Fermentation Characteristics of Fermented Milk with Streptococcus thermophilus CICC 6063 and Lactobacillus helveticus CICC 6064 and Volatile Compound Dynamic Profiles during Fermentation and Storage.

The lactic acid bacteria Streptococcus thermophilus and Lactobacillus helveticus are commonly used as starter cultures in dairy product production. This study aimed to investigate the characteristics of fermented milk using different ratios of these strains and analyze the changes in volatile compounds during fermentation and storage. A 10:1 ratio of Streptococcus thermophilus CICC 6063 to Lactobacillus helveticus CICC 6064 showed optimal fermentation time (4.2 h), viable cell count (9.64 log10 colony-forming units/mL), and sensory evaluation score (79.1 points). In total, 56 volatile compounds were identified and quantified by solid-phase microextraction and gas chromatography-mass spectrometry (SPME-GC-MS), including aldehydes, ketones, acids, alcohols, esters, and others. Among these, according to VIP analysis, 2,3-butanedione, acetoin, 2,3-pentanedione, hexanoic acid, acetic acid, acetaldehyde, and butanoic acid were identified as discriminatory volatile metabolites for distinguishing between different time points. Throughout the fermentation and storage process, the levels of 2,3-pentanedione and acetoin exhibited synergistic dynamics. These findings enhance our understanding of the chemical and molecular characteristics of milk fermented with Streptococcus thermophilus and Lactobacillus helveticus, providing a basis for improving the flavor and odor of dairy products during fermentation and storage.

Intestinal adipocytes transdifferentiate into myofibroblast-like cells and contribute to fibrosis in Crohn's disease.

BACKGROUND AND AIMS: Intestinal fibrotic stenosis is a major reason for surgery in Crohn's disease [CD], but the mechanism is unknown. Thus, we asked whether intestinal adipocytes contribute to intestinal fibrosis. Adipocytes were found to transdifferentiate into myofibroblasts and confirmed to be involved in mesenteric fibrosis in our recent study. Here, we investigated the role and possible mechanisms of intestinal adipocytes in intestinal fibrosis in CD. METHODS: The intestinal tissue of patients with CD with or without fibrotic stenosis [CDS or CDN] and normal intestinal tissue from individuals without CD were obtained to assess alterations in submucosal adipocytes in CDS and whether these cells transdifferentiated into myofibroblasts and participated in the fibrotic process. Human primary adipocytes and adipose organoids were used to evaluate whether adipocytes could be induced to transdifferentiate into myofibroblasts and to investigate the fibrotic behaviour of adipocytes. LPS/TLR4/TGF-ß signalling was also studied to explore the underlying mechanism. RESULTS: Submucosal adipocytes were reduced in number or even absent in CDS tissue, and the extent of the reduction correlated negatively with the degree of submucosal fibrosis. Interestingly, submucosal adipocytes in CDS tissue transdifferentiated into myofibroblast-like cells and expressed collagenous components, possibly due to stimulation by submucosally translocated bacteria. LPS-stimulated human primary adipocytes and adipose organoids also exhibited transdifferentiation and profibrotic behaviour. Mechanistically, TLR4-mediated TGF-ß signalling was associated with the transdifferentiation and profibrotic behaviour of intestinal adipocytes in CDS tissue. CONCLUSIONS: Intestinal adipocytes transdifferentiate into myofibroblasts and participate in the intestinal fibrosis process in CD, possibly through LPS/TLR4/TGF-ß signalling.

Backbone cyclization of Salmonella typhimurium diaminopropionate ammonia-lyase to enhance the activity and stability.

