Th2/Th1 Cytokine Imbalance Is Associated With Higher COVID-19 Risk Mortality

A major component of COVID-19 severe respiratory syndrome is the patient’s immune response to the SARS-CoV-2 virus and the consequential multi-organ inflammatory response. Several studies suggested a potential role of CD4+ T cells in COVID-19 severe respiratory syndrome. We first hypothesized that there is a type 2 helper (Th2)/type 1 helper (Th1) imbalance in older age, male, asthma, smokers, and high ACE2 expression phenotype in the airway of non-infected patients. Next, we hypothesized that a Th2/Th1 imbalance may predict higher mortality in COVID-19 infected hospitalized patients with and without patient reported current asthma. We first analyzed publicly available gene expression from the sputum of 118 moderate-to-severe asthma patients and 21 healthy controls, and from nasal epithelium of 26 healthy current smokers and 21 healthy never smokers. Secondly, we profiled 288 new serum proteomics samples measured at admission from patients hospitalized within the Mount Sinai Health System with positive SARS-CoV-2 infection. We first computed Th1 and Th2 pathway enrichment scores by gene set variation analysis and then compared the differences in Th2 and Th1 pathway scores between patients that died compared to those that survived, by linear regression. The level of Th2/Th1 imbalance, as determined by the enrichment score, was associated with age, sex, and ACE2 expression in sputum, and with active smoking status in nasal epithelium (p \u3c 0.05). Th2/Th1 imbalance at hospital admission in sera of patients was not significantly associated with death from COVID-19 (p = 0.11), unless evaluated in the asthmatic strata (p = 0.01). Using a similar approach we also observed a higher Th17/Th1 cytokine imbalance in all deceased patients compared to those that survived (p \u3c 0.001), as well as in the asthmatic strata only (p \u3c 0.01). Th2/Th1 imbalance is higher in the sera of asthma patients at admission that do not survive COVID-19, suggesting that the Th2/Th1 interplay may affect patient outcomes in SARS-CoV2 infection. In addition, we report that Th17/Th1 imbalance is increased in all patients that die of COVID-19

Direct fabrication of functional ultrathin single-crystal nanowires from quasi-one-dimensional van der Waals crystals

Micromechanical exfoliation of two-dimensional (2D) van der Waals materials has triggered an explosive interest in 2D material research. The extension of this idea to 1D van der Waals materials, possibly opening a new arena for 1D material research, has not yet been realized. In this paper, we demonstrate that 1D nanowire with sizes as small as six molecular ribbons, can be readily achieved in the Ta2(Pd or Pt)3Se8 system by simple micromechanical exfoliation. Exfoliated Ta2Pd3Se8 nanowires are n-type semiconductors, whereas isostructural Ta2Pt3Se8 nanowires are p-type semiconductors. Both types of nanowires show excellent electrical switching performance as the channel material for a field-effect transistor. Low-temperature transport measurement reveals a defect level inherent to Ta2Pd3Se8 nanowires, which enables the observed electrical switching behavior at high temperature (above 140 K). A functional logic gate consisting of both n-type Ta2Pd3Se8 and p-type Ta2Pt3Se8 field-effect transistors has also been successfully achieved. By taking advantage of the high crystal quality derived from the parent van der Waals bulk compound, our findings about the exfoliated Ta2(Pd or Pt)3Se8 nanowires demonstrate a new pathway to access single-crystal 1D nanostructures for the study of their fundamental properties and the exploration of their applications in electronics, optoelectronics, and energy harvesting

Quantum transport of the 2D surface state in a nonsymmorphic semimetal

In a topological semimetal with Dirac or Weyl points, the bulk-boundary correspondence principle predicts a gapless edge mode if the essential symmetry is still preserved at the surface. The detection of such topological surface state has been considered as the fingerprint prove for crystals with nontrivial topological bulk band. On the contrary, it has been proposed that even with symmetry broken at the surface, a new surface band can emerge in nonsymmorphic topological semimetals. The symmetry reduction at the surface lifts the bulk band degeneracies and produces an unusual “floating” surface band with trivial topology. Here, we first report quantum transport probing to ZrSiSe thin flakes and directly reveal transport signatures of this new surface state. Remarkably, though topologically trivial, such a surface band exhibits substantial two-dimensional Shubnikov–de Haas quantum oscillations with high mobility, which signifies a new protection mechanism and may open applications for quantum computing and spintronic devices

The impact of dupilumab treatment on SARS-CoV-2 T cell responses in atopic dermatitis patients

This work was supported by the Department of Dermatology at the Icahn School of Medicine at Mount Sinai and a grant from Regeneron and Sanofi. All funding sources reviewed and accepted the study design and the manuscript, with minimal input from Regeneron and Sanofi. Research reported in this publication was also supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number U01AI152036. Paolo Cravedi was supported by a grant from the National Institute of Allergy and Infectious Diseases under Award Number 3U01AI063594-17S1.Peer reviewe

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin