ABSTRACT
Alkaline lakes are extreme environments inhabited by diverse microbial extremophiles. However, large-scale distribution patterns, environmental adaptations, community assembly, and evolutionary dynamics of microbial communities remain largely underexplored. This study investigated the characteristics of microbial communities on rare and abundant taxa in alkaline lake sediments in west and northwest China. We observed that abundant taxa varied significantly with geographical distance, while rare taxa remained unaffected by regional differences. The assembly process of abundant taxa was influenced by dispersal limitation, whilst rare taxa were predominantly driven by heterogeneous selection. Network analysis indicated that rare taxa as core species for community interactions and community stability. Rare taxa exhibited higher speciation and transition rate than abundant taxa, serving as a genetic reservoir and potential candidates to become abundance taxa, highlighting their crucial role in maintaining microbial diversity. These insights underscore the significant influence of rare taxa on ecosystem biodiversity and stability in alkaline lakes.
Subject(s)
Bacteria , Biodiversity , Geologic Sediments , Lakes , Lakes/microbiology , Geologic Sediments/microbiology , China , Bacteria/classification , Bacteria/genetics , Bacteria/isolation & purification , Phylogeny , RNA, Ribosomal, 16S/genetics , Microbiota , Archaea/classification , Archaea/genetics , Archaea/isolation & purification , Hydrogen-Ion Concentration , Ecosystem , Alkalies/analysisABSTRACT
Five new compounds, including two sesquiterpenoid glycosides (1 and 2), two monoterpenoid glycosides (3 and 4), and a quinovose ester (5), together with four known compounds (6-9) were isolated from branches and leaves of Pittosporum pulchrum Gagnep. Their structures were established by 1D and 2D NMR, HR-ESI-MS, IR and UV spectral analyses. This is the first time to investigate the chemical constituents of P. pulchrum. Subsequently, the anti-inflammatory and antioxidant activities of different solvent fractions of ethanol extract and isolated compounds were evaluated. Dichloromethane and ethyl acetate fractions dramatically inhibited the production of NO in a concentration-dependent manner in LPS-induced RAW264.7 cells. Ethyl acetate and n-butanol fractions showed excellent DPPH radical scavenging activities with IC50 values of 24.31 µg/mL and 27.81 µg/mL, respectively. Compounds 7 and 8 might be potential natural antioxidants with IC50 values of 16.13 µM and 24.81 µM, respectively.
Subject(s)
Anti-Inflammatory Agents , Antioxidants , Phytochemicals , Plant Leaves , Plant Leaves/chemistry , Mice , RAW 264.7 Cells , Animals , Molecular Structure , Antioxidants/pharmacology , Antioxidants/isolation & purification , Antioxidants/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Glycosides/chemistry , Nitric Oxide/metabolism , Plant Stems/chemistry , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Sesquiterpenes/chemistry , China , Monoterpenes/isolation & purification , Monoterpenes/pharmacologyABSTRACT
PURPOSE: To assess T1 mapping performance in distinguishing between benign and malignant breast lesions and to explore its correlation with histopathologic features in breast cancer. METHODS: This study prospectively enrolled 103 participants with a total of 108 lesions, including 25 benign and 83 malignant lesions. T1 mapping, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) were performed. Two radiologists independently outlined the ROIs and analyzed T1 and apparent diffusion coefficient (ADC) values for each lesion, assessing interobserver reliability with the intraclass correlation coefficient (ICC). T1 and ADC values were compared between benign and malignant lesions, across different histopathological characteristics (histological grades, estrogen, progesterone and HER2 receptors expression, Ki67, N status). Receiver operating characteristic (ROC) analysis and Pearson correlation coefficient (ρ) were performed. RESULTS: T1 values showed statistically significant differences between benign and malignant groups (P < 0.001), with higher values in the malignant (1817.08 ms ± 126.64) compared to the benign group (1429.31 ms ± 167.66). In addition, T1 values significantly increased in the ER (-) group (P = 0.001). No significant differences were found in T1 values among HER2, Ki67, N status, and histological grades groups. Furthermore, T1 values exhibited a significant correlation (ρ) with ER (P < 0.01) and PR (P = 0.03). The AUC for T1 value in distinguishing benign from malignant lesions was 0.69 (95 % CI: 0.55 - 0.82, P = 0.005), and for evaluating ER status, it was 0.75 (95 % CI: 0.62 - 0.87, P = 0.002). CONCLUSIONS: T1 mapping holds the potential as an imaging biomarker to assist in the discrimination of benign and malignant breast lesions and assessing the ER expression status in breast cancer.
