Skin-Attached Arrayed Piezoelectric Sensors for Continuous and Safe Monitoring of Oculomotor Movements.

Abnormal oculomotor movements are known to be linked to various types of brain disorders, physical/mental shocks to the brain, and other neurological disorders, hence its monitoring can be developed into a simple but effective diagnostic tool. To overcome the limitations in the current eye-tracking system and electrooculography, a piezoelectric arrayed sensor system is developed using single-crystalline III-N thin-film transducers, which offers advantages of mechanical flexibility, biocompatibility, and high electromechanical conversion, for continuous monitoring of oculomotor movements by skin-attachable, safe, and highly sensitive sensors. The flexible piezoelectric eye movement sensor array (F-PEMSA), consisting of three transducers, is attached to the face temple area where it can be comfortably wearable and can detect the muscles' activity associated with the eye motions. Output voltages from upper, mid, and lower sensors (transducers) on different temple areas generate discernable patterns of output voltage signals with different combinations of positive/negative signs and their relative magnitudes for the various movements of eyeballs including 8 directional (lateral, vertical, and diagonal) and two rotational movements, which enable various types of saccade and pursuit tests. The F-PEMSA can be used in clinical studies on the brain-eye relationship to evaluate the functional integrity of multiple brain systems and cognitive processes.

Effect of a Porous Suture Containing Transforming Growth Factor Beta 1 on Healing After Rotator Cuff Repair in a Rat Model.

BACKGROUND: The healing failure rate after rotator cuff repair is considerably high. PURPOSE: To evaluate the effect of a porous suture containing transforming growth factor beta 1 (TGF-ß1) on the sustained release of TGF-ß1 and rotator cuff healing in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A porous suture was developed, and its tensile strength was measured. TGF-ß1 was delivered using the porous suture, and a TGF-ß1 release test and human fibroblast proliferation assay were performed. For the animal experiment, 30 rats were randomly allocated into 3 groups (n = 10 each). A bilateral supraspinatus tendon tear was made in all the rats, and repair was performed. Group 1 received repair only; group 2, repair and a single injection of TGF-ß1; and group 3, repair using the porous suture containing TGF-ß1. Eight weeks after repair, biomechanical and histological analyses were performed. RESULTS: The porous suture was successfully developed with mechanical properties compatible with the conventional suture, and the sustained release of TGF-ß1 from the porous suture was confirmed. In addition, the cell proliferation assay confirmed the biological safety of the porous suture. In the animal experiment, group 3 biomechanically exhibited the largest cross-sectional area and the highest ultimate failure load and ultimate stress (all P < .05). Histological examination revealed that group 3 showed significantly better collagen fiber density and tendon-to-bone maturation than did groups 1 and 2 (all P < .05). CONCLUSION: The porous suture containing TGF-ß1 could sustainedly and safely release TGF-ß1, and its use during rotator cuff repair could improve rotator cuff healing, as assessed on the basis of the biomechanical and histological changes in the rat model in this study. Considering the effectiveness, safety, and convenience of the porous suture without extra effort in surgery, the findings of the present study will have a far-reaching effect on the treatment of rotator cuff tears. CLINICAL RELEVANCE: The porous suture containing TGF-ß1 might improve healing after rotator cuff repair.

Effect of diabetes and corticosteroid injection on glenohumeral joint capsule in a rat stiffness model.

