Rhizoma coptidis can inhibit the excessive proliferation, inflammation, and transformation of lung fibroblasts into myofibroblasts.

BACKGROUND: Pulmonary fibrosis (PF) is a chronic, progressive, and irreversible heterogeneous disease of lung interstitial tissue. To combat progression of PF, new drugs are required to be developed. Rhizoma coptidis (COP), one of the main alkaloids of Coptis chinensis, is a traditional herbal medicine used to treat various inflammatory diseases. OBJECTIVE: To investigate the possible effects of Coptisine (Cop) on the growth, inflammation, as well as FMT of TNF-ß1-induced HFL1 cells and uncover the mechanism. MATERIAL AND METHODS: Human fetal lung fibroblast 1 (HFL1) was induced using 6ng/mL TGF-ß1 as a model of pulmonary fibrosis. CCK-8, Brdu, and transwell assays indicated the effects on cell growth as well as motility. qPCR and the corresponding kits indicted the effects on cell inflammation. Immunoblot showed the effects on FMT and further confirmed the mechanism. RESULTS: Coptisine inhibits excessive growth as well as motility of TNF-ß1-induced HFL1 cells. It further inhibits inflammation and ROS levels in TNF-ß1-induced HFL1 cells. Coptisine inhibits the FMT process of TNF-ß1-induced HFL1 cells. Mechanically, coptisine promotes the Nrf2/HO-1 pathway. CONCLUSION: Coptisine can inhibit the excessive growth, inflammation as well as FMT of lung fibroblasts into myofibroblasts. It could serve as a promising drug of PF.

Boosting Chemoselective Hydrogenation of Nitroaromatic via Synergy of Hydrogen Spillover and Preferential Adsorption on Magnetically Recoverable Pt@Fe2 O3.

It is highly desired but challenging to design high performance catalyst for selective hydrogenation of nitro compounds into amino compounds. Herein, a boosting chemoselective hydrogenation strategy on Pt@Fe2 O3 is proposed with gradient oxygen vacancy by synergy of hydrogen spillover and preferential adsorption. Experimental and theoretical investigations reveal that the nitro is preferentially adsorbed onto oxygen vacancy of Pt@Fe2 O3 , meanwhile, the H2 dissociated on Pt nanoparticles and then spillover to approach the nitro for selective hydrogenation (>99% conversion of 4-nitrostyrene, > 99% selectivity of 4-aminostyrene, TOF of 2351 h-1 ). Moreover, the iron oxide support endows the catalyst magnetic retrievability. This high activity, selectivity, and easy recovery strategy provide a promising avenue for selective hydrogenation catalysis of various nitroaromatic.

Pseudotyped Viruses.

Pseudotyped viruses have been constructed for many viruses. They can mimic the authentic virus and have many advantages compared to authentic viruses. Thus, they have been widely used as a surrogate of authentic virus for viral function analysis, detection of neutralizing antibodies, screening viral entry inhibitors, and others. This chapter reviewed the progress in the field of pseudotyped viruses in general, including the definition and the advantages of pseudotyped viruses, their potential usage, different strategies or vectors used for the construction of pseudotyped viruses, and factors that affect the construction of pseudotyped viruses.

Aggregation of high-frequency RBD mutations of SARS-CoV-2 with three VOCs did not cause significant antigenic drift.

Variants of SARS-CoV-2 continue to emerge, posing great challenges in outbreak prevention and control. It is important to understand in advance the impact of possible variants of concern (VOCs) on infectivity and antigenicity. Here, we constructed one or more of the 15 high-frequency naturally occurring amino acid changes in the receptor-binding domain (RBD) of Alpha, Beta, and Gamma variants. A single mutant of A520S, V367F, and S494P in the above three VOCs enhanced infectivity in ACE2-overexpressing 293T cells of different species, LLC-MK2 and Vero cells. Aggregation of multiple RBD mutations significantly reduces the infectivity of the possible three VOCs. Regarding neutralization, it is noteworthy that E484K, N501Y, K417N, and N439K predispose to monoclonal antibodies (mAbs) protection failure in the 15 high-frequency mutations. Most importantly, almost all possible VOCs (single RBD mutation or aggregation of multiple mutations) showed no more than a fourfold decrease in neutralizing activity with convalescent sera, vaccine sera, and immune sera of guinea pigs with different immunogens, and no significant antigenic drift was formed. In conclusion, our pseudovirus results could reduce the concern that the aggregation of multiple high-frequency mutations in the RBD of the spike protein of the three VOCs would lead to severe antigenic drift, and this would provide value for vaccine development strategies.

