Fair surface modification with mixed alkanethiols on gold nanoparticles through minimal unfair ligand exchange.

Surface modification with functional molecules is essential for introducing various surface properties. As gold nanoparticles (AuNPs) have extraordinary chemical, physical, and optical properties, control of their surface, mainly through modification with mixed alkanethiols via Au-S interactions, has attracted much attention. However, surface modification of AuNPs with mixed alkanethiols to provide a strictly regulated composition remains challenging. Further, there are very few methods that can easily establish the nature of ligands and their replacement with similar molecules at nanoparticle surfaces, limiting precise analyses. Herein, we demonstrate an unfair ligand exchange between oligo(ethylene glycol) (OEG)-attached alkanethiols as a source of unfair surface modification utilizing programable thermo-responsive properties of OEG-alkanethiols-modified AuNPs and fair surface modification with mixed OEG-alkanethiols by minimizing this effect. OEG-alkanethiols-modified AuNPs show an assembly/disassembly behavior in response to the solution temperature. Assembly temperature (T A) changes in the presence of other OEG-alkanethiols, confirming the ligand exchange between alkanethiols in an aqueous solution. Kinetic analyses indicate that the competitive exchange reaction of these two alkanethiols results in an unfair ligand exchange, which leads to gradual changes in surface composition. As this ligand exchange between alkanethiols takes a longer time compared to that from citric acid, which initially covered the AuNPs, exact surface modification of AuNPs with OEG-alkanethiols is performed by moderate reaction conditions (25 °C, several to 24 hours). This insight regarding "more prolonged reaction is not always better" could be widely applied for surface modifications with various thiol-ligands.

Pretreatment can alleviate programmed cell death in mesenchymal stem cells.

In this editorial, we delved into the article titled "Cellular preconditioning and mesenchymal stem cell ferroptosis." This groundbreaking study underscores a pivotal discovery: Ferroptosis, a type of programmed cell death, drastically reduces the viability of donor mesenchymal stem cells (MSCs) after engraftment, thereby undermining the therapeutic value of cell-based therapies. Furthermore, the article proposes that by manipulating ferroptosis mechanisms through preconditioning, we can potentially enhance the survival rate and functionality of MSCs, ultimately amplifying their therapeutic potential. Given the crucial role ferroptosis plays in shaping the therapeutic outcomes of MSCs, we deem it imperative to further investigate the intricate interplay between programmed cell death and the therapeutic effectiveness of MSCs.

WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common complication of acute and severe neurosurgery. Remodeling of N6-methyladenosine (m6A) stabilization may be an attractive treatment option for neurological dysfunction after TBI. In the present study, the authors explored the epigenetic methylation of RNA-mediated NLRP3 inflammasome activation after TBI. METHODS: Neurological dysfunction, histopathology, and associated molecules were examined in conditional knockout (CKO) WTAP [flox/flox, Camk2a-cre] , WTAP flox/flox , and pAAV-U6-shRNA-YTHDF1-transfected mice. Primary neurons were used in vitro to further explore the molecular mechanisms of action of WTAP/YTHDF1 following neural damage. RESULTS: The authors found that WTAP and m6A levels were upregulated at an early stage after TBI, and conditional deletion of WTAP in neurons did not affect neurological function but promoted functional recovery after TBI. Conditional deletion of WTAP in neurons suppressed neuroinflammation at the TBI early phase: WTAP could directly act on NLRP3 mRNA, regulate NLRP3 mRNA m6A level, and promote NLRP3 expression after neuronal injury. Further investigation found that YTH domain of YTHDF1 could directly bind to NLRP3 mRNA and regulate NLRP3 protein expression. YTHDF1 mutation or silencing improved neuronal injury, inhibited Caspase-1 activation, and decreased IL-1ß levels. This effect was mediated via suppression of NLRP3 protein translation, which also reversed the stimulative effect of WTAP overexpression on NLRP3 expression and inflammation. CONCLUSIONS: Our results indicate that WTAP participates in neuronal damage by protein translation of NLRP3 in an m6A-YTHDF1-dependent manner after TBI and that WTAP/m6A/YTHDF1 downregulation therapeutics is a viable and promising approach for preserving neuronal function after TBI, which can provide support for targeted drug development.

Synthesis of Ni decorated MoOx nanorod catalysts for efficient overall urea-water splitting.

