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Abstract Electron ptychography has emerged as a popular technology for high-resolution imaging by combining the high coherence of electron sources with the ultra-fast scanning electron coil. However, the limitations of conventional pixelated detectors, including poor dynamic range and slow data readout speeds, have posed restrictions in the past on conducting electron ptychography experiments. We used the Gatan STELA pixelated detector to capture sequential diffraction data of monolayer two-dimensional (2D) materials for ptychographic reconstruction. By using the pixelated detector and electron ptychography, we demonstrate the observation of the radiation damage at atomic resolution in Transition Metal Dichalcogenides (TMDs).

Particle plasmon resonance (PPR), or localized surface plasmon resonance (LSPR), utilizes intrinsic resonance in metal nanoparticles for sensor fabrication. While diffraction grating waveguides monitor bioaffinity adsorption with out-of-plane illumination, integrating them with PPR for biomolecular detection schemes remains underexplored. This study introduces a label-free biosensing platform integrating PPR with a diffraction grating waveguide. Gold nanoparticles are immobilized on a glass slide in contact with a sample, while a UV-assisted embossed diffraction grating is positioned opposite. The setup utilizes diffraction in reflection to detect changes in the environment’s refractive index, indicating biomolecular binding at the gold nanoparticle surface. The positional shift of the diffracted beam, measured with varying refractive indices of sucrose solutions, shows a sensitivity of 0.97 mm/RIU at 8 cm from a position-sensitive detector, highlighting enhanced sensitivity due to PPR–diffraction coupling near the gold nanoparticle surface. Furthermore, the sensor achieved a resolution of 3.1 × 10−4 refractive index unit and a detection limit of 4.4 pM for detection of anti-DNP. The sensitivity of the diffracted spot was confirmed using finite element method (FEM) simulations in COMSOL Multiphysics. This study presents a significant advancement in biosensing technology, offering practical solutions for sensitive, rapid, and label-free biomolecule detection.

BackgroundBoth the Sport Education (SE) model and Teaching Games for Understanding (TGfU) have been connected to the theory of situated learning, which is a game-centered curricular model. TGfU emphasizes tactical awareness, decision making, and skill execution. The SE model provides a complete season during physical education (PE) lessons. Therefore, it is worth exploring the integration of TGfU with SE (TGfU-SE) model in PE courses, and whether the hybrid TGfU-SE model can achieve better learning effects for students than the TGfU model alone.PurposeThe purpose of the study was to compare the difference in learning effects between the TGfU-SE model and the TGfU model on students’ learning motivation, sport enjoyment, responsibility, and game performance.MethodsThis study used a quasi-experimental design to compare different learning effects between the experimental group (TGfU-SE) and the control group (TGfU). The participants lived in Taiwan, including two junior high school PE teachers and four PE classes with a total of 90 students (TGfU-SE group, n = 46; TGfU group, n = 44). Each teacher taught two PE classes, one with an experimental group and one with a control group. This study used four research instruments, including the Responsibility Scale in Physical Education (RSPE), Learning Motivation Scale in Physical Education (LMSPE), Sport Enjoyment Scale in Physical Education (SESPE), and Game Performance assessment instrument (GPAI). Analysis of covariance (ANCOVA) and the independent t-test were used to analyze the data.ResultsThe results of this study showed that the TGfU-SE model had more positive learning effects on students’ learning motivation, sport enjoyment, responsibility, and game performance than the TGfU model.Conclusionwe concluded that the TGfU-SE model had a more positive influence on students’ learning performance than the TGfU model. It is suggested that the hybrid TGfU-SE model could be implemented effectively in the PE curriculum.

