Exploring Schizophrenia Classification Through Multimodal MRI and Deep Graph Neural Networks: Unveiling Brain Region-Specific Weight Discrepancies and Their Association With Cell-Type Specific Transcriptomic Features.

BACKGROUND AND HYPOTHESIS: Schizophrenia (SZ) is a prevalent mental disorder that imposes significant health burdens. Diagnostic accuracy remains challenging due to clinical subjectivity. To address this issue, we explore magnetic resonance imaging (MRI) as a tool to enhance SZ diagnosis and provide objective references and biomarkers. Using deep learning with graph convolution, we represent MRI data as graphs, aligning with brain structure, and improving feature extraction, and classification. Integration of multiple modalities is expected to enhance classification. STUDY DESIGN: Our study enrolled 683 SZ patients and 606 healthy controls from 7 hospitals, collecting structural MRI and functional MRI data. Both data types were represented as graphs, processed by 2 graph attention networks, and fused for classification. Grad-CAM with graph convolution ensured interpretability, and partial least squares analyzed gene expression in brain regions. STUDY RESULTS: Our method excelled in the classification task, achieving 83.32% accuracy, 83.41% sensitivity, and 83.20% specificity in 10-fold cross-validation, surpassing traditional methods. And our multimodal approach outperformed unimodal methods. Grad-CAM identified potential brain biomarkers consistent with gene analysis and prior research. CONCLUSIONS: Our study demonstrates the effectiveness of deep learning with graph attention networks, surpassing previous SZ diagnostic methods. Multimodal MRI's superiority over unimodal MRI confirms our initial hypothesis. Identifying potential brain biomarkers alongside gene biomarkers holds promise for advancing objective SZ diagnosis and research in SZ.

Construction of Prediction Model of Foodborne Disease Outbreaks and Its Trend Prediction - Guizhou Province, China, 2023-2025.

Objective: Foodborne diseases pose a significant public health concern globally. This study aims to analyze the correlation between disease prevalence and climatic conditions, forecast the pattern of foodborne disease outbreaks, and offer insights for effective prevention and control strategies and optimizing health resource allocation policies in Guizhou Province. Methods: This study utilized the χ2 test and four comprehensive prediction models to analyze foodborne disease outbreaks recorded in the Guizhou Foodborne Disease Outbreak system between 2012 and 2022. The best-performing model was chosen to forecast the trend of foodborne disease outbreaks in Guizhou Province, 2023-2025. Results: Significant variations were observed in the incidence of foodborne disease outbreaks in Guizhou Province concerning various meteorological factors (all P≤0.05). Among all models, the SARIMA-ARIMAX combined model demonstrated the most accurate predictive performance (RMSE: Prophet model=67.645, SARIMA model=3.953, ARIMAX model=26.544, SARIMA-ARIMAX model=26.196; MAPE: Prophet model=42.357%, SARIMA model=37.740%, ARIMAX model=15.289%, SARIMA-ARIMAX model=13.961%). Conclusion: The analysis indicates that foodborne disease outbreaks in Guizhou Province demonstrate distinct seasonal patterns. It is recommended to concentrate prevention efforts during peak periods. The SARIMA-ARIMAX hybrid model enhances the precision of monthly forecasts for foodborne disease outbreaks, offering valuable insights for future prevention and control strategies.

DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT.

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.

Zinc-associated phospholipid metabolic alterations and their impacts on ALT levels in workers.

Zinc (Zn) is an essential trace element that is required for various biological functions, but excessive exposure to Zn is associated with many disorders and even diseases. However, the health effects and underlying mechanisms of long-term and high concentration exposure of Zn remain to be unclear. In the present study, we investigated the association between occupational exposure to Zn and liver function indicators (like alanine aminotransferase (ALT)) in workers. We found a positive association between Zn exposure and ALT level in workers. Workers having higher blood Zn (7735.65 (1159.15) µg/L) shows a 30.4 % increase in ALT level compared to those with lower blood Zn (5969.30 (989.26) µg/L). Furthermore, we explored the effects of phospholipids (PLs) and their metabolism on ALT level and discovered that Zn exposure in workers was associated with changes in PL levels and metabolism, which had further effects on increased ALT levels in workers. The study provides insights into the relationship between occupational Zn exposure and liver function, highlights the risk of long-term exposure to high concentrations of Zn, and paves the way for understanding the underlying mechanisms of Zn exposure on human health.

