Genome mining of WOX-ARF gene linkage in Machilus pauhoi underpinned cambial activity associated with IAA induction.

As an upright tree with multifunctional economic application, Machilus pauhoi is an excellent choice in modern forestry from Lauraceae. The growth characteristics is of great significance for its molecular breeding and improvement. However, there still lack the information of WUSCHEL-related homeobox (WOX) and Auxin response factor (ARF) gene family, which were reported as specific transcription factors in plant growth as well as auxin signaling. Here, a total of sixteen MpWOX and twenty-one MpARF genes were identified from the genome of M. pauhoi. Though member of WOX conserved in the Lauraceae, MpWOX and MpARF genes were unevenly distributed on 12 chromosomes as a result of region duplication. These genes presented 45 and 142 miRNA editing sites, respectively, reflecting a potential post-transcriptional restrain. Overall, MpWOX4, MpWOX13a, MpWOX13b, MpARF6b, MpARF6c, and MpARF19a were highly co-expressed in the vascular cambium, forming a working mode as WOX-ARF complex. MpWOXs contains typical AuxRR-core and TGA-element cis-acting regulatory elements in this auxin signaling linkage. In addition, under IAA and NPA treatments, MpARF2a and MpWOX1a was highly sensitive to IAA response, showing significant changes after 6 hours of treatment. And MpWOX1a was significantly inhibited by NPA treatment. Through all these solid analysis, our findings provide a genetic foundation to growth mechanism analysis and further molecular designing breeding in Machilus pauhoi.

Treatment and prevention of chronic ankle instability: An umbrella review of meta-analyses.

BACKGROUND: Chronic ankle instability (CAI) is a common and highly disabling condition. Although several studies have evaluated and analyzed prevention and treatment strategies for CAI, an unbiased and systematic synthesis of evidence is required to provide the most powerful and comprehensive evidence-based measures for the its prevention and treatment of CAI. This study aimed to synthesize evidence from the existing literature addressing the treatment and prevention of CAI. METHODS: The PubMed, Embase, Cochrane, and Web of Science databases were systematically searched for relevant studies from inception to December 12, 2023. Data on effect sizes and corresponding 95 % confidence intervals for selected intervention measures were extracted. Systematic reviews were assessed for quality of included studies using a measurement tool (i.e., "AMSTAR 2"). RESULTS: In total, 37 studies were included, among which 21 (57 %) were of high or moderate quality. Strong evidence suggested that lower weight (P < 0.001), lower body mass index (P = 0.002), and non-stability defects (P = 0.04) significantly reduced the risk of developing CAI. Strong evidence supported exercise and moderate evidence supported manual therapy, acupuncture, and surgery for improving CAI. Additionally, external support plays an active role in the treatment process of CAI. CONCLUSION: This is the first study synthesizing evidence supporting interventions for the treatment and prevention of CAI. Low body weight and body mass index were effective preventive measures against CAI. Exercise, manual therapy, acupuncture, and surgery can improve ankle function in patients with CAI. Plantar sensory treatment and neuromuscular training may be good therapeutic options for patients with CAI. LEVEL OF EVIDENCE: Level I.

Hydrothermal Synthesis of ß-NiS Nanoparticles and Their Applications in High-Performance Hybrid Supercapacitors.

In this work, ß-NiS nanoparticles (NPs) were efficiently prepared by a straightforward hydrothermal process. The difference in morphology between these NiS NPs was produced by adding different amounts of thiourea, and the corresponding products were denoted as NiS-15 and NiS-5. Through electrochemical tests, the specific capacity (Cs) of NiS-15 was determined to be 638.34 C g-1 at 1 A g-1, compared to 558.17 C g-1 for NiS-5. To explore the practical application potential of such ß-NiS NPs in supercapacitors, a hybrid supercapacitor (HSC) device was assembled with activated carbon (AC) as an anode. Benefitting from the high capacity of the NiS cathode and the large voltage window of the device, the NiS-15//AC HSC showed a high energy density (Ed) of 43.57 W h kg-1 at 936.92 W kg-1, and the NiS-5//AC HSC provided an inferior Ed of 37.89 W h kg-1 at 954.79 W kg-1. Both HSCs showed excellent cycling performance over 6000 cycles at 10 A g-1. The experimental findings suggest that both NiS-15 and NiS-5 in this study can serve as potential cathodes for high-performance supercapacitors. This current synthesis method is simple and can be extended to the preparation of other transition metal sulfide (TMS)-based electrode materials with exceptional electrochemical properties.

