An induced mutation of ABC-transporter component VraF(K84E) contributes to vancomycin resistance and virulence in Staphylococcus aureus strain MW2.

Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S. aureus infections have become increasingly challenging. Vancomycin is considered to be one of the last-resort drugs for treating most methicillin-resistant S. aureus (MRSA), so it is of great significance to further reveal the mechanism of vancomycin resistance. VraFG is one of the few important ABC (ATP-binding cassette) transporters in S. aureus that can form TCS (two-component systems)/ABC transporter modules. ABC transporters can couple the energy released from ATP hydrolysis to translocate solutes across the cell membrane. In this study, we obtained a strain with decreased vancomycin susceptibility after serial passaging and selection. Subsequently, whole-genome sequencing was performed on this laboratory-derived strain MWA2 and a novel single point mutation was discovered in vraF gene, leading to decreased sensitivity to vancomycin and daptomycin. Furthermore, the mutation reduces autolysis of S. aureus and downregulates the expression of lytM, isaA, and atlA. Additionally, we observed that the mutant has a less net negative surface charge than wild-type strain. We also noted an increase in the expression of the dlt operon and mprF gene, which are associated with cell surface charge and serve to hinder the binding of cationic peptides by promoting electrostatic repulsion. Moreover, this mutation has been shown to enhance hemolytic activity, expand subcutaneous abscesses, reflecting an increased virulence. This study confirms the impact of a point mutation of VraF on S. aureus antibiotic resistance and virulence, contributing to a broader understanding of ABC transporter function and providing new targets for treating S. aureus infections.

Pharmacological Inhibition of P-Rex1/Rac1 Axis Blocked Angiotensin II-Induced Cardiac Fibrosis.

PURPOSE: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor-1 (P-Rex1), as one of the members of Rac-GEFs, has been proven to play a critical role in cancer progression and metastasis. Nonetheless, its role in cardiac fibrosis remains elusive. In the present study, we aimed to investigate whether and how the P-Rex1 mediates AngII-induced cardiac fibrosis. METHOD: A cardiac fibrosis mouse model was established by chronic AngII perfusion. The heart structure, function, pathological changes of myocardial tissues, oxidative stress, and cardiac fibrotic protein expression were determined in an AngII induced mouse model. To provide a molecular mechanism for P-Rex1 involvement in cardiac fibrosis, a specific inhibitor or siRNA was used to block P-Rex1, and target the relationship between Rac1-GTPase and its downstream effector. RESULTS: Blocking P-Rex1 showed down-regulation of its downstream effectors such as the profibrotic transcriptional regulator Paks, ERK1/2, and ROS generation. Intervention treatment with P-Rex1 inhibitor 1A-116 ameliorated AngII-induced abnormalities in heart structure and function. Moreover, pharmacological inhibition of the P-Rex1/Rac1 axis showed a protective effect in AngII-induced cardiac fibrosis through the down-regulation of collagen1, CTGF, and α-SMA expression. CONCLUSION: Our findings demonstrated for the first time that P-Rex1 was an essential signaling mediator in CFs activation and subsequent cardiac fibrosis, and 1A-116 could be a potential pharmacological development drug.

Strain Tunability of Perpendicular Magnetic Anisotropy in van der Waals Ferromagnets VI3.

Layered ferromagnets with strong magnetic anisotropy energy (MAE) have special applications in nanoscale memory elements in electronic circuits. Here, we report a strain tunability of perpendicular magnetic anisotropy in van der Waals (vdW) ferromagnets VI3 using magnetic circular dichroism measurements. For an unstrained flake, the M-H curve shows a rectangular-shaped hysteresis loop with a large coercivity (1.775 T at 10 K) and remanent magnetization. Furthermore, the coercivity can be enhanced to a maximum of 2.6 T under a 3.8% external in-plane tensile strain. Our DFT calculations show that the increased MAE under strain contributes to the enhancement of coercivity. Meanwhile, the strain tunability on the coercivity of CrI3, with a similar crystal structure, is limited. The main reason is the strong spin-orbit coupling in V3+ in VI6 octahedra in comparison with that in Cr3+. The strain tunability of coercivity in VI3 flakes highlights its potential for integration into vdW heterostructures.

