Yinhuang buccal tablet alters airway microbiota composition and metabolite profile in healthy humans.

ETHNOPHARMACOLOGICAL RELEVANCE: Perturbations in airway microbiota composition and disruption of microbe-metabolite interactions have been observed in respiratory infectious diseases (RIDs). The Yinhuang (YH) buccal tablet, as an ancient Chinese medicinal formula, has been traditionally employed for the management of upper RIDs. However, there is a lack of evidence for the effects of YH buccal tablets on upper respiratory tract microbiota and circulating metabolites. AIM OF THE STUDY: The aim of this study was to analyze the changes in respiratory microbiota composition and circulating metabolite profile after YH buccal tablets administration. MATERIALS AND METHODS: Throat swab samples and serum samples were collected from 60 healthy subjects for high-throughput 16S ribosomal RNA gene (16S rRNA) sequencing and non-targeted Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. RESULTS: Airway microbial composition changed significantly after YH administration. The abundance of Actinomyces and Prevotella_7 increased, while the abundance of potentially pathogenic Pseudomonas and Corynebacterium decreased. A total of 168 significant HMDB taxonomic metabolites were identified in serum samples, of which lipid metabolites accounted for the largest proportion. Correlation analysis showed that circulatory metabolites were significantly correlated with changes in airway microbiota composition. CONCLUSIONS: YH buccal tablets can inhibit opportunistic pathogens, increase beneficial microorganisms in the upper respiratory tract, and regulate the body's metabolic pathways. These findings provide insights into the mechanism of action of YH buccal tablets in the treatment and prevention of respiratory diseases.

Analysis of metabolic differences between Jiaosu fermented from dendrobium flowers and stems based on untargeted metabolomics.

Dendrobium officinale is an important traditional Chinese medicinal herb containing bioactive polysaccharides and alkaloids. This study characterized metabolite differences between jiaosu (fermented plant product) from Dendrobium flowers versus stems using untargeted metabolomics. The jiaosu was fermented by mixed fermentation of Saccharomyces cerevisiae, Lactobacillus bulgaricus and Streptococcus thermophilus. Liquid chromatography-mass spectrometry analysis identified 476 differentially expressed metabolites between the two Jiaosu products. Key results showed downregulation of flavonoid metabolism in Dendrobium Stems Edible Plant Jiaosu (SEP) but increased flavonoid synthesis in Dendrobium Flowers Edible Plant Jiaosu (FEP), likely an antioxidant response. SEP displayed upregulation of lignin metabolites with potential antioxidant properties. The findings demonstrate significant metabolite profile differences between SEP and FEP, providing the basis for developing functional jiaosu products targeting specific health benefits.

The multi-scale structure changes of γ-ray irradiated potato starch to mitigate pasting/digestion properties.

The comprehensive understanding of multi-scale structure of starch and how the structure regulates the pasting/digestion properties remain unclear. This work investigated the effects of γ-ray irradiation with different doses on multi-scale structure and pasting/digestion properties of potato starch. Results indicated that γ-ray at lower doses (<20 kGy) had little effect on micromorphology of starch, increased mainly the amylose content and the thickness of amorphous region while decreased crystallinity, double helix content and lamellar ordering. With the increase of dose, the internal structure of large granules was destroyed, resulting in the depolymerization of starch to form more short-chains and to reduce molecular weight. Meanwhile, amylose content decreased due to the depolymerization of amylose. The enhanced double helix content, crystallinity, lamellar ordering and structural compactness manifested the formation of the thicker and denser starch structure. These structure changes resulted in the decreased viscosity, the increased stability and anti- digestibility of paste.

Meta-analysis of selenium effects on the meat quality of broilers.

