[Metabolomic study on urine of chronic inflammation rats treated with Buyang Huanwu Decoction based on UPLC-Q-TOF-MS].

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 µg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.

Approaching the quantum limit in two-dimensional semiconductor contacts.

The development of next-generation electronics requires scaling of channel material thickness down to the two-dimensional limit while maintaining ultralow contact resistance1,2. Transition-metal dichalcogenides can sustain transistor scaling to the end of roadmap, but despite a myriad of efforts, the device performance remains contact-limited3-12. In particular, the contact resistance has not surpassed that of covalently bonded metal-semiconductor junctions owing to the intrinsic van der Waals gap, and the best contact technologies are facing stability issues3,7. Here we push the electrical contact of monolayer molybdenum disulfide close to the quantum limit by hybridization of energy bands with semi-metallic antimony ([Formula: see text]) through strong van der Waals interactions. The contacts exhibit a low contact resistance of 42 ohm micrometres and excellent stability at 125 degrees Celsius. Owing to improved contacts, short-channel molybdenum disulfide transistors show current saturation under one-volt drain bias with an on-state current of 1.23 milliamperes per micrometre, an on/off ratio over 108 and an intrinsic delay of 74 femtoseconds. These performances outperformed equivalent silicon complementary metal-oxide-semiconductor technologies and satisfied the 2028 roadmap target. We further fabricate large-area device arrays and demonstrate low variability in contact resistance, threshold voltage, subthreshold swing, on/off ratio, on-state current and transconductance13. The excellent electrical performance, stability and variability make antimony ([Formula: see text]) a promising contact technology for transition-metal-dichalcogenide-based electronics beyond silicon.

Microbial community succession in the fermentation of Qingzhuan tea at various temperatures and their correlations with the quality formation.

With the aim to reveal the microbial community succession at various temperatures in the fermentation of Qingzhuan tea (QZT), the Illumina NovaSeq sequencing was carried out to analyze bacterial and fungal community structure in tea samples collected from the fermentation set at various temperatures, i.e., 25 °C, 30 °C, 37 °C, 45 °C, 55 °C, and room temperature. The results showed that fermentation temperature profoundly affected the microbial community succession in the QZT fermentation. Microbial richness and community diversity decreased along with the increase of fermentation temperature. Despite the differences between microorganisms and their metabolic types among various temperatures, most bacteria and fungi showed positive correlations at the genera level. Klebsiella, Paenibacillus, Cohnella, and Pantoea were confirmed as the main bacterial genera, and Aspergillus and Cyberlindnera were the main fungal genera in QZT fermentation. The microbial genera (i.e. Aspergillus, Rhizomucor, Thermomyces, Ralstonia, Castellaniella, and Vibrio) were positively correlated with fermentation temperature (P < 0.05), while Klebsiella, Paenibacillus, and Aspergillus had good adaptability at different temperatures. Conversely, Pantoea and Cyberlindnera were only suitable for low temperature (≤37 °C) growth, and Thermomyces was only suitable for high temperature (>37 °C) growth. Aspergillus had a significant positive correlation with tea aroma quality (r = 0.64, p < 0.05). This study would help to understand the formation mechanism of QZT from microflora perspective.

Influence of thermophilic microorganism on non-volatile metabolites during high-temperature pile-fermentation of Chinese dark tea based on metabolomic analysis.

Pile-fermentation is a critical procedure for producing Chinese dark tea, during which thermophilic microorganisms would play an irreplaceable role. However, there have been little researches on the influences of thermophilic microorganism pile-fermentation (TMPF) in high-temperature of Chinese dark tea. Thus, we conducted high-performance liquid chromatography and nontargeted metabolomic to analyze the non-volatile metabolites of TMPF. Our results discovered that the amounts of ( -)-epigallocatechin gallate, ( -)-epigallocatechin, ( -)-epicatechin gallate, and ( -)-epicatechin were decreased significantly (p < 0.05) after TMPF. By using nontargeted metabolomic analysis, a total of 1733 ion features were detected. KEGG pathway enrichment analysis showed that TMPF had a significant impact on caffeine metabolism. Also, theophylline, 3-methylxanthine, and 1,3,7-trimethyluric acid were increased significantly after TMPF, which suggested that demethylation and oxidation reaction might be the main pathways of caffeine metabolism. This study provides a better understanding of the mechanism of TMPF during high-temperature for Chinese dark tea and lays a foundation for further research. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-022-01098-9.

