A Multi-dimensional Data Mining-based Study on the Prescriptions Developed by Professor Xu Zhiyin in Treating Thyroid Nodules.

OBJECTIVES: In this study, we employed a multi-dimensional data mining approach to examine the clinical instances where Professor Xu Zhiyin treated thyroid nodules. Our aim is to understand the patterns of symptoms, underlying causes, and treatment approaches used for thyroid nodules. By doing so, the intention is to distill the essential aspects, compile Professor Xu Zhiyin's clinical insights, and investigate his scholarly perspectives. METHODS: Professor Xu Zhiyin's clinical diagnoses and treatments spanning from 2009 to 2019 were entered into Microsoft Excel. Subsequently, the collected data was imported into the Medcase V5.2 system to facilitate data mining. Various techniques, such as frequency-based method, association rule analysis, and clustering, including a decentralized system clustering approach, were employed on a set of 346 cases involving patients with thyroid nodules that conformed to the specified criteria. The primary focus was on extracting insights regarding symptoms and the underlying causes from the medical records. By integrating these findings with Professor Xu Zhiyin's clinical expertise, we examined and summarized the outcomes of the data mining process. RESULTS: The fundamental prescriptions were successfully extracted using the techniques for mining across multiple dimensions. Utilizing the scattered grouping of these prescriptions and with reference to the cluster analysis of the frequency-linked system, the fundamental prescriptions proposed by Professor Xu Zhiyin for addressing thyroid nodules encompass the following ingredients: Glycyrrhiza uralensis Fisch, Cortex Moutan, Paeoniae radix rubra, Curcuma longa L., Radix Curcumae, persica seed, Citri Reticulatae Viride Pericarpium, Pinellia ternata, Spica Prunellae, Ostreae concha, Gleditsia sinensis spine, Tuckahoe and Radix Codonopsis. CONCLUSION: The fundamental prescriptions were acquired using the frequency approach, association rule technique, k-means clustering approach, and systematic clustering approach. The research findings corroborate one another, demonstrating that Professor Xu Zhiyin's approach to distinguishing and treating thyroid nodules is embodied in distinct prescriptions tailored to specific diseases.

[Adsorption Properties of Magnetic Phosphorous Camellia Oleifera Shells Biochar to Sulfamethoxazole in Water].

Magnetic phosphorous biochar （MPBC） was prepared from Camellia oleifera shells using phosphoric acid activation and iron co-deposition. The materials were characterized and analyzed through scanning electron microscopy （SEM）， X-ray diffractometry （XRD）， specific surface area and pore size analysis （BET）， Fourier infrared spectroscopy （FT-IR）， and X-ray photoelectron spectroscopy （XPS）. MPBC had a high surface area （1 139.28 m2·g-1） and abundant surface functional groups， and it could achieve fast solid-liquid separation under the action of an external magnetic field. The adsorption behavior and influencing factors of sulfamethoxazole （SMX） in water were investigated. The adsorbent showed excellent adsorption properties for SMX under acidic and neutral conditions， and alkaline conditions and the presence of CO32- had obvious inhibition on adsorption. The adsorption process conformed to the quasi-second-order kinetics and Langmuir model. The adsorption rate was fast， and the maximum adsorption capacity reached 356.49 mg·g-1. The adsorption process was a spontaneous exothermic reaction， and low temperature was beneficial to the adsorption. The adsorption mechanism was mainly the chemisorption of pyrophosphate surface functional groups （C-O-P bond） between the SMX molecule and MPBC and also included hydrogen bonding， π-π electron donor-acceptor （π-πEDA） interaction， and a pore filling effect. The development of MPBC adsorbent provides an effective way for resource utilization of waste Camellia oleifera shells and treatment of sulfamethoxazole wastewater.

Impact of age, sex, and thyroid autoimmunity on the association between selenium intake and type 2 diabetes mellitus.