The effects of sodium selenite or selenium yeast on the meat quality of broilers were searched in the literature published in the Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), PubMed, Web of Science, and Science Direct databases from January 1, 2010 to December 31, 2022. Meta-analysis was performed with Stata software (StataCorp. 2011), and the standardized mean difference (SMD) and its 95% confidence interval (CI) were calculated using a random effects model. Twenty of the identified 846 literature sources, which included 791 broilers, were screened. The meat quality indices considered were shear force, drip loss, cooking loss, water holding capacity (WHC), pH, and color. The source of heterogeneity was studied using sensitivity and subgroup analyses, and publication bias was evaluated using funnel plots. The results showed that the supplementation of selenium in the broiler diet significantly reduced the shear force (SMD = -0.67, 95% CI [-1.12, -0.22], P < 0.05) and drip loss (SMD = -0.84, 95% CI [-1.39, -0.30], P < 0.05) and increased the pH (SMD = 0.38, 95% CI [0.01, 0.75], P < 0.05) of broiler breast muscle; however, it had no significant effects on other indices. Funnel plots revealed a slight publication bias in the shear force and pH of breast muscle but none in the drip loss of breast muscle. The sensitivity analysis showed that the results were stable and reliable. In conclusion, selenium supplementation in broiler feed can improve some indices of broiler meat quality, and its inclusion in broiler diets is recommended, in conjunction with other minerals, which is of great significance to improve the quality, preservation time and economic benefits of chicken products.

Two rearranged acylphloroglucinols with moderate neuroprotective effects from Hypericum ascyron Linn.

Phytochemical studies on the leaves and twigs of Hypericum ascyron Linn. led to the isolation of two previously undescribed rearranged polycyclic polyprenylated acylphloroglucinols (PPAP) with a 4,5-seco-3(2H)-furanone skeleton, named hyperascone A and B (1-2). Additionally, a known PPAP tomoeone A (3) and two known xanthones 1,3,5 -trihydroxy-6-O-prenylxanthone (4) and 3,7-dihydroxy-1,6-dimethoxyxanthone (5) were also isolated. The structures of the compounds were determined by the analysis of their spectroscopic data including HRMS, NMR and ECD. All of the five isolated compounds exhibited neuroprotective effects against MPP+ and microglia activation induced damage of SH-SY5Y cells.

Carnosol alleviates sepsis-induced pulmonary endothelial barrier dysfunction by targeting nuclear factor erythroid2-related factor 2/sirtuin-3 signaling pathway to attenuate oxidative damage.

Excessive reactive oxygen species production during acute lung injury (ALI) will aggravate the inflammatory process and endothelial barrier dysfunction. Carnosol is a natural phenolic diterpene with antioxidant and anti-inflammatory properties, but its role in treating sepsis-induced ALI remains unclear. This study aims to explore the protective effects and underlying mechanisms of carnosol in sepsis-induced ALI. C57BL/6 mouse were preconditioned with carnosol for 1 h, then the model of lipopolysaccharide (LPS)-induced sepsis was established. The degree of pulmonary edema, oxidative stress, and inflammation were detected. Endothelial barrier function was evaluated by apoptosis and cell junctions. In vitro, Mito Tracker Green probe, JC-1 staining, and MitoSOX staining were conducted to investigate the effect of carnosol on mitochondria. Finally, we investigated the role of nuclear factor-erythroid 2-related factor (Nrf2)/sirtuin-3 (SIRT3) in carnosol against ALI. Carnosol alleviated LPS-induced pulmonary oxidative stress and inflammation by inhibiting excess mitochondrial reactive oxygen species production and maintaining mitochondrial homeostasis. Furthermore, carnosol also attenuated LPS-induced endothelial cell barrier damage by reducing vascular endothelial cell apoptosis and restoring occludin, ZO-1, and vascular endothelial-Cadherin expression in vitro and in vivo. In addition, carnosol increased Nrf2 nuclear translocation to promote SIRT3 expression. The protective effects of carnosol on ALI were largely abolished by inhibition of Nrf2/SIRT3. Our study has provided the first evidence that the Nrf2/SIRT3 pathway is a protective target of the endothelial barrier in ALI, and carnosol can serve as a potential therapeutic candidate for ALI by utilizing its ability to target this pathway.

