In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

[Q]: Glycyrrhetinic acid monoglucuronide (GAMG) is a great value-added and has considerable commercial interest due to its strong pharmacological activities and functional low-calorie sweetener. However GAMG is quite rare in natural plants, and it must be prepared from glycyrrhizin (GL) by hydrolysing one terminal glucuronic acid. -Glucuronidase is the key enzyme in the biotransformation of GL to GAMG, but its activities need to be enhanced to facilitate the industrial large-scale production of GAMG. In this study, we identified that isoliquiritigenin (ISL), as one of chemical compositions from the total flavonoids glycyrrhiza (TFG), can significantly enhance -glucuronidase activity in vitro. Measurements using high-performance liquid chromatography (HPLC) showed that the activity of -glucuronidase could be increased by 2.66-fold via the addition of ISL to a -glucuronidase solution that contained GL at a 3:10 molar ratio of ISL to GL. ISL was concluded to be an activator because ISL could reduce the K m and E a of -glucuronidase reacting with GL. This study sheds new light on the mechanism of glucuronidase and helps to make industrial production of GAMG through fermentation feasible. Published: xx xx xxxx OPEN www.nature.com/scientificreports/ 2 Scientific RepoRts | 7: 12503 |
[A]: Identification of isoliquiritigenin as an activator that stimulates the enzymatic production of glycyrrhetinic acid monoglucuronide OPEN

[Q]: Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. However, resistant strains may impose substantial challenges. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4-binding site (CD4bs). Site-directed mutagenesis revealed that several key epitope mutations facilitate resistance and are located in the inner domain, loop D, and 23/loop V5/24 of HIV-1 gp120. The resistance is largely correlated with binding affinity of antibodies to the envelope trimers expressed on the cell surface. Our results therefore demonstrate the existence of broadly resistant HIV-1 strains against CD4bs neutralizing antibodies. Treatment strategies based on the CD4bs bnAbs must overcome such resistance to achieve optimal clinical outcomes. Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. Among the bnAbs isolated to date, those targeting the CD4bs are the most abundant and thoroughly studied as they disrupt the crucial step of viral interaction with the cellular receptor molecule CD4. Despite the superior potency and breadth of these CD4bs bnAbs, each fails to neutralize a small but significant portion of pseudotyped virus panels. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4bs. Resistance is largely attributed to mutated residues within the epitopes or steric hindrance imposed by the bulky side-chain or glycan shield of the mutated residues, and is largely correlated with reduced binding avidity of the antibody to the quaternary trimeric envelope protein expressed on the PLOS Pathogens | https://doi.surface of the transfected cells. Treatment strategies based on the CD4bs bnAbs therefore must overcome such resistance to achieve optimal clinical outcomes. Recent scientific advances have identified a growing number of broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus type I (HIV-1), providing promising candidates for HIV-1 prevention and treatment [1] [2] [3] [4] [5] . Compared with bnAbs isolated in earlier studies, these bnAbs demonstrated broader and more potent activity against global HIV-1 panels and displayed impressive safety and efficacy profiles for therapeutic applications in a number of animal models and human clinical trials [1, [6] [7] [8] [9] [10] [11] . These results also offer the opportunity to tailor these antibodies and maximize their prevention and treatment potential. Broadly speaking, these bnAbs recognize six major "vulnerable sites" on the HIV-1 envelope glycoprotein gp160 (gp120 and gp41), which are (1) the CD4-binding site (CD4bs), (2) the V1V2 apex, (3) the V3 glycan, (4) the fusion peptide (FP), (5) subunit interface and (6) membrane proximal external region (MPER) of gp41[1-5]. These bnAbs neutralize HIV-1 by blocking viral entry into the target cells, although additional effector functions are likely at play, particularly in the context of in vivo infection and clinical application[1, 12-16]. Among the bnAbs isolated to date, those targeting the CD4bs are the most abundant and thoroughly studied as they disrupt the first and crucial step of viral interaction with the cellular receptor CD4 [3, 4, 17, 18] . In this step, the trimeric envelope glycoprotein, composed of gp120 and gp41, binds with the target cell through the receptor CD4, with either CCR5 or CXCR4 as co-receptor [19] [20] [21] . This triggers a cascade of conformational changes that fuses the viral envelope with the target membrane and releases the viral genome into the cell [22, 23] .More than two dozen CD4bs bnAbs have been isolated to date. This number is likely to grow with the advent of more specific and high-throughput techniques for isolating antibodies.For instance, the prototype VRC01 and its close relative VRC03, which effectively neutralize a panel of diverse pseudotyped viruses,were isolated from a clade-B infected individual [24] [25] [26] . The more recently isolated CD4bs bnAbs, such as 3BNC117, N6, N49P7, 3BNC60, VRC-PG04, VRC-PG20, NIH45-46, VRC-CH31, 12A12, CH103, 8ANC131, VRC13, and VRC16, have shown similar or even enhanced potency and breadth compared with VRC01 [1-5, 27, 28].The CD4bs bnAbs are classified into two groups based on their mode of recognition and heavy chain characteristics, such as the VRC01 class(3BNC117, N6, N49P7, 3BNC60, VRC-PG04, VRC-PG20, NIH45-46, VRC-CH31 and 12A12) and non-VRC01 classes (CH103, 8ANC131, VRC13 and VRC16) [17, 18] . Structurally, these bnAbs recognize residues within the inner domain, the Loop D, the CD4 binding loop, and the 23/loop V5/24 region [17, 18, [29] [30] [31] .The V1V2 and V3 loop also impact recognition,particularly in the context of the quaternary trimeric envelope protein [32] [33] [34] [35] [36] .The primary mechanism of neutralization mimics and competes with the CD4 receptorto bind HIV-1 gp120, thereby preventing bound trimers from transitioning to the subsequent steps required for membrane fusion, although evidence indicates that there are differences in the fine details of this process [17, 18, 35, 36] . Despite the superior potency and breadth of these CD4bs bnAbs, each fails to neutralize a small but significant portion of pseudotyped virus panels [17, 25, 27, 28, 37, 38].For instance, VRC01 is unable to neutralize about 10% of tested viruses [25] , and resistant strains have been isolated from patients infected with subtype B, subtype C, CRF07_BC, and CRF08_BC[29, [39] [40] [41] [42] . Furthermore, reports show thatVRC01-, 3BNC117-and N6-resistant strains have emerged in both animal models and human clinical trials [11, 15, [43] [44] [45] [46] [47] , indicating that resistant virus Broadly resistant HIV-1 against CD4bs antibodies PLOS Pathogens | https://doi.org/10.
[A]: Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies

