Reconstitution of RNA cap methylation reveals different features of SARS-CoV-2 and SARS-CoV methyltransferases.

Cap RNA methylations play important roles in the replication, evasion of host RNA sensor recognition, and pathogenesis. Coronaviruses possess both guanine N7- and 2'-O-ribose methyltransferases (N7-MTase and 2'-O-MTase) encoded by nonstructural protein (nsp) 14 and nsp16/10 complex, respectively. In this study, we reconstituted the two-step RNA methylations of N7-MTase and 2'-O-MTase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and demonstrated its common and different features in comparison with that of SARS-CoV. We revealed that the nsp16/10 2'-O-MTase of SARS-CoV-2 has a broader substrate selectivity than the counterpart of SARS-CoV and can accommodate both unmethylated and uncapped RNA substrates in a sequence-independent manner. Most intriguingly, the substrate selectivity of nsp16/10 complex is not determined by the apoenzyme of nsp16 MTase but by its cofactor nsp10. These results provide insight into the unique features of SARS-CoV-2 MTases and may help develop strategies to precisely intervene in the methylation pathway and pathogenesis of SARS-CoV-2.

Low-loss chalcogenide photonic devices with a secondary coating method.

In the traditional dry etching process for photonic device fabrication, the etching effect is influenced in many ways, usually resulting in relatively large sidewall roughness and high transmission loss. In this study, an effective method, namely the secondary coating method, is proposed to reduce the transmission loss of a Ge-Sb-Se chalcogenide waveguide and increase the quality factor (Q-factor) of a Ge-Sb-Se chalcogenide micro-ring resonator. The Ge-Sb-Se waveguide and micro-ring resonator are fabricated by ultraviolet exposure/electron beam lithography and inductively coupled plasma etching technology. Afterward, a 10 nm-thick Ge-Sb-Se thin film is deposited by thermal evaporation. The measurements show that after secondary coating, the sidewall roughness of the waveguide is reduced from 11.96 nm to 6.52 nm, with the transmission loss reduced from 2.63± 0.19 dB/cm to 1.86± 0.11 dB/cm at 1.55 µm wavelength. Keeping an equal coupling condition with equal radius and coupling distance, the Q-factor of the micro-ring resonator is improved by 47.5% after secondary coating. All results indicate that the secondary coating method is a feasible way to generate low-loss and high Q-factor integrated chalcogenide photonic devices.

Radial IR-GRIN lens prepared by multi-temperature fields manipulated gradient crystallization within chalcogenide glass.

Chalcogenide glass has achieved great success in manufacturing axial-type infrared gradient refractive index (IR-GRIN) lenses. However, studies on radial-type IR-GRIN lenses, which are more ideal for optical design, remain rare. The present study introduces what we believe to be a new method for preparing radial IR-GRIN lens by creating high refractive index (n) In2S3 nanocrystals within a 65GeS2-25In2S3-10CsCl (GIC, in molar percentage) glass matrix. Upon introduction of multi-temperature field manipulation, we have successfully achieved central crystallization and simultaneous gradient attenuation spreading toward the edge within GIC glass, providing a radial GRIN profile with Δn over 0.1 while maintaining excellent IR transparency. In addition, the optical and structural properties of the GIC GRIN samples were characterized. The relationship between Raman intensity and the n of glass ceramics at different heat treatment temperatures was investigated, thereby enabling the indirect confirmation of the presence of radial gradient crystallization within the prepared GIC GRIN samples through Raman intensity. Multiple experimental results have shown that this approach has excellent reproducibility and potential for large-scale productions.

Structure-Based Virtual Screening for Methyltransferase Inhibitors of SARS-CoV-2 nsp14 and nsp16.

The ongoing COVID-19 pandemic still threatens human health around the world. The methyltransferases (MTases) of SARS-CoV-2, specifically nsp14 and nsp16, play crucial roles in the methylation of the N7 and 2'-O positions of viral RNA, making them promising targets for the development of antiviral drugs. In this work, we performed structure-based virtual screening for nsp14 and nsp16 using the screening workflow (HTVS, SP, XP) of Schrödinger 2019 software, and we carried out biochemical assays and molecular dynamics simulation for the identification of potential MTase inhibitors. For nsp14, we screened 239,000 molecules, leading to the identification of three hits A1-A3 showing N7-MTase inhibition rates greater than 60% under a concentration of 50 µM. For the SAM binding and nsp10-16 interface sites of nsp16, the screening of 210,000 and 237,000 molecules, respectively, from ZINC15 led to the discovery of three hit compounds B1-B3 exhibiting more than 45% of 2'-O-MTase inhibition under 50 µM. These six compounds with moderate MTase inhibitory activities could be used as novel candidates for the further development of anti-SARS-CoV-2 drugs.

