U-Shape Pillar Strip for 3D Cell-Lumped Organoid Model (3D-COM) Mimicking Lung Cancer Hypoxia Conditions in High-Throughput Screening (HTS).

Hypoxia is a representative tumor characteristic associated with malignant progression in clinical patients. Engineered in vitro models have led to significant advances in cancer research, allowing for the investigation of cells in physiological environments and the study of disease mechanisms and processes with enhanced relevance. In this study, we propose a U-shape pillar strip for a 3D cell-lumped organoid model (3D-COM) to study the effects of hypoxia on lung cancer in a high-throughput manner. We developed a U-pillar strip that facilitates the aggregation of PDCs mixed with an extracellular matrix to make the 3D-COM in 384-plate array form. The response to three hypoxia-activated prodrugs was higher in the 3D-COM than in the 2D culture model. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α, which are markers of hypoxia, was also higher in the 3D-COM than in the 2D culture. The results show that 3D-COM better recapitulated the hypoxic conditions of lung cancer tumors than the 2D culture. Therefore, the U-shape pillar strip for 3D-COM is a good tool to study the effects of hypoxia on lung cancer in a high-throughput manner, which can efficiently develop new drugs targeting hypoxic tumors.

Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.

Copper-Based Two-Dimensional Metal-Organic Frameworks for Fenton-like Photocatalytic Degradation of Methylene Blue under UV and Sunlight Irradiation.

To efficiently degrade organic pollutants, photocatalysts must be effective under both ultraviolet (UV) radiation and sunlight. We synthesized a series of new metal-organic frameworks by using mild hydrothermal conditions. These frameworks incorporate three distinct bipyridyl ligands: pyrazine (pyr), 4,4'-bipyridine (bpy), and 1,2-bis(4-pyridyl)ethane (bpe). The resulting compounds are denoted as [Cu(pyz)(H2O)2MF6], [Cu(bpy)2(H2O)2]·MF6, and [Cu(bpe)2(H2O)2]·MF6·H2O [M = Zr (1, 3, and 5) and Hf (2, 4, and 6)]. All six compounds exhibited a two-dimensional crystal structure comprising infinitely nonintersecting linear chains. Compound 3 achieved 100% degradation of methylene blue (MB) after 8 min under UV irradiation and 100 min under natural sunlight in the presence of H2O2 as the electron acceptor. For compound 5, 100% MB degradation was achieved after 120 min under sunlight and 10 min under UV light. Moreover, reactive radical tests revealed that the dominant species involved in photocatalytic degradation are hydroxyl (•OH), superoxide radicals (•O2-), and photogenerated holes (h+). The photodegradation process followed pseudo-first-order kinetics, with photodegradation rate constants of 0.362 min-1 (0.039 min-1) for 3 and 0.316 min-1 (0.033 min-1) for 5 under UV (sunlight) irradiation. The developed photocatalysts with excellent activity and good recyclability are promising green catalysts for degrading organic pollutants during environmental decontamination.

The Effect of Telehealth on Patterns of Health Care Utilization and Medication Prescription in Patients with Diabetes or Hypertension During COVID-19: A Nationwide Study.

Background: In response to the coronavirus disease-19 pandemic, audio-based telehealth services for consultation and medication prescription were temporarily introduced in Korea. This study investigated the impact of telehealth services on patterns of health care utilization and medication prescription in patients with hypertension or diabetes. Methods: The 2019 to 2021 Health Insurance Review and Assessment Service claims data were used. The difference-in-difference approach was used to investigate the effect of telehealth services between the case and control group before and after the intervention period. The pre-intervention period was from February 24, 2019, to February 23, 2020, and the post-intervention period from February 24, 2020, to February 23, 2021. The control group included individuals who used in-person outpatient services and the case group those who utilized both telehealth and in-person services. Results: A total of 250,640 patients with hypertension and 154,212 patients with diabetes were included. The use of telehealth services was associated with an increase in outpatient visits in those with hypertension (0.07, p = 0.0027) and diabetes (0.32, p < 0.0001). A decrease in hospitalizations (-0.2%, p = 0.0007) and emergency department visits (-0.11%, p = 0.0016) was found in individuals with hypertension. Policy implementation also resulted in an increase in medication possession ratio (MPR) and the proportion of appropriate prescription in patients with hypertension (MPR: 3.0%, p < 0.0001, prescription: 3.1%, p < 0.0001) and diabetes (MPR: 3.4%, p < 0.0001, prescription: 1.7%, p < 0.0001). Conclusions: The findings confirm a relationship between implementing telehealth services and improved patterns of health care utilization and medication prescription, suggesting the potential benefit of telehealth in managing chronic diseases.