[Q]: The antigenic and biological properties of 6 strains of bovine coronavirus (BCV) derived from neonatal calf diarrhea (CD) and 8 strains of BCV from winter dysentery (WD) of adult cattle, propagated in HRT-18 cells, were compared to determine ifCD and WD strains belong to distinct serotypes or subtypes of BCV. All strains hemagglutinated both mouse and chicken erythrocytes at 4 C, but the ratios of hemagglutination titers with mouse erythrocytes compared to chicken erythrocytes showed diversity for both CD and WD strains. Some CD and WD strains did not hemagglutinate chicken erythrocytes at 37 C and showed receptordestroying enzyme activity against chicken erythrocytes. Hyperimmune antisera were produced in guinea pigs against 3 and 7 strains of BCV from CD and WD, respectively. No significant differences in antibody titers against these strains were observed by indirect immunofluorescence tests. However, in virus neutralization tests, antisera to 1 CD and 2 WD strains had 16-fold or lower antibody titers against 3 WD and 1 CD strains than against the homologous strains, and this variation reflected low antigenic relatedness values (R= 13-25%), suggesting the presence of different subtypes among BCV. In hemagglutination inhibition tests, some one-way antigenic variations among strains were also observed. These results suggest that some antigenic and biological diversity exists among BCV strains, but these variations were unrelated to the clinical source of the strains; i.e. CD or WD. Bovine coronavirus (BCV) is a primary cause of neonatal calf diarrhea (CD) worldwide [4, 13] . Bovine coronavirus is also associated with acute diarrhea in adult cattle during the winter season referred to as winter dysentery (WD) [4, 17, 18, 24, 26] . Besides infecting the small and large intestines of calves, BCV also possesses a tissue tropism for the upper respiratory tract [15] . H. Tsunemitsu and L. J. Saif Bovine coronavirus has four major structural proteins: the nucleocapsid protein (N), the transmembrane protein (M), the spike protein (S) and the hemagglutininesterase protein (HE) [21] . The S and HE proteins form fringes of longer and shorter surface projections, respectively [4] . Both proteins can cause hemagglutination (HA) and contain neutralizing epitopes [7, 20] . The HE protein also possesses receptor-destroying enzyme (RDE) which inactivates cellular receptors for BCV by hydrolyzing an ester bond to release acetate from C-9 of sialic acid [4, 27] . Because the primary isolation of BCV remains difficult, there have been only a few investigations on antigenic comparisons of BCV strains [6, 8, 11, 14] . Specifically, whether antigenic or biological differences exist between strains derived from CD and WD remains obscure [2] . The purpose of this study was to isolate BCV strains from feces derived from CD and WD in human rectal tumor (HRT-18) cells and to compare the antigenic and biological properties of these strains. and was propagated 8 times in HRT-18 cells. Six WD isolates of BCV designated as the TS, CN, BE, BM, AW and BW strains, were isolated from fecal samples of gnotobiotic calves which had been inoculated with fecal filtrates from affected adult dairy cows from 6 herds in the U.S.A. including Ohio (3 herds) and Wisconsin (3 herds), which were experiencing typical outbreaks of WD during the winters of 1987 to 1993. Three CD isolates of BCV designated as the DB2, OHC and SDC strains, were isolated from fecal samples of neonatal calves with acute diarrhea from 3 herds in the U.S.A. including Ohio (2 herds) and South Dakota (1 herd). A fourth CD isolate (JAZ) was isolated from a neonatal calf with acute diarrhea in Hokkaido, Japan. Virus isolation on HRT-18 cells was done as previously described [2, 25] except that 10 gg/ml of pancreatin (Gibco Laboratories, Grand Island, N.Y.) was added to the maintenance medium. Confirmation of the isolates as BCV was done by using immune electron microscopy [ 16] and immunofluorescence (IF) [2] with hyperimmune antiserum prepared against the Mebus strain ofCD BCV. The isolated viruses, which were passaged a total of 5 to 10 times in HRT-18 cells were plaque-purified at least once before use. Hyperimmune antisera were prepared in guinea pigs against 3 CD strains (Mebus, DB2, 216XF) and 7 WD strains (SD, BM, CN, AW, DBA, TS, BE) of BCV that had been propagated in HRT-18 cells for 6 to 11 passages and then purified on sucrose gradients [5] . These antisera were used for serological tests. Hemagglutination (HA) tests were conducted by the microtiter method [19] . Bovine coronavirus strains were purified from infected-cell culture supernatants,
[A]:
Antigenic and biological comparisons of bovine coronaviruses derived from neonatal calf diarrhea and winter dysentery of adult cattle Brief Report