Polygala tenuifolia willd. Extract alleviates LPS-induced acute lung injury in rats via TLR4/NF-κB pathway and NLRP3 inflammasome suppression.

BACKGROUND: Acute lung injury (ALI) has received considerable attention in the field of critical care as it can lead to high mortality rates. Polygala tenuifolia, a traditional Chinese medicine with strong expectorant properties, can be used to treat pneumonia. Owing to the complexity of its composition, the main active ingredient is not yet known. Thus, there is a need to identify its constituent compounds and mechanism of action in the treatment of ALI using advanced technological means. PURPOSE: We investigated the anti-inflammatory mechanism and constituent compounds with regard to the effect of P. tenuifolia Willd. extract (EPT) in lipopolysaccharide (LPS)-induced ALI in vivo and in vitro. METHODS: The UHPLC-Q-Exactive Orbitrap MS technology was used to investigate the chemical profile of EPT. Network pharmacology was used to predict the targets and pathways of action of EPT in ALI, and molecular docking was used to validate the binding of polygalacic acid to Toll-like receptor (TLR) 4. The main compounds were determined using LC-MS. A rat model of LPS-induced ALI was established, and THP-1 cells were stimulated with LPS and adenosine triphosphate (ATP) to construct an in vitro model. Pathological changes were observed using hematoxylin and eosin staining, Wright-Giemsa staining, and immunohistochemistry. The expression of inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) was determined using enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The LPS + ATP-induced inflammation model in THP-1 cells was used to verify the in vivo experimental results. RESULTS: Ninety-nine compounds were identified or tentatively deduced from EPT. Using network pharmacology, we found that TLR4/NF-κB may be a relevant pathway for the prevention and treatment of ALI by EPT. Polygalacic acid in EPT may be a potential active ingredient. EPT could alleviate LPS-induced histopathological lung damage and reduce the wet/dry lung weight ratio in the rat model of ALI. Moreover, EPT decreased the white blood cell and neutrophil counts in the bronchoalveolar lavage fluid and decreased the expression of genes and proteins of relevant inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) in lung tissues. It also increased the expression of endothelial-type nitric oxide synthase expression. Western blotting confirmed that EPT may affect TLR4/NF-κB and NLRP3 signaling pathways in vivo. Similar results were obtained in THP-1 cells. CONCLUSION: EPT reduced the release of inflammatory factors by affecting TLR4/NF-κB and NLRP3 signaling pathways, thereby attenuating the inflammatory response of ALI. Polygalacic acid is the likely compounds responsible for these effects.

Chromosome-level genome assembly of an oligophagous leaf beetle Ophraella communa (Coleoptera: Chrysomelidae).

The leaf beetle Ophraella communa LeSage (Coleoptera: Chrysomelidae) is an effective biological control agent of the common ragweed. Here, we assembled a chromosome-level genome of the O. communa by combining Illumina, Nanopore, and Hi-C sequencing technologies. The genome size of the final genome assembly is 733.1 Mb, encompassing 17 chromosomes, with an improved contig N50 of 7.05 Mb compared to the original version. Genome annotation reveals 25,873 protein-coding genes, with functional annotations available for 22,084 genes (85.35%). Non-coding sequence annotation identified 204 rRNAs, 626 tRNAs, and 1791 small RNAs. Repetitive elements occupy 414.41 Mb, constituting 57.76% of the genome. This high-quality genome is fundamental for advancing biological control strategies employing O. communa.

Male-derived phospholipase A2 enhances WD46 expression and increases fertility in Ophraella communa.

Successful bisexual reproduction requires interactions between males and females. Male-derived seminal fluid proteins (SFPs) transferred to females during mating profoundly affect females from pre- to post-mating, and the subsequent shift in female physiology enhances their fertility. SFPs have important evolutionary implications for the fitness of many insects. However, little is known about how females respond to male SFPs. In this study, we identified a male-derived SFP-phospholipase A2 (PLA2) in Ophraella communa. PLA2 is a vital enzyme in eicosanoid biosynthesis; however, it has not been identified as an insect SFP. We found that OcPLA2 is specifically expressed in males, especially in the male accessory glands (MAGs); it is transferred to the female during mating and functions as an SFP to enhance fertility. The expression of a female-derived gene encoding the WD repeat-containing protein 46 (WD46) was upregulated when OcPLA2 entered the female reproductive tract, and this contributed to female egg production by increasing triacylglycerol lipase (TGL) gene expression and the triglyceride (TG) content. This is the first study to identify PLA2 as an SFP in insects. Our findings also shed light on the regulatory role of OcPLA2 in beetle reproduction; the expression of OcPLA2 is initially correlated with female WD46 expression and later with the decline in TGL gene expression and the TG content. This represents a unique mechanism of reproductive regulation by an SFP.

