Reliable fabrication of 3D freestanding nanostructures via all dry stacking of incompatible photoresist.

Three-dimensional (3D) free-standing nanostructures based on electron-beam lithography (EBL) have potential applications in many fields with extremely high patterning resolution and design flexibility with direct writing. In numerous EBL processes designed for the creation of 3D structures, the multilayer resist system is pivotal due to its adaptability in design. Nevertheless, the compatibility of solvents between different layers of resists often restricts the variety of feasible multilayer combinations. This paper introduces an innovative approach to address the bottleneck issue by presenting a novel concept of multilayer resist dry stacking, which is facilitated by a near-zero adhesion strategy. The poly(methyl methacrylate) (PMMA) film is stacked onto the hydrogen silsesquioxane (HSQ) resist using a dry peel and release technique, effectively circumventing the issue of HSQ solubilization by PMMA solvents typically encountered during conventional spin-coating procedures. Simultaneously, a dry lift-off technique can be implemented by eschewing the use of organic solvents during the wet process. This pioneering method enables the fabrication of high-resolution 3D free-standing plasmonic nanostructures and intricate 3D free-standing nanostructures. Finally, this study presents a compelling proof of concept, showcasing the integration of 3D free-standing nanostructures, fabricated via the described technique, into the realm of Fabry-Perot cavity resonators, thereby highlighting their potential for practical applications. This approach is a promising candidate for arbitrary 3D free-standing nanostructure fabrication, which has potential applications in nanoplasmonics, nanoelectronics, and nanophotonics.

[Effect of Hei Xiaoyaosan regulating p38MAPK/Beclin-1/Bcl-2 pathway on autophagy level in Alzheimer's disease model rats].

To explore the effect of Hei Xiaoyaosan on autophagy levels in Alzheimer's disease(AD). A total of 100 4-month-old Wistar male rats were randomly selected as a blank group, and 10 rats were taken as a sham operation group and injected with 1 µL of normal saline on both sides of the hippocampus. The other rats were injected with Aß_(1-42) solution in the hippocampus to replicate the AD model. Fifty successfully modeled rats were selected and randomly divided into the model group, Aricatio group(0.5 mg·kg~(-1)), and high, medium, and low dose groups of Hei Xiaoyaosan(15.30, 7.65, and 3.82 g·kg~(-1)), with 10 rats in each group. The rats were administered by continuous gavage for 42 days. Morris water maze was used to detect the learning and memory ability of rats, and Hoechst staining was used to observe the pathological changes of nerve cells in the hippocampal CA1 region. The mRNA expression of p38MAPK, Beclin-1, and Bcl-2 was detected by RT-qPCR.Western blot was used to detect the expressions of p38MAPK, Beclin-1, Bcl-2, APP, and related proteins. The level of Aß_(1-42) in the hippocampus was detected by ELISA, and the expression level of LC3Ⅱ in the hippocampus was detected by immunohistochemistry. The experimental results showed that compared with the blank group, the learning and memory ability of rats in the model group decreased(P<0.01). The nuclei in the CA1 region of the hippocampus showed blue bright spots and were closely arranged. The mRNA expression of p38MAPK was up-regulated, and the mRNA expressions of Beclin-1 and Bcl-2 were down-regulated(P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were increased, while those of Beclin-1, Bcl-2, and p-Bcl-2 were decreased(P<0.01). The expression of Aß_(1-42) was increased(P<0.01). The relative expression of LC3Ⅱ decreased(P<0.01). Compared with the model group, the learning and memory ability of rats in each administration group was improved(P<0.05 or P<0.01). The nuclei in the CA1 region of the hippocampus gradually became clear, showing light blue. The mRNA expression of p38MAPK was down-regulated(P<0.01), and that of Beclin-1 and Bcl-2 was increased(P<0.05 or P<0.01). The expressions of p38MAPK, p-p38MAPK, and APP were down-regulated, while those of Beclin-1, Bcl-2, and p-Bcl-2 were up-regulated(P<0.05 or P<0.01). The expression of Aß_(1-42) was decreased(P<0.01). The relative expression of LC3Ⅱ was increased(P<0.01). It can be concluded that Hei Xiaoyaosan can improve the cognitive ability of AD model rats, and its potential mechanism may be related to regulating the p38MAPK/Beclin-1/Bcl-2 signaling pathway, increasing the level of autophagy, and reducing the accumulation of Aß_(1-42).