Substituting slow oxygen evolution reaction (OER) with thermodynamically favorable urea oxidation reaction (UOR) is considered as one of the feasible strategies for achieving energy-saving hydrogen production. Herein, a uniform layer of NiMoO4 nanorods was grown on nickel foam by a hydrothermal method. Then, a series of Ni-MoOx/NF-X nanorod catalysts comprising Ni/NiO and MoOx (MoO2/MoO3) were prepared through regulating annealing atmosphere and reduction temperature. The optimized Ni-MoOx/NF-3 with a large accessible specific area can act as a bifunctional catalyst for electrocatalytic anodic UOR and cathodic hydrogen evolution reaction (HER). At a current density of 100 mA cm-2, the introduction of urea can significantly reduce the overpotential of Ni-MoOx/NF-3 by 210 mV compared to OER. In addition, Ni-MoOx/NF-3 has a higher intrinsic activity than other catalysts. It only requires -0.21 and 1.38 V to reach 100 mA cm-2 in HER and UOR, respectively. Such an excellent performance can be attributed to the synergistic function between Ni and MoOx. The presence of metallic Ni and reduced MoOx in pairs is beneficial for improving the electrical conductivity and modulating the electronic structure, resulting in enhancing the electrocatalytic performance. When assembling Ni-MoOx/NF-3 into an overall urea-water splitting system, it can achieve energy-saving hydrogen production and effective removal of urea-rich wastewater.

Oroxin A alleviates early brain injury after subarachnoid hemorrhage by regulating ferroptosis and neuroinflammation.

BACKGROUND: Subarachnoid hemorrhage (SAH), a severe subtype of stroke, is characterized by notably high mortality and morbidity, largely due to the lack of effective therapeutic options. Although the neuroprotective potential of PPARg and Nrf2 has been recognized, investigative efforts into oroxin A (OA), remain limited in preclinical studies. METHODS: SAH was modeled in vivo through filament perforation in male C57BL/6 mice and in vitro by exposing HT22 cells to hemin to induce neuronal damage. Following the administration of OA, a series of methods were employed to assess neurological behaviors, brain water content, neuronal damage, cell ferroptosis, and the extent of neuroinflammation. RESULTS: The findings indicated that OA treatment markedly improved survival rates, enhanced neurological functions, mitigated neuronal death and brain edema, and attenuated the inflammatory response. These effects of OA were linked to the suppression of microglial activation. Moreover, OA administration was found to diminish ferroptosis in neuronal cells, a critical factor in early brain injury (EBI) following SAH. Further mechanistic investigations uncovered that OA facilitated the translocation of nuclear factor erythroid 2-related factor 2 (Nrf-2) from the cytoplasm to the nucleus, thereby activating the Nrf2/GPX4 pathway. Importantly, OA also upregulated the expression of FSP1, suggesting a significant and parallel protective effect against ferroptosis in EBI following SAH in synergy with GPX4. CONCLUSION: In summary, this research indicated that the PPARg activator OA augmented the neurological results in rodent models and diminished neuronal death. This neuroprotection was achieved primarily by suppressing neuronal ferroptosis. The underlying mechanism was associated with the alleviation of cellular death through the Nrf2/GPX4 and FSP1/CoQ10 pathways.

Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells.

In this editorial, we offer our perspective on the groundbreaking study entitled "Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells", recently published in World Journal of Stem Cells. Despite over three decades of research on the clinical application of mesenchymal stem cells (MSCs), only a few therapeutic products have made it to clinical use, due to multiple preclinical and clinical challenges yet to be addressed. The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics, which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs. As we delve deeper into the intricacies of pretreatment methodologies, we anticipate a transformative shift in the landscape of MSC-based therapies, ultimately contributing to improved patient outcomes and advancing the field as a whole.

A TonB dependent transporter YncD of Salmonella enterica Serovar Typhi possesses vaccine potential.

