PepPre: Promote Peptide Identification Using Accurate and Comprehensive Precursors.

Accurate and comprehensive peptide precursor ions are crucial to tandem mass-spectrometry-based peptide identification. An identification engine can derive great advantages from the search space reduction enabled by credible and detailed precursors. Furthermore, by considering multiple precursors per spectrum, both the number of identifications and the spectrum explainability can be substantially improved. Here, we introduce PepPre, which detects precursors by decomposing peaks into multiple isotope clusters using linear programming methods. The detected precursors are scored and ranked, and the high-scoring ones are used for subsequent peptide identification. PepPre is evaluated both on regular and cross-linked peptide data sets and compared with 11 methods. The experimental results show that PepPre achieves a remarkable increase of 203% in PSM and 68% in peptide identifications compared to instrument software for regular peptides and 99% in PSM and 27% in peptide pair identifications for cross-linked peptides, surpassing the performance of all other evaluated methods. In addition to the increased identification numbers, further credibility evaluations evidence the reliability of the identified results. Moreover, by widening the isolation window of data acquisition from 2 to 8 Th, with PepPre, an engine is able to identify at least 64% more PSMs, thereby demonstrating the potential advantages of wide-window data acquisition. PepPre is open-source and available at http://peppre.ctarn.io.

Metformin enhances T lymphocyte anti-tumor immunity by increasing the infiltration via vessel normalization.

Abnormal tumor vasculature blocks the extravasation of T lymphocytes into the tumor, thereby suppressing anti-tumor immunity. Recently, metformin has been shown to affect tumor vasculature and enhance T lymphocyte anti-tumor immunity. However, whether or how metformin affects T lymphocyte anti-tumor immunity via a vascular mechanism remains poorly understood. Herein, we show that a large number of CD8+ lymphocytes gathered in the peri-tumoral region, while very few infiltrated the tumor. Metformin administration increased the expression of anti-tumor immunity-associated genes and the number of tumor-infiltrating CD8+ lymphocytes. Injection of CD8 but not CD4 neutralization antibody into tumor-bearing mice significantly abrogated the anti-tumor effect of metformin. Critically, CD8+ lymphocytes were found to pass through the wall of perfused vessel. Further results of immunofluorescent staining showed that metformin greatly elevated tumor perfusion, which was accompanied by increased vascular maturity in the intratumoral region (ITR) but not peritumoral region (PTR). These findings provide evidence for the vascular mechanism involved in metformin-induced enhancement of T lymphocyte anti-tumor immunity. By remodeling the abnormal tumor vasculature, also called vessel normalization metformin increases vascular maturity and tumor perfusion, thus allowing more CD8+ lymphocytes to infiltrate the tumor.

Computed tomography for the diagnosis of solitary thin-walled cavity lung cancer.

BACKGROUND AND AIM: Lung cancer is the most commonly diagnosed neoplasm and the leading cause of cancer-related death worldwide. Despite the high incidence of lung cancer, the diagnosis of solitary thin-walled cavity lung cancer is rare. The aim of this review is to explore the potentials of computed tomography (CT) as diagnostic tool for solitary thin-walled cavity lung cancer. METHOD: The literature search was made in electronic databases including PudMed, Ovid SP, Embase, Web of Sciences, EBSCO and Wiley online by using relevant key terms. Because of the rarity of the subject, no precise exclusion or inclusion criteria were used for article selection and the outcome dissemination was decided to be more descriptive rather than quantitative. RESULTS: The detection of cavitation in lungs is frequently done utilizing chest radiographs CT scans. However, the diagnostic challenge remains the accurate detection of solitary thin-walled cavity lung cancer among the prevalence of cavitary lung lesions in multiple thoracic disorders including benign disorders, infectious disease and malignant tumors. Moreover, an accurate diagnosis of solitary thin-walled cavity lung cancer is further complicated by its subjective classification within the literature. In order to facilitate early diagnosis of this disease and circumvent the need for more invasive tests that may not be warranted, the overarching goal is to establish definitive radiological features of lung cavities that are indicative of malignancy. Herein, we describe the benefits of using CT to identify and diagnose solitary thin-walled cavity lung cancer, as well as explore the underlying mechanisms that contribute to thin-walled cavity formation in oncology patients. CONCLUSION: CT is the best modality for the noninvasive differentiation between malignant and nonmalignant cavities as it provides reliable information regarding the morphology and density of lesions. Besides, CT densitometry can efficiently detect the calcifications in lesions.