Search

IEEE802.1Qbv (Time-aware Shaper: TAS) in IEEE802.1-Time-Sensitive Networking (TSN) has recently been applied within user networks for realizing factory automation and remote control. As mass customization matures, TAS is expected to extend its coverage to not only user networks but also wide-area networks to realize ultra-low-latency (ULL) communication between remote locations. TAS is TSN technology expected to be used for long-distance communications because it can guarantee maximum latency limits. However, designing a TAS schedule is an NP-hard problem, which becomes more difficult as the amount of delay guarantee flow increases. This paper proposes a method to reduce the computational complexity of TAS schedules for the problem that the computation time increases exponentially as the amount of scheduled traffic (ST) flows increases. This problem has serious impacts on TAS scheduling in wide-area networks. In the proposed method, flows with the same characteristics are grouped to reduce the number of flows to be input into the scheduling calculation. This suppresses computation infeasibility in the NP-hard problem and improves the schedulability of ST flows. This paper contributes to realizing TAS over wide-area networks, which are currently underutilized.

Predicting the mechanical properties of polymer materials using machine learning is essential for the design of next-generation of polymers. However, the strong relationship between the higher-order structure of polymers and their mechanical properties hinders the mechanical property predictions based on their primary structures. To incorporate information on higher-order structures into the prediction model, X-ray diffraction (XRD) can be used. This study proposes a strategy to generate appropriate descriptors from the XRD analysis of the injection-molded polypropylene samples, which were prepared under almost the same injection molding conditions. To this end, first, Bayesian spectral deconvolution is used to automatically create high-dimensional descriptors. Second, informative descriptors are selected to achieve highly accurate predictions by implementing the black-box optimization method using Ising machine. This approach was applied to custom-built polymer datasets containing data on homo- polypropylene and derived composite polymers with the addition of elastomers. Results show that reasonable accuracy of predictions for seven mechanical properties can be achieved using only XRD.

Cancer-associated fibroblasts (CAFs) are a key component of the tumor microenvironment and significantly contribute to the progression of various cancers, including esophageal squamous cell carcinoma (ESCC). Our previous study established a direct co-culture system of human bone marrow-derived mesenchymal stem cells (progenitors of CAFs) and ESCC cell lines, which facilitates the generation of CAF-like cells and enhances malignancy in ESCC cells. In this study, we further elucidated the mechanism by which CAFs promote ESCC progression using cDNA microarray analysis of monocultured ESCC cells and those co-cultured with CAFs. We observed an increase in the expression and secretion of amphiregulin (AREG) and the expression and phosphorylation of its receptor EGFR in co-cultured ESCC cells. Moreover, AREG treatment of ESCC cells enhanced their survival and migration via the EGFR-Erk/p38 MAPK signaling pathway. Immunohistochemical analysis of human ESCC tissues showed a positive correlation between the intensity of AREG expression at the tumor-invasive front and the expression level of the CAF marker FAP. Bioinformatics analysis confirmed significant upregulation of AREG in ESCC compared with normal tissues. These findings suggest that AREG plays a crucial role in CAF-mediated ESCC progression and could be a novel therapeutic target for ESCC.

Abstract This review focuses on solvent‐free molecular liquid materials that exhibit changes in response to stimuli. Along with the recent development of soft functional materials, research on functional liquids possessing free deformability and ease of molding is becoming a new trend. A typical method for designing functional molecular liquids (FMLs) introduces flexible alkyl side‐chains around a π‐conjugation unit at the center of the molecule. As a result, the aggregation between π‐conjugated units is inhibited, and an entropy‐rich room temperature liquid is obtained. FMLs designed in this way can exhibit unique and exciting stimulus responses due to the high density of functional units and fluidity. Such notable features include electrochromism, phase transitions, and dynamic changes in the nanostructure. In addition, some stimulus responses are reversible and thanks to the fluidity, return to their initial state under relatively mild conditions, such as room temperature or slight heating. To elicit such effective stimulus responses, selecting an optimal π‐core, and modifying it with the appropriate alkyl side‐chains (length, branching, and substitution position) is essential. A deep understanding of the alkyl–π molecular design will enable the creation of more attractive stimuli‐responsive FMLs, which are of high value in advanced fields such as healthcare, security, sensors, soft electronics, and robotics.