Choline Intake Correlates with Cognitive Performance among Elder Adults in the United States.

OBJECTIVE: This research attempted to explore the neuroprotective effect of choline and establish evidence for future dietary recommendations and nutritional interventions to maintain a proper cognitive function among elders aged >60 years in the US. METHOD: This cross-sectional study retrieved data of 2,393 eligible elderly participants from the 2011-2014 National Health and Nutrition Examination Survey. Combining dietary and supplement choline intake, total choline intake was evaluated using the 24-hour dietary recall method and the dietary supplement questionnaire. Total choline intake was categorized into tertiles, which ranged at <187.60 mg/day (T1), 187.60-399.50 mg/day (T2), and >399.50 mg/day (T3). The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning subtest, Animal Fluency (AF) test, and Digit Symbol Substitution test (DSST) was used to measure cognitive function. Participants who scored the lowest 25th percentile in each cognitive test were classified in the low cognitive function (LC) group. Logistic regression models were implemented to examine the association between total choline intake and the incidence of LC. RESULTS: In the CERAD test, the risk of LC was significantly lower in T2 than T1 (OR: 0.668, 95% CI: 0.493-0.904, and P = 0.006) when adjusted for age, gender, BMI, alcohol consumption, and hypertension. Similarly, T2 was associated with a significantly lower risk of LC when assessed by the AF test (OR: 0.606, 95% CI: 0.580-0.724, and P < 0.001) and DSST (0.584, 95% CI: 0.515-0.661, and P < 0.001). In all three cognitive measures, the T3 of the total choline intake was not associated with cognitive function compared to T1. CONCLUSION: Total choline intake at 187.06-399.50 mg/day reduces the risk of LC by approximately 50% compared to intake at <187.6 mg/day. The findings of this research may be used to establish dietary recommendations and nutritional interventions to optimize the cognitive function among elders.

In Vitro Investigation of the Cytotoxic Activity of Emodin 35 Derivative on Multiple Myeloma Cell Lines.

BACKGROUND: Bortezomib is used for treating multiple myeloma (MM); however, it has considerable adverse effects. Emodin has been reported to exhibit inhibitory effects on MM cell lines. We investigated the efficacy of emodin 35 (E35), an emodin derivative, using U266 and MM1s cell lines in treating MM and the efficacy of combining bortezomib and E35. METHODS: MTT assays were used to observe the effects of E35 on MM cell growth. The effects on cellular apoptosis were then observed using Annexin V/propidium iodide (PI) staining assay. The expression of apoptosis-related genes, including the caspase family, was examined. The efficacy of combining bortezomib and E35 was investigated by examining the expression of the Akt/mTOR/4EBP1 signaling pathway-related proteins. RESULTS: We report that E35 inhibited the growth of U266 and MM1s cells by inducing cellular apoptosis. Moreover, E35 downregulated the expression of apoptosis-related genes and suppressed the phosphorylation of Akt/mTOR/4EBP1 signaling pathway-related genes, thus exhibiting synergistic effects with bortezomib. All observed effects were dose-dependent. CONCLUSION: The results showed that E35 exhibited cytotoxic effects in MM cell lines in protein levels. Thus, E35, particularly in combination with bortezomib, may be considered as a promising treatment for MM; however, this requires further investigation in vivo.

Comparative analysis of the transcriptome, methylome, and metabolome during pollen abortion of a seedless citrus mutant.

