Biogeography and assembly processes of abundant and rare soil microbial taxa in the southern part of the Qilian Mountain National Park, China.

Soil microorganisms play vital roles in regulating multiple ecosystem functions. Recent studies have revealed that the rare microbial taxa (with extremely low relative abundances, which are still largely ignored) are also crucial in maintaining the health and biodiversity of the soil and may respond differently to environmental pressure. However, little is known about the soil community structures of abundant and rare taxa and their assembly processes in different soil layers on the Qinghai-Tibet Plateau (QTP). The present study investigated the community structure and assembly processes of soil abundant and rare microbial taxa on the northeastern edge of the QTP. Soil microbial abundance was defined by abundant taxa, whereas rare taxa contributed to soil microbial diversity. The results of null model show that the stochastic process ruled the assembly processes of all sub-communities. Dispersal limitation contributed more to the assembly of abundant microbial taxa in the different soil layers. In contrast, drift played a more critical role in the assembly processes of the rare microbial taxa. In addition, in contrast to previous studies, the abundant taxa played more important roles in co-occurrence networks, most likely because of the heterogeneity of the soil, the sparsity of amplicon sequencing, the sampling strategy, and the limited samples in the present study. The results of this study improve our understanding of soil microbiome assemblies on the QTP and highlight the role of abundant taxa in sustaining the stability of microbial co-occurrence networks in different soil layers.

Soil properties and fungal community jointly explain N2O emissions following N and P enrichment in an alpine meadow.

Nutrient enrichment, such as nitrogen (N) and phosphorus (P), typically affects nitrous oxide (N2O) emissions in terrestrial ecosystems, predominantly via microbial nitrification and denitrification processes in the soil. However, the specific impact of soil property and microbial community alterations under N and P enrichment on grassland N2O emissions remains unclear. To address this, a field experiment was conducted in an alpine meadow of the northeastern Qinghai-Tibetan Plateau. This study aimed to unravel the mechanisms underlying N and P enrichment effects on N2O emissions by monitoring N2O fluxes, along with analyzing associated microbial communities and soil physicochemical properties. We observed that N enrichment individually or in combination with P enrichment, escalated N2O emissions. P enrichment dampened the stimulatory effect of N enrichment on N2O emissions, indicative of an antagonistic effect. Structural equation modeling (SEM) revealed that N enrichment enhanced N2O emissions through alterations in fungal community composition and key soil physicochemical properties such as pH, ammonium nitrogen (NH4+-N), available phosphorus (AP), microbial biomass carbon (MBC), and microbial biomass nitrogen (MBN)). Notably, our findings demonstrated that N2O emissions were significantly more influenced by fungal activities, particularly genera like Fusarium, rather than bacterial processes in response to N enrichment. Overall, the study highlights that N enrichment intensifies the role of fungal attributes and soil properties in driving N2O emissions. In contrast, P enrichment exhibited a non-significant effect on N2O emissions, which highlights the critical role of the fungal community in N2O emissions responses to nutrient enrichments in alpine grassland ecosystems.

Association Between Preoperative Long-Term Poor Sleep Quality and Postoperative Delirium in Elderly Patients Undergoing Cardiac Surgery: A Multi-Center Observational Study.

BACKGROUND: Delirium is a common complication in elderly patients after cardiac surgery, and sleep disorders have been suggested as a potential risk factor. However, few studies have explored the link between long-term preoperative poor sleep quality and postoperative delirium (POD) in this population. This study aimed to investigate the association between preoperative sleep quality and POD in elderly cardiac surgery patients. METHODS: The study enrolled 194 patients aged 60 years or older who underwent cardiac surgery. The Pittsburgh Sleep Quality Index (PSQI) objectively assessed preoperative sleep quality, while the Confusion Assessment Method screened for POD. The measurable outcomes encompassed the identification of risk factors associated with POD, while the secondary outcomes focused on factors influencing levels of consciousness. The statistical analysis is logistic regression analysis. RESULTS: Patients with POD had a higher prevalence of preoperative sleep disorders and higher PSQI scores than those without delirium (12.9 ± 5.1 vs 7.8 ± 3.4, P = .007). Logistic regression analysis demonstrated that the number of months with high PSQI scores and age were significantly associated with POD. The predictive ability of the number of months with high PSQI scores for POD was .762 (95% CI: .671-.854). Multivariate linear regression analysis revealed that preoperative sleep disorder was a significant predictor of exacerbation of POD (P < .05). CONCLUSION: This study suggests that long-term poor preoperative sleep quality, as assessed by the PSQI, is associated with an increased risk of POD in elderly patients undergoing cardiac surgery.

