mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications.

mRNA-based drugs have tremendous potential as clinical treatments, however, a major challenge in realizing this drug class will promise to develop methods for safely delivering the bioactive agents with high efficiency and without activating the immune system. With regard to mRNA vaccines, researchers have modified the mRNA structure to enhance its stability and promote systemic tolerance of antigenic presentation in non-inflammatory contexts. Still, delivery of naked modified mRNAs is inefficient and results in low levels of antigen protein production. As such, lipid nanoparticles have been utilized to improve delivery and protect the mRNA cargo from extracellular degradation. This advance was a major milestone in the development of mRNA vaccines and dispelled skepticism about the potential of this technology to yield clinically approved medicines. Following the resounding success of mRNA vaccines for COVID-19, many other mRNA-based drugs have been proposed for the treatment of a variety of diseases. This review begins with a discussion of mRNA modifications and delivery vehicles, as well as the factors that influence administration routes. Then, we summarize the potential applications of mRNA-based drugs and discuss further key points pertaining to preclinical and clinical development of mRNA drugs targeting a wide range of diseases. Finally, we discuss the latest market trends and future applications of mRNA-based drugs.

Wideband and Channel Switchable Mode Division Multiplexing (MDM) Optical Power Divider Supporting 7.682 Tbit/s for On-Chip Optical Interconnects.

Silicon photonics (SiPh) are considered a promising technology for increasing interconnect speed and capacity while decreasing power consumption. Mode division multiplexing (MDM) enables signals to be transmitted in different orthogonal modes in a single waveguide core. Wideband MDM components simultaneously supporting wavelength division multiplexing (WDM) and orthogonal frequency-division multiplexing (OFDM) can significantly increase the transmission capacity for optical interconnects. In this work, we propose, fabricate and demonstrate a wideband and channel switchable MDM optical power divider on an SOI platform, supporting single, dual and triple modes. The switchable MDM power divider consists of two parts. The first part is a cascaded Mach-Zehnder interferometer (MZI) for switching the data from their original TE0, TE1 and TE2 modes to different modes among themselves. After the target modes are identified, mode up-conversion and Y-branch are utilized in the second part for the MDM power division. Here, 48 WDM wavelength channels carrying OFDM data are successfully switched and power divided. An aggregated capacity of 7.682 Tbit/s is achieved, satisfying the pre-forward error correction (pre-FEC) threshold (bit-error-rate, BER = 3.8 × 10-3). Although up to three MDM modes are presented in the proof-of-concept demonstration here, the proposed scheme can be scaled to higher order modes operation.

Design Consideration, Numerical and Experimental Analyses of Mode-Division-Multiplexed (MDM) Silicon Photonics Integrated Circuit with Sharp Bends.

Due to the popularity of different high bandwidth applications, it is becoming increasingly difficult to satisfy the huge data capacity requirements, since the traditional electrical interconnects suffer significantly from limited bandwidth and huge power consumption. Silicon photonics (SiPh) is one of the important technologies for increasing interconnect capacity and decreasing power consumption. Mode-division multiplexing (MDM) allows signals to be transmitted simultaneously, at different modes, in a single waveguide. Wavelength-division multiplexing (WDM), non-orthogonal multiple access (NOMA) and orthogonal-frequency-division multiplexing (OFDM) can also be utilized to further increase the optical interconnect capacity. In SiPh integrated circuits, waveguide bends are usually inevitable. However, for an MDM system with a multimode bus waveguide, the modal fields will become asymmetric when the waveguide bend is sharp. This will introduce inter-mode coupling and inter-mode crosstalk. One simple approach to achieve sharp bends in multimode bus waveguide is to use a Euler curve. Although it has been reported in the literature that sharp bends based on a Euler curve allow high performance and low inter-mode crosstalk multimode transmissions, we discover, by simulation and experiment, that the transmission performance between two Euler bends is length dependent, particularly when the bends are sharp. We investigate the length dependency of the straight multimode bus waveguide between two Euler bends. High transmission performance can be achieved by a proper design of the waveguide length, width, and bend radius. By using the optimized MDM bus waveguide length with sharp Euler bends, proof-of-concept NOMA-OFDM experimental transmissions, supporting two MDM modes and two NOMA users, are performed.

TOR and RPS6 transmit light signals to enhance protein translation in deetiolating Arabidopsis seedlings.

