Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity.

During spaceflight, the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling. Therefore, the effects and mechanisms of microgravity on cardiac morphology, physiology, metabolism, and cellular biology need to be further investigated. Since China started constructing the China Space Station (CSS) in 2021, we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) to the Tianhe core module of the CSS. In this study, hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling. Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight, especially thiamine metabolism. The microgravity condition blocked the thiamine intake in hPSC-CMs. The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle. It decreased ATP production, which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs. More importantly, in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity. This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research. These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

Repetitive Transcranial Magnetic Stimulation Improves Neuropathy and Oxidative Stress Levels in Rats with Experimental Cerebral Infarction through the Nrf2 Signaling Pathway.

Ischemic stroke poses a serious threat to human health. Its high morbidity, disability, and lethality rates have led to it being a research hotspot. Cerebral ischemia reperfusion injury is a difficult point in the treatment of ischemic stroke. In recent years, studies have shown that repeated transcranial magnetic stimulation (rTMS) can enhance cerebral ischemic tolerance and have a significant protective effect on reperfusion injury after ischemia, but its specific mechanism is unknown. The Nrf2/pathway plays a vital role in ischemia-reperfusion injury in the body environment. Therefore, in this experiment, the middle cerebral artery occlusion (MCAO) reperfusion model of SD rats was made to simulate the occurrence of experimental cerebral infarction by the suture method. After treatment with rTMS, it was studied whether it can regulate the expression of Nrf2 and HO-1, affect the content of MDA and SOD activity, and then activate the Nrf2 pathway to exert its brain protection. The results showed that after MCAO reperfusion, the neurological deficit score of rats increased, and the time to remove the bilateral stickers and the time to cross the balance beam increased, suggesting the successful establishment of the experimental cerebral infarction model. Detecting the brain tissue of experimental cerebral infarction rats found that the expression of Nrf2 and HO-1 decreased, the content of MDA increased, and the activity of SOD decreased. After rTMS treatment, the neuromotor function of experimental cerebral infarction rats improved, the expression of Nrf2 and HO-1 in the brain tissue gradually increased, the content of MDA decreased, and the activity of SOD increased. It indicates that the expression of Nrf2 and HO-1 in experimental cerebral infarction rats is reduced. After treatment with rTMS, it can improve the neuromotor function damage of the rats and reduce the level of oxidative stress. The mechanism may be through promoting the activation of the Nrf2 signaling pathway, acting on the expression of antioxidant proteins, such as HO-1 and SOD1, reducing oxidative stress damage, and playing a protective effect on brain tissue.

Sodium butyrate ameliorates Corynebacterium pseudotuberculosis infection in RAW264.7 macrophages and C57BL/6 mice.

Corynebacterium pseudotuberculosis (CP) infection in livestock has become highly difficult to control. To decrease the incidence of CP infection, the supplementation of feed with non-antibiotic antibacterial substances is a potential approach. The aim of this study was to assess the effects of sodium butyrate (NaB), a potential alternative to antibiotics, on CP infection in RAW264.7 macrophages and C57BL/6 mice. Our data showed that NaB (2 mM) significantly ameliorated CPinfection in RAW264.7 macrophages and decreased the bacterial load in the spleens of infected mice. By real-time PCR, we found that NaB induced significant decreases in zinc-dependent superoxide dismutase (sodC) and tip protein C (spaC) expression in CP from infected-RAW264.7 cells and in phospholipase D (pld) and spaC expression in CP from the spleens of infected mice. NaB treatment significantly up-regulated cathelicidin-related antimicrobial peptide (cramp) expression in spleens of mice infected with CP. Furthermore, NaB alleviated histopathological changes in spleens of CP-infected mice. In conclusion, NaB ameliorated CP infection in RAW264.7 macrophages and C57BL/6 mice, and these effects may be related to the modulation of sodC, spaC, pld, and cramp expression.

Strategy of treating secundum atrial septal defect not referred to percutaneous closure.

