Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid. AIM: To investigate the mechanism by which F. nucleatum affects CRC occurrence and development. METHODS: Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function. RESULTS: Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation. CONCLUSION: F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.

Research hotspots of polycystic ovary syndrome and hyperandrogenism from 2008 to 2022: bibliometric analysis.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most frequent endocrine disorder in female adults, and hyperandrogenism (HA) is the typical endocrine feature of PCOS. This study aims to investigate the trends and hotspots in the study of PCOS and HA. METHODS: Literature on Web of Science Core Collection (WoSCC) from 2008 to 2022 was retrieved, and bibliometric analysis was conducted using VOSviewer and CiteSpace software. RESULTS: A total of 2,404 papers were published in 575 journals by 10,121 authors from 2,434 institutions in 86 countries. The number of publications in this field is generally on the rise yearly. The US, China and Italy contributed almost half of the publications. Monash University had the highest number of publications, while the University of Adelaide had the highest average citations and the Karolinska Institute had the strongest cooperation with other institutions. Lergo RS contributed the most to the field of PCOS and HA. The research on PCOS and HA mainly focused on complications, adipose tissue, inflammation, granulosa cells, gene and receptor expression. CONCLUSION: Different countries, institutions, and authors should facilitate cooperation and exchanges. This study will be helpful for better understanding the frontiers and hotspots in the areas of PCOS and HA.

Vanillin, a Newly Discovered Autotoxic Substance in Long-Term Potato Continuous Cropping Soil, Inhibits Plant Growth by Decreasing the Root Auxin Content and Reducing Adventitious Root Numbers.

Phenolic acids are known to reduce root biomass and hinder plant development, but it is unclear how they affect potato root traits. Over a 10 year field experiment, we found a negative correlation between the potato yield and continuous cropping years. The substantial reduction in adventitious root (AR) numbers was found to be primarily inhibited by soil vanillin accumulation. The study also found that vanillin had a more pronounced inhibitory effect on the potato yield than commonly reported ferulic acid and p-hydroxybenzoic acid. The decrease in yield was attributed to the reduction of root indole-3-acetic acid (IAA) content, which impeded the formation of AR. Exogenous IAA was found to increase the root IAA content and stimulate AR formation under vanillin stress, ultimately leading to an increase in the potato yield. This study provides valuable insights into potential strategies for the degradation of autotoxic substances and breeding of potato cultivars with enhanced resistance to autotoxicity.

Scientific Knowledge Graph of Dysmenorrhea: A Bibliometric Analysis from 2001 to 2021.

Purpose: This study aims to help researchers master the most active hotspots and trends quickly through bibliometric analysis in the field of dysmenorrhea. Methods: We retrieved literature on Web of Science from 2001 to 2021, and bibliometric analysis software CiteSpace was used in combination with VOSviewer. Results: We finally acquired 944 papers and an upward trend in articles continued in this field overall. Through the map, China contributed the most, followed by the USA and Turkey. For institutions, Beijing University of Chinese Medicine in China contributed the most, followed by National Yang-Ming University in Taiwan, China. Hsieh JC and Hellman KM were both the most prolific authors with 14 articles. Five major research groups, respectively, with Hsieh JC, Hellman KM, Zhu J, Liang F and Dun W were the key group. Dawood MY was the most dominant author and most frequently cited author. The Cochrane Database of Systematic Reviews Journal was the most productive, and the Fertility and Sterility Journal was the most cited. Advances in pathogenesis and management for primary dysmenorrhea written by Dawood MY was most cited and influential. Pathophysiology, the potential central mechanism, syndrome, evaluation index, diagnosis of adenomyosis-associated dysmenorrhea, treatment, etc., were the main trends and hotspots. Conclusion: Dysmenorrhea research has received a lot of attention from scholars. Strengthening international cooperation may promote the development of this field. The pathophysiology of dysmenorrhea, its impact on public health and its treatment are current research hotspots and are likely to be the focus of future study.

Effects of different altitudes on the structure and properties of potato starch.

The main element influencing the quality of potato starch is the environment. To investigate the effects of different altitude cultivation locations on the molecular structure and physicochemical properties of starch, two potato varieties, Jiusen No.1 B1 and Qingshu No.9 B2, were planted in three different altitude zones: A1 at low altitude (Chongzhou 450 m), A2 at middle altitude (Xichang 2800 m), and A3 at high altitude (Litang 3650 m). The results showed that the average volume, number, surface area diameter, average branched polymerization degree, crystallinity, and gelatinization temperature of two potato granules in high altitude areas were significantly lower than those in middle and low altitude areas were, and the gelatinization performance of potato starch was affected according to the correlation of starch structure characteristics. Potato starch with more short-branched chains and less long branched chains resulted in a lower gelatinization temperature in high altitude areas. The results showed that Jiusen No. 1 and Qingshu No. 9 were mainly affected by accumulated radiation and accumulated rainfall in Litang, a high altitude area, and by effective accumulated temperature in Xichang, a middle altitude area. This study quantified the influence of meteorological factors on the main starch quality of potato tubers. The results can be used as a theoretical basis for the scientific planting of high-quality potatoes.

