Cisd2 deficiency impairs neutrophil function by regulating calcium homeostasis via Calnexin and SERCA.

In the context of aging, the susceptibility to infectious diseases increases, leading to heightened morbidity and mortality. This phenomenon, termed immunosenescence, is characterized by dysregulation in the aging immune system, including abnormal alterations in lymphocyte composition, elevated basal inflammation, and the accumulation of senescent T cells. Such changes contribute to increased autoimmune diseases, enhanced infection severity, and reduced responsiveness to vaccines. Utilizing aging animal models becomes imperative for a comprehensive understanding of immunosenescence, given the complexity of aging as a physiological process in living organisms. Our investigation focuses on Cisd2, a causative gene for Wolfram syndrome, to elucidate on immunosenescence. Cisd2 knockout (KO) mice, serving as a model for premature aging, exhibit a shortened lifespan with early onset of aging-related features, such as decreased bone density, hair loss, depigmentation, and optic nerve degeneration. Intriguingly, we found that the Cisd2 KO mice present a higher number of neutrophils in the blood; however, isolated neutrophils from these mice display functional defects. Through mass spectrometry analysis, we identified an interaction between Cisd2 and Calnexin, a protein known for its role in protein quality control. Beyond this function, Calnexin also regulates calcium homeostasis through interaction with sarcoendoplasmic reticulum calcium transport ATPase (SERCA). Our study proposes that Cisd2 modulates calcium homeostasis via its interaction with Calnexin and SERCA, consequently influencing neutrophil functions.

Autistic and non-autistic transgender youth are similar in gender development and sexuality phenotypes.

Increasing rhetoric regarding the common intersection of autism and gender diversity has resulted in legislation banning autistic transgender youth from accessing standard of care supports, as well as legislative efforts banning all youth gender care in part justified by the proportional over-occurrence of autism. Yet, no study has investigated whether autistic and non-autistic transgender youth present fundamentally different gender-related phenotypes. To address this gap, we extensively characterized autism, gender diversity, and sexuality among autistic and non-autistic transgender binary youth (N = 66, Mage = 17.17, SDage = 2.12) in order to investigate similarities and/or differences in gender and sexuality phenotypes. Neither autism diagnostic status nor continuous autistic traits were significantly related to any gender or sexuality phenotypes. These findings suggest that the developmental and experiential features of gender diversity are very similar between autistic and non-autistic transgender adolescents. Future research is needed to determine whether the similarity in profiles is maintained over time into adulthood.

Molecular detection and characterization of Acanthamoeba infection in dogs and its association with keratitis in Korea.

Acanthamoeba infection is associated with keratitis in humans; however, its association with keratitis in dogs remains unclear. To investigate this possibility, we collected 171 conjunctival swab samples from dogs with eye-related diseases (65 with keratitis and 106 without keratitis) at Chungbuk National University Veterinary Teaching Hospital, Korea, from August 2021 to September 2022. Polymerase chain reaction identified 9 samples (5.3%) as Acanthamoeba positive; of these, 3 were from dogs with keratitis (4.6%) and 6 were from dogs without keratitis (5.7%). Our results indicated no significant association between Acanthamoeba infection and keratitis, season, sex, or age. All Acanthamoeba organisms found in this study had the genotype T4, according to 18S ribosomal RNA analysis. Acanthamoeba infection in dogs might have only a limited association with keratitis.

rhIL-7-hyFc and hIL-2/TCB2c combination promotes an immune-stimulatory tumor microenvironment that improves antitumor efficacy of checkpoint inhibitors.

