An amber-encoding helper phage for more efficient phage display of noncanonical amino acids.

Using an amber suppression-based noncanonical amino acid (ncAA) mutagenesis approach, the chemical space in phage display can be significantly expanded for drug discovery. In this work, we demonstrate the development of a novel helper phage, CMa13ile40, for continuous enrichment of amber obligate phage clones and efficient production of ncAA-containing phages. CMa13ile40 was constructed by insertion of a Candidatus Methanomethylophilus alvus pyrrolysyl-tRNA synthetase/PylT gene cassette into a helper phage genome. The novel helper phage allowed for a continuous amber codon enrichment strategy for two different libraries and demonstrated a 100-fold increase in packaging selectivity. CMa13ile40 was then used to create two peptide libraries containing separate ncAAs, Nϵ-tert-butoxycarbonyl-lysine and Nϵ-allyloxycarbonyl-lysine, respectively. These libraries were used to identify peptide ligands that bind to the extracellular domain of ZNRF3. Each selection showed differential enrichment of unique sequences dependent upon the ncAA used. Peptides from both selections were confirmed to have low micromolar affinity for ZNRF3 that was dependent upon the presence of the ncAA used for selection. Our results demonstrate that ncAAs in phages provide unique interactions for identification of unique peptides. As an effective tool for phage display, we believe that CMa13ile40 can be broadly applied to a wide variety of applications.

BRD4354 Is a Potent Covalent Inhibitor against the SARS-CoV-2 Main Protease.

Numerous organic molecules are known to inhibit the main protease (MPro) of SARS-CoV-2, the pathogen of Coronavirus Disease 2019 (COVID-19). Guided by previous research on zinc-ligand inhibitors of MPro and zinc-dependent histone deacetylases (HDACs), we identified BRD4354 as a potent inhibitor of MPro. The in vitro protease activity assays show that BRD4354 displays time-dependent inhibition against MPro with an IC50 (concentration that inhibits activity by 50%) of 0.72 ± 0.04 µM after 60 min of incubation. Inactivation follows a two-step process with an initial rapid binding step with a KI of 1.9 ± 0.5 µM followed by a second slow inactivation step, kinact,max of 0.040 ± 0.002 min-1. Native mass spectrometry studies indicate that a covalent intermediate is formed where the ortho-quinone methide fragment of BRD4354 forms a covalent bond with the catalytic cysteine C145 of MPro. Based on these data, a Michael-addition reaction mechanism between MPro C145 and BRD4354 was proposed. These results suggest that both preclinical testing of BRD4354 and structure-activity relationship studies based on BRD4354 are warranted to develop more effective anti-COVID therapeutics.

Boosted Near-Infrared Photothermal Conversion in Rare Earth Ions-Doped 2D SnSe Nanosheets for Solar-Powered Water Evaporation Systems.

Solar-powered water evaporation as a clean and abundant renewable energy-efficient desalination technology provides a promising strategy to solve the shortage of freshwater resources. However, the development and application of solar vapor technology are hindered by the relatively low near-infrared photothermal conversion efficiency of existing materials and the lack of effective improvement strategies. In this work, the conductivity characteristics of 2D semiconductors are capitalized on the high visible light absorption and ultra-low thermal. Specifically, rare-earth ion dopants into SnSe nanosheets, significantly boosting their near-infrared photothermal conversion efficiency and solar water evaporation performance are introduced. Remarkably, the photothermal conversion efficiency of the doped SnSe nanosheets surged from 51.56% to 82.11%, surpassing many previously reported photothermal materials. Furthermore, leveraging these nanosheets with enhanced photothermal conversion efficiency, a solar interfacial evaporation system is constructed. The evaporation rate of 2.17 kg m-2 h-1 and the efficiency of 96.5% can be achieved at one solar irradiance, and it also has good salt-resistance properties. The findings demonstrate the potential of rare earth ion-doped 2D semiconductor nanosheets in solar water evaporation, paving the way for future sustainable desalination solutions.

Efficient Solar-Driven Interfacial Water Evaporator using Hydrogel Modified Carbon-Based Biomass with Abundant Microchannels.