Solution-processed Er3+-Doped GeS2 chalcogenide glass films with NIR photoluminescence towards functional flexibility and integration.

Rare-earth doped chalcogenide films are major components in flexible and integrated photonic and optoelectronic devices for modern communication systems, metrology, and optical sensing. However, it is still challenging to develop a high concentration of rare-earth doping chalcogenide film with a smooth surface to realize efficient photoluminescence (PL). Here, we demonstrate that Er3+-doped GeS2 films are prepared by spin-coating based on a two-step dissolution process. Such a two-step process provides the high solubility of Er3+ in GeS2 films and exhibits efficient emission at ∼1.5 µm crossing the telecommunication C-band. The highest PL emission intensity is obtained in GeS2 films doped with 1.4 mol% of Er3+, and this PL in GeS2 films is reported for the first time. We propose adjustments of annealing parameters for improving the PL characteristics in such materials. Through the control precision of the heating rate and annealing temperature, the smooth surface of GeS2 films enables efficient photo-luminescence. This two-step dissolution-based strategy would pave a new path to design luminescent chalcogenide films for application in flexible and integrated optoelectronics and photonics.

Detection of copper ions in an aqueous solution by a dual-peak long period fiber grating functionalized with a polypyrrole-chitosan composite.

A dual-peak long period fiber grating (DP-LPFG) sensor functionalized by polypyrrole-chitosan composite was proposed for sensitive detection of Cu2+ ions in aqueous solution. The nitrogen atom on the polypyrrole ring and the amino group on the chitosan chain in the complex matrix can chelate the Cu2+ ions. Thus, the refractive index of the overlay changed and further modulated the transmission spectrum of DP-LPFG. After special design, the double peaks can move in opposite directions with the increase of Cu2+ ion concentration, thereby greatly improving detection sensitivity. The linear sensitivity of the fabricated sensor was measured to be 9.12 and 2.14 nm/ppm (0.61 and 0.14 nm/µM) for concentrations of 0.1-0.5 (1.5 µM-7.5 µM) and 0.5-2 ppm (7.5 µM-30 µM), respectively. In addition, the Langmuir isothermal model was used to evaluate the overall response of the sensor to Cu2+ ions quantitatively, and the detection limit was determined to be 0.05 ppb (0.75 nM). This ingenious sensor offers a new solution for sensitive detection of heavy metal ions in environmental water.

Embedded racetrack microring resonator sensor based on GeSbSe glasses.

In this article, a compact racetrack double microring resonator (MRR) sensor based on Ge28Sb12Se60 (GeSbSe) is investigated. The sensor device consists of a racetrack microring, an embedded small microring, and a strip waveguide. Electron beam lithography (EBL) and dry etching are used to fabricate the device. The compact racetrack double MRR device are obtained with Q-factor equal to 7.17 × 104 and FSR of 24 nm by measuring the transmission spectrum. By measuring different concentrations of glucose solutions, a sensitivity of 297 nm/RIU by linear fitting and an intrinsic limit of detection (iLOD) of 7.40 × 10-5 are obtained. It paves the way for the application of chalcogenide glasses in the field of biosensing.

High Q-factor, ultrasensitivity slot microring resonator sensor based on chalcogenide glasses: erratum.

We correct the error in [Opt. Express30, 3866 (2022)10.1364/OE.450092], Fig. 6(c). The unit of the vertical axis in the figure should be arbitrary units, not dB. All the conclusions are unchanged after the correction.

Embedded racetrack microring resonator sensor based on GeSbSe glasses: erratum.

We correct the error in [Opt. Express31, 1103(2023)10.1364/OE.478613] Fig. 5(c). The unit of the vertical axis in the figure should be arbitrary units, not dB. All the conclusions are not changed after the correction.

