Molecular electronics sensors on a scalable semiconductor chip: A platform for single-molecule measurement of binding kinetics and enzyme activity.

For nearly 50 years, the vision of using single molecules in circuits has been seen as providing the ultimate miniaturization of electronic chips. An advanced example of such a molecular electronics chip is presented here, with the important distinction that the molecular circuit elements play the role of general-purpose single-molecule sensors. The device consists of a semiconductor chip with a scalable array architecture. Each array element contains a synthetic molecular wire assembled to span nanoelectrodes in a current monitoring circuit. A central conjugation site is used to attach a single probe molecule that defines the target of the sensor. The chip digitizes the resulting picoamp-scale current-versus-time readout from each sensor element of the array at a rate of 1,000 frames per second. This provides detailed electrical signatures of the single-molecule interactions between the probe and targets present in a solution-phase test sample. This platform is used to measure the interaction kinetics of single molecules, without the use of labels, in a massively parallel fashion. To demonstrate broad applicability, examples are shown for probe molecule binding, including DNA oligos, aptamers, antibodies, and antigens, and the activity of enzymes relevant to diagnostics and sequencing, including a CRISPR/Cas enzyme binding a target DNA, and a DNA polymerase enzyme incorporating nucleotides as it copies a DNA template. All of these applications are accomplished with high sensitivity and resolution, on a manufacturable, scalable, all-electronic semiconductor chip device, thereby bringing the power of modern chips to these diverse areas of biosensing.

Loneliness Among Low-Income Older Immigrants Living in Subsidized Senior Housing: Does Perceived Social Cohesion Matter?

This study compared the level of loneliness among older immigrants residing in subsidized senior housing with that of non-immigrant residents. The study also sought to examine the differential influence of perceived social cohesion on loneliness among these groups. 231 study participants were recruited from subsidized senior housing in St. Louis and the Chicago area. Multiple regression analyses showed that there was a significant difference in loneliness between immigrants and non-immigrants (b = .3, SE = 0.150, p < .05). Also, perceived social cohesion was negatively associated with loneliness (b=-.102, SE = .022, p < .001). Furthermore, immigration status moderated the relationship (b=-.147, SE = .043, p < .01), showing immigrants may benefit more from higher perceived social cohesion in terms of loneliness. The results suggest that perceived social cohesion may act as an important community-level protective factor against loneliness, particularly for older immigrants residing in subsidized senior housing. Creating socially cohesive environments, particularly for this subgroup, could be a crucial strategy for mitigating loneliness. .

Paenibacillus arenosi sp. nov., a siderophore-producing bacterium isolated from coastal sediment.

In this study, strain CAU 1523T, a novel Gram-positive-positive bacterium isolated from marine sediment collected from the coast of Busan, Republic of Korea, was characterized using a polyphasic taxonomic approach. This strain showed growth at a temperature range of 20-37 °C (optimum, 30 °C), a pH range of 6.5-9.5 (optimum, 7.5), and in the presence of 0-3% (w/v) NaCl (optimum, 1%). Phylogenetic analysis based on 16S rRNA gene sequencing and 92 concatenated core genes indicated that CAU 1523T belonged to the genus Paenibacillus, sharing the highest sequence similarity with P. assamensis JCM 13186T (98.0%). CAU 1523T was differentiated from other Paenibacillus species by average nucleotide identity, average amino acid identity, and digital DNA-DNA hybridization values, using cut-off values of 95-96%, 90%, and 70%, respectively, for closely related strains. The genome of CAU 1523T possessed various biosynthetic gene clusters, one of which encoded a putative siderophore-interacting protein. Siderophore production by the isolate was confirmed using the qualitative chrome azurol sulfonate (CAS) agar assay. Based on its phylogenetic and physiological characteristics, strain CAU 1523T represents a novel, siderophore-producing species within the genus Paenibacillus, for which the name Paenibacillus arenosi sp. nov. is proposed, with the type strain CAU 1523T (= KCTC 43108T = MCCC 1K04063T).

Thauera sedimentorum sp. nov., Isolated from Coastal Sediment.

