Tumor-infiltrating immune cells and survival in head and neck squamous cell carcinoma: a retrospective computational study.

The immune infiltration profiles of the tumor microenvironment have effects on the prognosis of head and neck squamous cell carcinoma (HNSCC). Whereas, HNSCC is a heterogeneous group of tumors, but past work has not taken this into consideration. Herein, we investigate the associations between survival and the function of immune cells in different tumorigenic sites of HNSCC. 1149 samples of HNSCC were collected from publicly accessible databases. Based on gene expression data, CIBERSORTx was applied to determine the proportion of 22 immune cell subpopulations. In the Cox regression model, the associations between overall survival, disease-free survival, and immune cells were examined, modeling gene expression and immune cell proportion as quartiles. Consensus cluster analysis was utilized to uncover immune infiltration profiles. Regardless of tumor sites, CD8+ T cells and activated CD4 memory T cells were associated with favorable survival, while eosinophils were the opposite. The survival of the hypopharynx, oral cavity, and larynx subsites was somewhat affected by immune cells, while the survival of the oropharynx subsite potentially was the most impacted. High expression of TIGIT, CIITA, and CXCR6 was linked to better survival, mainly in the oropharynx subsite. Immune cell clusters with four distinct survival profiles were discovered, of which the cluster with a high CD8+ T cell content had a better prognosis. The immune-infiltration pattern is related to the survival of HNSCC to varying degrees depending on the tumor sites; forthcoming studies into immune-mediated infiltration profiles will lay the groundwork for treating HNSCC with precision therapy.

Gut microbial structural variation associates with immune checkpoint inhibitor response.

The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.

Patterns of immune infiltration and survival in endocrine therapy-treated ER-positive breast cancer: A computational study of 1900 patients.

Tumor-infiltrating immune cells (TIICs) play a critical role in breast cancer (BC) prognosis, but little is known regarding the efficacy of endocrine therapy in patients with ER-positive BC with diverse immunological phenotypes. To investigate whether TIICs affect survival after endocrine therapy in patients with different BC molecular subtypes, data were gathered from six studies totaling 1900 samples. CIBERSORTx was used to analyze the invasion of 22 immune cell subpopulations using a bulk gene expression profile. The relationships of immune-related metagenes and immune cell subsets with survival (distant metastasis-free survival, relapse-free survival, and overall survival) were studied using Cox regression models with cell proportions modeled in quartiles. The immune score and IGHG3 and LCK gene activity were linked to a better prognosis. Among the immune cells, monocytes, resting CD4+ memory T cells and plasma cells were correlated with prolonged survival, while neutrophils, Tregs, M0 macrophages, and M2 macrophages were associated with an unfavorable prognosis. Similar effects were reported for the luminal A subtype. In the luminal B subtype, γδ T cells and eosinophils were favorable prognostic factors. Covariate-adjusted multivariate Cox regression analysis revealed that high proportions of resting CD4+ memory T cells and resting dendritic cells were correlated with a good prognosis. Meanwhile, neutrophils were associated with an unfavorable prognosis. Understanding how monocytes and macrophages interact in the tumor microenvironment may be a promising study focus. Comprehensive research on the cellular immune response in tumors could help facilitate the development of new treatments.

Copious positron production by femto-second laser via absorption enhancement in a microstructured surface target.

Laser-driven positron production is expected to provide a non-radioactive, controllable, radiation tunable positron source in laboratories. We propose a novel approach of positron production by using a femto-second laser irradiating a microstructured surface target combined with a high-Z converter. By numerical simulations, it is shown that both the temperature and the maximum kinetic energy of electrons can be greatly enhanced by using a microstructured surface target instead of a planar target. When these energetic electrons shoot into a high Z converter, copious positrons are produced via Bethe-Heitler mechanism. With a laser (wavelength λ = 1 µm) with duration ~36 fs, intensity ~5.5 × 1020 W/cm2 and energy ~6 Joule, ~109 positrons can be obtained.

Species-specific profiles and risk assessment of perfluoroalkyl substances in coral reef fishes from the South China Sea.

The contamination profiles of sixteen perfluoroalkyl substances (PFAS) were examined in coral reef fish samples collected from the South China Sea (SCS) where no information about this topic was available in the literature. The results revealed that six PFAS were found in coral reef fish samples from the SCS. Perfluorooctane sulfonate (PFOS) was the most predominant PFAS contaminant detected in most of the samples, with the highest concentration value of 27.05 ng/g wet weight (ww) observed in Cephalopholis urodelus. Perfluoroundecanoic acid (PFUnDA) and Perfluorotridecanoic acid (PFTrDA) were the second and third dominant PFAS, respectively. Mean PFOS concentrations in muscle of seven coral reef fish varied from 0.29 ng/g ww in Lethrinus olivaceus to 10.78 ng/g ww in Cephalopholis urodelus. No significant linear relationship was observed between PFOS levels and coral reef fish traits (length, weight) collected in this region. Average daily intake of PFOS for the seven coral reef fishes ranged from 0.79 ng/kg/d for Lethrinus olivaceus to 29.53 ng/kg/d for Cephalopholis urodelus. The hazard ratio (HR) values for human consumption of PFOS-contaminated coral reef fishes ranged from 0.04 to 1.48, with Cephalopholis urodelus having the highest HR value of 1.18 (higher than 1) among the species, indicating frequent consumption of Cephalopholis urodelus might pose potential health risk to local population. The present work have provided the first hand data of PFAS in coral reef fishes in the SCS and indirectly demonstrated the existence of low level PFAS pollution in the SCS in China.

