Glycol-Split Heparin-Linked Prodrug Nanoparticles Target the Mitochondrion Apparatus for Cancer Metastasis Treatment.

The progression and metastasis of solid tumors rely strongly on neovascularization. However, angiogenesis inhibitors alone cannot meet the needs of tumor therapy. This study prepared a new drug conjugate (PTX-GSHP-CYS-ES2, PGCE) by combining polysaccharides (heparin without anticoagulant activity, GSHP), chemotherapeutic drugs (paclitaxel, PTX), and antiangiogenic drugs (ES2). Furthermore, a tumor-targeted prodrug nanoparticle delivery system is established. The nanoparticles appear to accumulate in the mitochondrial of tumor cells and achieve ES2 and PTX release under high glutathione and acidic environment. It has been confirmed that PGCE inhibited the expression of multiple metastasis-related proteins by targeting the tumor cell mitochondrial apparatus and disrupting their structure. Furthermore, PGCE nanoparticles inhibit migration, invasion, and angiogenesis in B16F10 tumor-bearing mice and suppress tumor growth and metastasis in vitro. Further in vitro and in vivo experiments show that PGCE has strong antitumor growth and metastatic effects and exhibits efficient anti-angiogenesis properties. This multi-targeted nanoparticle system potentially enhances the antitumor and anti-metastatic effects of combination chemotherapy and antiangiogenic drugs.

Semidiscrete optical vortex droplets in quasi-phase-matched photonic crystals.

What we believe is a new scheme for producing semidiscrete self-trapped vortices ("swirling photon droplets") in photonic crystals with competing quadratic (χ(2)) and self-defocusing cubic (χ(3)) nonlinearities is proposed. The photonic crystal is designed with a striped structure, in the form of spatially periodic modulation of the χ(2) susceptibility, which is imposed by the quasi-phase-matching technique. Unlike previous realizations of semidiscrete optical modes in composite media, built as combinations of continuous and arrayed discrete waveguides, the semidiscrete vortex "droplets" are produced here in the fully continuous medium. This work reveals that the system supports two types of semidiscrete vortex droplets, viz., onsite- and intersite-centered ones, which feature, respectively, odd and even numbers of stripes, N. Stability areas for the states with different values of N are identified in the system's parameter space. Some stability areas overlap with each other, giving rise to the multistability of states with different N. The coexisting states are mutually degenerate, featuring equal values of the Hamiltonian and propagation constant. An experimental scheme to realize the droplets is outlined, suggesting new possibilities for the long-distance transmission of nontrivial vortex beams in nonlinear media.

Vortex Solitons in Quasi-Phase-Matched Photonic Crystals.

We report solutions for stable compound solitons in a three-dimensional quasi-phase-matched photonic crystal with the quadratic (χ^{(2)}) nonlinearity. The photonic crystal is introduced with a checkerboard structure, which can be realized by means of the available technology. The solitons are built as four-peak vortex modes of two types, rhombuses and squares (intersite- and onsite-centered self-trapped states, respectively). Their stability areas are identified in the system's parametric space (rhombuses occupy an essentially broader stability domain), while all bright vortex solitons are subject to strong azimuthal instability in uniform χ^{(2)} media. Possibilities for experimental realization of the solitons are outlined.

Bifidobacterium lactis Probio-M8 improves bone metabolism in patients with postmenopausal osteoporosis, possibly by modulating the gut microbiota.