Construction of protein-protein interaction network in sulfate-reducing bacteria: Unveiling of global response to Hg.

Sulfate-reducing bacteria (SRB) play pivotal roles in the biotransformation of mercury (Hg). However, unrevealed global responses of SRB to Hg have restricted our understanding of details of Hg biotransformation processes. The absence of protein-protein interaction (PPI) network under Hg stimuli has been a bottleneck of proteomic analysis for molecular mechanisms of Hg transformation. This study constructed the first comprehensive PPI network of SRB in response to Hg, encompassing 67 connected nodes, 26 independent nodes, and 121 edges, covering 93% of differentially expressed proteins from both previous studies and this study. The network suggested that proteomic changes of SRB in response to Hg occurred globally, including microbial metabolism in diverse environments, carbon metabolism, nucleic acid metabolism and translation, nucleic acid repair, transport systems, nitrogen metabolism, and methyltransferase activity, partial of which could cover the known knowledge. Antibiotic resistance was the original response revealed by this network, providing insights into of Hg biotransformation mechanisms. This study firstly provided the foundational network for a comprehensive understanding of SRB's responses to Hg, convenient for exploration of potential targets for Hg biotransformation. Furthermore, the network indicated that Hg enhances the metabolic activities and modification pathways of SRB to maintain cellular activities, shedding light on the influences of Hg on the carbon, nitrogen, and sulfur cycles at the cellular level.

Probing the activated complex of the F + NH3 reaction via a dipole-bound state.

Experimental characterization of the transition state poses a significant challenge due to its fleeting nature. Negative ion photodetachment offers a unique tool for probing transition states and their vicinity. However, this approach is usually limited to Franck-Condon regions. For example, high-lying Feshbach resonances with an excited HF stretching mode (vHF = 2-4) were recently identified in the transition-state region of the F + NH3 → HF + NH2 reaction through photo-detaching FNH3- anions, but the direct photodetachment failed to observe the lower-lying vHF = 0,1 resonances and bound states due apparently to negligible Franck-Condon factors. Indeed, these weak transitions can be resonantly enhanced via a dipole-bound state (DBS) formed between an electron and the polar FNH3 species. In this study, we unveil a series of Feshbach resonances and bound states along the F + NH3 reaction path via a DBS by combining high-resolution photoelectron spectroscopy with high-level quantum dynamical computations. This study presents an approach for probing the activated complex in a reaction by negative ion photodetachment through a DBS.

Energy- and Angle-Resolved Scattering of Ne from Dodecane Liquid Surfaces: Theory Corroborating Experiment.

Motivated by recent experimental work by the Neumark group, we present here an all-atom molecular dynamics study of Ne scattering from a dodecane liquid surface with the objective of elucidating the fundamental aspects of gas-liquid dynamics. Using a fine-tuned force field, the GPU-accelerated simulations reproduced semiquantitatively the energy- and angle-resolved experimental results. The branching ratio between the impulsive scattering (IS) and thermal desorption (TD) channels exhibits a clear correlation with the incidence energy (Ei) and angle. Ne atoms with lower Ei values are more likely to be trapped, yielding an increased TD ratio. For a given Ei, a large incidence angle led to a higher IS ratio. The energy transfer between Ne atoms and liquid dodecane was found to be more sensitive to the deflection angle than to the incidence or reflection angle. With an increasing deflection angle, the fractional energy loss increases, suggesting that more kinetic energy is transferred to the liquid.

Precise Fabrication and Manipulation of Individual Polymer Nanofibers.

Polymer nanofibers hold promise in a wide range of applications owing to their diverse properties, flexibility, and cost effectiveness. In this study, we introduce a polymer nanofiber drawing process in a scanning electron microscope and focused ion beam (SEM/FIB) instrument with in situ observation. We employed a nanometer-sharp tungsten needle and prepolymer microcapsules to enable nanofiber drawing in a vacuum environment. This method produces individual polymer nanofibers with diameters as small as ∼500 nm and lengths extending to millimeters, yielding nanofibers with an aspect ratio of 2000:1. The attachment to the tungsten manipulator ensures accurate transfer of the polymer nanofiber to diverse substrate types as well as fabrication of assembled structures. Our findings provide valuable insights into ultrafine polymer fiber drawing, paving the way for high-precision manipulation and assembly of polymer nanofibers.

