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Abstract Background Mild cognitive impairment (MCI) is the stage between the expected cognitive decline of normal aging and the more serious decline of dementia. Previous studies have shown that regular exercise can improve cognition and physical performance in older adults. Walking is a low-technology and low-cost exercise that has been proven to improve cognition and mobility in healthy elderly individuals. However, no systematic review or meta-analysis has explored whether walking can improve cognitive function in older adults with MCI. This study aimed to explore the effects of walking interventions on cognitive functions in individuals with MCI. Methods In accordance with the PRISMA guidelines, MEDLINE, PubMed, SPORTDiscus, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, Airiti Library, and the National Digital Library of Theses and Dissertations in Taiwan were searched from inception to July 2023. Independent reviewers selected randomized clinical trials (RCT) that compared the effects of walking with no intervention or other exercises in individuals with MCI. The primary outcomes were cognitive functions, and the secondary outcome was walking endurance. Three reviewers independently conducted data extraction. The risk of bias was assessed using the Revised Cochrane Risk of Bias assessment tool. Results Fourteen RCTs were included in this review. The quality of evidence in these studies was rated as good to excellent. The results of the meta-analysis showed that the individuals with MCI had no significant improvement in cognitive function but had significant improvement in the 6-min walk test (Mean Difference=23.70, p=0.008) after walking interventions compared to no intervention or other exercises. Conclusion Walking intervention has no significant improvement on cognitive functions in older adults with MCI. However, walking induces beneficial effects on aerobic capacity. Trial registration This systematic review has the registration number CRD42021283753 on PROSPERO.

This study aims to develop a refractive-index sensor operating in the visible region using an all-dielectric metasurface, which was chosen for its advantages of low optical loss and narrow spectral bandwidth, compared to those of conventional metallic metasurfaces. COMSOL software was utilized as a calculation tool to simulate the resonant properties of an all-dielectric metasurface composed of a circular nanohole-structured titanium oxide (TiO2) thin film, with the aim of enhancing the sensitivity of the refractive index for sensing targets. The simulation focused on finding the best geometrical conditions for the all-dielectric metasurface to achieve high sensitivity. Two resonance modes observed in this metasurface were considered: the quasi-bound-state-in-the-continuum (qBIC) mode and the perfect-reflection (PR) mode. The simulated results demonstrated that high sensitivities of 257 nm/RIU at the PR mode and 94 nm/RIU at the qBIC mode in the visible spectral range could be obtained by periodically constructing the metasurface with a unit cell having a lattice constant of 350 nm, a nanohole radius of 160 nm, and a nanohole depth of 250 nm. Furthermore, the study showed that the resonance mode that enabled high sensitivity was the PR mode, with a sensitivity nearly three times larger than that of the qBIC mode and the ability to reach the highest reflectance at the resonance wavelength. The optimized feature had the highest reflectance at a resonant wavelength of 570.19 nm, and although the quality factor was 25.50, these designed parameters were considered sufficient for developing a refractive index biosensor with high sensitivity and optical efficiency when operating in the visible spectral range.

CmnC is an α-ketoglutarate (α-KG)-dependent non-heme iron oxygenase involved in the formation of the l-capreomycidine (l-Cap) moiety in capreomycin (CMN) biosynthesis. CmnC and its homologues, VioC in viomycin (VIO) biosynthesis and OrfP in streptothricin (STT) biosynthesis, catalyze hydroxylation of l-Arg to form β-hydroxy l-Arg (CmnC and VioC) or β,γ-dihydroxy l-Arg (OrfP). In this study, a combination of biochemical characterization and structural determination was performed to understand the substrate binding environment and substrate specificity of CmnC. Interestingly, despite having a high conservation of the substrate binding environment among CmnC, VioC, and OrfP, only OrfP can hydroxylate the substrate enantiomer d-Arg. Superposition of the structures of CmnC, VioC, and OrfP revealed a similar folds and overall structures. The active site residues of CmnC, VioC, and OrfP are almost conserved; however Leu136, Ser138, and Asp249 around the substrate binding pocket in CmnC are replaced by Gln, Gly, and Tyr in OrfP, respectively. These residues may play important roles for the substrate binding. The mutagenesis analysis revealed that the triple mutant CmnCL136Q,S138G,D249Y switches the substrate stereoselectivity from l-Arg to d-Arg with ∼6% relative activity. The crystal structure of CmnCL136Q,S138G,D249Y in complex with d-Arg revealed that the substrate loses partial interactions and adopts a different orientation in the binding site. This study provides insights into the enzyme engineering to α-KG non-heme iron oxygenases for adjustment to the substrate stereoselectivity and development of biocatalysts.

Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence. The impact of miR-4669 overexpression in Hep3B cells on tumor cell behavior and the tumor microenvironment was evaluated in vitro. In addition, the clinical value of exosomal miR-4669 for the prediction of treatment response to HCC downstaging therapies and following post-transplant HCC recurrence was explored. Overexpression of miR-4669 enhanced migration ability and led to acquired sorafenib resistance with an elevation of sirtuin 1 and long noncoding RNA associated with microvascular invasion. Active release of tumor-derived exosomes and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) contributed to generating an immunosuppressive tumor microenvironment through the induction of M2 macrophage polarization. The retrospective analysis demonstrated the clinical value of exosomal miR-4669 for predicting treatment response to HCC downstaging therapies and for risk assessment of post-transplant HCC recurrence. In summary, the present data demonstrate the impact of exosomal miR-4669 on HCC recurrence through the enhancement of tumor aggressiveness and generation of an immunosuppressive tumor microenvironment.

ABSTRACT: Introduction: The interplay between erectile dysfunction (ED) and premature ejaculation (PE) needs more studies to clarify. Aim: To evaluate the risk factors and temporal relationship for the coexistence of ED and PE. Methods: The data were derived from clinical history. Main Outcome Measure: The diagnosis of ED and PE was based on self-report and validated questionnaires. Results: Based on the chief complaint, 1,893 participants were recruited as ED group and 483 participants as PE group from 2014 to 2020. One third of ED and PE groups reported comorbid PE and ED. Of the ED group, 4.1% (n = 77) had lifelong PE, 18.0% (n = 341) had acquired PE and 9.7% (n = 184) had subjective or natural variable PE. Of the PE group, ED was reported in 22.0% (n = 40) of lifelong PE, 33.9% (n = 65) of acquired PE, and 37.6% (n = 41) of subjective or natural variable PE, P < .01. With adjustment of potential confounders, the ED severity was associated with increased risk of acquired PE, while acquired PE was associated with higher risk of ED than lifelong PE. In cases of comorbid lifelong PE and ED (n = 117), 22.2% reported the onset of both dysfunctions being about the same time, whereas 77.8% reported ED occurred behind PE with an average 23.3 years lag. In cases of comorbid acquired PE and ED (n = 406), 52.2% reported the onset of both dysfunctions being about the same time, 34.2% reported ED happened behind PE and 13.5% reported PE emerged behind ED. Conclusion: Organic pathogenesis was least likely to be responsible for the link between PE and ED. When acquired PE and ED coexist, treating ED first or concomitantly according to their temporal order is an appropriate management algorithm.Chieh‑Wen Chin, Chia Mu Tsai, Jen-Tai Lin, et al. A Cross-Sectional Observational Study on the Coexistence of Erectile Dysfunction and Premature Ejaculation. Sex Med 2021;9:100438.

Cytoskeleton proteins have been long recognized as structural proteins that provide the necessary mechanical architecture for cell development and tissue homeostasis. With the completion of the cancer genome project, scientists were surprised to learn that huge numbers of mutated genes are annotated as cytoskeletal or associated proteins. Although most of these mutations are considered as passenger mutations during cancer development and evolution, some genes show high mutation rates that can even determine clinical outcomes. In addition, (phospho)proteomics study confirms that many cytoskeleton-associated proteins, e.g., β-catenin, PIK3CA, and MB21D2, are important signaling mediators, further suggesting their biofunctional roles in cancer development. With emerging evidence to indicate the involvement of mechanotransduction in stemness formation and cell differentiation, mutations in these key cytoskeleton components may change the physical/mechanical properties of the cells and determine the cell fate during cancer development. In particular, tumor microenvironment remodeling triggered by such alterations has been known to play important roles in autophagy, metabolism, cancer dormancy, and immune evasion. In this review paper, we will highlight the current understanding of how aberrant cytoskeleton networks affect cancer behaviors and cellular functions through mechanotransduction.

