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Abstract Background α-1-syntrophin (SNTA1), a protein encoded by SNTA1, is highly expressed in human cardiomyocytes. Mutations in SNTA1 are associated with arrhythmia and cardiomyopathy. Previous research on SNTA1 has been based on non-human cardiomyocytes. This study was designed to identify the phenotype of SNTA1-deficiency using human cardiomyocytes. Methods SNTA1 was knocked out in the H9 embryonic stem cell line using the CRISPR-Cas9 system. H9SNTA1KO cells were then induced to differentiate into cardiomyocytes using small molecule inhibitors. The phenotypic discrepancies associated with SNTA1-deficient cardiomyocytes were investigated. Results SNTA1 was truncated at the 149th amino acid position of PH1 domain by a stop codon (TGA) using the CRISPR-Cas9 system. SNTA1-deficiency did not affect the pluripotency of H9SNTA1KO, and they retain their in vitro ability to differentiate into cardiomyocytes. However, H9SNTA1KO derived cardiomyocytes exhibited hypertrophic phenotype, lower cardiac contractility, weak calcium transient intensity, and lower level of calcium in the sarcoplasmic reticulum. Early treatment of SNTA1-deficient cardiomyocytes with ranolazine improved the calcium transient intensity and cardiac contractility. Conclusion SNTA1-deficient cardiomyocytes can be used to research the etiology, pathogenesis, and potential therapies for myocardial diseases. The SNTA1-deficient cardiomyocyte model suggests that the maintenance of cardiac calcium homeostasis is a key target in the treatment of myocardial-related diseases.

BackgroundNeuromyelitis Optica spectrum disorder (NMOSD) is severe relapsing and disabling autoimmune disease of the central nervous system. Its optimal first-line treatment to reduce relapse rate and ameliorate neurological disability remains unclear. We will conduct a prospective, multicenter, randomized, placebo-controlled clinical trial to study the safety and effectiveness of human umbilical cord mesenchymal stem cells (hUC–MSCs) in treating NMOSD.MethodsThe trial is planned to recruit 430 AQP4-IgG seropositive NMOSD patients. It consists of three consecutive stages. The first stage will be carried out in the leading center only and aims to evaluate the safety of hUC—MSCs. Patients will be treated with three different doses of hUC–MSCs: 1, 2, or 5 × 106 MSC/kg·weight for the low-, medium-, and high-dose group, respectively. The second and third stages will be carried out in six centers. The second stage aims to find the optimal dosage. Patients will be 1:1:1:1 randomized into the low-, medium-, high-dose group and the controlled group. The third stage aims to evaluate the effectiveness. Patients will be 1:1 randomized into the optimal dose and the controlled group. The primary endpoint is the first recurrent time and secondary endpoints are the recurrent times, EDSS scores, MRI lesion numbers, OSIS scores, Hauser walking index, and SF-36 scores. Endpoint events and side effects will be evaluated every 3 months for 2 years.DiscussionAlthough hUC–MSC has shown promising treatment effects of NMOSD in preclinical studies, there is still a lack of well-designed clinical trials to evaluate the safety and effectiveness of hUC–MSC among NMOSD patients. As far as we know, this trial will be the first one to systematically demonstrate the clinical safety and efficacy of hUC–MSC in treating NMOSD and might be able to determine the optimal dose of hUC–MSC for NMOSD patients.Trial registrationThe study was registered with the Chinese Clinical Trial Registry (CHICTR.org.cn) on 2 March 2016 (registration No. ChiCTR-INR-16008037), and the revised trial protocol (Protocol version 1.2.1) was released on 16 March 2020.