Pressure-Enhanced Ferromagnetism in Layered CrSiTe3 Flakes.

Despite recent advances in layered ferromagnets, ferromagnetic interactions in these materials are rather weak. Here, we report pressure-enhanced ferromagnetism in layered CrSiTe3 flakes revealed by high-pressure magnetic circular dichroism measurements. Below ∼3 GPa, CrSiTe3 undergoes a paramagnetic-to-ferromagnetic phase transition at ∼32 K, and the field-induced spin-flip in the ferromagnetic phase produces nearly zero hysteresis loops, demonstrating soft ferromagnetism. Above ∼4 GPa, a soft-to-hard ferromagnetic transition occurs, signaled by rectangular-shaped hysteresis loops with finite coercivity and remanent magnetization. Interestingly, as pressure increases, the Curie temperature and coercivity dramatically increase up to ∼138 K and 0.17 T at 7.8 GPa, respectively, in contrast to ∼36 K and 0.02 T at 4.6 GPa. It indicates a remarkable influence of pressure on exchange interactions, which is consistent with DFT calculations. The effective interaction between magnetic couplings and external pressure offers new opportunities in pursuit of high-temperature layered ferromagnets.

Optimization of Decoloration Conditions of Methylene Blue Wastewater by Penicillium P1.

The objective of this work was to optimize the decolorization of methylene blue dye wastewater by Penicillium P1. The influencing factors included initial methylene blue concentration, initial pH value, salinity and inoculation percentage of penicillium spores. The decolorization rate was optimized by response surface center composite design methods. The optimal optimization condition was methylene blue concentration 50 mg/L, pH value 3.61, salinity 3.7%, and inoculation percentage 3.21% (When the MSM was 100 ml), the predicted decolorization rate of methylene blue 85%. The UV and the FTIR spectrum analysis showed that the structure of methylene blue changed during the process of decolorization of methylene blue by Penicillium P1.

Phase Identification and Strong Second Harmonic Generation in Pure ε-InSe and Its Alloys.

Two-dimensional material indium selenide (InSe) has offered a new platform for fundamental research in virtue of its emerging fascinating properties. Unlike 2H-phase transition-metal dichalcogenides (TMDs), ε phase InSe with a hexagonal unit cell possesses broken inversion symmetry in all the layer numbers, and predicted to have a strong second harmonic generation (SHG) effect. In this work, we find that the as-prepared pure InSe, alloyed InSe1- xTe x and InSe1- xS x ( x = 0.1 and 0.2) are ε phase structures and exhibit excellent SHG performance from few-layer to bulk-like dimension. This high SHG efficiency is attributed to the noncentrosymmetric crystal structure of the ε-InSe system, which has been clearly verified by aberration-corrected scanning transmission electron microscopy (STEM) images. The experimental results show that the SHG intensities from multilayer pure ε-InSe and alloyed InSe0.9Te0.1 and InSe1- xS x ( x = 0.1 and 0.2) are around 1-2 orders of magnitude higher than that of the monolayer TMD systems and even superior to that of GaSe with the same thickness. The estimated nonlinear susceptibility χ(2) of ε-InSe is larger than that of ε-GaSe and monolayer TMDs. Our study provides first-hand information about the phase identification of ε-InSe and indicates an excellent candidate for nonlinear optical (NLO) applications as well as the possibility of engineering SHG response by alloying.

Optimization of Cr6+ Removal by Bacillus subtilis Strain SZMC 6179J from Chromium-Containing Soil.

