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BACKGROUND: This study aims to identify distinct microbial and functional biomarkers characteristic of body-first or brain-first subtypes of Parkinson's disease (PD). This could illuminate the unique pathogenic mechanisms within these subtypes. METHODS: In this cross-sectional study, we classified 36 well-characterized PD patients into body-first, brain-first, or undetermined subtypes based on the presence of premotor REM sleep behavior disorder (RBD) and cardiac meta-iodobenzylguanidine (MIBG) uptake. We then conducted an in-depth shotgun metagenomic analysis of the gut microbiome for each subtype and compared the results with those from age- and sex-matched healthy controls. RESULTS: Significant differences were found in the gut microbiome of body-first PD patients (n = 15) compared to both brain-first PD patients (n = 9) and healthy controls. The gut microbiome in body-first PD showed a distinct profile, characterized by an increased presence of Escherichia coli and Akkermansia muciniphila, and a decreased abundance of short-chain fatty acid-producing commensal bacteria. These shifts were accompanied by a higher abundance of microbial genes associated with curli protein biosynthesis and a lower abundance of genes involved in putrescine and spermidine biosynthesis. Furthermore, the combined use of premotor RBD and MIBG criteria was more strongly correlated with these microbiome differences than the use of each criterion independently. CONCLUSIONS: Our findings highlight the significant role of dysbiotic and pathogenic gut microbial alterations in body-first PD, supporting the body-first versus brain-first hypothesis. These insights not only reinforce the gut microbiome's potential as a therapeutic target in PD but also suggest the possibility of developing subtype-specific treatment strategies.

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BACKGROUND: Androgenetic alopecia (AGA) is a common form of hair loss. Androgens, such as testosterone and dihydrotestosterone, are the main causes of AGA. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) can reduce AGA. However, preparing therapeutic doses of MSCs for clinical use is challenging. Induced pluripotent stem cell-derived MSCs (iMSCs) are homogenous and easily expandable, enabling scalable production of EVs. Hyaluronic acid (HA) can exert various functions including free radical scavenging, immune regulation, and cell migration. Herein, we examined whether hyaluronic acid (HA) stimulation of iMSCs could produce EVs with enhanced therapeutic outcomes for AGA. METHODS: EVs were collected from iMSCs primed with HA (HA-iMSC-EVs) or without HA (iMSC-EVs). The characteristics of EVs were examined using dynamic light scattering, cryo-transmission electron microscopy, immunoblotting, flow cytometry, and proteomic analysis. In vitro, we compared the potential of EVs in stimulating the survival of hair follicle dermal papilla cells undergoing testosterone-mediated AGA. Additionally, the expression of androgen receptor (AR) and relevant growth factors as well as key proteins of Wnt/ß-catenin signaling pathway (ß-catenin and phosphorylated GSK3ß) was analyzed. Subsequently, AGA was induced in male C57/BL6 mice by testosterone administration, followed by repeated injections of iMSC-EVs, HA-iMSC-EVs, finasteride, or vehicle. Several parameters including hair growth, anagen phase ratio, reactivation of Wnt/ß-catenin pathway, and AR expression was examined using qPCR, immunoblotting, and immunofluorescence analysis. RESULTS: Both types of EVs showed typical characteristics for EVs, such as size distribution, markers, and surface protein expression. In hair follicle dermal papilla cells, the mRNA levels of AR, TGF-ß, and IL-6 increased by testosterone was blocked by HA-iMSC-EVs, which also contributed to the augmented expression of trophic genes related to hair regrowth. However, no notable changes were observed in the iMSC-EVs. Re-activation of Wnt/ß-catenin was observed in HA-iMSC-EVs but not in iMSC-EVs, as shown by ß-catenin stabilization and an increase in phosphorylated GSK3ß. Restoration of hair growth was more significant in HA-iMSC-EVs than in iMSC-EVs, and was comparable to that in mice treated with finasteride. Consistently, the decreased anagen ratio induced by testosterone was reversed by HA-iMSC-EVs, but not by iMSC-EVs. An increased expression of hair follicular ß-catenin protein, as well as the reduction of AR was observed in the skin tissue of AGA mice receiving HA-iMSC-EVs, but not in those treated with iMSC-EVs. CONCLUSIONS: Our results suggest that HA-iMSC-EVs have potential to improve AGA by regulating growth factors/cytokines and stimulating AR-related Wnt/ß-catenin signaling.

