AXL inhibition prevents RPA2/CHK1-mediated homologous recombination to increase PARP inhibitor sensitivity in hepatocellular carcinoma.

Homologous recombination defects (HRD) render cells fail to repair DNA double-strand break (DSB), which causes synthetic lethality in these cells with punch by poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Here, we reveal a receptor tyrosine kinase, AXL, whose inhibition leads to HRD in hepatocellular carcinoma (HCC) cells. AXL is upregulated in HCC tumors, which is positively correlated with low survival rates. AXL knockdown or AXL inhibition by bemcentinib reduces HR efficiency in HCC cells, and AXL plays its role in HR repair through its kinase activity. Furthermore, we find that AXL interacts with RPA2, enhancing the recruitment of RPA2 to DNA damage sites. Mechanistically, AXL promotes the tyrosinization of RPA2 at tyrosine 9, promoting the phosphorylation of CHK1, thereby strengthens the HR repair ability in HCC cells to resist DNA damage. In conclusion, our results reveal that AXL is a promising therapeutic biomarker for HCC patients, and present that targeting AXL-RPA2-CHK1 pathway together with PARP inhibitor will be effective therapeutic strategy in HCC.

Impact of High-Temperature Feeds on Gut Microbiota and MAFLD.

The purpose of this study is to investigate the effects of non-obese MAFLD on the gut microbiota and metabolic pathways caused by high-temperature processed meals. It was decided to divide the eighteen male Sprague-Dawley rats into three groups: the control group, the dry-fried soybeans (DFS) group, and the high-fat diet (HFD) group. Following the passage of twelve weeks, a series of physical, biochemical, histological, and microbiological examinations were carried out. There were distinct pathological abnormalities brought about by each diet. The DFS diet was found to cause the development of fatty liver and to demonstrate strong relationships between components of the gut microbiota, such as Akkermansia and Mucispirillum, and indices of liver health. Diet-induced changes in the gut microbiome have a significant impact on liver pathology in non-obese patients with metabolically altered liver disease (MAFLD), which suggests that dietary interventions that target gut microbiota could be used to manage or prevent the illness.

Comprehensive serum proteomics profiles and potential protein biomarkers for the early detection of advanced adenoma and colorectal cancer.

BACKGROUND: The majority of colorectal cancer (CRC) cases develop from precursor advanced adenoma (AA). With the development of proteomics technologies, blood protein biomarkers have potential applications in the early screening of AA and CRC in the general population. AIM: To identify serum protein biomarkers for the early screening of AA and CRC. METHODS: We collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at China-Japan Friendship Hospital. Quantitative proteomic analysis was performed using liquid chromatography-mass spectrometry/mass spectrometry and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. Prognosis was further analyzed based on public databases, and proteins expression in tissues were validated by immunohistochemistry. RESULTS: A total of 2132 proteins and 17365 peptides were identified in the serum samples. There were 459 upregulated proteins and 118 downregulated proteins in the NC vs AA group, 289 and 180 in the NC vs CRC group, and 52 and 248 in the AA vs CRC group, respectively. Bioinformatic analysis revealed that these DEPs had different functions and participated in extensive signaling pathways. We also identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, VASP (P < 0.01), LBP (P = 0.01), TUBGCP5 (P < 0.01), and DOK3 (P < 0.01) were associated with a poor prognosis. In addition, we propose that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors. CONCLUSION: Our study elucidated the serum proteomic profiles of AA and CRC patients, and the identified proteins, such as LBP and VASP, may contribute to the early detection of AA and CRC.

Analysis of Chemical Constituents of Miao Ethnomedicine Heiguteng Zhuifeng Huoluo Capsule (HZFC) and the Discovery of Active Substances in the Treatment of Rheumatoid Arthritis.

