Virtual sketching-based dental anatomy module improves learners' abilities to use computer-aided design to create dental restorations and prostheses.

Dental anatomy education for dental technology students should be developed in alignment with digital dental laboratory practices. We hypothesized that a virtually assisted sketching-based dental anatomy teaching module could improve students' acquisition of skills essential for digital restoration design. The second-year dental technology curriculum included a novel virtual technology-assisted sketching-based module for dental anatomy education. Pre- and post-course assessments evaluated students' skill sets and knowledge bases. Computer-aided design (CAD) scores were analyzed after one year to assess how the skills students developed through this module impacted their subsequent CAD performance. Participants who undertook the dental sketching-based teaching module demonstrated significantly improved theoretical knowledge of dental anatomy, dental aesthetic perception, and spatial reasoning skills. A partial least squares structural equation model indicated that the positive effects of this module on subsequent CAD performance were indirectly mediated by dental aesthetic perception, spatial reasoning, and practice time. A virtually assisted sketching-based dental anatomy teaching module significantly improved students' acquisition of skills and knowledge and positively mediated dental technology students' CAD performance.

A C-type lectin with dual carbohydrate recognition domains functions in innate immune response in Asian corn borer, Ostrinia furnacalis.

C-type lectins (CTLs) act as pattern recognition receptors (PRRs) to initiate the innate immune response in insects. A CTL with dual carbohydrate recognition domains (CRDs) (named immulectin-4 [IML-4]) was selected from the Ostrinia furnacalis transcriptome dataset for functional studies. We cloned the full-length complementary DNA of O. furnacalis IML-4 (OfIML-4). It encodes a 328-residue protein with a Glu-Pro-Asn (EPN) and Gln-Pro-Asp (QPD) motifs in 2 CRDs, respectively. OfIML-4 messenger RNA levels increased significantly upon the bacterial and fungal infection. Recombinant OfIML-4 (rIML-4) and its individual CRDs (rCRD1 and rCRD2) exhibited the binding ability to various microorganisms including Escherichia coli, Micrococcus luteus, Pichia pastoris, and Beauveria bassiana, and the cell wall components including lipopolysaccharide from E. coli, peptidoglycan from M. luteus or Bacillus subtilis, and curdlan from Alcaligenes faecalis. The binding further induced the agglutination of E. coli, M. luteus, and B. bassiana in the presence of calcium, the phagocytosis of Staphylococcus aureus by the hemocytes, in vitro encapsulation and melanization of nickel-nitrilotriacetic acid beads, and a significant increase in phenoloxidase activity of plasma. In addition, rIML-4 significantly enhanced the phagocytosis, nodulation, and resistance of O. furnacalis to B. bassiana. Taken together, our results suggest that OfIML-4 potentially works as a PRR to recognize the invading microorganisms, and functions in the innate immune response in O. furnacalis.

Dosing optimization of rituximab for primary membranous nephropathy by population pharmacokinetic and pharmacodynamic study.

Primary membranous nephropathy (PMN) is the most common cause for adult nephrotic syndrome. Rituximab has demonstrated promising clinical efficacy by random controlled trials and the off-label use is widely adopted in PMN. However, the standard dosage is borrowed from B cell lymphoma treatment with far more antigens and is oversaturated for PMN treatment, accompanied with additional safety risk and unnecessary medical cost. More than 15% serious adverse events were observed under standard dosage and low dose therapies were explored recently. Dose optimization by clinical trials is extremely time- and cost-consuming and can be significantly accelerated with the aid of model-informed drug development. Here, we aim to establish the first population pharmacokinetic and pharmacodynamic (PPK/PD) model for rituximab in PMN to guide its dosage optimization. Rituximab pharmacokinetic and pharmacodynamic data from 41 PMN patients in a retrospective study under a newly proposed monthly mini-dose were used to construct quantitative dose-exposure-response relationship via mechanistic target-mediated drug disposition (TMDD) model followed by regression between the reduction of anti-PLA2R titer and time after the treatment. The final model, validated by goodness-of-fit plots, visual predictive checks and bootstrap, was used to recommend the optimized dosing regimen by simulations. The model was well validated for PK/PD prediction. The systemic clearance and half-life are 0.54 L/h and 14.7 days, respectively. Simulation of a novel regimen (6 monthly doses of 100 mg) indicated the comparable ability and superior duration time of CD20+ B cell depletion compared with standard dosage, while the cumulative dosage and safety risk was significantly decreased. We established the first PPK/PD model and provide evidence to support the dosage optimization based on monthly mini-dose. Our study can also efficiently accelerate dosage optimization of novel anti-CD20 antibodies in PMN and other indications.

