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Starch biosynthesis is important for plant development and is a critical factor in crop quality and nutrition. As a complex metabolic pathway, the regulation of starch biosynthesis is still poorly understood. We here present the identification of candidate regulators for starch biosynthesis by gene coexpression analysis in rice (Oryza sativa). Starch synthesis genes can be grouped into type I (in seeds; sink tissues) and type II (in vegetative tissues; source tissues), and 307 and 621 coexpressed genes are putatively involved in the regulation of starch biosynthesis in rice seeds and vegetative tissues, respectively. Among these genes, Rice Starch Regulator1 (RSR1), an APETALA2/ethylene-responsive element binding protein family transcription factor, was found to negatively regulate the expression of type I starch synthesis genes, and RSR1 deficiency results in the enhanced expression of starch synthesis genes in seeds. Seeds of the knockout mutant rsr1 consistently show the increased amylose content and altered fine structure of amylopectin and consequently form the round and loosely packed starch granules, resulting in decreased gelatinization temperature. In addition, rsr1 mutants have a larger seed size and increased seed mass and yield. In contrast, RSR1 overexpression suppresses the expression of starch synthesis genes, resulting in altered amylopectin structure and increased gelatinization temperature. Interestingly, a decreased proportion of A chains in rsr1 results in abnormal starch granules but reduced gelatinization temperature, whereas an increased proportion of A chains in RSR1-overexpressing plants leads to higher gelatinization temperatures, which is novel and different from previous reports, further indicating the complicated regulation of starch synthesis and determination of the physicochemical properties of starch. These results demonstrate the potential of coexpression analysis for studying rice starch biosynthesis and the regulation of a complex metabolic pathway and provide informative clues, including the characterization of RSR1, to facilitate the improvement of rice quality and nutrition.

Plants make use of distinct types of DNA methylation characterized by their DNA methyltransferases and modes of regulation. One type, RNA-directed DNA methylation (RdDM), is guided by small interfering RNAs (siRNAs) to the edges of transposons that are close to genes, areas called mCHH islands in maize (Zea mays). Another type, chromomethylation, is guided by histone H3 lysine 9 methylation to heterochromatin across the genome. We examined DNA methylation and small RNA expression in plant tissues that were mutant for both copies of the genes encoding chromomethylases as well as mutants for both copies of the genes encoding DECREASED DNA METHYLATION1 (DDM1)-type nucleosome remodelers, which facilitate chromomethylation. Both sets of double mutants were nonviable but produced embryos and endosperm. RdDM was severely compromised in the double mutant embryos, both in terms of DNA methylation and siRNAs. Loss of 24-nucleotide siRNA from mCHH islands was coupled with a gain of 21-, 22-, and 24-nucleotide siRNAs in heterochromatin. These results reveal a requirement for both chromomethylation and DDM1-type nucleosome remodeling for RdDM in mCHH islands, which we hypothesize is due to dilution of RdDM components across the genome when heterochromatin is compromised.

Photocatalytic formation of hydrocarbons using solar energy via artificial photosynthesis is a highly desirable renewable-energy source for replacing conventional fossil fuels. Using an l -cysteine-based hydrothermal process, here we synthesize a carbon-doped SnS 2 (SnS 2 -C) metal dichalcogenide nanostructure, which exhibits a highly active and selective photocatalytic conversion of CO 2 to hydrocarbons under visible-light. The interstitial carbon doping induced microstrain in the SnS 2 lattice, resulting in different photophysical properties as compared with undoped SnS 2 . This SnS 2 -C photocatalyst significantly enhances the CO 2 reduction activity under visible light, attaining a photochemical quantum efficiency of above 0.7%. The SnS 2 -C photocatalyst represents an important contribution towards high quantum efficiency artificial photosynthesis based on gas phase photocatalytic CO 2 reduction under visible light, where the in situ carbon-doped SnS 2 nanostructure improves the stability and the light harvesting and charge separation efficiency, and significantly enhances the photocatalytic activity. Photocatalytic reduction of CO 2 to hydrocarbons is a promising route to both CO 2 utilization and renewable fuel production. Here the authors identify that carbon-doped SnS 2 possesses a high catalytic efficiency towards CO 2 reduction owing to low photogenerated charge recombination rates.

Keyboard instruments play a significant role in the music teaching process, providing students with an enjoyable musical experience while enhancing their music literacy. This study aims to investigate the current state of keyboard instrument teaching in preschool education, identify existing challenges, and propose potential solutions using the literature review method. In response to identified shortcomings, this paper proposes integrating intelligent technology and subject teaching through the application of teaching robots in keyboard instrument education. Specifically, a Convolutional Neural Network model of Deep Learning is employed for system debugging, enabling the teaching robot to analyze students’ images and movements during musical instrument play and deliver targeted teaching. Feedback from students who participated in keyboard instrument teaching with the robot indicates high satisfaction levels. This paper aims to diversify keyboard instruments’ teaching mode, introduce the practical application of robots in classroom teaching, and facilitate personalized teaching catering to individual students’ aptitudes.