Asunto(s)

Alopecia , Vesículas Extracelulares , Folículo Piloso , Ácido Hialurónico , Células Madre Mesenquimatosas , Vesículas Extracelulares/metabolismo , Alopecia/terapia , Alopecia/metabolismo , Alopecia/tratamiento farmacológico , Ácido Hialurónico/farmacología , Ácido Hialurónico/metabolismo , Animales , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Folículo Piloso/metabolismo , Folículo Piloso/efectos de los fármacos , Humanos , Vía de Señalización Wnt/efectos de los fármacos , Masculino , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/citología , Testosterona/farmacología , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ratones Endogámicos C57BL

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Debris flow hazards are often interpreted through back-calculated simulation analysis or empirical methods. The mobility of a debris flow is greatly influenced by mechanical and hydrological parameters. The strength parameters play important roles in the debris flow initiation and flow stages. In particular, the rheological parameters of yield strength and plastic viscosity directly affect the debris flow runout distance and velocity. One of the most important parameters to consider when evaluating debris flow hazards is the shear strength. This strength is called the residual shear strength in the failure stage and the yield strength in the post-failure stage. The residual shear strength obtained from ring shear tests can be related to the initiation of mass movements; the yield strength obtained from rheological tests can be related to the mobilization of debris flows. The residual shear stresses obtained from ring shear tests of weathered soils typically range between 10 and 100 kPa and strongly depend on the normal stress and shear velocity. When progressive slope failure (i.e., strain-softening behavior) occurs at a relatively shallow slope depth (e.g., < 1 m), the soil strength ranges from approximately 5-10 kPa. If the liquid limit state (i.e., solid‒liquid transition) is reached, the shear strength of the soil is approximately 2 kPa. Once the soil fails and mixes with ambient water along the slip surface, the yield strength decreases dramatically, resulting in high mobilization. A suggestion on how strength parameters can be applied to estimate debris flow mobility is presented by considering the 2011 Miryang debris flow, which occurred in weathered soil deposits in Miryang city, Republic of Korea. The best approach for debris flow yield strength estimation would be to consider the residual shear strength in the initiation stage, the yield strength in the flow stage, and the reduction in yield strength with the entrainment effect of the flow in the rapid fluidization stage.

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Herpes zoster (HZ), or shingles, is caused by reactivation of the varicella-zoster virus (VZV), which remains latent in the sensory ganglia until immunity wanes with age. The representative HZ vaccine, Shingrix is efficacious but causes side effects due to vaccine adjuvants. Therefore, the development of highly efficacious vaccines with minimal side effects is required. We developed chimeric adenovirus vector (ChimAd)-based HZ vaccine candidates encoding the VZV glycoprotein E (gE). These candidates include ChimAd-tPAgE, in which the signal peptide is replaced with tissue plasminogen activator (tPA), and ChimAd-WTgE, which retains the original signal peptide. C57BL/6 mice were immunized with VZV-vaccine candidates, and cellular and humoral immune responses were evaluated using interferon-γ ELISPOT and ELISA. The ChimAd-based HZ vaccines induced high levels of gE-specific antibodies and cell-mediated immunity. ChimAd-tPAgE (optimal dose: 1 × 107 IFU) elicited a more robust gE-specific T-cell response than Shingrix and Zostavax, showing potential as HZ prophylactic vaccines.

RESUMEN

This study focuses on the discovery of a single-component molecular resist for extreme ultraviolet (EUV) lithography by employing the ionizing radiation-induced decomposition of carbon-fluorine chemical bonds. The target material, DHP-L6, was synthesized by bonding perfluoroalkyl ether moieties to amorphous dendritic hexaphenol (DHP) with a high glass transition temperature. Upon exposure to EUV and electron beam irradiation, DHP-L6 films exhibited a decreasing solubility in fluorous developer media, resulting in negative-tone images. The underlying chemical mechanisms were elucidated by Fourier transform-infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy, and nanoindentation experiments. These analyses highlighted the possible electron-induced decomposition of C-F bonds in DHP-L6, leading to molecular network formation via recombination of the resulting C-centered radicals. Subsequent high-resolution lithographic patterning under EUV irradiation showed that DHP-L6 could create stencil patterns with a line width of 26 nm at an exposure dose of 110 mJ cm-2. These results confirm that single-component small molecular compounds with fluoroalkyl moieties can be employed as patterning materials under ionizing radiation. Nonetheless, additional research is required to reduce the relatively high exposure energy for high-resolution patterning and to enhance the line-edge roughness of the produced stencil.