A color-change fluorescence sensor for oleanolic acid based on chiral camphanic decorated bis-cyanostilbene.

Although various fluorescent sensors for biomolecules had been extensively reported, the effective fluorescent sensor was seldom reported for detecting oleanolic acid up to now. This work reports the first color-change fluorescence sensor for oleanolic acid based on a bridging bis-cyanostilbene derivative with chiral camphanic groups (C-BCS). C-BCS possessed the chartreuse fluorescence in aqueous media, which transferred to strong blue fluorescence in the presence of oleanolic acid. This sensing ability of C-BCS for oleanolic acid exhibited the high selectivity among all kinds of biomolecules and ions. The good linearity between the fluorescence intensity and concentration of oleanolic acid was acquired in the range of 0.2 × 10-6 to 8.0 × 10-6 M with the detecting limitation of 0.0582 µM. The 1:1 binding process was clarified as oleanolic acid located in the opening cavity composed of two bridging cyanostilbene units and two chiral camphanic groups based on multiple hydrogen bonds and hydrophobic interaction. The detecting ability of C-BCS was applied on sensing oleanolic acid in thin-layer chromatography analysis, imprinting experiment, tap water, and tea samples, suggesting the effective on-site sensing abilities of C-BCS for oleanolic acid in real samples and daily life.

Biosynthesis of Hybrid Neutral Lipids with Archaeal and Eukaryotic Characteristics in Engineered Saccharomyces cerevisiae.

Discovery of the Asgard superphylum of archaea provides new evidence supporting the two-domain model of life: eukaryotes originated from an Asgard-related archaeon that engulfed a bacterial endosymbiont. However, how eukaryotes acquired bacterial-like membrane lipids with a sn-glycerol-3-phosphate (G3P) backbone instead of the archaeal-like sn-glycerol-1-phosphate (G1P) backbone remains unknown. In this study, we reconstituted archaeal lipid production in Saccharomyces cerevisiae by expressing unsaturated archaeol-synthesizing enzymes. Using Golden Gate cloning for pathway assembly, modular gene replacement was performed, revealing the potential biosynthesis of both G1P- and G3P-based unsaturated archaeol by uncultured Asgard archaea. Unexpectedly, hybrid neutral lipids containing both archaeal isoprenoids and eukaryotic fatty acids were observed in recombinant S. cerevisiae. The ability of yeast and archaeal diacylglycerol acyltransferases to synthesize such hybrid lipids was demonstrated.

Robotic Construction and Screening of Lanthipeptide Variant Libraries in Escherichia coli.

Lanthipeptides are a major class of ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by thioether cross-links called lanthionine (Lan) and methyllanthionine (MeLan). Previously, we developed a method to produce mature lanthipeptides in recombinant Escherichia coli, but manual steps hinder large-scale analogue screening. Here we devised an automated workflow for creating and screening variant libraries of haloduracin, a two-component class II lanthipeptide. An integrated work cell of a synthetic biology foundry was programmed to robotically execute DNA library construction, host transformation, peptide production, mass spectrometry analysis, and activity screening by agar diffusion assay. For recombinantly produced Halα peptides, the sequence-activity relationship of 380 single-residue variants and >1300 triple-residue combinatorial variants were rapidly analyzed in microplates within weeks. The peptide expression levels in E. coli were also visualized via robotic creation and analysis of GFP-lanthipeptide fusions for select peptide mutants. Following shake-flask fermentation and purification, one Halα mutant was confirmed with enhanced specific antimicrobial activity relative to the wild-type peptide. Overall, this approach may be generally applicable for the high-throughput characterization and engineering of RiPP natural products.

Six-electron organic redoxmers for aqueous redox flow batteries.

We have developed a novel molecular design that enables six-electron redox activity in fused phenazine-based organic scaffolds. Combined electrochemical and spectroscopic tests successfully confirm the two-step 6e- redox mechanism. This work offers an opportunity for achieving energy-dense redox flow batteries, on condition that the solubility and stability issues are addressed.

Fusobacterium nucleatum Affects Cell Apoptosis by Regulating Intestinal Flora and Metabolites to Promote the Development of Colorectal Cancer.

