Milestones in understanding transport, sensing, and signaling of the plant nutrient phosphorus.

As an essential nutrient element, phosphorus (P) is primarily acquired and translocated as inorganic phosphate (Pi) by plant roots. Pi is often sequestered in the soil and becomes limited for plant growth. Plants have developed a sophisticated array of adaptive responses, termed P starvation responses, to cope with P deficiency by improving its external acquisition and internal utilization. Over the past 2 to 3 decades, remarkable progress has been made toward understanding how plants sense and respond to changing environmental P. This review provides an overview of the molecular mechanisms that regulate or coordinate P starvation responses, emphasizing P transport, sensing, and signaling. We present the major players and regulators responsible for Pi uptake and translocation. We then introduce how P is perceived at the root tip, how systemic P signaling is operated, and the mechanisms by which the intracellular P status is sensed and conveyed. Additionally, the recent exciting findings about the influence of P on plant-microbe interactions are highlighted. Finally, the challenges and prospects concerning the interplay between P and other nutrients and strategies to enhance P utilization efficiency are discussed. Insights obtained from this knowledge may guide future research endeavors in sustainable agriculture.

LncRNA SNHG3 discriminates rheumatoid arthritis from healthy individuals and regulates inflammatory response and oxidative stress via modulating miR-128-3p.

OBJECTIVES: This study evaluated the expression and significance of SNHG3 in Rheumatoid arthritis (RA) aiming to explore a biomarker and regulator for RA. METHODS: The expression of SNHG3 in serum and synovial tissue was compared between RA patients and healthy individuals using PCR. The RA animal models were induced by the porcine type II collagen with Wistar rats and validated by the foot volume and AI score. The human fibroblast-like synoviocytes (H-FLS) were treated with LPS to mimic the injury during RA onset and the cell growth was assessed by CCK8 assay. RESULTS: SNHG3 was significantly downregulated in the serum and synovial tissue of RA patients compared with healthy individuals. Downregulated SNHG3 could discriminate RA patients from healthy individuals with high sensitivity (0.875) and specificity (0.844). Porcine type II collagen induced increasing foot volume and AI scores of rats and SNHG3 was downregulated in RA rats. In LPS-induced H-FLS, SNHG3 negatively regulated miR-128-3p, and the alleviated effect of SNHG3 overexpression on cellular inflammation and oxidative stress was reversed by miR-128-3p upregulation. CONCLUSIONS: Serum SNHG3 was considered a potential diagnostic biomarker for RA from healthy individuals. SNHG3 regulated inflammatory response and oxidative stress via negatively modulating miR-128-3p.

Integrated analysis and clinical correlation analysis of hub genes, immune infiltration, and potential therapeutic agents related to lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is the most common complication of systemic lupus erythematosus (SLE). This study aimed to explore biomarkers, mechanisms, and potential novel agents regarding LN through bioinformatic analysis. METHOD: Four expression profiles were downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were acquired. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) pathway enrichment analyses of DEGs were performed using the R software. The protein-protein interaction (PPI) network was developed using the STRING database. Additionally, five algorithms were used to screen out the hub genes. Expression of the hub genes were validated using Nephroseq v5. CIBERSORT was used to evaluate the infiltration of immune cells. Finally, The Drug-Gene Interaction Database was used to predict potential targeted drugs. RESULT: FOS and IGF1 were identified as hub genes, with excellent specificity and sensitivity diagnosis of LN. FOS was also related to renal injury. LN patients had lower activated and resting dendritic cells (DCs) and higher M1 macrophages and activated NK cells than healthy control (HC). FOS had a positive correlation with activated mast cells and a negative correlation with resting mast cells. IGF1 had a positive correlation with activated DCs and a negative correlation with monocytes. The targeted drugs were dusigitumab and xentuzumab target for IGF1. CONCLUSION: We analyzed the transcriptomic signature of LN along with the landscape of the immune cell. FOS and IGF1 are promising biomarkers for diagnosing and evaluating the progression of LN. The drug-gene interaction analyses provide a list of candidate drugs for the precise treatment of LN.

A modified CVD method for the synthesis of monolayer MoS2and photoelectric improvement by HfO2passivation.

