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1.
Antimicrob Agents Chemother ; : AAC0184221, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35007129

RESUMO

Thirty-two healthy male subjects (8 per cohort) were randomized 6:2 to active:placebo. LSVT-1701, an anti-staphylococcal lysin, was administered intravenously as a 6 mg/kg single dose and as 1.5, 3, and 4.5 mg/kg twice daily for 4 days. LSVT-1701 exposure increased in a greater than dose proportional manner and did not accumulate. Treatment-emergent adverse events (TEAEs) were predominantly of mild intensity. The most common TEAEs were chills, pyrexia, headache, infusion site events, cough, rhinorrhea, and increases in C-reactive protein.

2.
Biosens Bioelectron ; 200: 113903, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973564

RESUMO

Site-selective drug effects on the ion-channel activities of γ-aminobutyric acid type A (GABAA) receptors are evaluated by using a nanovesicle-carbon nanotube hybrid device. Here, nanovesicles containing GABAA receptors are immobilized on the channel region of a carbon nanotube field-effect transistor. The receptor responses of this hybrid device to GABA are detected with a high sensitivity down to ∼1 aM even in the presence of other neurotransmitters. Further, sensitivity differences between two GABAA-receptor-subunit compositions of α5ß2γ2 and α1ß2γ2 are assessed by normalizing the dose-dependent responses obtained from these hybrid devices. Specifically, the GABA concentration that produces 50% of maximal response (EC50) is obtained as ∼10 pM for α5ß2γ2 subunits and ∼1 nM for α1ß2γ2 subunits of GABAA receptor. Significantly, the potency profiles of both antagonist and agonist of GABAA receptor can be evaluated by analyzing EC50 values in the presence and absence of those drugs. A competitive antagonist increases the EC50 value of GABA by binding to the same site as GABA, while an allosteric agonist reduces it by binding to a different site. These results indicate that this hybrid device can be a powerful tool for the evaluation of candidate drug substances modulating GABA-mediated neurotransmission.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Preparações Farmacêuticas , Receptores de GABA , Receptores de GABA-A/genética , Ácido gama-Aminobutírico
3.
Korean J Intern Med ; 37(1): 109-118, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35000375

RESUMO

BACKGROUND/AIMS: While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm. METHODS: The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath. RESULTS: The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm. CONCLUSION: We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.

4.
Metabolism ; 129: 155135, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35032546

RESUMO

BACKGROUND: Diabetes is associated with a high risk of fragility fracture. However, there are controversies regarding the effect of fluctuations in metabolic parameters on the risk of fracture. We aimed to investigate the associations of body weight or glucose variability or their combination with the risk of hip fracture in people with diabetes. METHODS: A population-based cohort study with 480,539 subjects over 40 years who had undergone three or more health examinations was performed. The degree of variability was evaluated using variability independent of the mean (VIM, 100 × standard deviation / meanbeta), coefficient of variation (CV), and average real variability (ARV, average of the absolute differences between consecutive values). High variability was defined as having values in the highest quartile. Cox proportional hazards models were used to estimate the risk of hip fracture. RESULTS: There were 2834 hip fracture events (0.59%) during the mean follow-up of 8.1 years. After multivariable adjustment for age, sex, alcohol consumption, smoking, regular exercise, income, glucose, body mass index, hemoglobin, estimated glomerular filtration rate, diabetes duration, diabetes treatment with multiple agents, and osteoporosis, the HRs (95% CI) of hip fracture were 1.36 (1.24-1.50) and 1.29 (1.16-1.43) for high body weight VIM and high glucose VIM, respectively. The HR (95% CI) of both high VIM group was 1.63 (1.44-1.83), suggesting an additive effect of variabilities in body weight and glucose. The results were consistent when using CV and ARV and in various sensitivity analyses. CONCLUSIONS: High variability in body weight and glucose levels is associated with an increased incidence rate and risk of hip fracture in people with diabetes.

