Low levels of Al stimulate the aboveground growth of Davidia involucrata saplings.

Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific importance. However, D. involucrata is now an endangered species and its natural range includes low pH soils which are increasingly impacted by acid rain, nitrogen deposition and imbalanced nutrient cycling. The combination of these stresses also poses the additional risk of aluminum (Al) toxicity. Since the responses of D. involucrata to low pH and aluminum toxicity have not been investigated previously, a hydroponic experiment was conducted to examine the growth of one year old D. involucrata saplings after 50 d growth in a range of pH and Al conditions. Plant biomass, morphology, antioxidant enzyme activity, mineral concentrations and plant ecological strategy were compared at pH 5.8 and pH 4.0 without added Al (AlCl3) and in 0.1, 0.2 and 0.5 mM Al at pH 4.0. Our results showed that compared with pH 5.8, pH 4.0 (without added Al) not only inhibited root and shoot growth but also limited accumulation of nitrogen (N) and phosphorus (P) in leaves of D. involucrate. However, low Al concentrations (0.1 and 0.2 mM Al) at pH 4.0 partially restored the aboveground growth and leaf N concentrations, suggesting an alleviation of H+ toxicity by low Al concentrations. Compared with low Al concentrations, 0.5 mM Al treatment decreased plant growth and concentrations of N, P, and magnesium (Mg) in the leaves, which demonstrated the toxicity of high Al concentration. The results based on plant ecological strategy showed that D. involucrate decreased the competitiveness and favored its stress tolerance as pH changed from 5.8 to 4.0. Meanwhile, the competitiveness and stress tolerance of D. involucrata increased and decreased at low Al concentrations, respectively, and decreased and increased at high Al concentration, respectively. These trade-offs in ecological strategy were consistent with the responses of growth and antioxidant enzyme activity, reflecting a sensitive adaptation of D. involucrata to acid and Al stresses, which may aid in sustaining population dynamics. These findings are meaningful for understanding the population dynamics of D. involucrata in response to aluminum toxicity in acid soils.

Integrating transcriptomics and metabolomics to analyze the defense response of Morus notabilis to mulberry ring rot disease.

Introduction: The mulberry industry has thrived in China for millennia, offering significant ecological and economic benefits. However, the prevalence of mulberry ring rot disease poses a serious threat to the quality and yield of mulberry leaves. Methods: In this study, we employed a combination of transcriptomic and metabolomic analyses to elucidate the changes occurring at the transcriptional and metabolic levels in Morus notabilis in response to this disease infestation. Key metabolites identified were further validated through in vitro inhibition experiments. Results: The findings revealed significant enrichment in Kyoto Encyclopedia of Genes and Genomes pathways, particularly those related to flavonoid biosynthesis. Notably, naringenin, kaempferol, and quercetin emerged as pivotal players in M. notabilis' defense mechanism against this disease pathogen. The upregulation of synthase genes, including chalcone synthase, flavanone-3-hydroxylase, and flavonol synthase, suggested their crucial roles as structural genes in this process. In vitro inhibition experiments demonstrated that kaempferol and quercetin exhibited broad inhibitory properties, while salicylic acid and methyl jasmonate demonstrated efficient inhibitory effects. Discussion: This study underscores the significance of the flavonoid biosynthesis pathway in M. notabilis' defense response against mulberry ring rot disease, offering a theoretical foundation for disease control measures.

Decreased MFN2 activates the cGAS-STING pathway in diabetic myocardial ischaemia-reperfusion by triggering the release of mitochondrial DNA.