The conventional sea water desalination technologies are not yet adopted worldwide, especially in the third world countries due to their high capital cost as well as large energy requirement. To solve this issue in a sustainable way an interfacial solar water evaporation device is designed and proposed in this article using the branches of Prunus serrulata (PB). The PB has abundant microchannels and shows excellent photothermal conversion capability after carbonization. Moreover, the easy access to raw materials and the facile fabrication process makes the solar water evaporating device very cost effective for seawater desalination application. Experiments show that in the presence of the fabricated evaporator the evaporation rate of water can reach 3.5 kg m-2 h-1 under 1 sun, which is superior to many similar experimental devices. In addition, its advantages, such as effective sewage purification capability, low cost, and environmental friendliness, make this evaporator highly competitive in the extensive promotion of this technology and can be considered as a new sustainable solution for seawater desalination with great application potential and prospects.

Multicolor tunable persistent luminescence mechanism in well-designed inorganic composites.

Herein, by ball milling CsPb(Br/I)3 quantum dot glass powder with Sr2MgSi2O7:Eu2+, Dy3+ phosphor, multicolor tunable long persistent luminescence (LPL) in inorganic composites with more than 700 min attenuation time can be obtained via a radiation photon reabsorption process. Attractively, the wide color gamut of LPL spectra overlaps the National Television System Committee space 74%. Notably, the luminescence intensity remains stable when the inorganic composites are composed with UV light for 100 h. Finally, practical anticounterfeiting application is successfully realized based on the prepared LPL inorganic composites. This work provides a new, to the best of our knowledge, perspective to achieve polychromatic adjustment of LPL.

Tunable afterglow Ca1 - xSrxAl2O4:Eu2+, Nd3+ phosphors with dependence of an excitation wavelength.

In the emerging field of high-capacity information encryption, multicolor, multitemporal, and multimodal luminescence inorganic materials are of great significance. However, conventional inorganic materials lack the flexibility to dynamically adjust the photon transition path, resulting in unicolor luminescence of the sample and reducing the reading and decoding levels. Herein, we elaborately designed the components for constructing dual-phase crystal fields for Eu2+ in phosphors based on a high temperature solid-state method. Specifically, SrAl2O4:Eu2+ crystal with a bright green afterglow and CaAl2O4:Eu2+ crystal with a blue afterglow were obtained in phosphors at the same time. As a result, a tunable afterglow behavior from blue to white was achieved due to the 4f65d1 → 4f7 transition of Eu2+ at different crystal field sites. Finally, the color tunable afterglow sample was used to explore the encryption and decryption processes of information, and the results showed that the prepared material has a good anti-counterfeiting performance, which is promising for the development of long persistent luminescent materials.

Research on optical performance of Ln2O2S:Er3+/Yb3+ (Ln = La/Gd/Y) phosphors based on different phonon energies.

It is crucial to explore the intrinsic mechanisms that influence thermometric sensitivity. This study investigates the optical performance of materials with the same crystal structure but different phonon energies. Ln2O2S:Er3+/Yb3+ (Ln = La/Gd/Y) phosphors with similar morphology and particle sizes were prepared to systematically study the influence of different phonon energy matrices on optical properties. The intrinsic mechanism was elucidated through the matching degree between the energy gap and phonon energy, Judd-Ofelt (J-O) theory, and quantum dielectric theory. It was ultimately concluded that the combination of high phonon energy with a large Ω2 and a small Ω6 is beneficial for enhancing the sensitivity of temperature sensing materials.

Preparation and Luminescence Properties of Broadband Orange-Emitting Persistent ScBaZn3GaO7:Bi3+ Phosphor.

This article describes a new kind of afterglow material, ScBaZn3GaO7:Bi3+, which was synthesized through a high-temperature solid-phase method. Its crystal structure, photoluminescent characteristics, and afterglow characteristics were studied and analyzed. Upon excitation at 344 nm, ScBaZn3GaO7:Bi3+ exhibits broadband emission with a central wavelength located at 571 nm (fwhm = 172.98 nm). The sample exhibits an internal quantum efficiency of 65.1%. The bright yellow persistent luminescence of the ScBaZn3GaO7:Bi3+ sample was observed after 365 nm irradiation. Thermoluminescence spectroscopy revealed four primary traps within ScBaZn3GaO7:Bi3+, with depths of 0.676, 0.794, 0.882, and 0.972 eV. The traps located at energy levels of 0.676 and 0.794 eV were identified as the key contributors to the sample's afterglow. Finally, the ScBaZn3GaO7:Bi3+ sample was combined with a UV-LED chip to fabricate a high-power warm white-light-emitting diode (WLED) device, indicating the potential application prospect of ScBaZn3GaO7:Bi3+ phosphor in single-phase warm WLEDs.

Bepridil is potent against SARS-CoV-2 in vitro.