PURPOSE: Postmenopausal osteoporosis (PMO) is usually managed by conventional drug treatment. However, prolonged use of these drugs cause side effects. Gut microbiota may be a potential target for treatment of PMO. This work was a three-month intervention trial aiming to evaluate the added effect of probiotics as adjunctive treatment for PMO. METHODS: Forty patients with PMO were randomized into probiotic (n = 20; received Bifidobacterium animalis subsp. lactis Probio-M8 [Probio-M8], calcium, calcitriol) and placebo (n = 20; received placebo material, calcium, calcitriol) groups. The bone mineral density of patients was measured at month 0 (0 M; baseline) and month 3 (3 M; after three-month intervention). Blood and fecal samples were collected 0 M and 3 M. Only 15 and 12 patients from Probio-M8 and placebo groups, respectively, provided complete fecal samples for gut microbiota analysis. RESULTS: No significant change was observed in the bone mineral density of patients at 3 M. Co-administering Probio-M8 improved the bone metabolism, reflected by an increased vitamin D3 level and decreased PTH and procalcitonin levels in serum at 3 M. Fecal metagenomic analysis revealed modest changes in the gut microbiome in both groups at 3 M. Interestingly, Probio-M8 co-administration affected the gut microbial interactive correlation network, particularly the short-chain fatty acid-producing bacteria. Probio-M8 co-administration significantly increased genes encoding some carbohydrate metabolism pathways (including ABC transporters, the phosphotransferase system, and fructose and mannose metabolism) and a choline-phosphate cytidylyltransferase. CONCLUSIONS: Co-administering Probio-M8 with conventional drugs/supplements was more efficacious than conventional drugs/supplements alone in managing PMO. Our study shed insights into the beneficial mechanism of probiotic adjunctive treatment. REGISTRATION NUMBER OF CLINICAL TRIAL: Chinese Clinical Trial Registry (identifier number: ChiCTR1800019268).

LINC02190 inhibits the embryo-endometrial attachment by decreasing ITGAD expression.

Recurrent implantation failure (RIF) is a challenge in the field of reproductive medicine, but mechanisms for its occurrence remain still unclear. Long non-coding RNAs (lncRNAs) have been found to play a vital role in many different diseases. In recent years, the differentially expressed lncRNAs have been reported in endometrial tissues. Here, we profiled dysregulated lncRNAs and mRNAs in the endometrial tissues of RIF patients and performed correlation analysis. We found that LINC02190 was upregulated in RIF endometrium and was bound to the integrin αD (ITGAD) mRNA promoter. Immunofluorescence assays were used to detect the location of ITGAD in the Ishikawa cell line and patients' endometrial biopsies. Overexpressed LINC02190 could decrease the expression of ITGAD and the adhesion rate of Ishikawa and JAR cells. Knockdown of the expression of LINC02190 significantly increased the ITGAD level, as well as the adhesion rate of Ishikawa and JAR cells. Furthermore, we demonstrated that the 150-250 bps of LINC02190 were the cis-elements involved in the regulation of ITGAD promoter activities. In conclusion, the results demonstrated that LINC02190 plays an important role in the occurrence of RIF, and the molecular mechanism may be associated with the embryo-endometrial attachment mediated by ITGAD. This study emphasizes the importance of lncRNAs in the occurrence of RIF and provides a potential new biomarker for diagnosis and therapies.

Gut Bifidobacterium responses to probiotic Lactobacillus casei Zhang administration vary between subjects from different geographic regions.