Comparison of model-specific histopathology in mouse models of COVID-19.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been identified as the causative agent of the current coronavirus disease 2019 pandemic. Development of animal models that parallel the clinical and pathologic features of disease are highly essential to understanding the pathogenesis of SARS-CoV-2 infection and the development of therapeutics and prophylactics. Several mouse models that express the human angiotensin converting enzyme 2 (hACE2) have been created, including transgenic and knock-in strains, and viral vector-mediated delivery of hACE2. However, the comparative pathology of these mouse models infected with SARS-CoV-2 are unknown. Here, we perform systematic comparisons of the mouse models including K18-hACE2 mice, KI-hACE2 mice, Ad5-hACE2 mice and CAG-hACE2 mice, which revealed differences in the distribution of lesions and the characteristics of pneumonia induced. Based on these observations, the hACE2 mouse models meet different needs of SARS-CoV-2 researches. The similarities or differences among the model-specific pathologies may help in better understanding the pathogenic process of SARS-CoV-2 infection and aiding in the development of effective medications and prophylactic treatments for SARS-CoV-2.

Third-order optical nonlinearity of CsPb(Br/I)3 metal halide perovskites nano-crystals embedded chalcogenide glass.

The nonlinear optical properties of emerging metal halide perovskites (MHP) materials are sufficiently intriguing that this topic has become the hotspots in the realm of material science. Hence, we investigate the third-order nonlinear optical properties of CsPbBrx/I3-x (x = 1, 2, 3) MHP nano-crystals (NCs) embedded chalcogenide glass (ChG) within a GeS2-Sb2S3 pseudo-binary system, by monitoring the composition, excitation wavelength and intensity dependencies via femtosecond Z-scan technique. We have found that the intrinsic large optical nonlinearity of ChG can be further enhanced because of the incorporation of MHP NCs, and that the optical nonlinearity of MHP-ChG containing pristine Br NCs is more pronounced compared to its counterparts with mixed Br/I NCs, due to a combination of multiple factors.

Narrow-bandwidth Bragg grating filter based on Ge-Sb-Se chalcogenide glasses.

Bragg grating (BG) filters play important roles in integrated photonics such as signal processing and optical sensing. In silicon-based counterpart photonic platforms, the application of narrow-bandwidth (Δλ) filters is often restrained by fabrication limitations. In this study, narrow-bandwidth BG filters based on Ge-Sb-Se chalcogenide materials are investigated. The structure of the filter is designed by optimizing the grating period, corrugation height, and grating number. The large corrugation of chalcogenide BG is more friendly and convenient for manufacturing process. The symmetric and asymmetric corrugation filters are then fabricated and characterized. Experimental results show a half-maximum bandwidth of 0.97 nm and 0.32 nm for symmetric and asymmetric filters, respectively, which demonstrates excellent narrow-bandwidth filtering performance of chalcogenide BG.

High Q-factor, ultrasensitivity slot microring resonator sensor based on chalcogenide glasses.

In this article, the chalcogenide slot waveguide is theoretically studied, and the highest power confinement factors of the slot region and the cladding region are obtained to be 36.3% and 56.7%, respectively. A high-sensitivity chalcogenide slot microring resonator sensor is designed and fabricated by electron-beam lithography and dry etching. The structure increases the sensitivity of the sensor compared with the conventional evanescent field waveguide sensor. The cavity has achieved a quality factor of 1 × 104 by fitting the resonant peaks with the Lorentzian profile, one of the highest quality factors reported for chalcogenide slot microring resonators. The sensor sensitivity is measured to be 471 nm/RIU, which leads to an intrinsic limit of detection of 3.3 × 10--4 RIU.

Rapid and sensitive detection of ammonia in water by a long period fiber grating sensor coated with sol-gel silica.

A sensitive ammonia sensor based on long-period fiber grating (LPFG) is designed and manufactured for the detection of ammonia concentration in water. Femtosecond laser direct writing technology is used to write LPFGs on standard single-mode silica fiber. A thin layer doped with basic dyes is coated on the optical fiber for sensing by using the sol-gel method. The thicknesses of sol-gel layers, which play a key role in the sensitivity of the LPFG sensor, were carefully studied. Experimental results show that LPFG with a functional layer of ∼340 nm has the best sensing performance, and the detection limit is 0.08 ppm. The response time of the sensor is less than one minute, and the sensor has good repeatability with a short recovery time. Compared with other organic molecules and ions in water, the proposed LPFG sensor has not only good reusability, but also selectivity for the detection of ammonia.

