WHIRLY Proteins, multi-layer regulators linking the nucleus and organelles in developmental and stress-induced senescence of plants.

Plant senescence is an integrated program of plant development that aims to remobilize nutrients and energy from senescing tissues to developing organs under developmental and stress-induced conditions. Upstream in the regulatory network, a small family of single-stranded DNA/RNA-binding proteins known as WHIRLYs occupy a central node, acting at multiple regulatory levels and via trans-localization between the nucleus and organelles. In this review, we summarize the current progress on the role of WHIRLY members in plant development and stress-induced senescence. WHIRLY proteins can be traced back in evolution to green algae. WHIRLY proteins trade off the balance of plant developmental senescence and stress-induced senescence through maintaining organelle genome stability via R-loop homeostasis, repressing the transcription at a configuration condition, recruiting RNA to impact organelle RNA editing and splicing, as evidenced in several species, WHIRLY proteins also act as retrograde signal transducers between organelles and the nucleus through protein modification and stromule or vesicle trafficking. In addition, WHIRLY proteins interact with hormones, ROS and environmental signals to orchestrate cell fate in an age-dependent manner. Finally, prospects for further research and promotion to improve crop production under environmental constraints are highlighted.

The effect of stir-frying on the aging of oat flour during storage: A study based on lipidomics.

In this study, we used the LC-ESI-MS/MS technique to elucidate the effects of stir-frying on the lipidomics of oat flour before and after storage. We detected 1540 lipids in 54 subclasses; triglycerides were the most abundant, followed by diacylglycerol, ceramide (Cer), digalactosyldiacylglycerol, cardiolipin, and phosphatidylcholine. Principal component analysis and orthogonal least squares discriminant analysis analyses showed that oat flour lipids were significantly different before and after storage in stir-fried oat flour and raw oat flour. After oat flour was stir-fried, most of the lipid metabolites in it were significantly downregulated, and the changes in lipids during storage were reduced. Sphingolipid metabolism and ether lipid metabolism were the key metabolic pathways, and Cer, PC, and lyso-phosphatidylcholine were the key lipid metabolites identified in the related metabolic pathways during oat flour storage. Frying inhibits lipid metabolic pathways during storage of oat flour, thereby improving lipid stability and quality during storage. This study laid the foundation for further investigating quality control and the mechanism of changes in lipids during the storage of oat flour.

The truncated AXIN1 isoform promotes hepatocellular carcinoma metastasis through SRSF9-mediated exon 9 skipping.

Axis inhibitor protein 1 (AXIN1) is a protein recognized for inhibiting tumor growth and is commonly involved in cancer development. In this study, we explored the potential molecular mechanisms that connect alternative splicing of AXIN1 to the metastasis of hepatocellular carcinoma (HCC). Transcriptome sequencing, RT‒PCR, qPCR and Western blotting were utilized to determine the expression levels of AXIN1 in human HCC tissues and HCC cells. The effects of the AXIN1 exon 9 alternative splice isoform and SRSF9 on the migration and invasion of HCC cells were assessed through wound healing and Transwell assays, respectively. The interaction between SRSF9 and AXIN1 was investigated using UV crosslink RNA immunoprecipitation, RNA pulldown, and RNA immunoprecipitation assays. Furthermore, the involvement of the AXIN1 isoform and SRSF9 in HCC metastasis was validated in a nude mouse model. AXIN1-L (exon 9 including) expression was downregulated, while AXIN1-S (exon 9 skipping) was upregulated in HCC. SRSF9 promotes the production of AXIN1-S by interacting with the sequence of exons 8 and 10 of AXIN1. AXIN1-S significantly promoted HCC cells migration and invasion by activating the Wnt pathway, while the opposite effects were observed for AXIN1-L. In vivo experiments demonstrated that AXIN1-L inhibited HCC metastasis, whereas SRSF9 promoted HCC metastasis in part by regulating the level of AXIN1-S. AXIN1, a tumor suppressor protein that targets the AXIN1/Wnt/ß-catenin signaling axis, may be a promising prognostic factor and a valuable therapeutic target for HCC.

Exercise activates interferon response of the liver via Gpld1 to enhance antiviral innate immunity.

