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Transforming growth factor ß (TGFß) is present in blood of patients who do not respond to anti-programmed cell death (ligand) 1 [PD-(L)1] treatment, and through synergy with vascular endothelial growth factor (VEGF), it helps to create an environment that promotes tumor immune evasion and immune tolerance. Therefore, simultaneous inhibition of TGFß/VEGF is more effective than targeting TGFß alone. In this study, the dual inhibitory mechanism of TU2218 was identified through in vitro analysis mimicking the tumor microenvironment, and its antitumor effects were analyzed using mouse syngeneic tumor models. TU2218 directly restored the activity of damaged cytotoxic T lymphocytes (CTLs) and natural killer cells inhibited by TGFß and suppressed the activity and viability of regulatory T cells. The inactivation of endothelial cells induced by VEGF stimulation was completely ameliorated by TU2218, an effect not observed with vactosertib, which inhibits only TGFß signaling. The combination of TU2218 and anti-PD1 therapy had a significantly greater antitumor effect than either drug alone in the poorly immunogenic B16F10 syngeneic tumor model. The mechanism of tumor reduction was confirmed by flow cytometry, which showed upregulated VCAM-1 expression in vascular cells and increased influx of CD8 + CTLs into the tumor. As another strategy, combination of anti-CTLA4 therapy and TU2218 resulted in high complete regression (CR) rates in CT26 and WEHI-164 tumor models. In particular, immunological memory generated by the combination of anti-CTLA4 and TU2218 in the CT26 model prevented the development of tumors after additional tumor cell transplantation, suggesting that the TU2218-based combination has therapeutic potential in immunotherapy.
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Inhibidores de Puntos de Control Inmunológico , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptor 2 de Factores de Crecimiento Endotelial Vascular , Animales , Ratones , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor Tipo I de Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/inmunología , Humanos , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Ratones Endogámicos C57BL , Femenino , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/efectos de los fármacos , Línea Celular Tumoral , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Inmunoterapia/métodosRESUMEN
The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we identify a specific dependence of the POU2F3 molecular subtype of SCLC (SCLC-P) on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. Treatment of SCLC-P cells with a proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases evicts POU2F3 and its coactivators from chromatin and attenuates downstream signaling. B cell malignancies which are dependent on the POU2F1/2 cofactor, POU2AF1, are also sensitive to mSWI/SNF ATPase degraders, with treatment leading to chromatin eviction of POU2AF1 and IRF4 and decreased IRF4 signaling in multiple myeloma cells. An orally bioavailable mSWI/SNF ATPase degrader significantly inhibits tumor growth in preclinical models of SCLC-P and multiple myeloma without signs of toxicity. This study suggests that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability.
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Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Factores de Transcripción , Humanos , Animales , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/patología , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Línea Celular Tumoral , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Factor 3 de Transcripción de Unión a Octámeros/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Transducción de Señal , Regulación Neoplásica de la Expresión Génica , Factor 2 de Transcripción de Unión a OctámerosRESUMEN
BACKGROUND: Effective bowel cleansing is essential for a successful colonoscopy. Laxatives, such as polyethylene glycol, are commonly used for bowel preparation. Vomiting is a frequent complication during bowel preparation, and forceful vomiting can potentially lead to esophageal perforation, as reported in several previous cases. However, pharyngeal perforation during bowel preparation has not been previously documented. Here, we present a case of pharyngeal perforation induced by forceful vomiting during bowel preparation. CASE SUMMARY: A 38-year-old man with a history of hypertension, dyslipidemia, diabetes mellitus, and end-stage renal disease on hemodialysis was admitted for evaluation of recurrent abdominal pain. The patient complained of sudden pain in the neck, throat, and anterior chest following forceful vomiting during bowel preparation. Physical examination revealed crepitus under the skin of the neck and anterior chest on palpation, and upper gastrointestinal endoscopy revealed pharyngeal perforation. The perforation site was located above the upper esophageal sphincter, which distinguished it from Boerhaave's syndrome. Conservative medical management was chosen after consultation with a thoracic surgeon and an otolaryngologist, considering the patient's mild symptoms, stable vital signs, and the small size of the lesion; the perforation resolved without endoscopic or surgical intervention. The patient was discharged from hospital two weeks after the perforation. CONCLUSION: Despite its rarity, pharyngeal perforation should be considered a potential complication of bowel preparation for colonoscopy.