Clinical efficacy of acupuncture in treating postoperative gastrointestinal dysfunction of colorectal cancer, a systematic review and Meta analysis. / é’ˆåˆºæ²»ç–—ç»“ç›´è‚ ç™Œæœ¯åŽèƒƒè‚ åŠŸèƒ½éšœç¢ç–—æ•ˆçš„ 系统评价和Meta分析.

OBJECTIVES: To evaluate the efficacy of acupuncture in the treatment of postoperative gastrointestinal dysfunction(POGD) of colorectal cancer. METHODS: Randomized controlled trials of acupuncture in the treatment of POGD were retrieved from 7 databases including PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Chinese Journal Service Platform, WanFang Data Knowledge Service Platform, and China Biology Medicine disc. The search period ranged from the inception of the databases to November 10th, 2022. The quality of the included literature was assessed using the Cochrane bias risk assessment tool and the modified Jadad scale. Meta analysis was conducted using RevMan 5.4. Regression analysis and bias risk analysis were performed using Stata 16.0. Trial sequential analysis was conducted using TSA 0.9 software. RESULTS: A total of 27 randomized controlled trials involving 2 629 patients were included. Intervention measures included manual acupuncture, electroacupuncture, transcutaneous acupoint electrical stimulation, warm acupuncture, and thumb-tack needle. The results showed that acupuncture treatment significantly reduced time to tolerance of liquid diet after surgery (MD=-13.70, 95% CI=ï¼»-17.94, -9.46ï¼½, P<0.000 01), time to first defecation (MD=-18.20, 95% CI=ï¼»-22.62, -13.78ï¼½, P<0.000 01), time to first flatus (MD=-16.31, 95% CI=ï¼»-20.32, -12.31ï¼½, P<0.000 01), time to bowel sounds recovery (MD=-11.91, 95% CI=ï¼»-14.01, -9.81ï¼½, P<0.000 01), and length of hospital stay (MD=-1.49, 95% CI=ï¼»-2.27, -0.70ï¼½, P=0.000 2). Regression analysis indicated that cancer type, study quality and number of acupuncture were the main sources of heterogeneity. Bias analysis suggested potential publication bias risks. Trial sequential analysis indicated that the required number of cases had been met and the conclusion was reliable. CONCLUSIONS: Acupuncture is an effective intervention for promoting gastrointestinal recovery in patients undergoing colorectal cancer surgery. Further large-sample and well-designed clinical trials are still needed to compare different acupuncture techniques.

Ginsenosides and Tumors: A Comprehensive and Visualized Analysis of Research Hotspots and Antitumor Mechanisms.

Background: Ginsenoside, the main active constituent of traditional Chinese medicine Ginseng, has been shown to play an important role in the prevention and treatment of cancer. However, the literature as well as the antitumor mechanisms of ginsenosides has not yet been systematically studied. Methods: We screened all relevant literature on ginsenosides and tumors from Web of Science during 2001-2021 and analyzed the extracted terms of these publications by VOSviewer and CiteSpace. DAVID online tool was used to perform Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathways analysis of ginsenoside-related genes. Cytoscape and String software were used to construct the interaction networks of ginsenoside-related genes and corresponding proteins. Results: A total of 919 publications were included in the study. A total of 122 identified keywords were mainly divided into 3 clusters: "pharmacological function research", "functional validation in animal models" and "anti-tumor efficacy and mechanism". The keywords of "oxidative stress" had the strongest citation burst in the past 5 years. A total of 50 genes were identified as ginsenoside-related genes in tumors. They have the function of regulating gene expression and apoptosis, and they are closely related to signaling pathways in cancers. Ginsenoside-related genes form a complex interactional network, in which TP53 and IL-6 are centrally located. Conclusions: We explored and revealed research hotspots related to the ginsenosides and tumors. More precise anti-tumor mechanism research will be promising in the future. TP53 and IL-6 may be the key points to comprehending the anti-tumor mechanism of ginsenosides.

