Efficacy and safety of perioperative melatonin for postoperative delirium in patients undergoing surgery: a systematic review and meta-analysis.

OBJECTIVE: To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). METHODS: We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery. RESULTS: In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54). CONCLUSION: Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.

DGAT2 Plays a Crucial Role to Control ESRRAPROX1 Transcriptional Network to Maintain Hepatic Mitochondrial Sustainability.

Background: Diacylglycerol O-acyltransferase 2 (DGAT2) synthesizes triacylglycerol (TG) from diacylglycerol; therefore, DGAT2 is considered as a therapeutic target for steatosis. However, the consequence of inhibiting DGAT2 is not fully investigated due to side effects including lethality and lipotoxicity. In this article, we observed the role of DGAT2 in hepatocarcinoma. Methods: The role of DGAT2 is analyzed via loss-of-function assay. DGAT2 knockdown (KD) and inhibitor treatment on HepG2 cell line was analyzed. Cumulative analysis of cell metabolism with bioinformatic data were assessed, and further compared with different cohorts of liver cancer patients and non-alcoholic fatty liver disease (NAFLD) patients to elucidate how DGAT2 is regulating cancer metabolism. Results: Mitochondrial function is suppressed in DGAT2 KD HepG2 cell along with the decreased lipid droplets. In the aspect of the cancer, DGAT2 KD upregulates cell proliferation. Analyzing transcriptome of NAFLD and hepatocellular carcinoma (HCC) patients highlights negatively correlating expression patterns of 73 lipid-associated genes including DGAT2. Cancer patients with the lower DGAT2 expression face lower survival rate. DGAT2 KD cell and patients' transcriptome show downregulation in estrogen- related receptor alpha (ESRRA) via integrated system for motif activity response analysis (ISMARA), with increased dimerization with corepressor prospero homeobox 1 (PROX1). Conclusion: DGAT2 sustains the stability of mitochondria in hepatoma via suppressing ESRRA-PROX1 transcriptional network and hinders HCC from shifting towards glycolytic metabolism, which lowers cell proliferation.

Prognostic prediction of sepsis patient using transformer with skip connected token for tabular data.

Sepsis is known as a common syndrome in intensive care units (ICU), and severe sepsis and septic shock are among the leading causes of death worldwide. The purpose of this study is to develop a deep learning model that supports clinicians in efficiently managing sepsis patients in the ICU by predicting mortality, ICU length of stay (>14 days), and hospital length of stay (>30 days). The proposed model was developed using 591 retrospective data with 16 tabular data related to a sequential organ failure assessment (SOFA) score. To analyze tabular data, we designed the modified architecture of the transformer that has achieved extraordinary success in the field of languages and computer vision tasks in recent years. The main idea of the proposed model is to use a skip-connected token, which combines both local (feature-wise token) and global (classification token) information as the output of a transformer encoder. The proposed model was compared with four machine learning models (ElasticNet, Extreme Gradient Boosting [XGBoost]), and Random Forest) and three deep learning models (Multi-Layer Perceptron [MLP], transformer, and Feature-Tokenizer transformer [FT-Transformer]) and achieved the best performance (mortality, area under the receiver operating characteristic (AUROC) 0.8047; ICU length of stay, AUROC 0.8314; hospital length of stay, AUROC 0.7342). We anticipate that the proposed model architecture will provide a promising approach to predict the various clinical endpoints using tabular data such as electronic health and medical records.

Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial.

BACKGROUND: The TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC. METHODS: Patients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2-4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety. RESULTS: Total 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively. CONCLUSIONS: GV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC. CLINICAL TRIAL REGISTRATION: NCT02854072.

Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.

Universal Platform for Robust Dual-Atom Doped 2D Catalysts with Superior Hydrogen Evolution in Wide pH Media.

