Immune checkpoint blockade (ICB) therapies have revolutionized the treatment of human cancers including lung adenocarcinoma (LUAD). However, our understanding of the immune subtyping of LUAD and its association with clinical response of immune checkpoint inhibitor remains incomplete. Here we performed molecular subtyping and association analysis of LUAD from the Cancer Genome Atlas (TCGA) and validated findings from TCGA cohort in 9 independent validation cohorts. We conducted consensus molecular subtyping with nonnegative matrix factorization (NMF). Potential response of ICB therapy was estimated with Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We identified 2 distinct subtypes of LUAD in TCGA cohort that were characterized by significantly different survival outcomes (i.e., high-and low-risk subtypes). The high-risk subtype was featured by lower TIDE score, upregulation of programmed death-ligand 1 (PD-L1) expression, and higher tumor mutation burden (TMB). The high-risk subtype also harbored significantly elevated cell cycle modulators CDK4/CDK6 and TP53 mutation. These observations were validated in 9 independent LUAD cohorts. Our findings suggest that immune checkpoint blockade therapy may be efficacious for high-risk subtype of LUAD patients.

Content-based video search reranking can be regarded as a process that uses visual content to recover the "true" ranking list from the noisy one generated based on textual information. This paper explicitly formulates this problem in the Bayesian framework, i.e., maximizing the ranking score consistency among visually similar video shots while minimizing the ranking distance, which represents the disagreement between the objective ranking list and the initial textbased. Different from existing point-wise ranking distance measures, which compute the distance in terms of the individual scores, two new methods are proposed in this paper to measure the ranking distance based on the disagreement in terms of pair-wise orders. Specifically, hinge distance penalizes the pairs with reversed order according to the degree of the reverse, while preference strength distance further considers the preference degree. By incorporating the proposed distances into the optimization objective, two reranking methods are developed which are solved using quadratic programming and matrix computation respectively. Evaluation on TRECVID video search benchmark shows that the performance improvement up to 21% on TRECVID 2006 and 61.11% on TRECVID 2007 are achieved relative to text search baseline. Categories and Subject Descriptors H.3.3 [Information Search and Retrieval]: Retrieval models General TermsAlgorithms, Experimentation, Performance * This work was performed when Xinmei Tian and Yichen Yang were visiting Microsoft Research Asia as research interns.Permission to make digital or hard copies of all or part of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for profit or commercial advantage and that copies bear this notice and the full citation on the first page. To copy otherwise, to republish, to post on servers or to redistribute to lists, requires prior specific permission and/or a fee. MM '08, October 26-31, 2008, Vancouver, British Columbia, Canada. Copyright 2008

The representative waste television recycling process was chosen as the object of this study, including manual dismantling and mechanical separation of printed circuit boards (PCBs) and cathode ray tubes (CRTs) in two independent workshops. During these recycling processes, fine particulate matter and heavy metals will be released into the air to impact the environment and the health of the workers. The mass concentrations of PM2.5 (particles below 2.5 μm diameter) in mechanical and dismantling workshops ranged from 252.6 to 290.8 μg/m(3) and from 112.7 to 169.4 μg/m(3), respectively. The average concentration of PM2.5 around the workshop was 98.5 μg/m(3). Meanwhile, the contents of PM10 (particles below 10 μm diameter) were all below the risk threshold, except that (360.4 μg/m(3)) monitored in the mechanical workshop. In two workshops, Pb (20.46 and 6.935 mg/g) was the most enriched metal in the PM2.5 samples, while in PM10, the concentration of Cu (27.76 and 31.80 mg/g) was the largest. The concentration of Cd was the least in both PM10 and PM2.5. Health risk assessment showed that the total hazard indexes for non-carcinogenic metal in PM2.5 monitored in mechanical and dismantling workshops and in the southeast of the workshops were 7.61, 3.01, and 1.57, respectively, all above the safety level. Furthermore, Pb (7.28 and 3.01) might possibly have a non-carcinogenic effect on the workers in two workshops, and the sequence of the hazard quotient (HQ) through the three exposure ways was ingestion > dermal contact > inhalation. The lifetime cancer risk of four targeted metals was Cr > Ni > Pb > Cd, which could be proven in all monitoring samples. This study aims to provide a large amount of valid data for the State Environmental Protection Department to develop relevant environmental standards and for companies to improve the waste television recycling system to be more efficiently and environmentally friendly.

The potent ability of CRISPR/Cas9 system to inhibit the expression of targeted gene is being exploited as a new class of therapeutics for a variety of diseases. However, the efficient and safe delivery of CRISPR/Cas9 into specific cell populations is still the principal challenge in the clinical development of CRISPR/Cas9 therapeutics.In this study, a flexible aptamer-liposome-CRISPR/Cas9 chimera was designed to combine efficient delivery and increased flexibility. Our chimera incorporated an RNA aptamer that specifically binds prostate cancer cells expressing the prostatespecific membrane antigen as a ligand. Cationic liposomes were linked to aptamers by the post-insertion method and were used to deliver therapeutic CRISPR/Cas9 that target the survival gene, polo-like kinase 1, in tumor cells. We demonstrate that the aptamer-liposome-CRISPR/Cas9 chimeras had a significant cell-type binding specificity and a remarkable gene silencing effect in vitro. Furthermore, silencing promoted a conspicuous regression of prostate cancer in vivo. Importantly, the approach described here provides a universal means of cell type-specific CRISPR/ Cas9 delivery, which is a critical goal for the widespread therapeutic applicability of CRISPR/Cas9 or other nucleic acid drugs.

Inspired by the chain reactions among silver nanoparticles, glucose oxidase (GOx) and intratumoral glucose, a degradable silver-based nanoplatform was developed for synergistic cancer starving-like/metal ion therapy.