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Jiunn-Song Jiang,1,2 Chew-Teng Kor,3 David Dar Kuo,4 Ching-Hsiung Lin,5,6 Chia-Chu Chang,7,8 Gau-Yang Chen,9,10 Cheng-Deng Kuo5,11 1Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 2Departments of Internal Medicine, Taipei Medical University School of Medicine, Taipei, Taiwan; 3Internal Medicine Research Center, Department of Research, Changhua Christian Hospital, Changhua, Taiwan; 4Architecture, Industrial Design Engineering, & Manufacturing Department, Mount San Antonio College, Walnut, CA, USA; 5Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 6Department of Respiratory Care, College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan; 7Division of Nephrology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan; 8Departmet of Internal Medicine, Chung-Shan Medical University School of Medicine, Taichung, Taiwan; 9Department of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan; 10Department of Internal Medicine, Ten-Chen General Hospital, Yangmei, Tao-Yuan, Taiwan; 11Laboratory of Biophysics, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan Purpose: It has been shown that the power spectral density (PSD) of heart rate variability (HRV) can be decomposed into a power-law function and a residual PSD (rPSD) with a more prominent high-frequency component than that in traditional PSD. This study investigated whether the residual HRV (rHRV) measures can better discriminate patients with acute myocardial infarction (AMI) from patients with patent coronary artery (PCA) than traditional HRV measures. Materials and methods: The rHRV and HRV measures of 48 patients with AMI and 69 patients with PCA were compared. Results: The high-frequency power of rHRV spectrum was significantly enhanced while the low-frequency and very low-frequency powers of rHRV spectrum were significantly suppressed, as compared to their corresponding traditional HRV spectrum in both groups of patients. The normalized residual high-frequency power (nrHFP = residual high-frequency power/residual total power) was significantly greater than the corresponding normalized high-frequency power in both groups of patients. Between-groups comparison showed that the nrHFP in AMI patients was significantly smaller than that in PCA patients. Receiver operating characteristic curve analysis showed that the nrHFP or nrHFP + normalized residual very low-frequency power (residual very low-frequency power/rTP) had better discrimination capability than the corresponding HRV measures for predicting AMI. Conclusions: Compared with traditional HRV measures, the rHRV measures can slightly better differentiate AMI patients from PCA patients, especially the nrHFP or nrHFP + normalized residual very low-frequency power. Keywords: heart rate variability, fractal, residual power spectrum, power-law function, acute myocardial infarction

Background: Diabetic ulcers (DUs) is a common complication of diabetes, for which the morbidity and mortality increasing annually worldwide. The deficiency of PD-L1 in keratinocytes (KCs) may be linked to the diabetic wound healing impediments., Objective: Our study utilized transgenic mice to assess the functions of epidermal KCs-specific PD-L1 in DUs treatment., Methods and Results: Epidermal KCs-specific PD-L1 knockouted mice demonstrate deteriorated healing rates, concomitant with exacerbated inflammatory infiltration and excessive angiogenesis. The streptozotocin-induced murine diabetes model was used to imitate DUs in-vivo context, and the delayed healing was found under diabetic conditions. We then generated transgenic mice overexpressing PD-L1 in the epidermis. PD-L1 overexpression accelerate the DUs healing process accompanied by a reduction in inflammatory infiltration and a corresponding decreasion of angiogenesis. Therefore, overexpression of PD-L1 accelerates the healing process of DUs., Conclusion: In sum, epidermal KCs-specific PD-L1 plays vital roles in epidermis regeneration, inflammatory infiltration, and angiogenesis during DUs restoration, and would not be easily to format fibrous scar. Our study elucidated a new therapeutic idea for slow-healing wound care., (Copyright © 2024. Published by Elsevier B.V.)

Two new cucurbitane-type triterpenoid saponins, 2,20 β ,22 β -trihydroxy-16 α ,23( R )-epoxycucurbita-1,5,24-triene-3,11-dione 2- O - β -D-glucopyranoside ( 1 ), 2,20 β ,22 α -trihydroxy-16 α ,23( S )-epoxycucurbita-1,5,11,24-tetraene-3-one 2- O - β -D-glucopyranoside ( 2 ) were isolated from the fruit of Citrullus colocynthis (L.) Schrad. Their structures were elucidated by mass spectrometry, IR, 1D, and 2D NMR spectroscopy, etc. Besides, both of the compounds showed significant hepatoprotective activities at 10  μ M against paracetamol-induced HepG2 cell damage.

Three new flavonoids including two isoflavanones sophortones A and B ( 1 and 2 ), and one chalcone sophortone C ( 3 ) were isolated from the roots of Sophora tonkinensis . Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithmsr. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis. A diagnostic model was developed using random forest algorithm and validated by receiver operating characteristic (ROC) curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by quantitative real-time PCR (qRT-PCR). We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P < 0.0001) and interleukins pathway (R = 0.79, P < 0.0001). Furthermore, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes., (© Crown copyright 2024.)