OBJECTIVE: To evaluate safety and effectiveness of intraoperative device closure for secundum atrial septal defect (ASD) not referred to percutaneous closure. DESIGN AND PATIENTS: From April 2010 to December 2018, 231 secundum ASD children (≤14 years) directly recommended to surgical repair were enrolled in this study. These patients were divided into two groups according to the parents' choice based on surgeons' recommendation. Follow-up evaluations were adopted at 2 weeks, 3 months, 6 months, and 12 months after the procedure and yearly thereafter. In Group A, 127 patients underwent an initial attempt at device closure. In Group B, 104 patients underwent a repair procedure under cardiopulmonary bypass. RESULTS: All patients survived. Group A had lower values of operation time, mechanical ventilation time, cardiac intensive care unit duration and amount of blood transfusion. Nevertheless, postoperative hospitalization time between two groups showed no statistical difference. In group A, 109 (85.83%) patients were successfully occluded, whereas 18 (14.17%) patients were converted to open-heart surgery. No severe complications occurred in the follow-up period. CONCLUSION: Intraoperative device closure is safe, effective procedure for selected cases with secundum ASDs which were not referred to percutaneous closure because of more suitable occluder selection, no "unbutton effect" and stitching enhancement.

Changes of cecal microflora in chickens following Eimeria tenella challenge and regulating effect of coated sodium butyrate.

Eimeria tenella, one of the most important parasitic protozoa in the genus Eimeria, is responsible for chicken caecal coccidiosis resulting in huge economic losses to poultry industry. The present study investigated the changes in caecal microflora of E. tenella-infected chickens and the regulating effect of coated sodium butyrate, a potential alternative to antibiotics. Using high-throughput sequencing of 16S rRNA V3-V4 region of bacteria we found significant changes in caecal microflora of E. tenella-infected chickens indicated by an increase of Firmicutes (mainly Ruminococcaceae, Lachnospiraceae and vadin BB60) and Proteobacteria (mainly Enterobacteriaceae) and a decrease of Bacteroidetes (predominantly Bacteroidaceae). Inclusion of coated sodium butyrate in the diet of chickens per se had no significant effect on caecal microflora of normal healthy chickens but significantly prevented the increase in Firmicute abundance and decrease of Bacteroidetes abundance in E. tenella-infected birds. No significant changes to caecal microflora were observed at the phylum level between control and E. tenella-infected birds given coated sodium butyrate. In conclusion, our results show that coated sodium butyrate can balance the disorders of cecal microflora caused by E. tenella; thus, it can be a useful supplement for the control of avian coccidiosis.

Role of 5-aminolevulinic acid in the salinity stress response of the seeds and seedlings of the medicinal plant Cassia obtusifolia L.

BACKGROUND: Soil salinity, one of the major abiotic stresses affecting germination, crop growth, and productivity, is a common adverse environmental factor. The possibility of enhancing the salinity stress tolerance of Cassia obtusifolia L. seeds and seedlings by the exogenous application of 5-aminolevulinic acid (ALA) was investigated. RESULT: To improve the salinity tolerance of seeds, ALA was applied in various concentrations (5, 10, 15, and 20 mg/L). To improve the salinity tolerance of seedlings, ALA was applied in various concentrations (10, 25, 50, and 100 mg/L). After 10 mg/L ALA treatment, physiological indices of seed germination (i.e., germination vigor, germination rate, germination index, and vigor index) significantly improved. At 25 mg/L ALA, there was a significant protection against salinity stress compared with non-ALA-treated seedlings. Chlorophyll content, total soluble sugars, free proline, and soluble protein contents were significantly enhanced. Increased thiobarbituric acid reactive species and membrane permeability levels were also inhibited with the ALA treatment. With the treatments of ALA, the levels of chlorophyll fluorescence parameters, i.e., the photochemical efficiency of photosystem II (Fv/Fm), photochemical efficiency (Fv'/Fm'), PSII actual photochemical efficiency (ΦPSII), and photochemical quench coefficient (qP), all significantly increased. In contrast, the non-photochemical quenching coefficient (NPQ) decreased. ALA treatment also enhanced the activities of superoxide dismutase, peroxidase, and catalase in seedling leaves. The highest salinity tolerance was obtained at 25 mg/L ALA treatment. CONCLUSION: The plant growth regulator ALA could be effectively used to protect C. obtusifolia seeds and seedlings from the damaging effects of salinity stress without adversely affecting plant growth.