Differential expression of microRNAs associated with neurodegenerative diseases and diabetic nephropathy in protein l-isoaspartyl methyltransferase-deficient mice.

Protein l-isoaspartyl methyltransferase (PIMT/PCMT1), an enzyme repairing isoaspartate residues in peptides and proteins that result from the spontaneous decomposition of normal l-aspartyl and l-asparaginyl residues during aging, has been revealed to be involved in neurodegenerative diseases (NDDs) and diabetes. However, the molecular mechanisms for a putative association of PIMT dysfunction with these diseases have not been clarified. Our study aimed to identify differentially expressed microRNAs (miRNAs) in the brain and kidneys of PIMT-deficient mice and uncover the epigenetic mechanism of PIMT-involved NDDs and diabetic nephropathy (DN). Differentially expressed miRNAs by sequencing underwent target prediction and enrichment analysis in the brain and kidney of PIMT knockout (KO) mice and age-matched wild-type (WT) littermates. Sequence analysis revealed 40 differentially expressed miRNAs in the PIMT KO mouse brain including 25 upregulated miRNAs and 15 downregulated miRNAs. In the PIMT KO mouse kidney, there were 80 differentially expressed miRNAs including 40 upregulated miRNAs and 40 downregulated miRNAs. Enrichment analysis and a systematic literature review of differentially expressed miRNAs indicated the involvement of PIMT deficiency in the pathogenesis in NDDs and DN. Some overlapped differentially expressed miRNAs between the brain and kidney were quantitatively assessed in the brain, kidney, and serum-derived exosomes, respectively. Despite being preliminary, these results may aid in investigating the pathological hallmarks and identify the potential therapeutic targets and biomarkers for PIMT dysfunction-related NDDs and DN.

Charge Reversion Simultaneously Enhances Tumor Accumulation and Cell Uptake of Layered Double Hydroxide Nanohybrids for Effective Imaging and Therapy.

Nanotheranostics have been actively sought in precision nanomedicine in recent years. However, insufficient tumor accumulation and limited cell uptake often impede the nanotheranostic efficacy. Herein, pH-sensitive charge-reversible polymer-coated layered double hydroxide (LDH) nanohybrids are devised to possess long circulation in blood but reserve surface charges in the weakly acidic tumor tissue to re-expose therapeutic LDH nanoparticles for enhanced tumor accumulation and cell uptake. In vitro experimental data demonstrate that charge-reversible nanohybrids mitigate the cell uptake in physiological conditions (pH 7.4), but remarkably facilitate internalization by tumor cells after charge reversion in the weakly acidic environment (pH 6.8). More significantly, about 6.0% of injected charge-reversible nanohybrids accumulate in the tumor tissue at 24 h post injection, far higher than the average accumulation (0.7%) reported elsewhere for nanoparticles. This high tumor accumulation clearly shows the tumor tissues in T1 -weighted magnetic resonance imaging. As a consequence, >95% inhibition of tumor growth in the B16F0-bearing mouse model is achieved via only one treatment combining RNAi and photothermal therapy under very mild irradiation (808 nm laser, 0.3 W cm-2 for 180 s). The current research thus demonstrates a new strategy to functionalize nanoparticles and simultaneously enhance their tumor accumulation and cell internalization for effective cancer theranostics.

Extension of the Swanepoel method for obtaining the refractive index of chalcogenide thin films accurately at an arbitrary wavenumber.

The well-known Swanepoel method was often used to obtain the refractive index (RI) of thin films at the wavenumber values corresponding to the extremes of the transmission interference fringes. But it is difficult to accurately obtain the RI of chalcogenide thin films, especially at an arbitrary wavenumber. So a regional approach method (RAM) was presented here to extend the Swanepoel method to an arbitrary wavenumber. In the RAM the RI at the arbitrary wavenumber was determined through dynamic matching. The calculated values were used to match the experimental transmittance. The accuracy of the RI is better than 0.5%. The RI of a well-known film was obtained by the RAM. And the results are in great agreement with the true values of the RI of the film which indicates the correctness and effectiveness of the RAM. Moreover, the transmission spectrum of Ge-Sb-Se film was measured in the ultra-broadband range of 2000-18000 cm-1 (555-5000 nm), and finally the RI of the film was obtained at the 22 wavenumbers of the spacer 600 cm-1 by the RAM.