Tumor-associated macrophages (TAMs), one of the major components of the tumor microenvironment, contribute to the progression of esophageal squamous cell carcinoma (ESCC). We previously established a direct co-culture system of human ESCC cells and macrophages and reported the promotion of malignant phenotypes, such as survival, growth, and migration, in ESCC cells. These findings suggested that direct interactions between cancer cells and macrophages contribute to the malignancy of ESCC, but its underlying mechanisms remain unclear. In this study, we compared the expression levels of the interferon-induced genes between mono- and co-cultured ESCC cells using a cDNA microarray and found that interferon-inducible protein 16 (IFI16) was most significantly upregulated in co-cultured ESCC cells. IFI16 knockdown suppressed malignant phenotypes and also decreased the secretion of interleukin-1α (IL-1α) from ESCC cells. Additionally, recombinant IL-1α enhanced malignant phenotypes of ESCC cells through the Erk and NF-κB signaling. Immunohistochemistry revealed that high IFI16 expression in human ESCC tissues tended to be associated with disease-free survival and was significantly associated with tumor depth, lymph node metastasis, and macrophage infiltration. The results of this study reveal that IFI16 is involved in ESCC progression via IL-1α and imply the potential of IFI16 as a novel prognostic factor for ESCC.

Abstract Background No studies have compared the outcomes of direct perineurial suture with vein graft cuff repair and indirect collagen allograft repair of the lingual nerve following an injury. Therefore, we evaluated and compared the outcomes of each over a 1-year observation period. We retrospectively assessed 20 patients who had undergone microneurosurgical repair of unilateral lingual nerve injuries at the Wakayama Medical University Hospital between May 2015 and March 2019. We utilized two different methods for lingual nerve repair, i.e., direct perineurial repair with a vein graft cuff and interpositional collagen allograft repair. Sensory and taste function in the lingual nerve were preoperatively evaluated using a static two-point discrimination test, superficial pain/tactile sensation test, tests for the pressure pain threshold (Semmens-Weinstein monofilament), test for thermal discrimination hot and cold sensation, and a taste discrimination test. These tests were performed again at 6 and 12 months postoperatively. Results Compared to the preoperative conditions, all patients showed improved sensory reactions. Functional sensory recovery outcomes were defined by Pogrel’s criteria, Medical Research Council Scale grades, and functional sensory recovery. In each group, all patients improved after the operation. However, the operation time was significantly shorter for an interpositional collagen allograft repair as compared to that for a direct perineurial repair with a vein graft cuff. Conclusions There were no statistically significant differences between the two repair Methods, except for the operation time. Both methods led to satisfactory results for all criteria. From an economic point of view, direct perineurial repair with a vein graft cuff is meaningful; however, the esthetic effect on the donor site should be considered. Conversely, interpositional collagen allograft repair has the advantage of a greatly shortened operation time.

Abstract Solvent-free fluidic materials possessing optoelectronic functions are expected to be major components in soft electronics applications. Conjugated polymers are promising targets for this purpose and their design approaches are classified into three types with respect to their structure: conjugation breaking (Type I), copolymerization with flexible polymers (Type II), and side chain engineering (Type III). In this short review, we highlight several early attempts to produce Type III conjugated polymers. We also present fully characterized Type III fluids recently developed by our group, with a brief summary of the structure–property relationship and fluidity-oriented functions. Introduction 1 Polymer Design 1.1 Fluidity of Polymeric Materials 1.2 Type III CPs with T g