Background and AimEndoscopic submucosal excavation (ESE) is commonly used to treat gastrointestinal stromal tumors (GISTs), especially for tumor sizes within 2 cm; compared with the conventical ESE, the efficacy and safety of the no-submucosal injection (NSI) ESE remains unclear. The aim of this study was to assess the clinical efficacy and safety of NSI-ESE for gastric stromal tumors.MethodsESE was performed in 102 patients at our hospital between January 2018 and January 2020, and the clinical features, surgical outcomes, complications, cost of performance, pathological diagnosis, and risk classification were evaluated.ResultsAll tumors were completely resected by endoscopic resection (ER), with a complete resection rate of 100%. It was achieved by ESE/EFTR (endoscopic full-thickness resection) in 49 cases with submucosal injection, and by ESE/EFTR in 53 cases with NSI-ESE. The mean surgical time in cases with submucosal injection was 25.86 ± 4.45 min, compared to the cases without submucosal injection (17.23 ± 3.47 min), and the difference was significant (p < 0.001); the exposure time of tumor, the time of complete excavation of tumor, procedure cost, and hospital stay in the NSI-ESE group were all lower than those cases with submucosal injection (p < 0.05). In the risk classification, 95 (93.1%) cases had a very low risk, 4 (4.0%) cases had a low risk, and 2 (2.0%) cases had a high risk. No recurrence or metastasis was observed during the follow-up period of 18 ± 6 months (range: 13–25 months).ConclusionsNSI-ESE is a feasible, effective, and safe treatment for gastric GISTs; compared to the conventional ESE, NSI-ESE has the following advantages: it decreases procedure time, it lowers the risk of perforation, and it is cost-effective.

Megalurothrips usitatus and Liriomyza trifolii are the main pests on cowpea crops. Developing green technology to control these pests is urgently needed, because they have developed high-level resistance to most insecticides. In this study, a self-developed UV-absorbing film greenhouse (UV-FG) was constructed, and its effects on controlling pests and plant quality were evaluated. The results showed that UV-FG could significantly reduce M. usitatus and L. trifolii populations. The height of cowpea in UV-FG was significantly higher than that in conventional greenhouse (C-FG) from the flowering stage to the harvest stage (p < 0.05). The average yield in UV-FG was 1199.67 kg per 667 m2, which was more than 10% higher than those in other treatments, and the single fruit weight and length of harvest period in UV-FG were significantly higher or longer than those of other treatments (p < 0.05). The contents of intrinsic nutrients showed no substantial differences between UV-FG and C-FG. The use of UV-FG could significantly reduce pest outbreak, improve crop yield, and greatly reduce pesticide residues. Our results showed that UV-blocking materials could become a valuable strategy for the integrated management of M. usitatus and L. trifolii in plants grown in enclosed environments. [ABSTRACT FROM AUTHOR]

Nausea and vomiting are one of the major complications of chemotherapy for cancers. The aim of this study is to investigate the emetic effects and mechanisms involving serotonin and dopamine of needleless transcutaneous electroacupuncture (TEA) at Neiguan (PC6) and Jianshi (PC5) on chemotherapy-induced nausea and vomiting in patients with cancers. Seventy-two patients with chemotherapy were randomly divided into sham-TEA group (sham-TEA, n = 34) and TEA group (n = 38). TEA was performed at PC 6 and PC 5 (1 h, bid) in combination with granisetron. Sham-TEA was delivered at nonacupoints using the same parameters. We found the following. (1) In the acute phase, the conventional antiemetic therapy using Ondansetron effectively reduced nausea and vomiting; the addition of TEA did not show any additive effects. In the delayed phase, however, TEA significantly increased the rate of complete control (P < 0.01) and reduced the nausea score (P < 0.05), compared with sham- TEA. (2) TEA significantly reduced serumlevels of 5-HT and dopamine in comparison with sham-TEA. Those results demonstrate that needleless transcutaneous electroacupuncture at PC6 using a watch-size digital stimulator improves emesis and reduces nausea in the delayed phase of chemotherapy in patients with cancers. This antiemetic effect is possibly mediated viamechanisms involving serotonin and dopamine. [ABSTRACT FROM AUTHOR]

