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wangianus clade, and the fourth one with moniliform rhizomes was named as P. bipinnatifidus clade. The population genetic structure analysis and D-statistics test showed the localized admixture among these species, which indicated that introgression had occurred among the related lineages continuously distributed in southeastern Yunnan and adjacent regions.Gene duplication and horizontal gene transfer (HGT) are two important but different forces for adaptive genome evolution. In eukaryotic organisms, gene duplication is considered to play a more important evolutionary role than HGT. However, certain fungal lineages have developed highly efficient mechanisms that avoid the occurrence of duplicated gene sequences within their genomes. While these mechanisms likely originated as a defense against harmful mobile genetic elements, they come with an evolutionary cost. A prominent example for a genome defense system is the RIP mechanism of the ascomycete fungus Neurospora crassa, which efficiently prevents sequence duplication within the genome and functional redundancy of the subsequent paralogs. Despite this tight control, the fungus possesses two functionally redundant sterol C-5 desaturase enzymes, ERG-10a and ERG-10b, that catalyze the same step during ergosterol biosynthesis. In this study, we addressed this conundrum by phylogenetic analysis of the two proteins and supporting topology tests. We obtained evidence that a primary HGT of a sterol C-5 desaturase gene from Tremellales (an order of Basidiomycota) into a representative of the Pezizomycotina (a subphylum of Ascomycota) is the origin of the ERG-10b sequence. The reconstructed phylogenies suggest that this HGT event was followed by multiple HGT events among other members of the Pezizomycotina, thereby generating a diverse group with members in the four classes Sordariomycetes, Xylonomycetes, Eurotiomycetes and Dothideomycetes, which all harbor the second sterol C-5 desaturase or maintained in some cases only the ERG-10b version of this enzyme. These results furnish an example for a gene present in numerous ascomycetous fungi but primarily acquired by an ancestral HGT event from another fungal phylum. Furthermore, these data indicate that HGT represents one mechanism to generate functional redundancy in organisms with a strict avoidance of gene duplications.Optimal conditioning regimens for older patients with myelofibrosis undergoing allogeneic hematopoietic cell transplant are not known. Likewise, the role of dose intensity is not clear. We conducted a nonrandomized, prospective, phase II trial using low-dose, later escalated to high-dose (myeloablative conditioning), busulfan with fludarabine (Bu-Flu) in myelofibrosis patients up to age 74 years. The first 15 patients received i.v. busulfan 130 mg/m2/day on days -3 and -2 ("low dose"); 31 patients received high-dose conditioning, either 100 mg/m2/day (days -5 to -2; n = 4) or pharmacokinetic-guided area under the curve of 4000 μmol/min (days -5 to -2; n = 27). The primary endpoint was day 100 nonrelapse mortality (NRM). Median age was 58 years (interquartile range [IQR], 53-63). Dynamic international prognostic scoring system-plus was intermediate (n = 28) or high (n = 18). Donors were related (n = 19) or unrelated (n = 27). Cumulative incidence of NRM was 9.7% (95% confidence interval [CI], 0-20.3) at day 100 and at 3 years in the high-dose group and 0% in the low-dose group at day 100, which increased to 20% (95% CI, 0-41.9) at 3 years. With a median follow-up of 5.1 years (IQR, 3.8-6), 3-year relapse was 32.3% (95% CI, 15.4-49.1) in high dose versus 53.3% (95% CI, 26.6-80.1) in low dose. Event-free survival was 58% (95% CI, 43-78) versus 27% (95% CI, 12-62), and overall survival was 74% (95% CI, 60-91) versus 60% (95% CI, 40-91). In multivariate analysis, high-dose busulfan had a trend toward lower relapse (hazard ratio, .44; 95% CI, .18-1.07; P = .07), with no impact on NRM. Intensifying the Bu-Flu regimen using pharmacokinetic-monitoring appears to be promising in reducing relapse without increasing NRM.Hematopoietic cell transplantation (HCT) is a well-established treatment to control and/or cure many malignant and nonmalignant diseases involving the hematopoietic system and some solid tumors. We report information about HCT procedures performed in the United States in 2018 and analyze trends and outcomes of HCT as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Overall, compared with 2017, the number of allogeneic HCTs performed in the United States increased by 1%, and the number of autologous HCTs decreased by 5%. Key findings are fewer autologous HCTs performed for non-Hodgkin lymphoma and increasing numbers of haploidentical HCTs, nearly all of which use post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis. There is a continuing increase in HCT in adults age >70 years, particularly for acute myelogenous leukemia and myelodysplastic syndromes. Survival rates by disease, disease stage, donor type, and age are presented. This report, prepared annually by the CIBMTR, provides a snapshot of current transplant activity in the United States. © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.Antibiotics are well-known disruptive elements of the intestinal microbiota and antibiotic-associated diarrhea appeared as the most common complication related with post-antibiotic dysbiosis. Lactobacillus rhamnosus GG (LGG) strain is very effective in preventing antibiotic-associated diarrhea in children and adults. However, as any probiotics, it is concerned by the loss of viability during storage and gastrointestinal transit. The aim of this study was to develop an encapsulation system suitable for the specific colonic delivery of LGG strain after oral administration. For this purpose, spray-dried Eudragit® S100 microparticles encapsulating LGG bacteria were developed by using an aqueous based spray-drying approach, avoiding