Recent evidence indicates that turning difficulty may correlate with trunk control; however, surface electromyography has not been used to explore trunk muscle activity during turning after stroke. This study investigated trunk muscle activation patterns during standing turns in healthy controls (HCs) and patients with stroke with turning difficulty (TD) and no TD (NTD). The participants with stroke were divided into two groups according to the 180° turning duration and number of steps to determine the presence of TD. The activation patterns of the bilateral external oblique and erector spinae muscles of all the participants were recorded during 90° standing turns. A total of 14 HCs, 14 patients with TD, and 14 patients with NTD were recruited. The duration and number of steps in the turning of the TD group were greater than those of the HCs, independent of the turning direction. However, the NTD group had a significantly longer turning duration than did the HC group only toward the paretic side. Their performance was similar when turning toward the non-paretic side; this result is consistent with electromyographic findings. Both TD and NTD groups demonstrated increased amplitudes of trunk muscles compared with the HC groups. Their trunk muscles failed to maintain consistent amplitudes during the entire movement of standing turns in the direction that they required more time or steps to turn toward (i.e., turning in either direction for the TD group and turning toward the paretic side for the NTD group). Patients with stroke had augmented activation of trunk muscles during turning. When patients with TD turned toward either direction and when patients with NTD turned toward the paretic side, the flexible adaptations and selective actions of trunk muscles observed in the HCs were absent. Such distinct activation patterns during turning may contribute to poor turning performance and elevate the risk of falling. Our findings provide insights into the contribution and importance of trunk muscles during turning and the association with TD after stroke. These findings may help guide the development of more effective rehabilitation therapies that target specific muscles for those with TD.

Abstract Background A recent study has demonstrated that a turning-based treadmill program yields greater improvements in gait speed and temporal symmetry than regular treadmill training in chronic stroke patients. However, it remains unknown how this novel and challenging gait training shapes the cortico-cortical network and cortico-spinal network during walking in chronic stroke patients. The purpose of this study was to examine how a novel type of gait training, which is an unfamiliar but effective task for people with chronic stroke, enhances brain reorganization. Methods Subjects in the experimental and control groups received 30 min of turning-based treadmill training and regular treadmill training, respectively. Cortico-cortical connectivity and cortico-muscular connectivity during walking and gait performance were assessed before and after completing the 12-session training. Results Eighteen subjects (n = 9 per group) with a mean age of 52.5 ± 9.7 years and an overground walking speed of 0.61 ± 0.26 m/s consented and participated in this study. There were significant group by time interactions for gait speed, temporal gait symmetry, and cortico-cortical connectivity as well as cortico-muscular connectivity in walk-related frequency (24–40 Hz) over the frontal-central-parietal areas. Compared with the regular treadmill training, the turning-based treadmill training resulted in greater improvements in these measures. Moreover, the increases in cortico-cortical connectivity and cortico-muscular connectivity while walking were associated with improvements in temporal gait symmetry. Conclusions Our findings suggest this novel turning-based treadmill training is effective for enhancing brain functional reorganization underlying cortico-cortical and corticomuscular mechanisms and thus may result in gait improvement in people with chronic stroke. Trial registration ACTRN12617000190303. Registered 3 February 2017, retrospectively registered.

Metaphors are compact packages of information with rich cultural background information. As one of the most powerful linguistic forms with non-literal meaning, metaphor detection in natural language processing can be both challenging and rewarding. We propose an innovative method for metaphor detection and classification leveraging culturally grounded eventive information. This culturally grounded information is organized based on ontological structure, which in turn facilitates further semantic processing of the result of our classification. As a culturally bound ontological system, the Chinese writing system has basic concepts organized according to semantic radicals, which are symbols containing rich eventive information that represent categorical concepts. This paper illustrates the basic design principles of applying ontological structures in metaphor detection by taking into account radicals representing body parts, instruments, materials, and movements. Our approach to leverage the eventive information of the Chinese writing system in metaphor detection is based on the fact that such information is available as an integral part of the writing system of any text. We hypothesize that eventive information can be accessed through the “embodied” source domain information represented by the radicals without syntactic processing or annotation. In terms of the theory of metaphor, we further hypothesize that eventive types in the embodied source domain maps to, and hence can help to predict, eventive meaning in the target domain of metaphor. Our studies show that the event information encoded in lexical items can facilitate classification of metaphoric events and identification of metaphors in Chinese texts effectively. We achieved improvements in Chinese metaphor detection over state-of-the-art approaches in our first classification experiment, and our proposed approach is shown to be generalizable in a second experiment involving new sets of characters with the same radicals.

Objective: Pheochromocytomas are catecholamine-producing neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia. There is no large-scale study in Taiwan at present. Our retrospective analysis was focused on clinical characteristics of Taiwanese patients with pheochromocytoma. Method: We retrospectively reviewed 48 patients who were pathologically proved as pheochromocytoma at the Kaohsiung Veterans General Hospital between Jan. 1990 and Jan. 2014. Parameters including patient and tumor characteristics, clinical presentation, treatment and long-term followup results were collected from the medical records. Metastasis was confirmed by pathologic proof using surgical removal or percutaneous biopsy. Result: Thirty-one patients (64.5%) had adrenal and 17 (35.4%) had extra-adrenal pheochromocytoma. The locations of extra-adrenal pheochromocytoma included the retroperitoneum in 6 patients (35%), head and neck in 4 (23%), scrotum in 2 (12%), urinary bladder in 2 patients (12%), multiple organs in 2 (12%), and mediastinum in 1 (6%). The most common symptom was sustained hypertension (52%). Five patients were diagnosed as malignant pheochromocytoma due to pathologically proved metastasis. Conclusion: Pheochromocytomas are rare neuro-endocrine tumors with a highly variable clinical presentation. Prompt surgical removal of pheochromocytoma ensures a better prognosis. Radical surgical removal of tumor with vigorous control of blood pressure is the mainstay to improve symptoms and survival for malignant pheochromocytoma. Multi-center and large-scale studies were warranted and Lifelong followup is strongly recommended for all patients with pheochromocytoma.

