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Abstract The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3β signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Scientific knowledge about the ancestral genome of core eudicot plant kingdom can potentially have profound impacts on both basic and applied research, including evolution, genetics, genomics, ecology, agriculture, forestry, and global climate. To investigate which plant conserves best the core eudicots common ancestor genome, we compared Arcto-Tertiary relict Nyssaceae and 30 other eudicot plant families. The genomes of Davidia involucrata (a known living fossil), Camptotheca acuminata and Nyssa sinensis, one per existent genus of Nyssaceae, were performed comparative genomic analysis. We found that Nyssaceae originated from a single Nyssaceae common tetraploidization event (NCT)– autotetraploidization 28–31 Mya after the core eudicot common hexaploidization (ECH). We identified Nyssaceae orthologous and paralogous genes, determined its chromosomal evolutionary trajectory, and reconstructed the Nyssaceae most recent ancestor genome. D. involucrata genome contained the entire seven paleochromosomes and 17 ECH-generated eudicot common ancestor chromosomes and was the slowest in mutation among the analyzed 42 species of 31 plant families. Combing both its high retention of paleochromosomes and its low mutation rate, D. involucrata provides the best case in conservation of the core eudicot paleogenome.

Background The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell‐cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. Methods and Results Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co‐Immunoprecipitation (Co‐IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO‐IP experiments. Results showed that the 1–265 domain of CHK1 directly binds to the 157–400 amino acids of PKM2. Furthermore, hiPSC‐CM (human iPS cell‐derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C‐domain‐mediated cardiac metabolic reprogramming. Conclusions This study demonstrates that the 1–265 amino acid domain of CHK1 binds to the 157–400 domain of PKM2 and activates PKM2‐mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Bivalves are affected by various stressors, such as global warming and microplastics, in the marine environment. Microplastics are one of the most concerning pollutants worldwide, and high seawater temperatures caused by global warming influence the survival of marine organisms. However, little is known about the combined effects of elevated temperature and microplastics (MPs) on marine organisms, and most studies conducted in recent years have investigated the two factors, respectively. Thus, it is necessary to investigate the combined effects of elevated temperature and MP exposure on marine life. The Pacific oyster Crassostrea gigas is a widely distributed marine mollusk, and has very important economic value. The aim of the current study was to explore the toxic effects of elevated temperature and microplastic co-exposure on the hemocyte function, immune-related gene expression, and energy metabolism of C. gigas. In the current study, oysters were exposed to three levels of microplastics (no microplastics, 6 μm microplastics: SPS-MPs, and 50~60 μm microplastics: LPS-MPs) and two temperature levels (20 ℃ and 25 ℃) for 21 days, and the phagocytosis rate and reactive oxygen species (ROS) content of hemocytes, glycogen content in digestive glands, and immune-related gene expression in digestive glands and gills were examined on the 21st day. 2', 7'-Dichlorodihydrofluorescein diacetate and fluorescent microspheres were used to measure the ROS content and phagocytosis ratein hemocytes of C. gigas by flow cytometry, respectively. The glycogen content was measured using detection kits. Total RNA was isolated by TRIzol reagent, and the concentration was measured by Nanodrop. M-MLV Reverse Transcriptase was used for cDNA synthesis. The expressions of immune-related genes [inhibitor of NF-κB (IκB), p53, and heat shock protein 90 (HSP90)] were examined by quantitative real-time PCR in the digestive glands and gills of oysters from each treatment group. Two-way ANOVA was used to analyze the interactive effects of elevated temperature and microplastics on tested parameters of oysters using SPSS software. The results showed that exposure to SPS-MPs could elevate ROS content and reduce phagocytosis in hemocytes, but no significant interaction was found between elevated temperature and microplastic effects on ROS content and phagocytosis rate in hemocytes (P > 0.05). The 25 ℃+LPS-MPs exposure significantly decreased phagocytosis in hemocytes compared with single LPS-MPs and elevated temperature exposures (P < 0.05). Single SPS-MPs exposure significantly decreased phagocytosis in hemocytes compared with single LPS-MPs exposure (P < 0.05). In digestive glands, there was a significant interaction between elevated temperature and microplastics in glycogen content (P < 0.05), and the combined exposure could increase the glycogen content compared with other treatments. In digestive glands, the 25 ℃+LPS-MPs exposure significantly increased glycogen content compared with single elevated temperature and single LPS-MPs exposure (P < 0.05). In digestive glands and gills, there was a significant interaction between elevated temperature and microplastics in the expressions of HSP90, IκB, and p53 genes (P < 0.05). The 25 ℃+SPS-MPs exposure significantly upregulated the expression of HSP90, IκB, and p53 genes in the digestive glands of oysters compared with single SPS-MPs and single elevated temperature exposures (P < 0.05). The 25 ℃+SPS-MPs exposure significantly downregulated the expression of the HSP90 gene in the gills of oysters compared with single SPS-MPs exposure (P < 0.05). Single elevated temperature and single microplastics exposure significantly upregulated the expression of the IκB gene compared with the control in gills (P < 0.05). The combined exposure of elevated temperature and microplastics showed a significant antagonistic effect on the expression of the p53 gene in gills. Microplastics exposure downregulated p53 gene expression compared with the control at 20 ℃, while it upregulated p53 gene expression compared with single elevated temperature at 25 ℃. These results indicated that the p53 gene plays an important role in regulating the immune response in both digestive glands and gills. The interaction between elevated temperature and microplastics on the mRNA expression of HSP90 and IκB genes in digestive glands of C. gigas was size-dependent: A synergistic effect was found between SPS-MPs and elevated temperature, and an antagonistic effect was found between LPS-MPs and elevated temperature. A significant antagonistic effect was found between elevated temperature and microplastics on the mRNA expression of the IκB gene in gills, and the regulation pattern was different from that in the digestive glands, indicating that the regulation effect of the IκB gene was tissue-specific. In conclusion, the combined exposure of elevated temperature and microplastics can increase the glycogen content in the digestive glands of C. gigas, induce an immune response in digestive glands and gills, and trigger the oxidative stress response in hemocytes. Microplastics can cause stronger oxidative stress in hemocytes than elevated temperature. Moreover, a significant interactive effect was found between elevated temperature and microplastics on glycogen content in digestive glands and the expression of immune-related genes (HSP90, p53, and IκB) in digestive glands and gills. The results of this study provide valuable information for evaluating the toxic effects of microplastics on marine organisms under a global warming background.