BACKGROUND: The association between dietary selenium(Se) intake and type 2 diabetes mellitus (T2DM) remains controversial. The present study aimed to investigate this association using data from the National Health and Nutrition Examination Survey (NHANES) database for the years 2007-2012. METHODS: Three thousand seventy three individuals aged 20 years and above were eligible for inclusion in this cross-sectional study. The average age of the participants was 50.74 years and the proportions of males and females were nearly equal (49.12% vs. 50.88%). The odds ratios (OR) of the association between dietary Se intake (log2-transformed) and T2DM were examined through the multivariate logistic regression model. Subgroup analyses were conducted based on age, sex, and thyroid autoimmunity to assess the potential impact of these variables on the relationship. Fitted smoothing curves and threshold effect analysis were conducted to describe the nonlinear relationship. RESULTS: In the fully adjusted model, a significant positive association between Se intake and T2DM was observed (OR = 1.49, 95% CI: 1.16, 1.90, p = 0.0017). After stratifying the data by age, sex, and thyroid autoimmunity, a significant positive association between Se intake and T2DM was observed in individuals under 65 years of age, males, and those with negative thyroid autoimmunity. A two-segment linear regression model was analyzed for sex stratification, revealing a threshold effect in males with an inflection point of 90.51 µg, and an inverted U-shaped relationship in females with an inflection point of 109.90 µg, respectively. CONCLUSIONS: The present study found a positive relationship between Se intake and the prevalence of T2DM. This association is particularly significant in younger individuals, males, and those with negative thyroid autoimmunity. Our results should be validated in future large prospective studies in different populations.

Effect of vinegar steaming on the composition and structure of Schisandra chinensis polysaccharide and its anti-colitis activity.

In this study, infrared spectroscopy, high-performance liquid chromatography, and matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) technology were applied to systematically explain the Schisandra chinensis's polysaccharide transformation in configuration, molecular weight, monosaccharide composition, and anti-ulcerative colitis (UC) activity after vinegar processing. Scanning electron microscopic results showed that the appearance of S. chinensis polysaccharide changed significantly after steaming with vinegar. The MALDI-TOF-MS results showed that the mass spectra of raw S. chinensis polysaccharides (RSCP) were slightly lower than those of vinegar-processed S. chinensis polysaccharides (VSCP). The RSCP showed higher peaks at m/z 1350.790, 2016.796, and 2665.985, all with left-skewed distribution, and the molecular weights were concentrated in the range of 1300-3100, with no higher peak above m/z 5000. The VSCPs showed a whole band below m/z 3000, with m/z 1021.096 being the highest peak, and the intensity decreased with the increase of m/z. In addition, compared to RSCPs, VSCPs can significantly increase the content of intestinal short-chain fatty acids (SCFAs). This study showed that the apparent morphology and molecular weight of S. chinensis's polysaccharides significantly changed after steaming with vinegar. These changes directly affect its anti-UC effect significantly, and its mechanism is closely related to improving the structure and diversity of gut microbiota and SCFA metabolism.

Secondary metabolites from the Actinomadura sp. and their cytotoxic activity.

Actinomadura sp., which is usually found in muddy habitats, produces various secondary metabolites with biological activities. In this study, five new compounds named formosensin A (1), formosensin B (2), oxanthroquinone-3-O-α-d-mannose (8), oxanthromicin A (9), and oxanthromicin B (10) were isolated from the culture of Actinomadura sp. together with five known compounds (3-7). Their structures were elucidated by extensive spectroscopic methods including NMR and MS. In particular, the absolute configurations of compounds 1 and 2 were determined using computational methods. Moreover, compounds 1-2 and 8-10 were screened for cytotoxic activity using a panel of human tumor cell lines. Compound 9 induced significant cytotoxicity in five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480) with IC50 values of 8.7, 17.5, 15.0, 17.8, and 14.6 µM, respectively. These findings suggested that compound 9 could provide therapeutic benefits in the treatment of tumor-related diseases.

Properties of konjac glucomannan/curdlan-based emulsion films incorporating camellia oil and the preservation effect as coatings on 'Kyoho' grapes.

