Root rot destabilizes the Sanqi rhizosphere core fungal microbiome by reducing the negative connectivity of beneficial microbes.

The stability of microbial communities, especially among core taxa, is essential for supporting plant health. However, the impacts of disease infection on the stability of rhizosphere fungal core microbiome remain largely unexplored. In this study, we delved into the effects of root rot infestation on the community structure, function, network complexity, and stability of Sanqi fungal core microbiomes, employing amplicon sequencing combined with co-occurrence network and cohesion analyses. Our investigation revealed that root rot disease led to a decrease in the α-diversity but an increase in the ß-diversity of the Sanqi fungal core microbiomes in the rhizosphere. Notably, Ilyonectria, Plectosphaerella, and Fusarium emerged as indicator species in the rhizosphere core microbiome of root rot-infected Sanqi plants, while Mortierella predominated as the dominant biomarker taxa in healthy soils. Additionally, root rot diminished the complexity and modularity of the rhizosphere networks by reducing the metrics associated with nodes, edges, degrees, and modularity. Furthermore, root rot resulted in a reduction in the proportion of negative connections in the network and the negative/positive cohesion of the entire core fungal microbiome. Particularly noteworthy was the observation that root rot infection destabilized the rhizosphere core fungal microbiome by weakening the negative connectivity associated with beneficial agents. Collectively, these results highlight the significance of the negative connectivity of beneficial agents in ensuring the stability of core microbial community.IMPORTANCERoot rot disease has been reported as the most devastating disease in the production process of artificial cultivated Sanqi ginseng, which seriously threatens the Sanqi industry. This study provides valuable insights into how root rot influences microbial relationships within the community. These findings open up opportunities for disease prevention and the promotion of plant health by regulating microbial interactions. In summary, the research sheds light on the ecological consequences of root rot on rhizosphere fungal microbiomes and offers potential strategies for managing soil-borne diseases and enhancing plant health.

Oleanolic acid inhibits hypoxic tumor-derived exosomes-induced premetastatic niche formation in hepatocellular carcinoma by targeting ERK1/2-NFκB signaling.

BACKGROUND: Pulmonary premetastatic niche (PMN) formation plays a key role in the lung metastasis of hepatocellular carcinoma (HCC). Hypoxia promotes the secretion of tumor-derived exosomes (TDEs) and facilitates the formation of PMN. However, the mechanisms remain unexplored. METHODS: TDEs from normoxic (N-TDEs) or hypoxic (H-TDEs) HCC cells were used to induce fibroblast activation in vitro and PMN formation in vivo. Oleanolic acid (OA) was intragastrically administered to TDEs-preconditioned mice. Bioinformatics analysis and drug affinity responsive target stability (DARTS) assays were performed to identify targets of OA in fibroblasts. RESULTS: H-TDEs induced activation of pulmonary fibroblasts, promoted formation of pulmonary PMN and subsequently facilitated lung metastasis of HCC. OA inhibited TDEs-induced PMN formation and lung metastasis and suppressed TDEs-mediated fibroblast activation. MAPK1 and MAPK3 (ERK1/2) were the potential targets of OA. Furthermore, H-TDEs enhanced ERK1/2 phosphorylation in fibroblasts in vitro and in vivo, which was suppressed by OA treatment. Blocking ERK1/2 signaling with its inhibitor abated H-TDEs-induced activation of fibroblasts and PMN formation. H-TDEs-induced phosphorylation of ERK1/2 in fibroblasts touched off the activation NF-κB p65, which was mitigated by OA. In addition, the ERK activator C16-PAF recovered the activation of ERK1/2 and NF-κB p65 in H-TDEs-stimulated MRC5 cells upon OA treatment. CONCLUSION: The present study offers insights into the prevention of TDEs-induced PMN, which has been insufficiently investigated. OA suppresses the activation of inflammatory fibroblasts and the development of pulmonary PMN by targeting ERK1/2 and thereby has therapeutic potential in the prevention of lung metastasis of HCC.

Land Use Change from Natural Tropical Forests to Managed Ecosystems Reduces Gross Nitrogen Production Rates and Increases the Soil Microbial Nitrogen Limitation.