Asunto(s)

Psoriasis , Índice de Severidad de la Enfermedad , Ustekinumab , Uveítis , Humanos , Psoriasis/tratamiento farmacológico , Ustekinumab/uso terapéutico , Ustekinumab/efectos adversos , Femenino , Masculino , Persona de Mediana Edad , Uveítis/tratamiento farmacológico , Adulto , Factores de Riesgo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adalimumab/uso terapéutico , Adalimumab/efectos adversos , Resultado del Tratamiento , Etanercept/uso terapéutico , Etanercept/efectos adversos , Medición de Riesgo , Fármacos Dermatológicos/uso terapéutico , Fármacos Dermatológicos/efectos adversos , Infliximab/uso terapéutico , Infliximab/efectos adversos

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Despite recent advances in cancer diagnostics and treatment, the mortality associated with lung cancer is still the highest in the world. Late-stage diagnosis, often accompanied by metastasis, is a major contributor to the high mortality rates, emphasizing the urgent need for reliable and readily accessible diagnostic tools that can detect biomarkers unique to lung cancer. Circulating factors, such as circulating tumor DNA and extracellular vesicles, from liquid biopsy have been recognized as diagnostic or prognostic markers in lung cancer. Numerous clinical studies are currently underway to investigate the potential of circulating tumor DNA, circulating tumor RNA, exosomes, and exosomal microRNA within the context of lung cancer. Those clinical studies aim to address the poor diagnostics and limited treatment options for lung cancer, with the ultimate goal of developing clinical markers and personalized therapies. In this review, we discuss the roles of each circulating factor, its current research status, and ongoing clinical studies of circulating factors in non-small cell lung cancer. Additionally, we discuss the circulating factors specifically found in lung cancer stem cells and examine approved diagnostic assays designed to detect circulating biomarkers in lung cancer patients.

RESUMEN

Neuropeptides are small molecules that mediate intercellular signaling and regulate physiological processes. Starfish possess various myoactive neuropeptides, including starfish myorelaxant peptide (SMP) and a calcitonin-type peptide with apical muscle relaxing properties. In this study, we report the purification of a neuropeptide from starfish (Patiria pectinifera) pyloric caeca extract using high-performance liquid chromatography (HPLC) and an in vitro bioassay to screen for fractions and peptides with relaxing effects on P. pectinifera apical muscle preparations. A series of HPLC steps using reversed-phase and cation-exchange columns yielded a purified peptide with muscle-relaxing effects. The purified peptide's structure was determined by LC-MS and Edman degradation, revealing a pentapeptide with an amidated C-terminus (NGFFYamide) and a molecular mass of 646.2930 Da. This is the first report of NGFFYamide purification from P. pectinifera through biochemical methods. The nucleotide sequence encoding the NGFFYamide precursor was determined, showing the presence of a conserved neurophysin domain in the C-terminal region. RT-qPCR results confirmed high expression in radial nerves cord, consistent with previous findings on NG peptides in echinoderms. In vitro pharmacological studies on muscle preparations from P. pectinifera and Asterias amurensis revealed differential relaxing activity of NGFFYamide on apical muscles, while its effects on tube foot preparations were similar in both species. NGFFYamide also induced potent contraction in P. pectinifera cardiac stomach. Comparison of three NG peptides (NGFFYamide, NGFFFamide, and NGIWYamide) on P. pectinifera cardiac stomach revealed varying potency, suggesting class-specific receptor interactions. Tachyphylaxis was observed in P. pectinifera apical muscle but not in A. amurensis, warranting further investigation. Based on these results, it is plausible that NGFFYamide could be involved in regulating locomotion and feeding behavior in P. pectinifera, consistent with findings in Asterias rubens.