In this study, the chemical substances of Heiguteng Zhuifeng Huoluo Capsule (HZFC) and its potential active ingredients for the treatment of rheumatoid arthritis (RA) were characterized and analyzed by medicinal chemistry combined with bioinformatics methods. Also, the potential active ingredients of HZFC against RA were verified by lipopolysaccharide (LPS)-induced macrophage activation model. The results showed that 79 chemical constituents were successfully identified, mainly including phenylpropanoids, flavonoids, and alkaloids. Among them, 13 active components were closely related to the nine core targets (FASN, ALOX5, EGFR, MMP1, CYP2D6, CNR1, AR, MAOA, and FKBP5) of HZFC in the treatment of RA. Molecular docking further proved that 13 active components had strong docking activity with 9 core targets. In the verification experiment of the LPS-induced RAW 264.7 macrophage model, the verified components (magnoflorine, N-feruloyltyramine, canadine, rutin, quercetin-3-O-glucoside, and pseudocolumbamine) all showed a clear inhibitory effect on the secretion of inflammatory factors in model cells. The above research results suggest that 13 components such as stepharanine, rutin, quercetin-3-O-glucoside, corydine methyl ether, canadine, 8-oxoepiberberine, disinomenine, deosinomenine glucoside, tuduranine, magnoflorine, isosinomenine, pseudocolumbamine, and N-feruloyltyramine may be the main active substances of HZFC in the treatment of RA.

Research progress on molecular biomarkers of acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common type of adult acute leukemia. The pathophysiology of the disease has been studied intensively at the cellular and molecular levels. At present, cytogenetic markers are an important basis for the early diagnosis, prognostic stratification and treatment of AML. However, with the emergence of new technologies, the detection of other molecular markers, such as gene mutations and epigenetic changes, began to play important roles in evaluating the occurrence and development of diseases. Recent evidence shows that identifying new AML biomarkers contributes to a better understanding of the molecular mechanism of the disease and is essential for AML screening, diagnosis, prognosis monitoring, and individualized treatment response. In this review, we summarized the promising AML biomarkers from four aspects, which contributing to a better understanding of the disease. Of course, it must be soberly aware that we have not listed all biomarkers of AML. Anyway, the biomarkers we mentioned are representative. For example, mutations in TP53, FLT3, and ASXL1 suggest poor prognosis, low remission rate, short survival period, and often require allogeneic hematopoietic stem cell transplantation. The CEBPA double mutation, NPM1 and CBF mutation suggest that the prognosis is good, the remission rate is high, the survival period is long, and the effect of chemotherapy or autotherapy is good. As for other mutations mentioned in the article, they usually predict a moderate prognosis. All in all, we hope it could provide a reference for the precise diagnosis and treatment of AML.

CircRNA circSTIL inhibits ferroptosis in colorectal cancer via miR-431/SLC7A11 axis.

Ferroptosis is an emerging programmed cell death and plays essential roles in tumorigenesis, including colorectal cancer (CRC). The present study intended to disclose the role of a novel oncogene circular RNA (circRNA) circSTIL in CRC phenotypes, especially ferroptosis. The expression of circSTIL was measured in CRC tissues and cells. Then, the impacts of circSTIL expression on the proliferation and ferroptosis of CRC cells were examined by loss-of-function assays in vitro. Bioinformatics, luciferase reporter assay and cell rescue assay were further performed to reveal the ceRNA-associated mechanism of circSTIL. CircSTIL was significantly upregulated in CRC. Cell proliferation was suppressed while ferroptosis was induced with the silencing of circSTIL in CRC cells. Interestingly, circSTIL competed with miR-431 for solute carrier family 7 member 11 (SLC7A11) binding. Additionally, miR-431 suppression or SLC7A11 overexpression overturned circSTIL silencing-mediated cell phenotypes in CRC cells. CircSTIL promotes CRC cell proliferation and suppresses ferroptosis in vitro via miR-431/SLC7A11 signaling, revealing the pathogenesis of CRC, and providing potential therapeutic targets of CRC.

The Investigation of Protein Profile and Meat Quality in Bovine Longissimus thoracic Frozen under Different Temperatures by Data-Independent Acquisition (DIA) Strategy.

The influence of freezing on the protein profile and quality traits in bovine Longissimus thoracic (LT) muscle was investigated by the data-independent acquisition (DIA) technique. Compared to fresh meat, a total of 262 proteins were identified as differential abundance proteins (DAPs) in four frozen groups (−12 °C, −18 °C, −38 °C, and −80 °C). According to the bioinformatics analysis, most of the DAPs in the significant Go terms and the KEGG pathway were structure proteins and enzymes. Proteome changes in the frozen bovine muscle at −12 °C and −18 °C were more significant than those at −38 °C and −80 °C. The result was consistent with the deterioration trend of the meat quality. The correlation analysis revealed that 17 proteins were correlated closely with the color, shear force, thawing loss, and cooking loss of the frozen meat, which could be used as putative biomarkers for frozen meat quality. MYO18A and ME3 are newly discovered proteins that are associated with frozen beef quality. In addition, CTTN and SERPINB6 were identified in frozen groups, which exhibited a significant inverse correlation with thawing loss (p < 0.01). These findings reveal the quality changes induced by freezing at the protein molecular level and provide new insights into the control of quality deterioration.