High dietary copper intake induces perturbations in the gut microbiota and affects host ovarian follicle development.

Increasing evidence has shown that gut microbes play an important role in the reproductive endocrine system and the development of polycystic ovary syndrome (PCOS). However, whether environmental factors are involved in these gut microbiota alterations has seldom been studied. In this study, we aimed to explore the crucial role of an imbalanced gut microbiota on abnormal ovarian follicle development induced by Cu. A 1:1 matched case-control study with 181 PCOS patients and 181 controls was conducted using a propensity score matching protocol. Information regarding dietary Cu intake was obtained from a face-to-face dietary intake interview. Alterations in the gut microbiota were detected by high-throughput 16 S rDNA sequencing. The results showed that dietary Cu intake was positively correlated with the risk of PCOS, and the risk threshold was approximately 1.992 mg/d. Compared with those with dietary Cu intakes lower than 1.992 mg/d, those who had a higher dietary Cu intake had a 1.813-fold increased risk of PCOS (OR=1.813, 95% CI: 1.150-2.857). PCOS patients had a lower relative abundance of Bacteroides than controls (P = 0.003), and Bacteroides played a partial mediating role between dietary Cu exposure and PCOS (Pindirect effect=0.026, 95% CI: 0.002-0.072). In addition, an animal model of Cu exposure through the diet showed that Cu can induce gut microbiota disorder; increase serum levels of LPS, MDA, and IL-6; and alter host ovarian steroidogenesis to affect ovarian follicle development. Staphylococcus played a partial mediating role between Cu exposure and CYP17A1 (Pg_Staphylococcus=0.083, 95% CI: 0.001-0.228). Overall, this study shows that long-term exposure to high dietary Cu levels can affect the composition of the gut microbiota, cause inflammation and oxidative stress, and then interfere with hormone signaling, ultimately affecting ovarian follicle development.

Copper exposure induces ovarian granulosa cell apoptosis by activating the caspase-dependent apoptosis signaling pathway and corresponding changes in microRNA patterns.

Environmental copper (Cu) contamination is a complex worldwide public health problem. However, information on the effects of Cu pollution on human reproduction is limited. Although our previous studies have indicated that Cu exposure disrupts ovarian folliculogenesis, the underlying mechanism needs to be further explored. In this study, human luteinized ovarian granulosa cells and a rat animal model were used to investigate whether Cu exposure affects ovarian follicle development by inducing apoptosis and to elucidate the possible mechanisms. The results showed that Cu exposure from weaning to sexual maturity significantly decreased the proportion of preantral follicles but increased the proportion of atretic follicles (P < 0.05). In addition, 6 mg/kg Cu increased the proportion of antral follicles, while 12 and 25 mg/kg Cu decreased it (P < 0.05). We also found that 6 mg/kg Cu exposure inhibited apoptosis of ovarian granulosa cells, while 12 and 25 mg/kg Cu promoted apoptosis (P < 0.05). Experiments on primary human luteinized ovarian granulosa cells suggested that higher levels of Cu exposure induced a significant increase in the mRNA levels of Bcl2 Bax , Fas, Caspase8, and Caspase3 (P < 0.05), and the protein levels of BAX, BCL2, CASPASE3, CASPASE8, CLE-CASPASE3, CLE-CASPASE8 and BAX/BCL2 were also increased (P < 0.05). miRNA chip analyses identified a total of 95 upregulated and 10 downregulated miRNAs in human luteinized granulosa cells exposed to Cu. Hsa-miR-19b-3p, hsa-miR-19a-3p, miR-548ar-3p, hsa-miR-652-5p, and hsa-miR-29b-5p were decreased after Cu exposure (P < 0.05). Additionally, the level of hsa-miR-144-5p was increased (P < 0.05). Together, our results reveal that Cu exposure induces abnormal ovarian folliculogenesis by inducing ovarian granulosa cell apoptosis, which is triggered by the caspase-dependent apoptosis signaling pathway, and that miRNAs may be involved in this process.

Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Sulfated Polysaccharides from Enteromorpha prolifera Attenuate Lipid Metabolism Disorders in Mice with Obesity Induced by a High-Fat Diet via a Pathway Dependent on AMP-Activated Protein Kinase.

BACKGROUND: Obesity-related metabolic diseases have recently evoked worldwide attention. Studies have demonstrated that Enteromorpha polysaccharide (EP) exerts lipid-lowering effects, but the underlying mechanism remains unclear. OBJECTIVES: We investigated whether EP regulates lipid metabolism disorders in mice with high-fat diet (HFD)-induced obesity via an AMP-activated protein kinase (AMPK)-dependent pathway. METHODS: Six-week-old male C57BL/6J mice (18 ± 2 g) were fed a normal diet (ND; 10% energy from fats) or an HFD (60% energy from fats) for 6 weeks to induce obesity and treated intragastrically with EP (200 mg/kg body weight) or distilled water (10 mL/kg body weight) for 8 weeks. Biochemical indicators, AMPK-dependent pathways, and lipid metabolism-related genes were evaluated to assess the effects of EP on HFD-induced lipid metabolism disorders. The essential role of AMPK in the EP-mediated regulation of lipid metabolism was confirmed using HFD-fed male Ampka2-knockout mice (aged 6 weeks; 17 ± 2 g) treated or not treated with the above-mentioned dose of EP. The data were analyzed by t-tests, 2-factor and 1-way ANOVAs. RESULTS: Compared to the ND, the HFD resulted in a greater body weight (24.3%), perirenal fat index (2.2-fold), and serum total cholesterol (24.66%) and LDL cholesterol (1.25-fold) concentrations (P < 0.05) and dysregulated the AMPK-dependent pathway and the expression of most lipid metabolism-related genes (P < 0.05). Compared to the HFD, EP treatment resulted in a lower perirenal fat index (31.22%) and LDL cholesterol concentration (23.98%) and partly reversed the dysregulation of the AMPK-dependent pathway and the altered expression of lipid metabolism-related genes (P < 0.05). Ampka2 knockout abolished the above-mentioned effects of EP in obese mice and the EP-mediated effects on the expression of lipid metabolism-related genes (P > 0.05). CONCLUSIONS: These findings suggest that EP can ameliorate lipid metabolism disorders in mice with HFD-induced obesity via an AMPK-dependent pathway.

Suspended 3D metallic dimers with sub-10 nm gap for high-sensitive SERS detection.

The suspended metallic nanostructures with tiny gaps have certain advantages in surface-enhanced Raman scattering (SERS) due to the coaction of the tiny metallic nanogaps and the substrate-decoupled electromagnetism resonant modes. In this study, we used the lithographic HSQ/PMMA electron-beam bilayer resist exposure combined with a deposition-induced nanogap-narrowing process to define elevated suspended metallic nanodimers with tiny gaps for surface-enhanced Raman spectroscopy detection. By adjusting the deposited metal thickness, the metallic dimers with sub-10 nm gaps can be reliably obtained. These dimers with tunable nanogaps successfully served as excellent SERS substrates, exhibiting remarkable high-sensitivity detection ability for crystal violet molecules. Systematic experiments and simulations were conducted to explain the origin of the improved SERS performance. The results showed that the 3D elevated suspended metallic dimers could achieve a higher SERS enhancement factor than the metallic dimers on HSQ pillars and a common Si substrate, demonstrating that this kind of suspended metallic dimer is a promising route for high-sensitive SERS detection and other plasmonic applications.

Arsenic exposure diminishes ovarian follicular reserve and induces abnormal steroidogenesis by DNA methylation.

