Interaction of the gut microbiota and brain functional connectivity in late-life depression.

BACKGROUND: Increasing evidence suggests an important role of the gut microbiome in the pathogenesis of mental disorders, including depression, along the microbiota-gut-brain axis. We sought to explore the interactions between gut microbe composition and neural circuits in late-life depression (LLD). METHODS: We performed fecal 16S ribosomal RNA (rRNA) sequencing and resting-state functional magnetic resonance imaging in a case-control cohort of older adults with LLD and healthy controls to characterize the association between gut microbiota and brain functional connectivity (FC). We used the Hamilton Depression Rating Scale (HAMD) to assess depressive symptoms. RESULTS: We included 32 adults with LLD and 16 healthy controls. At the genus level, the relative abundance of Enterobacter, Akkermansiaceae, Hemophilus, Burkholderia, and Rothia was significantly higher among patients with LDD than controls. Reduced FC within mood regulation circuits was mainly found in the frontal cortex (e.g., the right superior and inferior frontal gyrus, right lateral occipital cortex, left middle frontal gyrus, and left caudate) among patients with MDD. Group-characterized gut microbes among controls and patients showed opposite correlations with seed-based FC, which may account for the aberrant emotion regulation among patients with LDD. The abundance of Enterobacter (dominant genus among patients with LLD) was positively correlated with both HAMD scores (r = 0.49, p = 0.0004) and group-characterized FC (r = -0.37, p < 0.05), while Odoribacter (dominant genus among controls) was negatively correlated with both HAMD scores (r = -0.30, p = 0.04) and group-characterized FC. LIMITATIONS: The study's cross-sectional design and small sample size limit causal inferences; larger longitudinal studies are required for detailed subgroup analyses. CONCLUSION: We identified significant correlations between LDD-characterized gut microbes and brain FC, as well as depression severity, which may contribute to the pathophysiology of depression development among patients with LLD. Specific microbes were linked to altered brain connectivity, suggesting potential targets for treating LLD.

MetaSquare: an integrated metadatabase of 16S rRNA gene amplicon for microbiome taxonomic classification.

MOTIVATION: Taxonomic classification of 16S ribosomal RNA gene amplicon is an efficient and economic approach in microbiome analysis. 16S rRNA sequence databases like SILVA, RDP, EzBioCloud and HOMD used in downstream bioinformatic pipelines have limitations on either the sequence redundancy or the delay on new sequence recruitment. To improve the 16S rRNA gene-based taxonomic classification, we merged these widely used databases and a collection of novel sequences systemically into an integrated resource. RESULTS: MetaSquare version 1.0 is an integrated 16S rRNA sequence database. It is composed of more than 6 million sequences and improves taxonomic classification resolution on both long-read and short-read methods. AVAILABILITY AND IMPLEMENTATION: Accessible at https://hub.docker.com/r/lsbnb/metasquare_db and https://github.com/lsbnb/MetaSquare. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Enrichment of Prevotella intermedia in human colorectal cancer and its additive effects with Fusobacterium nucleatum on the malignant transformation of colorectal adenomas.

BACKGROUND: Owing to the heterogeneity of microbiota among individuals and populations, only Fusobacterium nucleatum and Bacteroides fragilis have been reported to be enriched in colorectal cancer (CRC) in multiple studies. Thus, the discovery of additional bacteria contributing to CRC development in various populations can be expected. We aimed to identify bacteria associated with the progression of colorectal adenoma to carcinoma and determine the contribution of these bacteria to malignant transformation in patients of Han Chinese origin. METHODS: Microbiota composition was determined through 16S rRNA V3-V4 amplicon sequencing of autologous adenocarcinomas, adenomatous polyps, and non-neoplastic colon tissue samples (referred to as "tri-part samples") in patients with CRC. Enriched taxa in adenocarcinoma tissues were identified through pairwise comparison. The abundance of candidate bacteria was quantified through genomic quantitative polymerase chain reaction (qPCR) in tissue samples from 116 patients. Associations of candidate bacteria with clinicopathological features and genomic and genetic alterations were evaluated through odds ratio tests. Additionally, the effects of candidate bacteria on CRC cell proliferation, migration, and invasion were evaluated through the co-culture of CRC cells with bacterial cells or with conditioned media from bacteria. RESULTS: Prevotella intermedia was overrepresented in adenocarcinomas compared with paired adenomatous polyps. Furthermore, co-abundance of P. intermedia and F. nucleatum was observed in tumor tissues. More notably, the coexistence of these two bacteria in adenocarcinomas was associated with lymph node involvement and distant metastasis. These two bacteria also exerted additive effects on the enhancement of the migration and invasion abilities of CRC cells. Finally, conditioned media from P. intermedia promoted the migration and invasion of CRC cells. CONCLUSION: This report is the first to demonstrate that P. intermedia is enriched in colorectal adenocarcinoma tissues and enhances the migration and invasion abilities of CRC cells. Moreover, P. intermedia and F. nucleatum exert additive effects on the malignant transformation of colorectal adenomas into carcinomas. These findings can be used to identify patients at a high risk of malignant transformation of colorectal adenomas or metastasis of CRC, and they can accordingly be provided optimal clinical management.