Subject(s)
Breast Neoplasms , Contrast Media , Humans , Female , Breast Neoplasms/diagnostic imaging , Middle Aged , Adult , Reproducibility of Results , Aged , Diagnosis, Differential , Prospective Studies , Diffusion Magnetic Resonance Imaging/methods , Sensitivity and SpecificityABSTRACT
Conventional microalgal-bacterial consortia have limited capacity to treat low-C/N wastewater due to carbon limitation and single nitrogen (N) removal mode. In this work, indigenous synergetic microalgal-bacterial consortia with high N removal performance and bidirectional interaction were successful in treating rare earth tailing wastewaters with low-C/N. Ammonia removal reached 0.89 mg N L-1 h-1, 1.84-fold more efficient than a common microalgal-bacterial system. Metagenomics-based metabolic reconstruction revealed bidirectional microalgal-bacterial interactions. The presence of microalgae increased the abundance of bacterial N-related genes by 1.5- to 57-fold. Similarly, the presence of bacteria increased the abundance of microalgal N assimilation by 2.5- to 15.8-fold. Furthermore, nine bacterial species were isolated, and the bidirectional promotion of N removal by the microalgal-bacterial system was verified. The mechanism of microalgal N assimilation enhanced by indole-3-acetic acid was revealed. In addition, the bidirectional mode of the system ensured the scavenging of toxic byproducts from nitrate metabolism to maintain the stability of the system. Collectively, the bidirectional enhancement system of synergetic microalgae-bacteria was established as an effective N removal strategy to broaden the stable application of this system for the effective treatment of low C/N ratio wastewater.
Subject(s)
Microalgae , Wastewater , Microalgae/metabolism , Denitrification , Nitrogen/metabolism , Bacteria/metabolism , BiomassABSTRACT
Metagenomic binning is an essential technique for genome-resolved characterization of uncultured microorganisms in various ecosystems but hampered by the low efficiency of binning tools in adequately recovering metagenome-assembled genomes (MAGs). Here, we introduce BASALT (Binning Across a Series of Assemblies Toolkit) for binning and refinement of short- and long-read sequencing data. BASALT employs multiple binners with multiple thresholds to produce initial bins, then utilizes neural networks to identify core sequences to remove redundant bins and refine non-redundant bins. Using the same assemblies generated from Critical Assessment of Metagenome Interpretation (CAMI) datasets, BASALT produces up to twice as many MAGs as VAMB, DASTool, or metaWRAP. Processing assemblies from a lake sediment dataset, BASALT produces ~30% more MAGs than metaWRAP, including 21 unique class-level prokaryotic lineages. Functional annotations reveal that BASALT can retrieve 47.6% more non-redundant opening-reading frames than metaWRAP. These results highlight the robust handling of metagenomic sequencing data of BASALT.
Subject(s)
Ecosystem , Metagenome , Silicates , Metagenome/genetics , Metagenomics/methodsABSTRACT
Microalgal technology holds great promise for both low C/N wastewater treatment and resource recovery simultaneously. Nevertheless, the advancement of microalgal technology is hindered by its reduced nitrogen removal efficiency in low C/N ratio wastewater. In this work, microalgae and waste oyster shells were combined to achieve a total inorganic nitrogen removal efficiency of 93.85% at a rate of 2.05 mg L-1 h-1 in low C/N wastewater. Notably, over four cycles of oyster shell reuse, the reactor achieved an average 85% ammonia nitrogen removal extent, with a wastewater treatment cost of only $0.092/ton. Moreover, microbial community analysis during the reuse of oyster shells revealed the critical importance of timely replacement in inhibiting the growth of non-functional bacteria (Poterioochromonas_malhamensi). The work demonstrated that the oyster shell - microalgae system provides a time- and cost-saving, environmental approach for the resourceful treatment of harsh low C/N wastewater.