Multiple TonB dependent transporters (TBDTs) contribute to bacterial virulence due to the importance roles that their substrates play in bacterial growth, and possess vaccine potential. A putative TBDT, YncD, had been identified as one of in vivo induced antigens during human infection of typhoid fever, and is required for the pathogenicity of Salmonella enterica Serovar Typhi. The present study was aimed to determine the function and immunogenicity of YncD. Homologous recombination method was used to construct an yncD-deletion mutant and cirA-iroN-fepA-deletion mutant from the wild-type S. Typhi Ty2. The growth of mutants and the wild-type strain were assessed in iron-deficient medium, as well as in human macrophage cells. Recombinant YncD protein was expressed and purified using Ni-NTA affinity chromatography and anion exchange. A mouse model was then used to evaluate the immunogenicity and protection efficacy of the recombinant YncD. Antibody levels, serum bactericidal efficiency, passive immune protection, opsonophagocysis were assayed to analyse the immunoprotection mechanism of the recombinant YncD. Our results showed that YncD is associated with the iron-uptake of S. Typhi. The yncD-deletion mutant displayed impaired growth in iron-deficient medium, comparable to that the cirA-iroN-fepA-deletion mutant did. The mutation of yncD markedly decreased bacterial growth within human macrophage cells. Moreover, subcutaneous immunization of mice with recombinant YncD elicited high levels of specific anti-YncD IgG, IgG1 and IgG2a, which protected the immunized mice against the intraperitoneal challenge of S. Typhi, and decreased bacterial burdens in the livers and spleens of the infected mice. Passive immunization using the immunized sera also efficiently protected the mice from the challenge of S. Typhi. Moreover, the immunized sera enhanced in vitro bactericidal activity of complement, and opsonophagocytosis. Our results showed that YncD displays a role in the iron-uptake of S. Typhi and possesses immunogenicity.

Radical-driven selective oxidation of benzyl alcohol on MnCoOx catalysts with no oxidant other than air in reactor.

Mn reinforced Co3O4 catalysts (MnCoOx) were prepared by a facile solid phase mixed foaming method with an in-situ heating enhancement for the formation of spinel phase mixed oxide species, and studied in the selective oxidation of benzyl alcohol just the air in reactor as oxygen donor. It was found that the MnCoOx catalysts are composed of relatively minimal spinel MnCo2O4 mixed oxide and massive Co3O4 to form MnCo2O4-Co3O4 oxide pair. The micro-domains of MnCo2O4-Co3O4 oxide pair present two redox couples of Mn3+/Mn2+ and Co3+/Co2+ instead of the single one of Co3+/Co2+ in Co3O4, and then dramatically enhance the formation of superoxide radicals (•O2-) species from the O2 in air, which can efficiently initiate the conversion of benzyl alcohol to benzaldehyde in a Fenton-like processes. With no oxidant other than air in reactor, the interaction between MnCo2O4 and Co3O4 in MnCoOx catalysts leads to a benzyl alcohol conversion up to 98 % with a 100 % benzaldehyde selectivity at atmospheric pressure while single component Co3O4 can only present a benzyl alcohol conversion at 37 %. This embodiment of highly efficient heterogeneous selective oxidation just with air as oxidant provides a probability for developing a low-cost and super-facile radical-induced selective oxidation process for alcohols.

Association of spouse's vision impairment with depressive symptoms and cognitive decline in partner: A nationally representative study in China.

BACKGROUND: Although several previous studies have reported on the relationship between vision impairment and caregiver mental health, mixed results were obtained, and only one study reported the association between spousal vision impairment and partner depression. Therefore, our study aimed to examine the association between spousal vision impairment and the partner's depressive symptoms and cognitive decline. METHODS: This cross-sectional study gathered baseline data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011. A total of 10,956 couples were included in the study. Vision impairment was assessed by respondents' self-reported distance or near vision. Multivariate logistic and linear regression were conducted to evaluate the association between the spouse's vision impairment and the partner's depressive symptoms and cognitive function. RESULTS: The prevalence of partners with depressive symptoms was significantly higher among spouses with vision impairment than among those without (43.3 % vs. 32.5 %; P < 0.001), and cognitive function was significantly lower (spousal vision impairment 14.4 ± 4.5 vs. no spousal vision impairment 15.5 ± 4.6; P < 0.001). After fully adjusting for potential confounders, the partner had greater odds of depressive symptoms for spouses with vision impairment than for those without (odds ratio: 1.525; 95 % confidence interval [CI]: 1.387 to 1.677). Furthermore, spousal vision impairment was negatively associated with the partner's cognitive function (ß = -0.640; 95 % CI: -0.840 to -0.440). Sensitivity analysis was performed, and consistent results were obtained (all P < 0.05). LIMITATIONS: Visual function was assessed by self-reporting. CONCLUSIONS: A spouse's vision impairment is associated with depressive symptoms and cognitive decline in the partner. The findings imply the importance of considering the partner's mental health when managing their spouse's vision impairment.

