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A series of bifunctional compounds have been discovered for their dual functionality as MER/AXL inhibitors and immune modulators. The furanopyrimidine scaffold, renowned for its suitability in kinase inhibitor discovery, offers at least three distinct pharmacophore access points. Insights from molecular modeling studies guided hit-to-lead optimization, which revealed that the 1,3-diketone side chain hybridized with furanopyrimidine scaffold that respectively combined amino-type substituent and 1H-pyrazol-4-yl substituent on the top and bottom of the aryl regions to produce 22 and 33, exhibiting potent antitumor activities in various syngeneic and xenograft models. More importantly, 33 demonstrated remarkable immune-modulating activity by upregulating the expression of total T-cells, cytotoxic CD8+ T-cells, and helper CD4+ T-cells in the spleen. These findings underscored the bifunctional capabilities of 33 (BPR5K230) with excellent oral bioavailability (F = 54.6%), inhibiting both MER and AXL while modulating the tumor microenvironment and highlighting its diverse applicability for further studies to advance its therapeutic potential.
Subject(s)
Antineoplastic Agents , Axl Receptor Tyrosine Kinase , Protein Kinase Inhibitors , Proto-Oncogene Proteins , Receptor Protein-Tyrosine Kinases , Tumor Microenvironment , c-Mer Tyrosine Kinase , Animals , Tumor Microenvironment/drug effects , Humans , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/metabolism , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/metabolism , c-Mer Tyrosine Kinase/antagonists & inhibitors , c-Mer Tyrosine Kinase/metabolism , Mice , Cell Line, Tumor , Structure-Activity Relationship , Drug Discovery , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemistry , Small Molecule Libraries/chemical synthesis , Female , Xenograft Model Antitumor Assays , Mice, Inbred BALB C , Cell Proliferation/drug effectsABSTRACT
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic Lactiplantibacillus plantarum PS128 (PS128) alleviates ASD symptoms in children. However, the mechanism underlying this improvement in ASD-associated behaviors remains unclear. Here, we used a well-established ASD mouse model, induced by prenatal exposure to valproic acid (VPA), to study the physiological roles of PS128 in vivo. Overall, we showed that PS128 selectively ameliorates behavioral abnormalities in social and spatial memory in VPA-induced ASD mice. Morphological examination of dendritic architecture further revealed that PS128 facilitated the restoration of dendritic arborization and spine density in the hippocampus and prefrontal cortex of ASD mice. Notably, PS128 was crucial for restoring oxytocin levels in the paraventricular nucleus and oxytocin receptor signaling in the hippocampus. Moreover, PS128 alters the gut microbiota composition and increases the abundance of Bifidobacterium spp. and PS128-induced changes in Bifidobacterium abundance positively correlated with PS128-induced behavioral improvements. Together, our results show that PS128 treatment can effectively ameliorate ASD-associated behaviors and reinstate oxytocin levels in VPA-induced mice, thereby providing a promising strategy for the future development of ASD therapeutics.
Subject(s)
Autism Spectrum Disorder , Disease Models, Animal , Probiotics , Social Behavior , Animals , Autism Spectrum Disorder/therapy , Autism Spectrum Disorder/microbiology , Mice , Probiotics/administration & dosage , Female , Male , Valproic Acid , Gastrointestinal Microbiome , Behavior, Animal/drug effects , Mice, Inbred C57BL , Hippocampus/metabolism , Pregnancy , Oxytocin/metabolism , Prefrontal Cortex/metabolism , Lactobacillus plantarum/physiology , HumansABSTRACT
Sn-3Ag-0.5Cu (SAC305)- and Sn-9Zn-based alloys (Sn-Zn-X, X = Al, In) are lead-free solders used in the fabrication of solder joints with Cu metallization. Electroplating is a facile technology used to fabricate Cu metallization. However, the addition of functional additive molecules in the plating solution may result in impurity residues in the Cu electroplated layer, causing damage to the solder joints. This study investigates the impurity effect on solder joints constructed by joining various solder alloys to the Cu electroplated layers. Functional additives are formulated to fabricate high-impurity and low-impurity Cu electroplated samples. The as-joined solder joint samples are thermally aged at 120 °C and 170 °C to explore the interfacial reactions between solder alloys and Cu. The results show that the impurity effect on the interfacial reactions between SAC305 and Cu is significant. Voids are massively formed at the SAC305/Cu interface incorporated with a high impurity content, and the Cu6Sn5 intermetallic compound (IMC) grows at a faster rate. In contrast, the growth of the Cu5Zn8 IMC formed in the SnZn-based solder joints is not significantly influenced by the impurity content in the Cu electroplated layers. Voids are not observed in the SnZn-based solder joints regardless of the impurity content, indicative of an insignificant impurity effect. The discrepancy of the impurity effect is rationalized by the differences in the IMC formation and associated atomic interdiffusion in the SAC305- and SnZn-based solder joints.