5.
Sci Rep ; 12(1): 32, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996994

RESUMO

Thin film-based optical sensors have been attracting increasing interest for use in developing technologies such as biometrics. Multilayered dielectric thin films with different refractive indices have been utilized to modulate the optical properties in specific wavelength bands for spectral selectivity of Thin Film Narrow Bandpass Filters (TFNBFs). Progress in TFNBF design has been made with the incorporation of metallic thin films. Narrower bandwidths with higher transmittance have been achieved in specific spectral bands. In this work, Ti/TiO2/SiO2 based multilayer thin films were prepared using pulsed-DC reactive sputtering. Computer simulations using the Essential Macleod Program allowed the optimal number of layers and thickness of the multilayer thin films to be determined to efficiently tailor the optical path transmitting specific wavelength bands. The addition of Ti metal layers within dielectric (TiO2/SiO2) multilayer thin films significantly changes the cutoff frequency of transmittance at specific wavelengths. Representative 26 multilayer films consisting of Ti, TiO2, and SiO2 show lower transmittance of 10.29% at 400 nm and 10.48% at 680 nm. High transmittance of 80.42% at 485 nm was observed, which is expected to improve the spectral selectivity of the TFNBF. This work provides a contribution to future simulation based design strategy based on experimental thin film engineering for potential industrial development opportunities such as optical biometrics.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34894110

RESUMO

INTRODUCTION: Vortioxetine has a positive effect on cognitive function in patients with major depressive disorder (MDD). This study aimed to examine the changes in cognitive function and EEG (spectral power and mismatch negativity (MMN)) in patients with MDD pre- and postvortioxetine treatment. METHODS: Thirty patients with MDD were included in the study. They were given vortioxetine (10-20mg po per day) for eight weeks. Depression and anxiety severities, social function (Korean version of the social adjustment scale (K-SAS)), and cognitive function (digit-symbol substitution Test (DSST), Korean version of the attentional control questionnaire (K-ACQ), and Korean version of the perceived deficits questionnaire for depression (K-PDQD)) were evaluated. Spectral power of EEG and MMN was also measured pre- and postvortioxetine treatment. RESULTS: Depression and anxiety severity, social function, and cognitive functioning significantly improved after vortioxetine treatment. Also, there was a significant decrease in the right central delta band and an increase in the right central beta 2 band following vortioxetine treatment. The changes in EEG spectral power were not related to changes in cognitive functions. Baseline MMN significantly predicted changes in DSST score after controlling for the baseline clinical variables. CONCLUSION: Vortioxetine treatment improved cognitive function and induced changes in EEG (decreased theta power and increased beta power) in patients with MDD. Our results suggest that greater negative MMN amplitude is associated with greater potential for cognitive improvement following vortioxetine treatment.

7.
Sci Rep ; 11(1): 23486, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34873277

RESUMO

We evaluated the predictive value of 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography/CT (PET/CT) for extended pathological T (pT) stages (≥ pT3a) in Renal cell carcinoma (RCC) patients at staging. Thirty-eight RCC patients who underwent 18F-FDG PET/CT at staging, followed by radical nephrectomy between September 2016 and September 2018, were included in this prospective study. Patients were classified into two groups (limited pT stage: stage T1/2, n = 17; extended pT stage: T3/4, n = 21). Univariate and multivariate logistic regression analyses were performed to identify clinicopathological and metabolic variables to predict extended pT stages. 18F-FDG metabolic parameters were compared in relation to International Society of Urological Pathology (ISUP) grade and lymphovascular invasion (LVI). In univariate analysis, maximum standardised uptake value, metabolic tumour volume (MTV), and ISUP grade were significant. In multivariate analysis, MTV was the only significant factor of extended pT stages. With a cut-off MTV of 21.2, an area under the curve was 0.944, which was higher than 0.824 for clinical T stages (p = 0.037). In addition, high MTV, but not tumour size, was significantly correlated with aggressive pathologic features (ISUP grade and LVI). High glycolytic tumour volume on 18F-FDG PET/CT in RCC patients at staging is predictive of extended pT stages which could aid decision-making regarding the best type of surgery.

