Huntingtin turnover: modulation of huntingtin degradation by cAMP-dependent protein kinase A (PKA) phosphorylation of C-HEAT domain Ser2550.

Huntington's disease (HD) is a neurodegenerative disorder caused by an inherited unstable HTT CAG repeat that expands further, thereby eliciting a disease process that may be initiated by polyglutamine-expanded huntingtin or a short polyglutamine-product. Phosphorylation of selected candidate residues is reported to mediate polyglutamine-fragment degradation and toxicity. Here to support the discovery of phosphosites involved in the life-cycle of (full-length) huntingtin, we employed mass spectrometry-based phosphoproteomics to systematically identify sites in purified huntingtin and in the endogenous protein by proteomic and phosphoproteomic analyses of members of an HD neuronal progenitor cell panel. Our results bring total huntingtin phosphosites to 95, with more located in the N-HEAT domain relative to numbers in the Bridge and C-HEAT domains. Moreover, phosphorylation of C-HEAT Ser2550 by cAMP-dependent protein kinase (PKA), the top hit in kinase activity screens, was found to hasten huntingtin degradation, such that levels of the catalytic subunit (PRKACA) were inversely related to huntingtin levels. Taken together, these findings highlight categories of phosphosites that merit further study and provide a phosphosite kinase pair (pSer2550-PKA) with which to investigate the biological processes that regulate huntingtin degradation and thereby influence the steady state levels of huntingtin in HD cells.

Everolimus exerts anticancer effects through inhibiting the interaction of matrix metalloproteinase-7 with syndecan-2 in colon cancer cells.

Previous work showed that matrix metalloproteinase-7 (MMP-7) regulates colon cancer activities through an interaction with syndecan-2 (SDC-2) and SDC-2-derived peptide that disrupts this interaction and exhibits anticancer activity in colon cancer. Here, to identify potential anticancer agents, a library of 1,379 Food and Drug Administration (FDA)-approved drugs that interact with the MMP-7 prodomain were virtually screened by protein-ligand docking score analysis using the GalaxyDock3 program. Among five candidates selected based on their structures and total energy values for interacting with the MMP-7 prodomain, the known mechanistic target of rapamycin kinase (mTOR) inhibitor, everolimus, showed the highest binding affinity and the strongest ability to disrupt the interaction of the MMP-7 prodomain with the SDC-2 extracellular domain in vitro. Everolimus treatment of the HCT116 human colon cancer cell line did not affect the mRNA expression levels of MMP-7 and SDC-2 but reduced the adhesion of cells to MMP-7 prodomain-coated plates and the cell-surface localization of MMP-7. Thus, everolimus appears to inhibit the interaction between MMP-7 and SDC-2. Everolimus treatment of HCT116 cells also reduced their gelatin-degradation activity and anticancer activities, including colony formation. Interestingly, cells treated with sirolimus, another mTOR inhibitor, triggered less gelatin-degradation activity, suggesting that this inhibitory effect of everolimus was not due to inhibition of the mTOR pathway. Consistently, everolimus inhibited the colony-forming ability of mTOR-resistant HT29 cells. Together, these data suggest that, in addition to inhibiting mTOR signaling, everolimus exerts anticancer activity by interfering with the interaction of MMP-7 and SDC-2, and could be a useful therapeutic anticancer drug for colon cancer.NEW & NOTEWORTHY The utility of cancer therapeutics targeting the proteolytic activities of MMPs is limited because MMPs are widely distributed throughout the body and involved in many different aspects of cell functions. This work specifically targets the activation of MMP-7 through its interaction with syndecan-2. Notably, everolimus, a known mTOR inhibitor, blocked this interaction, demonstrating a novel role for everolimus in inhibiting mTOR signaling and impairing the interaction of MMP-7 with syndecan-2 in colon cancer.

Enzymatic extraction of anthocyanins from the pomace of aronia (Aronia melanocarpa).