PURPOSE: To evaluate the effects of diabetes and corticosteroid injected in the joints on the shoulder motion, gait, and joint capsular properties in a rat stiffness model. METHODS: A total of 27 rats were randomly distributed into 3 groups-nondiabetes group (group A), diabetes group (group B), and diabetes plus steroid injection group (group C). The diabetes model was developed by inducing hyperglycemia with a submaximal dose of streptozotocin and the stiffness model by completely immobilizing the right shoulder of each animal in all groups with sutures passed between the scapula and humeral shaft. The left shoulder was used as an untreated control in all groups. Three weeks after immobilization, the sutures were removed in all groups, and a single dose of triamcinolone acetonide (0.5 mg/kg) was injected into the glenohumeral joint in group C. After 3 weeks of free activity, range of motion (ROM) evaluation, gait analysis by stride length, and capsular area measurement were performed in all rats. RESULTS: Hyperglycemia was successfully induced with a mean blood glucose level of 448.9±55.9 mg/dL in group B and 431.6±17.8 mg/dL in group C, which were significantly higher than 136.5±13.4 mg/dL in group A (P < .001). A significantly smaller ROM and stride length were found in the right (stiffness-induced) shoulder than that in the left (control) shoulder only in group B, and significantly larger capsular area in the right shoulder than that in the left shoulder in groups A and B (all P < .05). However, in group C, there were no differences between the right and left shoulders in all measurements (all P > .05). In case of the right shoulders in each group, group C showed significantly larger ROM (68° ± 11° vs. 42° ± 7°) and smaller capsular area (3934.4 ± 537.1 pixels vs. 7402.3 ± 1840.3 pixels) than group B (all P < .0167). CONCLUSIONS: The diabetic model had a detrimental effect on the development of stiffness by thickening the joint capsule, and an intra-articular steroid injection resolved the thickened joint capsule and restored shoulder motion.

Relationship between fatty infiltration and gene expression in patients with medium rotator cuff tear.

BACKGROUND: Fatty infiltration (FI) is a key prognostic factor that affects outcomes after rotator cuff repair and is radiologically evaluated using the Goutallier classification. The purpose of this study was to assess alterations in gene and protein expression according to the Goutallier classification in the supraspinatus muscle and any relationships among various gene expression profiles. METHODS: Twenty-four samples of the supraspinatus muscle from 12 patients with a high FI grade (grade 3 or 4) and 12 patients with a low FI grade (grade 1 or 2) with medium-sized tears were acquired during arthroscopic surgery. Alterations in the expression of genes and proteins associated with adipogenesis, fibrosis, inflammation, and muscle atrophy were compared between the high- and low-FI groups using reverse-transcription quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. RESULTS: mRNA expression of not only the adipogenic genes (peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α; P < .001 and P = .020) but also the fibrosis-related gene (α-smooth muscle actin; P < .001), inflammation-related genes (interleukin [IL]-1ß and tumor necrosis factor α; P = .041 and P = .039), and muscle atrophy-related genes (atrogin 1 and myostatin; P = .006 and P < .001) was higher in the high-FI group compared with that in the low-FI group. In addition, adipogenic gene expression was significantly correlated with the expression of other categories of genes (all P < .05, except atrogin 1). A correlation of gene and protein expression was observed for IL-1ß (P = .027) and myostatin (P = .029). CONCLUSIONS: The radiologic grading of FI was associated with the expression of various genes, including adipogenic, fibrotic, inflammatory, and atrophy-related genes, and these genes were closely correlated with each other in terms of expression. This information could be helpful in patient counseling.

Development and validation of the fall risk perception questionnaire for patients in acute care hospitals.

AIMS AND OBJECTIVES: This study aimed to develop a fall risk perception questionnaire for patients admitted to acute care hospitals and to establish its reliability and validity. BACKGROUND: To prevent falls during patients' hospitalisation, it is essential for them to accurately perceive their risk of falling. DESIGN: This methodological study was performed to develop a fall risk perception questionnaire. METHODS: After generating a preliminary questionnaire, two rounds of content validity testing were performed with nine experts. Following a pilot test, a convenience sample of 236 participants was recruited from an acute care hospital between 2 May 2018 and 15 December 2019. Construct, convergent and known-group validity of the questionnaire was evaluated, and reliability was estimated by calculating the internal consistency reliability coefficients. The study adhered to STROBE guidelines. RESULTS: Exploratory factor analysis yielded a three-factor solution with 27 items. The questionnaire showed statistically significant positive correlation with the Korean Falls Efficacy Scale-International and the Morse Fall Scale, thus establishing convergent validity. For known-group comparison, Morse Fall Scale scores were categorised into two groups by cut-off score. The risk for falls group had a significantly higher perceived fall risk than the no risk for falls group, thus establishing known-group validity. Cronbach's alpha values indicated good to excellent reliability for the overall questionnaire with 27 items and for each of the three subfactors. CONCLUSIONS: The fall risk perception questionnaire demonstrated satisfactory reliability and validity in an acute care hospital setting. RELEVANCE TO CLINICAL PRACTICE: Because understanding patients' perceptions of their fall risk is essential for preventing falls, it is necessary to regularly assess patients' fall risk perception using tools with established reliability and validity.