The Euphrates Poplar Responses to Abiotic Stress and Its Unique Traits in Dry Regions of China (Xinjiang and Inner Mongolia): What Should We Know?

At the moment, drought, salinity, and low-temperature stress are ubiquitous environmental issues. In arid regions including Xinjiang and Inner Mongolia and other areas worldwide, the area of tree plantations appears to be rising, triggering tree growth. Water is a vital resource in the agricultural systems of countries impacted by aridity and salinity. Worldwide efforts to reduce quantitative yield losses on Populus euphratica by adapting tree plant production to unfavorable environmental conditions have been made in response to the responsiveness of the increasing control of water stress. Although there has been much advancement in identifying the genes that resist abiotic stresses, little is known about how plants such as P. euphratica deal with numerous abiotic stresses. P. euphratica is a varied riparian plant that can tolerate drought, salinity, low temperatures, and climate change, and has a variety of water stress adaptability abilities. To conduct this review, we gathered all available information throughout the Web of Science, the Chinese National Knowledge Infrastructure, and the National Center for Biotechnology Information on the impact of abiotic stress on the molecular mechanism and evolution of gene families at the transcription level. The data demonstrated that P. euphratica might gradually adapt its stomatal aperture, photosynthesis, antioxidant activities, xylem architecture, and hydraulic conductivity to endure extreme drought and salt stress. Our analyses will give readers an understanding of how to manage a gene family in desert trees and the influence of abiotic stresses on the productivity of tree plants. They will also give readers the knowledge necessary to improve biotechnology-based tree plant stress tolerance for sustaining yield and quality trees in China's arid regions.

Parental Attachment and Proactive-Reactive Aggression in Adolescence: The Mediating Role of Self-Control and Perspective Taking.

Introduction: Identifying risk and protective factors of aggressive behavior during adolescence is beneficial for the intervention and prevention treatments. Although studies show that attachment quality is closely related to aggression, the underlying psychological mechanisms remain unclear. This study aimed to investigate the links of parental attachment with proactive and reactive aggression and to examine the mediating role of perspective taking and self-control among Chinese adolescents. Methods: A cluster sampling method was used to recruit participants from several high schools located in the central regions of China. A total of 2982 participants (Mage = 17.28, SD = 0.83, range 15~20 years; 1602 girls, 1380 boys) were included in the final analysis. Results: Correlation analysis showed that participants possessing higher attachment security with parents were more likely to report lower levels of proactive and reactive aggression. And, self-control and perspective taking were positively associated with parental attachment, and negatively associated with both types of aggression. Moreover, structural equation models indicated that parental attachment directly, and indirectly predicted proactive and reactive aggression through self-control and perspective taking. Discussion: Overall, this study contributes to a more comprehensive understanding of the explanatory mechanisms that link adolescent-parent attachment and aggression, and suggest that high quality of adolescent-parent interactions may promote adolescents' self-control and perspectives taking, which further reduces their aggression propensity.

The safety and efficacy of remimazolam tosylate combined with propofol in upper gastrointestinal endoscopy: A multicenter, randomized clinical trial.

INTRODUCTION: Hypotension is the most common adverse event under propofol-mediated sedation and is possible to cause varying degrees of damage to patients. Whereas remimazolam has a poorer sedative effect than propofol. AIM: The aim of this study was to explore the advantages of the combination of remimazolam tosylate and propofol. METHODS: 304 patients were divided into the remimazolam tosylate group (RT group), the propofol group (P group), and the remimazolam tosylate plus propofol group(R+T group). The primary outcome was the incidence of hypotension. Secondary outcomes included the results of sedation and recovery. The safety results mainly include the incidence of Hypotension, adverse respiratory events, postoperative nausea and vomiting, hiccup, cough, body movement and bradycardia. RESULTS: The incidence of hypotension was 56.7% in the P group, 12.6% in the RT group, and 31.3% in the R+P group, three groups of pairwise comparisons showed statistical differences, with P< 0.001. The incidence of body movement was significantly higher in the RT group (26.1%) than in the P group (10.3%) and the R+P group (12.5%), P = 0.004. The endoscopist satisfaction was higher in the P (3.87±0.44) and R+P (3.95±0.22)groups than in the RT(3.53±0.84) group. The incidence of adverse events, in descending order, was P group, RT group, and R+P group (93.8%vs.61.3%vs.42.7%). CONCLUSION: Co-administration had fewer adverse events than propofol monotherapy, also had a better sedative effect and higher endoscopist satisfaction than remimazolam monotherapy. TRIAL REGISTRATION: Clinical trial registration number: NCT05429086.