To make teaching personal and social responsibility (TPSR) more effective, this study aimed to determine whether integrating moral disengagement (MD) minimization strategies into TPSR can enhance students’ positive behaviors and reduce their misbehaviors in PE. A pretest-posttest quasi-experimental design was conducted with an experimental group and two control groups. One hundred forty-five students from nine classes in three middle schools were assigned to experimental group (TPSR + MD minimization strategies; N = 50), control group A (TPSR; N = 46), and control group B (general PE instruction; N = 49) respectively. A pretest was performed in the first week, and a posttest was performed in the 18th week. The results showed that integrating MD minimization strategies into TPSR could significantly reduce students’ misbehaviors in PE classes. However, the effects of the strategy on students’ positive behaviors (e.g., following rules, helping others, and cooperation) showed no improvement. This study made a breakthrough by finding that integrating MD minimization strategies could make TPSR more effective at reducing students’ misbehaviors. By understanding the psychosocial mechanisms behind student behavior in PE, we suggest that MD minimization strategies could be applied in the TPSR model.

Background/purpose: Early initiation of antiretroviral therapy (ART) reduces the risks for serious infections and mortality. We aimed to assess the outcomes of initiating ART among HIV-positive Taiwanese according to the CD4 cut-off values by the WHO recommendations. Methods: We reviewed medical records of patients with newly diagnosed HIV infection between 2004 and 2015 and 3 groups of patients were defined according to the timing of ART initiation based on CD4 count recommended by WHO: Group 1 between 2004 and 2009; Group 2 between 2010 and 2012; and Group 3 between 2013 and 2015. The primary outcome was all-cause mortality. All patients were followed until 2 years after the last patient was included in each group. Results: Of 2022 patients included, the mortality rate was 18.28, 14.01, and 9.10 deaths per 1000 person-years of follow-up (PYFU) in Groups 1, 2, and 3, respectively. In multivariable Cox regression analysis, factors associated with mortality were age (per 1-year increase, adjusted hazard ratio [AHR], 1.06; 95% CI, 1.05–1.08), presence of AIDS-defining disease at HIV diagnosis (AHR, 4.81; 95% CI, 2.99–7.74), solid-organ malignancy (AHR, 3.10; 95% CI, 1.86–5.18), and initiation of ART (AHR, 0.09; 95% CI, 0.05–0.16). By competing risk regression model for non-AIDS-related death, the AHR for Group 3 versus Group 1 was 0.27 (95% CI, 0.09–0.80). Conclusions: While continued efforts are needed to improve early diagnosis and linkage to care, initiation of cART improved survival among HIV-positive patients in Taiwan according to the increasing CD4 cut-off values that were recommended by the WHO.

Abstract The silkworm (Bombyx mori) and its pupae have been used for decades as nutritional additives and applied on the production of high-quality recombinant proteins via the baculovirus expression vector (BEV) system. The bio-capsule, the fat-rich body, and some body components of the silkworm pupae, which deliver antigens passing through the harsh environment of digestive tract and reaching the intestine, have been used as a vehicle for oral vaccines. In the present study, to develop a novel oral vaccine against porcine epidemic diarrhea virus (PEDV), the PEDV spike (S) protein was expressed in silkworm pupae and BmN cells using the BEV system. After three doses of oral administrations with 2-week intervals in pigs, neither PEDV S protein-specific humoral nor mucosal immune responses can be detected. The failure of eliciting the PEDV-specific immune response suggested that the BEV system using BmN cells or silkworm pupae as oral immunogen-expression vehicles was not able to overcome the immunological unresponsiveness, which was possibly due to gastrointestinal specific barriers and oral tolerance. Better strategies to enhance the delivery and immunogenicity of oral vaccines should be further investigated. Nevertheless, the PEDV S protein generated in the BmN cells and silkworm pupae herein provides an efficient tool to produce the recombinant antigen for future applications.