Atrogin1-induced loss of aquaporin 4 in myocytes leads to skeletal muscle atrophy.

The water channel aquaporin 4 (AQP4) regulates the flux of water across the cell membrane, maintaining cellular homeostasis. Since AQP4 is enriched in the sarcolemma of skeletal muscle, a functional defect in AQP4 may cause skeletal muscle dysfunction. To investigate a novel mechanism underlying skeletal muscle atrophy, we examined AQP4 expression and its regulation in muscle using the rotator cuff tear (RCT) model. Human and mouse AQP4 expression was significantly decreased in atrophied muscle resulting from RCT. The size and the number of myotubes were reduced following AQP4 knockdown. Atrogin 1-mediated ubiquitination of AQP4 was verified with an ubiquitination assay after immunoprecipitation of AQP4 with an anti-AQP4 antibody. In this study, we identified high mobility group box 1 (HMGB1) as a potent upstream regulator of atrogin 1 expression. Atrogin 1 expression was increased by recombinant mouse HMGB1 protein, and the HMGB1-induced atrogin 1 expression was mediated via NF-κB signaling. Our study suggests that loss of AQP4 appears to be involved in myocyte shrinkage after RCT, and its degradation is mediated by atrogin 1-dependent ubiquitination. HMGB1, in its function as a signaling molecule upstream of the ubiquitin ligase atrogin 1, was found to be a novel regulator of muscle atrophy.

Comprehensive pharmacogenomic characterization of gastric cancer.

BACKGROUND: Gastric cancer is among the most lethal human malignancies. Previous studies have identified molecular aberrations that constitute dynamic biological networks and genomic complexities of gastric tumors. However, the clinical translation of molecular-guided targeted therapy is hampered by challenges. Notably, solid tumors often harbor multiple genetic alterations, complicating the development of effective treatments. METHODS: To address such challenges, we established a comprehensive dataset of molecularly annotated patient derivatives coupled with pharmacological profiles for 60 targeted agents to explore dynamic pharmacogenomic interactions in gastric cancers. RESULTS: We identified lineage-specific drug sensitivities based on histopathological and molecular subclassification, including substantial sensitivities toward VEGFR and EGFR inhibition therapies in diffuse- and signet ring-type gastric tumors, respectively. We identified potential therapeutic opportunities for WNT pathway inhibitors in ALK-mutant tumors, a significant association between PIK3CA-E542K mutation and AZD5363 response, and transcriptome expression of RNF11 as a potential predictor of response to gefitinib. CONCLUSIONS: Collectively, our results demonstrate the feasibility of drug screening combined with tumor molecular characterization to facilitate personalized therapeutic regimens for gastric tumors.

Clinical Targeted Next-Generation sequencing Panels for Detection of Somatic Variants in Gliomas.

PURPOSE: Targeted next-generation sequencing (NGS) panels for solid tumors have been useful in clinical framework for accurate tumor diagnosis and identifying essential molecular aberrations. However, most cancer panels have been designed to address a wide spectrum of pan-cancer models, lacking integral prognostic markers that are highly specific to gliomas. MATERIALS AND METHODS: To address such challenges, we have developed a glioma-specific NGS panel, termed "GliomaSCAN," that is capable of capturing single nucleotide variations and insertion/deletion, copy number variation, and selected promoter mutations and structural variations that cover a subset of intron regions in 232 essential glioma-associated genes. We confirmed clinical concordance rate using pairwise comparison of the identified variants from whole exome sequencing (WES), immunohistochemical analysis, and fluorescence in situ hybridization. RESULTS: Our panel demonstrated high sensitivity in detecting potential genomic variants that were present in the standard materials. To ensure the accuracy of our targeted sequencing panel, we compared our targeted panel to WES. The comparison results demonstrated a high correlation. Furthermore, we evaluated clinical utility of our panel in 46 glioma patients to assess the detection capacity of potential actionable mutations. Thirty-two patients harbored at least one recurrent somatic mutation in clinically actionable gene. CONCLUSION: We have established a glioma-specific cancer panel. GliomaSCAN highly excelled in capturing somatic variations in terms of both sensitivity and specificity and provided potential clinical implication in facilitating genome-based clinical trials. Our results could provide conceptual advance towards improving the response of genomically guided molecularly targeted therapy in glioma patients.