Decoding the genome of bloodsucking midge Forcipomyia taiwana (Diptera: Ceratopogonidae): Insights into odorant receptor expansion.

Biting midges, notably those within the Ceratopogonidae family, have long been recognized for their epidemiological significance, both as nuisances and vectors for disease transmission in vertebrates. Despite their impact, genomic insights into these insects, particularly beyond the Culicoides genus, remain limited. In this study, we assembled the Forcipomyia taiwana (Shiraki) genome, comprising 113 scaffolds covering 130.4 Mbps-with the longest scaffold reaching 7.6 Mbps and an N50 value of 2.6 Mbps-marking a pivotal advancement in understanding the genetic architecture of ceratopogonid biting midges. Phylogenomic analyses reveal a shared ancestry between F. taiwana and Culicoides sonorensis Wirth & Jones, dating back approximately 124 million years, and highlight a dynamic history of gene family expansions and contractions within the Ceratopogonidae family. Notably, a substantial expansion of the odorant receptor (OR) gene family was observed, which is crucial for the chemosensory capabilities that govern biting midges' interactions with their environment, including host seeking and oviposition behaviors. The distribution of OR genes across the F. taiwana genome displays notable clusters on scaffolds, indicating localized tandem gene duplication events. Additionally, several collinear regions were identified, hinting at segmental duplications, inversions, and translocations, contributing to the olfactory system's evolutionary complexity. Among the 156 ORs identified in F. taiwana, 134 are biting midge-specific ORs, distributed across three distinct clades, each exhibiting unique motif features that distinguish them from the others. Through weighted gene co-expression network analysis, we correlated distinct gene modules with sex and reproductive status, laying the groundwork for future investigations into the interplay between gene expression and adaptive behaviors in F. taiwana. In conclusion, our study not only highlights the unique olfactory repertoire of ceratopogonid biting midges but also sets the stage for future studies into the genetic underpinnings of their unique biological traits and ecological strategies.

Identification of Sexually Dimorphic Genes in Pectoral Fin as Molecular Markers for Assessing the Sex of Japanese Silver Eels (Anguilla japonica).

The Japanese eel (Anguilla japonica) is an important species in East Asian aquaculture. However, the production of seedlings for this purpose still depends on natural resources, as the commercial production of glass eels is not yet possible. Confusion about the sex of silver eels is one of the factors affecting the success rate of artificial maturation. This study sought to devise a harmless method to precisely assess the sex of silver eels. Partial pectoral fins were collected from females and males and the total RNA was extracted for transcriptomic analysis to identify sexually dimorphic genes as molecular markers for sex typing. An online database was constructed to integrate the annotations of transcripts and perform comparative transcriptome analysis. This analysis identified a total of 29 candidate sexually dimorphic genes. Ten were selected for a real-time quantitative polymerase chain reaction (RT-qPCR) to validate the transcriptomic data and evaluate their feasibility as markers. The transcriptomic analysis and RT-qPCR data implicated three potential markers (LOC111853410, kera, and dcn) in sex typing. The expression of LOC111853410 was higher in females than in males. In contrast, the expression of kera and dcn was higher in males than in females. The ΔCT values of three markers were analyzed to determine their inferred thresholds, which can be used to determine the sex of Japanese eels. The results suggested that if a silver eel had a pectoral fin with the pectoral fin having the ΔCT of LOC111853410 < 11.3, the ΔCT of kera > 11.4, or the ΔCT of dcn > 6.5 can be assessed it could be assessed as female. Males could be assessed by the ΔCT of LOC111853410 > 11.3, the ΔCT of kera < 11.4, or the ΔCT of dcn < 6.5 in their pectoral fins. The molecular functions of these markers and the biological significance of their differential expression require further exploration.

