ß-Thalassemia gene editing therapy: Advancements and difficulties.

ß-Thalassemia is the world's number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of ß-pearl protein chains. This results in intramedullary destruction and premature lysis of red blood cells in peripheral blood. Among them, patients with transfusion-dependent ß-thalassemia face the problem of long-term transfusion and iron chelation therapy, which leads to clinical complications and great economic stress. As gene editing technology improves, we are seeing the dawn of a cure for the disease, with its reduction of ineffective erythropoiesis and effective prolongation of survival in critically ill patients. Here, we provide an overview of ß-thalassemia distribution and pathophysiology. In addition, we focus on gene therapy and gene editing advances. Nucleic acid endonuclease tools currently available for gene editing fall into 3 categories: zinc finger nucleases, transcription activator-like effector nucleases, and regularly interspaced short palindromic repeats (CRISPR-Cas9) nucleases. This paper reviews the exploratory applications and exploration of emerging therapeutic tools based on 3 classes of nucleic acid endonucleases in the treatment of ß-thalassemia diseases.

The Effects of Composite Alkali-Stored Spent Hypsizygus marmoreus Substrate on Carcass Quality, Rumen Fermentation, and Rumen Microbial Diversity in Goats.

The objective of this study was to investigate the effects of composite alkali-stored spent Hypsizygus marmoreus substrate (SHMS) on carcass quality, rumen fermentation, and rumen microbial diversity in goats. Twenty-four 6-month-old Chuanzhong black goats with similar body weights (20 ± 5 kg) were selected and randomly divided into four groups (n = 6 per group) and received four treatments: 0% (control group, CG); 20% (low-addition group, LG); 30% (moderate-addition group, MG); and 40% (high-addition group, HG) of SHMS-replaced silage corn and oat hay. The experiment lasted for 74 days (including a 14 d adaptation period and a 60 d treatment period). The results of this study showed that MG and HG significantly improved the marble score of goat meat (p < 0.05). The flesh color score significantly increased in each group (p < 0.05). The fat color scores significantly increased in LG and MG (p < 0.05). There were no significant effects on the pH value or shear force of the longissimus dorsi in each group (p > 0.05). The cooking loss in MG was higher than that in CG (p < 0.05). The histidine and tyrosine contents in each group of muscles significantly increased (p < 0.05), with no significant effect on fatty acids (p > 0.05). The rumen pH of MG significantly decreased (p < 0.05), while the total volatile fatty acids (TVFAs) and ammoniacal nitrogen (NH3-N) increased by 44.63% and 54.50%, respectively. The addition of the SHMS altered both the alpha and beta diversities of the rumen microbiota and significant differences in the composition and structure of the four microbial communities. The dominant bacterial phylum in each group were Firmicutes and Bacteroidetes, with Prevotella 1 as the dominant bacterial genus. Correlation analysis revealed that rumen bacteria are closely related to the animal carcass quality and rumen fermentation. In the PICRUSt prediction, 21 significantly different pathways were found, and the correlation network showed a positive correlation between the Prevotella 1 and 7 metabolic pathways, while the C5-branched dibasic acid metabolism was positively correlated with nine bacteria. In summary, feeding goats with an SHMS diet can improve the carcass quality, promote rumen fermentation, and alter the microbial structure. The research results can provide a scientific reference for the utilization of SHMS as feed in the goat industry.

Analysis of Rumen Degradation Characteristics, Attached Microbial Community, and Cellulase Activity Changes of Garlic Skin and Artemisia argyi Stalk.

The purpose of this study was to study the chemical composition, rumen degradation characteristics, surface attached microbial community and cellulase activity of garlic skin (GS) and Artemisia argyi stalk (AS), in order to explain their feeding value. Four 14-month-old healthy Min Dong male goats with permanent rumen fistula were selected as experimental animals. The rumen degradation characteristics of GS and AS were determined by using the nylon bag method, and the bacterial composition, cellulase activity and their relationship on the surface of the two groups were analyzed with high-throughput sequencing of 16S rRNA gene. The results showed that in GS and AS, the effective degradation rate (ED) values of dry matter (DM) were 42.53% and 37.12%, the ED values of crude protein (CP) were 37.19% and 43.38%, the ED values of neutral detergent fiber (NDF) were 36.83% and 36.23%, and the ED values of acid detergent fiber (ADF) were 33.81% and 34.77%. During rumen degradation, the richness and evenness of bacteria attached to the AS surface were higher. At the phylum level, Bacteroidetes and Firmicutes were always the main rumen bacteria in the two groups. At the genus level, fiber-degrading bacteria such as Prevotella, Treponema, and Ruminococcus showed higher levels in GS (p < 0.05). Compared with GS, the activity of ß-glucosidase (BG enzyme), endo-ß-1,4-glucanase (C1 enzyme), exo-ß-1,4-glucanase (Cx enzyme) and neutral xylanase (NEX enzyme) attached to AS surface showed a higher trend. Correlation analysis showed that the relative abundance of Succinivibrio and Rikenellaceae_RC9_gut_group was positively correlated with the rumen degradability of nutrients in GS, and the relative abundance of Christensenellaceae R-7_group, Succinivibrio and Ruminococcus was positively correlated with the rumen degradability of nutrients in AS. The conclusion of this study shows that AS has more potential to become ruminant roughage than GS. In addition, this study also revealed the relationship between cellulase activity and bacteria, which provided new information for us to better analyze the effects of GS and AS on the rumen of ruminants and provided an important theoretical basis for the development and utilization of agricultural by-products.

[Comparative study of reflectance spectroscopy of women's acupoints around menstruation].

Acupoint was reaction of viscera and its optical parameter was an important characteristic of tissue. In the present work, in order to discuss specificity of acupuncture on the response of qi and blood in human body, we compared the diffuse reflectance of Taichong (LV3), Taibai (SP3), and Chongyang (ST42) before, during and after menstruation. All the acupoints had the same shape of the spectrum and troughs were all at 423.16, 544.06 and 577.47 nm. The values of reflectance during menstruation were greater than before and after menstruation, especially for SP3 and ST42 (P < 0.05). SP3 and ST42 were more sensitive to the changes of qi and blood than LV3, and it was asymmetric and we found no evidence for the imbalance of the left side and right. These results indicated that acupoint diffuse reflectance changed with qi and blood, and that SP3 and ST42 had close relationship with menstruation. Diffuse reflectance may be possibly used in the quantitative analysis of qi and blood.