Influence of Smoking on the Expression of Genes and Proteins Related to Fat Infiltration, Inflammation, and Fibrosis in the Rotator Cuff Muscles of Patients With Chronic Rotator Cuff Tears: A Pilot Study.

PURPOSE: To evaluate the altered gene and protein expression patterns in the rotator cuff muscles of smokers and non-smokers with rotator cuff tears and to identify the smoking-associated key genetic factor(s) involved in rotator cuff muscle physiology. METHODS: Twenty-four samples of rotator cuff muscle from 12 current heavy smokers (mean age 61.8 ± 5.1 years) and age- and sex-matched 12 non-smokers (mean age 61.8 ± 6.9 years) with medium-sized tears were acquired during arthroscopic surgery. As a statistical method, the propensity score matching technique was used to select control group by 1:1 matching for age and sex. Inclusion criteria were patients who underwent arthroscopic repair for medium-sized full-thickness rotator cuff tears and those that were current smokers with a smoking history >20 packs/year. Patients lacking medium-sized tears, those with recent steroid injection history, isolated subscapularis tear, preoperative stiff shoulder, acute traumatic tear, or previous surgery on the same shoulder, or those that declined to participate were excluded. Alterations in the expression of genes and proteins associated with myogenesis, inflammation, adipogenesis, and muscle fibrosis were compared between smokers and non-smokers with reverse-transcription quantitative polymerase chain reaction, western blotting, and immunohistochemistry. RESULTS: Histologic analysis revealed increased inflammation and remarkable fat accumulation and fibrogenesis in the rotator cuff muscle from smokers compared with that from non-smokers. The mRNA expression levels of inflammatory high mobility group box 1 (HMGB1; P = .043), adipogenic CCAAT/enhancer-binding protein alpha (P = .046) and peroxisome proliferator-activated receptor gamma (PPARγ; P = .048), myogenic differentiation 1 (P = .032), fibrogenic alpha-smooth muscle actin (α-SMA; P = .033), and metalloproteinase 9 (P = .036) were significantly greater in samples from smokers than from non-smokers. A correlation was observed between gene and protein expression of HMGB1 (P = .034), PPARγ (P = .021), and α-SMA (P = .021). CONCLUSIONS: Smokers with rotator cuff tears showed high inflammation, large fat infiltration, and fibrosis in rotator cuff muscle that is associated with the increased expression of HMGB1, PPARγ, and α-SMA, respectively. LEVEL OF EVIDENCE: Case control study (Prognostic level III).

Pharmacogenomic analysis of patient-derived tumor cells in gynecologic cancers.

BACKGROUND: Gynecologic malignancy is one of the leading causes of mortality in female adults worldwide. Comprehensive genomic analysis has revealed a list of molecular aberrations that are essential to tumorigenesis, progression, and metastasis of gynecologic tumors. However, targeting such alterations has frequently led to treatment failures due to underlying genomic complexity and simultaneous activation of various tumor cell survival pathway molecules. A compilation of molecular characterization of tumors with pharmacological drug response is the next step toward clinical application of patient-tailored treatment regimens. RESULTS: Toward this goal, we establish a library of 139 gynecologic tumors including epithelial ovarian cancers (EOCs), cervical, endometrial tumors, and uterine sarcomas that are genomically and/or pharmacologically annotated and explore dynamic pharmacogenomic associations against 37 molecularly targeted drugs. We discover lineage-specific drug sensitivities based on subcategorization of gynecologic tumors and identify TP53 mutation as a molecular determinant that elicits therapeutic response to poly (ADP-Ribose) polymerase (PARP) inhibitor. We further identify transcriptome expression of inhibitor of DNA biding 2 (ID2) as a potential predictive biomarker for treatment response to olaparib. CONCLUSIONS: Together, our results demonstrate the potential utility of rapid drug screening combined with genomic profiling for precision treatment of gynecologic cancers.