What is the impact of one's chronic illness on his or her spouse's future chronic illness: a community-based prospective cohort study.

BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.

The impact of the COVID-19 pandemic on depression in community-dwelling older adults: a prospective cohort study.

BACKGROUND: There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults. METHODS: We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years. Among the 2308 participants who completed both the third and the fourth follow-up assessments, 58.4% completed their fourth follow-up before the outbreak of COVID-19 and the rest completed it during the pandemic. We conducted face-to-face diagnostic interviews using Mini International Neuropsychiatric Interview and used Geriatric Depression Scale. We performed generalized estimating equations and logistic regression analyses. RESULTS: The COVID-19 pandemic was associated with increased depressive symptoms in older adults [b (standard error) = 0.42 (0.20), p = 0.040] and a doubling of the risk for incident depressive disorder even in euthymic older adults without a history of depression (odds ratio = 2.44, 95% confidence interval 1.18-5.02, p = 0.016). Less social activities, which was associated with the risk of depressive disorder before the pandemic, was not associated with the risk of depressive disorder during the pandemic. However, less family gatherings, which was not associated with the risk of depressive disorder before the pandemic, was associated with the doubled risk of depressive disorder during the pandemic. CONCLUSIONS: The COVID-19 pandemic significantly influences the risk of late-life depression in the community. Older adults with a lack of family gatherings may be particularly vulnerable.

Description of Salinimicrobium tongyeongense sp. nov., isolated from seawater.

A Gram-stain-negative, non-motile by gliding and moderately halophilic rod-shaped bacterium HN-2-9-2T was isolated from seawater in Tongyeong, Republic of Korea. The strain grew at concentrations of 0.5‒7 % (w/v) NaCl, at pH 5.5‒8.5 and in a temperature range of 18‒45 °C. HN-2-9-2T shared the highest 16S rRNA gene sequence percentage with Salinimicrobium xinjiangense BH206T (98.2 %). The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridisation (dDDH) values between HN-2-9-2T and the S. xinjiangense BH206T were 76.0 %, 81.9 % and 19.7 %, respectively. The genome comprised 3 509 958 bp with a DNA G+C content of 43.0%. HN-2-9-2T contained MK-6 as the sole menaquinone. The predominant fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C17 : 0 3-OH, iso-C16 : 0, iso-C15 : 1G and summed feature 9, comprising iso-C17 : 1ω6c/C16 : 1 10-methyl. The polar lipids contained phosphatidylethanolamine, one unidentified phospholipid, two unidentified aminolipids, an unidentified glycolipid and six unidentified lipids. The polyphasic taxonomic properties indicate that the strain represents a novel species within the genus Salinimicrobium, for which the name Salinimicrobium tongyeongense sp. nov. is proposed. The type strain is HN-2-9-2T (=KCTC 82934T=NBRC 115920T).

Thermodynamic, Spectroscopic, and Structural Study on a Sodium Uranyl Tri-2-Methoxybenzoate Dodecahydrate Coordination Compound with Considerably Low Solubility in Acidic Conditions.