Coptis chinensis Franch., also named Chinese goldthread is a member of Ranunculaceae in the order Ranunculales and represents an important lineage of early eudicots with traditional medicinal value. In our study, by using syntenic analysis combined with phylogenomic analysis of C. chinensis and four other representative genomes from basal and core eudicots, we confirmed that the WGD event in C. chinensis was shared by Aquilegia coerulea and Papaver somniferum L. and quickly occurred after Ranunculales diverged from other eudicots, likely a Ranunculales common tetraploidization (RCT). The synonymous nucleotide substitutions at synonymous sites distribution of syntenic blocks across these genomes showed that the evolutionary rate of the P. somniferum genome is faster than that of the C. chinensis genome by approximately 13.7%, possibly due to Papaveraceaes having an additional special tetraploidization event (PST). After Ks correction, the RCT dated to 115–130 million years ago (MYA), which was close to the divergence of Ranunculaceaes and Papaveraceaes approximately 115.45–130.51 MYA. Moreover, we identified homologous genes related to polyploidization and speciation and constructed multiple sequence alignments with different reference genomes. Notably, the event-related subgenomes in the basal genomes all showed genomic fractionation bias, suggesting a likely allopolyploid nature of the RCT, PST and T-Alpha and T-Beta events in Tetracentron sinense. In addition, we detected that the sixteen P450 subfamilies were markedly expanded in the genomes of Ranunculales, and most of them were related to the RCT and PST events. We constructed a new platform for Early Eudicot Comparative Genomic Research (http://www.cgrpoee.top/index.html) to store more information. In summary, our findings support the WGD of C. chinensis shared by Ranunculales, which is likely an allotetraploidization event. This present effort offered new insights into the evolution of key polyploidization events and the genes related to secondary metabolites during the diversification of early eudicots.