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Neuropéptidos , Estrellas de Mar , Animales , Neuropéptidos/farmacología , Neuropéptidos/aislamiento & purificación , Neuropéptidos/química , Neuropéptidos/genética , Estrellas de Mar/química , Secuencia de Aminoácidos , Cromatografía Líquida de Alta Presión , Relajación Muscular/efectos de los fármacos

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Background: The long-term goal of anterior cruciate ligament (ACL) reconstruction is to prevent secondary osteoarthritis due to instability. Obesity itself is also a risk factor for osteoarthritis and shows an increase in its incidence, but little is known about the relationship between obesity and the outcome of ACL reconstruction. Purpose/Hypothesis: This study aimed to determine the relationship between the outcome of ACL reconstruction and obesity. It was hypothesized that obesity would be associated with the revision rate of ACL reconstruction and additional surgical treatment for osteoarthritis in patients who undergo ACL reconstruction. Study design: Cohort study; Level of evidence, 3. Methods: Claims and health screening data of the National Health Insurance Service were used to analyze patients who underwent ACL reconstruction between January 1, 2003, and December 31, 2021. The association between obesity and risk of revision ACL reconstruction and additional surgical treatment for osteoarthritis or meniscal lesion was analyzed. Body mass index (BMI) was used to classify patients as underweight (BMI, <18.5), normal weight (BMI, 18.5-24.9), overweight (BMI, 25.0-29.9), obese (BMI, 30.0-39.9), or morbidly obese (BMI, ≥40.0). Multivariable Cox proportional hazards model analysis was conducted. Results: A total of 56,734 patients were included. Of them, 311 (0.5%) patients were underweight, 26,613 (46.9%) were normal weight, 24,372 (43.0%) were overweight, 5324 (9.4%) were obese, and 114 (0.2%) patients were morbidly obese. The underweight group showed a significantly lower risk of revision ACL reconstruction than the normal weight group (hazard ratio [HR], 0.54; 95% CI, 0.31-0.93; P = .0273). However, the overweight, obese, and morbidly obese groups had no significant difference from the normal weight group. The risk of high tibial osteotomy (HTO) or total knee arthroplasty (TKA) was significantly high for the overweight (HR, 1.93; 95% CI, 1.70-2.19; P < .0001) and obese (HR, 2.71; 95% CI, 2.23-3.30; P < .0001) groups. Subgroup analysis performed in patients ≥40 years of age for the risk of HTO showed a significant increased risk in the overweight group (HR, 1.889; 95% CI, 1.56-2.29; P < .0001) and obese group (HR, 2.78; 95% CI, 2.10-3.69; P < .0001). Subgroup analysis performed in patients ≥50 years of age for the risk of TKA also showed a significant increased risk in the overweight group (HR, 2.03; 95% CI, 1.67-2.47; P < .0001) and obese group (HR, 2.53; 95% CI, 1.83-3.50; P < .0001). After adjusting for meniscal injury at index surgery by multivariate regression analysis, 1.87- and 2.75-fold increased risks of HTO were identified for the overweight and obese groups, respectively, for patients aged >40 years. For patients aged >50 years, 2.02-fold and 2.52-fold increased risks of TKA were observed for the overweight and obese groups, respectively. The risk of additional surgery due to the meniscal lesion was high for the overweight (HR, 1.09; 95% CI, 1.03-1.15; P = .002) and obese (HR, 1.10; 95% CI, 1.01-1.21; P = .0351) groups, while no significant difference was found for the underweight and morbidly obese groups. Conclusion: This study highlights that obesity does not increase the revision rate of ACL reconstruction. However, the risk of additional surgical treatment for osteoarthritis and meniscal lesions increased as BMI increased. Further investigation is needed to determine the efficacy of ACL reconstruction for preventing osteoarthritis in obese patients.

RESUMEN

This randomised double-blind placebo-controlled trial evaluated the efficacy and safety of fermented gold kiwi (FGK) in improving gastrointestinal health. A total of 100 participants were enrolled and randomly assigned to treatment or placebo groups. Over 8 weeks, the participants consumed an FGK or placebo preparation daily. Primary outcomes included changes in gastrointestinal symptoms assessed using the Gastrointestinal Symptom Rating Scale (GSRS) and the Korean version of the Nepean Dyspepsia Index (NDI-K), as well as quality of life assessed using the Functional Dyspepsia-related Quality of Life questionnaire. The FGK group showed significant improvements in GSRS and NDI-K total and subdomain scores compared with the placebo group. Moreover, the quality of life scores were significantly better in the FGK group than in the placebo group. Safety evaluations revealed no significant adverse events or clinically meaningful changes upon assessing laboratory test results. This study demonstrated that FGK is a safe and effective dietary supplement for improving gastrointestinal health in adults with gastrointestinal symptoms.