Layered 2D transition metal dichalcogenides (TMDs) have been suggested as efficient substitutes for Pt-group metal electrocatalysts in the hydrogen evolution reaction (HER). However, poor catalytic activities in neutral and alkaline electrolytes considerably hinder their practical applications. Furthermore, the weak adhesion between TMDs and electrodes often impedes long-term durability and thus requires a binder. Here, a universal platform is reported for robust dual-atom doped 2D electrocatalysts with superior HER performance over a wide pH range media. V:Co-ReS2 on a wafer scale is directly grown on oxidized Ti foil by a liquid-phase precursor-assisted approach and subsequently used as highly efficient electrocatalysts. The catalytic performance surpasses that of Pt group metals in a high current regime (≥ 100 mA cm-2 ) at pH ≥ 7, with a high durability of more than 70 h in all media at 200 mA cm-2 . First-principles calculations reveal that V:Co dual doping in ReS2 significantly reduces the water dissociation barrier and simultaneously enables the material to achieve the thermoneutral Gibbs free energy for hydrogen adsorption.

Creeping fat exhibits distinct Inflammation-specific adipogenic preadipocytes in Crohn's disease.

Creeping fat (CrF) is an extraintestinal manifestation observed in patients with Crohn's disease (CD). It is characterized by the accumulation of mesenteric adipose tissue (MAT) that wraps around the intestinal wall. Although the role of CrF in CD is still debated, multiple studies have highlighted a correlation between CrF and inflammation, as well as fibrostenosais of the intestine, which contributes to the worsening of CD symptoms. However, the mechanism underlying the potential role of CrF in the development of Crohn's fibrosis remains an enigma. This study aimed to analyze CrF comprehensively using single-cell RNA sequencing analysis. The data was compared with transcriptomic data from adipose tissue in other disease conditions, such as ulcerative colitis, lymphedema, and obesity. Our analysis classified two lineages of preadipocyte (PAC) clusters responsible for adipogenesis and fibrosis in CrF. Committed PACs in CrF showed increased cytokine expression in response to bacterial stimuli, potentially worsening inflammation in patients with CD. We also observed an increase in fibrotic activity in PAC clusters in CrF. Co-analyzing the data from patients with lymphedema, we found that pro-fibrotic PACs featured upregulated pentraxin-3 expression, suggesting a potential target for the treatment of fibrosis in CrF. Furthermore, PACs in CrF exhibited a distinct increase in cell-to-cell communication via cytokines related to inflammation and fibrosis, such as CCL, LIGHT, PDGF, MIF, and SEMA3. Interestingly, these interactions also increased in PACs of the lymphedema, whereas the increased MIF signal of PACs was found to be a distinct characteristic of CrF. In immune cell clusters in CrF, we observed high immune activity of pro-inflammatory macrophages, antigen-presenting macrophages, B cells, and IgG+ plasma cells. Finally, we have demonstrated elevated IgG+ plasma cell infiltration and increased pentraxin-3 protein levels in the fibrotic regions of CrF in CD patients when compared to MAT from both UC patients and healthy individuals. These findings provide new insights into the transcriptomic features related to the inflammation of cells in CrF and suggest potential targets for attenuating fibrosis in CD.

Caveolin-1 mediates the utilization of extracellular proteins for survival in refractory gastric cancer.

Despite advances in cancer therapy, the clinical outcome of patients with gastric cancer remains poor, largely due to tumor heterogeneity. Thus, finding a hidden vulnerability of clinically refractory subtypes of gastric cancer is crucial. Here, we report that chemoresistant gastric cancer cells rely heavily on endocytosis, facilitated by caveolin-1, for survival. caveolin-1 was highly upregulated in the most malignant stem-like/EMT/mesenchymal (SEM)-type gastric cancer cells, allowing caveolin-1-mediated endocytosis and utilization of extracellular proteins via lysosomal degradation. Downregulation of caveolin-1 alone was sufficient to induce cell death in SEM-type gastric cancer cells, emphasizing its importance as a survival mechanism. Consistently, chloroquine, a lysosomal inhibitor, successfully blocked caveolin-1-mediated endocytosis, leading to the marked suppression of tumor growth in chemorefractory gastric cancer cells in vitro, including patient-derived organoids, and in vivo. Together, our findings suggest that caveolin-1-mediated endocytosis is a key metabolic pathway for gastric cancer survival and a potential therapeutic target.

