We investigated the effect of international collaboration (in the form of international co-authorship) on the impact of publications of young universities (<50 years old), and compared to that of ...renowned old universities (>100 years old). The following impact indicators are used in this study, they are: (1) the 5-year citations per paper (CPP) data, (2) the international co-authorship rate, (3) the CPP differential between publications with and without international co-authorships, and (4) the difference between the percentage of international co-authored publications falling in the global top 10 % highly cited publications and the percentage of overall publications falling in the global top 10 % highly cited publications (Δ%
Top10%
). The increment of 5-year (2010–2014) field weighted citation impact (FWCI) of internationally co-authored papers over the 5-year overall FWCI of the institutions in SciVal
®
is used as another indicator to eliminate the effect of discipline difference in citation rate. The results show that, for most top institutions, the difference between the citations per paper (CPP) for their publications with and without international co-authorship is positive, with increase of up to 5.0 citations per paper over the period 1996–2003. Yet, for some Asian institutions, by attracting a lot of researchers with international background and making these collaborating “external” authors as internal researchers, these institutions have created a special kind of international collaboration that are not expressed in co-authorship, and the CPP gaps between publications with and without international co-authorship are relatively small (around 0–1 citations per paper increment) for these institutions. The top old institutions have higher CPP than young institutions, and higher annual research expenditures; while young universities have a higher relative CPP increment for the current 5-year period over the previous 5-year period. The Δ%
Top10%
for international co-authored publications is generally higher than that for all journal publications of the same institution. With the increase of international co-authorship ratio, the mean geographical collaboration distance (MGCD, an indication of increased international co-authorship) of one institution based on the Leiden Ranking data also increases, and young institutions have relatively higher CPP increment over MGCD increment. International co-authorship has a positive contribution to the FWCI of the institution, yet there are untapped potential to enhance the collaboration among young institutions.
Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs ...known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call “STINGel.” STINGel is an injectable peptide hydrogel that localizes and provides controlled release of CDN delivery, showing an 8-fold slower release rate compared to a standard collagen hydrogel. The carrier hydrogel is a positively charged, MultiDomain Peptide (MDP) which self-assembles to form a nanofibrous matrix and is easily delivered by syringe. The highly localized delivery of CDN from this nanostructured biomaterial affects the local histological response in a subcutaneous model, and dramatically improves overall survival in a challenging murine model of head and neck cancer compared to CDN alone or CDN delivered from a collagen hydrogel. This study demonstrates the feasibility of biomaterial-based immunotherapy platforms like STINGel as strategies for increasing the efficacy of CDN immunotherapies.
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The radiation pressure of light can act to damp and cool the vibrational motion of a mechanical resonator, but even if the light field has no thermal component, shot noise still sets a limit on the ...minimum phonon occupation. In optomechanical sideband cooling in a cavity, the finite off-resonant Stokes scattering defined by the cavity linewidth combined with shot noise fluctuations dictates a quantum backaction limit, analogous to the Doppler limit of atomic laser cooling. In our work, we sideband cool a micromechanical membrane resonator to the quantum backaction limit. Monitoring the optical sidebands allows us to directly observe the mechanical object come to thermal equilibrium with the optical bath. This level of optomechanical coupling that overwhelms the intrinsic thermal decoherence was not reached in previous ground-state cooling demonstrations.
Claudins are tight junction membrane proteins that are expressed in epithelia and endothelia and form paracellular barriers and pores that determine tight junction permeability. This review ...summarizes our current knowledge of this large protein family and discusses recent advances in our understanding of their structure and physiological functions.
G protein‐coupled estrogen receptor‐1 (GPER), a member of the G protein‐coupled receptor (GPCR) superfamily, mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. ...However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non‐BCSCs of three patient‐derived xenografts of ER−/PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER‐mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD‐Ser118 to sustain BCSC characteristics. Transfection with a dominant‐negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.