The strategy of emulsion coating was used for grape preservation. Camellia oil (CO) was incorporated with KGM/curdlan (KC) to fabricate KC-CO emulsion systems. KC-CO emulsions were analyzed by droplet size distribution and confocal laser scanning microscopy (CLSM), and KC-CO films were investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), mechanical properties, dissolution, gas permeability, water contact angle (WCA). KC-CO coating was used for preservation of 'Kyoho' grapes. The results indicated that the addition of CO had a positive effect on KC system. CO could form a uniform emulsion with KC, and the droplets were evenly dispersed in the KC matrix. KC-CO films displayed a continuous microstructure, and elongation at break (EAB) was improved, while tensile strength decreased. The dissolution, water vapor permeability (WVP), and WCA were significantly enhanced, while the permeability of oxygen and carbon dioxide exhibited no advantage compared with KC film. KC-CO-10 possessed optimal properties and was selected as an emulsion coating for preservation. The results suggested that KC-CO-10 significantly maintained the appearance, total solid and acid content of 'Kyoho' grapes, and delayed the weight loss and firmness decrease. This study contributed to the understanding of polysaccharide-lipid emulsion system and the applications.

Short-chain fatty acids (SCFAs) as potential resuscitation factors that promote the isolation and culture of uncultured bacteria in marine sediments.

Many marine bacteria are difficult to culture because they are dormant, rare or found in low-abundances. Enrichment culturing has been widely tested as an important strategy to isolate rare or dormant microbes. However, many more mechanisms remain uncertain. Here, based on 16S rRNA gene high-throughput sequencing and metabolomics technology, it was found that the short-chain fatty acids (SCFAs) in metabolites were significantly correlated with uncultured bacterial groups during enrichment cultures. A pure culture analysis showed that the addition of SCFAs to media also resulted in high efficiency for the isolation of uncultured strains from marine sediments. As a result, 238 strains belonging to 10 phyla, 26 families and 82 species were successfully isolated. Some uncultured rare taxa within Chlorobi and Kiritimatiellaeota were successfully cultured. Amongst the newly isolated uncultured microbes, most genomes, e.g. bacteria, possess SCFA oxidative degradation genes, and these features might aid these microbes in better adapting to the culture media. A further resuscitation analysis of a viable but non-culturable (VBNC) Marinilabiliales strain verified that the addition of SCFAs could break the dormancy of Marinilabiliales in 5 days, and the growth curve test showed that the SCFAs could shorten the lag phase and increase the growth rate. Overall, this study provides new insights into SCFAs, which were first studied as resuscitation factors in uncultured marine bacteria. Thus, this study can help improve the utilisation and excavation of marine microbial resources, especially for the most-wanted or key players. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00187-w.

Phosphorus storage and utilization strategies of two bloom-forming freshwater cyanobacteria.

The inter-relationships between cellular phosphorus (P) storage, dissolved inorganic P (DIP) uptake affinity, alkaline phosphatase activity (APA) and dissolved inorganic nitrogen (DIN) concentrations were studied in two ubiquitous diazotrophic freshwater cyanobacteria, Raphidiopsis raciborskii (six strains) and Chrysosporum ovalisporum (two strains). DIP uptake kinetics were measured using rates of incorporation of the radio-isotope, 33P and APA as a proxy for DOP-ester utilization. The study showed that DIP uptake of individual strains followed Michaelis-Menten kinetics (modified in our study to incorporate cellular P quotas), but differed with DIN and P availability, and between growth stages. High-affinity DIP uptake and APA were activated below a P quota threshold of approximately 0.01 µg P µg-1 C across the species and strains. C. ovalisporum had significantly higher APA and P quotas (per unit C and cell) but lower uptake affinity than R. raciborskii. Demand for DIP by C. ovalisporum increased when N fixation occurred, but typically not for R. raciborskii. Our results indicate that cyanobacterial species and strains differ in their strategies to P limiting conditions, and highlight the interplay between N and P. Physiological adaptations like APA and diazotrophy of cyanobacteria adapting to low DIP and/or DIN conditions may occur simultaneously and drive species dominance in oligotrophic environments.

Ferroptosis and Traditional Chinese Medicine for Type 2 Diabetes Mellitus.

