Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid.

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate; however, the molecular mechanisms underpinning its pathogenesis are not well elucidated. Here, a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus (SGIV), focusing on the roles of key metabolites. Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver. Furthermore, SGIV significantly reduced the contents of lipid droplets, triglycerides, cholesterol, and lipoproteins. Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways, with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid (ALA), consistent with disturbed lipid homeostasis in the liver. Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide, carbohydrate, amino acid, and lipid metabolism, supporting the conclusion that SGIV infection induced liver metabolic reprogramming. Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade. Of note, integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid (LA) metabolites, and the accumulation of L-glutamic acid (GA), accompanied by alterations in immune, inflammation, and cell death-related genes. Further experimental data showed that ALA, but not GA, suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host. Collectively, these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

A Comprehensive Analysis of the Peanut SQUAMOSA Promoter Binding Protein-like Gene Family and How AhSPL5 Enhances Salt Tolerance in Transgenic Arabidopsis.

SPL (SQUAMOSA promoter binding protein-like), as one family of plant transcription factors, plays an important function in plant growth and development and in response to environmental stresses. Despite SPL gene families having been identified in various plant species, the understanding of this gene family in peanuts remains insufficient. In this study, thirty-eight genes (AhSPL1-AhSPL38) were identified and classified into seven groups based on a phylogenetic analysis. In addition, a thorough analysis indicated that the AhSPL genes experienced segmental duplications. The analysis of the gene structure and protein motif patterns revealed similarities in the structure of exons and introns, as well as the organization of the motifs within the same group, thereby providing additional support to the conclusions drawn from the phylogenetic analysis. The analysis of the regulatory elements and RNA-seq data suggested that the AhSPL genes might be widely involved in peanut growth and development, as well as in response to environmental stresses. Furthermore, the expression of some AhSPL genes, including AhSPL5, AhSPL16, AhSPL25, and AhSPL36, were induced by drought and salt stresses. Notably, the expression of the AhSPL genes might potentially be regulated by regulatory factors with distinct functionalities, such as transcription factors ERF, WRKY, MYB, and Dof, and microRNAs, like ahy-miR156. Notably, the overexpression of AhSPL5 can enhance salt tolerance in transgenic Arabidopsis by enhancing its ROS-scavenging capability and positively regulating the expression of stress-responsive genes. These results provide insight into the evolutionary origin of plant SPL genes and how they enhance plant tolerance to salt stress.

Hidden hotspots of amphibian biodiversity in China.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.

TGF-ß1-triggered BMI1 and SMAD2 cooperatively regulate miR-191 to modulate bone formation.

Transforming growth factor ß 1 (TGF-ß1), as the most abundant signaling molecule in bone matrix, is essential for bone homeostasis. However, the signaling transduction of TGF-ß1 in the bone-forming microenvironment remains unknown. Here, we showed that microRNA-191 (miR-191) was downregulated during osteogenesis and further decreased by osteo-favoring TGF-ß1 in bone marrow mesenchymal stem cells (BMSCs). MiR-191 was lower in bone tissues from children than in those from middle-aged individuals and it was negatively correlated with collagen type I alpha 1 chain (COL1A1). MiR-191 depletion significantly increased osteogenesis and bone formation in vivo. Hydrogels embedded with miR-191-low BMSCs displayed a powerful bone repair effect. Mechanistically, transcription factors BMI1 and SMAD2 coordinately controlled miR-191 level. In detail, BMI1 and pSMAD2 were both upregulated by TGF-ß1 under osteogenic condition. SMAD2 activated miR-191 transcription, while BMI1 competed with SMAD2 for binding to miR-191 promoter region, thus disturbing the activation of SMAD2 on miR-191 and reducing miR-191 level. Altogether, our findings reveal that miR-191 regulated by TGF-ß1-induced BMI1 and SMAD2 negatively modulated bone formation and regeneration, and inhibition of miR-191 might be therapeutically useful to enhance bone repair in clinic.