Identification of candidate chemosensory genes in Bactrocera cucurbitae based on antennal transcriptome analysis.

The melon fly, Bactrocera cucurbitae (Coquillett) (Tephritidae: Diptera), is an invasive pest that poses a significant threat to agriculture in Africa and other regions. Flies are known to use their olfactory systems to recognise environmental chemical cues. However, the molecular components of the chemosensory system of B. cucurbitae are poorly characterised. To address this knowledge gap, we have used next-generation sequencing to analyse the antenna transcriptomes of sexually immature B. cucurbitae adults. The results have identified 160 potential chemosensory genes, including 35 odourant-binding proteins (OBPs), one chemosensory protein (CSP), three sensory neuron membrane proteins (SNMPs), 70 odourant receptors (ORs), 30 ionotropic receptors (IRs), and 21 gustatory receptors (GRs). Quantitative real-time polymerase chain reaction quantitative polymerase chain reaction was used to validate the results by assessing the expression profiles of 25 ORs and 15 OBPs. Notably, high expression levels for BcucOBP5/9/10/18/21/23/26 were observed in both the female and male antennae. Furthermore, BcucOROrco/6/7/9/13/15/25/27/28/42/62 exhibited biased expression in the male antennae, whereas BcucOR55 showed biased expression in the female antennae. This comprehensive investigation provides valuable insights into insect olfaction at the molecular level and will, thus, help to facilitate the development of enhanced pest management strategies in the future.

Effect of host shift on the gut microbes of Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae).

Background: Gut microbes play an important role in the adaptation of insects. Polyphagous insects usually undergo changes in gut microbiota after host shift. The Bactrocera cucurbitae have a wide range of hosts, but the dynamic of gut microorganisms during host shift have not been thoroughly investigated. To understand the role of gut microbes in insect adaptation, it is necessary to study the dynamics of insect gut microorganisms during host transfer. Methods: Using Bactrocera cucurbitae (Coquillett) (Diptera: Tephritidae) and its four hosts as study subjects, we investigated the dynamics of gut microbes during host transfer and the effects of different hosts on the gut microbial composition of B. cucurbitae. Results: The results showed that the Chao1 index of B. cucurbitae decreased significantly during host transfer, and the intestinal microorganisms were significantly affected by the original host, host, and generations. Furthermore, predicated changes in the abundance of secondary metabolite pathways after host transfer suggested that microorganisms may play an important role in the degradation of secondary metabolites, among which Providencia and Morganella have important functions in the gut of B. cucurbitae. Conclusion: This implied that microorganisms play a function in the host transfer process of B. cucurbitae and may be an important cofactor in the adaptation of B. cucurbitae to different hosts and environments, providing new research ideas for the future control of B. cucurbitae.

HDAC1: An Essential and Conserved Member of the Diverse Zn2+-Dependent HDAC Family Driven by Divergent Selection Pressure.

Zn2+-dependent histone deacetylases (HDACs) are enzymes that regulate gene expression by removing acetyl groups from histone proteins. These enzymes are essential in all living systems, playing key roles in cancer treatment and as potential pesticide targets. Previous phylogenetic analyses of HDAC in certain species have been published. However, their classification and evolutionary origins across biological kingdoms remain unclear, which limits our understanding of them. In this study, we collected the HDAC sequences from 1451 organisms and performed analyses. The HDACs are found to diverge into three classes and seven subclasses under divergent selection pressure. Most subclasses show species specificity, indicating that HDACs have evolved with high plasticity and diversification to adapt to different environmental conditions in different species. In contrast, HDAC1 and HDAC3, belonging to the oldest class, are conserved and crucial in major kingdoms of life, especially HDAC1. These findings lay the groundwork for the future application of HDACs.