Arsenic contamination is a worldwide public health problem, and the effect of arsenic on male reproduction has been extensively studied; however, data on the biotoxicity of arsenic in terms of female reproduction are more scarce. In this study, a human-cell-animal translational strategy was applied to explore the effect of arsenic exposure on ovarian steroidogenesis and its potential mechanism. We conducted a 1:1 propensity score matched case-control study involving 127 diminished ovarian reserve (DOR) cases and 127 healthy controls. The ovarian follicular fluid levels of 21 metal elements, including arsenic, were measured. The results showed that there were significant differences in follicular fluid metal profiles between DOR patients and controls and that arsenic, molybdenum, and strontium played important roles in DOR progression [OR (95 % CI): 2.203 (1.385, 3.503), 2.308 (1.490, 3.575) and 2.922 (1.864, 4.580), respectively]. In the primary ovarian granulosa cell culture model, we found that treatment with 8 µM arsenic for 24 and 48 h induced a decrease in human granulosa cell viability. The estradiol (E2) level was significantly decreased after arsenic exposure (P < 0.05), which was dependent on significant alterations (P < 0.05) in key enzymes in steroidogenesis. In addition, a model for sodium arsenite exposure through water in rats from weaning to sexual maturity was established. We evaluated ovarian development by monitoring the estrous cycle, observing ovarian pathology, and calculating the follicular proportion. RT-qPCR, Western blotting, and bisulfite-sequencing PCR were used to investigate the effect of arsenic exposure on ovarian steroidogenesis and its possible mechanism. The results indicated that steroidogenic factor-1 (SF-1) was an important target of the steroidogenesis disorder induced by arsenic exposure. Arsenic significantly increased the DNA methylation level (P < 0.05) in the promoter region of SF-1 to reduce its expression, subsequently decreasing the levels of steroidogenic acute regulatory protein (StAR), P450 cholesterol side-chain cleavage enzyme (CYP11A1), and aromatase (CYP19A1) (P < 0.05), leading to premature depletion of ovarian follicles.

Sub-5 nm Lithography with Single GeV Heavy Ions Using Inorganic Resist.

In this work, we demonstrate a process having the capability to realize single-digit nanometer lithography using single heavy ions. By adopting 2.15 GeV 86Kr26+ ions as the exposure source and hydrogen silsesquioxane (HSQ) as a negative-tone inorganic resist, ultrahigh-aspect-ratio nanofilaments with sub-5 nm feature size, following the trajectory of single heavy ions, were reliably obtained. Control experiments and simulation analysis indicate that the high-resolution capabilities of both HSQ resist and the heavy ions contribute the sub-5 nm fabrication result. Our work on the one hand provides a robust evidence that single heavy ions have the potential for single-digit nanometer lithography and on the other hand proves the capability of inorganic resists for reliable sub-5 nm patterning. Along with the further development of heavy-ion technology, their ultimate patterning resolution is supposed to be more accessible for device prototyping and resist evaluation at the single-digit nanometer scale.

Enhancing Plasmonic Spectral Tunability with Anomalous Material Dispersion.

The field confinement of plasmonic systems enables spectral tunability under structural variations or environmental perturbations, which is the principle for various applications including nanorulers, sensors, and color displays. Here, we propose and demonstrate that materials with anomalous dispersion, such as Ge in the visible, improve spectral tunability. We introduce our proposal with a semianalytical guided mode picture. Using Ge-based film (Ag/Au)-coupled gap plasmon resonators, we implement two architectures and demonstrate the improved tunability with single-particle dark-field scattering, ensemble reflection, and color generation. We observe three-fold enhancement of tunability with Ge nanodisks compared with that of Si, a normal-dispersion material in the visible. The structural color generation of large array systems, made of inversely fabricated Ge-Ag resonators, exhibits a wide gamut. Our results introduce anomalous material dispersion as an extra degree of freedom to engineer the spectral tunability of plasmonic systems, especially relevant for actively tunable plasmonics and metasurfaces.

Enhancing the stability of polymer nanostructures via ultrathin oxide coatings for nano-optical device applications.