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Mammalian switch/sucrose nonfermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, an orally bioavailable proteolysis-targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. Importantly, AU-24118 exhibited favorable pharmacokinetic profiles in preclinical analyses in mice and rats, and further toxicity testing in mice showed a favorable safety profile. As acquired resistance is common with targeted cancer therapeutics, experiments were designed to explore potential mechanisms of resistance that may arise with long-term mSWI/SNF ATPase PROTAC treatment. Prostate cancer cell lines exposed to long-term treatment with high doses of a mSWI/SNF ATPase degrader developed SMARCA4 bromodomain mutations and ABCB1 (ATP binding cassette subfamily B member 1) overexpression as acquired mechanisms of resistance. Intriguingly, while SMARCA4 mutations provided specific resistance to mSWI/SNF degraders, ABCB1 overexpression provided broader resistance to other potent PROTAC degraders targeting bromodomain-containing protein 4 and AR. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.
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Adenosina Trifosfatasas , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Ratas , Ratones , Animales , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Línea Celular , Cromatina , Mamíferos/genética , Antagonistas de Receptores Androgénicos , ADN Helicasas/genética , Proteínas Nucleares/genética , Factores de Transcripción/genéticaRESUMEN
Mammalian switch/sucrose non-fermentable (mSWI/SNF) ATPase degraders have been shown to be effective in enhancer-driven cancers by functioning to impede oncogenic transcription factor chromatin accessibility. Here, we developed AU-24118, a first-in-class, orally bioavailable proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases (SMARCA2 and SMARCA4) and PBRM1. AU-24118 demonstrated tumor regression in a model of castration-resistant prostate cancer (CRPC) which was further enhanced with combination enzalutamide treatment, a standard of care androgen receptor (AR) antagonist used in CRPC patients. Importantly, AU-24118 exhibited favorable pharmacokinetic profiles in preclinical analyses in mice and rats, and further toxicity testing in mice showed a favorable safety profile. As acquired resistance is common with targeted cancer therapeutics, experiments were designed to explore potential mechanisms of resistance that may arise with long-term mSWI/SNF ATPase PROTAC treatment. Prostate cancer cell lines exposed to long-term treatment with high doses of a mSWI/SNF ATPase degrader developed SMARCA4 bromodomain mutations and ABCB1 overexpression as acquired mechanisms of resistance. Intriguingly, while SMARCA4 mutations provided specific resistance to mSWI/SNF degraders, ABCB1 overexpression provided broader resistance to other potent PROTAC degraders targeting bromodomain-containing protein 4 (BRD4) and AR. The ABCB1 inhibitor, zosuquidar, reversed resistance to all three PROTAC degraders tested. Combined, these findings position mSWI/SNF degraders for clinical translation for patients with enhancer-driven cancers and define strategies to overcome resistance mechanisms that may arise.
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Vanadium redox flow batteries (VRFBs) have emerged as promising solutions for stationary grid energy storage due to their high efficiency, scalability, safety, near room-temperature operation conditions, and the ability to independently size power and energy capacities. The performance of VRFBs heavily relies on the redox couple reactions of V2+/V3+ and VO2+/VO2+ on carbon electrodes. Therefore, a thorough understanding of the surface functionality of carbon electrodes and their propensity for degradation during electrochemical cycles is crucial for designing VRFBs with extended lifespans. In this study, we present a coupled experimental-theoretical approach based on carbon K edge X-ray absorption spectroscopy (XAS) to characterize carbon electrodes prepared under different conditions and identify relevant functional groups that contribute to unique spectroscopic features. Atomic models were created to represent functional groups, such as hydroxyl, carboxyl, methyl, and aldehyde, bonded to carbon atoms in either sp2 or sp3 environments. The interactions between functionalized carbon and various solvated vanadium complexes were modeled using density functional theory. A library of carbon K-edge XAS spectra was generated for distinct carbon atoms in different functional groups, both before and after interacting with solvated vanadium complexes. We demonstrate how these simulated spectra can be used to deconvolve ex situ experimental spectra measured from carbon electrodes and to track changes in the electrode composition following immersion in different electrolytes or extended cycling within a functional VRFB. By doing so, we identify the active species present on the carbon electrodes, which play a crucial role in determining their electrochemical performance.