Ultra-thin sub-diffraction metalens with a wide field-of-view for UV focusing.

In recent years, wide field-of-view imaging technology based on a metasurface has been widely applied. However, works on the reported sub-diffraction metalens with a wide field-of-view indicate that multiple structures are essential to effectively eliminate aberrations, which results in a heavy device thickness and weakens the advantage of an ultra-thin metasurface. To solve this problem, according to the super-oscillation theory and the translational symmetry of quadratic phase, as well as the principle of virtual aperture diaphragm based on wave vector filter, this Letter demonstrates a sub-diffraction metalens combined with a single quadratic metalens and a wave vector filter. Our design not only realizes the super-resolution effects of 0.74 to 0.75 times the diffraction limit in the wide field-of-view of nearly 180° for the first time to our knowledge but also compresses the device thickness to the subwavelength order in principle. The proposed ultra-thin sub-diffraction metalens with a wide field-of-view is expected to be applied in the fields of super-resolution fast scanning imaging, information detection, small target recognition, and so on.

Synergistic Effect of Dual-Doped Carbon on Mo2C Nanocrystals Facilitates Alkaline Hydrogen Evolution.

Molybdenum carbide (Mo2C) materials are promising electrocatalysts with potential applications in hydrogen evolution reaction (HER) due to low cost and Pt-like electronic structures. Nevertheless, their HER activity is usually hindered by the strong hydrogen binding energy. Moreover, the lack of water-cleaving sites makes it difficult for the catalysts to work in alkaline solutions. Here, we designed and synthesized a B and N dual-doped carbon layer that encapsulated on Mo2C nanocrystals (Mo2C@BNC) for accelerating HER under alkaline condition. The electronic interactions between the Mo2C nanocrystals and the multiple-doped carbon layer endow a near-zero H adsorption Gibbs free energy on the defective C atoms over the carbon shell. Meanwhile, the introduced B atoms afford optimal H2O adsorption sites for the water-cleaving step. Accordingly, the dual-doped Mo2C catalyst with synergistic effect of non-metal sites delivers superior HER performances of a low overpotential (99 mV@10 mA cm-2) and a small Tafel slope (58.1 mV dec-1) in 1 M KOH solution. Furthermore, it presents a remarkable activity that outperforming the commercial 10% Pt/C catalyst at large current density, demonstrating its applicability in industrial water splitting. This study provides a reasonable design strategy towards noble-metal-free HER catalysts with high activity.

High-efficiency in situ amplitude and phase control of infrared light using topological polaritons.

Polaritons - material excitation coupled with light - are thought to hold the potential for the extreme control of light down to the atomic length scale because of their high field confinement and sub-wavelength scales. For practical applications, it is essential but still a formidable challenge to manipulate polaritons with high efficiency and a wide tunable range. These obstacles may be overcome by the topology of polaritons. In photonic systems composed of graphene/α-MoO3 heterostructures, the topology of the hybrid polariton characterized by the isofrequency curve can transform from open hyperbolas to closed ellipse-like curves, driven by the carrier concentrations of graphene. The electronic tunability of such topological polaritons offers a unique platform for two-dimensional energy transfer. Here, by introducing local gates to obtain a tunable spatial carrier density profile in the graphene/α-MoO3 heterostructure, the phase of the polariton is predicted to be efficiently tuned from 0 to 2π in situ. Remarkably, the reflectance and transmittance through the gap between local gates can also be modulated in situ from 0 to 1 with high efficiency, where the device length can be less than 100 nm. The modulation is achieved owing to the dramatic changes in the wave vector of polaritons near the topological transition point. The proposed structures not only have direct applications in two-dimensional optics such as total reflectors, phase (amplitude) modulators, and optical switches but also can serve as an important component for complex nano-optical devices.