Multistate Dynamics and Kinetics of CO2 Activation by Ta+ in the Gas Phase: Insights into Single-Atom Catalysis.

The activation of carbon dioxide (CO2) by a transition-metal cation in the gas phase is a unique model system for understanding single-atom catalysis. The mechanism of such reactions is often attributed to a "two-state reactivity" model in which the high-energy barrier of a spin state correlating with ground-state reactants is avoided by intersystem crossing (ISC) to a different spin state with a lower barrier. However, such a "spin-forbidden" mechanism, along with the corresponding dynamics, has seldom been rigorously examined theoretically, due to the lack of global potential energy surfaces (PESs). In this work, we report full-dimensional PESs of the lowest-lying quintet, triplet, and singlet states of the TaCO2+ system, machine-learned from first-principles data. These PESs and the corresponding spin-orbit couplings enable us to provide an extensive theoretical characterization of the dynamics and kinetics of the reaction between the tantalum cation (Ta+) and CO2, which have recently been investigated experimentally at high collision energies using crossed beams and velocity map imaging, as well as at thermal energies using a selected-ion flow tube apparatus. The multistate quasi-classical trajectory simulations with surface hopping reproduce most of the measured product translational and angular distributions, shedding valuable light on the nonadiabatic reaction dynamics. The calculated rate coefficients from 200 to 600 K are also in good agreement with the latest experimental measurements. More importantly, these calculations revealed that the reaction is controlled by intersystem crossing, rather than potential barriers.

Blood miRNAs as Potential Diagnostic Biomarkers for Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

Purpose: Investigate the efficacy of blood microRNAs (miRNAs) as diagnostic biomarkers for Chronic Obstructive Pulmonary Disease (COPD). Patients and Methods: We conducted a comprehensive search in English and Chinese databases, selecting studies based on predetermined criteria. Diagnostic parameters like summarized sensitivity (SSEN), summarized specificity (SSPE), summarized positive likelihood ratio (SPLR), summarized negative likelihood ratio (SNLR), and diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curves were analyzed using a bivariate model. Each parameter was accompanied by a 95% confidence interval (CI). Results: Eighteen high-quality studies were included. For diagnosing COPD with blood miRNAs, the SSEN was 0.83 (95% CI 0.76-0.89), SSPE 0.76 (95% CI 0.70-0.82), SPLR 3.50 (95% CI 2.66-4.60), SNLR 0.22 (95% CI 0.15-0.33), DOR 15.72 (95% CI 8.58-28.77), and AUC 0.86 (95% CI 0.82-0.88). In acute exacerbations, SSEN was 0.85 (95% CI 0.76-0.91), SSPE 0.80 (95% CI 0.73-0.86), SPLR 4.26 (95% CI 3.05-5.95), SNLR 0.19 (95% CI 0.12-0.30), DOR 22.29 (95% CI 11.47-43.33), and AUC 0.89 (95% CI 0.86-0.91). Conclusion: Blood miRNAs demonstrate significant accuracy in diagnosing COPD, both in general and during acute exacerbations, suggesting their potential as reliable biomarkers.

Oncogenic functions and therapeutic potentials of targeted inhibition of SMARCAL1 in small cell lung cancer.

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.

Leakage Proof, Flame-Retardant, and Electromagnetic Shield Wood Morphology Genetic Composite Phase Change Materials for Solar Thermal Energy Harvesting.