Efficient extraction of natural pigments is a key focus in enhancing the utilization of by-products for applications in the food industry. In this study, an enzymatic extraction method using Pectinex Ultra SP-L, Pectinex XXL, Novoshape, and Celluclast was used to investigate natural pigment production from the pomace of aronia, a commercially important plant. The method's performance was monitored using high-performance liquid chromatography with diode-array detection by measuring total and individual anthocyanin levels. Pectinex XXL (0.5%) yielded the highest total anthocyanin extraction (2082.41 ± 85.69 mg/100 g) in the single enzyme treatment, followed by Pectinex Ultra SP-L (0.05%), Celluclast (0.01%), and Novoshape (0.1%). Combining Pectinex XXL (0.25%) with Celluclast (0.01%) increased the extraction ratio of total anthocyanins (2 323.04 ± 61.32 mg/100 g) by ∼50.7% compared with that obtained using the solvent extraction method. This study demonstrated an effective enzymatic extraction method for application in the food industry.

Comparison of off-target pesticide drift in paddy fields from unmanned aerial vehicle spraying using cellulose deposition sampler.

Off-target pesticide drift in paddy fields following unmanned aerial vehicle (UAV) spraying was evaluated using cellulose deposition samplers (CDSs). An analytical method for quantifying ferimzone Z and E isomers deposited on CDSs was developed using LC-MS/MS. The suitability of the CDS method was confirmed by comparing deposition patterns on CDSs with residue levels in rice plant samples. To assess pesticide deposition in paddy fields, CDSs were strategically placed at varying distances from target areas, followed by UAV spraying. The fungicide agrochemicals were applied with and without adjuvants, and wind direction affected the drift trajectory for all treatment groups. Adjuvants, particularly soy lecithin as the major component, significantly enhanced pesticide deposition within the spray pathway while reducing drift rates relatively by 47.9-68.0 %. Higher wind speeds were found to exacerbate drift, but adjuvant-treated sprays showed less variability in deposition patterns under these conditions. Pesticide residues in harvested brown rice were found to be below the maximum residue limits (MRLs), ensuring safety for consumption. These findings highlight the importance of selecting appropriate adjuvants in UAV-based pesticide applications to optimize deposition efficiency and minimize environmental contamination.

The mediating effect of anxiety on the association between residual neurological impairment and post-stroke participation among persons with and without post-stroke depression.

Previous research has reported that residual neurological impairment and emotional factors play a role in regaining successful participation post-stroke. The objective of this study was to investigate the mediating impact of anxiety on the association between residual neurological impairment and participation in survivors with and without post-stroke depressive symptoms. Participants (N = 79) were classified into 2 categories, those with post-stroke depressive symptoms (N = 40) and those without post-stroke depressive symptoms (N = 39). Variables measured in this study: residual neurological impairment (NIH Stroke Scale Score), participation (Reintegration to Normal Living Index), depressive symptoms (Patient Health Questionnaire-9), and trait anxiety (State-Trait Anxiety Inventory). A regression-based mediation analysis was conducted for each group of participants. The majority of participants had some level of anxiety. Residual neurological impairment predicted participation in stroke survivors both with (ß = -.45, p = .003) and without (ß = -.45, p = .004) post-stroke depressive symptoms. Anxiety mediated this relationship in participants with depressive symptoms (ß = -.19, 95% CI = -.361 ∼ -.049), but not in participants without depressive symptoms (ß = -.18, 95% CI = -.014 ∼ .378). Depressive and anxious symptoms should both be addressed to best facilitate participation by stroke survivors.

Moderating Role of Self-Regulation Difficulties in the Momentary Associations Between Depressive Symptoms and Participation Poststroke.