Chromosome-level genome assembly of an agricultural pest Zeugodacus tau (Diptera: Tephritidae).

The fruit fly Zeugodacus tau (Diptera: Tephritidae) is a major pest of melons and other cucurbits in Southeast Asia. In this study, we used Illumina, Nanopore, and Hi-C sequencing technologies to assemble a reference genome of Z. tau at the chromosomal level. The assembled genome was 421.79 Mb and consisted of six chromosomes (one X-chromosome + five autosomes). The contig N50 was 4.23 Mb. We identified 20,922 protein-coding genes, of which 17,251 (82.45%) were functionally annotated. Additionally, we found 247 rRNAs, 435 tRNAs, 67 small nuclear RNAs, and 829 small RNAs in the genome. Repetitive elements accounted for 55.30 Mb (13.15%) of the genome. This high-quality genome assembly is valuable for evolutionary and genetic studies of Z. tau and its relative species.

Construction of a Banker Plant System via the Host Switch Trait of a Natural Enemy Aenasius bambawalei.

Understanding the most effective host switch patterns in parasitic wasps, specifically Aenasius bambawalei (AB), is crucial for effectively controlling pests like Penacoccus solenopsis (PSS). This study aims to elucidate AB's ideal host switch pattern and assess its utility in maintaining synchronization between AB and PSS, thereby aiding in PSS control. We examined various host switch patterns and cycles to evaluate their impact on AB's offspring's parasitism rates and fitness in laboratory conditions. Concurrently, we assessed the fitness of both PSS and AB on tomato plants using different banker plant systems to maintain field synchronization. Results indicate that the three-repeat T1 host switch pattern of PSS-Penacoccus solani (PSI)-PSS was the most effective. Additionally, a specific banker plant system, "System B", which provided succulent plants hosting PSI, was optimal for synchronizing AB and PSS in a summer greenhouse setting. Our findings underscore the importance of employing specific host switch patterns and banker plant systems to effectively control PSS in the field. This research offers foundational data for incorporating a banker plant system into integrated pest management strategies for enhanced PSS control.

Polygonum Cuspidatum Alcohol Extract Exerts Analgesic Effects via the MAPK/ERK Signaling Pathway.

Objective: Traditional Chinese medicine Polygonum cuspidatum (PC) has significant effects on reducing pain. In this study, we investigated the analgesic effects of the alcohol extract of PC on three types of inflammatory pain and explored its mechanism. Methods: Potential targets for the analgesic effects of the main active components of PC alcohol extract were screened by network pharmacology and molecular docking. Three different inflammatory pain mouse models (acetic acid twisting, formalin foot swelling, and xylene ear swelling) were used to study the analgesic effects of PC. The expression of latent signaling pathways in L4-6 spinal cord tissues in formalin foot swelling mice was evaluated using real-time qPCR (RT-qPCR), Western blot (WB), and immunohistochemistry (IHC) analyses. Results: Network pharmacology analysis shows that PC analgesic mechanism is related to the MAPK/ERK signaling pathway. The five main active components of PC have good docking ability with JNK and p38. PC alcohol extract significantly reduced the pain behavior and alleviated inflammatory reactions in three mouse models, inhibited the mRNA and protein phosphorylation levels of JNK, ERK, p38, and CREB in spinal cord tissues. Conclusion: PC alcohol extract can inhibit inflammation and alleviate pain, which is related to its inhibition of the MAPK/ERK signaling pathway in spinal cord. Thus, PC alcohol extract is a promising candidate for pain treatment.

Atractylodes lancea Rhizome Polysaccharide Alleviates Immunosuppression and Intestinal Mucosal Injury in Mice Treated with Cyclophosphamide.