Phase change materials (PCMs) offer a promising solution to address the challenges posed by intermittency and fluctuations in solar thermal utilization. However, for organic solid-liquid PCMs, issues such as leakage, low thermal conductivity, lack of efficient solar-thermal media, and flammability have constrained their broad applications. Herein, we present an innovative class of versatile composite phase change materials (CPCMs) developed through a facile and environmentally friendly synthesis approach, leveraging the inherent anisotropy and unidirectional porosity of wood aerogel (nanowood) to support polyethylene glycol (PEG). The wood modification process involves the incorporation of phytic acid (PA) and MXene hybrid structure through an evaporation-induced assembly method, which could impart non-leaking PEG filling while concurrently facilitating thermal conduction, light absorption, and flame-retardant. Consequently, the as-prepared wood-based CPCMs showcase enhanced thermal conductivity (0.82 W m-1 K-1, about 4.6 times than PEG) as well as high latent heat of 135.5 kJ kg-1 (91.5% encapsulation) with thermal durability and stability throughout at least 200 heating and cooling cycles, featuring dramatic solar-thermal conversion efficiency up to 98.58%. In addition, with the synergistic effect of phytic acid and MXene, the flame-retardant performance of the CPCMs has been significantly enhanced, showing a self-extinguishing behavior. Moreover, the excellent electromagnetic shielding of 44.45 dB was endowed to the CPCMs, relieving contemporary health hazards associated with electromagnetic waves. Overall, we capitalize on the exquisite wood cell structure with unidirectional transport inherent in the development of multifunctional CPCMs, showcasing the operational principle through a proof-of-concept prototype system.

Tertiary lymphoid structures as a potential prognostic biomarker for combined hepatocellular-cholangiocarcinoma.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC-CCA and to preliminarily explore the possible mechanism of TLS formation. METHODS: The TLSs, with different spatial distributions and densities, of 137 cHCC-CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan-Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC-CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry. RESULTS: A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC-CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC-CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC-CCA patients. Our findings suggested that CXCL12 expression in cHCC-CCA tissue was significantly correlated with TLS presence. CONCLUSION: The spatial distribution and density of TLSs revealing the characteristics of the cHCC-CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC-CCA.

MRI radiomics based on deep learning automated segmentation to predict early recurrence of hepatocellular carcinoma.

OBJECTIVES: To investigate the utility of deep learning (DL) automated segmentation-based MRI radiomic features and clinical-radiological characteristics in predicting early recurrence after curative resection of single hepatocellular carcinoma (HCC). METHODS: This single-center, retrospective study included consecutive patients with surgically proven HCC who underwent contrast-enhanced MRI before curative hepatectomy from December 2009 to December 2021. Using 3D U-net-based DL algorithms, automated segmentation of the liver and HCC was performed on six MRI sequences. Radiomic features were extracted from the tumor, tumor border extensions (5 mm, 10 mm, and 20 mm), and the liver. A hybrid model incorporating the optimal radiomic signature and preoperative clinical-radiological characteristics was constructed via Cox regression analyses for early recurrence. Model discrimination was characterized with C-index and time-dependent area under the receiver operating curve (tdAUC) and compared with the widely-adopted BCLC and CNLC staging systems. RESULTS: Four hundred and thirty-four patients (median age, 52.0 years; 376 men) were included. Among all radiomic signatures, HCC with 5 mm tumor border extension and liver showed the optimal predictive performance (training set C-index, 0.696). By incorporating this radiomic signature, rim arterial phase hyperenhancement (APHE), and incomplete tumor "capsule," a hybrid model demonstrated a validation set C-index of 0.706 and superior 2-year tdAUC (0.743) than both the BCLC (0.550; p < 0.001) and CNLC (0.635; p = 0.032) systems. This model stratified patients into two prognostically distinct risk strata (both datasets p < 0.001). CONCLUSION: A preoperative imaging model incorporating the DL automated segmentation-based radiomic signature with rim APHE and incomplete tumor "capsule" accurately predicted early postsurgical recurrence of a single HCC. CRITICAL RELEVANCE STATEMENT: The DL automated segmentation-based MRI radiomic model with rim APHE and incomplete tumor "capsule" hold the potential to facilitate individualized risk estimation of postsurgical early recurrence in a single HCC. KEY POINTS: A hybrid model integrating MRI radiomic signature was constructed for early recurrence prediction of HCC. The hybrid model demonstrated superior 2-year AUC than the BCLC and CNLC systems. The model categorized the low-risk HCC group carried longer RFS.

Endothelial HIF-2α Suppresses Retinal Angiogenesis in Neonatal Mice by Upregulating NOTCH Signaling.