Confined Generation of Homogeneously Dispersed Au and SnO2 Nanoparticles in Layered Silicate as Synergistic Catalysts.

With the aid of the confined conversion of layered silicate RUB-15, homogeneously dispersed Au and SnO2 nanoparticles (NPs) were generated in the confined layer space of RUB-15. The Au-SnO2/SiO2 composite was obtained with the structure that ultrafine Au and SnO2 NPs were supported on SiO2 lamellas. Benefited by the Sn(II)-assisted in situ reduction strategy, Au NPs were highly uniformed and evenly distributed in/on the RUB-15. This Au-SnO2/SiO2 composite was employed as a catalyst to the reduction of 4-nitrophenol showing excellent catalytic activity. The catalytic rate constant at room temperature was calculated to be 6.64 min-1, which was dramatically higher than that of Au/SiO2 composite produced by reduction with hydrazine hydrate on the same support of layered silicate RUB-15. The interaction between Au and SnO2 NPs increased the electron density around Au NPs, which was demonstrated to be an essential factor to the excellent catalytic activity of the Au-SnO2/SiO2 composite. The simple and universal synthesis method afforded precise control over the size/spatial arrangement of Au and SnO2 NPs on SiO2 lamellas. The high activity of the Au-SnO2/SiO2 composite demonstrated that the strategy used in this study has good potential application prospect. Furthermore, this work provided new perspective on the catalysis mechanism to the metal/semiconductor synergistic catalyst system.

A Robust Carbon Nanotube and PVDF-HFP Nanofiber Composite Superwettability Membrane for High-Efficiency Emulsion Separation.

Oil or chemical purification is significant not only for industrial safety production but also because it conforms to the principle of sustainable development. In this paper, based on the synergistic concept of superwettability and nanopores sieve effect, a superoleophilic and under-oil superhydrophobic carbon nanotube/poly(vinylidene fluoride-co-hexafluoropropylene) nanofiber composite membrane is prepared via electrospinning, pressure-driven filtration, and chemical vapor modification. The as-prepared membrane with durable mechanical and chemical stabilities achieves separation efficiency higher than 99.9% and high flux up to 632.5 L m-2 h-1 bar-1 for different water-in-oil emulsions. This membrane is highly promising for the petroleum and chemical industries for both product quality improvement and green recycling manufacturing processes.

A Multi-Wall Sn/SnO2 @Carbon Hollow Nanofiber Anode Material for High-Rate and Long-Life Lithium-Ion Batteries.

Multi-wall Sn/SnO2 @carbon hollow nanofibers evolved from SnO2 nanofibers are designed and programable synthesized by electrospinning, polypyrrole coating, and annealing reduction. The synthesized hollow nanofibers have a special wire-in-double-wall-tube structure with larger specific surface area and abundant inner spaces, which can provide effective contacting area of electrolyte with electrode materials and more active sites for redox reaction. It shows excellent cycling stability by virtue of effectively alleviating pulverization of tin-based electrode materials caused by volume expansion. Even after 2000 cycles, the wire-in-double-wall-tube Sn/SnO2 @carbon nanofibers exhibit a high specific capacity of 986.3 mAh g-1 (1 A g-1 ) and still maintains 508.2 mAh g-1 at high current density of 5 A g-1 . This outstanding electrochemical performance suggests the multi-wall Sn/SnO2 @ carbon hollow nanofibers are great promising for high performance energy storage systems.

Coral-like Au/TiO2 Hollow Nanofibers with Through-Holes as a High-Efficient Catalyst through Mass Transfer Enhancement.

One-dimensional (1D) hollow nanomaterials were widely used in the catalysis field. However, the inner surfaces of 1D hollow nanostructures could not be effectively utilized in liquid reaction because of diffusional limitation caused by the large ratio of length to diameter. In this work, a template-assisted coaxial electrospinning method was developed to prepare TiO2 hollow nanofibers with through-holes which were further employed as a carrier for Au nanoparticles. The Au/TiO2 hollow nanofibers with through-holes showed significant catalytic activity enhancement to the reduction of 4-nitrophenol in aqueous solution compared with solid and hollow nanofiber counterparts. The through-holes which provided unrestricted macropores for mass transfer in liquid solution were studied to be accounted for the catalytic activity enhancement. The through-hole structures can widen the application ranges and increase the efficiencies of zero-dimensional or 1D hollow nanomaterials.