Deetiolation is an essential developmental process transforming young plant seedlings into the vegetative phase with photosynthetic activities. Light signals initiate this important developmental process by triggering massive reprogramming of the transcriptome and translatome. Compared with the wealth of knowledge of transcriptional regulation, the molecular mechanism underlying this light-triggered translational enhancement remains unclear. Here we show that light-enhanced translation is orchestrated by a light perception and signaling pathway composed of photoreceptors, CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1), the phytohormone auxin, target of rapamycin (TOR), and ribosomal protein S6 (RPS6). In deetiolating Arabidopsis seedlings, photoreceptors, including phytochrome A and cryptochromes, perceive far-red and blue light to inactivate the negative regulator COP1, which leads to activation of the auxin pathway for TOR-dependent phosphorylation of RPS6. Arabidopsis mutants defective in TOR, RPS6A, or RPS6B exhibited delayed cotyledon opening, a characteristic of the deetiolating process to ensure timely vegetative development of a young seedling. This study provides a mechanistic view of light-triggered translational enhancement in deetiolating Arabidopsis.

Tricolor visible-light laser diodes based visible light communication operated at 40.665 Gbit/s and 2 m free-space transmission.

Visible light communication (VLC) can provide a dedicated, secure, and high data rate wireless transmission link. It has gained considerable attentions recently, and is considered as one of the promising technologies for beyond 5G mobile and wireless communications. In this work, we demonstrate a VLC system with a recorded data rate of 40.665 Gbit/s using tricolor red, green and blue (RGB) laser diodes (LDs) and polarization multiplexing. 2 m free-space transmission distance is achieved. The implementation of bit-loading, power-loading, and polarization multiplexing are discussed. Experimental bit-error-ratio (BER) results show that each of the 6 polarization and wavelength de-multiplexed channels can achieve the forward-error-correction (FEC) requirement.

Increased glutathione contributes to stress tolerance and global translational changes in Arabidopsis.

Although glutathione is well known for its reactive oxygen species (ROS) scavenging function and plays a protective role in biotic stress, its regulatory function in abiotic stress still remains to be elucidated. Our previous study showed that exogenously applied reduced glutathione (GSH) could improve abiotic stress tolerance in Arabidopsis. Here, we report that endogenously increased GSH also conferred tolerance to drought and salt stress in Arabidopsis. Moreover, both exogenous and endogenous GSH delayed senescence and flowering time. Polysomal profiling results showed that global translation was enhanced after GSH treatment and by the induced increase of GSH level by salt stress. By performing transcriptomic analyses of steady-state and polysome-bound mRNAs in GSH-treated plants, we reveal that GSH has a substantial impact on translation. Translational changes induced by GSH treatment target numerous hormones and stress signaling molecules, which might contribute to the enhanced stress tolerance in GSH-treated plants. Our translatome analysis also revealed that abscisic acid (ABA), auxin and jasmonic acid (JA) biosynthesis, as well as signaling genes, were activated during GSH treatment, which has not been reported in previously published transcriptomic data. Together, our data suggest that the increased glutathione level results in stress tolerance and global translational changes.

IRT1 degradation factor1, a ring E3 ubiquitin ligase, regulates the degradation of iron-regulated transporter1 in Arabidopsis.

Fe is an essential micronutrient for plant growth and development; plants have developed sophisticated strategies to acquire ferric Fe from the soil. Nongraminaceous plants acquire Fe by a reduction-based mechanism, and graminaceous plants use a chelation-based mechanism. In Arabidopsis thaliana, which uses the reduction-based method, iron-regulated transporter1 (IRT1) functions as the most important transporter for ferrous Fe uptake. Rapid and constitutive degradation of IRT1 allows plants to quickly respond to changing conditions to maintain Fe homeostasis. IRT1 degradation involves ubiquitination. To identify the specific E3 ubiquitin ligases involved in IRT1 degradation, we screened a set of insertional mutants in RING-type E3 ligases and identified a mutant that showed delayed degradation of IRT1 and loss of IRT1-ubiquitin complexes. The corresponding gene was designated IRT1 degradation factor1 (IDF1). Evidence of direct interaction between IDF1 and IRT1 in the plasma membrane supported the role of IDF1 in IRT1 degradation. IRT1 accumulation was reduced when coexpressed with IDF1 in yeast or Xenopus laevis oocytes. IDF1 function was RING domain dependent. The idf1 mutants showed increased tolerance to Fe deficiency, resulting from increased IRT1 levels. This evidence indicates that IDF1 directly regulates IRT1 degradation through its RING-type E3 ligase activity.

Protein/polysaccharide-based hydrogels loaded probiotic-mediated therapeutic systems: A review.