IMPORTANCE: Because depressive symptoms are momentarily associated with lower levels of participation poststroke, it is crucial to investigate what moderates such associations to identify a potential intervention target to reduce the momentary links between depressive symptoms and participation poststroke. Self-regulation seems to be a potential moderator of such associations. OBJECTIVE: To investigate the extent to which difficulties in self-regulation moderate the momentary associations between depressive symptoms and participation poststroke. DESIGN: This study uses a real-time, repeated-measures design using smartphone-based ecological momentary assessment surveys five times a day for 10 days. We performed multilevel modeling to uncover the momentary associations among the study variables. SETTING: Community. PARTICIPANTS: 39 people with stroke. OUTCOMES AND MEASURES: We obtained real-time data for difficulties in self-regulation (total, cognitive, behavioral, and emotion regulation), depressive symptoms, and participation in daily activities (performance in daily activities and satisfaction with performing daily activities). RESULTS: We included 1,612 survey responses in the analysis. Higher depressive symptoms were momentarily associated with lower levels of performance (ß = -0.05 to -0.07, p < .001) and satisfaction (ß = -0.04 to -0.06, p < .05), regardless of adjusting for self-regulation variables and other covariates. Difficulties in total self-regulation (ß = -0.01, p < .001) and emotion regulation (ß = -0.02, p < .001) magnified the negative associations between depressive symptoms and satisfaction with performing daily activities. CONCLUSIONS AND RELEVANCE: Using self-regulation and emotion regulation strategies may be a target for just-in-time intervention for reducing the momentary associations between depressive symptoms and satisfaction with performing daily activities poststroke. Plain-Language Summary: Depressive symptoms have immediate and real-time associations with lower levels of participation in daily activities in people with stroke. Self-regulation, including cognitive regulation (e.g., goal setting, planning strategies), behavioral regulation (e.g., controlling impulsive behaviors), and emotion regulation (e.g., managing negative feelings), may be an intervention target for reducing the immediate associations between depressive symptoms and lower levels of participation poststroke. Thus, we investigated whether difficulties in self-regulation variables magnify the negative real-time associations between depressive symptoms and participation poststroke. To obtain real-time data on difficulties in self-regulation variables, depressive symptoms, and participation (i.e., performance and satisfaction), we asked 39 community-dwelling people with stroke to answer smartphone surveys. The results showed that difficulties in total self-regulation and emotion regulation magnified the negative associations between depressive symptoms and satisfaction with performing daily activities. Our findings suggest that self-regulation and emotion regulation strategies may be a target for real-time intervention for reducing the momentary associations between depressive symptoms and satisfaction with performing daily activities poststroke.

Sophora genomes provide insight into the evolution of alkaloid metabolites along with small-scale gene duplication.

The genus Sophora (Fabaceae) includes medicinal plants that have been used in East Asian countries since antiquity. Sophora flavescens is a perennial herb indigenous to China, India, Japan, Korea, and Russia. Its dried roots have antioxidant, anti-inflammatory, antibacterial, apoptosis-modulating, and antitumor efficacy. The congeneric S. koreensis is endemic to Korea and its genome is less than half the size of that of S. flavescens. Nevertheless, this discrepancy can be used to assemble and validate the S. flavescens genome. A comparative genomic study of the two genomes can disclose the recent evolutionary divergence of the polymorphic phenotypic profiles of these species. Here, we used the PacBio sequencing platform to sequence and assemble the S. koreensis and S. flavescens genomes. We inferred that it was mainly small-scale duplication that occurred in S. flavescens. A KEGG analysis revealed pathways that might regulate the pharmacologically important secondary metabolites in S. flavescens and S. koreensis. The genome assemblies of Sophora spp. could be used in comparative genomics and data mining for various plant natural products.

Mutations causing Lopes-Maciel-Rodan syndrome are huntingtin hypomorphs.

Huntington's disease pathogenesis involves a genetic gain-of-function toxicity mechanism triggered by the expanded HTT CAG repeat. Current therapeutic efforts aim to suppress expression of total or mutant huntingtin, though the relationship of huntingtin's normal activities to the gain-of-function mechanism and what the effects of huntingtin-lowering might be are unclear. Here, we have re-investigated a rare family segregating two presumed HTT loss-of-function (LoF) variants associated with the developmental disorder, Lopes-Maciel-Rodan syndrome (LOMARS), using whole-genome sequencing of DNA from cell lines, in conjunction with analysis of mRNA and protein expression. Our findings correct the muddled annotation of these HTT variants, reaffirm they are the genetic cause of the LOMARS phenotype and demonstrate that each variant is a huntingtin hypomorphic mutation. The NM_002111.8: c.4469+1G>A splice donor variant results in aberrant (exon 34) splicing and severely reduced mRNA, whereas, surprisingly, the NM_002111.8: c.8157T>A NP_002102.4: Phe2719Leu missense variant results in abnormally rapid turnover of the Leu2719 huntingtin protein. Thus, although rare and subject to an as yet unknown LoF intolerance at the population level, bona fide HTT LoF variants can be transmitted by normal individuals leading to severe consequences in compound heterozygotes due to huntingtin deficiency.

