CDK8 and CDK19: positive regulators of signal-induced transcription and negative regulators of Mediator complex proteins.

We have conducted a detailed transcriptomic, proteomic and phosphoproteomic analysis of CDK8 and its paralog CDK19, alternative enzymatic components of the kinase module associated with transcriptional Mediator complex and implicated in development and diseases. This analysis was performed using genetic modifications of CDK8 and CDK19, selective CDK8/19 small molecule kinase inhibitors and a potent CDK8/19 PROTAC degrader. CDK8/19 inhibition in cells exposed to serum or to agonists of NFκB or protein kinase C (PKC) reduced the induction of signal-responsive genes, indicating a pleiotropic role of Mediator kinases in signal-induced transcriptional reprogramming. CDK8/19 inhibition under basal conditions initially downregulated a small group of genes, most of which were inducible by serum or PKC stimulation. Prolonged CDK8/19 inhibition or mutagenesis upregulated a larger gene set, along with a post-transcriptional increase in the proteins comprising the core Mediator complex and its kinase module. Regulation of both RNA and protein expression required CDK8/19 kinase activities but both enzymes protected their binding partner cyclin C from proteolytic degradation in a kinase-independent manner. Analysis of isogenic cell populations expressing CDK8, CDK19 or their kinase-inactive mutants revealed that CDK8 and CDK19 have the same qualitative effects on protein phosphorylation and gene expression at the RNA and protein levels, whereas differential effects of CDK8 versus CDK19 knockouts were attributable to quantitative differences in their expression and activity rather than different functions.

Development of a single-domain antibody to target a G-quadruplex located on the hepatitis B virus covalently closed circular DNA genome.

To achieve a virological cure for hepatitis B virus (HBV), innovative strategies are required to target the covalently closed circular DNA (cccDNA) genome. Guanine-quadruplexes (G4s) are a secondary structure that can be adopted by DNA and play a significant role in regulating viral replication, transcription, and translation. Antibody-based probes and small molecules have been developed to study the role of G4s in the context of the human genome, but none have been specifically made to target G4s in viral infection. Herein, we describe the development of a humanized single-domain antibody (S10) that can target a G4 located in the PreCore (PreC) promoter of the HBV cccDNA genome. MicroScale Thermophoresis demonstrated that S10 has a strong nanomolar affinity to the PreC G4 in its quadruplex form and a structural electron density envelope of the complex was determined using Small-Angle X-ray Scattering. Lentiviral transduction of S10 into HepG2-NTCP cells shows nuclear localization, and chromatin immunoprecipitation coupled with next-generation sequencing demonstrated that S10 can bind to the HBV PreC G4 present on the cccDNA. This research validates the existence of a G4 in HBV cccDNA and demonstrates that this DNA secondary structure can be targeted with high structural and sequence specificity using S10.

Compact mode converter on SOI based on a polygonal subwavelength grating structure.

In this Letter, we design and experimentally demonstrate compact mode converters with a lightning-like and arrow-like polygonal subwavelength grating (SWG) structure on a silicon-on-insulator (SOI) platform, which can convert the TE0 mode to the TE1 and TE2 modes, respectively. The footprints of the proposed TE0-1 and TE0-2 mode converters are only 4.44 × 1.3 and 5.89 × 1.8 µm2, respectively. The experimental results show the mode converters have a low insertion loss (<1 dB) and a broad bandwidth (>50 nm). The measured cross talks of the TE0-1 and TE0-2 mode converters are -7.2 dB and -10.3 dB, respectively. In addition, the proposed mode converters with the SWG structure have the advantage in fabrication, since only a one-step full-etching process is required.

The levels of women's awareness, experience, acceptability and preference for Vaginal Human Papillomavirus (HPV) self-sampling in three provinces of China: a cross-sectional study.