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The POU2F3-POU2AF2/3 (OCA-T1/2) transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we found that the POU2F3 molecular subtype of SCLC (SCLC-P) exhibits an exquisite dependence on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. SCLC-P cell lines were sensitive to nanomolar levels of a mSWI/SNF ATPase proteolysis targeting chimera (PROTAC) degrader when compared to other molecular subtypes of SCLC. POU2F3 and its cofactors were found to interact with components of the mSWI/SNF complex. The POU2F3 transcription factor complex was evicted from chromatin upon mSWI/SNF ATPase degradation, leading to attenuation of downstream oncogenic signaling in SCLC-P cells. A novel, orally bioavailable mSWI/SNF ATPase PROTAC degrader, AU-24118, demonstrated preferential efficacy in the SCLC-P relative to the SCLC-A subtype and significantly decreased tumor growth in preclinical models. AU-24118 did not alter normal tuft cell numbers in lung or colon, nor did it exhibit toxicity in mice. B cell malignancies which displayed a dependency on the POU2F1/2 cofactor, POU2AF1 (OCA-B), were also remarkably sensitive to mSWI/SNF ATPase degradation. Mechanistically, mSWI/SNF ATPase degrader treatment in multiple myeloma cells compacted chromatin, dislodged POU2AF1 and IRF4, and decreased IRF4 signaling. In a POU2AF1-dependent, disseminated murine model of multiple myeloma, AU-24118 enhanced survival compared to pomalidomide, an approved treatment for multiple myeloma. Taken together, our studies suggest that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability.
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This study presents a methodology for the coarse alignment of light detection and ranging (LiDAR) point clouds, which involves estimating the position and orientation of each station using the pinhole camera model and a position/orientation estimation algorithm. Ground control points are obtained using LiDAR camera images and the point clouds are obtained from the reference station. The estimated position and orientation vectors are used for point cloud registration. To evaluate the accuracy of the results, the positions of the LiDAR and the target were measured using a total station, and a comparison was carried out with the results of semi-automatic registration. The proposed methodology yielded an estimated mean LiDAR position error of 0.072 m, which was similar to the semi-automatic registration value of 0.070 m. When the point clouds of each station were registered using the estimated values, the mean registration accuracy was 0.124 m, while the semi-automatic registration accuracy was 0.072 m. The high accuracy of semi-automatic registration is due to its capability for performing both coarse alignment and refined registration. The comparison between the point cloud with refined alignment using the proposed methodology and the point-to-point distance analysis revealed that the average distance was measured at 0.0117 m. Moreover, 99% of the points exhibited distances within the range of 0.0696 m.
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This paper proposes a novel phase-resolved partial discharge (PRPD) sensor embedded in a MV-class bushing for high-accuracy insulation analysis. The design, fabrication, and evaluation of a PRPD sensor embedded in a MV-class bushing aimed to achieve the detection of partial discharge (PD) pulses that are phase-synchronized with the applied primary HV signal. A prototype PRPD sensor was composed of a flexible printed circuit board (PCB) with dual-sensing electrodes, utilizing a capacitive voltage divider (CVD) for voltage measurement, the D-dot principle for PD detection, and a signal transducer with passive elements. A PD simulator was prepared to emulate typical PD defects, i.e., a metal protrusion. The voltage measurement precision of the prototype PRPD sensor was satisfied with the accuracy class of 0.2 specified in IEC 61869-11, as the maximum corrected voltage error ratios and corrected phase errors in 80%, 100%, and 120% of the rated voltage (13.2 kilovolts (kV)) were less than 0.2% and 10 min, respectively. In addition, the prototype PRPD sensor had good linearity and high sensitivity for PD detection compared with a conventional electrical detection method. According to performance evaluation tests, the prototype PRPD sensor embedded in the MV-class bushing can measure PRPD patterns phase-synchronized with the primary voltage without any additional synchronization equipment or system. Therefore, the prototype PRPD sensor holds potential as a substitute for conventional commercial PD sensors. Consequently, this advancement could lead to the enhancement of power system monitoring and maintenance, contributing to the digitalization and minimization of power apparatus.