AIM: To report 5 cases with drug-induced bilateral acute ciliochoroidal effusion(DBACE)and myopic shift, with or without ocular hypertension(OHT), summarize patients' clinical characteristics and recovery process of DBACE, and investigate the possible pathophysiological mechanism.METHODS:A retrospective observational case study conducted from June 2017 to February 2021. The included patients were subjected to a series of ocular examinations listed as follows: 1)best corrected visual acuity; 2)intraocular pressure(IOP); 3)slit-lamp microscopy; 4)fundus photography; 5)ultrasound biomicroscopy(UBM); 6)subjective optometry; 7)axial length and anterior chamber depth. All patients were followed up every 2d until the diopters were completely restored to the state before the disease onset.RESULTS:In total, 5 patients aged 10-45 years old, including 3 female and 2 male patients, were enrolled in this study. All patients were bilaterally involved(5/5), and had myopic shift(5/5), of whom 3 patients had OHT(3/5). With the increase of age, myopic shift decreased, while OHT increased. Based on OHT, the dynamic aggravation process of DBACE was subdivided into 2 stages, stage 1(myopic shift without OHT)and stage 2(myopic shift with OHT). With the deterioration of DBACE, when myopic shift approached or exceeded the minimum amplitude of accommodation(MAA), IOP gradually rose, and DBACE progressed from stage 1 to stage 2. With the recovery of DBACE after discontinuing the suspicious drugs, DBACE in stage 2 first returned to stage 1, and then returned to normal.CONCLUSION:Pathophysiological mechanism of DBACE was subdivided into 2 stages, including stage 1(myopic shift without OHT)and stage 2(myopic shift with OHT). The transition between the two stages depends on the imbalance between myopic shift and MAA.

Societal Impact Statement Society anticipates a world in which more food and fiber must be produced at warmer temperatures, which, on the contrary, have greater constraints on the use of water and fertilizers. Tree legumes are often the climax vegetation on the semi‐arid and arid lands, covering ~25% of the planet, but the knowledge of their genomes is limited. A draft genome sequence for Prosopis alba, a salt and heat tolerant tree that is able to fix nitrogen under harsh conditions, yields new clues about its adaptations. Its rich genetic and ecological diversity makes Prosopis well‐suited to the investigation of gene functions important to its own greater utilization and/or the improvement of climate resilience of other crops. Summary In arid lands that comprise 41% of the Earth's surface and are growing, tree legumes are often the climax vegetation. Now found in much of arid America, Prosopis alba is a salt‐tolerant nitrogen‐fixing tree native to Argentina. We present a Prosopis alba genome assembly that is 707 Mb in size, comprising of 6087 contigs of up to 2,077,851 bp in length and of ~359.3 Mb (50.8%) being repetitive elements dominated (20.3%) by long terminal repeats (LTR) retrotransposons. Among a total of 57,572 coding sequences (CDS), 42,475 are putative protein coding genes with median length of 2748 bp. The Prosopis alba genome shares the legume‐common tetraploidy (LCT) but has not reduplicated, evolving 3.5% and 23.1% faster than Phaseolus vulgaris and Glycine max, respectively, since the LCT. The 50 most expanded gene families include many that are involved in ion homeostasis, perhaps related to drought and/or salt adaptation, together with photosynthetic genes carbonic anhydrase (CA), malate dehydrogenase (MDH) and malic enzyme and gene families involved in circadian clock systems, synthesis of brassinosteroids, auxin and gibberellin. Some expanded gene families include members showing molecular signatures of positive selection, as do numerous multi‐copy orthologous groups with features associated with pathogen resistance and single‐copy orthogroups related to drought and salt stress response, root and root hair development, nodulation, heavy metal detoxification and stay‐green habit. Coupling genomics‐based clues about possible causes of its striking physiological adaptations with rich diversity in ecological context offers means to further investigate functional roles of specific Prosopis genes/alleles.

The N-terminal sequences of proteins and their corresponding encoding sequences may play crucial roles in the heterologous expression. In this study, the secretory expression of alkaline pectin lyase APL in B. subtilis was investigated to explore the effects of the N-terminal 5–7 amino acid sequences of different signal peptides on the protein expression and secretion. It was identified for the first time that the first five amino acid sequences of the N-terminal of the signal peptide (SP-LipA) from Bacillus subtilis lipase A play an important role in promoting the expression of APL. Furthermore, it was revealed that SP-LipA resulted in higher secretory expression compared to other signal peptides in this study primarily due to its encoding of N-terminal amino acids with relatively higher transcription levels and its efficient secretion capacity. Based on this foundation, the recombinant strain constructed in this work achieved a new record for the highest extracellular yields of APL in B. subtilis, reaching 12,295 U/mL, which was 1.9-times higher than that expressed in the recombinant Escherichia coli strain previously reported. The novel theories uncovered in this study are expected to play significant roles in enhancing the expression of foreign proteins both inside and outside of cells.