KEY MESSAGE: Pollen abortion could be mainly attributed to abnormal meiosis in the mutant. Multiomics analysis uncovered significant epigenetic variations between the mutant and its wild type during the pollen abortion process. Male sterility caused by aborted pollen can result in seedless fruit. A seedless Ponkan mandarin mutant (bud sport) was used to compare the transcriptome, methylome, and metabolome with its progenitor to understand the mechanism of citrus pollen abortion. Cytological observations showed that the anther of the mutant could form microspore mother cells, although the microspores failed to develop fertile pollen at the anther dehiscence stage. Based on pollen phenotypic analysis, pollen abortion could be mainly attributed to abnormal meiosis in the mutant. A transcriptome analysis uncovered the molecular mechanisms underlying pollen abortion between the mutant and its wild type. A total of 5421 differentially expressed genes were identified, and some of these genes were involved in the meiosis, hormone biosynthesis and signaling, carbohydrate, and flavonoid pathways. A total of 50,845 differentially methylated regions corresponding to 15,426 differentially methylated genes in the genic region were found between the mutant and its wild type by the methylome analysis. The expression level of these genes was negatively correlated with their methylation level, especially in the promoter regions. In addition, 197 differential metabolites were identified between the mutant and its wild type based on the metabolome analysis. The transcription and metabolome analysis further indicated that the expression of genes in the flavonoid, carbohydrate, and hormone metabolic pathways was significantly modulated in the pollen of the mutant. These results indicated that demethylation may alleviate the silencing of carbohydrate genes in the mutant, resulting in excessive starch and sugar hydrolysis and thereby causing pollen abortion in the mutant.

Comparison of the Chemical Composition and Bioactive Components of Fruiting Bodies and Submerged Cultured Mycelia of the Willow Bracket Medicinal Mushroom, Phellinus igniarius (Agaricomycetes).

Chemical compositions and bioactive ingredients of dried fruiting bodies from Phellinus igniarius (CGMCC no. 50095) (P1) and submerged culture of Ph. igniarius dried mycelia (P2) were investigated in this study. It was found that glutamic acid was regarded as a major amino acid in P1 (1.20%) and was approximately 2.55-fold higher than that in P2 (0.47%). Total amino acids in P1 (5.36%) were slightly higher than in P2 (4.09%). The amounts of iron, zinc, copper, and manganese in P1 were 1.96-3.42 times as high as those in P2, whereas potassium, sodium, and magnesium in P2 were almost 2.94-6.88 times lower than in P1. Lead, mercury, and cadmium in P1 were significantly lower than in P2. The levels of polysaccharides and total triterpenoids in PI amounted to 0.29% and 2.3%, respectively, which are considerably higher values than those in P1 (7.72% and 6.88%, respectively). Galactosamine was only detected in the crude polysaccharide of P2. Other monosaccharides, except for galactose, were significantly different between the 2 samples. Crude polysaccharide of P2 was separated into 4 polysaccharides with different molecular weights, but crude polysaccharide in P1 was distributed between 2 different molecular weights. Major polysaccharides in P1 (93.78%) were distributed at about 205,212 Da, whereas the main polysaccharides of P2 (65.98%) were found at about 33,064 Da. The results indicated that submerged cultured mycelia from Ph. igniarius supplemented by its fruiting bodies can be used in medicinal applications.

Cordyceps industry in China.

