HN1-mediated activation of lipogenesis through Akt-SREBP signaling promotes hepatocellular carcinoma cell proliferation and metastasis.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, with more than 800,000 deaths each year, and its 5-year survival rate is less than 12%. The role of the HN1 gene in HCC has remained elusive, despite its upregulation in various cancer types. In our investigation, we identified HN1's heightened expression in HCC tissues, which, upon overexpression, fosters cell proliferation, migration, and invasion, unveiling its role as an oncogene in HCC. In addition, silencing HN1 diminished the viability and metastasis of HCC cells, whereas HN1 overexpression stimulated their growth and invasion. Gene expression profiling revealed HN1 silencing downregulated 379 genes and upregulated 130 genes, and suppressive proteins associated with the lipogenic signaling pathway networks. Notably, suppressing HN1 markedly decreased the expression levels of SREBP1 and SREBP2, whereas elevating HN1 had the converse effect. This dual modulation of HN1 affected lipid formation, hindering it upon HN1 silencing and promoting it upon HN1 overexpression. Moreover, HN1 triggers the Akt pathway, fostering tumorigenesis via SREBP1-mediated lipogenesis and silencing HN1 effectively curbed HCC tumor growth in mouse xenograft models by deactivating SREBP-1, emphasizing the potential of HN1 as a therapeutic target, impacting both external and internal factors, it holds promise as an effective therapeutic strategy for HCC.

Role of subcutaneous closed suction drain in the prevention of incisional surgical site infection after loop ileostomy reversal with purse-string skin closure: a retrospective observational study.

BACKGROUND: Surgical site infection (SSI) is not rare after loop ileostomy reversal. This study assessed the effects of a subcutaneous closed suction drain on reducing SSIs after loop ileostomy reversal with purse-string skin closure. METHODS: This retrospective study included 229 patients who underwent loop ileostomy reversal with purse-string closure at the Pusan National University Yangsan Hospital between January 2017 and December 2021. We divided the patients into those with a subcutaneous drain (SD group) and those without it (ND group). We analyzed variables that affected SSI occurrence in both groups. RESULTS: The SD and ND groups included 109 and 120 patients, respectively. The number of incisional SSIs was significantly lower in the SD than in the ND group (0 vs. 7 events). An average of 35.7 mL of fluid was collected in the drainage bulb during hospitalization. The C-reactive protein level on postoperative day 4 was significantly lower in the SD group than in the ND group. The insertion of a subcutaneous drain was the only factor associated with a reduced incidence of SSIs (p = 0.015). CONCLUSIONS: Subcutaneous closed suction drain with purse-string skin closure in loop ileostomy reversal can reduce incisional SSI occurrence.

Effectiveness of meditation for fatigue management: Insight from a comprehensive systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis revealed the effectiveness of meditation in addressing fatigue, given its widespread use as a remedy for sleep disturbances and fatigue. METHOD: We analyzed 29 randomized controlled trials from MEDLINE and the Cochrane Library, spanning from December 31, 2022. We conducted two metaanalyses using mean difference (MD) with normalized data and standardized mean difference (SMD) with original data. RESULTS: These trials included various populations, with baseline fatigue severity observed at 52.2 ± 16.0 points among 4104 participants. After an average meditation duration of 9.6 ± 4.7 weeks, fatigue scores decreased significantly by 6.4 points of MD [95% CI, 4.3-8.5] compared to controls. The most significant reduction occurred in the sub-healthy group (MD 8.2 [95% CI, 2.7 to 13.8]), followed by the general group (MD 6.9 [95% CI, 0.4 to 13.4]), and the disease group (MD 5.7 [95% CI, 3.4 to 8.0]). Notably, meditation-based anti-fatigue effects were particularly pronounced for mental fatigue (MD 10.0 [95% CI, 4.3 to 15.6]), especially with expert guidance and supplementary homework. CONCLUSION: These findings align with meta-analysis results using standardized mean difference (SMD), providing evidence for meditation as an effective nonpharmacological intervention for fatigue management, while also informing effective meditation approaches. REGISTRATION NUMBER: CRD42023395551 in PROSPERO.