Ferroptosis, an emerging form of regulated programmed cell death, has garnered significant attention in the past decade. It is characterized by the accumulation of lipid peroxides and subsequent damage to cellular membranes, which is dependent on iron. Ferroptosis has been implicated in the pathogenesis of various diseases, including tumors and diabetes mellitus. Traditional Chinese medicine (TCM) has unique advantages in preventing and treating type 2 diabetes mellitus (T2DM) due to its anti-inflammatory, antioxidant, immunomodulatory, and intestinal flora-regulating functions. Recent studies have determined that TCM may exert therapeutic effects on T2DM and its complications by modulating the ferroptosis-related pathways. Therefore, a comprehensive and systematic understanding of the role of ferroptosis in the pathogenesis and TCM treatment of T2DM is of great significance for developing therapeutic drugs for T2DM and enriching the spectrum of effective T2DM treatment with TCM. In this review, we review the concept, mechanism, and regulatory pathways of ferroptosis and the ferroptosis mechanism of action involved in the development of T2DM. Also, we develop a search strategy, establish strict inclusion and exclusion criteria, and summarize and analyze the application of the ferroptosis mechanism in TCM studies related to T2DM and its complications. Finally, we discuss the shortcomings of current studies and propose a future research focus.

Transcriptional and proteomic analysis.

Unintended effects of gene edit crops may pose safety issues. Omics is a useful tool for researchers to evaluate these unexpected effects. Transcriptome and proteomics analyses were performed for two gene editors, CRISPR-Cas9 and adenine base editor (ABE) gene edit rice, as well as corresponding wild-type plants (Nipponbare). Transcriptome revealed 520 and 566 rice differentially expressed genes (DEGs) in the Cas9/Nip and ABE/Nip comparisons, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that most DEGs participated in metabolism of terpenoids and polyketones, plant-pathogen interactions, and plant signal transduction. It mainly belongs to environmental adaptation. Proteomics revealed 298 and 54 rice differentially expressed proteins (DEPs) in the Cas9/Nip and ABE/Nip comparisons, respectively. KEGG pathway enrichment analysis showed that most DEPs participated in the biosynthesis of secondary metabolite and metabolic pathways.According to integrated transcriptomes and proteomics analysis, the results showed that no newly generated genes were identified as new transcripts of these differentially expressed genes, and gene edit tools had little effect on rice transcription levels and no new proteins were generated in the gene-edited rice.

Bloom-induced internal release controlling phosphorus dynamics in large shallow eutrophic Lake Taihu, China.

High phosphorus (P) concentrations are commonly observed in lakes during algal blooms despite massive efforts on external nutrient reduction. However, the knowledge about the relative contribution of internal P loading linked with algal blooms on lake phosphorus (P) dynamics remains limited. To quantify the effect of internal loading on P dynamics, we conducted extensive spatial and multi-frequency nutrient monitoring from 2016 to 2021 in Lake Taihu, a large shallow eutrophic lake in China, and its tributaries (2017-2021). The in-lake P stores (ILSP) and external loading were estimated and then internal P loading was quantified from the mass balance equation. The results showed that the in-lake total P stores (ILSTP) ranged from 398.5 to 1530.2 tons (t), and exhibited a dramatic intra- and inter-annual variability. The annual internal TP loading released from sediment ranged from 1054.3 to 1508.4 t, which was equivalent to 115.6% (TP loading) of the external inputs on average, and responsible for the fluctuations of ILSTP on a weekly scale. High-frequency observations exemplified that ILSTP increased by 136.4% during algal blooms in 2017, while by only 47.2% as a result of external loading after heavy precipitation in 2020. Our study demonstrated that both bloom-induced internal loading and storm-induced external loading are likely to run counter significantly to watershed nutrient reduction efforts in large shallow lakes. More importantly, bloom-induced internal loading is higher than storm-induced external loading over the short term. Given the positive feedback loop between internal P loadings and algal bloom in eutrophic lakes, which explains the significant fluctuation of P concentration while nitrogen concentration decreased. It is emphasized that internal loading and ecosystem restoration are unignorable in shallow lakes, particularly in the algal-dominated region.