Topotactic reduction is critical to a wealth of phase transitions of current interest, including synthesis of the superconducting nickelate Nd 0.8 Sr 0.2 NiO 2 , reduced from the initial Nd 0.8 Sr 0.2 NiO 3 /SrTiO 3 heterostructure. Due to the highly sensitive and often damaging nature of the topotactic reduction, however, only a handful of research groups have been able to reproduce the superconductivity results. A series of in situ synchrotron-based investigations reveal that this is due to the necessary formation of an initial, ultrathin layer at the Nd 0.8 Sr 0.2 NiO 3 surface that helps to mediate the introduction of hydrogen into the film such that apical oxygens are first removed from the Nd 0.8 Sr 0.2 NiO 3 / SrTiO 3 (001) interface and delivered into the reducing environment. This allows the square-planar / perovskite interface to stabilize and propagate from the bottom to the top of the film without the formation of interphase defects. Importantly, neither geometric rotations in the square planar structure nor significant incorporation of hydrogen within the films is detected, obviating its need for superconductivity. These findings unveil the structural basis underlying the transformation pathway and provide important guidance on achieving the superconducting phase in reduced nickelate systems., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Emerging from the intricate interplay of topology and magnetism, the giant anomalous Hall effect (AHE) is the most known topological property of the recently discovered kagomé ferromagnetic Weyl semimetal Co 3 Sn 2 S 2 with the magnetic Co atoms arranged on a kagomé lattice. Here it is reported that the AHE in Co 3 Sn 2 S 2 can be fine-tuned by an applied magnetic field orientated within ≈2° of the kagomé plane, while beyond this regime, it stays unchanged. Particularly, it can vanish in magnetic fields parallel to the kagomé plane and even decrease in magnetic fields collinear with the spin direction. This tunable AHE can be attributed to local spin switching enabled by the geometrical frustration of the magnetic kagomé lattice, revealing that spins in a kagomé ferromagnet change their switching behavior as the magnetic field approaches the kagomé plane. These results also suggest a versatile way to tune the properties of a kagomé magnet., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Background: Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear., Methods: We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6 flox/flox homozygous mice with UBC-creERT2 + transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration., Results: Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1β, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice., Conclusions: SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In this study, we redefine the diagnostic landscape of diabetic ulcers (DUs), a major diabetes complication. Our research uncovers new biomarkers linked to immunogenic cell death (ICD) in DUs by utilizing RNA-sequencing data of Gene Expression Omnibus (GEO) analysis combined with a comprehensive database interrogation. Employing a random forest algorithm, we have developed a diagnostic model that demonstrates improved accuracy in distinguishing DUs from normal tissue, with satisfactory results from ROC analysis. Beyond mere diagnosis, our model categorizes DUs into novel molecular classifications, which may enhance our comprehension of their underlying pathophysiology. This study bridges the gap between molecular insights and clinical practice. It sets the stage for transformative strategies in DUs management, marking a significant step forward in personalized medicine for diabetic patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Mycoplasma pneumoniae pneumonia (MPP) significantly impacts pediatric health, necessitating markers for early severe disease identification., Aim: To investigate the correlation between serum inflammatory marker and the severity of MPP in children., Methods: A prospective study was carried out from January 2023 to November 2023. A total of 160 children with MPP who underwent treatment were selected: 80 had severe MPP and 80 had mild MPP. Clinical and laboratory data were collected at the time of hospital admission and during hospitalization. Receiver operating characteristic curves were utilized to assess the diagnostic and prognostic for severe MPP., Results: Fever duration and length of hospitalization in pediatric patients with severe MPP exceeded those with mild MPP. The incidence of pleural effusion, lung consolidation, and bronchopneumonia on imaging was markedly elevated in the severe MPP cohort compared to the mild MPP cohort. In contrast to the mild cohort, there was a notable increase in C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate, lactic dehydrogenase, D-dimer, and inflammatory cytokines [interleukin (IL)-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α] in the severe MPP group were significantly higher., Conclusion: Serum inflammatory markers (CRP, PCT, IL-6, D-dimer, IL-10 and TNF-α) were considered as predictors in children with severe MPP., Competing Interests: Conflict-of-interest statement: All authors declare that there is no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Patients with cirrhosis are more susceptible to coronavirus disease 2019 (COVID-19) due to immune dysfunction. In this retrospective study we aimed to investigate whether suppression of mild systemic inflammation with selective cyclooxygenase-2 inhibitor (COX-2-I) during chronic care of cirrhotic patients would reduce the occurrence of acute decompensated events and improve patient prognosis of COVID-19., Methods: Medical records of cirrhotic patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were sequentially reviewed. The patients were divided into the COX-2-I and control groups depending on whether they took oral selective COX-2-I for over 3 months or not. The primary outcomes included the occurrence of severe/critical COVID-19, acute decompensated events, and acute-on-chronic liver failure (ACLF)., Results: After propensity score matching analysis, there were 314 cases in the control group and 118 cases in the COX-2-I group. Compared with the control group, the risk of severe/critical COVID-19 in the COX-2-I group was significantly decreased by 83.1% (p = 0.004). Acute decompensated events and ACLF occurred in 23 (7.32%) and nine (2.87%) cases in the control group, but none in the COX-2-I group (p = 0.003 and 0.122). The rate of hospitalization in the COX-2-I group was significantly lower than that of the control group (3.39% vs 13.06%, p = 0.003). No patient in the COX-2-I group required intensive care unit admission., Conclusions: Long-term intermittent oral administration of selective COX-2-I in cirrhotic patients significantly reduces the occurrence of severe/critical COVID-19, acute decompensated events, and ACLF. It may also be used for systemic inflammation caused by other pathogens., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Antiferromagnetic (AFM) materials are a pathway to spintronic memory and computing devices with unprecedented speed, energy efficiency, and bit density. Realizing this potential requires AFM devices with simultaneous electrical writing and reading of information, which are also compatible with established silicon-based manufacturing. Recent experiments have shown tunneling magnetoresistance (TMR) readout in epitaxial AFM tunnel junctions. However, these TMR structures are not grown using a silicon-compatible deposition process, and controlling their AFM order required external magnetic fields. Here are shown three-terminal AFM tunnel junctions based on the noncollinear antiferromagnet PtMn 3 , sputter-deposited on silicon. The devices simultaneously exhibit electrical switching using electric currents, and electrical readout by a large room-temperature TMR effect. First-principles calculations explain the TMR in terms of the momentum-resolved spin-dependent tunneling conduction in tunnel junctions with noncollinear AFM electrodes., (© 2024 The Authors. Advanced Materials published by Wiley‐VCH GmbH.)

Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 μM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In order to comprehensively evaluate the effects of vermicomposting on compost quality and the conversion of heavy metals under different control conditions, 109 studies were reviewed. The effects of earthworm species, pre-compost time, ventilation methods, initial C/N, initial pH, and initial moisture of the raw materials on compost quality and the heavy metal toxicity were quantitatively discussed during the vermicomposting process through Meta-analysis. The results showed that the six subgroups of factors all showed obvious influences on the compost quality and heavy metal toxicity. After vermicomposting, the contents of NO 3 - -N (116.2%), TN (29.1%), TP (31.2%), and TK (15.0%) were significantly increased, whereas NH 4 + -N (-14.8%) and C/N (-36.3%) were significantly decreased. Meanwhile, the total amount of Cu and Cr of the final compost and their bioavailability were significantly reduced. Considering the influences of grouping factors on compost quality and heavy metals, it is recommended to adjust the initial moisture of pile materials to 70%-80%, C/N to 30-85, and pH to 6-7 and to conduct pre-composting for 0-15 d; additionally, vermicomposting should be naturally placed when the composting is aimed at promoting the compost quality. If the main purpose is to weaken the perniciousness of heavy metals in the raw material, it is recommended to adjust the initial moisture of the material to 50%-60%, C/N to less than 30, and pH to 7-8; to conduct no pre-compost; regularly turn the piles; and use the earthworm Eudrilus eugeniae for vermicomposting.

Six new iridoid glycosides were isolated from the ethyl acetate fraction of the whole plants of Hedyotis diffusa Willd. They were identified as E -6- O-p -methoxycinnamoyl-10- O -acetyl scandoside acid methyl ester ( 1 ), Z -6- O-p -methoxycinnamoyl-10- O -acetyl scandoside acid methyl ester ( 2 ), E -6- O -caffeoyl scandoside methyl ester ( 3 ), E -6- O - p -coumaroyl-6'- O -acetyl scandoside methyl ester ( 4 ), Z -6- O - p -coumaroyl-6'- O -acetyl scandoside methyl ester ( 5 ), and E -6- O - p -coumaroyl-4'- O -acetyl scandoside methyl ester ( 6 ). The structures of them were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, and NMR). They were screened for anti-inflammatory effect, antioxidant effect, antitumor effect, and neuroprotective effect and did not show potent activities.

