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Background Patients with low to intermediate risk atrial fibrillation (AF), defined as non-gender CHA2DS2-VASc score of 0–1, are still at risk of stroke. This study verified the usefulness of ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/ml], Creatinine clearance [ Methods This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA2DS2-VASc score 0–1. The primary endpoint was the incidence of stroke with or without anti-thrombotic treatment (ATT). An ABCD score was also validated. Results Overall, 2694 patients (56.3±9.5 years; female, 726 [26.9%]) were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100P-Y for an ABCD score 0; 1.02/100P-Y for an ABCD score≥1. The ABCD score was superior to the non-gender CHA2DS2-VASc score in stroke risk stratification (C-index=0.618, P=0.015; net reclassification improvement=0.576, P=0.040; integrated differential improvement=0.033, P=0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score≥1 than in those without ATT (0.44/100P-Y versus 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11–0.63, P=0.003). Conclusion The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA2DS2-VASc score 0–1. Furthermore, NOAC with an ABCD score≥1 was associated with significantly lower stroke rate in AF patients with a non-gender CHA2DS2-VASc score 0–1. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Korean Disease Control and Prevention Agency

In this paper, a new robust computational method that applies the geometrical theory of diffraction (GTD) in conjunction with the ray tracing (RT) technique is developed to evaluate the electromagnetic scattering pattern due to a plane wave represented as beam of parallel rays incident on a rough surface of quite arbitrary statistical parameters. The development of the proposed technique is explained in detail taking into consideration the generation of the geometrical model of the rough surface. The Fresnel reflection model is applied under the assumption of arbitrary electrical and optical properties of the rough surface material. Also the polarization of the plane wave primarily incident on the rough surface is taken into consideration. The algorithm developed in the present work accounts for multiple bounces of an incident ray and, hence, it can be considered arbitrary higher-order GTD-RT technique. The accuracy of the obtained results is verified through the comparison with the experimental measurements of the scattering pattern of a light beam incident on rough sheets with specific statistical properties. The numerical results of the present work are concerned with investigating the dependence of the scattering pattern on the surface roughness, refractive index, angle of incidence, and the resolution of the geometric model of the rough surface. Also, it is shown that, for limited resolution of the rough surface model, the accuracy of the calculated scattered field depends on the angle of incidence of the primary beam and the surface roughness.

Somatics refers to body work and movement study that emphasize internal perception and experience. Recently, a new perspective has emerged that views somatics-based techniques as a kind of mindful movement. Somatic techniques as contemplative movement can improve emotional regulation ability through improvement of body awareness or interoception. Based on this background, the present study attempts to develop a somatics based program suitable for a group of clinical patients suffering from emotional dysregulation. This study plans to collect quantitative and qualitative data in order to clarify how interoception and the related emotional regulation ability change after the program. These findings will help to explore whether the somatics technique has potential as an emotion regulation program in the future. In addition, the results are expected to contribute to finding an alternative treatment modality for patients who have not achieved a sufficient effect with conventional psychotherapy.

At present, biomimetic antifouling research objects are mostly concentrated on the fast-moving marine organism, but the anti-fouling effect of the low-speed or static marine equipment is not obvious. This paper describes the anti-fouling mechanism of soft coral (Sarcophyton trocheliophorum), including the physical defense mechanism and the bactericidal ability of mucus and coral powder. As a sessile organisms, soft coral lacks escape mechanism. Therefore, the study on its antibacterial strategy is significant because it can provide theoretical guidance for static antifouling. Results showed that the live soft coral would molt in unfriendly environment, and the secreted mucus could defend themselves against fouling microorganism. Then, Liquid Chromatography-Mass Spectrometry (LC-MS) analysis was conducted to identify the bioactive compounds of the coral powder and mucus. Results revealed that both powder and mucus contained a wide variety of toxic components, which had bactericidal effects. Moreover, at the same concentration, the inhibitory effect of the main components on Gram-negative bacteria was stronger than that on positive bacteria. These findings enhance the understanding about the antifouling mechanism of soft coral and provide new ideas for design and prepare novel antifouling strategy to combat biofouling under static condition.

