Molecular basis of cross-species ACE2 interactions with SARS-CoV-2

The contribution of molecular pathology to the classification of thyroid tumors

Significant molecular advances have been undertaken for the past two decades in the field of thyroid follicular neoplasms, including a detailed genomic profile of papillary thyroid carcinoma (PTC) by The Cancer Genome Atlas (TCGA) project. These molecular discoveries led to a better understanding of the pathogenesis of thyroid neoplasms and resulted in reclassification of certain types of thyroid tumors.

This review discusses how, 1) the molecular profiles of follicular-patterned lesions led to the reclassification of the follicular variant of PTC into non-invasive follicular thyroid neoplasm with papillary like nuclei, 2) the genotyping of Hürthle cell neoplasm provided the rationale to classify these tumors independently from follicular adenomas and carcinomas, and 3) BRAF and RAS molecular signatures have the potential of subclassifying PTC and poorly differentiated thyroid carcinoma into clinically relevant molecular subtypes.

Molecular basis of cross-species ACE2 interactions with SARS-CoV-2-like viruses of pangolin origin

Pangolins have been suggested as potential reservoir of zoonotic viruses, including SARS-CoV-2 causing the global COVID-19 outbreak. Here, we study the binding of two SARS-CoV-2-like viruses isolated from pangolins, GX/P2V/2017 and GD/1/2019, to human angiotensin converting enzyme 2 (hACE2), the receptor of SARS-CoV-2.

We find that the spike protein receptor-binding domain (RBD) of pangolin CoVs binds to hACE2 as efficiently as the SARS-CoV-2 RBD in vitro. Furthermore, incorporation of pangolin CoVs RBDs allows entry of pseudotyped VSV particles into hACE2-expressing cells.

A screen for binding of pangolin CoV RBDs to ACE2 orthologs from various species suggests a broader host range than that of SARS-CoV-2. Additionally, cryo-EM structures of GX/P2V/2017 and GD/1/2019 RBDs in complex with hACE2 show their molecular binding in modes similar to SARS-CoV-2 RBD.

Introducing the Q498H substitution found in pangolin CoVs into the SARS-CoV-2 RBD expands its binding capacity to ACE2 homologs of mouse, rat and European hedgehog. These findings suggest that these two pangolin CoVs may infect humans, highlighting the necessity of further surveillance of pangolin CoVs.

The efficacy and safety of low-molecular-weight heparin calcium combined with Xueshuantong injections in the treatment of elderly acute deep venous thrombosis patients

Objective: To explore the therapeutic effect of low-molecular-weight heparin calcium (LMWH-Ca) combined with Xueshuantong injections in treating elderly acute deep venous thrombosis (ADVT) patients, and to analyze the effect of this combination on the coagulation function, hemorheology, and safety.

Methods: A total of 122 elderly patients with ADVT who were treated in our hospital were recruited as the study cohort. The patients were randomly divided into a control group (n=61) and an observation group (n=61).

The patients in the control group were given abdominal subcutaneous injections of low-molecular-weight heparin calcium (LMWH-Ca). The patients in the observation group were given intravenous drips of LMWH-Ca (low-molecular-weight heparin calcium) and Xueshuantong injections.

After the treatment, comparisons of the detumescence times of the affected limb, the differences in the circumferences of the lower limbs, the coagulation parameters, the overall response rates, the incidences of complications, and the hemorheological parameters were conducted between both groups.

Results: After the treatment, the detumescence times and the average differences in the circumferences of the lower limbs were significantly reduced (P<0.001; all P<0.001), the prothrombin times (PT) and the activated partial thromboplastin times (APTT) were significantly extended (all P<0.01), the overall response rate was higher (all P<0.05), and the three hemorheological parameters (high shear viscosity, low shear viscosity, and plasma viscosity) were lower in the observation group than they were in the control group (all P<0.001), there were no statistical differences in the fibrinogen (FIB) levels, the incidences of complications, or the incidences of adverse drug reactions between the two groups (P>0.05; P=0.343; P=0.298).

Conclusion: To sum up, low-molecular-weight heparin combined with Xueshuantong injections can effectively treat elderly ADVT patients, reduce the differences in the circumferences of the lower limbs, regulate the coagulation function, and improve the blood viscosity, so it is worthy of clinical promotion.

Keywords: Low-molecular-weight heparin calcium; Xueshuantong injections; acute deep venous thrombosis; elderly patients.


Wafer-Scale and Full-Coverage Two-Dimensional Molecular Monolayers Strained by Solvent Surface Tension Balance

Inspired by the outstanding properties discovered in two-dimensional materials, the bottom-up generation of molecular monolayers is becoming again extremely popular as a route to develop novel functional materials and devices with tailored characteristics and minimal materials consumption. However, achieving a full-coverage over a large-area still represents a grand challenge.

Here we report a molecular self-assembly protocol at the water surface in which the monolayers are strained by a novel solvent surface tension balance (SSTB) instead of a physical film balance as in the conventional Langmuir-Blodgett (LB) method. The obtained molecular monolayers can be transferred onto any arbitrary substrate including rigid inorganic oxides and metals, as well as flexible polymeric dielectrics.

As a proof-of-concept, their application as ideal modification layers of a dielectric support for high-performance organic field-effect transistors (OFETs) has been demonstrated. The field-effect mobilities of both p- and n-type semiconductors displayed dramatic improvements of 1-3 orders of magnitude on SSTB-derived molecular monolayer, reaching values as high as 6.16 cm2 V-1 s-1 and 0.68 cm2 V-1 s-1 for pentacene and PTCDI-C8, respectively.

This methodology for the fabrication of wafer-scale and defect-free molecular monolayers holds potential toward the emergence of a new generation of high-performance electronics based on two-dimensional materials.


Leave a Reply

Your email address will not be published. Required fields are marked *