A leucine-rich-repeat receptor-like kinase regulates pollen aperture formation in rice.

Apertures in pollen grains exhibit species-specific patterns and provide an ideal model for studying cell-surface patterning. Pollen apertures are critical for cereal crop fertility, and while DEFECTIVE IN APERTURE FORMATION1 (OsDAF1) and INAPERTURATE POLLEN1 (OsINP1) have been documented to participate in pollen aperture formation in rice (Oryza sativa), the molecular transduction pathway regulating aperture formation is largely unknown. Here, we report that a leucine-rich-repeat receptor-like kinase (LRR-RLK), AM1, plays a key role in rice pollen aperture formation. Mutations of OsAM1 lead to complete sterility due to disappearance of the pollen aperture and failure in pollen tube germination. OsAM1 encodes a LRR-RLK that belongs to the STRUBBELIG-receptor family. Similar to other reported aperture regulators, OsAM1 assembles to future aperture sites on tetrads after meiosis to regulate aperture formation. The extracellular and intracellular domain of OsAM1 interacts with OsINP1 and OsDAF1, respectively. However, despite their interaction and the absence of aperture formation in osam1 pollen grains, OsINP1 and OsDAF1 localize to future aperture sites at the tetrad stage. Mutation of OsINP1, however, disrupts normal localization of OsAM1, indicating that OsAM1 acts downstream of OsINP1. Our findings reveal the role of a LRR-RLK protein in pollen aperture formation and shed light on the regulatory network of pollen aperture formation.

Amino acid deprivation induces TXNIP expression by NRF2 downregulation.

Thioredoxin-interacting protein (TXNIP) is sensitive to oxidative stress and is involved in the pathogenesis of various metabolic, cardiovascular, and neurodegenerative disorders. Therefore, several studies have suggested that TXNIP is a promising therapeutic target for several diseases, particularly cancer and diabetes. However, the regulation of TXNIP expression under amino acid (AA)-restricted conditions is not well understood. In the present study, we demonstrated that TXNIP expression was promoted by the deprivation of AAs, especially arginine, glutamine, lysine, and methionine, in non-small cell lung cancer (NSCLC) cells. Interestingly, we determined that increased TXNIP expression induced by AA deprivation was associated with nuclear factor erythroid 2-related factor 2 (NRF2) downregulation, but not with activating transcription factor 4 (ATF4) activation. Furthermore, N-acetyl-l-cysteine (NAC), a scavenger of reactive oxygen species (ROS), suppressed TXNIP expression in NSCLC cells deprived of AA. Collectively, the induction of TXNIP expression by AA deprivation was mediated by ROS production, potentially through NRF2 downregulation. Our findings suggest that TXNIP expression may be associated with the redox homeostasis of AA metabolism and provide a possible rationale for a therapeutic strategy to treat cancer with AA restriction.

Exosomes derived from human dermal fibroblasts (HDFn-Ex) alleviate DNCB-induced atopic dermatitis (AD) via PPARα.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Skin barrier dysfunction is the initial step in the development of AD. Recently, exosomes have been considered as potential cell-free medicine for skin defects such as aging, psoriasis and wounds. The aim of this study was to investigate the effects of human dermal fibroblast-neonatal-derived exosome (HDFn-Ex) on AD. HDFn-Ex increased the expression of peroxisome proliferator activated receptor α (PPARα) and alleviated the 1-chloro-2,4-dinitrobenzene (DNCB)-mediated downregulation of filaggrin, involucrin, loricrin, hyaluronic acid synthase 1 (HAS1) and HAS2 in human keratinocyte HaCaT cells. However, these effects were inhibited by the PPARα antagonist GW6471. In the artificial skin model, HDFn-Ex significantly inhibited DNCB-induced epidermal hyperplasia and the decrease in filaggrin and HAS1 levels via a PPARα. In the DNCB-induced AD-like mouse model, HDFn-Ex administration reduced epidermis thickening and mast cell infiltration into the dermis compared to DNCB treatment. Moreover, the decreases in PPARα, filaggrin and HAS1 expression, as well as the increases in IgE and IL4 levels induced by DNCB treatment were reversed by HDFn-Ex. These effects were blocked by pre-treatment with GW6471. Furthermore, HDFn-Ex exhibited an anti-inflammatory effect by inhibiting the DNCB-induced increases in IκBα phosphorylation and TNF-α expression. Collectively, HDFn-Ex exhibited a protective effect on AD. Notably, these effects were regulated by PPARα. Based on our results, we suggest that HDFn-Ex is a potential candidate for treating AD by recovering skin barrier dysfunction and exhibiting anti-inflammatory activity.

Comparing underwater endoscopic submucosal dissection and conventional endoscopic submucosal dissection for large laterally spreading tumor: a randomized controlled trial (with video).

BACKGROUND AND AIMS: Colorectal endoscopic submucosal dissection (ESD) is challenging despite its usefulness. Underwater ESD (UESD) provides better traction and a clearer view of the submucosal layer than conventional ESD (CESD). This study compared the efficiency of UESD and CESD for large (20-50 mm) laterally spreading tumors (LSTs). METHODS: Preplanned sample size was calculated from our previous experience. As a result, 28 patients were required for the UESD group and CESD group each. The primary outcome was total procedure time; the secondary outcome was dissection speed. RESULTS: Fifty-six patients were enrolled, and a total of 28 patients were assigned to each group. The mean LST size was 31.6 mm and 31.3 mm in the UESD and CESD groups, respectively. Fibrosis was observed in 67.9% and 60.7% of patients in the UESD and CESD groups. Total procedure time (mean ± standard deviation) for the UESD group was significantly shorter than that for the CESD group (49.5 ± 20.3 minutes vs 75.7 ± 36.1 minutes; mean difference, -26.2 minutes; 95% confidence interval, -42.0 to -10.5 minutes). Dissection speed of the UESD group was significantly faster than that of the CESD group (21.9 ± 6.9 mm2/min vs 15.2 ± 7.3 mm2/min; mean difference, 6.7 mm2/min; 95% confidence interval, 2.8 to 10.4 mm2/min). There was no difference between groups in the R0 resection rate or en bloc resection rate. No perforations were observed in either group. CONCLUSIONS: UESD was superior to CESD in total procedure time and dissection speed. UESD can be recommended as the preferred method for the resection of large LSTs.

Correlation of LLT-1 and NLRC4 inflammasome and its effect on glioblastoma prognosis.

PURPOSE: LLT-1 is a well-known ligand for the natural killer (NK) cell inhibitory receptor NKRP1A. Here, we examined NLRC4 inflammasome components and LLT-1 expression in glioblastoma (GBM) tissues to elucidate potential associations and interactions between these factors. METHODS: GBM tissues were collected for RNA sequencing (RNA-seq) and Immunofluorescent experiments. Colocalization of LLT-1 and other proteins was assessed by immunofluorescence. Computational analyses utilized RNA-seq data from 296 to 52 patients from the Chinese Glioma Genome Atlas and CHA medical records, respectively. These data were subjected to survival, non-negative matrix factorization clustering, Gene Ontology enrichment, and protein-protein interaction analyses. Receptor-ligand interactions between tumor and immune cells were confirmed by single-cell RNA-seq analysis. RESULTS: In GBM tissues, LLT-1 was predominantly colocalized with glial fibrillary acidic protein (GFAP)-expressing astrocytes, but not with microglial markers like Iba-1. Additionally, LLT-1 and activated NLRC4 inflammasomes were mainly co-expressed in intratumoral astrocytes, suggesting an association between LLT-1, NLRC4, and glioma malignancy. High LLT-1 expression correlates with poor prognosis, particularly in the mesenchymal subtype, and is associated with TNF and NOD-like receptor signaling pathway enrichment, indicating a potential role in tumor inflammation and progression. At the single-cell level, mesenchymal-like malignant cells showed high NF, NLR, and IL-1 signaling pathway enrichment compared to other malignant cell types. CONCLUSION: We revealed an association between NLRC4 inflammasome activity and LLT-1 expression, suggesting a novel regulatory pathway involving TNF, inflammasomes, and IL-1, potentially offering new NK-cell-mediated anti-glioma approaches.

Cold Plasma Ameliorates Imiquimod-Induced Psoriasis-Like Skin Inflammation in Mice.