Assessment of Causality Between Diet-Derived Antioxidants and Primary Open-Angle Glaucoma: A Mendelian Randomization Study.

Purpose: This study aimed to investigate the genetic causal relationships among diet-derived circulating antioxidants, primary open-angle glaucoma (POAG), and glaucoma-related traits using two-sample Mendelian randomization (MR). Methods: Genetic variants associated with diet-derived circulating antioxidants (retinol, ascorbate, ß-carotene, lycopene, α-tocopherol, and γ-tocopherol) were assessed as absolute and metabolic instrumental variables. POAG and glaucoma-related traits data were derived from a large, recently published genome-wide association study database; these traits included intraocular pressure (IOP), macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell-inner plexiform layer (mGCIPL) thickness, and vertical cup-to-disc ratio (vCDR). MR analyses were performed per outcome for each exposure. Results: We found no causal association between six diet-derived antioxidants and POAG using the International Glaucoma Genetics Consortium data. For absolute antioxidants, the odds ratios (ORs) ranged from 1.011 (95% confidence interval [CI], 0.854-1.199; P = 0.895) per natural log-transformed ß-carotene to 1.052 (95% CI, 0.911-1.215; P = 0.490) for 1 µmol/L of ascorbate. For antioxidant metabolites, the OR ranged from 0.998 (95% CI, 0.801-1.244; P = 0.989) for ascorbate to 1.210 (95% CI, 0.870-1.682; P = 0.257) for γ-tocopherol, using log-transformed levels. A similar result was obtained with the FinnGen Biobank. Furthermore, our results showed no significant genetic association between six diet-derived antioxidants and glaucoma-related traits. Conclusions: Our study did not support a causal association among six diet-derived circulating antioxidants, POAG, and glaucoma-related traits. This suggests that the intake of antioxidants may not have a preventive effect on POAG and offers no protection to retinal nerve cells. Translational Relevance: This study provides valid evidence regarding the use of diet-derived antioxidants for glaucoma patients.

Copper Metabolism and Cuproptosis: Molecular Mechanisms and Therapeutic Perspectives in Neurodegenerative Diseases.

Copper is an essential trace element, and plays a vital role in numerous physiological processes within the human body. During normal metabolism, the human body maintains copper homeostasis. Copper deficiency or excess can adversely affect cellular function. Therefore, copper homeostasis is stringently regulated. Recent studies suggest that copper can trigger a specific form of cell death, namely, cuproptosis, which is triggered by excessive levels of intracellular copper. Cuproptosis induces the aggregation of mitochondrial lipoylated proteins, and the loss of iron-sulfur cluster proteins. In neurodegenerative diseases, the pathogenesis and progression of neurological disorders are linked to copper homeostasis. This review summarizes the advances in copper homeostasis and cuproptosis in the nervous system and neurodegenerative diseases. This offers research perspectives that provide new insights into the targeted treatment of neurodegenerative diseases based on cuproptosis.

Effects of Herpud1 in Methamphetamine-Induced Neuronal Apoptosis.

INTRODUCTION: Methamphetamine (METH) is an illicit psychoactive substance that can damage various organs in the body, especially the nervous system. We hypothesized that expression of homocysteine-inducible endoplasmic reticulum-resident with ubiquitin-like domain member 1 (Herpud1) protein would alleviate the induction of apoptosis following METH administration. METHODS: To test this hypothesis, we analysed the changes in Herpud1 expression and apoptosis in PC12 cells under different concentrations and exposure times of METH. Moreover, we examined the effects of Herpud1 knockdown on METH-induced neuronal apoptosis. Flow cytometry and Western blot analyses were used to evaluate apoptosis levels and the expression of apoptotic markers (cleaved caspase-3) in PC12 cells following Herpud1 knockdown by synthetic small interfering RNA (siRNA). RESULTS: Our results showed that Herpud1 expression was upregulated in PC12 cells following METH treatment, while endoplasmic reticulum stress (ERS) and apoptosis were also increased. Conversely, Herpud1 knockdown reduced METH-induced ERS and apoptosis levels in vitro. CONCLUSIONS: These results suggest that Herpud1 plays an essential role in METH-induced neuronal ERS and apoptosis and may represent a potential therapeutic gene target in METH-induced neurotoxicity.