Diaminopropionate ammonia-lyase transforms D and L isomers of 2,3-diaminopropionate to pyruvate and ammonia. It catalyzes D- and l-serine less effectively. L-2,3-diaminopropionate is a precursor in the biosynthesis of oxalyl diaminopropionate as a neurotoxin in certain legume species. In this work, we cyclized the diaminopropionate ammonia-lyase from Salmonella typhimurium in vitro using the redox-responsive split intein, and identified that backbone cyclization afforded the enzyme with the improved activity, thermal stability and resistance to the exopeptidase proteolysis, different from effects of the incorporated sequence recognized by tobacco vein mottling virus protease at C-terminus. Using analyses of three fluorescent dyes including 8-anilino-1-naphthalenesulfonic acid, N-phenyl-1-naphthylamine, and thioflavin T, the same amounts of the cyclic protein displayed less fluorescence than those of the linear protein upon the heat treatment. The cyclic enzyme displayed the enhanced activity in Escherichia coli cells using the designed novel reporter. In this system, d-serine was added to the culture and transported into the cytoplasm. It was transformed by pre-overexpression of the diaminopropionate ammonia-lyase, and untransformed d-serine was oxidized by the coproduced human d-amino acid oxidase to generate hydrogen peroxide. This oxidant is monitored by the HyPer indicator. The current results presented that the cyclized enzyme could be applied as a better candidate to block the neurotoxin biosynthesis in certain plant species.

Magnetic resonance guided adaptive post prostatectomy radiotherapy: Accumulated dose comparison of different workflows.

PURPOSE: The aim of this study was to assess the use of magnetic resonance guided adaptive radiotherapy (MRgART) in the post-prostatectomy setting; comparing dose accumulation for our initial seven patients treated with fully adaptive workflow on the Unity MR-Linac (MRL) and with non-adaptive plans generated offline. Additionally, we analyzed toxicity in patients receiving treatment. METHODS: Seven patients were treated with MRgART. The prescription was 70-72 Gy in 35-36 fractions. Patients were treated with an adapt to shape (ATS) technique. For each clinically delivered plan, a non-adaptive plan based upon the reference plan was generated and compared to the associated clinically delivered plan. A total of 468 plans were analyzed. Concordance Index of target and Organs at Risk (OARs) for each fraction with reference contours was analyzed. Acute toxicity was then assessed at six-months following completion of treatment with Common Terminology for Adverse Events (CTCAE) Toxicity Criteria. RESULTS: A total of 246 fractions were clinically delivered to seven patients; 234 fractions were delivered via MRgART and 12 fractions delivered via a traditional linear accelerator due to machine issues. Pre-treatment reference plans met CTV and OAR criteria. PTV coverage satisfaction was higher in the clinically delivered adaptive plans than non-adaptive comparison plans; 42.93% versus 7.27% respectively. Six-month CTCAE genitourinary and gastrointestinal toxicity was absent in most patients, and mild-to-moderate in a minority of patients (Grade 1 GU toxicity in one patient and Grade 2 GI toxicity in one patient). CONCLUSIONS: Daily MRgART treatment consistently met planning criteria. Target volume variability in prostate bed treatment can be mitigated by using MRgART and deliver satisfactory coverage of CTV whilst minimizing dose to adjacent OARs and reducing toxicity.

Targeting adenosine A2A receptors for early intervention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) continues to pose a significant threat to the vision of numerous children worldwide, primarily owing to the increased survival rates of premature infants. The pathologies of ROP are mainly linked to impaired vascularization as a result of hyperoxia, leading to subsequent neovascularization. Existing treatments, including anti-vascular endothelial growth factor (VEGF) therapies, have thus far been limited to addressing pathological angiogenesis at advanced ROP stages, inevitably leading to adverse side effects. Intervention to promote physiological angiogenesis during the initial stages could hold the potential to prevent ROP. Adenosine A2A receptors (A2AR) have been identified in various ocular cell types, exhibiting distinct densities and functionally intricate connections with oxygen metabolism. In this review, we discuss experimental evidence that strongly underscores the pivotal role of A2AR in ROP. In particular, A2AR blockade may represent an effective treatment strategy, mitigating retinal vascular loss by reversing hyperoxia-mediated cellular proliferation inhibition and curtailing hypoxia-mediated neovascularization in oxygen-induced retinopathy (OIR). These effects stem from the interplay of endothelium, neuronal and glial cells, and novel molecular pathways (notably promoting TGF-ß signaling) at the hyperoxia phase. We propose that pharmacological targeting of A2AR signaling may confer an early intervention for ROP with distinct therapeutic benefits and mechanisms than the anti-VEGF therapy.

Identification and quantification of viable Lacticaseibacillus rhamnosus in probiotics using validated PMA-qPCR method.