Prolyl hydroxylase domain (PHD) proteins are oxygen sensors that use intracellular oxygen as a substrate to hydroxylate hypoxia inducible factor (HIF)-α proteins, routing them for polyubiquitination and proteasomal degradation. Typically, HIF-α accumulation in hypoxic or PHD-deficient tissues leads to upregulated angiogenesis. Here we report unexpected retinal phenotypes associated with endothelial cell (EC)-specific gene targeting of Phd2 and Hif-2α. EC-specific Phd2 disruption suppressed retinal angiogenesis, despite HIF-α accumulation and VEGF-A upregulation. Suppressed retinal angiogenesis was observed both in development and in the oxygen-induced retinopathy (OIR) model. On the other hand, EC-specific deletion of Hif-1α, Hif-2α, or both did not affect retinal vascular morphogenesis. Strikingly, retinal angiogenesis appeared normal in mice double-deficient for endothelial PHD2 and HIF-2α. In PHD2-deficient retinal vasculature, Delta-like 4 (DLL4, a NOTCH ligand) and HEY2 (a NOTCH target) were upregulated by HIF-2α-dependent mechanisms. Inhibition of NOTCH signaling by a chemical inhibitor or DLL4 antibody partially rescued retinal angiogenesis. Taken together, our data demonstrate that HIF-2α accumulation in retinal ECs inhibits rather than stimulates retinal angiogenesis, in part by upregulating DLL4 expression and NOTCH signaling.

Impact of Gender-Role Attitudes and Mental Health on Hostile Sexism and Acceptance of Cosmetic Surgery.

BACKGROUND: Each year, tens of thousands of people worldwide choose to undergo cosmetic surgery in order to alter their appearance. In recent years, young people have gradually emerged to comprise the main driving force behind the increasing demand for cosmetic surgery. Previous studies have found that sexism may motivate young people to undergo such surgeries. However, few studies have been conducted to determine if this psychological mechanism influences the acceptance of cosmetic surgery among Chinese university students. METHODS: A total of 579 Chinese university students (280 girls and 299 boys, 17-20 years) volunteered to participate in the online survey. They completed a questionnaire containing the Ambivalent Sexism Inventory, the 12-item General Health Questionnaire, the Gender-Role Attitudes Questionnaire and the Acceptance of Cosmetic Surgery Scale. We firstly evaluated the underlying factor structure of the Acceptance of Cosmetic Surgery Scale using exploratory and confirmatory factor analyses, and exploring pattern of associations between the constructs was analyzed via path analysis. RESULTS: According to the findings, hostile sexism was associated with greater levels of acceptance toward cosmetic surgery. Moreover, gender-role attitudes mediated the link between hostile sexism and the acceptance of cosmetic surgery, and this mediation was positively influenced by general mental health. CONCLUSION: Our study contributes to a deeper understanding of Chinese university students' attitudes toward cosmetic surgery, hostile sexism may contribute to normalizing traditional gender stereotypes and encourage cosmetic surgery acceptability among Chinese university students. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Eosinophilic pulmonary disease with ulcerative colitis: A case report.

RATIONALE: Eosinophilic pulmonary disease (EPD) is a general term for a large group of diseases with complex etiology. Ulcerative colitis is an inflammatory bowel disease (IBD). Patients with IBD may have pulmonary involvement. We herein present a case of ulcerative colitis complicated with EPD. PATIENT CONCERNS: A 34-year-old woman with ulcerative colitis presented with dry cough. She had peripheral eosinophilia and apical ground glass opacities on CT (computed tomography) of her chest. Antibiotic treatment was ineffective. DIAGNOSES: Lung biopsy revealed eosinophil infiltration in the alveolar space and interstitial space, so EPD was considered. INTERVENTIONS: After oral administration of prednisone, the lung shadow on CT disappeared when the cough symptoms resolved. However, the symptoms recurred after drug withdrawal, and the lung shadow reappeared on imaging. The cough symptoms and lung shadow disappeared after oral prednisone was given again. Prednisone was slowly discontinued after 6 months of treatment. OUTCOMES: The patient stopped prednisone for half a year. No recurrence or abnormal CT findings were detected during the half-year follow-up. LESSONS: The clinical manifestations of EPD are atypical, laboratory and imaging findings are not specific, and it is difficult to make a definite diagnosis before lung biopsy. The diagnosis depends on pathological examination. Glucocorticoid treatment is effective, but some patients may relapse after drug withdrawal. Active follow-up after glucocorticoid treatment is very important for identifying disease recurrence. Patients with IBD are relatively prone to developing EPD. The etiology of EPD is complex. In clinical practice, we need to make a diagnosis and differential diagnosis to clarify its etiology.

