Fungal community structure shifts in litter degradation along forest succession induced by pine wilt disease.

Fungi play a crucial role in decomposing litter and facilitating the energy flow between aboveground plants and underground soil in forest ecosystems. However, our understanding how the fungal community involved in litter decomposition responds during forest succession, particularly in disease-driven succession, is still limited. This study investigated the activity of degrading enzyme, fungal community, and predicted function in litter after one year of decomposition in different types of forests during a forest succession gradient from coniferous to deciduous forest, induced by pine wilt disease. The results showed that the weight loss of needles/leaves and twigs did not change along the succession process, but twigs degraded faster than needles/leaves in both pure pine forest and mixed forest. In pure pine forest, peak activities of enzymes involved in carbon degradation (ß-cellobiosidase, ß-glucosidase, ß-D-glucuronidase, ß-xylosidase), nitrogen degradation (N-acetyl-glucosamidase), and organic phosphorus degradation (phosphatase) were observed in needles, which subsequently declined. The fungal diversity and evenness (Shannon's diversity and Shannon's evenness) dropped in twig from coniferous forest to mixed forest during the succession. The dominant phyla in needle/leaf and twig litters were Ascomycota (46.9%) and Basidiomycota (38.9%), with Lambertella pruni and Chalara hughesii identified as the most abundant indicator species. Gymnopus and Desmazierella showed positively correlations with most measured enzyme activities. Functionally, saprotrophs constituted the main trophic mode (47.65%), followed by Pathotroph-Saprotroph-Symbiotroph (30.95%) and Saprotroph-Symbiotroph (10.57%). The fungal community and predicted functional structures in both litter types shifted among different forest types along the succession. These findings indicate that the fungal community in litter decomposition responds differently to disease-induced succession, leading to significant shifts in both the fungal community structure and function.

In Vitro and In Vivo Anti-Cancer Activity of Lasiokaurin in a Triple-Negative Breast Cancer Model.

Due to its intricate heterogeneity, high invasiveness, and poor prognosis, triple-negative breast cancer (TNBC) stands out as the most formidable subtype of breast cancer. At present, chemotherapy remains the prevailing treatment modality for TNBC, primarily due to its lack of estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth receptor 2 (HER2). However, clinical chemotherapy for TNBC is marked by its limited efficacy and a pronounced incidence of adverse effects. Consequently, there is a pressing need for novel drugs to treat TNBC. Given the rich repository of diverse natural compounds in traditional Chinese medicine, identifying potential anti-TNBC agents is a viable strategy. This study investigated lasiokaurin (LAS), a natural diterpenoid abundantly present in Isodon plants, revealing its significant anti-TNBC activity both in vitro and in vivo. Notably, LAS treatment induced cell cycle arrest, apoptosis, and DNA damage in TNBC cells, while concurrently inhibiting cell metastasis. In addition, LAS effectively inhibited the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway and signal transducer and activator of transcription 3 (STAT3), thus establishing its potential for multitarget therapy against TNBC. Furthermore, LAS demonstrated its ability to reduce tumor growth in a xenograft mouse model without exerting detrimental effects on the body weight or vital organs, confirming its safe applicability for TNBC treatment. Overall, this study shows that LAS is a potent candidate for treating TNBC.

Nanobubble-induced significant reduction of the interfacial thermal conductance for few-layer graphene.

The heat transport properties of van der Waals layered structures are crucial for ensuring the reliability and longevity of high-performance optoelectronic equipment. Owing to the two-dimensional nature of atomic layers, the presence of bubbles is commonly observed within these structures. Nevertheless, the effect of bubbles on the interfacial thermal conductance remains unclear. Based on the elastic membrane theory and the improved van der Waals gas state equation, we develop an analytical formula to describe the influence of bubble shape on the interfacial thermal conductance. It shows that the presence of bubbles has a considerable impact on reducing the interfacial thermal conductance across graphene/graphene interfaces. More specifically, the presence of nanobubbles can result in a reduction of up to 53% in the interfacial thermal conductance. The validity of the analytical predictions is confirmed through molecular dynamic simulations. These results offer valuable insights into the thermal management of van der Waals layered structures in the application of next-generation electronic nanodevices.