Subject(s)
Animal Shells , Carbon , Microalgae , Nitrogen , Ostreidae , Waste Disposal, Fluid , Wastewater , Animals , Nitrogen/analysis , Nitrogen/metabolism , Microalgae/growth & development , Wastewater/chemistry , Animal Shells/chemistry , Waste Disposal, Fluid/methods , Water Pollutants, Chemical/analysisABSTRACT
BACKGROUND: Previous studies have indicated that amide proton transfer-weighted imaging (APTWI) could be utilized for differentiating benign and malignant tumors. The APTWI technology has increasingly being applied to breast tumor research in recent years. However, according to the latest literature retrieval, no relevant previous studies compared the value of APTWI and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) in distinguishing benign lesions from malignant lesions. In the present study, the application of APTWI and DCE for differentiating the benign and malignant breast lesions was investigated. PATIENTS AND METHODS: APTWI was performed on 40 patients (42 lesions) who were enrolled in this prospective study. The lesions were split into two groups, one with malignant breast lesions (n = 28) and the other with benign breast lesions (n = 14), based on the results of the histology. The measured image characteristics (APT value, apparent diffusion coefficient [ADC] value, and time-of-intensity-curve [TIC] type) were compared between the two groups, and the ROC curve was used to quantify the diagnostic performance on the basis of these factors. The correlation between the APT values and the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 expression levels and histological grades was examined using Spearman's correlation coefficient. RESULTS: The measured APT and ADC values showed a strong inter-observer agreement according to the intraclass correlation coefficients (0.954 and 0.825). Compared to benign lesions, malignant lesions had significantly higher APT values (3.18 ± 1.07 and 2.01 ± 0.51, p < 0.001). Based on APTWI, DCE, diffusion-weighted imaging (DWI), and ADC + APTWI, ADC + DCE, and DCE + APTWI, the area-under-the-curve values were 0.915, 0.815, 0.878, 0.921, 0.916, and 0.936, respectively. CONCLUSIONS: APTWI is a potentially promising method in differentiating benign and malignant breast lesions, and may it become a great substitute for DCE examination in the future.
Subject(s)
Contrast Media , Protons , Humans , Prospective Studies , Sensitivity and Specificity , Magnetic Resonance Imaging/methodsABSTRACT
Objective: To explore the clinical manifestations of glutamic acid decarboxylase 65 (GAD65) antibody-positive patients with extraocular symptoms and the possible mechanism. Method: Assays for the presence of GAD65 antibodies were performed on patients' serum and cerebral spinal fluid (CSF). The brain and ocular structures involved in eye movement were assessed via magnetic resonance imaging (MRI). Tests such as electromyography (EMG), particularly repetitive nerve stimulation (RNS), and neostigmine tests were utilized for differential diagnosis. Additionally, the interaction of GAD65 antibodies with muscle tissue was confirmed using immunofluorescence techniques. Result: Each patient exhibited symptoms akin to extraocular myasthenia gravis (MG), with two individuals reporting diplopia and two experiencing ptosis. GAD65 antibodies were detected in either the serum or CSF, which were shown to bind with monkey cerebellum slides and mouse muscle slides. Neuroimaging of the brain and extraocular muscles via MRI showed no abnormalities, and all patients tested negative for the neostigmine test, RNS via EMG, and the presence of MG antibodies. However, thyroid-related antibodies were found to be abnormal in four of the patients. Conclusion: Our results showed that GAD65 antibodies are not only associated with encephalitis, cerebellum ataxia or stiff-person syndrome caused by the decrease of GABAergic transmission but also diplopia and ptosis. Therefore, we should pay more attention to extraocular muscle paralysis patients without pathogenic antibodies directed against the components of neuromuscular junctions.
