Abstract
The separation of C
2
H
2
/CO
2
is not only industrially important for acetylene purification but also scientifically challenging owing to their high similarities in physical properties and ...molecular sizes. Ultramicroporous metal-organic frameworks (MOFs) can exhibit a pore confinement effect to differentiate gas molecules of similar size. Herein, we report the fine-tuning of pore sizes in sub-nanometer scale on a series of isoreticular MOFs that can realize highly efficient C
2
H
2
/CO
2
separation. The subtle structural differences lead to remarkable adsorption performances enhancement. Among four MOF analogs, by integrating appropriate pore size and specific binding sites, Cu(dps)
2
(SiF
6
) (SIFSIX-dps-Cu, SIFSIX = SiF
6
2-
, dps = 4.4’-dipyridylsulfide, also termed as NCU-100) exhibits the highest C
2
H
2
uptake capacity and C
2
H
2
/CO
2
selectivity. At room temperature, the pore space of SIFSIX-dps-Cu significantly inhibits CO
2
molecules but takes up a large amount of C
2
H
2
(4.57 mmol g
−1
), resulting in a high IAST selectivity of 1787 for C
2
H
2
/CO
2
separation. The multiple host-guest interactions for C
2
H
2
in both inter- and intralayer cavities are further revealed by dispersion-corrected density functional theory and grand canonical Monte Carlo simulations. Dynamic breakthrough experiments show a clean C
2
H
2
/CO
2
separation with a high C
2
H
2
working capacity of 2.48 mmol g
−1
.
The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses ...to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.
•SARS-CoV-2-specific antibodies are detected in COVID-19 convalescent subjects•Most COVID-19 convalescent individuals have detectable neutralizing antibodies•Cellular immune responses to SARS-CoV-2 are found in COVID-19 convalescent subjects•Neutralization antibody titers correlate with the numbers of virus-specific T cells.
In blood samples from COVID-19 convalescent subjects, Ni et al. have detected SARS-CoV-2-specific humoral and cellular immunity. Most subjects display serum neutralizing activities, which correlate with the numbers of virus-specific T cells.
Natural DNA is exquisitely evolved to store genetic information. The chirally inverted L-DNA, possessing the same informational capacity but resistant to biodegradation, may serve as a robust, ...bioorthogonal information repository. Here we chemically synthesize a 90-kDa high-fidelity mirror-image Pfu DNA polymerase that enables accurate assembly of a kilobase-sized mirror-image gene. We use the polymerase to encode in L-DNA an 1860 paragraph by Louis Pasteur that first proposed a mirror-image world of biology. We realize chiral steganography by embedding a chimeric D-DNA/L-DNA key molecule in a D-DNA storage library, which conveys a false or secret message depending on the chirality of reading. Furthermore, we show that a trace amount of an L-DNA barcode preserved in water from a local pond remains amplifiable and sequenceable for 1 year, whereas a D-DNA barcode under the same conditions could not be amplified after 1 day. These next-generation mirror-image molecular tools may transform the development of advanced mirror-image biology systems and pave the way for the realization of the mirror-image central dogma and exploration of their applications.
The gut microbiota has a crucial effect on regulating the intestinal mucosal immunity and maintaining intestinal homeostasis both in health and in disease state. Many effects are mediated by gut ...microbiota-derived metabolites and tryptophan, an essential aromatic amino acid, is considered important among many metabolites in the crosstalk between gut microbiota and the host. Kynurenine, serotonin, and indole derivatives are derived from the three major tryptophan metabolism pathways modulated by gut microbiota directly or indirectly. Aryl hydrocarbon receptor (AHR) is a cytoplasmic ligand-activated transcription factor involved in multiple cellular processes. Tryptophan metabolites as ligands can activate AHR signaling in various diseases such as inflammation, oxidative stress injury, cancer, aging-related diseases, cardiovascular diseases (CVD), and chronic kidney diseases (CKD). Accumulated uremic toxins in the body fluids of CKD patients activate AHR and affect disease progression. In this review, we will elucidate the relationship between gut microbiota-derived uremic toxins by tryptophan metabolism and AHR activation in CKD and its complications. This review will provide therapeutic avenues for targeting CKD and concurrently present challenges and opportunities for designing new therapeutic strategies against renal fibrosis.