PTEN regulated by gga-miR-20a-5p is involved in chicken macrophages inflammatory response to APEC infection via autophagy.

Colibacillosis, a bacterial disease caused by avian pathogenic E. coli (APEC), is a prevalent condition in the poultry industry, resulting in substantial economic losses annually. Previously, we identified PTEN as a crucial candidate gene that may play a significant role in chicken's immune response to APEC infection. Bioinformatics analysis indicated that the PTEN protein was unstable, hydrophilic and nuclear localization, with multiple putative phosphorylation sites and a high degree of similarity to duck and goose PTEN. Moreover, PTEN exhibited high expression levels in various tissues such as the stomach, cecum, small intestine, spleen, thymus, harderian gland, muscle, cerebrum, cerebellum, lung, and liver in comparison to heart tissue. Overexpression of PTEN resulted in a significant promotion of the expression level of pro-apoptosis genes and inflammatory mediators, as well as the production of NO, with or without APEC infection, which led to cellular injury. Furthermore, overexpression of PTEN was found to regulate the expression levels of autophagy related genes, regardless of APEC infection. Additionally, PTEN was a target gene of gga-miR-20a-5p and regulated by gga-miR-20a-5p upon APEC infection. Taken together, these findings establish a foundation for investigating the biological function of chicken PTEN, providing a potential target for future treatments against APEC infection as well as the breeding of genetically resistant poultry.

RNA-Activatable Near-Infrared Photosensitizer for Cancer Therapy.

Photodynamic therapy (PDT) has recently come to the forefront as an exceptionally powerful and promising method for the treatment of cancer. Existing photosensitizers are predominantly engineered to target diverse biomolecules, including proteins, DNA, lipids, and carbohydrates, and have proven to greatly enhance the efficacy or specificity of PDT. However, it is noteworthy that there exists a conspicuous scarcity of photosensitizers specifically designed to target RNAs. Recognizing the crucial and multifaceted roles played by RNAs in various cellular processes and disease states, we have ventured into the development of a novel RNA-targeting photosensitizer, named Se-718, designed specifically for PDT-based cancer therapy. Se-718 has been engineered to exhibit a high molar absorption coefficient in the NIR region, which is crucial for effective PDT. More importantly, Se-718 has demonstrated a distinct RNA-targeting capability, as evidenced through rigorous testing in both circular dichroism and fluorescence experiments. Furthermore, Se-718 has been shown to display both type I and type II photodynamic properties. This unique characteristic enables the efficient killing of cancer cells under a wide range of oxygen conditions, both normoxic (21% O2) and hypoxic (2% O2). The IC50 of Se-718 can be as low as 100 nM, and its light-to-dark toxicity ratio is an impressive 215 times higher, outperforming most photosensitizers currently available. Moreover, in vivo studies conducted with tumor-bearing mice have demonstrated the excellent antitumor effects and high safety profile of Se-718. Considering the outstanding PDT efficacy of Se-718, we are optimistic that the development of RNA-targeting photosensitizers may provide an innovative and highly effective option for cancer therapeutics in the near future.

MiR-20a-5p Targeting the TGFBR2 Gene Regulates Inflammatory Response of Chicken Macrophages Infected with Avian Pathogenic E. coli.

Avian pathogenic E. coli (APEC) causes localized and systemic infections and are a threat to human health. microRNAs (miRNAs) play critical roles in inflammation and immune regulation following pathogen invasion. However, the related regulatory mechanism remains unclear. This study aimed to elucidate the involvement of chicken microRNA-20a-5p (gga-miR-20a-5p) in host defense against APEC in chickens and the underlying mechanisms. We evaluated the expression levels of gga-miR-20a-5p in chicken tissues and cells and observed a significant decrease in expression following APEC infection. Dual luciferase reporter assays showed that gga-miR-20a-5p directly targeted transforming growth factor-beta receptor 2 (TGFBR2), specifically by binding to the 3'-untranslated region (3'UTR) of TGFBR2. Overexpression of gga-miR-20a-5p markedly reduced both the mRNA and protein levels of TGFBR2, whereas inhibition of gga-miR-20a-5p significantly increased expression. Mechanistic investigations revealed that overexpression of gga-miR-20a-5p also attenuated the expression levels of the pro-inflammatory cytokines IL8, TNFα, IL6, and IL1ß, whereas inhibition of gga-miR-20a-5p had the opposite effects. Collectively, our findings suggest that gga-miR-20a-5p regulates the immune response during APEC infection by targeting TGFBR2, thereby suppressing inflammatory cytokine production. This study provides valuable insights into the role of gga-miR-20a-5p in the host defense against APEC.