Differentiation between intraspinal schwannoma and meningioma by MR characteristics and clinic features.

OBJECTIVES: To retrospectively review the MRI characteristics and clinic features and evaluate the effectiveness of MR imaging in differentiating intraspinal schwannomas and meningiomas, with the excised histopathologic findings as the reference standard. MATERIALS AND METHODS: One hundred and four schwannomas (M/F, 57:47) and 53 meningiomas (M/F, 13:40) underwent MR examinations before surgical treatment. Simple clinic data and imaging findings were considered:(a) location (craniocaudal and axial), (b) size, (c) morphology, (d) dural contact, (e) signal characteristics, (f) enhancement degree and patterns. The usefulness of the algorithm for differential diagnosis was examined between the two tumors. RESULTS: Interobserver agreement was good (κ = 0.7-0.9). Ten cases meningiomas demonstrated multiple lesions. There was a female predominance in the meningiomas (P < 0.001). Meningiomas predominantly were located in the ventral or anterolateral areas of thoracic regions, while schwannomas in the posterolateral areas of the thoracic and the lumbar regions (P < 0.001). Mean size of the lesions was 1.47 ± 0.36 cm for meningioma, and 2.02 ± 1.13 cm for schwannoma (P < 0.001). A dumbbell shape with intervertebral foramen widening could detect schwannomas, while the "dural tail sign" did meningiomas (P < 0.001). Hypointense and miscellaneous signal implied meningioma on T1WIs (P < 0.001). Isointense was more frequently observed in the meningiomas, while the fluid signal intensity and miscellaneous signal in the schwannomas on T2WIs (P < 0.001). Schwannomas usually manifested rim enhancement, while meningiomas diffuse enhancement (P = 0.005). There were six variables including the logistic equation (age, size, dural tail sign, morphology, T2WI, and axial location). The accuracy of the algorithm in diagnosis of schwannomas was 87.1%. CONCLUSIONS: Combination of clinic data and MRI performs significantly for differentiating between intraspinal meningiomas and schwannomas.

Pd Nanoparticles Confined in the Porous Graphene-like Carbon Nanosheets for Olefin Hydrogenation.

As a novel type of defective graphene, porous graphene has been considered an excellent support material for metal clusters, as the interaction between defective carbon atoms surrounded with the metal nanoparticles (NPs) is very different from that on the ordinary supported catalyst. In this work, we reported a facile three-step method to confine the Pd NPs and grow the graphene-like carbon nanosheets (GLCs) in the same interlayer space of the layered silicate, generating embedded Pd NPs in the pores of porous GLCs in situ. The Pd@GLC nanocomposite exhibited not only high activity and stability than the common commercial Pd/C catalyst for the hydrogenation of olefins but also superior ability of resisting high temperature, which benefitted from the two-dimensional structure of layered GLCs, the confinement of Pd, and the increased edge and defect of the unsaturated carbon atoms in GLCs.

Salidroside attenuates hypoxia-induced pulmonary arterial smooth muscle cell proliferation and apoptosis resistance by upregulating autophagy through the AMPK-mTOR-ULK1 pathway.