Plant-derived polysaccharides, such as Atractylodes lancea rhizome polysaccharide (ALP), are good immune regulators. However, the immune regulatory mechanism of the ALP is unknown. This study aimed to evaluate the effects of ALP on the intestinal mucosal barrier and intestinal mucosal immunity of immunosuppressed mice. We also compared the activity of raw Atractylodes lancea rhizome polysaccharide (SALP) with wheat bran processed bran-fried Atractylodes lancea rhizome polysaccharide (FALP; both at 1.2 g/kg/d for mice). Our results showed that ALP effectively increased the immune organ index and blood cell count, stimulated the secretion of cytokines, and promoted the expression of occludin and zonula occludens-1 (ZO-1). ALP also promoted the expression of T cells and the secretion of sIgA. Furthermore, ALP alleviated the gut microbiota disorder in Cy-treated mice and increased the relative abundances of Lactobacillus and Faecalibaculum. ALP reversed the decrease in the level of SCFAs and promoted the expression of G protein-coupled receptor 43 (GPR43). To our knowledge, this study was the first to explore how the ALP protects the intestinal mucosal barrier and enhances intestinal mucosal immunity by alleviating the gut microbiota imbalance and metabolic disorders of SCFAs. FALP was more therapeutic than SALP, suggesting that FALP could be developed as a promising functional food component.

Rapid response of midgut bacteria in Bactrocera tau (Walker) (Diptera: Tephritidae) to lambda-cyhalothrin- and spinosad-induced stress.

In recent decades, the increasingly widespread application of chemical pesticides has exacerbated the emergence of insecticide resistance among insect pests. In this study, we examined the rapid response of bacteria in the midgut of the fruit fly Bactrocera tau (Walker) (Diptera: Tephritidae) to stress induced by the insecticides lambda-cyhalothrin and spinosad by analyzing the bacterial community structure and diversity in the midguts of 4-day-old B. tau. The results revealed that 4-day-old B. tau females were more resistant to lambda-cyhalothrin and spinosad than their 4-day-old male counterparts. Alpha- and beta-diversity analyses revealed no significant differences between male and female B. tau with respect to the diversity and richness of gut bacteria in response to the same treatments. In response to treatment with lambda-cyhalothrin and spinosad at lethal concentration 50 (LC50), we detected significant changes in the structure and diversity of the bacterial community in the midguts of both male and female B. tau. Particularly among the dominant bacterial genera, there were decreases in the relative abundances of Citrobacter, Enterobacter, Klebsiella, and Pectobacterium. Increases were observed in the relative abundances of Dysgonomonas, Erwinia, and Providencia. Our findings provide a theoretical basis for gaining a better understanding of the relationships between midgut bacteria and the insecticide resistance of B. tau.

Feeding on rapid cold hardening Ambrosia artemisiifolia enhances cold tolerance of Ophraella communa.

Low temperatures greatly influence newly introduced species, and increased cold tolerance can facilitate their establishment in new environments. The invasive alien species Ambrosia artemisiifolia is distributed at high latitudes and altitudes, where it suffers more from cold stress than it would at low latitudes or altitudes. Whether cold stress influences the accumulation of cryoprotectants and cold tolerance in A. artemisiifolia, and further influences the cold tolerance of its biological control agent, Ophraella communa, through feeding remain unknown. We investigated the levels of cryoprotectants and metabolic changes in A. artemisiifolia. We found that the level of total sugar, trehalose, proline, and other cold responsible metabolites increased in A. artemisiifolia after rapid cold-hardening (RCH) treatment, when compared to normal plants. These indicated that RCH treatment could improve the cold-hardiness of A. artemisiifolia. We then investigated the levels of cryoprotectants and metabolic changes in O. communa. We found that O. communa fed on RCH-treated A. artemisiifolia had higher levels of total sugar, trehalose, proline, glycerol, lipid, lower water content, lower super-cooling point, and increased cold tolerance compared to O. communa fed on normal A. artemisiifolia. This suggested that O. communa fed on cold-hardened A. artemisiifolia could increase its cold tolerance. Results showed a trophic transmission in insect cold tolerance. Our study enriches the theoretical basis for the co-evolution of cold tolerance in invasive and herbivorous insects.

Atractylenolide III Ameliorates Bile Duct Ligation-Induced Liver Fibrosis by Inhibiting the PI3K/AKT Pathway and Regulating Glutamine Metabolism.