A spontaneous crystallization of an uranium(VI)-organic coordination compound with sodium and 2-methoxybenzoate (2-mba) was observed in acidic solutions, and the solubility product, molecular vibrations, crystal structure, thermal stability, and emission properties of the atypically low-soluble U(VI) complex (Na[UO2(2-mba)3]·12H2O(s)) were fully investigated for the first time. A long-term solubility experiment and speciation modeling gave a solubility product of log Ks,0 = -12.18 ± 0.02 (T = 25 °C and I = 0.1 M NaClO4), and vibrational analyses confirmed the overall molecular structure of complex and the frequencies of characteristic stretching motions of uranyl moiety as well. The crystal quality of Na[UO2(2-mba)3]·12H2O(s) was improved by a digestion method, and X-ray diffraction analysis of the single crystalline specimen verified that the newly studied uranyl-organic compound contains one-dimensional channels with a diameter of 20 Å along the [001] direction; the sodium and water molecules are arranged in the channel structures. In the coordination environment around uranyl, three aromatic carboxylates are symmetrically bound in the equatorial plane of uranyl coplanarily, and the unit [UO2(2-mba)3]- complexes are further extended along the plane to form the layered-morphologies. The three-dimensional packing of [UO2(2-mba)3]- anions is driven by the parallel-displaced π-stacking of aromatic rings with a centroid-centroid distance of 3.7 Å. Additional thermogravimetric analysis confirmed that the Na[UO2(2-mba)3]·12H2O(s) is stable up to 250 °C, and dehydration and release of the organic ligand were subsequently observed beyond that temperature. Photoluminescence spectrum of the Na[UO2(2-mba)3]·12H2O(s) clearly displayed the characteristic U(VI) emission, and a band spacing between the ground electronic states of U(VI) uranyl was evaluated to be 831 ± 14 cm-1. Such detailed characterization of the unique Na[UO2(2-mba)3]·12H2O(s) is advancing upon a systematic understanding of the structural effects of the aromatic model ligands on U(VI) complexation, with relevance to the environmental chemistry of U(VI) and crystal engineering for development of diverse uranyl-organic frameworks.

Evidence of risky driving in Korean older adults: A longitudinal cohort.

OBJECTIVES: The aim of this study was to determine the differences in the risk factors for dangerous driving between older adults with normal cognition and those with cognitive impairment. DESIGN: The driving risk questionnaire (DRQ) that was applied to a community-dwelling older adult cohort and 2 years of accident/violation records from the National Police Agency were analyzed. We conducted regression analyses with the presence or absence of risky driving based on records (accidents + violations) 2 years before and after evaluation as a dependent variable and dichotomized scores of each risky driving factor as independent variables. RESULTS: According to four identified factors-crash history, safety concern, reduced mileage, and aggressive driving-significant associations were found between risky driving over the past 2 years and crash history and for aggressive driving in the normal cognition group. In the cognitive impairment group, only crash history was significantly associated, although safety concerns showed a trend toward significance. CONCLUSIONS: In this study, it was suggested that the factors of DRQ have a significant association with actual risky driving. Our results are expected to contribute to establishing the evidence for evaluating and predicting risky driving and advising whether to continue driving in clinics.

Description of Brachybacterium sillae sp. nov., a thermophilic bacterium isolated from a hot spring.

The taxonomic position of strain EF45031T, isolated from the Neungam Carbonate hot spring, was examined using the polyphasic taxonomic approach. Strain EF45031T shared the highest percentage of 16S rRNA gene sequence with Brachybacterium nesterenkovii CIP 104813 T (97.7%). The average nucleotide identity (ANI), average amino acid identity (AAI), and digital DNA-DNA hybridization (dDDH) values between strain EF45031T and the type strains B. nesterenkovii CIP 104813 T and B. phenoliresistens Phenol-AT were 77.0%, 69.15%, 21.9% and 75.73%, 68.81%, 20.5%, respectively. Phylogenomic analysis using an up-to-date bacterial core gene (UBCG) set revealed that strain EF45031T belonged to the genus Brachybacterium. Growth occurred between 25 and 50 ℃ at pH 6.0-9.0 and could tolerate salinity up to 5% (w/v). Strain had anteiso-C15:0 and anteiso-C17:0 as major fatty acids. Menaquinone-7 (MK-7) was the predominant respiratory menaquinone. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, three aminolipids, and two unidentified glycolipids. The cell-wall peptidoglycan contained meso-diaminopimelic acid as a diagnostic diamino acid. The genome comprised 2,663,796 bp, with a G + C content of 70.9%. Stress-responsive periplasmic chaperone/protease coding genes were identified in the genome of EF45031T and were not detected in other Brachybacterium species. The polyphasic taxonomic properties indicate that the strain represents a novel species within the genus Brachybacterium, for which the name Brachybacterium sillae sp. nov. is proposed. The type strain is EF45031T (= KCTC 49702 T = NBRC 115869 T).

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Platelet-rich plasma injection for empty nose syndrome: A case report.