The removal rate of Cr6+ has been explored by the optimized removal conditions. Five Cr-resistant strains were isolated from chromium-contained soil. The most efficient strain S1 was identified as Bacillus subtilis strain SZMC 6179J through 16S rDNA. Response surface methodology (RSM) was used to investigate the effects of four independent variables, including initial pH, initial Cr6+ concentration (mg/L), time (h) and inoculation percentage (%). RSM revealed that when pH was 5.02, time was 24.0 h, inoculation percentage was 4.64% (v/v) and initial concentration of Cr6+ was 55.0 mg/L, the optimal condition was obtained. Under the optimum conditions, the actual response values for Bacillus subtilis strain SZMC 6179J was 93.50%. The pH was the most significant factor towards removal rate of Cr6+. The result showed that the removal mechanism of Cr6+ by Bacillus subtilis strain SZMC 6179J was reduction under normal conditions. The removal mechanism of Cr6+ by Bacillus subtilis strain SZMC 6179J was adsorption under adverse conditions.

Association of maternal allergy with human milk soluble CD14 and fatty acids, and early childhood atopic dermatitis.

BACKGROUND: This study aimed to investigate whether maternal allergy is associated with soluble CD14 (sCD14) and fatty acid composition in different stages of lactation and the onset of atopic dermatitis (AD) in early childhood. METHODS: In total, 443 mother-child groups (445 children) were enrolled in the Prediction of Allergies in Taiwanese Children birth cohort study. Colostrum and mature milk at 2 months postpartum (2-month HM) were collected from lactating mothers. Information regarding parental allergy histories and physician-diagnosed atopic diseases was obtained using age-specific questionnaires (0-2 years). We compared sCD14 levels and the composition of 30 fatty acids in the colostrum and 2-month HM, respectively, between allergic and non-allergic mothers and between children with and without AD by the age of 2 years. RESULTS: In total, 185 (41.8%) mothers presented with allergies, and 154 (34.6%) children had physician-diagnosed AD by the age of 2 years. Both in the colostrum and 2-month HM of 289 lactating mothers, sCD14 levels were significantly lower in allergic mothers whose children presented with AD compared with children who did not (P = 0.015 and 0.044, respectively). Among the children with AD who were born to non-allergic mothers, sCD14 levels were lower. However, the result was not statistically significant (P = 0.376 and 0.264, respectively). Our data revealed the lack of associations between fatty acid composition and AD (P > 0.05). CONCLUSION: Decreased sCD14 levels in the colostrum and 2-month HM were associated with AD at 2 years of age, particularly among children born to mothers with allergies.

Unraveling the Raman Enhancement Mechanism on 1T'-Phase ReS2 Nanosheets.

2D transition metal dichalcogenides materials are explored as potential surface-enhanced Raman spectroscopy substrates. Herein, a systematic study of the Raman enhancement mechanism on distorted 1T (1T') rhenium disulfide (ReS2 ) nanosheets is demonstrated. Combined Raman and photoluminescence studies with the introduction of an Al2 O3 dielectric layer unambiguously reveal that Raman enhancement on ReS2 materials is from a charge transfer process rather than from an energy transfer process, and Raman enhancement is inversely proportional while the photoluminescence quenching effect is proportional to the layer number (thickness) of ReS2 nanosheets. On monolayer ReS2 film, a strong resonance-enhanced Raman scattering effect dependent on the laser excitation energy is detected, and a detection limit as low as 10-9 m can be reached from the studied dye molecules such as rhodamine 6G and methylene blue. Such a high enhancement factor achieved through enhanced charge interaction between target molecule and substrate suggests that with careful consideration of the layer-number-dependent feature and excitation-energy-related resonance effect, ReS2 is a promising Raman enhancement platform for sensing applications.

SNPs in the Toll1 receptor of Litopenaeus vannamei are associated with immune response.

