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Although proteinuria is a risk factor for heart failure (HF), proteinuria can be reversible or persistent. Our objective was to explore the link between changes in the proteinuria status and the risk of HF. We included participants from a Korean national health screening cohort who underwent health examinations in 2003–2004 and 2005–2006 and had no history of HF. Participants were categorized into four groups: proteinuria-free, proteinuria-resolved, proteinuria-developed, and proteinuria-persistent. The outcome of interest was the occurrence of HF. The study included 1,703,651 participants, among whom 17,543 (1.03%) were in the proteinuria-resolved group and 4585 (0.27%) were in the proteinuria-persistent group. After a median follow-up period of 14.04 years (interquartile range 14.19–15.07), HF occurred in 75,064 (4.41%) participants. A multivariable Cox proportional hazards regression analysis indicated that the proteinuria-persistent group had a higher risk of HF compared with the proteinuria-free group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 2.03–2.36, p < 0.001). In a further pairwise comparison analysis, participants in the proteinuria-resolved group had a relatively low risk of HF compared with those in the proteinuria-persistent group (HR: 0.64, 95% CI: 0.58–0.70, p < 0.001). In conclusion, the risk of HF can change with alterations in the proteinuria status. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases. However, recent studies have shown that chronic PPI use is associated with the progression of endothelial senescence and cerebrovascular diseases. We hypothesized that PPI users might be vulnerable to fast progression of cerebral small vessel disease (SVD) with cumulative effects. Four hundred and eleven patients, who underwent brain magnetic resonance imaging, more than twice between January 2010 and December 2016 were screened. Patients aged < 50 years, and those who had concomitant diseases that might affect the progression of cerebral SVD were excluded. Baseline characteristics were collected. We evaluated the severity of SVD using the Fazekas score, the number of cerebral microbleeds (CMBs), and assessed the progression of SVD or CMBs based on the cumulative dose of PPIs. Among the included patients (N = 137), 39 were PPI ever-users. Univariate Cox regression analysis showed that PPI use was independently associated with the progression of Fazekas score only in the deep white matter hyperintensities (WMH) (hazard ratio [HR] 2.891, 95% confidence interval [CI] 1.210–6.906, P = 0.017). In multivariate Cox regression analysis, long-term PPI use was associated with a progression of Fazekas score in the deep WMH (HR 3.453, 95% CI 1.027–9.475, P = 0.045). However, PPI use was not associated with the progression of CMB. The present study results suggest that long-term use of PPIs is associated with the progression of deep cerebral WMH. Further research is needed using a large number of patients to validate this relationship. [ABSTRACT FROM AUTHOR]

• Volume reduction of gray matter (GM) was identified after brain RT in glioma patients. • GM area of cognition and execution of movement showed the greatest volume reduction. • Female and elderly patients were most susceptible to RT-induced GM reduction. • Each region had a specific threshold age affecting significant GM volume reduction. We evaluated volumetric changes in the gray matter (GM) after radiotherapy (RT) and identified factors that were strongly associated with GM volume reduction. A total of 461 magnetic resonance imagings (MRI) from 105 glioma patients treated with postoperative RT was retrospectively analyzed. Study patients' MRIs were collected at five time points: before RT and 1 month, 6 months, 1 year, and 2 years after RT. Using the 'FastSurfer' platform, a deep learning-based neuroimaging pipeline, 73 regions were automatically segmented from longitudinal MRIs and their volumetric changes were calculated. Regions were grouped into 10 functional fields. A multivariable linear mixed-effects model was established to identify the potential predictors of significant volume reduction. The median age was 50 years (range, 16–86 years). Forty-seven (44.8 %) patients were female and 68 (64.8 %) had glioblastoma. Postoperative RT was delivered at 54–60 Gy with or without concurrent chemotherapy. At 2 years after RT, the median volumetric changes in the overall, ipsilateral, and contralateral GM were −3.5%, −4.5%, and −2.4%, respectively. The functional fields of cognition and execution of movement showed the greatest volume reductions. In the multivariable linear mixed model, female sex (normalized coefficient = −0.14, P < 0.001) and the interaction between age at RT and days after RT (normalized coefficient = −6.48e-6, P < 0.001) were significantly associated with GM reduction. The older patients received RT, the greater volume reduction was seen over time. However, in patients with relatively younger age (e.g., 45, 50, and 60 years for hippocampus, Broca area, and Wernicke area, respectively), the volume was not significantly reduced. GM volume reduction was identified after RT that could lead to long-term treatment sequelae. Particularly for susceptible patients, individualized treatment and prevention strategies are needed. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to investigate the effect of gradual dipyridamole titration and the incidence of dipyridamole-induced headache in patients with ischemic stroke or transient ischemic attack (TIA). Methods: A randomized, double-blind, double-placebo, parallel group, phase 4 clinical trial (KCT0005457) was conducted between July 1, 2019, and February 25, 2020, at 15 medical centers in South Korea. The study included patients aged >19 years diagnosed with a noncardioembolic ischemic stroke or TIA within the previous 3 weeks. The participants were randomized 1:1:1 to receive Adinox® (aspirin 25 mg/dipyridamole 200 mg) and aspirin (100 mg) once daily for the first 2 weeks followed by Adinox® twice daily for 2 weeks (titration group), Adinox® twice daily for 4 weeks (standard group), and aspirin 100 mg once daily for 4 weeks (control group). The primary endpoint was incidence of headache over 4 weeks. The key secondary endpoint was mean cumulative headache. Results: Ninety-six patients were randomized into the titration (n = 31), standard (n = 32), and control (n = 33) groups. The titration and standard groups (74.1% vs. 74.2%, respectively) showed no difference in the primary endpoint. However, the mean cumulated headache was significantly lower in the titration group than in the standard group (0.31 ± 0.46 vs. 0.58 ± 0.51, p = 0.023). Further, adverse drug reactions were more common in the standard group than in the titration group (28.1% vs. 9.7%, respectively, p = 0.054), although not significantly different. Conclusion: The titration strategy was effective in lowering the incidence of cumulative dipyridamole-induced headache. [ABSTRACT FROM AUTHOR]