Identification and Functional Analysis of Novel Long Intergenic RNA in Chicken Macrophages Infected with Avian Pathogenic Escherichia coli.

Avian pathogenic E. coli (APEC), a widespread bacterium, results in serious economic losses to the poultry industry annually, and it poses a threat to human health due to the contaminated retail poultry meat and eggs. Recently, it has been demonstrated that long non-coding RNAs played important roles in regulating gene expression and the animal immune response. This study aimed to systematically explore the function of the novel long intergenic non-coding transcript, lincRNA-73240, upon APEC infection. A bioinformatics analysis indicated that lincRNA-73240 had no coding ability and a relative stable secondary structure with multiple hairpin rings. Moreover, the RT-qPCR results showed that lincRNA-73240 was highly expressed in lungs, heart, liver, spleen, cecum tonsils, thymus, ileum, bursa of Fabricius, harderian gland, and muscles in comparison to the cerebrum. Additionally, overexpression of lincRNA-73240 can promote the expression levels of inflammation, apoptosis, autophagy, and oxidative stress-related genes, as well as the production of reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO) upon APEC infection, which lead to cellular injury and apoptosis. These findings collectively establish a foundation for the study of the biological function of chicken lincRNA-73240 and provide a theoretical basis for further research on the molecular mechanisms of the chicken immune response.

Multidimensional analysis of TMEM132A in pan-cancer: unveiling its potential as a biomarker for treatment response prediction.

Background: TMEM132A is a transmembrane protein that regulates gastric cancer cell malignancy and overall survival in bladder cancer patients. However, while some studies have investigated the involvement of TMEM132A in specific cancers, further systematic studies are required to elucidate its specific mechanisms of action in different cancer types. Methods: We investigated the pan-cancer role of TMEM132A using several databases. We analyzed TMEM132A expression and its correlation with clinical survival, immune checkpoints, tumor stemness score, prognostic value, immunomodulators, genomic profiles, immunological characteristics, immunotherapy and functional enrichment. Results: First, it was observed that TMEM132A expression levels were higher in the majority of tumors compared to non-tumor tissues. In addition, high TMEM132A expression may have a higher prognostic value in some cancers. Furthermore, TMEM132A was significantly associated with immune checkpoints, immunomodulators, prognosis, immunomodulatory genes, tumor stemness score, cell function status and immune infiltration in most tumors. Further analysis of TMEM132A-related gene enrichment, mutation sites and types, RNA modification and genomic heterogeneity showed that the major mutations of TMEM132A were missense mutations and that TMEM132A plays a very important role in UCEC, LUAD and LIHC. Finally, these results suggest that high TMEM132A expression may be associated with a better response to specific immunotherapies. Conclusion: This comprehensive study uncovers an important function for TMEM132A in different types of cancer. It also has the potential to identify TMEM132A as a potential biomarker for predicting treatment response. This may help us to better understand how TMEM132A plays a role in cancer and provide valuable insights for developing personalised treatments.

Identification and functional analysis of circular RNA expression profiles associated with ammonia exposure in chicken lungs.

Ammonia acts as a detrimental atmospheric pollutant, posing a sever threat to respiratory tract health and causing lung injury in humans and animals. Circular RNAs (circRNAs) are a distinctive class of non-coding RNA generated by back-splicing of linear RNA, implicated in various biological processes. However, their role in the immune response of chicken lungs to ammonia exposure remains unclear. In this study, we examined the expression profiles of circRNAs in chicken lungs under ammonia stimulation. In total, 61 differentially expressed (DE) circRNAs were identified between the ammonia exposure and control groups, including 17 up-regulated and 44 down-regulated circRNAs. The source genes of these DE circRNAs were predominantly enriched in Influenza A, SNARE interactions in vesicular transport, and Notch signaling pathway. Notably, nine DE circRNAs (circNBAS, circMTIF2, circXPO1, circSNX24, circRAB11A, circARID3B, circUSP54, circPPARA, and circERG) were selected for validation the reliability and authenticity of RNA-seq data. Results showed the back-splicing circular structure, as well as the reliability and accuracy of RNA-seq data in quantifying circRNA expression, as the RT-qPCR results were in agreement with the RNA-seq data. Moreover, we constructed the circRNA-miRNA-mRNA regulatory networks and identified several regulatory networks in chicken lungs under ammonia stimulation, including circRAB11A-gga-miR-191b-3p-BRD2 and circARID3B-gga-miR-1696-CKS2. Taken together, our study delineates the circRNA expression profile and their potential roles in the immune response of chicken lungs to ammonia exposure. These findings offer insights into molecular mechanisms that may mitigate diseases associated with ammonia induced respiratory tract pollution in humans and animals.