Crosslinking reactions of a model aminated lignin compound as a platform for building thermosetting polymers for lignin-based bio adhesives.

As millions of tons of kraft lignin are being wasted, a potential application is to use its crosslinking reactions to build thermosetting bio adhesives. However, the crosslinking reactions between lignin molecules are not fully understood. The present study aims to elucidate the crosslinking reactions of the model lignin compound guaiacylglycerol-ß-guaiacyl ether (GGE) via one-step hydroxymethylation/ amination with formaldehyde and diethylenetriamine (DETAM), or one-step glyoxylation/ amination with glyoxal and DETAM via liquid NMR techniques such as 1H NMR, 13C NMR, 2D 1H-13C, and 1H-15N HSQC NMR. Specifically, the 2D 1H-13C HSQC NMR spectra confirm the presence of -CH2-NH- with a chemical shift of 1H 2.6-3.6/13C 40-60 ppm, and the formation of methylene linkages via the crosslinking reaction. Also, the 2D 1H-15N HSQC NMR spectra clearly detect the formation of amide and imine bonds at 1H 7.8/15N 110 and 1H 8.07/15N 121.5 ppm from the crosslinked GGE.

Glycogen Phosphorylase Inhibitor Promotes Hair Growth via Protecting from Oxidative-Stress and Regulating Glycogen Breakdown in Human Hair follicles.

Hair growth cycles are mainly regulated by human dermal papilla cells (hDPCs) and human outer root sheath cells (hORSCs). Protecting hDPCs from excessive oxidative stress and hORSCs from glycogen phosphorylase (PYGL) is crucial to maintaining the hair growth phase, anagen. In this study, we developed a new PYGL inhibitor, Hydroxytrimethylpyridinyl Methylindolecarboxamide (HTPI) and assessed its potential to prevent hair loss. HTPI reduced oxidative damage, preventing cell death and restored decreased level of anagen marker ALP and its related genes induced by hydrogen peroxide in hDPCs. Moreover, HTPI inhibited glycogen degradation and induced cell survival under glucose starvation in hORSCs. In ex-vivo culture, HTPI significantly enhanced hair growth compared to the control with minoxidil showing comparable results. Overall, these findings suggest that HTPI has significant potential as a therapeutic agent for the prevention and treatment of hair loss.

Effect of fractional picosecond laser therapy using a diffractive optical lens on histological tissue reaction.

BACKGROUND AND OBJECTIVES: Fractional ablative resurfacing techniques are preferred treatments for facial rejuvenation of aged skin. This study was performed to investigate the cutaneous effects of using a fractional picosecond laser at 1064 nm with a diffractive lens. METHODS: The penetration depth according to the location of the handpiece tip was evaluated using an acrylic panel. Laser induced optical breakdown (LIOB) and cutaneous damage were observed after hematoxylin and eosin staining in guinea pigs. Collagen formation was evaluated using Victoria staining, Masson's trichrome (MT) staining, and immunohistochemical staining for collagen type III. RESULTS: The penetration depth for LEVEL 1 was 499.98-935.23 µm (average: 668.75 ± 182.84 µm); the LIOB cavity area was 1664.17 ± 650.52 µm2. The penetration depth of LEVEL 2 was 257.12-287.38 µm (average: 269.77 ± 14.55 µm) with an LIOB cavity area of 1335.85 ± 214.41 µm2. At LEVEL 3, that was 36.17-53.69 µm (average: 52.15 ± 20.81 µm) and the LIOB cavity area was 1312.67 ± 1069.12 µm2. No epidermal tissue damage was observed and collagen formation was observed from day 14 under all conditions. CONCLUSION: Diffractive optical element (DOE) lens arranged laser treatment system controlled the position of LIOB occurrence and an irradiating area.

Characteristics of the epicardial adipose tissue measured by low-dose chest computed tomography according to the metabolic health/obesity status.