Design and Fabrication of Hypercrosslinked Covalent Organic Adsorbents for Selective Uranium Extraction.

Uranium detection and extraction are necessary for the ecological environment as the growing demand for nuclear energy. Hence, exploring stable materials with excellent performance in uranium extraction and detection is highly desired. Herein, by amidoxime-functionalizing tetrafluoroterephthalonitrile (TFTPN) crosslinked hydroquinone (bP), phloroglucinol (tP), and 4,4',4″-trihydroxytriphenylmethane (tBP), three covalent organic polymers (COPs) bPF-AO, tPF-AO, and tBPF-AO with different crosslinked architectures are fabricated. Uranium extraction and detection related to the difference in molecule construction were systemically investigated, giving some reference for the rational design and fabrication of advanced materials for the removal and monitoring of uranium in the environment. The tPF-AO with a compact steric structure achieves the highest theoretical maximum adsorption capacity of 578.9 ± 15.2 mg g-1 and the best recyclability. The scattering electron center and U(VI) selective binding sites endow tBPF-AO with excellent capability in selective detection for U(VI), with a limit of detection of 24.2 nmol L-1, which is well below the standard for U(VI) in drinking water of the World Health Organization (WHO). Moreover, the COPs possess prominent physicochemical stability and recyclability, and more importantly, the PAE-based COPs are derived from inexpensive industry materials with easy processing methods, providing an efficient and economical way for the detection and adsorption of uranium.

Dahuang-Taoren, a botanical drug combination, ameliorates adenomyosis via inhibiting Rho GTPases.

Introduction: Dahuang-Taoren (DT) is a classic combination of botanical drugs applied to treat pain-related diseases in ancient China. Today, DT is frequently applied for dysmenorrhea of adenomyosis (AM) in the clinic. Growing evidence indicates Rho GTPases may play an essential role in AM progression. However, the potential mechanism of DT on Rho GTPases in AM remains unclear. Methods: The expressions of Rho GTPases in the patients with AM were evaluated. Further, pituitary transplantation-induced AM mice and the primary AM endometrial stromal cells (AMESCs) were subjected to DT intervention. Results: The results revealed that the expressions of Rho GTPases were significantly upregulated in both AM patients and AM mice. The DT could reduce pathological infiltration, relieve hyperalgesia, and alleviate cytoskeleton remodeling in AM mice. Besides, the migration and invasion of AMESCs were markedly inhibited after exposure to DT. Discussion: These effects may be linked to the decreased Rho GTPases expression. The results may offer a novel explanation of DT against AM.

Selective Inhibition of PTP1B by New Anthraquinone Glycosides from Knoxia valerianoides.

Protein tyrosine phosphatase 1B (PTP1B) is highly validated as a therapeutic target for type 2 diabetes. However, active site-directed PTP1B inhibitors generally suffer from poor selectivity and bioavailability. Inspired by the identification of a unique anthraquinone-coumarin hybrid from Knoxia valerianoides exhibiting good specificity for PTP1B over the highly homologous T-cell protein tyrosine phosphatase (TCPTP), further chemical investigation of this plant species led to the isolation of nine new anthraquinone glycosides (1-9) and two known ones (10 and 11). Structures were characterized by a combination of spectroscopic analyses and chemical methods. All compounds showed PTP1B inhibitory activities with IC50 values ranging from 1.05 to 13.74 µM. Compounds 4 and 8 exhibited greater than 64-fold selectivity over TCPTP. Enzyme kinetic studies revealed that compounds 4 and 7 behaved as mixed-type inhibitors. Docking studies predicted similar binding modes of these compounds at the allosteric site positioned between helices α3 and α6.

Soil Fungal Community Structure and Function Shift during a Disease-Driven Forest Succession.