8.
J Anim Breed Genet ; 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34902178

RESUMO

The genetic improvement of Hanwoo is dependent on the estimated breeding value (EBV) of pedigree-based Korean proven bull's number, and the genetic evaluation for cows is difficult due to insufficient pedigree and test records. Genomic selection involves utilizing the individual's genotype to estimate the breeding value (BV) and is determined to be an appropriate evaluation method for cows who lack test information. This study used pedigree and genotype to estimate and analyse BV and accuracy of Hanwoo cows in the Gyeongnam area using pedigree best linear unbiased prediction (PBLUP) and genomic best linear unbiased prediction (GBLUP). The test group acquired pedigree and genotype of 919 Hanwoo cows in the Gyeongnam area. The traits used for analysis were carcass weight (CWT), eye muscle areas (EMA), backfat thickness (BFT) and marbling score (MS). PBLUP used Reference group 1 containing the pedigree and phenotype of 919 Hanwoo cows and 545,483 heads to construct the numeric relationship matrix and estimated the EBV and accuracy. GBLUP used Reference group 2 containing the genotype and phenotype of 919 Hanwoo cows and 17,226 heads to construct the genomic relationship matrix and estimated the genomic EBV (GEBV) and accuracy. In the order of CWT, EMA, BFT and MS, the accuracy of PBLUP was 0.488, 0.480, 0.482 and 0.486 while the accuracy of GBLUP was higher with 0.779, 0.758, 0.766 and 0.791. And for 104 cows without relationship coefficient on pedigree to the reference group, the accuracy as PBLUP was estimated to be 0, but for GBLUP, it was possible to estimate the accuracy for all individuals. If GBLUP is applied to cows raised in general farms, the genetic evaluation can be performed even on animals without pedigree and high-accuracy estimation, enabling selection of excellent cows. Accordingly, by securing the genetic diversity of cows, it is expected to increase the profitability of farms by decreasing the inbreeding rate and increasing efficiency of elite calf production.

9.
Nature ; 600(7889): 439-443, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34912084

RESUMO

Fractional Chern insulators (FCIs) are lattice analogues of fractional quantum Hall states that may provide a new avenue towards manipulating non-Abelian excitations. Early theoretical studies1-7 have predicted their existence in systems with flat Chern bands and highlighted the critical role of a particular quantum geometry. However, FCI states have been observed only in Bernal-stacked bilayer graphene (BLG) aligned with hexagonal boron nitride (hBN)8, in which a very large magnetic field is responsible for the existence of the Chern bands, precluding the realization of FCIs at zero field. By contrast, magic-angle twisted BLG9-12 supports flat Chern bands at zero magnetic field13-17, and therefore offers a promising route towards stabilizing zero-field FCIs. Here we report the observation of eight FCI states at low magnetic field in magic-angle twisted BLG enabled by high-resolution local compressibility measurements. The first of these states emerge at 5 T, and their appearance is accompanied by the simultaneous disappearance of nearby topologically trivial charge density wave states. We demonstrate that, unlike the case of the BLG/hBN platform, the principal role of the weak magnetic field is merely to redistribute the Berry curvature of the native Chern bands and thereby realize a quantum geometry favourable for the emergence of FCIs. Our findings strongly suggest that FCIs may be realized at zero magnetic field and pave the way for the exploration and manipulation of anyonic excitations in flat moiré Chern bands.