Healthy behavioral patterns could modulate organ functions to enhance the body's immunity. However, how exercise regulates antiviral innate immunity remains elusive. Here, we found that exercise promotes type I interferon (IFN-I) production in the liver and enhances IFN-I immune activity of the body. Despite the possibility that many exercise-induced factors could affect IFN-I production, we identified Gpld1 as a crucial molecule, and the liver as the major organ to promote IFN-I production after exercise. Exercise largely loses the efficiency to induce IFN-I in Gpld1-/- mice. Further studies demonstrated that exercise-produced 3-hydroxybutanoic acid (3-HB) critically induces Gpld1 expression in the liver. Gpld1 blocks the PP2A-IRF3 interaction, thus enhancing IRF3 activation and IFN-I production, and eventually improving the body's antiviral ability. This study reveals that exercise improves antiviral innate immunity by linking the liver metabolism to systemic IFN-I activity and uncovers an unknown function of liver cells in innate immunity.

Discovery of the Highly Selective and Potent STAT3 Inhibitor for Pancreatic Cancer Treatment.

Signal transducer and activator of transcription 3 (STAT3) is an attractive cancer therapeutic target. Unfortunately, targeting STAT3 with small molecules has proven to be very challenging, and for full activation of STAT3, the cooperative phosphorylation of both tyrosine 705 (Tyr705) and serine 727 (Ser727) is needed. Further, a selective inhibitor of STAT3 dual phosphorylation has not been developed. Here, we identified a low nanomolar potency and highly selective small-molecule STAT3 inhibitor that simultaneously inhibits both STAT3 Tyr705 and Ser727 phosphorylation. YY002 potently inhibited STAT3-dependent tumor cell growth in vitro and achieved potent suppression of tumor growth and metastasis in vivo. More importantly, YY002 exhibited favorable pharmacokinetics, an acceptable safety profile, and superior antitumor efficacy compared to BBI608 (STAT3 inhibitor that has advanced into phase III trials). For the mechanism, YY002 is selectively bound to the STAT3 Src Homology 2 (SH2) domain over other STAT members, which strongly suppressed STAT3 nuclear and mitochondrial functions in STAT3-dependent cells. Collectively, this study suggests the potential of small-molecule STAT3 inhibitors as possible anticancer therapeutic agents.

Characterization of SIPs-type aquaporins and their roles in response to environmental cues in rice (Oryza sativa L.).

BACKGROUND: Aquaporins (AQPs) facilitate water diffusion across biological membranes and are involved in all phases of growth and development. Small and basic intrinsic proteins (SIPs) belong to the fourth subfamily of the plant AQPs. Although SIPs are widely present in higher plants, reports on SIPs are limited. Rice is one of the major food crops in the world, and water use is an important factor affecting rice growth and development; therefore, this study aimed to provide information relevant to the function and environmental response of the rice SIP gene family. RESULTS: The rice (Oryza sativa L. japonica) genome encodes two SIP-like genes, OsSIP1 and OsSIP2, whose products are predominantly located in the endoplasmic reticulum (ER) membrane but transient localization to the plasma membrane is not excluded. Heterologous expression in a yeast aquaglyceroporin-mutant fps1Δ showed that both OsSIP1 and OsSIP2 made the cell more sensitive to KCl, sorbitol and H2O2, indicating facilitated permeation of water and hydrogen peroxide. In addition, the yeast cells expressing OsSIP2 were unable to efflux the toxic methylamine taken up by the endogenous MEP permeases, but OsSIP1 showed subtle permeability to methylamine, suggesting that OsSIP1 may have a wider conducting pore than OsSIP2. Expression profiling in different rice tissues or organs revealed that OsSIP1 was expressed in all tissues tested, whereas OsSIP2 was preferentially expressed in anthers and weakly expressed in other tissues. Consistent with this, histochemical staining of tissues expressing the promoter-ß-glucuronidase fusion genes revealed their tissue-specific expression profile. In rice seedlings, both OsSIPs were upregulated to varied levels under different stress conditions, including osmotic shock, high salinity, unfavorable temperature, redox challenge and pathogen attack, as well as by hormonal treatments such as GA, ABA, MeJA, SA. However, a reduced expression of both OsSIPs was observed under dehydration treatment. CONCLUSIONS: Our results suggest that SIP-like aquaporins are not restricted to the ER membrane and are likely to be involved in unique membrane functions in substrate transport, growth and development, and environmental response.

Deep learning and radiomics-based approach to meningioma grading: exploring the potential value of peritumoral edema regions.