Mitigation mechanism of zinc oxide nanoparticles on cadmium toxicity in tomato.

Cadmium (Cd) pollution seriously reduces the yield and quality of vegetables. Reducing Cd accumulation in vegetables is of great significance for improving food safety and sustainable agricultural development. Here, using tomato as the material, we analyzed the effect of foliar spraying with zinc oxide nanoparticles (ZnO NPs) on Cd accumulation and tolerance in tomato seedlings. Foliar spraying with ZnO NPs improved Cd tolerance by increasing photosynthesis efficiency and antioxidative capacity, while it reduced Cd accumulation by 40.2% in roots and 34.5% in leaves but increased Zn content by 33.9% in roots and 78.6% in leaves. Foliar spraying with ZnO NPs also increased the contents of copper (Cu) and manganese (Mn) in the leaves of Cd-treated tomato seedlings. Subsequent metabonomic analysis showed that ZnO NPs exposure alleviated the fluctuation of metabolic profiling in response to Cd toxicity, and it had a more prominent effect in leaves than in roots. Correlation analysis revealed that several differentially accumulated metabolites were positively or negatively correlated with the growth parameters and physiol-biochemical indexes. We also found that flavonoids and alkaloid metabolites may play an important role in ZnO NP-alleviated Cd toxicity in tomato seedlings. Taken together, the results of this study indicated that foliar spraying with ZnO NPs effectively reduced Cd accumulation in tomato seedlings; moreover, it also reduced oxidative damage, improved the absorption of trace elements, and reduced the metabolic fluctuation caused by Cd toxicity, thus alleviating Cd-induced growth inhibition in tomato seedlings. This study will enable us to better understand how ZnO NPs regulate plant growth and development and provide new insights into the use of ZnO NPs for improving growth and reducing Cd accumulation in vegetables.

A Comparison Between Before and During the Pandemic in Nonsuicidal Self-Injury Behaviors of Bipolar Disorder.

ABSTRACT: The aim of this study was to assess the feature change of nonsuicidal self-injury (NSSI) behaviors in bipolar disorder before and during the pandemic. A total of 115 adolescents with NSSI were evaluated using a Wechsler Intelligence Scale for Children-Fourth Edition, Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version, and some related scales. In comparison with the 2017 group, female sex, borderline personality disorder, self-reported internalizing disorders, anxiety/depression, and thinking disorders were all related with the 2021 and 2019 groups. The 2019 group was linked to a variety of somatic issues. Negative life experiences, bullying, eating disorders, social issues, depressed feelings, performance and social anxiety, and rejection sentiments were all linked to NSSI. Both shared and differential features between before and during the pandemic may represent possible change for diagnostic and preventative interventions of NSSI in patients with bipolar disorder. Therefore, the doctor should adjust the treatment strategy based on changing of features between before and during the pandemic.

Study on the Electrochemiluminescence of Pentaphenylpyrrole in the Aqueous Phase Based on Structure-Regulated Strategy.

Heterocyclic nitrogen compounds play a vital role in luminescent materials, but most of them face the challenges of aggregation-caused quenching (ACQ) and poor water solubility. In this work, we present the nitrogen heterocyclic pentaphenylpyrrole (PentaPP) with an excellent aggregation-induced electrochemiluminescence (AIE-ECL) performance in the aqueous phase through the comparison of the elegant ECL luminophore 5,10,15,20-tetraphenylporphyrin (TPP). Further studies suggest that such unique AIE-ECL arises from its propeller-like noncoplanar structure and the large conjugation from the phenyl groups on the ring. In addition, the new ECL analysis could feature some advantages of AIE characteristic, water compatibility, and strong signal and finally achieve the ultrasensitive detection toward the explosive 2,4,6-trinitrophenol (TNP) with a lower detection limit (1.1 nM). This study does not only benefit to solve the two key problems mentioned before but also enriches the fundamentals and applications for ECL and pyrrole research.

