Graph Theoretical Analysis of Brain Structural Connectivity in Patients with Alcohol Dependence.

This study aimed to compare brain structural connectivity using graph theory between patients with alcohol dependence and social drinkers. The participants were divided into two groups; the alcohol group (N=23) consisting of patients who had been hospitalized and had abstained from alcohol for at least three months and the control group (N=22) recruited through advertisements and were social drinkers. All participants were evaluated using 3T magnetic resonance imaging. A total of 1000 repeated whole-brain tractographies with random parameters were performed using DSI Studio. Four hundred functionally defined cortical regions of interest (ROIs) were parcellated using FreeSurfer based on the Schaefer Atlas. The ROIs were overlaid on the tractography results to generate 1000 structural connectivity matrices per person, and 1000 matrices were averaged into a single matrix per subject. Graph analysis was performed through igraph R package. Graph measures were compared between the two groups using analysis of covariance, considering the effects of age and smoking pack years. The alcohol group showed lower local efficiency than the control group in the whole-brain (F=5.824, p=0.020), somato-motor (F=5.963, p=0.019), and default mode networks (F=4.422, p=0.042). The alcohol group showed a lower global efficiency (F=5.736, p=0.021) in the control network. The transitivity of the alcohol group in the dorsal attention network was higher than that of the control (F=4.257, p=0.046). Our results imply that structural stability of the whole-brain network is affected in patients with alcohol dependence, which can lead to ineffective information processing in cases of local node failure.

Anti-Neuroinflammatory Effects of the Human Milk Oligosaccharide, 2'-Fucosyllactose, Exerted via Modulation of M2 Microglial Activation in a Mouse Model of Ischemia-Reperfusion Injury.

Cerebral ischemic stroke is one of the leading causes of death and disability worldwide. 2'-fucosyllactose (2'-FL), a human milk oligosaccharide, exerts anti-inflammatory effects and plays a protective role in arterial thrombosis; however, its role in ischemic stroke remains unclear. This study aimed to investigate the neuroprotective effects of 2'-FL and its potential mechanisms in a mouse model of ischemic stroke. Neurological score and behavior tests revealed that 2'-FL promoted the recovery of neurological deficits and motor function in middle cerebral artery occlusion (MCAO) mice, and that 2'FL led to a reduction in the size of cerebral infarct. Biochemical studies showed that administration of 2'-FL led to a reduction of reactive oxygen species (ROS)-related products in the brain of MCAO mice. 2'-FL upregulated IL-10 and downregulated TNF-α level. In addition, 2'-FL enhanced M2-type microglial polarization and upregulated CD206 expression at 7 days after MCAO. At 3 days after MCAO, 2'-FL increased IL-4 levels and activated STAT6. Our data show that 2'-FL reduced the neurological symptoms of ischemic stroke and ROS accumulation in the brain through IL-4/STAT6-dependent M2-type microglial polarization in MCAO mice. These results demonstrate that 2'-FL is a potentially effective therapeutic agent for ischemic stroke.

2'-Fucosyllactose and 3-Fucosyllactose Alleviates Interleukin-6-Induced Barrier Dysfunction and Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Modulating the Intestinal Microbiome.

Ulcerative colitis is an inflammatory bowel disease (IBD) with relapsing and remitting patterns, and it is caused by varied factors, such as the intestinal inflammation extent and duration. We examined the preventative effects of human milk oligosaccharides (HMOs) on epithelial barrier integrity and intestinal inflammation in an interleukin (IL)-6-induced cell model and dextran sodium sulfate (DSS)-induced acute mouse colitis model. HMOs including 2'-fucosyllactose (FL) and 3-FL and positive controls including fructooligosaccharide (FOS) and 5-acetylsalicylic acid (5-ASA) were orally administrated once per day to C57BL/6J mice with colitis induced by 5% DSS in the administered drinking water. 2'-FL and 3-FL did not affect the cell viability in Caco-2 cells. Meanwhile, these agents reversed IL-6-reduced intestinal barrier function in Caco-2 cells. Furthermore, 2'-FL and 3-FL reversed the body weight loss and the remarkably short colon lengths in DSS-induced acute colitis mice. Moreover, 2'-FL and 3-FL obviously protected the decreasing expression of zonula occluden-1 and occludin in colon tissue relative to the findings in the DSS-treated control group. 2'-FL and 3-FL significantly reduced IL-6 and tumor necrosis factor-α levels in serum relative to the control findings. The summary of these results shows that HMOs prevent colitis mainly by enhancing intestinal barrier function and advancing anti-inflammatory responses. Therefore, HMOs might suppress inflammatory responses and represent candidate treatments for IBD that protect intestinal integrity.