BACKGROUND: The primary screening technique for precancerous lesions and cervical cancer is human papillomavirus (HPV) testing, and HPV self-sampling has been shown to be consistent with clinician sampling in terms of the accuracy of the results and may improve cervical cancer screening rates. The aim of this study was to understand the level of awareness, experience, acceptability, and preference for vaginal HPV self-sampling among women in Jiangsu, Zhejiang, and Shanghai, China, and to analyze the possible influencing factors to determine the feasibility of implementing self-sampling. METHODS: Overall, 1793 women were included in the data analysis. A self-administered questionnaire was utilized. In addition to descriptive analysis, univariate and multivariate analyses were used to explore the associations between sociodemographic features, history of cervical cancer screening, and the level of awareness, experience, acceptability, and preference for HPV self-samples. RESULTS: The participants' level of awareness of and experience with HPV self-sampling were moderate. A total of 88.8% of participants rated the acceptability as "high", and self-sampling was preferred by 64.2% of them for cervical cancer screening. People aged 45 to 54 years showed a preference for both clinician sampling(OR = 1.762 (1.116-2.163)) and self-sampling (OR = 1.823 (1.233-2.697)). Those who had graduated from high school or above (OR = 2.305 (1.517-3.503), OR = 2.432 (1.570-3.768), OR = 3.258 (2.024-5.244)) preferred clinician-sampling, and those with a bachelor's degree or above (OR = 1.664 (1.042-2.657)) preferred self-sampling. Middle- and high-income individuals showed no preference for either sampling method (OR < 1). CONCLUSIONS: HPV self-sampling is widely accepted, but awareness, experience and preferences need to be improved. These results may help to adjust public health strategies for the early inclusion of HPV self-sampling as a screening method in national initiatives to prevent cervical cancer.

Ultra-compact, low-loss,TE0- and TE1-compatible mode waveguide bends.

Waveguide bends have become an interesting research direction because they allow highly curved light transmission in a limited space. Here, we propose waveguide bends supporting two TE modes by etching slots and adding germanium arcs in the inner side of a waveguide bend. Simulations show that the bending radius of our proposed base-mode T E 0 waveguide bend drops to 500 nm and its insertion loss (IL) is reduced to 0.13 dB with footprints as small as 0.75µm×0.75µm. For the higher-order T E 1 mode waveguide bend, we adjust the introduced structure in combination with the light field distribution. The IL of the waveguide bend is also reduced to 0.18 dB with footprints as small as 1.85µm×1.85µm. T E 0 mode has 410 nm bandwidth in the optical communication band while T E 1 mode has 330 nm bandwidth by keeping I L<0.5d B. Through the analysis of these structural characteristics, we believe that this method still has great potential in higher-order mode transmission.

Low loss and ultra-broadband design of an integrated 3 dB power splitter centered at 2 µm.

Because chemical gas is sensitive to absorption in the 2 µm band, and 2 µm matches the absorption band of the remote sensing material, many remote sensors and optical sensors are designed to operate in the 2 µm wavelength region. In this paper, we designed an integrated 3 dB power splitter centered at 2 µm. The study of this device is built on a silicon-on-insulator (SOI) platform. We introduced a subwavelength grating (SWG) to improve the performance of the device. We used the three-dimensional finite-difference time-domain (3D FDTD) method to analyze the effect of the structure on the power splitter. The insertion loss (IL) of the fundamental TE mode is only 0.04 dB at 2 µm and its bandwidth of IL <0.45d B is 940 nm (1570-2510 nm). It is suitable for multidomain and all-band photonic integrated circuits at 2 µm.

Identification of Potential Protein Targets in Extracellular Vesicles Isolated from Chemotherapy-Treated Ovarian Cancer Cells.

Despite the ongoing clinical trials and the introduction of novel treatments over the past few decades, ovarian cancer remains one of the most fatal malignancies in women worldwide. Platinum- and paclitaxel-based chemotherapy is effective in treating the majority of patients with ovarian cancer. However, more than 70% of patients experience recurrence and eventually develop chemoresistance. To improve clinical outcomes in patients with ovarian cancer, novel technologies must be developed for identifying molecular alterations following drug-based treatment of ovarian cancer. Recently, extracellular vesicles (EVs) have gained prominence as the mediators of tumor progression. In this study, we used mass spectrometry to identify the changes in EV protein signatures due to different chemotherapeutic agents used for treating ovarian cancer. By examining these alterations, we identified the specific protein induction patterns of cisplatin alone, paclitaxel alone, and a combination of cisplatin and paclitaxel. Specifically, we found that drug sensitivity was correlated with the expression levels of ANXA5, CD81, and RAB5C in patients receiving cisplatin with paclitaxel. Our findings suggest that chemotherapy-induced changes in EV protein signatures are crucial for the progression of ovarian cancer.