Molybdenum disulfide (MoS2) is an emerging class of new materials with a wide range of potential practical applications. However, the uncontrollability of monolayer MoS2synthesized by traditional chemical vapor deposition method and the low responsivity of MoS2photodetectors limit its further development in the field of photoelectric detection. To achieve controlled growth of monolayer MoS2and construct MoS2photodetectors with a high responsivity, we propose a novel single crystal growth strategy of high-quality MoS2by controlling the Mo to S vapor ratio near the substrate, and deposit a layer of hafnium oxide (HfO2) on the surface of MoS2to enhance the performance of the pristine metal-semiconductor-metal structure photodetector. At a reverse bias of 8 V, the HfO2passivated MoS2photodetector features an extremely high responsivity of1201AW-1,a response time of around 0.5 s, and a detectivity of7.7×1011Jones.Meanwhile, we deeply investigate the effect of the HfO2layer on the performance of the fabricated MoS2photodetector and propose a physical mechanism to interpret the obtained experiment results. These results might facilitate a better understanding on the performance modulation of the MoS2photodetectors and accelerate the development of MoS2-based optoelectronic devices.

Exploration of the molecular mechanisms, shared gene signatures, and MicroRNAs between systemic lupus erythematosus and diffuse large B cell lymphoma by bioinformatics analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex heterogeneous systemic autoimmune disease. Previous studies have shown that SLE may be related to diffuse large B cell lymphoma (DLBCL), but the mechanism of their relationship is still unclear. The present study aimed to explore the common genetic molecular mechanisms, core shared genes, and miRNAs between SLE and DLBCL as well as to investigate the diagnostic markers of DLBCL. METHODS: The SLE and DLBCL microarray data were downloaded from the comprehensive Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules. Four core shared genes were screened out by various algorithms and validated in other cohorts. Finally, we constructed a common core gene-miRNA network using the human microRNA disease database (HMDD) and TarBase. RESULTS: Using WGCNA, four modules were identified as important modules for SLE and DLBCL. Enrichment analysis of the shared genes showed that the highly activated NF-κB pathway was a common feature of the pathophysiology. Four core shared genes, namely, PSMB10, PSMB4, TAF10, and NFΚBIA, were screened out. These core shared genes were significantly upregulated in both diseases, and they may be potential diagnostic markers of DLBCL. The core gene-miRNA network showed that miR-155-5p, regulating the shared NF-κB pathway, may play an important role in the susceptibility of SLE patients to DLBCL. CONCLUSION: The present study revealed that NF-κB pathway in SLE may be a crucial susceptible factor for DLBCL. In addition, we identified PSMB10, PSMB4, TAF10, NFΚBIA and miR-155 involved in the common pathogenesis as potential biomarkers and therapeutic targets for DLBCL.

Association between schizophrenia and prostate cancer risk: Results from a pool of cohort studies and Mendelian randomization analysis.

BACKGROUND: Observational studies analyzing the risk of prostate cancer in schizophrenia patients have generated mixed results. We performed a meta-analysis and a Mendelian randomization (MR) analysis to evaluate the relationship and causality between schizophrenia and the risk of prostate cancer. METHODS: A comprehensive and systematic search of cohort studies was conducted, and a random-effects model meta-analysis was performed to calculate the standardized incidence ratios (SIRs) for prostate cancer incidence among schizophrenia patients versus the general population. To investigate the correlation between genetically-predicted schizophrenia and prostate cancer risk, we used summary statistics from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium (61,106 controls and 79,148 cases), and 75 schizophrenia-associated single nucleotide polymorphisms (SNP) from European descent as the instrumental variable. RESULTS: In the meta-analysis of 13 cohort studies with 218,076 men involved, a decreased risk of prostate cancer was observed among schizophrenia patients [SIR 0.610; 95% confidence interval (CI) 0.500-0.740; p < 0.001] with significant heterogeneity (I2 = 83.3%; p < 0.001). However, MR analysis did not sustain the link between genetically-predicted schizophrenia and prostate cancer [odds ratio (OR) 1.033; 95% CI 0.998-1.069; p = 0.065]. The result was robust against extensive sensitivity analyses. CONCLUSIONS: Our study indicated a decreased risk of prostate cancer in schizophrenia patients through meta-analysis, while MR analysis did not support the connection between schizophrenia and prostate cancer. Due to the interaction of genetic variants between binary exposures, we need to be cautious in interpreting and presenting causal associations. Moreover, further research is needed to investigate underlying factors that might link schizophrenia to the risk of prostate cancer.

Growth of lateral graphene/h-BN heterostructure on copper foils by chemical vapor deposition.