Liver lipidomics analysis reveals the anti-obesity and lipid-lowering effects of gypnosides from heat-processed Gynostemma pentaphyllum in high-fat diet fed mice.

BACKGROUND: In traditional Chinese medicine, Gynostemma pentaphyllum (G. pentaphyllum) is widely used to treat conditions associated with hyperlipidemia, and its therapeutic potential has been demonstrated in numerous studies. However, the mechanism of lipid metabolism in hyperlipidemic by G. pentaphyllum, especially heat-processed G. pentaphyllum is not yet clear. PURPOSE: The aim of this study was to investigate the therapeutic mechanism of gypenosides from heat-processed G. pentaphyllum (HGyp) in hyperlipidemic mice by means of a lipidomics. METHODS: The content of the major components of HGyp was determined by ultra-performance liquid chromatography-electrospray ionization ion trap mass spectrometry (UPLC-ESI-MS). An animal model of hyperlipidaemia was constructed using C57BL/6J mice fed with high-fat diet. HGyp was also administered at doses of 50, 100 and 200 mg/kg, all for 12 weeks. Serum parameters were measured, histological sections were prepared and liver lipidome analysis using UPLC-MS coupled with multivariate statistical analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to analyze the genes and proteins associated with lipid lowering in HGyp. RESULTS: HGyp reduced body weight, serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) and hepatic lipid accumulation in hyperlipidemic obese mice. To explore specific changes in lipid metabolism in relation to HGyp administration, lipid analysis of the liver was performed. Orthogonal partial least squares discriminant analysis (OPLS-DA) score plots showed that HGyp altered lipid metabolism in HFD mice. In particular, fatty acids (FA), triglycerides (DG), TG and ceramides (CER) were significantly altered. Eleven lipids were identified as potential lipid biomarkers, namely TG (18:2/20:5/18:2), TG (18:2/18:3/20:4), DG (18:3/20:0/0:0), Cer (d18:1/19:0), Cer (d16:1/23:0), Ceramide (d18:1/9Z-18:1), PS (19:0/18:3), PS (20:2/0:0), LysoPC (22:5), LysoPE (0:0/18:0), PE (24:0/16:1). Western blot and qRT-PCR analysis showed that these metabolic improvements played a role by down-regulating genes and proteins related to fat production (SREBP1, ACC1, SCD1), up-regulating genes and proteins related to lipid oxidation (CPTA1, PPARα) and lipid transport decomposition in the bile acid pathway (LXRα, PPARγ, FXR, BSEP). CONCLUSION: The lipid-lowering effect of gypenosides from heat-processed G. pentaphyllum is regulate lipid homeostasis and metabolism.

Study on the Influence of the Preparation Method of Konjac Glucomannan-Silica Aerogels on the Microstructure, Thermal Insulation, and Flame-Retardant Properties.

Natural polysaccharides with high viscosity, good thermal stability, and biocompatibility can improve the mechanical properties of inorganic silica aerogels and enhance their application safety. However, the effects of the preparation methods of polysaccharide-silica aerogels on their microstructure and application properties have not been systematically studied. To better investigate the effect of the microstructure on the properties of aerogel materials, two aerogels with different structures were prepared using Konjac glucomannan (KGM) and tetraethoxysilane (TEOS) via physical blending (KTB) and co-precursor methods (KTC), respectively. The structural differences between the KTB and KTC aerogels were characterized, and the thermal insulation and fire-retardant properties were further investigated. The compressive strength of the KTC aerogels with a cross-linked interpenetrating network (IPN) structure was three times higher than that of the KTB aerogels, while their thermal conductivity was 1/3 of that of the KTB aerogels. The maximum limiting oxygen index (LOI) of the KTC aerogels was 1.4 times, the low peak heat release rate (PHRR) was reduced by 61.45%, and the lowest total heat release (THR) was reduced by 41.35% compared with the KTB aerogels. The results showed that the KTC aerogels with the IPN have better mechanical properties, thermal insulation, and fire-retardant properties than the simple physically blending KTB aerogels. This may be due to the stronger hydrogen-bonding interactions between KGM and silica molecules in the KTC aerogels under the unique forcing effect of the IPN, thus enhancing their structural stability and achieving complementary properties. This work will provide new ideas for the microstructure design of aerogels and the research of new thermal insulation and fire-retardant aerogels.