Treatment Outcomes of Sinonasal Malignancies Involving the Orbit.

Objective Orbital invasion is associated with a poor prognosis in cases of sinonasal malignancy. This study aimed to analyze the oncological outcomes of sinonasal malignancies involving the orbit. Patients and Methods We reviewed the medical records of 116 patients with a sinonasal malignancy who had orbital invasion at initial diagnosis and followed up at least 6 months between June 1991 and October 2017 at a single institute. The overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) rates according to the clinicopathological factors, extent to orbit, and treatment modality were compared. Results Patients were mainly treated with surgery and postoperative radiation ( n = 39, 33.6%) and concurrent chemoradiation ( n = 72, 62.1%). Only five patients (5.1%) underwent orbital exenteration. The OS, DSS, and PFS rates significantly decreased in patients older than 60 years of age and in patients with a higher Charlson Comorbidity Index Score (each p < 0.001). The OS and DSS rates were higher in patients at clinical T3 and N0 stage than in patients at clinical T4 and N1-2 stage (each p < 0.05). There were no significant differences in survival and local control rates according to the extent of orbital invasion, treatment modalities, and orbital preservation. However, neoadjuvant chemotherapy and adjuvant radiation or concurrent chemoradiation increased survival rates in the patients treated with surgery. Conclusion Orbit preservation and relatively successful oncological outcome could be obtained with surgery and adjuvant radiation or concurrent chemoradiation.

Hippocampal Subfields and White Matter Connectivity in Patients with Subclinical Geriatric Depression.

Despite an abundance of research related to the functional and structural changes of the brain in patients with geriatric depression, knowledge related to early alterations such as decreased white matter connectivity and their association with cognitive decline remains lacking. We aimed to investigate early alterations in hippocampal microstructure and identify their associations with memory function in geriatric patients with subclinical depression. Nineteen participants with subclinical geriatric depression and 19 healthy controls aged ≥65 years exhibiting general cognitive function within the normal range were included in the study and underwent assessments of verbal memory. Hippocampal subfield volumes were determined based on T1-weighted magnetization-prepared rapid gradient echo (T1-MPRAGE) images, while group tractography and connectometry analyses were conducted using diffusion tensor images. Our findings indicated that the volumes of whole bilateral hippocampus, cornus ammonis (CA) 1, molecular layer, left subiculum, CA3, hippocampal tail, right CA4, and granule cell/molecular layers of the dentate gyrus (GC-ML-DG) were significantly smaller in the subclinical depression group than in the control group. In the subclinical depression group, verbal learning was positively correlated with the volumes of the CA1, GC-ML-DG, molecular layer, and whole hippocampus in the right hemisphere. The fractional anisotropy of the bilateral fornix was also significantly lower in the subclinical depression group and exhibited a positive correlation with verbal learning and recall in both groups. Our results suggest that hippocampal microstructure is disrupted and associated with memory in patients with subclinical depression.

Effects of taurine and ginseng extracts on energy metabolism during exercise and their anti-fatigue properties in mice.

