P2Y Receptors in Bone - Anabolic, Catabolic, or Both?

P2Y receptors, including eight subtypes, are G protein-coupled receptors that can be activated by extracellular nucleotides. Nearly all P2Y receptors are expressed in bone cells, suggesting their involvements in bone physiology and pathology. However, their exact roles in bone homeostasis are not entirely clear. Therefore, this mini review summarizes new research developments regarding individual P2Y receptors and their roles in bone biology, particularly detailing those which execute both anabolic and catabolic functions. This dual function has highlighted the conundrum of pharmacologically targeting these P2Y receptors in bone-wasting diseases. Further research in finding more precise targeting strategy, such as promoting anabolic effects via combining with physical exercise, should be prioritized.

Metal-Organic Frameworks and Their Composites Towards Biomedical Applications

Owing to their unique features, including high cargo loading, biodegradability, and tailorability, metal–organic frameworks (MOFs) and their composites have attracted increasing attention in various fields. In this review, application strategies of MOFs and their composites in nanomedicine with emphasis on their functions are presented, from drug delivery, therapeutic agents for different diseases, and imaging contrast agents to sensor nanoreactors. Applications of MOF derivatives in nanomedicine are also introduced. Besides, we summarize different functionalities related to MOFs, which include targeting strategy, biomimetic modification, responsive moieties, and other functional decorations. Finally, challenges and prospects are highlighted about MOFs in future applications.

A recurring YYDRxG pattern in broadly neutralizing antibodies to a conserved site on SARS-CoV-2, variants of concern, and related viruses

Studying the antibody response to SARS-CoV-2 informs on how the human immune system can respond to antigenic variants as well as other SARS-related viruses. Here, we structurally and functionally characterized a potent human antibody ADI-62113 that also neutralizes SARS-CoV- 2 variants of concern and cross-reacts with many other sarbecoviruses. A YYDRxG motif encoded by IGHD3-22 in CDR H3 facilitates targeting to a highly conserved epitope on the SARS-CoV-2 receptor binding domain. A computational search for a YYDRxG pattern in publicly available sequences identified many antibodies with broad neutralization activity against SARS-CoV-2 variants and SARS-CoV. Thus, the YYDRxG motif represents a common convergent solution for the human humoral immune system to counteract sarbecoviruses. These findings also suggest an epitope targeting strategy to identify potent and broadly neutralizing antibodies that can aid in the design of pan-sarbecovirus vaccines and antibody therapeutics.

An Exploration of the Green Targeting Strategy – Green Brand Positioning Strategy Linkage: A Qualitative Study

The importance of the relation between targeting and positioning strategies is amplified in the context of the green market, as a result of the difficulty that many companies face in attracting an important customer base. The purpose of this paper is to provide a perspective on the relation between the targeting strategy and the green brand positioning strategy.

A Combined Histone Deacetylases Targeting Strategy to Overcome Venetoclax Plus Azacitidine Regimen Resistance in Acute Myeloid Leukaemia: Three Case Reports

The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who were unresponsive to venetoclax plus azacitidine (VA) but were successfully treated with VA when chidamide was added to the regimen. MCL1 is one of the anti-apoptotic proteins. Chidamide targets the MCL1 protein, which may permit venetoclax resistance when upregulated. We determined MCL1 protein expression in different AML cell lines, and chidamide could downregulate MCL1 expression in venetoclax resistance AML cells. In general, our experience showed that the chidamide/VA combination could improve the condition of R/R AML patients who are resistant to VA. Formally evaluating this regimen in R/R AML patients may be meaningful.

Strategi Segmenting, Targeting dan Positioning dalam Membentuk Brand Image Kafe Pan Java

Marketing is the main activity carried out to maintain business benefit, develop, and receive. Therefore, to attract consumers to make purchases, business people must be able to implement STP (Segmenting, Targeting, Positioning) strategy. This study aims to determine the segmenting, targeting, and positioning strategies used by Pan Java Cafe in forming a brand image. The method used in this research is descriptive qualitative, with data collection through interview and documentation. Then the data are analyzed using data reduction, data presentation and drawing conclusion. The results shows that the Pan Java strategy segmentation is based on Demographic, Psychographic and Behavioral segmentation. In the targeting strategy, Pan Java Cafe sets a target, where only the marketing team is in the upper middle class community such as Civil Servant (PNS), student, teacher, lecturer, and tourist. Meanwhile, Pan Java's strategic positioning positions its business as a tourist village or cafe that offers a place with a different, unique, comfortable, and safe atmosphere. Currently, Pan Java has formed a brand image as a cafe which is made up of local products.

Final Targeting Strategy for the SDSS-IV APOGEE-2S Survey

APOGEE is a high-resolution (R ∼ 22,000), near-infrared, multi-epoch, spectroscopic survey of the Milky Way. The second generation of the APOGEE project, APOGEE-2, includes an expansion of the survey to the Southern Hemisphere called APOGEE-2S. This expansion enabled APOGEE to perform a fully panoramic mapping of all of the main regions of the Milky Way; in particular, by operating in the H band, APOGEE is uniquely able to probe the dust-hidden inner regions of the Milky Way that are best accessed from the Southern Hemisphere. In this paper we present the targeting strategy of APOGEE-2S, with special attention to documenting modifications to the original, previously published plan. The motivation for these changes is explained as well as an assessment of their effectiveness in achieving their intended scientific objective. In anticipation of this being the last paper detailing APOGEE targeting, we present an accounting of all such information complete through the end of the APOGEE-2S project; this includes several main survey programs dedicated to exploration of major stellar populations and regions of the Milky Way, as well as a full list of programs contributing to the APOGEE database through allocations of observing time by the Chilean National Time Allocation Committee and the Carnegie Institution for Science. This work was presented along with a companion article, Beaton et al. (2021), presenting the final target selection strategy adopted for APOGEE-2 in the Northern Hemisphere.