Neutral pullulanases, having a good application prospect in trehalose production, showed a limited expression level. In order to address this issue, two approaches were utilized to enhance the yield of a new neutral pullulanase variant (PulA3E) in B. subtilis. One involved using multiple copies of genome integration to increase its expression level and fermentation stability. The other focused on enhancing the PulA-type atypical secretion pathway to further improve the secretory expression of PulA3E. Several strains with different numbers of genome integrations, ranging from one to four copies, were constructed. The four-copy genome integration strain PD showed the highest extracellular pullulanase activity. Additionally, the integration sites ytxE, ytrF, and trpP were selected based on their ability to enhance the PulA-type atypical secretion pathway. Furthermore, overexpressing the predicated regulatory genes comEA and yvbW of the PulA-type atypical secretion pathway in PD further improved its extracellular expression. Three-liter fermenter scale-up production of PD and PD-ARY yielded extracellular pullulanase activity of 1767.1 U/mL at 54 h and 2465.1 U/mL at 78 h, respectively. Finally, supplementing PulA3E with 40 U/g maltodextrin in the multi-enzyme catalyzed system resulted in the highest trehalose production of 166 g/L and the substrate conversion rate of 83%, indicating its potential for industrial application.

Industrial heavy metal-contaminated wastewater is one of the main water pollution problems. Adsorbents are a promising method for the removal of heavy metal contaminants. Herein, polyaspartic acid/carboxymethyl poplar sawdust hydrogels (PASP/CMPP) and ascorbic acid/carboxymethyl poplar sawdust hydrogels (VC/CMPP) were prepared by aqueous polymerization using alkalized poplar sawdust (CMPP) as the substrate and PASP and vitamin C (VC) as modifiers. The effective results, provided by the characterization analysis of SEM and BET, indicate that the surface of the PASP/CMPP hydrogel has a larger number of loose pores and a larger pore volume than the VC/CMPP hydrogel. The treatment effects of the two hydrogels on simulated wastewater containing Cd(II) were investigated by a batch of experiments. The results showed that PASP/CMPP had a better adsorption effect than VC/CMPP under the same adsorption conditions. Interestingly, the solid concentration effect was found in the process of sorption kinetics and sorption isotherms. The sorption kinetic curves of Cd(II) on PASP/CMPP were well-fitted by the quasi-second-order kinetics under different adsorbent concentrations. The adsorption conforms to Langmuir and Freundlich adsorption isotherm models. More importantly, PASP/CMPP composites are expected to be used as a new kind of environmental adsorbent for wastewater treatment. HIGHLIGHTS Hydrogels of PASP/CMPP were prepared.; The hydrogels of PASP/CMPP exhibit enhanced sorption capacities for Cd(II).; The hydrogels of PASP/CMPP are potential sorbents for wastewater treatment.; The solid concentration effect was found in the process of sorption kinetics and sorption isotherms.; The synthesis of PASP/CMPP hydrogels provides a win-win strategy.;

Vitrification is currently the primary choice worldwide for high-level nuclear waste immobilization. This study investigated the crystallization behaviors of glasses containing 24%(mass fraction) and 30% simulated high-level nuclear waste, respectively, under different temperatures. According to X-ray diffraction, Raman spectroscopy and scanning electronic microscopy results, dendritic powellite(CaMoO4) phase and string-like Zr-cerianite (ZrxCe1-xO2) are the main crystalline phases when the glasses are heat treated at 800 ℃, while a great amount of hollow hexagonal oxyapatite(Ca2Ln8(SiO4)6O2) phases are observed in addition when the glasses are heated at 950 ℃. The chemical durability test shows that the heat treatment decreases the total normalized leaching mass loss of glass by about 1/3, with main contributions from B, Na, Mo and Ca. The normalized leaching mass loss of the glasses after heat treatment at 950 ℃ is smaller than that after heat treatment at 800 ℃. It indicates that the heat treatment of glass for crystallization improves glass durability.

