BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21.

BACKGROUND: Diabetic cardiomyopathy (DCM) is one of leading causes of diabetes-associated mortality. The gut microbiota-derived branched-chain amino acids (BCAA) have been reported to play a central role in the onset and progression of DCM, but the potential mechanisms remain elusive. RESULTS: We found the type 1 diabetes (T1D) mice had higher circulating BCAA levels due to a reduced BCAA degradation ability of the gut microbiota. Excess BCAA decreased hepatic FGF21 production by inhibiting PPARα signaling pathway and thereby resulted in a higher expression level of cardiac LAT1 via transcription factor Zbtb7c. High cardiac LAT1 increased the levels of BCAA in the heart and then caused mitochondrial damage and myocardial apoptosis through mTOR signaling pathway, leading to cardiac fibrosis and dysfunction in T1D mice. Additionally, transplant of faecal microbiota from healthy mice alleviated cardiac dysfunction in T1D mice, but this effect was abolished by FGF21 knockdown. CONCLUSIONS: Our study sheds light on BCAA-mediated crosstalk among the gut microbiota, liver and heart to promote DCM and FGF21 serves as a key mediator. Video Abstract.

Enhancing lucerne (Medicago sativa) yield and nutritional quality: a meta-analysis of fertilization types and environmental factors in China.

Introduction: Lucerne (Medicago sativa), is a cornerstone of China's livestock industry, however, due to the backward agronomic strategies and technology, lucerne in China faces cultivation challenges that result in lower productivity and quality than global standards. Therefore, we undertook a meta-analysis to evaluate the impact of five distinct fertilization types on lucerne yield and nutritional quality in various locations in China. The fertilizer practices included manure application, combined mineral fertilizer and manure application (FM), biological fertilizer application, unbalanced application of two or more mineral fertilizer types, and balanced mineral fertilizer application. Furthermore, we investigate influential factors of yield and quality of lucerne under fertilization, including climatic variables (mean annual precipitation, mean annual temperature), initial soil properties (soil organic carbon; total nitrogen, pH), and agronomic factors (seeding rate, harvest frequency, and lucerne stand age). Methods: Our study analyzed 53 published papers to discern the most beneficial fertilizer for enhancing lucerne yield and nutritional quality. Results and discussion: The results showed that the fertilizer practices, on average, significantly improved yield by 31.72% and crude protein content by 11.29%, with FM emerging as the most effective, this is because mineral fertilizers provide available nutrients for lucerne, manure provides essential organic matter for microorganisms and improve soil properties. In addition, the fertilizer practices significantly reduced neutral and acid detergent fiber contents by 6.28% and 8.50%, respectively, while increasing ash content and relative feeding value. Furthermore, climatic variables, soil properties, and planting system factors such as sowing date and harvest frequency significantly affected yield and nutritional quality. The practical implications of our results emphasize the need for balanced and strategic fertilizer application to optimize lucerne production and highlight the potential to adjust cultivation practices according to environmental conditions. Balanced and strategic fertilizer application can simultaneously improve soil properties, enhance soil carbon sequestration, and reduce the emission of greenhouse gases from the soil, which is a vital measure for realizing sustainable agricultural development.

Bacillus velezensis HN-2: a potent antiviral agent against pepper veinal mottle virus.