Subject(s)
Myasthenia Gravis , Oculomotor Muscles , Animals , Mice , Humans , Diplopia , Neostigmine , Antibodies , Myasthenia Gravis/diagnosis , ParalysisABSTRACT
BACKGROUND AND OBJECTIVES: Brain radial enhancement pattern on magnetic resonance imaging (MRI) has been identified as typical lesions in autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A). However, the authors encountered several patients without GFAP-IgG showing that such specific imaging. In the present study, we reported the clinical pictures of 5 GFAP-IgG-negative patients with GFAP-A specific imaging pattern. METHODS: Data was retrospectively obtained from June 2013 through April 2023, and five GFAP-IgG-negative patients with valid data were recruited. Clinical information was either obtained by the investigators or retrieved from the referring clinicians and included prodromal symptoms, neurologic manifestations, comorbidities, results of ancillary studies. RESULTS: Altogether five GFAP-IgG-negative patients with "meningoencephalitis/encephalitis" manifestations and brain radial perivascular enhancement were confirmed. One patient had peripheral lymphoma. Four patients had other autoimmune antibody in serum and/or cerebrospinal fluid, of which one patient had positive aquaporin IgG. Clinical features of the five patients included headache, fever, epilepsy and abnormal behavioral symptoms. MRI of patients revealed radial perivascular gadolinium enhancement extending from the lateral ventricles to the white matter suggestive of autoimmune GFAP-A. CONCLUSION: GFAP-A-like disorders with radial perivascular enhancement could be found in GFAP-IgG-negative patients with or without neoplasm, which could provide new insight into the differential diagnosis of GFAP-A.
Subject(s)
Contrast Media , Gadolinium , Humans , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Retrospective Studies , Brain/diagnostic imaging , Brain/metabolism , Autoantibodies , Immunoglobulin G/metabolism , Astrocytes/metabolismABSTRACT
The genus Rimicaris is the dominant organism living in hydrothermal vents. However, little research has been done on the functions of their intestinal flora. Here, we investigated the potential functions of Deferribacterota, which is dominant in the intestine of Rimicaris kairei from the Central Indian Ridge. In total, six metagenome-assembled genomes (MAGs) of Deferribacterota were obtained using the metagenomic approach. The six Deferribacterota MAGs (Def-MAGs) were clustered into a new branch in the phylogenetic tree. The six Def-MAGs were further classified into three species, including one new order and two new genera, based on the results of phylogenetic analysis, relative evolutionary divergence (RED), average nucleotide identity (ANI), average amino acid identity (AAI) and DNA-DNA hybridization (DDH) values. The results of the energy metabolism study showed that these bacteria can use a variety of carbon sources, such as glycogen, sucrose, salicin, arbutin, glucose, cellobiose, and maltose. These bacteria have a type II secretion system and effector proteins that can transport some intracellular toxins to the extracellular compartment and a type V CRISPR-Cas system that can defend against various invasions. In addition, cofactors such as biotin, riboflavin, flavin mononucleotide (FMN), and flavin adenine dinucleotide (FAD) synthesized by R. kairei gut Deferribacterota may also assist their host in surviving under extreme conditions. Taken together, the potential function of Deferribacterota in the hydrothermal R. kairei gut suggests its long-term coevolution with the host.
ABSTRACT
BACKGROUND: Various approaches using epidural analgesia have been employed for relieving labor pain and promoting spontaneous delivery. We aimed to evaluate the effect of nalbuphine and ropivacaine versus fentanyl and ropivacaine on the duration of delivery in parturients. METHODS: Clinical data of 160 full-term primiparous women who received either nalbuphine or fentanyl in combination with ropivacaine infusion for epidural labor analgesia in our hospital from December 2020 to May 2022 were retrospectively analyzed. The participants were divided into two groups based on anesthesia methods: nalbuphine group (NR group, n = 78) received 0.2 mg/mL nalbuphine combined with 0.1% ropivacaine hydrochloride for patient-controlled epidural analgesia (PCEA) and fentanyl group (FR group, n = 82) received 2 ug/mL fentanyl citrate and 0.1% ropivacaine hydrochloride for PCEA. Both groups received an epidural blockade for labor analgesia at lumbar 2-3 interspace. The duration of the first, second, and third stages of labor, the onset of analgesia, and time before delivery (T0), 15 min of analgesia (T1), 30 min of analgesia (T2), full opening of the uterine opening (T3),exerts force during childbirth(T4), heart rate (HR), blood pressure (BP), blood saturation (SpO2), visual analogue pain scale (VAS) score, Ramsay sedation score, and modified Bromage score, and 5 min were recorded at 2 h postpartum (T5). The neonatal Apgar score, neonatal behavioral neurological assessment (NBNA) score, maternal nausea, vomiting, and itchy skin were recorded. RESULTS: Compared with the FR group, the first stage of labor duration (p < 0.05) and total duration of labor (p < 0.05) were shortened and the onset of analgesia (p < 0.05) was increased in the NR group. NR group had lower incidence of urinary retention than FR group (p < 0.05). The maternal and neonatal investigational parameters and scores had no significant difference between the two groups. CONCLUSIONS: Nalbuphine combined with ropivacaine in epidural block labor has a faster onset of analgesia and has a lower incidence of urinary retention than fentanyl combined with ropivacaine, and nalbuphine shortens the duration of the first and total stages of labor. Both nalbuphine and fentanyl can reduce pain during labor, have little effect on maternal hemodynamics, and have no significant effect on neonatal Apgar or NBNA scores.