Cingulate white matter mediates the effects of fecal Ruminococcus on neuropsychiatric symptoms in patients with amyloid-positive amnestic mild cognitive impairment.

BACKGROUND: Microbiota-gut-brain axis interacts with one another to regulate brain functions. However, whether the impacts of gut dysbiosis on limbic white matter (WM) tracts contribute to the neuropsychiatric symptoms (NPS) in patients with amyloid-positive amnestic mild cognitive impairment (aMCI+), have not been explored yet. This study aimed to investigate the mediation effects of limbic WM integrity on the association between gut microbiota and NPS in patients with aMCI+. METHODS: Twenty patients with aMCI + and 20 healthy controls (HCs) were enrolled. All subjects underwent neuropsychological assessments and their microbial compositions were characterized using 16S rRNA Miseq sequencing technique. Amyloid deposition inspected by positron emission tomography imaging and limbic WM tracts (i.e., fornix, cingulum, and uncinate fasciculus) detected by diffusion tensor imaging were additionally measured in patients with aMCI+. We employed a regression-based mediation analysis using Hayes's PROCESS macro in this study. RESULTS: The relative abundance of genera Ruminococcus and Lactococcus was significantly decreased in patients with aMCI + versus HCs. The relative abundance of Ruminococcus was negatively correlated with affective symptom cluster in the aMCI + group. Notably, this association was mediated by WM integrity of the left cingulate gyrus. CONCLUSIONS: Our findings suggest Ruminococcus as a potential target for the management of affective impairments in patients with aMCI+.

Complementary Analysis for Undetectable Microplastics from Contact Lenses to Aquatic Environments via Fourier Transform Infrared Spectroscopy.

Although microplastics (MPs) are intrinsically toxic and function as vectors for organic micropollutants, their discharge from wastewater treatment plant effluents and human activity remains unknown owing to the limitations of detection and treatment technologies. It is imperative to quantify MPs from human activities involving the consumption of various plastic products. This study warns that contact lenses can generate MPs and nanoplastics (NPs) after being discharged into aquatic environments. Identification via micro-Fourier transform infrared spectroscopy revealed that the fragmented particles (from a few tens to a few hundred micrometres) could not be detected as poly(2-hydroxyl methacrylate), the component of contact lenses, owing to changes in its chemical properties. After the degradation process, the median size of the contact lens particles decreased from 313 to 85 µm. Approximately 300,600 g of contact lens waste is discharged into sewage systems daily in the United States of America (USA), where 45 million people wear contact lenses and throw away one-fifth of them every day. Contact lens waste (1 g) has the potential to release 5653.3-17,773.3 particles of MPs. This implies that the currently reported MP amounts in the environmental matrix exclude significant amounts of MPs and NPs from discharged contact lenses. The identification method should be examined, and a registration of the disposal process should be established.

Oral health of older Koreans by region and family status in 2020-2021.

OBJECTIVE: To describe the oral health of older people by region and family status using data from the National Health and Nutrition Survey. BACKGROUND: As the ageing of Korean society intensifies, health inequalities based on region and family status are also deepening. METHODS: Data from the 8th National Health and Nutrition Survey (2020-2021) conducted by the Korea Centers for Disease Control and Prevention were used, and a total of 3437 older people aged 65 or older were selected as study participants. Chewing discomfort and oral health behaviours were assessed by region and family status using multivariable logistic regression analysis with the complex sample survey design. RESULTS: We found an association between living alone and greater chewing discomfort. Residing in rural areas was also associated with a higher prevalence of this. In urban areas, chewing discomfort was 1.27 times higher among older people living alone than in those not living alone, while in rural areas, the discomfort was 1.52 times higher among the older people who lived alone. CONCLUSIONS: Region and family status were associated with greater chewing discomfort in older people. In Korean society, where the number of single-person older people households is increasing, along with the ageing population, attention to resolving the disparities in oral health in older people is needed.