Efficient Cr(VI) removal by pyrite/porous biochar: Critical role of potassium salt and sulphur.

The excessive accumulation of hexavalent chromium (Cr(VI)) in the environment poses a risk to environment and human health. In the present study, a potassium bicarbonate-modified pyrite/porous biochar composite (PKBC) was prepared in a one-step process and applied for the efficient removal of Cr(VI) in wastewater. The results showed that PKBC can significantly remove Cr(VI) within 4 h over a wide range of pH (2-11). Meanwhile, the PKBC demonstrated remarkable resistance towards interference from complex ions. The addition of potassium bicarbonate increased the pore structure of the material and promoted the release of Fe2+. The reduction of Cr(VI) in aqueous solution was primarily attributed to the Fe(II)/Fe(III) redox cycle. The sulphur species achieved Fe(II)/Fe(III) cycle through electron transfer with iron, thus ensuring the continuous reduction capacity of PKBC. Besides, the removal rate was also maintained at more than 85% in the actual water samples treatment process. This work provides a new way to remove hexavalent chromium from wastewater and demonstrates the potential critical role of potassium bicarbonate and sulphur.

A novel approach involving reversed placement of endobronchial valves combined with retrograde methylene blue instillation for the localization of multifocal bronchopleural fistula.

The bronchopleural fistula (BPF) is a pathological communication between the bronchus and the pleural space. Diagnosing BPF poses a significant challenge for physicians, particularly when identifying multifocal BPFs. Traditionally, retrograde instillation of methylene blue (MB) into the pleural cavity with simultaneous observation with a bronchoscope has been used to locate a BPF. However, MB instillation is not effective in identifying multifocal BPFs. In this article, we report a new method for locating multifocal BPFs which involves placing the endobronchial valve (EBV) in reverse combined with retrograde MB instillation. First, the thoracic cavity is filled with MB solution. Then, using bronchoscopy, the location of a BPF can be identified as the MB solution flows into the bronchus. Secondly, an EBV is deployed in reverse in the bronchus where the identified BPF is located. Retrograde MB instillation is then repeated to locate any additional BPFs until no new ones are found. Two cases were reported using this novel method to identify multifocal BPFs, and each case was ultimately diagnosed with 2 BPFs. After precisely locating all the BPFs, the EBVs are then removed and placed forward in the target bronchi for treating the BPFs. During the follow-up period, no recurrence of BPFs was observed. We conclude that reversed placement of EBVs combined with retrograde MB instillation appears to be an effective approach for locating multifocal BPFs.

The complete mitochondrial genome of the Baishanzu horned toad Boulenophrys baishanzuensis (Anura: Megophryidae).

The mitochondrial genome (mitogenome) of Boulenophrys baishanzuensis (Anura: Megophryidae) was sequenced by the Illumina platform. The assembled circular mitogenome of B. baishanzuensis had a total length of 17,040 bp, with a GC content of 41.25%. It consisted of 13 protein-coding genes (PCGs), two rRNA genes, 22 tRNA genes, and a D-loop region. The majority of the PCGs were encoded by the H-strand, while one PCG (nad6) and eight tRNA genes (tRNA-Gln, tRNA-Ala, tRNA-Asn, tRNA-Cys, tRNA-Tyr, tRNA-Ser2, tRNA-Glu, and tRNA-Pro) were encoded in the L-strand. Phylogenetic analysis revealed that the newly sequenced species formed a clade with other Boulenophrys species, while the genus Boulenophrys itself formed a sister group with the genus Atympanophrys.

Stereodivergent Protein Engineering of Fatty Acid Photodecarboxylase for Light-Driven Kinetic Resolution of Sec-Alcohol Oxalates.