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In response to the increasing number of carbapenem-resistant Enterobacterales (CRE), we investigated carbapenemase-producing Klebsiella pneumoniae and non-K. pneumoniae epidemiology and genetics. We collected 76 clinical Enterobacterales and 4 stool surveillance Escherichia coli isolates resistant to ertapenem or imipenem. Using polymerase chain reaction (PCR) and DNA sequencing, we assessed carbapenemases, extended-spectrum ß-lactamases, and AmpC ß-lactamases. Molecular typing via pulsed-field gel electrophoresis (PFGE) and conjugation experiments were conducted to examine resistance gene transfer. Among the 80 isolates, 96.2% harbored at least one carbapenemase gene, with blaOXA-48 in 87.5%. KPC-2 and IMP-8 carbapenemases were found in 15.0 and 22.5% of the isolates, respectively, with 27.5% having 2 or more carbapenemase genes. The PFGE analysis revealed the presence of diverse genotypes. PCR-based plasmid replicon typing identified IncA/C as the most prevalent type among K. pneumoniae isolates (26/29), and IncF and IncFIB among E. coli isolates (22/28). Conjugal transfer was successful for plasmids encoding OXA-48, CTX-M-3, CTX-M-14, CMY-2, and other ß-lactamases, except the KPC-2 gene. In conclusion, our study highlights high carbapenemase prevalence in CRE, primarily OXA-48. Multiple carbapenemases within strains were common, and PFGE showed diverse patterns in these carbapenem-resistant isolates.
Subject(s)
Carbapenems , Escherichia coli , Carbapenems/pharmacology , Escherichia coli/genetics , Prevalence , Taiwan/epidemiology , Bacterial Proteins/genetics , beta-Lactamases/genetics , Klebsiella pneumoniae/genetics , Hospitals , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacologyABSTRACT
Carbapenem-resistant ST11_KL64 Klebsiella pneumoniae emerged as a significant public health concern in Taiwan, peaking between 2013 and 2015, with the majority of isolates exhibiting OXA-48 as the sole carbapenemase. In this study, we employed whole-genome sequencing to investigate the molecular underpinnings of ST11_KL64 isolates collected from 2013 to 2021. Phylogenomic analysis revealed a notable genetic divergence between the ST11_KL64 strains in Taiwan and those in China, suggesting an independent evolutionary trajectory. Our findings indicated that the ST11_KL64_Taiwan lineage originated from the ST11_KL64 lineage in Brazil, with recombination events leading to the integration of ICEKp11 and a 27-kb fragment at the tRNAASN sites, shaping its unique genomic landscape. To further elucidate this unique sublineage, we examined the plasmid contents. In contrast to ST11_KL64_Brazil strains, which predominantly carried blaKPC-2, ST11_KL64_Taiwan strains exhibited the acquisition of an epidemic blaOXA-48-carrying IncL plasmid. Additionally, ST11_KL64_Taiwan strains consistently harbored a multi-drug resistance IncC plasmid, along with a collection of gene clusters that conferred resistance to heavy metals and the phage shock protein system via various Inc-type plasmids. Although few, there were still rare ST11_KL64_Taiwan strains that have evolved into hypervirulent CRKP through the horizontal acquisition of pLVPK variants. Comprehensive characterization of the high-risk ST11_KL64 lineage in Taiwan not only sheds light on its epidemic success but also provides essential data for ongoing surveillance efforts aimed at tracking the spread and evolution of ST11_KL64 across different geographical regions. Understanding the molecular underpinnings of CRKP evolution is crucial for developing effective strategies to combat its emergence and dissemination.