A Gram-negative, strictly aerobic, rod-shaped, non-spore-forming bacterium, designated CAU 1555T, was isolated from a sediment sample collected on Jeju Island, Republic of Korea. Growth of the isolate was observed at 20-37 °C (optimum at 30 °C) and pH 5.5-10.0 (optimum at 8.0). Phylogenetic analysis based on the result of 16S rRNA gene sequences revealed that strain CAU 1555T belonged to the genus Thauera and was closely related to Thauera hydrothermalis GD-2T (98.4% sequence similarity), Thauera lacus D20T (96.6%), and Thauera linaloolentis 47LolT (95.5%). Strain CAU 1555T possessed phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid, and one aminophospholipid as the major polar lipids; Q-8 as the predominant respiratory quinone; and C16:0, summed feature 3 (comprising C16:1ω6c and/or C16:1ω7c), and summed feature 8 (comprising C18:1 ω7c/ C18:1 ω6c) as the major fatty acids. The average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH) values between the new isolate and T. hydrothermalis GD-2T were 84.5%, 86.4%, and 28.0%, respectively. Whole-genome sequencing of strain CAU 1555T revealed 3,955,289 bp with a DNA G + C content of 68.0 mol%. Based on the results of its polyphasic properties and genomic analysis, the isolate represents a novel species within the genus Thauera, for which the name Thauera sedimentorum sp. nov. is proposed, with CAU 1555T (= KCTC 72546T = MCCC 1K04065T) as the type strain.

Diagnostic Performance of an Artificial Intelligence System in Breast Ultrasound.

OBJECTIVES: We study the performance of an artificial intelligence (AI) program designed to assist radiologists in the diagnosis of breast cancer, relative to measures obtained from conventional readings by radiologists. METHODS: A total of 10 radiologists read a curated, anonymized group of 299 breast ultrasound images that contained at least one suspicious lesion and for which a final diagnosis was independently determined. Separately, the AI program was initialized by a lead radiologist and the computed results compared against those of the radiologists. RESULTS: The AI program's diagnoses of breast lesions had concordance with the 10 radiologists' readings across a number of BI-RADS descriptors. The sensitivity, specificity, and accuracy of the AI program's diagnosis of benign versus malignant was above 0.8, in agreement with the highest performing radiologists and commensurate with recent studies. CONCLUSION: The trained AI program can contribute to accuracy of breast cancer diagnoses with ultrasound.

Halarcobacter arenosus sp. nov., isolated from marine sediment.

A Gram-stain-negative, slightly curved, rod-shaped bacterial strain CAU 1517T was isolated from marine sediment in Busan, the Republic of Korea. The taxonomic position of strain CAU 1517T was investigated via a polyphasic approach comprising phenotypic, chemotaxonomic and phylogenetic properties. Strain CAU 1517T grew optimally at 30 °C, pH 7.5 and in the presence of 7% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequencing revealed that strain CAU 1517T belongs to the genus Halarcobacter and is most closely related to Halarcobacter bivalviorum LMG 26154T (96.5% similarity). The average nucleotide identity and digital DNA-DNA hybridization values between strain CAU 1517T and members of genus Halarcobacter ranged from were 76.7-78.0% and 19.5-21.2%, respectively. The strain contained menaquinone-6 (MK-6) as the only respiratory quinone, and C16:0, summed feature 3 (C16:1 ω7c/C16:1 ω6c), and summed feature 8 (C18:1ω7c/C18:1ω6c) as the major fatty acids. The polar lipid pattern consisted of diphosphatidylglycerol, phosphatidylethanolamine, and two unidentified aminophospholipids. The G+C content was 28.2 mol%. Therefore, it has been demonstrated that the isolate represents a novel species of the genus Halarcobacter, for which the name Halarcobacter arenosus sp. nov., is proposed. The type strain is CAU 1517T (=KCTC 72232T =NBRC 113955T).

Cohnella pontilimi sp. nov., isolated from tidal-flat mud.