The Fe and N co-functionalized catalyst is controllably synthesized by three-step strategy. Prussian blue (PB) and poly 2,6-diaminopyridine (PDAP) are preferentially selected to synthesize a core-shell structure attributed to their advantageous properties. Under pyrolysis process, carbonized PDAP serves as a block layer to prevent Fe-based nanoparticles from aggregation and increase the content of N. By adjusting the thickness of shell and pyrolysis temperature, the catalytic activity can be optimized. The optimized catalyst exhibits good catalytic performance in terms of onset and half-wave potentials, limiting-diffusion current density and durability. Moreover, the relationship between structure and effect is analyzed. It is found that the optimal catalyst presents excellently active for ORR stemming from a comprehensive effect, containing higher density of active site, higher surface area, porosity structure, and good conductivity of catalyst.

C1q/tumor necrosis factor (TNF)-related protein 12 (CTRP12) is a secretory protein that participates in the regulation of glucose and lipid metabolism in obesity and diabetes. Its role in cardiovascular disease, particularly sepsis-induced cardiac injury, is unclear. Here, we stimulated cardiomyocytes with lipopolysaccharide (LPS) to establish an in vitro cardiomyocyte injury model and CTRP12 was overexpressed with an adenovirus delivery system. Overexpression of CTRP12 reduced the transcription and release of pro-inflammatory cytokines from LPS-stimulated cardiomyocytes, including TNFα, interleukin-1 (IL-1), and IL-6. Reactive oxygen species (ROS) level increased and the oxidation/redox system was disturbed in LPS-stimulated cardiomyocytes, as evident from the decrease in superoxide dismutase activity and an increase in reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and malondialdehyde level. CTRP12 overexpression decreased the increasing level of ROS and ameliorated the unbalance in the oxidation/redox system in LPS-stimulated cardiomyocytes. The viability of cardiomyocytes decreased after LPS stimulation, and the cells underwent apoptosis. CTRP12-overexpressing cardiomyocytes showed a decrease in the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells, and the ratio of B cell lymphoma (Bcl)-1/Bax in these cells was recovered. In comparison with the control group, LPS-stimulated cardiomyocytes showed reduced expression of nuclear factor E2-related factor 2 (NRF2), while CTRP12-overexpressing cardiomyocytes showed elevated NRF2 expression. Small-interfering RNA-mediated silencing of NRF2 expression in cardiomyocytes resulted in the inhibition of the protective effects of CTRP12. Thus, CTRP12 ameliorated injury in LPS-stimulated cardiomyocytes in an NRF2-dependent manner.