Background: Lifelong antiretroviral therapy (ART) is recommended for HIV-1 infected patients but may lead to intolerance or poor adherence. Structured treatment interruption (STI) is a strategy for drug holiday or to boost HIV-specific immunity. But the long-term outcome of STI was never reported in literature. Methods: This is a single-center observational study. We followed the HIV-infected patients who already had a stable viral suppression and voluntarily started temporary STI with a fixed 12-week interval after counseling, evaluation and education. HIV-1-specific T cell response was also measured in some patients. Results: Totally 34 HIV-infected patients received temporary STI since July, 2006. 18 patients completed 10-year follow-up. All patients received protease inhibitors (PI)-based ART before and during temporary STI. The patients received temporary STI with a period of 36–85 weeks. All of them reached viral suppression after 12 weeks of restarting continuous ART. No viral rebound or opportunistic disease was recorded during follow-up. No adverse event or comorbidity was attributed to STI. The plasma viral load (PVL) at the end of STI was significantly lower than baseline PVL in patients with a longer duration of STI (≤36 weeks vs. >36 weeks, P = 0.005). The T cell response study revealed that cyclically increased HIV-1-specific T cell response after starting STI in patients with baseline CD4+ count >350/μL. Conclusion: Temporary STI may not lead to worse long-term outcome among highly selected patients. The policy may partially control viral replication through reminding the HIV-1 specific T cell immunity. Keywords: HIV-1, Antiretroviral treatment (ART), Structured treatment interruption (STI)

Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an ongoing pandemic. Detection and vaccination are essential for disease control, but they are distinct and complex operations that require significant improvements. Here, we developed an integrated detection and vaccination system to greatly simplify these efforts. We constructed recombinant baculoviruses to separately display the nucleocapsid (N) and spike (S) proteins of SARS-CoV-2. Insect cells infected by the recombinant baculoviruses were used to generate a cell-based system to accurately detect patient serum. Notably, although well-recognized by our newly developed detection system in which S-displaying insect cells acted as antigen, anti-S antibodies from many patients were barely detectable by Western blot, evidencing that COVID-19 patients primarily produce conformation-dependent anti-S antibodies. Furthermore, the same baculovirus constructs can display N (N-Bac) or S (S-Bac) on the baculovirus envelope and serve as vector vaccines. Animal experiments show that S-Bac or N-Bac immunization in mice elicited a strong and specific antibody response, and S-Bac in particular stimulated effective neutralizing antibodies without the need for adjuvant. Our integrated system maintains antigen conformation and membrane structure to facilitate serum detection and antibody stimulation. Thus, compared with currently available technologies, our system represents a simplified and efficient platform for better SARS-CoV-2 detection and vaccination.

Our previous studies demonstrated that collapsin response mediator protein 2 (CRMP2) is associated with obesity and, in addition, that hyperglycemia-suppressed CRMP2 augments malignant traits of colorectal cancer and is associated with advanced tumor stage. Regulation of CRMP2 profile was further explored in this study using 3T3-L1 pre-adipocyte adipogenesis as a study model for illustrating the roles of CRMP2 in metabolic homeostasis. Hyperglycemia inhibited expression of CRMP2, adipogenic machinery and adipocyte markers. CRMP2 displayed f-CRMP2 (62~66 kDa) and s-CMRP2 (58 kDa) isoforms at the growth arrest phase. Expression of s-CRMP2 was coupled with the mitotic clonal expansion (MCE) phase to direct cell proliferation and rapidly down-regulated in post-mitotic cells. In the late differentiation phase, f-CRMP2 was co-localized with tubulin in the cortical area. Insulin-enhanced CRMP2-glucose transporter 4 (GLUT4) co-localization and CRMP2 puncta on lipid droplets (LDs) suggested participation of CRMP2 in GLUT4 translocation and LD fusion. Collectively, the CRMP2 functional profile must be finely controlled to adjust cytoskeletal stability for meeting dynamic cellular needs. Manipulating the s-CRMP2/f-CRMP2 ratio and thus the cytoskeleton dynamics is anticipated to improve glucose uptake and insulin sensitivity. In summary, our data provide molecular evidence explaining the functions of CRMP2 in physiological, pathological and disease progression in metabolic homeostasis and disorders related to metabolic abnormalities, including cancer.