A Gram-positive, aerobic, endospore-forming, rod-shaped bacterial strain, CAU 1483 T, was isolated from tidal-flat mud in the Republic of Korea. It grew optimally at 30 °C, in a pH 7.0 medium with 2% (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain CAU 1483 T formed a separate clade within Paenibacillaceae together with members of the genus Cohnella. Strain CAU 1483 T exhibited the highest 16S rRNA gene sequence similarity (97.1%) to C. candidum 18JY8-7 T. Whole genome of strain CAU 1483 T was 4.29 Mb in size with a 53.7 mol% G + C content, and included 4046 coding sequences and included 4046 coding sequences, some of which associated with stress response. The average nucleotide identity and digital DNA-DNA hybridization similarity between strain CAU 1483 T and related members of the genus Cohnella were 71.8-74.9% and 22.6-33.9%, respectively. The major respiratory quinone present in this strain was menaquinone-7. Strain CAU 1483 T contained anteiso-C15:0 and iso-C16:0 as the major fatty acids, while its polar lipids consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, lysyl-phosphatidylglycerol, phosphatidylcholine, three unidentified aminophospholipids, two unidentified lipids and an unidentified phospholipid. Peptidoglycan type was A1γ meso-Dpm. On the basis of taxonomic characterization, strain CAU 1483 T constitutes a novel species, for which the name Cohnella pontilimi sp. nov. is proposed. The type strain of this novel species is CAU 1483 T (= KCTC 43047 T = NBRC 113953 T).

Echinicola arenosa sp. nov., isolated from marine sand.

A novel bacterium, designated CAU 1574T, was isolated from marine sand. Cells were Gram stain negative, aerobic, gliding and rod shaped. Growth was observed at 20-37 °C (optimum, 30 °C), a pH of 5.5-10.0 (optimum, 8.0), and 0-3.0% (w/v) NaCl concentrations (optimum, 1%). Based on the results of 16S rRNA gene sequence analyses, strain CAU 1574T belonged to the genus Echinicola, and showed the highest similarity to Echinicola shivajiensis JCM 17847T (97.5%). Phylogenomic analysis based on consisting of 92 core genes extracted from the genome sequences showed that strain CAU 1574T was affiliated with species in the genus Echinicola. The average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH) values between strain CAU 1574T and the closely related species were below the cut-off values of 95-96, 90, and 70%, respectively used for species demarcation. The chemotaxonomic data of CAU 1574T were as follows: major isoprenoid quinone, MK-7; predominant polar lipids, phosphatidylethanolamine, two unidentified aminophospholipids and two unidentified lipids; major fatty acids, iso-C15:0, summed feature 3 (C16:1 ω6c/C16:1 ω7c). The 5.4 Mb genome included 20 contigs and 4237 protein-coding genes with a 39.8 mol% G + C content. Based on the phylogenetic, phenotypic, and physiological result, strain CAU 1574T represents a novel species of this genus Echinicola, for which the name Echinicola arenosa sp. nov. is proposed. The type strain is CAU 1574T (= KCTC 82410T = MCCC 1K05669T).

Chachezhania sediminis sp. nov., isolated from marine sediment.

A Gram-stain-negative, aerobic, non-motile, rod-shaped bacterial strain (CAU 1508T) was isolated from marine sediment collected in the Republic of Korea. Growth was observed at 10-45 °C (optimum, 30 °C), pH 4.0-11.0 (optimum, pH 6.0-8.0) and with 0-8.0 % (w/v) NaCl (optimum, 2-4 %). The isolate formed a monophyletic clade in the phylogenetic analyses using 16S rRNA gene and whole-genome sequences, exhibiting the highest similarity to Chachezhania antarctica SM1703T (96.5 %), and representing a distinct branch within the genus Chachezhania (family Rhodobacteraceae). Its whole genome sequence was 5.59 Mb long, with a G+C content of 65.7 mol% and 2183 predicted genes belonging to six functional categories. The average nucleotide identity and digital DNA-DNA hybridization values between CAU 1508T and C. antarctica SM1703T were 79.1 and 22.2 %, respectively. The predominant cellular fatty acids were C19 : 0 cyclo ω8c and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, two unidentified phospholipids and one unidentified aminophospholipid. The sole isoprenoid quinone was ubiquinone 10. Phenotypic phylogenetic properties supported the classification of CAU 1508T as representing a novel species of the genus Chachezhania, with the proposed name Chachezhania sediminis sp. nov. The type strain is CAU 1508T (=KCTC 62999T=NBRC 113697T).