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G protein‐coupled estrogen receptor‐1 (GPER) mediates estrogen‐induced proliferation of normal and malignant breast epithelial cells. However, the role of GPER in breast cancer stem cells (BCSC) biology remains unclear. Here, using patient‐derived xenografts of ER–/PR+ breast cancer, the authors found higher expression of GPER in BCSCs than non‐BCSCs. Moreover, the results indicated that stemness features were sustained via GPER‐mediated PKA/BAD phosphorylation. Stimulation by the GPER ligand tamoxifen enhanced BCSC cell viability and population and BAD phosphorylation. The findings revealed a vital role of GPER‐mediated signaling pathways in BCSC survival, suggesting GPER as a potential therapeutic target for eradicating BCSCs.
Gene-expression deconvolution is used to quantify different types of cells in a mixed population. It provides a highly promising solution to rapidly characterize the tumor-infiltrating immune ...landscape and identify cold cancers. However, a major challenge is that gene-expression data are frequently contaminated by many outliers that decrease the estimation accuracy. Thus, it is imperative to develop a robust deconvolution method that automatically decontaminates data by reliably detecting and removing outliers. We developed a new machine learning tool, Fast And Robust DEconvolution of Expression Profiles (FARDEEP), to enumerate immune cell subsets from whole tumor tissue samples. To reduce noise in the tumor gene expression datasets, FARDEEP utilizes an adaptive least trimmed square to automatically detect and remove outliers before estimating the cell compositions. We show that FARDEEP is less susceptible to outliers and returns a better estimation of coefficients than the existing methods with both numerical simulations and real datasets. FARDEEP provides an estimate related to the absolute quantity of each immune cell subset in addition to relative percentages. Hence, FARDEEP represents a novel robust algorithm to complement the existing toolkit for the characterization of tissue-infiltrating immune cell landscape. The source code for FARDEEP is implemented in R and available for download at https://github.com/YuningHao/FARDEEP.git.
3D laboratory tissue cultures have emerged as an alternative to traditional 2D culture systems that do not recapitulate native cell behavior. The discrepancy between in vivo and in vitro ...tissue‐cell‐molecular responses impedes understanding of human physiology in general and creates roadblocks for the discovery of therapeutic solutions. Two parallel approaches have emerged for the design of 3D culture systems. The first is biomedical engineering methodology, including bioengineered materials, bioprinting, microfluidics, and bioreactors, used alone or in combination, to mimic the microenvironments of native tissues. The second approach is organoid technology, in which stem cells are exposed to chemical and/or biological cues to activate differentiation programs that are reminiscent of human (prenatal) development. This review article describes recent technological advances in engineering 3D cultures that more closely resemble the human brain. The contributions of in vitro 3D tissue culture systems to new insights in neurophysiology, neurological diseases, and regenerative medicine are highlighted. Perspectives on designing improved tissue models of the human brain are offered, focusing on an integrative approach merging biomedical engineering tools with organoid biology.
This review outlines current bioengineering and organoid technology approaches to developing 3D in vitro models of the human brain. Advances in generating representative microenvironments to observe and manipulate cellular behavior are described, with emphasis on opportunities to combine these approaches to generate advanced tissue models that are suitable for modeling human brain development, disease, and injury.
The long non-coding RNA, HOTTIP, has an important role in tumorigenesis. It is known that HOTTIP regulates HOX gene family; however, its regulatory mechanism in esophageal squamous cell carcinoma ...(ESCC) remains elusive. In this study, we investigated the role of HOTTIP in ESCC and observed that HOTTIP/HOXA13 was upregulated in ESCC and promoted cell proliferation and metastasis in vivo and in vitro. Interestingly, harboring a miR-30b-binding site, HOTTIP as a molecular sponge mainly regulated miR-30b level in the nucleus and modulated the repression of HOXA13 mediated by miR-30b in the cytoplasm, resulting in the positive HOTTIP/HOXA13 correlation. In addition, HOTTIP upregulated snail1 by competitively binding miR-30b, subsequently promoting epithelial-mesenchymal transition (EMT) and invasion. HOTTIP directly bound the adaptor protein WDR5 and drove histone H3 lysine 4 trimethylation and HOXA13 gene transcription in ESCC cells. In conclusion, our findings indicated that HOTTIP modulated HOXA13 at both the transcriptional and posttranscriptional levels in ESCC cells and HOTTIP-miR-30b-HOXA13 axis may serve as potential diagnostic markers or drug targets for ESCC therapies.
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