Cordyceps, as a general term, describes a group of ascomycetous fungi growing on arthropods and other related fungi. Some cordyceps have been used in traditional Chinese medicine for centuries and cordyceps-derived products are currently a big industry in China. A number of medicinal and health products have been developed and extensively commercialized from natural Chinese cordyceps, its anamorphic fungus (Hirsutella sinensis), and other fungi known as Chinese cordyceps. The lack of a defined classification system for medicinal cordyceps fungi is a source of confusion in the industry and the public, and even among pharmaceutical scientists. This review summarizes the cordyceps fungi currently used in the industry in China with a special reference to clarify Chinese cordyceps and associated fungi. Cordyceps militaris, Cordyceps guangdongensis and Isaria cicadae are well recognized and commercialized cordyceps fungi in China. Except the natural Chinese cordyceps and its anamorphic fungus, Paecilomyces hepiali, Mortierella hepiali, Cephalosporium sinensis and Clonostachys rosea isolated from natural Chinese cordyceps are classified as Chinese cordyceps-associated fungi. P. hepiali is a cordyceps fungus based on current phylogenetic analysis of Hypocreales, while M. hepiali is a fungus in the Zygomycetes and should only be treated as associated fungus of Chinese cordyceps. C. sinensis and C. rosea belong to the Hypocreales and their relationship to cordyceps fungi should be further studied. The exploitation of the resources of cordyceps fungi and their quality control in the industry should be major topics for future studies. Cooperation between the industry and the research community will enhance the whole cordyceps industry.

A novel effect of imidazole derivative KK-42 on increasing survival of Aeromonas hydrophila challenged prawn Macrobrachium nipponense.

Imidazole derivative KK-42 is well known as the insect growth regulator. Here we find that KK-42 pretreatment could promote the survival of Macrobrachium nipponense infected with Aeromonas hydrophila, which is considered to be possibly related to the prophenoloxidase (proPO), a conserved copper-containing enzyme that plays an important role in defense against pathogens. In this study, a full-length of proPO gene from M. nipponense haemocytes, designated as MnproPO, was firstly cloned and characterized. The full-length cDNA contained 2428 bp with a 2013 bp open reading frame encoding a putative proPO protein of 671 amino acids with a predicted molecular mass of 76.5 kDa and pI of 7.31. It was predicted to possess all the expected features of proPO members, including two putative copper-binding sites with six histidine residues and a thiol ester-like motif. Sequence analysis showed that MnproPO exhibited the highest amino acid sequence similarity (93%) to a proPO of Macrobrachium rosenbergii. The gene was expressed highly in haemocytes and weakly in hepatopancreas. Real-time PCR analysis revealed that the MnproPO expression increased significantly at 3, 12 and 24 h after KK-42 treatment, the PO activity also importantly rose from 6 to 48 h in KK-42-treated prawns and reached the maximum at 24 h with a 2.3-fold higher than that in control group. Injection of A. hydrophila could stimulate the MnproPO transcription and PO activity whether or not the prawns were pretreated by KK-42, the mRNA level increased obviously only at 3 h and 6 h after the bacterium injection (challenged control), but increased constantly during the phase of experiment except at 6 h under the condition of KK-42 pretreatment (challenged treatment group). The change trend of PO activity was basically similar to that of MnproPO expression. Our present results demonstrate that the MnproPO expression as well as PO activity may be induced by KK-42, which is likely one of the molecular mechanisms of KK-42 acts for increasing survival of the prawn infected with A. hydrophila.

[Effect of extracted liquid from qianlietongyu on the proliferation and apoptosis on prostatic smooth muscle cells in vitro].

OBJECTIVE: To explore the effect of extracted liquid from Qianlietongyu on the proliferation or apoptosis on prostatic smooth muscle cells in vitro. METHODS: After extracted liquid from Qianlietongyu treated the cultured prostatic smooth muscle cells, the anti proliferative and apoptotic indices were assessed by MTT assy and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) respectively. RESULTS: There was a significant dose-effect relationship between the concentration of extracted liquid from Qianlietongyu and the antiproliferative index on prostatic smooth muscle cells in vitro (P < 0.01), but there was no markedly difference in the apoptosis index between the group of extracted liquid from Qianlietongyu and control group ( P > 0.05). CONCLUSION: Extracted liquid from Qianlietongyu may show significant antiproliferative effect on prostatic smooth muscle cells in vitro, without inducing apoptosis.