Stereodivergent engineering of one enzyme to create stereocomplementary variants for synthesizing optically pure molecules with tailor-made (R) or (S) configurations on an optional basis is highly desirable and challenging. This study aimed to engineer fatty acid photodecarboxylase from Chlorella variabilis (CvFAP) using the focused rational iterative site-specific mutagenesis (FRISM) strategy to obtain two highly stereocomplementary variants with excellent selectivity (both giving products with up to 99 % e.e.). These variants were used for the CvFAP-catalyzed light-driven kinetic resolution of oxalates or oxamic acids prepared from the corresponding sec-alcohols or amines, providing a new biotransformation process for preparing chiral sec-alcohols and amines. Molecular dynamics simulation, kinetic data and transient spectra revealed the source of selectivity. This study represents the first example of the kinetic resolution of sec-alcohols or amines catalyzed by a pair of stereocomplementary CvFAPs.

Global hidden spillover effects among concurrent green initiatives.

Concurrently implemented green initiatives to combat global environmental crises may be curtailed or even sacrificed given the ongoing global economic contraction. We collected empirical data and information about green initiatives from 15 sites or countries worldwide. We systematically explored how specific policy, intended behaviors, and gains of given green initiative may interact with those of other green initiatives concurrently implemented in the same geographic area or involving the same recipients. Surprisingly, we found that spillover effects were very divergent: one initiative could reduce the gain of another by 22 % âˆ¼ 100 %, representing alarming losses, while in other instances, substantial co-benefits could arise as one initiative can increase the gain of another by 9 % âˆ¼ 310 %. Leveraging these effects will help countries keep green initiatives with significant co-benefits but stop initiatives with substantial spillover losses in the face of widespread budget cuts, better meeting the United Nations' sustainable development goals.

The protease Lon prolongs insect lifespan by responding to reactive oxygen species and degrading mitochondrial transcription factor A.

Diapause is a widespread adaptation of insects that enables them to survive during unfavorable seasons and is characterized by suppressed metabolism and increased lifespan. Previous works have demonstrated that high levels of reactive oxygen species (ROS) and hypoxia-inducible factor-1α (HIF-1α) in the pupal brain of the moth Helicoverpa armigera induce diapause and extend lifespan by downregulating mitochondrial transcription factor A (TFAM). However, the molecular mechanisms of ROS-HIF-1α regulating metabolic activity to extend lifespan are still poorly understood. Here, we show that the mitochondrial abundance in diapause-type pupal brains is markedly lower than that in their nondiapause-type pupae, suggesting that ROS-HIF-1α signaling negatively regulates the number of mitochondria. The protease Lon, a major mitochondrial matrix protease, can respond to ROS signals. It is activated by transcription factor HIF-1α, which specifically binds the LON promoter to promote its expression. A high level of LON mediates the degradation of TFAM, which is a crucial factor in regulating mitochondrial abundance and metabolic activity. We believe this is the first report that a previously unrecognized regulatory pathway, ROS-HIF-1α-LON-TFAM, reduces mitochondrial activity to induce diapause, extending insect lifespan.

Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial.

BACKGROUND: Many patients experience lower-extremity swelling following total knee arthroplasty (TKA), which impedes recovery. Diosmin is a semisynthetic flavonoid that is often utilized to treat swelling and pain caused by chronic venous insufficiency. We aimed to evaluate the efficacy and safety of diosmin in reducing lower-extremity swelling and pain as well as in improving functional outcomes following TKA. METHODS: This study was designed as a randomized, controlled multicenter trial and conducted in 13 university-affiliated tertiary hospitals. A total of 330 patients undergoing TKA were randomized to either receive or not receive diosmin postoperatively. The diosmin group received 0.9 g of diosmin twice per day for 14 consecutive days starting on the day after surgery, whereas the control group received neither diosmin nor a placebo postoperatively. The primary outcome was lower-extremity swelling 1, 2, 3, and 14 days postoperatively. The secondary outcomes were postoperative pain assessed with use of a visual analogue scale, Hospital for Special Surgery score, range of knee motion, levels of the inflammatory biomarkers C-reactive protein and interleukin-6, and complications. RESULTS: At all postoperative time points, diosmin was associated with significantly less swelling of the calf, thigh, and upper pole of the patella as well as with significantly lower pain scores during motion. However, no significant differences in postoperative pain scores at rest, Hospital for Special Surgery scores, range of motion, levels of inflammatory biomarkers, or complication rates were found between the diosmin and control groups. CONCLUSIONS: The use of diosmin after TKA reduced lower-extremity swelling and pain during motion and was not associated with an increased incidence of short-term complications involving the outcomes studied. However, further studies are needed to continue exploring the efficacy and safety of diosmin use in TKA. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Pathologically catalyzed physical coating restores the intestinal barrier for inflammatory bowel disease therapy.