Background: Pepper veinal mottle virus (PVMV) belongs to the genus Potyvirus within the family Potyviridae and is a major threat to pepper production, causing reduction in yield and fruit quality; however, efficient pesticides and chemical treatments for plant protection against viral infections are lacking. Hence, there is a critical need to discover highly active and environment-friendly antiviral agents derived from natural sources. Bacillus spp. are widely utilized as biocontrol agents to manage fungal, bacterial, and viral plant diseases. Particularly, Bacillus velezensis HN-2 exhibits a strong antibiotic activity against plant pathogens and can also induce plant resistance. Methods: The experimental subjects employed in this study were Bacillus velezensis HN-2, benzothiadiazole, and dufulin, aiming to evaluate their impact on antioxidant activity, levels of reactive oxygen species, activity of defense enzymes, and expression of defense-related genes in Nicotiana benthamiana. Furthermore, the colonization ability of Bacillus velezensis HN-2 in Capsicum chinense was investigated. Results: The results of bioassays revealed the robust colonization capability of Bacillus velezensis HN-2, particularly in intercellular spaces, leading to delayed infection and enhanced protection against PVMV through multiple plant defense mechanisms, thereby promoting plant growth. Furthermore, Bacillus velezensis HN-2 increased the activities of antioxidant enzymes, thereby mitigating the PVMV-induced ROS production in Nicotiana benthamiana. Moreover, the application of Bacillus velezensis HN-2 at 5 dpi significantly increased the expression of JA-responsive genes, whereas the expression of salicylic acid-responsive genes remained unchanged, implying the activation of the JA signaling pathway as a crucial mechanism underlying Bacillus velezensis HN-2-induced anti-PVMV activity. Immunoblot analysis revealed that HN-2 treatment delayed PVMV infection at 15 dpi, further highlighting its role in inducing plant resistance and promoting growth and development. Conclusions: These findings underscore the potential of Bacillus velezensis HN-2 for field application in managing viral plant diseases effectively.

Modulation of choline and lactate metabolism by basic fibroblast growth factor mitigates neuroinflammation in type 2 diabetes: Insights from 1H-NMR metabolomics analysis.

BACKGROUND: Type 2 diabetes (T2D), a chronic metabolic disease, occurs brain dysfunction accompanied with neuroinflammation and metabolic disorders. The neuroprotective effects of the basic fibroblast growth factor (bFGF) have been well studied. However, the mechanism underlying the anti-inflammatory effects of bFGF remains elusive. METHODS: In this study, db/db mice were employed as an in vivo model, while high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells were used as in vitro models. Liposomal transfection of MyD88 DNA plasmid was used for MyD88-NF-κB pathway studies. And western blotting, flow cytometry and qPCR were employed. 1H-NMR metabolomics was used to find out metabolic changes. RESULTS: bFGF mitigated neuroinflammatory and metabolic disorders by inhibiting cortical inflammatory factor secretion and microglia hyperactivation in the cortex of db/db mice. Also, bFGF was observed to inhibit the MyD88-NF-κB pathway in high glucose (HG)-induced SY5Y cells and LPS-induced BV2 cells in in vitro experiments. Moreover, the 1H-NMR metabolomics results showed that discernible disparities between the cortical metabolic profiles of bFGF-treated db/db mice and their untreated counterparts. Notably, excessive lactate and choline deficiency attenuated the anti-inflammatory protective effect of bFGF in SY5Y cells. CONCLUSION: bFGF ameliorates neuroinflammation in db/db mice by inhibiting the MyD88-NF-kB pathway. This finding expands the potential application of bFGF in the treatment of neuroinflammation-related cognitive dysfunction.

Optimizing irrigation and nitrogen addition to balance grassland biomass production with greenhouse gas emissions: A mesocosm study.

Achieving a balance between greenhouse gas mitigation and biomass production in grasslands necessitates optimizing irrigation frequency and nitrogen addition, which significantly influence grassland productivity and soil nitrous oxide emissions, and consequently impact the ecosystem carbon dioxide exchange. This study aimed to elucidate these influences using a controlled mesocosm experiment where bermudagrass (Cynodon dactylon L.) was cultivated under varied irrigation frequencies (daily and every 6 days) with (100 kg ha-1) or without nitrogen addition; measurements of net ecosystem carbon dioxide exchange, ecosystem respiration, soil respiration, and nitrous oxide emissions across two cutting events were performed as well. The findings revealed a critical interaction between water-filled pore space, regulated by irrigation, and nitrogen availability, with the latter exerting a more substantial influence on aboveground biomass growth and ecosystem carbon dioxide exchange than water availability. Moreover, the total dry matter was significantly higher with nitrogen addition compared to without nitrogen addition, irrespective of the irrigation frequency. In contrast, soil nitrous oxide emissions were observed to be significantly higher with increased irrigation frequency and nitrogen addition. The effects of nitrogen addition on soil respiration components appeared to depend on water availability, with autotrophic respiration seeing a significant rise with nitrogen addition under limited irrigation (5.4 ± 0.6 µmol m-2 s-1). Interestingly, the lower irrigation frequency did not result in water stress, suggesting resilience in bermudagrass. These findings highlight the importance of considering interactions between irrigation and nitrogen addition to optimize water and nitrogen input in grasslands for a synergistic balance between grassland biomass production and greenhouse gas emission mitigation.