Activation of the NLRP1 inflammasome and its ligand recognition in the antibacterial immune response of common carp (Cyprinus carpio).

NLRP1 (NLR family pyrin domain containing 1) is the first member of NOD-like receptors (NLRs) which can form inflammasome and play critical roles in innate immunity and pathogenesis of various diseases. To date, many NLRs and inflammasome-related genes have been identified in teleost, however, the activation of NLRP1 inflammasome is only found in zebrafish, and the activator of fish NLRP1 is unclear. In the present study, the activation of CcNLRP1 inflammasome and its function in innate immune defence of common carp was investigated. The expression of CcNLRP1 was induced in immune-related tissues of common carp upon challenge with Edwardsiella tarda and Aeromonas hydrophila. The colocalization of CcNLRP1 and CcASC, ASC oligomerization, and interaction between CcNLRP1CARD and CcASC was observed in 293T, Hela and EPC cells, suggesting that the CcNLRP1 inflammasome was activated in common carp. Furthermore, we found that MDP may be the specific ligand of CcNLRP1, which can activate the CcNLRP1 inflammasome. Taken together, the present study identifies a new inflammasome in common carp, and is beneficial to the control of infectious diseases in carp farming.

Transcriptome analysis and protein-protein interaction in resistant and susceptible families of Japanese flounder (Paralichthys olivaceus) to understand the mechanism against Edwardsiella tarda.

Edwardsiella tarda is one of the most harmful bacterial pathogens for aquaculture flatfish. After artificial infection of 47 Japanese flounder (Paralichthys olivaceus) families, resistant and susceptible families were identified in this study. High-throughput sequencing was performed on the liver transcriptome of uninfected groups (PoRU and PoSU) and infected groups (PoRC and PoSC). Through assembly and annotation, a total of 3012 and 1386 differentially expressed genes (DEGs) were identified in PoRU vs. PoSU and PoRC vs. PoSC. The significant enrichment pathways between PoRU and PoSU were mainly in metabolic and biosynthesis pathways. A total of thirty dominant enrichment pathways between PoRC and PoSC mainly focused on some immune-related pathways, including the hematopoietic cell lineage, cytokine-cytokine receptor interaction, complement and coagulation cascades, antigen processing and presentation, the intestinal immune network for immunoglobulin A (IgA) production and T/B cell receptor signaling pathway. Under the protein-protein interaction (PPI) analysis, hub genes, including CD molecules, complement component factors and chemokines, were identified in the network, and 16 core genes were differentially expressed in resistant and sustainable families in quantitative polymerase chain reaction (qPCR) validation. This study represents the first transcriptome analysis based on resistant and susceptible families and provides resistant genes to understand the potential molecular mechanisms of antibacterial function in marine fish. The results obtained in this study provide crucial information on gene markers for resistant breeding of Japanese flounder.

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma.

Refractory/relapsed B cell lymphoma patients who received the available anti-CD19 chimeric antigen receptor (CAR) T cells may still experience a short duration of remission. Here in this study, we evaluated the safety and efficacy of a novel dominant-negative programmed cell death-1 (PD-1) armored anti-CD19 CAR T cells. A total of 9 patients (including 4 diffuse large B cell lymphomas, DLBCL, 2 transformed follicular lymphomas, TFL, and 3 follicular lymphomas, FL) received the novel CAR T cells infusion at a dose of more than 1 × 106/kg. Grade ≥ 3 cytokine release syndrome (CRS) and neurotoxicity were observed in 11.1% (n = 1/9) and 11.1% (n = 1/9) of patients, respectively. The overall response rate (ORR) was 77.8% (n = 7/9) and complete response (CR) rate was 55.6% (n = 5/9). Two patients have ongoing CR (all at 20+ months). CAR T cells expanded after infusion and continued to be detectable at 12+ months in patients with ongoing CR. This novel CD19-CAR T cell was safe and effective with durable remissions in patients with refractory/relapsed B cell lymphoma.

Real-time molecular characterization of air pollutants in a Hong Kong residence: Implication of indoor source emissions and heterogeneous chemistry.