BACKGROUND: Epicardial adipose tissue (EAT) is associated with the development of cardiovascular disease and long-term survival. This study aimed to assess the characteristics of EAT according to the metabolic health and obesity status using low-dose chest computed tomography (CT). METHODS: A total of 1074 asymptomatic adults who underwent a medical health check-up were enrolled. Subjects were categorized into the following four groups according to the metabolic health and obesity status: metabolically healthy non-obese (MHNO); metabolically unhealthy non-obese (MUNO); metabolically healthy obese (MHO); and metabolically unhealthy obese (MUO). EAT on low-dose chest CT was measured by using automatic, quantitative measurement software. RESULTS: MUO showed the highest EAT volume and lowest EAT radiodensity in comparison with MHNO (p < 0.001). The MUNO (n = 70), MHO (n = 259), and MUO (n = 231) groups had increased EAT volume (ß [95 % CI], 37.65 [23.11,52.18], 56.79 [47.56,66.02], 84.85 [74.59,95.11] respectively, all p < 0.001), decreased EAT radiodensity (ß [95 % CI], - 3.22 [- 4.59,- 1.85], - 4.48 [- 5.30,- 3.66], - 6.03 [- 6.90,- 5.16] respectively, all p < 0.001) in comparison with the MHNO (n = 514) group by using multivariable linear regression models. CONCLUSIONS: Both metabolic abnormalities and obesity were closely associated with EAT characteristics. Characteristics of EAT are similar in MHO and MUNO. This finding suggests that MHO is not a favorable condition in terms of cardiac health, as assessed by the characteristics of EAT. The combination of obesity and metabolically unhealthy status has a synergistic adverse effect on EAT. Measurement of EAT could be a useful imaging biomarker for evaluation of an individual's metabolic health/obesity status.

The efficacy of adipose stem cell-derived exosomes in hair regeneration based on a preclinical and clinical study.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent hair loss disorder with psychological repercussions. Traditional treatments have limitations, leading to the exploration of regenerative therapies such as exosomes derived from adipose tissue stem cells (ASC-Exosomes). METHODS: First, using human hair follicle (HF) dermal papilla cells (hDPCs) treated with ASC-Exosomes, ALP, VCAN, ß-catenin, and LEF-1 levels with RT-PCR and p-GSK3ß, GSK3ß, ß-catenin, ALP, and ß-actin levels with western blot analysis were assessed. Hair shaft elongation test and assay for ALP, Ki-67, and ß-catenin were done using human HF organ culture. Patients with AGA had ASC-Exosomes treatment and were evaluated for hair counts, photographic assessments, subjective satisfaction, and safety profiles. RESULTS: ASC-Exosomes impact hDPCs, increasing proliferation and the upregulation of hair growth-related genes, including ALP, VCAN, ß-catenin, and LEF-1. The Wnt/ß-catenin pathway was activated, indicating their role in promoting hair growth. ASC-Exosomes also promoted hair shaft elongation and ALP activity, suggesting a potential for hair regeneration. Thirty participants with AGA enrolled and treated over 24 weeks. The subjects experienced a significant increase in total hair density, improved global photographic assessments, and reported higher subjective satisfaction without severe adverse reactions. CONCLUSION: This research contributes to the growing body of evidence supporting the use of exosomes in hair loss treatment, offering a safe and effective alternative for individuals with AGA.

PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.

Our recent studies have identified p21-activated kinase 4 (PAK4) as a key regulator of lipid catabolism in the liver and adipose tissue, but its role in glucose homeostasis in skeletal muscle remains to be explored. In this study, we find that PAK4 levels are highly upregulated in the skeletal muscles of diabetic humans and mice. Skeletal muscle-specific Pak4 ablation or administering the PAK4 inhibitor in diet-induced obese mice retains insulin sensitivity, accompanied by AMPK activation and GLUT4 upregulation. We demonstrate that PAK4 promotes insulin resistance by phosphorylating AMPKα2 at Ser491, thereby inhibiting AMPK activity. We additionally show that skeletal muscle-specific expression of a phospho-mimetic mutant AMPKα2S491D impairs glucose tolerance, while the phospho-inactive mutant AMPKα2S491A improves it. In summary, our findings suggest that targeting skeletal muscle PAK4 may offer a therapeutic avenue for type 2 diabetes.