Intestinal epithelia impairment of inflammatory bowel disease (IBD) leads to the leakage of bacteria and antigens and the consequent persistent immune imbalance. Restoring the epithelial barrier is a promising therapeutic target but lacks effective and safe clinical interventions. By identifying the catalase (CAT) presence in the IBD pathological environment, we herein develop a CAT-catalyzed pathologically coating on the damaged epithelial barrier to inhibit intestinal leakage for IBD therapy. With the codelivery of CaO2 (a CAT substrate) and dopamine, the nanosystem can enable CAT-catalyzed oxygen (O2) production and in-situ polymerization of dopamine and then yield a thin and integrative polydopamine (PDA) coating on the intestinal barrier due to the highly adhesive property of PDA. In vivo study demonstrates that PDA coating provides not only a protective barrier by restricting intestinal leakage but also a favorable anti-inflammation effect. Beyond drug management, this work provides a physical repair strategy via catalyzed coating for IBD therapy.

Natural capital investments in China undermined by reclamation for cropland.

Globally, rising food demand has caused widespread biodiversity and ecosystem services loss, prompting growing efforts in ecological protection and restoration. However, these efforts have been significantly undercut by further reclamation for cropland. Focusing on China, the world's largest grain producer, we found that at the national level from 2000 to 2015, reclamation for cropland undermined gains in wildlife habitat and the ecosystem services of water retention, sandstorm prevention, carbon sequestration and soil retention by 113.8%, 63.4%, 52.5%, 29.0% and 10.2%, respectively. To achieve global sustainability goals, conflicts between inefficient reclamation for cropland and natural capital investment need to be alleviated.

IL-9 promotes methicillin-resistant Staphylococcus aureus pneumonia by regulating the polarization and phagocytosis of macrophages.

In this study, we examined the effect of Il9 deletion on macrophages in methicillin-resistant Staphylococcus aureus (MRSA) infection. MRSA-infected mice were employed for the in vivo experiments, and RAW264.7 cells were stimulated with MRSA for the in vitro experiments. Macrophage polarization was determined by flow cytometry and quantitative real-time PCR; macrophage phagocytosis was assessed by flow cytometry and laser scanning confocal microscopy; cell apoptosis was assessed by flow cytometry and western blotting. Il9 deletion markedly elevated macrophage phagocytosis and M2 macrophages in MRSA infection, which was accompanied by elevated expression of Il10 and Arg1 and reduced expression of Inos, tumor necrosis factor-α (Tnfα), and Il6. Il9 deletion also inhibited macrophage apoptosis in MRSA infection, which was manifested by elevated B-cell lymphoma 2 (BCL-2) protein level and reduced protein levels of cleaved cysteine protease 3 (CASPASE-3) and BCL2-Associated X (BAX). Both the in vivo and in vitro experiments further showed the activation of phosphoinositide 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB) signaling pathway in MRSA infection and that the regulation of Il9 expression may be dependent on Toll-like receptor (TLR) 2/PI3K pathway. The above results showed that Il9 deletion exhibited a protective role against MRSA infection by promoting M2 polarization and phagocytosis of macrophages and the regulation of Il9 partly owing to the activation of TLR2/PI3K pathway, proposing a novel therapeutic strategy for MRSA-infected pneumonia.

Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells.

BACKGROUND: Liver fibrosis is the common pathological process associated with the occurrence and development of various chronic liver diseases. At present, there is still a lack of effective prevention and treatment methods in clinical practice. Hepatic stellate cell (HSC) plays a key role in liver fibrogenesis. In recent years, the study of liver fibrosis targeting HSC autophagy has become a hot spot in this research field. Angiotensin-converting enzyme 2 (ACE2) is a key negative regulator of renin-angiotensin system, and its specific molecular mechanism on autophagy and liver fibrosis needs to be further explored. AIM: To investigate the effect of ACE2 on hepatic fibrosis in mice by regulating HSC autophagy through the Adenosine monophosphate activates protein kinases (AMPK)/mammalian target of rapamycin (mTOR) pathway. METHODS: Overexpression of ACE2 in a mouse liver fibrosis model was induced by injection of liver-specific recombinant adeno-associated virus ACE2 vector (rAAV2/8-ACE2). The degree of liver fibrosis was assessed by histopathological staining and the biomarkers in mouse serum were measured by Luminex multifactor analysis. The number of apoptotic HSCs was assessed by terminal deoxynucleoitidyl transferase-mediated dUTP nick-end labeling (TUNEL) and immunofluorescence staining. Transmission electron microscopy was used to identify the changes in the number of HSC autophagosomes. The effect of ACE2 overexpression on autophagy-related proteins was evaluated by multicolor immunofluorescence staining. The expression of autophagy-related indicators and AMPK pathway-related proteins was measured by western blotting. RESULTS: A mouse model of liver fibrosis was successfully established after 8 wk of intraperitoneal injection of carbon tetrachloride (CCl4). rAAV2/8-ACE2 administration reduced collagen deposition and alleviated the degree of liver fibrosis in mice. The serum levels of platelet-derived growth factor, angiopoietin-2, vascular endothelial growth factor and angiotensin II were decreased, while the levels of interleukin (IL)-10 and angiotensin- (1-7) were increased in the rAAV2/8-ACE2 group. In addition, the expression of alpha-smooth muscle actin, fibronectin, and CD31 was down-regulated in the rAAV2/8-ACE2 group. TUNEL and immunofluorescence staining showed that rAAV2/8-ACE2 injection increased HSC apoptosis. Moreover, rAAV2/8-ACE2 injection notably decreased the number of autophagosomes and the expression of autophagy-related proteins (LC3I, LC3II, Beclin-1), and affected the expression of AMPK pathway-related proteins (AMPK, p-AMPK, p-mTOR). CONCLUSION: ACE2 overexpression can inhibit HSC activation and promote cell apoptosis by regulating HSC autophagy through the AMPK/mTOR pathway, thereby alleviating liver fibrosis and hepatic sinusoidal remodeling.

Habitat-specific conservation priorities of multidimensional diversity patterns of amphibians in China effectively contribute to the '3030' target.