OBJECTIVES: Cold plasma has shown efficacy in various dermatological applications by reduces inflammatory responses and modulating cytokine expression. Therefore, this study aimed to investigate the therapeutic effects of cold plasma on psoriasis. METHODS: In psoriasis HaCaT cells with cold plasma, we confirmed the expression of inflammatory cytokines involved in psoriasis formation and MAPK pathway, cell cycle, and apoptosis-related factors. In psoriasis-like BALB/c mice model, the effects of cold plasma treatment on skin were visually assessed. The expression of psoriasis-related factors was confirmed through qPCR, Western blotting, and Immunohistochemistry. RESULTS: Cold plasma led to a reduction in inflammatory cytokines including IL-17A, IL-23A, IL-24, IL-1ß, and TNF-α in the psoriasis cell line. It also modulated factors involved in the MAPK pathway and the cell cycle. In the psoriasis-like mice model, cold plasma resulted in improvements in skin thickness, erythema, scaling, and PASI. Additionally, decreases in inflammatory cytokines like INF-γ, IL-23, and S100a7 were observed, along with improvements in MAPK pathway activation, apoptosis, and other psoriasis-related factors. CONCLUSION: Through in vitro and in vivo studies, our research highlights the potential of cold plasma as a novel therapeutic approach for psoriasis. Furthermore, cold plasma could serve as an adjunctive treatment for skin immunological diseases.

Single acute and repeated subacute toxicity evaluations of Annona atemoya leaf extract with in vitro anti-inflammatory potential.

The nutraceutical and biological potential of Annona atemoya, a fruiting plant, has been reported. We and others have demonstrated that A. atemoya leaf extract (AAL) has various pharmacological properties, such as antioxidant, antimicrobial, and neuroprotective effects. However, knowledge about the safety and potential toxicity of AAL remains limited. We aimed to assess the potential toxicity of AAL using acute and repeated subacute oral toxicity tests in rats. In both acute and repeated subacute toxicity test, no AAL-related behavioral abnormalities or changes in mortality, food intake, body weight were observed up to a dosage of 2000 mg/kg, indicating that the median lethal dose of AAL is higher than 2000 mg/kg. In subacute toxicity tests, no significant changes in hematological and biochemical parameters, urinalysis results, and histopathological variables were observed. Therefore, the no-observed-adverse-effect level (NOAEL) of orally administered AAL was estimated to be 2000 mg/kg/day in male and female rats. We also examined the effect of AAL on the inflammatory reaction in lipopolysaccharide (LPS)-stimulated BV-2 cells. AAL treatment significantly inhibited the LPS-stimulated increases in the levels of nitric oxide (NO) and inflammatory cytokines, implying that AAL has an anti-inflammatory effect. Quality control analysis revealed that two marker compounds, rutin and isoquercitrin, were present at 27.570 and 4.322 mg/g, respectively, in a freeze-dried AAL sample and were completely eluted within 27 min. The extraction recovery was 99.47-103.80%, and the precision was ≤2.79%. Overall, these findings suggest the safety, anti-inflammatory activity, and standardization of AAL.

OsLRR-RLP2 Gene Regulates Immunity to Magnaporthe oryzae in Japonica Rice.

Rice is an important cereal crop worldwide, the growth of which is affected by rice blast disease, caused by the fungal pathogen Magnaporthe oryzae. As climate change increases the diversity of pathogens, the disease resistance genes (R genes) in plants must be identified. The major blast-resistance genes have been identified in indica rice varieties; therefore, japonica rice varieties with R genes now need to be identified. Because leucine-rich repeat (LRR) domain proteins possess R-gene properties, we used bioinformatics analysis to identify the rice candidate LRR domain receptor-like proteins (OsLRR-RLPs). OsLRR-RLP2, which contains six LRR domains, showed differences in the DNA sequence, containing 43 single-nucleotide polymorphisms (SNPs) in indica and japonica subpopulations. The results of the M. oryzae inoculation analysis indicated that indica varieties with partial deletion of OsLRR-RLP2 showed susceptibility, whereas japonica varieties with intact OsLRR-RLP2 showed resistance. The oslrr-rlp2 mutant, generated using clustered regularly interspaced palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), showed increased pathogen susceptibility, whereas plants overexpressing this gene showed pathogen resistance. These results indicate that OsLRR-RLP2 confers resistance to rice, and OsLRR-RLP2 may be useful for breeding resistant cultivars.