Epinephelus coioides Sec3 promotes Singapore grouper iridovirus infection by negatively regulates immune response.

Exocyst, a protein complex, plays a crucial role in various cellular functions, including cell polarization, migration, invasion, cytokinesis, and autophagy. Sec3, known as Exoc1, is a key subunit of the Exocyst complex and can be involved in cell survival and apoptosis. In this study, two subtypes of Sec3 were isolated from Epinephelus coioides, an important marine fish in China. The role of E. coioides Sec3 was explored during Singapore grouper iridovirus (SGIV) infection, an important pathogen of marine fish which could induce 90 % mortality. E. coioides Sec3 sequences showed a high similarity with that from other species, indicating the presence of a conserved Sec3 superfamily domain. E. coioides Sec3 mRNA could be detected in all examined tissues, albeit at varying expression levels. SGIV infection could upregulate E. coioides Sec3 mRNA. Upregulated Sec3 significantly promoted SGIV-induced CPE, and the expressions of viral key genes. E. coioides Sec3 could inhibit the activation of NF-κB and AP-1, as well as SGIV-induced cell apoptosis. The results illustrated that E. coioides Sec3 promotes SGIV infection by regulating the innate immune response.

Associations between brain imaging-derived phenotypes and cognitive functions.

We aimed to evaluate the potential causal relationship between brain imaging-derived phenotypes and cognitive functions via Mendelian randomization analyses. Genetic instruments for 470 brain imaging-derived phenotypes were selected from a genome-wide association study based on the UK Biobank (n = 33,224). Statistics for cognitive functions were obtained from the genome-wide association study based on the UK Biobank. We used the inverse variance weighted Mendelian randomization method to investigate the associations between brain imaging-derived phenotypes and cognitive functions, and reverse Mendelian randomization analyses were performed for significant brain imaging-derived phenotypes to examine the reverse causation for the identified associations. We identified three brain imaging-derived phenotypes to be associated with verbal-numerical reasoning, including cortical surface area of the left fusiform gyrus (beta, 0.18 [95% confidence interval, 0.11 to 0.25], P = 4.74 × 10-7), cortical surface area of the right superior temporal gyrus (beta, 0.25 [95% confidence interval, 0.15 to 0.35], P = 6.30 × 10-7), and orientation dispersion in the left superior longitudinal fasciculus (beta, 0.14 [95% confidence interval, 0.09 to 0.20], P = 8.37 × 10-7). The reverse Mendelian randomization analysis indicated that verbal-numerical reasoning had no effect on these three brain imaging-derived phenotypes. This Mendelian randomization study identified cortical surface area of the left fusiform gyrus, cortical surface area of the right superior temporal gyrus, and orientation dispersion in the left superior longitudinal fasciculus as predictors of verbal-numerical reasoning.

ESF1 and MIPEP proteins promote estrogen receptor-positive breast cancer proliferation and are associated with patient prognosis.

BACKGROUND: Estrogen receptor-positive (ER+) breast cancer accounts for two-thirds of all breast cancers, and its early and late recurrences still threaten patients' long-term survival and quality of life. Finding candidate tumor antigens and potential therapeutic targets is critical to addressing these unmet needs. METHOD: The isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to identify the differentially expressed proteins (DEPs) between ER + breast cancer and corresponding adjacent normal tissue. Candidate DEPs were screened by bioinformatic analyses, and their expression was confirmed by immunohistochemical (IHC) staining and western blot. A series of in vitro experiments, including wound healing assay, colony formation, and cell cycle assay, were performed to reveal the functions of selected DEPs. Additionally, their clinical significances were further analyzed. RESULT: A total of 369 DEPs (fold change ≥ 2.0 or ≤ 0.66, P < 0.05) were discovered. Compared with normal tissue, 358 proteins were up-regulated and 11 proteins were down-regulated in ER + breast cancer. GO and KEGG enrichment analysis showed that DEPs were closely associated with RNA regulation and metabolic pathways. STRING analysis found ESF1 and MIPEP were the hub genes in breast cancer, whose increased expressions were verified by the IHC staining and western blot. Knocking down ESF1 and MIPEP inhibited colony formation and increased cell apoptosis. Besides, knocking down ESF1 inhibited wound healing but not MIPEP. In addition, ESF1 and MIPEP expression were negatively associated with patient prognosis. CONCLUSION: The upregulation of ESF1 and MIPEP promoted ER + breast cancer proliferation, which might provide novel targets for the development of new therapies.