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Agastache rugosa, also known as Korean mint, is a perennial plant from the Lamiaceae family that is traditionally used for various ailments and contains antioxidant and antibacterial phenolic compounds. Molecular breeding of A. rugosa can enhance secondary metabolite production and improve agricultural traits, but progress in this field has been delayed due to the lack of chromosome-scale genome information. Herein, we constructed a chromosome-level reference genome using Nanopore sequencing and Hi-C technology, resulting in a final genome assembly with a scaffold N50 of 52.15 Mbp and a total size of 410.67 Mbp. Nine pseudochromosomes accounted for 89.1% of the predicted genome. The BUSCO analysis indicated a high level of completeness in the assembly. Repeat annotation revealed 561,061 repeat elements, accounting for 61.65% of the genome, with Copia and Gypsy long terminal repeats being the most abundant. A total of 26,430 protein-coding genes were predicted, with an average length of 1,184 bp. The availability of this chromosome-scale genome will advance our understanding of A. rugosa's genetic makeup and its potential applications in various industries.
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Genoma de Planta , Mentha , Cromosomas , Mentha/genética , Anotación de Secuencia Molecular , Filogenia , República de CoreaRESUMEN
Pseudomonas aeruginosa is the primary opportunistic human pathogen responsible for a range of acute and chronic infections; it poses a significant threat to immunocompromised patients and is the leading cause of morbidity and mortality for nosocomial infections. Its high resistance to a diverse array of antimicrobial agents presents an urgent health concern. Among the mechanisms contributing to resistance in P. aeruginosa, the horizontal acquisition of antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) has gained recognition as a substantial concern in clinical settings, thus indicating that a comprehensive understanding of ARG dissemination within the species is strongly required for surveillance. Here, two approaches, including a systematic literature analysis and a genome database survey, were employed to gain insights into ARG dissemination. The genome database enabled scrutinizing of all the available sequence information and various attributes of P. aeruginosa isolates, thus providing an extensive understanding of ARG dissemination within the species. By integrating both approaches, with a primary focus on the genome database survey, mobile ARGs that were linked or correlated with MGEs, important sequence types (STs) carrying diverse ARGs, and MGEs responsible for ARG dissemination were identified as critical factors requiring strict surveillance. Although human isolates play a primary role in dissemination, the importance of animal and environmental isolates has also been suggested. In this study, 25 critical mobile ARGs, 45 critical STs, and associated MGEs involved in ARG dissemination within the species, are suggested as critical factors. Surveillance and management of these prioritized factors across the One Health sectors are essential to mitigate the emergence of multidrug-resistant (MDR) and extensively resistant (XDR) P. aeruginosa in clinical settings.
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Antibacterianos , Pseudomonas aeruginosa , Animales , Humanos , Farmacorresistencia Microbiana/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
P-type Cu-Se thin films were deposited on glass substrates at room temperature using radio frequency magnetron sputtering by a single multi-component CuSe2 target. When using a multi-component target, the impact of the sputtering power on the homogeneity and stoichiometry within the thin films should be investigated in the depth direction to demonstrate a secondary effect on the electrical and optical properties of the thin films. Systematic characterization of the Cu-Se thin films, including the morphology, microstructure, chemical composition, and depth-directional chemical bonding state and defect structure of the thin films, revealed that the sputtering power played an important role in the homogeneity and stoichiometry of the thin films. At very low and very high sputtering power levels, the Cu-Se thin films exhibited more deviations from stoichiometry, while an optimized sputtering power resulted in more homogenous thin films with improved stoichiometry across the entire thin film thickness in the X-ray photoelectron spectroscopy depth profile, despite showing Se deficiency at all depths. A rapid decrease in carrier concentration, indicating a reduction in the net effect of total defects, was obtained at the optimized sputtering power with less deviation from stoichiometry in the Cu-Se thin films and the closest stoichiometric ratio at an intermediate depth.
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Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory disease. IgG4-RD can affect any organ system, including the pancreas, bile ducts, salivary glands, mesentery, and retroperitoneum. On the other hand, small intestine involvement is extremely rare. This paper describes a case of IgG4-RD involving the small bowel, particularly at the distal ileum. An 81-year-old female was admitted to the authors' hospital complaining of abdominal pain, dyspepsia, and hematochezia. The laboratory tests, including tumor markers and IgG4, were within normal limits. A colonoscopy did not show any abnormal findings. Abdominal computed tomography revealed segmental aneurysmal dilatation and wall thickening at the distal ileum, suggesting malignant conditions, such as small bowel lymphoma. The patient underwent an exploratory laparoscopy and ileocecectomy to differentiate a malignancy. A histopathology examination revealed dense lymphoplasmacytic infiltration, storiform fibrosis, and IgG4-positive plasma cells (>50 per high power field). The patient was finally diagnosed with IgG4-RD. The patient was followed up in the outpatient clinic for five years without recurrence. This paper suggests that a radical resection without maintenance therapy can be a treatment option, particularly when the IgG4-RD manifests as a localized gastrointestinal tract lesion.