Bifidobacteria are health-promoting human gut inhabitants, but accurate species-level composition of the gut bifidobacteria and their responses to probiotic intervention have not been fully explored. This was a follow-up work of our previous study, in which 104 volunteers from six different Asiatic regions (Singapore, Indonesia, Xinjiang, Gansu, Inner Mongolia, Mongolia) were recruited. The gut microbiota and their responses towards Lactobacillus casei Zhang (LCZ) intervention were characterized (at days 0, 7, and 14; 14 days after stopping probiotic intake), and region-based differential responses were observed after LCZ intervention. This study further investigated changes in the species-level gut bifidobacteria by PacBio small-molecule real-time sequencing (SMRT) using bifidobacteria-specific primers. Firstly, this study found that Bifidobacterium adolescentis (42.58%) and Bifidobacterium breve (26.34%) were the core species across the six Asiatic regions. Secondly, principal coordinate analysis of probiotic-induced changes in the gut bifidobacterial microbiota (represented by weighted UniFrac distances) grouped the six regions into two clusters, namely northern (Xinjiang, Gansu, Inner Mongolia, and Mongolia) and southern (Singapore, Indonesia) regions. Thirdly, LCZ intervention induced region-based differential responses of gut bifidobacterial microbiota. The relative abundance of Bifidobacterium animalis in subjects from northern but not southern region substantially increased after LCZ intervention. Moreover, LCZ intervention significantly increased the weighted UniFrac distances in the southern but not northern subjects 7 days after LCZ intervention. The gut B. adolescentis correlated significantly and negatively with the weighted UniFrac distances of the baseline gut bifidobacterial microbiota in subjects of northern but not southern region, suggesting a possible homeostatic effect of LCZ on the gut bifidobacterial population of northern but not southern subjects. Collectively, our study found that probiotic-induced responses of the gut bifidobacterial microbiota varied with subjects' geographic origins, and B. adolescentis might play a role in maintaining the overall stability of the gut bifidobacterial population. KEY POINTS: • The core species in the six Asiatic regions are Bifidobacterium adolescentis and Bifidobacterium breve. • The gut bifidobacterial microbiota in people from various geographic origins showed different responses on probiotic administration.

Geometric phase with full-wedge and half-wedge rotation in nonlinear frequency conversion.

When the quasi-phase matching (QPM) parameters of the χ(2) nonlinear crystal rotate along a closed path, geometric phase will be generated in the signal and idler waves that participate in the nonlinear frequency conversion. In this paper, we study two rotation schemes, full-wedge rotation and half-wedge rotation, of the QPM parameters in the process of fully nonlinear three-wave mixing. These two schemes can effectively suppress the uncertainty in creating the geometric phase in the nonlinear frequency conversion process when the intensity of the pump is depleted. The finding of this paper provides an avenue toward constant control of the geometric phase in nonlinear optics applications and quantum information processing.

Adjunctive treatment with probiotics partially alleviates symptoms and reduces inflammation in patients with irritable bowel syndrome.

PURPOSE: Irritable bowel syndrome (IBS) is a functional bowel disorder. This study aimed to assess the effect of a probiotic product (containing Lactobacillus casei Zhang, Lactobacillus plantarum P-8, and Bifdobacterium animalis subsp. lactis V9) as an adjunct to a routine regimen in IBS management. METHODS: Forty-five patients with IBS were randomized into the probiotic (n = 24) and control (n = 21) groups, receiving the routine regimen with or without probiotics for 28 days, respectively. Serum and fecal samples were collected and analyzed. RESULTS: The IBS-symptom severity score (P < 0.01), serum levels of IL-6 (P < 0.01) and TNF-α (P < 0.001) were significantly lower in the probiotic group than the control group at day 28. The probiotic adjunctive treatment resulted in significant decreases in some bacterial genera that worsen IBS, such as Bacteroides (P < 0.01), Escherichia (P < 0.05), and Citrobacter (P < 0.05), significant decreases were also observed in some beneficial genera in the control group, including Bifidobacterium (P < 0.05), Eubacterium (P < 0.05), Dorea (P < 0.01), and Butyricicoccus (P < 0.05). Furthermore, significant correlations were found between some monitored parameters and compositional changes in the fecal microbiota, suggesting that the clinical improvement of IBS was likely associated with gut microbiota modulation. The enterotype analysis revealed that the initial fecal microbiota composition could influence clinical outcomes. CONCLUSIONS: The adjunctive use of probiotics with a routine regimen showed additional clinical effectiveness compared to the routine regimen alone in managing IBS. A pretreatment gut microbiome analysis might help tailor a personalized probiotic regimen to optimize treatment effects.

Both sampling seasonality and geographic origin contribute significantly to variations in raw milk microbiota, but sampling seasonality is the more determining factor.