Self-Sensing Cementitious Composites with Hierarchical Carbon Fiber-Carbon Nanotube Composite Fillers for Crack Development Monitoring of a Maglev Girder.

In view of high-performance, multifunctional, and low-carbon development of infrastructures, there is a growing demand for smart engineering materials, making infrastructures intelligent. This paper reports a new-generation self-sensing cementitious composite (SSCC) incorporated with a hierarchically structured carbon fiber (CF)-carbon nanotube (CNT) composite filler (CF-CNT), which is in situ synthesized by directly growing CNT on CF. Various important factors including catalyst, temperature, and gas composition are considered to investigate their kinetic and thermodynamic influence on CF-CNT synthesis. The reciprocal architecture of CF-CNT not only alleviates the CNT aggregation, but also significantly improves the interfacial bonding between CF-CNT and matrix. Due to the synergic and spatially morphological effects of CF-CNT, that is, the formation of widely distributed multiscale reinforcement networks, SSCCs with CF-CNTs exhibit high mechanical properties and electrical conductivity as well as excellent self-sensing performances, particularly enhanced sensing repeatability. Moreover, the SSCCs with CF-CNTs are integrated into a full-scale maglev girder to devise a smart system for crack development monitoring. The system demonstrates high sensitivity and fidelity to capture the initiation of cracks/damage, as well as progressive and sudden damage events until the complete failure of the maglev girder, indicating its considerable potential for structural health monitoring of infrastructures.

On-chip multifunctional polarizer based on phase change material.

Polarizers are used to eliminate the undesired polarization state and maintain the other one. The phase change material Ge2Sb2Se4Te1 (GSST) has been widely studied for providing reconfigurable function in optical systems. In this paper, based on a silicon waveguide embedded with a GSST, which is able to absorb light by taking advantage of the relatively large imaginary part of its refractive index in the crystalline state, a multifunctional polarizer with transverse electric (TE) and transverse magnetic (TM) passages has been designed. The interconversion between the two types of polarizers relies only on the state switching of GSST. The size of the device is 7.5µm∗4.3µm, and the simulation results showed that the extinction ratio of the TE-pass polarizer is 45.37 dB and the insertion loss is 1.10 dB at the wavelength of 1550 nm, while the extinction ratio (ER) of the TM-pass polarizer is 20.09 dB and the insertion loss (IL) is 1.35 dB. For the TE-pass polarizer, a bandwidth broader than 200 nm is achieved with ER>20dB and IL<2.0dB over the wavelength region from 1450 to 1650 nm  and for the TM-pass polarizer, ER>15dB and IL<1.5dB in the wavelength region from 1525 to 1600 nm, with a bandwidth of approximately 75 nm.

Highly efficient and tunable polarization rotator based on lithium niobate on an insulator.

The lithium niobate on an insulator (LNOI) platform has greatly advanced the development of integrated photonics recently, where efficient polarization management components are indispensable. In this work, we propose a highly efficient and tunable polarization rotator based on the LNOI platform and the low-loss optical phase change material antimony triselenide (S b 2 S e 3). The key polarization rotation region is formed by a LNOI waveguide with a cross section of the double trapezoidal shape and a S b 2 S e 3 layer deposited atop the LNOI waveguide in an asymmetrical way, where an isolating layer of silicon dioxide is sandwiched between them to reduce the material absorption loss. Based on such a structure, we have achieved the efficient polarization rotation in a length of only 17.7 µm, where the polarization conversion efficiency and insertion loss are 99.6% (99.2%) and 0.38 dB (0.4 dB) for the trans-electric (TE)-to-trans-magnetic (TM) rotation. If we further change the phase state of the S b 2 S e 3 layer, other polarization rotation angles besides 90° can also be obtained for the same device, revealing a tunable function. We believe that the proposed device and design scheme could offer an efficient method for realizing the polarization management on the LNOI platform.

High-performance thin-film lithium niobate electro-optic modulator based on etching slot and ultrathin silicon film.