Recent outbreaks of enterically transmitted infections, including acute hepatitis A and shigellosis, have raised the concerns of increasing Entamoeba histolytica infection (EHI) among people living with HIV (PLWH) in Taiwan. This study investigated the prevalence of EHI, its temporal trends, and associated factors among newly diagnosed PLWH in Taiwan. Medical records of newly diagnosed PLWH at six medical centers in Taiwan between 2009 and 2018 were reviewed. The annual prevalence of invasive amoebiasis and seroprevalence of E. histolytica were determined and examined by the Cochran-Armitage test. The clinical characteristics associated with invasive amoebiasis and seropositivity for E. histolytica were analyzed in multivariable regression models. Among 5362 patients seeking HIV care at six medical centers in Taiwan during the 10-year study period, 119 (2.2%) had invasive amoebiasis at the time or within six months of their HIV diagnosis. Among 3499 who had indirect hemagglutination antibody (IHA) determined, 284 (8.1%) had positive IHA (≥1:32) and 205 (5.9%) had high-titre IHA (≥1:128). The prevalence of invasive amoebiasis increased from 1.3% in 2012 to 3.3% in 2018 (p = 0.024). Invasive amoebiasis was independently associated with a greater age, men who have sex with men, rapid plasma reagin titre ≥1:4, and concurrent shigellosis and giardiasis. Increasing prevalence of invasive amoebiasis among newly diagnosed PLWH in Taiwan calls for strategies to prevent ongoing transmission in this population. Routine screening of EHI for early diagnosis and treatment is recommended, especially among men who have sex with men and those who present with other sexually or enterically transmitted infections.

The interlayer coupling in van der Waals heterostructures is sensitive to the interlayer atomic registry. Here, the authors investigate the polarisation properties of epitaxially grown, commensurate WSe2/MoSe2 heterobilayers with well-defined atomic registry, and observe negative, circularly polarized photoluminescence from interlayer excitons.

Monolayer transition metal dichalcogenides have so far been thought to be direct bandgap semiconductors. Here, the authors revisit this assumption and find that unstrained monolayer WSe2 is an indirect-gap material, as evidenced by the observed photoluminescence intensity-energy correlation.

Porcine epidemic diarrhea virus (PEDV) is a coronavirus that causes serious and highly contagious enteric disease in swine worldwide. In this study, we constructed a recombinant baculovirus (S-Bac) expressing full-length spike protein of the virulent epidemic genotype 2b (G2b) PEDV strain for serological studies of infected pigs. We found that most spike-specific antibodies produced upon PEDV infection in pigs are conformation-specific and they could be detected on S-Bac-infected insect cells by immunofluorescent assay, but they were insensitive to Western blot analysis, the typical method for antiserum analysis. These results indicated that spike conformation is crucial for serum recognition. Since it is difficult to purify trimeric spike membrane protein for conventional enzyme-linked immunosorbent assay (ELISA), we used S-Bac to generate a novel cell-based ELISA for convenient PEDV detection. We analyzed 100 pig serum samples, and our cell-based ELISA exhibited a sensitivity of 100%, a specificity of 97%, and almost perfect agreement [Cohen’s kappa coefficient value (κ) = 0.98] with immunocytochemical staining results. Our cell-based ELISA rapidly presented antigen for proper detection of conformation-specific antibodies, making PEDV detection more convenient, and it will be useful for detecting many viral diseases in the future.

This paper reassesses the detrimental effect on fatigue performance of welded structural steel joints due to thicker sections based on an extensive fatigue strength test database, taken from research programmes worldwide over the past half century, mostly from the offshore oil and gas and marine industries. The data entries in the database were evaluated to ensure its data integrity. Statistical analyses on these S-N data were performed with or without the thickness correction at different exposure levels to a corrosive environment, in order to re-evaluate the suitability of current standards in regard to the thickness effect. The study concentrated on T-joints, transverse butt-welded joints and tubular joints, as these are the most commonly used joint types in the offshore wind industry. The analysis indicates a general agreement of fatigue strength with the thickness effects in current standards for in-air conditions, but great conservatism for corrosive environments. In addition, the statistical models determined in this study can be used for a broader range of studies, such as probabilistic fatigue analysis.

