Suppression of FM-to-AM conversion in third-harmonic generation at the retracing point of a crystal

FM-to-AM conversion can cause many negative effects (e.g., reducing of margin against damage to the optics, and etc.) on performances of third-harmonic conversion system. In this letter, the FM-to-AM conversion effect in third-harmonic generation is investigated both at and away from the retracing point of type-II KDP crystal. Obtained results indicate that the FM-to-AM conversion can be suppressed effectively when the crystal works at the retracing point.Comment: 8 pages, 5 figures, 1 tabl

Chemical Approaches to Stem Cell Biology and Therapeutics

Small molecules that modulate stem cell fate and function offer significant opportunities that will allow the full realization of the therapeutic potential of stem cells. Rational design and screening for small molecules have identified useful compounds to probe fundamental mechanisms of stem cell self-renewal, differentiation, and reprogramming and have facilitated the development of cell-based therapies and therapeutic drugs targeting endogenous stem and progenitor cells for repair and regeneration. Here, we will discuss recent scientific and therapeutic progress, as well as new perspectives and future challenges for using chemical approaches in stem cell biology and regenerative medicine

Chemical approaches to studying stem cell biology

Stem cells, including both pluripotent stem cells and multipotent somatic stem cells, hold great potential for interrogating the mechanisms of tissue development, homeostasis and pathology, and for treating numerous devastating diseases. Establishment of in vitro platforms to faithfully maintain and precisely manipulate stem cell fates is essential to understand the basic mechanisms of stem cell biology, and to translate stem cells into regenerative medicine. Chemical approaches have recently provided a number of small molecules that can be used to control cell self-renewal, lineage differentiation, reprogramming and regeneration. These chemical modulators have been proven to be versatile tools for probing stem cell biology and manipulating cell fates toward desired outcomes. Ultimately, this strategy is promising to be a new frontier for drug development aimed at endogenous stem cell modulation

From oncolytic peptides to oncolytic polymers: A new paradigm for oncotherapy

Traditional cancer therapy methods, especially those directed against specific intracellular targets or signaling pathways, are not powerful enough to overcome tumor heterogeneity and therapeutic resistance. Oncolytic peptides that can induce membrane lysis-mediated cancer cell death and subsequent anticancer immune responses, has provided a new paradigm for cancer therapy. However, the clinical application of oncolytic peptides is always limited by some factors such as unsatisfactory bio-distribution, poor stability, and off-target toxicity. To overcome these limitations, oncolytic polymers stand out as prospective therapeutic materials owing to their high stability, chemical versatility, and scalable production capacity, which has the potential to drive a revolution in cancer treatment. This review provides an overview of the mechanism and structure-activity relationship of oncolytic peptides. Then the oncolytic peptides-mediated combination therapy and the nano-delivery strategies for oncolytic peptides are summarized. Emphatically, the current research progress of oncolytic polymers has been highlighted. Lastly, the challenges and prospects in the development of oncolytic polymers are discussed

UV-induced modification of fused silica: Insights from ReaxFF-based molecular dynamics simulations

This article discusses molecular dynamics simulations performed to present evidence that silica structure in both short and medium ranges is directly modified by UV-induced defects

Nomogram predictive model for in-hospital mortality risk in elderly ICU patients with urosepsis

Abstract Background Urinary tract infection (UTI) is a common cause of sepsis. Elderly patients with urosepsis in intensive care unit (ICU) have more severe conditions and higher mortality rates owing to factors such as advanced age, immunosenescence, and persistent host inflammatory responses. However, comprehensive studies on nomograms to predict the in-hospital mortality risk in elderly patients with urosepsis are lacking. This study aimed to construct a nomogram predictive model to accurately assess the prognosis of elderly patients with urosepsis and provide therapeutic recommendations. Methods Data of elderly patients with urosepsis were extracted from the Medical Information Mart for Intensive Care (MIMIC) IV 2.2 database. Patients were randomly divided into training and validation cohorts. A predictive nomogram model was constructed from the training set using logistic regression analysis, followed by internal validation and sensitivity analysis. Results This study included 1,251 patients. LASSO regression analysis revealed that the Glasgow Coma Scale (GCS) score, red cell distribution width (RDW), white blood count (WBC), and invasive ventilation were independent risk factors identified from a total of 43 variables studied. We then created and verified a nomogram. The area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) of the nomogram were superior to those of the traditional SAPS-II, APACHE-II, and SOFA scoring systems. The Hosmer-Lemeshow test results and calibration curves suggested good nomogram calibration. The IDI and NRI values showed that our nomogram scoring tool performed better than the other scoring systems. The DCA curves showed good clinical applicability of the nomogram. Conclusions The nomogram constructed in this study is a convenient tool for accurately predicting in-hospital mortality in elderly patients with urosepsis in ICU. Improving the treatment strategies for factors related to the model could improve the in-hospital survival rates of these patients

An Ursolic Acid Derived Small Molecule Triggers Cancer Cell Death through Hyperstimulation of Macropinocytosis

Macropinocytosis is a transient endocytosis that internalizes extracellular fluid and particles into vacuoles. Recent studies suggest that hyperstimulation of macropinocytosis can induce a novel nonapoptotic cell death, methuosis. In this report, we describe the identification of an ursolic acid derived small molecule (compound <b>17</b>), which induces cancer cell death through hyperstimulation of macropinocytosis. <b>17</b> causes the accumulation of vacuoles derived from macropinosomes based on transmission electron microscopy, time-lapse microscopy, and labeling with extracellular fluid phase tracers. The vacuoles induced by <b>17</b> separate from other cytoplasmic compartments but acquire some characteristics of late endosomes and lysosomes. Inhibiting hyperstimulation of macropinocytosis with the specific inhibitor amiloride blocks cell death, implicating that <b>17</b> leads to cell death via macropinocytosis, which is coincident with methuosis. Our results uncovered a novel cell death pathway involved in the activity of <b>17</b>, which may provide a basis for further development of natural-product-derived scaffolds for drugs that trigger cancer cell death by methuosis