Background/Aims: Intestinal flora, especially Fusobacterium nucleatum (Fn), can affect the development of colorectal cancer (CRC). In this study, we examined the composition of intestinal flora and their metabolites in the tissues, serum and feces of CRC patients. Materials and Methods: CRC tissues, adjacent normal colonic tissues, fecal and serum samples were collected from CRC patients who received surgical treatment between January 2018 and January 2020. Fecal and serum samples were collected from healthy individuals for comparison. In addition, fecal samples were collected from BALB/c female mice. SW480, a human CRC cell line, was utilized for in vitro studies. The experiments involved 1H-NMR-based metabolomics analysis, targeted and untargeted mass spectrometry analysis, and intestinal flora 16S rDNA V4 region sequencing. Results: The abundance of Bacteroides and propionic acid concentration were decreased and that of Lactobacillus and lactic acid concentration were increased in CRC tissues. In addition, the abundances of Ruminococcus, Prevotella, and Sutterell were decreased in CRC patients. The levels of leucine and isoleucine were decreased in the serum and tumor tissues of CRC patients. Aspartate, glutamate and glutathione levels were elevated in the tissues of CRC patients only. The serum glutamine, tyrosine, valine, alanine, and histidine levels were decreased significantly. Lactic acid inhibited and propionic acid promoted apoptosis among SW480 CRC cells. Conclusion: Fn affected the apoptosis of CRC cells and promoted the progression of CRC by affecting the distribution of intestinal flora, which altered the concentrations of metabolites such as lactic acid, propionic acid. Intestinal flora could regulate amino acid metabolism.

Fusobacterium nucleatum Promotes the Progression of Colorectal Cancer Through Cdk5-Activated Wnt/ß-Catenin Signaling.

BACKGROUND/AIMS: Growing evidence supports the direct link of Fusobacterium nucleatum with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of F. nucleatum on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/ß-catenin signaling pathway. MATERIALS AND METHODS: CRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for in vitro mechanistic investigations. RESULTS: The abundance of F. nucleatum was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. In vitro investigations revealed that F. nucleatum significantly enhanced the proliferation and migration of CRC cells. Furthermore, F. nucleatum significantly induced the expression of Cdk5 and activation of the Wnt/ß-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of F. nucleatum on cellular processes and Wnt/ß-catenin signaling in relation to the progression of CRC. CONCLUSION: The results of this study demonstrate that F. nucleatum orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/ß-catenin signaling to modulate CRC progression. Thus, in-depth investigations of F. nucleatum-associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.

Fabrication and evaluation of flexible electrowetting display with support pillars.

With the development of portable and wearable devices, flexible displays have attracted extensive interest and have become increasingly important in our daily life. In this study, a flexible electrowetting display (FEWD) was proposed and fabricated. To prevent a short circuit between the top and bottom electrodes, various types of support pillars were fabricated on the top substrates through a photolithography technique. The FEWD was measured under positive and negative bending conditions, with the applied voltage increasing from 0 to 24 V. The aperture ratio and response time were investigated to better evaluate and understand the performance of the FEWD. The mechanical properties of the support pillars and the FEWD were evaluated by means of compression force and cyclic bending tests, respectively. The results showed that the FEWD operated properly at 24 V under a bending curvature of 0.25 cm-1, achieving the largest aperture ratio of 54.96%. Moreover, the oil movement could be influenced by the support pillars in the pixel. With the advantages of both optical performance and flexibility, an FEWD with support pillars is a novel item for future development of reflective transparent displays and provides a promising strategy for developing flexible, wearable, and visible devices.

Transcriptomic responses of the marine cyanobacterium Prochlorococcus to viral lysis products.

Viral infection of marine phytoplankton releases a variety of dissolved organic matter (DOM). The impact of viral DOM (vDOM) on the uninfected co-occurring phytoplankton remains largely unknown. Here, we conducted transcriptomic analyses to study the effects of vDOM on the cyanobacterium Prochlorococcus, which is the most abundant photosynthetic organism on Earth. Using Prochlorococcus MIT9313, we showed that its growth was not affected by vDOM, but many tRNAs increased in abundance. We tested tRNA-gly and found that its abundance increased upon addition of glycine. The decreased transcript abundances of N metabolism genes also suggested that Prochlorococcus responded to organic N compounds in vDOM. Addition of vDOM to Prochlorococcus reduced the maximum photochemical efficiency of photosystem II and CO2 fixation while increasing its respiration rate, consistent with differentially abundant transcripts related to photosynthesis and respiration. One of the highest positive fold-changes was observed for the 6S RNA, a noncoding RNA functioning as a global transcriptional regulator in bacteria. The high level of 6S RNA might be responsible for some of the observed transcriptional responses. Taken together, our results revealed the transcriptional regulation of Prochlorococcus in response to viral lysis products and suggested its metabolic potential to utilize organic N compounds.

F-CphI represents a new homing endonuclease family using the Endo VII catalytic motif.