Effect of Fatty Acid-Binding Protein 4 Inhibition on Rotator Cuff Muscle Quality: Histological, Biomechanical, and Biomolecular Analysis.

BACKGROUND: A rotator cuff tear (RCT) induces fatty acid-binding protein 4 (FABP4) expression, resulting in ectopic fat accumulation in the rotator cuff muscle. PURPOSE: To evaluate whether FABP4 inhibition reduces fatty infiltration and improves muscle physiology after RCT in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Human supraspinatus muscle and deltoid muscle tissues were acquired from patients with RCTs during arthroscopic surgery, and FABP4 expression in the supraspinatus muscle was evaluated as compared with the intact deltoid muscle. A rat RCT model was established by detaching the supraspinatus tendon, after which a specific FABP4 inhibitor was locally injected into the supraspinatus muscle 4 times at 3-day intervals starting 2 weeks after the surgery. Body weight and blood glucose levels were measured at 2 and 4 weeks after the RCT, and the mRNA and protein expressions of various target molecules (including FABP4), histological changes, and biomechanical tensile strength were assessed in the supraspinatus muscles at 4 weeks after the RCT. RESULTS: The expression of human FABP4 was significantly increased in the torn rotator cuff muscle as compared with the intact deltoid muscle. In the rat model, the mRNA and protein expressions of FABP4 and HIF1α were significantly increased by the RCT as compared with the control. The FABP4 inhibitor treatment significantly decreased FABP4 expression when compared with the vehicle treatment; however, HIF1α expression was not significantly decreased versus the vehicle treatment. Histologically, RCT induced noticeable muscle fatty infiltration, which was remarkably reduced by the local injection of the FABP4 inhibitor. Biomechanically, the tensile strength of the rotator cuff muscle after the RCT was significantly improved by the FABP4 inhibitor in terms of load to failure and total energy to failure. CONCLUSION: RCT induces FABP4 expression in human and rat rotator cuff muscles. The FABP4 inhibitor drastically decreased the histological fatty infiltration caused by RCT and improved the tensile strength of the rotator cuff muscle. CLINICAL RELEVANCE: FABP4 inhibitor may have a beneficial effect on the muscle quality after RCT.

Hepatitis C Virus Induces the Ubiquitin-Editing Enzyme A20 via Depletion of the Transcription Factor Upstream Stimulatory Factor 1 To Support Its Replication.

Tumor necrosis factor alpha-induced protein 3 (TNFAIP3), also known as A20, is a ubiquitin-editing enzyme capable of ubiquitination or deubiquitination of its target proteins. In this study, we show that hepatitis C virus (HCV) infection could induce the expression of A20 via the activation of the A20 promoter. The induction of A20 by HCV coincided with the loss of upstream stimulatory factor 1 (USF-1), a transcription factor known to suppress the A20 promoter. The role of USF-1 in the regulation of the A20 promoter in HCV-infected cells was confirmed by the chromatin immunoprecipitation (ChIP) assay, and its depletion was apparently mediated by proteasomes, as USF-1 could be stabilized by the proteasome inhibitor MG132 to suppress the A20 expression. As the overexpression of A20 enhanced the replication of HCV and the silencing of A20 had the opposite effect, A20 is a positive regulator of HCV replication. Our further studies indicated that A20 enhanced the activity of the HCV internal ribosome entry site (IRES). In conclusion, our results demonstrated that HCV could induce the expression of A20 via the depletion of USF-1 to enhance its replication. Our study provided important information for further understanding the interaction between HCV and its host cells.IMPORTANCE Hepatitis C virus establishes chronic infection in approximately 85% of the patients whom it infects. However, the mechanism of how HCV evades host immunity to establish persistence is unclear. In this report, we demonstrate that HCV could induce the expression of the ubiquitin-editing enzyme A20, an important negative regulator of the tumor necrosis factor alpha (TNF-α) and NF-κB signaling pathways. This induction of A20 enhanced HCV replication as it could stimulate the HCV IRES activity to enhance the translation of HCV proteins. The induction of A20 was mediated by the depletion of USF-1, a suppressor of the A20 promoter. Our study thus provides important information for further understanding the interaction between HCV and its host cells.