Soil properties rather than plant diversity mediate the response of soil bacterial community to N and P additions in an alpine meadow.

The alpine meadow on the Qinghai-Tibetan Plateau, which is susceptible to global climate change and human activities, is subject to nutrient addition such as nitrogen (N) and phosphorus (P) to enhance soil available nutrients and ecosystem productivity. Soil bacterial community partly drivers the effects of nutrient additions on ecosystem processes, whereas the factors influencing N and P additions on bacterial community in alpine meadows are not well documented. We conducted a N and P addition experiment in an alpine meadow ecosystem on the Qinghai-Tibetan Plateau with four treatments: untreated control (CK), N addition (N), P addition (P), and NP addition (NP). We employed a high-throughput Illumina Miseq sequencing technology to investigate the response of soil bacterial community to short-term N and P additions. N and P additions decreased soil bacterial richness (OTU numbers and Chao 1 index), and P addition decreased soil bacterial diversity (Shannon and Simpson indices). N addition directly induced the change of soil N H 4 + - N , and decreased plant diversity. The N and P additions reduced soil bacterial community diversity, whose response was independent with plant diversity. Additionally, nutrient additions altered soil bacterial community composition, which were highly correlated with soil properties (i.e. pH, N H 4 + - N , and TP) as shown by RDA. Consistently, structural equation modeling results revealed that N addition indirectly acted on soil bacterial community through altering soil available nutrients and pH, while P addition indirectly affected bacterial community by increasing soil P availability. These findings imply that more attention should be paid to soil properties in regulating belowground biodiversity process in alpine meadows under future environmental change scenario.

Precipitation increase counteracts warming effects on plant and soil C:N:P stoichiometry in an alpine meadow.

Temperature and precipitation are expected to increase in the forthcoming decades in the northeastern Qinghai-Tibetan Plateau, with uncertain effects of their interaction on plant and soil carbon:nitrogen:phosphorus (C:N:P) stoichiometry in alpine ecosystems. A two-year field experiment was conducted to examine the effects of warming, precipitation increase, and their interaction on soil and plant C:N:P stoichiometry at functional groups and community level in an alpine meadow. Warming increased aboveground biomass of legumes and N:P ratios of grasses and community, but did not affect soil C:N:P stoichiometry. The piecewise structural equation model (SEM) indicated that the positive effect of warming on community N:P ratio was mainly resulted from its positive influence on the aboveground biomass of functional groups. Precipitation increase reduced C:N ratios of soil, grasses, and community, indicating the alleviation in soil N-limitation and the reduction in N use efficiency of plant. SEM also demonstrated the decisive role of grasses C:N:P stoichiometry on the response of community C:N:P stoichiometry to precipitation increase. The interaction of warming and precipitation increase did not alter plant community and soil, N:P and C:P ratios, which was resulting from their antagonistic effects. The stable soil and plant community C:N:P stoichiometry raised important implications that the effect of warming was offset by precipitation increase. Our study highlights the importance of considering the interaction between warming and precipitation increase when predicting the impacts of climate change on biogeochemical cycles in alpine meadow ecosystems.

Richness and distribution of endangered orchid species under different climate scenarios on the Qinghai-Tibetan Plateau.

Predicting the potential influences of climate change on the richness and distribution is essential for the protection of endangered species. Most orchid species are narrowly distributed in specific habitats and are very vulnerable to habitat disturbance, especially for endangered orchid species on the Qinghai-Tibetan Plateau (QTP). In this study, we simulated the potential influences of climate change on the richness and distribution of 17 endangered orchid species on the QTP using the MaxEnt model based on the shared socioeconomic pathways scenarios (SSPs) in the 2050s and 2070s. The results showed that aspect, annual precipitation, elevation, mean temperature of driest quarter, topsoil pH (H2O), and topsoil sand fraction had a large influence on the potential distribution of endangered orchid species on the QTP. The area of potential distribution for orchid species richness ranging from 6 to 11 under the current climate scenario was 14,462 km2 (accounting for 0.56% of QTP), and it was mostly distributed in the southeastern part of QTP. The area of orchid species richness ranging from 6 to 11 under SSP370 in the 2070s was the smallest (9,370 km2: only accounting for 0.36% of QTP). The largest area of potential distribution for orchid species richness ranging from 6 to 11 was 45,394 km2 (accounting for 1.77% of QTP) under SSP585 in the 2070s. The total potential distribution area of 17 orchid species richness all increased from the 2050s to the 2070s under SSP126, SSP245, SSP370, and SSP585. The orchid species richness basically declined with the increasing elevation under current and future climate scenarios. The mean elevation of potential distribution for orchid species richness ranging from 6 to 11 under different climate scenarios was between 3,267 and 3,463 m. The mean elevation of potential distribution for orchid species richness ranging from 6 to 11 decreased from SSP126 (3,457 m) to SSP585 (3,267 m) in the 2070s. Based on these findings, future conservation plans should be concentrated on the selection of protected areas in the southeastern part of QTP to protect the endangered orchid species.