Polymer nanostructures have drawn tremendous attention due to their wide applications in nanotechnology. However, the morphology of the polymer nanostructures is fragile under harsh conditions such as high-power irradiation and organic-solution environments during the fabrication or the measurement processes, significantly limiting their potential applications. In this work, we propose and demonstrate a simple approach to improve the stability of polymer nanostructures by coating a conformal ultrathin oxide film via atomic-layer deposition. Due to the refractory and dense coating of the oxide layer, the stability of polymer structures is enhanced by the prohibition of deformation occurrences from thermally induced reflow and organic solution. As a proof of concept, poly(methyl methacrylate) (PMMA) nanostructures coated with a sub-10-nm TiO2layer are demonstrated, and the structures exhibit high temperature stability at 180 °C and good resistance to soluble damage from organic solutions. Subsequently, the mechanism of the improved thermal stability is analyzed via mechanical simulations. Such an effective approach is proposed to significantly broaden the application of polymer nanostructures as functional elements for optical structures/devices that require excellent thermal and chemical stability.

Fabrication of single-nanometer metallic gaps via spontaneous nanoscale dewetting.

Ultrasmall metallic nanogaps are of great significance for wide applications in various nanodevices. However, it is challenging to fabricate ultrasmall metallic nanogaps by using common lithographic methods due to the limited resolution. In this work, we establish an effective approach for successful formation of ultrasmall metallic nanogaps based on the spontaneous nanoscale dewetting effect during metal deposition. By varying the initial opening size of the exposed resist template, the influence of dewetting behavior could be adjusted and tiny metallic nanogaps can be obtained. We demonstrate that this method is effective to fabricate diverse sub-10 nm gaps in silver nanostructures. Based on this fabrication concept, even sub-5 nm metallic gaps were obtained. SERS measurements were performed to show the molecular detection capability of the fabricated Ag nanogaps. This approach is a promising candidate for sub-10 nm metallic gaps fabrication, thus possessing potential applications in nanoelectronics, nanoplasmonics, and nano-optoelectronics.

Periodic planar Fabry-Perot nanocavities with tunable interference colors based on filling density effects.

Structural colors of high performance and economically feasible fabrication are desired in various applications. Herein, we demonstrate that reflective full-color filters based on the interference effect can be realized in periodic Fabry-Perot (F-P) nanocavity arrays of the same thickness. Enabled by simply adjusting the nanocavity size and array period, the resonant wavelengths can be successively tuned in the whole visible light range, which is mainly attributed to the varied effective refractive index introduced by the different filling density of the F-P nanocavity. Compared to the plasmonic colors utilizing the similar nanostructures, the proposed interference colors offer unique advantages of higher color contrast, wider gamut, and lower fabrication requirements. Besides, these color filters do not involve modulating the vertical dimensions of the F-P nanocavities, which is conducive to the monolithic integration of multicolor optical cavities and their large-area applications in consumable products combined with replica patterning techniques, such as nanoimprinting and soft lithography.

Trichromatic and Tripolarization-Channel Holography with Noninterleaved Dielectric Metasurface.

Metasurfaces hold great potentials for advanced holographic display with extraordinary information capacity and pixel sizes in an ultrathin flat profile. A dual-polarization channel to encode two independent phase profiles or spatially multiplexed meta-holography by interleaved metasurfaces are captivated popular solutions to projecting multiplexed and vectorial images. However, the intrinsic limit of orthogonal polarization-channels, their crosstalk due to coupling between meta-atoms, and interleaving-induced degradation of efficiency and reconstructed image quality set great barriers for sophisticated meta-holography from being widely adopted. Here we report a noninterleaved TiO2 metasurface holography, and three distinct phase profiles are encoded into three orthogonal polarization bases with almost zero crosstalk. The corresponding three independently constructed intensity profiles are therefore assigned to trichromatic (RGB) beams, resulting in high-quality and high-efficiency vectorial meta-holography in the whole visible regime. Our strategy presents an unconventionally advanced holographic scheme by synergizing trichromatic colors and tripolarization channels, simply realized with a minimalist noninterleaved metasurface. Our work unlocks the metasurface's potentials on massive information storage, polarization optics, polarimetric imaging, holographic data encryption, etc.

Prediction on transmission trajectory of COVID-19 based on particle swarm algorithm.