11.
J Anim Sci Technol ; 63(6): 1232-1246, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34957440

RESUMO

Recently, the cattle genome sequence has been completed, followed by developing a commercial single nucleotide polymorphism (SNP) chip panel in the animal genome industry. In order to increase statistical power for detecting quantitative trait locus (QTL), a number of animals should be genotyped. However, a high-density chip for many animals would be increasing the genotyping cost. Therefore, statistical inference of genotype imputation (low-density chip to high-density) will be useful in the animal industry. The purpose of this study is to investigate the effect of the reference population size and marker density on the imputation accuracy and to suggest the appropriate number of reference population sets for the imputation in Hanwoo cattle. A total of 3,821 Hanwoo cattle were divided into reference and validation populations. The reference sets consisted of 50k (38,916) marker data and different population sizes (500, 1,000, 1,500, 2,000, and 3,600). The validation sets consisted of four validation sets (Total 889) and the different marker density (5k [5,000], 10k [10,000], and 15k [15,000]). The accuracy of imputation was calculated by direct comparison of the true genotype and the imputed genotype. In conclusion, when the lowest marker density (5k) was used in the validation set, according to the reference population size, the imputation accuracy was 0.793 to 0.929. On the other hand, when the highest marker density (15k), according to the reference population size, the imputation accuracy was 0.904 to 0.967. Moreover, the reference population size should be more than 1,000 to obtain at least 88% imputation accuracy in Hanwoo cattle.

12.
Endocrinol Metab (Seoul) ; 36(6): 1254-1267, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34897261

RESUMO

BACKGROUND: We analyzed hemoglobin A1c (HbA1c) levels and various lung function test results in healthy individuals after a 6-year follow-up period to explore the influence of lung function changes on glycemic control. METHODS: Subjects whose HbA1c levels did not qualify as diabetes mellitus (DM) and who had at least two consecutive lung function tests were selected among the people who visited a health promotion center. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV/FVC ratio, and forced expiratory flow 25% to 75% (FEF25%-75%), were divided into four groups based on their baseline quantiles. To evaluate future DM onset risk in relation to lung function changes, the correlation between baseline HbA1c levels and changes in lung function parameters after a 6-year follow-up period was analyzed. RESULTS: Overall, 17,568 individuals were included; 0.9% of the subjects were diagnosed with DM. The individuals included in the quartile with FEV1/FVC ratio values of 78% to 82% had lower risk of DM than those in the quartile with FEV1/FVC ratio values of ≥86% after adjusting for age, sex, and body mass index (P=0.04). Baseline percent predicted FEV1, FVC, FEV1/FVC ratio, and FEF25%-75%, and differences in the FEV1/FVC ratio or FEF25%-75%, showed negative linear correlations with baseline HbA1c levels. CONCLUSION: Healthy subjects with FEV1/FVC ratio values between 78% and 82% had 40% lower risk for future DM. Smaller differences and lower baseline FEV1/FVC ratio or FEF25%-75% values were associated with higher baseline HbA1c levels. These findings suggest that airflow limitation affects systemic glucose control and that the FEV1/FVC ratio could be one of the factors predicting future DM risk in healthy individuals.

13.
Polymers (Basel) ; 13(22)2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34833243

RESUMO

This study reports the preparation of a polybutylene succinate (PBS) film reinforced with pure cellulose nanofibril (PCNF) and lignocellulose nanofibril (LCNF) by a two-step process that consists of solvent dispersion and twin-screw extrusion. Compared to the conventional one-step process, this method offered improved mechanical properties. The addition of 5% CNF increased the tensile properties up to 18.8%. Further, the effect of the lignin content was also studied by using LCNF as a reinforcement. The LCNF was prepared with and without a deep eutectic solvent (DES) pretreatment to gain LCNF with a lignin content that varied between 5, 19, and 30%. The mechanical properties results show that a 5% addition of LCNF to the PBS matrix increased its tensile strength and elastic modulus. Further, the morphological and thermal properties of the composites were also studied in detail.