Background: Walking while performing cognitive and motor tasks simultaneously interferes with gait performance and may lead to falls in older adults with mild cognitive impairment (MCI). Executive function, which seems to play a key role in dual-task gait performance, can be improved by combined physical and cognitive training. Virtual reality (VR) has the potential to assist rehabilitation, and its effect on physical and cognitive function requires further investigation. The purpose of this study was to assess the effects of VR-based physical and cognitive training on executive function and dual-task gait performance in older adults with MCI, as well as to compare VR-based physical and cognitive training with traditional combined physical and cognitive training.Method: Thirty-four community-dwelling older adults with MCI were randomly assigned into either a VR-based physical and cognitive training (VR) group or a combined traditional physical and cognitive training (CPC) group for 36 sessions over 12 weeks. Outcome measures included executive function [Stroop Color and Word Test (SCWT) and trail making test (TMT) A and B], gait performance (gait speed, stride length, and cadence) and dual-task costs (DTCs). Walking tasks were performed during single-task walking, walking while performing serial subtraction (cognitive dual task), and walking while carrying a tray (motor dual task). The GAIT Up system was used to evaluate gait parameters including speed, stride length, cadence and DTCs. DTC were defined as 100 * (single-task gait parameters − dual-task gait parameters)/single-task gait parameters.Results: Both groups showed significant improvements in the SCWT and single-task and motor dual-task gait performance measures. However, only the VR group showed improvements in cognitive dual-task gait performance and the DTC of cadence. Moreover, the VR group showed more improvements than the CPC group in the TMT-B and DTC of cadence with borderline significances.Conclusion: A 12-week VR-based physical and cognitive training program led to significant improvements in dual-task gait performance in older adults with MCI, which may be attributed to improvements in executive function.

Modality exclusivity norms have been developed in different languages for research on the relationship between perceptual and conceptual systems. This paper sets up the first modality exclusivity norms for Chinese, a Sino-Tibetan language with semantics as its orthographically relevant level. The norms are collected through two studies based on Chinese sensory words. The experimental designs take into consideration the morpho-lexical and orthographic structures of Chinese. Study 1 provides a set of norms for Mandarin Chinese single-morpheme words in mean ratings of the extent to which a word is experienced through the five sense modalities. The degrees of modality exclusivity are also provided. The collected norms are further analyzed to examine how sub-lexical orthographic representations of sense modalities in Chinese characters affect speakers' interpretation of the sensory words. In particular, we found higher modality exclusivity rating for the sense modality explicitly represented by a semantic radical component, as well as higher auditory dominant modality rating for characters with transparent phonetic symbol components. Study 2 presents the mean ratings and modality exclusivity of coordinate disyllabic compounds involving multiple sense modalities. These studies open new perspectives in the study of modality exclusivity. First, links between modality exclusivity and writing systems have been established which has strengthened previous accounts of the influence of orthography in the processing of visual information in reading. Second, a new set of modality exclusivity norms of compounds is proposed to show the competition of influence on modality exclusivity from different linguistic factors and potentially allow such norms to be linked to studies on synesthesia and semantic transparency.