The synthesis of lateral heterostructures assembled by atomically-thin materials with distinct intrinsic properties is important for future heterojunction-embedded two-dimensional (2D) devices. Here we report an etching-assisted chemical vapor deposition method to synthesize large-area continuous lateral graphene/hexagonal boron nitride (Gr/h-BN) heterostructures on carbon-containing copper foils. The h-BN film is first synthesized on the copper foil, followed by hydrogen etching, and then epitaxial graphene domains are grown to form continuous lateral heterostructures. Analyses, including Raman spectroscopy, atomic force microscopy, scanning electron microscopy, x-ray photoelectron spectroscopy, and ultraviolet-visible absorption spectroscopy, are used to characterize the coexistence of both materials and the highly continuous nature of this lateral heterostructure. This facile and scalable synthesizing method enables the potential usage of Gr/h-BN heterostructure in both fundamental studies and related 2D devices.

Evolution of microRNA827 targeting in the plant kingdom.

Unlike most ancient microRNAs, which conservatively target homologous genes across species, microRNA827 (miR827) targets two different types of SPX (SYG1/PHO81/XPR1)-domain-containing genes, NITROGEN LIMITATION ADAPTATION (NLA) and PHOSPHATE TRANSPORTER 5 (PHT5), in Arabidopsis thaliana and Oryza sativa to regulate phosphate (Pi) transport and storage, respectively. However, how miR827 shifted its target preference and its evolutionary history are unknown. Based on target prediction analysis, we found that in most angiosperms, miR827 conservatively targets PHT5 homologs, but in Brassicaceae and Cleomaceae it preferentially targets NLA homologs, and we provide evidence for the transition of target preference during Brassicales evolution. Intriguingly, we found a lineage-specific loss of the miR827-regulatory module in legumes. Analysis of miR827-mediated cleavage efficiency and the expression of PHT5 in A. thaliana indicated that accumulation of mutations in the target site and the exclusion of the target site by alternative transcriptional initiation eliminated PHT5 targeting by miR827. Here, we identified a transition of miR827 target preference during plant evolution and revealed the uniqueness of miR827-mediated regulation among conserved plant miRNAs. Despite the change in its target preference, upregulation of miR827 by Pi starvation and its role in regulating cellular Pi homeostasis were retained.

Graphene-Based Fluorescence-Quenching-Related Fermi Level Elevation and Electron-Concentration Surge.

Intermolecular p-orbital overlaps in unsaturated π-conjugated systems, such as graphene and fluorescent molecules with aromatic structure, serve as the electron-exchanged path. Using Raman-mapping measurements, we observe that the fluorescence intensity of fluorescein isothiocyanate (FITC) is quenched by graphene, whereas it persists in graphene-absent substrates (SiO2). After identifying a mechanism related to photon-induced electron transfer (PET) that contributes to this fluorescence quenching phenomenon, we validate this mechanism by conducting analyses on Dirac point shifts of FITC-coated graphene. From these shifts, Fermi level elevation and the electron-concentration surge in graphene upon visible-light impingements are acquired. Finally, according to this mechanism, graphene-based biosensors are fabricated to show the sensing capability of measuring fluorescently labeled-biomolecule concentrations.

Nitrogen limitation adaptation, a target of microRNA827, mediates degradation of plasma membrane-localized phosphate transporters to maintain phosphate homeostasis in Arabidopsis.

Members of the Arabidopsis thaliana phosphate transporter1 (PHT1) family are key players in acquisition of Pi from the rhizosphere, and their regulation is indispensable for the maintenance of cellular Pi homeostasis. Here, we reveal posttranslational regulation of Pi transport through modulation of degradation of PHT1 proteins by the RING-type ubiquitin E3 ligase, nitrogen limitation adaptation (NLA). Loss of function of NLA caused high Pi accumulation resulting from increases in the levels of several PHT1s at the protein rather than the transcript level. Evidence of decreased endocytosis and ubiquitination of PHT1s in nla mutants and interaction between NLA and PHT1s in the plasma membranes suggests that NLA directs the ubiquitination of plasma membrane-localized PHT1s, which triggers clathrin-dependent endocytosis followed by endosomal sorting to vacuoles. Furthermore, different subcellular localization of NLA and phosphate2 (pho2; a ubiquitin E2 conjugase) and the synergistic effect of the accumulation of PHT1s and Pi in nla pho2 mutants suggest that they function independently but cooperatively to regulate PHT1 protein amounts. Intriguingly, NLA and PHO2 are the targets of two Pi starvation-induced microRNAs, miR827 and miR399, respectively. Therefore, our findings uncover modulation of Pi transport activity in response to Pi availability through the integration of a microRNA-mediated posttranscriptional pathway and a ubiquitin-mediated posttranslational regulatory pathway.

