Long-term Effect of Hematopoietic Stem Cell Transplantation on the Quality of Life of Patients with ß-thalassemia Major in Guangxi, China - A Cross-sectional Study.

OBJECTIVE: The purpose of our study was to compare the quality of life (QOL) of patients with hematopoietic stem cell transplantation (HSCT) for more than 2 years for ß -thalassemia major (ß-TM) with that of ß-TM patients with conventional therapy (blood infusion and iron chelation) and that of the general population. METHODS: This was a cross-sectional comparative study on the QOL of 225 ß-TM patients treated with blood transfusion and iron chelation therapy, 133 ß-TM patients who had undergone HSCT or 270 ageand sex-matched healthy individuals from Guangxi, China. Child-self and parent-proxy reports of the PedsQL 4.0 Generic Core Scales were used to prospectively evaluate QOL. RESULTS: The incidence of acute GVHD was 14.3% (grade III-IV in 4.5% of patients), and that of chronic GVHD was 3.8%. This was lower than that of previous studies since the inclusion of anti-thymocyte globulin (ATG). Patients who underwent transplantation from a voluntary donor had higher QOL scores and lower rates of acute GVHD, chronic GVHD and comorbidities than those receiving stem cell sources from an HLA mismatched related donor (haploidentical donor). Transplants with PBSCs or UCBT, PBSCT+BMT, BMT, or BMT+UCBT as stem cell sources did not have any impact on QOL. The QOL of ß-TM patients was very similar to that of the general population. More complications (P<0.001), shorter post-transplantation time (P<0.001), and older age at HSCT (P=0.01) were associated with poorer child QOL (P=0.020). Additional analyses investigating QOL of ß-TM patients receiving conventional treatment with ß-TM revealed poorer outcomes than the cohort of transplanted patients. CONCLUSION: ß-TM patients can be cured by HSCT and regain QOL as good as that of the general population. ß-TM patients are suggested to undergo HSCT as soon as possible to avoid complications related to iron overload and blood infusion.

Advances in plant-derived C-glycosides: Phytochemistry, bioactivities, and biotechnological production.

C-glycosides represent a large group of natural products with a C-C bond between the aglycone and the sugar moiety. They exhibit great structural diversity, wide natural distribution, and significant biological activities. By the end of 2021, at least 754 C-glycosides and their derivatives have been isolated and characterized from plants. Thus far, 66 functional C-glycosyltransferases (CGTs) have been discovered from plants, and provide green and efficient approaches to synthesize C-glycosides. Herein, advances in plant-derived C-glycosides are comprehensively summarized from aspects of structural diversity and identification, bioactivities, and biotechnological production. New strategies to discover novel C-glycosides and CGTs, as well as the applications of biotechnological methods to produce C-glycosides in the future are also discussed.

GuRhaGT, a highly specific saponin 2''-O-rhamnosyltransferase from Glycyrrhiza uralensis.

A highly regio- and donor-specific 2''-O-rhamnosyltransferase GuRhaGT was characterised from the medicinal plant Glycyrrhiza uralensis. GuRhaGT could efficiently catalyse rhamnosylation at 2''-OH of the C-3 glycosyl moiety of triterpenoid saponins.

The data of an all-solid-state acupuncture needle based potentiometric microelectrode for in vivo monitoring of calcium ions in rat cerebrospinal fluid.

These data contain the details of the fabrication of the calcium ion-selective microelectrode (Ca2+-ISµEs) modified with poly(3,4-ethylenedioxythiophene)-poly(sodium 4-styrenesulfonate) (PEDOT(PSS)) as solid contact. The electrochemical impedance spectroscopy was carried out for the investigation of the resistance of the Ca2+-ISµEs. The thickness of the solid contact and the calcium ion-selective membrane was investigated by SEM. Potential-time curve of the electrodeposition of the PEDOT/PSS film onto the surface of the microelectrodes under the applied current of 0.5 µA for 200 s was recorded. The proposed Ca2+-ISµE was optimized through conditioning in different CaCl2 solutions ranged from 1.0 × 10-6 to 3.1 × 10-3 M for different time before use. The anti-fouling property of the Ca2+-ISµEs against proteins was investigated through taking BSA as the model protein. The developed Ca2+-ISµEs were used for the in vivo monitoring of the calcium ions in rat cerebrospinal fluid under the stimuli of the spinal cord transection in a living animal.