Adverse childhood experiences (ACEs) are known to be closely related to depression, anxiety and sleep problems. However, it remains unclear whether adolescents with ACEs have sleep problems regardless of depression or anxiety or under a mediating effect from depression or anxiety. Therefore, our aim was to examine whether depression or anxiety mediates the relationship between ACEs and sleep problems in adolescents by using a community sample. The Early Trauma Inventory Self Report–Short Form (ETISR-SF) and List of Threatening Experiences Questionnaire (LTE-Q) were used to assess traumatic ACEs. Ultimately, data from 737 students (M = 448, F = 289, 15.1 ± 1.4 years old) were included in the statistical analysis. A total of 576 (78.1%) participants reported that they had experienced one or more ACEs. Adolescents with ACEs had higher levels of depression, anxiety and sleep problems than did adolescents without ACEs, and boys tended to experience more trauma than girls. Depression and anxiety partially mediated the relationship between ACEs and sleep problems. The results of this study suggest the need for depression and anxiety interventions for adolescents with ACEs to reduce the long-term consequences, including sleep problems and physical health problems.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite aggressive treatment clinical outcomes for RMS have not improved for three decades, emphasizing the need to uncover the molecular underpinnings of the disease. RMS has been presumed to originate from derailed muscle progenitors based on the histologic appearance and gene expression pattern of the tumors resembling embryonic developing skeletal muscle. However, an origin restricted to skeletal muscle does not explain RMS occurring in tissues devoid of skeletal muscle such as the prostate, bladder, and salivary gland. Previously, we described that activation of Sonic Hedgehog signaling through expression of a conditional, constitutively active Smoothened allele, SmoM2, under control of a presumed adipocyte-restricted adipose protein 2 (aP2)-Cre recombinase transgene in mice gives rise to aggressive skeletal muscle tumors. These tumors display the histologic and molecular characteristics of human embryonal fusion-negative RMS (FN-RMS). This model suggested a potential non-myogenic origin of FN-RMS and an avenue to explain FN-RMS development in anatomic sites devoid of skeletal muscle. Lineage tracing showed that RMS can originate from cell reprogramming and transdifferentiation of endothelial progenitor cells. Hedgehog pathway activation in committed endothelial progenitors results in Tbx1 expression and subsequent Myod1 expression driving a partially myogenic program characteristic of FN-RMS. Our work identifies reprogramming cell fate as a mechanism of transformation in pediatric sarcoma and illustrates that it is dangerous to assume the cell of origin from the characteristics of the tumor cell. The cell-reprogramming mechanism that shifts endothelial progenitors to muscle-like cells provides a unique system to define the core regulatory circuitry controlling RMS cell fate and to determine in vivo if targeting this network is a therapeutic vulnerability. Genomic profiling of human FN-RMS failed to uncover a unique mutation that drives oncogenesis. However, the PTEN cis-regulatory region is hypermethylated in more than 90% of all human FN-ERMS tumors, resulting in decreased expression. However, inhibiting the PI3K/AKT/mTOR pathway has had varied efficacy in RMS. In our RMS mouse model, PTEN localizes to the cytoplasm and nucleus, suggesting that PTEN could have functions other than regulating the PI3K/AKT/mTOR pathway. We demonstrate that Pten loss cooperates in RMS tumorigenesis and results in tumors more reflective of human FN-RMS. We show that Pten loss drives expression of the transcription factor PAX7 and identified PAX7 as a dependency in human FN-RMS. Furthermore, Pax7 deletion completely rescues the deleterious effects of Pten loss but also alters tumor cell fate, giving rise to a smooth muscle tumor. Thus, PTEN loss drives the expression of PAX7, a key member of the RMS core regulatory circuitry dictating tumor cell fate. This highlights a synthetic essential relationship between PTEN and PAX7 in FN-RMS tumor maintenance and tumor-fate decisions. Citation Format: Mark E. Hatley, Casey G. Langdon, Katherine E. Gadek, Matthew R. Garcia, Catherine J. Drummond, Jason A. Hanna, Hongjian E. Jin, Jerold E. Rehg. Rhabdomyosarcoma: visions through the looking glass [abstract]. In: Proceedings of the AACR Special Conference: Sarcomas; 2022 May 9-12; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2022;28(18_Suppl):Abstract nr IA013.

Lung squamous cell carcinoma (LUSC) is one of the most common subtypes of lung cancer that accounts for ~50% of all lung cancer cases. Long noncoding RNA (lncRNA) PSMG3-antisense (AS) 1 has been suggested to play an important role in various types of cancer. Therefore, the aim of the present study was to investigate the role of PSMG3-AS1 using clinical specimens and data from 130 patients with LUSC. The expression levels of PSMG3-AS1 and miR-143-3p were detected in LUSC specimens, and the correlation between lncRNA PSMG3-AS1 expression and patient clinical characteristics was analyzed. Cell Counting Kit-8, Transwell migration and invasion assays were used to investigate the functional role of PSMG3-AS1 in LUSC. The mechanism of PSMG3-AS1 on LUSC cells was also investigated using a luciferase activity assay with wild-type or mutated PSMG3-AS1. PSMG3-AS1 was found to be upregulated in LUSC, and high expression was associated with positive lymph node metastasis and a higher TNM stage. The results of multivariate Cox regression analysis revealed that PSMG3-AS1 may serve as an independent prognostic indicator in LUSC. Furthermore, inhibiting PSMG3-AS1 expression reduced tumor cell proliferative, migratory and invasive abilities. Moreover, PSMG3-AS1 was found to be closely associated with miR-143-3p in LUSC, and thus may become a potential prognostic marker and therapeutic target for the treatment of LUSC in the future.