Abstract Background Gene conversion has an important effect on duplicate genes produced by polyploidization. Poplar (Populus trichocarpa) and willow (Salix brachista) are leading models and excellent green plants in the Salicaceae. Although much attention has been paid to the evolution of duplicated genes in poplar and willow, the role of conversion between duplicates generated from polyploidization remains poorly understood. Results Here, through genomic synteny analyses, we identified duplicate genes generated by the Salicaceae common tetraploidization (SCT) in the poplar and willow genomes. We estimated that at least 0.58% and 0.25% of poplar and willow duplicates were affected by whole-gene conversion after the poplar-willow divergence, with more (5.73% and 2.66%) affected by partial-gene conversion. Moreover, we found that the converted duplicated genes were unevenly distributed on each chromosome in the two genomes, and the well-preserved homoeologous chromosome regions may facilitate the conversion of duplicates. Notably, we found that conversion maintained the similarity of duplicates, likely contributing to the conservation of certain sequences, but is essentially accelerated the rate of evolution and increased species divergence. In addition, we found that converted duplicates tended to have more similar expression patterns than nonconverted duplicates. We found that genes associated with multigene families were preferentially converted. We also found that the genes encoding conserved structural domains associated with specific traits exhibited a high frequency of conversion. Conclusions Extensive conversion between duplicate genes generated from the SCT contributes to the diversification of the family Salicaceae and has had long-lasting effects on those genes with important biological functions.

In previous studies, researchers have used singing to treat respiratory function in patients with spinal cord injury. However, few studies have examined the way in which vocal training affects respiratory neural plasticity in patients with spinal cord injury. Vocal respiratory training (VRT) is a type of vocal muscle-related treatment that is often a component of music therapy (MT) and focuses on strengthening respiratory muscles and improving lung function. In this randomized controlled study, we analyzed the therapeutic effects of VRT on respiratory dysfunction at 3 months after cervical spinal cord injury. Of an initial group of 37 patients, 26 completed the music therapy intervention, which comprised five 30-minute sessions per week for 12 weeks. The intervention group (n = 13) received VRT training delivered by professional certified music therapists. The control group (n = 13) received respiratory physical therapy delivered by professional physical therapists. Compared with the control group, we observed a substantial increase in respiratory function in the intervention group after the 12-week intervention. Further, the nerve fiber bundles in the respiratory center in the medulla exhibited a trend towards increased diversification, with an increased number, path length, thickness, and density of nerve fiber bundles. These findings provide strong evidence for the effect of music therapeutic VRT on neural plasticity. This study was approved by the Ethics Committee of China Rehabilitation Research Center (approval No. 2020-013-1) on April 1, 2020, and was registered with the Chinese Clinical Trial Registry (registration No. ChiCTR2000037871) on September 2, 2020.

BackgroundCalcific aortic valve disease (CAVD) is a progressive disease resulting in severe calcific aortic stenosis (AS), and there is increasing interest in the discovery of novel biomarkers to identify patients with potential future calcific AS at an early stage. This study aimed to determine whether follistatin-like 1 (FSTL1) is associated with calcific AS events and its exact role in aortic valve calcification.MethodsA prospective observational cohort study involving 656 patients was performed to investigate the relationship between serum FSTL1 and calcific AS incidence during a follow-up of 5 years. Furthermore, we detected FSTL1 levels in valvular interstitial cells (VICs) from calcified valves and explored the effects of FSTL1 on VIC osteogenic differentiation in vitro as well as the signaling pathways involved.ResultsDuring a median follow-up of 5 years, lower FSTL1 levels were associated with a significantly higher risk of calcific AS events (log rank test, P = 0.007). In addition, Cox multivariable regression analyses verified the predictive value of FSTL1 after adjusting for both demographic features and laboratory confounders. Consistent with our results for serum, a lower concentration of FSTL1 was observed in calcified human valves (n = 11) and mainly colocalized with VICs. Recombinant human FSTL1 (rhFSTL1) stimulation inhibited calcium deposition, alkaline phosphatase (ALP) activity, and osteogenic gene expression partly through the downregulation of the ERK1/2 pathway.ConclusionTaken together, this study provides a strong rationale to consider FSTL1 as a potential therapeutic target for calcific AS.