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An acyl radical reaction of bicyclo[2.2.2]octenone to yield either rearranged or cyclized isotwistane products is described. The influence of ring strain on the reaction was demonstrated by alternating the sizes of the fused ring in the starting material. DFT calculations showed that the reaction is under thermodynamic control and proceeds via a 5-exo-trig cyclization intermediate, which undergoes either hydrogen-atom transfer (HAT) to give a cyclized product or rearrangement via a twistane intermediate to give a rearranged product.
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Purpose: The prevalence of children myopia in Taiwan is among the highest in the world. The study aimed to understand the status of the final prescription of the spectacle prescribed by the Taiwan optometrists when they conducted the visual inspection of elementary school, middle school and high school students, and to evaluate the influencing factors of their decision-making behavior. Methods: Among the attendants of the continuing education course activities held by optometrist associations in Taiwan, an anonymous questionnaire survey was given on the spot to optometrists who have passed the national examination. This study received 442 questionnaire surveys, including 174 optometrists and 268 assistant optometrists. The data were analyzed by using chi-square test in IBM SPSS. Results: There are statistically significant differences in the decision-making of spectacle prescription for myopia of -1.00D~-1.50D and -2.25D~-2.50D in the primary school stage between optometrists and assistant optometrists. There are also significant differences for myopia of -2.25D and above in the middle school students. By the time of high school, there are significant differences for myopia from -0.75D to -3.25D and above. The higher the grade, the greater the difference in the final prescription of the spectacles given. As for the judgment factors of the final prescription, only children among elementary school and junior high school show a statistically significant difference in professional judgment between optometrists and assistant optometrists. There is no significant difference in the judgment factors for high school children. Depending on the educational level of optometrists and assistant optometrists and their distribution area, the prescription decisions are also different. Conclusion: The optometrists prefer to prescribe full correction for schoolchildren, while the assistant optometrists mostly prescribe under-correction in prescriptions for low-degree myopia and lower grades. Further investigation is needed to study its impact on children's visual health.
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Long-term potentiation (LTP) is one of the major cellular mechanisms for learning and memory. Activity-dependent increases in surface AMPA receptors (AMPARs) are important for enhanced synaptic efficacy during LTP. Here, we report a novel function of a secretory trafficking protein, ICA69, in AMPAR trafficking, synaptic plasticity, and animal cognition. ICA69 is first identified as a diabetes-associated protein well characterized for its function in the biogenesis of secretory vesicles and trafficking of insulin from ER, Golgi to post-Golgi in pancreatic beta cells. In the brain, ICA69 is found in the AMPAR protein complex through its interaction with PICK1, which binds directly to GluA2 or GluA3 AMPAR subunits. Here, we showed that ICA69 regulates PICK1's distribution in neurons and stability in the mouse hippocampus, which in turn can impact AMPAR function in the brain. Biochemical analysis of postsynaptic density (PSD) proteins from hippocampi of mice lacking ICA69 (Ica1 knockout) and their wild-type littermates revealed comparable AMPAR protein levels. Electrophysiological recording and morphological analysis of CA1 pyramidal neurons from Ica1 knockout also showed normal AMPAR-mediated currents and dendrite architecture, indicating that ICA69 does not regulate synaptic AMPAR function and neuron morphology at the basal state. However, genetic deletion of ICA69 in mice selectively impairs NMDA receptor (NMDAR)-dependent LTP but not LTD at Schaffer collateral to CA1 synapses, which correlates with behavioral deficits in tests of spatial and associative learning and memory. Together, we identified a critical and selective role of ICA69 in LTP, linking ICA69-mediated synaptic strengthening to hippocampus-dependent learning and memory.
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Electroplated Cu has been extensively applied in advanced electronic packaging, and its mechanical properties are critical for reliability. In this study, Cu foils fabricated through electroplating with various bis-(3-sulfopropyl) disulfide (SPS) concentrations are examined using tensile tests. The SPS concentration affects the grain size of the electroplated Cu foils, resulting in different mechanical properties. A significant Hall-Petch effect, [Formula: see text], is demonstrated for the electroplated Cu foils. The different concentrations of impurities identified through time-of-flight secondary ion mass spectrometry correspond to the different grain sizes, determining the transgranular and intergranular fracture during the tensile test. The results demonstrate that the SPS concentration controlling the microstructures of the electroplated Cu results in a Hall-Petch effect on the mechanical properties of the electroplated Cu foils.