Seventeen undescribed iridoid derivatives (1-17) and four known compounds (18-21) were isolated from the whole plant of Hedyotis diffusa Willd. Their structures were elucidated based on unambiguous spectroscopic data (UV, IR, HRESIMS, CD, and 1D and 2D NMR). It is noteworthy that compounds 1-8, which possess unique long-chain aliphatic acid moiety, were reported for the first time among the iridoid natural products. All compounds were evaluated for their anti-inflammatory activities in lipopolysaccharide-induced RAW 264.7 cells. Compounds 2, 4, and 6 showed significant suppression effects on nitric oxide production, with IC 50 values of 5.69, 6.16, and 6.84 μM, respectively. The structure-activity relationships of these compounds indicated that long-chain aliphatic moieties at C-10 might be the key group for their anti-inflammatory activities. The therapeutic properties of these iridoid derivatives could give an insight into utilizing H. diffusa as a natural source of anti-inflammatory agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Six undescribed lavandulylated flavonoids (1-6) were isolated from the roots of Sophora flavescens. Remarkably, compounds 1 and 2, which were composed of a flavane unit and a phloroglucinol unit, were the first reported dimers. Compounds 3 and 4 were the first reported neoflavonoids with lavandulyl units. Compounds 5 and 6 were chalcone with oxidized lavandulyl units. Their structures were fully characterized by cumulative analyses of UV, IR, HRESIMS, NMR and ECD spectroscopic data, along with computational calculations through density functional theory. Compounds 1 and 2 showed significant protein tyrosine phosphatase-1B inhibitory activities with IC 50 values of 2.669 and 3.596 μM, respectively., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Diabetic ulcers (DUs) are a common complication of diabetes with high morbidity, poor prognosis, and a high socio-economic burden. The main pathological manifestations of DUs are chronic inflammation, impaired re-epithelialization, and impaired angiogenesis. During the inflammatory phase, neutrophils are one of the main DU cell types and act by releasing neutrophil extracellular traps (NETs), leading to poor healing in DUs. This review summarizes the role of neutrophils in the pathology and treatment of DUs, with a view to potential novel therapies and therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Diabetes mellitus (DM) can lead to diabetic ulcers (DUs), which are the most severe complications. Due to the need for more accurate patient classifications and diagnostic models, treatment and management strategies for DU patients still need improvement. The difficulty of diabetic wound healing is caused closely related to biological metabolism and immune chemotaxis reaction dysfunction. Therefore, the purpose of our study is to identify metabolic biomarkers in patients with DU and construct a molecular subtype-specific prognostic model that is highly accurate and robust. RNA-sequencing data for DU samples were obtained from the Gene Expression Omnibus (GEO) database. DU patients and normal individuals were compared regarding the expression of metabolism-related genes (MRGs). Then, a novel diagnostic model based on MRGs was constructed with the random forest algorithm, and classification performance was evaluated utilizing receiver operating characteristic (ROC) analysis. The biological functions of MRGs-based subtypes were investigated using consensus clustering analysis. A principal component analysis (PCA) was conducted to determine whether MRGs could distinguish between subtypes. We also examined the correlation between MRGs and immune infiltration. Lastly, qRT-PCR was utilized to validate the expression of the hub MRGs with clinical validations and animal experimentations. Firstly, 8 metabolism-related hub genes were obtained by random forest algorithm, which could distinguish the DUs from normal samples validated by the ROC curves. Secondly, DU samples could be consensus clustered into three molecular classifications by MRGs, verified by PCA analysis. Thirdly, associations between MRGs and immune infiltration were confirmed, with LYN and Type 1 helper cell significantly positively correlated; RHOH and TGF-β family remarkably negatively correlated. Finally, clinical validations and animal experiments of DU skin tissue samples showed that the expressions of metabolic hub genes in the DU groups were considerably upregulated, including GLDC, GALNT6, RHOH, XDH, MMP12, KLK6, LYN, and CFB. The current study proposed an auxiliary MRGs-based DUs model while proposing MRGs-based molecular clustering and confirmed the association with immune infiltration, facilitating the diagnosis and management of DU patients and designing individualized treatment plans., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8 + cells (representing CD8 + T cells) and CD57 + cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA + cells and GSDMB + cells were predominantly expressed in immune cells, especially in CD8  +  T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA + merged CD8 + T cells (0.11%) and GSDMB + merged CD57 + cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma., (© 2023. The Author(s).)

Six undescribed tanshinones, (+)-2-Cl-tanshindiol C (1), (-)-2-Cl-tanshindiol C (2), (+)-tanshinoic acid D (3), (-)-tanshinoic acid D (4), (-)-tanshinoic acid E (5), and (+)-tanshinoic acid E (6), were isolated from the rhizome of Salvia miltiorrhiza Bunge. Their structures were elucidated based on the spectroscopic data (UV, IR, HR-ESI-MS, and NMR). The bioactive assays of all these compounds for the antioxidant activities in cardiomyocytes upon hypoxia stimulation were evaluated. The results suggested that compounds 5 and 6 exhibited good antioxidant activities in cardiomyocytes and the cell survival rates were 46.3% and 57.9% (10 -5  mol/L), respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Titanium nitride is a material of interest for many superconducting devices such as nanowire microwave resonators and photon detectors. Thus, controlling the growth of TiN thin films with desirable properties is of high importance. This work aims to explore effects in ion beam-assisted sputtering (IBAS), were an observed increase in nominal critical temperature and upper critical fields are in tandem with previous work on Niobium nitride (NbN). We grow thin films of titanium nitride by both, the conventional method of DC reactive magnetron sputtering and the IBAS method, to compare their superconducting critical temperatures [Formula: see text] as functions of thickness, sheet resistance, and nitrogen flow rate. We perform electrical and structural characterizations by electric transport and x-ray diffraction measurements. Compared to the conventional method of reactive sputtering, the IBAS technique has demonstrated a 10% increase in nominal critical temperature without noticeable variation in the lattice structure. Additionally, we explore the behavior of superconducting [Formula: see text] in ultra-thin films. Trends in films grown at high nitrogen concentrations follow predictions of mean-field theory in disordered films and show suppression of superconducting [Formula: see text] due to geometric effects, while nitride films grown at low nitrogen concentrations strongly deviate from the theoretical models., (© 2023. © UChicago Argonne, LLC, Operator of Argonne National Laboratory.)