An electro-optic modulator (EOM) is an indispensable component to connect the electric and optical fields. Here, we propose a high-performance, thin-film lithium niobate-based EOM, where the modulation waveguide is formed by an etching slot on the lithium niobate film and the deposit of an ultrathin silicon film in the slot region. Therefore, a small mode size and high mode energy can be simultaneously achieved in the LN region with a high EO coefficient, which will be beneficial to increase the EO overlap and gradually decrease in the mode size. Further, we employed a waveguide structure to construct a typical Mach-Zehnder interference-type EOM. According to the requirements of high-speed traveling wave modulation, we conduct the index matching, impedance matching, and low-loss operation. From the results, the key half-wave voltage length product and 3 dB modulation bandwidth are, respectively, 1.45 V cm and 119 GHz in a modulation length of 4 mm. Moreover, a larger 3 dB bandwidth also can be achieved by shortening the modulation length. Therefore, we believe the proposed waveguide structure and EOM will provide new ways to enhance the performance of LNOI-based EOMs.

Reconfigurable TE-pass polarizer based on lithium niobate waveguide assisted by Ge2Sb2Te5 and silicon nitride.

On-chip polarization management components play a critical role in tackling polarization dependence in the lithium-niobate-on-insulator (LNOI) platform. In this work, we proposed a reconfigurable TE-pass polarizer based on optical phase change material (GST) and the LNOI wafer. The key region is formed by a hybrid GST-S i 3 N 4 layer symmetrically deposited atop the centerline of the LNOI waveguide along the propagation direction where the GST is sandwiched in the middle of the S i 3 N 4 layer. Whether the polarizer will take effect depends on the phase states of the GST layer and the graphene and aluminum oxide layers are coated atop the G S T-S i 3 N 4 layer as the microheater to control the conversion of phase states. The proposed device length is 7.5 µm with an insertion loss (IL)=0.22 dB and extinction ratio (ER)=32.8 dB at the wavelength of 1550 nm. Moreover, it also has a high ER (>25d B) and a low IL (<0.5d B) in the operating bandwidth of 200 nm. Such a high-performance TE-pass polarizer paves a new way for applications of photonics integrated circuits.

Experience and acceptability for HPV self-sampling among women in Jiangsu province, China: a cross-sectional survey.

This aim of this study was to investigate women's knowledge about HPV along with their experience and acceptability of self-sampling in Jiangsu province, China. A total of 862 women aged 25-63 years old from Jiangsu province who purchased an HPV self-sampling test kit were invited to complete a questionnaire designed by the authors. Participants had high acceptability for HPV self-sampling with a mean score of 4.2 (95% [CI], 4.1-4.22) out of 5 points. 27% of participants preferred clinician-sampling, 33% preferred self-sampling, other 40% expressed no preference. Women with good knowledge about HPV and with a good experience with HPV self-sampling were more acceptable for self-sampling (P < 0.05). The biggest concern about HPV self-sampling of the participants includes 'specimens' spoilage', 'incorrect sampling', 'can't get results in time', and so on. HPV self-sampling can be used to improve cervical cancer screening coverage and participation rates in China.

Cancer screening and can be an alternative primary screening for cervical cancer.•What the results of this study add? This study adds new findings about Chinese women's experience and acceptability of HPV self-sampling. We found that most women had high acceptability for HPV self-sampling in Jiangsu province, China, and high knowledge about HPV as well as good•What is already known on this subject? HPV self-sampling testing was proven to be useful for improving the uptake rate of cervical experience of self-sampling can improve the acceptability for self-sampling in women.•What the implications are of these findings for clinical practice and/or further research? Further research should assess the acceptability of women with less education or who never screened.

Hepatitis D virus-induced interferon response and administered interferons control cell division-mediated virus spread.