Development, Validation, and Comparison of Image-Based, Clinical Feature-Based and Fusion Artificial Intelligence Diagnostic Models in Differentiating Benign and Malignant Pulmonary Ground-Glass Nodules.

Objective: This study aimed to develop effective artificial intelligence (AI) diagnostic models based on CT images of pulmonary nodules only, on descriptional and quantitative clinical or image features, or on a combination of both to differentiate benign and malignant ground-glass nodules (GGNs) to assist in the determination of surgical intervention. Methods: Our study included a total of 867 nodules (benign nodules: 112; malignant nodules: 755) with postoperative pathological diagnoses from two centers. For the diagnostic models to discriminate between benign and malignant GGNs, we adopted three different artificial intelligence (AI) approaches: a) an image-based deep learning approach to build a deep neural network (DNN); b) a clinical feature-based machine learning approach based on the clinical and image features of nodules; c) a fusion diagnostic model integrating the original images and the clinical and image features. The performance of the models was evaluated on an internal test dataset (the "Changzheng Dataset") and an independent test dataset collected from an external institute (the "Longyan Dataset"). In addition, the performance of automatic diagnostic models was compared with that of manual evaluations by two radiologists on the 'Longyan dataset'. Results: The image-based deep learning model achieved an appealing diagnostic performance, yielding AUC values of 0.75 (95% confidence interval [CI]: 0.62, 0.89) and 0.76 (95% CI: 0.61, 0.90), respectively, on both the Changzheng and Longyan datasets. The clinical feature-based machine learning model performed well on the Changzheng dataset (AUC, 0.80 [95% CI: 0.64, 0.96]), whereas it performed poorly on the Longyan dataset (AUC, 0.62 [95% CI: 0.42, 0.83]). The fusion diagnostic model achieved the best performance on both the Changzheng dataset (AUC, 0.82 [95% CI: 0.71-0.93]) and the Longyan dataset (AUC, 0.83 [95% CI: 0.70-0.96]), and it achieved a better specificity (0.69) than the radiologists (0.33-0.44) on the Longyan dataset. Conclusion: The deep learning models, including both the image-based deep learning model and the fusion model, have the ability to assist radiologists in differentiating between benign and malignant nodules for the precise management of patients with GGNs.

Kinsenoside alleviates inflammation and fibrosis in experimental NASH mice by suppressing the NF-κB/NLRP3 signaling pathway.

BACKGROUND: Non-alcoholic steatohepatitis (NASH) has replaced viral hepatitis as the main driver of the rising morbidity and mortality associated with cirrhosis and liver cancer worldwide, while no FDA-approved therapies are currently known. Kinsenoside (KD), naturally isolated from Anoectochilus roxburghii, possesses multiple biological activities, including lipolysis, anti-inflammation, and hepatoprotection. However, the effects of KD on NASH remain unclear. PURPOSE: This study aimed to explore the roles of KD in NASH and its engaged mechanisms. METHODS: Two typical animal models of NASH, mice fed a methionine-choline-deficient (MCD) diet (representing non-obese NASH) and mice fed a high-fat and -fructose diet (HFFD) (representing obese NASH), were used to investigate the effect of KD on NASH in vivo. Transcriptome sequencing was performed to elucidate the underlying mechanisms of KD. Lipopolysaccharide (LPS)-stimulated THP-1 cells and transforming growth factor ß1 (TGF-ß1)-activated LX-2 cells were applied to further explore the effects and mechanisms of KD in vitro. RESULTS: The intragastric administration of KD remarkably alleviated MCD/HFFD-induced murine NASH almost in a dose-dependent manner. Specifically, KD reduced lipid accumulation, inflammation, and fibrosis in the liver of NASH mice. KD ameliorated alanine aminotransferase (ALT), aspartate aminotransferase (AST), superoxide dismutase (SOD), and malondialdehyde (MDA) abnormalities. In addition, it decreased the level of serum proinflammatory factors (IL-12p70, IL-6, TNF-α, MCP-1, IFN-γ) and the hepatic expression of typical fibrosis-related molecules (α-SMA, Col-I, TIMP-1). Mechanically, KD attenuated the MCD/HFFD-induced NASH through the inhibition of the NF-κB/NLRP3 signaling pathway. Consistently, KD reduced inflammation stimulated by LPS in THP-1 cells via suppressing the NF-κB/NLRP3 pathway. Furthermore, it prevented the activation of LX-2 cells directly, by inhibiting the proliferation stimulated by TGF-ß1, and indirectly, by inactivating the NLRP3 inflammasome in macrophages. CONCLUSION: For the first time, the practical improvement of NASH by KD was revealed. Our study found that KD exerted its alleviative effects on NASH through the inhibition of the NF-κB/NLRP3 signaling pathway. Given its hepatoprotective and nontoxic properties, KD has the potential to be a novel and effective drug to treat NASH.