Tolls and Toll-like receptors (TLRs) are important regulators in the innate immune system and their genetic variations usually affect the host's susceptibility/resistance to pathogen infections. In this study, we report on the single nucleotide polymorphisms (SNPs) of Toll1 in Litopenaeus vannamei (LvToll1) and how this is associated with immune response. PCR-DGGE analysis revealed genetic polymorphisms in LvToll1 at both the genomic DNA (gDNA) and cDNA levels. Using high-throughput sequencing, 223 SNPs were identified at the gDNA level, of which 145 were non-synonymous SNP (nsSNP), with 3 nsSNPs having frequency over 1%. On the other hand, 60 SNPs were identified at the cDNA level including 38 nsSNPs and 4 nsSNPs with frequency over 1%. Upon challenging shrimps with Streptococcus iniae, Vibrio parahaemolyticus and white spot syndrome virus (WSSV), LvToll1 was shown to generate 6, 4 and 4 novel bands, respectively when analyzed with PCR-DGGE. Sequencing analysis of these bands showed that they contained 6, 4 and 2 nsSNPs, respectively. Moreover, the nsSNP C1526T was detected in S. iniae-resistant but not in susceptible shrimps. Most significantly, the C1526T mutation could shorten the α-helix of the LRR domain and was predicted to affect the function of LvToll1, indicating that SNP C1526T might be associated with shrimp's resistance to pathogen infections. In sum, our findings here reveal that the genetic polymorphisms of Toll receptor are linked with the immune response to pathogen infections in L. vannamei.

Grassland gross carbon dioxide uptake based on an improved model tree ensemble approach considering human interventions: global estimation and covariation with climate.

Grassland ecosystems act as a crucial role in the global carbon cycle and provide vital ecosystem services for many species. However, these low-productivity and water-limited ecosystems are sensitive and vulnerable to climate perturbations and human intervention, the latter of which is often not considered due to lack of spatial information regarding the grassland management. Here by the application of a model tree ensemble (MTE-GRASS) trained on local eddy covariance data and using as predictors gridded climate and management intensity field (grazing and cutting), we first provide an estimate of global grassland gross primary production (GPP). GPP from our study compares well (modeling efficiency NSE = 0.85 spatial; NSE between 0.69 and 0.94 interannual) with that from flux measurement. Global grassland GPP was on average 11 ± 0.31 Pg C yr-1 and exhibited significantly increasing trend at both annual and seasonal scales, with an annual increase of 0.023 Pg C (0.2%) from 1982 to 2011. Meanwhile, we found that at both annual and seasonal scale, the trend (except for northern summer) and interannual variability of the GPP are primarily driven by arid/semiarid ecosystems, the latter of which is due to the larger variation in precipitation. Grasslands in arid/semiarid regions have a stronger (33 g C m-2  yr-1 /100 mm) and faster (0- to 1-month time lag) response to precipitation than those in other regions. Although globally spatial gradients (71%) and interannual changes (51%) in GPP were mainly driven by precipitation, where most regions with arid/semiarid climate zone, temperature and radiation together shared half of GPP variability, which is mainly distributed in the high-latitude or cold regions. Our findings and the results of other studies suggest the overwhelming importance of arid/semiarid regions as a control on grassland ecosystems carbon cycle. Similarly, under the projected future climate change, grassland ecosystems in these regions will be potentially greatly influenced.

Docosahexaenoic acid reduces sterol regulatory element binding protein-1 and fatty acid synthase expression and inhibits cell proliferation by inhibiting pAkt signaling in a human breast cancer MCF-7 cell line.