Empty nose syndrome (ENS) is a relatively rare disease found in patients who have undergone sinonasal surgery, characterized by excessive reduction of the turbinate, causing intranasal turbulence and loss of receptors within the nasal mucosa. Patients diagnosed with the disease usually experience symptoms including dryness of the nose, nasal pain, paradoxical nasal obstruction, and crusts in the nasal cavity. ENS can be treated with conservative care such as nasal irrigation or nasal moisturizers. Accurate efficacy of surgical treatment of ENS is often difficult to predict and is accompanied by operational obstacles and complications. Platelet-rich plasma (PRP) has recently gained attention as a regenerative therapy in several medical fields. We present two cases of ENS treated by injection of PRP as a simple and less invasive method, and describe its efficacy with nasal endoscopy and subjective questionnaires.

Latarjet procedure without capsular repair produces favorable clinical results and avoids limitation in external rotation.

PURPOSE: This study aimed at analyzing the range of motion (ROM) and other clinical outcomes in patients with > 20% glenoid bone loss who underwent the Latarjet procedure with or without anterior capsule repair. METHODS: This retrospective study included 47 patients with > 20% glenoid bone loss who underwent the classic Latarjet procedure from 2016 to 2021. Of these, 25 did not undergo capsular repair (no-capsular-repair group; group I) whereas 22 patients did (capsular-repair group; group II). The Rowe score, American Shoulder and Elbow Surgeons score, Visual Analogue Scale, ROM, recurrence, and complications were evaluated before and 3, 6, and 12 months after the surgery. A goniometer was used to measure the forward flexion and external rotation (arm adducted, 90° abducted) of both shoulders. The ROM deficit was measured as the difference from the contralateral healthy shoulder. RESULTS: The external rotation in arm adduction at 3 and 6 months after surgery showed significantly better results in group I than group II(p = 0.002 at 3 months; p = 0.005 at 6 months). The deficit in external rotation with arm adduction was also significantly lower in group I at 3 months (p = 0.001) and 6 months (p = 0.001) after surgery. However, external rotation with arm adduction at 12 months after surgery did not significantly differ between the groups. Moreover, the ROM in external rotation with 90° arm abduction was significantly better in group I than that in group II at 3, 6, and 12 months postoperatively (p = 0.002, p = 0.001, and p = 0.005, respectively). The deficit in external rotation with 90° arm abduction gradually decreased with time after surgery and differed significantly between the groups. However, the difference in deficit between the two groups at 12 months after surgery did not exceed the measurement error. All clinical scores significantly improved after surgery compared to before surgery; however, the improvement did not significantly differ between the two groups. CONCLUSION: The Latarjet procedure without capsular repair showed good laxity restoration and clinical results with less early postoperative external rotation limitation than that achieved by the same procedure with capsular repair. However, external rotation deficit at 1 year after surgery did not show a clinically relevant difference difference between the two groups. LEVEL OF EVIDENCE: Level III.

An Automated High-Throughput Screening (HTS) Spotter for 3D Tumor Spheroid Formation.

Three-dimensional (3D) culture platforms have been adopted in a high-throughput screening (HTS) system to mimic in vivo physiological microenvironments. The automated dispenser has been established commercially to enable spotting or distributing non-viscous or viscous biomaterials onto microplates. However, there are still challenges to the precise and accurate dispensation of cells embedded in hydrogels such as Alginate- and Matrigel-extracellular matrices. We developed and improved an automated contact-free dispensing machine, the ASFA SPOTTER (V5 and V6), which is compatible with 96- and 384-pillar/well plates and 330- and 532-micropillar/well chips for the support of 3D spheroid/organoid models using bioprinting techniques. This enables the distribution of non-viscous and viscous biosamples, including chemical drugs and cancer cells, for large-scale drug screening at high speed and small volumes (20 to 4000 nanoliters) with no damage to cells. The ASFA SPOTTER (V5 and V6) utilizes a contact-free method that minimizes cross-contamination for the dispensation of encapsulated tissue cells with highly viscous scaffolds (over 70%). In particular, the SPOTTER V6 does not require a washing process and offers the advantage of almost no dead volume (defined as additional required sample volume, including a pre-shot and flushing shot for dispensing). It can be successfully applied for the achievement of an organoid culture in automation, with rapid and easy operation, as well as miniaturization for high-throughput screening. In this study, we report the advantages of the ASFA SPOTTER, which distributes standard-sized cell spots with hydrogels onto a 384-pillar/well plate with a fast dispensing speed, small-scale volume, accuracy, and precision.