We evaluated the feasibility of the Framingham stroke risk score (FSRS) and atherosclerotic cardiovascular disease (ASCVD) risk scores for asymptomatic carotid stenosis (ACS). In addition, we developed novel risk prediction models for ischemic stroke and composite outcomes by combining ultrasonographic parameters and conventional cardiovascular risk scores. We retrospectively enrolled 612 patients with ACS greater than 50% over 7 years and evaluated them using transcranial Doppler and carotid duplex ultrasonography. In total, 150 patients were included in the analysis. During the mean 5-year follow-up, 6 ischemic strokes and 25 composite events were detected. Among all ultrasonographic parameters, only a higher peak-systolic velocity/end-diastolic velocity ratio was detected and significantly associated with an increased risk of relevant ischemic stroke (hazard ratio: 1.502, 95% confidence interval: 1.036–1.968). The C-statistics of the FSRS and ASCVD risk scores were 0.646 and 0.649, respectively, for relevant ischemic stroke, and 0.612 and 0.649, respectively, for composite outcomes. C-statistics of the FSRS and ASCVD risk scores combined with ultrasonographic parameters increased to 0.937 and 0.941, respectively, for ischemic stroke, and 0.856 and 0.886, respectively, for composite outcomes. The study suggests that inclusion of ultrasonographic parameters in conventional cardiovascular scores helps identify the risk of further vascular events in ACS patients. [ABSTRACT FROM AUTHOR]

Endophytic bacteria, a rich source of bioactive secondary metabolites, are ideal candidates for environmentally benign agents. In this study, an endophytic strain, Streptomyces sp. AE170020, was isolated and selected for the purification of nematicidal substances based on its high nematicidal activity. Two highly active components, aureothin and alloaureothin, were identified, and their chemical structures were determined using spectroscopic analysis. Both compounds suppressed the growth, reproduction, and behavior of Bursaphelenchus xylophilus. In in vivo experiments, the extracts of strain Streptomyces sp. AE170020 effectively suppressed the development of pine wilt disease in 4-year-old plants of Pinus densiflora. The potency of secondary metabolites isolated from endophytic strains suggests applications in controlling Bursaphelenchus xylophilus and opens an avenue for further research on exploring bioactive substances against the pine wood nematode. [ABSTRACT FROM AUTHOR]

Background and purpose: Although it is not recognized as essential to test for antiphospholipid antibody (aPL) in stroke of unknown cause, aPL‐related stroke may account for a considerable number of cryptogenic strokes. We aimed to assess the current status and diagnostic value of aPL testing in cryptogenic stroke patients. Methods: Consecutive patients admitted with acute ischemic stroke were examined to confirm the factors associated with performing aPL testing and with positive aPL test results in real‐world practice. Cryptogenic stroke patients were separately examined in the same manner. The antibody profiles of cryptogenic stroke patients with aPL positivity were compared by age. Results: Among 2947 patients, 606 (20.6%) were tested for aPLs and 129 (21.3%) were positive. Physicians tended to perform aPL testing in patients aged <50 years and in cryptogenic stroke patients. Cryptogenic stroke was a strong predictor of positive aPL results (adjusted odds ratio 3.70, 95% confidence interval 2.38–5.76). However, aPL positivity did not differ by age in stroke patients. Among 283 cryptogenic stroke patients, 136 (48.1%) were tested for aPLs and 56 (41.2%) were positive. aPL tests were performed predominantly in patients aged <50 years rather than in older patients, even among cryptogenic stroke patients. The two age groups had similar positivity rates of >40% (<50 years: 43.2%; ≥50 years: 40.4%; p = 0.92) and their antibody profiles were similar. Conclusions: A significant number of patients with cryptogenic stroke had positive aPL results regardless of age. aPL testing may offer additional diagnostic opportunities in cryptogenic stroke patients, and thus may reduce the incidence of cryptogenic stroke. [ABSTRACT FROM AUTHOR]

We report the case of long-term follow-up of brain magnetic imaging of cerebral amyloid angiopathy. Cerebral amyloid angiopathy is often considered a major cause of spontaneous intracerebral hemorrhage in the elderly. This case illustrates the markedly progressive clinical and radiological features of the vasculopathic process in 10 years. [ABSTRACT FROM AUTHOR]