"Comfort women" are survivors of sexual slavery by the Imperial Japanese Army during World War II, who endured extensive trauma including massive rape and physical torture. While previous studies have been focused on the trauma of the survivors themselves, the effects of the trauma on the offspring has never been evaluated before. In this article, we reviewed the first study on the offspring of former "comfort women" and aimed to detect the evidence of transgenerational transmission of trauma. In-depth psychiatric interviews and the Structured Clinical Interview for DSM-5 Axis I Disorders were conducted with six offspring of former "comfort women." Among the six participants, five suffered from at least one psychiatric disorder including major depressive disorder, panic disorder, posttraumatic stress disorder, adjustment disorder, insomnia disorder, somatic symptom disorder, and alcohol use disorder. Participants showed similar shame and hyperarousal symptoms as their mothers regarding stimuli related to the "comfort woman" issue. Increased irritability, problems with aggression control, negative worldview, and low self-esteem were evident in the children of mothers with posttraumatic stress disorder. Finding evidence of transgenerational transmission of trauma in offspring of "comfort women" is important. Future studies should include more samples and adopt a more objective method.

Gastric carcinoma, one of the most aggressive and lethal human malignancies, is associated with poor prognosis despite progress in therapeutic strategies. This study examined the potential function and mechanism of action of microRNA‐125b‐5p (miR‐125b‐5p) in the pathogenesis of gastric carcinoma. We recognized that miR‐125b‐5p was elevated in gastric carcinoma, and its decreased expression was associated with a better prognosis. Loss‐of‐function assays showed that miR‐125b‐5p suppression inhibited the proliferative and invasive abilities of gastric cancer cells. Furthermore, RING1 and YY1‐binding protein (RYBP) was found to be target gene for miR‐125b‐5p action; miR‐125b‐5p negatively regulates RYBP expression. According to the results of rescue experiments, RYBP downregulation partially counteracted the miR‐125b‐5p silence‐mediated inhibitory function in gastric cancer progression. Collectively, these data elucidated the molecular mechanisms of the miR‐125b‐5p/RYBP axis in gastric cancer invasion and growth.

GIPR activity in α cells is required for the complete metabolic response to a meal., Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid–stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in β cells. Moreover, we demonstrate that GIP activity in α cells contributes to insulin secretion by invoking paracrine α to β cell communication. Last, specific loss of GIPR activity in α cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in α cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

OBJECTIVE: To compare the success rate and safety of the short-axis (SAX) approach and long- axis (LAX) approach to ultrasound-guided central venous cannulation. METHODS: Electronic bibliographic databases including PubMed, Cochrane Library, Science Direct, and Web of Science were searched for randomized controlled trials comparing ultrasound-guided central venous cannulation via the LAX and SAX approaches published during the period from January, 2011 to October, 2017. We extracted the data from the eligible studies and assessed the first-attempt success rate, overall puncture success rate and complication rate of the two approaches. The relative risk (RR) with the 95% CI was calculated using a fixed or random effects model. RESULTS: Seven randomized controlled trials were included for meta-analysis. The results showed that the first-attempt success rate was significantly higher in the SAX group than in the LAX group (RR=1.27, 95%CI: 1.11-1.46; P=0.0005, I(2)=49%), but the overall puncture success rate did not differ significantly between the two approaches (RR=1.04, 95%CI: 0.97-1.10; P=0.27, I(2)=84%). The incidence of accidental arterial puncture with the SAX approach was significantly lower than that with the LAX approach (RR=1.04; 95%CI: 1.01-1.08; P=0.01, I(2)=30%). CONCLUSION: Ultrasound-guided central venous cannulation via the SAX approach, as compared with the LAX approach, can increase first-attempt success rate and reduce the incidence of accidental arterial puncture.