Due to the high health risks associated with indoor air pollutants and long-term exposure, indoor air quality has received increasing attention. In this study, we put emphasis on the molecular composition, source emissions, and chemical aging of air pollutants in a residence with designed activities mimicking ordinary Hong Kong homes. More than 150 air pollutants were detected at molecular level, 87 of which were quantified at a time resolution of not less than 1 hour. The indoor-to-outdoor ratios were higher than 1 for most of the primary air pollutants, due to emissions of indoor activities and indoor backgrounds (especially for aldehydes). In contrast, many secondary air pollutants exhibited higher concentrations in outdoor air. Painting ranked first in aldehyde emissions, which also caused great enhancement of aromatics. Incense burning had the highest emissions of particle-phase organics, with vanillic acid and syringic acid as markers. The other noteworthy fingerprints enabled by online measurements included linoleic acid, cholesterol, and oleic acid for cooking, 2,5-dimethylfuran, stigmasterol, iso-/anteiso-alkanes, and fructose isomers for smoking, C28 -C34 even n-alkanes for candle burning, and monoterpenes for the use of air freshener, cleaning agents, and camphor oil. We showed clear evidence of chemical aging of cooking emissions, giving a hint of indoor heterogeneous chemistry. This study highlights the value of organic molecules measured at high time resolutions in enhancing our knowledge on indoor air quality.

Microcracks on the Rat Root Surface Induced by Orthodontic Force, Crack Extension Simulation, and Proteomics Study.

Root resorption is a common complication during orthodontic treatment. Microcracks occur on the root surface after an orthodontic force is applied and may be related to the root resorption caused by the orthodontic process. However, the mechanisms underlying root resorption induced by microcracks remain unclear. In this study, a rat orthodontic model was used to investigate the biological mechanisms of root resorption caused by microcracks. First, the first molar was loaded with 0.5-N orthodontic force for 7 days, and microcracks were observed on the root apex surface using a scanning electron microscope. Second, to describe the mechanical principle resulting in microcracks, a finite element model of rat orthodontics was established, which showed that a maximum stress on the root apex can cause microcrack extension. Third, after 7 days of loading in vivo, histological observation revealed that root resorption occurred in the stress concentration area and cementoclasts appeared in the resorption cavity. Finally, proteomics analysis of the root apex area, excluding the periodontal ligament, revealed that the NOX2, Aifm1, and MAPK signaling pathways were involved in the root resorption process. Microcrack extension on the root surface increases calcium ion concentrations, alters the proteins related to root resorption, and promotes cementoclast formation.

Proteomics analysis of the hypothalamus in spontaneously hypertensive rats treated with twirling reinforcing manipulation, twirling reducing manipulation or electroacupuncture.

Hypertension is one of the primary risk factors for cardiovascular diseases. Numerous proteins serve a critical role in hypertension. Acupuncture has been widely used as a treatment for hypertension in China. The results of the current study suggested that electroacupuncture (EA), twirling reinforcing manipulation (TRFM) and twirling reducing manipulation (TRDM) may be useful in the treatment of hypertension. Additionally, proteome analysis of spontaneously hypertensive rats treated with EA, TRFM and TRDM was performed. There were 117 (EA group), 61 (TRFM group) and 86 (TRDM group) differentially expressed proteins (DEPs) identified in the respective experimental groups compared with the model group. Moreover, parallel reaction monitoring assays were used to validate the reliability of the DEPs. The majority of the results were consistent with previous proteomics results, in particular that for expression of neudesin neurotrophic factor (NENF). NENF may potentially represent an antihypertensive drug target.

Untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease induced by high-temperature-processed feed in Sprague-Dawley rats.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. In our early clinical data and questionnaire analysis of NAFLD, it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity. The consumption of high-temperature-processed foods such as fried food, hot pot and barbecue is closely related to the occurrence of nonobese NAFLD. Reducing the intake of this kind of food can reduce disease severity and improve prognosis. AIM: To explore the untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease in Sprague-Dawley rats induced by high-temperature-processed feed. METHODS: Fifty-four male Sprague-Dawley rats were divided into three groups: The control group received a standard diet; the nonfried soybeans (NDFS) group received 60% NDFS and 40% basic feed and the dry-fried soybeans (DFS) group received 60% DFS and 40% basic feed. Six rats were sacrificed at week 4, 8, and 12 in each group. The food intake, body weight, Lee's index, liver index, serological index and hepatic histopathology were assessed. Untargeted metabolomics characteristics were used to analyze the changes in liver metabolites of rats at week 12. Correlations between metabolites and pathology scores between the DFS and control groups and between the DFS and NDFS groups were analyzed. We selected some of the metabolites, both within the pathway and outside of the pathway, to explain preliminarily the difference in liver pathology in the three groups of rats. RESULTS: There were no statistically significant differences in the food intake, body weight, Lee's index or serological index between the DFS group and the control group (P > 0.05). At week 8 and week 12, the steatosis scores in the DFS group were significantly higher than those in the other two groups (P < 0.05). At week 12, the liver index of the DFS group was the lowest (NDFS group vs DFS group, P < 0.05). The fibrosis score in the DFS group was significantly higher than those in the other two groups (P < 0.05). The correlation analysis of the liver pathology score and differential metabolites in the DFS and NDFS groups showed that there were 10 strongly correlated substances: Five positively correlated substances and five negatively correlated substances. The positively correlated substances included taurochenodeoxycholate-3-sulfate, acetylcarnitine, 20a,22b-dihydroxycholesterol, 13E-tetranor-16-carboxy-LTE4 and taurocholic acid. The negatively correlated substances included choline, cholesterane-3,7,12,25-tetrol-3-glucuronide, nicotinamide adenine dinucleotide phosphate, lysoPC [16:1 (9Z)] and glycerol 3-phosphate. The correlation analysis of the liver pathology score and differential metabolites in the DFS and control groups showed that there were 13 strongly correlated substances: Four positively correlated substances and 9 negatively correlated substances. The positively correlated substances included 4-hydroxy-6-eicosanone, 3-phosphoglyceric acid, 13-hydroxy-9-methoxy-10-oxo-11-octadecenoic acid and taurochenodeoxycholate-3-sulfate. The negatively correlated substances included lysoPC [16:1(9Z)], S-(9-hydroxy-PGA1)-glutathione, lysoPC [20:5 (5Z, 8Z, 11Z, 14Z, 17Z)], SM (d18:1/14:0), nicotinamide adenine dinucleotide phosphate, 5,10-methylene-THF, folinic acid, N-lactoyl-glycine and 6-hydroxy-5-methoxyindole glucuronide. CONCLUSION: We successfully induced liver damage in rats by using a specially prepared high-temperature-processed feed and explored the untargeted metabolomics characteristics.

Coupling 16S rDNA Sequencing and Untargeted Mass Spectrometry for Milk Microbial Composition and Metabolites from Dairy Cows with Clinical and Subclinical Mastitis.

The internal environment of the cow's udder directly affects the udder health and milk quality. 16S rDNA sequencing and liquid chromatography-mass spectrometry (LC-MS) methods were used to investigate the significant differences in milk microbial diversity and metabolites among cows that are healthy (H) and those suffering from subclinical mastitis (SM) and clinical mastitis (CM). Results uncovered more than 16 and 192 differently abundant microbiota at the phylum and genus levels, respectively, and 673 different levels of metabolites enriched in 20 pathways in milk among the 3 groups. This study revealed the positive relevance between Staphylococcus and Streptococcus and ceramide in milk from CM cows. Similarly, Acinetobacter and Corynebacterium were positively associated with testosterone glucuronide and 5-methyl-tetrahydrofolate, in milk from SM cows. On the basis of the combined analysis of microbiome and metabolome, this study indicated that, apart from the exogenous pathogens, some beneficial symbiotic bacteria, such as Dietzia, Aeromicrobium, Alistipes, and Sphingobacterium, rarely reported in milk have been found to be significantly reduced during mastitis.

Analysis of Difference in Microbial Community and Physicochemical Indices Between Surface and Central Parts of Chinese Special-Flavor Baijiu Daqu.

Special-flavor Baijiu is a unique Baijiu in Jiangxi Province, China, whose uniqueness mainly depends on the unique production process of special-flavor Baijiu Daqu. However, the microbial structure and physicochemical indices of different parts of the special-flavor Baijiu Daqu are still unknown. This greatly reduces the actual value of Daqu in the production of special-flavor Baijiu. Therefore, culture-dependent and Illumina MiSeq sequencing methods were used to analyze the microbial structure of special-flavor Baijiu Daqu. The results indicated that there was a complicated microbial diversity in Chinese special-flavor Baijiu Daqu. The predominant bacterial communities were Bacillales, Lactobacillales, and Rhodospirillales, while Saccharomycetales and Eurotiales were the predominant fungal communities. Significant differences in microbial community and distribution were shown between the surface and central parts of Daqu. Acetobacter and Pichia genera were the predominant microorganisms in the surface part of Daqu, whereas Aspergillus, Kroppenstedtia, Oceanobacillus, and Bacillus genera were the predominant microorganisms in the central part of Daqu. Meantime, the different microbial distributions between the surface and central parts of Daqu caused the significant differences in the physicochemical indices. These results can provide an important theoretical basis for improving the brewing process and the quality of special-flavor Baijiu.