BACKGROUND & AIMS: Besides HBV-dependent de novo infection, cell division-mediated spread contributes to HDV persistence and dampens the effect of antivirals that abrogate de novo infection. Nonetheless, the combination of these antivirals with interferons (IFNs) showed strong synergism in recent clinical trials, implying a complementary mode-of-action of IFNs. Therefore, we investigated the effect of IFN response on cell division-mediated HDV spread. METHODS: Cells infected with HDV were passaged to undergo cell division. The effect of the IFN response was evaluated by blocking HDV-induced IFN activation, by applying different IFN treatment regimens, and by adjusting HDV infection doses. RESULTS: Cell division-mediated HDV spread was highly efficient following infection of HuH7NTCP cells (defective in IFN production), but profoundly restricted in infected IFN-competent HepaRGNTCP cells. Treatment with IFN-α/-λ1 inhibited HDV spread in dividing HuH7NTCP cells, but exhibited a marginal effect on HDV replication in resting cells. Blocking the HDV-induced IFN response with the JAK1/2 inhibitor ruxolitinib or knocking down MDA5 augmented HDV spread in dividing HepaRGNTCP cells. The virus-induced IFN response also destabilized HDV RNA in dividing cells. Moreover, the effect of exogenous IFNs on cell division-mediated HDV spread was more pronounced at low multiplicities of infection with weak virus-induced IFN responses. CONCLUSIONS: Both HDV-induced IFN response and exogenous IFN treatment suppress cell division-mediated HDV spread, presumably through acceleration of HDV RNA decay. Our findings demonstrate a novel mode-of-action of IFN, explain the more pronounced effect of IFN therapy in patients with lower HDV serum RNA levels, and provide insights for the development of combination therapies. LAY SUMMARY: Chronic hepatitis D is a major health problem. The causative pathogen hepatitis D virus (HDV) can propagate through viral particle-mediated infection and the division of infected cells. Although viral particle-dependent infection can be blocked by recently developed drugs, therapies addressing the cell division route have not been reported. Taking advantage of relevant cell culture models, we demonstrate that the widely used immune modulator interferon can efficiently suppress HDV spread through cell division. This work unveils a new function of interferon and sheds light on potentially curative combination therapies.

Nuclear PYHIN proteins target the host transcription factor Sp1 thereby restricting HIV-1 in human macrophages and CD4+ T cells.

Members of the family of pyrin and HIN domain containing (PYHIN) proteins play an emerging role in innate immunity. While absent in melanoma 2 (AIM2) acts a cytosolic sensor of non-self DNA and plays a key role in inflammasome assembly, the γ-interferon-inducible protein 16 (IFI16) restricts retroviral gene expression by sequestering the transcription factor Sp1. Here, we show that the remaining two human PYHIN proteins, i.e. myeloid cell nuclear differentiation antigen (MNDA) and pyrin and HIN domain family member 1 (PYHIN1 or IFIX) share this antiretroviral function of IFI16. On average, knock-down of each of these three nuclear PYHIN proteins increased infectious HIV-1 yield from human macrophages by more than an order of magnitude. Similarly, knock-down of IFI16 strongly increased virus transcription and production in primary CD4+ T cells. The N-terminal pyrin domain (PYD) plus linker region containing a nuclear localization signal (NLS) were generally required and sufficient for Sp1 sequestration and anti-HIV-1 activity of IFI16, MNDA and PYHIN1. Replacement of the linker region of AIM2 by the NLS-containing linker of IFI16 resulted in a predominantly nuclear localization and conferred direct antiviral activity to AIM2 while attenuating its ability to form inflammasomes. The reverse change caused nuclear-to-cytoplasmic relocalization of IFI16 and impaired its antiretroviral activity but did not result in inflammasome assembly. We further show that the Zn-finger domain of Sp1 is critical for the interaction with IFI16 supporting that pyrin domains compete with DNA for Sp1 binding. Finally, we found that human PYHIN proteins also inhibit Hepatitis B virus and simian vacuolating virus 40 as well as the LINE-1 retrotransposon. Altogether, our data show that IFI16, PYHIN1 and MNDA restrict HIV-1 and other viral pathogens by interfering with Sp1-dependent gene expression and support an important role of nuclear PYHIN proteins in innate antiviral immunity.

Broadband and high extinction ratio TE-pass/TM-stop polarizer at 850 nm using chirped subwavelength gratings.

A polarizer is used to eliminate undesired polarization states and maintain an orthogonal one. The polarizer we proposed is designed on a silicon nitride (Si3N4) on insulator platform to achieve low-loss operation at the 850 nm wavelength region. Compared with conventional polarizer structures, chirped subwavelength gratings (SWG) are introduced in the proposed device's main body to extend the wavelength band of the leakage mode, i.e., TM polarization state. Owing to the broadband nature of leakage mode, the operating bandwidth, which is defined as the wavelength region with extinction ratio (ER) higher than 20 dB, is increased dramatically. The simulation results show that the TE polarization state passes through the proposed polarizer with a high ER=46.24dB and a low insertion loss (IL)=0.13dB at 850 nm. A bandwidth broader than 171 nm is achieved with ER>20dB and IL<1dB over the wavelength region from 775 to 946 nm.

An Adaptive and Robust Control Strategy for Real-Time Hybrid Simulation.