[Effect of exogenous carbon monoxide donor hematin on seed germination and physiological characteristics of Cassia obtusifolia seedlings under NaCl stress].

OBJECTIVE: In order to get the method to improve the salt resistance of seeds and seedlings for Cassia obtusbifolia under NaCl stress, seed germination and physiological characteristics of C. obtusifolia seedlings were studied. METHOD: Several physiological indexes of C. obtusifolia seeds treated with exogenous carbon monoxide donor hematin under NaCl stress like the germination vigor, germination rate, germination index and vigor index were measured. And other indexes like the relative water content, the contents of photosynthetic pigment, chlorophyll fluorescence parameters, the contents of soluble sugar, protein and proline, malondialdehyde (MDA), the activities of superoxide (SOD), peroxidase (POD) and catalase (CAT) were also measured. RESULT: The germination indexes of C. obtusifolia seeds under NaCl stress had been inhibited obviously. But after the treatment of hematin, every germination indexes were all increased. The result showed that the treatment of exogenous CO donor hematin obviously improved the germination vigor, germination rate, germination index and vigor index, increased the content of chlorophyll a, chlorophyll b, total chlorophyll, improved the photochemical efficiency of photosystem II (Fv/Fm), photochemical efficiency (Fv'/Fm'), PS II actual photochemical efficiency (phiPS II), photochemical quench coefficient (qP), decreased non-photochemical quenching coefficient (NPQ) and the content of malondialdehyde (MDA) , increased the relative water content of leaves and the content of soluble surge, protein and proline. Meanwhile, the results also indicated that CO improved the activities of superoxide (SOD), peroxidase (POD) and catalase (CAT). The effects of CO could be reversed when CO scavenger Hb is added. CONCLUSION: Exogenous CO donor hematin with appropriate concentration could significantly alleviate the damages to the seeds and seedlings of C. obtusifolia under NaCl stress and promote the salt resistance of the seeds and seedlings through improving the germination indexes, the photochemical efficiency and the antioxidase activities of the seedlings.

[Effects of "3414" fertilizer application on the yield of Fagopyrum cymosum].

OBJECTIVE: To study the effects of different fertilizer applications on the yield of Fagopyrum cymosum and explore the hese scheme for getting the maximum yield on purple soil in the Chongqing-west. METHODS: Experiment with implementing plan of "3414"; The quality Assessment by the contents of bipoly-chrysanthemin; The data process program under the Excel 2003, SPSS 13.0, MatlaB 7.0, Word 2003 environments. RESULTS: Various fertilizer combinations had different transformation efficiency which the N3P2K2 combination was the maximum 97.09% and the NOP2K2 combination was the minimum 4.32%; The NOP2K2 combination had the lowest yield except of the bland group which was 186 kg/667 m2; When the N fertilizer Rate was controlled in the level of 15 kg/667 m2 The yied had no obvious change as the increase of another two kinds fertilizer rate; Three kinds of function could better reflect the relationships between fertilizer and yields, which all of the R2 value were above 0.88; The best one was N K function with the maximum R2; The blank group had maximum content 8.67% of bipoly-chrysanthemin and the content had a little decrease as the increase of N or K, but all higher than 7.14% which were planted in Bei Jing area. CONCLUSIONS: Various fertilizer combinations influenced the transformation efficiency of N, P, K;N is the key fertilizer on purple soil; Reconmentation funtion was N,K function which could be as the guiding function; F; Fertilizer would not influence the quality of Fagopyrum cymosum.

[Effect of zinc sulphate and PEG priming on ageing seed germination and antioxidase activities of Perilla frutescens seedlings].

