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Introduction: Cancer stem cells have been described in lung adenocarcinoma‐associated malignant pleural effusion. They show clinically important features, including the ability to initiate new tumours and resistance to treatments. However, their correlation with the three‐dimensional tumour structures in the effusion is not well understood. Methods: Cell blocks produced from lung adenocarcinoma patients' pleural effusion were examined for cancer stem cell‐related markers Nanog and CD133 using immunocytochemistry. The three‐dimensional cancer cell structures and CD133 expression patterns were visualized with tissue‐clearing technology. The expression patterns were correlated with tumour cell structures, genetic variants and clinical outcomes. Results: Thirty‐nine patients were analysed. Moderate‐to‐strong Nanog expression was detected in 27 cases (69%), while CD133 was expressed by more than 1% of cancer cells in 11 cases (28%). Nanog expression was more homogenous within individual specimens, while CD133 expression was detected in single tumour cells or cells within small clusters instead of larger structures in 8 of the 11 positive cases (73%). Although no statistically significant correlation between the markers and tumour genetic variants or patient survival was observed, we recorded seven cases with follow‐up specimens after cancer treatment, and four (57%) showed a change in stem cell‐related marker expression corresponding to treatment response. Conclusions: Lung adenocarcinoma cells in the pleural effusion show variable expression of cancer stem cell‐related markers, some showing a correlation with the size of cell clusters. Their expression level is potentially correlated with cancer treatment effects. [ABSTRACT FROM AUTHOR]

Background: The tumour microenvironment (TME) is a specialised niche involving intercellular communication among cancer cells and various host cells. Among the host cells, the quantity and quality of immune cells within the TME play essential roles in cancer development and management. The immunologically suppressive, so‐called 'cold' TME established by a series of tumour–host interactions, including generating immunosuppressive cytokines and recruiting regulatory host immune cells, is associated with resistance to therapies and worse clinical outcomes. Main body: Various therapeutic approaches have been used to target the cold TME, including immune checkpoint blockade therapy and adoptive T‐cell transfer. A promising, less explored therapeutic strategy involves targeting TME‐associated exosomes. Exosomes are nanometer‐sized, extracellular vesicles that transfer material from donor to recipient cells. These particles can reprogram the recipient cells and modulate the TME. In particular, exosomes from haematopoietic cells are known to promote or suppress cancer progression under specific conditions. Understanding the effects of haematopoietic cell‐secreted exosomes may foster the development of therapeutic exosomes (tExos) for personalised cancer treatment. However, the development of exosome‐based therapies has unique challenges, including scalable production, purification, storage and delivery of exosomes and controlling batch variations. Clinical trials are being conducted to verify the safety, feasibility, availability and efficacy of tExos. Conclusion: This review summarises our understanding of how haematopoietic cell‐secreted exosomes regulate the TME and antitumour immunity and highlights present challenges and solutions for haematopoietic cell‐derived exosome‐based therapies. [ABSTRACT FROM AUTHOR]

The clinical characteristics of malignant melanoma are highly variable between patient populations of different ethnicities. To explore the underlining genetic variations, we reviewed the clinical data of 242 malignant melanoma cases from Taiwan and among them submitted formalin‐fixed paraffin‐embedded tissue samples from 37 patients for whole‐exome sequencing to identify the mutational signatures, tumor mutation burden and specific gene mutations. The genomic profiles and clinical outcomes were compared with the information derived from the publicly available TCGA and TGEN databases. Mutation signature 12 was the dominant signature in Taiwanese patients and represented approximately 45% of the mutation signatures observed. In contrast, mutation signature 7 was the most prominent among cases available in the TCGA database. Common gene mutations found in the TCGA melanoma dataset were not frequently found in melanomas from Taiwanese patients. There were a significant number of specific gene mutations that exclusively occurred in acral subtype but not in non‐acral subtype melanomas, and vice versa. While certain common mutations form a shared core of genetic features, there appear to be specific genetic pathways that are involved in the occurrence of melanomas that grow in non‐UV‐exposed areas. Our findings have shed light on the tumorigenesis pathways involved in malignant melanoma. [ABSTRACT FROM AUTHOR]