BACKGROUND: The cause of aggravation of diabetic myocardial damage is yet to be elucidated; damage to mitochondrial function has been a longstanding focus of research. During diabetic myocardial ischaemia-reperfusion (MI/R), it remains unclear whether reduced mitochondrial fusion exacerbates myocardial injury by generating free damaged mitochondrial DNA (mitoDNA) and activating the cGAS-STING pathway. METHODS: In this study, a mouse model of diabetes was established (by feeding mice a high-fat diet (HFD) plus a low dose of streptozotocin (STZ)), a MI/R model was established by cardiac ischaemia for 2 h and reperfusion for 30 min, and a cellular model of glycolipid toxicity induced by high glucose (HG) and palmitic acid (PA) was established in H9C2 cells. RESULTS: We observed that altered mitochondrial dynamics during diabetic MI/R led to increased mitoDNA in the cytosol, activation of the cGAS-STING pathway, and phosphorylation of the downstream targets TBK1 and IRF3. In the cellular model we found that cytosolic mitoDNA was the result of reduced mitochondrial fusion induced by HG and PA, which also resulted in cGAS-STING signalling and activation of downstream targets. Moreover, inhibition of STING by H-151 significantly ameliorated myocardial injury induced by MFN2 knockdown in both the cell and mouse models. The use of a fat-soluble antioxidant CoQ10 improved cardiac function in the mouse models. CONCLUSIONS: Our study elucidated the critical role of cGAS-STING activation, triggered by increased cytosolic mitoDNA due to decreased mitochondrial fusion, in the pathogenesis of diabetic MI/R injury. This provides preclinical insights for the treatment of diabetic MI/R injury. Video Abstract.

Changes to PUFA-PPAR pathway during mesaconitine induced myocardial coagulative necrosis.

Coagulation necrosis is characterized by the denaturation of structural proteins and lysosomal enzymes; its occurrence in myocardium can lead to heart failure. Current studies on myocardial injury primarily focus on inflammation, hypertrophy, and hemorrhage, while those on myocardial coagulation necrosis are still limited. Mesaconitine (MA), a C19 diester diterpenoid alkaloid derived from Aconitum carmichaelii Debx, has strong cardiotoxicity. During this study, the myocardial cells of SD rats showed significant coagulative necrosis after 6 days of oral administration of MA at a dose of 1.2 mg/kg/day. Investigations of its biological mechanism showed abnormal levels of polyunsaturated fatty acids (PUFAs) and Peroxisome proliferator activated receptors Alpha (PPARα) pathway related protein. Moreover, MA affected the PPARα signaling pathway through interactions with proteins such as POR, TFAM and GPD1, indirectly indicating that these above proteins are important targets for blocking myocardial coagulative necrosis. This study thus discusses the effects of the use of cardiotoxic compound, MA, to initiate myocardial coagulative necrosis and its associated toxic mechanisms.

Scutellarin Alleviates Ischemic Brain Injury in the Acute Phase by Affecting the Activity of Neurotransmitters in Neurons.

Cerebral ischemic stroke is a common neuron loss disease that is caused by the interruption of the blood supply to the brain. In order to enhance the CIS outcome, both identifying the treatment target of ischemic brain damage in the acute phase and developing effective therapies are urgently needed. Scutellarin had been found to be beneficial to ischemic injuries and has been shown to have potent effects in clinical application on both stroke and myocardial infarction. However, whether scutellarin improves ischemic brain damage in the acute phase remains unknown. In this study, the protective effects of scutellarin on ischemic brain damage in the acute phase (within 12 h) were illustrated. In middle cerebral artery occlusion and reperfusion (MCAO/R) modeling rats, the Z-Longa score was significantly down-regulated by 25% and 23.1%, and the brain infarct size was reduced by 26.95 ± 0.03% and 25.63 ± 0.02% when responding to high-dose and low-dose scutellarin treatments, respectively. H&E and TUNEL staining results indicated that the neuron loss of the ischemic region was improved under scutellarin treatment. In order to investigate the mechanism of scutellarin's effects on ischemic brain damage in the acute phase, changes in proteins and metabolites were analyzed. The suppression of scutellarin on the glutamate-inducing excitatory amino acid toxicity was strongly indicated in the study of both proteomics and metabolomics. A molecular docking experiment presented strong interactions between scutellarin and glutamate receptors, which score much higher than those of memantine. Further, by performing a parallel reaction monitoring-mass spectrometry (PRM-MS) study on both the cortex and hippocampus tissue of the ischemic region, we screened the scutellarin-regulating molecules that are involved in both the release and transportation of neurotransmitters. It was found that the aberrant levels of glutamate receptors, including EAAT2, GRIN1, GRIN2B, and GRM1, as well as of other glutamatergic pathway-involving proteins, including CAMKK2, PSD95, and nNOS, were significantly regulated in the ischemic cortex. In the hippocampus, EAAT2, GRIN1, nNOS, and CAM were significantly regulated. Taken together, scutellarin exerts potent effects on ischemic brain damage in the acute phase by regulating the activity of neurotransmitters and reducing the toxicity of excitatory amino acids in in neurons.