BACKGROUND/OBJECTIVES: Ginseng extract (GSE) and taurine (TR) are widely used antifatigue resources in functional foods. However, the mechanism underlying the antifatigue effects of GSE and TR are still unclear. Hence, we investigated whether GSE and TR have synergistic effects against fatigue in mice. MATERIALS/METHODS: L6 cells were treated with different concentrations of TR and GSE, and cell viability was determined using 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium. Oxidative stress was analyzed by immunocytochemistry using MitoTracker™ Red FM and an anti-8-oxoguanine antibody. Respiratory gas analysis was performed to investigate metabolism. Expression of an activated protein kinase was analyzed using immunohistochemistry. Gene expression of cluster of differentiation 36 and pyruvate dehydrogenase lipoamide kinase isozyme 4 was measured using reverse transcription-polymerase chain reaction. Mice were orally administered TR, GSE, or their combination for 30 days, and then fatigue-related parameters, including lactate, blood urea nitrogen, and glycogen, were measured after forced swimming. RESULTS: TR and GSE reduced oxidative stress levels in hydrogen peroxide-stimulated L6 cells and enhanced the oxygen uptake and lipid metabolism in mice after acute exercise. After oral administration of TR or GSE for 30 days, the fatigue-related parameters did not change in mice. However, the mice administered GSE (400 mg/kg/day) alone for 30 days could swim longer than those from the other groups. Further, no synergistic effect was observed after the swimming exercise in mice treated with the TR and GSE combination for 30 days. CONCLUSIONS: Taken together, our data suggest that TR and GSE may exert antifatigue effects in mice after acute exercise by enhancing oxygen uptake and lipid oxidation.

A network pharmacology approach to explore the potential role of Panax ginseng on exercise performance.

PURPOSE: As Panax ginseng C. A. Meyer (ginseng) exhibits various physiological activities and is associated with exercise, we investigated the potential active components of ginseng and related target genes through network pharmacological analysis. Additionally, we analyzed the association between ginseng-related genes, such as the G-protein-coupled receptors (GPCRs), and improved exercise capacity. METHODS: Active compounds in ginseng and the related target genes were searched in the Traditional Chinese Medicine Database and Analysis Platform (TCMSP). Gene ontology functional analysis was performed to identify biological processes related to the collected genes, and a compound-target network was visualized using Cytoscape 3.7.2. RESULTS: A total of 21 ginseng active compounds were detected, and 110 targets regulated by 17 active substances were identified. We found that the active compound protein was involved in the biological process of adrenergic receptor activity in 80%, G-protein-coupled neurotransmitter in 10%, and leucocyte adhesion to arteries in 10%. Additionally, the biological response centered on adrenergic receptor activity showed a close relationship with G protein through the beta-1 adrenergic receptor gene reactivity. CONCLUSION: According to bioavailability analysis, ginseng comprises 21 active compounds. Furthermore, we investigated the ginseng-stimulated gene activation using ontology analysis. GPCR, a gene upregulated by ginseng, is positively correlated to exercise. Therefore, if a study on this factor is conducted, it will provide useful basic data for improving exercise performance and health.

Disrupted Association Between Empathy and Brain Structure in Attention-Deficit/Hyperactivity Disorder.

OBJECTIVES: To investigate the relationship between brain structure and empathy in early adolescents with attention-deficit/hyperactivity disorder (ADHD). METHODS: Nineteen early adolescents with ADHD and 20 healthy controls underwent 3T MRI. All the participants were assessed for different aspects of empathy using measures including the Interpersonal Reactivity Index and Empathy Quotient. Cortical thickness and subcortical structural volume based on T1-weighted scans were analyzed using FreeSurfer. RESULTS: Cognitive empathy (t=-2.52, p=0.016) and perspective taking (t=-2.10, p=0.043) were impaired in the ADHD group compared with the control group. The cluster encompassing the left posterior insular, supramarginal, and transverse temporal cortices [cluster-wise p-value (CWP)=0.001], which are associated with emotional empathy, was significantly smaller in the ADHD group, and the volume of the left nucleus accumbens was greater than that of the control group (F=10.12, p=0.003, effect size=0.22). In the control group, the left superior temporal (CWP=0.002) and lingual cortical (CWP=0.035) thicknesses were positively associated with cognitive empathy, while the right amygdala volume was positively associated with empathic concern (Coef=14.26, t=3.92, p=0.001). However, there was no significant correlation between empathy and brain structure in the ADHD group. CONCLUSION: The ADHD group had a smaller volume of the cortical area associated with emotional empathy than the control group, and there was no brain region showing significant correlation with empathy, unlike in the control group.

White matter integrity in alcohol-dependent patients with long-term abstinence.