“Comfort women” refers to young women and girls who were forced into sexual slavery by the Imperial Japanese military during World War II. They were abducted from their homes in countries under Imperial Japanese rule, mostly from Korea, and the rest from China, Philippines, Malaysia, Taiwan, Indonesia, the Netherlands, etc. “Comfort women” endured extreme trauma involving rape, sexual torture, physical abuse, starvation, threats of death, and witnessed many others being tortured and killed. This article reviews all the studies that have investigated the psychiatric or psychosocial sequelae of the survivors of the Japanese military sexual slavery. Most importantly, a recent study which conducted a psychiatric evaluation on the former “comfort women” currently alive in South Korea is introduced. The participants’ unmarried rate was relatively high and their total fertility rate was relatively low. Majority of the participants reported having no education and being the low economic status. They showed high current and lifetime prevalence of posttraumatic disorder, major depressive disorder, somatic symptom disorder, social anxiety disorder, panic disorder, and alcohol use disorder. Participants showed high suicidality and majority of the participants still reported being ashamed of being former “comfort women” after all these years. This article high-lights the fact that the trauma has affected the mental health and social functioning of former “comfort women” throughout their lives, and even to the present day.

A remote control system based on the Internet and machine vision is designed in this study for tracked vehicles. The system consists of remote monitoring, remote control, and visual navigation subsystems. The on-board computer receives control commands issued by the monitoring center and controls the speed and steering angle of the tracked vehicles. The front camera collects navigation line information, and the collected image is processed by filtering, gray processing, binarization processing, and interference elimination to obtain the center point coordinates of the navigation line. Proportional-integral-derivative (PID), fuzzy PID, and neural network control algorithms are compared based on the distance and angle deviations of the preview point to control the operation of tracked vehicles through simulation. The Internet remote control system with the fuzzy PID control algorithm is then tested on a tracked vehicle. Experimental results indicate that the trajectory of the tracked vehicle fits the navigation path well.

Nowadays, injectable electroactive hydrogels have received much attention in biomedical field. In this article, an electroactive copolymer was successfully synthesized by chemical coupling of tetraaniline (TA) onto the chain end of Pluronic ® F127. The structure of the resultant copolymer was characterized by Fourier transform infrared spectroscopy (FT-IR), ultraviolet–visible spectroscopy (UV–vis), and 1 H NMR. Cyclic voltammetry (CV) measurements of the copolymer solution indicated good electroactivity. Moreover, the electroactive copolymer showed temperature-responsive sol-gel transitions in aqueous media. Gelation properties of the hydrogels were also studied by rheometer and the results showed that the introduction of TA segment could enhance the mechanical properties of hydrogel. Based on the analyses of 13 C NMR spectra and dynamic light scattering (DLS), the sol-gel transition mechanism was attributed to the dehydration of PEG chains in F127. The MTT assay revealed that the TA conjugated F127 copolymer showed excellent biocompatibility. And the copolymer could form gel in vivo at 15 min post injection. Therefore, this biocompatible copolymer acted as injectable electroactive hydrogels may have great potential in biomedical uses.

This study presented a graphene platelet/silicone rubber (GPL/SR) composite as a drag reduction material, inspired by the boundary heating drag reduction mechanism of dolphin skin. Graphene was added as a thermally conductive filler at weight fractions of 0.17 wt%, 0.33 wt% and 0.67 wt% to pristine silicone rubber (PSR). Tests of the thermal conductivity and tensile properties showed that the thermal conductivity of all three GPL/SR materials of 0.17 wt%, 0.33 wt% and 0.67 wt% graphene were 20%, 40% and 50% higher than that of the PSR, respectively, and the elastic modulus of the 0.17 wt% GPL/SR materials was lowest. Droplet velocity testing, which can reflect the drag reduction mechanism of the heating boundary controlled by the GPL/SR composite, was performed between 0.33 wt% GPL/SR, which typically exhibits good mechanical properties and thermal conductivity performance, and the PSR. The results showed that on the 0.33 wt% GPL/SR, the droplet velocity was higher and the rolling angle was lower, implying that the GPL/SR composite had a drag-reducing function. In terms of the drag reduction mechanism, the heat conductivity performance of the GPL/SR accelerated the heat transfer between the GPL/SR composite surface and the droplet. The forces between the molecules decreased and the droplet dynamic viscosity was reduced. The drag of a sliding water droplet was proportional to the dynamic viscosity, which resulted in drag reduction. The application of GPL/SR material to the control fluid medium should have important value for fluid machinery.