Objective.To address the challenge of meningioma grading, this study aims to investigate the potential value of peritumoral edema (PTE) regions and proposes a unique approach that integrates radiomics and deep learning techniques.Approach.The primary focus is on developing a transfer learning-based meningioma feature extraction model (MFEM) that leverages both vision transformer (ViT) and convolutional neural network (CNN) architectures. Additionally, the study explores the significance of the PTE region in enhancing the grading process.Main results.The proposed method demonstrates excellent grading accuracy and robustness on a dataset of 98 meningioma patients. It achieves an accuracy of 92.86%, precision of 93.44%, sensitivity of 95%, and specificity of 89.47%.Significance.This study provides valuable insights into preoperative meningioma grading by introducing an innovative method that combines radiomics and deep learning techniques. The approach not only enhances accuracy but also reduces observer subjectivity, thereby contributing to improved clinical decision-making processes.

Positive Association of Pulse Pressure with Presence of Albuminuria in Chinese Adults with Prediabetes: A Community-Based Study.

Purpose: There has been limited evidence for the association between pulse pressure (PP) and proteinuria in prediabetes. The aim of our study was to explore the association between PP and albuminuria in community-dwelling Chinese adults with prediabetes. Materials and Methods: PP and urinary albumin-to-creatinine ratio (ACR) were measured in 2012 prediabetic patients and 3596 control subjects with normal glucose tolerance. Multivariate logistic regression models were used to evaluate the possible association of PP with the risk of presence of albuminuria. Results: PP was positively associated with the presence of albuminuria, and subjects in the higher PP quartiles had higher urinary ACR and presence of albuminuria as compared with those in the lowest quartile in both prediabetes and control groups (all P < 0.01). Multivariate logistic regression analysis demonstrated that the highest PP quartile was positively associated with increased risk of presence of albuminuria in all prediabetic subjects [odds ratio (OR): 2.289, 95% confidence interval (CI) 1.364-3.842, P < 0.01) and prediabetic subjects without anti-hypertensive drugs (OR: 1.932, 95% CI 1.116-3.343, P < 0.01), whereas higher PP quartile has nothing to do with the risk of presence of albuminuria in control subjects with and without anti-hypertensive drugs after adjustment for potential confounders (all P > 0.01). Consistently, stratified analysis showed that in the prediabetes group, the risks of presence of albuminuria progressively elevated with increasing PP quartiles in men, those aged 60 years or older, and with overweight/obesity, normal high-density lipoprotein cholesterol, and appropriate low-density lipoprotein cholesterol (all P for trend <0.05). Conclusion: Higher PP is independently related to increased risk of presence of albuminuria in community-dwelling Chinese adults with prediabetes.

Carbon doping enhances the fluoride removal performance of aluminum-based adsorbents.

Excessive fluoride presence in water poses significant environmental and public health risks, necessitating the development of effective remediation techniques. Conventional aluminum-based adsorbents face inherent limitations such as limited pH range and low adsorption capacity. To overcome these challenges, we present a facile solvent-thermal method for synthesizing a carbon-doped aluminum-based adsorbent (CDAA). Extensive characterization of CDAA reveals remarkable features including substantial carbon-containing groups, unsaturated aluminum sites, and a high pH at point of zero charge (pHpzc). CDAA demonstrates superior efficiency and selectivity in removing fluoride contaminants, surpassing other adsorbents. It exhibits exceptional adaptability across a broad pH spectrum from 3 to 12, with a maximum adsorption capacity of 637.4 mg/g, more than 110 times higher than alumina. The applicability of the Langmuir isotherm and pseudo-second-order models effectively supports these findings. Notably, CDAA exhibits rapid kinetics, achieving near-equilibrium within just 5 min. Comprehensive analyses utilizing Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) offer detailed insights into the mechanisms involving electrostatic attraction, ion exchange, and ligand exchange. Carbon-based groups play a role in ligand exchange processes, synergistically interacting with the unsaturated aluminum structure to provide a multitude of adsorption sites. The exceptional attributes of CDAA establish its immense potential as a transformative solution for the pressing challenge of fluoride removal from water sources.

Highly-dispersed 2D NiFeP/CoP heterojunction trifunctional catalyst for efficient electrolysis of water and urea.