In materials science, both controllable and uncontrollable descriptors can be used to characterize materials. Examples of controllable descriptors include the composition of elements and fabrication processes; in contrast, uncontrollable descriptors are generated by experimental data characterizing particular samples, such as raw spectral data or specific gravity. In this study, we consider an experimental design to obtain a highly accurate prediction model where the uncontrollable descriptors of materials are features and its material properties are labels. In general, as uncontrollable descriptors are more closely related to material properties, predictions based on them will be more accurate. The goal of the experimental design in the present study is not the improvement of the material properties as such but the prediction of their properties. To realize this design, we select appropriate controllable descriptors for the synthesis of the candidate material that improve the prediction accuracy when the corresponding uncontrollable descriptors and material properties are added to the training data. We propose two experimental design methods, one based on Bayesian optimization and the other on uncertainty sampling. Using a polymer database in which controllable and uncontrollable descriptors, and mechanical properties are recorded, we confirm that our method can select an appropriate candidate material to train a highly accurate prediction model in which the material properties are predicted by uncontrollable descriptors. Our proposed method can be applied to materials developments where uncontrollable descriptors are more easily obtained by experiments than obtaining target material properties; it will also be useful for extracting the relationship between structure and properties of a material.

Abstract Background Various inflammatory conditions may present with musculoskeletal symptoms similar to those of polymyalgia rheumatica (PMR). We investigated findings on 18F-fluorodexoxyglucose (FDG)-positron emission tomography/computed tomography (PET/CT) images that may differentiate PMR from polymyalgia-like illnesses. Methods We analyzed data from 25 patients with new-onset polymyalgia-like illnesses who fulfilled Bird’s diagnostic criteria for PMR and had undergone FDG–PET/CT scan. To assess the uptake by major joints and synovial bursae, particularly at PMR-specific sites (shoulder, sternoclavicular, and hip joints, interspinous bursae, ischial tuberosities, and greater trochanters), we used visual scoring system to score FDG uptake: 0, no uptake (same as bone); 1, slight uptake; 2, moderate uptake (same as the liver); 3, greater uptake than the liver; and 4, uptake as strong as in the cerebellum. Results The final diagnoses were PMR in 17 patients and non-PMR in eight patients (three malignancies, two infections, one cholesterol crystal embolism, one ANCA-associated vasculitis, and one undefined diagnosis). Although the serum MMP-3 levels were significantly higher in patients with PMR, C-reactive protein and erythrocyte sedimentation rate mean values did not differ between the two groups. In PMR-specific sites, FDG accumulations were observed in all cases of PMR, with a high PET-positive score of 2.00 (range, 0–3), but it was low in non-PMR cases, with a PET-positive score of 1.00 (range, 0–3). Conclusions The FDG accumulation patterns in polymyalgia-like illness differ from those in PMR, despite the similar clinical presentations of both conditions. An FDG–PET/CT scan is useful for differentiating PMR from other polymyalgia-like illnesses.

Here, we report the photophysical structure–property relationship of porphyrins adsorbed on gold nanoparticles. The number of porphyrin–alkanethiolate adsorbates per particle was adjusted by a post-synthetic thiol/thiolate exchange reaction on 1-dodecanethiolate–protected gold nanoparticles. Even with a low loading level of adsorbates (

Abstract Background The prognosis of recovery following microneurosurgery for injured lingual nerves varies among individual cases. This study aimed to investigate if recovery ratios of sensory and taste functions are improved by the microneurosurgery within 6 months after lingual nerve injury. Methods We retrospectively assessed 70 patients who underwent microneurosurgery at the Wakayama Medical University Hospital for lingual nerve injuries between July 2004 and December 2016. Sensory and taste functions in lingual nerves were preoperatively evaluated using a static two-point discrimination test, an intact superficial pain/tactile sensation test, and a taste discrimination test. They were evaluated again at 12 and at 24 months postoperatively. The abundance ratio of Schwann cells in the excised traumatic neuromas was analyzed with ImageJ software following immunohistochemistry with anti S-100β antibody. Results In early cases (microneurosurgery within 6 months after the injury), recovery ratios of sensory and taste functions were not significantly different at 24 months after microneurosurgery compared with later cases (microneurosurgery more than 6 months after the injury). Meanwhile, the ratio of patients with taste recovery within 12 months after microneurosurgery was significantly decreased in late cases compared with early cases. The abundance ratio of Schwann cells in traumatic neuroma was also significantly lower in later cases. Conclusion Microneurosurgery more than 6 months after lingual nerve injury did not lead to decreased recovery ratio of sensory and taste functions, but it did lead to prolonged recovery of taste. This delay may be associated with a decrease in the abundance ratio of Schwann cells in traumatic neuromas.