The newly evolved circuits in layer III of primate dorsolateral prefrontal cortex (dlPFC) generate the neural representations that subserve working memory. These circuits are weakened by increased cAMP-K(+) channel signaling, and are a focus of pathology in schizophrenia, aging, and Alzheimer's disease. Cognitive deficits in these disorders are increasingly associated with insults to mGluR3 metabotropic glutamate receptors, while reductions in mGluR2 appear protective. This has been perplexing, as mGluR3 has been considered glial receptors, and mGluR2 and mGluR3 have been thought to have similar functions, reducing glutamate transmission. We have discovered that, in addition to their astrocytic expression, mGluR3 is concentrated postsynaptically in spine synapses of layer III dlPFC, positioned to strengthen connectivity by inhibiting postsynaptic cAMP-K(+) channel actions. In contrast, mGluR2 is principally presynaptic as expected, with only a minor postsynaptic component. Functionally, increase in the endogenous mGluR3 agonist, N-acetylaspartylglutamate, markedly enhanced dlPFC Delay cell firing during a working memory task via inhibition of cAMP signaling, while the mGluR2 positive allosteric modulator, BINA, produced an inverted-U dose–response on dlPFC Delay cell firing and working memory performance. These data illuminate why insults to mGluR3 would erode cognitive abilities, and support mGluR3 as a novel therapeutic target for higher cognitive disorders.

The influence of elastic deformation and elastic modulus on the release of adhered bacteria was investigated in this paper. Four silicone elastomers (SE) with different elastic moduli and one rigid polystyrene sheet were prepared to verify the antifouling effect of elastic deformation. The SE film has an elastic deformation effect under the stimulus of fluid medium, which makes the surface unstable. That could reduce the adhesion of fouling organisms and provide a foul-release basis. Distinct anti-adhesion properties were observed in our study in that cells more easily adhered to the rigid surface than the elastic surfaces under hydrodynamic conditions. However, the bacterial attachment test showed a similar antifouling performance of SE and the rigid surface under static conditions. To investigate the anti-adhesion ability of the elastic surface and rigid surface, the bacterial adhesive kinetics were studied by Discrete Element Method (DEM)–Computational Fluid Dynamics (CFD) coupling simulation. Results indicated the number of bacteria adhering on the elastic wall was significantly lower than on the rigid wall. And as the elastic modulus increased, the bacterial adhesion increased accordingly within a certain range. This work should not only enhance understanding of elastomer-based antifouling materials, but also facilitate the design and construction of other types non-toxic foul-release materials.

In order to solve the shortage of competent healthcare manpower at the village level of Yunnan Province, We compared the training mode of Kunming Medical University and The Medical Educational Center, Hat Yai of PSU. The aim of this study is to compare the difference of the two institutions and learn from each other's advantages.The review covered relevant policy areas and stipulations governing general practitioner training for both countries. Qualitative research was done by using a questionnaire developed in house by the project team, students from the inaugural cohort at KMU and students from the MECH. In Qualitative research, in-depth interviews were carried out with the teaching administration and students from both schools.In Kunming Medical University, besides the conventional lectures, teaching methods such as case based learning and problem based learning have been worked into the basic science, laboratory, and clerkship/internship sessions. The desired end product is a general practitioner. The curriculum emphasizes general practice and clinical exposure during the course being guided and informed by the "Undergraduate Medical Education Standard-Clinical Medicine" and the "General Practitioner Training Guidelines" about teaching methods. In Prince of Songkla University, the first and second phases consist of basic science and preclinical integrated topics taught at PSU. For the third and final phase, the students have core clinical modules and selective at MECH where the methods are learner centered, problem based, integrated and set in the context of community primary healthcare practice.We should start with the integration of the medical disciplines and the humanities, so as to restore the lost "art of doctoring". We need to integrate the various foundational and clinical disciplines into an organ system based curriculum, not just in form, but also in function and purpose.