BACKGROUND: Recombinant human interleukin (rhIL)-7-hyFc (efineptakin alfa; NT-I7) is a potent T-cell amplifier, with two IL-7 molecules fused to IgD/IgG4 elements. rhIL-7-hyFc promotes extensive infiltration of CD8+ T cells into the tumor, concurrently increasing the numbers of intratumoral PD-1+CD8+ T cells. The hIL-2/TCB2 complex (SLC-3010) inhibits tumor growth by preferential activation of CD122 (IL-2Rß)high CD8+ T cells and natural killer cells, over regulatory T cells (Tregs). We investigated the underlying mechanisms of rhIL-7-hyFc and hIL-2/TCB2c antitumor activity and the potential synergistic efficacy, specifically focusing on tumor-specific CD8+ cells within the tumor and the tumor-draining lymph nodes (tdLN). METHODS: MC38 and CT26 tumor-bearing mice were administered with 10 mg/kg rhIL-7-hyFc intramuscularly and 0.9 mg/kg hIL-2/TCB2c intravenously. Anti-PD-1 monoclonal antibody was administered intraperitoneally three times at 3-day intervals at a dose of 5 mg/kg. Tumor volume was measured to assess efficacy. To compare the composition of immune cells between each monotherapy and the combination therapy, we analyzed tumors and tdLNs by flow cytometry. RESULTS: Our data demonstrate that the combination of rhIL-7-hyFc and hIL-2/TCB2c increases efficacy and generates an immune-stimulatory tumor microenvironment (TME). The TME is characterized by an increased infiltration of tumor-specific CD8+ T cells, and a decreased frequency of CD39highTIM-3+ Treg cells. Most importantly, rhIL-7-hyFc increases infiltration of a CD62L+Ly108+ early progenitor population of exhausted CD8+ T cells (TPEX), which may retain long-term proliferation capacity and replenish functional effector CD8+ T cells. hIL-2/TCB2c induces differentiation of CD62L+Ly108+ TPEX rapidly into CD101+ terminally differentiated subsets (terminally exhausted T cell (TEX term)). Our study also demonstrates that rhIL-7-hyFc significantly enhances the proliferation rate of TPEX in the tdLNs, positively correlating with their abundance within the tumor. Moreover, rhIL-7-hyFc and hIL-2/TCB2c can overcome the limited therapeutic effectiveness of PD-1 blockade, culminating in the complete regression of tumors. CONCLUSIONS: rhIL-7-hyFc can expand and maintain the progenitor pool of exhausted CD8+ T cells, whereas hIL-2/TCB2c promotes their differentiation into TEX term. Together, this induces an immune-stimulatory TME that improves the efficacy of checkpoint blockade.

Tailored Band Alignment for Improved Carrier Transport in Composition-Controlled Sb2(S,Se)3.

Sb2(S,Se)3 is a highly available energy material with a tunable bandgap by adjusting the S/Se ratio. Increasing the Se ratio can enhance the efficiency of Sb2(S,Se)3 solar cells, with a higher short-circuit current (JSC). However, the accompanying decrease in the open-circuit voltage (VOC) restricts further improvement. The defect passivation is important, since it can reduce carrier recombination, enhancing the VOC. In this study, the relevance of the S/Se ratio, defect concentration, and VOC was investigated. The samples with or without the deposition of Se-rich Sb2(S,Se)3 onto S-rich Sb2(S,Se)3 were used for defect characterization. Different surface compositions were confirmed by Raman spectroscopy. The complicated subdefect states of S-rich Sb2(S,Se)3 were shown through photoluminescence and conductive atomic force microscopy, and a decrease in the defect concentration was observed through surface photovoltage. The improvement of JSC via bandgap grading and the simultaneous VOC improvement by defect passivation resulted in efficient cell performance.

Polygenic Scores Clarify the Relationship Between Mental Health and Gender Diversity.