Changes in Perianchor Cyst Formation Over Time After Rotator Cuff Repair: Influential Factors and Outcomes.

BACKGROUND: There is a lack of knowledge about the changes in perianchor cysts over time and the factors related to perianchor cysts. PURPOSE: To evaluate the changes in perianchor cyst formation and anchor absorption over time after arthroscopic rotator cuff repair with a biocomposite suture anchor and to evaluate the factors affecting perianchor cyst persistence and their relationship with patient outcomes. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Forty consecutive patients (mean age, 61.10 ± 5.79 years) who underwent arthroscopic repair for medium- to large-sized rotator cuff tears using a single type of biocomposite (poly-L-lactic acid/polyglycolic acid-beta tricalcium phosphate) medial-row anchor were prospectively enrolled. Postoperative magnetic resonance imaging (MRI) at 2 different time points (6 and 18 months) was performed, and perianchor cyst formation, anchor absorption, and healing failures were evaluated using postoperative MRI. Demographic and clinical data were collected, and functional outcomes at a minimum of 18 months after surgery were assessed. RESULTS: Perianchor cysts were observed in 24 patients (60.0% total; grade 1: 35.0%; grade 2: 10.0%; grade 3: 7.5%; grade 4: 7.5%) at 6 months, and 7 patients (18.4% total; grade 1: 7.9%; grade 2: 5.3%; grade 3: 2.6%; grade 4: 2.6%) had a persistent perianchor cyst at 18 months after surgery. No anchors were absorbed at 6 months, but 73.7% of patients revealed complete or near-full absorption at 18 months. Patients with persistent perianchor cysts showed a significantly larger tear size in the anteroposterior dimension ( P = .002) and greater retraction ( P < .001). There were no differences in healing failures and functional outcomes between patients with and without persisting perianchor cysts (all P > .05). No differences were found in perianchor cyst formation and anchor absorption between anchors inserted in the greater tuberosity and the lesser tuberosity (all P > .05). CONCLUSION: The incidence and severity of perianchor cysts decreased with time, and most biocomposite suture anchors were absorbed at 18 months after surgery. Persisting perianchor cysts correlated with a larger tear size in the anteroposterior dimension and greater retraction.

Improvement in Light Extraction Efficiency of InGaN/GaN Blue Light Emitting Diodes Using Sidewall Texturing.

Herein, we reported the effects of the geometric morphology of the sidewall on the extraction efficiency of GaN-based light-emitting diodes (LEDs). We performed numerical analysis based on the ray-tracing method. We found that the extraction efficiency of the LEDs increased with the texturing of the sidewall. The light output intensity of the LEDs (at an injection current of 100 mA) increased by 13.8% after sidewall texturing. These results confirmed that the geometric morphology of the sidewall plays an important role in improving the extraction efficiency of LEDs.

Survival Benefit of Perioperative Chemotherapy in Patients with Locally Advanced Gastric Cancer: a Propensity Score Matched Analysis.