The natural characteristics of protein/polysaccharide-based hydrogels, as a potential drug delivery platform, have attracted extensive attention. Probiotics have attracted renewed interest in drug research because of their beneficial effects on host health. The idea of using probiotics loaded on protein/polysaccharide-based hydrogels as potential drugs to treat different diseases has been put forward and shows great prospects. Based on this, in this review, we highlight the design strategy of hydrogels loaded probiotic-mediated therapy systems and review the potential diseases that have been proved to be treatable in the laboratory, including promoting wound healing and improving intestinal health and vaginal health, and discuss the challenges existing in the current design.

General Strategies for Preparing Hybrid Polymer/Quantum Dot Nanocomposites for Color Conversion.

Quantum dots (QDs), with their exceptional optical properties, have emerged as promising candidates to replace traditional phosphors in lighting and display technologies. This study delves into the integration strategies of QDs within glass and polymer matrices to engineer advanced quantum dot color converters (QDCCs) at the industrial scale for practical applications. To achieve enhancements in the photostability and thermal stability of QDCCs, we explore two distinct approaches: the dispersion of QDs in a hydrophilic glass matrix via a sol-gel process and the incorporation of QDs into a non-polar acrylate monomer to formulate QD/polymer nanocomposites. This research further investigates the optical behaviors of these composites, focusing on their light-scattering and propagation mechanisms, which are critical for optimizing light extraction efficiency in QDCCs. Additional optical film and light-scattering particles can improve color conversion efficiency by ~140%. These advancements present a significant step forward in the development of high-performance, energy-efficient, QD-based lighting and display systems.

Enhanced Photostability of Core/Shell Quantum Dots under Intense Blue Light Irradiation through Positive Photoaging Mechanism.

Photostability of semiconductor core/shell quantum dots (QDs) has historically been perceived as intricate and unpredictable. Notably, the long-term luminescence stability of QDs under light exposure does not seem to consistently correspond with their characteristics in the absence of light. In this study, we propose a positive photoaging mechanism of QDs, integrating both ligand/shell-induced photobrightening and surface photo-oxidation, to deal with the photostability nuances. When QDs are subjected to higher energy light, their photobrightening and photodarkening conjointly determine the photostability. Enhanced photostability may not be simply attributed to a thicker shell or the presence of ligands. When adjusted with an optimal shell thickness and supplemented with negatively charged ligands, QDs exhibit enhanced photostability in both solvents and polymers.

Role of ARABIDOPSIS A-FIFTEEN in regulating leaf senescence involves response to reactive oxygen species and is dependent on ETHYLENE INSENSITIVE2.

Leaf senescence is a highly regulated developmental process that is coordinated by several factors. Many senescence-associated genes (SAGs) have been identified, but their roles during senescence remain unclear. A sweet potato (Ipomoea batatas) SAG, named SPA15, whose function was unknown, was identified previously. To understand the role of SPA15 in leaf senescence further, the orthologue of SPA15 in Arabidopsis thaliana was identified and characterized, and it was named ARABIDOPSIS A-FIFTEEN (AAF). AAF was expressed in early senescent leaves and in tissues with highly proliferative activities. AAF was localized to the chloroplasts by transient expression in Arabidopsis mesophyll protoplasts. Overexpression of AAF (AAF-OX) in Arabidopsis promoted, but the T-DNA insertion mutant (aaf-KO), delayed age-dependent leaf senescence. Furthermore, stress-induced leaf senescence caused by continuous darkness was enhanced in AAF-OX but suppressed in aaf-KO. Transcriptome analysis of expression profiles revealed up-regulated genes related to pathogen defence, senescence, and oxidative stress in 3-week-old AAF-OX plants. Indeed, elevated levels of reactive oxygen species (ROS) and enhanced sensitivity to oxidative and dark stress were apparent in AAF-OX but reduced in aaf-KO. ETHYLENE INSENSITIVE2 (EIN2) was required for the dark- and ROS-induced senescence phenotypes in AAF-OX and the induction of AAF expression by treatment with the immediate precursor of ethylene, 1-aminocyclopropane-1-carboxylic acid. The results indicate the functional role of AAF is an involvement in redox homeostasis to regulate leaf senescence mediated by age and stress factors during Arabidopsis development.

4-Bromo-2-[1-(4-eth-oxy-phen-yl)-1-methyl-eth-yl]-1-methyl-benzene.