Accurately profiling and characterizing factors shaping raw milk microbiota would provide practical information for detecting microbial contamination and unusual changes in milk. The current work was an observational study aiming to profile the microbiota of raw milk collected across wide geographic regions in China in different seasons and to investigate the contribution of geographical, seasonal, and environmental factors in shaping the raw milk microbiota. A total of 355 raw cow milk samples from healthy Holsteins and 41 environmental samples (farm soil and surface of milking room floor) were collected from 5 dairy farms in 5 Chinese provinces (namely, Daqing in Heilongjiang province, Jiaozuo in Henan province, Qingyuan in Guangdong province, Suqian in Jiangsu province, and Yinchuan in Ningxia Hui Autonomous Region) in January, May, and September 2018. The microbial communities in raw milk and farm environmental samples were determined using the PacBio small-molecule real-time circular consensus sequencing, which generated high-fidelity microbiota profiles based on full-length 16S rRNA genes; such technology was advantageous in producing accurate species-level information. Our results showed that both seasonality and sampling region were significant factors influencing the milk microbiota; however, the raw milk microbiota was highly diverse according to seasonality, and sampling region was the less determining factor. The wide variation in raw milk microbial communities between samples made it difficult to define a representative species-level core milk microbiota. Nevertheless, 3 most universal milk-associated species were identified: Lactococcus lactis, Enhydrobacter aerosaccus, and Acinetobacter lwoffii, which were consistently detected in 99%, 95%, and 94% of all analyzed milk samples, respectively (n = 355). The top taxa accounting for the overall seasonal microbiota variation were Bacillus (Bacillus cereus, Bacillus flexus, Bacillus safensis), Lactococcus (Lactococcus lactis, Lactococcus piscium, Lactococcus raffinolactis), Lactobacillus (Lactobacillus helveticus, Lactobacillus delbrueckii), Lactiplantibacillus plantarum, Streptococcus agalactiae, Enhydrobacter aerosaccus, Pseudomonas fragi, and Psychrobacter cibarius. Unlike the milk microbiota, the environmental microbiota did not exhibit obvious pattern of seasonal or geographic variation. However, this study was limited by the relatively low number and types of environmental samples, making it statistically not meaningful to perform further correlation analysis between the milk and environmental microbiota. Nevertheless, this study generated novel information on raw milk microbiota across wide geographic regions of China and found that seasonality was more significant in shaping the raw milk microbiota compared with geographic origin.

Changes in physico-chemical characteristics and viable bacterial communities during fermentation of alfalfa silages inoculated with Lactobacillus plantarum.

This study investigated the effect of inoculating Lactobacillus (L.) plantarum PS-8 in fermentation of alfalfa silages. We monitored the fermentation characteristics and bacterial population dynamics during the ensiling process. PacBio single molecule real time sequencing was combined with propidium monoazide (PMA) treatment to monitor the viable microbiota dynamics. We found that inoculating L. plantarum PS-8 may improve the silage quality by accelerating acidification, reducing the amounts of clostridia, coliform bacteria, molds and yeasts, elevating the protein and organic acid contents (except butyrate), and enhancing lactic acid bacteria (LAB) while suppressing harmful microorganisms. Some significant differential abundant taxa were found between the PMA-treated and non-treated microbiota. For example, the relative abundances of L. brevis, L. plantarum, and Pediococcus pentosaceus were significantly higher in the PMA-treated group than the non-PMA-treated group, suggesting obvious differences between the viable and non-viable microbiota. It would thus be necessary to distinguish between the viable and non-viable microbial communities to further understand their physiological contribution in silage fermentation. By tracking the dynamics of viable microbiota in relation with changes in the physico-chemical parameters, our study provided novel insights into the beneficial effects of inoculating L. plantarum PS-8 in silage fermentation and the physiological function of the viable bacterial communities.