The identification and quantification of viable bacteria at the species/strain level in compound probiotic products is challenging now. Molecular biology methods, e.g., propidium monoazide (PMA) combination with qPCR, have gained prominence for targeted viable cell counts. This study endeavors to establish a robust PMA-qPCR method for viable Lacticaseibacillus rhamnosus detection and systematically validated key metrics encompassing relative trueness, accuracy, limit of quantification, linear, and range. The inclusivity and exclusivity notably underscored high specificity of the primers for L. rhamnosus, which allowed accurate identification of the target bacteria. Furthermore, the conditions employed for PMA treatment were fully verified by 24 different L. rhamnosus including type strain, commercial strains, etc., confirming its effective discrimination between live and dead bacteria. A standard curve constructed by type strain could apply to commercial strains to convert qPCR Cq values to viable cell numbers. The established PMA-qPCR method was applied to 46 samples including pure cultures, probiotics as food ingredients, and compound probiotic products. Noteworthy is the congruity observed between measured and theoretical values within a 95% confidence interval of the upper and lower limits of agreement, demonstrating the relative trueness of this method. Moreover, accurate results were obtained when viable L. rhamnosus ranging from 103 to 108 CFU/mL. The comprehensive appraisal of PMA-qPCR performances provides potential industrial applications of this new technology in quality control and supervision of probiotic products.

Development of a SNP-based strain-identified method for Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047 using pan-genomics analysis.

The health benefits conferred by probiotics is specific to individual probiotic strains, highlighting the importance of identifying specific strains for research and production purposes. Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047 are exceedingly valuable for commercial use with an excellent mixed-culture fermentation. To differentiate these 2 strains from other S. thermophilus and L. delbrueckii ssp. bulgaricus, a specific, sensitive, accurate, rapid, convenient, and cost-effective method is required. In this study, we conducted a pan-genome analysis of S. thermophilus and L. delbrueckii ssp. bulgaricus to identify species-specific core genes, along with strain-specific single-nucleotide polymorphisms (SNPs). These genes were used to develop suitable PCR primers, and the conformity of sequence length and unique SNPs was confirmed by sequencing for qualitative identification at the strain level. The results demonstrated that SNPs analysis of PCR products derived from these primers could distinguish CICC 6038 and CICC 6047 accurately and reproducibly from the other strains of S. thermophilus and L. delbrueckii ssp. bulgaricus, respectively. The strain-specific PCR method based on SNPs herein is universally applicable for probiotics identification. It offers valuable insights into identifying probiotics at the strain level that is fit-for-purpose in quality control and compliance assessment of commercial dairy products.

Selection and application of highly specific Salmonella typhimurium aptamers against matrix interference.

In practical applications, the structure and performance of aptamers can be influenced by the presence of sample matrices, which interferes with the specific binding between the aptamer and its target. In this work, to obtain aptamer chains resistant to matrix interference, four typical food matrices were introduced as negative selection targets and selection environments in the process of selecting aptamers for Salmonella typhimurium using the systematic evolution of ligands by exponential enrichment (SELEX) technology. As a result, some highly specific candidate aptamers for Salmonella typhimurium (BB-34, BB-37, ROU-8, ROU-9, ROU-14, ROU-24, DAN-3, NAI-12, and NAI-21) were successfully obtained. Based on the characterization results of secondary structure, affinity, and specificity of these candidate aptamers, ROU-24 selected in the pork matrix and BB-34 selected in the binding buffer were chosen to develop label-free fluorescence aptasensors for the sensitive and rapid detection of the Salmonella typhimurium and verify the performance against matrix interference. The ROU-24-based aptasensor demonstrated a larger linear range and better specificity compared to the BB-34-based aptasensor. Meanwhile, the recovery rate of the ROU-24-based aptasensor in real sample detection (ranging from 94.2% to 110.7%) was significantly higher than that of the BB-34-based aptasensor. These results illustrated that the negative selection of food matrices induced in SELEX could enhance specific binding between the aptamer and its target and the performance against matrix interference. Overall, the label-free fluorescence aptasensors were developed and successfully validated in different foodstuffs, demonstrating a theoretical and practical basis for the study of aptamers against matrix interference.

A gas-driven capillary based on the synergy of the catalytic and photothermal effect of PB@Au for Salmonella typhimurium detection.