In title compound, C(18)H(21)BrO, the dihedral angle between two rings is 85.72°. No classical hydrogen bonds are found and only van der Waals forces stabilize the crystal packing.

Total Knee Arthroplasty Using a Medial Pivot or Posterior Cruciate-Stabilizing Prosthesis in Chinese Patients.

There is an unmet need for a prosthesis designed according to the anatomical parameters of the Chinese population. This study aims to compare the use of a medial pivot (MP) implant or posterior cruciate ligament (PCL) substitution (posterior-stabilized [PS]) prosthesis for unilateral total knee arthroplasty (TKA) in a Chinese population. The medical records of patients undergoing unilateral TKA with an MP implant (Group A) or a PS prosthesis (Group B) at our institution between January 2010 and December 2011 were retrospectively reviewed. Patients were followed up for 5 years. Preoperatively and at the December 2016 postoperative follow-up, the Hospital for Special Surgery scoring system (HSS knee score) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score were measured to evaluate TKA outcomes. This study included 49 patients in Group A and 51 in Group B. As of December 2016, there were no significant differences in the preoperative/postoperative changes in any category of the HSS knee score or WOMAC score between the groups. There were no postoperative complications in either group during the 5-year follow-up. There were no periprosthetic infections or need for revision surgery. One patient in Group A experienced aching and a small amount of effusion in the articular cavity that was attributed to overexertion. In conclusion, there were no significant differences in midterm outcomes in Chinese patients receiving an MP implant or a PS prosthesis for unilateral TKA. These data suggest that the MP and PCL substitution design are safe and effective for unilateral TKA in China.

Investigation of Luminescence Enhancement and Decay of QD-LEDs: Interface Reactions between QDs and Atmospheres.

We investigated the current unsolved problem of short-term enhancement and long-term decay of the luminescence intensity of quantum dots (QDs)-based light-emitting diodes (LEDs) in applications for lighting and displays, and proved that the interface interaction between the QD surface and atmospheres plays a key role in the QD-LED operation process. It is suggested that the initial luminescence enhancement of QD-LEDs would be caused by the QD surface-adsorbed species, such as ligands and gas molecules, rather than QDs themselves, whereas the luminescence decay is correlated to the interface reactions between QDs and photo-generated reactive oxygen species, which leads to formations of sulfate, hydroxide, and oxide compounds after QDs are illuminated by 450 nm blue light in oxygen and water environments according to surface analysis and theoretic thermodynamic calculations. It was also found that involvement of water in the QD-LED operation can cause crystal merging of QDs possibly because of the surface sulfates in the presence of water.

Efficacy of naproxen prophylaxis for the prevention of heterotopic ossification after hip surgery: a meta-analysis.

BACKGROUND: This meta-analysis aimed to assess whether the specific nonsteroidal anti-inflammatory drug (NSAID) naproxen has a role in reducing the occurrence of heterotopic ossification after hip surgery. METHODS: Potential studies were identified in the following electronic databases: PubMed, EMBASE, Web of Science, Cochrane Library, and Google. We included studies involving hip surgery patients in which the intervention group received naproxen and the control group received placebo. The occurrence of heterotopic ossification and complications were the final outcomes. Stata 13.0 was used for the meta-analysis. RESULTS: Four randomized controlled trials (RCTs) involving 269 patients were ultimately included in this meta-analysis. The use of naproxen was associated with a significant reduction in the occurrence of heterotopic ossification at 1.5-, 3-, 6-, and 12-month follow-ups (P < 0.05). There was no significant difference in the occurrence of complications between treatment and control groups (P > 0.05). CONCLUSION: Our analysis indicates that naproxen can decrease the occurrence of heterotopic ossification without increasing complications in hip surgery patients. Due to the limited number of studies included, more high-quality RCTs are needed to identify the optimal dose of naproxen.

Novel Bacillus cereus strain from electrokinetically remediated saline soil towards the remediation of crude oil.

