Squalene, a valuable acyclic triterpene, can be used as a chemical commodity for pharmacology, flavor, and biofuel industries. Microbial production of squalene has been of great interest due to its ...limited availability, and increasing prices extracted from animal and plant tissues. Here we report genetic perturbations that synergistically improve squalene production in Saccharomyces cerevisiae. As reported previously, overexpression of a truncated HMG‐CoA reductase 1 (tHMG1) led to the accumulation 20‐fold higher squalene than a parental strain. In order to further increase squalene accumulation in the tHMG1 overexpressing yeast, we introduced genetic perturbations—known to increase lipid contents in yeast—to enhance squalene accumulation as lipid body is a potential storage of squalene. Specifically, DGA1 coding for diacylglycerol acyltranferase was overexpressed to enhance lipid biosynthesis, and POX1 and PXA2 coding for acyl‐CoA oxidase and a subunit of peroxisomal ABC transporter were deleted to reduce lipid β‐oxidation. Simultaneous overexpression of tHMG1 and DGA1 coding for rate‐limiting enzymes in the mevalonate and lipid biosynthesis pathways led to over 250‐fold higher squalene accumulation than a control strain. However, deletion of POX1 and PXA2 in the tHMG1 overexpressing yeast did not improve squalene accumulation additionally. Fed‐batch fermentation of the tHMG1 and DGA1 co‐overexpressing yeast strain resulted in the production of squalene at a titer of 445.6 mg/L in a nitrogen‐limited minimal medium. This report demonstrates that increasing storage capacity for hydrophobic compounds can enhance squalene production, suggesting that increasing lipid content is an effective strategy to overproduce a hydrophobic molecule in yeast.
This study focused on the genetic perturbations eliciting improved lipid production and enhanced squalene accumulation in Saccharomyces cerevisiae. The engineered strains, with simultaneous overexpression of tHMG1 and DGA1 coding for rate‐limiting enzymes in the mevalonate and lipid biosynthesis pathways, showed over 250‐fold higher squalene accumulation than a control strain. The results indicated that increasing storage capacity for hydrophobic compounds enhances squalene production.
Photocatalytic synthesis of hydrogen peroxide (H2O2) is a potential clean method, but the long distance between the oxidation and reduction sites in photocatalysts hinders the rapid transfer of ...photogenerated charges, limiting the improvement of its performance. Here, a metal‐organic cage photocatalyst, Co14(L−CH3)24, is constructed by directly coordinating metal sites (Co sites) used for the O2 reduction reaction (ORR) with non‐metallic sites (imidazole sites of ligands) used for the H2O oxidation reaction (WOR), which shortens the transport path of photogenerated electrons and holes, and improves the transport efficiency of charges and activity of the photocatalyst. Therefore, it can be used as an efficient photocatalyst with a rate of as high as 146.6 μmol g−1 h−1 for H2O2 production under O2‐saturated pure water without sacrificial agents. Significantly, the combination of photocatalytic experiments and theoretical calculations proves that the functionalized modification of ligands is more conducive to adsorbing key intermediates (*OH for WOR and *HOOH for ORR), resulting in better performance. This work proposed a new catalytic strategy for the first time; i.e., to build a synergistic metal‐nonmetal active site in the crystalline catalyst and use the host–guest chemistry inherent in the metal‐organic cage (MOC)to increase the contact between the substrate and the catalytically active site, and finally achieve efficient photocatalytic H2O2 synthesis.
Two stable CoII‐based metal‐organic cages are efficient catalysts for photocatalytic synthesis of H2O2 in pure water and O2 or air atmospheres. The metal‐nonmetal active site operates synergistically during photocatalytic H2O2 synthesis and the reaction substrate can more fully contact the catalytically active site through host–guest chemistry of cages, ultimately achieving a high H2O2 production rate.
The dilemma between the thickness and accessible active site triggers the design of porous crystalline materials with mono‐layered structure for advanced photo‐catalysis applications. Here, a kind of ...sub‐nanometer mono‐layered nanosheets (Co‐MOF MNSs) through the exfoliation of specifically designed Co3 cluster‐based metal–organic frameworks (MOFs) is reported. The sub‐nanometer thickness and inherent light‐sensitivity endow Co‐MOF MNSs with fully exposed Janus Co3 sites that can selectively photo‐reduce CO2 into formic acid under simulated flue gas. Notably, the production efficiency of formic acid by Co‐MOF MNSs (0.85 mmol g−1 h−1) is ≈13 times higher than that of the bulk counterpart (0.065 mmol g−1 h−1) under a simulated flue gas atmosphere, which is the highest in reported works up to date. Theoretical calculations prove that the exposed Janus Co3 sites with simultaneously available sites possess higher activity when compared with single Co site, validating the importance of mono‐layered nanosheet morphology. These results may facilitate the development of functional nanosheet materials for CO2 photo‐reduction in potential flue gas treatment.