Qualitative Analysis of Nitrogen and Sulfur Compounds in Vacuum Gas Oils via Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry.

Analysis of the heavy fractions in crude oil has been important in petroleum industries. It is well known that heavy fractions such as vacuum gas oils (VGOs) include heteroatoms, of which sulfur and nitrogen are often characterized in many cases. We conducted research regarding the molecular species analysis of VGOs. Further refine processes using VGOs are becoming important when considering carbon recycling. In this work, we attempted to classify compounds within VGOs provided by Kuwait Institute for Scientific Research. Two VGOs were priorly distillated from Kuwait Export crude and Lower Fars crude. Quantitative analysis was performed mainly using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOFMS). MALDI-TOF-MS has been developed for analyzing high-molecular-weight compounds such as polymer and biopolymers. As matrix selection is one of the most important aspects in MALDI-TOFMS, the careful selection of a matrix was firstly evaluated, followed by analysis using a Kendrick plot with nominal mass series (z*). The objective was to evaluate if this work could provide an effective classification of VGOs compounds. The Kendrick plot is a well-known method for processing mass data. The difference in the Kendrick mass defect (KMD) between CnH2n-14S and CnH2n-20O is only 0.0005 mass units, which makes it difficult in general to distinguish these compounds. However, since the z* value showed effective differences during the classification of these compounds, qualitative analysis could be possible. The analysis using nominal mass series showed the potential to be used as an effective method in analyzing heavy fractions.

Neuregulin-1 reverses anxiety-like behavior and social behavior deficits induced by unilateral micro-injection of CoCl2 into the ventral hippocampus (vHPC).

Neuregulin-1 (NRG1) is an epidermal growth factor family member with essential roles in the developing and adult nervous systems. In recent years, establishing evidence has collectively suggested that NRG1 is a new modulator of central nervous system (CNS) injury and disease, with multifaceted roles in neuroprotection, remyelination, neuroinflammation, and other repair mechanisms. NRG1 signaling exerts its effects via the tyrosine kinase receptors ErbB2-ErbB4. The NRG1/ErbB network in CNS pathology and repair has evolved, primarily in recent years. In the present study, we demonstrated that a unilateral microinjection of CoCl2 into the ventral hippocampus (vHPC) induced hypoxic insult and led to anxiety-related behaviors and deficit sociability in mice. NRG1 treatment significantly alleviated the CoCl2-induced increase of hypoxic-related molecules and behavioral abnormalities. Furthermore, NRG1 reduced the CoCl2-induced neuroinflammation and neuronal deficits in the vHPC or primary hippocampal neurons in mice. Collectively, these results suggest that NRG1 ameliorates hypoxia by alleviating synaptic deficits and behavioral abnormalities of the CoCl2-induced vHPC hypoxic model.

Exploring the Magnetic Properties of Individual Barcode Nanowires using Wide-Field Diamond Microscopy.

A barcode magnetic nanowire typically comprises a multilayer magnetic structure in a single body with more than one segment type. Interestingly, due to selective functionalization and novel interactions between the layers, it has attracted significant attention, particularly in bioengineering. However, analyzing the magnetic properties at the individual nanowire level remains challenging. Herein, the characterization of a single magnetic nanowire is investigated at room temperature under ambient conditions based on magnetic images obtained via wide-field quantum microscopy with nitrogen-vacancy centers in diamond. Consequently, critical magnetic properties of a single nanowire can be extracted, such as saturation magnetization and coercivity, by comparing the experimental result with that of micromagnetic simulation. This study opens up the possibility for a versatile in situ characterization method suited to individual magnetic nanowires.

A myosin XI adaptor, TAPE, is essential for pollen tube elongation in rice.