Public Perception Towards Drug Abuse in South Korea: The Effects of Overconfidence and Affirmation.

OBJECTIVE: The abuse of prescription drugs and over-the-counter medicines has been a major issue addressed as a serious public health problem worldwide. This study explored factors contributing to substance abuse in Korea by examining the status of substance abuse among Korean adults and evaluating their knowledge, attitudes, and intentions toward substance abuse. METHODS: Data were collected online from a sample of participants 19 years old or older from May 20 to June 1, 2020 (n=1,020). The survey consisted of questions on demographics, perceptions of drug risk, motives for drug use, and attitudes toward drug addiction treatment. Principal component and multiple logistic regression analyses were used to explore the factors contributing to the perception of drug abuse. RESULTS: In the multivariate regression analysis, overconfidence in handling drug usage, acceptance of addictive substances, and affirmation of public support for drug abuse were associated with opioid abuse (Nagelkerke R2=0.486), and additionally affirmation of legal cannabis usage and motivation to use diet pills were associated with diet pill abuse (Nagelkerke R2=0.569). CONCLUSION: The findings of this study suggest that the actual situation of substance abuse among Korean adults increases awareness of and attitudes toward drug use related to substance abuse.

Nonlinear sound-sheet microscopy: imaging opaque organs at the capillary and cellular scale.

Light-sheet fluorescence microscopy has revolutionized biology by visualizing dynamic cellular processes in three dimensions. However, light scattering in thick tissue and photobleaching of fluorescent reporters limit this method to studying thin or translucent specimens. Here we show that non-diffractive ultrasonic beams used in conjunction with a cross-amplitude modulation sequence and nonlinear acoustic reporters enable fast and volumetric imaging of targeted biological functions. We report volumetric imaging of tumor gene expression at the cm 3 scale using genetically encoded gas vesicles, and localization microscopy of currently uncharted cerebral capillary networks using intravascular microbubble contrast agents. Nonlinear sound-sheet microscopy provides a ∼64x acceleration in imaging speed, ∼35x increase in imaged volume and ∼4x increase in classical imaging resolution compared to the state-of-the-art in biomolecular ultrasound.

A Causality Assessment Framework for COVID-19 Vaccines and Adverse Events at the COVID-19 Vaccine Safety Research Center.

During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024. This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels-high, moderate, limited, or insufficient-while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as "convincingly supports" ("evidence established" in the 2024 NASEM report), "favors acceptance," "favors rejection," or "inadequate to accept or reject." The CoVaSC has established an independent committee to conduct causality assessments using the weight-of-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-of-evidence framework and to detail the considerations involved in its practical application in the CoVaSC.

Fully Automatic Quantitative Measurement of Equilibrium Radionuclide Angiocardiography Using a Convolutional Neural Network.