Abstract Background Duplicated gene pairs produced by ancient polyploidy maintain high sequence similarity over a long period of time and may result from illegitimate recombination between homeologous chromosomes. The genomes of Asian cultivated rice Oryza sativa ssp. indica (XI) and Oryza sativa ssp. japonica (GJ) have recently been updated, providing new opportunities for investigating ongoing gene conversion events and their impact on genome evolution. Results Using comparative genomics and phylogenetic analyses, we evaluated gene conversion rates between duplicated genes produced by polyploidization 100 million years ago (mya) in GJ and XI. At least 5.19–5.77% of genes duplicated across the three rice genomes were affected by whole-gene conversion after the divergence of GJ and XI at ~ 0.4 mya, with more (7.77–9.53%) showing conversion of only portions of genes. Independently converted duplicates surviving in the genomes of different subspecies often use the same donor genes. The ongoing gene conversion frequency was higher near chromosome termini, with a single pair of homoeologous chromosomes, 11 and 12, in each rice genome being most affected. Notably, ongoing gene conversion has maintained similarity between very ancient duplicates, provided opportunities for further gene conversion, and accelerated rice divergence. Chromosome rearrangements after polyploidization are associated with ongoing gene conversion events, and they directly restrict recombination and inhibit duplicated gene conversion between homeologous regions. Furthermore, we found that the converted genes tended to have more similar expression patterns than nonconverted duplicates. Gene conversion affects biological functions associated with multiple genes, such as catalytic activity, implying opportunities for interaction among members of large gene families, such as NBS-LRR disease-resistance genes, contributing to the occurrence of the gene conversion. Conclusion Duplicated genes in rice subspecies generated by grass polyploidization ~ 100 mya remain affected by gene conversion at high frequency, with important implications for the divergence of rice subspecies.

The current randomized controlled trial was performed at the China Rehabilitation Science Institute, China to test the hypothesis that musical auditory stimulation has positive effects on the autonomic nervous system of patients with disorder of consciousness. Although past studies have recommended that patients with disorder of consciousness listen to patient-preferred music, this practice is not universally accepted by researchers. Twenty patients with severe disorder of consciousness listened to either therapist-selected (n = 10, 6 males and 4 females; 43.33 ± 18.76 years old) or patient-preferred (n = 10, 5 males and 5 females, 48.83 ± 18.79 years old) musical therapy, 30 minutes/day, 5 times/week for 6 weeks. The results showed no obvious differences in heart rate variability-related parameters including heart rate, standard deviation of normal-to-normal R-R intervals, and the root-mean-square of successive heartbeat interval differences of successive heartbeat intervals between the two groups of patients. However, percentage of differences exceeding 50 ms between adjacent normal number of intervals, low-frequency power/high-frequency power, high-frequency power norm, low-frequency power norm, and total power were higher in patients receiving therapist-selected music than in patients receiving their own preferred music. In contrast, this relationship was reversed for the high-frequency power and very-low-frequency band. These results suggest that compared with preferred musical stimulation, therapist-selected musical stimulation resulted in higher interactive activity of the autonomic nervous system. Therefore, therapist-selected musical stimulation should be used to arouse the autonomic nervous system of patients with disorder of consciousness. This study was approved by the Institutional Ethics Committee of China Rehabilitation Research Center, China (approval No. 2018-022-1) on March 12, 2018 and registered with the Chinese Clinical Trial Registry (registration number ChiCTR1800017809) on August 15, 2018.

Abstract Background Increasing evidence showed that carbamylated lipoprotein accelerated atherosclerosis. However, whether such modification of high-density lipoprotein (HDL) particles alters in type 2 diabetes mellitus (T2DM) patients and facilitates vascular complications remains unclear. We aimed to investigate the alteration of the carbamylation in HDL among T2DM patients and clarify its potential role in atherogenesis. Methods A total of 148 consecutive T2DM patients undergoning angiography and 40 age- and gender-matched control subjects were included. HDL was isolated from plasma samples, and the concentration of HDL carbamyl-lysine (HDL-CBL) was measured. Furthermore, the HDL from subjects and in-vitro carbamylated HDL (C-HDL) was incubated with endothelial cells and monocyte to endothelial cell adhesion. Adhesion molecule expression and signaling pathway were detected. Results Compared with the control group, the HDL-CBL level was remarkably increased in T2DM patients (6.13 ± 1.94 vs 12.00 ± 4.06 (ng/mg), P