The electrocatalytic production of "green hydrogen", such as through the electrolysis of water or urea has been vigorously advocated to alleviate the energy crisis. However, their electrode reactions including oxygen evolution reaction (OER), urea oxidation reaction (UOR), and hydrogen evolution reaction (HER) all suffer from sluggish kinetics, which urgently need catalysts to accelerate the processes. Herein, we design and prepare an OER/UOR/HER trifunctional catalyst by transforming the homemade CoO nanorod into a two-dimensional (2D) ultrathin heterojunction nickel-iron-cobalt hybrid phosphides nanosheet (NiFeP/CoP) via a hydrothermal-phosphorization method. Consequently, a strong electronic interaction was found among the Ni2P/FeP4/CoP heterogeneous interfaces, which regulates the electronic structure. Besides the high mass transfer property of 2D nanosheet, Ni2P/FeP4/CoP displays improved OER/UOR/HER performance. At 10 mA cm-2, the OER overpotential reaches 274 mV in 1.0 M KOH, and the potential of UOR is only 1.389 V in 1.0 M KOH and 0.33 M urea. More strikingly, the two-electrode systems for electrolysis water and urea-assisted electrolysis water assembled by NiFeP/CoP could maintain long-term stability for 35 h and 12 h, respectively. This work may help to pave the way for upcoming research horizons of multifunctional electrocatalysts.

Colon-targeted hydroxyethyl starch-curcumin microspheres with high loading capacity ameliorate ulcerative colitis via alleviating oxidative stress, regulating inflammation, and modulating gut microbiota.

Curcumin (CUR) is a natural polyphenol that holds promise for treating ulcerative colitis (UC), yet oral administration of CUR exhibits limited bioavailability and existing formulations for oral delivery of CUR often suffer from unsatisfactory loading capacity. This study presents hydroxyethyl starch-curcumin microspheres (HC-MSs) with excellent CUR loading capacity (54.52 %), and the HC-MSs can further encapsulate anti-inflammatory drugs dexamethasone (DEX) to obtain a combination formulation (DHC-MSs) with high DEX loading capacity (19.91 %), for combination therapy of UC. The microspheres were successfully engineered, retaining the anti-oxidative and anti-inflammatory activities of parental CUR and demonstrating excellent biocompatibility and controlled release properties, notably triggered by α-amylase, facilitating targeted drug delivery to inflamed sites. In a mouse UC model induced by dextran sulfate sodium, the microspheres effectively accumulated in inflamed colons and both HC-MSs and DHC-MSs exhibited superior therapeutic efficacy in alleviating UC symptoms compared to free DEX. Moreover, mechanistic exploration uncovered the multifaceted therapeutic mechanisms of these formulations, encompassing anti-inflammatory actions, mitigation of spleen enlargement, and modulation of gut microbiota composition. These findings underscore the potential of HC-MSs and DHC-MSs as promising formulations for UC, with implications for advancing treatment modalities for various inflammatory bowel disorders.

Novel antimicrobial peptides against Cutibacterium acnes designed by deep learning.

The increasing prevalence of antibiotic resistance in Cutibacterium acnes (C. acnes) requires the search for alternative therapeutic strategies. Antimicrobial peptides (AMPs) offer a promising avenue for the development of new treatments targeting C. acnes. In this study, to design peptides with the specific inhibitory activity against C. acnes, we employed a deep learning pipeline with generators and classifiers, using transfer learning and pretrained protein embeddings, trained on publicly available data. To enhance the training data specific to C. acnes inhibition, we constructed a phylogenetic tree. A panel of 42 novel generated linear peptides was then synthesized and experimentally evaluated for their antimicrobial selectivity and activity. Five of them demonstrated their high potency and selectivity against C. acnes with MIC of 2-4 µg/mL. Our findings highlight the potential of these designed peptides as promising candidates for anti-acne therapeutics and demonstrate the power of computational approaches for the rational design of targeted antimicrobial peptides.

MORF9-dependent specific plastid RNA editing inhibits root growth under sugar starvation in Arabidopsis.

Multiple organellar RNA editing factor (MORF) complex was shown to be highly associated with C-to-U RNA editing of vascular plant editosome. However, mechanisms by which MORF9-dependent plastid RNA editing controls plant development and responses to environmental alteration remain obscure. In this study, we found that loss of MORF9 function impaired PSII efficiency, NDH activity, and carbohydrate production, rapidly promoted nuclear gene expression including sucrose transporter and sugar/energy responsive genes, and attenuated root growth under sugar starvation conditions. Sugar repletion increased MORF9 and MORF2 expression in wild-type seedlings and reduced RNA editing of matK-706, accD-794, ndhD-383 and ndhF-290 in the morf9 mutant. RNA editing efficiency of ndhD-383 and ndhF-290 sites was diminished in the gin2/morf9 double mutants, and that of matK-706, accD-794, ndhD-383 and ndhF-290 sites were significantly diminished in the snrk1/morf9 double mutants. In contrast, overexpressing HXK1 or SnRK1 promoted RNA editing rate of matK-706, accD-794, ndhD-383 and ndhF-290 in leaves of morf9 mutants, suggesting that HXK1 partially impacts MORF9 mediated ndhD-383 and ndhF-290 editing, while SnRK1 may only affect MORF9-mediated ndhF-290 site editing. Collectively, these findings suggest that sugar and/or its intermediary metabolites impair MORF9-dependent plastid RNA editing resulting in derangements of plant root development.