The Role of CPNE7 (Copine-7) in Colorectal Cancer Prognosis and Metastasis.

Colorectal cancer (CRC) is one of the most common and deadly cancers in the world. However, no effective treatment for the disease has yet been found. For this reason, several studies are being carried out on the treatment of CRC. Currently, there is limited understanding of the role of CPNE7 (copine-7) in CRC progression and metastasis. The results of this study show that CPNE7 exerts an oncogenic effect in CRC. First, CPNE7 was shown to be significantly up-regulated in CRC patient tissues and CRC cell lines compared to normal tissues according to IHC staining, qRT-PCR, and western blotting. Next, this study used both systems of siRNA and shRNA to suppress CPNE7 gene expression to check the CPNE7 mechanism in CRC. The suppressed CPNE7 significantly inhibited the growth of CRC cells in in vitro experiments, including migration, invasion, and semisolid agar colony-forming assay. Moreover, the modified expression of CPNE7 led to a decrease in the levels of genes associated with epithelial-mesenchymal transition (EMT). The epithelial genes E-cadherin (CDH1) and Collagen A1 were upregulated, and the levels of mesenchymal genes such as N-cadherin (CDH2), ZEB1, ZEB2, and SNAIL (SNAL1) were downregulated after CPNE7 inhibition. This study suggests that CPNE7 may serve as a potential diagnostic biomarker for CRC patients.

Nutrient-specific proteomic analysis of the mucin degrading bacterium Akkermansia muciniphila.

Akkermansia muciniphila is a prominent mucin-degrading bacterium that acts as a keystone species in regulating the human gut microbiota. Despite recently increasing research into this bacterium and its relevance to human health, a high-resolution database of its functional proteins remains scarce. Here, we provide a proteomic overview of A. muciniphila grown in different nutrient conditions ranging from defined to complex. Of 2318 protein-coding genes in the genome, we identified 841 (40%) that were expressed at the protein level. Overall, proteins involved in energy production and carbohydrate metabolism indicate that A. muciniphila relies mainly on the Embden-Meyerhof-Parnas pathway, and produces short-chain fatty acids through anaerobic fermentation in a nutrient-specific manner. Moreover, this bacterium possesses a broad repertoire of glycosyl hydrolases, together with putative peptidases and sulfatases, to cleave O-glycosylated mucin. Of them, putative mucin-degrading enzymes (Amuc_1220, Amuc_1120, Amuc_0052, Amuc_0480, and Amuc_0060) are highly abundant in the mucin-supplemented media. Furthermore, A. muciniphila uses mucin-derived monosaccharides as sources of energy and cell wall biogenesis. Our dataset provides nutrient-dependent global proteomes of A. muciniphila ATCC BAA-835 to offer insights into its metabolic functions that shape the composition of the human gut microbiota via mucin degradation.

Cell Proliferation Receptor-Enhanced 3D High-Throughput Screening Model for Optimized Drug Efficacy Evaluation in Breast Cancer Cells.

A higher correlation of epidermal growth factor receptor (EGFR)-targeting drugs has been reported with the use of the cell proliferation receptor-enhanced three-dimensional high-throughput screening model (CPRE 3D-HTS model) compared with two-dimensional (2D) cell-based HTS. A greater expression of differential human EGFR 2 (HER2) protein between HER2-positive and HER2-negative cell lines was observed in breast cancer (BC) cell lines cultured using the CPRE 3D-HTS model compared with 2D-cultured cells. When using 2D-cultured cells, properties such as the expression of the cell proliferation receptor are lost as the cells attach to the bottom of the well plate. In an effort to solve this problem, the CPRE 3D-HTS model expressing high cell proliferation receptors was optimized by the selection of alginate as the extracellular matrix. Results from the use of the CPRE 3D-HTS model showed higher drug resistance with increased expression of drug resistance-related proteins. Of particular interest, a higher correlation of HER2-targeted drugs was observed with the use of the CPRE 3D-HTS model. In order to validate this higher correlation of target drugs observed in the CPRE 3D-HTS model, the results of Western blot analysis and high content imaging analysis were analyzed, which confirmed that 3D-cultured BC cell lines showed a greater difference in the expression of HER2-positive and HER2-negative BC cell lines than 2D-cultured cells. Thus, the use of CPRE 3D-HTS using a 384-pillar plate resulted in increased accuracy when screening HER2-targeted drugs in BC, and it is a very useful platform for analyzing the efficacy of targeted drugs by enhancing the expression of HER2.