ObjectiveOverweight and obesity in preschoolers might develop into childhood and even adulthood obesity. Overweight and obesity have been shown to be negatively related with cardiorespiratory fitness (CRF) in children and adults but few studies did among preschoolers. We aimed to evaluate whether excess body adipose is negatively associated with CRF in both the submaximal and maximal effort of preschool children in exercise testing and to examine if there is difference to achieve maximal effort during exercise testing between preschoolers with normal and excess body adipose.MethodsData of 106 preschoolers aged 4-6 that received symptom-limited treadmill exercise testing was analyzed. Anthropometry was measured by vector bioelectrical impedance analysis. Excess body adipose was defined as (1) 'overweight' and 'obesity' by body mass index (BMI), (2) fat mass index (FMI) greater than the sex- and age-specific 75th percentile of whole subjects, and (3) fat-free mass index (FFMI) smaller than the sex- and age-specific 25th percentile. CRF was indicated by metabolic equivalent (MET) at anaerobic threshold (AT MET), peak MET, oxygen uptake efficiency slope (OUES) calculated by the 50% (OUES-50) and the entire (OUES-100) duration of the exercise testing.ResultsPreschoolers with excess body adipose by three different definitions (BMI, FMI, and FFMI) all had poorer ability to perform maximal effort (p = 0.004, 0.043, and 0.007, respectively). Preschoolers with excess body adipose by BMI and FFMI classifications had lower OUES-50 (p = 0.018, and 0.001, respectively), and lower OUES-100 (p = 0.004, and 0.001, respectively) than peers with normal body adipose during exercise testing while those with excess body adipose by FMI classification showed no significant differences from peers with normal body adipose in both OUES-50 and OUES-100.ConclusionsPreschoolers with excess body adipose had lower CRF significantly during treadmill exercise testing. Weight control and health promotion should start as early as possible.

Pemphigus vulgaris (PV) is an autoimmune disease in which the autoantibody, immunoglobulin G, is directed against the keratinocytes in the epidermis. The classic presentations of PV are flaccid vesicles or bullae over the oral mucosa, trunk, groin, and extremities. The age of onset is usually between 40 and 60 years, and cases of PV in children or adolescent patients are rare. Here, we present a 17-year-old boy who had painful oral ulcers for 3 months initially and bullae spreading to the whole body in the following days. Paraneoplastic pemphigus was another differential diagnosis due to the atypical appearance of the skin lesion. However, PV was confirmed by hematoxylin and eosin staining and immunofluorescence examination of the skin biopsy specimens. The patient had a good response to corticosteroid treatment and the immunosuppressive agent, rituximab.

Host factors play a pivotal role in regulating virus infection. Uncovering the mechanism of how host factors are involved in virus infection could pave the way to defeat viral disease. In this study, we characterized a lipid transfer protein, designated NbLTP1 in Nicotiana benthamiana, which was downregulated after Bamboo mosaic virus (BaMV) inoculation. BaMV accumulation significantly decreased in NbLTP1-knockdown leaves and protoplasts compared with the controls. The subcellular localization of the NbLTP1-orange fluorescent protein (OFP) was mainly the extracellular matrix. However, when we removed the signal peptide (NbLTP1/ΔSP-OFP), most of the expressed protein targeted chloroplasts. Both NbLTP1-OFP and NbLTP1/ΔSP-OFP were localized in chloroplasts when we removed the cell wall. These results suggest that NbLTP1 may have a secondary targeting signal. Transient overexpression of NbLTP1 had no effect on BaMV accumulation, but that of NbLTP1/ΔSP significantly increased BaMV expression. NbLTP1 may be a positive regulator of BaMV accumulation especially when its expression is associated with chloroplasts, where BaMV replicates. The mutation was introduced to the predicted phosphorylation site to simulate the phosphorylated status, NbLTP/ΔSP/P(+), which could still assist BaMV accumulation. By contrast, a mutant lacking calmodulin-binding or simulates the phosphorylation-negative status could not support BaMV accumulation. The lipid-binding activity of LTP1 was reported to be associated with calmodulin-binding and phosphorylation, by which the C-terminus functional domain of NbLTP1 may play a critical role in BaMV accumulation.

This study explores the issues involving pragmatic inferences with prosodic cues. Although there is a well-established literature from multiple languages demonstrating how different pragmatic inferences can be applied to the same syntactic structure, few studies discuss whether prosody can determine types of alternative sets based on the same syntactic structure. In Mandarin Chinese, the same sentence containing a numeral-classifier phrase as a negative polarity item can be employed for two types of scalar inferences based on either the numeral or the noun. The sentence wo yi zhi mayi dou mei kan dao (“I didn’t even see one ant”) can induce two different scalar inferences: Quantity-contrast (‘I did not see one ant, much less two ants, three ants, and so on’ by drawing a contrast against the minimal quantity of one), and Type-contrast (‘I did not see an ant, much less a dog, a cat, a human being, and so on’ by drawing a contrast against the minimally surprising type, that of ants). Taking advantage of similar sentences with the syntactic structure and lexical items, our study examines whether prosodic conditions can guide people to choose pragmatic inferences from a set of options based on the same syntactic structure. The experiments of this study are designed to answer whether prosody interacts with contextual information in this grammatical structure. The results suggest that Mandarin speakers can use sentence prosody to determine which inference is intended, at least in experimental contexts that directly probe explicit awareness of prosody. Prosody does play a role in inducing scalar inferences, but contextual information can override the effects of prosody. Each prosodic pattern can evoke a specific set of scalar inferences, but quantity-contrast inferences are favored over type-contrast inferences. Our experiments show that prosodic prominence can serve as a linguistic cue to pragmatic inferences.