Effects of Interfacial Electron Transport on Field Electron Emission from Carbon Nanotube Paste Emitters.

Field electron emission from carbon nanotubes (CNT) is preceded by the transport of electrons from the cathode metal to emission sites. Specifically, a supporting layer indispensable for adhesion of CNT paste emitters onto the cathode metal would impose a potential barrier, depending on its work function and interfacial electron transport behaviors. In this paper, we investigated the supporting layer of silicon carbide and nickel nanoparticles reacted onto a Kovar alloy (Fe-Ni-Co) cathode substrate, which has been adopted for reliable CNT paste emitters. The X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and electrical conductivity measurements showed that the reaction of silicon carbide and nickel nanoparticles on the Kovar metal strongly depends upon the post-vacuum-annealing conditions and can be classified into two procedures of a diffusion-induced reaction (DIR) and a diffusion-limited reaction (DLR). The prolonged annealing at 750 °C for 5 h before the main annealing of the CNT paste emitters at 800 °C for 5 min led to the DIR that has enhanced the Ni silicide phase and a lower potential barrier for the interfacial electron transport, resulting in increased and weakly temperature-dependent field electron emission from the CNT paste emitters. On the other hand, the DLR with only the main anneal of the CNT paste emitters at 800 °C for 5 min gave rise to a higher potential barrier for the electron transport and so lower and strongly temperature-dependent field electron emission. From the results of the interfacial electron transport for the DIR and DLR mechanisms in the CNT paste emitters, we concluded that the ambient temperature dependency of field electron emission from CNT tips in the moderate range of up to 400 °C, still controversial, is mainly attributed to the supporting layer of the CNT emitter rather than its intrinsic electron emission.

Gene signature from cutaneous autoimmune diseases provides potential immunotherapy-relevant biomarkers in melanoma.

Immune checkpoint inhibitors (ICIs) are promising agents for treating melanoma. Given that autoimmune skin diseases exhibit hyper immune reaction, investigation of immune cells from autoimmune skin disease is crucial to validate the effectiveness of ICIs in melanoma treatment. We employed multipanel markers to predict the response to immune checkpoint inhibitors by characterizing the gene expression signatures of skin immune cells in systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis (PS). By analyzing single-cell RNA sequencing data from each dataset, T cell gene signatures from autoimmune skin diseases exhibit a complex immune response in tumors that responded to immunotherapy. Based on that CD86 and CD80 provide essential costimulatory signals for T cell activation, we observed that interaction of CD86 signaling has been enhanced in the T cells of patients with SLE, AD, and PS. Our analysis revealed a common increase in CD86 signals from dendritic cells (DCs) to T cells in patients with SLE, AD, and PS, confirming that dendritic cells produce pro-inflammatory cytokines to activate T cells. Thus, we hypothesize that T cell gene signatures from autoimmune skin diseases exhibit a pro-inflammatory response and have the potential to predict cancer immunotherapy. Our study demonstrated that T cell gene signatures derived from inflammatory skin diseases, particularly SLE and PS, hold promise as potential biomarkers for predicting the response to immune checkpoint blockade therapy in patients with melanoma. Our data provide an understanding of the immune-related characteristics and differential gene expression patterns in autoimmune skin diseases, which may represent promising targets for melanoma immunotherapy.

Unraveling the surface self-reconstruction of Fe-doped Ni-thiophosphate for efficient oxygen evolution reaction.

Surface self-reconstruction of oxygen evolution reaction (OER) electrocatalysts generally occurs during the electrochemical activation process. Herein, we study the surface self-reconstruction of a 2D layered Fe-doped Ni-thiophosphate (NixFe1-xPS3) nanosheet. The role of Fe in the surface self-reconstruction of NiPS3 during the OER is investigated by using an in situ Raman analysis. Formation of amorphous metal/non-metal oxide layers on the surface of NixFe1-xPS3 can efficiently act as the ultimate catalytic center for the OER.

