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.
This study evaluated the effects of Bacillus fermentation on soybean meal protein (SBMP) microstructure and major anti‐nutritional factors (ANFs) in soybean meal (SBM). The Bacillus siamensis isolate ...JL8 producing high yield of protease at 519·1 U g−1 was selected for the laboratory production of fermented soybean meal (FSBM). After 24 h fermentation, the FSBM showed better properties compared with those of SBM, the ANFs such as glycinin, β‐conglycinin and trypsin inhibitor significantly decreased by 86·0, 70·3 and 95·01%, while in vitro digestibility and absorbability increased by 8·7 and 18·9% respectively. Scanning electron microscopy (SEM) image of fermented soybean meal protein showed smaller aggregates and looser network than that of SBMP. Secondary structure examination of proteins revealed fermentation significantly decreased the content of β‐sheet structure by 43·2% and increased the random coil structure by 59·9%. It is demonstrated that Bacillus fermentation improved the nutritional quality of SBM through degrading ANFs and changing the microstructure of SBMP.
Significance and Impact of the Study
There is limited information about the structural property changes of soybean protein during fermentation. In this study, physicochemical analysis of soybean meal protein showed evidence that the increase in in vitro digestibility and absorbability of fermented soybean meal reflected the decrease in β‐conformation and destruction of original structure in soybean meal protein. The results directly gained the understanding of nutritional quality improvement of soybean meal by Bacillus fermentation, and supply the potential use of Bacillus siamensis for fermented soybean meal production.
Significance and Impact of the Study: There is limited information about the structural property changes of soybean protein during fermentation. In this study, physicochemical analysis of soybean meal protein showed evidence that the increase in in vitro digestibility and absorbability of fermented soybean meal reflected the decrease in β‐conformation and destruction of original structure in soybean meal protein. The results directly gained the understanding of nutritional quality improvement of soybean meal by Bacillus fermentation, and supply the potential use of Bacillus siamensis for fermented soybean meal production.
A Nationwide Nitrogen Deposition Monitoring Network (NNDMN) containing 43 monitoring sites was established in China to measure gaseous NH3, NO2, and HNO3 and particulate NH4+ and NO3− in air and/or ...precipitation from 2010 to 2014. Wet/bulk deposition fluxes of Nr species were collected by precipitation gauge method and measured by continuous-flow analyzer; dry deposition fluxes were estimated using airborne concentration measurements and inferential models. Our observations reveal large spatial variations of atmospheric Nr concentrations and dry and wet/bulk Nr deposition. On a national basis, the annual average concentrations (1.3–47.0 μg N m−3) and dry plus wet/bulk deposition fluxes (2.9–83.3 kg N ha−1 yr−1) of inorganic Nr species are ranked by land use as urban > rural > background sites and by regions as north China > southeast China > southwest China > northeast China > northwest China > Tibetan Plateau, reflecting the impact of anthropogenic Nr emission. Average dry and wet/bulk N deposition fluxes were 20.6 ± 11.2 (mean ± standard deviation) and 19.3 ± 9.2 kg N ha−1 yr−1 across China, with reduced N deposition dominating both dry and wet/bulk deposition. Our results suggest atmospheric dry N deposition is equally important to wet/bulk N deposition at the national scale. Therefore, both deposition forms should be included when considering the impacts of N deposition on environment and ecosystem health.
As a major component of the LAMOST Galactic surveys, the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC) aims to survey a significant volume of the Galactic thin/thick discs and halo ...for a contiguous sky area of over 3400 deg2 centred on the Galactic anticentre (|b| ≤ 30°, 150 ≤ l ≤ 210°), and obtain λλ3700–9000 low-resolution (R ∼ 1800) spectra for a statistically complete sample of ∼3 M stars of all colours down to a limiting magnitude of r ∼ 17.8 mag (to 18.5 mag for limited fields). Together with Gaia, the LSS-GAC will yield a unique data set to advance our understanding of the structure and assemblage history of the Galaxy, in particular its disc(s). In addition to the main survey, the LSS-GAC will also target hundreds of thousands objects in the vicinity fields of M 31 and M 33 and survey a significant fraction (over a million) of randomly selected very bright stars (r ≤ 14 mag) in the Northern hemisphere. During the Pilot and the first year Regular Surveys of LAMOST, a total of 1042 586 750 867 spectra of a signal-to-noise ratio S/N(7450 Å) ≥ 10 S/N(4650 Å) ≥ 10 have been collected. In this paper, we present a detailed description of the target selection algorithm, survey design, observations and the first data release of value-added catalogues (including radial velocities, effective temperatures, surface gravities, metallicities, values of interstellar extinction, distances, proper motions and orbital parameters) of the LSS-GAC.