[Rapid identification of components in Wuzhuyu Decoction using UHPLC Q-Exactive Orbitrap MS~n and molecular network technology].

Wuzhuyu Decoction, the classical formula recorded in the Treatise on Febrile Diseases(Shang Han Lun), has been included in the Catalogue of Ancient Classic Prescriptions(the First Batch). Consisting of Euodiae Fructus, Ginseng Radix et Rhizoma, Zingiberis Rhizoma Recens, and Jujubae Fructus, it is effective in warming the middle, tonifying deficiency, dispelling cold, and descending adverse Qi, and is widely applied clinically with remarkable efficacies. For a classical formula, the chemical composition is the material basis and an important premise for quantity value transfer. This study aimed to establish a rapid identification method of chemical components in Wuzhuyu Decoction by high-resolution mass spectrometry(HR-MS) and molecular network. AQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was used for sample separation, and acetonitrile-0.1% formic acid in water was used as mobile phases for gradient elution. Q-Exactive Orbitrap MS data were collected in positive and negative ion modes, and GNPS molecular network was plotted according to the similarity of MS/MS fragmentation modes. Cytoscape 3.6.1 was used to screen molecular clusters with similar structures. Finally, the chemical components of Wuzhuyu Decoction were rapidly identified according to the controls, as well as the information of retention time, accurate relative molecular weight of HR-MS, and MS/MS multistage fragments. A total of 105 chemical components were identified in Wuzhuyu Decoction. This study can provide data for the follow-up quality control, standard substance research, and pharmacodynamic material research on Wuzhuyu Decoction, as well as references for the rapid qualitative analysis of the chemical components of Chinese medicine.

Predicting the distributions of Scleroderma guani (Hymenoptera: Bethylidae) under climate change in China.

The wasp Scleroderma guani is an important parasitic natural enemy of a variety of stem borers such as longicorn beetles. Studying and clarifying the suitable area of this wasp plays an important role in controlling stem borers. Based on information about the actual distribution of S. guani and on a set of environmental variables, MaxEnt niche model and ArcGIS were exploited to predict the potential distribution of this insect in China. This work simulated the geographical distribution of potential climatic suitability of S. guani in China at present and in different periods in the future. Combining the relative percent contribution score of environmental factors and the Jackknife test, the dominant environmental variables and their appropriate values restricting the potential geographical distribution of S. guani were screened. The results showed that the prediction of the MaxEnt model was highly in line with the actual distribution under current climate conditions, and the simulation accuracy was very high. The distribution of S. guani is mainly affected by bio18 (Precipitation of Warmest Quarter), bio11 (Mean Temperature of Coldest Quarter), bio13 (Precipitation of Wettest Month), and bio3 (Isothermality). The suitable habitat of S. guani in China is mainly distributed in the Northeast China Plain, North China Plain, middle-lower Yangtze Plain, and Sichuan Basin, with total suitable area of 547.05 × 104 km2, accounting for 56.85% of China's territory. Furthermore, under the RCP2.6, RCP4.5, and RCP8.5 climate change scenarios in the 2050s and 2090s, the areas of high, medium, and low suitability showed different degrees of change compared to nowadays, exhibiting expansion trend in the future. This work provides theoretical support for related research on pest control and ecological protection.

Vegetarian diet duration's influence on women's gut environment.

