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"Heng, Heng"
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Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies
Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.
Journal Article
Mesenchymal stromal cell apoptosis is required for their therapeutic function
Multipotent mesenchymal stromal cells (MSCs) ameliorate a wide range of diseases in preclinical models, but the lack of clarity around their mechanisms of action has impeded their clinical utility. The therapeutic effects of MSCs are often attributed to bioactive molecules secreted by viable MSCs. However, we found that MSCs underwent apoptosis in the lung after intravenous administration, even in the absence of host cytotoxic or alloreactive cells. Deletion of the apoptotic effectors BAK and BAX prevented MSC death and attenuated their immunosuppressive effects in disease models used to define MSC potency. Mechanistically, apoptosis of MSCs and their efferocytosis induced changes in metabolic and inflammatory pathways in alveolar macrophages to effect immunosuppression and reduce disease severity. Our data reveal a mode of action whereby the host response to dying MSCs is key to their therapeutic effects; findings that have broad implications for the effective translation of cell-based therapies.
Mesenchymal stromal cells (MSCs) demonstrate therapeutic benefits in multiple diseases, but the mechanisms remain unclear as infused MSCs do not persist in the body. Here, the authors show that MSC apoptosis is an important mechanistic element, as MSCs rendered genetically incapable of apoptosis lose their ability to ameliorate disease.
Journal Article
The comparison between adenocarcinoma and squamous cell carcinoma in lung cancer patients
BackgroundThere are several studies comparing the difference between adenocarcinoma (AC) and squamous cell carcinoma (SqCC) of lung cancer. However, seldom studies compare the different overall survival (OS) between AC and SqCC at same clinical or pathological stage. The aim of the study was to investigate the 5-year OS between AC and SqCC groups.MethodsData were obtained from the Taiwan Society of Cancer Registry. There were 48,296 non-small cell lung cancer (NSCLC) patients analyzed between 2009 and 2014 in this retrospective study. We analyzed both the AC and SqCC groups by age, gender, smoking status, Charlson co-morbidity index (CCI) score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage I–IV and causes of death. We used propensity score matching to reduce the bias.ResultsThe AC and SqCC groups are significantly different in age, gender, smoking status, CCI score, clinical TNM stage, pathological stage, tumor location, histologic grade, pleura invasion, performance status, treatment, stage-specific 5-year OS rate in each clinical stage and causes of death (p < 0.0001). The stage-specific 5-year OS rates between AC and SqCC were 79% vs. 47% in stage I; 50% vs. 32% in stage II; 27% vs. 13% in stage III; 6% vs. 2% in stage IV, respectively (all p values < 0.0001).ConclusionsAC and SqCC have significantly different outcomes in lung cancer. We suggest that these two different cancers should be analyzed separately to provide more precise outcomes in the future.
Journal Article
Topological operators and completeness of spectrum in discrete gauge theories
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bstract
In many gauge theories, the existence of particles in every representation of the gauge group (also known as completeness of the spectrum) is equivalent to the absence of one-form global symmetries. However, this relation does not hold, for example, in the gauge theory of non-abelian finite groups. We refine this statement by considering topological operators that are not necessarily associated with any global symmetry. For discrete gauge theory in three spacetime dimensions, we show that completeness of the spectrum is equivalent to the absence of certain Gukov-Witten topological operators. We further extend our analysis to four and higher spacetime dimensions. Since topological operators are natural generalizations of global symmetries, we discuss evidence for their absence in a consistent theory of quantum gravity.
Journal Article
The great reclamation
\"A sweeping novel set in Singapore during the years leading up to its independence from British colonial powers, about one young boy from a rural fishing family and the love story that will shape his life and complicate the fate of his larger community\"-- Provided by publisher.
Book
Non-KREEP origin for Chang’e-5 basalts in the Procellarum KREEP Terrane
Mare volcanics on the Moon are the key record of thermo-chemical evolution throughout most of lunar history
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. Young mare basalts—mainly distributed in a region rich in potassium, rare-earth elements and phosphorus (KREEP) in Oceanus Procellarum, called the Procellarum KREEP Terrane (PKT)
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—were thought to be formed from KREEP-rich sources at depth
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. However, this hypothesis has not been tested with young basalts from the PKT. Here we present a petrological and geochemical study of the basalt clasts from the PKT returned by the Chang’e-5 mission
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. These two-billion-year-old basalts are the youngest lunar samples reported so far
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. Bulk rock compositions have moderate titanium and high iron contents with KREEP-like rare-earth-element and high thorium concentrations. However, strontium–neodymium isotopes indicate that these basalts were derived from a non-KREEP mantle source. To produce the high abundances of rare-earth elements and thorium, low-degree partial melting and extensive fractional crystallization are required. Our results indicate that the KREEP association may not be a prerequisite for young mare volcanism. Absolving the need to invoke heat-producing elements in their source implies a more sustained cooling history of the lunar interior to generate the Moon’s youngest melts.
Isotopic analysis of basalt clasts returned from the Moon by the Chang’e-5 mission indicates that the rocks were derived from a mantle source that lacked potassium, rare-earth elements and phosphorus.
Journal Article