PURPOSE: The aim of this study was to generate deep learning-based regions of interest (ROIs) from equilibrium radionuclide angiography datasets for left ventricular ejection fraction (LVEF) measurement. PATIENTS AND METHODS: Manually drawn ROIs (mROIs) on end-systolic and end-diastolic images were extracted from reports in a Picture Archiving and Communications System. To reduce observer variability, preprocessed ROIs (pROIs) were delineated using a 41% threshold of the maximal pixel counts of the extracted mROIs and were labeled as ground-truth. Background ROIs were automatically created using an algorithm to identify areas with minimum counts within specified probability areas around the end-systolic ROI. A 2-dimensional U-Net convolutional neural network architecture was trained to generate deep learning-based ROIs (dlROIs) from pROIs. The model's performance was evaluated using Lin's concordance correlation coefficient (CCC). Bland-Altman plots were used to assess bias and 95% limits of agreement. RESULTS: A total of 41,462 scans (19,309 patients) were included. Strong concordance was found between LVEF measurements from dlROIs and pROIs (CCC = 85.6%; 95% confidence interval, 85.4%-85.9%), and between LVEF measurements from dlROIs and mROIs (CCC = 86.1%; 95% confidence interval, 85.8%-86.3%). In the Bland-Altman analysis, the mean differences and 95% limits of agreement of the LVEF measurements were -0.6% and -6.6% to 5.3%, respectively, for dlROIs and pROIs, and -0.4% and -6.3% to 5.4% for dlROIs and mROIs, respectively. In 37,537 scans (91%), the absolute LVEF difference between dlROIs and mROIs was <5%. CONCLUSIONS: Our 2-dimensional U-Net convolutional neural network architecture showed excellent performance in generating LV ROIs from equilibrium radionuclide angiography scans. It may enhance the convenience and reproducibility of LVEF measurements.

Target-Driven Tissue-Agnostic Drug Approvals-A New Path of Drug Development.

The regulatory approvals of tumor-agnostic therapies have led to the re-evaluation of the drug development process. The conventional models of drug development are histology-based. On the other hand, the tumor-agnostic drug development of a new drug (or combination) focuses on targeting a common genomic biomarker in multiple cancers, regardless of histology. The basket-like clinical trials with multiple cohorts allow clinicians to evaluate pan-cancer efficacy and toxicity. There are currently eight tumor agnostic approvals granted by the Food and Drug Administration (FDA). This includes two immune checkpoint inhibitors, and five targeted therapy agents. Pembrolizumab is an anti-programmed cell death protein-1 (PD-1) antibody that was the first FDA-approved tumor-agnostic treatment for unresectable or metastatic microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) solid tumors in 2017. It was later approved for tumor mutational burden-high (TMB-H) solid tumors, although the TMB cut-off used is still debated. Subsequently, in 2021, another anti-PD-1 antibody, dostarlimab, was also approved for dMMR solid tumors in the refractory setting. Patients with fusion-positive cancers are typically difficult to treat due to their rare prevalence and distribution. Gene rearrangements or fusions are present in a variety of tumors. Neurotrophic tyrosine kinase (NTRK) fusions are present in a range of pediatric and adult solid tumors in varying frequency. Larotrectinib and entrectinib were approved for neurotrophic tyrosine kinase (NTRK) fusion-positive cancers. Similarly, selpercatinib was approved for rearranged during transfection (RET) fusion-positive solid tumors. The FDA approved the first combination therapy of dabrafenib, a B-Raf proto-oncogene serine/threonine kinase (BRAF) inhibitor, plus trametinib, a mitogen-activated protein kinase (MEK) inhibitor for patients 6 months or older with unresectable or metastatic tumors (except colorectal cancer) carrying a BRAFV600E mutation. The most recent FDA tumor-agnostic approval is of fam-trastuzumab deruxtecan-nxki (T-Dxd) for HER2-positive solid tumors. It is important to identify and expeditiously develop drugs that have the potential to provide clinical benefit across tumor types.

Polyamine and EIF5A hypusination downstream of c-Myc confers targeted therapy resistance in BRAF mutant melanoma.