Subject(s)
Copper , Disulfides , Reproducibility of Results , Drug Packaging , Edible GrainABSTRACT
BACKGROUND: Chronic kidney disease (CKD) has a strong negative impact on patients. Finding ways to improve CKD patients' conditions by shared decision-making is receiving much attention. However, little attention has been paid to influencing antecedents and effects of shared decision-making. Meanwhile, as advanced technologies bring in new communication devices, effects of different types of communications used in shared decision-making need to be addressed. OBJECTIVE: This study proposes a research framework to determine the influencing antecedents of shared decision-making, and to evaluate the effects of shared decision-making on patient outcomes when they are computer-mediated and when the decision-makers communicate face-to-face. METHODS: A cross-section survey was conducted and a total of 48 valid samples were obtained. The participants were CKD Stage III, IV, or V patients who had received medical treatment in a hospital in Taiwan. The collected data were subjected to an independent t-test and partial least squares analysis to validate the research framework. RESULTS: Doctor-patient communication (DPC) and doctor-patient relationship (DPR) have no significant direct impact on patient outcomes. Nevertheless, both DPC and DPR significantly impact shared decision-making which in turn impacts patient outcomes. Moreover, patients who use computer-mediated communication were found to have significantly higher perceptions of shared decision-making than those who did not. CONCLUSIONS: The incidence and prevalence of end-stage renal disease in Taiwan are among the highest in the world. The results of this study can serve as a reference for hospitals to improve CKD patients' outcomes. Meanwhile, during the COVID-19 pandemic, this study suggested hospitals should encourage shared decision-making with computer-mediated communication to ensure that patients receive proper treatment and have the desired outcomes.
Subject(s)
COVID-19 , Renal Insufficiency, Chronic , Humans , Decision Making, Shared , Physician-Patient Relations , Cross-Sectional Studies , Decision Making , Pandemics , Communication , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Patient ParticipationABSTRACT
The performance improvement of advanced electronic packaging material is an important topic to meet the stringent demands of modern semiconductor devices. This paper studies the incorporation of nano-alumina powder and thermoplastic elastomer (TPE) into thermoplastic polystyrene matrix to tune the thermal and mechanical properties after injection molding process. In the sample preparation, acetone was employed as a solvent to avoid the powder escape into surrounding during the mechanical mixing in a twin-screw mixer. The pressure and shear force were able to mix the composite with good uniformity in compositions. The samples with different compositions were fabricated using injection molding. The measured results showed that adding 5 wt.% of TPE into the simple polystyrene was able to raise the melt flow index from 12.3 to 13.4 g/10 min while the thermal decomposition temperature remained nearly unchanged. Moreover, the addition of small amount of nano-alumina powder could quickly improve the mechanical property by raising its storage modulus. For example, the addition of 3 wt.% of nano-alumina powder had an increase of 7.3% in storage modulus. Over doping of nano-alumina powder in the composite, such as 10 wt.%, on the other hand, lowered the storage modulus from 2404 MPa to 2069 MPa. The experimental study demonstrated that the tuning in the polystyrene's thermal and mechanical properties is feasible by composition modification with nano-alumina powder and TPE. The better concentration of the additives should be determined according to the specific applications.
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Solder/Cu joints are important components responsible for interconnection in microelectronics. Construction of the solder/Cu joints through liquid/solid (L/S) reactions accompanies the formation of the Cu-Sn intermetallic compounds (IMCs) at the joint interface. The Cu6Sn5 IMC exhibits remarkable distinctions in thickness and morphology upon increasing the L/S reaction time. Effects of the initial characteristics of thickness and morphology on the growth kinetics of Cu6Sn5 during subsequent isothermal aging were investigated. SAC305 solder was reflowed on a Cu electroplated layer at 265 °C for 1 to 60 min to produce the Cu6Sn5 IMC with different thickness and morphology at the SAC305/Cu interface. The as-fabricated SAC305/Cu joint samples were aged at 200 °C for 72 to 360 h to investigate the growth kinetics of Cu6Sn5. The results show that the initial characteristics of thickness and morphology significantly influenced the growth kinetics of Cu6Sn5 during the subsequent solid/solid (S/S) reaction. A prolonged L/S reaction time of 60 min (L/S-60) produced a scallop-type Cu6Sn5 IMC with a larger grain size and a thicker thickness, which reduced the quantity of fast diffusion path (grain boundary) and the magnitude of concentration gradient, thus slowing down the growth rate of Cu6Sn5. According to the growth kinetics analysis, the growth rate constant of Cu6Sn5 could be remarkably reduced to 0.151 µm/h0.5 for the L/S-60 sample, representing a significant reduction of 70 % compared to that of the L/S-1 sample (0.508 µm/h0.5 for L/S reaction time of 1 min).