Ultrasensitive enhanced Raman spectroscopy by hybrid surface-enhanced and interference-enhanced Raman scattering with metal-insulator-metal structures.

High-sensitivity, reproducible, and low-cost substrate has been a major obstacle for practical sensing application of surface-enhancement Raman scattering (SERS). In this work, we report a type of simple SERS substrate which is composed of metal-insulator-metal (MIM) structure of Ag nanoisland (AgNI)-SiO2-Ag film (AgF). The substrates are fabricated by only evaporation and sputtering processes, which are simple, fast and low-cost. By combining the hotspots and interference-enhanced effects in AgNIs and the plasmonic cavity (SiO2) between AgNIs and AgF, the proposed SERS substrate shows an enhancement factor (EF) of 1.83 × 108 with limit of detection (LOD) down to 10-17 mol/L for rhodamine 6 G (R6G) molecules. The EFs are ∼18 times higher than that of conventional AgNIs without MIM structure. In addition, the MIM structure shows excellent reproducibility with relative standard deviation (RSD) less than 9%. The proposed SERS substrate is fabricated only with evaporation and sputtering technique and the conventionally used lithographic methods or chemical synthesis are not required. This work provides a simple way to fabricate ultrasensitive and reproducible SERS substrates which show great promise for developing various biochemical sensors with SERS.

Sigmoido-vesical fistula secondary to sigmoid colon cancer presenting as urinary tract infection with Lactococcus lactis: A case report.

A colovesical fistula is a pathological communication between the colon and bladder. The symptoms include pneumaturia, fecaluria, and a lower urinary tract infection. The diagnosis is based on clinical symptoms, but the symptoms are not specific. Therefore, confirming the diagnosis is challenging. Urine cultures performed in patients with colovesical fistulas usually show growth of Escherichia coli or mixed growth of bowel organisms. Urinary tract infections caused by Lactococcus lactis are very rare, as it is rarely considered pathogenic in humans. We report the case of a 70-year-old woman who presented with symptoms of a recurrent urinary tract infection. Urine cultures were positive for L. lactis. Abdominopelvic computed tomography (CT) revealed focal thickening of the bladder wall and gas in the bladder. Cystoscopic examination and colonoscopy revealed sigmoid colon cancer and a sigmoido-vesical fistula. Laparoscopic surgical treatment was done. The patient recovered and was discharged 3 weeks later without chemoradiotherapy. On follow-up after 6 months, the patient was asymptomatic and stable. To our knowledge, this is the second reported case of L. lactis infection of the urinary tract and the first reported case in adults. L. lactis infection usually indicates the presence of serious underlying diseases such as malignancies, uncontrolled diabetes, and organ failure.

Carpal tunnel syndrome caused by tophi in the superficial flexor tendon: a case report.

Carpal tunnel syndrome (CTS) is the most common disease among peripheral nerve entrapment diseases. CTS is often caused by the hyperplasia of the transverse carpal ligament and edema of tissue in the carpal tunnel, resulting in compression of the median nerve. Specific manifestations of CTS include numbness, loss of skin sensation in the palm and three and a half fingers on the radial side, and decreased muscle strength; however, CTS caused by wrist tophi is very rare. To our knowledge, CTS with median nerve compression caused by tophi in the superficial flexor tendon of the index finger of the wrist has not been reported before. Here, we will report a case of CTS caused by tophi in the wrist in a 37-year-old patient with no history of gout. CTS caused by tophi is uncommon, but if the patient has high uric acid, CTS may be due to tophi.

A planar ultraviolet objective lens for optical axis free imaging nanolithography by employing optical negative refraction.