Asunto(s)

Dispepsia , Calidad de Vida , Humanos , Método Doble Ciego , Femenino , Masculino , Adulto , Persona de Mediana Edad , Dispepsia/tratamiento farmacológico , Alimentos Fermentados , Resultado del Tratamiento , Suplementos Dietéticos , Fermentación

RESUMEN

There are many graft choices for anterior cruciate ligament (ACL) reconstruction, including autografts and allografts. The choice of graft has been identified as a significant factor affecting the outcome of ACL reconstruction. This study aimed to determine whether allograft or autograft is better for avoiding revisional ACL reconstruction. The National Health Insurance Service-Health screening database analyzed 146,122 patients who underwent ACL reconstruction surgery from Jan. 1, 2002, to Dec. 31, 2021. The study was conducted in two groups, autograft or allograft, and the rates of revision ACL reconstruction between the two groups were compared. Propensity score matching and multivariable Cox Proportional Hazard model analysis were used. The significant predictors for complications (p < 0.05) were as follows. The total of patients with ACL reconstruction was 146,122. Allograft was used in 121,148 patients, and autograft was used in 24,974 patients. 9.2% of the allograft group and 8.7% of the autograft group underwent revision ACL reconstruction. (P < .0001) 70.0% & 63.6% of patients underwent revision surgery within 1 year in the allograft & autograft groups, respectively. In summary, using autograft in primary ACL reconstruction is helpful in lowering the rate of revision surgery.

Asunto(s)

Reconstrucción del Ligamento Cruzado Anterior , Reoperación , Humanos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Masculino , Femenino , Estudios Retrospectivos , Adulto , Reoperación/estadística & datos numéricos , Adulto Joven , Persona de Mediana Edad , Adolescente , Autoinjertos , Lesiones del Ligamento Cruzado Anterior/cirugía , Trasplante Autólogo , Aloinjertos , Trasplante Homólogo/métodos , Ligamento Cruzado Anterior/cirugía

RESUMEN

BACKGROUND: It is necessary to determine whether the sequence of maxillary and mandibular surgeries in bimaxillary orthognathic surgery affects the accuracy of surgical outcomes. PURPOSE: The study aimed to measure and compare the accuracy among patients who underwent maxilla-first versus mandible-first bimaxillary surgery to correct a class III skeletal pattern. STUDY DESIGN, SETTING, SAMPLE: This retrospective cohort study included consecutive patients treated by a single surgeon at one center using Le Fort I and bilateral sagittal split osteotomy surgery. Exclusions included patients scheduled for one-jaw or maxilla-segmental surgery and those with craniofacial syndromes, such as clefts. PREDICTOR VARIABLE: The predictor variable was operative sequence for bimaxillary operations, divided into maxilla- or mandible-first groups. OUTCOME VARIABLE: The outcome variable was accuracy, measured using linear discrepancies between landmarks in the virtual plan and actual operative outcomes. The measurement of linear discrepancy that was closer to 0 was considered the more accurate result. COVARIATES: Sex, age, maxilla sagittal rotation degree, amount of posterior maxilla impaction, mandibular autorotation (°), and intermediate splint thickness (mm) were the covariates. ANALYSES: Statistical analysis was performed using Student's t-test and Pearson's correlation, with statistical significance set at P < .05. RESULTS: The sample comprised 60 patients with a mean age of 22.8 ± 3.7 years, of whom 36 (60%) were male. In the maxilla-first group, there were 30 subjects (60% male; mean age: 23.1 ± 4.2 years), with a mean mandibular autorotation of 0.41° (range: 0°-2.5°). The mandible-first group comprised 30 patients (60% male; mean age: 22.6 ± 3.3 years), with a mean mandibular autorotation of 5.46° (range: 1.9°-9.2°). The linear discrepancies for all landmarks did not significantly differ between mandible- and maxilla-first groups (P > .18). The mean three-dimensional discrepancies for all landmarks in maxilla-first group was 1.23 ± 0.5 mm and 1.23 ± 0.33 mm in mandible-first group, with no significant difference observed between the groups (P > .98). The amount of mandibular autorotation for intermediate splint application showed no significant correlation with the linear discrepancies (P > .58). CONCLUSION AND RELEVANCE: In patients with skeletal class III malocclusion, mandible-first surgery in bimaxillary orthognathic surgery demonstrates accurate outcomes comparable to maxilla-first surgery.