Aureimonas fodinaquatilis sp. nov., isolated from coal mine wastewater.

A Gram stain-negative, aerobic, non-motile, short, rod-shaped bacterial strain CAU 1482T was isolated from coal mine wastewater in Hongcheon, Korea. It grew well at 30 °C, pH 8.5, 2% NaCl (w/v). 16S rRNA-based phylogeny indicated that CAU 1482T forms a distinct lineage within Aureimonas with high similarity to Aureimonas frigidaquae CW5T (98.2%), Aureimonas altamirensis S21BT (98.0%), and Aureimonas glaciei B5-2T (96.3%). The predominant cellular fatty acids were C18:1 2-OH, C16:0, C18:1 ω7c, and/or C18:1 ω6c (summed feature 8), with Q-10 as the major isoprenoid quinone. The polar lipid profile comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified aminolipids, and three unidentified lipids. The 3.9-Mb genome included 8 contigs and 3599 protein-coding genes with a 56.7 mol% G + C content. Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain CAU 1482T and closely related strains of A. frigidaquae CW5T and A. altamirensis S21BT were 72.2‒72.4% and 18.7‒18.8%, respectively. These phenotypic, chemotaxonomic, and phylogenetic data support CAU 1482T as a novel Aureimonas species, for which the name Aureimonas fodinaquatilis sp. nov. is proposed. The type strain is CAU 1482T (= KCTC 62995T = NBRC 113692T).

Ruegeria sediminis sp. nov., isolated from tidal flat sediment.

A Gram-stain-negative, aerobic, non-motile, rod-shaped bacterial strain, designated CAU 1488T, was isolated from tidal flat sediment, and its taxonomic position was investigated using a polyphasic approach. The organism grew optimally at a temperature of 30 °C, at pH 7.0-7.5 and in the presence of 0-6 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1488T forms a lineage distinct from Ruegeria marisrubri ZGT 118T (97.9 %), Ruegeria marina ZH17T (97.6 %), Ruegeria lacuscaerulensis ITI 1157T (97.5 %), Ruegeria pomeroyi DSS-3T (97.1 %), Ruegeria profundi ZGT108T (97.0 %), Ruegeria intermedia CC-GIMAT-2T (96.8 %), Ruegeria atlantica CECT 4292T (96.7 %) and Ruegeria kandeliae J95T (95.9 %). Genome sequencing revealed that CAU 1488T had a genome size of 4.23 Mbp and a G+C content of 63.2 mol%. Overall genome related indexes including average nucleotide identity and digital DNA-DNA hybridization values were 75.0-83.0 % and 26.2 %, which are below the cutoffs of 95 and 70 %, respectively, indicating that strain CAU 1488T represents a distinct species from the members of the genus Ruegeria. The predominant quinone was ubiquinone-10 (Q-10). The major fatty acids were summed feature 8 (C18 : 1 ω7c/ω6c; 60.7 %) and its polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and unidentified aminolipids. On the basis of phenotypic, chemotaxonomic and genomic data, strain CAU 1488T constitutes a novel species of the genus Ruegeria, for which the name Ruegeria sediminis sp. nov. is proposed. The type strain is CAU 1488T (=KCTC 62996T=NBRC 113693T).

Arenibacterium halophilum gen. nov., sp. nov., a halotolerant bacterium in the family Rhodobacteraceae isolated from a coastal sand dune.

