Together, our study helps develop a proper understanding of Bla1 beta-lactamase and its interaction with inhibitory molecules. This study would facilitate comprehending the catalytic divergence of beta-lactamases and the newly emergent resistant strains, focusing on the new generation of therapeutics being less prone to antimicrobial resistance. Given the observed olfactory and gustatory dysfunctions in patients with COVID-19 and recent findings on taste receptors possible important activities in the immune system, we elected to estimate the correlation between COVID-19 mortality and polymorphism of a particular type of bitter taste receptor gene called TAS2R38, in a worldwide epidemiological point of view. Pooled rate of each of the rs713598, rs1726866, rs10246939, and PAV/AVI polymorphisms of the TAS2R38 gene was obtained in different countries using a systematic review methodology and its relationship with the mortality of COVID-19. https://www.selleckchem.com/ Data were analyzed by the comprehensive meta-analysis software and SPSS. There was only a significant reverse Pearson correlation in death counts and PAV/AVI ratio, p=0.047, r=-0.503. Also, a significant reverse correlation of PAV/AVI ratio and death rate was seen, r=-0.572 p=0.021. rs10246939 ratio had a significant positive correlation with death rate, r=0.851 p=0.031. Further analysis was not significant. Our results showed that the higher presence of PAV allele than AVI, and a higher rate of G allele than A in rs10246939 polymorphism in a country, could be associated with lower COVID-19 mortality. While assessing all three polymorphisms showed a huge diversity worldwide. Due to extraoral activities of bitter taste receptor genes, especially in mucosal immunity, this gene seems to be a good candidate for future studies on COVID-19 pathophysiology. Also, the high worldwide diversity of TAS2R38 genes polymorphism and its possible assassination with mortality raises concerns about the efficiency of vaccine projects in different ethnicities. Due to extraoral activities of bitter taste receptor genes, especially in mucosal immunity, this gene seems to be a good candidate for future studies on COVID-19 pathophysiology. Also, the high worldwide diversity of TAS2R38 genes polymorphism and its possible assassination with mortality raises concerns about the efficiency of vaccine projects in different ethnicities.Follicle stimulating hormone (FSH), composed of FSHα and FSHβ subunits, is essential for female follicle development and male spermatogenesis. The recombinant human FSH (rhFSH) products on the market are mainly generated from mammalian cells and are expensive. Large animal mammary gland bioreactors are urgently needed to produce large amounts of rhFSH. However, there are currently no effective methods to prepare rhFSH by large animals mainly due to the fact that excessive accumulation of FSH might cause many adverse effects in animals. We herein report the development and characterization of functional self-assembled rhFSH produced in goat mammary epithelial cells (GMECs). FSHα and FSHβ stably expressed in Chinese hamster ovary (CHO) cell lines were secreted into culture medium and well glycosylated. Importantly, FSHα and FSHβ expressed apart were able to assemble into functional FSH. We next inserted human FSHα or FSHβ gene separately into goat β-Lactoglobulin locus in GMECs by CRISPR/Cas9. Inactive FSHα and FSHβ subunits expressed from GMECs assembled into rhFSH as analyzed by His-tag pull down assay. Functional assessment of rhFSH by cAMP induction assay, mouse ovulation induction and rat ovarian weight gain experiments showed that the bioactivity of self-assembled rhFSH expressed by GMECs was comparable to that of Gonal-F both in vitro and in vivo. Our study demonstrated that FSHα and FSHβ can be separately expressed and assembled into functional rhFSH, and provided the basis for future preparing FSH by goat mammary gland bioreactor with less health problems on the producing animals.The adrenal cortex plays pivotal roles in the maintenance of blood volume, responsiveness to stress and the development of gender characteristics. Gender differences of human adrenal cortex have been recently reported and attracted increasing interests. Gender differences occur from the developing stage of the adrenal, in which female subjects had more activated stem cells with higher renewal capacity resulting in gender-associated divergent structures and functions of cortical zonations of human adrenal. Female subjects generally have the lower blood pressure with the lower renin levels and ACE activities than male subjects. In addition, HPA axis was more activated in female than male, which could possibly contribute to gender differences in coping with various stressful events in our life. Of particular interest, estrogens were reported to suppress RAAS but activate HPA axis, whereas androgens had opposite effects. In addition, adrenocortical disorders in general occur more frequently in female with more pronounced adrenocortical hormonal abnormalities possibly due to their more activated WNT and PRK signaling pathways with more abundant activated adrenocortical stem cells present in female adrenal glands. Therefore, it has become pivotal to clarify the gender influence on both clinical and biological features of adrenocortical disorders. We herein reviewed recent advances in these fields.Overcoming the radiosensitivity of chondrosarcoma (CS), the second most common primary bone tumor, is needed. Radioresistance is attributed to cancer stem cells (CSCs) in many malignancies. Disulfiram (DSF), an FDA-approved anti-alcoholism drug, complexed with Cu (DSF/Cu) can radiosensitize epithelial CSCs. This prompted us to investigate the radiosensitizing effect of DSF/Cu on CS CSCs (CCSCs). The radiosensitizing effects of DSF/Cu on CCSCs were investigated in vitro using cell lines SW1353 and CS-1. Stemness was identified independently by flow cytometry for CCSCs (ALDH+CD133+), sphere-forming ability, and Western blot analysis of stemness gene protein expression. The radiosensitizing effect of DSF/Cu was studied in an orthotopic CS xenograft mouse model by analyzing xenograft growth and residual xenografts for stemness. CCSCs were found to be resistant to single-dose (IR) and fractionated irradiation (FIR). IR and FIR increased CS stemness. Combined with DSF/Cu in vitro and in vivo, IR and FIR eliminated CS stemness.