A kind of sub‐nanometer mono‐layered nanosheets (Co‐MOF MNSs) is successfully prepared with remarkable performance in selective CO2 photo‐reduction into formic acid under simulated flue gas.
This is the first randomised controlled trial for assessment of the immunogenicity and safety of a candidate non-replicating adenovirus type-5 (Ad5)-vectored COVID-19 vaccine, aiming to determine an ...appropriate dose of the candidate vaccine for an efficacy study.
This randomised, double-blind, placebo-controlled, phase 2 trial of the Ad5-vectored COVID-19 vaccine was done in a single centre in Wuhan, China. Healthy adults aged 18 years or older, who were HIV-negative and previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-free, were eligible to participate and were randomly assigned to receive the vaccine at a dose of 1 × 1011 viral particles per mL or 5 × 1010 viral particles per mL, or placebo. Investigators allocated participants at a ratio of 2:1:1 to receive a single injection intramuscularly in the arm. The randomisation list (block size 4) was generated by an independent statistician. Participants, investigators, and staff undertaking laboratory analyses were masked to group allocation. The primary endpoints for immunogenicity were the geometric mean titres (GMTs) of specific ELISA antibody responses to the receptor binding domain (RBD) and neutralising antibody responses at day 28. The primary endpoint for safety evaluation was the incidence of adverse reactions within 14 days. All recruited participants who received at least one dose were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, NCT04341389.
603 volunteers were recruited and screened for eligibility between April 11 and 16, 2020. 508 eligible participants (50% male; mean age 39·7 years, SD 12·5) consented to participate in the trial and were randomly assigned to receive the vaccine (1 × 1011 viral particles n=253; 5 × 1010 viral particles n=129) or placebo (n=126). In the 1 × 1011 and 5 × 1010 viral particles dose groups, the RBD-specific ELISA antibodies peaked at 656·5 (95% CI 575·2–749·2) and 571·0 (467·6–697·3), with seroconversion rates at 96% (95% CI 93–98) and 97% (92–99), respectively, at day 28. Both doses of the vaccine induced significant neutralising antibody responses to live SARS-CoV-2, with GMTs of 19·5 (95% CI 16·8–22·7) and 18·3 (14·4–23·3) in participants receiving 1 × 1011 and 5 × 1010 viral particles, respectively. Specific interferon γ enzyme-linked immunospot assay responses post vaccination were observed in 227 (90%, 95% CI 85–93) of 253 and 113 (88%, 81–92) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Solicited adverse reactions were reported by 183 (72%) of 253 and 96 (74%) of 129 participants in the 1 × 1011 and 5 × 1010 viral particles dose groups, respectively. Severe adverse reactions were reported by 24 (9%) participants in the 1 × 1011 viral particles dose group and one (1%) participant in the 5 × 1010 viral particles dose group. No serious adverse reactions were documented.
The Ad5-vectored COVID-19 vaccine at 5 × 1010 viral particles is safe, and induced significant immune responses in the majority of recipients after a single immunisation.
National Key R&D Programme of China, National Science and Technology Major Project, and CanSino Biologics.
A practical, Pd(0)/Pd(II)-catalyzed reaction was developed for phenol-directed C–H activation/C–O cyclization using air as an oxidant. The turnover-limiting step of the process was found to be C–O ...reductive elimination instead of C–H activation. This reaction can tolerate a variety of functional groups and is complementary to the previous methods for the synthesis of substituted dibenzofurans.
High-precision permeability prediction is of great significance to tight sandstone reservoirs. However, while considerable progress has recently been made in the machine learning based prediction of ...reservoir permeability, the generalization of this approach is limited by weak interpretability. Hence, an interpretable XGBoost model is proposed herein based on particle swarm optimization to predict the permeability of tight sandstone reservoirs with higher accuracy and robust interpretability. The porosity and permeability of 202 core plugs and 6 logging curves (namely, the gamma-ray (GR) curve, the acoustic curve (AC), the spontaneous potential (SP) curve, the caliper (CAL) curve, the deep lateral resistivity (RILD) curve, and eight lateral resistivity (RFOC) curve) are extracted along with three derived variables (i.e., the shale content, the AC slope, and the GR slope) as data sets. Based on the data preprocessing, global and local interpretations are performed according to the Shapley additive explanations (SHAP) analysis, and the redundant features in the data set are screened to identify the porosity, AC, CAL, and GR slope as the four most important features. The particle swarm optimization algorithm is then used to optimize the hyperparameters of the XGBoost model. The prediction results of the PSO-XGBoost model indicate a superior performance compared with that of the benchmark XGBoost model. In addition, the reliable application of the interpretable PSO-XGBoost model in the prediction of tight sandstone reservoir permeability is examined by comparing the results with those of two traditional mathematical regression models, five machine learning models, and three deep learning models. Thus, the interpretable PSO-XGBoost model is shown to have more advantages in permeability prediction along with the lowest root mean square error, thereby confirming the effectiveness and practicability of this method.