A Gram-stain-negative, non-pigmented, non-spore-forming, motile, strictly aerobic bacterial strain, designated CAU 1492T, was isolated from a coastal sand dune and its taxonomic position was examined using a polyphasic approach. Cells of strain CAU 1492T grew optimally at 30 °C, pH 7.0 and in 3 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence of CAU 1492T showed that it formed a distinct lineage within the family Rhodobacteraceae as a separate deep branch, with 96.8 % or lower sequence similarity values to representatives of the genera Marivita, Donghicola, Sulfitobacter, Marinovum, Phaeobacter, Primorskyibacter, Roseovarius and Aestuariihabitans. Strain CAU 1492T was closely related to Marivita geojedonensis DPG-138T (96.8 %), Donghicola eburneus SW-277T (96.7 %), Sulfitobacter porphyrae SCM-1T (96.7 %), Marinovum algicola FF3T (96.6 %) and Aestuariihabitans beolgyonensis BB-MW15T (96.4 %) based on 16S rRNA gene sequences. The major cellular fatty acids of strain CAU 1492T were cyclo-C19 : 0 ω8c and summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c). The polar lipid pattern was composed of phosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid and an unidentified aminolipid. The strain contained Q-10 as the sole respiratory quinone. The draft genome of strain CAU 1492T was 4.63 Mb with a DNA G+C content of 63.1 mol%. The genome includes 4292 protein-coding genes and a five rRNA operons. On the basis of the phenotypic, chemotaxonomic and genomic data, strain CAU 1492T represents a novel genus in the family Rhodobacteraceae for which the name Arenibacterium halophilum gen. nov., sp. nov. is proposed. The type strain of Arenibacterium halophilum is CAU 1492T (=KCTC 62998T=NBRC 113696T).

Pontimicrobium aquaticum gen. nov., sp. nov., a bacterium in the family Flavobacteriaceae isolated from seawater.

A Gram-stain-negative, yellow-pigmented, non-spore-forming, non-motile, rod-shaped, catalase-positive, strictly aerobic bacterial strain, designated CAU 1491T, was isolated from seawater and its taxonomic position was examined using a polyphasic approach. Cells of strain CAU 1491T grew optimally at 30 °C, pH 7.5 and in 2.0 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence of CAU 1491T showed that it formed a distinct lineage within the family Flavobacteriaceae as a separate deep branch, with 97.0 % or lower sequence similarity to representatives of the genera Lacinutrix, Gaetbulibacter and Aquibacter. The major cellular fatty acids of strain CAU 1491T were iso-C15 : 0, iso-C15 : 1 G, iso-C17 : 0 3-OH and summed feature 3. The polar lipid pattern consisted of diphosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine and an unidentified phospholipid. The strain contained MK-6 as the sole respiratory quinone. Genome sequencing revealed that strain CAU 1491T has a genome size of 3.13 Mbp and a G+C content of 32.4 mol%. On the basis of the phenotypic, chemotaxonomic and genomic data, strain CAU 1491T represents a new genus and species in the family Flavobacteriaceae for which the name Pontimicrobium aquaticum gen. nov., sp. nov. is proposed. The type strain of Pontimicrobium aquaticum is CAU 1491T (=KCTC 72003T=NBRC 113695T).

Experimental and Theoretical Studies on the Mechanism of DDQ-Mediated Oxidative Cyclization of N-Aroylhydrazones.

The controversial single-electron-transfer process, frequently proposed in many 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated reactions, was investigated experimentally and theoretically using the oxidative cyclization of aroylhydrazone with DDQ. DDQ-mediated oxadiazole formation involves several processes, including cyclization to form an oxadiazole ring and N-H bond cleavage, either by proton, hydride, or hydrogen atom transfer. The detailed mechanistic study using the M06-2X density functional theory, and the 6-31+G(d,p) basis set, suggests that the pathways involving radical ion pair (RIP) intermediates, which resulted from single-electron transfer (SET), were found to be energetically nearly identical to the pathway without the SET. The substituent-dependent reactivity of oxadiazole formation was consistent with the free energy profiles of both pathways, with or without the SET. This result indicates that in addition to the electron-transfer pathway, the nucleophilic addition/elimination pathway for DDQ should be considered as a possible mechanism of the oxidative transformation reaction using DDQ.

Bioactive proteins delivery through core-shell nanofibers for meniscal tissue regeneration.