A real-time hybrid simulation (RTHS) is a promising technique to investigate a complicated or large-scale structure by dividing it into numerical and physical substructures and conducting cyber-physical tests on it. The control system design of an RTHS is a challenging topic due to the additional feedback between the physical and numerical substructures, and the complexity of the physical control plant. This paper proposes a novel RTHS control strategy by combining the theories of adaptive control and robust control, where a reformed plant which is highly simplified compared to the physical plant can be used to design the control system without compromising the control performance. The adaptation and robustness features of the control system are realized by the bounded-gain forgetting least-squares estimator and the sliding mode controller, respectively. The control strategy is validated by investigating an RTHS benchmark problem of a nonlinear three-story steel frame The proposed control strategy could simplify the control system design and does not require a precise physical plant; thus, it is an efficient and practical option for an RTHS.

Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections.

BACKGROUND: Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T-cell response. We therefore designed an immunotherapy driven by naive healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry. METHODS: Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV-specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes. RESULTS: The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice. CONCLUSIONS: We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation.

Assembly and infection efficacy of hepatitis B virus surface protein exchanges in 8 hepatitis D virus genotype isolates.

BACKGROUND & AIMS: Chronic HDV infections cause the most severe form of viral hepatitis. HDV requires HBV envelope proteins for hepatocyte entry, particle assembly and release. Eight HDV and 8 HBV genotypes have been identified. However, there are limited data on the replication competence of different genotypes and the effect that different HBV envelopes have on virion assembly and infectivity. METHODS: We subcloned complementary DNAs (cDNAs) of all HDV and HBV genotypes and systematically studied HDV replication, assembly and infectivity using northern blot, western blot, reverse-transcription quantitative PCR, and in-cell ELISA. RESULTS: The 8 HDV cDNA clones initiated HDV replication with noticeable differences regarding replication efficacy. The 8 HBV-HBsAg-encoding constructs all supported secretion of subviral particles, however variations in envelope protein stoichiometry and secretion efficacy were observed. Co-transfection of all HDV/HBV combinations supported particle assembly, however, the respective pseudo-typed HDVs differed with respect to assembly kinetics. The most productive combinations did not correlate with the natural geographic distribution, arguing against an evolutionary adaptation of HDV ribonucleoprotein complexes to HBV envelopes. All HDVs elicited robust and comparable innate immune responses. HBV envelope-dependent differences in the activity of the EMA-approved entry inhibitor bulevirtide were observed, however efficient inhibition could be achieved at therapeutically applied doses. Lonafarnib also showed pan-genotypic activity. CONCLUSIONS: HDVs from different genotypes replicate with variable efficacies. Variations in HDV genomes and HBV envelope proteins are both major determinants of HDV egress and entry efficacy, and consequently assembly inhibition by lonafarnib or entry inhibition by bulevirtide. These differences possibly influence HDV pathogenicity, immune responses and the efficacy of novel drug regimens. LAY SUMMARY: HDV requires the envelope protein of HBV for assembly and to infect human cells. We investigated the ability of different HDV genotypes to infect cells and replicate. We also assessed the effect that envelope proteins from different HBV genotypes had on HDV infectivity and replication. Herein, we confirmed that genotypic differences in HDV and HBV envelope proteins are major determinants of HDV assembly, de novo cell entry and consequently the efficacy of novel antivirals.

Etched circular waveguide-based on-chip silicon mode-order converters.

Mode-order converters act as the vital higher-order mode sources for on-chip multimode applications. Here, we propose a silicon-based mode-order conversion scheme by leveraging etching slots on the circular waveguide. Through designing and optimizing the etching slots and circular waveguide, the mode-order conversion from input TE0 mode to output TE1 mode has been achieved with the mode conversion efficiency of 99.1%, modal crosstalk of -25.7dB, and insertion loss of 0.21 dB, respectively, in a mode conversion size of ∼8µm×8µm (TE0-TE1). For the device fabrication, only one-step lithography and etching processes will be required, and the requirements of slot width (600 nm) and slot gap (1.49 µm) would be very beneficial for the device fabrication. Moreover, the proposed device scheme can also help achieve other higher-order mode conversions, such TE0-TE2 and TE0-TE3, where their structural parameters and performances are also analyzed. With these features of relatively good device performance, compact size, easy fabrication, and functional scalability, we believe the proposed scheme would be applied in the on-chip multimode applications to enhance their transmission capacities.