Amphibia is the most threatened animal group among all land vertebrates in the context of anthropogenic global change. Filling the conservation gaps for this taxonomic group could help achieve the ambitious target of covering 30 % of the land by 2030 ('3030' target) set by the 15-th meeting of the Conference of the Parties (COP15). In this study, we compiled the most up-to-date occurrence records and corresponding species-specific traits and phylogenies of amphibians in China (particularly those newly described in the past decade) to explore the spatial distribution patterns of multidimensional diversity (including taxonomic, functional, and phylogenetic) for different species groups (including all, endemic and threatened). Additionally, a new conservation gap index (CGI) was proposed and applied to the analysis of multi-objective conservation strategies. The results showed that the spatial distribution of taxonomic, functional and phylogenetic diversity of amphibians in China is markedly geographically diverse, with common hotspots for all three concentrated in the humid mountainous regions of southern China. The CGI, which is independent of arbitrary threshold selection and grid cell size, showed that the conservation gap for amphibians in China is largest in biomes such as tropical and subtropical moist broadleaf forests and temperate broadleaf and mixed forests. The multi-objective conservation analysis revealed that the Yangtze River basin, Pearl River basin and Southeast Basin in China have pivotal roles in achieving the '3030' target due to their high taxonomic, phylogenetic and functional diversity, relatively high proportion of threatened and endemic species, and low coverage of existing nature reserves. Notably, sustainable management of less-protected habitats, including farmlands and grasslands, can reduce the area requirement of strict protection for reaching the '3030' conservation goal. This study provides practical strategies for guiding amphibian conservation by systematically integrating multidimensional biodiversity information, habitat features and the spatial distributions of the existing natural reserves.

Characterization of TCF-1 and its relationship between CD8+ TIL densities and immune checkpoints and their joint influences on prognoses of lung adenocarcinoma patients.

BACKGROUND: T cell factor-1 (TCF-1) + stem-like tumor-infiltrating lymphocytes (stem-like TILs) are important memory cells in the tumor microenvironment. However, their relationship with clinicopathological features, CD8+ TIL densities, immune checkpoint inhibitors (ICs), and prognostic values remain unknown for lung adenocarcinomas (LUADs). In this study, we aimed to characterize TCF-1+ TILs and their prognostic significance in patients with surgically resected LUADs. METHODS: Expression of TCF-1, CD8, and ICs including programmed death-1 (PD-1), lymphocyte activating-3 (LAG-3), and T cell immunoglobulin and mucin-domain containing-3 (TIM-3) in TILs were estimated using immunohistochemistry of resected LUADs. The association between TCF-1 expressions and clinicopathological characteristics of patient prognoses were analyzed. RESULTS: Positive TCF-1 expression significantly correlated with advanced pathological stage, tumor grade, CD8+ TILs density, TIM-3 expression, LAG-3 expression, and PD-1 expression. TCF-1 positivity was significantly associated with a better recurrence-free survival (RFS), and overall survival (OS). Subgroup analysis revealed that the TCF-1+/CD8+ group had the best RFS and OS, while the TCF-1-/CD8- group had the worst RFS and OS. Similarly, patients with TCF-1 + PD-1- had the best prognoses and patients with TCF-1-PD-1+ had the worst prognoses. CONCLUSION: TCF-1 had relatively high positive expression and special clinicopathological features in patients with LUAD. TCF-1+ TILs were related to CD8 density, TIM-3 expression, LAG-3 expression, and PD-1 expression, and were associated with better prognoses in LUAD patients. A combination of TCF-1 and CD8 densities or PD-1 expression further stratified patients into different groups with distinct prognoses.

16S full-length gene sequencing analysis of intestinal flora in breast cancer patients in Hainan Province.

Breast cancer has become the number one cancer in the world, and intestinal flora may be closely linked to it. Geographic location also has an important impact on human intestinal flora. We conducted the first study on the intestinal flora of breast cancer patients and non-breast cancer patients in a tropical region - Hainan Province in China. At the same time, Pacbio platform based on third-generation sequencing was used for the first time to conduct 16S full-length sequencing of fecal microorganism DNA. We completed the species diversity analysis and differential species analysis of the intestinal flora between the two groups, inferred their functional genetic composition and performed functional difference analysis. There were statistically significant differences in alpha diversity between the two groups in Hainan Province. By species composition difference analysis, at the phylum level, Bacteroidales (P = 0.006) and Firmicutes (P = 0.002) was differed between the two groups, and at the genus level, 17 breast cancer-related differential species such as Bacteroides were screened. According to the five grouping methods including ER level, PR level, HER2 status, Ki67 index and histological grade of breast cancer patients, 4, 1, 9, 6, 5 differential microbiota were screened out respectively, which were in total 25 (P < 0.05 for all subgroups) . The functional prediction and difference analysis revealed two functional metabolisms with significant differences between the two groups of microbes (P < 0.05). These results suggest that breast cancer is associated with changes in the composition and function of intestinal flora. These microflora and functional differences may become biomarkers or new targets for diagnosis and treatment of breast cancer.