Subject(s)
Analgesia, Epidural , Nalbuphine , Urinary Retention , Pregnancy , Infant, Newborn , Female , Humans , Ropivacaine , Retrospective Studies , Pain , FentanylSubject(s)
Dog Diseases , Influenza A virus , Orthomyxoviridae Infections , Reassortant Viruses , Animals , Dogs , China/epidemiology , Influenza A virus/genetics , Phylogeny , Reassortant Viruses/genetics , Orthomyxoviridae Infections/veterinary , Orthomyxoviridae Infections/virology , Dog Diseases/virology , FarmsABSTRACT
Canine circovirus (CanineCV) is a single-stranded DNA virus that circulates in dogs and wild carnivores around the world. It has been suggested to be associated with diseases of respiratory and gastrointestinal systems, though its pathogenic potential remains unclear. Currently, CanineCV is divided into six genotypes (genotype 1-6), and genotypes 2, 3, and 4 have been described in China. In this study, 359 blood samples from pet dogs with or without clinical signs were collected in Harbin city. After PCR screening, a total of 34 samples were tested positive for CanineCV, and nine full-length genome sequences were recovered from positive samples. Pairwise sequence comparison showed that they shared 82.4-99.3% genome-wide identity with other CanineCVs available in GenBank. Additionally, recombination events were detected, all of which were determined to be associated with sequences obtained in China. The reconstructed phylogenetic tree based on the recombination-free complete genome sequences revealed that the complete genome sequences generated herein were clustered into genotypes 1 and 3. Furthermore, purifying selection was the dominant evolutionary pressure acting on the genomes of CanineCV. These results expand the knowledge about the genetic diversity of CanineCV circulating in China, and also promote us to better understand the evolution of CanineCV.
Subject(s)
Circovirus , Dogs , Animals , Phylogeny , Circovirus/genetics , Genome, Viral , Genotype , China/epidemiologyABSTRACT
To explore the autoimmune response and outcome in the central nervous system (CNS) at the onset of viral infection and correlation between autoantibodies and viruses. METHODS: A retrospective observational study was conducted in 121 patients (2016-2021) with a CNS viral infection confirmed via cerebrospinal fluid (CSF) next-generation sequencing (cohort A). Their clinical information was analysed and CSF samples were screened for autoantibodies against monkey cerebellum by tissue-based assay. In situ hybridisation was used to detect Epstein-Barr virus (EBV) in brain tissue of 8 patients with glial fibrillar acidic protein (GFAP)-IgG and nasopharyngeal carcinoma tissue of 2 patients with GFAP-IgG as control (cohort B). RESULTS: Among cohort A (male:female=79:42; median age: 42 (14-78) years old), 61 (50.4%) participants had detectable autoantibodies in CSF. Compared with other viruses, EBV increased the odds of having GFAP-IgG (OR 18.22, 95% CI 6.54 to 50.77, p<0.001). In cohort B, EBV was found in the brain tissue from two of eight (25.0%) patients with GFAP-IgG. Autoantibody-positive patients had a higher CSF protein level (median: 1126.00 (281.00-5352.00) vs 700.00 (76.70-2899.00), p<0.001), lower CSF chloride level (mean: 119.80±6.24 vs 122.84±5.26, p=0.005), lower ratios of CSF-glucose/serum-glucose (median: 0.50[0.13-0.94] vs 0.60[0.26-1.23], p=0.003), more meningitis (26/61 (42.6%) vs 12/60 (20.0%), p=0.007) and higher follow-up modified Rankin Scale scores (1 (0-6) vs 0 (0-3), p=0.037) compared with antibody-negative patients. A Kaplan-Meier analysis revealed that autoantibody-positive patients experienced significantly worse outcomes (p=0.031). CONCLUSIONS: Autoimmune responses are found at the onset of viral encephalitis. EBV in the CNS increases the risk for autoimmunity to GFAP.