In the Qaidam Basin, Soil Nutrients Directly or Indirectly Affect Desert Ecosystem Stability under Drought Stress through Plant Nutrients.

The low nutrient content of soil in desert ecosystems results in unique physiological and ecological characteristics of plants under long-term water and nutrient stress, which is the basis for the productivity and stability maintenance of the desert ecosystem. However, the relationship between the soil and the plant nutrient elements in the desert ecosystem and its mechanism for maintaining ecosystem stability is still unclear. In this study, 35 sampling sites were established in an area with typical desert vegetation in the Qaidam Basin, based on a drought gradient. A total of 90 soil samples and 100 plant samples were collected, and the soil's physico-chemical properties, as well as the nutrient elements in the plant leaves, were measured. Regression analysis, redundancy analysis (RDA), the Theil-Sen Median and Mann-Kendall methods, the structural equation model (SEM), and other methods were employed to analyze the distribution characteristics of the soil and plant nutrient elements along the drought gradient and the relationship between the soil and leaf nutrient elements and its impact on ecosystem stability. The results provided the following conclusions: Compared with the nutrient elements in plant leaves, the soil's nutrient elements had a more obvious regularity of distribution along the drought gradient. A strong correlation was observed between the soil and leaf nutrient elements, with soil organic carbon and alkali-hydrolyzed nitrogen identified as important factors influencing the leaf nutrient content. The SEM showed that the soil's organic carbon had a positive effect on ecosystem stability by influencing the leaf carbon, while the soil's available phosphorus and the mean annual temperature had a direct positive effect on stability, and the soil's total nitrogen had a negative effect on stability. In general, the soil nutrient content was high in areas with a low mean annual temperature and high precipitation, and the ecosystem stability in the area distribution of typical desert vegetation in the Qaidam Basin was low. These findings reveal that soil nutrients affect the stability of desert ecosystems directly or indirectly through plant nutrients in the Qaidam Basin, which is crucial for maintaining the stability of desert ecosystems with the background of climate change.

Wnt/ß-catenin signaling within multiple cell types dependent upon kramer regulates Drosophila intestinal stem cell proliferation.

The gut epithelium is subject to constant renewal, a process reliant upon intestinal stem cell (ISC) proliferation that is driven by Wnt/ß-catenin signaling. Despite the importance of Wnt signaling within ISCs, the relevance of Wnt signaling within other gut cell types and the underlying mechanisms that modulate Wnt signaling in these contexts remain incompletely understood. Using challenge of the Drosophila midgut with a non-lethal enteric pathogen, we examine the cellular determinants of ISC proliferation, harnessing kramer, a recently identified regulator of Wnt signaling pathways, as a mechanistic tool. We find that Wnt signaling within Prospero-positive cells supports ISC proliferation and that kramer regulates Wnt signaling in this context by antagonizing kelch, a Cullin-3 E3 ligase adaptor that mediates Dishevelled polyubiquitination. This work establishes kramer as a physiological regulator of Wnt/ß-catenin signaling in vivo and suggests enteroendocrine cells as a new cell type that regulates ISC proliferation via Wnt/ß-catenin signaling.

Reactivity-Tunable Fluorescent Platform for Selective and Biocompatible Modification of Cysteine or Lysine.

Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine-selective warheads face challenges due to cross-reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro- or phenoxy-substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy-NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH-overexpressed cancer cells. Conversely, alkoxy-NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti-interfering ability against thiols. Leveraging a proximity-driven approach, alkoxy-NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

Advances in Microfluidic Paper-Based Analytical Devices (µPADs): Design, Fabrication, and Applications.

Microfluidic Paper-based Analytical Devices (µPADs) have emerged as a new class of microfluidic systems, offering numerous advantages over traditional microfluidic chips. These advantages include simplicity, cost-effectiveness, stability, storability, disposability, and portability. As a result, various designs for different types of assays are developed and investigated. In recent years, µPADs are combined with conventional detection methods to enable rapid on-site detection, providing results comparable to expensive and sophisticated large-scale testing methods that require more time and skilled personnel. The application of µPAD techniques is extensive in environmental quality control/analysis, clinical diagnosis, and food safety testing, paving the way for on-site real-time diagnosis as a promising future development. This review focuses on the recent research advancements in the design, fabrication, material selection, and detection methods of µPADs. It provides a comprehensive understanding of their principles of operation, applications, and future development prospects.