Background: Premorbid undernutrition has been proven to have an adverse effect on the prognosis of stroke patients. The evaluation of nutritional status is important, but there is no universally accepted screen methodology. Purpose: We aimed to use the geriatric nutritional risk index (GNRI) for evaluating the effect of premorbid undernutrition on short-term outcomes in patients with acute ischemic stroke. Methods: A total of 1,906 patients were included for analysis. Baseline characteristics were collected. We evaluated the nutritional status of the patients using the GNRI and body mass index(BMI). The GNRI was calculated as {1.519×serum albumin(g/dL) + 41.7×present weight (kg)/ideal body weight (kg)}. All patients were categorized into four groups on the basis of the GNRI score. Results: Among the included patients, 546 patients had an unfavorable outcomes. The proportion of patients with moderate and severe risk, assessed in GNRI, was significantly higher in the unfavorable outcome group compared to the favorable outcome group (33.3% vs 15.0%). The increased risk of premorbid undernutrition was associated with an increased risk of unfavorable outcome in a dose-response manner after adjusting for covariates. Conclusions: This study demonstrated that GNRI was associated with poor prognosis in patients with acute ischemic stroke. GNRI may be used to screen patients at high risk for unfavorable outcome. [ABSTRACT FROM AUTHOR]

Background: Until recently, it is generally considered safe to perform magnetic resonance imaging (MRI) in patients with an intrathecal drug administration system (ITDAS) device. In this study, we presented a case of morphine overdose due to ITDAS malfunction during MRI evaluation for the diagnosis of stroke.Case Presentation: A 58-year-old woman was referred to the emergency department for left-sided hemiparesis and dysarthria. She had undergone ITDAS implantation 4 years ago because of intractable back pain. Her brain MRI examination did not show any abnormalities except an old hemorrhagic infarction in the right basal ganglia. After MRI was performed, her symptoms completely resolved. Approximately 3 h after the MRI scan, the patient showed progressive stuporous consciousness and decreased respiration with decreased peripheral oxygen saturation of 80%. Initial arterial blood gas analysis revealed respiratory acidosis with hypoxia and hypercapnia. We suspected the opioid overdose for her unconciousness, small and sluggish pupils, and slow respiration. The patient regained consciousness within 3 min after the administration of naloxone with severe anxiety and irritability, without any respiratory symptoms or focal neurological deficits. In the pump interrogation and actual reservoir checks performed 6 h after the MRI scan, there was no significant difference between the expected reservoir volume and actual reservoir volume. Follow-up MRI performed to rule out posterior circulation infarction showed no structural lesions. The patient was eventually discharged without further neurologic or functional deterioration, with diagnosis of transient ischemia attack for initial symptoms of focal neurologic deficits.Conclusion: Although both ex vivo and in vivo studies have provided evidence that ITDAS devices are MRI-compatible, the pump is made of titanium and has ferromagnetic components. Since misdiagnosis of overinfusion could lead to mortality, early awareness of overinfusion of the intrathecal drug is needed to all clinicians in case of performing MRI in ITDAS implanted patients. [ABSTRACT FROM AUTHOR]

Objective: Periodic limb movements (PLMs) can increase the risk of cardiovascular disease and mortality. Small vessel disease (SVD) has been considered a precursor to symptomatic stroke. We aimed to investigate the association between PLMs and cerebral SVD.Methods: We enrolled participants who visited our clinic for the evaluation of sleep disturbance and underwent overnight polysomnography and brain magnetic resonance imaging. The processing steps included rating and analyzing white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), asymptomatic lacunar infarctions (ALIs), perivascular spaces (PVSs), and calculating the total SVD score. Logistic regression and correlation analyses were used to examine the association between PLMs during sleep (PLMS) and SVD.Results: A total of 31 (19 men and 12 women) patients with PLMS index ≥ 15/h were enrolled. The mean age was 61.7 years and the median PLMS index was 46.5/h. A total of 29 controls (16 men and 13 women) with PLMS index < 5/h were also included. PLMS index was positively associated with an increase in WMHs, ALIs, and PVSs (odds ratio [OR] = 1.022, 95% confidence interval [CI] = 1.003-1.040, p = 0.008; OR = 1.024, 95% CI = 1.006-1.043, p = 0.010; OR = 1.029, 95% CI = 1.010-1.049, p = 0.003, respectively). Correlation analyses revealed that total SVD score was significantly correlated with PLMS index (r = 0.504, p < 0.001).Conclusions: An elevated PLMS index was associated with an increase in WMHs, ALIs, PVSs, and total SVD burden. Our study suggests that PLMS is a marker for SVD, which carries a potential risk for progression to overt stroke or cognitive impairment. [ABSTRACT FROM AUTHOR]

Highlights • As bio-based production strategies mature, engineering transport across membranes remains a critical barrier. • Careful membrane protein expression is required for function without negatively impacting cellular growth and metabolism. • Synthetic biology offers genetic circuits to better control membrane protein expression. Abstract Membrane proteins are involved in a diverse array of cellular functions and part of many important metabolic pathways. As such, they are attractive targets in the pharmaceutical and bio-based chemical industries. Despite their great potential, many challenges remain before membrane proteins gain widespread success in biotechnology. The two biggest issues are that expression of membrane proteins leads to inhibition of cellular growth and metabolism, and native membrane proteins often lack a desired function or specificity for use in engineered processes. To address these issues, protein engineering and synthetic biology approaches are leading the charge to develop membrane proteins for biotechnological applications. Here, we describe current methods for engineering membrane proteins and optimizing their expression levels in bacteria. We highlight success stories and describe challenges that still face this growing field. [ABSTRACT FROM AUTHOR]