We examine whether investors react to a significant change in balance sheets, absent a significant change in underlying economics. Beginning in 2019, ASC 842 requires the recognition of operating leases, which were previously only disclosed in the footnotes to the financial statements. This change in accounting standard results in firms with significant operating leases recognizing a considerable increase in debt. We find that firms with significant operating leases, on average, earn negative returns around the initial recognition of their operating leases. For example, firms in the top decile of operating lease intensity experience a mean abnormal return of -3.10% around their first quarter 2019 earnings announcements. We do not find that concurrent trade tensions between the United States and China explain the valuation decline. Our results provide timely, new evidence consistent with equity market prices reflecting an inadequate level of fundamental analysis.

Working memory relies on the dorsolateral prefrontal cortex (dlPFC), where microcircuits of pyramidal neurons enable persistent firing in the absence of sensory input, maintaining information through recurrent excitation. This activity relies on acetylcholine, although the molecular mechanisms for this dependence are not thoroughly understood. This study investigated the role of muscarinic M1 receptors (M1Rs) in the dlPFC using iontophoresis coupled with single-unit recordings from aging monkeys with naturally occurring cholinergic depletion. We found that M1R stimulation produced an inverted-U dose response on cell firing and behavioral performance when given systemically to aged monkeys. Immunoelectron microscopy localized KCNQ isoforms (Kv7.2, Kv7.3, and Kv7.5) on layer III dendrites and spines, similar to M1Rs. Iontophoretic manipulation of KCNQ channels altered cell firing and reversed the effects of M1R compounds, suggesting that KCNQ channels are one mechanism for M1R actions in the dlPFC. These results indicate that M1Rs may be an appropriate target to treat cognitive disorders with cholinergic alterations.

Many Gram-negative bacterial pathogens antagonize anti-bacterial immunity through translocated effector proteins that inhibit pro-inflammatory signaling. In addition, the intracellular pathogen Salmonella enterica serovar Typhimurium initiates an anti-inflammatory transcriptional response in macrophages through its effector protein SteE. However, the target(s) and molecular mechanism of SteE remain unknown. Here, we demonstrate that SteE converts both the amino acid and substrate specificity of the pleiotropic serine/threonine kinase GSK3. SteE itself is a substrate of GSK3 and phosphorylation of SteE is required for its activity. Remarkably, phosphorylated SteE then forces GSK3 to phosphorylate the non-canonical substrate STAT3 on tyrosine-705. This results in STAT3 activation and both GSK3 and STAT3 are required for SteE-mediated upregulation of the anti-inflammatory M2 macrophage marker IL-4Rα. Overall, the conversion of GSK3 to a tyrosine-directed kinase represents an unprecedented example of how a bacterial virulence protein reprograms innate immune signalling to establish an anti-inflammatory environment.

Cognitive deficits in psychiatric and age-related disorders generally involve dysfunction of the dorsolateral prefrontal cortex (dlPFC), but there are few treatments for these debilitating symptoms. Group II metabotropic glutamate receptors (mGluR2/3), which couple to Gi/Go, have been a focus of therapeutics based on rodent research, where mGluR2/3 have been shown to reduce axonal glutamate release and increase glial glutamate uptake. However, this strategy has had mixed results in patients, and understanding mGluR2/3 mechanisms in primates will help guide therapeutic interventions. The current study examined mGluR2/3 localization and actions in the primate dlPFC layer III circuits underlying working memory, where the persistent firing of 'Delay cells' is mediated by N-methyl-d-aspartate receptors and weakened by cAMP-PKA-potassium channel signaling in dendritic spines. Immunoelectron microscopy identified postsynaptic mGluR2/3 in the spines, in addition to the traditional presynaptic and astrocytic locations. In vivo iontophoretic application of the mGluR2/3 agonists (2R, 4R)-APDC or LY379268 onto dlPFC Delay cells produced an inverted-U effect on working memory representation, with enhanced neuronal firing following low doses of mGluR2/3 agonists. The enhancing effects were reversed by an mGluR2/3 antagonist or by activating cAMP signaling, consistent with mGluR2/3 inhibiting postsynaptic cAMP signaling in spines. Systemic administration of these agonists to monkeys performing a working memory task also produced an inverted-U dose-response, where low doses improved performance but higher doses, similar to clinical trials, had mixed effects. Our data suggest that low doses of mGluR2/3 stimulation may have therapeutic effects through unexpected postsynaptic actions in dlPFC, strengthening synaptic connections and improving cognitive function.