14.
Sci Rep ; 11(1): 22007, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759276

RESUMO

Default mode network (DMN) is a set of functional brain structures coherently activated when individuals are in resting-state. In this study, we constructed multi-frequency band resting-state EEG-based DMN functional network models for major psychiatric disorders to easily compare their pathophysiological characteristics. Phase-locking values (PLVs) were evaluated to quantify functional connectivity; global and nodal clustering coefficients (CCs) were evaluated to quantify global and local connectivity patterns of DMN nodes, respectively. DMNs of patients with post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), panic disorder, major depressive disorder (MDD), bipolar disorder, schizophrenia (SZ), mild cognitive impairment (MCI), and Alzheimer's disease (AD) were constructed relative to their demographically-matched healthy control groups. Overall DMN patterns were then visualized and compared with each other. In global CCs, SZ and AD showed hyper-clustering in the theta band; OCD, MCI, and AD showed hypo-clustering in the low-alpha band; OCD and MDD showed hypo-clustering and hyper-clustering in low-beta, and high-beta bands, respectively. In local CCs, disease-specific patterns were observed. In the PLVs, lowered theta-band functional connectivity between the left lingual gyrus and the left hippocampus was frequently observed. Our comprehensive comparisons suggest EEG-based DMN as a useful vehicle for understanding altered brain networks of major psychiatric disorders.

15.
J Biol Res (Thessalon) ; 28(1): 22, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814951

RESUMO

BACKGROUND: Peroxiredoxins (Prxs) are antioxidant enzymes that protect cells from oxidative stress induced by several factors. They regulate several signaling pathways, such as metabolism, immune response, and intracellular reactive oxygen species (ROS) homeostasis. Epithelial-mesenchymal transition (EMT) is a transforming process that induces the loss of epithelial features of cancer cells and the gain of the mesenchymal phenotype. The EMT promotes metastasis and cancer cell progression mediated by several pathways, such as mitogen-activated protein kinases (MAPKs) and epigenetic regulators. METHODS: We used Prx6 overexpressed and downregulated HCT116 cells to study the mechanism between Prx6 and colon cancer. The expression of Prx6, GAPDH, Snail, Twist1, E-cadherin, Vimentin, N-cadherin, ERK, p-ERK, p38, p-p38, JNK, and p-JNK were detected by Western blotting. Additionally, an animal study for xenograft assay was conducted to explore the function of Prx6 on tumorigenesis. Cell proliferation and migration were determined by IncuCyte Cell Proliferation and colony formation assays. RESULTS: We confirmed that the expression of Prx6 and EMT signaling highly occurs in HCT116 compared with that in other colon cancer cell lines. Prx6 regulates the EMT signaling pathway by modulating EMT-related transcriptional repressors and mesenchymal genes in HCT116 colon cancer cells. Under the Prx6-overexpressed condition, HCT116 cells proliferation increased significantly. Moreover, the HCT116 cells proliferation decreased in the siPrx6-treated cells. Eleven days after HCT116 cell injection, Prx6 was overexpressed in the HCT116-injected mice, and the tumor volume increased significantly compared with that of the control mice. Furthermore, Prx6 regulates EMT signaling through p38 phosphorylation in colon cancer cells. CONCLUSION: We suggested that Prx6 regulates EMT signaling pathway through p38 phosphorylation modulation in HCT116 colon cancer cells.

16.
Sci Rep ; 11(1): 22749, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34815435

RESUMO

Childhood trauma (ChT) is a risk factor for psychosis. Negative lifestyle factors such as rumination, negative schemas, and poor diet and exercise are common in psychosis. The present study aimed to perform a network analysis of interactions between ChT and negative lifestyle in patients and controls. We used data of patients with early-stage psychosis (n = 500) and healthy controls (n = 202). Networks were constructed using 12 nodes from five scales: the Brief Core Schema Scale (BCSS), Brooding Scale (BS), Dietary Habits Questionnaire, Physical Activity Rating, and Early Trauma Inventory Self Report-Short Form (ETI). Graph metrics were calculated. The nodes with the highest predictability and expected influence in both patients and controls were cognitive and emotional components of the BS and emotional abuse of the ETI. The emotional abuse was a mediator in the shortest pathway connecting the ETI and negative lifestyle for both groups. The negative others and negative self of the BCSS mediated emotional abuse to other BCSS or BS for patients and controls, respectively. Our findings suggest that rumination and emotional abuse were central symptoms in both groups and that negative others and negative self played important mediating roles for patients and controls, respectively.Trial Registration: ClinicalTrials.gov identifier: CUH201411002.