Ethnopharmacological Relevance: Diabetic ulcers (DUs) are one of the most severe complications of diabetes, and efficacious therapeutic means are currently lacking. Sheng-ji Hua-yu (SJHY) ointment is a classical Chinese traditional prescription that can significantly attenuate DU defects, but the specific mechanism remains to be fully elucidated., Aim of the Study: In order to verify the underlying mechanism of SJHY ointment in accelerating the closure of DUs., Materials and Methods: Modular pharmacology and molecular docking were utilized to predict the therapeutic targets of SJHY ointment against DUs. Male db/db diabetic mice and HaCaT cell models induced by methylglyoxal were used to validate the findings., Results: CCN1 was proven to be the core target of SJHY ointment involved in DUs treatment. CCN1 up-regulated by SJHY treatment (0.5 g/cm 2 /day) at the mRNA and protein levels was detected on Day9 after wounding. With CCN1 knockdown, accelerated cell proliferation, migration, and anti-inflammatory effect of SJHY treatment (10 mg/L) were reversed., Conclusions: SJHY ointment ameliorates cutaneous wound healing by up-regulating CCN1., (Copyright © 2022 Elsevier B.V. All rights reserved.)

What causes Cooper pairs to form in unconventional superconductors is often elusive because experimental signatures that connect to a specific pairing mechanism are rare. Here, we observe distinct dependences of the superconducting transition temperature T c on carrier density n 2D for electron gases formed at KTaO 3 (111), (001) and (110) interfaces. For the (111) interface, a remarkable linear dependence of T c on n 2D is observed over a range of nearly one order of magnitude. Further, our study of the dependence of superconductivity on gate electric fields reveals the role of the interface in mediating superconductivity. We find that the extreme sensitivity of superconductivity to crystallographic orientation can be explained by pairing via inter-orbital interactions induced by an inversion-breaking transverse optical phonon and quantum confinement. This mechanism is also consistent with the dependence of T c on n 2D . Our study may shed light on the pairing mechanism in other superconducting quantum paraelectrics., (© 2023. The Author(s).)

The purpose of this study was to predict the carcass characteristics of broilers using support vector regression (SVR) and artificial neural network (ANN) model methods. Data were obtained from 176 yellow feather broilers aged 100-day-old (90 males and 86 females). The input variables were live body measurements, including external measurements and B-ultrasound measurements. The predictors of the model were the weight of abdominal fat and breast muscle in male and female broilers, respectively. After descriptive statistics and correlation analysis, the datasets were randomly divided into train set and test set according to the ratio of 7:3 to establish the model. The results of this study demonstrated that it is feasible to use machine learning methods to predict carcass characteristics of broilers based on live body measurements. Compared with the ANN method, the SVR method achieved better prediction results, for predicting breast muscle (male: R 2  = 0.950; female: R 2  = 0.955) and abdominal fat (male: R 2  = 0.802; female: R 2  = 0.944) in the test set. Consequently, the SVR method can be considered to predict breast muscle and abdominal fat of broiler chickens, except for abdominal fat in male broilers. However, further revaluation of the SVR method is suggested., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, and current therapies have limited efficacy on PDAC. The DEAH-box helicase 9 (DHX9) is widely reported to influence cell biological behavior via regulating DNA replication, genomic stability, transcription, translation, and microRNA biogenesis. However, the prognostic role of DHX9 in PDAC remains unclear. Thus, the objective of this study is to investigate the prognostic value of DHX9 expression in PDAC patients., Methods: Tumor specimens from PDAC patients with surgical resection were obtained, and DHX9 was stained and analyzed in this study. Univariate and multivariate Cox regression analyses were utilized to identify independent risk factors of overall survival (OS) and recurrence-free survival (RFS). The prognostic nomograms for predicting OS and RFS were established to obtain superior predictive power., Results: Among the enrolled 110 patients, 61 patients were identified as having high expression of DHX9. The correlation analysis revealed that higher DHX9 expression in PDAC was prone to have advanced N stage ( p = 0.010) and TNM stage ( p = 0.017). For survival, the median OS (21.0 vs. 42.0 months, p < 0.001) and RFS (12.0 vs. 24.0 months, p < 0.001) of patients in the high DHX9 group were significantly shorter than those in the low DHX9 group. Within the univariate and multivariate analyses, American Joint Committee on Cancer (AJCC) N stage ( p = 0.036) and DHX9 expression ( p = 0.041) were confirmed as independent prognostic factors of OS, while nerve invasion ( p = 0.031) and DHX9 expression ( p = 0.005) were independent prognostic factors of RFS. Finally, the novel prognostic nomograms for OS and RFS were established and showed superior predictive accuracy., Conclusion: This study identified the independent prognostic value of DHX9 for RFS and OS in resected PDAC patients, and higher DHX9 expression was prone to have an earlier recurrence and shorter OS. Therefore, DHX9 may be a promising and valuable biomarker and a potential target for treating PDAC. More accurate and promising predictive models would be achieved when DHX9 is incorporated into nomograms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Cui, Lu, Wu, Jiang and Ding.)