This study aimed to predict the transmission trajectory of the 2019 Corona Virus Disease (COVID-19). The particle swarm optimization (PSO) algorithm was combined with the traditional susceptible exposed infected recovered (SEIR) infectious disease prediction model to propose a SEIR-PSO prediction model on the COVID-19. In addition, the domestic epidemic data from February 25, 2020 to March 20, 2020 in China were selected as the training set for analysis. The results showed that when the conversion rate, recovery rate, and mortality rate of the SEIR-PSO model were 1/5, 1/15, and 1/13, its predictive effect on the number of people diagnosed with COVID-19 was the closest to the real data; and the SEIR-PSO model showed a mean-square errors (MSE) value of 1304.35 and mean absolute error (MAE) value of 1069.18, showing the best prediction effect compared with the susceptible infectious susceptible (SIS) model and the SEIR model. In contrary to the standard particle swarm optimization (SPSO) and linear weighted particle swarm optimization (LPSO), which were two classical improved PSO algorithms, the reliability and diversity of the SEIR-PSO model were higher. In summary, the SEIR-PSO model showed excellent performance in predicting the time series of COVID-19 epidemic data, and showed reliable application value for the prevention and control of COVID-19 epidemic.

Strongly coupled evenly divided disks: a new compact and tunable platform for plasmonic Fano resonances.

Plasmonic artificial molecules are promising platforms for linear and nonlinear optical modulation at various regimes including the visible, infrared and terahertz bands. Fano resonances in plasmonic artificial structures are widely used for controlling spectral lineshapes and tailoring of near-field and far-field optical response. Generation of a strong Fano resonance usually relies on strong plasmon coupling in densely packed plasmonic structures. Challenges in reproducible fabrication using conventional lithography significantly hinders the exploration of novel plasmonic nanostructures for strong Fano resonance. In this work, we propose a new class of plasmonic molecules with symmetric structure for Fano resonances, named evenly divided disk, which shows a strong Fano resonance due to the interference between a subradiant anti-bonding mode and a superradiant bonding mode. We successfully fabricated evenly divided disk structures with high reproducibility and with sub-20 nm gaps, using our recently developed sketch and peel lithography technique. The experimental spectra agree well with the calculated response, indicating the robustness of the Fano resonance for the evenly divided disk geometry. Control experiments reveal that the strength of the Fano resonance gradually increases when increasing the number of split parts on the disk from three to eight individual segments. The Fano-resonant plasmonic molecules that can also be reliably defined by our unique fabrication approach open up new avenues for application and provide insight into the design of artificial molecules for controlling light-matter interactions.

Comparison of two intense pulsed light patterns for treating patients with meibomian gland dysfunction.

PURPOSE: The objective of this was to determine the efficacy of different patterns of intense pulsed light (IPL) therapy in patients with meibomian gland dysfunction (MGD). MATERIALS AND METHOD: IPL treatment was administered in 124 eyes of 62 patients with MGD-associated dry eye disease (DED). These patients were divided randomly into two groups treated with different IPL patterns. The first group was treated with "Optimal Pulse Technology" (OPT) (n = 29) and received three consecutive treatments (10-14 J/cm2) with three weeks between treatments. The other group was treated with "Intense Regulated Pulsed Light" (IRPL) (n = 33) and received four treatments (9-13 J/cm2) on days (D)1, D15, D45, and D75. The Ocular Surface Disease Index (OSDI), fluorescein breakup time (FTBUT), first and the average of noninvasive keratograph tear breakup times (NIKBUT), Schirmer I tests, conjunctival hyperemia, corneal fluorescent staining (CFS), tear meniscus height (TMH), MG secretion, and dropout were examined before each treatment and at one and three months after treatment. RESULTS: Compared to baseline, the clinical symptoms and signs in both groups were significantly improved at one and three months after IPL treatment. However, compared to the IRPL group, the OPT-treated group showed significant improvement in the clarity of MG secretions (P = 0.001), the number of MGs yielding clear or cloudy liquid secretions (P < 0.001), the total MG secretion score (P < 0.001) in lower eyelid, the lid margin score in upper (P < 0.001) and lower eyelids (P = 0.013), the first NIKBUT (P = 0.009), and FTBUT (P = 0.006). CONCLUSIONS: These results suggest that IPL has significant clinical value in treating patients with MGD. OPT IPL treatment was more effective in improving MG function in lower eyelids and partial tear film signs than IRPL IPL treatment. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov, and the clinical trial accession number is NCT02481167.

