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.
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.
We present improved germanium-based constraints on sub-GeV dark matter via dark matter-electron (χ-e) scattering using the 205.4 kg·day dataset from the CDEX-10 experiment. Using a novel calculation ...technique, we attain predicted χ-e scattering spectra observable in high-purity germanium detectors. In the heavy mediator scenario, our results achieve 3 orders of magnitude of improvement for m_{χ} larger than 80 MeV/c^{2} compared to previous germanium-based χ-e results. We also present the most stringent χ-e cross-section limit to date among experiments using solid-state detectors for m_{χ} larger than 90 MeV/c^{2} with heavy mediators and m_{χ} larger than 100 MeV/c^{2} with electric dipole coupling. The result proves the feasibility and demonstrates the vast potential of a new χ-e detection method with high-purity germanium detectors in ultralow radioactive background.
Coal fly ash, an industrial by-product, is derived from coal combustion in thermal power plants. It is one of the most complex anthropogenic materials, and its improper disposal has become an ...environmental concern and resulted in a waste of recoverable resources. There is a pressing and ongoing need to develop new recycling methods for coal fly ash. The present review first describes the generation, physicochemical properties and hazards of coal fly ash at the global level, and then focuses on its current and potential applications, including use in the soil amelioration, construction industry, ceramic industry, catalysis, depth separation, zeolite synthesis, etc. Finally, the advantages and disadvantages of these applications, the mode of fly ash utilization worldwide and directions for future research are considered.
Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective ...equipment (PPE) such as N95 face mask and protective eyewear while attending to patients.
We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated.
This is a cross-sectional study among healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire.
A total of 158 healthcare workers participated in the study. Majority 126/158 (77.8%) were aged 21-35 years. Participants included nurses 102/158 (64.6%), doctors 51/158 (32.3%), and paramedical staff 5/158 (3.2%). Pre-existing primary headache diagnosis was present in about a third 46/158 (29.1%) of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards 7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, P < .0001 or medical ICU 7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, P < .0001. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR = 4.20, 95% CI 1.48-15.40; P = .030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; P = .012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either "agreed" or "strongly agreed" that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance.
Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.
A search for exotic dark matter (DM) in the sub-GeV mass range has been conducted using 205 kg day data taken from a p-type point contact germanium detector of the CDEX-10 experiment at China's ...Jinping underground laboratory. New low-mass dark matter searching channels, neutral current fermionic DM absorption (χ+A→ν+A) and DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), have been analyzed with an energy threshold of 160 eVee. No significant signal was found; thus new limits on the DM-nucleon interaction cross section are set for both models at the sub-GeV DM mass region. A cross section limit for the fermionic DM absorption is set to be 2.5×10^{-46} cm^{2} (90% C.L.) at DM mass of 10 MeV/c^{2}. For the DM-nucleus 3→2 scattering scenario, limits are extended to DM mass of 5 and 14 MeV/c^{2} for the massless dark photon and bound DM final state, respectively.
Purpose
Obesity is the main driving factor for comorbidities in Prader–Willi syndrome (PWS) patients due to overeating behaviors. The gut microbiota has been implicated in the etiology of obesity and ...associated comorbidities. The purpose of the present study was to characterize the fecal microbiota in Chinese patients with PWS and compare it to that of patients with obesity as well as healthy controls.
Methods
We conducted a cross-sectional study with 35 PWS patients (PWS), 35 patients with obesity (OB), and 35 healthy controls (HC). Metagenomic sequencing was performed in stool samples.
Results
The composition of the fecal microbiota in PWS patients differed from that of participants in the OB and HC groups. It was characterized by increased
Akkermansia Eubacterium, Eubacterium rectale
, and
Roseburia intestinalis
and decreased
Parabacteroides
and
Phascolarctobacterium
. Additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was lower in PWS patients than in patients with obesity. Spearman rank correlation analysis showed that
Achromobacter
,
Acidiphilium
,
Xylophilus
, and
Frisingicoccus
were significantly negatively correlated with HOMA-IR.
Conclusion
The composition of the gut microbiota in Chinese PWS patients differed from that in patients with obesity, which might contribute to higher insulin sensitivity in PWS patients.
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•A highly sensitive formaldehyde gas sensor was developed based on ST-cut quartz surface acoustic waves (SAWs).•Bacterial cellulose are effective to enhance the sensitivity of ...polyethyleneimine to formaldehyde and reduce response time.•Key sensing mechanism is the mass loading effect caused by the reversible nucleophilic addition reaction.•The developed SAW sensor has good selectivity and stability.
Surface acoustic wave (SAW)-based formaldehyde gas sensor using bi-layer nanofilms of bacterial cellulose (BC) and polyethyleneimine (PEI) was developed on an ST-cut quartz substrate using sol-gel and spin coating processes. BC nanofilms significantly improve the sensitivity of PEI films to formaldehyde gas, and reduces response and recovery times. The BC films have superfine filamentary and fibrous network structures, which provide a large number of attachment sites for the PEI particles. Measurement results obtained using in situ diffuse reflectance Fourier transform infrared spectroscopy showed that the primary amino groups of PEI strongly adsorb formaldehyde molecules through nucleophilic reactions, thus resulting in a negative frequency shift of the SAW sensor due to the mass loading effect. In addition, experimental results showed that the frequency shifts of the SAW devices are determined by thickness of PEI film, concentration of formaldehyde and relative humidity. The PEI/BC sensor coated with three layers of PEI as the sensing layer showed the optimal sensing performance, which had a frequency shift of 35.6 kHz for 10 ppm formaldehyde gas, measured at room temperature and 30 % RH. The sensor also showed good selectivity and stability, with a low limit of detection down to 100 ppb.
To evaluate the effect of the different doses of antithymocyte globulin (ATG) on the incidence of acute GVHD among patients receiving hematopoietic SCT without ex vivo T-cell-depletion from ...haploidentical donors, 224 patients with standard-risk hematological malignancy were randomized in this study. One hundred and twelve patients received 6 mg/kg ATG, whereas the remaining patients received 10 mg/kg ATG. This study was registered at http://www.chictr.org as No. ChiCTR-TRC-11001761. The incidence of grade III-IV acute GVHD was higher in the ATG-6 group (16.1%, 95% confidence interval (CI), 9.1-23.1%) than in the ATG-10 group (4.5%, CI, 0.7-8.3%, P=0.005, 95% CI for the difference, -19.4% to -3.8%). EBV reactivation occurred more frequently in the ATG-10 group (25.3%, 17.1-33.5%) than in the ATG-6 group (9.6% (4.0-15.2%), P=0.001). The 1-year disease-free survival rates were 84.3% (77.3-91.3%) and 86.0% (79.2-92.8%) for the ATG-6 group and ATG-10 groups, respectively (P=0.88). In conclusion, although 6 mg/kg ATG applied in haploidentical transplantation decreased the risk of EBV reactivation compared with 10 mg/kg ATG, this treatment exposes patients to a higher risk for severe acute GVHD.
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