Transcriptomics analysis of LINC02202/XBP1 axis in melanoma: Implications for drug targeting and PD-1 monoclonal antibody efficacy.

Malignant melanoma (MM) is a highly aggressive and deadly form of skin cancer, primarily caused by recurrence and metastasis. Therefore, it is crucial to investigate the regulatory mechanisms underlying melanoma recurrence and metastasis. Our study has identified a potential targeted regulatory relationship between LINC02202, miR-526b-3p and XBP1 in malignant melanoma. Through the regulation of the miR-526b-3p/XBP1 signalling pathway, LINC02202 may play a role in tumour progression and immune infiltration and inhibiting the expression of LINC02202 can increase the efficacy of immunotherapy for melanoma. Our findings shed light on the impact of LINC02202/XBP1 on the phenotype and function of malignant melanoma cells. Furthermore, this study provides a theoretical foundation for the development of novel immunotherapy strategies for malignant melanoma.

Application of synthetic biology strategies to promote biosynthesis of fatty acids and their derivatives.

Fatty acids and their derivatives are indispensable biomolecules in all organisms, and can be used as intermediates in the synthesis of pharmaceuticals, biofuels and pesticides, and thus their demand has increased dramatically in recent years. In addition to serving as structural components of cell membranes and metabolic energy, fatty acids and their derivatives can also be used as signal transduction and regulatory bioactive molecules to regulate cell functions. Biosynthesis of fatty acids and their derivatives through microbial catalysis provides green and alternative options to meet the goal. However, the low biosynthetic titer of fatty acids and their derivatives limits their industrial production and application. In this review, we first summarize the metabolic pathways and related enzymes of fatty acids and their derivatives biosynthesis. Then, the strategies and research progress of biosynthesis of fatty acids and derivatives through metabolic and enzyme engineering were reviewed. The biosynthesis of saturated fatty acids (medium chain fatty acids and long chain fatty acids), bioactive fatty acids (PUFAs, oxylipins, ether lipids), and their derivatives with microbial and enzymatic catalysis were respectively summarized. Finally, synthetic biology strategies to improve fatty acids and their derivatives production through enzyme rational design, carbon metabolism flux, cofactors balance, and metabolic pathways design were discussed. The review provides references and prospects for fatty acids and their derivatives biosynthesis and industrial production.

Efficacy and Safety of Topical Traditional Chinese Medicine Monotherapy in Persistent HPV Infection Among Males.

Objective: We studied the efficacy and safety of traditional Chinese medicine paiteling treatment of persistent human papillomavirus (HPV) infection in males. Methods: The study included 159 male patients with persistent HPV infection between January 2018 and July 2022, and categorized into the treatment group (n = 96) and control group (n = 63) based on the treatment. The treatment group was externally treated with paiteling diluent for 4 consecutive days and then stopped for 3 days. The total course of treatment was one month. The treatment group underwent a second test six months after treatment. The control group did not receive any therapy and underwent a second test in the seventh month. Results: 19 of the 159 patients were lost during the 6-month follow-up period, leaving 140 patients. The male HPV infection peaks between the ages of 26-35 years 73(52.14%), and its prevalence decrease with age. 84 (60.0%) were single type infections, and 22 (15.71%) had at least 3 types infections. There were 76 (54.29%) patients with the high-risk types, 34 (24.29%) with the low-risk types, and 30 (21.43%) with the mixed types. After 6 months, complete negative conversion rates and negative conversion rates were 74.7% and 90.8% in the treatment group respectively, compared to the control group (P < .01). A comparison of negative conversion rates among different types reveals that 16 type (89.5%) and 6 type (92.3%) had statistical differences, (P < .01) and (P < .05) respectively. Multivariate analysis revealed that the vaccine status of sexual partners was a protective factor (OR = 0.050-0.848) and multi-type infection was a risk factor (OR = 1.807-22.527) for the curative effect. Conclusion: Paiteling is convenient, safe, and effective for the treatment of persistent HPV infection in males.

Multicell-Fold: geometric learning in folding multicellular life.

During developmental processes such as embryogenesis, how a group of cells fold into specific structures, is a central question in biology. However, it remains a major challenge to understand and predict the behavior of every cell within the living tissue over time during such intricate processes. Here we present a geometric deep-learning model that can accurately capture the highly convoluted interactions among cells. We demonstrate that multicellular data can be represented with both granular and foam-like physical pictures through a unified graph data structure, considering both cellular interactions and cell junction networks. Using this model, we achieve interpretable 4-D morphological sequence alignment, and predicting cell rearrangements before they occur at single-cell resolution. Furthermore, using neural activation map and ablation studies, we demonstrate cell geometries and cell junction networks together regulate morphogenesis at single-cell precision. This approach offers a pathway toward a unified dynamic atlas for a variety of developmental processes.

Repeat DNA methylation is modulated by adherens junction signaling.

Through its involvement in gene transcription and heterochromatin formation, DNA methylation regulates how cells interact with their environment. Nevertheless, the extracellular signaling cues that modulate the distribution of this central chromatin modification are largely unclear. DNA methylation is highly abundant at repetitive elements, but its investigation in live cells has been complicated by methodological challenges. Utilizing a CRISPR/dCas9 biosensor that reads DNA methylation of human α-satellite repeats in live cells, we here uncover a signaling pathway linking the chromatin and transcriptional state of repetitive elements to epithelial adherens junction integrity. Specifically, we find that in confluent breast epithelial cell monolayers, α-satellite repeat methylation is reduced by comparison to low density cultures. This is coupled with increased transcriptional activity at repeats. Through comprehensive perturbation experiments, we identify the junctional protein E-cadherin, which links to the actin cytoskeleton, as a central molecular player for signal relay into the nucleus. Furthermore, we find that this pathway is impaired in cancer cells that lack E-cadherin and are not contact-inhibited. This suggests that the molecular connection between cell density and repetitive element methylation could play a role in the maintenance of epithelial tissue homeostasis.

Learning Dynamics from Multicellular Graphs with Deep Neural Networks.

Multicellular self-assembly into functional structures is a dynamic process that is critical in the development and diseases, including embryo development, organ formation, tumor invasion, and others. Being able to infer collective cell migratory dynamics from their static configuration is valuable for both understanding and predicting these complex processes. However, the identification of structural features that can indicate multicellular motion has been difficult, and existing metrics largely rely on physical instincts. Here we show that using a graph neural network (GNN), the motion of multicellular collectives can be inferred from a static snapshot of cell positions, in both experimental and synthetic datasets.

Vimentin is a key regulator of cell mechanosensing through opposite actions on actomyosin and microtubule networks.

The cytoskeleton is a complex network of interconnected biopolymers consisting of actin filaments, microtubules, and intermediate filaments. These biopolymers work in concert to transmit cell-generated forces to the extracellular matrix required for cell motility, wound healing, and tissue maintenance. While we know cell-generated forces are driven by actomyosin contractility and balanced by microtubule network resistance, the effect of intermediate filaments on cellular forces is unclear. Using a combination of theoretical modeling and experiments, we show that vimentin intermediate filaments tune cell stress by assisting in both actomyosin-based force transmission and reinforcement of microtubule networks under compression. We show that the competition between these two opposing effects of vimentin is regulated by the microenvironment stiffness. These results reconcile seemingly contradictory results in the literature and provide a unified description of vimentin's effects on the transmission of cell contractile forces to the extracellular matrix.