VDAC1, as a downstream molecule of MLKL, participates in OGD/R-induced necroptosis by inducing mitochondrial damage.

Ischemia-reperfusion (I/R) injury constitutes a significant risk factor for a range of diseases, including ischemic stroke, myocardial infarction, and trauma. Following the restoration of blood flow post-tissue ischemia, oxidative stress can lead to various forms of cell death, including necrosis, apoptosis, autophagy, and necroptosis. Recent evidence has highlighted the crucial role of mitochondrial dysfunction in I/R injury. Nevertheless, there remains much to be explored regarding the molecular signaling network governing cell death under conditions of oxidative stress. Voltage-dependent anion channel 1 (VDAC1), a major component in the outer mitochondrial membrane, is closely involved in the regulation of cell death. In a cellular model of oxygen-glucose deprivation and reoxygenation (OGD/R), which effectively simulates I/R injury in vitro, our study reveals that OGD/R induces VDAC1 oligomerization, consequently exacerbating cell death. Furthermore, we have revealed the translocation of mixed lineage kinase domain-like protein (MLKL) to the mitochondria, where it interacts with VDAC1 following OGD/R injury, leading to an increased mitochondrial membrane permeability. Notably, the inhibition of MLKL by necrosulfonamide hinders the binding of MLKL to VDAC1, primarily by affecting the membrane translocation of MLKL, and reduces OGD/R-induced VDAC1 oligomerization. Collectively, our findings provide preliminary evidence of the functional association between MLKL and VDAC1 in the regulation of necroptosis.

The Role of Sgt1 in Methamphetamine/Hyperthermia-induced Necroptosis.

INTRODUCTION: Methamphetamine (METH) is a synthetic drug widely abused globally and can result in hyperthermia (HT) and psychiatric symptoms. Our previous studies showed that heat shock protein 90 alpha (HSP90α) plays a vital role in METH/HT-elicited neuronal necroptosis; however, the detailed mechanism of HSP90α regulation remained obscure. METHODS: Herein, we demonstrated a function of the suppressor of G-two allele of SKP1 (Sgt1) in METH/HT-induced necroptosis. Sgt1 was mainly expressed in neurons, co-located with HSP90α, and increased in rat striatum after METH treatment. METH/HT injury triggered necroptosis and increased Sgt1 expression in PC-12 cells. RESULT: Data from computer simulations indicated that Sgt1 might interact with HSP90α. Geldanamycin (GA), the specific inhibitor of HSP90α, attenuated the interaction between Sgt1 and HSP90α. Knockdown of Sgt1 expression did not affect the expression level of HSP90α. Still, it inhibited the expression of receptor-interacting protein 3 (RIP3), mixed lineage kinase domain-like protein (MLKL), p-RIP3, and p-MLKL, as well as necroptosis induced by METH/HT injury. CONCLUSION: In conclusion, Sgt1 may regulate the expression of RIP3, p-RIP3, MLKL, and p-MLKL by assisting HSP90α in affecting the METH/HT-induced necroptotic cell death.

Pyroptosis-related gene signature elicits immune response in rosacea.

Rosacea is a complex chronic inflammatory skin disorder with high morbidity. Pyroptosis is known as a regulated inflammatory cell death. While its association with immune response to various inflammatory disorders is well established, little is known about its functional relevance of rosacea. So, we aimed to explore and enrich the pathogenesis involved in pyroptosis-related rosacea aggravations. In this study, we evaluated the pyroptosis-related patterns of rosacea by consensus clustering analysis of 45 ferroptosis-related genes (FRGs), with multiple immune cell infiltration analysis to identify the pyroptosis-mediated immune response in rosacea using GSE65914 dataset. The co-co-work between PRGs and WGCNA-revealed hub genes has established using PPI network. FRG signature was highlighted in rosacea using multi-transcriptomic and experiment analysis. Based on this, three distinct pyroptosis-related rosacea patterns (non/moderate/high) were identified, and the notably enriched pathways have revealed through GO, KEGG and GSEA analysis, especially immune-related pathways. Also, the XCell/MCPcount/ssGSEA/Cibersort underlined the immune-related signalling (NK cells, Monocyte, Neutrophil, Th2 cells, Macrophage), whose hub genes were identified through WGCNA (NOD2, MYD88, STAT1, HSPA4, CXCL8). Finally, we established a pyroptosis-immune co-work during the rosacea aggravations. FRGs may affect the progression of rosacea by regulating the immune cell infiltrations. In all, pyroptosis with its mediated immune cell infiltration is a critical factor during the development of rosacea.

