Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms ...underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups.
A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. We separated gene expression patterns from tumor, stromal, and immune cell gene using a non-negative matrix factorization algorithm. We correlated the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Six independent datasets containing 838 HNSC samples were used for validation.
Approximately 40% of HNSCs in the cohort (211/522) were identified to show enriched inflammatory response, enhanced cytolytic activity, and active interferon-γ signaling (all, P < 0.001). We named this new molecular class of tumors the Immune Class. Then we found it contained two distinct microenvironment-based subtypes, characterized by markers of active or exhausted immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-β signaling pathway activation and poor survival (all, P < 0.05). An enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis were associated with Active Immune Class (all, P < 0.05). The robustness of these immune molecular subgroups was verified in the validation cohorts, and Active Immune Class showed potential response to programmed cell death-1 blockade (P = 0.01).
This study revealed a novel Immune Class in HNSC; two subclasses characterized by active or exhausted immune responses were also identified. These findings provide new insights into tailoring immunotherapeutic strategies for different HNSC subgroups.
Topological Dirac and Weyl semimetals not only host quasiparticles analogous to the elementary fermionic particles in high-energy physics, but also have a non-trivial band topology manifested by ...gapless surface states, which induce exotic surface Fermi arcs1,2. Recent advances suggest new types of topological semimetal, in which spatial symmetries protect gapless electronic excitations without high-energy analogues3–11. Here, using angle-resolved photoemission spectroscopy, we observe triply degenerate nodal points near the Fermi level of tungsten carbide with space group \P\bar{6}m2\ (no. 187), in which the low-energy quasiparticles are described as three-component fermions distinct from Dirac and Weyl fermions. We further observe topological surface states, whose constant-energy contours constitute pairs of ‘Fermi arcs’ connecting to the surface projections of the triply degenerate nodal points, proving the non-trivial topology of the newly identified semimetal state.
In quantum field theory, Lorentz invariance leads to three types of fermion-Dirac, Weyl and Majorana. Although the existence of Weyl and Majorana fermions as elementary particles in high-energy ...physics is debated, all three types of fermion have been proposed to exist as low-energy, long-wavelength quasiparticle excitations in condensed-matter systems. The existence of Dirac and Weyl fermions in condensed-matter systems has been confirmed experimentally, and that of Majorana fermions is supported by various experiments. However, in condensed-matter systems, fermions in crystals are constrained by the symmetries of the 230 crystal space groups rather than by Lorentz invariance, giving rise to the possibility of finding other types of fermionic excitation that have no counterparts in high-energy physics. Here we use angle-resolved photoemission spectroscopy to demonstrate the existence of a triply degenerate point in the electronic structure of crystalline molybdenum phosphide. Quasiparticle excitations near a triply degenerate point are three-component fermions, beyond the conventional Dirac-Weyl-Majorana classification, which attributes Dirac and Weyl fermions to four- and two-fold degenerate points, respectively. We also observe pairs of Weyl points in the bulk electronic structure of the crystal that coexist with the three-component fermions. This material thus represents a platform for studying the interplay between different types of fermions. Our experimental discovery opens up a way of exploring the new physics of unconventional fermions in condensed-matter systems.
Summary
Osteosarcopenia is defined as the concomitant occurrence of sarcopenia and osteoporosis/osteopenia. This study aimed to clarify whether osteosarcopenia implies a greater risk of fractures, ...mortality, and falls and to draw attention to osteosarcopenia.
Introduction
Osteosarcopenia, which is characterized by the co-existence of osteoporosis/osteopenia and sarcopenia, is one of the most challenging geriatric syndromes. However, the association between osteosarcopenia and the risk of falls, fractures, disability, and mortality is controversial.
Methods
We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from their inception to March 18, 2021, for cohort studies on the relationship between osteosarcopenia and fractures, falls, and mortality. Two reviewers independently extracted data and assessed study quality. A pooled analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using fixed or random-effects models.
Results
Eight cohort studies including 19,836 participants showed that osteosarcopenia significantly increased the risk of fracture (OR 2.46, 95% CI 1.83–3.30,
P
heterogeneity
= 0.006,
I
2
= 63.0%), three cohort studies involving 2601 participants indicated that osteosarcopenia significantly increased the risk of mortality (OR 1.66, 95% CI 1.23–2.26,
P
heterogeneity
= 0.214,
I
2
= 35.2%), and three cohort studies involving 3144 participants indicated that osteosarcopenia significantly increased the risk of falls (OR 1.62, 95% CI 1.28–2.04,
P
heterogeneity
= 0.219,
I
2
= 34.1%). No publication bias existed among the studies regarding the association between osteosarcopenia and fractures. The findings were robust according to the subgroup and sensitivity analyses.
Conclusions
This pooled analysis demonstrated that osteosarcopenia significantly increased the risk of fractures, falls, and mortality, thus highlighting its relevance in daily life. Therefore, we suggest that elderly persons should be aware of the risks associated with osteosarcopenia.