PURPOSE: It has been reported that the survival of patients with locally advanced gastric cancer (LAGC) is better in East Asia countries than in developed western countries; however, the prognosis of LAGC remains poor. This study aimed to evaluate the effects of perioperative chemotherapy on the long-term survival of East Asia patients with LAGC. MATERIALS AND METHODS: From October 2006 through August 2008, 43 patients with LAGC received perioperative S-1 combined with weekly docetaxel in a phase II study (neoadjuvant group). These patients were matched using propensity scores to patients who underwent surgery without neoadjuvant chemotherapy during the same period (surgery group). The surgical outcomes and long-term survivals were compared between the 2 groups. RESULTS: After matching, 43 and 86 patients were included in the neoadjuvant and surgery groups, respectively, and there was no significant difference in their baseline characteristics. Although the operating time was longer in the neoadjuvant group, there was no significant difference in postoperative complications between the 2 groups. The neoadjuvant group had a significantly higher 5-year overall survival (OS) rate (73.3% vs. 51.1%, P=0.005) and a trend towards higher 5-year progression-free survival (PFS) (62.8% vs. 49.9%, P=0.145). In the multivariate analysis, perioperative chemotherapy was an independent factor for OS, with a hazard ratio of 0.4 (P=0.005) and a marginal effect on the PFS (P=0.054). CONCLUSIONS: Perioperative chemotherapy was associated with better long-term survival without increasing postoperative complications in the setting of D2 surgery for patients with LAGC, suggesting that perioperative chemotherapy can be a therapeutic option in East Asia countries.

Regulation of Apolipoprotein E Trafficking by Hepatitis C Virus-Induced Autophagy.

Apolipoprotein E (ApoE) plays an important role in the maturation and infectivity of hepatitis C virus (HCV). By analyzing the subcellular localization of ApoE in Huh7 hepatoma cells that harbored an HCV subgenomic RNA replicon, we found that ApoE colocalized with autophagosomes. This colocalization was marginally detected in HCV-infected cells, apparently due to the depletion of ApoE by HCV, as treatment with bafilomycin A1 (BafA1), a vacuolar ATPase inhibitor that inhibits autophagic protein degradation, partially restored the ApoE level and enhanced its colocalization with autophagosomes in HCV-infected cells. The role of HCV-induced autophagy in the degradation of ApoE was further supported by the observations that nutrient starvation, which induces autophagic protein degradation, led to the loss of ApoE in HCV subgenomic RNA replicon cells and that the knockdown of ATG7, a protein essential for the formation of autophagic vacuoles, increased the ApoE level in cells with productive HCV replication. Interestingly, the inhibition of autophagy by ATG7 knockdown reduced the colocalization of ApoE with the HCV E2 envelope protein and the HCV titers released from cells. In contrast, the treatment of cells with BafA1 enhanced the colocalization of ApoE and HCV E2 and increased both intracellular and extracellular HCV titers. These results indicated that autophagy played an important role in the trafficking of ApoE in HCV-infected cells. While it led to autophagic degradation of ApoE, it also promoted the interaction between ApoE and HCV E2 to enhance the production of infectious progeny viral particles.IMPORTANCE Hepatitis C virus (HCV) is one of the most important human pathogens. Its virion is associated with apolipoprotein E (ApoE), which enhances its infectivity. HCV induces autophagy to enhance its replication. In this report, we demonstrate that autophagy plays an important role in the trafficking of ApoE in HCV-infected cells. This leads to the degradation of ApoE by autophagy. However, if the autophagic protein degradation is inhibited, ApoE is stabilized and colocalized with autophagosomes. This leads to its enhanced colocalization with the HCV E2 envelope protein and increased production of infectious progeny viral particles. If autophagy is inhibited by suppressing the expression of ATG7, a gene essential for the formation of autophagosomes, the colocalization of ApoE with E2 is reduced, resulting in the reduction of progeny viral titers. These results indicate an important role of autophagy in the transport of ApoE to promote the production of infectious HCV particles.

Augmented Quantum Yield of a 2D Monolayer Photodetector by Surface Plasmon Coupling.

Monolayer (1L) transition metal dichalcogenides (TMDCs) are promising materials for nanoscale optoelectronic devices because of their direct band gap and wide absorption range (ultraviolet to infrared). However, 1L-TMDCs cannot be easily utilized for practical optoelectronic device applications (e.g., photodetectors, solar cells, and light-emitting diodes) because of their extremely low optical quantum yields (QYs). In this investigation, a high-gain 1L-MoS2 photodetector was successfully realized, based on the surface plasmon (SP) of the Ag nanowire (NW) network. Through systematic optical characterization of the hybrid structure consisting of a 1L-MoS2 and the Ag NW network, it was determined that a strong SP and strain relaxation effect influenced a greatly enhanced optical QY. The photoluminescence (PL) emission was drastically increased by a factor of 560, and the main peak was shifted to the neutral exciton of 1L-MoS2. Consequently, the overall photocurrent of the hybrid 1L-MoS2 photodetector was observed to be 250 times better than that of the pristine 1L-MoS2 photodetector. In addition, the photoresponsivity and photodetectivity of the hybrid photodetector were effectively improved by a factor of ∼1000. This study provides a new approach for realizing highly efficient optoelectronic devices based on TMDCs.