Background: Gender-diverse individuals are at increased risk for mental health problems, but it is unclear whether this is due to shared environmental or genetic factors. Methods: In two SPARK samples, we tested for associations of 16 polygenic scores (PGSs) with quantitative measures of gender diversity and mental health. In study 1, 639 independent adults (59% autistic) reported their mental health with the Adult Self-Report and their gender diversity with the Gender Self-Report (GSR). The GSR has 2 dimensions: binary (degree of identification with the gender opposite that implied by sex designated at birth) and nonbinary (degree of identification with a gender that is neither male nor female). In study 2 (N = 5165), we used a categorical measure of gender identity. Results: In study 1, neuropsychiatric PGSs were positively associated with Adult Self-Report scores: externalizing was positively associated with the attention-deficit/hyperactivity disorder PGS (ß = 0.10 [0.03-0.17]), and internalizing was positively associated with the PGSs for depression (ß = 0.07 [0-0.14]) and neuroticism (ß = 0.10 [0.03-0.17]). Interestingly, GSR scores were not significantly associated with any neuropsychiatric PGS. However, GSR nonbinary was positively associated with the cognitive performance PGS (ß = 0.11 [0.05-0.18]), with the effect size comparable in magnitude to the associations of the neuropsychiatric PGSs with the Adult Self-Report. Additionally, GSR binary was positively associated with the nonheterosexual sexual behavior PGS (ß = 0.07 [0-0.14]). In study 2, the cognitive performance PGS effect replicated; transgender and nonbinary individuals had higher PGSs (t316 = 4.16). Conclusions: We showed that while gender diversity is phenotypically positively associated with mental health problems, the strongest PGS associations with gender diversity were with the cognitive performance PGS, not the neuropsychiatric PGSs.

This research explores the connection between gender diversity, mental health, and genetic factors. It reveals that gender-diverse individuals often experience more mental health issues. Interestingly, rather than finding evidence linking these mental health challenges to genetic risk factors, the study discovered a replicable positive correlation between gender diversity and genetic markers for higher cognitive performance. This suggests that gender-diverse individuals typically have more of these cognitive performance gene variants. Finally, the study presents some early evidence suggesting that interactions between the environment (e.g., stigma) and genetic risk explain some of the elevated risk to mental health in gender-diverse individuals.

Beneficial Effect of Sirolimus-Pretreated Mesenchymal Stem Cell Implantation on Diabetic Retinopathy in Rats.

BACKGROUND: Diabetic retinopathy (DR) is a vision-threatening complication that affects virtually all diabetic patients. Various treatments have been attempted, but they have many side effects and limitations. Alternatively, stem cell therapy is being actively researched, but it faces challenges due to a low cell survival rate. In this study, stem cells were pretreated with sirolimus, which is known to promote cell differentiation and enhance the survival rate. Additionally, the subconjunctival route was employed to reduce complications following intravitreal injections. METHODS: Diabetes mellitus was induced by intraperitoneal injection of 55 mg/kg of streptozotocin (STZ), and DR was confirmed at 10 weeks after DM induction through electroretinogram (ERG). The rats were divided into four groups: intact control group (INT), diabetic retinopathy group (DR), DR group with subconjunctival MSC injection (DR-MSC), and DR group with subconjunctival sirolimus-pretreated MSC injection (DR-MSC-S). The effects of transplantation were evaluated using ERG and histological examinations. RESULTS: The ERG results showed that the DR-MSC-S group did not significantly differ from the INT in b-wave amplitude and exhibited significantly higher values than the DR-MSC and DR groups (p < 0.01). The flicker amplitude results showed that the DR-MSC and DR-MSC-S groups had significantly higher values than the DR group (p < 0.01). Histological examination revealed that the retinal layers were thinner in the DR-induced groups compared to the INT group, with the DR-MSC-S group showing the thickest retinal layers among them. CONCLUSIONS: Subconjunctival injection of sirolimus-pretreated MSCs can enhance retinal function and mitigate histological changes in the STZ-induced DR rat model.

Cellular Stress Responses against Coronavirus Infection: A Means of the Innate Antiviral Defense.