Forest succession is important for sustainable forest management in terrestrial ecosystems. However, knowledge about the response of soil microbes to forest disease-driven succession is limited. In this study, we investigated the soil fungal biomass, soil enzyme activity, and fungal community structure and function in forests suffering succession processes produced by pine wilt disease from conifer to broadleaved forests using Illumina Miseq sequencing coupled with FUNGuild analysis. The results showed that the broadleaved forest had the highest fungal biomass and soil enzyme activities in C, N, and S cycles, whereas the conifer forest had the highest enzyme activity in the P cycle. Along the succession, the fungal diversity and richness significantly increased (P < 0.05). The fungal communities were dominated by Ascomycota (42.0%), Basidiomycota (38.0%), and Mortierellomycota (9.5%), among which the abundance of Ascomycota significantly increased (P < 0.05), whereas that of Basidiomycota and Mortierellomycota decreased (P < 0.05). The abundance of species Mortierella humilis, Lactarius salmonicolor, and Russula sanguinea decreased, whereas that of Mortierella minutissima increased (P < 0.05). The forests in different succession stages formed distinct fungal communities and functional structures (P < 0.05). Functionally, the saprotrophs, symbiotrophs, and pathotrophs were the dominant groups in the conifer, mixed, and broadleaved forests, respectively. Soil pH and soil organic carbon were the key factors influencing the fungal community and functional structures during the succession. These findings provide useful information for better understanding the plant-microbe interaction during forest succession caused by forest disease. IMPORTANCE The studies on soil fungal communities in disease-driven forest succession are rare. This study showed that during the disease-driven forest succession, the soil enzyme activity, soil fungal diversity, and biomass increased along succession. The disease-driven forest succession changed the soil fungal community structure and function, in which the symbiotrophs were the most dominant group along the succession. These findings provide useful information for better understanding the plant-microbe interaction during forest succession caused by forest disease.

The impact of biochar on wood-inhabiting bacterial community and its function in a boreal pine forest.

Biochar is considered to be a possible means of carbon sequestration to alleviate climate change. However, the dynamics of the microbial community during wood decomposition after biochar application remain poorly understood. In this study, the wood-inhabiting bacterial community composition and its potential functions during a two-year decomposition period after the addition of different amounts of biochar (0.5 kg m-2 and 1.0 kg m-2), and at different biochar pyrolysis temperatures (500 °C and 650 °C), in a boreal Scots pine forest, were analyzed using Illumina NovaSeq sequencing combined with Functional Annotation of Prokaryotic Taxa (FAPROTAX). The results showed that the wood decomposition rates increased after biochar addition to the soil surface in the second year. Treatment with biochar produced at high temperatures increased the diversity of wood-inhabiting bacteria more than that produced at low temperatures (P < 0.05). The wood-inhabiting bacterial diversity and species richness decreased with decomposition time. The biochar treatments changed the wood-inhabiting bacterial community structure during the decomposition period. The pyrolysis temperature and the amount of applied biochar had no effect on the bacterial community structure but shifted the abundance of certain bacterial taxa. Similarly, biochar application shifted the wood-inhabiting bacterial community function in the first year, but not in the second year. The wood-inhabiting bacterial community and function were affected by soil pH, soil water content, and soil total nitrogen. The results provide useful information on biochar application for future forest management practices. Long-term monitoring is needed to better understand the effects of biochar application on nutrient cycling in boreal forests.

An ester derivative of tenacigenin B from Marsdenia tenacissima (Roxb.) Wight et Arn reversed paclitaxel-induced MDR in vitro and in vivo by inhibiting both P-gp and MRP2.