Protective Effects of Clinacanthus nutans (Burm.f.) Lindau Aqueous Extract on HBV Mouse Model by Modulating Gut Microbiota and Liver Metabolomics.

Background: Clinacanthus nutans (Burm.f.) Lindau (C. nutans) has been used in the therapy of hepatitis B (HB) and is effective; however, the mechanism of action has not been elucidated. Objective: To investigate the protective effects of C. nutans aqueous extract on the hepatitis B virus (HBV) mouse model based on correlation analysis between gut microbiota and liver metabolomics. Materials and Methods: We firstly constructed the animal model by high-pressure injection of pcDNA3.1(+)/HBV plasmid into the tail vein and treated it with C. nutans. The biomarkers and inflammatory cytokines of HB were detected by enzyme-linked immunosorbent assay and quantitative PCR; the Illumina-MiSeq platform was used for investigating gut microbiota; the LC-MS/MS method was utilized on screening liver tissue metabolites; multiomics joint analysis was performed using the R program. Results: Compared with the modeling group, C. nutans significantly decreased the expression levels of HBsAg, IL-1ß, TNF-α(P < 0.05) in the serum, and cccDNA (P < 0.05) in the liver tissues of mice. C. nutans dramatically reduced the ratio of Firmicutes and Bacteroidetes (P < 0.05) and significantly declined the proportion of Lactobacillaceae and Lactobacillus(P < 0.05), dramatically increasing the relative abundance of Bacteroidales_S24-7_group, Rikenellaceae, and Alistipes(P < 0.05); LC-MS/MS analysis results showed that C. nutans dramatically upregulate hippuric acid, L-histidine, trehalose, D-threitol, and stachyose and downregulate uridine 5'-diphosphate, cholic acid, trimethylamine N-oxide, CDP-ethanolamine, and phosphorylcholine (P < 0.05). The correlation analysis revealed that C. nutans affects the related metabolite levels of hippuric acid and cholic acid through the modulation of crucial bacteria (Alistipes) (P < 0.01), exerting specific anti-inflammatory effects. Conclusion: These results suggest that C. nutans exerts protective effects in HBV model mice, showing the therapeutic potential for anti-HBV infection.

(±)-Zanthonitidumines A and B: Two new benzophenanthridine alkaloids enantiomers from Zanthoxylum nitidum and their anti-inflammatory activity.

Two new benzophenanthridine alkaloids enantiomers (±)-zanthonitidumines A (1) and B (2), along with seven known analogues (3-9), were isolated from Zanthoxylum nitidium. Their structures were elucidated on the basis of extensive spectroscopic techniques and ECD data. Compound 2 exhibited the most significant inhibition of IL-6 generation as well as TNF-α release which suggest that it may be a potential anti-inflammatory agent.

Alpiniae oxyphylla fructus extract promotes longevity and stress resistance of C. elegans via DAF-16 and SKN-1.