BACKGROUND: Recent studies have shown that both adenosine monophosphate activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR) are energy sensors and are related to autophagy. Our recent reports have shown that salidroside can exert protective effects against hypoxia-induced pulmonary arterial smooth muscle cell (PASMC) proliferation and apoptosis resistance through the AMPK pathway. This study aims to explore the relationship among AMPK, mTOR and ULK1 in PASMCs under hypoxic conditions and to investigate whether the protective effects of salidroside are related to the autophagic cell death pathway. METHODS: Rat PASMCs were cultured and divided into five groups: the normoxia, hypoxia, hypoxia + MHY1485 (mTOR agonist), hypoxia + rapamycin (mTOR inhibitor) and hypoxia + salidroside groups. Hypoxic cells were treated as indicated for 24 h. Cell viability was evaluated by the CCK-8 assay. Cell apoptosis was measured by the TUNEL assay. The autophagy flux of PASMCs was evaluated with tandem mRFP-GFP fluorescence microscopy. Autophagosomes were detected by electron microscopy. Protein expression of LC3, p62, AMPK, P-AMPK (Thr 172), P-ULK1 (Ser 555 and Ser 317), mTOR, P-mTOR (Ser 2448), ULK1 and P-ULK1 (Ser 757) was detected by western blot assay. RESULTS: PASMC proliferation and apoptosis resistance were observed under hypoxic conditions. Autophagy flux, the number of autophagosomes and the LC3II/LC3I ratio were increased in the hypoxia group compared with the normoxia group, whereas p62 expression was decreased. Treatment with rapamycin or salidroside reversed hypoxia-induced PASMC proliferation and apoptosis resistance and further increased autophagy flux, autophagosome levels and the LC3II/LC3I ratio but decreased p62 expression. Treatment with MHY1485 reversed hypoxia-induced PASMC apoptosis resistance and decreased autophagy flux as well as increased autophagosome levels, the LC3II/LC3I ratio and p62 expression. P-AMPK (Thr 172) and P-ULK1 (Ser 555) of the AMPK-ULK1 pathway were increased in the hypoxia group and were further increased in the salidroside group. Rapamycin and MHY1485 had no effect on either P-AMPK (Thr 172) or P-ULK1 (Ser 555). Phosphorylation of ULK1 at serine 317 did not significantly affect the five groups. Furthermore, P-mTOR (Ser 2448) and P-ULK1 (Ser 757) of the AMPK-mTOR-ULK1 pathway were decreased in the hypoxia group and were further decreased in the salidroside group. MHY1485 increased the expression of both P-mTOR(Ser 2448) and P-ULK1(Ser 757), whereas rapamycin had the opposite effect. CONCLUSIONS: Salidroside might inhibit hypoxia-induced PASMC proliferation and reverse apoptosis resistance via the upregulation of autophagy through both the AMPKα1-ULK1 and AMPKα1-mTOR-ULK1 pathways.

Noncontact Synergistic Effect between Au Nanoparticles and the Fe2O3 Spindle Inside a Mesoporous Silica Shell as Studied by the Fenton-like Reaction.

An Au-Fe2O3@mesoporous SiO2 nanoreactor with a multiyolks/shell structure was synthesized through a multistep method. In this nanoreactor, the spindle Fe2O3 and Au nanoparticles were inside the same mesoporous SiO2 shell as the yolks but in a noncontact manner. The noncontact synergistic effect between Au nanoparticles and the Fe2O3 spindle was studied with a Fenton-like reaction. The catalytic activity of the Au-Fe2O3@mesoporous SiO2 nanoreactor to the Fenton-like reaction for the degradation of organic dyes was dramatically enhanced by the noncontact synergistic effect.

Changes in left ventricular synchrony and systolic function in dilated cardiomyopathy patients with fragmented QRS complexes.

AIMS: Fragmented QRS (f-QRS) complexes are associated with adverse cardiovascular events in patients with coronary heart disease; however, the effects on patients with dilated cardiomyopathy (DCM) remain elusive. This study is to investigate the changes of left ventricular (LV) synchrony and systolic function in DCM patients with f-QRS complexes. METHODS AND RESULTS: Twenty DCM patients with f-QRS complexes and 29 DCM patients without f-QRS (n-QRS) complexes were enrolled. The LV segmental longitudinal, radial and circumferential time to peak strain and general longitudinal systolic strain, radial strain, circumferential strain were measured, respectively, by speckle tracking imaging. The LV segmental standard deviations and maximal differences were also calculated. The LV dyssynchrony was defined as the time in peak anteroseptal wall to posterior wall strain >130 ms or longitudinal strain delay index >25%. The mean QRS durations in f-QRS and n-QRS groups were not different (P = ns). The incidence of LV dyssynchrony was 15/20 (75%) vs. 5/29 (17%) in two groups (P < 0.01). Two patients died of sudden death in f-QRS group during 2 years follow-up; however, no death in n-QRS group (P < 0.05). Patients in f-QRS group showed worsening LV dyssynchrony in f-QRS group after 2 years follow-up (P < 0.05). Overall, LV function was comparable at baseline (P = ns), but had significantly worsened only in the f-QRS group (P < 0.05). CONCLUSION: The f-QRS complex is significantly associated with LV dyssynchrony in DCM patients and can be used as a reliable index to evaluate ventricular synchrony and predict the prognosis in DCM patients with narrow QRS complexes.