BACKGROUND: Fatty acid synthase (FASN), the major enzyme in de novo fatty acid synthesis, is highly expressed in breast cancer and its expression is reduced by polyunsaturated fatty acids (PUFAs) in liver. We previously found a positive association between rat mammary tumor levels of the n-6 PUFA arachidonic acid (AA) and tumor weight. We examined the roles of the major n-3 PUFA, docosahexaenoic acid (DHA, 22:6n-3), and the major n-6 PUFA, AA, in FASN expression in, and proliferation of, human breast cancer MCF-7 cells. METHODS: The cells were treated for 48 h with BSA or 60 µM BSA-bound DHA, AA, or oleic acid (OA, 18:1n-9), then were incubated with or without estradiol or insulin. Western blot and 3H-thymidine incorporation assay were used to determine the role of DHA on FASN regulation and MCF-7 cell proliferation. RESULTS: DHA, but neither AA nor OA, inhibits estradiol-induced and insulin-induced expression of the precursor of sterol regulatory element binding protein-1 (p-SREBP-1), its mature form (m-SREBP-1), and FASN. Estradiol or insulin stimulation increased the pAkt/Akt and pS6/S6 ratios, expression of p-SREBP-1, m-SREBP-1, and FASN, and cell proliferation, and these effects were decreased by DHA. The DHA-induced decrease in FASN expression resulted from reduced pAkt/Akt signaling and not pERK1/2/ERK1/2 signaling. In addition, DHA enhanced the inhibitory effect of LY294002 on pAkt signaling and expression of p-SREBP-1, m-SREBP-1, and FASN. However, addition of rapamycin, an inhibitor of the mTOR signaling pathways, 1 h before addition of estradiol or insulin increased the pAkt/Akt ratio and FASN expression, and this effect was inhibited by addition of DHA 48 h before rapamycin. CONCLUSION: We conclude that, in MCF-7 cells, DHA inhibits pAKT signaling and thus expression of p-SREBP-1, m-SREBP-1, and FASN and cell proliferation.

Effects of Bithiophene Imide Fusion on the Device Performance of Organic Thin-Film Transistors and All-Polymer Solar Cells.

Two new bithiophene imide (BTI)-based n-type polymers were synthesized. f-BTI2-FT based on a fused BTI dimer showed a smaller band gap, a lower LUMO, and higher crystallinity than s-BTI2-FT containing a BTI dimer connected through a single bond. s-BTI2-FT exhibited a remarkable electron mobility of 0.82 cm2 V-1 s-1 , and f-BTI2-FT showed a further improved mobility of 1.13 cm2 V-1 s-1 in transistors. When blended with the polymer donor PTB7-Th, f-BTI2-FT-based all-polymer solar cells (all-PSCs) attained a PCE of 6.85 %, the highest value for an all-PSC not based on naphthalene (or perylene) diimide polymer acceptors. However, s-BTI2-FT all-PSCs showed nearly no photovoltaic effect. The results demonstrate that f-BTI2-FT is one of most promising n-type polymers and that ring fusion offers an effective approach for designing polymers with improved electrical properties.

Click Synthesis, Aggregation-Induced Emission and Chirality, Circularly Polarized Luminescence, and Helical Self-Assembly of a Leucine-Containing Silole.

By introducing chiral leucine pendants to silole scaffold, leucine-containing silole (Silole-Leu) is synthesized and it is endowed with not only aggregation-induced emission and circular dichroism, but excellent chiral polarized luminescence as well. Silole-Leu also has the capacity to self-assemble into nano/micro helical luminescent fibers and the dimension of the fibers can be tuned by adjusting the ratio and volume of mixed solvents for evaporation as revealed by atomic force microscope, scanning electron microscope, and fluorescence microscope. The characteristic helicity of microfibers is directly visualized for the first time by using fluorescence microscope.

A biphasic response pattern of lipid metabolomics in the stage progression of hepatitis B virus X tumorigenesis.