Abstract Background Programmed cell death ligand 1 (PD-L1) is an immune checkpoint molecule that attenuates the immune response. PD-L1 contributes to failed antitumor immunity; thereby, blockade of PD-L1 with monoclonal antibody enhances the immune response. Recently, it was reported that PD-L1 was regulated by protein 53 (p53). Besides, cytokeratin 17 (CK17) is thought to be a diagnostic marker of oral squamous cell carcinoma (OSCC). Our aim was to evaluate the correlation between the immunohistochemical expression of PD-L1, p53 and CK17 with clinicopathological characteristics and disease-specific survival in patients with OSCC. Methods A total of 48 patients with OSCC were included in this study. Immunohistochemical staining was performed to evaluate the correlation among the expressions of PD-L1, p53 and CK17, and furthermore the correlation among various clinicopathological factors, PD-L1, p53 and CK17. Results The positive rate of p53, CK17, PD-L1 (tumor cells) and PD-L1 (tumor-infiltrating lymphocytes) was 63.2%, 91.7%, 48.9% and 57.1%. A statistically significant correlation between p53 expression and T stage and TNM stage (p = 0.049, p = 0.03, respectively) was observed. Also, a statistically significant correlation between p53 and PD-L1 (TCs) expression (p = 0.0009) was observed. Five-year disease-specific survival rate was not significantly correlated with gender, TNM stage, p53 expression, PD-L1 expression and CK17 expression. Conclusion The expression of p53 and PD-L1 shows significantly positive correlation in oral squamous cell carcinoma in tumor cells. Also, a significant correlation between p53 expression and T stage and TNM stage was observed. No other significant correlation between PD-L1 staining or CK17 and clinical or pathologic characteristics was identified.

Abstract Background The lingual nerve plays an important role in multiple functions, including gustatory sensation and contact sensitivity and thermosensitivity. Misdiagnosed conservative treatments for serious lingual nerve (LN) injuries can induce the patient to serious mental disability. After continuous observation and critical diagnosis of the injury, in cases involving significant disruption of lingual nerve function, microneurosurgical reconstruction of the nerve is recommended. Direct anastomosis of the torn nerve ends without tension is the recommended approach. However, in cases that present significant gaps between the injured nerve ends, nerve grafts or conduits (tubes of various materials) are employed. Recently, various reconstruction materials for peripheral nerves were commercially offered especially in the USA, but the best method and material is still unclear in the world. There currently exists no conventional protocol for managing LN neurosensory deficiency in regard to optimal methods and the timing for surgical repair. In Japan, the allograft collagen nerve for peripheral nerves reconstruction was permitted in 2017, and we tried to use this allograft nerve and got a recommendable result. Case presentation This report is a long-term abandoned torn LN reconstructed with allograft nerve induced by the lower third molar extraction. Conclusions In early sick period, with the exact diagnosis, the LN disturbance should be managed. In a serious condition, the reconstruction with allograft nerve is one of the recommendable methods.

