Advancement in the understanding of lung tumor biology enables continued refinement of lung cancer classification, reflected in the recently introduced 2015 World Health Organization classification ...of lung cancer. In small biopsy or cytology specimens, special emphasis is placed on separating adenocarcinomas from the other lung cancers to effectively select tumors for targeted molecular testing. In resection specimens, adenocarcinomas are further classified based on architectural pattern to delineate tissue types of prognostic significance. Neuroendocrine tumors are divided into typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma based on a combination of features, especially tumor cell proliferation rate.
AbstractHepatitis B virus (HBV) infection causes chronic hepatitis and has long term complications. Individuals ever infected with HBV are at risk of viral reactivation under certain circumstances. ...This review summarizes studies on HBV persistence and reactivation with a focus on the definitions and mechanisms. Emphasis is placed on the interplay between HBV replication and host immunity as this interplay determines the patterns of persistence following viral acquisition. Chronic infections exhibit as overt persistence when a defective immune response fails to control the viral replication. The HBV genome persists despite an immune response in the form of covalently closed circular DNA (cccDNA) and integrated DNA, rendering an occult state of viral persistence in individuals whose infection appears to have been resolved. We have described HBV reactivation that occurs because of changes in the virus or the immune system. This review aims to raise the awareness of HBV reactivation and to understand how HBV persists, and discusses the risks of HBV reactivation in a variety of clinical settings.
ZBP1 has been characterized as a critical innate immune sensor of not only viral RNA products but also endogenous nucleic acid ligands. ZBP1 sensing of the Z‐RNA produced during influenza virus ...infection induces cell death in the form of pyroptosis, apoptosis, and necroptosis (PANoptosis). PANoptosis is a coordinated cell death pathway that is driven through a multiprotein complex called the PANoptosome and enables crosstalk and co‐regulation among these processes. During influenza virus infection, a key step in PANoptosis and PANoptosome assembly is the formation of the ZBP1‐NLRP3 inflammasome. When Z‐RNA is sensed, ZBP1 recruits RIPK3 and caspase‐8 to activate the ZBP1‐NLRP3 inflammasome. Several other host factors have been found to be important for ZBP1‐NLRP3 inflammasome assembly, including molecules involved in the type I interferon signaling pathway and caspase‐6. Additionally, influenza viral proteins, such as M2, NS1, and PB1‐F2, have also been shown to regulate the ZBP1‐NLRP3 inflammasome. This review explains the functions of ZBP1 and the mechanistic details underlying the activation of the ZBP1‐NLRP3 inflammasome and the formation of the PANoptosome. Improved understanding of the ZBP1‐NLRP3 inflammasome will direct the development of therapeutic strategies to target infectious and inflammatory diseases.
Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression
. Diagnostic applications have been proposed for ...inflammatory bowel disease diagnosis and prognosis
, colorectal cancer prescreening
and therapeutic choices in melanoma
. Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic
and cardiovascular diseases
. To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks.
•Proton conduction.•Metal organic framework.•Metal phosphonates.•Hydrogen bond.
This review covers basic design principles and offers a cross-section of the current status of phosphonate MOFs as ...proton conductors. Metal phosphonates are often sustained by strong bonds that render them very stable materials. The phosphonate group can also coordinate as a protonated species. These factors, coupled with the inherent structural versatility intrinsic to any metal organic framework family, are the foundation of their interest as proton conducting materials. This review summarizes the recent progress in this topical field as well as some of the existing challenges for further development. The present state of application of the materials is still largely in the academic domain but increasingly, new structures with the necessary proton conducting ability and stability to merit further development as membranes are being reported. The review concludes with a discussion of future challenges for development of this promising field.
In practical applications, particularly in flexible manufacturing systems, there is a high level of uncertainty. A type-2 fuzzy logic system (T2FS) has several parameters and an enhanced ability to ...handle high levels of uncertainty. This article proposes an improved artificial immune system (IAIS) algorithm to solve a special case of the flexible job shop scheduling problem (FJSP), where the processing time of each job is a nonsymmetric triangular interval T2FS (IT2FS) value. First, a novel affinity calculation method considering the IT2FS values is developed. Then, four problem-specific initialization heuristics are designed to enhance both quality and diversity. To enhance the exploitation abilities, six local search approaches are conducted for the routing and scheduling vectors, respectively. Next, a simulated annealing method is embedded to accept antibodies with low affinity, which can enhance the exploration abilities of the algorithm. Moreover, a novel population diversity heuristic is presented to eliminate antibodies with high crowding values. Five efficient algorithms are selected for a detailed comparison, and the simulation results demonstrate that the proposed IAIS algorithm is effective for IT2FS FJSPs.
Covalent organic frameworks (COFs) have attracted much attention for various applications, while developing COFs with biomedical functions remains a big challenge. Most COFs are built purely from ...organic molecules, no carbon dots (CDs)‐based COFs have been exploited to date. In this work, diamine molecules p‐phenylenediamine and BODIPY are selected as model monomers to react with aldehyde‐containing CDs and construct nanoscale COFs, named CCOF‐1 and CCOF‐2, respectively. After the modification with poly(ethylene glycol) (PEG), the formed CCOF‐1@PEG and CCOF‐2@PEG are stable and well‐dispersible in aqueous media. The merits of CCOF‐2@PEG containing favorable physiological stability, good biocompatibility, and strong reactive oxygen species generation ability enable it to act as an excellent photodynamic therapy (PDT) agent for tumor treatment. The high PDT therapeutic efficiency for inhibiting cell proliferation and tumor growth was well shown by in vitro and in vivo experiments. This work demonstrates a new strategy for fabricating functional COF‐based platforms for biomedical applications.
Carbon dots can serve as a building block to fabricate covalent organic frameworks named CCOF‐1 and CCOF‐2 by conjugation with p‐phenylenediamine/BODIPY. CCOF‐2@PEG possesses high aqueous dispersibility, excellent physiological stability, good biocompatibility, and remarkable reactive oxygen species generation ability. The in vitro and in vivo experiments fully establish the potent cancer cell killing effect and antitumor efficacy of CCOF‐2@PEG.
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