Epigenomic landscape exhibits interferon signaling suppression in the patient of myocarditis after BNT162b2 vaccination.

After the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a novel mRNA vaccine (BNT162b2) was developed at an unprecedented speed. Although most countries have achieved widespread immunity from vaccines and infections, yet people, even who have recovered from SARS-CoV-2 infection, are recommended to receive vaccination due to their effectiveness in lowering the risk of recurrent infection. However, the BNT162b2 vaccine has been reported to increase the risk of myocarditis. To our knowledge, for the first time in this study, we tracked changes in the chromatin dynamics of peripheral blood mononuclear cells (PBMCs) in the patient who underwent myocarditis after BNT162b2 vaccination. A longitudinal study of chromatin accessibility using concurrent analysis of single-cell assays for transposase-accessible chromatin with sequencing and single-cell RNA sequencing showed downregulation of interferon signaling and upregulated RUNX2/3 activity in PBMCs. Considering BNT162b2 vaccination increases the level of interferon-α/γ in serum, our data highlight the immune responses different from the conventional responses to the vaccination, which is possibly the key to understanding the side effects of BNT162b2 vaccination.

FT-GAT: Graph neural network for predicting spontaneous breathing trial success in patients with mechanical ventilation.

BACKGROUND AND OBJECTIVES: Intensive care unit (ICU) physicians perform weaning procedures considering complex clinical situations and weaning protocols; however, liberating critical patients from mechanical ventilation (MV) remains challenging. Therefore, this study aims to aid physicians in deciding the early liberation of patients from MV by developing an artificial intelligence model that predicts the success of spontaneous breathing trials (SBT). METHODS: We retrospectively collected data of 652 critical patients (SBT success: 641, SBT failure: 400) who received MV at the Chungbuk National University Hospital (CBNUH) ICU from July 2020 to July 2022, including mixed and trauma ICUs. Patients underwent SBTs according to the CBNUH weaning protocol or physician's decision, and SBT success was defined as extubation performed by the physician on the SBT day. Additionally, our dataset comprised 11 numerical and 2 categorical features that can be obtained for any ICU patient, such as vital signs and MV setting values. To predict SBT success, we analyzed tabular data using a graph neural network-based approach. Specifically, the graph structure was designed considering feature correlation, and a novel deep learning model, called feature tokenizer graph attention network (FT-GAT), was developed for graph analysis. FT-GAT transforms the input features into high-dimensional embeddings and analyzes the graph via the attention mechanism. RESULTS: The quantitative evaluation results indicated that FT-GAT outperformed conventional models and clinical indicators by achieving the following model performance (AUROC): FT-GAT (0.80), conventional models (0.69-0.79), and clinical indicators (0.65-0.66) CONCLUSIONS: Through timely detection critical patients who can succeed in SBTs, FT-GAT can help prevent long-term use of MV and potentially lead to improvement in patient outcomes.

Anti-Leukemic Effects of Idesia polycarpa Maxim Branch on Human B-Cell Acute Lymphoblastic Leukemia Cells.

Patients with pediatric B-cell acute lymphoblastic leukemia (B-ALL) have a high survival rate, yet the prognosis of adults and patients with relapsed/refractory disease is relatively poor. Therefore, it is imperative to develop new therapeutic strategies. Here, we screened 100 plant extracts from South Korean Flora and investigated their anti-leukemic effect using CCRF-SB cells as a B-ALL model. The top cytotoxic extract identified in this screening was the Idesia polycarpa Maxim. branch (IMB), which efficiently inhibited the survival and proliferation of CCRF-SB cells, while having minimal to no impact on normal murine bone marrow cells. Mechanistically, the IMB-induced proapoptotic effect involves the increase of caspase 3/7 activity, which was shown to be associated with the disruption of the mitochondrial membrane potential (MMP) through the reduction in antiapoptotic Bcl-2 family expression. IMB also promoted the differentiation of CCRF-SB cells via the upregulation of the expression of differentiation-related genes, PAX5 and IKZF1. Given that resistance to glucocorticoid (GC) is often found in patients with relapsed/refractory ALL, we investigated whether IMB could restore GC sensitivity. IMB synergized GC to enhance apoptotic rate by increasing GC receptor expression and downmodulating mTOR and MAPK signals in CCRF-SB B-ALL cells. These results suggest that IMB has the potential to be a novel candidate for the treatment of B-ALL.