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Enfermedad Relacionada con Inmunoglobulina G4 , Femenino , Humanos , Anciano de 80 o más Años , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Enfermedad Relacionada con Inmunoglobulina G4/patología , Células Plasmáticas/patología , Tracto Gastrointestinal , Intestino Delgado/patología , Inmunoglobulina GRESUMEN
Foot-and-mouth disease (FMD) is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are routinely used to induce an immune response; however, it requires an extended period of time to produce sufficient antibodies to prevent viral infection. In this study, we evaluated the increased effectiveness of the FMD vaccine structural protein (SP) antibody by administrating the Amino-Zn adjuvant to 100 pigs from 3 test pig farms in their feed. The FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and the hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of the FMD vaccine SP antibodies in the 0.2% Amino-Zn-administered group was significantly increased compared to that of the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8, and 16 weeks after the second vaccination (p < 0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. The IFN-γ and IgA levels were significantly increased by Amino-Zn administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p < 0.05). On the other hand, serum AST, and CPK (p < 0.001) were significantly decreased by Amino-Zn administration. These results show that the administration of Amino-Zn is effective in enhancing the antibody titer and immunogenicity of the FMD vaccine and can be used as an oral adjuvant (OrAd) to prevent viral diseases, such as FMD.
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Objectives: This study aimed to evaluate the clinical efficacy and safety of PE extracts developed for the purpose of relieving pain and improving knee joint function on semi-healthy people with mild knee joint pain. Methods: A randomized, double-blind, two-arm, single-center, placebo-controlled clinical trial was conducted. Individuals with knee joint pain and a visual analogue scale (VAS) score < 50 mm were included in the study, and participants with radiological arthritis were excluded. Participants were administered either PFE or a placebo capsule (700 mg, twice a day) orally for eight weeks. The comparisons of the changed VAS score and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores between the PFE and placebo groups were primary outcomes, while the five inflammation-related laboratory tests including cartilage oligomeric matrix protein, cyclooxygenase-2, neutrophil and lymphocyte ratio, high sensitive C-reactive protein, and erythrocyte sedimentation rate were secondary outcomes. Also, a safety assessment was done. Results: Eighty participants (mean age, 38.4 ± 14.0, male: female, 28:52) were enrolled; 75 completed the trial (PFE 36 and placebo 39). After eight weeks, both VAS and WOMAC scores were reduced in the PFE and placebo groups. The changed scores were significantly higher in the PFE group compared to the placebo group: 19.6 ± 10.9 vs. 6.8 ± 10.5; VAS scores (p < 0.001), and 20.5 ± 14.7 vs. 9.3 ± 16.5; total WOMAC scores (p < 0.01) including the sub-scores for pain, stiffness, and functions. No significant changes were reported in the five inflammation-related laboratory parameters. All adverse events were considered minor and unlikely to result from the intervention. Conclusion: Eight weeks of PFE intake was more effective than placebo in reducing knee joint pain and improving knee joint function in sub-healthy people with mild knee joint pain, and there were no major safety concerns. Clinical Trial Registration: https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=23101&status=5&seq_group=19745, identifier CRIS: KCT0007219.
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In this study, the composition of lead-free piezoelectric ceramics (1 - x)(Bi0.5Na0.5)TiO3-x(Ba0.5Sr0.5)TiO3 with excellent piezoelectric properties was investigated. Crystal analysis and electrical and piezoelectric properties were analyzed according to the content of the BST composition. A phase change from rhombohedral to tetragonal structure was observed in 0.12 BST, and the densest and most uniform microstructure was confirmed in this composition. The dielectric constant increased from 905 to 1692 as the composition of BST increased to 0.12 BST. Afterward, as the composition of BST increased, the permittivity tended to decrease. Additionally, at 0.12 BST, Pr was the highest at 23.34 µC/cm2. The piezoelectric charge constant (d33) and the electromechanical coupling coefficient (kp) were 152 pC/N and 0.37, respectively, and showed the highest values at 0.12 BST. Curie temperature (Tm) was analyzed 242 °C at 0.12 BST, the optimal composition. It was confirmed that the characteristics of 0.12 BST were excellent in all conditions. Therefore, it was confirmed that 0.12 BST is the optimal composition for (1 - x)BNT-xBST piezoelectric ceramics.