Subject(s)
Encephalitis , Epstein-Barr Virus Infections , Male , Humans , Female , Autoimmunity , Retrospective Studies , Herpesvirus 4, Human , Autoantibodies , Immunoglobulin GABSTRACT
Bovine hepacivirus (BovHepV) is a member of the genus Hepacivirus of the family Flaviviridae, which can cause acute or persistent infections in cattle. Currently, BovHepV strains identified in cattle populations worldwide can be classified into two genotypes with eight subtypes in genotype 1. BovHepV has been identified in a wide geographic area in China. Interestingly, the viral RNA of BovHepV has also been detected in ticks in Guangdong province, China. In this study, Rhipicephalus microplus tick samples were collected in Heilongjiang province, northeastern China, and BovHepV was screened with an overall positive rate of 10.9%. Sequence comparison and phylogenetic analysis showed that the BovHepV strains detected in this study belong to the subtype G. This is the first report about the detection of BovHepV in ticks in Heilongjiang province, China, which expands our knowledge that ticks may be a transmission vector of BovHepV.
ABSTRACT
Polyploids recurrently emerge in angiosperms, but most polyploids are likely to go extinct before establishment due to minority cytotype exclusion, which may be specifically a constraint for dioecious plants. Here we test the hypothesis that a stable sex-determination system and spatial/ecological isolation facilitate the establishment of dioecious polyploids. We determined the ploidy levels of 351 individuals from 28 populations of the dioecious species Salix polyclona, and resequenced 190 individuals of S. polyclona and related taxa for genomic diversity analyses. The ploidy survey revealed a frequency 52% of tetraploids in S. polyclona, and genomic k-mer spectra analyses suggested an autopolyploid origin for them. Comparisons of diploid male and female genomes identified a female heterogametic sex-determining factor on chromosome 15, which probably also acts in the dioecious tetraploids. Phylogenetic analyses revealed two diploid clades and a separate clade/grade of tetraploids with a distinct geographic distribution confined to western and central China, where complex mountain systems create higher levels of environmental heterogeneity. Fossil-calibrated phylogenies showed that the polyploids emerged during 7.6-2.3 million years ago, and population demographic histories largely matched the geological and climatic history of the region. Our results suggest that inheritance of the sex-determining system from the diploid progenitor as intrinsic factor and spatial isolation as extrinsic factor may have facilitated the preservation and establishment of polyploid dioecious populations.
Subject(s)
Diploidy , Tetraploidy , Humans , Phylogeny , Biological Evolution , PolyploidyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Callicarpa longissima is a typical Yao ethnomedicine that has been used to treat arthritis in China. Our previous study found that the dichloromethane extract (DCME) of C. longissima showed anti-inflammatory activity in vitro. However, the anti-inflammatory mechanism and detailed chemical composition of DCME remain unclear, which lead to the original interest of this study. AIM OF THE STUDY: The study aimed to evaluate the anti-inflammatory properties of the DCME from C. longissima and further explore the accurate chemical components responsible for this active extract. MATERIALS AND METHODS: The anti-inflammatory activity of DCME in vivo was tested with carrageenan-induced mice paw edema model. Its anti-inflammatory mechanism was explored with LPS-stimulated RAW264.7 macrophages model. The compounds in DCME were isolated by repeated column chromatography and their structures were identified on the basis of nuclear magnetic resonance spectroscopy. The anti-inflammatory activities of the isolates in vitro were also tested by suppressing releases of inflammatory mediators (NO, IL-6 and TNF-α) in RAW264.7 macrophages model. In addition, the molecular docking analysis, which evaluated the potential interaction between the compounds and Toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB), was performed. RESULTS: DCME effectively alleviated the mice paw edema induced by carrageenan. In LPS-stimulated RAW264.7â¯cells, DCME significantly decreased the production of interleukin (IL)-6 and tumor necrosis factor α (TNF-α) via inhibiting their mRNA transcription, down-regulated the expression of TLR4 and myeloid differentiation factor 88, inhibited the phosphorylation of alpha inhibitor of NF-κB (IκBα), NF-κB p65, and degradation of IκBα. Twelve diterpenoid phenols were identified from DCME, and they not only showed different inhibitory effects on the production of NO, IL-6 and TNF-α in LPS-stimulated RAW264.7â¯cells, but also could bind to TLR4 and NF-κB as analyzed by molecular docking. CONCLUSIONS: Taken together, DCME from C. longissima could inhibit inflammatory response both in vitro and in vivo, which is mainly attributed to the synergistic effect of abundant diterpenoid phenols through inhibiting the TLR4/NF-κB signaling pathway, and might be a promising agent for the treatment of inflammatory diseases.