Eight new arnebinol B-based meroterpenoids ((-)-1, 2, 3, (-)-5, and 7-10) with a constrained 6/10/5 tricyclic backbone were isolated from the roots of Arnebia euchroma. The planar and steric structures of these new compounds were unambiguously elucidated by extensive spectroscopic analyses, X-ray diffraction crystallography, and ECD calculations. The predominant relative orientation between H-7 and the Z double bond with a methyl substituent in the rigid 10-membered carbocycle, along with the planar chirality of the Z double bond was analyzed and discussed for the first time. The illustration of the planar chirality derived from the Z double bond should be paid great importance during the structure elucidation on these homologous meroterpenoids. All the isolated meroterpenoids were screened for their cytotoxicities against the HCT-8, PANC-1, HGC-27, HepG2, and PC9 cell lines, and compounds (+)-5 and (-)-5 exhibited the most potent cytotoxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

To further reveal the active ingredients of Danshen, we systematically studied its chemical components and obtained two new lithospermic acid derivatives (compounds 1 and 2) together with five known phenylpropionic acids (compounds 3-7) from the dried rhizomes of Salvia miltiorrhiza. The structures of the two new compounds were determined by multiple spectral analyses (UV, IR, HR-ESI-MS, NMR, and ECD). In addition, the absolute configurations were established by chiral analysis and calculated and experimental circular dichroism spectra. Biological research indicated that compound 1 could significantly inhibit the proliferation of isoproterenol (ISO)-treated cardiac fibroblasts (AC16 cells), and MMP9 was found to be the most likely target of compound 1. The protein expression and mRNA levels of MMP9 were increased in ISO-induced AC16 cells, which could be reversed by treatment with compound 1. Furthermore, this treatment could alleviate the migration and activation of ISO-induced cardiac fibroblasts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A series of 4-thiosubstituted flavan derivatives (1-44) were designed and synthesized. The target compounds were assayed for inhibitory activity against α-glucosidase in vitro, and the results indicated that all compounds displayed significant effects in the range of IC 50  = 1.03-7.48 μM compared to that of acarbose, the positive control drug. Structure-activity relationship (SAR) studies indicated that the hydroxyl groups in the flavan B ring, the electron withdrawing groups, and the length of the alkyl chains are important for this biological activity. In addition, some compounds were tested for their tolerance to sucrose in mice, and compound 44 exhibited activity comparable to that of acarbose. Docking analysis indicated that compound 44 binds to the enzyme in a pocket close to the catalytic site, similar to acarbose., (Copyright © 2022. Published by Elsevier B.V.)

Diabetic ulcers (DUs), a devastating complication of diabetes, are intractable for limited effective interventions in clinic. Based on the clinical samples and bioinformatic analysis, we found lower level of CCN1 in DU individuals. Considering the accelerated proliferation effect in keratinocytes, we propose the therapeutic role of CCN1 supplementation in DU microenvironment. To address the challenge of rapid degradation of CCN1 in protease-rich diabetic healing condition, we fabricated a nanoformulation of CCN1 (CCN1-NP), which protected CCN1 from degradation and significantly raised CCN1 intracellular delivery efficiency to 6.2-fold. The results showed that the intracellular CCN1 exhibited a greater anti-inflammatory and proliferative/migratory activities once the extracellular signal of CCN1 was blocked in vitro. The nanoformulation unveils a new mechanism that CCN1 delivered into cells interacted with Eukaryotic translation initiation factor 3 subunit A (EIF3A) to downregulate autophagy-related 7 (ATG7). Furthermore, topical application of CCN1-NP had profound curative effects on delayed wound healing in diabetes both in vitro and in vivo. Our results illustrate a novel mechanism of intracellular EIF3A/CCN1/ATG7 axis triggered by nanoformulation and the therapeutic potential of CCN1-NP for DU management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Psoriasis is a chronic and immune-mediated skin disorder that currently has no cure. Pyroptosis has been proved to be involved in the pathogenesis and progression of psoriasis. However, the role pyroptosis plays in psoriasis remains elusive. Methods: RNA-sequencing data of psoriasis patients were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed pyroptosis-related genes (PRGs) between psoriasis patients and normal individuals were obtained. A principal component analysis (PCA) was conducted to determine whether PRGs could be used to distinguish the samples. PRG and immune cell correlation was also investigated. Subsequently, a novel diagnostic model comprising PRGs for psoriasis was constructed using a random forest algorithm (ntree = 400). A receiver operating characteristic (ROC) analysis was used to evaluate the classification performance through both internal and external validation. Consensus clustering analysis was used to investigate whether there was a difference in biological functions within PRG-based subtypes. Finally, the expression of the kernel PRGs were validated in vivo by qRT-PCR . Results: We identified a total of 39 PRGs, which could distinguish psoriasis samples from normal samples. The process of T cell CD4 memory activated and mast cells resting were correlated with PRGs. Ten PRGs, IL-1β, AIM2, CASP5, DHX9, CASP4, CYCS, CASP1, GZMB, CHMP2B, and CASP8, were subsequently screened using a random forest diagnostic model. ROC analysis revealed that our model has good diagnostic performance in both internal validation (area under the curve [AUC] = 0.930 [95% CI 0.877-0.984]) and external validation (mean AUC = 0.852). PRG subtypes indicated differences in metabolic processes and the MAPK signaling pathway. Finally, the qRT-PCR results demonstrated the apparent dysregulation of PRGs in psoriasis, especially AIM2 and GZMB. Conclusion: Pyroptosis may play a crucial role in psoriasis and could provide new insights into the diagnosis and underlying mechanisms of psoriasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Song, Zhang, Fei, Chen, Luo, Jiang, Ru, Xiang, Li, Luo and Kuai.)

