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Two new phytoecdysteroids, (25S)-20,22-O-(R-ethylidene)inokosterone (1) and 20,22-O-(R-3-methoxycarbonyl)propylidene-20-hydroxyecdysone (2), together with six known phytoecdysteroids 3-8 were isolated from the roots of Achyranthes bidentata Blume. The new structures were established on the basis of spectroscopic studies and chemical evidences. The absolute configuration at C-25 in the structure of known compound 3 was determined by chemical and spectroscopic means. [ABSTRACT FROM AUTHOR]

Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life. Graphical abstract of repeated subarachnoid administrations of hUC-MSCs in treating SCI. Following inclusion assessment, appropriate SCI subjects whose chronicity are no less than two months receive baseline evaluation. In this non blinded study, all participants receive a maximum of four times of administration at the interval of one calendar month each time. At each time point of stem cell transplantation and post-administration follow-up, regular follow-ups for both safety and efficacy outcomes are performed for a maximum of eight times, which is expected at the first, second, third, and fourth transplantation, as well as one, three, six and 12 months after the final hUC-MSCs transplantation Image, graphical abstract [ABSTRACT FROM AUTHOR]

Zika virus (ZIKV) was once considered an obscure member of the large and diverse family of mosquito-borne flaviviruses, and human infections with ZIKV were thought to be sporadic, with mild and self-limiting symptoms. The large-scale ZIKV epidemics in the Americas and the unexpected uncovering of a link to congenital birth defects escalated ZIKV infections to the status of a global public health emergency. Recent studies that combined reverse genetics with modelling in multiple systems have provided evidence that ZIKV has acquired additional amino acid substitutions at the same time as congenital Zika syndrome and other birth defects were detected. In this Progress article, we summarize the evolution of ZIKV during its spread from Asia to the Americas and discuss potential links to pathogenesis.