Recent advances in understanding the regulatory mechanism of plasma membrane H+-ATPase through the brassinosteroid signaling pathway.

The polyhydroxylated steroid phytohormone brassinosteroids (BRs) control many aspects of plant growth, development and responses to environmental changes. Plasma membrane (PM) H+-ATPase, the well-known PM proton pump, is a central regulator in plant physiology, which mediates not only plant growth and development, but also adaptation to stresses. Recent studies highlight that PM H+-ATPase is at least partly regulated via the BR signaling. Firstly, the BR cell surface receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and multiple key components of BR signaling directly or indirectly influence PM H+-ATPase activity. Secondly, the SMALL AUXIN UP RNA (SAUR) gene family physically interacts with BRI1 to enhance organ development of Arabidopsis by activating PM H+-ATPase. Thirdly, RNA-sequencing (RNA-seq) assays showed that the expression of some SAUR genes is upregulated under the light or sucrose conditions, which is related to the phosphorylation state of the penultimate residue of PM H+-ATPase in a time-course manner. In this review, we describe the structural and functional features of PM H+-ATPase, and summarize recent progress toward understanding the regulatory mechanism of PM H+-ATPase by BRs, and briefly introduce how PM H+-ATPase activity is modulated by its own biterminal regions and the post-translational modifications.

IGFBP-rP1 is a potential therapeutic target in androgenic alopecia.

The available interventions for androgenic alopecia (AGA), the most common type of hair loss worldwide, remain limited. The insulin growth factor (IGF) system may play an important role in the pathogenesis of AGA. However, the exact role of IGF binding protein-related protein 1 (IGFBP-rP1) in hair growth and AGA has not been reported. In this study, we first found periodic variation in IGFBP-rP1 during the hair cycle transition in murine hair follicles (HFs). We further demonstrated that IGFBP-rP1 levels were lower in the serum and scalp HFs of individuals with AGA than in those of healthy controls. Subsequently, we verified that IGFBP-rP1 had no cytotoxicity to human outer root sheath cells (HORSCs) and that IGFBP-rP1 reversed the inhibitory effects of DHT on the migration of HORSCs in vitro. Finally, a DHT-induced AGA mouse model was created. The results revealed that the expression of IGFBP-rP1 in murine HFs was downregulated after DHT treatment and that subcutaneous injection of IGFBP-rP1 delayed catagen occurrence and prolonged the anagen phase of HFs in mice with DHT-induced AGA. The present work shows that IGFBP-rP1 is involved in hair cycle transition and exhibits great therapeutic potential for AGA.

DDX4 enhances antiviral activity of type I interferon by disrupting interaction of USP7/SOCS1 and promoting degradation of SOCS1.

DEAD-box helicase (DDX) family members play differential roles in regulating innate antiviral immune response. However, the physiological roles played by DDX4 in antiviral innate immunity remain unclear. In this study, we unveiled that DDX4 acts as a positive regulatory molecule of Type-I interferon (IFN-I)-mediated antiviral activity. Our findings demonstrate that IFN-I upregulates DDX4 protein levels, and subsequently, overexpression of DDX4 enhances the IFN-I-mediated signaling pathway. This creates a positive feedback loop that amplifies the antiviral response. DDX4 was found to bind with deubiquitinase ubiquitin-specific protease 7 (USP7), leading to the disruption of the interaction between USP7 and suppressor of cytokine signaling 1 (SOCS1) and the subsequent degradation of SOCS1. This process enhances the antiviral function of IFN-I. Our findings provide new insights into the regulatory role of DDX4 in the IFN-I response.IMPORTANCEDDX4, identified as a putative RNA helicase that modulates RNA secondary structure through RNA binding, is primarily acknowledged for its role in regulating mRNA translation within the germline. Nevertheless, the extent of DDX4's involvement in the antiviral innate immune response remains largely unexplored. This study presents evidence of a previously unrecognized positive feedback loop between DDX4 and the antiviral response, suggesting that disruption of this loop may serve as a novel mechanism for viral evasion. Furthermore, our findings elucidate a positive regulatory mechanism by which the DDX4/USP7/SOCS1 axis mediates the antiviral activity of Type-I interferon, which provides new insight into strategies for improving the efficacy of IFN-based antiviral therapy.