Understanding the underlying mechanisms of soil microbial nitrogen (N) utilization under land use change is critical to evaluating soil N availability or limitation and its environmental consequences. A combination of soil gross N production and ecoenzymatic stoichiometry provides a promising avenue for nutrient limitation assessment in soil microbial metabolism. Gross N production via 15N tracing and ecoenzymatic stoichiometry through the vector and threshold element ratio (Vector-TER) model were quantified to evaluate the soil microbial N limitation in response to land use changes. We used tropical soil samples from a natural forest ecosystem and three managed ecosystems (paddy, rubber, and eucalyptus sites). Soil extracellular enzyme activities were significantly lower in managed ecosystems than in a natural forest. The Vector-TER model results indicated microbial carbon (C) and N limitations in the natural forest soil, and land use change from the natural forest to managed ecosystems increased the soil microbial N limitation. The soil microbial N limitation was positively related to gross N mineralization (GNM) and nitrification (GN) rates. The decrease in microbial biomass C and N as well as hydrolyzable ammonium N in managed ecosystems led to the decrease in N-acquiring enzymes, inhibiting GNM and GN rates and ultimately increasing the microbial N limitation. Soil GNM was also positively correlated with leucine aminopeptidase and ß-N-acetylglucosaminidase. The results highlight that converting tropical natural forests to managed ecosystems can increase the soil microbial N limitation through reducing the soil microbial biomass and gross N production.

Curcumin-loaded pH-sensitive carboxymethyl chitosan nanoparticles for the treatment of liver cancer.

In this study, the pH-responsive API-CMCS-SA (ACS) polymeric nanoparticles (NPs) based on 1-(3-amino-propyl) imidazole (API), stearic acid (SA), and carboxymethyl chitosan (CMCS) were fabricated for the effective transport of curcumin (CUR) in liver cancer. CUR-ACS-NPs with various degrees of substitution (DS) were employed to prepare through ultrasonic dispersion method. The effect of different DS on NPs formation was discussed. The obtained CUR-ACS-NPs (DSSA=12.4%) had high encapsulation rate (more than 85%) and uniform particle size (186.2 ± 1.42 nm). The CUR-ACS-NPs showed better stability than the other groups. Drug release from the CUR-ACS-NPs was pH-dependent, and more than 90% or 65% of CUR was released in 48 h in weakly acid medium (pH 5.0 or 6.0, respectively). Additionally, the CUR-ACS-NPs increased the intracellular accumulation of CUR and demonstrated high anticancer effect on HepG2 cells compared with the other groups. CUR-ACS-NPs prolonged the retention time of the drug, and the area under the curve (AUC) increased significantly in vivo. The in vivo antitumor study further revealed that the CUR-ACS-NPs exhibited the capability of inhibiting tumor growth and lower systemic toxicity. Meanwhile, CUR, CUR-CS-NPs, and CUR-ACS-NPs could be detected in the evaluated organs, including tumor, liver, spleen, lung, heart, and kidney in distribution studies. Among them, CUR-ACS-NPs reached the maximum concentration at the tumor site, indicating the tumor-targeting properties. In short, the results suggested that CUR-ACS-NPs could act a prospective drug transport system for effective delivery of CUR in cancer treatment.

COIMMR: a computational framework to reveal the contribution of herbal ingredients against human cancer via immune microenvironment and metabolic reprogramming.