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We aimed to determine the relationship between the use of analgesics prescribed for pain management and the onset and progression of mood disorders using a large-scale cohort database. We calculated hazard ratios (HR) with 95% confidence intervals (CI) for patient risk of developing mood disorders based on age, income, health-related variables, disease history, Charlson comorbidity index, and analgesics prescription behavior (Models 1-3). Additionally, we determined the risk of mood disorder occurrence by age group (Model 4) using a proportional hazards regression model. The age- and income-adjusted HR (Model 1) was 1.8275. The age-, income-, BMI-, and physical-activity-adjusted HR (Model 2) was 1.882. The fully adjusted HR (Model 3) was 1.698. Compared with no analgesic use, nonregular use (HR = 1.386) and regular use (HR = 1.698) was associated with a higher risk of mood disorders. Among patients older than 50 years, those who participated in physical activity (less than five days) had a lower risk of mood disorders than those who did not. This suggests that it may be useful for preventing mood disorders in older cancer survivors. A high risk of comorbidities and regular use of analgesics are risk factors for developing mood disorders. Therefore, our results suggest that cancer survivors with a high risk of comorbidities and a history of regular analgesic use should undergo careful psychiatric consultation.

RESUMEN

Co-occurring mutations in KEAP1 in STK11/LKB1-mutant NSCLC activate NFE2L2/NRF2 to compensate for the loss of STK11-AMPK activity during metabolic adaptation. Characterizing the regulatory crosstalk between the STK11-AMPK and KEAP1-NFE2L2 pathways during metabolic stress is crucial for understanding the implications of co-occurring mutations. Here, we found that metabolic stress increased the expression and phosphorylation of SQSTM1/p62, which is essential for the activation of NFE2L2 and AMPK, synergizing antioxidant defense and tumor growth. The SQSTM1-driven dual activation of NFE2L2 and AMPK was achieved by inducing macroautophagic/autophagic degradation of KEAP1 and facilitating the AXIN-STK11-AMPK complex formation on the lysosomal membrane, respectively. In contrast, the STK11-AMPK activity was also required for metabolic stress-induced expression and phosphorylation of SQSTM1, suggesting a double-positive feedback loop between AMPK and SQSTM1. Mechanistically, SQSTM1 expression was increased by the PPP2/PP2A-dependent dephosphorylation of TFEB and TFE3, which was induced by the lysosomal deacidification caused by low glucose metabolism and AMPK-dependent proton reduction. Furthermore, SQSTM1 phosphorylation was increased by MAP3K7/TAK1, which was activated by ROS and pH-dependent secretion of lysosomal Ca2+. Importantly, phosphorylation of SQSTM1 at S24 and S226 was critical for the activation of AMPK and NFE2L2. Notably, the effects caused by metabolic stress were abrogated by the protons provided by lactic acid. Collectively, our data reveal a novel double-positive feedback loop between AMPK and SQSTM1 leading to the dual activation of AMPK and NFE2L2, potentially explaining why co-occurring mutations in STK11 and KEAP1 happen and providing promising therapeutic strategies for lung cancer.Abbreviations: AMPK: AMP-activated protein kinase; BAF1: bafilomycin A1; ConA: concanamycin A; DOX: doxycycline; IP: immunoprecipitation; KEAP1: kelch like ECH associated protein 1; LN: low nutrient; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEFs: mouse embryonic fibroblasts; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: NFE2 like bZIP transcription factor 2; NSCLC: non-small cell lung cancer; PRKAA/AMPKα: protein kinase AMP-activated catalytic subunit alpha; PPP2/PP2A: protein phosphatase 2; ROS: reactive oxygen species; PPP3/calcineurin: protein phosphatase 3; RPS6KB1/p70S6K: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TCL: total cell lysate; TFEB: transcription factor EB; TFE3: transcription factor binding to IGHM enhancer 3; V-ATPase: vacuolar-type H+-translocating ATPase.