Background: Aging is associated with the loss of muscle strength and difficulties in functional activities. The aim of this study was to investigate the changes of muscle strength and functional activities during aging in male and female individuals. Methods: This study was a cross-sectional study recruiting healthy individuals aged 40–89 years. The muscle strength of bilateral hip flexors, knee extensors, and ankle plantar flexors were measured. Activities including functional reach test, timed up and go test, and alternating stair stepping were also measured. Results: A total of 373 male and 371 female individuals participated in this study. The muscle strength of hip flexors and knee extensors were all significantly decreased after age 80 years as compared with the age group of 40–49 years in both male and female groups. The abilities of functional reach and timed up and go task were significantly decreased after age 70 years in the male group and decreased after age 60 years in the female group as compared with the age group of 40–49 years. Conclusion: We noted that the muscle strength and functional activities were decreased earlier in female than male individuals. The decrease of functional activities during the aging process seems to be earlier than the decrease of muscle strength. It is important to implement functional activities training in addition to strengthening exercise to maintain functional levels of the geriatric population.

Primary tubulovillous adenomas are scarcely encountered in the urinary tract, and most of these tumors arise from the intestinal segments of urinary reconstruction. We report the extremely rare case of tubulovillous adenomas primarily occurring in the urinary bladder in this article. A 50-year-old female patient initially presented with painless gross hematuria for several times within 1 month. Image studies, including abdominal ultrasonography and computed tomography, demonstrated one urinary bladder tumor with suspicious perivesical invasion. The diagnosis was made by a transurethral resection and histopathology, and no involvement of muscularis propria was confirmed. Although the pathogenesis and clinical behavior are not well understood, tubulovillous adenomas may have a tendency to undergo malignant transformation into the form of invasive adenocarcinomas. Complete resection and rigorous follow-up are strongly recommended.

The aim of this study was to examine the feasibility of ureteroscope-assisted double-J stenting following laparoscopic ureterolithotomy and to evaluate the effects of retrograde ureteroscopic access exerted on the sutured ureterotomy site. From January 2002 to December 2011, 30 patients with proximal ureteral stone underwent ureteroscopic double-J stenting of the ureter following retroperitoneal laparoscopic ureterolithotomy. Patient demographics and perioperative parameters, including the degree of hydronephrosis, urine leakage, and drainage time, were retrospectively reviewed. These data were compared with those of 30 consecutive patients who received open ureterolithotomy and intracorporeal ureteral double-J stenting. In addition, a PubMed search was conducted and the related literature on the placement of a ureteral stent was reviewed. Twenty-eight patients successfully underwent ureteral double-J stenting with ureteroscopic access. No malposition of the ureteral stent was identified in the ureteroscopic group, but two patients in the intracorporeal group required postoperative adjustment of the stent. Residual stone fragments were found during stent placement in three patients in the ureteroscopic group and holmium:yttrium–aluminum–garnet laser lithotripsy was immediately performed. There was no significant difference in postoperative outcomes or complication rates between the two groups. Ureteroscope-assisted ureteral double-J stenting is a simple and safe alternative allowing intraluminal navigation along the entire ureter, correct stent placement, and prompt treatment of residual stone fragments, without radiation exposure. In addition, ureteral disruption and urinary extravasation may not be concerns for ureteroscopic access with continuous normal saline irrigation.

The prevalence of upper tract urothelial carcinoma (UTUC) in Taiwan is relatively higher than thatin Western countries. Aristolochic acid (AA), which is widely used in traditional Chinese herbology, is now recognized to be one of the carcinogens for UTUC. Numerous UTUC patients have chronic kidney diseases or end-stage renal diseases; however, little literature hasreported on theoncogenic pathway of AA-related UTUC. The aim of our study was to identify the potential target treatment for AA-related UTUC. Here, we established an AA pre-exposure followed bya 3-methylcholanthrene (MCA) stimulus tumorigenic cell model. We not only demonstrated that AA pre-exposure MCA stimulus tumorigenic cells have more behaviors of cell migration and invasion by enhancing the metalloproteinases (MMP) activity, which is compatible with clinical findings of AA-related UTUC, but we also validated that AA pre-exposure MCA stimulus tumorigeniccells could be activated through the mitogen-activated protein kinases (MAPK) pathway. We further dissected the route of the MAPK pathway and found that the p38 and extracellular signal regulated kinases (ERK) sub-pathways might play essential roles in AA pre-exposure urothelial cancer cell lines. This consequence was also corroborated with a tissue study in AA-exposed patients.