the use of organic solvents. Carbohydrates were added to the formulation since they are widely used as protective agents of bacteria against the harmful effect of dehydration stress. Here, both Surface Enhanced Raman Scattering (SERS) and conventional plate count methods showed that carbohydrates increased the survival ratio of bacteria after spray-drying from 3 to more than 50%. Moreover, these protective agents ensured low residual moisture content thus providing great stability of the cells in the spray-dried powder during storage. Significant improvement of the cell viability in simulated gastro intestinal fluid (SGIF) was observed for encapsulated cells as compared with free LGG bacteria for which no viable cell was detectable after 1 h incubation in gastric fluid only. As a consequence, 4.5 × 107 CFU/g of encapsulated LGG were found viable after incubation of microparticles 1 h in Simulated Gastric Fluid followed by 6 h in Simulated Intestinal Fluid, corresponding to less than 3 log reduction of viable cells during the 7 h incubation in Simulated Gastro Intestinal Fluid. These results attested that the developed encapsulation system is suitable for its use as a bacteria carrier for specific colonic delivery.Hypercholesterolemia has been documented to drive hormone-dependent breast cancer (BC) progression and resistance to hormonal therapy. Proprotein convertase subtilisin/kexin type-9 (PCSK9) regulates cholesterol metabolism through binding to LDL receptor (LDLR) and targeting the receptor for lysosomal degradation. Inhibition of PCSK9 is an established strategy to treat hypercholesterolemia. SAR405 mouse Pseurotin A (PS) is a unique spiro-heterocyclic γ-lactam alkaloid isolated from the fungus Aspergillus fumigatus. Preliminary studies indicated that PS lowered PCSK9 secretion in cultured HepG2 hepatocellular carcinoma cells, with an IC50 value of 1.20 μM. Docking studies suggested the ability of PS to bind at the PCSK9 narrow interface pocket that accommodates LDLR. Surface plasmon resonance (SPR) showed PS ability to inhibit the PCSK9-LDLR interaction at a concentration range of 10-150 μM. PS showed in vitro dose-dependent reduction of PCSK9, along with increased LDLR levels in hormone-dependent BT-474 and T47D breast cand any pathological changes. The results of this study provide the first evidence for the suppression of the hormone-dependent breast tumor progression and recurrence by targeting the PCSK9-LDLR axis. PS is a novel first-in-class PCSK9-targeting lead appropriate for the use to control hormone-dependent BC progression and recurrence.Secoisolariciresinol diglucoside (SDG) is the main phytoestrogen component of flaxseed known as an antioxidant. Current study focused on the effect of SDG in white adipose tissue (WAT) browning. Browning of WAT is considered as a promising treatment strategy for metabolic diseases. To demonstrate the effect of SDG as an inducer of browning, brown adipocyte markers were investigated in inguinal WAT (iWAT) of high fat diet-fed obese mice and genetically obese db/db mice after SDG administration. SDG increased thermogenic factors such as uncoupling protein 1, peroxisome proliferator-activated receptor gamma coactivator 1 alpha and PR domain containing 16 in iWAT and brown adipose tissue (BAT) of mice. Similar results were shown in beige-induced 3T3-L1 adipocytes and primary cultured brown adipocytes. Furthermore, SDG increased factors of mitochondrial biogenesis and activation. We also observed SDG-induced alteration of AMP-activated protein kinase α (AMPKα). As AMPKα is closely related in the regulation of adipogenesis and thermogenesis, we then evaluated the effect of SDG in AMPKα-inhibited conditions. Genetic or chemical inhibition of AMPKα demonstrated that the role of SDG on browning and thermogenesis was dependent on AMPKα signaling. In conclusion, our data suggest SDG as a potential candidate for improvement of obesity and other metabolic disorders.Corona virus disease (COVID-19) has now spread to all parts of the world and almost all countries are battling against it. This study aimed to assess the efficacy and safety of Integrated Traditional Chinese and Western Medicine (Hereinafter referred to as "Integrated Medicine") to COVID-19. We searched six major Chinese and English databases to identify randomized controlled trials (RCTs) and case-control studies (CCSs) of Integrated Medicine on COVID-19. Two reviewers independently screened, identified studies, and extracted data. Cochrane Risk of Bias tool and the Newcastle-Ottawa Scale were used to assess the quality of included RCTs and CCSs, respectively. Stata (version 13.0; StataCorp) was used to perform meta-analyses with the random-effects model. Risk ratio (RR) was used for dichotomous data while the weighted mean difference (WMD) was adopted for continuous variables as effect size, both of which were demonstrated in effect size and 95% confidence intervals (CI). A total of 11 studies were included. Four were RCTs and seven were CCSs. The sample size of including studies ranged from 42 to 200 (total 982). The traditional Chinese medicine included Chinese medicine compound drugs (QingFei TouXie FuZhengFang) and Chinese patent medicine (e.g. Shufeng Jiedu Capsule, Lianhua Qingwen granules). Compared with the control group, the overall response rate [RR = 1.230, 95%CI (1.113, 1.359), P = 0.000], cure rate [RR = 1.604, 95%CI (1.181, 2.177), P = 0.002], severity illness rate [RR = 0.350, 95%CI (0.154, 0.792), P = 0.012], and hospital stay [WMD = -1.991, 95%CI (-3.278, -0.703), P = 0.002] of the intervention group were better. In addition, Integrated Medicine can improve the disappearance rate of fever, cough, expectoration, fatigue, chest tightness and anorexia and reduce patients' fever, and fatigue time (P less then 0.05). This review found that Integrated Medicine had better effects and did not increase adverse drug reactions for COVID-19. More high-quality RCTs are needed in the future.