Improving Text-to-SQL with a Hybrid Decoding Method.

Text-to-SQL is a task that converts natural language questions into SQL queries. Recent text-to-SQL models employ two decoding methods: sketch-based and generation-based, but each has its own shortcomings. The sketch-based method has limitations in performance as it does not reflect the relevance between SQL elements, while the generation-based method may increase inference time and cause syntactic errors. Therefore, we propose a novel decoding method, Hybrid decoder, which combines both methods. This reflects inter-SQL element information and defines elements that can be generated, enabling the generation of syntactically accurate SQL queries. Additionally, we introduce a Value prediction module for predicting values in the WHERE clause. It simplifies the decoding process and reduces the size of vocabulary by predicting values at once, regardless of the number of conditions. The results of evaluating the significance of Hybrid decoder indicate that it improves performance by effectively incorporating mutual information among SQL elements, compared to the sketch-based method. It also efficiently generates SQL queries by simplifying the decoding process in the generation-based method. In addition, we design a new evaluation measure to evaluate if it generates syntactically correct SQL queries. The result demonstrates that the proposed model generates syntactically accurate SQL queries.

Heterogeneous early illness courses of Korean patients with bipolar disorders: replication of the staging model.

BACKGROUND: Clinical staging of bipolar disorder (BD) requires application of real-world data, as the next step in hypothesis. This study used the staging model to analyze the long-term course of BD in Korean patients based on clinical features and treatment responses to map the progression of bipolar illness from its early phase after the onset of illness. METHODS: A total of 136 patients diagnosed with BD-I (n = 62) or BD-II (n = 74) were recruited. Their progressive stages were retrospectively evaluated. A multi-state model was used to calculate the probability of progression to each stage. Hazard ratios of covariates expected to influence different courses of BD were calculated. Using the Alda score, long-term responses to mood stabilizers depending on the current stage were compared. RESULTS: Several sub-populations showed varied courses during the first five years after the onset of illness, with 41.5% remaining in stage 2 and 53% progressing to higher stages with shortened time for transition. Profiles of patients with BD-I and BD-II were different, suggesting biologically distinct groups. Comorbid psychiatric disorders, such as obsessive-compulsive disorder (OCD) and bulimia nervosa (BN) were associated with a recurrent course (stage 3a or 3b) or a malignant course (stage 3c or 4). Early age of onset, shorter duration of illness, older age at the start of medication, and poor response to lithium affected the illness progression. CONCLUSION: We were able to apply the stage model based on episode recurrence patterns in early illness courses of Korean patients with BD. The stage progression pattern differed from the early phase in BD-I and BD-II patients. Psychotic comorbidity, age at onset, age at starting psychiatric treatment showed associations with the illness progression.

Using Implementation Science to Guide the Process of Adapting a Patient Engagement Intervention for Inpatient Spinal Cord Injury/Disorder Rehabilitation.