Lactylation: the novel histone modification influence on gene expression, protein function, and disease.

Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential "writers" and "erasers" responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.

TransPTM: a transformer-based model for non-histone acetylation site prediction.

Protein acetylation is one of the extensively studied post-translational modifications (PTMs) due to its significant roles across a myriad of biological processes. Although many computational tools for acetylation site identification have been developed, there is a lack of benchmark dataset and bespoke predictors for non-histone acetylation site prediction. To address these problems, we have contributed to both dataset creation and predictor benchmark in this study. First, we construct a non-histone acetylation site benchmark dataset, namely NHAC, which includes 11 subsets according to the sequence length ranging from 11 to 61 amino acids. There are totally 886 positive samples and 4707 negative samples for each sequence length. Secondly, we propose TransPTM, a transformer-based neural network model for non-histone acetylation site predication. During the data representation phase, per-residue contextualized embeddings are extracted using ProtT5 (an existing pre-trained protein language model). This is followed by the implementation of a graph neural network framework, which consists of three TransformerConv layers for feature extraction and a multilayer perceptron module for classification. The benchmark results reflect that TransPTM has the competitive performance for non-histone acetylation site prediction over three state-of-the-art tools. It improves our comprehension on the PTM mechanism and provides a theoretical basis for developing drug targets for diseases. Moreover, the created PTM datasets fills the gap in non-histone acetylation site datasets and is beneficial to the related communities. The related source code and data utilized by TransPTM are accessible at https://www.github.com/TransPTM/TransPTM.

Age-Related Macular Degeneration: A Disease of Cellular Senescence and Dysregulated Immune Homeostasis.

Age-related macular degeneration (AMD) is a degenerative ocular disease primarily affecting central vision in the elderly. Its pathogenesis is complex, involving cellular senescence and immune homeostasis dysregulation. This review investigates the interaction between these two critical biological processes in AMD pathogenesis and their impact on disease progression. Initially, cellular senescence is analyzed, with particular emphasis on retinal damage induced by senescent retinal pigment epithelial cells. Subsequently, the occurrence of immune homeostasis dysregulation within the retina and its mechanistic role in AMD areis explored. Furthermore, the paper also discusses in detail the interplay between cellular senescence and immune responses, forming a vicious cycle that exacerbates retinal damage and may influence treatment outcomes. In summary, a deeper understanding of the interrelation between cellular senescence and immune dysregulation is vital for the developing innovative therapeutic strategies for AMD.

Unveiling the molecular complexity of proliferative diabetic retinopathy through scRNA-seq, AlphaFold 2, and machine learning.

Background: Proliferative diabetic retinopathy (PDR), a major cause of blindness, is characterized by complex pathogenesis. This study integrates single-cell RNA sequencing (scRNA-seq), Non-negative Matrix Factorization (NMF), machine learning, and AlphaFold 2 methods to explore the molecular level of PDR. Methods: We analyzed scRNA-seq data from PDR patients and healthy controls to identify distinct cellular subtypes and gene expression patterns. NMF was used to define specific transcriptional programs in PDR. The oxidative stress-related genes (ORGs) identified within Meta-Program 1 were utilized to construct a predictive model using twelve machine learning algorithms. Furthermore, we employed AlphaFold 2 for the prediction of protein structures, complementing this with molecular docking to validate the structural foundation of potential therapeutic targets. We also analyzed protein-protein interaction (PPI) networks and the interplay among key ORGs. Results: Our scRNA-seq analysis revealed five major cell types and 14 subcell types in PDR patients, with significant differences in gene expression compared to those in controls. We identified three key meta-programs underscoring the role of microglia in the pathogenesis of PDR. Three critical ORGs (ALKBH1, PSIP1, and ATP13A2) were identified, with the best-performing predictive model demonstrating high accuracy (AUC of 0.989 in the training cohort and 0.833 in the validation cohort). Moreover, AlphaFold 2 predictions combined with molecular docking revealed that resveratrol has a strong affinity for ALKBH1, indicating its potential as a targeted therapeutic agent. PPI network analysis, revealed a complex network of interactions among the hub ORGs and other genes, suggesting a collective role in PDR pathogenesis. Conclusion: This study provides insights into the cellular and molecular aspects of PDR, identifying potential biomarkers and therapeutic targets using advanced technological approaches.