BACKGROUND: BRAF inhibitors are widely employed in the treatment of melanoma with the BRAF V600E mutation. However, the development of resistance compromises their therapeutic efficacy. Diverse genomic and transcriptomic alterations are found in BRAF inhibitor resistant melanoma, posing a pressing need for convergent, druggable target that reverse therapy resistant tumor with different resistance mechanisms. METHODS: CRISPR-Cas9 screens were performed to identify novel target gene whose inhibition selectively targets A375VR, a BRAF V600E mutant cell line with acquired resistance to vemurafenib. Various in vitro and in vivo assays, including cell competition assay, water soluble tetrazolium (WST) assay, live-dead assay and xenograft assay were performed to confirm synergistic cell death. Liquid Chromatography-Mass Spectrometry analyses quantified polyamine biosynthesis and changes in proteome in vemurafenib resistant melanoma. EIF5A hypusination dependent protein translation and subsequent changes in mitochondrial biogenesis and activity were assayed by O-propargyl-puromycin labeling assay, mitotracker, mitoSOX labeling and seahorse assay. Bioinformatics analyses were used to identify the association of polyamine biosynthesis with BRAF inhibitor resistance and poor prognosis in melanoma patient cohorts. RESULTS: We elucidate the role of polyamine biosynthesis and its regulatory mechanisms in promoting BRAF inhibitor resistance. Leveraging CRISPR-Cas9 screens, we identify AMD1 (S-adenosylmethionine decarboxylase 1), a critical enzyme for polyamine biosynthesis, as a druggable target whose inhibition reduces vemurafenib resistance. Metabolomic and proteomic analyses reveal that polyamine biosynthesis is upregulated in vemurafenib-resistant cancer, resulting in enhanced EIF5A hypusination, translation of mitochondrial proteins and oxidative phosphorylation. We also identify that sustained c-Myc levels in vemurafenib-resistant cancer are responsible for elevated polyamine biosynthesis. Inhibition of polyamine biosynthesis or c-Myc reversed vemurafenib resistance both in vitro cell line models and in vivo in a xenograft model. Polyamine biosynthesis signature is associated with poor prognosis and shorter progression free survival after BRAF/MAPK inhibitor treatment in melanoma cohorts, highlighting the clinical relevance of our findings. CONCLUSIONS: Our findings delineate the molecular mechanisms involving polyamine-EIF5A hypusination-mitochondrial respiration pathway conferring BRAF inhibitor resistance in melanoma. These targets will serve as effective therapeutic targets that can maximize the therapeutic efficacy of existing BRAF inhibitors.

Comparison of laser and traditional lancing devices for capillary blood sampling in patients with diabetes mellitus and high bleeding risk.

PURPOSE: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia. METHODS: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared. RESULTS: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups. CONCLUSION: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value.

Hair Growth Promoting Effects of 15-Hydroxyprostaglandin Dehydrogenase Inhibitor in Human Follicle Dermal Papilla Cells.

Prostaglandin E2 (PGE2) is known to be effective in regenerating tissues, and bimatoprost, an analog of PGF2α, has been approved by the FDA as an eyelash growth promoter and has been proven effective in human hair follicles. Thus, to enhance PGE2 levels while improving hair loss, we found dihydroisoquinolinone piperidinylcarboxy pyrazolopyridine (DPP), an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), using DeepZema®, an AI-based drug development program. Here, we investigated whether DPP improved hair loss in human follicle dermal papilla cells (HFDPCs) damaged by dihydrotestosterone (DHT), which causes hair loss. We found that DPP enhanced wound healing and the expression level of alkaline phosphatase in DHT-damaged HFDPCs. We observed that DPP significantly down-regulated the generation of reactive oxygen species caused by DHT. DPP recovered the mitochondrial membrane potential in DHT-damaged HFDPCs. We demonstrated that DPP significantly increased the phosphorylation levels of the AKT/ERK and activated Wnt signaling pathways in DHT-damaged HFDPCs. We also revealed that DPP significantly enhanced the size of the three-dimensional spheroid in DHT-damaged HFDPCs and increased hair growth in ex vivo human hair follicle organ culture. These data suggest that DPP exhibits beneficial effects on DHT-damaged HFDPCs and can be utilized as a promising agent for improving hair loss.

A Novel Method of Self-Cross-Linking of Syringaldehyde with Activated Methoxy Groups via Cross-Coupling for Lignin-Based Wood Adhesives.