Abstract Background Through the analysis of clinical data, we attempted to investigate the etiology and determine the risk of severe iatrogenic lingual nerve injuries in the removal of the mandibular third molar. Methods A retrospective chart review was performed for patients who had undergone microsurgical repair of lingual nerve injuries. The following data were collected and analyzed: patient sex, age, nerve injury side, type of impaction (Winter’s classification, Pell and Gregory’s classification). Ratios for the respective lingual nerve injury group data were compared with the ratios of the respective data for the control group, which consisted of data collected from the literature. The data for the control group included previous patients that encountered various complications during the removal of the mandibular third molar. Results The lingual nerve injury group consisted of 24 males and 58 females. The rate of female patients with iatrogenic lingual nerve injuries was significantly higher than the control groups. Ages ranged from 15 to 67 years, with a mean age of 36.5 years old. Lingual nerve injury was significantly higher in the patient versus the control groups in age. The lingual nerve injury was on the right side in 46 and on the left side in 36 patients. There was no significant difference for the injury side. The distoangular and horizontal ratios were the highest in our lingual nerve injury group. The distoangular impaction rate in our lingual nerve injury group was significantly higher than the rate for the control groups. Conclusion Distoangular impaction of the mandibular third molar in female patients in their 30s, 40s, and 50s may be a higher risk factor of severe lingual nerve injury in the removal of mandibular third molars.

Though electret materials are attractive for realizing flexible mechanoelectrical devices, these materials are typically solid films. Here, the authors report stretchable ‘liquid-electret’ devices consisting solvent-free liquid porphyrins that show piezoelectric and electroacoustic functionality.

Psychological stress is deeply involved in the pathophysiology of not only mental illness but also functional gastrointestinal disorders. In the present study, we examined the relationship between psychological stress and abnormality of stool properties, focusing on the alteration of plasma glucocorticoid and guanylin (GN)/uroguanylin (UGN) expression in the colon. A murine model of chronic social defeat stress (CSDS) was established by exposing a C57BL/6N intruder mouse to a CD-1 aggressor mouse for 3–5 min. Thereafter the mice were kept in the same cage but separated by a divider for the remainder of the day. This procedure was repeated for 10 consecutive days, and then a social interaction test was performed to evaluate social avoidance. Fresh fecal and blood samples were collected for stool property analysis and measurement of the plasma glucocorticoid level by ELISA. The expression of GN, UGN, and guanylate cyclase 2C in the colonic tissues was examined by real-time RT-PCR and immunohistochemistry. Moreover, Lovo cells were stimulated with dexamethasone, and the expression of GN/UGN mRNA was examined. In the CSDS group, the time spent in the social interaction zone was significantly shorter when the CD-1 aggressor mouse was present than when it was absent. The social interaction ratio was also significantly lower in the CSDS group relative to the controls. The mean Bristol scale score was significantly lower in the CSDS group, but the fecal sodium concentration did not differ between CSDS mice and controls. The level of plasma corticosterone was significantly higher in the CSDS group than in the controls immediately after the 10th day of CSDS. The expression of both GN and UGN was significantly decreased in the CSDS mice. GN was expressed in all colonic epithelial cells, and UGN was expressed in ovoid or pyramidal epithelial cells in the colonic mucosa. The expression of both GN and UGN was significantly decreased in the CSDS mice relative to controls. The expression of both GN and UGN was significantly suppressed in Lovo cells upon stimulation with dexamethasone. Psychological stress-induced glucocorticoid may suppress colonic GN/UGN expression, resulting in a change in stool properties leading to constipation.

Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of Lactobacillus was markedly increased and that of Clostridium was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.

Abstract Background Amyloid A amyloidosis is one of the most common forms of amyloidosis. It is secondary to rheumatoid arthritis, which is difficult to manage and has a poor prognosis. We present a patient with rheumatoid arthritis and amyloid A amyloidosis who was treated with tocilizumab, a humanized monoclonal antibody against interleukin 6 receptor, resulting in improvement in both proteinuria and gastrointestinal symptoms; however, amyloid deposition remained. Case presentation A 67-year-old woman who had previously been treated for rheumatoid arthritis presented with abdominal pain and diarrhea. Right renal cell carcinoma was found, and amyloid A amyloidosis was diagnosed concomitantly based on colon biopsy. The renal cell carcinoma was resected, and the non-cancerous part of the renal tissue also showed amyloid A deposition. Following surgery, protein levels in the urine increased to the nephrotic range, and administration of tocilizumab was initiated, which resulted in resolution of the proteinuria. The patient’s gastrointestinal symptoms were also alleviated. However, repeat colon biopsy showed amyloid deposition. Conclusions This case of amyloid A amyloidosis suggests that amyloid deposition indicates only structural change of the affected tissue, and that it is not amyloid deposition per se that causes the clinical symptoms of amyloidosis.