Metabolic syndrome has closely linked to the development of human hepatocellular carcinoma (HCC). By using the hepatitis B virus (HBV) X (HBx) transgenic mouse model, we studied the dynamic evolution of serum and liver profiles of lipids and global cDNA expression at different stages of HBx tumorigenesis. We observed that the lipid (triglycerides, cholesterol, and fatty acids) profiles revealed a biphasic response pattern during the progression of HBx tumorigenesis: a small peak at early phase and a large peak or terminal switch at the tumor phase. By analyzing cDNA microarray data, the early peak correlated to the oxidative stress and pro-inflammatory response, which then resolved at the middle phase and were followed by the terminal metabolic switch in the tumor tissues. Five lipid metabolism-related genes, the arachidonate 5-lipoxygenase, lipoprotein lipase, fatty acid binding protein 4, 1-acylglycerol-3-phosphate O-acyltransferase 9, and apolipoprotein A-IV were identified to be significantly activated in HBx transgenic HCCs and further validated in human HBV-related HCCs. Inhibition of these lipid genes could reverse the effect of HBx on lipid biosynthesis and suppress HBx-induced cell proliferation in vitro. Our results support the concept that metabolic syndrome plays an important role in HBV tumorigenesis. The dysregulation of lipid metabolic genes may predict the disease progression to HCC in chronic hepatitis B patients.

[Lactose intolerance in neonates with non-infectious diarrhea].

OBJECTIVE: To investigate the development of lactose intolerance in neonates with non-infectious diarrhea and its association with diarrhea, and to evaluate the diagnostic values of fecal pH value and urine galactose determination for neonatal lactase deficiency. METHODS: Seventy hospitalized neonates who developed non-infectious diarrhea between October 2012 and June 2015 were enrolled as the diarrhea group, and 162 hospitalized neonates without non-infectious diarrhea were enrolled as the non-diarrhea group. Test paper was used to determine fecal pH value. The galactose oxidase method was used to detect urine galactose. The neonates with positive galactose oxidase were diagnosed with lactase deficiency, and those with lactase deficiency and diarrhea were diagnosed with lactose intolerance. According to the results of urine galactose detection, 69 neonates in the diarrhea group who underwent urine galactose detection were classified into lactose intolerance group (45 neonates) and lactose tolerance group (24 neonates), and their conditions after treatment were compared between the two groups. The follow-up visits were performed for neonates with diarrhea at 3 months after discharge. RESULTS: Fecal pH value and positive rate of urine galactose (65% vs 54%) showed no significant differences between the diarrhea and non-diarrhea groups (P>0.05). Fecal pH value showed no significant difference between the lactose intolerance and lactose tolerance groups (P>0.05), while the neonates in the lactose intolerance group had a significantly longer time to recovery of defecation than those in the lactose tolerance group (P<0.05). CONCLUSIONS: The incidence of lactase deficiency is high in neonates, and diarrhea due to lactose intolerance tends to occur. Determination of fecal pH value has no significance in the diagnosis of lactose intolerance in neonates with diarrhea.

Tuning the singlet-triplet energy gap of AIE luminogens: crystallization-induced room temperature phosphorescence and delay fluorescence, tunable temperature response, highly efficient non-doped organic light-emitting diodes.

In this contribution, we finely tuned the singlet-triplet energy gap (ΔEST) of AIE-active materials to modulate their fluorescence, phosphorescence and delay fluorescence via rational molecular design and investigated the possible ways to harvest their triplet energy in OLEDs. Noteworthily, two molecules o-TPA-3TPE-o-PhCN and o-TPA-3TPE-p-PhCN with larger ΔEST values (0.59 eV and 0.45 eV, respectively) emitted efficient long-lived low temperature phosphorescence in their glassy solutions and exhibited efficient crystallization-induced room temperature phosphorescence (RTP). Meanwhile, it was the first time to observe a novel crystallization-induced delay fluorescence phenomenon in another AIE-active molecule p-TPA-3TPE-p-PhCN owing to its very small ΔEST value (0.21 eV). It was also found that molecules with various ΔEST values showed significantly different temperature sensitivity. Non-doped electroluminescent (EL) devices using these molecules as light-emitting layers were fabricated, exhibiting external quantum efficiencies (EQE) higher than theoretical values of purely singlet emitter type devices. Particularly, p-TPA-3TPE-p-PhCN showed outstanding device performances with high luminance and efficiencies up to 36,900 cd m(-2), 11.2 lm W(-1), 12.8 cd A(-1) and 4.37%, respectively, considering that its solid-state quantum yield was only 42%. All the above observations suggested that tuning the ΔEST values of AIE materials is a powerful methodology to generate many more interesting and meaningful optoelectronic properties.