Liver fibrosis is one of the leading causes of hepatic sclerosis and hepatocellular carcinoma worldwide. However, the complex pathophysiological mechanisms of liver fibrosis are unknown, and no specific drugs are available to treat liver fibrosis. Atractylenolide III (ATL III) is a natural compound isolated from the plant Atractylodes lancea (Thunb.) DC. that possesses antioxidant properties and the ability to inhibit inflammatory responses. In this study, cholestatic hepatic fibrosis was induced in mice using a bile duct ligation (BDL) model and treated with 10 mg/kg and 50 mg/kg of ATL III via gavage for 14 days. ATL III significantly reduced the liver index, lowered serum ALT and AST levels, and reduced liver injury in bile-duct-ligated mice. In addition, ATL III significantly attenuated histopathological changes and reduced collagen deposition. ATL III reduced the expression of fibrosis-related genes α-smooth muscle actin (α-SMA), Collagen I (col1a1), Collagen IV (col4a2), and fibrosis-related proteins α-SMA and col1a1 in liver tissue. Using RNA sequencing (RNA-seq) to screen molecular targets and pathways, ATL III was found to affect the PI3K/AKT singling pathway by inhibiting the phosphorylation of PI3K and AKT, thereby ameliorating BDL-induced liver fibrosis. Gas chromatography-mass spectrometry (GC-MS) was used to evaluate the effect of ATL III on liver metabolites in BDL mice. ATL III further affected glutamine metabolism by down-regulating the activity of glutamine (GLS1) and glutamine metabolism. ATL III further affected glutamine metabolism by down-regulating the activity of glutaminase (GLS1), as well as glutamine metabolism. Therefore, we conclude that ATL III attenuates liver fibrosis by inhibiting the PI3K/AKT pathway and glutamine metabolism, suggesting that ATL III is a potential drug candidate for treating liver fibrosis.

Quercetin ameliorates nonalcoholic fatty liver disease (NAFLD) via the promotion of AMPK-mediated hepatic mitophagy.

The global incidence of nonalcoholic fatty liver disease (NAFLD) has been surging in recent years, however, no drug is currently approved to treat this disease. Quercetin, a natural flavonoid abundant in plants and fruits, has been reported to alleviate NAFLD, however, the exact molecular mechanism remains unclear. This study aims to further elucidate its potential mechanism of action. The beneficial effects and the underlying mechanism of quercetin in alleviating NAFLD were explored both in vitro and in vivo, by employing chemical inhibitors of autophagosomes (3-methyladenine, 3-MA), autolysosomes (chloroquine, CQ), AMPK (Compound C, CC) and SIRT1 (selisistat, EX-527). The levels of intracellular lipids, reactive oxygen species, mitochondria function, autophagy, and mitophagy were assessed by fluorescent labeling and examined using flow cytometry or confocal microscopy. Key protein expressions of autophagy, mitophagy, and inflammation were also determined. In vivo, quercetin was shown to dose-dependently effectively alleviate NAFLD, but intraperitoneal injection of 3-MA could block the beneficial effects of quercetin on body weight, liver weight, serum ALT/AST, hepatic ROS and inflammation. In vitro, quercetin could reduce intracellular lipids (Nile Red staining) and ROS/DHE accumulation, which could be also blocked by 3-MA or CQ. Furthermore, we found that CC could abrogate the protective effects of quercetin on lipid and ROS accumulation in vitro. Also, CC abolished the proautophagic and anti-inflammatory effects of quercetin, as shown by western blot determination and Lyso-Tracker labeling. Importantly, mitophagy, a specific form of mitochondria-targeted autophagy, was enhanced by quercetin, as demonstrated by PINK1/Parkin protein variation and immunofluorescence colocalization of autophagosomes and mitochondria, which could also be blocked by the intervention of CC. This study demonstrates that quercetin prevents NAFLD through AMPK-mediated mitophagy and suggests that promoting mitophagy via an upregulation of AMPK may be a promising therapeutic strategy against NAFLD.

The carboxypeptidase B and carbonic anhydrase genes play a reproductive regulatory role during multiple matings in Ophraella communa.