Background: Alpiniae Oxyphylla Fructus (AOF) is Traditional Chinese medicine and a dietary supplements for centuries, which posseses cardiotonic, neuroprotective, antioxidant, warming the kidney and nourish the spleen, these biological fuction is related to potential anti-aging properties. However, little is known about their effects on aging. This work aimed to investigate the effects of extracts of AOF on longevity and stress resistance in Caenorhabditis elegans (C. elegans) and the mechanisms that underlie its effects. Methods: Wild-type (WT) strand of C.elegans (N2)worms were cultured in growth medium with or without AOF. First, we examined the effects of AOF on lifespan, reproduction and healthspan assay, stress resistance and oxidative analysis, lipofuscin levels. Second, The levels of ROS and MDA, the antioxidant enzyme activities were examined to explore the underlying mechanism of AOF. Finally, the expression of the longevity-related genes were investigated to further understand the AOF's underlying mechanism. Results: The lifespan of C. elegans was prolonged by 23.44% after treatment with high-dose AOF (100 ug/ml). AOF alleviated aging-related declines in C. elegans health and enhanced resistance to heat shock. Furthermore, AOF decreased reactive oxygen species and malondialdehyde, increased the activities of superoxide dismutase and catalase, and reduced accumulation of fat. AOF upregulated the expression of sod-3, gst-4, daf-16, and skn-1 but downregulated the expression of daf-2 and age-1 and accelerated the translocation of DAF-16 into the nucleus. The extended lifespan induced by AOF was reversed in daf-16(mu86) and skn-1(zu135) mutants, indicating that this gene is involved in AOF-regulated longevity. Conclusion: Our findings demonstrated that AOF extends lifespan and healthspan and enhances stress via boosting the activity of the antioxidant enzyme and controlling the expression of genes associated with insulin/IGF signaling and SKN-1 pathways. As a result, this work suggested AOF as a possible candidate to reduce the signs of aging by activating and inhibiting target genes.

Antioxidative and Cytoprotective Effects of Ganoderma applanatum and Fomitopsis pinicola in PC12 Adrenal Phaeochromocytoma Cells.

Considering the impact of oxidative stress on the development of many diseases, together with the role of natural antioxidants in maintaining physiological balance in humans, medicinal mushrooms are potential sources of bioactive compounds against many diseases. In the present work, in vitro evaluation of the biological activities of the alcoholic extracts of two wild tree mushrooms, namely, Ganoderma applanatum and Fomitopsis pinicola, has been performed. Extraction of G. applanatum (GAE) and F. pinicola (FPE) was conducted with 60% ethanol and 100% ethanol sequentially. UPLC-MS/MS identification was conducted on the two mushrooms extracts. A total of 15 substances were identified in GAE, including 3 spiro meroterpenoids and 12 triterpenoids; a total of 14 chemical constituents were iden¬tified in FPE, including 8 triterpenoids, 4 triterpene glycosides, 1 lanosterol, and 1 lanostanoid. The resulting extracts were examined for their in vitro antioxidative and cytoprotective effects against AAPH-induced oxidative damage. Our results demonstrated that both extracts have potent antioxidative activities, when GAE was 0.2 mg/mL, the clearance rates of DPPH and ABTS have reached 93.34% and 99.93%, respectively. When FPE was 1.4 mg/mL and 0.6 mg/mL, the scavenging rates of DPPH and ABTS have reached 91.76% and 100%, respectively. Both the alcoholic extracts of G. applanatum and F. pinicola were able to protect the AAPH-induced damage and could effectively inhibit cell aging via ß-galactosidase (SA ß-gal) staining activity test and scanning electron microscopy analysis.

Network pharmacology-based approach uncovers the JAK/STAT signaling mechanism underlying paederia scandens extract treatment of rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease. Paederia scandens (Lour.) Merr is a common folk remedy used in Hainan, China, to dispel the wind and dampness associated with RA. METHODS: The active components of Paederia scandens were extracted using network pharmacology. The potential targets of active components were used to determine activated pathways, and the in vitro effects of Paederia scandens extracts were verified in RA fibroblast-like synoviocytes (HFLS-RA). RESULTS: We identified 27 active components using ultra-high-performance liquid chromatography (UHPLC)-quadrupole time-of-flight (QTOF)-mass spectrometry (MS). Among the major target genes with high connectivity, IL-1ß, PI3K, TNF, and JAK2 are known to play key roles in RA development. High-affinity interactions were identified between active compounds in Paederia scandens extract and Janus kinase JAK 2, which are key components of the JAK-signal transducer and activator of transcription (STAT) signaling pathway. In HFLS-RA cells, Paederia scandens extract treatment reduced the mRNA levels of IL-6, IL-1ß, and IL-17. Paederia scandens extract treatment also significantly inhibited the phosphorylation of JAK 2 and STAT3, regulating cell proliferation. CONCLUSIONS: Based on these results, we confirmed that Paederia scandens has potential for application as a therapeutic and preventive food and acts through the modulation and suppression of JAK-STAT pathway activation to control the inflammatory response in RA.