OBJECTIVES: This study aimed to describe the process of adapting an evidence-based patient engagement intervention, enhanced medical rehabilitation (E-MR), for inpatient spinal cord injury/disease (SCI/D) rehabilitation using an implementation science framework. DESIGN: We applied the collaborative intervention planning framework and included a community advisory board (CAB) in an intervention mapping process. SETTING: A rehabilitation hospital. PARTICIPANTS: Stakeholders from inpatient SCI/D rehabilitation (N=7) serving as a CAB and working with the research team (N=7) to co-adapt E-MR. INTERVENTIONS: E-MR. MAIN OUTCOME MEASURES: Logic model and matrices of change used in CAB meetings to identify areas of intervention adaptation. RESULTS: The CAB and research team implemented adaptations to E-MR, including (1) identifying factors influencing patient engagement in SCI/D rehabilitation (eg, therapist training); (2) revising intervention materials to meet SCI/D rehabilitation needs (eg, modified personal goals interview and therapy trackers to match SCI needs); (3) incorporating E-MR into the rehabilitation hospital's operations (eg, research team coordinated with CAB to store therapy trackers in the hospital system); and (4) retaining fidelity to the original intervention while best meeting the needs of SCI/D rehabilitation (eg, maintained core E-MR principles while adapting). CONCLUSIONS: This study demonstrated that structured processes guided by an implementation science framework can help researchers and clinicians identify adaptation targets and modify the E-MR program for inpatient SCI/D rehabilitation.

Association between smokeless tobacco use and cigarette smoking amount by age.

BACKGROUND: The use of smokeless tobacco has increased worldwide among young people. This study aimed to investigate the association between smokeless tobacco use and cigarette smoking amount in adult smoker groups stratified by age. METHOD: 2013-2015 National Health Interview Survey was used. A total of 19,635 subjects were included in our analysis. Propensity score matching was used to adjust for selection and any other bias. Generalized estimating equation was used to analyze the association between smokeless tobacco use and cigarette smoking amount by age. RESULTS: All 580 smokeless tobacco users were matched to 2,900 non-smokeless tobacco users. Among those who were aged under 30, smokeless tobacco use was positively associated with the number of cigarettes used per day. Smokeless tobacco users who were aged under 30 and tried quitting smoking used more cigarettes than those who did non-smokeless tobacco users. CONCLUSIONS: The present study revealed that among those who were aged under 30, smokeless tobacco use was positively associated with the number of cigarettes used per day. This study could contribute to understand the behaviors and tendencies of smoking in young adulthood and to establish effective smoking cessation methods for their age.

A Chip Antenna for Bluetooth Earphones with Cross-Head Interference Tested from Received-Signal Sensing.

In this paper, a novel chip antenna and its function in wireless connectivity are presented for Bluetooth (BLT) earphones. The chip antenna is a metamaterial so compact (<λ/8), as the size of 4.9 × 13.0 × 2.0 mm3, that when it is mounted on the realistic PCB, it can be held in the enclosure of the BLT earphone. This setting does not degrade the resonance (S11 < −10 dB) of the proposed antenna. As two earphones in a pair are demanded to communicate with each other, one shares an RF signal with the other and they take turns as the master and slave. The received signal sensing is conducted with the latest model of human head-ear-phantom located between the earphones to mimic the real use-case and cross-head interference. Electromagnetic simulation of the antenna is done and verified by fabrication and measurement. Particularly, received-signal strength indications between the proposed antennas in the earphones are experimentally obtained as −67.5 dBm and −70 dBm without and with the head-ear-phantom, respectively, much greater than −120 dBm, the limit of detection, and implying acceptable connectivity and invulnerability over cross-head-interference problems.

Smart License Plate in Combination with Fluorescent Concentrator for Vehicular Visible Light Communication System.

Vehicle-to-vehicle communication based on visible light communication has gained much attention. This work proposes a smart license plate receiver incorporated with a fluorescent concentrator, enabling a fast vehicle-to-vehicle communication with a large field of view and high optical gain. Communication performance is experimentally analyzed using off-the-shelf light-emitting diode-based headlamps for low-latency direct line of sight channel. Additionally, a blue laser diode-based beam-steering and tracking system, through image processing of taillights with a steerable mirror, is investigated. Data rates of 54 Mbps from the headlamps and 532 Mbps from the beam-steering channel with ±25° are demonstrated. In addition, real-time video streaming through the beam-steering channel is presented.

An On-Film AMC Antenna Insert-Molded in Earbuds with Enhancement in In-Ear and In Situ Received-Signal Sensing.