RESUMEN

Marine organisms, such as sea urchins like Heliocidaris crassispina, produce bioactive substances with antimicrobial activity to protect themselves from the high density of microorganisms in their habitats. One such substance, Echinochrome A (Ech A), has been isolated from various sea urchins' shells and spines using strong acidic solutions and organic solvents. Ech A, however, has not been reported from the coelomic fluid of H. crassispina. In this study, we report the antimicrobial activity of H. crassispina coelomic fluid extract against various microbes, evaluating its potential for purifying potent antimicrobial materials. Upon confirming the extract as a promising source of antimicrobial materials, we isolated antimicrobial compounds from the extract. A series of HPLC steps were taken to purify antimicrobial materials from the H. crassispina coelomic fluid extract, resulting in the isolation of two single absorbance peaks showing antimicrobial activity against Staphylococcus aureus. One peak consisted of a single antimicrobial compound with a molecular weight (MW) corresponding to Ech A, while the other peak comprised five MWs inferred to be those of Ech A and its oxidative products. The elution of Ech A in two separate peaks may be attributable to the presence of Ech A's isomer, as reported in several previous studies. The use of the environmentally friendly extraction method in procurement of Ech A from the coelomic fluid would contribute to the implementation of risk-reducing extraction method for researchers studying Ech A from sea urchins.

Asunto(s)

Staphylococcus aureus , Animales , Staphylococcus aureus/efectos de los fármacos , Anthocidaris/química , Antiinfecciosos/farmacología , Antiinfecciosos/química , Erizos de Mar/química , Cromatografía Líquida de Alta Presión , Antibacterianos/farmacología , Antibacterianos/química , Naftoquinonas

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In the autonomous driving industry, there is a growing trend to employ long-wave infrared (LWIR)-based uncooled thermal-imaging cameras, capable of robustly collecting data even in extreme environments. Consequently, both industry and academia are actively researching contrast-enhancement techniques to improve the quality of LWIR-based thermal-imaging cameras. However, most research results only showcase experimental outcomes using mass-produced products that already incorporate contrast-enhancement techniques. Put differently, there is a lack of experimental data on contrast enhancement post-non-uniformity (NUC) and temperature compensation (TC) processes, which generate the images seen in the final products. To bridge this gap, we propose a histogram equalization (HE)-based contrast enhancement method that incorporates a region-based clipping technique. Furthermore, we present experimental results on the images obtained after applying NUC and TC processes. We simultaneously conducted visual and qualitative performance evaluations on images acquired after NUC and TC processes. In the visual evaluation, it was confirmed that the proposed method improves image clarity and contrast ratio compared to conventional HE-based methods, even in challenging driving scenarios such as tunnels. In the qualitative evaluation, the proposed method demonstrated upper-middle-class rankings in both image quality and processing speed metrics. Therefore, our proposed method proves to be effective for the essential contrast enhancement process in LWIR-based uncooled thermal-imaging cameras intended for autonomous driving platforms.

RESUMEN

With the continued evolution of DNA sequencing technologies, the role of genome sequence data has become more integral in the classification and identification of Bacteria and Archaea. Six years after introducing EzBioCloud, an integrated platform representing the taxonomic hierarchy of Bacteria and Archaea through quality-controlled 16S rRNA gene and genome sequences, we present an updated version, that further refines and expands its capabilities. The current update recognizes the growing need for accurate taxonomic information as defining a species increasingly relies on genome sequence comparisons. We also incorporated an advanced strategy for addressing underrepresented or less studied lineages, bolstering the comprehensiveness and accuracy of our database. Our rigorous quality control protocols remain, where whole-genome assemblies from the NCBI Assembly Database undergo stringent screening to remove low-quality sequence data. These are then passed through our enhanced identification bioinformatics pipeline which initiates a 16S rRNA gene similarity search and then calculates the average nucleotide identity (ANI). For genome sequences lacking a 16S rRNA sequence and without a closely related genomic representative for ANI calculation, we apply a different ANI approach using bacterial core genes for improved taxonomic placement (core gene ANI, cgANI). Because of the increase in genome sequences available in NCBI and our newly introduced cgANI method, EzBioCloud now encompasses a total of 109 835 species, of which 21 964 have validly published names. 47 896 are candidate species identified either through 16S rRNA sequence similarity (phylotypes) or through whole genome ANI (genomospecies), and the remaining 39 975 were positioned in the taxonomic tree by cgANI (species clusters). Our EzBioCloud database is accessible at www.ezbiocloud.net/db.

Asunto(s)

Archaea , Bacterias , Genoma Bacteriano , Microbiota , ARN Ribosómico 16S , ARN Ribosómico 16S/genética , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Archaea/genética , Archaea/clasificación , Filogenia , Bases de Datos Genéticas , Genoma Arqueal , Análisis de Secuencia de ADN , Biología Computacional/métodos

RESUMEN

BACKGROUND/AIMS: Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI. METHODS: A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups. RESULTS: The percentage change of LDL-C level at 1-3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1-3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001). CONCLUSION: Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.