Abstract Solvent-free, nonvolatile, room-temperature alkylated-π functional molecular liquids (FMLs) are rapidly emerging as a new generation of fluid matter. However, precision design to tune their physicochemical properties remains a serious challenge because the properties are governed by subtle π-π interactions among functional π-units, which are very hard to control and characterize. Herein, we address the issue by probing π-π interactions with highly sensitive pyrene-fluorescence. A series of alkylated pyrene FMLs were synthesized. The photophysical properties were artfully engineered with rational modulation of the number, length, and substituent motif of alkyl chains attached to the pyrene unit. The different emission from the excimer to uncommon intermediate to the monomer scaled the pyrene-pyrene interactions in a clear trend, from stronger to weaker to negligible. Synchronously, the physical nature of these FMLs was regulated from inhomogeneous to isotropic. The inhomogeneity, unexplored before, was thoroughly investigated by ultrafast time-resolved spectroscopy techniques. The result provides a clearer image of liquid matter. Our methodology demonstrates a potential to unambiguously determine local molecular organizations of amorphous materials, which cannot be achieved by conventional structural analysis. Therefore this study provides a guide to design alkylated-π FMLs with tailorable physicochemical properties.

Objective This study was to examine in vivo digestibility, nitrogen balance and ruminal fermentation of tamarind (Tamarind indica) kernel powder extract residue (TKPER) compared to soybean products and by-products in wethers. Methods Four wethers with initial body weight (BW) of 51.6±5.5 kg were assigned in a 4×4 Latin square design to investigate nutritional characteristics of TKPER, dry heat soybean (SB), dry soybean curd residue (SBCR) and soybean meal (SBM) feeding with ryegrass straw (R) at a ratio of 1:1 at 2% of BW in dry matter (DM) on a daily basis. Results The digestibility of DM, crude protein, and ether extract (EE) of TKPER-R diet were 57.0%, 87.0%, and 86.0%, respectively. Higher non-fiber carbohydrates digestibility was observed in TKPER-R diet (83.2%) than in SB-R diet (73.9%, p

Although probiotics may be useful for the treatment of irritable bowel syndrome (IBS), it is unclear how probiotics play a role in colonic mucosal integrity and immunity. Here, we aimed to investigate the effect of Bifidobacterium bifidum G9-1 (BBG9-1) on colonic mucosal integrity and macrophage behavior in rats subjected to maternal separation (MS) as a model of IBS. MS pups were individually separated from their mother rats, and a proportion of the MS rats were orally administered BBG9-1. The colonic mucosal permeability was evaluated by Ussing chamber assay. The expression of tight junction proteins and cytokines and the population of CD80-positive cells was examined in the colonic tissues by real-time reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Caco2 cells were stimulated with cytokines and the transepithelial electric resistance (TEER) was measured. MS rats showed significantly higher colonic permeability and lower claudin 4 expression in the colonic epithelium relative to controls. The number of CD80-positive macrophages was significantly increased in the colonic mucosa of MS rats, accompanied by the increase of IL-6 and IFN-γ expression. BBG9-1 treatment ameliorated the increase of M1 macrophage and IL-6/IFN-γ expression in the colonic tissue of MS rats. Simultaneously, BBG9-1 treatment improved the enhanced mucosal permeability and the decreased claudin 4 expression in the colon of MS rats. IL-6 and IFN-γ, whose expression is enhanced in the colon of MS rats, significantly decreased TEER in Caco2 cells in vitro. Probiotic BBG9-1 has a preventive effect on the acceleration of colonic permeability and M1 macrophage population in maternally separated rats.