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In smart cities, a large amount of optical camera equipment is deployed and used. Closed-circuit television (CCTV), unmanned aerial vehicles (UAVs), and smartphones are some examples of such equipment. However, additional information about these devices, such as 3D position, orientation information, and principal distance, is not provided. To solve this problem, the structured mobile mapping system point cloud was used in this study to investigate methods of estimating the principal point, position, and orientation of optical sensors without initial given values. The principal distance was calculated using two direct linear transformation (DLT) models and a perspective projection model. Methods for estimating position and orientation were discussed, and their stability was tested using real-world sensors. When the perspective projection model was used, the camera position and orientation were best estimated. The original DLT model had a significant error in the orientation estimation. The correlation between the DLT model parameters was thought to have influenced the estimation result. When the perspective projection model was used, the position and orientation errors were 0.80 m and 2.55°, respectively. However, when using a fixed-wing UAV, the estimated result was not properly produced owing to ground control point placement problems.
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Teléfono Inteligente , Dispositivos Aéreos No Tripulados , Ciudades , Modelos LinealesRESUMEN
Coronavirus disease 2019 (COVID-19), the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by symptoms such as fever, fatigue, a sore throat, diarrhea, and coughing. Although various new vaccines against COVID-19 have been developed, early diagnostics, isolation, and prevention remain important due to virus mutations resulting in rapid and high disease transmission. Amino acid substitutions in the major diagnostic target antigens of SARS-CoV-2 may lower the sensitivity for the detection of SARS-CoV-2. For this reason, we developed specific monoclonal antibodies that bind to epitope peptides as antigens for the rapid detection of SARS-CoV-2 NP. The binding affinity between antigenic peptides and monoclonal antibodies was investigated, and a sandwich pair for capture and detection was employed to develop a rapid biosensor for SARS-CoV-2 NP. The rapid biosensor, based on a monoclonal antibody pair binding to conserved epitopes of SARS-CoV-2 NP, detected cultured virus samples of SARS-CoV-2 (1.4 × 103 TCID50/reaction) and recombinant NP (1 ng/mL). Laboratory confirmation of the rapid biosensor was performed with clinical specimens (n = 16) from COVID-19 patients and other pathogens. The rapid biosensor consisting of a monoclonal antibody pair (75E12 for capture and the 54G6/54G10 combination for detection) binding to conserved epitopes of SARS-CoV-2 NP could assist in the detection of SARS-CoV-2 NP under the circumstance of spreading SARS-CoV-2 variants.
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Anticuerpos Monoclonales/metabolismo , Anticuerpos Antivirales/metabolismo , Técnicas Biosensibles/métodos , Epítopos/metabolismo , Proteínas de la Nucleocápside/metabolismo , SARS-CoV-2/inmunología , Proteínas Virales/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Antivirales/inmunología , Epítopos/genética , Epítopos/inmunología , Humanos , Inmunoensayo , Ratones , Ratones Endogámicos BALB C , Proteínas de la Nucleocápside/genética , Proteínas de la Nucleocápside/inmunología , Péptidos/inmunología , Péptidos/metabolismo , Unión Proteica , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , Proteínas Virales/inmunologíaRESUMEN
Through the formation of an electron donor-acceptor (EDA) complex, strain-release aminopyridylation of [1.1.1]propellane with N-aminopyridinium salts as bifunctional reagents enabled the direct installation of amino and pyridyl groups onto bicyclo[1.1.1]pentane (BCP) frameworks in the absence of an external photocatalyst. The robustness of this method to synthesize 1,3-aminopyridylated BCPs under mild and metal-free conditions is highlighted by the late-stage modification of structurally complex biorelevant molecules. Moreover, the strategy was extended to P-centered and CF3 radicals for the unprecedented incorporation of such functional groups with pyridine across the BCP core in a three-component coupling. This practical method lays the foundation for the straightforward construction of new valuable C4-pyridine-functionalized BCP chemical entities, thus significantly expanding the range of accessibility of BCP-type bioisosteres for applications in drug discovery.