Immune evasion and metabolism reprogramming have been regarded as two vital hallmarks of the mechanism of carcinogenesis. Thus, targeting the immune microenvironment and the reprogrammed metabolic processes will aid in developing novel anti-cancer drugs. In recent decades, herbal medicine has been widely utilized to treat cancer through the modulation of the immune microenvironment and reprogrammed metabolic processes. However, labor-based herbal ingredient screening is time consuming, laborious and costly. Luckily, some computational approaches have been proposed to screen candidates for drug discovery rapidly. Yet, it has been challenging to develop methods to screen drug candidates exclusively targeting specific pathways, especially for herbal ingredients which exert anti-cancer effects by multiple targets, multiple pathways and synergistic ways. Meanwhile, currently employed approaches cannot quantify the contribution of the specific pathway to the overall curative effect of herbal ingredients. Hence, to address this problem, this study proposes a new computational framework to infer the contribution of the immune microenvironment and metabolic reprogramming (COIMMR) in herbal ingredients against human cancer and specifically screen herbal ingredients targeting the immune microenvironment and metabolic reprogramming. Finally, COIMMR was applied to identify isoliquiritigenin that specifically regulates the T cells in stomach adenocarcinoma and cephaelin hydrochloride that specifically targets metabolic reprogramming in low-grade glioma. The in silico results were further verified using in vitro experiments. Taken together, our approach opens new possibilities for repositioning drugs targeting immune and metabolic dysfunction in human cancer and provides new insights for drug development in other diseases. COIMMR is available at https://github.com/LYN2323/COIMMR.

The loss of microbial autotoxin degradation functions is associated with the decline of beneficial bacterial agents induced by phenolic acids.

Continuous cultivation of medicinal plants can disrupt the rhizosphere's microbial community. There is still a need to know about the beneficial bacterial community, their putative drivers, and the potential functions they may have. This study used different growth years of Sanqi ginseng (Panax notoginseng) with root rot to look at the beneficial microbial community structure, the function of microbial carbon source utilization, and the function of rhizosphere soil metabolism. The beneficial bacterial community changed and the relative abundance of beneficial agents was suppressed significantly with the successive Sanqi ginseng plantings. The carbon source utilization capacity and diversity increased significantly, whereas three autotoxin degradation-related pathways (biosynthesis of other secondary metabolites, metabolism of terpenoids and polyketides, and xenobiotics biodegradation and metabolism) were downregulated considerably with planting year extended. The changes in the beneficial agents were driven by the shifts in phenolic acid profiles, and the decline of beneficial microbes led to the loss of microbial autotoxin degradation functions. Overall, these results provide insight into beneficial microbes, microbial functions, phenolic acids, and their interactions, and these findings are essential for maintaining healthy and sustainable cultivation of Sanqi ginseng. IMPORTANCE Sanqi ginseng is a valuable perennial Chinese herb with various benefits for human health. However, continuous cultivation causes a high incidence of root rot disease, which leads to decreased yield and serious economic losses and ultimately impedes the sustainable development of Chinese medicine production. The significance of this study is to reveal the pattern of changes in beneficial bacteria and their related functions in root rot diseased rhizosphere with the successive planting years of Sanqi ginseng. This study found that the decline of beneficial bacterial agents mediated by phenolic acid profiles appears to be associated with the loss of microbial autotoxin degradation functions. This result may have new implications for deciphering the causes of Sanqi ginseng's continuous cropping obstacles.

Effects of Solidago canadensis L. on mineralization-immobilization turnover enhance its nitrogen competitiveness and invasiveness.

The effects of exotic plants on soil nitrogen (N) transformations may influence species invasion success. However, the complex interplay between invasive plant N uptake and N transformation in soils remains unclear. In the present study, a series of 15N-labeled pot experiments were carried out with Solidago canadensis L. (S. canadensis), an invasive plant, and the Ntrace tool was used to clarify the preferred inorganic N form and its effects on soil N transformation. According to the results, nitrate-N (NO3--N) uptake rates by S. canadensis were 2.38 and 2.28 mg N kg-1 d-1 in acidic and alkaline soil, respectively, which were significantly higher than the ammonium-N (NH4+-N) uptake rates (1.76 and 1.56 mg N kg-1 d-1, respectively), indicating that S. canadensis was a NO3--N-preferring plant, irrespective of pH condition. Gross N mineralization rate was 0.41 mg N kg-1 d-1 in alkaline soil in the presence of S. canadensis L., which was significantly lower than that in the control (no plant, CK, 2.44 mg N kg-1 d-1). Gross autotrophic nitrification rate also decreased from 5.95 mg N kg-1 d-1 in the CK to 0.04 mg N kg-1 d-1 in the presence of S. canadensis in alkaline soil. However, microbial N immobilization rate increased significantly from 1.09 to 2.16 mg N kg-1 d-1, and from 0.02 to 2.73 mg N kg-1 d-1 after S. canadensis planting, in acidic and alkaline soil, respectively. Heterotrophic nitrification rate was stimulated in the presence of S. canadensis to provide NO3--N to support the N requirements of plants and microbes. The results suggested that S. canadensis can influence the mineralization-immobilization turnover (MIT) to optimize its N requirements while limiting N supply for other plants in the system. The results of the present study enhance our understanding of the competitiveness and mechanisms of invasion of alien plants.