Altered profiles of fecal metabolites correlate with visceral hypersensitivity and may contribute to symptom severity of diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Fecal metabolites are associated with gut visceral sensitivity, mucosal immune function and intestinal barrier function, all of which have critical roles in the pathogenesis of irritable bowel syndrome (IBS). However, the metabolic profile and pathophysiology of IBS are still unclear. We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea (IBS-D). AIM: To investigate the fecal metabolite composition and the role of metabolites in IBS-D pathophysiology. METHODS: Thirty IBS-D patients and 15 age- and sex-matched healthy controls (HCs) underwent clinical and psychological assessments, including the IBS Symptom Severity System (IBS-SSS), an Italian modified version of the Bowel Disease Questionnaire, the Bristol Stool Form Scale (BSFS), the Hospital Anxiety and Depression Scale, and the Visceral Sensitivity Index. Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator. Fecal metabolites, including amino acids and organic acids, were measured by targeted metabolomics approaches. Correlation analyses between these parameters were performed. RESULTS: The patients presented with increased stool water content, more psychological symptoms and increased visceral hypersensitivity compared with the controls. In fecal metabolites, His [IBS-D: 0.0642 (0.0388, 0.1484), HC: 0.2636 (0.0780, 0.3966), P = 0.012], Ala [IBS-D: 0.5095 (0.2826, 0.9183), HC: 1.0118 (0.6135, 1.4335), P = 0.041], Tyr [IBS-D: 0.1024 (0.0173, 0.4527), HC: 0.5665 (0.2436, 1.3447), P = 0.018], Phe [IBS-D: 0.1511 (0.0775, 0.3248), HC: 0.3967 (0.1388, 0.7550), P = 0.028], and Trp [IBS-D: 0.0323 (0.0001, 0.0826), HC: 0.0834 (0.0170, 0.1759), P = 0.046] were decreased in IBS-D patients, but isohexanoate [IBS-D: 0.0127 (0.0060, 0.0246), HC: 0.0070 (0.0023, 0.0106), P = 0.028] was significantly increased. Only Tyr was mildly correlated with BSFS scores in all subjects (r = -0.347, P = 0.019). A possible potential biomarker panel was identified to correlate with IBS-SSS score (R 2 Adjusted = 0.693, P < 0.001). In this regression model, the levels of Tyr, Val, hexanoate, fumarate, and pyruvate were significantly associated with the symptom severity of IBS-D. Furthermore, visceral sensation, including abdominal pain and visceral hypersensitivity, was correlated with isovalerate, valerate and isohexanoate. CONCLUSION: Altered profiles of fecal metabolites may be one of the origins or exacerbating factors of symptoms in IBS-D via increasing visceral sensitivity.

Green synthesis of mesoporous γ-Al2O3 from coal fly ash with simultaneous on-site utilization of CO2.

Mesoporous Al2O3 with crystalline framework walls has expanded all over the world due to the various potential applications especially in catalysis. Here, we develop a green and facile approach for the conversion of coal fly ash (CFA) into ordered mesoporous γ-Al2O3. The practical and promising lime-sinter method was comprehensively studied for the extraction of aluminum from CFA as a first step. The extraction efficiency of aluminum could reach up to 87.42%, through calcining with CaCO3 at 1390°C for 1 h and then dissolving in Na2CO3 solution at 70°C for 0.5 h. Combined with the urgent demand for CO2 emission reduction, simulated purified flue gas was introduced to precipitate the Al(OH)3 precursors without structure-directing agents for just 1 h, followed by calcining at only 400°C or 550°C. A series of characterizations were conducted to discuss the effect of precipitation temperature and calcination temperature, resulting the superior product (Al2O3-65/550) with high surface area (230.3 m2 g-1), crystalline γ-Al2O3 phase and ordered mesostructure. This proposed strategy, integrating the on-site recycling of CFA and utilization of CO2, appears to be promising for scalable production of mesoporous γ-Al2O3.