De novo transcriptome assembly for the five major organs of Zanthoxylum armatum and the identification of genes involved in terpenoid compound and fatty acid metabolism.

BACKGROUND: Zanthoxylum armatum (Z. armatum) is a highly economically important tree that presents a special numbing taste. However, the underlying regulatory mechanism of the numbing taste remains poorly understood. Thus, the elucidation of the key genes associated with numbing taste biosynthesis pathways is critical for providing genetic information on Z. armatumand the breeding of high-quality germplasms of this species. RESULTS: Here, de novo transcriptome assembly was performed for the five major organs of Z. armatum, including the roots, stems, leaf buds, mature leaves and fruits. A total of 111,318 unigenes were generated with an average length of 1014 bp. Additionally, a large number of SSRs were obtained to improve our understanding of the phylogeny and genetics of Z. armatum. The organ-specific unigenes of the five major samples were screened and annotated via GO and KEGG enrichment analysis. A total of 53 and 34 unigenes that were exclusively upregulated in fruit samples were identified as candidate unigenes for terpenoid biosynthesis or fatty acid biosynthesis, elongation and degradation pathways, respectively. Moreover, 40 days after fertilization (Fr4 stage) could be an important period for the accumulation of terpenoid compounds during the fruit development and maturation of Z. armatum. The Fr4 stage could be a key point at which the first few steps of the fatty acid biosynthesis process are promoted, and the catalysis of subsequent reactions could be significantly induced at 62 days after fertilization (Fr6 stage). CONCLUSIONS: The present study realized de novo transcriptome assembly for the five major organs of Z. armatum. To the best of our knowledge, this study provides the first comprehensive analysis revealing the genes underlying the special numbing taste of Z. armatum. The assembled transcriptome profiles expand the available genetic information on this species and will contribute to gene functional studies, which will aid in the engineering of high-quality cultivars of Z. armatum.

PacBio sequencing reveals bacterial community diversity in cheeses collected from different regions.

Cheese is a fermented dairy product that is popular for its unique flavor and nutritional value. Recent studies have shown that microorganisms in cheese play an important role in the fermentation process and determine the quality of the cheese. We collected 12 cheese samples from different regions and studied the composition of their bacterial communities using PacBio small-molecule real-time sequencing (Pacific Biosciences, Menlo Park, CA). Our data revealed 144 bacterial genera (including Lactobacillus, Streptococcus, Lactococcus, and Staphylococcus) and 217 bacterial species (including Lactococcus lactis, Streptococcus thermophilus, Staphylococcus equorum, and Streptococcus uberis). We investigated the flavor quality of the cheese samples using an electronic nose system and we found differences in flavor-quality indices among samples from different regions. We found a clustering tendency based on flavor quality using principal component analysis. We found correlations between lactic acid bacteria and the flavor quality of the cheese samples. Biodegradation and metabolism of xenobiotics, and lipid-metabolism-related pathways, were predicted to contribute to differences in cheese flavor using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). This preliminary study explored the bacterial communities in cheeses collected from different regions and their potential genome functions from the perspective of flavor quality.

Excessive activation of NMDA receptor inhibits the protective effect of endogenous bone marrow mesenchymal stem cells on promoting alveolarization in bronchopulmonary dysplasia.