In this paper, a novel thin and flexible antenna is proposed for earbuds to gain an improvement in their wireless signal-sensing capability as a film-based artificial magnetic conductor (AMC) structure. As antenna designs for earbuds face challenges of being embedded beneath the top cover of the earbud, conformal to curved surfaces, and very close to metallic ground and touch-panel parts, as well as scarce degrees of freedom from feeding conditions and functional degradation by human tissue, unlike conventional techniques such as quasi quarter-wavelength radiators on LDS and epoxy molding compounds (relatively thick and pricy), an antenna of a metal pattern on a film is made with another film layer as the AMC to mitigate problems of the antenna in a small and curved space of an insert-molded wireless device. The antenna was designed, fabricated, and embedded in earbud mockups to work for the 2.4 GHz Bluetooth RF link, and its functions were verified by RF and antenna measurement, showing that it could overcome the limitations in impedance matching with only lumped elements and poor radiation by the ordinary schemes. The input reflection coefficient and antenna efficiency were 10 dB and 9% better than other methods. In particular, the on-film AMC antenna (OFAA) presents robustness against deterioration by the human tissue, when it is placed in the ear phantom at the workbench and implemented in an in situ test using a large zorb ball mimicking a realistic sensing environment. This yielded an RSSI enhancement of 20-30 dB.

Substituted Syndecan-2-Derived Mimetic Peptides Show Improved Antitumor Activity over the Parent Syndecan-2-Derived Peptide.

We previously showed that a synthetic peptide (S2-P) corresponding to a portion of the human syndecan-2 (SDC2) sequence can bind to the pro-domain of matrix metalloproteinase-7 (MMP-7) to inhibit colon cancer activities. Since S2-P had a relatively weak binding affinity for the MMP-7 pro-domain, we herein modified the amino acid sequence of S2-P to improve the anticancer potential. On the basis of the interaction structure of S2-P and MMP-7, four peptides were generated by replacing amino acids near Tyr 51, which is critical for the interaction. The SDC2-mimetic peptides harboring an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-D) or with an Ala-to-Phe substitution at the N-terminal side of Tyr 51 and an Ala-to-Asp substitution at the C-terminal side of Tyr 51 (S2-FE) showed improved interaction affinities for the MMP-7 pro-domain. Compared to S2-P, S2-FE was better able to inhibit the SDC2-MMP-7 interaction, the cell surface localization of MMP-7, the gelatin degradation activity of MMP-7, and the cancer activities (cell migration, invasion, and colony-forming activity) of human HCT116 colon cancer cells in vitro. In vivo, S2-FE inhibited the primary tumor growth and lung metastasis of CT26 mouse colon cancer cells in a xenograft mouse model. Together, these data suggest that S2-FE could be useful therapeutic anticancer peptides for colon cancer.

Ecological Momentary Assessment of Social Interactions: Associations With Depression, Anxiety, Pain, and Fatigue in Individuals With Mild Stroke.

OBJECTIVES: To examine real-time relationships between social interactions and poststroke mood and somatic symptoms in participants' daily environments. DESIGN: Prospective observational study using smartphone-based ecological momentary assessment (EMA) surveys 5 times a day for 2 weeks. Multilevel models were used to analyze data for concurrent and lagged associations. SETTING: Community. PARTICIPANTS: Adults (N=48) with mild stroke. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: EMA measures of self-appraisal of social interactions (confidence, satisfaction, and success), as well as mood (depression and anxiety) and somatic (pain and fatigue) symptoms. RESULTS: In concurrent associations, increased depressed mood was associated with reduced ratings of all aspects of social interactions. Fatigue was associated with reduced ratings of social satisfaction and success. In lagged associations, increased anxious mood preceded increased subsequent social confidence. Higher average social satisfaction, confidence, and success were related to lower momentary fatigue, anxious mood, and depressed mood at the next time point. Regarding clinicodemographic factors, being employed was concurrently related to increased social interactions. An increased number of comorbidities predicted higher somatic, but not mood, symptoms at the next time point. CONCLUSIONS: This study provides preliminary evidence of dynamic relationships between social interactions and somatic and mood symptoms in individuals with mild stroke. Interventions to not only address the sequelae of symptoms, but also to promote participation in social activities in poststroke life should be explored.