[Retracted] MicroRNA­202 inhibits endometrial stromal cell migration and invasion by suppressing the K­Ras/Raf1/MEK/ERK signaling pathway.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the Transwell invasion assay data shown in Figs. 2C and 4B were strikingly similar to data appearing in different form in a paper by different authors at a different research institute that had already been submitted for publication. Owing to the fact that the contentious data in the above article had already been submitted for publication prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 2078­2088, 2020; DOI: 10.3892/ijmm.2020.4749].

Kreotoxin A administration inhibits hyperproliferation and inflammation of human ear keloid tissue and keloid-derived fibroblasts by downregulating HIF-1α expression.

Keloids represent a prevalent dermal fibroproliferative disorder. They only affect humans and exhibit several tumor characteristics, such as excessive extracellular matrix (ECM) deposition, which usually occurs after skin injury. Kreotoxin type A (KTA) can inhibit the release of acetylcholine, and thereby inhibit the proliferation of keloid fibroblasts and reducing the formation of scars. Thus, KTA could be used as a therapeutic agent for keloids. However, the mechanisms of action of KTA in keloid treatment remain unclear. In this study, we aimed to explore the underlying mechanisms of action of KTA in human keloid treatment using human tissue and a cell-based model. Integrative microarray analysis revealed that hypoxia-inducible factor 1-alpha (HIF-1α) expression was frequently upregulated in hypertrophic scar and keloid tissues, whereas it was downregulated in the KTA-treated samples. Furthermore, KTA addition to keloid-derived fibroblasts (KDFs) reduced the growth rate and viability, induced apoptosis, and decreased inflammation and oxidative stress in KDFs. However, overexpression of HIF-1α restored cell number and survival, decreased apoptosis, and promoted inflammation and oxidative stress in KTA-treated KDFs. Furthermore, KTA treatment reduced the expression of ECM proteins, including vascular endothelial growth factor (VEGF), collagen I and III, whereas HIF-1α overexpression abolished the effects of KTA on KDFs. In conclusion, our findings provide novel insights into the mechanisms of action of KTA as a potential therapeutic agent for keloids via modulating HIF-1α expression.

An esculentin-1 homolog from a dark-spotted frog (Pelophylax nigromaculatus) possesses antibacterial and immunoregulatory properties.

BACKGROUND: Esculentin-1, initially discovered in the skin secretions of pool frogs (Pelophylax lessonae), has demonstrated broad-spectrum antimicrobial activity; however, its immunomodulatory properties have received little attention. RESULTS: In the present study, esculentin-1 cDNA was identified by analysing the skin transcriptome of the dark-spotted frog (Pelophylax nigromaculatus). Esculentin-1 from this species (esculentin-1PN) encompasses a signal peptide, an acidic spacer peptide, and a mature peptide. Sequence alignments with other amphibian esculentins-1 demonstrated conservation of the peptide, and phylogenetic tree analysis revealed its closest genetic affinity to esculentin-1P, derived from the Fukien gold-striped pond frog (Pelophylax fukienensis). Esculentin-1PN transcripts were observed in various tissues, with the skin exhibiting the highest mRNA levels. Synthetic esculentin-1PN demonstrated antibacterial activity against various pathogens, and esculentin-1PN exhibited bactericidal activity by disrupting cell membrane integrity and hydrolyzing genomic DNA. Esculentin-1PN did not stimulate chemotaxis in RAW264.7, a murine leukemic monocyte/macrophage cell line. However, it amplified the respiratory burst and augmented the pro-inflammatory cytokine gene (TNF-α and IL-1ß) expression in RAW264.7 cells. CONCLUSIONS: This novel finding highlights the immunomodulatory activity of esculentin-1PN on immune cells.