Cellular stress responses are crucial for maintaining cellular homeostasis. Stress granules (SGs), activated by eIF2α kinases in response to various stimuli, play a pivotal role in dealing with diverse stress conditions. Viral infection, as one kind of cellular stress, triggers specific cellular programs aimed at overcoming virus-induced stresses. Recent studies have revealed that virus-derived stress responses are tightly linked to the host's antiviral innate immunity. Virus infection-induced SGs act as platforms for antiviral sensors, facilitating the initiation of protective antiviral responses called "antiviral stress granules" (avSGs). However, many viruses, including coronaviruses, have evolved strategies to suppress avSG formation, thereby counteracting the host's immune responses. This review discusses the intricate relationship between cellular stress responses and antiviral innate immunity, with a specific focus on coronaviruses. Furthermore, the diverse mechanisms employed by viruses to counteract avSGs are described.

Evaluation of ciliary cleft changes after phacoemulsification using ultrasound biomicroscopy in dogs with cataracts.

Introduction: Glaucoma is one of the most serious complications that causes irreversible blindness after phacoemulsification in dogs; however, a clear mechanism has not been elucidated. This study aimed to analyse the possible anatomical factors associated with glaucoma after phacoemulsification using parameters that reflect the anatomical characteristics of dogs. Materials and methods: A total of 69 eyes of 48 dogs were included in this study. The patients were divided into three groups: normal eye (n = 18), cataract (n = 39), and post-phacoemulsification for at least 2 months after surgery (post-phaco, n = 12). For further analysis, the dogs were subdivided into two groups according to cataract stage: phacoemulsification non-candidate and candidate groups. Non-cataracts and incipient cataracts were categorized into the non-candidate group, whereas immature and mature cataracts were categorized into the candidate group. Measurements of the ciliary cleft parameters, including the area of the ciliary cleft (CCA), length of the ciliary cleft (CCL), width of the ciliary cleft (CCW), iridocorneal angle, and angle opening distance, were obtained using ultrasound biomicroscopy. Results: CCA, CCL, and CCW were significantly higher in the candidate group than in the non-candidate group. CCA, CCL, and CCW were significantly reduced in the post-phaco group compared to those in the cataract group. Based on these results, we found that the ciliary cleft expanded in cataract-affected eyes and narrowed after phacoemulsification. This may indicate that the space between the trabecular meshworks became narrower, potentially leading to an increase in the resistance of the aqueous humor. Conclusion: A narrowed ciliary cleft after phacoemulsification may be an anatomical factor associated with glaucoma.

Tacrolimus Improves Therapeutic Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Diabetic Retinopathy by Suppressing DRP1-Mediated Mitochondrial Fission.

Diabetic retinopathy (DR) is a leading cause of blindness in diabetic patients. Umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) are emerging as a promising new drug for degenerative disease associated with diabetes. Recent studies have shown that high glucose-increased excessive calcium levels are a major risk factor for mitochondrial reactive oxygen species (mtROS) accumulation and apoptosis. This study aimed to investigate the role of high glucose-induced NFATC1 signaling in mitochondrial oxidative stress-stimulated apoptosis and the effect of tacrolimus on the therapeutic efficacy of subconjunctival transplantation of UCB-MSCs in a DR rat model. High glucose increased mtROS and cleaved caspase-9 expression in UCB-MSCs. High glucose conditions increased O-GlcNAcylated protein expression and nuclear translocation of NFATC1. Tacrolimus pretreatment recovered high glucose-induced mtROS levels and apoptosis. In the DR rat model, subconjunctival transplantation of tacrolimus-pretreated MSCs improved retinal vessel formation, retinal function, and uveitis. In high glucose conditions, tacrolimus pretreatment reduced protein and mRNA expression levels of DRP1 and inhibited mitochondrial fission. In conclusion, we demonstrated that high glucose-induced O-GlcNAcylation activates NFATC1 signaling, which is important for DRP1-mediated mitochondrial fission and mitochondrial apoptosis. Finally, we proposed NFATC1 suppression by tacrolimus as a promising therapeutic strategy to improve the therapeutic efficacy of UCB-MSC transplantation for DR treatment.