Differences in gut microbiota correlate with symptoms and regional brain volumes in patients with late-life depression.

Depression is associated with gut dysbiosis that disrupts a gut-brain bidirectional axis. Gray matter volume changes in cortical and subcortical structures, including prefrontal regions and the hippocampus, have also been noted in depressive disorders. However, the link between gut microbiota and brain structures in depressed patients remains elusive. Neuropsychiatric measures, stool samples, and structural brain images were collected from 36 patients with late-life depression (LLD) and 17 healthy controls. 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities for quantitation of microbial composition, abundance, and diversity. T1-weighted brain images were assessed with voxel-based morphometry to detect alterations in gray matter volume between groups. Correlation analysis was performed to identify the possible association between depressive symptoms, brain structures and gut microbiota. We found a significant difference in the gut microbial composition between patients with late-life depression (LLD) and healthy controls. The genera Enterobacter and Burkholderia were positively correlated with depressive symptoms and negatively correlated with brain structural signatures in regions associated with memory, somatosensory integration, and emotional processing/cognition/regulation. Our study purports the microbiota-gut-brain axis as a potential mechanism mediating the symptomatology of LLD patients, which may facilitate the development of therapeutic strategies targeting gut microbes in the treatment of elderly depressed patients.

Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer.

Studies have reported the effects of the gut microbiota on colorectal cancer (CRC) chemotherapy, but few studies have investigated the association between gut microbiota and targeted therapy. This study investigated the role of the gut microbiota in the treatment outcomes of patients with metastatic CRC (mCRC). We enrolled 110 patients with mCRC and treated them with standard cancer therapy. Stool samples were collected before administering a combination of chemotherapy and targeted therapy. Patients who had a progressive disease (PD) or partial response (PR) for at least 12 cycles of therapy were included in the study. We further divided these patients into anti-epidermal growth factor receptor (cetuximab) and anti-vascular endothelial growth factor (bevacizumab) subgroups. The gut microbiota of the PR group and bevacizumab-PR subgroup exhibited significantly higher α-diversity. The ß-diversity of bacterial species significantly differed between the bevacizumab-PR and bevacizumab-PD groups (P = 0.029). Klebsiella quasipneumoniae exhibited the greatest fold change in abundance in the PD group than in the PR group. Lactobacillus and Bifidobacterium species exhibited higher abundance in the PD group. The abundance of Fusobacterium nucleatum was approximately 32 times higher in the PD group than in the PR group. A higher gut microbiota diversity was associated with more favorable treatment outcomes in the patients with mCRC. Bacterial species analysis of stool samples yielded heterogenous results. K. quasipneumoniae exhibited the greatest fold change in abundance among all bacterial species in the PD group. This result warrants further investigation especially in a Taiwanese population.

A metagenomics study of hexabromocyclododecane degradation with a soil microbial community.

Hexabromocyclododecanes (HBCDs) are globally prevalent and persistent organic pollutants (POPs) listed by the Stockholm Convention in 2013. They have been detected in many environmental media from waterbodies to Plantae and even in the human body. Due to their highly bioaccumulative characterization, they pose an urgent public health issue. Here, we demonstrate that the indigenous microbial community in the agricultural soil in Taiwan could decompose HBCDs with no additional carbon source incentive. The degradation kinetics reached 0.173 day-1 after the first treatment and 0.104 day-1 after second exposure. With additional C-sources, the rate constants decreased to 0.054-0.097 day-1. The hydroxylic debromination metabolites and ring cleavage long-chain alkane metabolites were identified to support the potential metabolic pathways utilized by the soil microbial communities. The metagenome established by Nanopore sequencing showed significant compositional alteration in the soil microbial community after the HBCD treatment. After ranking, comparing relative abundances, and performing network analyses, several novel bacterial taxa were identified to contribute to HBCD biotransformation, including Herbaspirillum, Sphingomonas, Brevundimonas, Azospirillum, Caulobacter, and Microvirga, through halogenated / aromatic compound degradation, glutathione-S-transferase, and hydrolase activity. We present a compelling and applicable approach combining metagenomics research, degradation kinetics, and metabolomics strategies, which allowed us to decipher the natural attenuation and remediation mechanisms of HBCDs.