Background Non-alcoholic fatty liver disease (NAFLD) is a growing health crisis in the general population of the United States (U.S.), but the relationship between systemic immune-inflammation (SII) index and NAFLD is not known. Methods We collected data from the National Health and Nutrition Examination Survey 2017–2018. Next, propensity score matching (PSM), collinearity analysis, restricted cubic spline (RCS) plot, logistic regression, quantile regression analysis, subgroup analysis, mediation analysis, and population attributable fraction were used to explore the association of the SII with risk of NAFLD. Results A total of 665 participants including the 532 Non-NAFLD and 133 NAFLD were enrolled for further analysis after PSM analysis. The RCS results indicated that there was a linear relationship between the SII and controlled attenuation parameter (p for nonlinear = 0.468), the relationship also existed after adjustment for covariates (p for nonlinear = 0.769). The logistic regression results indicated that a high SII level was an independent risk factor for NAFLD (OR = 3.505, 95% CI: 1.092–11.249, P  < 0.05). The quantile regression indicated that at higher quantiles (0.90, and 0.95) the SII was significantly associated with NAFLD ( p  < 0.05). Mediation analysis indicated that alanine aminotransferase (ALT), triglycerides, and blood urea nitrogen (BUN) were partially contribute to the relationship between SII and NAFLD. The population attributable fractions indicated that 23.19% (95% CI: 8.22%, 38.17%) of NAFLD cases could be attributed to SII corresponding to 133 NAFLD cases. Conclusion There was a positive linear relationship between the SII and the risk of NAFLD. The ALT, triglycerides, and BUN had a partial mediating effect on the relationship between the SII and NAFLD.

Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding neuropsychiatric safety of Glucagon-like peptide-1 agonists (GLP-1RAs). As real-world evidence is very limited, we explored the association between GLP-1RA and suicide/self-injury by mining the FDA Adverse Event Reporting System (FAERS) database. The FAERS database was queried from 2005 Q2 to 2023 Q2. The Reporting Odds Ratio (ROR) and Empirical Bayes Geometric Mean (EBGM) were used to conduct the disproportionality analysis. A total of 534 GLP-1RA-associated suicide/self-injury cases were reported in the FAERS during the study period. GLP-1RA did not cause a disproportionate increase in overall suicidal and self-injurious cases (ROR: 0.16, 95%CI 0.15-0.18, P < 0.001; EBGM05: 0.15). Stratified analyses found no safety signal of suicide/injury for GLP-1RA in both females and males. The ROR for suicide/self-injury with GLP-1RA was slightly elevated (ROR: 2.50, 95%CI 1.02-6.13, P = 0.05) in children, while the EBGM05 was < 2 in this population. No significant signal value was observed in other age groups. No over-reporting of suicide/self-injury was identified for GLP-1RA before or after the COVID-19 pandemic outbreak. The cases of suicide or self-injury reported to FAERS do not indicate any overall safety signal attributable to GLP-1RA at this time. Subgroup analysis revealed a marginal elevation of ROR for suicide and self-injury with GLP-1RA in children, but no safety signal was detected by EBGM05 in this population. Further large-scale prospective investigations are still warranted to further confirm this finding.

P2-type sodium manganese-rich layered oxides are promising cathode candidates for sodium-based batteries because of their appealing cost-effective and capacity features. However, the structural distortion and cationic rearrangement induced by irreversible phase transition and anionic redox reaction at high cell voltage (i.e., >4.0 V) cause sluggish Na-ion kinetics and severe capacity decay. To circumvent these issues, here, we report a strategy to develop P2-type layered cathodes via configurational entropy and ion-diffusion structural tuning. In situ synchrotron X-ray diffraction combined with electrochemical kinetic tests and microstructural characterizations reveal that the entropy-tuned Na 0.62 Mn 0.67 Ni 0.23 Cu 0.05 Mg 0.07 Ti 0.01 O 2 (CuMgTi-571) cathode possesses more {010} active facet, improved structural and thermal stability and faster anionic redox kinetics compared to Na 0.62 Mn 0.67 Ni 0.37 O 2 . When tested in combination with a Na metal anode and a non-aqueous NaClO 4 -based electrolyte solution in coin cell configuration, the CuMgTi-571-based positive electrode enables an 87% capacity retention after 500 cycles at 120 mA g −1 and about 75% capacity retention after 2000 cycles at 1.2 A g −1 . The use of Mn-rich layered cathodes in Na-based batteries is hindered by inadequate cycling reversibility and sluggish anionic redox kinetics. Here, the authors report a strategy to stabilize the structure and promote anionic redox via configurational entropy and ion-diffusion structural tuning.