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Covalent organic frameworks (COFs) are of great interest in the energy and optoelectronic fields due to their high porosity, superior thermal stability, and highly ordered conjugated architecture, which are beneficial for charge migration, charge separation, and light harvesting. In this study, polyimide COFs (PI-COFs) are synthesized through the condensation reaction of pyromellitic dianhydride (PMDA) with tris(4-aminophenyl) amine (TAPA) and then doped in the TiO2 photoelectrode of a dye-sensitized solar cell (DSSC) to co-work with N719 dye to explore their functionality. As a benchmark, the pristine DSSC without the doping of PI-COFs exhibits a power conversion efficiency of 9.05% under simulated one sun illumination. The doping of 0.04 wt % PI-COFs contributes an enhanced short-circuit current density (JSC) from 17.43 to 19.03 mA/cm2, and therefore, the cell efficiency is enhanced to 9.93%. The enhancement of JSC is attributed to the bifunctionality of PI-COFs, which enhances the charge transfer/injection and suppresses the charge recombination through the host (PI-COF)-guest (N719 dye) interaction. In addition, the PI-COFs also function as a cosensitizer and contribute a small quantity of photoinduced electrons upon sunlight illumination. Surface modification of oxygen plasma improves the hydrophilicity of PI-COF particles and reinforces the heterogeneous linkage between PI-COF and TiO2 nanoparticles, giving rise to more efficient charge injection. As a result, the champion cell exhibits a high power conversion efficiency of 10.46% with an enhanced JSC of 19.43 mA/cm2. This methodology of increasing solar efficiency by modification of the photoelectrode with the doping of PI-COFs in the TiO2 nanoparticles is promising in the development of DSSCs.
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BACKGROUND: Castration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4AâKDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC. METHODS: In this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts. RESULTS: Myricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone. CONCLUSIONS: These results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC.
Subject(s)
Antineoplastic Agents , Biological Products , Flavonoids , Prostatic Neoplasms, Castration-Resistant , Androgens/pharmacology , Androgens/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Cell Line, Tumor , Cell Proliferation , Drug Resistance, Neoplasm , Flavonoids/pharmacology , Glycolates , Glycols/pharmacology , Glycols/therapeutic use , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/pharmacology , Male , Nitriles/pharmacology , Nitriles/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Receptors, Androgen/therapeutic useABSTRACT
OBJECTIVES: A nosocomial salmonellosis outbreak caused by Salmonella enterica serovar Goldcoast occurred in a respiratory care ward (RCW) of a hospital in central Taiwan between December 24, 2020, and January 21, 2021. Ten isolates recovered from 10 RCW residents were resistant to extended-spectrum cephalosporins. The resistance mechanism needs to be investigated. METHODS: Whole-genome sequencing and antimicrobial susceptibility testing were conducted to determine the genetic resistance determinants and the phenotypic resistance in the isolates. RESULTS: Each of the 10 outbreak isolates harbored an IncHI2 plasmid that carried 15 antimicrobial resistance genes aac(3)-IId, aadA22, aph(3')-Ia, aph(6)-Id, arr-2, blaCTX-M-55, blaLAP-2, blaTEM-1, dfrA14, floR, lnu(F), qnrS13, sul2, sul3, tet(A), an efflux pump regulatory gene ramAp and an IncL plasmid carried a blaOXA-48. The outbreak strains were expected to be resistant to numerous antimicrobials, including aminoglycosides, b-lactams /inhibitors, tetracycline, rifamycin, lincosamide, sulfonamides, trimethoprim, phenicols, fluoroquinolones, and carbapenems. Two outbreak isolates displayed higher minimum inhibitory concentrations than the other eight isolates to cefmetazole and carbapenems, which was linked to a deficiency of a major facilitator superfamily transporter in the two isolates. CONCLUSION: The carbapenem-resistant outbreak strains could have been derived from extensively drug-resistant S. enterica Goldcoast strains, which have been a major pathogen in Taiwan since 2018, through the acquisition of a blaOXA-48-carrying plasmid. Special efforts are needed in Taiwan to monitor the spread of extremely resistant strains.