Two-dimensional structure Au nanosheets are super active for the catalytic reduction of 4-nitrophenol.

Two-dimensional structure Au nanosheets with a polygon morphology and controlled thicknesses of ∼15 nm, ∼35 nm, and ∼50 nm were successfully synthesized by a one-step solution reduction method. Scanning and transmission electron microscopy (SEM and TEM), selected area electron diffraction (SEAD) analyses, and X-ray diffraction (XRD) were used to thoroughly study the structure and the formation mechanism of the nanosheets. The catalytic activity of the Au nanosheets was investigated for the reduction of 4-nitrophenol (4-NP) by UV-visible absorption spectroscopy. Against all expectation, the Au nanosheets with such a big lateral (more than 1 µm) size exhibited superior catalytic activity on the selective reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4. On the other hand, the catalytic activity does closely depend on the thickness of the nanosheets; that is, it decreases with increasing thickness. The reaction can be completed in less than 1 min when catalyzed by Au nanosheets about 15 nm thick. The 100% conversion efficiency was further demonstrated after two catalytic cycles with the thinnest Au nanosheets.

Zebra-Patterned Stretchable Helical Yarn for Triboelectric Self-Powered Multifunctional Sensing.

Smart textiles capable of both energy harvesting and multifunctional sensing are highly desirable for next-generation portable electronics. However, there are still challenges that need to be conquered, such as the innovation of an energy-harvesting model and the optimization of interface bonding between fibers and active materials. Herein, inspired by the spiral structure of natural vines, a highly stretchable triboelectric helical yarn (TEHY) was manufactured by twisting the carbon nanotube/polyurethane nanofiber (CNT/PU NF) Janus membrane. The TEHY had a zebra-stripe-like design that was composed of black interval conductive CNTs and white insulative PU NFs. Due to the different electron affinity, the zebra-patterned TEHY realized a self-frictional triboelectric effect because the numerous microscopic CNT/PU triboelectric interfaces generated an alternating current in the external conductive circuit without extra external friction layers. The helical geometry combined with the elastic PU matrix endowed TEHY with superelastic stretchability and outstanding output stability after 1000 cycles of the stretch-release test. By virtue of the robust mechanical and electrical stability, the TEHY can not only be used as a high-entropy mechanical energy harvester but also serve as a self-powered sensor to monitor the stretching or deforming stimuli and human physiological activities in real time. These merits manifested the versatile applications of TEHY in smart fabrics, wearable power supplies, and human-machine interactions.

Designing of anisotropic gradient surfaces for directional liquid transport: Fundamentals, construction, and applications.

Many biological surfaces are capable of transporting liquids in a directional manner without energy consumption. Inspired by nature, constructing asymmetric gradient surfaces to achieve desired droplet transport, such as a liquid diode, brings an incredibly valuable and promising area of research with a wide range of applications. Enabled by advances in nanotechnology and manufacturing techniques, biomimetics has emerged as a promising avenue for engineering various types of anisotropic material system. Over the past few decades, this approach has yielded significant progress in both fundamental understanding and practical applications. Theoretical studies revealed that the heterogeneous composition and topography mainly govern the wetting mechanisms and dynamics behavior of droplets, including the interdisciplinary aspects of materials, chemistry, and physics. In this review, we provide a concise overview of various biological surfaces that exhibit anisotropic droplet transport. We discussed the theoretical foundations and mechanisms of droplet motion on designed surfaces and reviewed recent research advances in droplet directional transport on designed plane surfaces and Janus membranes. Such liquid-diode materials yield diverse promising applications, involving droplet collection, liquid separation and delivery, functional textiles, and biomedical applications. We also discuss the recent challenges and ongoing approaches to enhance the functionality and application performance of anisotropic materials.

Temperature-responsive smart nanoreactors: poly(N-isopropylacrylamide)-coated Au@mesoporous-SiO2 hollow nanospheres.