PHGDH preserves one-carbon cycle to confer metabolic plasticity in chemoresistant gastric cancer during nutrient stress.

Molecular classification of gastric cancer (GC) identified a subgroup of patients showing chemoresistance and poor prognosis, termed SEM (Stem-like/Epithelial-to-mesenchymal transition/Mesenchymal) type in this study. Here, we show that SEM-type GC exhibits a distinct metabolic profile characterized by high glutaminase (GLS) levels. Unexpectedly, SEM-type GC cells are resistant to glutaminolysis inhibition. We show that under glutamine starvation, SEM-type GC cells up-regulate the 3 phosphoglycerate dehydrogenase (PHGDH)-mediated mitochondrial folate cycle pathway to produce NADPH as a reactive oxygen species scavenger for survival. This metabolic plasticity is associated with globally open chromatin structure in SEM-type GC cells, with ATF4/CEBPB identified as transcriptional drivers of the PHGDH-driven salvage pathway. Single-nucleus transcriptome analysis of patient-derived SEM-type GC organoids revealed intratumoral heterogeneity, with stemness-high subpopulations displaying high GLS expression, a resistance to GLS inhibition, and ATF4/CEBPB activation. Notably, coinhibition of GLS and PHGDH successfully eliminated stemness-high cancer cells. Together, these results provide insight into the metabolic plasticity of aggressive GC cells and suggest a treatment strategy for chemoresistant GC patients.

Whole blood transcriptome analysis in dairy calves experimentally challenged with bovine herpesvirus 1 (BoHV-1) and comparison to a bovine respiratory syncytial virus (BRSV) challenge.

Bovine herpesvirus 1 (BoHV-1), is associated with several clinical syndromes in cattle, among which bovine respiratory disease (BRD) is of particular significance. Despite the importance of the disease, there is a lack of information on the molecular response to infection via experimental challenge with BoHV-1. The objective of this study was to investigate the whole-blood transcriptome of dairy calves experimentally challenged with BoHV-1. A secondary objective was to compare the gene expression results between two separate BRD pathogens using data from a similar challenge study with BRSV. Holstein-Friesian calves (mean age (SD) = 149.2 (23.8) days; mean weight (SD) = 174.6 (21.3) kg) were either administered BoHV-1 inoculate (1 × 107/mL × 8.5 mL) (n = 12) or were mock challenged with sterile phosphate buffered saline (n = 6). Clinical signs were recorded daily from day (d) -1 to d 6 (post-challenge), and whole blood was collected in Tempus RNA tubes on d six post-challenge for RNA-sequencing. There were 488 differentially expressed (DE) genes (p < 0.05, False Discovery rate (FDR) < 0.10, fold change ≥2) between the two treatments. Enriched KEGG pathways (p < 0.05, FDR <0.05); included Influenza A, Cytokine-cytokine receptor interaction and NOD-like receptor signalling. Significant gene ontology terms (p < 0.05, FDR <0.05) included defence response to virus and inflammatory response. Genes that are highly DE in key pathways are potential therapeutic targets for the treatment of BoHV-1 infection. A comparison to data from a similar study with BRSV identified both similarities and differences in the immune response to differing BRD pathogens.

Antibacterial and Antiviral Properties of Pinus densiflora Essential Oil.