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima is a medicinal plant, used as a raw material for cancer treatment in China. In our previous studies, 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B (MT2), the main steroid aglycone isolated from M. tenacissima, was found to significantly enhance the antitumor activity of paclitaxel (PTX) in vivo. However, it is unclear whether MT2 reverses multidrug resistance (MDR) in tumors. AIM OF THE STUDY: To determine the role and mechanism of MT2 in reversing tumor MDR. MATERIALS AND METHODS: MDR cell line HeLa/Tax was established from the human cervical carcinoma cell line HeLa by long-term exposure to subtoxic concentrations of PTX and was used to evaluate the ability of MT2 to restore chemosensitivity of cells both in vitro and in a nude mouse model. The expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) was determined using western blotting and immunohistochemistry. The substrate transport function was assessed using an MDR function assay kit. The binding modes of MT2 and P-gp were determined using the conformation-sensitive anti-P-gp antibodies. The permeability and transport properties of MT2 were analyzed in Caco-2 cell monolayers. RESULTS: Compared to parental cells, HeLa/Tax cells overexpress P-gp and MRP2 and are approximately 100-360 fold more resistant to the anticancer drugs PTX, docetaxel, and vinblastine. MT2 at 5 or 10 µmol/L significantly increased the sensitivity of HeLa/Tax to these three anticancer drugs (18-56-fold decrease in IC50 value) and suppressed the expression of P-gp and MRP2. Knockdown of P-gp with small interfering RNA partially reversed MT2-induced sensitivity to PTX in HeLa/Tax cells. Moreover, MT2 directly inhibited P-gp-mediated substrate transport while interacting with membrane P-gp in non-substrate ways. MT2 was highly permeable and could not be transported in the Caco-2 cell monolayers. In nude mice bearing HeLa/Tax xenografts, the combination treatment with MT2 and PTX exerted a synergistic inhibitory effect on the growth of tumors and the expression of P-gp and MRP2 without increasing toxicity. CONCLUSION: MT2 is a potential agent for reversing MDR. It impedes membrane drug efflux pumps by suppressing P-gp and MRP2 expression, and directly inhibiting the transport function of P-gp.

Natural Prenylated Xanthones as Potential Inhibitors of PI3k/Akt/mTOR Pathway in Triple Negative Breast Cancer Cells.

Three prenylated xanthones, garcinone E (1: ), bannaxanthone D (2: ) and bannanxanthone E (3: ) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1:  - 3: were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1:  - 3: exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1:  - 3: in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1:  - 3: had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2: significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.

Soil Fungal Community Structure in Boreal Pine Forests: From Southern to Subarctic Areas of Finland.

The boreal forest environment plays an important role in the global C cycle due to its high carbon storage capacity. However, relatively little is known about the forest fungal community at a regional scale in boreal forests. In the present study, we have re-analyzed the data from our previous studies and highlighted the core fungal community composition and potential functional groups in three forests dominated by Scots pine (Pinus sylvestris L.) in Finland, and identified the fungal generalists that appear across geographic locations despite differences in local conditions. The three forests represent subarctic, northern and southern boreal forest, and are all in an un-managed state without human interference or management. The subarctic and northern areas are subject to reindeer grazing. The results showed that the three locations formed distinct fungal community structures (P < 0.05). Compared to the two northern locations, the southern boreal forest harbored a greater abundance of Zygomycota, Lactarius, Mortierella Umbelopsis, and Tylospora, in which aspect there were no differences between the two northern forests. Cortinarius, Piloderma, and Suillus were the core fungal genera in the boreal Scots pine forest. Functionally, the southern boreal forest harbored a greater abundance of saprotroph, endophytes and fungal parasite-lichen, whereas a greater abundance of ectomycorrhizal fungi was observed in the northern boreal forests. Moreover, the pathotroph and wood saprotrophs were commonly present in these three regions. The three locations formed two distinct fungal community functional structures, by which the southern forest was clearly separated from the two northern forests, suggesting a distance-decay relationship via geographic location. This study provides useful information for better understanding the common fungal communities and functions in boreal forests in different geographical locations.

The Impact of Pine Wood Nematode Infection on the Host Fungal Community.

Pine wilt disease (PWD), caused by pinewood nematode (PWN) Bursaphelenchus xylophilus, is globally one of the most destructive diseases of pine forests, especially in China. However, little is known about the effect of PWD on the host microbiome. In this study, the fungal community and functional structures in the needles, roots, and soil of and around Pinus thunbergii naturally infected by PWN were investigated by using high-throughput sequencing coupled with the functional prediction (FUNGuild). The results showed that fungal richness, diversity, and evenness in the needles of diseased trees were significantly lower than those of healthy ones (p < 0.05), whereas no differences were found in the roots and soil. Principal coordinate analysis (PCoA) showed that the fungal community and functional structures significantly differed only in the needles of diseased and healthy trees, but not in the soil and roots. Functionally, the saprotrophs had a higher abundance in the needles of diseased trees, whereas symbiotrophs abundance was higher in the needles of healthy trees (linear discriminant analysis (LDA) > 2.0, p < 0.05). These results indicated that PWN infection primarily affected the fungal community and functional structures in the needles of P. thunbergii, but not the roots and soil.