A new strain SWH-15 was successfully isolated after initial electrokinetic remediation experiment using the same saline soil sampled from Shengli Oilfield, China. Four methods (morphological and biochemical characteristics, whole-cell fatty acid methyl esters (FAMEs) analysis, 16S rRNA sequence analysis and DNA G + C content and DNA-DNA hybridization analysis) were used to identify the taxonomic status of SWH-15 and confirmed that SWH-15 was a novel species of the Bacillus (B.) cereus group. Then, we assessed the degrading ability of the novel strain SWH-15 to crude oil through a microcosm experiment with four treatments, including control (CK), bioremediation using SWH-15 (Bio), electrokinetic remediation (EK), and combined bioremediation and electrokinetic remediation (Bio + EK). The results showed that the Bio + EK combined remediation treatment was more effective than the CK, Bio, and EK treatments in degrading crude oil contaminants. Bioaugmentation, by addition of the strain SWH-15 had synergistic effect with EK in Bio + EK treatment. Bacterial community analysis showed that electrokinetic remediation alone significantly altered the bacterial community of the saline soil. The addition of the strain SWH-15 alone had a weak effect on the bacterial community. However, the strain SWH-15 boosted the growth of other bacterial species in the metabolic network and weakened the impact of electrical field on the whole bacterial community structure in the Bio + EK treatment.

Investigation of Ag-TiO2 Interfacial Reaction of Highly Stable Ag Nanowire Transparent Conductive Film with Conformal TiO2 Coating by Atomic Layer Deposition.

The atomic layer deposition (ALD) technique is applied to coat Ag nanowires (NWs) with a highly uniform and conformal TiO2 layer to improve the stability and sustainability of Ag NW transparent conductive films (TCFs) at high temperatures. The TiO2 layer can be directly deposited on Ag NWs with a surface polyvinylpyrrolidone (PVP) coat that acts a bed for TiO2 seeding in the ALD process. The ALD TiO2 layer significantly enhances the thermal stability at least 100 fold when aged between 200-400 °C and also provides an extra function of violet-blue light filtration for Ag NW TCFs. Investigation into the interaction between TiO2 and Ag reveals that the conformal TiO2 shell could effectively prevent Ag from 1D-to-3D ripening. However, Ag could penetrate the conformal TiO2 shell and form nanocrystals on the TiO2 shell surface when it is aged at 400 °C. According to experimental data and thermodynamic evaluation, the Ag penetration leads to an interlayer composed of mixed Ag-Ag2O-amorphous carbon phases and TiO2-x at the Ag-TiO2 interface, which is thought to be caused by extremely high vapor pressure of Ag at the Ag-TiO2 interface at a higher temperature (e.g., 400 °C).

Note: All-digital pulse-shrinking time-to-digital converter with improved dynamic range.

This paper proposes an all-digital pulse-shrinking time-to-digital converter (TDC) using the offset error cancellation circuitry to widen its dynamic range and to improve its accuracy. Although the TDC based on a pulse-shrinking mechanism can achieve a sub-gate resolution without circuit complexity, it possesses an undesired offset error that results in a nonzero lower bound appeared in its dynamic range and then affects its accuracy. The proposed cancellation circuitry for eliminating the offset error consists of a time adder with a delay line and a time subtractor with an identical delay line. The experimental TDC is implemented on Xilinx field programmable gate arrays and it also functions successfully in improving its dynamic range.

Wide gamut white light emitting diodes using quantum dot-silicone film protected by an atomic layer deposited TiO2 barrier.

Wide gamut light emitting diodes using quantum dot-silicone film protected by atomic layer deposited TiO2 film were demonstrated. The core/shell QDs with multi-emission peaks were synthesised by a one-pot approach, in which the emission wavelength and colour composition were in situ adjusted during the synthetic process.

CMOS time-to-digital converter based on a pulse-mixing scheme.

This paper proposes a new pulse-mixing scheme utilizing both pulse-shrinking and pulse-stretching mechanisms to improve the performance of time-to-digital converters (TDCs). The temporal resolution of the conventional pulse-shrinking mechanism is determined by the size ratio between homogeneous and inhomogeneous elements. The proposed scheme which features double-stage operation derives its resolution according to the time difference between pulse-shrinking and pulse-stretching amounts. Thus, it can achieve greater immunity against temperature and ambient variations than that of the single-stage scheme. The circuit area also can be reduced by the proposed pulse-mixing scheme. In addition, this study proposes an improved cyclic delay line to eliminate the undesirable shift in the temporal resolution successfully. Therefore, the effective resolution can be controlled completely by the pulse-mixing unit to improve accuracy. The proposed TDC composed of only one cyclic delay line and one counter is fabricated in a TSMC CMOS 0.35-µm DPQM process. The chip core occupies an extremely small area of 0.02 mm(2), which is the best among the related works. The experimental result shows that an effective resolution of around 53 ps within ±13% variation over a 0-100 °C temperature range is achieved. The power consumption is 90 µW at a sample rate of 1000 samples/s. In addition to the reduced area, the proposed TDC circuit achieves its resolution with less thermal-sensitivity and better fluctuations caused by process variations.