SARS-CoV-2 variants with NSP12 P323L/G671S mutations display enhanced virus replication in ferret upper airways and higher transmissibility.

With the emergence of multiple predominant SARS-CoV-2 variants, it becomes important to have a comprehensive assessment of their viral fitness and transmissibility. Here, we demonstrate that natural temperature differences between the upper (33°C) and lower (37°C) respiratory tract have profound effects on SARS-CoV-2 replication and transmissibility. Specifically, SARS-CoV-2 variants containing the NSP12 mutations P323L or P323L/G671S exhibit enhanced RNA-dependent RNA polymerase (RdRp) activity at 33°C compared with 37°C and high transmissibility. Molecular dynamics simulations and microscale thermophoresis demonstrate that the NSP12 P323L and P323L/G671S mutations stabilize the NSP12-NSP7-NSP8 complex through hydrophobic effects, leading to increased viral RdRp activity. Furthermore, competitive transmissibility assay reveals that reverse genetic (RG)-P323L or RG-P323L/G671S NSP12 outcompetes RG-WT (wild-type) NSP12 for replication in the upper respiratory tract, allowing markedly rapid transmissibility. This suggests that NSP12 P323L or P323L/G671S mutation of SARS-CoV-2 is associated with increased RdRp complex stability and enzymatic activity, promoting efficient transmissibility.

Preventive Effects of Exosome-Rich Conditioned Medium From Amniotic Membrane-Derived Mesenchymal Stem Cells for Diabetic Retinopathy in Rats.

Purpose: Diabetic retinopathy (DR) is an important disease that causes vision loss in many diabetic patients. Stem cell therapy has been attempted for treatment of this disease; however, it has some limitations. This study aimed to evaluate the preventive efficacy of exosome-rich conditioned medium (ERCM) derived from amniotic membrane stem cells for DR in rats. Methods: Twenty-eight 8-week-old male Sprague-Dawley rats were divided into three groups: group 1, normal control (Con) group; group 2, diabetes mellitus (DM) group; and group 3, DM with ERCM-treated (DM-ERCM) group. DM was induced by intraperitoneal injection of streptozotocin. The DM-ERCM group received ERCM containing 1.2 × 109 exosomes into subconjunctival a total of four times every 2 weeks. Results: On electroretinogram, the DM-ERCM group had significantly higher b-wave and flicker amplitudes than those in the DM group. In fundoscopy, retinal vascular attenuation was found in both the DM and DM-ERCM groups; however, was more severe in the DM group. On histology, the ganglion cell and nerve fiber layer rates of the total retinal layer significantly increased in the DM group compared with the Con group, whereas the DM-ERCM group showed no significant difference compared with the Con group. Cataracts progressed significantly more in the DM group than that in the DM-ERCM group and there was no uveitis in the DM-ERCM group. Conclusions: Subconjunctival ERCM delayed the progression of DR and cataracts and significantly reduced the incidence of uveitis. Translational Relevance: Our study shows the clinical potential of minimally invasive exosome-rich conditioned medium treatment to prevent diabetic retinopathy.

Enhanced Cholesterol-Lowering and Antioxidant Activities of Soymilk by Fermentation with Lactiplantibacillus plantarum KML06.

This study aimed to evaluate the cholesterol-lowering and antioxidant activities of soymilk fermented with probiotic Lactobacillaceae strains and to investigate the production of related bioactive compounds. Lactiplantibacillus plantarum KML06 (KML06) was selected for the fermentation of soymilk because it has the highest antioxidant, cholesterol-lowering, and ß-glucosidase activities among the 10 Lactobacillaceae strains isolated from kimchi. The genomic information of strain KML06 was analyzed. Moreover, soymilk fermented with KML06 was evaluated for growth kinetics, metabolism, and functional characteristics during the fermentation period. The number of viable cells, which was similar to the results of radical scavenging activities and cholesterol assimilation, as well as the amount of soy isoflavone aglycones, daidzein, and genistein, was the highest at 12 h of fermentation. These results indicate that soymilk fermented with KML06 can prevent oxidative stress and cholesterol-related problems through the production of soy isoflavone aglycones.