Pollen tube (PT) elongation is important for double fertilization in angiosperms and affects the seed-setting rate and, therefore, crop productivity. Compared to Arabidopsis (Arabidopsis thaliana L.), information on PT elongation in rice (Oryza sativa L.) is limited by the difficulty in obtaining homozygous mutants. In a screen of T-DNA insertional mutants, we identified a mutant in the Tethering protein of actomyosin transport in pollen tube elongation (TAPE) gene with an unusual segregation ratio by genotyping analysis. A CRISPR/Cas9 knockout mutant of TAPE that produced a short PT was sterile, and TAPE was expressed specifically in pollen grains. TAPE is a homolog of a myosin XI adaptor in Arabidopsis with three tetratricopeptide repeat and Phox and Bem1 protein domains. TAPE showed latrunculin B-sensitive, actin-dependent localization to the endoplasmic reticulum. Yeast two-hybrid screening and transcriptome analysis revealed that TAPE interacted with pollen-specific LIM protein 2b and elongation factor 1-alpha. Loss of TAPE affected transcription of 1,259 genes, especially genes related to cell organization, which were downregulated. In summary, TAPE encodes a myosin XI adaptor essential for rice PT elongation.

Grass-Specific EPAD1 Is Essential for Pollen Exine Patterning in Rice.

The highly variable and species-specific pollen surface patterns are formed by sporopollenin accumulation. The template for sporopollenin deposition and polymerization is the primexine that appears on the tetrad surface, but the mechanism(s) by which primexine guides exine patterning remain elusive. Here, we report that the Poaceae-specific EXINE PATTERN DESIGNER 1 (EPAD1), which encodes a nonspecific lipid transfer protein, is required for primexine integrity and pollen exine patterning in rice (Oryza sativa). Disruption of EPAD1 leads to abnormal exine pattern and complete male sterility, although sporopollenin biosynthesis is unaffected. EPAD1 is specifically expressed in male meiocytes, indicating that reproductive cells exert genetic control over exine patterning. EPAD1 possesses an N-terminal signal peptide and three redundant glycosylphosphatidylinositol (GPI)-anchor sites at its C terminus, segments required for its function and localization to the microspore plasma membrane. In vitro assays indicate that EPAD1 can bind phospholipids. We propose that plasma membrane lipids bound by EPAD1 may be involved in recruiting and arranging regulatory proteins in the primexine to drive correct exine deposition. Our results demonstrate that EPAD1 is a meiocyte-derived determinant that controls primexine patterning in rice, and its orthologs may play a conserved role in the formation of grass-specific exine pattern elements.

Phytochemistry of ginsenosides: Recent advancements and emerging roles.

Ginsenosides, a group of tetracyclic saponins, accounts for the nutraceutical and pharmaceutical relevance of the ginseng (Panax sp.) herb. Owing to the associated therapeutic potential of ginsenosides, their demand has been increased significantly in the last two decades. However, a slow growth cycle, low seed production, and long generation time of ginseng have created a gap between the demand and supply of ginsenosides. The biosynthesis of ginsenosides involves an intricate network of pathways with multiple oxidation and glycosylation reactions. However, the exact functions of some of the associated genes/proteins are still not completely deciphered. Moreover, ginsenoside estimation and extraction using analytical techniques are not feasible with high efficiency. The present review is a step forward in recapitulating the comprehensive aspects of ginsenosides including their distribution, structural diversity, biotransformation, and functional attributes in both plants and animals including humans. Moreover, ginsenoside biosynthesis in the potential plant sources and their metabolism in the human body along with major regulators and stimulators affecting ginsenoside biosynthesis have also been discussed. Furthermore, this review consolidates biotechnological interventions to enhance the biosynthesis of ginsenosides in their potential sources and advancements in the development of synthetic biosystems for efficient ginsenoside biosynthesis to meet their rising industrial demands.

Pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation in children: a propensity score-matched analysis.