Proteinuria is associated with cardiovascular disease. However, the relationship between changes in proteinuria status and hypertension remains unclear. This study aimed to explore the association between changes in proteinuria status and the risk of developing hypertension with the data from the Korean National Health Insurance Database. We included participants without prior hypertension history who underwent their first health examination in 2003–2004 and a second examination in 2005–2006. Based on their proteinuria status during these two examinations, participants were classified into four groups: the proteinuria-free, proteinuria-resolved, proteinuria-developed, and chronic proteinuria groups. The study outcome was the incidence of hypertension. The study included 935,723 participants followed for a median of 14.2 years (mean age: 40.96 ± 11.01, 62.5% male participants). During this period, 346,686 (37.1%) cases of hypertension were reported. The chronic proteinuria group had the highest hypertension risk, followed by the proteinuria-developed, proteinuria-resolved, and proteinuria-free groups (p < 0.001). Those who recovered from proteinuria had a lower risk of developing hypertension than those with chronic proteinuria (hazard ratio: 0.58; 95% confidence interval: 0.53–0.63, p < 0.001). In contrast, individuals who developed proteinuria had a higher risk of hypertension than proteinuria-free individuals (hazard ratio: 1.31; 95% confidence interval: 1.26–1.35, p < 0.001). Our findings suggest a significant association between proteinuria status changes and hypertension. Effective management of proteinuria may potentially decrease the risk of developing hypertension. [ABSTRACT FROM AUTHOR]

Advancement in metabolic engineering of microorganisms has enabled bio-based production of a range of chemicals, and such engineered microorganism can be used for sustainable production leading to reduced carbon dioxide emission there. One area that has attained much interest is microbial hydrocarbon biosynthesis, and in particular, alkanes and alkenes are important high-value chemicals as they can be utilized for a broad range of industrial purposes as well as 'drop-in' biofuels. Some microorganisms have the ability to biosynthesize alkanes and alkenes naturally, but their production level is extremely low. Therefore, there have been various attempts to recruit other microbial cell factories for production of alkanes and alkenes by applying metabolic engineering strategies. Here we review different pathways and involved enzymes for alkane and alkene production and discuss bottlenecks and possible solutions to accomplish industrial level production of these chemicals by microbial fermentation. [ABSTRACT FROM AUTHOR]

Currently, the majority of tools in synthetic biology have been designed and constructed for model organisms such as Escherichia coli and Saccharomyces cerevisiae. In order to broaden the spectrum of organisms accessible to such tools, we established a synthetic biological platform, called CoryneBrick, for gene expression in Corynebacterium glutamicum as a set of E. coli- C. glutamicum shuttle vectors whose elements are interchangeable with BglBrick standard parts. C. glutamicum is an established industrial microorganism for the production of amino acids, proteins, and commercially promising chemicals. Using the CoryneBrick vectors, we showed various time-dependent expression profiles of a red fluorescent protein. This CoryneBrick platform was also applicable for two-plasmid expression systems with a conventional C. glutamicum expression vector. In order to demonstrate the practical application of the CoryneBrick vectors, we successfully reconstructed the xylose utilization pathway in the xylose-negative C. glutamicum wild type by fast BglBrick cloning methods using multiple genes encoding for xylose isomerase and xylulose kinase, resulting in a growth rate of 0.11 ± 0.004 h and a xylose uptake rate of 3.35 mmol/gDW/h when 1 % xylose was used as sole carbon source. Thus, CoryneBrick vectors were shown to be useful engineering tools in order to exploit Corynebacterium as a synthetic platform for the production of chemicals by controllable expression of the genes of interest. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the effectiveness, feasibility, and complications of additional gastroduodenal stent placement after primary gastroduodenal stenting in patients with recurrent obstructive symptoms. The study uses the gastric outlet obstruction (GOO) score improvement and clinical success rates for the analysis of the data from 68 patients. Results show that placing additional stent for the treatment of patients with recurrent GOO is feasible and effective.

Abstract: 1-Hydroxy-2-methyl-2-(E)-butenyl-4-diphosphate reductase (HDR) or isopentenyl diphosphate synthase (IDS) is an enzyme at the final step of the MEP pathway. The multi-copy nature of IDS gene in a gymnosperm Ginkgo biloba is known. To evaluate the function of each isogene, the roles of the promoters were examined in Arabidopsis model. Among the promoters of GbIDS series, about 1.3 kb of GbIDS1pro and 1.5 kb of GbIDS2pro were cloned and fused with GUS. The GbIDS1pro::GUS was introduced into Arabidopsis to show GUS expression in most organs except for roots, petals, and stamina, whereas the GbIDS2pro::GUS was expressed only in the young leaves, internodes where the flower and shoot branched, and notably in primary root junction. This pattern of GUS expression correlated with high transcript level of GbIDS2 compared to that of GbIDS1 in Ginkgo roots. Methyl jasmonate (MeJA) treatment resulted in down-regulated GbIDS1pro activity in Arabidopsis leaves and upregulated GbIDS2pro activity in roots. The same pattern of gene regulation in roots was also seen upon treatments of gibberellins, abscisic acid, and indole butyric acid. [Copyright &y& Elsevier]