Subject(s)
Cross Infection , Salmonella Infections , Salmonella enterica , Anti-Bacterial Agents/pharmacology , Carbapenems/pharmacology , Cross Infection/epidemiology , Disease Outbreaks , Drug Resistance, Multiple, Bacterial/genetics , Hospitals , Humans , Salmonella , Salmonella Infections/epidemiology , Serogroup , Taiwan/epidemiologyABSTRACT
This study focuses on the cooperative attitude and intention of retail stores in Taiwan to cooperate with the government's related pandemic prevention measures. The study is based on the Theory of Planned Behavior (TPB). The study includes factors such as perceived risk of infection, job stress, pandemic prevention IT (information technology) convenience, pandemic prevention attitude, and pandemic prevention intention. Pandemic prevention attitude is used as a mediating variable to establish the research framework. This study collected research data through a questionnaire survey. A total of 457 valid questionnaires were collected through an electronic questionnaire platform. The findings showed that perceived risk of infection and pandemic prevention IT convenience had a positive and significant effect on pandemic prevention attitude (ß = 0.567; ß = 0.422) and pandemic prevention intention (ß = 0.424; ß = 0.296). Job stress has a significant negative effect on attitude (ß = -0.173). In addition, job stress influenced intention through attitudes. Finally, perceived risk, job stress, and IT convenience had high explanatory power (R2 = 0.706) on attitudes. Perceived risk, IT convenience, and attitude also had moderate explanatory power (R2 = 0.588) on prevention intention. The study also suggests practical recommendations to improve and cooperate with pandemic prevention intention.
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Lactobacillus plantarum PS128 has been reported as a psychobiotic to improve mental health through the gut-brain axis in experimental animal models. To explore its mechanism of action in the gut, this study aimed to analyze the effects of L. plantarum PS128 ingestion on naïve and loperamide (Lop)-induced constipation mice. We found that, in the two mouse models, the weight, number, and water content of feces in the L. plantarum PS128 group were higher than those in the vehicle control group. Histological observation revealed that L. plantarum PS128 increased the level of colonic mucins including the major mucin MUC2. In addition, the charcoal meal test showed that L. plantarum PS128 significantly increased the small intestine transit in naïve mice, but not in the Lop-treated mice. Since intestinal serotonin has been found to modulate motility, we further analyzed the expression of genes related to serotonin signal transduction in the small intestine of naïve mice. The results showed that L. plantarum PS128 significantly altered the expression levels of Tph1, Chga, Slc6a4, and Htr4, but did not affect the expression levels of Tph2, Htr3a, and Maoa. Furthermore, immunohistochemistry revealed that L. plantarum PS128 significantly increased the number of serotonin-containing intestinal cells in mice. Taken together, our results suggest that L. plantarum PS128 could promote intestinal motility, mucin production, and serotonin signal transduction, leading to a laxative effect in mice.