Enhancing the component intra- and interrelationship of Elymus nutans mono- and mixed sowing communities via adjusting sowing patterns in the Qinghai Tibetan Plateau.

Spatial arrangement is a key factor in maintaining community yield and stability via regulating component intra-/interspecific competition in an alpine climate environment. A 2-yr field trial was conducted on the Qinghai Tibetan Plateau, including cross row (S_C), double row (S_D), single row (S_R), broadcast (M_B), dependent row (M_D) and independent row (M_I). Our results showed that S_C could avoid intraspecific competition by reasonable spatial arrangement, which favored the dominant component growth (1st year: leaf; 2nd year: stem and reproductive organ). For mixed communities, RII (relative interaction intensity) implied that interspecific competition also embodied on dominant component, and higher Elymus nutans component advantages seriously limited Onobrychis viciifolia's components growth in the 2nd year. More details displayed that E. nutans in M_B or M_D produced the maximum system yield via increasing leaf investment at the initial stages and stem investment after July 2019. Besides, M_I possessed lower component numbers than M_B and M_D in the unit area. PCA analysis revealed that component numbers or biomasses changed synchronously, besides the E. nutans of S_C, M_B, and M_D presented significant discrepancies compared to other treatments in September 2019, which verified the effect of sowing patterns on component growth (P < 0.05), but O. viciifolia in different sowing patterns was similar in the 2nd year. Considering the adaptability and production for the environment of the Qinghai Tibetan Plateau, S_C is recommended for the promoted effect on component biomasses. M_B and M_D, with the merit of spacing utilization as well as higher resistance to variation in seasonal growth conditions via optimizing interspecific relationships for mixed communities, are adapted for increasing yield via component harvesting. Our results unveiled the potential of optimizing spatial usage efficiency via controlling component growth characteristics and stressed the importance of dynamic change of dominant components to enhance forage system production in alpine regions.

Determination of the water-use patterns for two xerophyte shrubs by hydrogen isotope offset correction.

The stable hydrogen and oxygen isotope technique is typically used to explore plant water uptake; however, the accuracy of the technique has been challenged by hydrogen isotope offsets between plant xylem water and its potential source water. In this study, the soil hydrogen and oxygen isotope waterline was used to correct the hydrogen isotope offsets for Salix psammophila and Caragana korshinskii, two typical shrub species on the Chinese Loess Plateau. Five different types of isotopic data [(i) δ18O, (ii) δ2H, (iii) combination δ18O with δ2H, (iv) corrected δ2H and (v) combination δ18O with corrected δ2H] were separately used to determine the water-use patterns of the two shrubs. The δ2H offset values of S. psammophila and C. korshinskii did not show significant temporal variation among the sampling months (May, July and September) but showed notable differences between the two shrubs (-0.4 ± 0.5‰ in S. psammophila vs -4.3 ± 0.9‰ in C. korshinskii). The obtained water absorption proportion (WAP) of S. psammophila in the different soil layers (0-20, 20-60 and 60-200 cm) did not differ significantly among the five different input data types. However, compared with the input data types (iii) and (v), the data types (i), (ii) and (iv) overestimated the WAP of C. korshinskii in the 0-20 cm soil layer and underestimated that in the 60-200 cm layer. The data type (iii) overestimated the WAP of C. korshinskii in 0-20 cm soil layer (25.9 ± 0.8%) in July in comparison with the WAP calculated based on data type (v) (19.1 ± 1.1%). The combination of δ18O and corrected δ2H, i.e., data type (v), was identified as the best data type to determine the water use patterns of C. korshinskii due to the strong correlation between the calculated WAP and soil water content and soil sand content. In general, S. psammophila mainly used (57.9-62.1%) shallow soil water (0-60 cm), whereas C. korshinskii mainly absorbed (52.7-63.5%) deep soil water (60-200 cm). We confirm that the hydrogen isotope offsets can cause significant errors in determining plant water uptake of C. korshinskii, and provide valuable insights for accurately quantifying plant water uptake in the presence of hydrogen isotope offsets between xylem and source water. This study is significant for facilitating the application of the stable hydrogen and oxygen isotope technique worldwide, and for revealing the response mechanism of shrub key ecohydrological and physiological processes to the drought environment in similar climate regions.