CoAt-Mixer: Self-attention deep learning framework for left ventricular hypertrophy using electrocardiography.

Left ventricular hypertrophy is a significant independent risk factor for all-cause mortality and morbidity, and an accurate diagnosis at an early stage of heart change is clinically significant. Electrocardiography is the most convenient, economical, and non-invasive method for screening in primary care. However, the coincidence rate of the actual left ventricular hypertrophy and diagnostic findings was low, consequently increasing the interest in algorithms using big data and deep learning. We attempted to diagnose left ventricular hypertrophy using big data and deep learning algorithms, and aimed to confirm its diagnostic power according to the differences between males and females. This retrospective study used electrocardiographs obtained at Yonsei University Wonju Severance Christian Hospital, Wonju, Korea, from October 2010 to February 2020. Binary classification was performed for primary screening for left ventricular hypertrophy. Three datasets were used for the experiment: the male, female, and entire dataset. A cutoff for binary classification was defined as the meaningful as a screening test (<132 g/m2 vs. ≥132 g/m2, <109 g/m2 vs. ≥109 g/m2). Six types of input were used for the classification tasks. We attempted to determine whether electrocardiography had predictive power for left ventricular hypertrophy diagnosis. For the entire dataset, the model achieved an area under the receiver operating characteristic (AUROC) curve of 0.836 (95% CI, 0.833-838) with a sensitivity of 78.37% (95% CI, 76.79-79.95). For the male dataset, the AUROC was 0.826 (95% CI, 0.822-830) with a sensitivity of 76.73% (95% CI, 75.14-78.33). For the female dataset, the AUROC was 0.772 (95% CI, 0.769-775) with a sensitivity of 72.90% (95% CI, 70.33-75.46). Our model confirmed that left ventricular hypertrophy can be classified to some extent using electrocardiography, demographics, and electrocardiography features. In particular, a learning environment that considered gender differences was constructed. Consequently, the difference in diagnostic power between men and women was confirmed. Our model will help patients with suspected left ventricular hypertrophy to undergo screening tests at a low cost. In addition, our research and attempts will show the expected effect that gender-consideration approaches can help with various currently proposed diagnostic methods.

Deep Learning Algorithms for Estimation of Demographic and Anthropometric Features from Electrocardiograms.

The electrocardiogram (ECG) has been known to be affected by demographic and anthropometric factors. This study aimed to develop deep learning models to predict the subject's age, sex, ABO blood type, and body mass index (BMI) based on ECGs. This retrospective study included individuals aged 18 years or older who visited a tertiary referral center with ECGs acquired from October 2010 to February 2020. Using convolutional neural networks (CNNs) with three convolutional layers, five kernel sizes, and two pooling sizes, we developed both classification and regression models. We verified a classification model to be applicable for age (<40 years vs. ≥40 years), sex (male vs. female), BMI (<25 kg/m2 vs. ≥25 kg/m2), and ABO blood type. A regression model was also developed and validated for age and BMI estimation. A total of 124,415 ECGs (1 ECG per subject) were included. The dataset was constructed by dividing the entire set of ECGs at a ratio of 4:3:3. In the classification task, the area under the receiver operating characteristic (AUROC), which represents a quantitative indicator of the judgment threshold, was used as the primary outcome. The mean absolute error (MAE), which represents the difference between the observed and estimated values, was used in the regression task. For age estimation, the CNN achieved an AUROC of 0.923 with an accuracy of 82.97%, and a MAE of 8.410. For sex estimation, the AUROC was 0.947 with an accuracy of 86.82%. For BMI estimation, the AUROC was 0.765 with an accuracy of 69.89%, and a MAE of 2.332. For ABO blood type estimation, the CNN showed an inferior performance, with a top-1 accuracy of 31.98%. For the ABO blood type estimation, the CNN showed an inferior performance, with a top-1 accuracy of 31.98% (95% CI, 31.98-31.98%). Our model could be adapted to estimate individuals' demographic and anthropometric features from their ECGs; this would enable the development of physiologic biomarkers that can better reflect their health status than chronological age.