Paclitaxel (trade name Taxol) is a rare diterpenoid with anticancer activity isolated from Taxus . At present, paclitaxel is mainly produced by the semi-synthetic method using extract of Taxus tissues as raw materials. The studies of regulatory mechanisms in paclitaxel biosynthesis would promote the production of paclitaxel through tissue/cell culture approaches. Here, we systematically identified 990 transcription factors (TFs), 460 microRNAs (miRNAs), and 160 phased small interfering RNAs (phasiRNAs) in Taxus chinensis to explore their interactions and potential roles in regulation of paclitaxel synthesis. The expression levels of enzyme genes in cone and root were higher than those in leaf and bark. Nearly all enzyme genes in the paclitaxel synthesis pathway were significantly up-regulated after jasmonate treatment, except for GGPPS and CoA Ligase . The expression level of enzyme genes located in the latter steps of the synthesis pathway was significantly higher in female barks than in male. Regulatory TFs were inferred through co-expression network analysis, resulting in the identification of TFs from diverse families including MYB and AP2. Genes with ADP binding and copper ion binding functions were overrepresented in targets of miRNA genes. The miRNA targets were mainly enriched with genes in plant hormone signal transduction, mRNA surveillance pathway, cell cycle and DNA replication. Genes in oxidoreductase activity, protein-disulfide reductase activity were enriched in targets of phasiRNAs. Regulatory networks were further constructed including components of enzyme genes, TFs, miRNAs, and phasiRNAs. The hierarchical regulation of paclitaxel production by miRNAs and phasiRNAs indicates a robust regulation at post-transcriptional level. Our study on transcriptional and posttranscriptional regulation of paclitaxel synthesis provides clues for enhancing paclitaxel production using synthetic biology technology.

Gingko biloba accumulates high levels of secondary metabolites of pharmaceutical value. Ginkgo calli develop a typical browning that reduces its regenerative capacity and thus its usefulness. To elucidate the browning mechanism, histological, transcriptomic, and metabolic alterations were compared between green and browning calli derived from immature ginkgo embryos. Histological observations revealed that browning calli had a more loosely arranged cell structure and accumulated more tannins than in green calli. Integrated metabolic and transcriptomic analyses showed that phenylpropanoid metabolism was specifically activated in the browning calli, and 428 differentially expressed genes and 63 differentially abundant metabolites, including 12 flavonoid compounds, were identified in the browning calli compared to the green calli. Moreover, the expression of flavonol synthase ( FLS ) and UDP-glucuronosyl-transferase ( UGT ) genes involved in the flavonoid pathway was more than tenfold higher in browning calli than in green calli, thus promoting biosynthesis of flavonol, which serves as a substrate to form glycosylated flavonoids. Flavonoid glycosides constituted the major coloring component of the browning calli and may act in response to multiple stress conditions to delay cell death caused by browning. Our results revealed the cellular and biochemical changes in browning callus cells that accompanied changes in expression of browning-related genes, providing a scientific basis for improving ginkgo tissue culturability.

Aim Sacubitril/valsartan is a new cardiovascular agent characterized by its dual inhibition on the reninangiotensin system (RAS) and the neprilysin. As neprilysin also involved itself in the degradation of amyloid‐β, there is an ongoing concern about the effect of sacubitril/valsartan on cognition, especially in case of long‐term administration. Methods The FDA Adverse Event Reporting System (FAERS) was mined between 2015Q3 and 2022Q4 to analyze the association between sacubitril/valsartan and adverse events (AEs) involving dementia. Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs) with “broad” and “narrow” preferred terms (PTs) relevant to dementia was applied to systematically search demented AE reports. The Empirical Bayes Geometric Mean (EBGM) from Multi‐Item Gamma Poisson Shrinker (MGPS) and proportional reporting ratio with Chi‐square (PRR, χ2) were used to calculate the disproportionality. Results We filtered the query for indication and identified 80,316 reports with heart failure indication in FAERS during the analytical period. Among all the reports, sacubitril/valsartan was listed as primary suspected or secondary suspected drug in 29,269 cases. No significantly elevated reporting rates of narrow dementia were evident with sacubitril/valsartan. The EBGM05 for narrow dementia‐related AEs associated with sacubitril/valsartan was 0.88 and the PRR (χ2) was 1.22 (2.40). Similarly, broad demented complications were not over‐reported in the heart failure patients administrated with sacubitril/valsartan (EBGM05 1.11; PRR 1.31, χ2 109.36). Conclusion The number of dementia‐related cases reported to FAERS generate no safety signal attributable to sacubitril/valsartan in patients with heart failure for now. Further follow‐ups are still warranted to address this question. What is already known about this subject: There is an ongoing concern about the effect of sacubitril/valsartan on cognition, especially in case of long‐term administration. So far, results of related researches were still insufficient to show compelling evidence for long‐term cognitive safety of sacubitril/valsartan. What this study adds: This study mined the FAERS between 2015Q3 and 2022Q4 to analyze the association between sacubitril/valsartan and adverse events (AEs) involving dementia. Dementia‐related AEs were not over‐reported in the heart failure patients administrated with sacubitril/valsartan, suggesting that there is no safety signal generated attributable to sacubitril/valsartan for now.