Identification of downstream components of ubiquitin-conjugating enzyme PHOSPHATE2 by quantitative membrane proteomics in Arabidopsis roots.

MicroRNA399-mediated regulation of the ubiquitin-conjugating enzyme UBC24/phosphate2 (PHO2) is crucial for Pi acquisition and translocation in plants. Because of a potential role for PHO2 in protein degradation and its association with membranes, an iTRAQ (for isobaric tags for relative and absolute quantitation)- based quantitative membrane proteomic method was employed to search for components downstream of PHO2. A total of 7491 proteins were identified from Arabidopsis thaliana roots by mass spectrometry, 35.2% of which were predicted to contain at least one transmembrane helix. Among the quantifiable proteins, five were significantly differentially expressed between the wild type and pho2 mutant under two growth conditions. Using immunoblot analysis, we validated the upregulation of several members in phosphate transporter1 (PHT1) family and phosphate transporter traffic facilitator1 (PHF1) in pho2 and demonstrated that PHO2 mediates the degradation of PHT1 proteins. Genetic evidence that loss of PHF1 or PHT1;1 alleviated Pi toxicity in pho2 further suggests that they play roles as downstream components of PHO2. Moreover, we showed that PHO2 interacts with PHT1s in the postendoplasmic reticulum compartments and mediates the ubiquitination of endomembrane-localized PHT1;1. This study not only uncovers a mechanism by which PHO2 modulates Pi acquisition by regulating the abundance of PHT1s in the secretory pathway destined for plasma membranes, but also provides a database of the membrane proteome that will be widely applicable in root biology research.

Study on the diffusion mechanism of graphene grown on copper pockets.

A correlation between graphene domains grown on the outer and the inner surfaces of Cu pockets is found, which discloses a new graphene growth mechanism based on the fast diffusion of carbon atoms through the 25 micro-meter-thick Cu foil, confirmed by isotopic labeling. Subsequently, on the outer surface of the Cu pocket, bilayer graphene with a coverage of about 78% is grown.

Transgenic plants that express the phytoplasma effector SAP11 show altered phosphate starvation and defense responses.

Phytoplasmas have the smallest genome among bacteria and lack many essential genes required for biosynthetic and metabolic functions, making them unculturable, phloem-limited plant pathogens. In this study, we observed that transgenic Arabidopsis (Arabidopsis thaliana) expressing the secreted Aster Yellows phytoplasma strain Witches' Broom protein11 shows an altered root architecture, similarly to the disease symptoms of phytoplasma-infected plants, by forming hairy roots. This morphological change is paralleled by an accumulation of cellular phosphate (Pi) and an increase in the expression levels of Pi starvation-induced genes and microRNAs. In addition to the Pi starvation responses, we found that secreted Aster Yellows phytoplasma strain Witches' Broom protein11 suppresses salicylic acid-mediated defense responses and enhances the growth of a bacterial pathogen. These results contribute to an improved understanding of the role of phytoplasma effector SAP11 and provide new insights for understanding the molecular basis of plant-pathogen interactions.

Increased phosphate transport of Arabidopsis thaliana Pht1;1 by site-directed mutagenesis of tyrosine 312 may be attributed to the disruption of homomeric interactions.

Members of the Pht1 family of plant phosphate (Pi) transporters play vital roles in Pi acquisition from soil and in planta Pi translocation to maintain optimal growth and development. The study of the specificities and biochemical properties of Pht1 transporters will contribute to improving the current understanding of plant phosphorus homeostasis and use-efficiency. In this study, we show through split in vivo interaction methods and in vitro analysis of microsomal root tissues that Arabidopsis thaliana Pht1;1 and Pht1;4 form homomeric and heteromeric complexes. Transient and heterologous expression of the Pht1;1 variants, Pht1;1(Y312D), Pht1;1(Y312A) and Pht1;1(Y312F), was used to analyse the role of a putative Pi binding residue (Tyr 312) in Pht1;1 transporter oligomerization and function. The homomeric interaction among Pht1;1 proteins was disrupted by mutation of Tyr 312 to Asp, but not to Ala or Phe. In addition, the Pht1;1(Y312D) variant conferred enhanced Pi transport when expressed in yeast cells. In contrast, mutation of Tyr 312 to Ala or Phe did not affect Pht1;1 transport kinetics. Our study demonstrates that modifications to the Pht1;1 higher-order structure affects Pi transport, suggesting that oligomerization may serve as a regulatory mechanism for modulating Pi uptake.