Efficient selective catalytic reduction of NO by novel carbon-doped metal catalysts made from electroplating sludge.

Electroplating sludges, once regarded as industrial wastes, are precious resources of various transition metals. This research has thus investigated the recycling of an electroplating sludge as a novel carbon-doped metal (Fe, Ni, Mg, Cu, and Zn) catalyst, which was different from a traditional carbon-supported metal catalyst, for effective NO selective catalytic reduction (SCR). This catalyst removed >99.7% NO at a temperature as low as 300 °C. It also removed NO steadily (>99%) with a maximum specific accumulative reduced amount (MSARA) of 3.4 mmol/g. Gas species analyses showed that NO removal was accompanied by evolving N2 and CO2. Moreover, in a wide temperature window, the sludge catalyst showed a higher CO2 selectivity (>99%) than an activated carbon-supported metal catalyst. Structure characterizations revealed that carbon-doped metal was transformed to metal oxide in the sludge catalyst after the catalytic test, with most carbon (2.33 wt %) being consumed. These observations suggest that NO removal over the sludge catalyst is a typical SCR where metals/metal oxides act as the catalytic center and carbon as the reducing reagent. Therefore, our report probably provides an opportunity for high value-added utilizations of heavy-metal wastes in mitigating atmospheric pollutions.

An exploration for research-oriented teaching model in biology teaching.

Training innovative talents, as one of the major aims for Chinese universities, needs to reform the traditional teaching methods. The research-oriented teaching method has been introduced and its connotation and significance for Chinese university teaching have been discussed for years. However, few practical teaching methods for routine class teaching were proposed. In this paper, a comprehensive and concrete research-oriented teaching model with contents of reference value and evaluation method for class teaching was proposed based on the current teacher-guiding teaching model in China. We proposed that the research-oriented teaching model should include at least seven aspects on: (1) telling the scientific history for the skills to find out scientific questions; (2) replaying the experiments for the skills to solve scientific problems; (3) analyzing experimental data for learning how to draw a conclusion; (4) designing virtual experiments for learning how to construct a proposal; (5) teaching the lesson as the detectives solve the crime for learning the logic in scientific exploration; (6) guiding students how to read and consult the relative references; (7) teaching students differently according to their aptitude and learning ability. In addition, we also discussed how to evaluate the effects of the research-oriented teaching model in examination.

Simple Isopropanol-Assisted Direct Soft Imprint Lithography for Residue-Free Microstructure Patterning.

A direct soft imprint lithography was proposed to realize the direct fabrication of residue-free, well-shaped functional patterns through a single step. This imprint method requires only a simply prepared isopropanol-treated polydimethylsiloxane (PDMS) stamp without any additional resists. Residue-free Ag patterns were successfully fabricated on different substrates by directly imprinting the Ag ink with the isopropanol-treated PDMS stamp. Furthermore, the coffee-ring effect of the imprinting Ag patterns can be eliminated by optimizing the imprinting time, isopropanol-treating time, and imprinting temperatures. Studies show that the residual Ag ink in the contact region can be absorbed by the isopropanol-treated PDMS stamp due to the "like dissolves like" principle. Finally, this method was employed to fabricate the Ag electrodes for the thin-film transistors, attaining a mobility of ∼8 cm2 V-1 s-1, which is comparable to those with vacuum-processed electrodes. This process provides a simple, low-cost, residue-free, coffee-ring-free, and fast patterning method in the field of microelectronics.