Background: Nematodes are parasitic animals that cause over 100 billion US dollars loss in agricultural business. The whole-genomes of two Streptomyces strains, Streptomyces spectabilis KCTC9218T and Streptomyces sp. AN091965, were sequenced. Both strains produce spectinabilin, an antinematode drug. Its secondary metabolism was examined to aid the development of an efficient nematicidal drug-producing host strain. Results: The whole-genome sequences of S. spectabilis KCTC9218T and Streptomyces sp. AN091965 were analyzed using PacBio and Illumina sequencing platforms, and assembled using hybrid methodology. The total contig lengths for KCTC9218T and AN091965 were 9.97 Mb and 9.84 Mb, respectively. A total of 8,374 and 8,054 protein-coding genes, as well as 39 and 45 secondary metabolite biosynthetic gene clusters were identified in KCTC9218T and AN091965, respectively. 18.4 ± 6.45 mg/L and 213.89 ± 21.30 mg/L of spectinabilin were produced by S. spectabilis KCTC9218T and Streptomyces sp. AN091965, respectively. Pine wilt disease caused by nematode was successfully prevented by lower concentration of spectinabilin injection than that of abamectin recommended by its manufacturer. Production of multiple antinematode drugs, including spectinabilin, streptorubin B, and undecylprodigiosin was observed in both strains using high-resolution liquid chromatography mass spectrometry (LC–MS) analysis. Conclusions: Whole-genome sequencing of spectinabilin-producing strains, coupled with bioinformatics and mass spectrometry analyses, revealed the production of multiple nematicidal drugs in the KCTC9218T and AN091965 strains. Especially, Streptomyces sp. AN091965 showed high production level of spectinabilin, and this study provides crucial information for the development of potential nematicidal drug producers. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has led to changes in stroke patients' healthcare use. This study evaluated changes in Korean stroke patients' health-seeking behaviors and stroke care services using data from the Korean Stroke Registry (KSR). Methods: We reviewed data from patients with acute stroke and transient ischemic attack (TIA) during 2019 (before COVID-19 period) and 2020 (COVID-19 period). Outcomes included patient characteristics, time from stroke onset to hospital arrival, and in-hospital stroke pathways. Subgroup analyses were performed for an epidemic region (Daegu city and Gyeongsangbuk-do region, the D-G region). Results: The study included 1,792 patients from the pre-COVID-19 period and 1,555 patients from the COVID-19 period who visited hospitals that contribute to the KSR. During the COVID-19 period, the D-G region had two-thirds the number of cases (vs. the pre-CO-VID-19 period) and a significant decrease in the proportion of patients with TIA (9.97%–2.91%). Unlike other regions, the median onset-to-door time increased significantly in the D-G region (361 min vs. 526.5 min, p = 0.016), and longer onset-to-door times were common for patients with mild symptoms and who were in their 60s or 70s. The number of patients who underwent intravenous thrombolysis also decreased during the COVID-19 period, although the treatment times were not significantly different between the 2 periods. Discussion/Conclusion: Korean stroke patients in a CO-VID-19 epidemic region exhibited distinct changes in health-seeking behaviors. Appropriate triage system and public education regarding the importance of early treatment are needed during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH. [ABSTRACT FROM AUTHOR]

Abstract Terpenoids are the most diverse natural products with many industrial applications and are all synthesized from simple precursors, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP). In plants, IPP is synthesized by two distinct metabolic pathways – cytosolic mevalonate (MVA) pathway for C15 sesquiterpene and C30 triterpene, and plastidic methylerythritol phosphate (MEP) pathway for C10 monoterpene and C20 diterpene. A number of studies have altered the metabolic gene expressions in either the MVA or MEP pathway to increase terpene production; however, it remains unknown if the alteration of the acetyl-CoA pool in plastid fatty acid biosynthesis can influence terpenoid flux. Here, we focused on the fact that acetyl-CoA is the precursor for both fatty acid biosynthesis in plastid and terpene biosynthesis in cytosol, and the metabolic impact of increased plastidic acetyl-CoA level on the cytosolic terpene biosynthesis was investigated. In tobacco leaf infiltration studies, the acetyl-CoA carboxylase complex (the enzyme supplying malonyl-CoA in plastid) was partially inhibited by overexpressing the inactive form of biotin carboxyl carrier protein (BCCP) by a negative dominant effect. Overexpression of BCCP showed 1.4–2.4-fold increase of sesquiterpenes in cytosol; however, surprisingly overexpression of BCCP linked to truncated HMG-CoA reductase (tHMGR) by a cleavable peptide 2A showed 20–40-fold increases of C15 sesquiterpenes (α-bisabolol, amorphadiene, and valerenadiene) and a 6-fold increase of C30 β-amyrin. α-Bisabolol and β-amyrin production reached 28.8 mg g-1 and 9.8 mg g-1 dry weight, respectively. Detailed analyses showed that a large increase in flux was achieved by the additive effect of BCCP- and tHMGR- overexpression, and an enhanced tHMGR activity by 2A peptide tag. Kinetic analyses showed that tHMGR-2A has a three-fold higher k cat value than tHMGR. The tHMGR-2A-BCCP1 co-expression strategy in this work provides a new insight into metabolic cross-talks and can be a generally applicable approach to over-produce sesqui- and tri-terpene in plants. Highlights • Acetyl CoA is a precursor for both fatty acid (FA) and mevalonate (MVA) pathways. • FA and MVA metabolism occur in plastid and cytosol, respectively, in plant. • Inhibition of FA metabolism in plastid increases MVA metabolic flux in cytosol. • Activity of 3-hydroxy-3-methylglutaryl CoA reductase is enhanced by peptide tag. • Up to 10–30 mg sesqui- and triterpenes can be produced per g dry weight in tobacco. [ABSTRACT FROM AUTHOR]