OBJECTIVE: To explore the method for improving the aging resistance of seeds and seedlings of Perilla frutescens through study on seed germination and physiological characteristics of P. frutescens seedlings. METHOD: Several physiological indexes of P. frutescens seeds treated by different concentrations of ZnSO4 and PEG were measured. And other indexes like the activities of malondialdehyde (MDA), superoxide (SOD), peroxidase (POD) and catalase (CAT) were also determined. RESULT: The germination indexes of P. frutescens aging seeds treated by different concentrations of ZnSO4 and PEG were all increased. And the seeds that treated by ZnSO4 (600 mg x L(-1)) and PEG (20%) showed the most significantly increase in every index. The germination vigor were 64.7% and 66.8%, the germination rate were 78.7% and 79.4%, the germination index were 11.8 and 12.2, the vigor index were 0.091 1 and 0.0939 respectively. The content of MDA was decreased under different treatment. The activities of three enzymes include SOD, POD and CAT were increased by different treatment of ZnSO4 (0.28, 4.71, 3.82 U x mg(-1) respectively) and PEG (0.29, 4.93, 4.18 U x mg(-1) respectively). CONCLUSION: ZnSO4 with concentration of 600 mg x L(-1) and PEG with concentration of 20% could significantly alleviate the damages to the seeds and seedlings of P. frutescens by aging and promote the aging resistance of the seeds and seedlings.

[RAPD analysis for genetic diversity of medicinal plant Coptis omeiensis].

OBJECTIVE: To discuss the genetic diversity of Coptis omeiensis. METHOD: The genetic diversity of 110 individuals from 10 populations was analyzed by RAPD. RESULT: 14 primers were selected to produce highly reproducible RAPD bands. Among 132 amplified bands, 98 showed polymorphism, the percentage of polymorphic bands reached to 74.24%. Nei's gene diversity index (H) was 0.2863, Shannon's information index (I) was 0.3624, G(st) was 0.2305. The genetic distance coefficient and the similarity were 0.1931-0.5245 and 0.5016-0.8843, respectively. CONCLUSION: There exists a held high genetic diversity in C. omeiensis and the majority of genetic variation occurs in the populations. By cluster analysis, the geographical distribution is very obvious. The RAPD marker can be used for the analysis of the genetic diversity and genetic variation of C. omeiensis.

[RAPD analysis for genetic diversity of Fagopyrum cymosum].

OBJECTIVE: To study the genetic diversity of Fagopyrum cymosum. METHOD: The genetic diversity of 87 individuals from 10 populations was analyzed by random amplified polymorphic DNA (RAPD). RESULT: Twelve primers were selected to produce highly reproducible RAPD bands. Among 85 amplified bands, seventy-five showed polymorphism, the percentage of polymorphic bands reached to 88.24%. Nei's gene diversity index (H) was 0. 3103, Shannon information index (I) was 0.5632, Gst was 0.1924. The genetic similarity coefficient and the genetic distance were 0.6720-0.9678 and 0.0328-0.3975, respectively. CONCLUSION: F. cymosum shows high genetic diversity and the majority of genetic variation occurs in populations. By cluster analysis, the geographical distribution is very obvious. The RAPD marker can be used for the analysis of the genetic diversity and genetic variation of F. cymosum.

[ISSR analysis of genetic diversity of Coptis deltoidea].

OBJECTIVE: To study the genetic diversity of Coptis deltoidea. METHOD: The genetic diversity of 90 individuals from 8 populations was analyzed by ISSR. RESULT: Twelve primers were selected to produce highly reproducible ISSR bands. Among 128 amplified bands, 94 showed polymorphism, the percentage of polymorphic bands reached 73.44%. Nei's gene diversity index (H) was 0.1925, Shannon's information index (I) was 0.3028, Gst was 0.7212. The genetic distance coefficient and similarity were 0.0858-0.2314 and 0.8046-0.9425, respectively. CONCLUSION: C. deltoidea held a high genetic diversity and the majority of genetic variation occurs among populations. By cluster analysis, the geographical distribution is very obvious. The ISSR marker can be used for the analysis of genetic diversity and genetic variation of C. deltoidea.