ABSTRACT: Based on association studies on amounts of alcohol consumed and cortical and subcortical structural shrinkage, we investigated the effect of chronic alcohol consumption on white matter pathways using probabilistic tractography.Twenty-three alcohol-dependent men (with an average sobriety of 13.1 months) from a mental health hospital and 22 age-matched male healthy social drinkers underwent 3T magnetic resonance imaging. Eighteen major white matter pathways were reconstructed using the TRActs Constrained by UnderLying Anatomy tool (provided by the FreeSurfer). The hippocampal volumes were estimated using an automated procedure. The lifetime drinking history interview, Alcohol Use Disorder Identification Test, Brief Michigan Alcoholism Screening Test, and pack-years of smoking were also evaluated.Analysis of covariance controlling for age, cigarette smoking, total motion index indicated that there was no definite difference of diffusion parameters between the 2 groups after multiple comparison correction. As hippocampal volume decreased, the fractional anisotropy of the right cingulum-angular bundle decreased. Additionally, the axial diffusivity of right cingulum-angular bundle was positively correlated with the alcohol abstinence period.The results imply resilience of white matter in patients with alcohol dependence. Additional longitudinal studies with multimodal methods and neuropsychological tests may improve our findings of the changes in white matter pathways in patients with alcohol dependence.

Effect of Renal and Left Ventricular Function on Serial Pulmonary Arterial Pressure Changes after Device Closure of Atrial Septal Defect.

BACKGROUND: The age of candidates for device closure of atrial septal defect (ASD) has been increasing. Thus, concerns exist about dyspnea aggravation or atrial fibrillation development after device closure due to augmentation of left ventricular (LV) and left atrial (LA) preload. This study aimed to examine patterns and determinants of serial pulmonary arterial pressure and left ventricular filling pressure changes after device closure of ASD. METHODS: Among the 86 consecutive patients who underwent percutaneous device closure of ASD, those with end-stage renal disease or those without pre- or postprocedural Doppler data were excluded. The clinical, transesophageal, and transthoracic echocardiographic findings of 78 patients were collected at baseline, one-day postprocedure, and one-year follow-up. RESULTS: The mean age of study patients was 49.8 ± 15.0 years, and the average maximal defect diameter and device size were 20.2 ± 6.0 mm and 23.8 ± 6.4 mm. Four patients (5.6%) underwent new-onset atrial fibrillation, and five patients (6.4%) took diuretics within one-year after closure. Some patients (n = 21; 27%) exhibited paradoxically increased tricuspid regurgitant velocity (TRV) one-day postprocedure; they also were older with lower e', glomerular filtration rate, and LV ejection fraction and a higher LA volume index. However, even in these patients, TRV deceased below baseline levels one-year later. Both E/e' and LA volume index significantly increased immediately after device closure, but all decreased one-year later. Larger defect size and higher TRV were significantly correlated with immediate E/e' elevation. CONCLUSION: In older, renal, diastolic, and systolic dysfunctional patients with larger LA and scheduled for larger device implantation, peri-interventional preload reduction therapy would be beneficial.

Development of fluorescent Escherichia coli for a whole-cell sensor of 2'-fucosyllactose.

2'-Fucosyllactose (2'-FL), a major component of fucosylated human milk oligosaccharides, is beneficial to human health in various ways like prebiotic effect, protection from pathogens, anti-inflammatory activity and reduction of the risk of neurodegeneration. Here, a whole-cell fluorescence biosensor for 2'-FL was developed. Escherichia coli (E. coli) was engineered to catalyse the cleavage of 2'-FL into L-fucose and lactose by constitutively expressing α-L-fucosidase. Escherichia coli ∆L YA, in which lacZ is deleted and lacY is retained, was employed to disable lactose consumption. E. coli ∆L YA constitutively co-expressing α-L-fucosidase and a red fluorescence protein (RFP) exhibited increased fluorescence intensity in media containing 2'-FL. However, the presence of 50 g/L lactose reduced the RFP intensity due to lactose-induced cytotoxicity. Preadaptation of bacterial strains to fucose alleviated growth hindrance by lactose and partially recovered the fluorescence intensity. The fluorescence intensity of the cell was linearly proportional to 1-5 g/L 2'-FL. The whole-cell sensor will be versatile in developing a 2'-FL detection system.