A nanoreactor with temperature-responsive poly(N-isopopylacrylamide) (PNIPAM) coated on the external pore mouth of mesoporous silica hollow spheres and Au nanoparticles at the internal pore mouth were fabricated. Such spatial separation allows both Au nanoparticles and PNIPAM to function without interfering with each other. Transmission electron microscopy (TEM), thermogravimetric analysis (TGA), Fourier transform infrared (FTIR) spectra, and temperature-dependent optical transmittance curves demonstrate successful grafting of PNIPAM. This nanoreactor shows repeated on/off catalytic activity switched by temperature control. It shows excellent catalytic activity toward 4-nitrophenol (4-NP) reduction at 30 °C [below lower critical solution temperature (LCST) of PNIPAM] with a turnover frequency (TOF) of 14.8 h(-1). However, when the temperature was 50 °C (above LCST), the TOF dropped to 2.4 h(-1). Kinetic studies indicated that diffusion into the mesopores of the catalyst was the key factor, and the temperature-responsive behavior of PNIPAM was able to control this diffusion.

Bilayer Nanoporous Polyethylene Membrane with Anisotropic Wettability for Rapid Water Transportation/Evaporation and Radiative Cooling.

Both sweat drainage and evaporation play important roles in achieving personal moisture and thermal management during sweat-producing exercises. However, it remains a great challenge to simultaneously realize thermal management through radiative cooling for human body without perspiration. Herein, we report a bilayer nanoporous polyethylene membrane with anisotropic wettability, which possesses superior radiative cooling ability (∼2.6 °C lower than that of cotton) without perspiration. Meanwhile, it realizes efficient sweat drainage and good evaporation cooling property (∼1.0 °C lower than that of cotton) in perspiration to avoid sticky and hot sensation. In addition, it can also block water and fine particulate matter owing to the hydrophobic nanoporous structure. By virtue of the outstanding personal thermal and moisture management performance, it is expected that this study provides inspiration for designing new clothing and medical protective suits with more comfortable microclimates and reducing energy consumption for global sustainability.

Continuous g-C3N4 layer-coated porous TiO2 fibers with enhanced photocatalytic activity toward H2 evolution and dye degradation.

TiO2/g-C3N4 composite photocatalysts with various merits, including low-cost, non-toxic, and environment friendliness, have potential application for producing clean energy and removing organic pollutants to deal with the global energy shortage and environmental contamination. Coating a continuous g-C3N4 layer on TiO2 fibers to form a core/shell structure that could improve the separation and transit efficiency of photo-induced carriers in photocatalytic reactions is still a challenge. In this work, porous TiO2 (P-TiO2)@g-C3N4 fibers were prepared by a hard template-assisted electrospinning method together with the g-C3N4 precursor in an immersing and calcination process. The continuous g-C3N4 layer was fully packed around the P-TiO2 fibers tightly to form a TiO2@g-C3N4 core/shell composite with a strong TiO2/g-C3N4 heterojunction, which greatly enhanced the separation efficiency of photo-induced electrons and holes. Moreover, the great length-diameter ratio configuration of the fiber catalyst was favorable for the recycling of the catalyst. The P-TiO2@g-C3N4 core/shell composite exhibited a significantly enhanced photocatalytic performance both in H2 generation and dye degradation reactions under visible light irradiation, owing to the specific P-TiO2@g-C3N4 core/shell structure and the high-quality TiO2/g-C3N4 heterojunction in the photocatalyst. This work offers a promising strategy to produce photocatalysts with high efficiency in visible light through a rational structure design.

Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses.

A steep rise in Omicron reinfection cases suggests that this variant has increased immune evasion ability. To evaluate its antigenicity relationship with other variants, antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were cross-tested against pseudotyped variants. The neutralization activity against Omicron was markedly reduced when other VOCs or VOIs were used as immunogens, and Omicron (BA.1)-elicited sera did not efficiently neutralize the other variants. However, a Beta or Omicron booster, when administered as the 4th dose 3-months after the 3rd dose of any of the variants, could elicit broad neutralizing antibodies against all of the current variants including Omicron BA.1. Further analysis with 280 available antigen-antibody structures and quantification of immune escape from 715 reported neutralizing antibodies provide explanations for the observed differential immunogenicity. Three distinct clades predicted using an in silico algorithm for clustering of sarbecoviruses based on immune escape provide key information for rational design of vaccines.