, a dual-targeted glutathione (GSH)-responsive nanoparticle system (T+A@Glu-NP) is designed and synthesized for the co-delivery of ARV-825 and TMZ.

The structural Basis of NMN synthesis catalyzed by NadV from Haemophilus ducreyi.

NMN is a precursor in the biosynthesis of NAD, a molecule that plays a crucial role within cells. Supplementation with NMN can elevate NAD levels in the blood, improving symptoms of diabetes, neurodegenerative diseases, and cancer, as well as providing anti-aging benefits. Escherichia coli was engineered to heterologously express nicotinamide phosphoribosyltransferase (Nampt), enabling the recombinant E.

Pan-cancer analysis of the role of α2C-adrenergic receptor (ADRA2C) in human tumors and validation in glioblastoma multiforme models.

Several studies have reported the relationship between α2C-adrenergic receptor (ADRA2C) and both neoplastic and non-neoplastic diseases. However, a comprehensive pan-cancer analysis is currently lacking. Utilizing the RNA sequencing (RNA-seq) datasets from The Cancer Genome Atlas (TCGA) database, the roles of ADRA2C in human pan-cancer were analyzed through a variety of bioinformatics approaches, including R programming language and single-cell sequencing data analysis, .

Current advance of nanotechnology in diagnosis and treatment for malignant tumors.

Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment.

Tumor-Specific Nano-Herb Delivery System with High L-Arginine Loading for Synergistic Chemo and Gas Therapy against Cervical Cancer.

Cancer metastasis poses significant challenges in current clinical therapy. Osthole (OST) has demonstrated efficacy in treating cervical cancer and inhibiting metastasis. Despite these positive results, its limited solubility, poor oral absorption, low bioavailability, and photosensitivity hinder its clinical application.

m6A-dependent mature miR-151-5p accelerates the malignant process of HNSCC by targeting LYPD3.

miRNA has emerged as a crucial regulator in various of pathological and physiological processes, yet its precise mechanism of action the detailed mechanism of their action in Head and neck squamous cell carcinoma (HNSCC) remains incompletely understood. This study sheds light on the role of mi-151-5p, revealing its significantly elevated expression in tumor cells, which notably enhances the invasion and migration of HNSCC cells. This effect is achieved through directly targeting LY6/PLAUR Domain Containing 3 (LYPD3) by miR-151-5p, involving complementary binding to the 3'-untranslated regions (3'-UTR) in the mRNA of LYPD3.

PiRNA-4447944 promotes castration-resistant growth and metastasis of prostate cancer by inhibiting NEFH expression through forming the piRNA-4447944-PIWIL2-NEFH complex.

Castration-resistant prostate cancer (CRPC) is the leading cause of prostate cancer (PCa)-related death in males, which occurs after the failure of androgen deprivation therapy (ADT). PIWI-interacting RNAs (piRNAs) are crucial regulators in many human cancers, but their expression patterns and roles in CRPC remain unknown. In this study, we performed small RNA sequencing to explore CRPC-associated piRNAs using 10 benign prostate tissues, and 9 paired hormone-sensitive PCa (HSPCa) and CRPC tissues from the same patients.

Immunostimulatory CKb11 gene combined with immune checkpoint PD-1/PD-L1 blockade activates immune response and simultaneously overcomes the immunosuppression of cancer.

Immunosuppression tumor microenvironment (TME) seriously impedes anti-tumor immune response, resulting in poor immunotherapy effect of cancer. This study develops a folate-modified delivery system to transport the plasmids encoding immune stimulatory chemokine CKb11 and PD-L1 inhibitors to tumor cells, resulting in high CKb11 secretion from tumor cells, successfully activating immune cells and increasing cytokine secretion to reshape the TME, and ultimately delaying tumor progression. The chemokine CKb11 enhances the effectiveness of tumor immunotherapy by increasing the infiltration of immune cells in TME.

PA28γ coordinates the cross-talk between cancer-associated fibroblasts and tumor cells to promote OSCC progression via HDAC1/E2F3/IGF2 signaling.

PA28γ overexpression is aberrant and accompanied by poor patient prognosis in various cancers, the precise regulatory mechanism of this crucial gene in the tumor microenvironment remains incompletely understood. In this study, using oral squamous cell carcinoma as a model, we demonstrated that PA28γ exhibits high expression in cancer-associated fibroblasts (CAFs), and its expression significantly correlates with the severity of clinical indicators of malignancy. Remarkably, we found that elevated levels of secreted IGF2 from PA28γ CAFs can enhance stemness maintenance and promote tumor cell aggressiveness through the activation of the MAPK/AKT pathway in a paracrine manner.

Enhancing genome-wide populus trait prediction through deep convolutional neural networks.

As a promising model, genome-based plant breeding has greatly promoted the improvement of agronomic traits. Traditional methods typically adopt linear regression models with clear assumptions, neither obtaining the linkage between phenotype and genotype nor providing good ideas for modification. Nonlinear models are well characterized in capturing complex nonadditive effects, filling this gap under traditional methods.