Production and Characterization of Anti-Inflammatory Monascus Pigment Derivatives.

The prevention and treatment of chronic inflammation using food-derived compounds are desirable from the perspectives of marketing and safety. Monascus pigments, widely used as food additives, can be used as a chronic inflammation treatment. Orange Monascus pigments were produced by submerged fermentation in a 5 L bioreactor, and multiple orange Monascus pigment derivatives with anti-inflammatory activities were synthesized using aminophilic reaction. A total of 41 types of pigment derivatives were produced by incorporating amines and amino acids into the orange pigments. One derivative candidate that inhibited nitric oxide (NO) production in Raw 264.7 cells and exhibited low cell cytotoxicity was identified via in vitro assay. The 2-amino-4 picoline derivative inhibited NO production of 48.4%, and exhibited cell viability of 90.6%. Expression of inducible NO synthase, an important enzyme in the NO synthesis pathway, was suppressed by such a derivative in a dose-dependent manner. Therefore, this derivative has potential as a functional food colorant with anti-inflammatory effects.

Cognitive and Emotional Empathy in Young Adolescents: an fMRI Study.

OBJECTIVES: We investigated the differences in cognitive and emotional empathic ability between adolescents and adults, and the differences of the brain activation during cognitive and emotional empathy tasks. METHODS: Adolescents (aged 13-15 years, n=14) and adults (aged 19-29 years, n=17) completed a range of empathic ability questionnaires and were scanned functional magnetic resonance imaging (fMRI) during both cognitive and emotional empathy task. Differences in empathic ability and brain activation between the groups were analyzed. RESULTS: Both cognitive and emotional empathic ability were significantly lower in the adolescent compared to the adult group. Comparing the adolescent to the adult group showed that brain activation was significantly greater in the right transverse temporal gyrus (BA 41), right insula (BA 13), right superior parietal lobule (BA 7), right precentral gyrus (BA 4), and right thalamus whilst performing emotional empathy tasks. No brain regions showed significantly greater activation in the adolescent compared to the adult group while performing cognitive empathy task. In the adolescent group, scores of the Fantasy Subscale in the Interpersonal Reactivity Index, which reflects cognitive empathic ability, negatively correlated with activity of right superior parietal lobule during emotional empathic situations (r=-0.739, p=0.006). CONCLUSION: These results strongly suggest that adolescents possess lower cognitive and emotional empathic abilities than adults do and require compensatory hyperactivation of the brain regions associated with emotional empathy or embodiment in emotional empathic situation. Compensatory hyperactivation in the emotional empathy-related brain areas among adolescents are likely associated with their lower cognitive empathic ability.

Herb-Drug Interaction of Red Ginseng Extract and Ginsenoside Rc with Valsartan in Rats.

The purpose of this study was to investigate the herb-drug interactions involving red ginseng extract (RGE) or ginsenoside Rc with valsartan, a substrate for organic anion transporting polypeptide (OATP/Oatp) transporters. In HEK293 cells overexpressing drug transporters, the protopanaxadiol (PPD)-type ginsenosides- Rb1, Rb2, Rc, Rd, Rg3, compound K, and Rh2-inhibited human OATP1B1 and OATP1B3 transporters (IC50 values of 7.99-68.2 µM for OATP1B1; 1.36-30.8 µM for OATP1B3), suggesting the herb-drug interaction of PPD-type ginsenosides involving OATPs. Protopanaxatriol (PPT)-type ginsenosides-Re, Rg1, and Rh1-did not inhibit OATP1B1 and OATP1B3 and all ginsenosides tested didn't inhibit OCT and OAT transporters. However, in rats, neither RGE nor Rc, a potent OATP inhibitor among PPD-type ginsenoside, changed in vivo pharmacokinetics of valsartan following repeated oral administration of RGE (1.5 g/kg/day for 7 days) or repeated intravenous injection of Rc (3 mg/kg for 5 days). The lack of in vivo herb-drug interaction between orally administered RGE and valsartan could be attributed to the low plasma concentration of PPD-type ginsenosides (5.3-48.4 nM). Even high plasma concentration of Rc did not effectively alter the pharmacokinetics of valsartan because of high protein binding and the limited liver distribution of Rc. The results, in conclusion, would provide useful information for herb-drug interaction between RGE or PPD-type ginsenosides and Oatp substrate drugs.