Sustained Delivery of Transforming Growth Factor ß1 by Use of Absorbable Alginate Scaffold Enhances Rotator Cuff Healing in a Rabbit Model.

BACKGROUND: The failure rate for healing after rotator cuff repair is relatively high. PURPOSE: To establish a system for sustained release of transforming growth factor ß1 (TGF-ß1) using an alginate scaffold and evaluate the effects of the sustained release of TGF-ß1 on rotator cuff healing in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: Before the in vivo animal study, a standard MTS assay was performed to evaluate cell proliferation and metabolic activity on the alginate scaffold. Additionally, an enzyme-linked immunosorbent assay was performed to confirm the capacity of the sustained release of TGF-ß1-containing alginate scaffold. Once the in vitro studies were completed, bilateral supraspinatus tendon repairs were performed in 48 rabbits that were allocated to 3 groups (n = 16 each) (group 1, supraspinatus repair only; group 2, supraspinatus repair with TGF-ß1 single injection; group 3, supraspinatus repair with TGF-ß1 sustained release via an alginate-based delivery system). Biomechanical and histological analyses were performed to evaluate the quality of tendon-to-bone healing at 12 weeks after rotator cuff repair. RESULTS: The cell proliferation rate of the alginate scaffold was 122.30% compared with the control (fresh medium) group, which confirmed that the alginate sheet had no cytotoxicity and enhanced cell proliferation. Additionally, the level of TGF-ß1 was found to increase with time on the alginate scaffold. Biomechanically, group 3 exhibited a significantly heightened ultimate failure load compared with groups 1 and 2 (group 1, 74.89 ± 29.82 N; group 2, 80.02 ± 34.42 N; group 3, 108.32 ± 32.48 N; P = .011) and more prevalent midsubstance tear compared with group 1 ( P = .028). However, no statistical differences were found in the cross-sectional area of the supraspinatus tendon (group 1, 32.74 ± 9.38; group 2, 33.76 ± 8.89; group 3, 34.80 ± 14.52; P = .882) and ultimate stress (group 1, 2.62 ± 1.13 MPa; group 2, 2.99 ± 1.81 MPa; group 3, 3.62 ± 2.24 MPa; P = .317). Histologically, group 3 exhibited a significantly heightened modified total Bonar score (group 1, 5.00 ± 1.54; group 2, 6.12 ± 1.85; group 3, 7.50 ± 1.31; P = .001). In addition, the tendon-to-bone interface for group 3 demonstrated better collagen orientation, continuity, and organization, and the area of new fibrocartilage formation was more evident in group 3. CONCLUSION: At 12 weeks after rotator cuff repair, the authors found improved biomechanical and histological outcomes for sustained release of TGF-ß1 using alginate scaffold in a rabbit model. CLINICAL RELEVANCE: The alginate-bound growth factor delivery system might improve healing after rotator cuff repair in humans.

Role of the Growth Temperature in MoS2 Growth by Chemical Vapor Deposition.

In this paper, we discuss the effect of synthesis temperature on the lateral growth of MoS2 thin films in chemical vapor deposition. With increasing temperature, surface coverage with MoS2 triangular islands is significantly improved due to an increase in the density of nuclei and fully continuous MoS2 thin film is grown when the growth temperature reached 800 °C. The MoS2 triangular islands grown at the temperature from 650 to 750 °C are monolayer and highly crystalline, whereas the large-area continuous film grown at the temperature of 800 °C is composed of double-layer or overlapping MoS2 nanosheets. Our research provides that synthesis temperature is the key to growth large area and high quality single crystal MoS2 films.