Simple and seamless broadband optical frequency comb generation using an InAs/InP quantum dot laser.

A simple and seamless broadband optical frequency comb (OFC) generator is proposed and experimentally demonstrated using a Fabry-Perot quantum dot mode-locked laser combined with a dual-driven LiNbO3 Mach-Zehnder modulator driven by a low-power radio frequency (RF) signal. It is experimentally demonstrated that the 10-dB seamless bandwidth of the OFC is 8.2 nm (1.02 THz), which has 62 and 40 comb lines for frequency intervals of 16.56 GHz and 24.84 GHz, respectively. The single-sideband phase noise is as low as -112 and -108 dBc/Hz at an offset of 10 kHz, respectively, for the photodetector-converted 16.56 and 24.84 GHz frequency carriers. Correspondingly, the RF linewidths of the 16.56 GHz and 24.84 GHz carriers are about 251 Hz-263 Hz, respectively. Using a QD laser, an ultra-low phase noise and quasi-tunable broadband OFC generator is obtained easily.

Engineering of a self-adjuvanted iTEP-delivered CTL vaccine.

Cytotoxic T lymphocyte (CTL) epitope peptide-based vaccines are widely used in cancer and infectious disease therapy. We previously generated an immune-tolerant elastin-like polypeptides (iTEPs)-based carrier to deliver a peptide CTL vaccine and enhance the efficiency of the vaccine. To further optimize the vaccine carrier, we intended to potentiate its function by designing an iTEP-based carrier that was able to deliver adjuvant and a vaccine epitope as one molecule. Thus, we fused a 9-mer H100, a peptide derived from the high-mobility group box 1 protein (HMGB1) that could induce activation of dendritic cells (DCs), with an iTEP polymer to generate a new iTEP polymer named H100-iTEP. The H100-iTEP still kept the feature of reversible phase transition of iTEPs and should be able to be used as a polymer carrier to deliver peptide vaccines. The expression levels of CD80/CD86 on DCs were assessed using flow cytometry. The iTEP fusion-stimulated IL-6 secretion by DCs was measured with ELISA. Activation of antigen-specific CD8+ T cells induced by iTEP fusions was examined through a B3Z hybridoma cell activation assay. In vivo CTL activation promoted by iTEP fusions was detected by an IFN-γ-based ELISPOT assay. The iTEP fused with H100 could induce maturation of DCs in vitro as evidenced by increased CD80 and CD86 expression. The iTEP fusion also promoted activation of DCs by increasing secretion of a proinflammatory cytokine IL-6. The N-terminus or C-terminus fusion of H100 to iTEP had a similar effect and a reduced form of cysteine in iTEP fusions was required for DC stimulation. iTEP fusions potentiated a co-administrated CTL vaccine by increasing an antigen-specific CTL response in vitro and in vivo. When the H100-iTEP was fused to a CTL epitope to generate a one-molecule vaccine, this self-adjuvanted vaccine elicited a stronger antigen-specific CTL response than a vaccine adjuvanted by Incomplete Freund's Adjuvant. Thus, we have successfully generated a functional, one-molecule iTEP-based self-adjuvanted vaccine.

Investigation on Spectral Characteristic and Threshold Behavior of Network Structure of Ge-Sb-S Chalcogenide Glasses.

Two series of chalcogenide glasses in Ge-Sb-S ternary system were synthesized with melt-quenching method. The phycochemical properties and spectral characteristic of glasses with different content of Ge and Sb were obtained with a series of measurements, and the systematic analysis on the change of optical properties was conducted in terms of microstructure of glasses combined with the Raman spectra. With constraint theory based on mean coordination number (Z), we described the variation trend of network structure directly. It was found that as long as the value of Z reaches 2.6, new vibration peaks would be formed in the Raman spectra indicating the presence of threshold behavior as well as the change of the network structure of the Ge-Sb-S glasses which could be expressed in a specific varition in the number of metal bonds and the nonmetal bonds. The appearance of new functional groups in the network have changed the total bond energy of glasses, and then affected the energy band structure of glasses representing the corresponding threshold behavior of the value of optical band gap (Eopg).