Lithography is one of the most key technologies for integrated circuit (IC) manufacturing and micro/nano-functional device fabrication, while the imaging objective lens plays one important role. Due to the curved surface of the conventional objective lens, the imaging field of view is limited and the objective lens system is complex. In this paper, a planar objective lens based on the optical negative refraction principle is demonstrated for achieving optical axis free and long depth of focus imaging nanolithography. Through employing a hyperbolic metamaterial composed of silver/titanium dioxide multilayers, plasmonic waveguide modes could be generated in multilayers, which results in optical negative refraction and then flat imaging at ultraviolet wavelength. The corresponding imaging characteristics are investigated in simulation and experiment. At the I-line wavelength of 365 nm, the highest imaging resolution of 165 nm could be realized in the 100 nm photoresist layer under the working gap of 100 nm between the objective lens and substrate. Moreover, this planar objective lens has good ability for cross-scale and two-dimensional imaging lithography, and is similar to a conventional projection objective lens. It is believed that this kind of planar objective lens will provide a promising avenue for low-cost nanofabrication scenarios in the near future.

Overexpressed SNRPB/D1/D3/E/F/G correlate with poor survival and immune infiltration in hepatocellular carcinoma.

BACKGROUND: Prior reports have indicated that the abnormal expression of small nuclear ribonucleoproteins (snRNPs) genes is related to malignant tumors. However, in hepatocellular carcinoma (HCC), the precise role of snRNPs is not well understood. Therefore, the purpose of this study was to evaluate the prognostic roles of SNRPB/D1/D2/D3/E/F/G and their correlation to immune infiltration in HCC. METHODS: The study was carried out via the following databases, software, and experimental validation: ONCOMINE, GEPIA2, UALCAN, The Cancer Genome Atlas, Gene Expression Omnibus, ArrayExpress, Kaplan-Meier plotter, cBioPortal, STRING, DAVID 6.8, TIMER, Cytoscape software, and immunohistochemistry experiments. RESULTS: Overexpressed SNRPB/D1/D2/D3/E/F/G proteins were found in HCC tissues. The transcription levels of 7 snRNPs genes were related to the TP53 mutation and tumor grades. SNRPB/D1/D2/D3/F/G expression was significantly correlated with cancer staging, whereas SNRPE was not. Moreover, Kaplan-Meier survival analysis showed that upregulation of SNRPB/D1/D2/E/G was relevant to worse OS in HCC patients, especially in patients with alcohol consumption and those without viral hepatitis. Multivariate Cox regression analysis indicated that expression of SNRPB/D1/D3/E/F/G were independent prognostic factors for unfavorable OS in HCC. In addition, a high mutation rate of snRNPs genes (44%) was also found in HCC. The mRNA expression levels of snRNPs were meaningfully and positively related to six types of infiltrating immune cells (B cells, CD4+ T cells, CD8+ T cells, neutrophil, macrophage, and dendritic cells). Also, SNRPB/D1/G genes were significantly associated with molecular markers of various immune cells in HCC. CONCLUSIONS: SNRPB/D1/D3/E/F/G are potential prognostic biomarkers for a short OS in HCC, and SNRPB/D1/G were novel immune therapy targets in HCC patients.

Generation of A Space-Variant Vector Beam with Catenary-Shaped Polarization States.

We demonstrate the generation of a space-variant vector beam with catenary-shaped polarization states based on the polarization interferometry. With a spatial light modulator and a common path interferometric configuration, two orthogonally circularly polarized beams with different phase modulation overlap each other, yielding the vector beams. In addition, the polarization states of this vector beam are scalable to the arbitrary spatial distribution because of its great flexibility and universal applicability. It is expected that this vector beam may have many potential and intriguing applications in the micro/nano material processing, liquid crystal elements fabrication and optical micro-manipulation, and so on.

Deep subwavelength interference lithography with tunable pattern period based on bulk plasmon polaritons.