Although sessile serrated adenoma/polyps (SSA/Ps) may arise through a pathway different from the traditional adenoma–carcinoma sequence, details of SSA/P tumorigenesis still remain unclear. Fusobacterium nucleatum (Fn) is frequently detected in colorectal cancer (CRC) tissues and may play a pivotal role in colorectal carcinogenesis. Here, we investigated the relationship between Fn and the β-catenin/REG Iα axis in SSA/Ps and their involvement in the proliferation of these lesions. Fn was detected in SSA/Ps by fluorescence in situ hybridization using a Fn-targeted probe, and expression of β-catenin, REG Iα and Ki67 was examined using immunohistochemistry. Sixteen of 30 SSA/P lesions (53.3%) were positive for Fn. Eighteen SSA/P lesions (60%) showed β-catenin immunoreactivity in the tumor cell nuclei. A significant majority of Fn-positive lesions showed nuclear expression of β-catenin (87.5%) and higher REG Iα scores and Ki67 labeling indices relative to Fn-negative lesions. The SSA/P lesions expressing β-catenin in nuclei had significantly higher REG Iα scores and Ki67 labeling indices than those expressing β-catenin on cytomembranes. The REG Iα score was positively correlated with the Ki67 labeling index in SSA/P lesions. The treatment with Wnt agonist SKL2001 promoted nuclear β-catenin translocation and enhanced REG Ia expression in Caco2 cells. Fn may play a role in the proliferation of SSA/P lesions through promotion of β-catenin nuclear translocation and REG Iα expression.

Summary:. We report a case, function preservation of the upper lip after tumor resection was possible using residual orbicularis oris muscle and attached levator labii superioris alaeque nasi. Patient was 67-year-old male with squamous cell carcinoma at the vermilion border. The tumor was resected with an 8-mm margin, leaving the oral mucosa as intact as possible. To reconstruct the red lip, we used the oral mucosa as a rotational transposition flap. The white lip was reconstructed with a cheek rotation flap. A levator labii superioris alaque nasi muscle flap, which was attached to the remaining orbicularis oris muscle, was used to increase marginal lip volume. The movement of the reconstructed lip was good. At 9 postoperative months, induration of the red lip was palpable, and we suspected that the blood supply to the levator labii superioris alaque nasi was borderline insufficient. Slight drooping of the reconstructed lip occurred. We dissected this was caused by dissection of mid facial muscles from orbicularis oris muscle to ease downward rotation of the cheek flap and obscure the original nasolabial fold. Although some drooping and induration of the lip occurred, the white and red lip were reconstructed in a single-stage procedure, which resulted in good movement and preserved the function of the orbicularis oris muscle.

Transcription activator-like effector nucleases (TALENs) are artificial nucleases harboring a customizable DNA-binding domain and a FokI nuclease domain. The high specificity of the DNA-binding domain and the ease of design have enabled researchers to use TALENs for targeted mutagenesis in various organisms. Here, we report the development of TALEN-dependent targeted gene disruption in the crustacean Daphnia magna, the emerging model for ecological and toxicological genomics. First, a reporter transgene DsRed2 (EF1α-1::DsRed2) was targeted. Using the Golden Gate method with a GoldyTALEN scaffold, we constructed homodimeric and heterodimeric TALENs containing wild-type and ELD/KKR FokI domains. mRNAs that coded for either the customized homodimeric or heterodimeric TALENs were injected into one-cell-stage embryos. The high mortality of embryos injected with homodimeric TALEN mRNAs prevented us from detecting mutations. In contrast, embryos injected with heterodimeric TALEN mRNAs survived and 78%–87% of the adults lost DsRed2 fluorescence in a large portion of cells throughout the body. In addition, these adults produced non-fluorescent progenies, all of which carried mutations at the dsRed2 locus. We also tested heterodimeric TALENs targeted for the endogenous eyeless gene and found that biallelic mutations could be transmitted through germ line cells at a rate of up to 22%. Both somatic and heritable mutagenesis efficiencies of TALENs were higher than those of the CRISPR/Cas9 system that we recently developed. These results suggest that the TALEN system may efficiently induce heritable mutations into the target genes, which will further contribute to the progress of functional genomics in D. magna.