Exploring pharmacological active ingredients of traditional Chinese medicine by pharmacotranscriptomic map in ITCM.

With the emergence of high-throughput technologies, computational screening based on gene expression profiles has become one of the most effective methods for drug discovery. More importantly, profile-based approaches remarkably enhance novel drug-disease pair discovery without relying on drug- or disease-specific prior knowledge, which has been widely used in modern medicine. However, profile-based systematic screening of active ingredients of traditional Chinese medicine (TCM) has been scarcely performed due to inadequate pharmacotranscriptomic data. Here, we develop the largest-to-date online TCM active ingredients-based pharmacotranscriptomic platform integrated traditional Chinese medicine (ITCM) for the effective screening of active ingredients. First, we performed unified high-throughput experiments and constructed the largest data repository of 496 representative active ingredients, which was five times larger than the previous one built by our team. The transcriptome-based multi-scale analysis was also performed to elucidate their mechanism. Then, we developed six state-of-art signature search methods to screen active ingredients and determine the optimal signature size for all methods. Moreover, we integrated them into a screening strategy, TCM-Query, to identify the potential active ingredients for the special disease. In addition, we also comprehensively collected the TCM-related resource by literature mining. Finally, we applied ITCM to an active ingredient bavachinin, and two diseases, including prostate cancer and COVID-19, to demonstrate the power of drug discovery. ITCM was aimed to comprehensively explore the active ingredients of TCM and boost studies of pharmacological action and drug discovery. ITCM is available at http://itcm.biotcm.net.

Self-Sacrificially Degradable Pseudo-Semiconducting Polymer Nanoparticles that Integrate NIR-II Fluorescence Bioimaging, Photodynamic Immunotherapy, and Photo-Activated Chemotherapy.

Semiconducting polymers (SP) hold great promise for cancer phototherapy due to their excellent optical properties; however, their clinical application is still hampered by their poor biodegradability. Herein, a self-sacrificially biodegradable pseudo-semiconducting polymer (PSP) for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and photoactivated chemotherapy (PACT) is reported. The PSP can further co-assemble with an amphiphilic polyester with pendant doxorubicin (DOX) in its side chains via reactive oxygen species (ROS)-responsive thioketal linkages (PEDOX ), which are denoted as NP@PEDOX /PSP. The NP@PEDOX /PSP can accumulate at tumor sites and generate ROS for photodynamic immunotherapy as well as near-infrared-II fluorescence (NIR-II) for bioimaging upon irradition at 808 nm. The ROS could break up thioketal linkages in PEDOX , resulting in rapid doxorubicin (DOX) release for PACT. Finally, both PEDOX and PSP are degraded sacrificially by intracellular glutathione (GSH), resulting in the dissociation of NP@PEDOX /PSP. This work highlights the application of self-sacrificially degradable PSP for NIR-II fluorescence bioimaging, photodynamic immunotherapy, and PACT in cancer therapy.

Integrated hepatic single-cell RNA sequencing and untargeted metabolomics reveals the immune and metabolic modulation of Qing-Fei-Pai-Du decoction in mice with coronavirus-induced pneumonia.