Ultra-bright γ-ray flashes and dense attosecond positron bunches from two counter-propagating laser pulses irradiating a micro-wire target.

We propose a novel scheme to generate ultra-bright ultra-short γ-ray flashes and high-energy-density attosecond positron bunches by using multi-dimensional particle-in-cell simulations with quantum electrodynamics effects incorporated. By irradiating a 10 PW laser pulse with an intensity of 1023 W/cm2 onto a micro-wire target, surface electrons are dragged-out of the micro-wire and are effectively accelerated to several GeV energies by the laser ponderomotive force, forming relativistic attosecond electron bunches. When these electrons interact with the probe pulse from the other side, ultra-short γ-ray flashes are emitted with an ultra-high peak brightness of 1.8 × 1024 photons s-1mm-2mrad-2 per 0.1%BW at 24 MeV. These photons propagate with a low divergence and collide with the probe pulse, triggering the Breit-Wheeler process. Dense attosecond e-e+ pair bunches are produced with the positron energy density as high as 1017 J/m3 and number of 109. Such ultra-bright ultra-short γ-ray flashes and secondary positron beams may have potential applications in fundamental physics, high-energy-density physics, applied science and laboratory astrophysics.

New quantitative classification of the anatomical relationship between impacted third molars and the inferior alveolar nerve.

BACKGROUND: Before extracting impacted lower third molars, dentists must first identify the spatial relationship between the inferior alveolar nerve (IAN) and an impacted lower third molar to prevent nerve injury from the extraction. Nevertheless, the current method for describing the spatial relationship between the IAN and an impacted lower third molar is deficient. Therefore, the objectives of this study were to: (1) evaluate the relative position between impacted lower third molars and the IAN; and (2) investigate the relative position between impacted lower third molars and the IAN by using a cylindrical coordinate system. METHODS: From the radiology department's database, we selected computed tomography images of 137 lower third molars (from 75 patients) requiring removal and applied a Cartesian coordinate system by using Mimics, a medical imaging software application, to measure the distribution between impacted mandibular third molars and the IAN. In addition, the orientation of the lower third molar to the IAN was also measured, but by using a cylindrical coordinate system with the IAN as the origin. RESULTS: According to the Cartesian coordinate system, most of the IAN runs through the inferior side of the third molar (78.6 %), followed by the lingual side (11.8 %), and the buccal side (8.9 %); only 0.7 % is positioned between the roots. Unlike the Cartesian coordinate system, the cylindrical coordinate system clearly identified the relative position, r and θ, between the IAN and lower third molar. CONCLUSIONS: Using the cylindrical coordinate system to present the relationship between the IAN and lower third molar as (r, θ) might provide clinical practitioners with a more explicit and objective description of the relative position of both sites. However, comprehensive research and cautious application of this system remain necessary.

[Construction and primary analysis of subtractive library induced by soybean mosaic virus (SMV)].

SMV is one of main diseases of soybean, which could affect yields and quality of soybean seriously. It was effective to soybean breeding by studying the expression of resistant gene to SMV with molecular technology. In this study, a soybean resistance line, DongNong 8143, was used to construct a subtractive cDNA library by SSH from soybean leaves inoculated by SMV No.1 at primary stage. cDNA dominantly or specifically expressed in infected leaves was purified using PCR Purification Kit and cloned into pGEM-T easy vector. Colonies were grown on LB-agar plates containing ampicillin, X-gal and IPTG. A subtractive plasmid library was constructed by SSH. Then the library was transformed to host bacteria E. coli DH5alpha, and the titer of the library was measured as 2 x 10(3) . 64 clones were picked up randomly and sequenced. Of them there is 50 clones which result of sequenced were good. The length of EST fragment varied from 136bp to 691bp, and the average length is 456bp. Among them, 41 sequences has poly(A). Through ESTs were compared with sequences in unigene database of GeneBank with BLASTn and BLASTx algorithm, 38 ESTs of them had comparatively clear results and the percent of them in acquired ESTs is 74%. The EST expression profile showed that the resistance-related genes include cell protection, signal transduction, restrict pathogen growth, system acquired resistance, and house-keeping gene. There are 12 ESTs, which have not comparatively clear results, that maybe new genes.