Brevilin A, a Natural Sesquiterpene Lactone Inhibited the Growth of Triple-Negative Breast Cancer Cells via Akt/mTOR and STAT3 Signaling Pathways.

PURPOSE: Triple-negative breast cancer (TNBC) is a a breast cancer subtype characterized by a lack of estrogen receptor, progesterone receptor and human epidermal growth receptor 2 and is associated with poorer prognoses when compared to other breast cancers. Thus, novel anti-cancer agents with high efficacy are urgently needed. Brevilin A (BA), a natural sesquiterpene lactone, has been reported to exhibit anti-cancer effects. However, the effects of BA on TNBC have not yet been demonstrated. In this study, we investigated the anti-TNBC effects and the underlying mechanism of BA, in vitro and in vivo. METHODS: Two TNBC cell lines and a xenograft mouse model were employed to assess the effects of BA. Cell viability was detected by MTT assay. Cell cycle status and apoptosis were evaluated by flow cytometry. Cell migration was measured by wound-healing assay. Protein expression was measured by Western blotting analysis. The in vivo anti-cancer activity of BA was assessed in orthotopic tumor xenograft mice. RESULTS: BA significantly inhibited the growth of TNBC cells in a dose- and time-dependent manner via induction of cell cycle arrest at G2/M phase arrest and apoptosis. BA also inhibited tumor cell migration. BA significantly downregulated the expression of Akt, mTOR, Stat3 and their phosphorylation, and thus inhibiting the activation of the Akt/mTOR and STAT3 signaling pathways. Furthermore, oral administration of BA at 25 or 50 mg/kg leads to significant inhibition of tumor growth and proliferation in tumor xenograft model mice. CONCLUSION: BA significantly inhibited the growth and migration of TNBC cells, and induced cell cycle arrest and apoptosis. These inhibitory effects were associated with the suppression of the Akt/mTOR and Stat3 signal pathways. Based on our findings, BA possesses a promising candidate for development as an anti-cancer therapeutic drug against TNBC.

Arnicolide D Inhibits Triple Negative Breast Cancer Cell Proliferation by Suppression of Akt/mTOR and STAT3 Signaling Pathways.

Triple-Negative Breast Cancer (TNBC) is a most dangerous breast cancer subtype. The naturally occurring sesquiterpene lactone, arnicolide D (AD), has proven effective against a variety of tumors, however, the inhibitory effects of AD against TNBC and the underlying mechanisms remain unclear. In the present study, two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and an MDA-MB-231 xenograft mouse model were employed to investigate the anti-TNBC effects of AD in vitro and in vivo. Cell viability was assessed by MTT assay. Cell cycle arrest and apoptosis were analyzed by flow cytometry. Protein levels were determined by immunoblotting. In vitro studies demonstrated that AD significantly decreased cell viability, and induced G2/M cell cycle arrest and apoptosis. In vivo assays showed that oral administration of 25 or 50 mg/kg AD for 22 days led to a reduction of tumor weights by 24.7% or 41.0%, without appreciable side effects. Mechanistically, AD inhibited the activation of Akt/mTOR and STAT3 signaling pathways. Based on our findings, AD is a promising candidate for development as an adjunctive therapeutic drug for TNBC.

Age and Species of Eucalyptus Plantations Affect Soil Microbial Biomass and Enzymatic Activities.