BACKGROUND: Although Qing-Fei-Pai-Du decoction (QFPDD) is extensively used clinically to treat COVID-19 patients, the mechanism by which it modulates the immunological and metabolic functions of liver tissue remains unknown. PURPOSE: The purpose of this study is to investigate the mechanism of action of QFPDD in the treatment of mice with coronavirus-induced pneumonia by combining integrated hepatic single-cell RNA sequencing and untargeted metabolomics. METHODS: We developed a human coronavirus pneumonia model in BALB/c mice by infecting them with human coronavirus HCoV-229E with stimulating them with cold-damp environment. We initially assessed the status of inflammation and immunity in model mice treated with or without QFPDD by detecting peripheral blood lymphocytes and inflammatory cytokines. Then, single-cell RNA sequencing and untargeted metabolomics were performed on mouse liver tissue. RESULTS: HCoV-229E infection in combination with exposure to a cold-damp environment significantly decreased the percentage of peripheral blood lymphocytes (CD4+ and CD8+ T cells, B cells) in mice, which was enhanced by QFPDD therapy. Meanwhile, the levels of inflammatory cytokines such as IL-6, TNF-α, and IFN-γ were significantly increased in mouse models but significantly decreased by QFPDD treatment. Single-cell RNA sequencing analysis showed that QFPDD could attenuate disease-associated alterations in gene expression, core transcriptional regulatory networks, and cell-type composition. Computational predictions indicated that QFPDD rectified the observed aberrant patterns of cell-cell communication. Additionally, the metabolic profiles of liver tissue in the Model group were distinct from mice in the Control group, and QFPDD significantly regulated hepatic purine metabolism. CONCLUSION: To the best of our knowledge, this study is the first to integrate hepatic single-cell RNA sequencing and untargeted metabolomics into a TCM formula and these valuable findings indicate that QFPDD can improve immune function and reduce liver injury and inflammation.

Effects of ammonium-based nitrogen addition on soil nitrification and nitrogen gas emissions depend on fertilizer-induced changes in pH in a tea plantation soil.

Tea (Camellia sinensis L.) plants have an optimal pH range of 4.5-6.0, and prefer ammonium (NH4+) over nitrate (NO3-); strong soil acidification and nitrification are thus detrimental to their growth. Application of NH4+-based fertilizers can enhance nitrification and produce H+ that can inhibit nitrification. However, how soil acidification and nitrification are interactively affected by different NH4+-based fertilizers in tea plantations remains unclear. The objective of this research was to evaluate the effect of the application of different forms and rates of NH4+-based fertilizers on pH, net nitrification rates, and N2O and NO emissions in an acidic tea plantation soil. We conducted a 35-day aerobic incubation experiment using ammonium sulphate, urea and ammonium bicarbonate applied at 0, 100 or 200 mg N kg-1 soil. Urea and ammonium bicarbonate significantly increased both soil pH and net nitrification rates, while ammonium sulphate did not affect soil pH but reduced net nitrification rates mainly due to the acidic nature of the fertilizer. We found that the effect of different NH4+-based nitrogen on soil nitrification depended on the impact of the fertilizers on soil pH, and nitrification played an important role in NO emissions, but not in N2O emissions. Overall, urea and ammonium bicarbonate application decoupled crop N preference and the form of N available in spite of increasing soil pH. We thus recommend the co-application of urease and nitrification inhibitors when urea is used as a fertilizer and nitrification inhibitors when ammonium bicarbonate is used as a fertilizer in tea plantations.

[Response of Soil Enzyme Activity and Chemical Properties to Nitrogen Addition in a Korean Pine Plantation].

Soil enzymes participate in numerous complex biochemical processes that take place in the soil and play an important role in the material circulation of terrestrial ecosystems. To explore the response of soil enzyme activities and chemical properties to nitrogen deposition in temperate forests, this study analyzed four soil enzyme activities based on the nitrogen addition experiment plot of Korean pine (Pinus koraiensis) plantation, which was located in the Liangshui National Natural Reserve, Heilongjiang Province. The results showed that the activities of N-acetyl-glucosidase (NAG) and alkaline phosphatase (AKP) increased significantly with increasing nitrogen application concentration. The activity of beta-glucosidase (BG) and acid phosphatase (ACP) was not significantly different among different nitrogen application treatments. The contents of total carbon, total nitrogen, total phosphorus, and available nitrogen and four enzyme activity in the upper soil (0-10 cm) under the same nitrogen application level were significantly higher than those in the lower soil (10-20 cm), but the pH values were not significantly different. Total carbon has an extremely significant positive correlation with NAG, BG, AKP, and ACP. Total nitrogen has an obvious or extremely significant positive correlation with BG, NAG, and AKP as well as ACP. The available nitrogen has an obvious and highly significant positive correlation with NAG and AKP. The total phosphorus has an obvious and extremely significant positive correlation with ACP and AKP, respectively. The nitrogen application level and the soil layer had different effects on soil enzyme activity and soil chemical properties. Long-term large input of nitrogen can directly or indirectly change soil chemical properties and affect soil enzyme activity.