Rapid detection method for Salmonella typhimurium is vital to prevent the spread of food-borne diseases. In this work, a gas-driven capillary detection method was established to achieve sensitive and rapid detection of Salmonella typhimurium using the catalytic and photothermal synergy of Prussian blue-nanogold (PB@Au) nanomaterials. The immuno-PB@Au probe attached to the capillary by specific identification of target bacteria catalyzed the H2O2 under laser irradiation, driving the H2O2 liquid column to move (ΔL) by producing gas, and achieving the quantitative detection of Salmonella typhimurium. After detailed optimization of the critical performance parameters of the gas-driven capillary assay, the limit of detection (LOD) after laser irradiation and being catalyzed by PB@Au was calculated to be 37 CFU mL-1 through the determination of different concentrations of target bacteria. Furthermore, the detection performances of the gas-driven capillary method were evaluated in detail, and the recoveries ranging from 92.9 ± 4.7 % to 107.7 ± 4.1 % were achieved using the spiked actual samples with complex matrices, indicating that the established rapid assay can offer promising strategies for the monitoring and controlling of food-borne pathogenic bacteria.

Fermentation characteristics and postacidification of yogurt by Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047 at optimal inoculum ratio.

This study aimed to investigate the symbiosis between Streptococcus thermophilus CICC 6038 and Lactobacillus delbrueckii ssp. bulgaricus CICC 6047. In addition, the effect of their different inoculum ratios was determined, and comparison experiments of fermentation characteristics and storage stability of milk fermented by their monocultures and cocultures at optimal inoculum ratio were performed. We found the time to obtain pH 4.6 and ΔpH during storage varied among 6 inoculum ratios (1:1, 2:1, 10:1, 19:1, 50:1, 100:1). By the statistical model to evaluate the optimal ratio, the ratio of 19:1 was selected, which exhibited high acidification rate and low postacidification with pH values remaining between 4.2 and 4.4 after a 50-d storage. Among the 3 groups included in our analyses (i.e., the monocultures of S. thermophilus CICC 6038 [St] and Lb. bulgaricus CICC 6047 [Lb] and their cocultures [St+Lb] at 19:1), the coculture group showed higher acidification activity, improved rheological properties, richer typical volatile compounds, more desirable sensor quality after the fermentation process than the other 2 groups. However, the continuous accumulation of acetic acid during storage showed that acetic acid was more highly correlated with postacidification than d-lactic acid for the Lb group and St+Lb group. Our study emphasized the importance of selecting an appropriate bacterial consortium at the optimal inoculum ratio to achieve favorable fermentation performance and enhanced postacidification stability during storage.

Optimized carbonization of coffee shell via response surface methodology: A circular economy approach for environmental remediation.

The disposal of coffee shell waste on farmland, is a common practice that can causing the environmental and waste valuable resources. Carbonization has been identified as an effective method for transforming coffee shells into useful products that mitigate environmental pollution. Through the response surface methodology, the carbonization conditions of the coffee shells were optimized and its potential as a biochar-based slow-release urea fertilizer was explored. Experiments were conducted on coffee shell performance under varying carbonization conditions such as temperature (600-1000 °C), time (1-5 h), and heating rate (5-20 °C/min). The results indicated that the ideal urea adsorption was 56.3 mg/g, achieved under carbonization conditions of 2.83 h, 809 °C, and 15.3 °C/min. The optimal nutrient release rate within seven days was 45.4% under carbonization conditions of 3.19 h, 813 °C, and 15.0 °C/min. The infrared spectroscopy analysis indicates that carbonization conditions influenced the absorption peak intensity of coffee shell biochar, while the functional group types remain unchanged. The biochar exhibits diverse functional groups and abundant pores, making it a promising candidate for use as a biochar-based fertilizer material. Overall, the findings demonstrate an effective waste management approach that significantly reduces environmental pollutants while remediating pollution.

Radiogenomic analysis of cellular tumor-stroma heterogeneity as a prognostic predictor in breast cancer.