Soil microorganisms and extracellular enzymes play important roles in soil nutrient cycling. Currently, China has the second-largest area of eucalyptus plantations in the world. Information on the effects of eucalyptus age and species of trees on soil microbial biomass and enzyme activities, however, is limited. In this paper, the soil microbial biomass and enzyme activities were studied in eucalyptus plantations with different ages (1 and 5+ years) and species of trees (E. urophylla×E. grandis, E. camaldulens and E. pellita) in South China. The results showed that both plantation age and eucalyptus species could affect the total microbial biomass and fungal biomass, whereas the bacterial biomass was affected only by plantation age. The fungal biomass and the fungi-to-bacteria ratio significantly increased along with increasing plantation age. Similarly, the plantation age and eucalyptus species significantly affected the enzyme activities associated with carbon cycling (ß-xylosidase, ß-d-glucuronidase, ß-cellobiosidase and ß-glucosidase). The activities of ß-d-glucuronidase and ß-glucosidase were significantly higher in the E. camaldulens plantation. The enzymes involved in nitrogen (N-acetyl-glucosamidase) and sulfur (sulfatase) cycling were only affected by the eucalyptus plantation age and species, respectively. The results highlight the importance of the age and species of eucalyptus plantations on soil microbial activities.

Synthesis and Evaluation of Novel Anticancer Compounds Derived from the Natural Product Brevilin A.

Cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018, and this burden continues to increase. Therefore, there is a clear and urgent need for novel drugs with increased efficacy for the treatment of different cancers. Previous research has demonstrated that brevilin A (BA) exerts anticancer activity in various cancers, including human multiple myeloma, breast cancer, lung cancer, and colon carcinoma, suggesting the anticancer potential present in the chemical scaffold of BA. Here, we designed and synthesized a small library of 12 novel BA derivatives and evaluated the biological anticancer effects of the compounds in various cancer cell lines. The results of this structure-activity relationship study demonstrated that BA derivatives BA-9 and BA-10 possessed significantly improved anticancer activity toward lung, colon, and breast cancer cell lines. BA-9 and BA-10 could more effectively reduce cancer cell viability and induce DNA damage, cell-cycle arrest, and apoptosis when compared with BA. Our findings represent a significant step forward in the development of novel anticancer entities.

Anti-cancer Activity of Centipeda minima Extract in Triple Negative Breast Cancer via Inhibition of AKT, NF-κB, and STAT3 Signaling Pathways.

Breast cancer is the most commonly diagnosed cancer in females worldwide. Estimates from the World Health Organization (WHO) International Agency for Research on Cancer, suggest that globally, there were around 2.1 million new breast cancer cases and 627,000 deaths due to breast cancer in 2018. Among the subtypes of breast cancer, triple negative breast cancer (TNBC) is the most aggressive and carries the poorest prognosis, largest recurrence, and lowest survival rate. Major treatment options for TNBC patients are mainly constrained to chemotherapy, which can be accompanied by severe side effects. Therefore, development of novel and effective anti-cancer drugs for the treatment of TNBC are urgently required. Centipeda minima is a well-known traditional Chinese herbal medicine that has historically been used to treat rhinitis, sinusitis, relieve pain, and reduce swelling. Recent studies have shown that Centipeda minima exhibited efficacy against certain cancers, however, to date, no studies have been conducted on its effects in breast cancer. Here, we aimed to investigate the anti-cancer activity of the total extract of Centipeda minima (CME), and its underlying mechanism, in TNBC. In MDA-MB-231, we found that CME could significantly reduce cell viability and proliferation, induce apoptosis and inhibit cancer cell migration and invasion, in a dose and time-dependent manner. We showed that CME may potentially act via inhibition of multiple signaling pathways, including the EGFR, PI3K/AKT/mTOR, NF-κB, and STAT3 pathways. Treatment with CME also led to in vitro downregulation of MMP-9 activity and inhibition of metastasis. Further, we demonstrated that CME could significantly reduce tumor burden in MDA-MB-231 xenograft mice, without any appreciable side effects. Based on our findings, CME is a promising candidate for development as a therapeutic with high efficacy against TNBC.

Bacterial Community Structure of Pinus Thunbergii Naturally Infected by the Nematode Bursaphelenchus Xylophilus.