Mimicking the ultrastructural morphology of the meniscus with nanofiber scaffolds, coupled with controlled growth-factor delivery to the appropriate cells, can help engineer tissue with the potential to grow, mature, and regenerate after in vivo implantation. We electrospun nanofibers encapsulating platelet-derived growth factor (PDGF-BB), which is a potent mitogen and chemoattractant in a core of serum albumin contained within a shell of polylactic acid. We controlled the local PDGF-BB release by adding water-soluble polyethylene glycol to the polylactic acid shell to serve as a porogen. The novel core-shell nanofibers generated 3D scaffolds with an interconnected macroporous structure, with appropriate mechanical properties and with high cell compatibility. Incorporating PDGF-BB increased cell viability, proliferation, and infiltration, and upregulated key genes involved in meniscal extracellular matrix synthesis in human meniscal and synovial cells. Our results support proof of concept that these core-shell nanofibers can create a cell-favorable nanoenvironment and can serve as a system for sustained release of bioactive factors.

Differences in and correlations between cognitive abilities and brain volumes in healthy control, mild cognitive impairment, and Alzheimer disease groups.

The purpose of this study is to investigate differences in and correlations between cognitive abilities and brain volumes in healthy control (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD) groups. The Korean Version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K), which is used to diagnose AD, was used to measure the cognitive abilities of the study subjects, and the volumes of typical brain components related to AD diagnosis-cerebrospinal fluid (CSF), gray matter (GM), and white matter (WM)-were acquired. Of the CERAD-K subtests, the Boston Naming Test distinguished significantly among the HC, MCI, and AD groups. GM and WM volumes differed significantly among the three groups. There was a significant positive correlation between Boston Naming Test scores and GM and WM volumes. In conclusion, the Boston Naming Test and GM and WM brain volumes differentiated the three tested groups accurately, and there were strong correlations between Boston Naming Test scores and GM and WM volumes. These results will help to establish a test method that differentiates the three groups accurately and is economically feasible.

Subsidized Senior Housing in the US: A Scoping Review.

Subsidized senior housing (SSH) is important to support healthy aging among vulnerable subgroups of older adults, yet progress in developing and expanding SSH has been limited. This scoping review had two research questions: (1) What are the trends in SSH empirical studies? (2) What are the main topics in the existing literature on SSH in the US? We reviewed a total of 61 articles and found several notable trends, including a focus on racial and ethnic minorities, cognitive impairment among SSH residents, and collaborative partnerships between housing operators and healthcare providers. More than half of the studies were quantitative, while the rest were qualitative or mixed-methods. The lack of longitudinal or causal design research reflects the limited empirical knowledge of SSH. Four themes emerged: health and well-being, healthcare use and health behaviors, social relations, and housing relocation. We discussed implications for future research and program development efforts in SSH.

H-Scan Discrimination for Tumor Microenvironmental Heterogeneity in Melanoma.

OBJECTIVE: Melanoma is a form of malignant skin cancer that exhibits significant inter-tumoral differences in the tumor microenvironment (TME) secondary to genetic mutations. The heterogeneity may be subtle but can complicate the treatment of metastatic melanoma, contributing to a high mortality rate. Therefore, developing an accurate and non-invasive procedure to discriminate microenvironmental heterogeneity to facilitate therapy selection is an important goal. METHODS: In vivo murine melanoma models that recapitulate human disease using synchronous implanted YUMM 1.7 (Yale University Mouse Melanoma) and YUMMER 1.7 (Yale University Mouse Melanoma Exposed to Radiation) murine melanoma lines were investigated. Mice were treated with antibodies to modulate the immune response and longitudinally scanned with ultrasound (US). US radiofrequency data were processed using the H-scan analysis, attenuation estimation and B-mode processing to extract five US features. The measures were used to compare different TMEs (YUMMER vs. YUMM) and responses to immunomodulatory therapies with CD8 depletion or programmed cell death protein 1 (PD-1) inhibition. RESULTS: Multiparametric analysis produced a combined H-scan parameter, resolving significant differences (i) between untreated YUMMER and YUMM and (ii) between untreated, PD-1-treated and CD8-treated YUMMER. However, more importantly, the B-mode and attenuation measures failed to differentiate YUMMER and YUMM and to monitor treatment responses, indicating that H-scan is required to differentiate subtle differences within the TME. CONCLUSION: We anticipate that the H-scan analysis could discriminate heterogeneous melanoma metastases and guide diagnosis and treatment selection, potentially reducing the need for invasive biopsies or immunologic procedures.