Purpose: This study investigated the effects of a Teaching Personal and Social Responsibility (TPSR)-based physical education (PE) program on students' responsibility and tripartite efficacy beliefs (i.e., self-efficacy, other-efficacy, and relation-inferred self-efficacy (RISE)). Methods: A quasiexperimental design with pretest and posttest quantitative methods was applied. The participants were 114 students assigned to the control or experimental group. Results: The results indicated that compared with both control group students and their own baseline values, the experimental group reported significant improvements in responsibility, self-efficacy, other-efficacy, and RISE. Conclusions: Implementing the TPSR model in PE can not only positively affect students' responsibility but also boost students' efficacy beliefs through the model's five formats (e.g. awareness talk) and application strategies (e.g. empowerment). PE educators are encouraged to strictly comply with implementing details of the TPSR model to effectively improve efficacy beliefs.

Many mini-implantable devices have been developed and fabricated for diagnostic and treatment purposes. Wireless implantable biomicrosystems provide a desirable approach for long-term physiological signal monitoring. In this study, we implemented a wireless implantable biomicrosystem for bladder-cavity pressure measurements in a freely moving rabbit. To manage the power more effectively, a magnetic reed switch was applied to turn on/off the implantable module using a neodymium–iron–boron (NdFeB) magnet. The measured bladder pressure signal was wirelessly transmitted from the implantable module to a host unit. Our results indicated that the implantable biomicrosystem exhibited satisfactory performance and safety, as evidenced by an error percentage of less than ±1% for pressure measurements and less than 2 °C of a temperature rise under normal operation. The wireless biomicrosystem was implanted into the bladder cavity of a rabbit. Bladder pressure was simultaneously measured by both the biomicrosystem and conventional cystometry in the animal. The two signals were similar during the voiding phase, with a correlation coefficient of 0.885. Additionally, the biomicrosystem coated with polydimethylsiloxane in this study showed no cytotoxicity, which confirmed its biocompatibility. In conclusion, we demonstrated a good biocompatible wireless biomicrosystem which showed good reproducibility with respect to pressure monitoring by conventional cystometry. Further studies are needed to confirm the results of this preliminary feasibility study for actual clinical applications.

As emerging evidence suggesting neurodegenerative diseases and metabolic diseases have common pathogenesis, we hypothesized that the neurite outgrowth-controlling collapsin response mediator protein 2 (CRMP2) was involved in energy homeostasis. Therefore, putative roles of CRMP2 in adipocyte differentiation (adipogenesis) and lipid metabolism were explored and addressed in this study. CRMP2 expression profiles were in vitro and in vivo characterized during adipogenic process of 3T3-L1 pre-adipocytes and diet-induced obese (DIO) mice, respectively. Effects of CRMP2 on lipid metabolism and deposits were also analyzed. Our data revealed that CRMP2 expression pattern was coupled with adipogenic stages. CRMP2 overexpression inhibited cell proliferation at MCE phase, and significantly reduced lipid contents by down-regulating adipogenesis-driving transcription factors and lipid-synthesizing enzymes. Interestingly, GLUT4 translocation and the lipid droplets fusion were disturbed in CRMP2-silencing cells by affecting actin polymerization. Moreover, adipose CRMP2 was significantly increased in DIO mice, indicating CRMP2 is associated with obesity. Accordingly, CRMP2 exerts multiple functions in adipogenesis and lipid deposits through mediating cell proliferation, glucose/lipid metabolism and cytoskeleton dynamics. The present study identifies novel roles of CRMP2 in mediating adipogenesis and possible implication in metabolic disorders, as well as provides molecular evidence supporting the link of pathogenesis between neurodegenerative diseases and metabolic abnormalities.