High-β_{θe} (a ratio of the electron thermal pressure to the poloidal magnetic pressure) steady-state long-pulse plasmas with steep central electron temperature gradient are achieved in the ...Experimental Advanced Superconducting Tokamak. An intrinsic current is observed to be modulated by turbulence driven by the electron temperature gradient. This turbulent current is generated in the countercurrent direction and can reach a maximum ratio of 25% of the bootstrap current. Gyrokinetic simulations and experimental observations indicate that the turbulence is the electron temperature gradient mode (ETG). The dominant mechanism for the turbulent current generation is due to the divergence of ETG-driven residual flux of current. Good agreement has been found between experiments and theory for the critical value of the electron temperature gradient triggering ETG and for the level of the turbulent current. The maximum values of turbulent current and electron temperature gradient lead to the destabilization of an m/n=1/1 kink mode, which by counteraction reduces the turbulence level (m and n are the poloidal and toroidal mode number, respectively). These observations suggest that the self-regulation system including turbulence, turbulent current, and kink mode is a contributing mechanism for sustaining the steady-state long-pulse high-β_{θe} regime.
We experimentally realize a universal set of single-bit and two-bit geometric quantum gates by adiabatically controlling solid-state spins in a diamond defect. Compared with the nonadiabatic ...approach, the adiabatic scheme for geometric quantum computation offers a unique advantage of inherent robustness to parameter variations, which is explicitly demonstrated in our experiment by showing that the single-bit gates remain unchanged when the driving field amplitude varies by a factor of 2 or the detuning fluctuates in a range comparable to the inverse of the gate time. The reported adiabatic control technique and its convenient implementation offer a paradigm for achieving quantum computation through robust geometric quantum gates, which is important for quantum information systems with parameter-fluctuation noise such as those from the inhomogeneous coupling or the spectral diffusion.
Abstract Background Obesity has become a major health problem in contemporary society and it is closely related to many chronic diseases, so it is an important issue for measuring adiposity ...accurately and predicting its future. Prevention and treatment of overweight and obesity has become one of the key prevention and treatment of metabolic disorders. Objective In this study, we compared the ability of the four anthropometric indicators (body mass index, waist circumstance, waist–height ratio, waist-to-hip ratio) to identify metabolic disorders (hypertension, hyperlipidaemia, hyperglycemia and hyperuricemia) by receiver operating characteristic (ROC) curve analyses and to provide evidence for clinical practice. Methods In this large scale cross-sectional study, 13,275 Han adults (including 7595 males and 5680 females) received physical examination between January, 2009 and January, 2010 in Xuanwu Hospital of Capital Medical University were investigated by the means of questionnaire, Meanwhile, the physical examination and serological results were recorded. A package known as Statistical Package for Social Scientist (SPSS) was employed to analyse the responses while t -test, one-way analysis of variance (ANOVA), ROC analysis and chi-square statistical methods were used to test the hypotheses. Results WC, WHtR, WHR and BMI were all significantly ( P < 0.001) correlated with all metabolic risk factors regardless of gender. And the area under the curve (AUC) of WHtR was significantly greater than that of WC, BMI or WHR in the prediction of hypertension, hyperlipidaemia, hyperglycemia and hyperuricemia. Conclusion Our data show that WHtR was the best predictor of various metabolic disorders. The diagnostic value in descending order was WHtR > WHR > WC > BMI. Therefore we recommend WHtR in assessment of obese patients, in order to better assess the risks of their metabolic diseases.
We report, for the first time, the long-awaited detection of diffuse gamma rays with energies between 100 TeV and 1 PeV in the Galactic disk. Particularly, all gamma rays above 398 TeV are observed ...apart from known TeV gamma-ray sources and compatible with expectations from the hadronic emission scenario in which gamma rays originate from the decay of π^{0}'s produced through the interaction of protons with the interstellar medium in the Galaxy. This is strong evidence that cosmic rays are accelerated beyond PeV energies in our Galaxy and spread over the Galactic disk.
High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to ...investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.
We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.
In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group 14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038, while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.
Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.
ClinicalTrials.gov NCT02915432.
Abstract
We present the second release of value-added catalogues of the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC DR2). The catalogues present values of radial velocity Vr, ...atmospheric parameters – effective temperature Teff, surface gravity log g, metallicity Fe/H, α-element to iron (metal) abundance ratio α/Fe (α/M), elemental abundances C/H and N/H and absolute magnitudes MV and $M_{K_{\rm s}}$ deduced from 1.8 million spectra of 1.4 million unique stars targeted by the LSS-GAC since 2011 September until 2014 June. The catalogues also give values of interstellar reddening, distance and orbital parameters determined with a variety of techniques, as well as proper motions and multiband photometry from the far-UV to the mid-IR collected from the literature and various surveys. Accuracies of radial velocities reach 5 km s−1 for the late-type stars, and those of distance estimates range between 10 and 30 per cent, depending on the spectral signal-to-noise ratios. Precisions of Fe/H, C/H and N/H estimates reach 0.1 dex, and those of α/Fe and α/M reach 0.05 dex. The large number of stars, the contiguous sky coverage, the simple yet non-trivial target selection function and the robust estimates of stellar radial velocities and atmospheric parameters, distances and elemental abundances make the catalogues a valuable data set to study the structure and evolution of the Galaxy, especially the solar-neighbourhood and the outer disc.
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