Temporal fault‐zone observations are important to better understand the evolution of fault structure and stress configuration. However, long‐term monitoring in the fault zone is rare after a large earthquake. Here, we use seismic data in the fault zone at 1‐km depth from the Taiwan Chelungpu‐fault Drilling Project to study long‐term anisotropy after the 1999 Mw7.6 Chi‐Chi earthquake. The direct S‐wave splitting measurements resolve the overall weak anisotropy in the shallow crust. In order to resolve fault damage zone anisotropy, we perform coda cross‐correlation technique for 794 microearthquakes between 2007 and 2013. We estimate the temporal change in background shear‐wave velocity, fast shear‐wave polarization direction (FSP), and strength of anisotropy (Aani) in the fault damage zone. We show the average FSP direction is N93°E with a significant Aani of about 12%, likely due to the pervasive vertical microcracks created after the earthquake. Temporal variations of anisotropy exhibit seasonal variation with periodicity every 9–12 months that correlates with rainfall events. Furthermore, long‐term anisotropy shows a gradual rotation of FSP direction of about 15° during the first 4 years of observation. At the same time, the strength of anisotropy reduced from 17% to 10% and shear‐wave velocity increased, suggesting the fault healed after the earthquake. This study reports in‐situ evidence for two key observations: (a) long‐term, fault‐zone healing after a major earthquake and (b) modulation of 1‐km deep fault‐zone properties by surficial hydrologic processes. These observations may provide constraints on the response of the fault damage zone in the interseismic period. Plain Language Summary: Earthquakes are generated when rocks slip quickly along a fault. Damage produced by fault rupture is often observed in an area with enhanced fracture networks called the fault damage zone. Fractures inside the damage zone can open or close in response to the background stress. Therefore, observing fault fractures may provide useful information on how the background stresses evolve in the fault. Here, we observe the time‐dependent change of fractures in the fault damage zone through seismic anisotropy analysis. We measure the velocity difference of a seismic shear‐wave in different azimuths to determine the anisotropy. The azimuth of the fastest shear‐wave indicates the dominant fracture orientation inside the fault damage zone. We use borehole seismometers installed within the Chelungpu fault in Taiwan to study the long‐term anisotropy after a major earthquake, and found the fault‐zone is highly damaged with fractures aligning with the tectonic stress direction. Anisotropy varies seasonally due to fluid pressure changes in fault zone fractures during and after rainfall events. In addition, we observe a long‐term anisotropy change that might indicate fracture closure. This study presents a unique observational dataset which allows us to better understand fault zone evolution after a large earthquake. Key Points: A 7‐year (2007–2013) fault‐zone seismic anisotropy is presented from the Taiwan Chelungpu‐fault Drilling Project borehole seismic arrayAverage fast shear‐wave direction of N93°E and anisotropy strength of 12% are observed after the Chi‐Chi earthquakeAnisotropy varies seasonally with rainfalls. Long‐term anisotropy from 17% to 10% with increasing velocity suggests fault healing [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor therapy has revolutionized lung adenocarcinoma therapy. Treatment with antibodies against the immune checkpoint molecules programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) can induce a durable response in a subset of patients. Immunohistochemistry characterization of tumor PD‐L1 expression using either a histopathology specimen or a cytopathology specimen has been shown to correlate with treatment response. However, the current practice relies on pathologists' visual estimation of tumor PD‐L1 staining, which can be variable in certain conditions. Highlighting tumor cells via double immunostaining with PD‐L1 and thyroid transcription factor‐1 (TTF‐1) may improve estimation accuracy. Methods: We performed PD‐L1 single staining and PD‐L1/TTF‐1 double staining in 42 pairs of cytopathology and histopathology specimens from lung adenocarcinoma patients. An experienced pathologist visually estimated PD‐L1 expression in each case and placed tumor PD‐L1 expression into 1 of 3 categories: <1%, 1%‐49%, or ≥50%. A medical technologist also performed estimations of the same cases based on a count of 200 tumor cells, and the results were compared. Results: PD‐L1/TTF‐1 double immunohistochemistry could better identify the PD‐L1–positive tumor cells in cytopathology specimens compared with PD‐L1 single staining. The concordance of PD‐L1 expression categorization between the pathologist's visual estimation and the medical technologist's counting was increased by double staining in cytopathology specimens (Cohen's weighted kappa: single stain, 0.784; double stain, 0.880). Double staining reduced possible error in the pathologist's visual estimation of PD‐L1 expression from 9.5% to 4.8%. The benefit was not observed in histopathology specimens. Conclusion: A simple PD‐L1/TTF‐1 double immunohistochemistry technique can be applied successfully to cytopathology specimens in better identifying patients who can potentially benefit from immune checkpoint blockade treatment. Double immunohistochemical staining with programmed death‐ligand 1 (PD‐L1) and thyroid transcription factor‐1 can increase the scoring accuracy of lung adenocarcinoma cell PD‐L1 expression in cytopathology specimens. The double staining procedure does not introduce a systemic bias in tumor PD‐L1 staining level. [ABSTRACT FROM AUTHOR]