In vivo evaluation of the anti-obesity effects of combinations of Monascus pigment derivatives.

The prevention and treatment of obesity using naturally derived compounds is desirable in terms of marketing and safety in the nutraceutical and functional food markets. One of the noticeable effects of Monascus pigment derivatives is the inhibition/deactivation of lipid metabolism. Our earlier studies reported that threonine (Thr), tryptophan (Trp), and 2-(p-tolyl)-ethylamine (TEA) derivatives of Monascus pigment showed cholesterol-lowering, lipase-inhibitory, and adipogenic differentiation-inhibitory activities, respectively. In this work, we investigated the in vivo anti-obesity effects of a combination of Thr, Trp and TEA derivatives. C57BL/6 mice were fed a high-fat diet (HFD) and simultaneously administered one of three 1 : 1 mixtures of Thr, Trp, and TEA derivatives. After 10 weeks of feeding, the weight gains of mice fed with three combined derivatives decreased by 20.3-37.9%, compared to mice fed the HFD. The epididymal adipose tissue (EAT) weights of mice fed with the combined derivatives decreased by 42.3-60.5% compared to the HFD group, and their EAT size decreased. Transverse micro-CT imaging revealed reduction of the subcutaneous and visceral fat layers of test mice. Our results confirm that Monascus-fermented pigment derivatives have in vivo anti-obesity effects and their combinations provide a higher efficacy in the reduction of body weight and EAT weights as well as lipid accumulation in mice. The key to accomplishing high anti-obesity effect was combining Thr and Trp derivatives, which provide higher effectiveness than other combined derivatives. These observations offer a potential use of Monascus pigment derivatives as a therapeutic approach to prevention and/or treatment of obesity.

Associations Between Skeletal Muscle Mass, Grip Strength, and Physical and Cognitive Functions in Elderly Women: Effect of Exercise with Resistive Theraband.

PURPOSE: The purpose of this study was to identify the relationships between muscle mass, muscle strength, and physical and cognitive functions and to examine the effects of resistive Theraband® exercise on sarcopenia-associated variables in the older population. METHODS: A total of 28 elderly women (age: 69.90 ± 0.8 years) participated in this study, 15 of whom underwent elastic band exercise for 1 hour per day, twice per week for 8 weeks. The correlation analysis was conducted to identify the associations between body composition, skeletal muscle mass indices, grip strength, and physical and cognitive functions. All variables were assessed at baseline and post-exercise. RESULTS: Skeletal muscle mass was significantly associated with grip strength and physical function. Gait speed was positively correlated with grip strength and physical function, but not with cognitive function. Theraband® exercise significantly improved gait speed and physical function. CONCLUSION: The present data suggest that skeletal muscle mass is highly correlated with grip strength and physical function. Eight weeks of resistive Theraband® exercise favorably affects sarcopenia by improving gait speed and mobility of elderly women.

Management of Ménière's Disease: How Does the Coexistence of Vestibular Migraine Affect Outcomes?

OBJECTIVE: To report the incidence of vestibular migraine (VM) in patients with Ménière's disease (MD) and investigate whether management outcomes of MD differ by the association of VM. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care academic center. PATIENTS: MD patients (n = 251) with/without VM who were managed for 5 years in a dizziness clinic. MAIN OUTCOME MEASURES: Influence of VM on management outcomes and hearing at the latest follow-up in stepwise management options. RESULTS: Incidence of VM was 35% in MD patients. VM was more common in women than men (40 vs. 22%) and in probable MD than definite MD (43 vs. 29%). Bilateral MD was more frequent with coexistence of VM than without VM in definite MD (14 vs. 0%) as well as probable MD (24 vs. 7%). At the latest follow-up, preventive medications were effective in controlling vertigo in most (80%) patients (74%/90% in definite/probable MD). Additional intratympanic steroids were required in 16% (20%/10% in definite/probable MD) and intratympanic gentamicin or surgeries in 9 (6%) patients with intractable MD. The percentage of intractable MD did not differ with coexistence of VM, though definite MD showed a significantly higher percentage of intractable MD than probable MD (6 vs. 0%, respectively, p = 0.002). Worsening hearing was more frequent in definite MD than probable MD (19 vs. 4%), and association of VM did not influence the incidence of worsening hearing. CONCLUSIONS: Coexistence of VM was about 30 to 40% in definite and probable MD, especially frequent in bilateral MD (77%) and women with probable MD (50%), requiring identification of coexisting VM while managing MD patients. Management outcomes and worsening hearing in MD patients are not dependent on the coexistence of VM, when both are managed.