BACKGROUND: The tumor microenvironment and intercellular communication between solid tumors and the surrounding stroma play crucial roles in cancer initiation, progression, and prognosis. Radiomics provides clinically relevant information from radiological images; however, its biological implications in uncovering tumor pathophysiology driven by cellular heterogeneity between the tumor and stroma are largely unknown. We aimed to identify radiogenomic signatures of cellular tumor-stroma heterogeneity (TSH) to improve breast cancer management and prognosis analysis. METHODS: This retrospective multicohort study included five datasets. Cell subpopulations were estimated using bulk gene expression data, and the relative difference in cell subpopulations between the tumor and stroma was used as a biomarker to categorize patients into good- and poor-survival groups. A radiogenomic signature-based model utilizing dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was developed to target TSH, and its clinical significance in relation to survival outcomes was independently validated. RESULTS: The final cohorts of 1330 women were included for cellular TSH biomarker identification (n = 112, mean age, 57.3 years ± 14.6) and validation (n = 886, mean age, 58.9 years ± 13.1), radiogenomic signature of TSH identification (n = 91, mean age, 55.5 years ± 11.4), and prognostic (n = 241) assessments. The cytotoxic lymphocyte biomarker differentiated patients into good- and poor-survival groups (p < 0.0001) and was independently validated (p = 0.014). The good survival group exhibited denser cell interconnections. The radiogenomic signature of TSH was identified and showed a positive association with overall survival (p = 0.038) and recurrence-free survival (p = 3 × 10-4). CONCLUSION: Radiogenomic signatures provide insights into prognostic factors that reflect the imbalanced tumor-stroma environment, thereby presenting breast cancer-specific biological implications and prognostic significance.

[Effects of Cytokines on Early Death in Patients with Newly Diagnosed Acute Promyelocytic Leukemia].

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION: Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.

Backbone Cyclization of Flavin Mononucleotide-Based Fluorescent Protein Increases Fluorescence and Stability.

Flavin mononucleotide-binding proteins or domains emit cyan-green fluorescence under aerobic and anaerobic conditions, but relatively low fluorescence and less thermostability limit their application as reporters. In this work, we incorporated the codon-optimized fluorescent protein from Chlamydomonas reinhardtii with two different linkers independently into the redox-responsive split intein construct, overexpressed the precursors in hyperoxic Escherichia coli SHuffle T7 strain, and cyclized the target proteins in vitro in the presence of the reducing agent. Compared with the purified linear protein, the cyclic protein with the short linker displayed enhanced fluorescence. In contrast, cyclized protein with incorporation of the long linker including the myc-tag and human rhinovirus 3C protease cleavable sequence emitted slightly increased fluorescence compared with the protein linearized with the protease cleavage. The cyclic protein with the short linker also exhibited increased thermal stability and exopeptidase resistance. Moreover, induction of the target proteins in an oxygen-deficient culture rendered fluorescent E. coli BL21 (DE3) cells brighter than those overexpressing the linear construct. Thus, the cyclic reporter can hopefully be used in certain thermophilic anaerobes.

Use of the selected metal-dependent enzymes for exploring applicability of human annexin A1 as a purification tag.

Several fusion tags have been developed for non-chromatographic fusion protein purification. Previously, we identified that human annexin A1 as a novel N-terminal purification tag was used for purifying the fusion proteins produced in Escherichia coli through precipitation in 10 mM Ca2+ buffer, and redissolution of the precipitate in 15 mM EDTA buffer. In this work, we selected four metal-dependent enzymes including E. coli 5-aminolevulinate dehydratase, yeast 3-hydroxyanthranilate 3,4-dioxygenase, maize serine racemase and copper amine oxidase for investigating the annexin A1 tag applicability. Fusion of the His6-tag or the enzyme changed the behavior of precipitation-redissolution. The relatively high recovery yields of three tagged enzymes with the improved purities were obtained through two rounds of purification, whereas low recovery yield of the annexin A1 tagged maize amine oxidase was prepared. The added EDTA displayed different abilities to redissolve the fusion proteins precipitates in two precipitation-redissolution cycles. It inactivated three enzymes and obviously inhibited the activity of the fused maize serine racemase. Based on current findings, we believe that four enzymes could be applied for evaluating applicability of the proteins or peptides as affinity tags for chromatographic purification in a calcium dependent manner.

Catalytic hydrothermal liquefaction of alkali lignin for monophenols production over homologous biochar-supported copper catalysts in water.