The extension of the cosmic-ray spectrum beyond 1 petaelectronvolt (PeV; 10
electronvolts) indicates the existence of the so-called PeVatrons-cosmic-ray factories that accelerate particles to PeV ...energies. We need to locate and identify such objects to find the origin of Galactic cosmic rays
. The principal signature of both electron and proton PeVatrons is ultrahigh-energy (exceeding 100 TeV) γ radiation. Evidence of the presence of a proton PeVatron has been found in the Galactic Centre, according to the detection of a hard-spectrum radiation extending to 0.04 PeV (ref.
). Although γ-rays with energies slightly higher than 0.1 PeV have been reported from a few objects in the Galactic plane
, unbiased identification and in-depth exploration of PeVatrons requires detection of γ-rays with energies well above 0.1 PeV. Here we report the detection of more than 530 photons at energies above 100 teraelectronvolts and up to 1.4 PeV from 12 ultrahigh-energy γ-ray sources with a statistical significance greater than seven standard deviations. Despite having several potential counterparts in their proximity, including pulsar wind nebulae, supernova remnants and star-forming regions, the PeVatrons responsible for the ultrahigh-energy γ-rays have not yet been firmly localized and identified (except for the Crab Nebula), leaving open the origin of these extreme accelerators.
Summary
What is Known and Objective: The pathogenic mechanism of antituberculosis drug‐induced hepatotoxicity (ATDH) is thought to involve drug‐metabolizing enzymes including N‐acetyl transferase2 ...(NAT2), cytochrome P4502E1 (CYP2E1) and glutathione S‐transferase (GST) M1, T1. The associations between genetic polymorphisms of those genes and ATDH have been reported but with inconsistent results. Moreover, most studies were hospital‐based retrospective studies and not prospective. We aimed to investigate possible associations of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms with ATDH using a more robust case–control study nested in a population‐based prospective antituberculosis treatment cohort.
Methods: A total of 4304 patients with smear‐positive tuberculosis (TB) who received standard short‐course chemotherapy were monitored for 6–9 months. Incidence density sampling method was adopted to select controls and 4 : 1 matched with each ATDH cases by age (±5 years), sex, treatment history, disease severity and drug dosage. The CYP2E1, GSTM1 and GSTT1 polymorphisms were genotyped using PCR–RFLP and multiplex PCR methods. Conditional logistic regression model was used to calculate odds ratio (OR) and 95% confidence interval (CI), as well as corresponding P‐values.
Results and Discussion: A total of 89 ATDH cases and 356 controls were included in this study. There was no statistically significant association between CYP2E1 RsaI c1/c1 genotype or DraI C/C genotype and ATDH (OR = 0·99, 95% CI:0·62–1·59; OR = 1·13, 95% CI: 0·40–3·20, respectively) compared with CYP2E1 RsaI c1/c2 or c2/c2 genotypes or DraI D/D genotype, or between GSTM1/GSTT1 null genotypes and ATDH (OR = 1·22, 95% CI: 0·76–1·96; OR = 0·96, 95% CI: 0·60–1·52, respectively) compared with non‐null genotypes.
What is new and Conclusion: This is the first study of the involvement of CYP2E1, GSTM1 and GSTT1 genetic polymorphisms in ATDH using a nested case–control population‐based prospective cohort design. We could not confirm positive associations of genetic polymorphisms of CYP2E1 RsaI, CYP2E1 DraI, GSTM1 null and GSTT1 null with ATDH reported by various groups, in our Chinese TB population.
Superelastic conducting fibers with improved properties and functionalities are needed for diverse applications. Here we report the fabrication of highly stretchable (up to 1320%) sheath-core ...conducting fibers created by wrapping carbon nanotube sheets oriented in the fiber direction on stretched rubber fiber cores. The resulting structure exhibited distinct short- and long-period sheath buckling that occurred reversibly out of phase in the axial and belt directions, enabling a resistance change of less than 5% for a 1000% stretch. By including other rubber and carbon nanotube sheath layers, we demonstrated strain sensors generating an 860% capacitance change and electrically powered torsional muscles operating reversibly by a coupled tension-to-torsion actuation mechanism. Using theory, we quantitatively explain the complementary effects of an increase in muscle length and a large positive Poisson's ratio on torsional actuation and electronic properties.
Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory ...(LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.
Abstract
Einstein–Podolsky–Rosen (EPR) steering is a quantum effect based on quantum entanglement and it is the key resource for building quantum networks because of its useful properties. Based on ...the criterion for genuine multipartite EPR steering, the genuine quadripartite EPR steering is confirmed and it can be generated by a spontaneous parametric down-conversion cascaded process with two sum-frequency generations in an optical superlattice. This occurs either below the oscillation threshold and without oscillation threshold. The influence of the parameters of cascaded nonlinear process on the quadripartite EPR steering among signal, idler, and two sum-frequency beams are also discussed. Choosing appropriate nonlinear parameters can achieve good quadripartite quantum steering. This scheme of the generation of genuine quadripartite EPR steering has potential applications in quantum communication and computing.
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