Eudicots account for ~75% of living angiosperms, containing important food and energy crops. Recently, high-quality genome sequences of several eudicots including Aquilegia coerulea and Nelumbo nucifera have become available, providing an opportunity to investigate the early evolutionary characteristics of eudicots. We performed genomic hierarchical and event-related alignments to infer homology within and between representative species of eudicots. The results provide strong evidence for multiple independent polyploidization events during the early diversification of eudicots, three of which are likely to be allopolyploids: The core eudicot-common hexaploidy (ECH), Nelumbo-specific tetraploidy (NST), and Ranunculales-common tetraploidy (RCT). Using different genomes as references, we constructed genomic alignment to list the orthologous and paralogous genes produced by polyploidization and speciation. This could provide a fundamental framework for studying other eudicot genomes and gene(s) evolution. Further, we revealed significantly divergent evolutionary rates among these species. By performing evolutionary rate correction, we dated RCT to be ~118–134 million years ago (Mya), after Ranunculales diverged with core eudicots at ~123–139 Mya. Moreover, we characterized genomic fractionation resulting from gene loss and retention after polyploidizations. Notably, we revealed a high degree of divergence between subgenomes. In particular, synonymous nucleotide substitutions at synonymous sites (Ks) and phylogenomic analyses implied that A. coerulea might provide the subgenome(s) for the gamma-hexaploid hybridization.

Background The pericoronary fat attenuation index (FAI) is assessed using standard coronary computed tomography angiography, and it has emerged as a novel imaging biomarker of coronary inflammation. The present study assessed whether increased pericoronary FAI values on coronary computed tomography angiography were associated with vulnerable plaque components and their intracellular cytokine levels in patients with non‐ST elevation acute coronary syndrome. Methods and Results A total of 195 lesions in 130 patients with non‐ST elevation acute coronary syndrome were prospectively included. Lesion‐specific pericoronary FAI, plaque components and other plaque features were evaluated by coronary computed tomography angiography. Local T cell subsets and their intracellular cytokine levels were detected by flow cytometry. Lesions with pericoronary FAI values >−70.1 Hounsfield units exhibited spotty calcification (43.1% versus 25.0%, P=0.015) and low‐attenuation plaques (17.6% versus 4.2%, P=0.016) more frequently than lesions with lower pericoronary FAI values. Further quantitative plaque compositional analysis showed that increased necrotic core volume (Pearson’s r=0.324, P

Background The neonatal heart maintains its entire regeneration capacity within days after birth. Using quantitative phosphoproteomics technology, we identified that SGK3 (serine/threonine‐protein kinase 3) in the neonatal heart is highly expressed and activated after myocardial infarction. This study aimed to uncover the function and related mechanisms of SGK3 on cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. Methods and Results The effect of SGK3 on proliferation and oxygen glucose deprivation/reoxygenation– induced apoptosis in isolated cardiomyocytes was evaluated using cardiomyocyte‐specific SGK3 overexpression or knockdown adenovirus5 vector. In vivo, gain‐ and loss‐of‐function experiments using cardiomyocyte‐specific adeno‐associated virus 9 were performed to determine the effect of SGK3 in cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. In vitro, overexpression of SGK3 enhanced, whereas knockdown of SGK3 decreased, the cardiomyocyte proliferation ratio. In vivo, inhibiting the expression of SGK3 shortened the time window of cardiac regeneration after apical resection in neonatal mice, and overexpression of SGK3 significantly promoted myocardial repair and cardiac function recovery after ischemia/reperfusion injury in adult mice. Mechanistically, SGK3 promoted cardiomyocyte regeneration and myocardial repair after cardiac injury by inhibiting GSK‐3β (glycogen synthase kinase‐3β) activity and upregulating β‐catenin expression. SGK3 also upregulated the expression of cell cycle promoting genes G1/S‐specific cyclin‐D1, c‐myc (cellular‐myelocytomatosis viral oncogene), and cdc20 (cell division cycle 20), but downregulated the expression of cell cycle negative regulators cyclin kinase inhibitor P 21 and cyclin kinase inhibitor P 27. Conclusions Our study reveals a key role of SGK3 on cardiac repair after apical resection or ischemia/reperfusion injury, which may reopen a novel therapeutic option for myocardial infarction.