The present study compared the developmental ability and gene expression pattern at 4‐cell, 8‐cell, morula, and blastocyst stages of porcine nuclear transfer (NT) embryos from fetal fibroblasts (FFs) and mesenchymal stem cells (MSCs), in vitro fertilized (IVF), and in vivo derived embryos. MSC‐NT embryos showed enhanced blastocyst formation, higher total cell number, and a low incidence of apoptosis compared to FF‐NT embryos. Alterations in the expression pattern of genes implicated in transcription and pluripotency (Oct4, Stat3, Nanog), DNA methylation (Dnmt1, Dnmt3a), histone deacetylation (Hdac2), growth factor signaling, and imprinting (Igf2, Igf2r) and apoptosis (Bax, Bcl2) regulation were observed in NT embryos. The expression of transcripts in MSC‐NT embryos more closely followed that of the in vivo derived embryos compared with FF‐NT embryos. In conclusion, MSCs with a relatively undifferentiated genome might serve as suitable donors that could be more efficiently reprogrammed to re‐activate expression of early embryonic genes in porcine NT. Developmental Dynamics 236:435–446, 2007. © 2006 Wiley‐Liss, Inc. [ABSTRACT FROM AUTHOR]

In the present study, we have characterized an isolated population of porcine bone marrow mesenchymal stem cells (MSCs) for multilineage commitment and compared the developmental potential of cloned embryos with porcine MSCs and fetal fibroblasts (FFs). MSCs exhibited robust alkaline phosphatase activity and later transformed into mineralized nodules following osteoinduction. Furthermore, MSCs underwent adipogenic and chondrogenic differentiation by producing lipid droplets and proteoglycans, respectively. Primary cultures of FFs from a female fetus at ∼30 day of gestation were established. Donor cells at 3-4 passage were employed for nuclear transfer (NT). Cell cycle analysis showed that the majority of MSCs in confluence were in the G0/G1 stage. Cumulus-oocyte complexes were matured and fertilized in vitro (IVF) as control. The cleavage rate was significantly (P<0.05) higher in IVF than in NT embryos with MSCs and FFs (84.5±4.6% vs. 52.2±5.4% and 50.8±5.2%, respectively). However, blastocyst rates in IVF and NT embryos derived from MSCs (20.6±2.5% and 18.4±3.0%) did not differ, but were significantly (P<0.05) higher than NT derived from FFs (9.5±2.1%). Total cell number and the ratio of ICM to total cells among blastocysts cloned from MSCs (34.4±5.2 and 0.38±0.08, respectively) were significantly (P<0.05) higher than those from FFs (22.6±5.5 and 0.18±0.12, respectively). Proportions of TUNEL positive cells in NT embryos from FFs (7.3±1.8%) were significantly (P<0.05) higher than in MSCs (4.6±1.3%) and IVF (2.5±0.9%). The results clearly demonstrate that multipotent bone marrow MSCs have a greater potential as donor cells than FFs in achieving enhanced production of cloned porcine embryos. [ABSTRACT FROM AUTHOR]

In this study, the effects of nitrate feeding on microalgal growth and associated CO2 fixation were evaluated, as a strategy to enhance carbon fixation by increasing the duration of the exponential phase of cell growth in the batch operation of a photobioreactor. Two species of green algae, Chlorella and Scenedesmus, and two species of cyanobacteria, Microcystis ichthyoblabe and Microcystis aeruginosa, were used after adaptation to a 15% (v/v) CO2 environment. In the absence of nitrate feeding, nitrate concentrations declined rapidly and soon became a limiting factor. Nitrate feeding, administered in fed-batch mode to maintain 15–20 ppm of NO3-N, allowed for an extension of the exponential growth phase by more than 3 days, as well as a higher cell density, which subsequently resulted in an increase in photoautotrophic carbon fixation. The increases in the carbon fixation rate were in the ranges of 56.1–56.6% for the green algae, and between 68.2–68.8% for the cyanobacteria. The results indicated that intermittent nitrate feeding was a viable strategy for the augmentation of fixation productivity, and may thus be effectively applied as a substitute for conventional medium change, which has traditionally been employed in order to prolong the active growth duration. [ABSTRACT FROM AUTHOR]