Guided by a computational docking analysis, about 30 Food and Drug Administration/European Medicines Agency (FDA/EMA)-approved small-molecule medicines were characterized on their inhibition of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro). Of these small molecules tested, six displayed a concentration that inhibits response by 50% (IC50) value below 100 µM in inhibiting Mpro, and, importantly, three, that is, pimozide, ebastine, and bepridil, are basic molecules that potentiate dual functions by both raising endosomal pH to interfere with SARS-CoV-2 entry into the human cell host and inhibiting Mpro in infected cells. A live virus-based modified microneutralization assay revealed that bepridil possesses significant anti-SARS-CoV-2 activity in both Vero E6 and A459/ACE2 cells in a dose-dependent manner with low micromolar effective concentration, 50% (EC50) values. Therefore, the current study urges serious considerations of using bepridil in COVID-19 clinical tests.

Effects of Habitual Dietary Change on the Gut Microbiota and Health of Silkworms.

Diet plays a crucial role in shaping the gut microbiota and overall health of animals. Traditionally, silkworms are fed fresh mulberry leaves, and artificial diets do not support good health. The aim of this study was to explore the relationship between the dietary transition from artificial diets to mulberry leaves and the effects on the gut microbiota and physiological changes in silkworms as a model organism. With the transition from artificial diets to mulberry leaves, the diversity of the silkworm gut microbiota increased, and the proportion of Enterococcus and Weissella, the dominant gut bacterial species in silkworms reared on artificial diets, decreased, whereas the abundance of Achromobacter and Rhodococcus increased. Dietary transition at different times, including the third or fifth instar larval stages, resulted in significant differences in the growth and development, immune resistance, and silk production capacity of silkworms. These changes might have been associated with the rapid adaptation of the intestinal microbiota of silkworms to dietary transition. This study preliminarily established a dietary transition-gut microbial model in silkworms based on the conversion from artificial diets to mulberry leaves, thus providing an important reference for future studies on the mechanisms through which habitual dietary changes affect host physiology through the gut microbiome.

Circadian clock regulates developmental time through ecdysone and juvenile hormones in Bombyx mori.

The circadian clock plays an integral role in hormone biosynthesis and secretion. However, how the circadian clock precisely coordinates hormonal homeostasis to maintain normal animal development remains unclear. Here, we show that knocking out the core clock gene Cryptochrome 1 (Cry1) significantly delays the developmental time in Bombyx mori. This study focuses on the ecdysone and juvenile hormone signalling pathways of fifth instar larvae with the longest developmental time delay. We found that the mutant reduced prothoracicotropic hormone synthesis in the brain, and could not produce sufficient ecdysone in the prothoracic gland, resulting in a delayed peak of 20-hydroxyecdysone titre in the hemolymph of fifth instar larvae, prolonging developmental time. Moreover, further investigation revealed that the mutant enhanced juvenile hormone biosynthesis and signalling pathway and that this higher juvenile hormone titre also resulted in prolonged developmental time in fifth instar larvae. Our results provide insights into the molecular mechanisms by which the circadian clock regulates animal development by maintaining hormonal homeostasis.

Efficient and tunable emission CsPbClxBr3-x quantum dot glass for overcoming the lack of cyan gap in WLED.

Recently, the photoluminescence (PL) performance and stability of cyan emission perovskite quantum dot (PQD) were found to be inferior to other color emitting PQDs, which greatly limits their practical applications. In this Letter, CsPbClxBr3-x PQD glass with excellent hydrothermal stability is successfully synthesized by a high-temperature melting method. Results review that the vacancy defects in [PbBr6]4- octahedra can be effectively compensated by excessive halogen doping, resulting in an improvement in the photoluminescence quantum yield (PLQY) of PQDs from 24.73% to 65.62%. In addition, compared to white light emitting diode (WLED) synthesized with commercial fluorescent powders, the introduction of CsPbCl2Br1 PQD glass effectively fills the cyan gap. Moreover, the WLED displays the color-rendering index (CRI) of 87 at correlated color temperature (CCT) of 5257 K, and the color gamut area reaches 126% of the National Television System Committee (NTSC). This work provides an effective way for improving the PL performance of PQDs and brings CsPbClxBr3-x PQD glass significant prospect in the optoelectronic applications.

Enhanced blue afterglow in Ce-doped boroaluminate glass modified by Na.