Seminal fluid proteins (SFPs) are key factors in sexual reproduction and are transferred to females during mating with sperm. SFPs have a nutritional value because they protect and activate sperm storage and release to optimize fecundity. Multiple matings promote ovipositioning in several insect species. Therefore, insects may obtain more SFP through multiple matings to maximize reproduction, but this process has not yet been clearly confirmed. Here, the relationship between multiple matings and the SFPs in Ophraella communa (Coleoptera: Chrysomelidae), a biological control agent of the common ragweed Ambrosia artemisiifolia (Asterales: Asteraceae), was studied. Multiple matings significantly increased female fecundity and ovary egg deposition. Carboxypeptidase B (OcCpb) and carbonic anhydrase (OcCa) genes were identified as putative SFP genes in O. communa and they showed strong male-biased expression. Additionally, OcCpb and OcCa expression was upregulated in the bursa copulatrix of mating females compared to that in virgin females, but their expression gradually declined after copulation. Furthermore, OcCpb and OcCa knockdown in males led to a decrease in insect fecundity compared to that in the control. The reproductive tract of females mated with dsRNA-treated males was dissected and observed and, notably, the ovaries produced significantly fewer eggs. These data suggest that OcCpb and OcCa play regulatory roles during multiple matings in O. communa.

Therapeutic effects and mechanism of Atractylodis rhizoma in acute lung injury: Investigation based on an Integrated approach.

Acute lung injury (ALI) is characterized by an excessive inflammatory response. Atractylodes lancea (Thunb.) DC. is a traditional chinese medicine with good anti-inflammatory activity that is commonly used clinically for the treatment of lung diseases in China; however, its mechanism of against ALI is unclear. We clarified the therapeutic effects of ethanol extract of Atractylodis rhizoma (EEAR) on lipopolysaccharide (LPS)-induced ALI by evaluation of hematoxylin-eosin (HE) stained sections, the lung wet/dry (W/D) ratio, and levels of inflammatory factors as indicators. We then characterized the chemical composition of EEAR by ultra-performance liquid chromatography and mass spectrometry (UPLC-MS) and screened the components and targets by network pharmacology to clarify the signaling pathways involved in the therapeutic effects of EEAR on ALI, and the results were validated by molecular docking simulation and Western blot (WB) analysis. Finally, we examined the metabolites in rat lung tissues by gas chromatography and mass spectrometry (GC-MS). The results showed that EEAR significantly reduced the W/D ratio, and tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) levels in the lungs of ALI model rats. Nineteen components of EEAR were identified and shown to act synergetically by regulating shared pathways such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling pathways. Ferulic acid, 4-methylumbelliferone, acetylatractylodinol, atractylenolide I, and atractylenolide III were predicted to bind well to PI3K, AKT and MAPK1, respectively, with binding energies < -5 kcal/mol, although only atractylenolide II bound with high affinity to MAPK1. EEAR significantly inhibited the phosphorylation of PI3K, AKT, p38, and ERK1/2, thus reducing protein expression. EEAR significantly modulated the expression of metabolites such as D-Galactose, D-Glucose, serine and D-Mannose. These metabolites were mainly concentrated in the galactose and amino acid metabolism pathways. In conclusion, EEAR alleviates ALI by inhibiting activation of the PI3K-AKT and MAPK signaling pathways and regulating galactose metabolism, providing a new direction for the development of drugs to treat ALI.

Shiwei Qingwen decoction regulates TLR4/NF-κB signaling pathway and NLRP3 inflammasome to reduce inflammatory response in lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shiwei Qingwen decoction (SWQ), a Chinese herbal formula based on the classic traditional Chinese medicine prescription Yu Ping Feng San, has shown efficacy in preventing and treating early pneumonia with good clinical outcomes. However, its underlying mechanism is yet unclear. AIM OF THE STUDY: To clarify the preventive and therapeutic effects of SWQ on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the underlying mechanism by which SWQ influences pneumonia. MATERIALS AND METHODS: First, the chemical composition of SWQ was preliminarily determined by high performance liquid chromatography (HPLC), and the impact of SWQ (3.27, 6.55, and 13.1 g/kg) was assessed in the LPS-induced ALI rat model. Next, its inflammatory pathway was determined via network pharmacology. Finally, the molecular mechanism of SWQ was validated using a rat ALI model and a THP-1 cell inflammation model. RESULTS: HPLC identified chlorogenic acid, prime-O-glucosylcimifugin, calycosin, and 5-O-methylaminoside in the chemical profile of SWQ. In the ALI model, SWQ alleviated ALI by reducing lung wet/dry weight ratio (W/D) and preventing histopathological damage to the lungs. At the same time, SWQ decreased penetration of inflammatory mediators by upregulating AQP1 and AQP5 and endothelial nitric oxide synthase (eNOS). Pretreatment with SWQ downregulated white blood cells and neutrophils count in BALF and suppressed LPS-induced expression levels of MPO, NE, and pro-inflammatory factors (TNF-α, IL-1ß, IL-6, and iNOS). Network pharmacology showed that SWQ was associated with TLR4/NF-κB inflammation pathway. Moreover, pretreatment with SWQ reduced the expression level of TLR4/NF-κB signaling pathway-associated proteins (TLR4, Myd88, p-IκB, and p-p65) and NLRP3 inflammasome (NLRP3, ASC, caspase-1, and cleaved-IL-1ß) in vivo and vitro. CONCLUSIONS: The present study demonstrates that SWQ can reduce inflammation in ALI by inhibiting TLR4/NF-κB and NLRP3 inflammasome activation.