We studied the role of bone marrow mesenchymal stem cells (MSCs) in our established model of bronchopulmonary dysplasia (BPD) induced by intrauterine hypoxia in the rat. First, we found that intrauterine hypoxia can reduce the number of MSCs in lungs and bone marrow of rat neonates, whereas the administration of granulocyte colony-stimulating factor or busulfan to either motivate or inhibit bone marrow MSCs to lungs altered lung development. Next, in vivo experiments, we confirmed that intrauterine hypoxia also impaired bone marrow MSC proliferation and decreased cell cycling activity. In vitro, by using the cultured bone marrow MSCs, the proliferation and the cell cycling activity of MSCs were also reduced when N-methyl-d-aspartic acid (NMDA) was used as an NMDA receptor (NMDAR) agonist. When MK-801 or memantine as NMDAR antagonists in vitro or in vivo was used, the reduction of cell cycling activity and proliferation were partially reversed. Furthermore, we found that intrauterine hypoxia could enhance the concentration of glutamate, an amino acid that can activate NMDAR, in the bone marrow of neonates. Finally, we confirmed that the increased concentration of TNF-ɑ in the bone marrow of neonatal rats after intrauterine hypoxia induced the release of glutamate and reduced the cell cycling activity of MSCs, and the latter could be partially reversed by MK-801. In summary, intrauterine hypoxia could decrease the number of bone marrow MSCs that could affect lung development and lung function through excessive activation of NMDAR that is partially caused by TNF-ɑ.

NMDA receptor activation inhibits the antifibrotic effect of BM-MSCs on bleomycin-induced pulmonary fibrosis.

Endogenous glutamate (Glu) release and N-methyl-d-aspartate (NMDA) receptor (NMDAR) activation are associated with lung injury in different animal models. However, the underlying mechanism is unclear. Bone marrow-derived mesenchymal stem cells (BM-MSCs), which show potential use for immunomodulation and tissue protection, play a protective role in pulmonary fibrosis (PF) process. Here, we found the increased Glu release from the BM cells of bleomycin (BLM)-induced PF mice in vivo. BLM stimulation also increased the extracellular Glu in BM-MSCs via the antiporter system xc- in vitro. The gene expression of each subunit of NMDAR was detected in BM-MSCs. NMDAR activation inhibited the proliferation, migration, and paracrine function of BM-MSCs in vitro. BM-MSCs were derived from male C57BL/6 mice, transfected with lentiviral vectors carrying the enhanced green fluorescence protein gene, pretreated with NMDA, and transplanted into the female recipient mice that were intratracheally injected with BLM to induce PF. Transplantation of NMDA-pretreated BM-MSCs significantly aggravated PF as compared with that in the normal BM-MSCs transplantation group. The sex determination gene Y chromosome and green fluorescence protein genes of BM-MSCs were detected to observe BM-MSCs homing in the fibrotic lungs. Moreover, NMDAR activation inhibited BM-MSC migration by downregulating the stromal cell-derived factor-1/C-X-C chemokine receptor type 4 signaling axis. NMDAR activation aggravated the transforming growth factor-ß1-induced extracellular matrix production in alveolar epithelial cells and fibroblasts through the paracrine effects of BM-MSCs. In summary, these findings suggested that NMDAR activation-mediated Glu excitotoxicity induced by BLM in BM-MSCs abolished the therapeutic effects of normal BM-MSCs transplantation on BLM-induced PF.

Analysis of the Gut Microbial Diversity of Dairy Cows During Peak Lactation by PacBio Single-Molecule Real-Time (SMRT) Sequencing.

BACKGROUND: The gut microbes of dairy cows are strongly associated with their health, but the relationship between milk production and the intestinal microbiota has seldom been studied. Thus, we explored the diversity of the intestinal microbiota during peak lactation of dairy cows. METHODS: The intestinal microbiota of nine dairy cows at peak lactation was evaluated using the Pacific Biosciences single-molecule real-time (PacBio SMRT) sequencing approach. RESULTS: A total of 32,670 high-quality 16S rRNA gene sequences were obtained, belonging to 12 phyla, 59 families, 107 genera, and 162 species. Firmicutes (83%) were the dominant phylum, while Bacteroides (6.16%) was the dominant genus. All samples showed a high microbial diversity, with numerous genera of short chain fatty acid (SCFA)-producers. The proportion of SCFA producers was relatively high in relation to the identified core intestinal microbiota. Moreover, the predicted functional metagenome was heavily involved in energy metabolism. CONCLUSIONS: This study provided novel insights into the link between the dairy cow gut microbiota and milk production.