The Korean mountains are home to the Korean red pine (Pinus densiflora). Pine needle oil has been used as a food additive and a traditional herbal medicine; however, any health-related properties of its trunk oil remain unknown. Herein, we assessed antibacterial and antiviral properties of essential oil extracted from the trunk of P. densiflora. Th extracted oil was hydrodistilled using a Clevenger apparatus and analyzed using gas chromatography-mass spectrometry. The antimicrobial activity of the oil was tested using the microbroth dilution technique against 10 bacterial species (6 g-positive and 4 g-negative) and fungi. The extract exerted strong antimicrobial activity against Vibrio parahaemolyticus, Bacillus cereus, Listeria monocytogenes, Propionibacterium acnes, and Malassezia furfur (minimum inhibitory concentration = 10 mL/L). Additionally, it exhibited dose-dependent activity against influenza virus A and feline coronavirus. Furthermore, among 20 identified constituents accounting for 98.7% of the oil contents, the major components included 3-cyclohexene-1-methanol (10.12%), 2-(4-methylcyclohexyl)-2-propanol (9.09%), fenchone (8.14%), O-isopropyltoluene (6.35%), and isothymol methyl ether (6.14%). The P. densiflora trunk essential oil showed antibacterial and antiviral activities that depended on its chemical composition and the microbial strains tested herein. The essential oil can be used as an antimicrobial agent and disinfectant.

Resource Allocation in Downlink VLC-NOMA Systems for Factory Automation Scenario.

Industry 4.0 requires high-speed data exchange that includes fast, reliable, low-latency, and cost-effective data transmissions. As visible light communication (VLC) can provide reliable, low-latency, and secure connections that do not penetrate walls and are immune to electromagnetic interference; it can be considered a solution for Industry 4.0. The non-orthogonal multiple access (NOMA) technique can achieve high spectral efficiency using the same frequency and time resources for multiple users. It means that smaller amounts of resources will be used compared with orthogonal multiple access (OMA). Therefore, handling multiple data transmissions with VLC-NOMA can be easier for factory automation than OMA. However, as the transmit power is split, the reliability is reduced. Therefore, this study proposed a deep neural network (DNN)-based power-allocation algorithm (DBPA) to improve the reliability of the system. Further, to schedule multiple nodes in VLC-NOMA system, a priority-based user-pairing (PBUP) scheme is proposed. The proposed techniques in VLC-NOMA system were evaluated in terms of the factory automation scenario and showed that it improves reliability and reduces missed deadlines.

WNT5A drives interleukin-6-dependent epithelial-mesenchymal transition via the JAK/STAT pathway in keloid pathogenesis.

Background: Keloid scarring is a fibroproliferative disease caused by aberrant genetic activation with an unclear underlying mechanism. Genetic predisposition, aberrant cellular responses to environmental factors, increased inflammatory cytokines and epithelial-mesenchymal transition (EMT) phenomena are known as major contributors. In this study, we aimed to identify the molecular drivers that initiate keloid pathogenesis. Methods: Bulk tissue RNA sequencing analyses of keloid and normal tissues along with ex vivo and in vitro tests were performed to identify the contributing genes to keloid pathogenesis. An animal model of inflammatory keloid scarring was reproduced by replication of a skin fibrosis model with intradermal bleomycin injection in C57BL/6 mice. Results: Gene set enrichment analysis revealed upregulation of Wnt family member 5A (WNT5A) expression and genes associated with EMT in keloid tissues. Consistently, human keloid tissues and the bleomycin-induced skin fibrosis animal model showed significantly increased expression of WNT5A and EMT markers. Increased activation of the interleukin (IL)-6/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway and subsequent elevation of EMT markers was also observed in keratinocytes co-cultured with WNT5A-activated fibroblasts or keloid fibroblasts. Furthermore, WNT5A silencing and the blockage of IL-6 secretion via neutralizing IL-6 antibody reversed hyperactivation of the STAT pathway and EMT markers in keratinocytes. Lastly, STAT3 silencing significantly reduced the EMT-like phenotypes in both keratinocytes and IL-6-stimulated keratinocytes. Conclusions: Intercellular communication via the WNT5A and STAT pathways possibly underlies a partial mechanism of EMT-like phenomena in keloid pathogenesis. IL-6 secreted from WNT5A-activated fibroblasts or keloid fibroblasts activates the JAK/STAT signaling pathway in adjacent keratinocytes which in turn express EMT markers. A better understanding of keloid development and the role of WNT5A in EMT will promote the development of next-generation targeted treatments for keloid scars.