Background: Human cytomegalovirus (CMV) is a lifelong, often asymptomatic infection, with the virus maintained in latently infected myeloid cells. Patients receiving chemotherapy for cancer are at high risk of reactivation of latent CMV, which may further contribute to host immune exhaustion, ultimately leading to a poor antitumor response. Pre-emptive anti-CMV medication may, therefore, serve as an adjunct therapy, preventing deterioration of the patient's immunity during treatment for cancer. The present study evaluated ganciclovir treatment's in vitro effects on CMV-associated T cell exhaustion and the antitumor capacity of cells from cancer patients. Methods: Peripheral blood mononuclear cells from patients with various types of cancers were treated with or without ganciclovir. Cells were then analyzed for T cell subpopulations and activation markers using flow cytometry, and their antitumor capacity was tested after exposure to dendritic cell–A549 fusion cells. Results: Following ganciclovir treatment, there was a redistribution of T cell subpopulations which was clearly distinct from the baseline pattern of T cell exhaustion. Treatment resulted in increases in early differentiated proportions, including naive (untreated control cells vs. ganciclovir treated cells, p

Background: Direction change while walking is a complex task of locomotor activity and is necessary during daily activities, but little is known about whether aging alters turn-related characteristics compared with straight walking. The objective of this study was to investigate the effects of aging on the biomechanical characteristics and walking velocity during circular turning. Methods: The participants included 17 healthy older adults (65–80 years old) and 16 young adults. Walking velocity, the first and second peak knee flexion, ankle plantarflexion, ankle dorsiflexion, and electromyographic amplitudes of the rectus femoris, biceps femoris, tibialis anterior, and gastrocnemius medialis were measured during walking along a 5 m straight path and a 5 m circumference curved path with a radius of 0.8 m. Results: The two groups made comparable decreases in turning velocity as compared with straight walking, but older adults decreased the second peak knee flexion instead of the second peak ankle plantarflexion, and the knee remained flexed during the loading response. Older people also needed higher amplitudes of the tibialis anterior in the outer leg, and biceps femoris in the inner leg, to facilitate turning, which were not seen in young adults. Moreover, older adults did not decrease amplitudes of the rectus femoris and biceps femoris in the outer leg, and tibialis anterior in the inner leg, as noted in young adults. Conclusion: Aging does not exert further effects on turning velocity, but older adults use different biomechanical strategies to turn.

The magnetostrictive microcantilever (MSMC) as a high-performance transducerwas introduced for the development of biosensors. The principle and characterization ofMSMC are presented. The MSMC is wireless and can be easily actuated and sensed usingmagnetic field/signal. More importantly, the MSMC exhibits a high Q value and works well inliquid. The resonance behavior of MSMC is characterized in air at different pressures and indifferent liquids, respectively. It is found that the Q value of the MSMC in water reaches about40. Although the density and viscosity of the surrounding media affect the resonancefrequency and the Q value of MSMC, the density has a stronger influence on the resonancefrequency and the viscosity has a stronger influence on the Q value, which result in that, forMSMC in air at pressure of less than 100 Pa, the resonance frequency of MSMC is almostindependent of the pressure, while the Q value increases with decreasing pressure. MSMCarray was developed and characterized. It is experimentally demonstrated that thecharacterization of an MSMC array is as simple as the characterization of a single MSMC. Afilamentous phage against Salmonella typhimurium was utilized as bio-recognition unit todevelop an MSMC based biosensor. The detection of S. typhimurium in water demonstratedthat the MSMC works well in liquid.

Phage-based magnetoelastic (ME) biosensors have been studied as an in-situ, real-time, wireless, direct detection method of foodborne pathogens in recent years. This paper investigates an ME biosensor method for the detection of Salmonella Typhimurium on fresh spinach leaves. A procedure to obtain a concentrated suspension of Salmonella from contaminated spinach leaves is described that is based on methods outlined in the U.S. FDA Bacteriological Analytical Manual for the detection of Salmonella on leafy green vegetables. The effects of an alternative pre-enrichment broth (LB broth vs. lactose broth), incubation time on the detection performance and negative control were investigated. In addition, different blocking agents (BSA, Casein, and Superblock) were evaluated to minimize the effect of nonspecific binding. None of the blocking agents was found to be superior to the others, or even better than none. Unblocked ME biosensors were placed directly in a concentrated suspension and allowed to bind with Salmonella cells for 30 min before measuring the resonant frequency using a surface-scanning coil detector. It was found that 7 h incubation at 37 °C in LB broth was necessary to detect an initial spike of 100 cfu/25 g S. Typhimurium on spinach leaves with a confidence level of difference greater than 95% (p < 0.05). Thus, the ME biosensor method, on both partly and fully detection, was demonstrated to be a robust and competitive method for foodborne pathogens on fresh products.