Screening of compound-formulated Bacillus and its effect on plant growth promotion.

Bacillus bacteria can produce abundant secondary metabolites that are useful for biocontrol, especially in maintaining plant root microecology, and for plant protection. In this study, we determine the indicators of six Bacillus strains for colonization, promotion of plant growth, antimicrobial activity, and other aspects, with the aim of obtaining a compound bacteriological agent to construct a beneficial Bacillus microbial community in plant roots. We found that there was no significant difference in the growth curves of the six Bacillus strains over 12 h. However, strain HN-2 was found to have the strongest swimming ability and the highest bacteriostatic effect of n-butanol extract on the blight-causing bacteria Xanthomonas oryzae pv. oryzicola. The hemolytic circle produced by the n-butanol extract of strain FZB42 was the largest (8.67 ± 0.13 mm) and had the greatest bacteriostatic effect on the fungal pathogen Colletotrichum gloeosporioides, with a bacteriostatic circle diameter of 21.74 ± 0.40 mm. Strains HN-2 and FZB42 can rapidly form biofilms. Time-of-flight mass spectrometry and hemolytic plate tests showed that strains HN-2 and FZB42 may have significantly different activities because of their ability to produce large quantities of lipopeptides (i.e., surfactin, iturin, and fengycin). Different growth-promoting experiments revealed that the strains FZB42, HN-2, HAB-2, and HAB-5 had better growth-promoting potential than the control, and therefore these four strains were compounded in an equal ratio and used to treat pepper seedlings through root irrigation. We found an increase in the stem thickness (13%), leaf dry weight (14%), leaf number (26%), and chlorophyll content (41%) of pepper seedlings treated with the composite-formulated bacterial solution compared to the optimal single-bacterial solution treatment. Furthermore, several of these indicators increased by an average of 30% in the composite solution-treated pepper seedlings compared with the control water treatment group. In conclusion, the composite solution obtained by compounding strains FZB42 (OD600 = 1.2), HN-2 (OD600 = 0.9), HAB-2 (OD600 = 0.9), and HAB-5 (OD600 = 1.2) in equal parts highlights the advantages of a single bacterial solution, which includes achieving good growth promotion and antagonistic effects against pathogenic bacteria. The promotion of this compound-formulated Bacillus can reduce the application of chemical pesticides and fertilizers; promote plant growth and development; avoid the imbalances of soil microbial communities and thus reduce the risk of plant disease; and provide an experimental basis for the production and application of various types of biological control preparations in the future.

Effect analysis of multi-department cooperation in improving etiological submission rates before antibiotic treatment.

Increased bacterial drug resistance has become a serious global public health problem. The application of antibiotics involves various clinical departments, and the rational application of antibiotics is the key to improving their efficacy. To provide a basis for further improving the etiological submission rate and standardizing the rational use of antibiotics, this article discusses the intervention effect of multi-department cooperation in improving the etiological submission rate before antibiotic treatment. A total of 87 607 patients were divided into a control group (n = 45 890) and an intervention group (n = 41 717) according to whether multi-department cooperation management was implemented. The intervention group involved the patients hospitalized from August to December 2021, while the control group involved the patients hospitalized from August to December 2020. The submission rates of the two groups; the rates before antibiotic treatment at the unrestricted use level, the restricted use level, and the special use level in departments; and the timing of submission were compared and analysed. The overall differences in the etiological submission rates before antibiotic treatment at the unrestricted use level (20.70% vs 55.98%), the restricted use level (38.23% vs 66.58%), and the special use level (84.92% vs 93.14%) were statistically significant before and after intervention (P < .05). At a more specific level, the etiological submission rates of different departments before antibiotic treatment at the unrestricted use level, the restricted use level, and the special use level were improved, but the special activities of multi-department cooperation management did not improve the submission timing significantly. Multi-department cooperation can effectively improve the etiological submission rates before antimicrobial treatment, but it is necessary to improve measures for specific departments to improve long-term management and incentive and restraint mechanisms.

WITHDRAWN: Conjugation of Ruthenium Drugs to Nanocellulose using Boronic Ester

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