Subject(s)
Callicarpa , Diterpenes , Animals , Mice , NF-kappa B/metabolism , NF-KappaB Inhibitor alpha/metabolism , Methylene Chloride/adverse effects , Interleukin-6/metabolism , Carrageenan/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Toll-Like Receptor 4/metabolism , Lipopolysaccharides/pharmacology , Molecular Docking Simulation , Signal Transduction , Anti-Inflammatory Agents/adverse effects , Diterpenes/pharmacology , Edema/chemically induced , Edema/drug therapyABSTRACT
Fish represent a large part of the taxonomic diversity of vertebrates and are of high commercial value. However, the factors influencing the gut microbiota composition of freshwater fish over large spatial scales remain unclear. Therefore, this study explored gut microbiome diversity in 24 fish species from the Yellow River, which spans over 1500 km across China. The results showed that geographical distance, host phylogeny and diet significantly influenced gut microbial community diversity, whereas sex, body length and body weight had minimal influence. Geographical distance was the primary factor shaping gut microbiota, and dissimilarity in microbial community structure increased with an increase in geographical distance, which was mainly driven by dispersal limitation. The microbial communities were more homogeneous at higher host taxonomic resolutions due to the dominant role of homogeneous selection in community convergence. Phylosymbiosis was observed across all host species, with a stronger pattern in Cypriniformes, which harbour host-specific microbial taxa. Host diet explained little variation in gut microbiome diversity, although it was significant for all diversity metrics tested. These findings collectively suggest that the geographical and host-based patterns of fish gut microbiota tend to be shaped by different ecological forces across the Yellow River. The present work provides a robust assessment of multiple factors driving fish gut microbial community assembly and offers insight into the mechanisms underlying shifts in fish gut microbiota in rivers across large spatial scales.
Subject(s)
Gastrointestinal Microbiome , Animals , Gastrointestinal Microbiome/genetics , Rivers , Fishes , Biological Evolution , Phylogeny , Diet , RNA, Ribosomal, 16S/geneticsABSTRACT
Obesity has become a global epidemic disease as it is closely associated with a chronic low-grade inflammatory state that results in metabolic dysfunction. Ramulus Mori (Sangzhi) alkaloids (SZ-A) derived from Morus alba L. were licensed to treat type 2 diabetes (T2DM) in 2020. In this study, we explored the effect of SZ-A on adipose tissue metabolism and inflammation using an obesity model induced by a high-fat diet (HFD). C57BL/6J mice were fed high fat for 14 weeks and followed by SZ-A 400 mg/kg treatment via gavage for another six weeks, during which they were still given the high-fat diet. The results showed that SZ-A notably reduced body weight and serum levels of lipid metabolism-related factors, such as triglycerides (TG) and total cholesterol (TC); and inflammation-related factors, namely tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), fibrinogen activator inhibitor-1 (PAI-1), angiopoietin-2 (Ang-2), and leptin (LEP), in the HFD-induced mice. SZ-A increased the protein and mRNA expression of lipid metabolism-related factors, including phosphorylated acetyl coenzyme A carboxylase (p-ACC), phosphorylated hormone-sensitive triglyceride lipase (p-HSL), adipose triglyceride lipase (ATGL), and peroxisome proliferator-activated receptor-alpha (PPARα), in adipose tissue. Immunohistochemistry results demonstrated that SZ-A significantly reduced the infiltration of pro-inflammatory M1-type macrophages in epididymal fat. The data also suggested that SZ-A down-regulates the transcriptional levels of inflammatory factors Il6, Tnfα, monocyte chemoattractant protein-1 (Mcp1), and F4/80, and up-regulates interleukin 4 (Il4), interleukin 10 (Il10), and interleukin 13 (Il13) in adipose tissue. Overall, the results indicate that SZ-A exhibits potential in regulating lipid metabolism and ameliorating obesity-linked adipose inflammation.