Classical swine fever virus (CSFV) causes a broad range of disease in pigs, from acute symptoms including high fever and hemorrhages, to chronic disease or unapparent infection, depending on the virus strain. CSFV belongs to the genus Pestivirus of the family Flaviviridae. It carries a single-stranded positive-sense RNA genome. An internal ribosomal entry site (IRES) in the 5' untranslated region (UTR) drives the translation of a single open reading frame encoding a 3898 amino acid long polypeptide chain. The open reading frame is followed by a 3' UTR comprising four highly structured stem-loops. In the present study, a synthetic RNA composed of the 5' and 3' UTRs of the CSFV genome devoid of any viral coding sequence and separated by a luciferase gene cassette (designated 5'UTR-Luc-3'UTR) triggered apoptotic cell death as early as 4 h post-transfection. The apoptosis was measured by DNA laddering analysis, TUNEL assay, annexin-V binding determined by flow cytometry, and by analysis of caspase activation. Contrasting with this, only trace DNA laddering was observed in cells transfected with the individual 5' or 3' UTR RNA; even when the 5' UTR and 3' UTR were co-transfected as separate RNA molecules, DNA laddering did not reach the level induced by the chimeric 5'UTR-Luc-3'UTR RNA. Interestingly, RNA composed of the 5'UTR and of stem-loop I of the 3'UTR triggered much stronger apoptosis than the 5' or 3'UTR alone. These results indicate that the 5' and 3' UTRs act together in cis induce apoptosis. We furthered obtained evidence that the UTR-mediated apoptosis required double-stranded RNA and involved translation shutoff possibly through activation of PKR.

To investigate the plant genes affected by Bamboo mosaic virus (BaMV) infection, we applied a cDNA-amplified fragment length polymorphism technique to screen genes with differential expression. A serine/threonine kinase-like (NbSTKL) gene of Nicotiana benthamiana is upregulated after BaMV infection. NbSTKL contains the homologous domain of Ser/Thr kinase. Knocking down the expression of NbSTKL by virus-induced gene silencing reduced the accumulation of BaMV in the inoculated leaves but not in the protoplasts. The spread of GFP-expressing BaMV in the inoculated leaves is also impeded by a reduced expression of NbSTKL. These data imply that NbSTKL facilitates the cell-to-cell movement of BaMV. The subcellular localization of NbSTKL is mainly on the cell membrane, which has been confirmed by mutagenesis and fractionation experiments. Combined with the results showing that active site mutation of NbSTKL does not change its subcellular localization but significantly affects BaMV accumulation, we conclude that NbSTKL may regulate BaMV movement on the cell membrane by its kinase-like activity. Moreover, the transient expression of NbSTKL does not significantly affect the accumulation of Cucumber mosaic virus (CMV) and Potato virus X (PVX); thus, NbSTKL might be a specific protein facilitating BaMV movement.

Abstract Background TP53 mutation is present in about 50.8% of lung adenocarcinomas, frequently in combination with other genetic alterations. However, a rare subset harbors the TP53 mutation alone. Methods Next‐generation sequencing was performed in 844 lung adenocarcinomas diagnosed by fine needle aspiration. Fourteen cases (1.7%) showed isolated TP53 alteration and were subjected to a comprehensive analysis. Results The average age at diagnosis was 65.7 years (range 48–79); 9 males and 5 females. All were smokers with an average pack‐year of 40.7 (range 10–70). Ten had metastases, mostly in the brain (n = 4) and pleura (n = 4). After a follow‐up period of up to 102 months, 9 died, 3 were alive free of disease, 1 was alive with disease, and 1 was lost to follow‐up. The median survival was 12.2 months. Most tumors exhibited poor differentiation, composed of solid sheets with moderate to severe atypia, increased mitotic activity, and necrotic background. Half were positive for TTF‐1 and showed p53 overexpression. PD‐L1 was positive in 5 cases. Most alterations were missense mutations in exons 5–8, and this mutation type was associated with p53 overexpression. Tumors with combined missense mutation and truncated protein had higher PD‐L1 expression along with a trend towards an increase in tumor mutational burden (TMB). CEBPA deletion of undetermined significance was the most common copy number alteration. Conclusion Isolated TP53 mutation was seen in association with smoking, high‐grade cytomorphologic features, adverse prognosis, and recurrent CEBPA deletions. These tumors tend to have strong PD‐L1 expression and high TMB, suggesting potential benefit from immune checkpoint inhibitors. Hence, the recognition of this molecular group has prognostic and therapeutic implications.