Association analysis of the IKZF4 gene with Alopecia Areata in the Chinese Han population.

Objective: The IKZF4(Ikaros family zinc finger 4) gene encodes Eos, a zinc finger transcription factor that belongs to the Ikaros family. High expression of Eos on Treg cells is important for the suppression of autoimmune responses and immune homeostasis. It has been suggested that the SNP in IKZF4 may influence the pathogenesis of AA(alopecia areata). The purpose of this study was to explore the relationship between IKZF4 polymorphism and AA in the Chinese Han population. Methods: We examined 459 patients and 434 controls in this study. The rs1701704 polymorphism was evaluated using HRM analysis and direct sequencing. Results: The prevalence of the C/C, A/C, and A/A genotypes in AA patients was 7.4%, 37.5% and 55.1%, respectively. There were significant differences in genotype distribution and allele frequencies between AA and the control group (P < .0001). The frequency of the C allele in the AA group was significantly higher (P < .0001), and the frequencies of the C allele and C/C genotype in patients with family history were higher (P < .0001; P = .001). Conclusions: The rs1701704 SNP of IKZF4 may be a genetic marker for assessing the risk of AA in the Chinese Han population.

CD206 modulates the role of M2 macrophages in the origin of metastatic tumors.

Tumor metastasis is a key factor affecting the life of patients with malignant tumors. For the past hundred years, scientists have focused on how to kill cancer cells and inhibit their metastasis in vivo, but few breakthroughs have been made. Here we hypothesized a novel mode for cancer metastasis. We show that the phagocytosis of apoptotic tumor cells by macrophages leads to their polarization into the M2 phenotype, and that the expression of stem cell related as well as drug resistance related genes was induced. Therefore, it appears that M2 macrophages have "defected" and have been transformed into the initial "metastatic cancer cells", and thus are the source, at least in part, of the distal tissue tumor metastasis. This assumption is supported by the presence of fused cells with characteristics of both macrophage and tumor cell observed in the peripheral blood and ascites of patients with ovarian cancer. By eliminating the expression of CD206 in M2 macrophages using siRNA, we show that the growth and metastasis of tumors was suppressed using both in vitro cell line and with experimental in vivo mouse models. In summary, we show that M2 macrophages in the blood circulation underwent a "change of loyalty" to become "cancer cells" that transformed into distal tissue metastasis, which could be suppressed by the knockdown of CD206 expression.

Novel Signaling Pathway and NSC689534 as a Potential Drug Candidate for Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy of the skin, and its incidence is increasing annually. Once cSCC becomes metastatic, its associated mortality rate is much higher than that of cSCC in situ. However, the current treatments for progressive cSCC have several limitations. The aim of this study was to suggest a potential compound for future research that may benefit patients with cSCC. METHODS: In this study, we screened the following differentially expressed genes from the Gene Expression Omnibus database: GSE42677, GSE45164, GSE66359, and GSE98767. Using strategies such as protein-protein interaction network analysis and the CYTOSCAPE plugin MCODE, key modules were identified and then verified by Western blotting. Subsequently, related signalling pathways were constituted in the SIGNOR database. Finally, molecular docking analyses and cell viability assay were used to identify a potential candidate drug and verify its growth inhibition ability to A431 cell line. RESULTS: Fifty-one common differentially expressed genes were screened and two key modules were identified. Among them, three core genes were extracted, constituting two signalling pathways, both of which belong to the module associated with mitotic spindles and cell division. A pathway involving CDK1, the TPX2-KIF11 complex, and spindle organization was validated in a series of analyses, including analyses for overall survival, genetic alteration, and molecular structure. Molecular docking analyses identified the pyridine 2-carbaldehyde thiosemicarbazone (NSC689534), which interacts with TPX2 and KIF11, as a potential candidate for the treatment of cSCC. CONCLUSIONS: NSC689534 might be a candidate drug for cSCC targeting TPX2 and KIF11, which are hub genes in cSCC.