PA28γ induces dendritic cell maturation and activates T-cell immune responses in oral lichen planus.

Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa, the mechanism of its inflammatory progression has not yet been fully elucidated. PA28γ plays a significant role in a variety of immune-related diseases. However, the exact role of PA28γ in the pathogenesis of OLP remains unclear.

Univariable and multivariable Mendelian randomization study identified the key role of gut microbiota in immunotherapeutic toxicity.

Background: In cancer patients receiving immune checkpoint inhibitors (ICIs), there is emerging evidence suggesting a correlation between gut microbiota and immune-related adverse events (irAEs). However, the exact roles of gut microbiota and the causal associations are yet to be clarified.

Methods: To investigate this, we first conducted a univariable bi-directional two-sample Mendelian randomization (MR) analysis.

Inhibition of TNBC Cell Growth by Paroxetine: Induction of Apoptosis and Blockage of Autophagy Flux.

The strategy of drug repurposing has gained traction in the field of cancer therapy as a means of discovering novel therapeutic uses for established pharmaceuticals. Paroxetine (PX), a selective serotonin reuptake inhibitor typically utilized in the treatment of depression, has demonstrated promise as an agent for combating cancer. Nevertheless, the specific functions and mechanisms by which PX operates in the context of triple-negative breast cancer (TNBC) remain ambiguous.

HER2 targeted therapy in colorectal Cancer: Current landscape and future directions.

Colorectal cancer (CRC) is one of the most common causes of tumor-related deaths globally. Despite recent improvements in the comprehensive therapy of malignancy, metastatic CRC continues to have a poor prognosis. Human epidermal growth factor receptor 2 (HER2) is an established oncogenic driver, which is successfully targeted for breast and gastric cancers.

A Targeted and Responsive Nanoprodrug Delivery System for Synergistic Glioma Chemotherapy.

Doxorubicin (DOX) is widely used as a chemotherapeutic agent for both hematologic and solid tumors and is a reasonable candidate for glioma treatment. However, its effectiveness is hindered by significant toxicity and drug resistance. Moreover, the presence of the blood-brain barrier (BBB) brings a crucial challenge to glioma therapy.

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN- release and subsequently upregulate PDL-1 expression on tumor cells.

Current and promising therapies based on the pathogenesis of Graves' ophthalmopathy.

Graves' ophthalmopathy (GO) is a hyperthyroidism-related and immune-mediated disease that poses a significant threat to human health. The pathogenesis of GO primarily involves T cells, B cells, and fibroblasts, suggesting a pivotal role for the thyrotropin-antibody-immunocyte-fibroblast axis. Traditional treatment approaches for Graves' disease (GD) or GO encompass antithyroid drugs (ATDs), radioactive iodine, and beta-blockers.

Advances and challenges of immunotherapies in NK/T cell lymphomas.

Natural killer (NK)/T cell lymphoma (NKTCL) is a rare subtype of Epstein-Barr virus (EBV)-associated non-Hodgkin lymphoma characterized by poor clinical outcomes. It is more common in East Asian and Latin American countries. Despite the introduction of asparaginase/pegaspargase-based chemotherapy, the prognosis of patients with advanced NKTCL needs to be improved, and few salvage treatment options are available for relapsed/refractory patients who fail chemotherapy.

HSPA8 Activates Wnt/β-Catenin Signaling to Facilitate BRAF V600E Colorectal Cancer Progression by CMA-Mediated CAV1 Degradation.

BRAF V600E attracts wide attention in the treatment of colorectal cancer (CRC) as stratifying and predicting a refractory classification of CRC. Recent evidence indicates that Wnt/β-catenin signaling is broadly activated and participates in the refractoriness of BRAF V600E CRC, but the underlying molecular mechanism needs to be elucidated. Here, heat shock 70 kDa protein 8 (HSPA8), an essential regulator in chaperone-mediated autophagy (CMA), is identified as a potential therapeutic target for advanced BRAF V600E CRC.

Deficiency of inflammation-sensing protein neuropilin-2 in myeloid-derived macrophages exacerbates colitis via NF-κB activation.

Neuropilin-2 (NRP2) is a multifunctional protein engaged in the regulation of angiogenesis, lymphangiogenesis, axon guidance, and tumor metastasis, but its function in colitis remains unclear. Here, we found that NRP2 was an inflammation-sensing protein rapidly and dramatically induced in myeloid cells, especially in macrophages, under inflammatory contexts. NRP2 deficiency in myeloid cells exacerbated dextran sulfate sodium salt-induced experimental colitis by promoting polarization of M1 macrophages and colon injury.

COV2Var, a function annotation database of SARS-CoV-2 genetic variation.

The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, has resulted in the loss of millions of lives and severe global economic consequences. Every time SARS-CoV-2 replicates, the viruses acquire new mutations in their genomes. Mutations in SARS-CoV-2 genomes led to increased transmissibility, severe disease outcomes, evasion of the immune response, changes in clinical manifestations and reducing the efficacy of vaccines or treatments.