In vivo monitoring of calcium ions in rat cerebrospinal fluid using an all-solid-state acupuncture needle based potentiometric microelectrode.

Acupuncture needles are regarded as ideal materiel for the development of microelectrodes for in vivo sensing. In this work, an all-solid-state ion-selective microelectrode (ISµE) has been developed by coating a calcium ion-selective membrane on an acupuncture needle tip with a diameter of less than 80 µm, which is modified with poly(3,4-ethylenedioxythiophene)-poly(sodium 4-styrenesulfonate) as solid contact. The proposed Ca2+-ISµE shows a Nernstian response toward Ca2+ in the range from 1.0 × 10-6 to 3.1 × 10-3 M with a slope of 30.8 ± 0.9 mV/decade (R2 = 0.999), and the detection limit is 1.2 × 10-7 M. The Ca2+-ISµE has been used for in vivo monitoring of the calcium changes in rat cerebrospinal fluid (CSF) under the injury of spinal cord transection. The results demonstrate that the calcium concentration in CSF increases sharply from the normal level of 20.6 ± 1.72 µM (n = 3) to 133.2 ± 7.63 µM (n = 3) with a severe fluctuation after spinal cord damage. Thus, the proposed Ca2+-ISµE is available for in vivo monitoring of calcium ions with high temporal resolution and flexibility. The detection system can be extended to measure other ions in CSF by changing different ion-selective membranes.

A 90-day Sub-chronic Oral Toxicity Assessment of Mulberry Extract in Sprague Dawley Rats.

Mulberry extract from Fructus Mori contains an anthocyanin pigment and has been widely used as a food additive in China and other Eastern Asian countries. Only few research has been done on toxicological profiling of mulberry extract for its safety evaluation; however, the data is inconclusive. In the current study, mulberry extract of 4200, 1400, or 466 mg/kg were orally administrated to Sprague Dawley rats for 90 consecutive days followed by a recovery period of 28 days. No abnormalities were detected in body weights, food intake, ophthalmological, hematological, coagulation, clinical chemistry, and organ weights parameters. Discoloration of urine (red, purple, and brown) and feces (black), along with bedding material (purple) were observed in the 4200 mg/kg group. Further, microscopic examination revealed brown granules in the renal tubular cells for rats in 4200 and 1400 mg/kg groups. Since these changes were associated with excretory effect of the extract, the No Observed Adverse Effect Level was determined to be 4200 mg/kg, which was equivalent to the 1058.5 mg/kg of anthocyanin.

An integrated approach to reveal the chemical changes of Ligustri Lucidi Fructus during wine steaming processing.

Ligustri Lucidi Fructus (LLF) is a traditional Chinese medicine to treat osteopathic and hepatic diseases. Wine steaming is the major processing method for LLF in Chinese Pharmacopoeia, but the chemical changes involved are still unclear. In this study, a research strategy was proposed to reveal the chemical changes during wine steaming processing of LLF. Firstly, in total 104 compounds were tentatively identified using UHPLC/Orbitrap-MS. Secondly, potential chemical changes were revealed by comparing the peak areas of the 104 compounds between LLF and the corresponding wine-steamed LLF (WLLF). The results indicated that iridoid and phenylethanoid esters were readily hydrolyzed during wine steaming processing, while organic acids, flavonoids, and triterpenes were stable. Finally, 7 selected compounds were simultaneously determined in 21 batches of LLF/WLLF samples using a 10-min UPLC/UV method. The contents of 4 esters decreased from 3.64% to 2.71%, and the contents of 3 potential hydrolysis products increased from 0.27% to 0.88% after processing. Our study indicated that hydrolysis of iridoid and phenylethanoid esters such as specneuzhenide was responsible for the chemical changes during the wine processing of LLF. The proposed strategy could be employed to investigate the chemical changes of other herbs during processing.