OBJECTIVES: To investigate the incidence, risk factors, and clinical outcomes of pleuroparenchymal fibroelastosis (PPFE) in pediatric hematopoietic stem cell transplantation (HSCT) recipients. METHODS: This single-center, retrospective, case-control study included 738 consecutive patients who underwent chest CT more than 3 months after HSCT. We identified patients who fulfilled the diagnostic criteria for PPFE and assessed their clinical characteristics and radiologic findings. Propensity score-matched analysis was performed using four covariates (age, sex, HSCT type, and primary disease). The risk factors and clinical outcomes of PPFE were analyzed using the Fine and Gray regression model and stratified log-rank test in the matched groups. RESULTS: PPFE was identified in 4% (31/738, 8.3 ± 3.1 years, 15 males) of the pediatric HSCT recipients with a median time of 2.7 years after HSCT, and it occurred following allogeneic (5%, 15/317), autologous (4%, 15/379), or both (2%, 1/42). Matching yielded 30 and 130 cases in the PPFE and control groups, respectively. The PPFE group showed more frequent late-onset noninfectious pulmonary complications (LONIPCs) and pneumonia more than 3 months after HSCT (p < 0.05). Multivariable analysis showed a significantly higher risk of PPFE in HSCT recipients who had pneumonia more than 3 months after HSCT (hazard ratio = 10.78 [95% confidence interval: 4.29, 27.13], p < 0.001). The PPFE group showed higher mortality (73%, 22/30) and poorer median overall survival (6.8 years [95% confidence interval: 4.1, 9.5]) than the control group (p < 0.001). CONCLUSIONS: PPFE represents a severe type of LONIPC after HSCT. HSCT recipients with pneumonia after HSCT may have an increased risk of PPFE. KEY POINTS: • The incidence of pleuroparenchymal fibroelastosis is not negligible (4%), and it can occur after either allogeneic or autologous hematopoietic stem cell transplantation. • Pleuroparenchymal fibroelastosis after hematopoietic stem cell transplantation showed poor outcome with a high mortality rate of 73% and median overall survival of 6.8 years. • After hematopoietic stem cell transplantation, pneumonia may increase the risk of pleuroparenchymal fibroelastosis development in children. • Lung biopsy should not be indicated in patients with pleuroparenchymal fibroelastosis findings on chest CT as it can cause refractory pneumothorax without helping the diagnosis.

Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy.

BACKGROUND: The present study was designed to explore the pathological role of non-canonical NLRC4 inflammasome in glioma. METHODS: This retrospective study included bioinformatical analysis, including survival, gene ontology, ssGSEA, cox regression, IPA and drug repositioning with TCGA and DepMap database. Experimental validations were conducted in glioma patient's sample and evaluated with histological or cellular functional analysis. RESULT: Clinical dataset analysis revealed that non-canonical NLRC4 inflammasomes significantly contribute to glioma progression and poor survival rates. Experimental validation was revealed that the expression of non-canonical NLRC4 inflammasomes were co-localized with astrocytes in malignant gliomas, with a sustained clinical correlation observed between astrocytes and inflammasome signatures. Indeed, the formation of an inflammatory microenvironment increased in malignant gliomas, leading to pyroptosis, known as inflammatory cell death. Molecular interaction analysis revealed that NF-κB pathways potentially serve as the connecting point between the canonical and noncanonical pathways of the NLRC4 inflammasome. Finally, drug repositioning analysis of non-canonical NLRC4 inflammasome-associated molecules revealed that MK-5108, PF4981517, and CTEP may represent effective options for glioma therapy. CONCLUSION: The findings of this study suggest that non-canonical NLRC4 inflammasomes contribute to poor prognosis in patients with glioma and induce an inflammatory microenvironment. We propose the pathological phenomenon of non-canonical NLRC4 inflammasomes and several therapeutic strategies based on the modulation of the inflammatory tumor microenvironment.

Phototoxicity-free blue light for enhancing therapeutic angiogenic efficacy of stem cells.

Low-level light therapy (LLLT) is a safe and noninvasive technique that has drawn attention as a new therapeutic method to treat various diseases. However, little is known so far about the effect of blue light for LLLT due to the generation of reactive oxygen species (ROS) that can cause cell damage. We introduced a blue organic light-emitting diode (bOLED) as a safe and effective light source that could generate a low amount of heat and luminance compared to conventional light sources (e.g., light-emitting diodes). We compared phototoxicity of bOLED light with different light fluences to human adipose-derived stem cells (hADSC). We further explored molecular mechanisms involved in the therapeutic efficacy of bOLED for enhancing angiogenic properties of hADSC, including intracellular ROS control in hADSCs. Using optimum conditions of bOLED light proposed in this study, photobiomodulation and angiogenic properties of hADSCs were enhanced. These findings might open new methods for using blue light in LLLT. Such methods can be implemented in future treatments for ischemic disease.

