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Vitamins maintain growth and development in humans, animals, and plants. Because plants serve as essential producers of vitamins, increasing the vitamin contents in plants has become a goal of crop breeding worldwide. Here, we begin with a summary of the functions of vitamins. We then review the achievements to date in elucidating the molecular mechanisms underlying how vitamins are synthesized, transported, and regulated in plants. We also stress the exploration of variation in vitamins by the use of forward genetic approaches, such as quantitative trait locus mapping and genome-wide association studies. Overall, we conclude that exploring the diversity of vitamins could provide new insights into plant metabolism and crop breeding.
High-frequency oscillatory ventilation (HFOV) can have negative hemodynamic effects in neonates. We aimed to assess systemic, cerebral, and cardiac hemodynamic changes in preterm neonates with respiratory distress syndrome (RDS) on HFOV.

This observational study was conducted from June 2017 until May 2019 on 100 preterm neonates with RDS that needed switching from conventional mechanical ventilation to HFOV. Initial and Follow up capillary blood gas, echocardiographic examination, cranial ultrasound, and Doppler study of cerebral, celiac, superior mesenteric, and renal arteries using resistive index (RI) were performed before, 24 h, and 72 h after the use of HFOV.

There was no statistically significant difference as regards cardiac function, heart rate, or intraventricular hemorrhage on follow up measurements. However blood pressure, left ventricular dimensions, and volumes statistically increased after HFOV. There was a statistically significant decrease in the pulmonary artery systolic pressure after the use of HFOV. After the use of HFOV, there was a statistically significant increase in the superior vena cava flow and left ventricular output while right ventricular output values initially increased then slightly decreased but still higher than the initial values. RI of cerebral, superior mesenteric, celiac, and renal arteries significantly decreased on follow up measurements which reflected increased blood flow in these arteries.

HFOV had no negative effect on the cerebral, systemic, or cardiac hemodynamics when applied at optimum MAP. Therefore, concerns about negative hemodynamic effects of HFOV should not discourage the use of HFOV when deemed clinically indicated provided the use of optimum MAP.
HFOV had no negative effect on the cerebral, systemic, or cardiac hemodynamics when applied at optimum MAP. Therefore, concerns about negative hemodynamic effects of HFOV should not discourage the use of HFOV when deemed clinically indicated provided the use of optimum MAP.The emergence of multidrug resistance (MDR) in Proteus mirabilis clinical isolates is a growing public health concern and has serious implications for wildlife. What is the role of wildlife has been become one of the hot issues in disseminating antimicrobial resistance (AMR). Here, fifty-four P.mirabilis isolates from 12 different species were identified. Among them, 25 isolates were determined to be MDR by profile of antimicrobial susceptibility, 10 MDR P.mirabilis isolates were subjected to comparative genomic analysis by whole genome sequencing (WGS). Comprehensive analysis showed that chromosome of P.mirabilis isolates mainly carries multidrug-resistance complex elements harboring resistance to carbapenems genes blaOXA-1, blaNDM-1 and blaTEM-1. Class I integron is the insertion hotspot of IS26, it can be inserted into type I integron at different sites, thus forming a variety of multiple drug resistance decision sites. At the same time, Tn21, Tn7, SXT / R391 Mobile elements cause widespread spread of this drug resistance genes. In conclusion, P.mirabilis isolates from wildlife showed higher resistance to commonly used clinic drugs comparing to those from human. Therefore, wild animals carrying multidrug resistance (MDR) clinical isolates should be paid attention to by the public health. This article is protected by copyright. All rights reserved.Leukemic stem cells (LSCs) comprise a very rare cell population that results in the development of acute myeloid leukemia. The selective targeting of drivers in LSCs with small molecule inhibitors holds promise for treatment of acute myeloid leukemia. Recently, we reported the identification of inhibitors of the histone lysine demethylase JMJD1C that preferentially kill MLL rearranged acute leukemia cells. Here, we report the identification of jumonji domain modulator #7 (JDM-7). Surface plasmon resonance analysis showed that JDM-7 binds to JMJD1C and its family homolog JMJD1B. JDM-7 did not significantly suppress cell proliferation in liquid cell culture at higher doses, although it led to a significant decrease in semi-solid colony formation experiments at lower concentrations. Moreover, low doses of JDM-7 did not suppress the proliferation of erythroid progenitor cells. We identified that JDM-7 downregulates the LSC self-renewal gene HOXA9 in leukemia cells. We further found that the structure of JDM-7 is similar to that of tadalafil, a drug approved by the US Food and Drug Administration. Molecular docking and surface plasmon resonance analysis showed that tadalafil binds to JMJD1C. Moreover, similar to JDM-7, tadalafil suppressed colony formation of leukemia cells in semi-solid cell culture at a concentration that did not affect primary umbilical cord blood cells. In summary, we have identified JDM-7 and tadalafil as potential JMJD1C modulators that selectively inhibit the growth of LSCs.
We reviewed our experience treating patients with localized extraskeletal Ewing sarcoma (EES) to determine optimal local management strategies for this rare disease.