Nitrogen deposition affects both net and gross soil nitrogen transformations in forest ecosystems: A review.

Nitrogen (N) deposition has rapidly increased and is influencing forest ecosystem processes and functions on a global scale. Understanding process-specific N transformations, i.e., gross N transformations, in forest soils in response to N deposition is of great significance to gain mechanistic insights on the linkages between global N deposition and N availability or loss in forest soils. In this paper, we review factors controlling N mineralization, nitrification and N immobilization, particularly in relation to N deposition, discuss the limitations of net N transformation studies, and synthesize the literature on the effect of N deposition on gross N transformations in forest ecosystems. We found that more than 97% of published papers evaluating the effect of N deposition (including N addition experiments that simulate N deposition) on soil N cycle determined net rates of mineralization and nitrification, showing that N deposition significantly increased those rates by 24.9 and 153.9%, respectively. However, studies on net N transformation do not provide a mechanistic understanding of the effect of N deposition on N cycling. To date, a small number of studies (<20 published papers) have directly quantified the effect of N deposition on gross N transformation rates, limiting our understanding of the response of soil N cycling to N deposition. The responses to N deposition of specific N transformation processes such as autotrophic nitrification, heterotrophic nitrification, dissimilatory nitrate reduction to ammonium, N mineralization, and N immobilization are poorly studied. Future research needs to use more holistic approaches to study the impact of N deposition on gross N transformation rates, N loss and retention, and their microbial-driven mechanisms to provide a better understanding of the processes involved in N transformations, and to understand the differential responses between forest and other ecosystems.

[Intervention effect of Qingzao Runfei Huazhuo Xingxue decoction on PM2.5-induced pulmonary injury in mice].

OBJECTIVE: To study the effects of Qingzao Runfei Huazhuo Xingxue decoction (QRHXD) on inflammatory reaction and histopathology in mice with PM2.5-induced pulmonary injury, and to approach the possible mechanism of prevention and treatment of traditional Chinese medicine on lung injury induced by haze. METHODS: Fifty healthy male C57BL/6 mice were randomly divided into five groups (n = 10): namely control, PM2.5, PM2.5 + low-, moderate-, and high-dose groups. The PM2.5 suspensions at a dosage of 40 mg/kg was respectively given to mice by the nasal instillation for reproduction of mouse model of lung injury induced by PM2.5, and the mice in control group were given the same volume of normal saline. The mice in PM2.5 + low-, moderate-, and high-dose QRHXD groups were given 15, 25, 50 mL×kg-1×d-1 QRHXD by oral perfusion daily for consecutive 21 days at the next day of model reproduction (the QRHXD included: Pear 75 g, Bulbus Fritillariae Cirrhosae 10 g, Radix Stemonae 8 g, Rhizoma Pinelliae 8 g, Radix Platycodi 6 g, Aster 10 g, Almond 5 g, Lily 6 g, Rhodiola 4 g, Lotus 3 g, Fructrs Liquidambaris 6 g, Radix Paeoniae Rubra 5 g, Semen Cassiae 6 g). The mice in control and PM2.5 groups were given equivalent volume of normal saline respectively. After treatment for 21 days, the mice were sacrificed, and the left lung was harvested for bronchoalveolar lavage, and the bronchoalveolar lavage fluid (BALF) was collected for determination of levels of acid phosphatase (ACP), alkaline phosphatase (AKP), lactic dehydrogenase (LDH), and albumin (ALB). The right lung was harvested for histopathology observation under light microscope using hematoxylin and eosine (HE) staining. RESULTS: After intranasal instillation of PM2.5 suspension, the levels of ACP, AKP, LDH, and ALB in PM2.5 group were significantly higher than those in control group [ACP (U/L): 3.9±0.4 vs. 1.7±0.3, AKP (U/L): 9.0±1.5 vs. 4.8±0.3, LDH (U/L): 416.7±44.4 vs. 112.5±20.3, ALB (mg/L): 198.7±32.4 vs. 65.8±21.3, all P < 0.05]. Under light microscope, the PM2.5 particles were collected, the alveolar septa were thickened, and the inflammatory cells in the alveolar cavity and pulmonary interstitium were found. On the contrary, after administration of QRHXD, a significant reduction of biochemical indexes was found, which showed a dose-dependent manner. The parameters of PM2.5 + high-dose QRHXD group were significantly lower than those in PM2.5 group [ACP (U/L): 2.1±0.8 vs. 3.9±0.4, AKP (U/L): 5.3±1.4 vs. 9.0±1.5, LDH (U/L): 146.6±29.8 vs. 416.7±44.4, ALB (mg/L): 88.5±26.7 vs. 198.7±32.4, all P < 0.05]. At the same time, the pathological changes in lung tissue were better with the increase of the dose. CONCLUSIONS: QRHXD can reduce the pulmonary inflammatory response and tissue damage caused by PM2.5, with the increase concentration of Chinese medicine, and the effect is more obvious. This may be related to the immune response of the human body to regulate inflammatory mediators, which provide basis for the treatment of pulmonary injury induced by PM2.5.