Objective: Rehabilitation of disabled children with autism has become a challenge for current rehabilitation centres. This study conducted psychological investigations on disabled children and analysed the symptoms and characteristics of autism in these children to develop more reasonable rehabilitation treatment plans that would help the children receive psychological counselling and effective rehabilitation., Subjects and Methods: This study investigated 107 disabled children from the Disabled Rehabilitation Research Centre of the South China Minority Autonomous Region. Using the PEP-3 scale as a research tool, a questionnaire was developed to investigate and collect data on the mental health of disabled children. The survey was conducted from 2017 to 2021, and 107 children's mental health data were collected in the form of questionnaires based on PEP-3 evaluation indicators. After cleaning the data, the questionnaire data were screened and processed. Descriptive statistical and correlation analysis tools were used for model analysis to understand the overall data distribution and the potential relationships among various data variables., Results: The results of correlation analysis showed that cognition, language expression, language understanding, emotion, and social interaction in the subtest of developmental behaviour were the main indicators of the degree of autism in children. These indicators had a strong and significant correlation with the comprehensive score. Moreover, these indicators had a significant correlation with the individual self-care and adaptive behaviours reported by the children's caregivers. Small muscles, big muscles, and imitation (vision and movement) indicators had a significant correlation with problematic behaviours and physical fitness, and language and cognitive indicators also had a strong correlation with emotion and social interaction., Conclusions: Emphasis should be placed on the improvement of the language and cognitive abilities of disabled children with autism, and corresponding rehabilitation plans, and training can be formulated according to children with different degrees of illness to get a better rehabilitation outcome. Further, identification of key indicators of autism will be of help in aiding the development of rehabilitation treatment for disabled children with autism and formulation of long-term rehabilitation plans.