An unprecedented ergostane with a 6/6/5 tricyclic 13(14 → 8)abeo-8,14-seco skeleton from Talaromyces adpressus.

Talasterone A (1), an unprecedented 6/6/5 tricyclic 13(14 â†’ 8)abeo-8,14-seco-ergostane steroid, together with two known congeners dankasterone B (2) and (14ß,22E)-9,14-dihydroxyergosta-4,7,22-triene-3,6-dione (3), were characterized from Talaromyces adpressus. The structure of 1 with absolute configuration was elucidated based on NMR spectroscopic data and ECD calculation. Compound 2 belongs to a class of unconventional 13(14 â†’ 8)abeo-ergostanes, which have been renewed via the 1,2-migration of C-13-C-14 bond to C-8. In addition, compound 1 represents the first example of ergostane with a tricyclic 13(14 â†’ 8)abeo-8,14-seco-ergostane skeleton. The proposed biosynthetic pathway was established with the support of the coisolation of the known congeners from the producing organism. It is especially noteworthy that compound 1 exhibited potent anti-inflammatory activity with an IC50 value of 8.73 ± 0.66 µM, inhibiting the NF-κB pathway and thus reducing the production of proinflammatory cytokines.

Norprzewalsone A, a Rearranged Polycyclic Polyprenylated Acylphloroglucinol with a Spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] Core from Hypericum przewalskii.

Norprzewalsone A (1), a rearranged polyprenylated polycyclic acylphloroglucinol (PPAP) with a new carbon skeleton, along with a new congener, norprzewalsone B (2), were isolated from Hypericum przewalskii. Compound 1 possessed a new 5/6/5/6/6 pentacyclic ring system based on a spiro[cyclopentane-1,3'-tricyclo[7.4.0.01,6]tridecane] core, which might be derived from the common [3.3.1]-type bicyclic polyprenylated acylphloroglucinol (BPAP) via the key retro-Claisen, intramolecular cyclization, and Diels-Alder cyclization reactions. Their structures and absolute configurations were confirmed by spectroscopic data, calculated 1D NMR data with DP4+ probability analyses, and electronic circular dichroism calculations and comparison. More significantly, compound 1 exhibited a moderate inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells.

Methyl 6-O-cinnamoyl-α-d-glucopyranoside Ameliorates Acute Liver Injury by Inhibiting Oxidative Stress Through the Activation of Nrf2 Signaling Pathway.

Excessive stimulation of hepatotoxins and drugs often lead to acute liver injury, while treatment strategies for acute liver injury have been limited. Methyl 6-O-cinnamoyl-α-d-glucopyranoside (MCGP) is a structure modified compound from cinnamic acid, a key chemical found in plants with significant antioxidant, anti-inflammatory, and antidiabetic effects. In this study, we investigated the effects and underlying mechanisms of MCGP on acetaminophen (APAP)- or carbon tetrachloride (CCl4)-induced acute liver injury. As a result, MCGP inhibited cell death and apoptosis induced by APAP or CCl4, and suppressed the reactive oxygen species (ROS) generation stimulated by H2O2 in liver AML12 cells. In vivo, MCGP alleviated APAP/CCl4-induced hepatic necrosis and resumed abnormal aminotransferase activities and liver antioxidase activities. In addition, MCGP depressed APAP- or CCl4-induced oxidative stress through the suppression of CYP2E1 and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. MCGP also enhanced the number of PCNA-positive hepatocytes, increased hepatic PCNA and Bcl-XL, and decreased BAX expression in APAP-/CCl4-intoxicated mice. Furthermore, MCGP activated the GSDMD-N/cleaved caspase 1 pathway. In summary, MCGP might act as a potential therapeutic drug against drug-induced and chemical-induced acute liver injuries, and its underlying mechanisms might engage on the pressing of oxidative stress, refraining of hepatocyte apoptosis, and facilitating of liver regeneration.