Microbial synthesis of medium chain aliphatic hydrocarbons, attractive drop-in molecules to gasoline and jet fuels, is a promising way to reduce our reliance on petroleum-based fuels. In this study, we enabled the synthesis of straight chain hydrocarbons (C7–C13) by yeast Saccharomyces cerevisiae through engineering fatty acid synthases to control the chain length of fatty acids and introducing heterologous pathways for alkane or 1-alkene synthesis. We carried out enzyme engineering/screening of the fatty aldehyde deformylating oxygenase (ADO), and compartmentalization of the alkane biosynthesis pathway into peroxisomes to improve alkane production. The two-step synthesis of alkanes was found to be inefficient due to the formation of alcohols derived from aldehyde intermediates. Alternatively, the drain of aldehyde intermediates could be circumvented by introducing a one-step decarboxylation of fatty acids to 1-alkenes, which could be synthesized at a level of 3 mg/L, 25-fold higher than that of alkanes produced via aldehydes. [ABSTRACT FROM AUTHOR]

Ion exchange technology is the most effective and economical to remove heat stable salts (HSS) in CO 2 absorption processes. However, the disadvantage of high waste generation remains an unsolved problem. This study attempted to reduce the amount of waste generated during the Zr(OH) 5 − regeneration process through resource recovery by using ZrCl 4 coagulant, then recycling the recovered Zr(OH) 4 precipitate to produce Zr(OH) 5 − regenerant. The experimental results showed a waste coagulant efficiency of about 75%. The coagulation mechanism was suggested based on the conductivity and zeta potential analysis. The recovered Zr(OH) 4 had no differences in terms of chemical composition and regeneration efficiency, when compared with virgin material. These results indicate that the recovery and recycling of Zr(OH) 4 from the waste stream using ZrCl 4 as a coagulant reduced a large amount of the waste generated from the ion exchange process. [ABSTRACT FROM AUTHOR]

The synthesis of two bifunctional chelates, 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) conjugates of benzothiazoles (H3L3a and H3L3b), and the corresponding gadolinium complexes (GdL3a and GdL3b) was achieved. The intracellular and tumor-specific nature of GdL3a and GdL3b were confirmed by magnetic resonance images of the cytosols and nuclei of various cell lines. The two complexes displayed antitumor activities with varying degrees of growth-inhibition and total-growth-inhibition values depending on the types of tumor cells. They caused morphological changes in tumor cell lines at much lower concentrations of gadolinium ([Gd] ≥ 50 μ M) than their predecessors, DO3A-( p-aniline benzothiazole) conjugates (H3L1), and its GdIII complex (GdL1) required concentrations that were almost four times as high ([Gd] ≥ 200 μ M). [ABSTRACT FROM AUTHOR]

The effect of SO2on theloss of 2-amino-2-methyl-1-propanol (AMP)/ammonia (NH3)solution and simultaneous removal of CO2and SO2into aqueous AMP/NH3solution was investigated. Solventloss and selectivity of CO2were studied using a reactorconstructed of stainless steel and a wetted wall column. The lossesof NH3from solution containing 1 wt % NH3,30 wt % AMP + 1 wt % NH3, and 30 wt % AMP + 1 wt % NH3loaded with 0.5 mol of CO2/mol at 313 K were 0.0179,0.013, and 0.010, respectively. The initial degradation rate constantsfor the CO2/SO2-loaded AMP solution were 0.000 21–0.003 186h–1, higher than those for the CO2-loadedsolution of 0.000 9–0.000 95 h–1. Selective absorption of CO2into aqueous AMP/NH3solution decreased from 0.99 to 1.48 as a function of SO2partial pressure (1, 3, 5, 10, and 15 kPa). [ABSTRACT FROM AUTHOR]