17.
Endocrinol Metab (Seoul) ; 36(5): 1007-1015, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34674499

RESUMO

BACKGROUND: Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk. METHODS: Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4. RESULTS: The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for allcause mortality remained. CONCLUSION: The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

18.
Nat Metab ; 3(10): 1385-1399, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34675440

RESUMO

Metabolic engineering often entails concurrent engineering of substrate utilization, central metabolism and product synthesis pathways, inevitably creating interdependency with native metabolism. Here we report an alternative approach using synthetic pathways for C1 bioconversion that generate multicarbon products directly from C1 units and hence are orthogonal to the host metabolic network. The engineered pathways are based on formyl-CoA elongation (FORCE) reactions catalysed by the enzyme 2-hydroxyacyl-CoA lyase. We use thermodynamic and stoichiometric analyses to evaluate FORCE pathway variants, including aldose elongation, α-reduction and aldehyde elongation. Promising variants were prototyped in vitro and in vivo using the non-methylotrophic bacterium Escherichia coli. We demonstrate the conversion of formate, formaldehyde and methanol into various products including glycolate, ethylene glycol, ethanol and glycerate. FORCE pathways also have the potential to be integrated with the host metabolism for synthetic methylotrophy by the production of native growth substrates as demonstrated in a two-strain co-culture system.

19.
APL Bioeng ; 5(4): 041505, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34703969

RESUMO

The liver plays important roles in drug metabolism and homeostasis. The metabolism and biotransformation can not only affect the efficacy of drugs but also result in hepatotoxicity and drug-induced liver injury. Understanding the complex physiology of the liver and the pathogenetic mechanisms of liver diseases is essential for drug development. Conventional in vitro models have limitations in the ability to predict drug effects, due to the lack of physiological relevance. Recently, the liver-on-a-chip platform has been developed to reproduce the microarchitecture and in vivo environment of the liver. These efforts have improved the physiological relevance of the liver tissue used in the platform and have demonstrated its applicability to drug screening and disease models. In this review, we summarize the recent development of liver-on-a-chip models that closely mimic the in vivo liver environments and liver diseases.

20.
Int J Hematol ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34617186

RESUMO

Isolated extramedullary relapse (EMR) without bone marrow relapse (BMR) after allogeneic hematopoietic cell transplantation (allo-HCT) is a rare condition in patients with acute lymphoblastic leukemia (ALL), and the role of immunotherapeutic agents for these patients remains unclear. We analyzed treatment outcomes of blinatumomab or inotuzumab ozogamicin (INO) as first- or second-line salvage therapy in nine patients with Philadelphia chromosome-negative B-cell precursor ALL presenting with isolated EMR after previous allo-HCT. In seven patients receiving blinatumomab as first-line salvage therapy, 4 (57.1%) achieved complete remission (CR). Among the three patients without remission after blinatumomab, two switched to INO and subsequently showed responses {one CR and one partial response [PR]}, and one switched to multiagent chemotherapy that led to CR. In the two patients receiving first-line salvage therapy with INO, one showed PR and the other achieved CR. Overall, 6 (66.7%) of nine patients achieved CR, and five of them proceeded to allo-HCT in CR. The median overall survival after relapse was 27.8 months. In conclusion, both blinatumomab and INO showed good response rates and a safe bridging role to second allo-HCT in patients with isolated EMR. However, clinical differences between isolated EMR and EMR with BMR remain to be elucidated.

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