Interference lithography based on surface plasmon polaritons has been proven to break the diffraction limit and deliver the high imaging resolution. However, most previously reported studies suffer from the inflexible pattern pitch for a certain structure ascribed to fixed excitation mode, which limits the applications in micro-/nano- fabrications. In this work, the large area deep subwavelength interference lithography with tunable pattern period based on bulk plasmon polaritons (BPPs) is proposed. By simply tuning the incident angle, the spatial frequencies of the selected BPPs modes squeezed through hyperbolic metamaterial changes correspondingly. As a result, the pitch of the interference pattern is continuously altered. The results demonstrate that one-dimensional and two-dimensional periodic patterns with pitch resolution ranging from 45 nm (~λ/10) to 115 nm (~λ/4) can be generated under 436 nm illumination. Additionally, the general method of designing such an interference lithography system is also discussed, which can be used for nanoscale fabrication in this fashion.

Launching deep subwavelength bulk plasmon polaritons through hyperbolic metamaterials for surface imaging with a tuneable ultra-short illumination depth.

Hyperbolic metamaterials (HMMs) composed of multiple nanometal-dielectric films are proposed for launching deep subwavelength bulk plasmon polaritons (BPPs) as uniform, large area surface imaging illumination sources with a skin depth even beyond 10 nm. Benefiting from the coupled plasmon modes over a wide wavevector range in HMMs, the illumination depth could be continually tuned, simply by adjusting the incidence angle of light impinged on a grating structure for BPP excitation. As an example, the illumination depths of 19-63 nm at a light wavelength of 532 nm are demonstrated with SiO2-Ag multifilms. Moreover, the structure holds its deep subwavelength illumination depth for a broad light wavelength range, resembling that of light total internal reflection in a prism with an ultra high refractive index. Furthermore, a fluorescent nanoparticle based micro-zone system was employed for estimating the illumination depth of the HMM structure. The method is believed to provide access for surface imaging features in ultra thin layers especially for bio-samples.

Electro-optical phenomena based on ionic liquids in an optofluidic waveguide.

An optofluidic waveguide with a simple two-terminal electrode geometry, when filled with an ionic liquid (IL), forms a lateral electric double-layer capacitor under a direct current (DC) electric field, which allows the realization of an extremely high carrier density in the vicinity of the electrode surface and terminals to modulate optical transmission at room temperature under low voltage operation (0 to 4 V). The unique electro-optical phenomenon of ILs was investigated at three wavelengths (663, 1330 and 1530 nm) using two waveguide geometries. Strong electro-optical modulations with different efficiencies were observed at the two near-infrared (NIR) wavelengths, while no detectable modulation was observed at 663 nm. The first waveguide geometry was used to investigate the position-dependent modulation along the waveguide; the strongest modulation was observed in the vicinity of the electrode terminal. The modulation phase is associated with the applied voltage polarity, which increases in the vicinity of the negative electrode and decreases at the positive electrode. The second waveguide geometry was used to improve the modulation efficiency. Meanwhile, the electro-optical modulations of seven ILs were compared at an applied voltage ranging from ±2 V to ±3.5 V. The results reveal that the modulation amplitude and response speed increase with increasing applied voltage, as well as the electrical conductivity of ILs. Despite the fact that the response speed isn't fast due to the high ionic density of ILs, the modulation amplitude can reach up to 6.0 dB when a higher voltage (U = ±3.5 V) is applied for the IL [Emim][BF4]. Finally, the physical explanation of the phenomenon was discussed. The effect of the change in IL structure on the electro-optical phenomena was investigated in another new experiment. The results reveal that the electro-optical phenomenon is probably caused mainly by the change in carrier concentration (ion redistribution near charged electrodes), which induces the enhancement and suppression of NIR optical absorption (contributed by C-H and N-H groups) in the vicinity of the negative electrode and positive electrode, respectively.

Subwavelength imaging of a multilayered superlens with layers of nonequal thickness.

We propose a multilayered superlens comprising alternately layered metal and dielectric films with layers of nonequal thickness to realize subwavelength imaging, even when permittivities of the metal and dielectric are mismatched. Based on ideal imaging conditions, the exact constraint relations about the thickness of each dielectric layer and the permittivity of the surrounding medium of the multilayered superlens are first acquired when the superlens is modeled by the effective medium theory. Theoretical analysis and numerical simulations indicate that a multilayered superlens with constraint relations can realize subwavelength imaging at wavelengths of 335 to 385 nm.