Extracorporeal cardiopulmonary resuscitation for adult out-of-hospital cardiac arrest patients: time-dependent propensity score-sequential matching analysis from a nationwide population-based registry.

BACKGROUND: There is inconclusive evidence regarding the effectiveness of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) patients. We aimed to evaluate the association between ECPR and neurologic recovery in OHCA patients using time-dependent propensity score matching analysis. METHODS: Using a nationwide OHCA registry, adult medical OHCA patients who underwent CPR at the emergency department between 2013 and 2020 were included. The primary outcome was a good neurological recovery at discharge. Time-dependent propensity score matching was used to match patients who received ECPR to those at risk for ECPR within the same time interval. Risk ratios (RRs) and 95% confidence intervals (CIs) were estimated, and stratified analysis by the timing of ECPR was also performed. RESULTS: Among 118,391 eligible patients, 484 received ECPR. After 1:4 time-dependent propensity score matching, 458 patients in the ECPR group and 1832 patients in the no ECPR group were included in the matched cohort. In the matched cohort, ECPR was not associated with good neurological recovery (10.3% in ECPR and 6.9% in no ECPR; RR [95% CI] 1.28 [0.85-1.93]). In the stratified analyses according to the timing of matching, ECPR with a pump-on within 45 min after emergency department arrival was associated with favourable neurological outcomes (RR [95% CI] 2.51 [1.33-4.75] in 1-30 min, 1.81 [1.11-2.93] in 31-45 min, 1.07 (0.56-2.04) in 46-60 min, and 0.45 (0.11-1.91) in over 60 min). CONCLUSIONS: ECPR itself was not associated with good neurological recovery, but early ECPR was positively associated with good neurological recovery. Research on how to perform ECPR at an early stage and clinical trials to evaluate the effect of ECPR is warranted.

Novel terpestacin derivatives with l-amino acid residue as anticancer agents against U87MG-derived glioblastoma stem cells.

Based on the natural product terpestacin, seventeen derivatives (1-17) with various l-amino acid side chains were designed and synthesized. Their anticancer activities against U87MG-derived glioblastoma stem cells (GSCs) were evaluated, and compounds 5, 11, 13 and 15 showed strong abilities to inhibit the proliferation (IC50 = 2.8-6.9 µM) and tumorsphere formation of GSCs. Besides, compounds 13 and 15 could effectively induce apoptosis and significantly inhibit the invasion of GSCs (95 and 97 % inhibition, respectively, at 2.5 µM). The levels of CD133 marker in GSCs also decreased in dose-dependent manners after the treatment of these active compounds. Compared to terpestacin and the positive control A1938, our derivatives showed stronger activities and compounds 13 and 15 are promising candidates for further development as anticancer agents by targeting GSCs.

A comparison of dyeing efficacy between hair-oxidation-based and hair-coating-based shampoos for the treatment of gray hair.

BACKGROUND: The process of hair dyeing causes hair damage, and periodic re-dyeing is required for newly grown hair. To avoid these hassles, hair color shampoos have been developed and are widely used. In this study, we compared the effects of two hair color shampoos with different dyeing principles to analyze the function of hair color shampoos. We analyzed hair tresses treated by hair-oxidation- and hair-coating-based shampoos. MATERIALS AND METHODS: We measured the color, tensile properties, softness, elasticity, gloss, moisture content, and protein content of the hair tresses dyed with color shampoos. The hair structures were analyzed by scanning and transmission electron microscopies (SEM and TEM) and a hydroxy radical-based method. RESULTS: The shampoo based on hair coating enhanced the hair dyeing effect and roughness, whereas that based on hair oxidation improved the color retention and moisture content in the hair tresses. Frictional resistance, gloss, and elasticity of the hair tresses were similar for the two products. However, according to the results of the protein loss test, TEM, and hydroxyl radical staining, the shampoo based on hair oxidation showed a longer dyeing retention compared to that based on hair coating but caused cuticle damage. CONCLUSION: These results show that the two shampoos with different dyeing principles exhibit different hair dyeing abilities and hair health indices. Therefore, we recommend that hair color shampoos should be used according to the requirements of an individual.