Endocytosing Escherichia coli as a Whole-Cell Biocatalyst of Fatty Acids.

Whole cell biocatalysts can be used to convert fatty acids into various value-added products. However, fatty acid transport across cellular membranes into the cytosol of microbial cells limits substrate availability and impairs membrane integrity, which in turn decreases cell viability and bioconversion activity. Because these problems are associated with the mechanism of fatty acid transport through membranes, a whole-cell biocatalyst that can form caveolae-like structures was generated to promote substrate endocytosis. Caveolin-1 ( CAV1) expression in Escherichia coli increased both the fatty acid transport rate and intracellular fatty acid concentrations via endocytosis of the supplemented substrate. Furthermore, fatty-acid endocytosis alleviated substrate cytotoxicity in E. coli. These traits attributed to bacterial endocytosis resulted in dramatically elevated biotransformation efficiencies in fed-batch and cell-recycle reaction systems when caveolae-forming E. coli was used for the bioconversion of ricinoleic acid (12-hydroxyoctadec-9-enoic acid) to ( Z)-11-(heptanoyloxy) undec-9-enoic acid. We propose that CAV1-mediated endocytosing E. coli represents a versatile tool for the biotransformation of hydrophobic substrates.

Study on the copper(II)-doped MIL-101(Cr) and its performance in VOCs adsorption.

The metal-organic framework (MOF) materials, MIL-101(Cr), and copper-doped MIL-101(Cr) (Cu@MIL-101(Cr)) were prepared through hydrothermal method and were used to remove volatile organic compounds (VOCs) in this study. Morphological characterization demonstrated that MIL-101(Cr) and Cu-3@MIL-101(Cr) were octahedral crystal, with specific surface area of 3367 and 2518 m2/g, respectively. The results of XRD, TG, and FTIR showed that the copper doping procedure would not alter the skeleton structure, but it would affect the crystallinity and thermal stability of MIL-101(Cr). Besides, MIL-101(Cr) and Cu-3@MIL-101(Cr) displayed good removal efficiencies on benzene sorption, and the maximum sorption capacity was 103.4 and 114.4 mg/g, respectively. In competitive adsorptions, the order of adsorption priority on Cu-3@MIL-101(Cr) was as follows: ethylbenzene > toluene > benzene. Hence, it could be concluded that MIL-101(Cr) and copper-doped MIL-101(Cr) demonstrated good performance in VOCs adsorption and showed a promising potential for large-scale applications in the removal of VOCs. Graphical abstract ᅟ.

Verification of land-atmosphere coupling in forecast models, reanalyses and land surface models using flux site observations.

We confront four model systems in three configurations (LSM, LSM+GCM, and reanalysis) with global flux tower observations to validate states, surface fluxes, and coupling indices between land and atmosphere. Models clearly under-represent the feedback of surface fluxes on boundary layer properties (the atmospheric leg of land-atmosphere coupling), and may over-represent the connection between soil moisture and surface fluxes (the terrestrial leg). Models generally under-represent spatial and temporal variability relative to observations, which is at least partially an artifact of the differences in spatial scale between model grid boxes and flux tower footprints. All models bias high in near-surface humidity and downward shortwave radiation, struggle to represent precipitation accurately, and show serious problems in reproducing surface albedos. These errors create challenges for models to partition surface energy properly and errors are traceable through the surface energy and water cycles. The spatial distribution of the amplitude and phase of annual cycles (first harmonic) are generally well reproduced, but the biases in means tend to reflect in these amplitudes. Interannual variability is also a challenge for models to reproduce. Our analysis illuminates targets for coupled land-atmosphere model development, as well as the value of long-term globally-distributed observational monitoring.