Description of Microbacterium neungamense sp. nov. isolated from a hot spring.

The Gram-positive, nonmotile, rod-shaped bacterium EF45044T was isolated from a hot spring in Chungju, South Korea. The strain was able to grow at concentrations of 0‒5% (w/v) NaCl, at pH 6.0‒10.0 and in the temperature range of 18‒50 °C. Strain EF45044T showed the highest 16S rRNA gene sequence similarity (98.2%) with Microbacterium ketosireducens DSM 12510T, and the digital DNA‒DNA hybridization (dDDH), average amino acid identity (AAI), and average nucleotide identity (ANI) values were all lower than the accepted species threshold. Strain EF45044T contained MK‒12 and MK‒13 as the predominant respiratory quinones and anteiso‒C17:0, anteiso‒C15:0, and iso‒C16:0 as the major fatty acids. Diphosphatidylglycerol, phosphatidylglycerol, and glycolipid were detected as the major polar lipids. The cell-wall peptidoglycan contained ornithine. The DNA G + C content was 71.4 mol%. Based on the polyphasic data, strain EF45044T (= KCTC 49703T) presents a novel species of the genus Microbacterium, for which the name Microbacterium neungamense sp. nov. is proposed.

Mood disorders increase mortality mainly through dementia: A community-based prospective cohort study.

OBJECTIVE: The effects of mood disorders on mortality may be mediated by their effects on the risk of dementia, and interventions to reduce the occurrence of dementia may reduce their overall mortality. This study aimed to investigate the direct effects of depressive and bipolar disorders on the 6-year risk of mortality and also their indirect effects on mortality due to their effect on the risk of dementia. METHODS: A total of 5101 Koreans were selected from a community-based prospective cohort study, and 6-year risks of mortality and dementia in participants with depressive and bipolar disorders were estimated by Cox proportional hazard analysis. The direct and indirect effects of depressive and bipolar disorders on the risk of mortality were estimated using structural equation modeling. RESULTS: The depressive and bipolar disorder groups showed 51% and 85% higher 6-year mortality, and 82% and 127% higher risk of dementia, respectively, compared to euthymic controls. The effects of depressive and bipolar disorders on mortality were mainly mediated by their effects on the risk of dementia in a structural equation model. The direct effects of each mood disorder on mortality were not significant. CONCLUSION: Both depressive and bipolar disorders increased the risks of mortality and dementia, and the effects of mood disorders on mortality were mainly mediated through dementia. As dementia occurs later in life than mood disorders, measures to prevent it may effectively reduce mortality in individuals with a history of mood disorders, as well as being more feasible than attempting to control other causes of death.

High-Throughput 3D Tumor Spheroid Array Platform for Evaluating Sensitivity of Proton-Drug Combinations.

Proton beam therapy (PBT) is a critical treatment modality for head and neck squamous cell carcinoma (HNSCC). However, not much is known about drug combinations that may improve the efficacy of PBT. This study aimed to test the feasibility of a three-dimensional (3D) tumor-spheroid-based high-throughput screening platform that could assess cellular sensitivity against PBT. Spheroids of two HNSCC cell lines-Fadu and Cal27-cultured with a mixture of Matrigel were arrayed on a 384-pillar/well plate, followed by exposure to graded doses of protons or targeted drugs including olaparib at various concentrations. Calcein staining of HNSCC spheroids revealed a dose-dependent decrease in cell viability for proton irradiation or multiple targeted drugs, and provided quantitative data that discriminated the sensitivity between the two HNSCC cell lines. The combined effect of protons and olaparib was assessed by calculating the combination index from the survival rates of 4 × 4 matrices, showing that Cal27 spheroids had greater synergy with olaparib than Fadu spheroids. In contrast, adavosertib did not synergize with protons in both spheroids. Taken together, we demonstrated that the 3D pillar/well array platform was a useful tool that provided rapid, quantitative data for evaluating sensitivity to PBT and drug combinations. Our results further supported that administration of the combination of PBT and olaparib may be an effective treatment strategy for HNSCC patients.