MiR-122-5p regulates the mevalonate pathway by targeting p53 in non-small cell lung cancer.

The 5-year survival rate of non-small cell lung cancer (NSCLC) patients is very low. MicroRNAs (miRNAs) are involved in the occurrence of NSCLC. miR-122-5p interacts with wild-type p53 (wtp53), and wtp53 affects tumor growth by inhibiting the mevalonate (MVA) pathway. Therefore, this study aimed to evaluate the role of these factors in NSCLC. The role of miR-122-5p and p53 was established in samples from NSCLC patients, and human NSCLC cells A549 using the miR-122-5p inhibitor, miR-122-5p mimic, and si-p53. Our results showed that inhibiting miR-122-5p expression led to the activation of p53. This inhibited the progression of the MVA pathway in the NSCLC cells A549, hindered cell proliferation and migration, and promoted apoptosis. miR-122-5p was negatively correlated with p53 expression in p53 wild-type NSCLC patients. The expression of key genes in the MVA pathway in tumors of p53 wild-type NSCLC patients was not always higher than the corresponding normal tissues. The malignancy of NSCLC was positively correlated with the high expression of the key genes in the MVA pathway. Therefore, miR-122-5p regulated NSCLC by targeting p53, providing potential molecular targets for developing targeted drugs.

Host-Plant Selection Behavior of Ophraella communa, a Biocontrol Agent of the Invasive Common Ragweed Ambrosia artemisiifolia.

Understanding the host-selection behavior of herbivorous insects is important to clarify their efficacy and safety as biocontrol agents. To explore the host-plant selection of the beetle Ophraella communa, a natural enemy of the alien invasive common ragweed (Ambrosia artemisiifolia), we conducted a series of outdoor choice experiments in cages in 2010 and in open fields in 2010 and 2011 to determine the preference of O. communa for A. artemisiifolia and three non-target plant species: sunflower (Helianthus annuus), cocklebur (Xanthium sibiricum), and giant ragweed (Ambrosia trifida). In the outdoor cage experiment, no eggs were found on sunflowers, and O. communa adults rapidly moved from sunflowers to the other three plant species. Instead, adults preferred to lay eggs on A. artemisiifolia, followed by X. sibiricum and A. trifida, although very few eggs were observed on A. trifida. Observing the host-plant selection of O. communa in an open sunflower field, we found that O. communa adults always chose A. artemisiifolia for feeding and egg laying. Although several adults (<0.02 adults/plant) stayed on H. annuus, no feeding or oviposition were observed, and adults quickly transferred to A. artemisiifolia. In 2010 and 2011, 3 egg masses (96 eggs) were observed on sunflowers, but they failed to hatch or develop into adults. In addition, some O. communa adults crossed the barrier formed by H. annuus to feed and oviposit on A. artemisiifolia planted in the periphery, and persisted in patches of different densities. Additionally, only 10% of O. communa adults chose to feed and oviposit on the X. sibiricum barrier. These findings suggest that O. communa poses no threat to the biosafety of H. anunuus and A. trifida and exhibits a robust dispersal capacity to find and feed on A. artemisiifolia. However, X. sibiricum has the potential to be an alternative host plant for O. communa.