Lung-specific MCEMP1 functions as an adaptor for KIT to promote SCF-mediated mast cell proliferation.

Lung mast cells are important in host defense, and excessive proliferation or activation of these cells can cause chronic inflammatory disorders like asthma. Two parallel pathways induced by KIT-stem cell factor (SCF) and FcεRI-immunoglobulin E interactions are critical for the proliferation and activation of mast cells, respectively. Here, we report that mast cell-expressed membrane protein1 (MCEMP1), a lung-specific surface protein, functions as an adaptor for KIT, which promotes SCF-mediated mast cell proliferation. MCEMP1 elicits intracellular signaling through its cytoplasmic immunoreceptor tyrosine-based activation motif and forms a complex with KIT to enhance its autophosphorylation and activation. Consequently, MCEMP1 deficiency impairs SCF-induced peritoneal mast cell proliferation in vitro and lung mast cell expansion in vivo. Mcemp1-deficient mice exhibit reduced airway inflammation and lung impairment in chronic asthma mouse models. This study shows lung-specific MCEMP1 as an adaptor for KIT to facilitate SCF-mediated mast cell proliferation.

A digital light processing 3D-printed artificial skin model and full-thickness wound models using silk fibroin bioink.

A three-dimensional (3D) artificial skin model offers diverse platforms for skin transplantation, disease mechanisms, and biomaterial testing for skin tissue. However, implementing physiological complexes such as the neurovascular system with living cells in this stratified structure is extremely difficult. In this study, full-thickness skin models were fabricated from methacrylated silk fibroin (Silk-GMA) and gelatin (Gel-GMA) seeded with keratinocytes, fibroblasts, and vascular endothelial cells representing the epidermis and dermis layers through a digital light processing (DLP) 3D printer. Printability, mechanical properties, and cell viability of the skin hydrogels fabricated with different concentrations of Silk-GMA and Gel-GMA were analyzed to find the optimal concentrations for the 3D printing of the artificial skin model. After the skin model was DLP-3D printed using Gel-GMA 15% + Silk-GMA 5% bioink, cultured, and air-lifted for four weeks, well-proliferated keratinocytes and fibroblasts were observed in histological analysis, and increased expressions of Cytokeratin 13, Phalloidin, and CD31 were noted in immunofluorescence staining. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound-healing capabilities of the skin hydrogel. When the epidermal growth factor (EGF) was applied, enhanced wound healing in the epidermis and dermis layer with the proliferation of keratinocytes and fibroblasts was observed. Also, the semi-quantitative reverse transcription-polymerase chain reaction revealed increased expression of Cytokeratin 13, fibroblast growth factor, and CD31 in the EGF-treated group relative to the control group. The DLP 3D-printed artificial skin model was mechanically stable and biocompatible for more than four weeks, demonstrating the potential for application in skin tissue engineering. STATEMENT OF SIGNIFICANCE: A full-thickness artificial skin model was 3D-printed in this study with a digital light processing technique using silk fibroin and gelatin, which mimics the structural and cellular compositions of the human skin. The 3D-printed skin hydrogel ensured the viability of the cells in the skin layers that proliferated well after air-lifting cultivation, shown in the histological analysis and immunofluorescence stainings. Furthermore, full-thickness skin wound models were 3D-printed to evaluate the wound healing capabilities of the skin hydrogel, which demonstrated enhanced wound healing in the epidermis and dermis layer with the application of epidermal growth factor on the wound compared to the control. The bioengineered hydrogel expands the applicability of artificial skin models for skin substitutes, wound models, and drug testing.