The recent Zika virus （ZIKV） epidemic in Latin America coincided with a marked increase in microcephaly in newborns. However, the causal link between maternal ZIKV infection and malformation of the ...fetal brain has not been firmly established. Here we show a vertical transmission of ZIKV in mice and a marked effect on fetal brain development. We found that intraperitoneal （i.p.） injection of a contemporary ZIKV strain in pregnant mice led to the infection of radial gila cells （RGs） of dorsal ventricular zone of the fetuses, the primary neural progenitors responsi- ble for cortex development, and caused a marked reduction of these cortex founder cells in the fetuses. Interestingly, the infected fetal mice exhibited a reduced cavity of lateral ventricles and a discernable decrease in surface areas of the cortex. This study thus supports l;he conclusion that vertically transmitted ZIKV affects fetal brain development and provides a valuable animal model for the evaluation of potential therapeutic or preventative strategies.
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved ...vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse model. Cryo-electron microscopy characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a previously uncharacterized conformational epitope, which was only accessible when the RBD was in an open conformation. Biochemical, cellular, virological, and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncovered broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.
The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical ...isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
Since December 2019, a novel coronavirus SARS-CoV-2 has emerged and rapidly spread throughout the world, resulting in a global public health emergency. The lack of vaccine and antivirals has brought ...an urgent need for an animal model. Human angiotensin-converting enzyme II (ACE2) has been identified as a functional receptor for SARS-CoV-2. In this study, we generated a mouse model expressing human ACE2 (hACE2) by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young and aged hACE2 mice sustained high viral loads in lung, trachea, and brain upon intranasal infection. Although fatalities were not observed, interstitial pneumonia and elevated cytokines were seen in SARS-CoV-2 infected-aged hACE2 mice. Interestingly, intragastric inoculation of SARS-CoV-2 was seen to cause productive infection and lead to pulmonary pathological changes in hACE2 mice. Overall, this animal model described here provides a useful tool for studying SARS-CoV-2 transmission and pathogenesis and evaluating COVID-19 vaccines and therapeutics.
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•Human ACE2 knockin mice were generated by using CRISPR/Cas9 technology•SARS-CoV-2 leads to robust replication in lung, trachea, and brain•SARS-CoV-2 causes interstitial pneumonia and elevated cytokine in aged hACE2 mice•High dose of SARS-CoV-2 can establish infection via intragastric route in hACE2 mice
The COVID-19 pandemic has brought an urgent need for small animal models. Here, Sun et al. established an ACE2 humanized mouse by CRISPR/Cas9 knockin technology. These hACE2 mice are susceptible to SARS-CoV-2 infection upon intranasal inoculation, and the resulting pulmonary infection and pathological changes resemble those observed in COVID-19 patients.
A robust and highly active homogeneous chiral nickel–phosphine complex for the asymmetric hydrogenation of aliphatic γ‐ and δ‐ketoacids has been discovered. The hydrogenation could proceed smoothly ...in the presence of 0.0133 mol% catalyst loading (S/C=7500). The coordination chemistry and catalytic behavior of Ni(OTf)2 with (S,S)‐Ph‐BPE were explored by 1H NMR and HRMS. The mechanistic studies revealed that a proton promoted the activation of the substrate C=O bond and controlled the stereoselectivity through hydrogen bonds. A series of chiral γ‐ and δ‐alkyl substituted lactones were obtained in high yields with excellent enantioselectivities (up to 98 % yield and 99 % ee). In addition, this catalytic system also demonstrated that levulinic acid produced from a biomass feedstock was converted into chiral γ‐valerolactone without loss of ee value.
A robust and efficient nickel–phosphine complex has been discovered for the asymmetric hydrogenation of aliphatic ketoacids. A proton promoted the activation of C=O bonds and controlled the stereoselectivity through hydrogen bonds to obtain the corresponding products in high yields with excellent enantioselectivities.
Chronoamperometry was used to study the dynamics of Pt nanoparticle (NP) collision with an inert ultramicroelectrode via electrocatalytic amplification (ECA) in the hydrogen evolution reaction. ECA ...and dynamic light scattering (DLS) results reveal that the NP colloid remains stable only at low proton concentrations (1.0 mm) under a helium (He) atmosphere, ensuring that the collision events occur at genuinely single NP level. Amperometry of single NP collisions under a He atmosphere shows that each discrete current profile of the collision event evolves from spike to staircase at more negative potentials, while a staircase response is observed at all of the applied potentials under hydrogen‐containing atmospheres. The particle size distribution estimated from the diffusion‐controlled current in He agrees well with electron microscopy and DLS observations. These results shed light on the interfacial dynamics of the single nanoparticle collision electrochemistry.
Evolution or stability? Under a helium atmosphere, the electrochemical catalytic current profile of the hydrogen evolution reaction on a single platinum nanoparticle (Pt NP) evolves from a spike to a staircase at more negative potentials on the underlying inert ultramicroelectrode (UME). Under a hydrogen atmosphere, the current profile stabilizes as a staircase at all polarized potentials but at least 5 times lower than that in helium.
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