The alkali metal Na+ is commonly applied as a charge compensator to optimize afterglow performance but rarely reported as a structural regulator to modify afterglow behavior in long afterglow glass materials. In this paper, by preparing the Na + -modified Ce-doped boroaluminate glasses under a high-temperature reducing atmosphere, super-five times brighter blue-violet afterglow lasting up to 30 min was obtained. Results show that appropriate Na+ doping loosens the glass structure and widens the bandgap, thereby regulating most of the electron capture-release modes. This work provides new insights into the behavior of afterglow enhancement in alkali metal-doped glasses.

Broadband La2LiSbO6: Cr3+ Phosphors with Double Luminescent Centers for NIR pc-LEDs.

The La2LiSbO6: xCr3+ phosphors were synthesized by means of a high-temperature solid-phase method. Based on the differences in ionic radius, valence state, and formation energy, the substitution sites of Cr3+ ions are discussed in detail. The optimized doping concentration of Cr3+ is determined to be 0.01. Under 517 nm excitation, the La2LiSbO6: 0.01Cr3+ phosphor presents a wide emission band (from 700 to 1350 nm) with a peak centered at 952 nm. Additionally, its corresponding full width at half-maximum is 155 nm, and the internal quantum efficiency reaches 62.4%. Meanwhile, the emission intensity of the La2LiSbO6: 0.01Cr3+ phosphor at 373 K is about 63.7% of that at room temperature, exhibiting good thermal stability. Aiming to fabricate a near-infrared phosphor-converted light-emitting diode device, the La2LiSbO6: 0.01Cr3+ phosphor is mixed with epoxy adhesive and cured on a green light-emitting diode chip. Under the irradiation of the fabricated light-emitting diode device, fruits and writing in the dark environment can be captured by a near-infrared camera. Hence, the La2LiSbO6: 0.01Cr3+ phosphor is promising for night vision.

[Zn2+-Ge4+] co-substitutes [Ga3+-Ga3+] to coordinately broaden the near-infrared emission of Cr3+ in Ga2O3 phosphors.

Here, a "chemical unit co-substitution" method is used to improve the near-infrared (NIR) emission of phosphors, using [Zn2+-Ge4+] to co-substitute [Ga3+-Ga3+] sites to reduce crystal field splitting to affect the structure of gallium oxide. A series of broadband NIR phosphors are synthesized by a high-temperature solid-phase method, and their phase structures, crystal structures, morphologies, diffuse reflectance spectra, and luminescence lifetimes are investigated. The Ga1.68(Zn-Ge)0.3O3:0.02Cr3+ (GZGOC) phosphor exhibits NIR wide-band emission, with a peak wavelength of 766 nm and a half-width of 138 nm. Meanwhile, the quantum yield of photoluminescence can reach 81.2%. The phosphor has good thermal stability. When the temperature reaches 373 K, its emission intensity still remains at 73.4% of that at room temperature. A 460 nm LED chip and this phosphor are used to fabricate a phosphor-converted light emitting diode (pc-LED) device which can be used as a NIR light source. All these results show the application potential of the as-prepared phosphor in NIR imaging.

The clock gene Cryptochrome 1 is involved in the photoresponse of embryonic hatching behavior in Bombyx mori.

The hatching of insect eggs is a classic circadian behavior rhythm controlled by the biological clock. Its function is considered to impose a daily rhythm on the embryo, allowing it to hatch within a permissible time window. However, the molecular pathways through which the clock affects embryonic hatching behavior remain unclear. Here, we utilized a clock gene Cryptochrome1 (Cry1) knockout mutant to dissect the pathways by which the circadian clock affects embryonic hatching rhythm in the silkworm. In the Cry1 mutant, the embryo hatching rhythm was disrupted. Under the constant light or constant dark incubation conditions, mutant embryos lost their hatching rhythm, while wild-type embryos hatch exhibiting free-running rhythm. In the light-dark cycle (LD), the hatching rhythm of CRY1-deficient silkworms could not be entrained by the LD photoperiod during the incubation period. The messenger RNA levels and enzymatic activities of Cht and Hel in the mutant embryos were significantly reduced at circadian time 24 (CT24). Transcriptome analysis revealed significant differences in gene expression at CT24 between the Cry1 knockout mutant and the wild-type, with 2616 differentially expressed genes identified. The enriched Gene Ontology pathway includes enzyme activity, energy availability, and protein translation. Short neuropeptide F signaling was reduced in the CT24 embryonic brain of the mutant, the expression of the neuropeptide PTTH was also reduced and the rhythm was lost, which further affects ecdysteroid signaling. Our results suggested that the silkworm circadian clock affects neuropeptide-hormone signaling as well as physiological functions related to hatching, which may regulate the hatching rhythm.