Asunto(s)

Anticuerpos Monoclonales Humanizados , Anticolesterolemiantes , LDL-Colesterol , Infarto del Miocardio , Intervención Coronaria Percutánea , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , LDL-Colesterol/sangre , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Factores de Tiempo , Biomarcadores/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/sangre , Dislipidemias/diagnóstico , Inhibidores de PCSK9 , Proproteína Convertasa 9

RESUMEN

Tetramethylammonium hydroxide (TMAH), which is a chemical used in the electronic industry, is classified as a hazardous material (HAZMAT class 8) that threatens aquatic ecosystems and human health. Consequently, numerous studies have attempted to remove TMAH using various treatment methods, including advanced oxidation processes such as ozone, UV, or Fenton oxidation. However, prior research has indicated a low kinetic rate of TMAH removal. In this context, we proposed an alternative to TMAH degradation by combining a cold plasma (CP) process with periodate oxidation. As for the kinetics of TMAH removal, the kinetic constant was improved by 5 times (0.1661 and 0.0301 for 40.56 and 2.2 W, respectively) as the electric power of a CP system increased from 2.2 to 40.56 W. The kinetic constant of a 40.56 W CP system further increased by 54 times (1.6250) than a 2 W CP system when 4 mM periodate was used simultaneously. As a result, the integrated CP/periodate system represented 2 times higher TMAH removal efficiency (29.5%) than a 2 W CP system (14.4%). This excellent TMAH degradation capability of the integrated CP/periodate system became pronounced at pH 10 and 25 °C. Overall, the integrated CP/periodate system is expected to be a viable management option for effectively controlling hazardous TMAH chemicals.

Asunto(s)

Oxidación-Reducción , Compuestos de Amonio Cuaternario , Contaminantes Químicos del Agua , Cinética , Compuestos de Amonio Cuaternario/química , Ácido Peryódico/química , Gases em Plasma , Animales

RESUMEN

BACKGROUND: Both stereotactic radiosurgery (SRS) and percutaneous glycerol rhizotomy are excellent options to treat TN in patients unable to proceed with microvascular decompression. However, the influence of prior SRS on pain outcomes following rhizotomy is not well understood. METHODS: We retrospectively reviewed all patients undergoing percutaneous rhizotomy at our institution from 2011 to 2022. Only patients undergoing percutaneous glycerol rhizotomy following SRS (SRS-rhizotomy) or those undergoing primary glycerol rhizotomy were considered. We collected basic demographic, clinical, and pain characteristics for each patient. Additionally, we characterized pain presentation and perioperative complications. Immediate failure of procedure was defined as presence of TN pain symptoms within 1-week of surgery, and short-term failure was defined as presence of TN pain symptoms within 3-months of surgery. A multivariate logistic regression model was used to evaluate the relationship of a history SRS and failure of procedure following percutaneous glycerol rhizotomy. RESULTS: Of all patients reviewed, 30 had a history of SRS prior to glycerol rhizotomy whereas 371 underwent primary percutaneous glycerol rhizotomy. Patients with a history of SRS were more likely to endorse V3 pain symptoms, p = 0.01. Additionally, patients with a history of SRS demonstrated higher preoperative BNI pain scores, p = 0.01. Patients with a history of SRS were more likely to endorse preoperative numbness, p < 0.0001. A history of SRS was independently associated with immediate failure [OR = 5.44 (2.06-13.8), p < 0.001] and short-term failure of glycerol rhizotomy [OR = 2.41 (1.07-5.53), p = 0.03]. Additionally, increasing age was found to be associated with lower odds of short-term failure of glycerol rhizotomy [OR = 0.98 (0.97-1.00), p = 0.01] CONCLUSIONS: A history of SRS may increase the risk of immediate and short-term failure following percutaneous glycerol rhizotomy. These results may be of use to patients who are poor surgical candidates and require multiple noninvasive/minimally invasive options to effectively manage their pain.

Asunto(s)

Glicerol , Radiocirugia , Rizotomía , Insuficiencia del Tratamiento , Neuralgia del Trigémino , Humanos , Neuralgia del Trigémino/cirugía , Rizotomía/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Radiocirugia/métodos , Estudios Retrospectivos , Adulto , Resultado del Tratamiento