Multiparametric ultrasound imaging for early-stage steatosis: Comparison with magnetic resonance imaging-based proton density fat fraction.

BACKGROUND: The prevalence of liver diseases, especially steatosis, requires a more convenient and noninvasive tool for liver diagnosis, which can be a surrogate for the gold standard biopsy. Magnetic resonance (MR) measurement offers potential, however ultrasound (US) has better accessibility than MR. PURPOSE: This study aims to suggest a multiparametric US approach which demonstrates better quantification and imaging performance than MR imaging-based proton density fat fraction (MRI-PDFF) for hepatic steatosis assessment. METHODS: We investigated early-stage steatosis to evaluate our approach. An in vivo (within the living) animal study was performed. Fat inclusions were accumulated in the animal livers by feeding a methionine and choline deficient (MCD) diet for 2 weeks. The animals (n = 19) underwent US and MR imaging, and then their livers were excised for histological staining. From the US, MR, and histology images, fat accumulation levels were measured and compared: multiple US parameters; MRI-PDFF; histology fat percentages. Seven individual US parameters were extracted using B-mode measurement, Burr distribution estimation, attenuation estimation, H-scan analysis, and shear wave elastography. Feature selection was performed, and the selected US features were combined, providing quantification of fat accumulation. The combined parameter was used for visualizing the localized probability of fat accumulation level in the liver; This procedure is known as disease-specific imaging (DSI). RESULTS: The combined US parameter can sensitively assess fat accumulation levels, which is highly correlated with histology fat percentage (R = 0.93, p-value < 0.05) and outperforms the correlation between MRI-PDFF and histology (R = 0.89, p-value < 0.05). Although the seven individual US parameters showed lower correlation with histology compared to MRI-PDFF, the multiparametric analysis enabled US to outperform MR. Furthermore, this approach allowed DSI to detect and display gradual increases in fat accumulation. From the imaging output, we measured the color-highlighted area representing fatty tissues, and the fat fraction obtained from DSI and histology showed strong agreement (R = 0.93, p-value < 0.05). CONCLUSIONS: We demonstrated that fat quantification utilizing a combination of multiple US parameters achieved higher performance than MRI-PDFF; therefore, our multiparametric analysis successfully combined selected features for hepatic steatosis characterization. We anticipate clinical use of our proposed multiparametric US analysis, which could be beneficial in assessing steatosis in humans.

1-Kestose Blocks UVB-Induced Skin Inflammation and Promotes Type I Procollagen Synthesis via Regulating MAPK/AP-1, NF-κB and TGF-ß/Smad Pathway.

Solar UVB irradiation cause skin photoaging by inducing the high expression of matrix metalloproteinase (MMPs) to inhibit the expression of Type1 procollagen synthesis. 1-Kestose, a natural trisaccharide, has been indicated to show a cytoprotective role in UVB radiation-induced-HaCaT cells. However, few studies have confirmed the anti-aging effects. In the present study, we evaluated the anti-photoaging and pathological mechanism of 1-kestose using Human keratinocytes (HaCaT) cells. The results found that 1-kestose pretreatment remarkably reduced UVB-generated reactive oxygen species (ROS) accumulation in HaCaT cells. 1-Kestose suppressed UVB radiation-induced MMPs expressions by blocking MAPK/AP-1 and NF-κB p65 translocation. 1-Kestose pretreatment increased Type 1 procollagen gene expression levels by activating TGF-ß/Smad signaling pathway. Taken together, our results demonstrate that 1-kestose may serve as a potent natural trisaccharide for inflammation and photoaging prevention.