A Gram-positive, aerobic, rod-shaped, non-spore-forming bacterium, designated as BN140041T, was isolated from cave soil at Gubyeongsan Mountain, Boeun-gun, Chungbuk province in Republic of Korea. Phylogenetic analysis of the 16S rRNA gene sequence showed that the strain is closely related to Nocardioides silvaticus S-34 T, N. pelophilus THG-T63T, and N. immobilis FLL521T with 97.4%, 97.1%, and 96.8% similarity. The draft genome length was 4.27 Mb containing 424 contigs with a DNA G + C content of 70.5 mol%. The ANI value between strain BN140044T and its closely related species N. silvaticus S-34 T was 82.6%. The genome sequence of BN140041T displayed a key enzyme involved in the bioremediation of organic pollutants. The diagnostic diamino acid of peptidoglycan was LL-2,6-diaminopimelic acid. The major respiratory quinone was MK-8(H4), and the major fatty acids (> 5% of the total fatty acids) were iso-C16:0 (55.3%), C18:1ω9c (7.7%) and iso-C17:0 (5.7%). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, and phosphatidylinositol. The results of genotypical, physiological, and biochemical characterization allow the phenotypic differentiation of strain BN140041T from related the Nocardioides strains. Therefore, strain BN140041T represents a novel species of the genus Nocardioides, for which we propose the name Nocardioides antri sp. nov. The type strain is BN140041T (= KCTC 49080 T = CCTCC AB 2018226 T). [ABSTRACT FROM AUTHOR]

Background: There is growing interest in the use of new biomarkers such as glycated albumin (GA), but data are limited in acute ischemic stroke. We explored the impact of GA on short-term functional outcomes as measured using the modified Rankin Scale (mRS) at 3 months compared to glycated hemoglobin (HbA1c). Methods: A total of 1163 AIS patients from two hospitals between 2016 and 2019 were included. Patients were divided into two groups according to GA levels (GA < 16% versus GA ≥ 16%). Results: A total of 518 patients (44.5%) were included in the GA ≥ 16% group. After adjusting for multiple covariates, the higher GA group (GA ≥ 16%) had a 1.4-fold risk of having unfavorable mRS (95% CI 1.02–1.847). However, HbA1c was not significantly associated with 3-month mRS. In addition, GA ≥ 16% was independently associated with unfavorable short-term outcomes only in patients without diabetes. Conclusions: In light of these results, GA level might be a novel prognostic biomarker compared to HbA1c for short-term stroke outcome. Although the impact of GA is undervalued in the current stroke guidelines, GA monitoring should be considered in addition to HbA1c monitoring. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke patients with active cancer frequently experience early neurological deterioration (END); however, the predictors of END are not well studied. The neutrophil to lymphocyte ratio (NLR) has recently been described as a predictor of poor outcomes in cancer and stroke. However, its role in cancer-related stroke has not been addressed. Aim: We aimed to evaluate the association between the NLR and END in cancer-related stroke patients. Methods: We included 85 cryptogenic stroke patients with active cancer. END was defined as an increase ≥ 4 on the total National Institutes of Health Stroke Scale (NIHSS) score within 72 hours of admission. The NLR was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. We obtained the NLR during the following three periods: at admission, 1–3 days after admission (D 1–3 NLR) and 4–7 days after admission (D 4–7 NLR). Results: END occurred in 15 (18%) of the 85 patients. END was significantly associated with the initial NIHSS score, infarction volume, and the D 1–3 NLR. In multivariate analysis, a higher D 1–3 NLR, measured before END events, remained an independent predictor of END [adjusted odds ratio = 2.78, 95% confidence interval = 1.09–7.08, P = 0.032]. In terms of temporal changes in the NLR, the END group showed a tendency toward temporal increase in the NLR at D 1–3 (P = 0.061) with subsequent decrements in the D 4–7 NLR (P = 0.088), while the non-END group showed no significant changes in the NLR between periods. Conclusions: This study demonstrated that a higher NLR could predict END events in cryptogenic stroke patients with active cancer. However, the results should be confirmed in further large prospective studies. [ABSTRACT FROM AUTHOR]

Background: Stroke in cancer patients is not rare but is a devastating event with high mortality. However, the predictors of mortality in stroke patients with cancer have not been well addressed. D-dimer could be a useful predictor because it can reflect both thromboembolic events and advanced stages of cancer. Aim: In this study, we evaluate the possibility of D-dimer as a predictor of 30-day mortality in stroke patients with active cancer. Methods: We included 210 ischemic stroke patients with active cancer. The 30-day mortality data were collected by reviewing medical records. We also collected follow-up D-dimer levels in 106 (50%) participants to evaluate the effects of treatment response on D-dimer levels. Results: Of the 210 participants, 30-day mortality occurred in 28 (13%) patients. Higher initial NIHSS scores, D-dimer levels, and CRP levels as well as frequent cryptogenic mechanism, systemic metastasis, multiple vascular territory lesion, hemorrhagic transformation, and larger infarct volume were related to 30-day mortality. In the multivariate analysis, D-dimer [adjusted OR (aOR) = 2.19; 95% CI, 1.46–3.28, P < 0.001] predicted 30-day mortality after adjusting for confounders. The initial NIHSS score (aOR = 1.07; 95% CI, 1.00–1.14, P = 0.043) and hemorrhagic transformation (aOR = 3.02; 95% CI, 1.10–8.29, P = 0.032) were also significant independent of D-dimer levels. In the analysis of D-dimer changes after treatment, the mortality group showed no significant decrease in D-dimer levels, despite treatment, while the survivor group showed the opposite response. Conclusions: D-dimer levels may predict 30-day mortality in acute ischemic stroke patients with active cancer. [ABSTRACT FROM AUTHOR]