The Genome of Medicinal Plant Macleaya cordata Provides New Insights into Benzylisoquinoline Alkaloids Metabolism.

The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids (BIAs) such as sanguinarine (SAN) and chelerythrine (CHE), but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding 13C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M. cordata, the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.

Design, Synthesis, and Structure-Activity Relationship of New Pyrimidinamine Derivatives Containing an Aryloxy Pyridine Moiety.

The pyrimidinamine diflumetorim is an ideal template for the discovery of agrochemical lead compounds due to its unique mode of action, novel chemical structure, and lack of reported resistance. To develop a new pyrimidinamine fungicide effective against cucumber downy mildew (CDM), a series of new pyrimidinamine derivatives containing an aryloxy pyridine moiety were designed and synthesized by employing the recently reported intermediate derivatization method (IDM). The structures of all compounds were identified by 1H NMR, elemental analyses, HRMS, and X-ray diffraction. Bioassays demonstrated that some of the title compounds exhibited excellent fungicidal activities against CDM. Compound 9 gave the best activity (EC50 = 0.19 mg/L), which is significantly better than the commercial fungicides diflumetorim, flumorph, and cyazofamid. The relationship between structure and fungicidal activity of the synthesized pyrimidinamines was explored. The study showed that compound 9 is a promising fungicide candidate for further development.

Nardosinane-type sesquiterpenoids of Nardostachys chinensis Batal.

Four new nardosinane-type sesquiterpenoids nardosinanones F-I (1-2, 4-5), along with eight known sesquiterpenoids (3, 6-12) were isolated from the underground parts of Nardostachys chinensis Batal. Their structures were elucidated on the basis of extensive spectroscopic analysis. Compounds 1 and 2 were new nardosinane sesquiterpenoids processing a rare 4,11-epoxy group in nature. In addition, compounds 1, 5-7, 11 and 12 showed protective effects on neonatal rat cardiomyocyte injury induced by hydrogen peroxide.

Isolation and identification of phase I metabolites of phillyrin in rats.

Phillyrin was one of the main chemical constituents of the fruit of Forsythia suspensa (Thunb.) Vahl. It showed various bioactivities including antioxidant and anti-inflammatory activities. However, the metabolism of phillyrin remained unknown. This report described the isolation and identification of phase I metabolites of phillyrin in rats. Nine metabolites including six new ones were isolated by various column chromatographies and high-performance liquid chromatography. Their structures were elucidated by extensive spectroscopic analysis. The antiviral activities of phillyrin and the metabolites were evaluated against influenza A (H3N2) virus. Among them, one metabolite M8 showed moderate activity with the IC50 value of 26.39 µM, and three metabolites (M2, M3, M9) showed weak antiviral activities at the concentration of 100 µM. Based on the structures of the metabolites, possible metabolic pathways of phillyrin in rats were also proposed.