Retropharyngeal abscess is occasionally seen in children, but is less common in adults where it usually occurs secondary to iatrogenic oropharynx trauma or a perforated foreign body in the oropharynx. Spinal epidural abscess in combination with a retropharyngeal abscess, which may cause rapid and irreversible neurological deterioration, is not often found, as indicated by the very few reports in the literature. Here we report a 52-year-old male with a clinical history of seizure and mental retardation since childhood who presented at our emergency room with severe sore throat of 1 day’s duration. A chicken bone was removed successfully. However, he complained of progressive dysphagia, sore throat and posterior neck pain during the following 5 days. Flexible fiber-laryngoscopy showed bulging of the retropharyngeal wall and a small ulcer at the right posterior pharyngeal wall. A neck computed tomography (CT) scan showed a retropharyngeal abscess at the oropharynx and hypopharynx level. His symptoms showed partial improvement after the administration of intravenous antibiotics. However, 2 weeks later he developed high fever, posterior neck pain and flaccid tetra-paresia. Emergent neck CT scan revealed a mild retropharyngeal abscess and epidural abscess formation between the second and third cervical vertebrae. The patient’s family refused drainage of the pre-vertebral and epidural pus. After receiving 2 months of antibiotics, the patient regained the mobility of his limbs

A new variant of the porcine epidemic diarrhea virus (PEDV) is an emerging swine disease, killing considerable numbers of neonatal piglets in North America and Asia in recent years. To generate immunogens mimicking the complex spike (S) protein folding with proper posttranslational modification to mount a robust immune response against the highly virulent PEDV, two baculoviruses displaying the full-length S protein (S-Bac) and the S1 protein (S1-Bac) of the virulent Taiwan genotype 2b (G2b) PEDV Pintung 52 (PEDV-PT) strain were constructed. Intramuscular immunizations of mice and piglets with the S-Bac and S1-Bac demonstrated significantly higher levels of systemic anti-PEDV S-specific IgG, as compared with control group. Our results also showed that piglets in the S-Bac group elicited superior PEDV-specific neutralizing antibodies than those of the S1-Bac and control groups. The highly virulent PEDV-PT strain challenge experiment showed that piglets immunized with S-Bac and S1-Bac showed milder clinical symptoms with significantly less fecal viral shedding as compared with non-immunized control piglets. More importantly, piglets immunized with the S-Bac exhibited no to mild clinical signs, with a delayed, minimal viral shedding. Our results demonstrated that the S-Bac could serve as a safe, easy to manipulate, and effective vaccine candidate against the PEDV infection.

This work experimentally investigated the fluid flow and heat transfer characteristics of the pin-fin heat sink with the oscillating air flow. The oscillating air flow would be unstable in the passages among the fins due to the periodical change of flow rate. It might enhance the overall heat-transfer performance. At the present study, the pin-fin heat sinks with various fin heights were installed in the rectangular channel, resulting in different bypass clearances between the pin fins and the shroud of the test channel. The smoke flow visualizations for the oscillating-flow system were completed. The heat-transfer tests under the asymmetrically heated condition were performed to obtain the average Nusselt numbers. The smoke lines with obvious waves in the transverse direction were found in the results of the flow visualizations. By comparing to the steady flow system, there was about 20∼34% increment in the overall heat-transfer performance at the operating state without bypass clearance. However, if the bypass clearance was too big, the heat-exchange capacity of the oscillating flow was less than that of the steady flow. It demonstrates that the oscillating flow promotes the cooling performance of pin-fin heat sink at the non-bypass and specified bypass conditions.

Nature Communications 6: Article number: 8963 (2015); Published: 25 November 2015; Updated: 1 February 2016 The original version of this Article contained a typographical error in the spelling of the author Chang-Hsiao Chen, which was incorrectly given as Chiang-Hsiao Chen. This has now been corrected in both the PDF and HTML versions of the Article.