BACKGROUND: Nutrient composition of vegetarian diets is greatly different from that of omnivore diets, which may fundamentally influence the gut microbiota and fecal metabolites. The interactions between diet pattern and gut environment need further illustration. This study aims to compare the difference in the gut microbiota and fecal metabolites between vegetarian and omnivore female adults and explore associations between dietary choices/duration and gut environment changes. METHODS: In this study, investigations on the fecal metabolome together with the gut microbiome were performed to describe potential interactions with quantitative functional annotation. In order to eliminate the differences brought by factors of gender and living environment, 80 female adults aged 20 to 48 were recruited in the universities in Beijing, China. Quantitative Insights Into Microbial Ecology (QIIME) analysis and Ingenuity Pathway Analysis (IPA) were applied to screen differential data between groups from gut microbiota and fecal metabolites. Furthermore, weighted gene correlation network analysis (WGCNA) was employed as the bioinformatics analysis tool for describing the correlations between gut microbiota and fecal metabolites. Moreover, participants were further subdivided by the vegetarian diet duration for analysis. RESULTS: GPCR-mediated integration of enteroendocrine signaling was predicted to be one of the regulatory mechanisms of the vegetarian diet. Intriguingly, changes in the gut environment which occurred along with the vegetarian diet showed attenuated trend as the duration increased. A similar trend of returning to "baseline" after a 10-year vegetarian diet was detected in both gut microbiota and fecal metabolome. CONCLUSIONS: The vegetarian diet is beneficial more than harmful to women. Gut microbiota play roles in the ability of the human body to adapt to external changes.

An explanation for fluctuations of icariin content in Epimedium production process.

Epimedium has beneficial effects in nourishing and building up the body and is widely used in practical production of Epimedium preparations. As one of the major active compounds in Epimedium preparations, icariin is be used as a quality control index of industrial manufacture. However, content of icariin was observed to increase to uncertain extent in pharmaceutical production, which might bring difficulties in quality control. The content fluctuation mainly occurred in high-temperature extraction process. The aim of this study is to investigate what happen to flavonol-glycosides in Epimedium under heating treatment. Ultra-Performance Liquid Chromatography-Linear Ion Trap Mass Spectrometer was applied to profile the transformation rule of flavonol-glycosides in Epimedium and search for an explanation for the increase in icariin content under heating treatment. 56 compounds were found to have significantly changed and their structures were identified, among which 15 flavonol-glycosides were proposed to play a role in icariin content variation. Further studies were conducted based on 8 flavonol-glycosides standard substances to obtain more credible data. Finally, Baohuoside II, 2"-o-rhamnosylicariside II, Epimedin A1, Epimedin A, Epimedin B, Epimedin C, Baohuoside I and Anhydroicaritin were found to transform into icariin during the heating process. This study provides an evidence for the quality control study of Epimedium preparation, as well as reference for chemical researches in natural pharmacy.

Design and Fabrication of a Novel Dual-Frequency Confocal Ultrasound Transducer for Microvessels Super-Harmonic Imaging.

Recently, super-harmonic ultrasound imaging technology has caused much attention due to its capability of distinguishing microvessels from the tissues surrounding them. However, the fabrication of a dual-frequency confocal transducer is still a challenge. In this work, 270- [Formula: see text] PMN-PT single crystal 1-3 composite and 28- [Formula: see text] PVDF thick film, acting as transmission layer and receiving layer, respectively, are integrated in a novel co-focusing structure. To realize delicate wave propagation control, microwave transmission line theory is introduced to design such structure. Two acoustic filter layers, 13- [Formula: see text] copper layer and 39- [Formula: see text] Epoxy 301 layer, are indispensable and should be added between two piezoelectric layers. Therefore, an acoustic issue can be overcome via an electrical method and the successful achievement of a dual-frequency (5 MHz/30 MHz) ultrasound transducer with a confocal distance of 8 mm can be realized. The super-harmonic ultrasound imaging experiment is conducted using this kind of device. The 3-D image of 110- [Formula: see text]-diameter phantom tube injected with microbubbles can be obtained. These promising results demonstrate that this novel dual-frequency (5 MHz/30 MHz) confocal ultrasound transducer is potentially usable for microvascular medical imaging application in the future.

Sagittaria sagittifolia polysaccharide interferes with arachidonic acid metabolism in non-alcoholic fatty liver disease mice via Nrf2/HO-1 signaling pathway.