Brucea javanica Oil Emulsion Promotes Autophagy in Ovarian Cancer Cells Through the miR-8485/LAMTOR3/mTOR/ATG13 Signaling Axis.

Background: Ovarian cancer is a common malignant tumor of the female reproductive tract, with the highest mortality rate. At present, no effective approaches to improve the survival rate exist. B. javanica Oil Emulsion (BJOE), an extract from B. javanica (L.) Merr. [Simaroubaceae], exhibits antitumor effects and can increase the sensitivity of radiotherapy and chemotherapy in many types of cancers. MiR-8485, a discovered miRNA, has been shown to be involved in the occurrence and development of tumors. The purpose of this study was to investigate the effect of BJOE on the regulation of mammalian rapamycin target protein (mTOR) autophagy signal pathway and related autophagy factors on ovarian cancer cells through miR-8485. Methods: The main chemical constituents of BJOE were determined by UHPLC-MS/MS. Detection of miR-8485 expression in ovarian cancer cells treated with BJOE by quantitative reverse transcription polymerase chain reaction (qRT-PCR). CCK8 experiment and flow cytometry were used to observe the effects of BJOE and overexpression of miR-8485 on cell proliferation and apoptosis. Then, monodansylcadaverine (MDC) fluorescence staining was used to observe the changes of autophagy vesicles before and after the effect of BJOE and overexpressed miR-8485 on cancer cells. Next, the binding sites between miR8485 and mammalian rapamycin target protein activator 3 (LAMTOR3) were detected by double luciferase reporter assay. Furthermore, qRT-PCR and Western blot experiments were used to explore the changes of autophagy-related factors LAMTOR3, mTOR and autophagy-related 13 (ATG13), and microtubule associated protein 1 light chain 3 beta (LC3-Ⅱ) after BJOE and overexpression of miR-8485, in addition to autophagy inhibitor (3-MA) for rescue experiment verification. Results: The qRT-PCR results showed that the expression of miR-8485 increased after BJOE treatment in the SKOV3 cell. The CCK8 assay and flow cytometry analysis revealed that both BJOE and miR-8485 overexpression inhibited the proliferation and promoted the apoptosis of the SKOV3 cell. MDC fluorescence staining showed that BJOE and miR-8485 overexpression led to a significant increase in autophagy vesicles in the SKOV3 cell. Double luciferase reporter assay confirmed the existence of binding sites between miR8485 and LAMTOR3. The results of qRT-PCR and Western blot showed that BJOE and overexpressed miR-8485 downregulated the expression of LAMTOR3 and mTOR and up-regulated the expression of ATG13 and LC3-Ⅱ. Conclusion: 1) MiR-8485 may be the key factor of BJOE in promoting autophagy and apoptosis and inhibiting cell proliferation of ovarian cancer cells; 2) BJOE may play an antitumor role by regulating LAMTOR3/mTOR/ATG13 signaling axis through miR-8485 to promote autophagy in ovarian cancer cells.

Schindler's legacy: from eutrophic lakes to the phosphorus utilization strategies of cyanobacteria.

David Schindler and his colleagues pioneered studies in the 1970s on the role of phosphorus in stimulating cyanobacterial blooms in North American lakes. Our understanding of the nuances of phosphorus utilization by cyanobacteria has evolved since that time. We review the phosphorus utilization strategies used by cyanobacteria, such as use of organic forms, alternation between passive and active uptake, and luxury storage. While many aspects of physiological responses to phosphorus of cyanobacteria have been measured, our understanding of the critical processes that drive species diversity, adaptation and competition remains limited. We identify persistent critical knowledge gaps, particularly on the adaptation of cyanobacteria to low nutrient concentrations. We propose that traditional discipline-specific studies be adapted and expanded to encompass innovative new methodologies and take advantage of interdisciplinary opportunities among physiologists, molecular biologists, and modellers, to advance our understanding and prediction of toxic cyanobacteria, and ultimately to mitigate the occurrence of blooms.