Melodic intonation therapy (MIT) positively impacts the speech function of patients suffering from aphasia and strokes. Fixed-pitch melodies and phrases formulated in MIT provide the key to the target language to open the language pathway. This randomized controlled trial compared the effects of music therapy-based MIT and speech therapy on patients with non-fluent aphasia. The former is more effective in the recovery of language function in patients with aphasia. Forty-two participants were enrolled in the study, and 40 patients were registered. The participants were randomly assigned to two groups: the intervention group (n = 20; 16 males, 4 females; 52.90 ± 9.08 years), which received MIT, and the control group (n = 20; 15 males, 5 females; 54.05 ± 10.81 years), which received speech therapy. The intervention group received MIT treatment for 30 min/day, five times a week for 8 weeks, and the control group received identical sessions of speech therapy for 30 min/day, five times a week for 8 weeks. Each participant of the group was assessed by a Boston Diagnostic Aphasia Examination (BDAE) at the baseline (t1, before the start of the experiment), and after 8 weeks (t2, the experiment was finished). The Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) were also measured on the time points. The best medical care of the two groups is the same. Two-way ANOVA analysis of variance was used only for data detection. In the spontaneous speech (information), the listening comprehension (right or wrong, word recognition, and sequential order) and repetitions of the intervention group were significantly higher than the control group in terms of the cumulative effect of time and the difference between groups after 8 weeks. The intervention group has a significant time effect in fluency, but the results after 8 weeks were not significantly different from those in the control group. In terms of naming, the intervention group was much better than the control group in spontaneous naming. Regarding object naming, reaction naming, and sentence completing, the intervention group showed a strong time accumulation effect. Still, the results after 8 weeks were not significantly different from those in the control group. These results indicate that, compared with speech therapy, MIT based on music therapy is a more effective musical activity and is effective and valuable for the recovery of speech function in patients with non-fluent aphasia. As a more professional non-traumatic treatment method, MIT conducted by qualified music therapists requires deeper cooperation between doctors and music therapists to improve rehabilitating patients with aphasia. The Ethics Committee of the China Rehabilitation Research Center approved this study (Approval No. 2020-013-1 on April 1, 2020) and was registered with the Chinese Clinical Trial Registry (Registration number: Clinical Trials ChiCTR2000037871) on September 3, 2020.

Background: Emerging studies have described and analyzed epidemiological, clinical, laboratory, and radiological features of COVID-19 patients. Yet, scarce information is available regarding the association of lipid profile features and disease severity and mortality.Methods: We conducted a prospective observational cohort study to investigate lipid profile features in patients with COVID-19. From 9 February to 4 April 2020, a total of 99 patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were included in the study. Dynamic alterations in lipid profiles were recorded and tracked. Outcomes were followed up until 4 April 2020.Results: We found that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-1 (apoA-1) levels were significantly lower in the severe disease group, with mortality cases showing the lowest levels (p < 0.0001). Furthermore, HDL-C and apoA-1 levels were independently associated with disease severity (apoA-1: odds ratio (OR): 0.651, 95% confidence interval (CI): 0.456–0.929, p = 0.018; HDL-C: OR: 0.643, 95% CI: 0.456–0.906, p = 0.012). For predicting disease severity, the areas under the receiver operating characteristic curves (AUCs) of HDL-C and apoA-1 levels at admission were 0.78 (95% CI, 0.70–0.85) and 0.85 (95% CI, 0.76–0.91), respectively. For in-hospital deaths, HDL-C and apoA-1 levels demonstrated similar discrimination ability, with AUCs of 0.75 (95% CI, 0.61–0.88) and 0.74 (95% CI, 0.61–0.88), respectively. Moreover, patients with lower serum concentrations of apoA-1 (

Objective: The objective of the present study is to investigate the inhibitory effects of sinomenine (SIN) on angiogenesis in a collagen-induced arthritis (CIA) mouse model. Methods: Arthritis assessments for all mice were recorded. The histopathological assessments were performed following haematoxylin and eosin (HE) staining. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) analyses were used to detect the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and angiopoietin 1 (ANG-1) in the serum and in the membrane. Immunohistochemistry was employed to detect the synovium microvessel density (MVD). Results: Compared with the CIA model group, SIN significantly ameliorated swelling and erythema extension, decreased the arthritis index, reduced inflammation, cartilage damage and bone erosion, and lessened the number of CD31 positive cells on the synovium. Moreover, the levels of HIF-1α, VEGF and ANG-1 in the synovium and in the peripheral serum were increased in the untreated CIA model group but were significantly reduced in the 30 mg/kg, 100 mg/kg and 300 mg/kg SIN treatment groups. Conclusion: SIN could mitigate CIA by inhibiting angiogenesis, and the mechanism may associate with the HIF-1α–VEGF–ANG-1 axis. Additionally, our study provides a referable experimental basis for the use of SIN for the treatment of rheumatoid arthritis.