PHO2-dependent degradation of PHO1 modulates phosphate homeostasis in Arabidopsis.

The Arabidopsis thaliana pho2 mutant, which is defective in a ubiquitin-conjugating E2 enzyme, displays inorganic phosphate (Pi) toxicity as a result of enhanced uptake and root-to-shoot translocation of Pi. To elucidate downstream components of the PHO2-dependent regulatory pathway, we identified two pho2 suppressors as carrying missense mutations in PHO1, which has been implicated in Pi loading to the xylem. In support of the genetic interaction between PHO1 and PHO2, we found that the protein level of PHO1 is increased in pho2, whereas such accumulation is ameliorated in both pho2 suppressors. Results from cycloheximide and endosomal Cys protease inhibitor E-64d treatments further suggest that PHO1 degradation is PHO2 dependent and involves multivesicular body-mediated vacuolar proteolysis. Using the transient expression system of tobacco (Nicotiana tabacum) leaves, we demonstrated that PHO1 and PHO2 are partially colocalized and physically interact in the endomembranes, where the ubiquitin conjugase activity of PHO2 is required for PHO1 degradation. In addition, reduced PHO1 expression caused by PHO1 mutations impede Pi uptake, indicating a functional association between xylem loading and acquisition of Pi. Together, our findings uncover a pivotal molecular mechanism by which PHO2 modulates the degradation of PHO1 in the endomembranes to maintain Pi homeostasis in plants.

Long-distance call from phosphate: systemic regulation of phosphate starvation responses.

Phosphate (Pi) is an essential nutrient for plants but is normally fixed in soil, which limits plant growth and reproduction. In response to low availability of Pi, shoots and roots react differently but cooperatively to improve Pi acquisition from the rhizosphere and adjust Pi distribution and metabolism within plants. Shoot and root responses are coordinated by the trafficking of various kinds of systemic signals through the vasculature. Mutual communication between different tissues is necessary to integrate the environmental stimuli with the internal cues at the whole-plant level. Different approaches have been used to monitor or manipulate components in the vascular stream to reveal several candidates of systemic signals from roots or shoots, including photosynthates, phytohormones, microRNAs, and Pi. In addition, the downstream signalling pathways mediated by these signals have been discovered. The crosstalk among different signalling pathways has been revealed, showing the complexity of the Pi signalling network. In this review, we summarize the approaches used for studying systemic signalling and discuss recent progress and challenges in investigating the systemic signalling pathway that integrates Pi starvation responses to maintain Pi at physiological concentrations. Knowledge gained from this study may help improve the phosphorus use efficiency of crops.

Clinical significance of long non-coding RNA NORAD in rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that may cause joint deformities and seriously affect the normal life of the patients. In order to enable patients to receive timely attention and treatment, this study developed new diagnostic markers by exploring the expression and molecular mechanism of the long non-coding RNA NORAD (NORAD) in RA. METHODS: Participants including 77 RA patients and 52 healthy persons were enrolled, and the corresponding clinical data and serum samples were obtained. The NORAD and miR-204-5p expression were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The content of inflammatory cytokines (IL-6, TNF-α) were determined through enzyme-linked immunosorbent assay (ELISA). Luciferase activity reporter assay demonstrated the association between NORAD and miR-204-5p. In addition, receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of NORAD, and Pearson's correlation analysis was applied for the correlation analysis. RESULTS: NORAD was enriched in RA serum with high diagnostic value. Simultaneously, IL-6 and TNF-α levels were also upregulated (P < 0.001). The C-reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR) and anti-cyclic citrullinated peptide antibody (Anti-CCP) levels in RA patients were generally elevated (P < 0.001). NORAD was positively correlated with the levels of clinical indicators and inflammatory factors (P < 0.0001). Mechanistically, NORAD may affect the progression of RA by targeting and negatively regulating miR-204-5p. CONCLUSIONS: There is a correlation between NORAD and the processes of RA, and NORAD has the potential to predict and diagnose the occurrence of RA.