Dissection of the general two-step di-C-glycosylation pathway for the biosynthesis of (iso)schaftosides in higher plants.

Schaftoside and isoschaftoside are bioactive natural products widely distributed in higher plants including cereal crops and medicinal herbs. Their biosynthesis may be related with plant defense. However, little is known on the glycosylation biosynthetic pathway of these flavonoid di-C-glycosides with different sugar residues. Herein, we report that the biosynthesis of (iso)schaftosides is sequentially catalyzed by two C-glycosyltransferases (CGTs), i.e., CGTa for C-glucosylation of the 2-hydroxyflavanone aglycone and CGTb for C-arabinosylation of the mono-C-glucoside. The two enzymes of the same plant exhibit high homology but remarkably different sugar acceptor and donor selectivities. A total of 14 CGTa and CGTb enzymes were cloned and characterized from seven dicot and monocot plants, including Scutellaria baicalensis, Glycyrrhiza uralensis, Oryza sativa ssp. japonica, and Zea mays, and the in vivo functions for three enzymes were verified by RNA interference and overexpression. Through transcriptome analysis, we found homologous genes in 119 other plants, indicating this pathway is general for the biosynthesis of (iso)schaftosides. Furthermore, we resolved the crystal structures of five CGTs and realized the functional switch of SbCGTb to SbCGTa by structural analysis and mutagenesis of key amino acids. The CGT enzymes discovered in this paper allow efficient synthesis of (iso)schaftosides, and the general glycosylation pathway presents a platform to study the chemical defense mechanisms of higher plants.

Metatranscriptome analysis reveals environmental and diel regulation of a Heterosigma akashiwo (raphidophyceae) bloom.

Despite numerous laboratory studies on physiologies of harmful algal bloom (HAB) species, physiologies of these algae during a natural bloom are understudied. Here, we investigated a bloom of the raphidophyte Heterosigma akashiwo in the East China Sea in 2014 using metabarcode (18S rDNA) and metatranscriptome sequencing. Based on 18S rDNA analyses, the phytoplankton community shifted from high diversity in the pre-bloom stage to H. akashiwo predominance during the bloom. A sharp decrease in ambient dissolved inorganic phosphate and strong up-regulation of phosphate and dissolved organic phosphorus (DOP) uptake genes, including the rarely documented (ppGpp)ase, in H. akashiwo from pre-bloom to bloom was indicative of rapid phosphorus uptake and efficient utilization of DOP that might be a driver of the H. akashiwo bloom. Furthermore, observed up-regulated expression of mixotrophy-related genes suggests potential contribution of mixotrophy to the bloom. Accelerating photosynthetic carbon fixation was also implied by the up-regulation of carbonic anhydrase genes during the bloom. Notably, we also observed a strong morning-to-afternoon shift in the expression of many genes. Our findings provide insights into metabolic processes likely important for H. akashiwo bloom formation, and suggest the need to consider timing of sampling in field studies on this alga.

High-throughput high-content imaging assays for identification and characterization of selective AXL pathway inhibitors.

Receptor tyrosine kinases (RTKs) regulate a wide range of important biological activities, including cell proliferation, differentiation, migration, and apoptosis. Abnormalities in RTKs are involved in numerous diseases, including cancer and other proliferative disorders. AXL belongs to the TAM (Tyso3, AXL, and Mer) family of RTKs. The AXL signaling pathway represents an attractive target for the treatment of diseases, such as cancer. Using phospho-AKT as readout, a high-throughput 384-well cell-based assay was established in the NCI-H1299 human non-small cell lung carcinoma cell line to evaluate compound potency in inhibiting AXL pathway activation. In addition, a counter screen assay was established in the same cellular background to differentiate AXL kinase inhibitors from AXL receptor antagonists, which block the interaction of AXL and its natural ligand GAS6. These cell-based functional assays are useful tools in the identification and optimization of small molecules and biological reagents for potential therapeutics for the treatment of GAS6/AXL-related diseases.