Background: Placement of self-expandable nitinol stents is useful for the treatment of esophageal and upper gastrointestinal (GI) obstruction. However, complications such as stent migration, tumor overgrowth, and bleeding occur. Although stent migration and tumor overgrowth are well documented in previous studies, the occurrence of bleeding has not been fully evaluated.Purpose: To evaluate the incidence, management strategies, and predictors of bleeding after placement of self-expandable nitinol stents in patients with esophageal and upper GI obstruction.Material and Methods: We retrospectively reviewed the medical records and results of computed tomography and endoscopy of 1485 consecutive patients with esophageal and upper GI obstructions who underwent fluoroscopically guided stent placement.Results: Bleeding occurred in 25 of 1485 (1.7%) patients 0 to 348 days after stent placement. Early stent-related bleeding occurred in 10 patients (40%) and angiographic embolization was used for 5/10. Late bleeding occurred in 15 patients (60%) and endoscopic hemostasis was used for 7/15. Twenty-two of 25 (88%) patients with bleeding had received prior radiotherapy and/or chemotherapy.Conclusion: Bleeding is a rare complication after placement of expandable nitinol stents in patients with esophageal and upper GI obstruction, but patients with early bleeding may require embolization for control. Care must be exercised on placing stents in patients who have received prior radiotherapy or chemotherapy. [ABSTRACT FROM AUTHOR]

The untranscribed DNA sequences of the intergenic spacer regions (ISR) in the groESL were analyzed to resolve the ambiguity within phylogenetically close GRAS and non-GRAS species. The sequencing results of amplified polymerase chain reaction (PCR) products using groESL-ISR-specific primers accurately distinguished L. plantarum and L. pentosus , which were not distinguished by 16 S rRNA sequences. Furthermore, the 20 selected major probiotics species were divided into several groups according to the length (22–91 bp) and homology (65–99%) of their ISR sequences, and this discrimination was consistent with core-genome-based differentiation. Therefore, ISR sequence-based species identification showed more accurate results than 16 S rRNA sequence-based identification and represented genome-based speciation. • L. plantarum and L. pentosus cannot be distinguished by the 16 S rRNA sequence. • The groESL operon sequences are species-specific. • The groESL operon sequences represented whole-genome-based taxonomy. • The groESL ISRs are proposed as a target sequence alternative to 16 S rRNA sequencing. • In this report, ISR sequences of probiotics and universal primers for PCR amplification are provided. [ABSTRACT FROM AUTHOR]

Background: Poststroke hyperglycemia is associated with poor outcomes. Most prior studies used initial glucose as an indicator of poststroke hyperglycemia without considering glycemic control status at the time of stroke occurrence. We aimed to investigate the effect of an admission-glucose gap on short-term functional outcomes in acute ischemic stroke (AIS). Methods: We enrolled patients with AIS or transient ischemic attack who had been admitted within 7 days of symptom onset to three stroke centers from May 2016 to December 2019. The admission-glucose gap between estimated average glucose levels (eAG) and initial glucose level (eAG–initial glucose) was categorized into four groups. The short-term functional outcome was evaluated using the modified Rankin Scale (mRS) score at 3 months after stroke onset and was dichotomized. Results: Among 1332 included subjects, 548 (41.1%) had poor short-term functional outcomes. After adjusting for multiple variables, a severe negative glucose gap (eAG–initial glucose ≤ −50 mg/dL) was significantly associated with poor short-term functional outcome (OR, 1.573; 95% CI, 1.101–2.248). After dichotomizing glycemic control status, its significance was only maintained in the good glycemic control group (HbA1c < 6.5%) (OR, 1.914; 95% CI, 1.155–3.169). Conclusions: An elevated admission-glucose gap, in which the initial glucose level was much higher than the estimated glucose level was based on HbA1c, was associated with poor stroke prognosis. In addition to admission-glucose levels, glycemic control status at the time of stroke onset should be considered when predicting short-term stroke outcomes. [ABSTRACT FROM AUTHOR]

Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Backgrounds: Radioimmunotherapy (RIT) serves as a targeted therapy for non-Hodgkin lymphomas (NHL). Although HIF(Hypoxia-inducible factors)-1α is an important biomarker during radiation therapy, its role in NHL is unclear. Atorvastatin (ATV) is used as a combination drug for chemotherapy. Methods: We investigated whether ATV downregulated tumor radio-resistance and enhanced the anticancer effect of 131I-RTX (rituximab) in Raji xenograft mouse models. First, the increased uptake and enhanced therapeutic effect of 131I-RTX by ATV was confirmed using molecular imaging in Raji xenograft subcutaneous model and orthotropic model with SPECT and IVIS images. Second, we examined the profile of differentially expressed miRNAs using miRNA array. Results: We found that miR-346 inhibited HIF-1α/VEGF (Vascular endothelial growth factor) during ATV combination therapy with 131I-RTX. The underlying mechanism of ATV involved induction of anti-angiogenesis and radiosensitivity by downregulating HIF-1α in Raji cells. Conclusion: Our findings suggested that combination therapy with ATV and 131I-RTX is a promising strategy for enhancing the potency of 131I-RTX therapy in poorly responding patients and those with radio-resistance. [ABSTRACT FROM AUTHOR]