Constructing an advanced catalytic system for the purposeful liquefaction of lignin into chemicals has presented a significant prospect for sustainable development. In this work, the catalytic process of mesoporous homologous biochar (HBC) derived from alkali lignin supported copper catalysts (Cu/HBC) was reported for catalytic liquefaction of alkali lignin to monophenols. The characterization results revealed HBC promoted the formation of metal-support strong interaction and the generation of oxygen vacancies, enhancing the acid sites of Cu/HBC. Under the optimal conditions (0.2 g alkali lignin, 280 °C, 0.05 g Cu/HBC, 6 h, 18 mL water), the monophenol yield reached 75.01 ± 0.76 mg/g, and the bio-oil yield was 57.98 ± 1.76%. The copious mesopores, high surface area, and rich acidic sites were responsible for the high activity of Cu/HBC, which significantly outperformed the controlled catalysts, such as HBC, commercial activated carbon (AC), and reported Ni/AC, Ni/MCM-41, etc. In four consecutive runs, the catalytic performance of Cu/HBC was only reduced by 3.65% per cycle. Interestingly, catechol was selectively produced with Cu/HBC, which provided an effective strategy for the conversion of G/S-type lignin to catechyl phenolics (C-type). These findings indicate that the Cu/HBC will be a promising substitution of noble metal-supported catalysts for conversion biomass into high value-added phenolics.

Construction of a fecal immune-related protein-based biomarker panel for colorectal cancer diagnosis: a multicenter study.

Purpose: To explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis. Patients and methods: Three independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC). Results: In the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue. Conclusion: A novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.

Bryostatin-1 attenuates intestinal ischemia/reperfusion-induced intestinal barrier dysfunction, inflammation, and oxidative stress via activation of Nrf2/HO-1 signaling.

Bryostatin-1 (Bryo-1) exerts antioxidative stress effects in multiple diseases, and we confirmed that it improves intestinal barrier dysfunction in experimental colitis. Nevertheless, there are few reports on its action on intestinal ischemia/reperfusion (I/R). In this study, we mainly explored the effect of Bryo-1 on intestinal I/R injury and determined the mechanism. C57BL/6J mice underwent temporary superior mesenteric artery (SMA) obturation to induce I/R, on the contrary, Caco-2 cells suffered to oxygen and glucose deprivation/reperfusion (OGD/R) to establish the in vitro model. RAW264.7 cells were stimulated with LPS to induce macrophage inflammation. The drug gradient experiment was used to demonstrate in vivo and in vitro models. Bryo-1 ameliorated the intestinal I/R-induced injury of multiple organs and epithelial cells. It also alleviated intestinal I/R-induced barrier disruption of intestines according to the histology, intestinal permeability, intestinal bacterial translocation rates, and tight junction protein expression results. Bryo-1 significantly inhibited oxidative stress damages and inflammation, which may contribute to the restoration of intestinal barrier function. Further, Bryo-1 significantly activated Nrf2/HO-1 signaling in vivo. However, the deletion of Nrf2 in Caco-2 and RAW264.7 cells attenuated the protective functions of Bryo-1 and significantly abolished the anti-inflammatory effect of Bryo-1 on LPS-induced macrophage inflammation. Bryo-1 protects intestines against I/R-induced injury. It is associated with intestinal barrier protection, as well as inhibition of inflammation and oxidative stress partly through Nrf2/HO-1 signaling.

Low-temperature highly selective water delignification based on geopolymer materials.

Delignification pretreatment is the main source of high cost and high pollution in biomass processing. This paper reports on a simple cheap geopolymers-based highly selective and efficient pretreatment process for delignification under low-temperature water-cooking without discharging black liquor. The geopolymer with a SiO2/Al2O3 ratio of 4.4 showed the largest number of acidic sites and highest catalytic activity. Under mild reaction conditions (mGeopolymer/mFiber = 1/4, 90 min and 90 °C), the delignification rates of woody (eucalyptus) and herbaceous (bagasse) biomass increased by up to 38.90% and 62.20%, respectively. Moreover, the low-alkali black liquor produced by the new water delignification process facilitates subsequent water treatment, eliminating the need for alkali recovery. This study confirms the immense application prospects of geopolymers for the highly selective delignification of most biomass fibre. This study will develop a low-temperature water-cooking process for the delignification of papermaking or biomass processing without wastewater discharge.