To clarify the consistency and efficiency of four methods for myocardial extracellular volume (ECV) measurement (manual method using dual-energy iodine [manual ECV iodine ], manual method using subtraction [manual ECV sub ], automatic ECV iodine , automatic ECV sub ) in patients with ischaemic cardiomyopathy. Fifty patients with ischaemic cardiomyopathy who underwent coronary computed tomography angiography (CCTA) following dual-energy computed tomography (CT) with late iodine enhancement (LIE-DECT) were included. LIE with ischaemic patterns representing scarring could be detected using iodine maps in all patients. The global and remote ECVs of non-scarred myocardium were measured using four methods (manual ECV iodine , automatic ECV iodine , manual ECV sub , and automatic ECV sub ). The consistency and time cost of the four methods were analysed. There were no significant differences in the mean global ECVs or remote ECVs among the four methods (p > 0.05). ECV iodine resulted in a lower Bland-Altman limit of agreement than that of ECV sub for both global and remote measurements. Intraclass correlation coefficients of the automatic and manual ECV iodine measurements demonstrated better concordance (0.804 and 0.859, respectively) than those of automatic and manual ECV sub (0.607 and 0.669, respectively) for both global and remote measurements. The measurement time for automatic ECV was less than that for manual ECV for both global and remote ECV measurements (all p < 0.001). ECV measurement using dual-energy iodine yielded good concordance, and the automatic method has the advantages of being simple and convenient, which can become a useful tool for quantification of myocardial fibrosis., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To measure the myocardial extracellular volume (ECV) in patients with heart failure with preserved ejection fraction (HFpEF) using dual-energy computed tomography with late iodine enhancement (LIE-DECT) and to evaluate the relationship between ECV and risk of HFpEF and cardiac structure and function., Methods: A total of 112 consecutive patients with HFpEF and 80 consecutive subjects without heart disease (control group) who underwent LIE-DECT were included. All patients were divided into ischaemic and non-ischaemic groups according to the LIE patterns detected using iodine maps. The ischaemic scar burden was calculated in the ischaemic HFpEF group. Iodine maps and haematocrit were used to measure ECV in the non-ischaemic HFpEF group and remote ECV of the non-scarred myocardium in the ischaemic HFpEF group, respectively. Cardiac structural and functional variables were collected., Results: ECV in patients with non-ischaemic HFpEF (n = 77) and remote ECV in patients with ischaemic HFpEF (n = 35) were significantly higher than those in control subjects (p < 0.001). Multivariate logistic regression analysis revealed that after adjusting for age, sex, body mass index, smoking, and drinking, a higher ECV/remote ECV was still associated with non-ischaemic HFpEF and ischaemic HFpEF (p < 0.001). A positive correlation was established between ECV and cardiac structural and functional variables (p < 0.05) in all participants. Subgroup analysis showed that ECV/remote ECV and ischaemic scar burden positively correlated with heart failure classification in the HFpEF subgroup (p < 0.05)., Conclusion: ECV/remote ECV elevation was significantly associated with non-ischaemic and ischaemic HFpEF. Remote ECV and LIE may have synergistic effects in the risk assessment of ischaemic HFpEF., Key Points: • ECV/remote ECV elevation is associated not only with non-ischaemic HFpEF but also with ischaemic HFpEF. • ECV/remote ECV and ischaemic scar burden are correlated with cardiac structure and function., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Seven new phenolic acids, 7, 8-epiblechnic acid (1), 8-epiblechnic acid 9-ehthyl-9'-methyl ester (2), 9'-ehyl-isolithospermate (3), 9''-methyl-isolithospermate (4), 9'-ethyl-9''-methyl-isolithospermate (5), 9', 9''-dimethyl-isolithospermate (6), sebesteniod E (7), were isolated from the roots of Salvia miltiorrhiza. Their structures were elucidated by detailed spectroscopic means including UV, IR, HRESIMS, and NMR data spectra. The bioactive assays of compounds 1-7 against neuroprotection activities were determined. The results suggested that compound 4 exhibited a moderate glutamate-induced neuroprotective activity and the cell survival rate was 24.0% (10 -5  mol/L), while compound 2 showed weak activity (survival rate: 7.58%, 10 -5  mol/L), using PHPB (survival rate: 7.56%, 10 -5  mol/L) as positive control., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A phytochemistry of the whole plant of Agrimonia pilosa led to the discovery of two new nortriterpenoids, agrimonorterpenes A and B (1 and 2), together with one known triterpenoid fupenzic acid (3) and seven known sesquiterpenoids (4-10). The new structures were determined as 19α-hydroxy-2-oxo-nor-A (3)-urs-11,12-dien-28-oic acid (1) and 2, 19β-dihydroxy-3-oxo-23-noroleana-1, 4, 12-trien-28-oic acid (2) by the spectroscopic data of UV, IR, HR-ESI-MS, and NMR. Notably, the structure of 1 possessed a rare five-membered A- ring. And this is the first time to discover the sesquiterpenoids (4-10) from A. pilosa. Compound 3 displayed the selective cytotoxicity against HCT116, BGC823, and HepG2 cell lines with the IC 50 values of 16.31 μM, 21.94 μM, and 23.40 μM, respectively., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Diabetic wounds are a protracted complication of diabetes mainly characterised by chronic inflammation, obstruction of epithelialization, damaged blood vessels and collagen production (maturation), as well as neuropathy. As a non-coding RNA (ncRNA) that lack coding potential, long non-coding RNAs (lncRNAs) have recently been reported to play a salient role in diabetic wound healing. Here, this review summarises the roles of lncRNAs in the pathology and treatments of diabetic wounds, providing references for its potential clinical diagnostic criteria or therapeutic targets in the future., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Ethnopharmacological Relevance: Sheng-ji Hua-yu (SJHY) formula is a Chinese herbal prescription for diabetic ulcers (DUs) treatment, which can accelerate wound reconstruction and shorten the healing time. However, its mechanism role maintains unclear., Aim of the Study: To elucidate the molecular mechanisms of SJHY application on DUs., Materials and Methods: To begin with, transcriptome sequencing was adopted to identified differentially expression mRNAs among normal ulcers, DUs, and DUs + SJHY treatment in vivo. Liquid chromatography-tandem mass spectrometry was applied for the quality control of SJHY formula. GO and KEGG enrichment analysis were used to identify the mechanisms underlying the therapeutic effect of SJHY formula, and then gene set enrichment analysis and ingenuity pathway analysis were conducted for functional analysis. Further, qPCR detection was performed in vivo for validation., Results: SJHY administration could regulate the glucose metabolic process, AMPK and HIF-1 pathway to accelerate healing processes of DUs. Besides, CRHR1, SHH, and GAL were identified as the critical targets, and SLC6A3, GRP, FGF23, and CYP27B1 were considered as the upstream genes of SJHY treatment. Combined with animal experiments, the prediction results were validated in DUs mice model., Conclusions: This study used modular pharmacology analysis to identify the biomarkers of SJHY formula and provide the potential therapeutic targets for DUs treatment as well., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Persistent chronic inflammation and delayed epithelialization lead to stalled healing in diabetic ulcers (DUs). PD-L1 shows anti-inflammatory and proliferative activities in healing defects, whereas its function in DU pathogenesis remains unknown. Lower levels of PD-L1 were found in DU tissues, and exogenous PD-L1 has therapeutic effects in the healing process by accelerating re-epithelialization and attenuating prolonged inflammation, which contributed to the delayed wound closure. We detected the downstream effectors of PD-L1 using transcriptional profiles and screened the interacting proteins using immunoprecipitation in combination with mass spectrometry and coimmunoprecipitation assays. The biological functions of eIF3I‒PD-L1‒IRS4 axis were tested both in vivo and in vitro. Finally, we validated the expression levels of eIF3I, PD-L1, and IRS4 in DU tissues from human clinical samples by immunohistochemistry staining. Mechanistically, PD-L1 binds to eIF3I and promotes cutaneous diabetic wound healing by downregulating IRS4. These findings identify that the eIF3I‒PD-L1‒IRS4 axis contributes to wound healing defects, which can serve as a potential therapeutic target in DUs., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)