[LIMR is involved in the inhibitory effect of antiflammin-1 on epithelial-mesenchymal transition in A549 cells].

Epithelial-mesenchymal transition (EMT) occurring in alveolar epithelial cells plays an important role in the development and progression of pulmonary fibrosis. Previous studies showed that antiflammin-1 (the active fragment of uteroglobin) effectively inhibited bleomycin-induced pulmonary fibrosis. However, its mechanism is still far from being clarified. In this study, we investigated the effects of antiflammin-1 on EMT in A549 cells induced by transforming growth factor-ß1 (TGF-ß1) and the underlying mechanism by using morphological observation and Western blot. The results showed that the expression of α-smooth muscle actin (α-SMA) increased significantly while the expression of E-cadherin decreased significantly in A549 cells following treatment with TGF-ß1 concomitant with morphological change of A549 cells from pebble-like shape epithelial cells to spindle-like mesenchymal shape. This process of EMT in A549 cells induced by TGF-ß1 was significantly inhibited when A549 cells were co-incubated with TGF-ß1 and antiflammin-1. Furthermore, the anti-lipocalin interacting membrane receptor (LIMR) antibody and PD98059 (an ERK signaling pathway blocker) attenuated the inhibitory effect of antiflammin-1 on TGF-ß1-induced EMT, respectively. Our findings indicate that antiflammin-1 can inhibit EMT in A549 cells induced by TGF-ß1, which is related to LIMR and its downstream ERK signaling pathway.

Comparative profiling of hepatopancreas transcriptomes in satiated and starving Pomacea canaliculata.

BACKGROUND: Although Pomacea canaliculata is native to South and Central America, it has become one of the most abundant invasive species worldwide and causes extensive damage to agriculture and horticulture. Conventional physical and chemical techniques have been used to eliminate P. canaliculata, but the effects are not ideal. Therefore, it is important to devise a new method based on a greater understanding of the biology of P. canaliculata. However, the molecular mechanisms underlying digestion and absorption in P. canaliculata are not well understood due to the lack of available genomic information for this species, particularly for digestive enzyme genes. RESULTS: In the present study, hepatopancreas transcriptome sequencing produced over 223 million high-quality reads, and a global de novo assembly generated a total of 87,766 unique transcripts (unigenes), of which 19,942 (22.7%) had significant similarities to proteins in the UniProt database. In addition, 296,675 annotated sequences were associated with Gene Ontology (GO) terms. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was performed for the unique unigenes, and 262 pathways (p-value < 10-5) in P. canaliculata were found to be predominantly related to plant consumption and coarse fiber digestion and absorption. These transcripts were classified into four large categories: hydrolase, transferase, isomerase and cytochrome P450. The Reads Per Kilobase of transcript per Million mapped reads (RPKM) analysis showed that there were 523 down-regulated unigenes and 406 up-regulated unigenes in the starving apple snails compared with the satiated apple snails. Several important genes are associated with digestion and absorption in plants: endo-beta-1, 4-glucanase, xylanase, cellulase, cellulase EGX1, cellulase EGX3 and G-type lysozyme genes were identified. The qRT-PCR results confirmed that the expression patterns of these genes (except for the longipain gene) were consistent with the RNA-Seq results. CONCLUSIONS: Our results provide a more comprehensive understanding of the molecular genes associated with hepatopancreas functioning. Differentially expressed genes corresponding to critical metabolic pathways were detected in the transcriptome of starving apple snails compared with satiated apple snails. In addition to the cellulase gene, other genes were identified that may be important factors in plant matter metabolism in P. canaliculata, and this information has the potential to expedite the study of digestive physiology in apple snails.

Changes in soil bacterial community characteristics in patches of different vegetation types under different stages of restoration in the desert of northern China.