Enhanced extraordinary optical transmission and refractive-index sensing sensitivity in tapered plasmonic nanohole arrays.

The phenomenon of extraordinary optical transmission (EOT) caused by light through metallic nanohole arrays has attracted significant attention due to its potential applications for monolithic color filters and ultrasensitive label-free biosensing. However, the EOT spectra of these nanohole arrays have multiple resonance peaks that are spectrally close to each other due to the multiple resonance modes generated by different media on the upper and lower surfaces of metal. In addition, owing to the absorption loss of metal and the scattering of holes, the EOT resonance peaks have low transmission coefficient for practical applications. In this work, utilizing a tapered nanohole arrays structure which is stacked by multiple cylindrical holes with the same depth but different radii, we show that tapered nanohole arrays can effectively suppress the excitation of multiple resonance peaks, and a single EOT peak emerges in the transmission spectrum and simultaneously exhibits significantly enhanced transmission (∼7 times) and narrow linewidth (∼15 nm). The enhanced EOT of tapered nanohole arrays can be also found in other wavelength regions and plasmonic materials. Benefiting from isolated transmission peak, high transmission efficiency and extremely narrow linewidth, a highly sensitive plasmonic nanosensor with sensitivity of 1580 nm/RIU and figure of merit of 105 can be attained. We believe that the tapered nanohole structure would enable applications for ultrasensitive sensors, switches and efficient filters.

Short channel monolayer MoS2 field-effect transistors defined by SiO x nanofins down to 20 nm.

Layered semiconductors such as transition metal dichalcogenides (TMDs) with proper bandgaps complement the zero-bandgap drawback of graphene, demonstrating great potential for post-silicon complementary metal-oxide-semiconductor technology. Among the TMD family, molybdenum disulfide (MoS2) is highly attractive for its atomically thin body, large bandgap and decent mechanical and chemical stability. However, current nanofabrication techniques hardly satisfy the requirements of short channel and convenient preparation simultaneously. Here, we demonstrate a simple and effective approach to fabricate short channel chemical vapor deposition (CVD) monolayer MoS2 field-effect transistors (FET) with channel length down to 20 nm. Electron-beam lithography based on high-resolution negative-tone hydrogen silsesquioxane electron resists were applied to create 20 nm wide SiO x lines, defining the short channel length. The 20 nm MoS2 FET displays ON-sate current in excess of 100 µA µm-1. The corresponding current ON/OFF ratio at room temperature reaches 105. We carefully studied the short channel effect of as-fabricated MoS2 FETs. Combining with the large-scale growth of CVD method, our results will pave a way for short channel device applications based on atomically thin two-dimensional semiconductors.

Portable and Label-Free Detection of Blood Bilirubin with Graphene-Isolated-Au-Nanocrystals Paper Strip.

Point-of-care testing (POCT) devices represent a growing field that aims to develop low-cost, rapid, sensitive diagnostic testing platforms that are portable and self-contained. Surface-enhanced Raman spectroscopy (SERS) is an approach has shown high potential in POCT technology. However, the specificity or ability to uniquely detect a desired biomarker in complex biological samples is a key factor for translating SERS technologies to POCT. Herein, we fabricated cellulose SERS strips (CS) decorated with novel plasmonic nanoparticles, termed graphene-isolated-Au-nanocrystals (GIANs), for the portable detection of complex biological samples. This CS@GIANs SERS strip was used to detect free bilirubin (BR) in the blood of newborns, a biomarker of jaundice, without sample labeling or prepreparation. CS@GIANs showed superior affinity to hydrophobic BR molecules compared to typical SERS substrate, which reduced the steric hindrance effect from the nonspecific binding of BR with serum albumin in blood and improved sensitivity. Meanwhile, with the separation property of cellulose chromatography papers, CS@GIANs showed superior anti-interference to other biomolecules that had been previously adsorbed on the SERS strip. Moreover, the SERS signal from the graphitic shell of GIANs could be used as a stable internal calibration standard, which improved the reproducibility and accuracy of Raman analysis. Such a cellulose SERS strip holds high potential for enhancing current efforts in the development of rapid and low-cost point-of-care diagnostic testing.