As steric hindrance, methoxy groups are limiting the valorization of hardwood lignin. This paper reports a novel method of self-cross-linking of the syringaldehyde with activated methoxy groups (-OCH3) via cross-coupling reaction to obtain thermosetting polymers for lignin-based wood adhesives. The methoxy groups of syringaldehyde have been activated via cross-coupling reaction by substituting Ar-OCH3 with Ar-CH2-SiMe3, and dichloromethane, leading to cross-linking via methylene bridges to build a thermosetting polymer. FTIR spectra showed a decrease in the intensity of a -CH3 and -OH group, owing to the substitution of the methoxy group. 13C NMR spectra also supported these results with the -SiMe3 signal that disappeared after the cross-linking reaction. Furthermore, cross-linking between the activated methoxy groups was confirmed with a strong exothermic peak at 130 °C, resulting in an increase in the adhesion strength as hot-pressing temperature increased from 160 to 180 °C. These results suggest that the cross-linking between the activated methoxy groups of syringaldehyde is an important understanding of valorizing hardwood lignin via building thermosetting polymers for lignin-based adhesives.

Deep learning-based measurement of split glomerular filtration rate with 99mTc-diethylenetriamine pentaacetic acid renal scan.

PURPOSE: To develop a deep learning (DL) model for generating automated regions of interest (ROIs) on 99mTc-diethylenetriamine pentaacetic acid (DTPA) renal scans for glomerular filtration rate (GFR) measurement. METHODS: Manually-drawn ROIs retrieved from a Picture Archiving and Communications System were used as ground-truth (GT) labels. A two-dimensional U-Net convolutional neural network architecture with multichannel input was trained to generate DL ROIs. The agreement between GFR values from GT and DL ROIs was evaluated using Lin's concordance correlation coefficient (CCC) and slope coefficients for linear regression analyses. Bias and 95% limits of agreement (LOA) were assessed using Bland-Altman plots. RESULTS: A total of 24,364 scans (12,822 patients) were included. Excellent concordance between GT and DL GFR was found for left (CCC 0.982, 95% confidence interval [CI] 0.981-0.982; slope 1.004, 95% CI 1.003-1.004), right (CCC 0.969, 95% CI 0.968-0.969; slope 0.954, 95% CI 0.953-0.955) and both kidneys (CCC 0.978, 95% CI 0.978-0.979; slope 0.979, 95% CI 0.978-0.979). Bland-Altman analysis revealed minimal bias between GT and DL GFR, with mean differences of - 0.2 (95% LOA - 4.4-4.0), 1.4 (95% LOA - 3.5-6.3) and 1.2 (95% LOA - 6.5-8.8) mL/min/1.73 m² for left, right and both kidneys, respectively. Notably, 19,960 scans (81.9%) showed an absolute difference in GFR of less than 5 mL/min/1.73 m². CONCLUSION: Our DL model exhibited excellent performance in the generation of ROIs on 99mTc-DTPA renal scans. This automated approach could potentially reduce manual effort and enhance the precision of GFR measurement in clinical practice.

Korean Consensus Criteria for the Severity Classification of Alopecia Areata.

BACKGROUND: A set of criteria for severity classification is essential in alopecia areata (AA). Currently, no guidelines are universally accepted for defining AA severity. OBJECTIVE: This study aimed to establish a set of consensus criteria for classifying the severity of and identifying treatment refractoriness in AA. METHODS: A preliminary draft of the definition for moderate-to-severe AA was crafted based on available evidence, and members of the Korean Hair Research Society (KHRS) subsequently endorsed the recommendation through an online survey. RESULTS: In the first Delphi round, consensus was attained on 15 questions. After refining certain items in the second round, consensus was achieved on 23 out of 26 questions. The KHRS first defined AA severity using the severity of alopecia tool (SALT). SALT ≥50 was defined as severe, 20≤ SALT <50 as moderate, and SALT <20 as mild. Moderate AA was considered severe if it meets one or more of the following criteria: dermatology life quality index >10, presence of accompanying eyebrow or eyelash loss, positive hair loss activity, or treatment-refractory AA. CONCLUSION: These consensus criteria can help clinicians accurately diagnose AA, provide appropriate treatment, and monitor its progression.