Abstract: Observations show that microseismic events from the same location can have similar source durations but different seismic moments, violating the commonly assumed scaling. We use numerical simulations of earthquake sequences to demonstrate that strength variations over seismogenic patches provide an explanation of such behavior, with the event duration controlled by the patch size and event magnitude determined by how much of the patch area is ruptured. We find that stress drops estimated by typical seismological analyses for the simulated sources significantly increase with the event magnitude, ranging from 0.006 to 8 MPa. However, the actual stress drops determined from the on‐fault stress changes are magnitude‐independent and ~3 MPa. Our findings suggest that fault heterogeneity results in local deviations in the moment‐duration scaling and earthquake sources with complex shapes of the ruptured area, for some of which stress drops may be significantly (~100–1,000 times) underestimated by the typical seismological methods. [ABSTRACT FROM AUTHOR]

Summary: Unlike most ancient microRNAs, which conservatively target homologous genes across species, microRNA827 (miR827) targets two different types of SPX (SYG1/PHO81/XPR1)‐domain‐containing genes, NITROGEN LIMITATION ADAPTATION (NLA) and PHOSPHATE TRANSPORTER 5 (PHT5), in Arabidopsis thaliana and Oryza sativa to regulate phosphate (Pi) transport and storage, respectively. However, how miR827 shifted its target preference and its evolutionary history are unknown. Based on target prediction analysis, we found that in most angiosperms, miR827 conservatively targets PHT5 homologs, but in Brassicaceae and Cleomaceae it preferentially targets NLA homologs, and we provide evidence for the transition of target preference during Brassicales evolution. Intriguingly, we found a lineage‐specific loss of the miR827‐regulatory module in legumes. Analysis of miR827‐mediated cleavage efficiency and the expression of PHT5 in A. thaliana indicated that accumulation of mutations in the target site and the exclusion of the target site by alternative transcriptional initiation eliminated PHT5 targeting by miR827. Here, we identified a transition of miR827 target preference during plant evolution and revealed the uniqueness of miR827‐mediated regulation among conserved plant miRNAs. Despite the change in its target preference, upregulation of miR827 by Pi starvation and its role in regulating cellular Pi homeostasis were retained. [ABSTRACT FROM AUTHOR]

Breast cancer is a common cancer leading to many deaths among females. Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two highly expressed inflammatory mediators to be induced by the protein kinase C (PKC) signaling via various inflammatory stimuli and both contribute significantly to cancer metastasis/progression. Glucosamine has been shown to act as an anti-inflammation molecule. The aim of this study was to clarify the role and acting mechanism of glucosamine during the PKC-regulation of COX-2/IL-8 expression and the associated impact on breast cancer. In MCF-7 breast cancer cells, glucosamine effectively suppresses the PKC induction of COX-2 and IL-8 promoter activity, mRNA and protein levels, as well as the production of prostaglandin E2 (PGE2) and IL-8. Glucosamine is able to promote COX-2 protein degradation in a calpain-dependent manner and IL-8 protein degradation in calpain-dependent and proteasome-dependent manners. The MAPK and NF-κB pathways are involved in PKC-induced COX-2 expression, but only the NF-κB pathway is involved in PKC-induced IL-8 expression. Glucosamine attenuates PKC-mediated IκBα phosphorylation, nuclear NF-κB translocation, and NF-κB reporter activation. Both PGE2 and IL-8 promote cell proliferation and IL-8 induces cell migration; thus, glucosamine appears to suppress PKC-induced cell proliferation and migration. Furthermore, glucosamine significantly inhibits the growth of breast cancer xenografts and this is accompanied by a reduction in COX-2 and IL-8 expression. In conclusion, glucosamine seems to attenuate the inflammatory response in vitro and in vivo and this occurs, at least in part by targeting to the NF-κB signaling pathway, resulting in an inhibition of breast cancer cell growth. J. Cell. Physiol. 230: 2240-2251, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

3D printing technology sparks a paradigm shift in one‐step production, mass customization, and waste minimization. Of late, tremendous advances have been made in 3D printing research, including electronic components, energy‐storage gadgets, and medical therapeutic widgets. Lasers with enormous applicable values, ranging from information communication, to health treatment, to industrial manufacturing, have pervasively penetrated and significantly contributed to modern society. However, until now, the platform of 3D printed lasers is absent in all published work. Here, 3D printing technique endowed with great versatility and accessibility allows the possibility to export any desired laser item free from geometrical restraints, constitutional constraints, and skill limitations. Furthermore, based on the biodissolvability, biodegradability, and biocompatibility of the filament, customized 3D printed random laser devices for speckle‐free bioimaging and large‐scale phototherapy are constructed to investigate inherent multistructures and multifunctional biological systems, providing an excellent solution for intriguing yet challenging issues from extremely complicated groups. It is envisioned that 3D printed random lasers will pave the way for a series of long‐anticipated proofs of concept, such as full‐field imaging implants, microfluidic laser sensors, and photonic circuit systems. [ABSTRACT FROM AUTHOR]