Low Expression of BIRC5-206 Promotes Cancer Progression in Nasopharyngeal Carcinoma via Enhancing Expression of Stem Cell Markers.

OBJECTIVE: Survivin is highly expressed in various malignant tumor cells and positively related to poor prognosis and drug resistance. This study aimed to explore the role of non-coding splice variant of Survivin, BIRC5-206 (ENST00000589892.1) in the progression of nasopharyngeal carcinoma (NPC), a malignant tumor that highly occurs in the southern region of China. METHODS: shRNA was used to knockdown BIRC5-206 mRNA level in CNE-2 and HOPNE-1 cells. Then, cell death, migration, invasion and clone formation ability of CNE-2 and HOPNE-1 cells were detected by flow cytometry, scratch-healing experiments, transwell invasion assay and clone formation assay, respectively. CD44+ and CD133+ positive cells were determined via Flow cytometry. Oct4, Nanog and SOX2 protein levels in CNE-2 and HOPNE-1 cells were measured by Western blot. RESULTS: BIRC5-206 decreased significantly in NPC cell lines. Silencing of BIRC5-206 suppressed the apoptosis, facilitated the migration, invasion and proliferation of both HONE1 and CNE-2 cells. In addition, knockdown of BIRC5-206 significantly promoted the expression cancer stem cell marker (CD44 and CD133) and pluripotency markers (Oct4, Sox2 and Nanog). CONCLUSIONS: BIRC5-206 might facilitate NPC tumor progression by inducing the transformation of NPC cells to cancer stem cells.

Selective Antagonism of Lactiplantibacillus plantarum and Pediococcus acidilactici against Vibrio and Aeromonas in the Bacterial Community of Artemia nauplii.

Empiric probiotics are commonly consumed by healthy individuals as a means of disease prevention, pathogen control, etc. However, controversy has existed for a long time regarding the safety and benefits of probiotics. Here, two candidate probiotics, Lactiplantibacillus plantarum and Pediococcus acidilactici, which are antagonistic to Vibrio and Aeromonas species in vitro, were tested on Artemia under in vivo conditions. In the bacterial community of Artemia nauplii, L. plantarum reduced the abundance of the genera Vibrio and Aeromonas and P. acidilactici significantly increased the abundance of Vibrio species in a positive dosage-dependent manner, while higher and lower dosages of P. acidilactici increased and decreased the abundance of the genus Aeromonas, respectively. Based on the liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) analyses of the metabolite of L. plantarum and P. acidilactici, pyruvic acid was used in an in vitro test to explain such selective antagonism; the results showed that pyruvic acid was conducive or suppressive to V. parahaemolyticus and beneficial to A. hydrophila. Collectively, the results of this study demonstrate the selective antagonism of probiotics on the bacterial community composition of aquatic organisms and the associated pathogens. IMPORTANCE Over the last decade, the common preventive method for controlling potential pathogens in aquaculture has been the use of probiotics. However, the mechanisms of probiotics are complicated and mostly undefined. At present, less attention has been paid to the potential risks of probiotic use in aquaculture. Here, we investigated the effects of two candidate probiotics, L. plantarum and P. acidilactici, on the bacterial community of Artemia nauplii and the in vitro interactions between these two candidate probiotics and two pathogens, Vibrio and Aeromonas species. The results demonstrated the selective antagonism of probiotics on the bacterial community composition of an aquatic organism and its associated pathogens. This research contributes to providing a basis and reference for the long-term rational use of probiotics and to reducing the inappropriate use of probiotics in aquaculture.