Netrin-1 Alleviates Early Brain Injury by Regulating Ferroptosis via the PPARγ/Nrf2/GPX4 Signaling Pathway Following Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a type of stroke with high morbidity and mortality. Netrin-1 (NTN-1) can alleviate early brain injury (EBI) following SAH by enhancing peroxisome proliferator-activated receptor gamma (PPARγ), which is an important transcriptional factor modulating lipid metabolism. Ferroptosis is a newly discovered type of cell death related to lipid metabolism. However, the specific function of ferroptosis in NTN-1-mediated neuroprotection following SAH is still unclear. This study aimed to evaluate the neuroprotective effects and the possible molecular basis of NTN-1 in SAH-induced EBI by modulating neuronal ferroptosis using the filament perforations model of SAH in mice and the hemin-stimulated neuron injury model in HT22 cells. NTN-1 or a vehicle was administered 2 h following SAH. We examined neuronal death, brain water content, neurological score, and mortality. NTN-1 treatment led to elevated survival probability, greater survival of neurons, and increased neurological score, indicating that NTN-1-inhibited ferroptosis ameliorated neuron death in vivo/in vitro in response to SAH. Furthermore, NTN-1 treatment enhanced the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPX4), which are essential regulators of ferroptosis in EBI after SAH. The findings show that NTN-1 improves neurological outcomes in mice and protects neurons from death caused by neuronal ferroptosis. Furthermore, the mechanism underlying NTN-1 neuroprotection is correlated with the inhibition of ferroptosis, attenuating cell death via the PPARγ/Nrf2/GPX4 pathway and coenzyme Q10-ferroptosis suppressor protein 1 (CoQ10-FSP1) pathway.

PANoptosis signaling enables broad immune response in psoriasis: From pathogenesis to new therapeutic strategies.

Background: Accumulating evidence suggests that regulated cell death, such as pyroptosis, apoptosis, and necroptosis, is deeply involved in the pathogenesis of psoriasis. As a newly recognized form of systematic cell death, PANoptosis is involved in a variety of inflammatory disorders through amplifying inflammatory and immune cascades, but its role in psoriasis remains elusive. Objectives: To reveal the role of PANoptosis in psoriasis for a potential therapeutic strategy. Methods: Multitranscriptomic analysis and experimental validation were used to identify PANoptosis signaling in psoriasis. RNA-seq and scRNA-seq analyses were performed to establish a PANoptosis-mediated immune response in psoriasis, which revealed hub genes through WGCNA and predicted disulfiram as a potential drug. The effect and mechanism of disulfiram were verified in imiquimod (IMQ)-induced psoriasis. Results: Here, we found a highlighted PANoptosis signature in psoriasis patients through multitranscriptomic analysis and experimental validation. Based on this, two distinct PANoptosis patterns (non/high) were identified, which were the options for clinical classification. The high-PANoptosis-related group had a higher response rate to immune cell infiltration (such as M1 macrophages and keratinocytes). Subsequently, WGCNA showed the hub genes (e.g., S100A12, CYCS, NOD2, STAT1, HSPA4, AIM2, MAPK7), which were significantly associated with clinical phenotype, PANoptosis signature, and identified immune response in psoriasis. Finally, we explored disulfiram (DSF) as a candidate drug for psoriasis through network pharmacology, which ameliorated IMQ-mediated psoriatic symptoms through antipyroptosis-mediated inflammation and enhanced apoptotic progression. By analyzing the specific ligand-receptor interaction pairs within and between cell lineages, we speculated that DSF might exert its effects by targeting keratinocytes directly or targeting M1 macrophages to downregulate the proliferation of keratinocytes. Conclusions: PANoptosis with its mediated immune cell infiltration provides a roadmap for research on the pathogenesis and therapeutic strategies of psoriasis.