In desert areas, the process of mobile sandy land changing to semi-fixed sandy land and eventually to fixed sandy land after undergoing vegetation restoration is inevitable. The presence of shrub patches and herb patches is common in this restoration process. No relevant studies have reported the soil bacterial community characteristics of different vegetation-type patches (shrub patches and herb patches) under different stages of restoration. Therefore, we utilized long-established experimental plots to collect soil from 0-20 cm soil layer under shrub patches (dominated by Salix psammophila) and herb patches under different stages of restoration (i.e., mobile sand land, semi-fixed sand land, and fixed sand land), by determining soil physicochemical properties, enzyme activities, and soil bacterial communities. Our results found that soil bacterial α-diversity under different restoration stages showed higher shrub patches than herb patches. The dominant bacterial communities (phyla) in shrub patches and herb patches at different recovery stages were Actinobacteria, Proteobacteria, and Bacteroidota. When the mobile sandy land returned to fixed sandy land, the relative abundance of Actinobacteria and Bacteroidota gradually decreased under shrub patches and herb patches, while the relative abundance of Proteobacteria increased significantly. In addition, herb patches significantly increased the relative abundance of bacteria (genus) relative to shrub patches at different stages of recovery. Soil nutrients, soil fine particles, and soil enzyme activities were significantly higher under shrub patches than under herb patches when fixed sandy land due to differences in life form and architecture between shrub patches and herb patches. Based on this, soil bacterial community composition and diversity under shrub patches were driven by more soil properties during the restoration of sandy land. This study complements the dynamic recovery processes and driving mechanisms of soil bacterial community structure under different vegetation patches in sandy areas, especially in the context of global climate change.

Aberrantly High FBXO31 Impairs Oocyte Quality in Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI), which is defined as loss of ovarian function that occurs before the age of 40, causes menstrual disturbances, infertility, and diverse health problems in females. Despite the limited understanding of the molecular basis underlying POI pathology, we had previously demonstrated that the cooperation of miR-106a and FBXO31 plays a pivotal role in diminished ovarian reserve (DOR), with FBXO31 serving as a putative target of miR-106a. In this study, we found that FBXO31 is aberrantly expressed in granulosa cells of POI patients, leading to accumulated reactive oxygen species (ROS) and cell apoptosis via the p53/ROS pathway. Furthermore, our results demonstrated that high levels of FBXO31 in mouse ovaries impair oocyte quality. Our study revealed that FBXO31 may serve as a novel indicator and play a significant role in the etiology of POI.

Long-Term Tracking of the Effects of Colostrum-Derived Lacticaseibacillus rhamnosus Probio-M9 on Gut Microbiota in Mice with Colitis-Associated Tumorigenesis.

Intestinal bacteria play important roles in the progression of colitis-associated carcinogenesis. Colostrum-derived Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9) has shown a protective effect in a colitis-associated cancer (CAC) model, but detailed metagenomic analysis had not been performed. Here, we investigated the preventive effects of the probiotic Probio-M9 on CAC-model mice, tracking the microbiota. Feces were obtained at four time points for evaluation of gut microbiota. The effect of Probio-M9 on tight junction protein expression was evaluated in co-cultured Caco-2 cells. Probio-M9 treatment decreased the number of tumors as well as stool consistency score, spleen weight, inflammatory score, and macrophage expression in the CAC model. Probio-M9 accelerated the recovery of the structure, composition, and function of the intestinal microbiota destroyed by azoxymethane (AOM)/dextran sulfate sodium (DSS) by regulating key bacteria (including Lactobacillus murinus, Muribaculaceae bacterium DSM 103720, Muribaculum intestinale, and Lachnospiraceae bacterium A4) and pathways from immediately after administration until the end of the experiment. Probio-M9 co-culture protected against lipopolysaccharide-induced impairment of tight junctions in Caco-2 cells. This study provides valuable insight into the role of Probio-M9 in correcting gut microbiota defects associated with inflammatory bowel disease carcinogenesis and may have clinical application in the treatment of inflammatory carcinogenesis.