Galectin-1 orchestrates an inflammatory tumor-stroma crosstalk in hepatoma by enhancing TNFR1 protein stability and signaling in carcinoma-associated fibroblasts.

Most cases of hepatocellular carcinoma (HCC) arise with the fibrotic microenvironment where hepatic stellate cells (HSCs) and carcinoma-associated fibroblasts (CAFs) are critical components in HCC progression. Therefore, CAF normalization could be a feasible therapy for HCC. Galectin-1 (Gal-1), a ß-galactoside-binding lectin, is critical for HSC activation and liver fibrosis. However, few studies has evaluated the pathological role of Gal-1 in HCC stroma and its role in hepatic CAF is unclear. Here we showed that Gal-1 mainly expressed in HCC stroma, but not cancer cells. High expression of Gal-1 is correlated with CAF markers and poor prognoses of HCC patients. In co-culture systems, targeting Gal-1 in CAFs or HSCs, using small hairpin (sh)RNAs or an therapeutic inhibitor (LLS30), downregulated plasminogen activator inhibitor-2 (PAI-2) production which suppressed cancer stem-like cell properties and invasion ability of HCC in a paracrine manner. The Gal-1-targeting effect was mediated by increased a disintegrin and metalloprotease 17 (ADAM17)-dependent TNF-receptor 1 (TNFR1) shedding/cleavage which inhibited the TNF-α → JNK → c-Jun/ATF2 signaling axis of pro-inflammatory gene transcription. Silencing Gal-1 in CAFs inhibited CAF-augmented HCC progression and reprogrammed the CAF-mediated inflammatory responses in a co-injection xenograft model. Taken together, the findings uncover a crucial role of Gal-1 in CAFs that orchestrates an inflammatory CSC niche supporting HCC progression and demonstrate that targeting Gal-1 could be a potential therapy for fibrosis-related HCC.

A Yes-Associated Protein (YAP) and Insulin-Like Growth Factor 1 Receptor (IGF-1R) Signaling Loop Is Involved in Sorafenib Resistance in Hepatocellular Carcinoma.

The role of a YAP-IGF-1R signaling loop in HCC resistance to sorafenib remains unknown. METHOD: Sorafenib-resistant cells were generated by treating naïve cells (HepG2215 and Hep3B) with sorafenib. Different cancer cell lines from databases were analyzed through the ONCOMINE web server. BIOSTORM-LIHC patient tissues (46 nonresponders and 21 responders to sorafenib) were used to compare YAP mRNA levels. The HepG2215_R-derived xenograft in SCID mice was used as an in vivo model. HCC tissues from a patient with sorafenib failure were used to examine differences in YAP and IGF-R signaling. RESULTS: Positive associations exist among the levels of YAP, IGF-1R, and EMT markers in HCC tissues and the levels of these proteins increased with sorafenib failure, with a trend of tumor-margin distribution in vivo. Blocking YAP downregulated IGF-1R signaling-related proteins, while IGF-1/2 treatment enhanced the nuclear translocation of YAP in HCC cells through PI3K-mTOR regulation. The combination of YAP-specific inhibitor verteporfin (VP) and sorafenib effectively decreased cell viability in a synergistic manner, evidenced by the combination index (CI). CONCLUSION: A YAP-IGF-1R signaling loop may play a role in HCC sorafenib resistance and could provide novel potential targets for combination therapy with sorafenib to overcome drug resistance in HCC.

Electrically-Tunable Blue Phase Liquid Crystal Microlens Array Based on a Photoconductive Film.

This paper proposes an effective approach to fabricate a blue phase liquid crystal (BPLC) microlens array based on a photoconductive film. Owing to the characteristics of photo-induced conducting polymer polyvinylcarbazole (PVK), in which conductivity depends on the irradiation of UV light, a progressive mask resulting in the variation of conductivity is adopted to produce the gradient distribution of the electric field. The reorientations of liquid crystals according to the gradient distribution of the electric field induce the variation of the refractive index. Thus, the incident light experiences the gradient distribution of the refractive index and results in the focusing phenomenon. The study investigates the dependence of lens performance on UV exposure time, the focal length of the lens, and focusing intensities with various incident polarizations. The BPLC microlens array exhibits advantages such as electrically tunability, polarization independence, and fast response time.