Pine wilt disease (PWD) caused by the nematode Bursaphelenchus xylophilus is a devastating disease in conifer forests in Eurasia. However, information on the effect of PWD on the host microbial community is limited. In this study, the bacterial community structure and potential function in the needles, roots, and soil of diseased pine were studied under field conditions using Illumina MiSeq coupled with Phylogenetic Investigation of Communities by Reconstruction of Unobserved states (PICRUSt) software. The results showed that the community and functional structure of healthy and diseased trees differed only in the roots and needles, respectively (p < 0.05). The needles, roots, and soil formed unique bacterial community and functional structures. The abundant phyla across all samples were Proteobacteria (41.9% of total sequence), Actinobacteria (29.0%), Acidobacteria (12.2%), Bacteroidetes (4.8%), and Planctomycetes (2.1%). The bacterial community in the healthy roots was dominated by Acidobacteria, Planctomycetes, and Rhizobiales, whereas in the diseased roots, Proteobacteria, Firmicutes, and Burkholderiales were dominant. Functionally, groups involved in the cell process and genetic information processing had a higher abundance in the diseased needles, which contributed to the difference in functional structure. The results indicate that PWD can only affect the host bacteria community structure and function in certain anatomical regions of the host tree.

7-methoxyflavanone alleviates neuroinflammation in lipopolysaccharide-stimulated microglial cells by inhibiting TLR4/MyD88/MAPK signalling and activating the Nrf2/NQO-1 pathway.

OBJECTIVES: Neuroprotective potential of 7-methoxyflavanone (7MF) and its underlying mechanism was investigated. METHODS: Inhibitory effects of 7MF on microglial activation and neuroinflammation were evaluated by employment of lipopolysaccharide (LPS)-induced BV2 microglial cells. Changes in expression of genes and proteins of interest were investigated by RT-qPCR analysis and Western blot analysis. Inhibitory effects of 7MF on microglial overactivation were verified in LPS-treated C57BL/6J mice using ionized calcium-binding adaptor molecule-1 (Iba1) in the brain and interleukin-6 (IL-6) in serum as indicators. KEY FINDINGS: In BV2 cells, pretreatment with 7MF antagonized LPS-induced production of inflammatory factors IL-6, tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Mechanistic studies revealed reduced expression of Toll-like receptor 4 (TLR4), myeloid differentiation factor-88 (MyD88), phosphorylated forms of c-Jun N-terminal kinase (p-JNK) and extracellular signal-regulated kinases 1/2 (p-ERK) but increased nuclear accumulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and cellular expression of NAD(P)H quinone dehydrogenase-1 (NQO-1) by 7MF. In LPS-treated mice, pretreatment with 7MF reduced the brain level of Iba1 and serum level of IL-6. CONCLUSIONS: 7-methoxyflavanone inhibited LPS-stimulated TLR4/MyD88/MAPK signalling and activated Nrf2-mediated transcription of antioxidant protein NQO-1, showing antineuroinflammatory effect, so it is a potential neuroprotective agent.

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant cancers in Southeast Asia and Southern China. Centipeda minima extract (CME) had previously demonstrated anti-cancer effects in human NPC. Brevilin A, a sesquiterpene lactone isolated from C. minima, has been reported to exhibit biological activities. In this study, we investigated its anti-NPC effect and further explored its molecular mechanisms. The effects of brevilin A were tested in the NPC cell lines CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. Effects of brevilin A on cell viability were determined by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. The molecular mechanism of cell cycle regulation and apoptosis were investigated via Western blot. Results showed that brevilin A inhibited NPC cell viability in a concentration- and time-dependent manner. Brevilin A induced cell cycle arrest at G2/M and induced apoptosis. Western blot results demonstrated that brevilin A could down-regulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, while up-regulating cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by brevilin A showed dynamic changes according to dose and time. In the tumor xenograft model, brevilin A could reduce tumor growth, at a similar magnitude to cisplatin. However, notably, whereas cisplatin treatment led to significant weight loss in treated mice, treatment with brevilin A did not, indicating its relative lack of toxicity. Taken together, brevilin A regulated cell cycle, activated the caspase signaling pathway, and inhibited PI3K/AKT/mTOR and STAT3 signaling pathways in vitro, and exhibited similar efficacy to the common chemotherapeutic cisplatin in vivo, without its associated toxicity. These findings provide a framework for the preclinical development of brevilin A as a chemotherapeutic for NPC.