Subject(s)
Lactobacillus plantarum , Probiotics , Animals , Disease Models, Animal , Gastrointestinal Motility , Lactobacillus plantarum/metabolism , Loperamide , Mice , Mucins/metabolism , Serotonin , Signal TransductionABSTRACT
Introduction. Antimicrobial resistance associated with animal hosts is easily transmitted to humans either by direct contact with resistant organisms or by transferring resistance genes into human pathogens.Gap statement. There are limited studies on antimicrobial resistance genes and genetic elements of multidrug-resistant (MDR) Escherichia coli in veterinary hospitals in Taiwan.Aim. The aim of this study was to investigate antimicrobial resistance genes in multidrug-resistant Escherichia coli from animals.Methodology. Between January 2014 and August 2015, 95 multidrug-resistant Escherichia coli isolates were obtained from pigs (n=66), avians (n=18), and other animals (n=11) in a veterinary hospital in Taiwan. Susceptibility testing to 24 antimicrobial agents of 14 antimicrobial classes was performed. Antimicrobial resistance genes, integrons, and insertion sequences were analysed by polymerase chain reaction and nucleotide sequencing. Pulsed-field gel electrophoresis (PFGE), and multi-locus sequence typing were used to explore the clonal relatedness of the study isolates.Results. Different antimicrobial resistance genes found in these isolates were associated with resistance to ß-lactams, tetracycline, phenicols, sulfonamides, and aminoglycosides. Fifty-five of 95 E. coli isolates (55/95, 57.9â%) were not susceptible to extended-spectrum cephalosporins, and bla CTX-M-55 (11/55, 20.0â%) and bla CMY-2 (40/55, 72.7â%) were the most common extended-spectrum ß-lactamase (ESBL) and AmpC genes, respectively. Both bla CTX-M and bla CMY-2 were present on conjugative plasmids that contained the insertion sequence ISEcp1 upstream of the bla genes. Plasmid-mediated FOX-3 ß-lactamase-producing E. coli was first identified in Taiwan. Forty isolates (40/95, 42â%) with class 1 integrons showed seven resistance phenotypes. Genotyping of 95 E. coli isolates revealed 91 different XbaI pulsotypes and 52 different sequence types. PFGE analysis revealed no clonal outbreaks in our study isolates.Conclusion. This study showed a high diversity of antimicrobial resistance genes and genotypes among MDR E. coli isolated from diseased livestock in Taiwan. To our knowledge, this is the first report of plasmid-mediated ESBL in FOX-3 ß-lactamase-producing E. coli isolates in Taiwan. MDR E. coli isolates from animal origins may contaminate the environment, resulting in public health concerns, indicating that MDR isolates from animals need to be continuously investigated.
Subject(s)
Drug Resistance, Multiple, Bacterial/genetics , Escherichia coli Infections , Escherichia coli , Animals , Anti-Bacterial Agents/pharmacology , Birds/microbiology , Escherichia coli/classification , Escherichia coli/drug effects , Escherichia coli Infections/veterinary , Hospitals, Animal , Multilocus Sequence Typing , Swine/microbiology , Taiwan/epidemiology , beta-Lactamases/geneticsABSTRACT
The development of multiple intelligences used to focus on kindergartens and elementary schools as educational experts and officials considered that the development of students' multiple intelligences should be cultivated from childhood and slowly promoted to other levels. Nevertheless, the framework of multiple intelligences should not be simply promoted in kindergartens and elementary schools, but was also suitable in high schools, universities, and even graduate schools or in-service training. Taking employees in Southern Taiwan Science Park as the research subjects, total 314 employees in high-tech industry are preceded the 16-week (3 h per week for total 48 h) experimental teaching research. The research results show that (1) teaching with multiple intelligences would affect learning motivation, (2) teaching with multiple intelligences would affect learning achievement, and (3) learning motivation reveals remarkably positive effects on learning achievement. According to the results to proposed discussions, it is expected to help high-tech industry, when developing human resource potential, effectively well-utilize people's gifted uniqueness.
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Epoxy with low viscosity and good fluidity before curing has been widely applied in the packaging of electronic and electrical devices. Nevertheless, its low flexibility and toughness renders the requirement of property improvement before it can be widely acceptable in dynamic loading applications. This study investigates the possible use of 2-hydroxyethyl methacrylate (HEMA) toughening agent and nano-powders, such as alumina, silicon dioxide, and carbon black, to form epoxy composites for dynamic property improvement. Considering the different combinations of the nano-powders and HEMA toughener, the Taguchi method with an L9 orthogonal array was adopted for composition optimization. The dynamic storage modulus and loss tangent of the prepared specimen were measured by employing a dynamic mechanical analyzer. With polynomial regression, the curve-fitted relationships of the glass transition temperature and storage modulus with respect to the design factors were obtained. It was found that although the raise in the weight fraction of nano-powders was beneficial in increasing the rigidity of the epoxy composite, an optimal amount of HEMA toughener existed for its best damping improvement.