Sixty patients with localized EES treated at our institution between 1994 and 2018 were reviewed. The Kaplan-Meier method was used to estimates disease outcomes.

The median follow-up time was 74 months (interquartile range [IQR], 17-121). Half the patients (n = 30) received combined-modality local therapy (CMT) with both surgery and radiation therapy (RT), whereas the other half received single-modality local therapy (SMT) with either surgery or RT. All patients received chemotherapy. The 5-year overall survival was 76%. Twenty-two patients (37%) developed recurrence at a median time of 15 months (IQR, 5-56 months) resulting in 3-year progression-free survival (PFS) of 65%. On univariate analysis, the use of both neoadjuvant and adjuvant chemotherapy was associated with improved 5-year PFS (71% vs. 50%, p = .04) compared with those who recelocal therapy is likely adequate in select patients with favorable disease features, which has the advantage of ensuring prompt administration of systemic therapy. A multi-institutional collaborative effort is warranted to determine which patients may benefit from de-escalated local therapy.
Extraskeletal Ewing sarcoma is a rare chemosensitive sarcoma whose clinical course more closely follows Ewing sarcoma of bone rather than that of other soft tissue sarcomas. Based on this study, combined-modality local therapy did not confer a local control advantage compared with single-modality local therapy. Therefore, single-modality local therapy is likely adequate in select patients with favorable disease features, which has the advantage of ensuring prompt administration of systemic therapy. A multi-institutional collaborative effort is warranted to determine which patients may benefit from de-escalated local therapy.Sotagliflozin, a dual sodium-glucose co-transporter (SGLT)1/SGLT2 inhibitor, is currently approved in Europe as an adjunct to optimal insulin therapy in adults with type 1 diabetes (T1D) and a body mass index (BMI) ≥ 27 kg/m2 . In this post hoc analysis, efficacy at 24 weeks and safety at 52 weeks from pooled phase 3 clinical trials were evaluated in patients with baseline BMI ≥ 27 kg/m2 . Sotagliflozin 200 mg and 400 mg added to insulin reduced glycated haemoglobin level and increased time in range assessed by continuous glucose monitoring versus placebo and also reduced body weight and systolic blood pressure. Differences in efficacy endpoints between sotagliflozin and placebo tended to be greater among patients with BMI ≥ 27 kg/m2 compared to those with baseline BMI less then  27 kg/m2 . Consistent with published results for the entire population, fewer severe hypoglycaemia and documented hypoglycaemia ≤3.1 mmol/L events and a higher incidence of diabetic ketoacidosis occurred with sotagliflozin versus placebo in patients with BMI ≥ 27 kg/m2 . Sotagliflozin as an adjunct to optimized insulin therapy in overweight/obese patients with T1D addressed some unmet needs and may help achieve optimal glycaemic control, mitigating weight gain without increasing hypoglycaemia risk in this high-risk population.Quick identification of the complex composition of traditional Chinese medicine only through liquid-mass spectrometry technology is difficult. Especially the identification of isomers and co-eluting compounds is even more difficult. In this study, an approach of multidimensional data modes based on ultra-performance liquid chromatography coupled with traveling wave ion mobility quadrupole time-of-flight mass spectrometry was proposed to quickly and comprehensively identify the compounds in Platycodi Radix. First, data-independent acquisition, high-definition acquisition, and tandem mass spectrometry acquisition modes were used to acquire integrated multidimensional mass spectral data. Second, summarize the diagnostic ions of compounds according to the fragmentation pathway of references. Third, unknown compounds and isomers were identified via the UNIFI™ software with an in-house library. Finally, a total of 87 compounds were identified, seven compounds were explicitly identified by comparing the retention time and fragment ions with the references. Fourteen compounds were first detected in the Platycodi Radix, four of them tentatively were identified by comparing with previous literature, eight compounds were observed and reported for the first time by comparing typical fragmentation pathway with the known standard substances in this paper. This research strategy has a certain potential for the analysis of complex components of other traditional Chinese medicine.In this study, we investigated the ability of the Polysaccharide from the Eggs of Strongylocentrotus nudus (SEP) to regulate cellular autophagy and apoptosis in leukaemia cells. Human acute myeloid leukaemia (AML) cells (HL60) and murine AML cells (L1210) treated with SEP were used to assess viability using Cell Counting Kit-8, cytotoxicity by measuring lactate dehydrogenase release, the generation of reactive oxygen species (ROS) by DCFH-DA staining. In addition, we utilized a mouse model of leukaemia in which L1210 cells were injected into DBA/2 mice by sub-axillary injection. Treatment with SEP decreased cell viability, increased in cytotoxicity and increased the release of ROS in a dose-dependent manner. SEP treatment was also associated with the activation of pro-apoptotic proteins cleaved caspase-3, cleaved caspase-9 and cleaved poly (ADP-ribose) polymerase (PARP). click here Activation of the apoptotic pathway led to the release of cytochrome C (CytoC) into the cytosol of the cell resulting in decreased membrane potential.
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