BACKGROUNDS: Non-alcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases especially in developed countries. Modern research shows an obvious protective effect of Sagittaria sagittifolia L. (Alismataceae) on glucose and lipid metabolism disorders. Previous studies had reported that Sagittaria sagittifolia polysaccharide (SSP) has potent protective effects on drug-induced liver injury. Based on this, we speculated that Sagittaria sagittifolia polysaccharide also has protective effects on NAFLD and performed experiments to explore this more. METHODS: Outstanding protective effects of SSP against NAFLD in mice was observed with Hematoxylin and Eosin (H&E) and uranium acetate-citrate stain in our prophase research. By performing bioinformatics analysis on plasma metabolic data which is obtained from ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS), we found the regulatory mechanisms and key nodes behind the beneficial effect with IPA (Ingenuity Pathway Analysis) software. Immunohistochemical staining and Western blot were performed for further validation on expression variations of key proteins. RESULTS: Regulatory pathways were enriched with 33 significant differential metabolites that responded to SSP treatment in plasma, and specifically, the ones related to arachidonic acid metabolism showed high participation. Moreover, the expression patterns of upstream regulators, Nrf2 and HO-1, were found to be significantly regulated upon SSP treatment. CONCLUSIONS: In conclusion, our findings illustrated a novel perspective that SSP exerts preventive protection against high-fat diet-induced NAFLD by interfering with arachidonic acid metabolism via Nrf2/HO-1 signaling pathway in liver oxidative stress, providing an attractive point for the breakthrough of related natural medicine development.

Protective Effects and Metabolic Regulatory Mechanisms of Shenyan Fangshuai Recipe on Chronic Kidney Disease in Rats.

BACKGROUND: Chronic kidney disease (CKD) is one of the major causes of renal damage. Shenyan Fangshuai Recipe (SFR), a modified prescription of traditional medicine in China, showed potent effects in alleviating edema, proteinuria, and hematuria of CKD in clinical practices. In this study, we aimed to investigate scientific evidence-based efficacy as well as metabolic regulations of SFR in CKD treatment. MATERIALS AND METHODS: The effect of SFR on CKD was observed in a rat model which is established with oral administration of adenine-ethambutol mixture for 21 days. Further, metabolites in serum were detected and identified with ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Metabolomics study was performed using Ingenuity Pathway Analysis (IPA) software. RESULTS: With H&E staining and Masson's trichrome, the results showed that chronic kidney damage is significantly rescued with SFR treatment and recovered to an approximately normal condition. Along with 44 differential metabolites discovered, the regulation of SFR on CKD was enriched in glycine biosynthesis I, mitochondrial L-carnitine shuttle pathway, phosphatidylethanolamine biosynthesis III, sphingosine-1-phosphate signaling, L-serine degradation, folate transformations I, noradrenaline and adrenaline degradation, salvage pathways of pyrimidine ribonucleotides, cysteine biosynthesis III (Mammalia), glycine betaine degradation, and cysteine biosynthesis/homocysteine degradation. Further, TGFß-1 and MMP-9 were observed playing roles in this regulatory process by performing immunohistochemical staining. CONCLUSION: SFR exerts potent effects of alleviating glomerular sclerosis and interstitial fibrosis in the kidney, mainly via integrated regulations on metabolism and production of homocysteine, L-carnitine, and epinephrine, as well as the expression of TGFß-1. This study provides evidence for SFR's protective effects on CKD and reveals the metabolic mechanism behind these benefits for the first time.

Flexible and powerful strategy for qualitative and quantitative analysis of valepotriates in Valeriana jatamansi Jones using high-performance liquid chromatography with linear ion trap Orbitrap mass spectrometry.

Valeriana jatamansi Jones is an important medicinal plant and its quality is closely related to its region of origin. In the current study, we utilized a flexible and powerful strategy for comprehensive evaluation of the quality diversity for 15 regions in China. The method was based on a hybrid linear ion trap-Orbitrap mass spectrometry platform. For structure characterization, fragmentation patterns were detected by analyzing a series of standard compounds using data dependent multistage mass spectrometry acquisition. A fragment ion database for valepotriates was established, and the acquired data were high throughput filtered by fragment ion search for compound identification. For quantitative purposes, we normalized the mass spectrometry data of 15 samples using SIEVE 2.0 and the differences in composition were analyzed using principal component analysis combined with hierarchical clustering analysis. The results identified a total of 92 compounds from Valeriana jatamansi Jones. Samples from Dali, Kunming, and Baoshan have better qualities and concentrations of the main active constituents. To verify our strategy, we compared the valtrate, acevaltrate, and baldrinal contents using high-performance liquid chromatography with diode array detector. We developed and validated a comprehensive qualitative and quantitative analytical method to achieve quality control of Valeriana jatamansi Jones.