Summary:. It is difficult to totally reconstruct the lip, achieving good functional and aesthetic results. There have been few reports of reconstructing complete lip defects. Moreover, upper and lower lip necrosis by purpura fulminans has not been reported. We present a case of a 60-year-old male purpura fulminans patient with upper and lower lip necrosis. Fortunately, our patient had retained his oral commissure function. We reconstructed this defect with an orbicularis oris muscle-skin-mucosal pedicled flap derived from the region between the nasolabial folds for upper lip; a similar bipedicled flap for the lower lip and the donor site was closed with a dual-skin paddled anterolateral thigh flap. Postoperative results were satisfactory, that is, no lip tightness or aperture restriction was seen, and symmetry had been achieved. The new lips exhibited complete sensory recovery. Drooling was minimal during rest and feeding. We could select a method that combined the advantages of local and free flaps. We consider our method for this defect is superior to those described in previous studies, in that the restoration of lip sensation and oral sphincter function can be achieved to some extent in 1 stage while preserving the oral commissure function.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) is widely used for mediating the knock-in of foreign DNA into the genomes of various organisms. Here, we report a process of CRISPR/Cas-mediated knock-in via non-homologous end joining by the direct injection of Cas9/gRNA ribonucleoproteins (RNPs) in the crustacean Daphnia magna, which is a model organism for studies on toxicology, ecology, and evolution. First, we confirmed the cleavage activity of Cas9 RNPs comprising purified Cas9 proteins and gRNAs in D. magna. We used a gRNA that targets exon 10 of the eyeless gene. Cas9 proteins were incubated with the gRNAs and the resulting Cas9 RNPs were injected into D. magna eggs, which led to a typical phenotype of the eyeless mutant, i.e., eye deformity. The somatic and heritable mutagenesis efficiencies were up to 96% and 40%, respectively. Second, we tested the CRISPR/Cas-mediated knock-in of a plasmid by the injection of Cas9 RNPs. The donor DNA plasmid harboring the fluorescent reporter gene was designed to contain the gRNA recognition site. The co-injection of Cas9 RNPs together with the donor DNAs resulted in generation of one founder animal that produced fluorescent progenies. This transgenic Daphnia had donor DNA at the targeted genomic site, which suggested the concurrent cleavage of the injected plasmid DNA and genomic DNA. Owing to its simplicity and ease of experimental design, we suggest that the CRISPR/Cas-mediated knock-in method represents a promising tool for studying functional genomics in D. magna.

Organic π-conjugated molecules with extremely rich and tailorable electronic and optical properties are frequently utilized for the fabrication of optoelectronic devices. To achieve high solubility for facile solution processing and desirable softness for flexible device fabrication, the rigid π units were in most cases attached by alkyl chains through chemical modification. Considerable numbers of alkylated-π molecular systems with versatile applications have been reported. However, a profound understanding of the molecular state control through proper alkyl chain substitution is still highly demanded because effective applications of these molecules are closely related to their physical states. To explore the underlying rule, we review a large number of alkylated-π molecules with emphasis on the interplay of van der Waals interactions (vdW) of the alkyl chains and π–π interactions of the π moieties. Based on our comprehensive investigations of the two interactions’ impacts on the physical states of the molecules, a clear guidance for state control by alkyl-π engineering is proposed. Specifically, either with proper alkyl chain substitution or favorable additives, the vdW and π–π interactions can be adjusted, resulting in modulation of the physical states and optoelectronic properties of the molecules. We believe the strategy summarized here will significantly benefit the alkyl-π chemistry toward wide-spread applications in optoelectronic devices.