Variation of growth and transcriptome responses to arbuscular mycorrhizal symbiosis in different foxtail millet lines.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) have been applied to promote the growth of different crop species, but knowledge about the impacts of symbiosis on foxtail millet at the physiological and molecular levels have remained limited. In this study, we compared the mycorrhization phenotypes of one cultivar and three different landraces and performed a comprehensive transcriptomic analysis to assess the effects of genetic variation on the responses to symbiosis. RESULTS: Our results showed that colonization by AMF did not enhance biomass accumulation but significantly increased grain production only in three lines. More than 2,000 genes were affected by AMF colonization in all lines. Most AM symbiosis-conserved genes were induced, but the induction levels varied between lines. Gene Ontology (GO) analysis showed that Biological Function terms related to nitrogen transport and assimilation were only enriched in TT8. Similarly, two of phosphate starvation-induced phosphate transporters were only simultaneously downregulated in TT8. In the other two lines, the enrichment of GO terms associated with cell wall reorganization and lignification was observed, though the effects were different. CONCLUSION: This study reveals the impacts of genetic variation of millet lines on the responses to AM symbiosis and provides information regarding AMF application for millet production.

[Renaissance of prepectoral implant-based breast reconstruction: theoretical basis and research status].

Objective: To overview the theoretical basis and research status of prepectoral implant-based breast reconstruction. Methods: The domestic and foreign researches on the application of prepectoral implant-based breast reconstruction in breast reconstruction were retrospectively analyzed. The theoretical basis, clinical advantages, and limitations of this technique were summarized and the future development trend in this field was discussed. Results: The recent advances in breast cancer oncology, the development of materials and the concept of oncology reconstruction have provided a theoretical basis for prepectoral implant-based breast reconstruction. The selection of patients and the experience of surgeons are crucial for postoperative outcomes. Ideal thickness and blood flow of flaps are the most important considerations for the selection of prepectoral implant-based breast reconstruction. However, its long-term reconstruction outcomes and clinical benefits and risks in Asian populations still need to be confirmed by more studies. Conclusion: Prepectoral implant-based breast reconstruction has a broad application prospect in breast reconstruction following mastectomy. However, the evidence is limited at present. Randomized study with long-term follow-up is urgently in need to provide sufficient evidence to evaluate the safety and reliability of prepectoral implant-based breast reconstruction.

Genes associated with cellular senescence favor melanoma prognosis by stimulating immune responses in tumor microenvironment.

PURPOSE: Skin cutaneous melanoma (SKCM), a malignant tumor from melanocytes, is the fifth most prevalent tumor. Immune checkpoint inhibitor (ICI) immunotherapy improves prognosis of SKCM, but immune response varies for different populations. Cellular senescence in the tumor microenvironment (TME) promotes antitumor immunity, mediated by dendritic cells (DC) and CD8+ T cells. Therefore, we sought to explore the role of cellular senescence in the TME of SKCM through bioinformatics and machine learning. METHODS: First, we obtained 93 cellular senescence-prognosis genes (CSPGs) by univariate survival analysis. Thereafter, 23 optimal CSPGs were obtained by least absolute shrinkage and selection operator (lasso) analysis. Based on the riskscore obtained by lasso analysis and clinical information from multivariate cox, we obtained the nomogram of SKCM, which was validated in the validation cohort. Based on the riskscore, the patients were split into low- and high-risk groups. Functional differences between the two groups were analyzed using Metascape and GSEA, and immune infiltration differences were achieved by multiple algorithms. We obtained a risk prediction nomogram for the validated SKCM based on the lasso model by univariate and multivariate cox regression analysis. RESULTS: In the low-risk group, immune responses were in an active state. NK, CD8+ T, DC, macrophages, and neutrophils were significantly upregulated, and ICI-relevant genes were notably upregulated. With the differentially expressed genes (DEGs) and optimal CSPGs, we obtained the hub genes: NOX4, NTN4, PROX1, and TRPM8. The hub genes were mainly expressed by cancer-associated fibroblasts (CAFs) and endothelial cells by single cell analysis, which were mainly associated with angiogenesis. CONCLUSION: Genes associated with cellular senescence favor SKCM prognosis by stimulating immune responses in TME. Patients with high expression of cellular senescence associated genes in the TME might have better benefit from ICI immunotherapy. Cellular senescence functions as a pro-tumor agent in mesenchymal cells and needs further study.