Discovery of bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum wilsonii.

Eleven new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperwilsones A-K (1-11), along with five known PPAPs (12-16), were isolated from Hypericum wilsonii. Their structures were established via spectroscopic methods, the careful analysis of calculated and experimental electronic circular dichroism (ECD) spectra, single-crystal X-ray diffraction, the modified Mosher's method, and [Rh2(OCOCF3)4]-induced ECD. Hyperwilsone A (1) and hyperwilsone B (2) possessed the unique acetal functionality. Hyperwilsone C (3) was a rare example of [3.3.1]-type PPAP possessing a 3-isopropylfuran moiety. In bioassay, compounds 9 and 10 showed potent anti-inflammatory activity against LPS-induced NO production by inhibiting the nuclear translocation of NF-κB p65 and thus reducing the production of proinflammatory cytokines. Compounds 5, 8, 11, and 14 exhibited moderate inhibitory activity against SUDHL-4 and HL60 cancer cells with IC50 values in the range of 5.74-19.82 µM.

New Polyketides With Anti-Inflammatory Activity From the Fungus Aspergillus rugulosa.

Two new polyketide compounds, asperulosins A and B (1-2), and one new prenylated small molecule, asperulosin C (3), along with nine known compounds (4-12), were isolated and identified from a fungus Aspergillus rugulosa. Their structures were extensively elucidated via HRESIMS, 1D, and 2D NMR analysis. The absolute configurations of the new compounds were determined by the comparison of their electronic circular dichroism (ECD), calculated ECD spectra, and the detailed discussion with those in previous reports. Structurally, compounds 1 and 2 belonged to the polyketide family and were from different origins. Compound 2 was constructed by five continuous quaternary carbon atoms, which occur rarely in natural products. All of the isolates were evaluated for anti-inflammatory activity against the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Among those, compounds 1 and 5 showed a significant inhibitory effect on NO production with IC50 values of 1.49 ± 0.31 and 3.41 ± 0.85 µM, respectively. Additionally, compounds 1 and 5 markedly increased the secretion of anti-inflammatory cytokine IL10 while suppressing the secretion of pro-inflammatory cytokines IL6, TNF-α, IFN-γ, MCP-1, and IL12. Besides, 1 and 5 inhibited the transcription level of pro-inflammatory macrophage markers IL6, IL1ß, and TNF-α while remarkably elevating the anti-inflammatory factor IL10 and M2 macrophage markers ARG1 and CD206. Moreover, 1 and 5 restrained the expression and nuclear translocation of NF-κB, as well as its downstream signaling proteins COX-2 and iNOS. All these results suggest that 1 and 5 have potential as anti-inflammatory agents, with better or comparable activities than those of the positive control, dexamethasone.

Terpene-Shikimate conjugated meroterpenoids from the endophytic fungus Guignardia mangiferae.

Nine undescribed shikimate-conjugated meroterpenes, as well as nine known compounds, were isolated from solid cultures of the fungus Guignardia mangiferae, an endophyte obtained from the leaves of Dendrobium nobile. The structures of these undescribed compounds were characterized by analyses of their 1D and 2D NMR and HRESIMS data, and their absolute configurations were assigned by single-crystal X-ray crystallography, electronic circular dichroism (ECD) calculations, modified Mosher's method, and Mo2(OCOCH3)4-induced ECD experiments. Of these compounds, mangnardone A represents the first example of terpene-shikimate-conjugated meroterpenoid with a hydroxy group at C-5. In addition, the X-ray diffraction analysis of mangnardone I is the first example to confirm the structure of bicycloalternarene (BCA) meroterpenoid by single-crystal data. Nine undescribed meroterpenes inhibited nitric oxide (NO) production in LPS-induced RAW 264.7 cells with IC50 values in the range of 4.7-40.0 µM.