BACKGROUND: There are six known families of homing endonucleases, LAGLIDADG, GIY-YIG, HNH, His-Cys box, PD-(D/E)-XK, and EDxHD, which are characterized by their conserved residues. Previously, we discovered a novel homing endonuclease F-CphI encoded by ORF177 of cyanophage S-PM2. F-CphI does not resemble any characterized homing endonucleases. Instead, the C-terminus of F-CphI aligns well with the N-terminal catalytic domain of a Holliday junction DNA resolvase, phage T4 endonuclease VII (Endo VII). RESULTS: A PSI-BLAST search resulted in a total of 313 Endo VII motif-containing sequences in sequenced genomes. Multiple sequence alignment showed that the catalytically important residues of T4 Endo VII were all well conserved in these proteins. Our site-directed mutagenesis studies further confirmed that the catalytically important residues of T4 Endo VII were also essential for F-CphI activity, and thus F-CphI might use a similar protein fold as Endo VII for DNA cleavage. A phylogenetic tree of the Endo VII motif-containing sequences showed that putative resolvases grouped into one clade while putative homing endonucleases and restriction endonucleases grouped into another clade. CONCLUSIONS: Based on the unique conserved residues, we proposed that F-CphI represents a new homing endonuclease family, which was named the DHHRN family. Our phylogenetic analysis could be used to predict the functions of many previously unknown proteins.

Picocyanobacteria and deep-ocean fluorescent dissolved organic matter share similar optical properties.

Marine chromophoric dissolved organic matter (CDOM) and its related fluorescent components (FDOM), which are widely distributed but highly photobleached in the surface ocean, are critical in regulating light attenuation in the ocean. However, the origins of marine FDOM are still under investigation. Here we show that cultured picocyanobacteria, Synechococcus and Prochlorococcus, release FDOM that closely match the typical fluorescent signals found in oceanic environments. Picocyanobacterial FDOM also shows comparable apparent fluorescent quantum yields and undergoes similar photo-degradation behaviour when compared with deep-ocean FDOM, further strengthening the similarity between them. Ultrahigh-resolution mass spectrometry (MS) and nuclear magnetic resonance spectroscopy reveal abundant nitrogen-containing compounds in Synechococcus DOM, which may originate from degradation products of the fluorescent phycobilin pigments. Given the importance of picocyanobacteria in the global carbon cycle, our results indicate that picocyanobacteria are likely to be important sources of marine autochthonous FDOM, which may accumulate in the deep ocean.

Preliminary experimental investigation of an X-band Cerenkov-type high power microwave oscillator without guiding magnetic field.

Among high power microwave (HPM) generators without guiding magnetic field, Cerenkov-type oscillator is expected to achieve a relatively high efficiency, which has already been realized in X-band in our previous simulation work. This paper presents the preliminary experimental investigations into an X-band Cerenkov-type HPM oscillator without guiding magnetic field. Based on the previous simulation structure, some modifications regarding diode structure were made. Different cathode structures and materials were tested in the experiments. By using a ring-shaped graphite cathode, microwave of about one hundred megawatt level was generated with a pure center frequency of 9.14 GHz, and an efficiency of about 1.3%. As analyzed in the paper, some practical issues reduce the efficiency in experiments, such as real features of the electron beam, probable breakdown regions on the cathode surface which can damage the diode, and so forth.

Development of EST-SSR markers in Barringtonia racemosa (Lecythidaceae) and cross-amplification in related species.

PREMISE OF THE STUDY: Microsatellite markers were identified and characterized to study the genetic diversity and structure of Barringtonia racemosa (Lecythidaceae). METHODS AND RESULTS: Based on the transcriptome data of B. racemosa, 30 primer pairs were initially designed and tested, of which 15 were successfully amplified and displayed clear polymorphisms across the 43 individuals from three distant populations tested in the study. The results showed that the number of alleles per locus ranged from two to seven and the expected heterozygosity and observed heterozygosity per locus varied from 0 to 0.772 and from 0 to 0.933, respectively. CONCLUSIONS: The expressed sequence tag-simple sequence repeat (EST-SSR) markers described here will be useful for studying genetic diversity and structure of B. racemosa. Furthermore, all loci were successfully cross-amplified in B. asiatica and B. acutangula and will be of great value for genetic studies across this genus.

Development and characterization of EST-SSR markers in the invasive weed Mikania micrantha (Asteraceae).

PREMISE OF THE STUDY: Microsatellite markers were developed for the invasive species Mikania micrantha to investigate its invasion history. Transcriptome sequencing projects offer a potential source for the development of new markers. METHODS AND RESULTS: Sixteen polymorphic simple sequence repeat (SSR) markers derived from ESTs were identified and screened in 36 samples of M. micrantha. The number of alleles per locus ranged from two to four, with an average of 2.7 alleles per locus. The expected heterozygosity and observed heterozygosity ranged from 0 to 0.7754 and 0 to 0.8333, respectively. CONCLUSIONS: These EST-SSR markers may be useful for further investigation of the population genetics of M. micrantha as additional tools to trace its invasion history.