Inhibition of Expression of the Circadian Clock Gene Cryptochrome 1 Causes Abnormal Glucometabolic and Cell Growth in Bombyx mori Cells.

Cryptochrome is the earliest discovered photoreceptor protein in organisms. However, the effect of CRY (BmCRY), the clock protein in Bombyx mori, on the body or cell metabolism remains unclear. In this study, we continuously interfered with the expression of the BmCry1 gene (Cry1-KD) in the silkworm ovary cell line (BmN), and the BmN cells developed abnormally, with accelerated cell growth and a smaller nucleus. Metabolomics was used to identify the cause of the abnormal development of Cry1-KD cells based on gas chromatography/liquid chromatography-mass spectrometry. A total of 56 differential metabolites including sugars, acids, amino acids, and nucleotides were identified in wild-type and Cry1-KD cells. KEGG enrichment analysis showed that BmCry1 knockdown resulted in significantly upregulated glycometabolism in BmN cells, indicated by glucose-6-phosphate, fructose-6-phosphate, and pyruvic acid levels. The activities of key enzymes BmHK, BmPFK, and BmPK as well as their mRNA levels further confirmed that the glycometabolism level of Cry1-KD cells was significantly increased. Our results show that a possible mechanism of BmCry1 knockdown leading to abnormal cell development is the elevated level of glucose metabolism in cells.

Picomole-Scale Transition Metal Electrocatalysis Screening Platform for Discovery of Mild C-C Coupling and C-H Arylation through in Situ Anodically Generated Cationic Pd.

Development of new transition-metal-catalyzed electrochemistry promises to improve overall synthetic efficiency. Here, we describe the first integrated platform for online screening of electrochemical transition-metal catalysis. It utilizes the intrinsic electrochemical capabilities of nanoelectrospray ionization mass spectrometry (nano-ESI-MS) and picomole-scale anodic corrosion of a Pd electrode to generate and evaluate highly efficient cationic catalysts for mild electrocatalysis. We demonstrate the power of the novel electrocatalysis platform by (1) identifying electrolytic Pd-catalyzed Suzuki coupling at room temperature, (2) discovering Pd-catalyzed electrochemical C-H arylation in the absence of external oxidant or additive, (3) developing electrolyzed Suzuki coupling/C-H arylation cascades, and (4) achieving late-stage functionalization of two drug molecules by the newly developed mild electrocatalytic C-H arylation. More importantly, the scale-up reactions confirm that new electrochemical pathways discovered by nano-ESI can be implemented under the conventional electrolytic reaction conditions. This approach enables in situ mechanistic studies by capturing various intermediates including transient transition metal species by MS, and thus uncovering the critical role of anodically generated cationic Pd catalyst in promoting otherwise sluggish transmetalation in C-H arylation. The anodically generated cationic Pd with superior catalytic efficiency and novel online electrochemical screening platform hold great potential for discovering mild transition-metal-catalyzed reactions.

Highly efficient green emission Cs4PbBr6 quantum dots with stable water endurance.

To date, quantum dots (QDs) based on perovskite materials with high photoluminescence quantum yield (PLQY) and stability have rarely been reported. In this work, Cs4PbBr6 QDs glass ceramic with high PLQY and water stability is obtained, and the research results confirm that the strong green emission originates from the trapping of free excitons by internal Br vacancies. The rise of Br vacancies and the spontaneous growth of multi-morphology Cs4PbBr6 QDs under the influence of air humidity increase the PLQY to 89.62%. Compared with pure QDs, the Cs4PbBr6 QDs maintain high-intensity luminescence after being immersed in water for up to 150 days. In short, this paper puts forward a new, to the best of our knowledge, and valuable perspective for investigating the luminescence of Cs4PbBr6 QDs glass ceramic derived from related work.

Dual-mode optical thermometry design in K3YSi2O7:Eu multi-site phosphor.

In this study, a dual-mode optical thermometer is designed based on radiative transitions from Eu3+ and Eu2+ ions at different K3YSi2O7 lattice sites. In the luminescence-intensity-ratio strategy, a ratiometric signal composed of Eu3+:5D0→7F1 and Eu3+:5D0→7F2 emissions at 593 and 616 nm, respectively, is employed. Meanwhile, the intensity ratio of the 593-nm emission under O2-→Eu3+ charge transfer excitation (λex = 249 nm) to that upon Eu2+:4f7→4f65d1 excitation (λex = 349 nm) is selected as a thermometric parameter in the single-band-ratio approach. The study findings show that combining the two strategies is conducive to the improvements in sensing-sensitive and anti-interference performance.