Over the past 200 years, the most famous and important heteroatom Keggin architecture in polyoxometalates has only been synthesized with Mo, W, V, or Nb. Now, the self‐assembly of two phosphate ...(PO43−)‐centered polyoxo‐titanium clusters (PTCs) is presented, PTi16 and PTi12, which display classic heteroatom Keggin and its trivacant structures, respectively. Because TiIV has lower oxidate state and larger ionic radius than MoVI, WVI, VV, and NbV, additional TiIV centres in these PTCs are used to stabilize the resultant heteroatom Keggin structures, as demonstrated by the cooresponding theoretical calculation results. These photoactive PTCs can be utilized as efficient photocatalysts for highly selective CO2‐to‐HCOOH conversion. This new discovery indicates that the classic heteroatom Keggin family can be assembled with Ti, thus opening a research avenue for the development of PTC chemistry.
One of the family: A TiIV‐based heteroatom Keggin and its trivacant lacunary architectures were structurally synthesized as a polyoxo‐titanium cluster. They exhibited a very high selectivity and activity for photocatalytic CO2‐to‐HCOOH conversion.
Purposefully designing the well‐defined catalysts for the selective electroreduction of CO2 to C2H4 is an extremely important but challenging work. In this work, three crystalline trinuclear copper ...clusters (Cu3‐X, X=Cl−, Br−, NO3−) have been designed, containing three active Cu sites with the identical coordination environment and appropriate spatial distance, delivering high selectivity for the electrocatalytic reduction of CO2 to C2H4. The highest faradaic efficiency of Cu3‐X for CO2‐to‐C2H4 conversion can be adjusted from 31.90 % to 55.01 % by simply replacing the counter anions (NO3−, Cl−, Br−). The DFT calculation results verify that Cu3‐X can facilitate the C−C coupling of identical *CHO intermediates, subsequently forming molecular symmetrical C2H4 product. This work provides an important molecular model system and a new design perspective for electroreduction of CO2 to C2 products with symmetrical molecular structure.
A molecular model catalyst system (Cu3‐X) with predesigned catalytically active sites has been constructed to achieve the selective electroreduction of CO2 to C2H4. The active Cu sites display an appropriate spatial distance, resulting in high faradaic efficiencies.
Visible‐light driven photoconversion of CO2 into energy carriers is highly important to the natural carbon balance and sustainable development. Demonstrated here is the adenine‐dependent CO2 ...photoreduction performance in green biomimetic metal–organic frameworks. Photocatalytic results indicate that AD‐MOF‐2 exhibited a very high HCOOH production rate of 443.2 μmol g−1 h−1 in pure aqueous solution, and is more than two times higher than that of AD‐MOF‐1 (179.0 μmol g−1h−1) in acetonitrile solution. Significantly, experimental and theoretical evidence reveal that the CO2 photoreduction reaction mainly takes place at the aromatic nitrogen atom of adenine molecules through a unique o‐amino‐assisted activation rather than at the metal center. This work not only serves as an important case study for the development of green biomimetic photocatalysts used for artificial photosynthesis, but also proposes a new catalytic strategy for efficient CO2 photoconversion.
Eco‐friendly terms: Two biomimetic metal–organic frameworks (MOFs) were assembled with eco‐friendly components and used as photocatalysts for CO2‐to‐HCOOH conversion. One of the synthesized MOFs exhibited a very high HCOOH production rate of 443.2 μmol g−1 h−1 in pure aqueous solution.
Photoluminescence is a radiative recombination process of electron–hole pairs. Self-trapped excitons (STEs), occurring in a material with soft lattice and strong electron–phonon coupling, emit ...photons with broad spectrum and large Stokes shift. Recently, series halide perovskites with efficient STE emission have been reported and showed promise for solid-state lighting. In this Perspective, we present an overview of various photoluminescence phenomena with the emphasis on the mechanism and characteristics of emission derived from STEs. This is followed by the introduction of STE emission in hybrid halide perovskites. We then introduce all-inorganic STE emitters and focus in particular on the mechanism of STEs in double-perovskite Cs2AgInCl6 and strategies for efficiency improvement. Finally, we summarize the current photoluminescence and electroluminescence applications of STE emitters as well as the potential in luminescent solar concentrators and provide an overview of future research opportunities.
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