Combination of hyperthermia and intravesical chemotherapy for the treatment of pT1 stage bladder cancer: A retrospectively clinical study.

PURPOSE: To evaluate the efficiency and safety of combined local bladder hyperthermia and intravesical chemotherapy (IVC) for the treatment of patients with pT1 stage bladder cancer. METHOD: A total of 189 patients with pT1 who underwent transurethral resection of bladder cancer (TURBT) were retrospectively reviewed. After TURBT, the patients with low-grade urothelial carcinoma (UC) were treated with either an IVC with pirarubicin (THP) protocol or chemo-thermotherapy (CHT) with THP protocol, whereas patients with high-grade UC were treated with either an intravesical immunotherapy (IVI) with bacillus Calmette-Guerin (BCG) protocol or CHT protocol, patients' characteristics, tumor biological features, and follow-up data were analyzed and compared between CHT and IVC group in low-grade UC, CHT, and IVI group in high-grade UC, respectively. RESULTS: The median follow-up time was 24 months. In patients with low-grade UC, the median recurrence free survival (RFS) interval and costs of treatment in CHT group were significantly higher than those in IVC group (p = .01, p < .001, respectively), CHT was associated with higher RFS compared with IVC by Kaplan-Meier analysis, and three patients in IVC group upgraded to high grade when tumor recurred, whereas no cases were found upgraded in CHT group, p = .38. In patients with high-grade UC, tumor recurrence rates at 12 (p = .004) and 24 months (p = .004) after TURBT, rate of complications (p = .04)-especially for hematuresis (p = .03) and irritation symptoms (p = .04)-the median costs of treatment (p < .001) in CHT group were significantly lower than those in IVI group, RFS interval, health-related quality of life) at 12 and 24 months after TURBT in CHT group was significantly higher than those in IVI group (p < .001, p = .002, and p < .001, respectively), and CHT was associated with higher RFS compared with IVI by Kaplan-Meier analysis. The rate of patients upstaged to pT2 in CHT group seemed lower than that in IVI group, but there was no significantly statistical difference (14.3% vs. 24%, p = .58). CONCLUSION: CHT has a beneficial prophylactic effect in patients with pT1 bladder cancer, especially in patients with high-grade UC, which is much more effective and safer than BCG, meanwhile it costs less compared with BCG.

A Dual-Function Hemicyanine Material with Highly Efficient Photothermal and Photodynamic Effect Used for Tumor Therapy.

Small molecular organic optical agents with synergistic effects of photothermal therapy (PTT) and photodynamic therapy (PDT), hold credible promise for anti-tumor therapy by overcoming individual drawbacks and enhancing photon utilization efficiency. However, developing effective dual-function PTT-PDT photosensitizers (PSs) for efficient synergistic phototherapy remains challenging. Here, a benz[c,d]indolium-substituted hemicyanine named Rh-BI, which possesses a high photothermal conversion efficiency of 41.67% by exhaustively suppressing fluorescence emission, is presented. Meanwhile, the rotating phenyl group at meso-site induces charge recombination to enhance the molar extinction coefficient up to 13.58 × 104 M-1cm-1, thereby potentiating the photodynamic effect. Under 808 nm irradiation, Rh-BI exhibits significant phototoxicity in several cancer cell types in vitro with IC50 values as low as ≈0.5 µM. Moreover, treatment of 4T1 tumor-bearing mice with Rh-BI under laser irradiation successfully inhibits tumor growth. In a word, an effective strategy is developed to build PTT-PDT dual-functional optical materials based on hemicyanine backbone for tumor therapy by modulating conjugation system interaction to adjust the energy consumption pathway.

Fine molecular structure and digestibility changes of potato starch irradiated with electron beam and X-ray.

The change of digestibility of starch irradiated with different types from the perspective of fine structure is not well understood. In this work, the change of internal structure, molecular weight and chain-length distribution, helical structure, lamellar structure, fractal structure and digestibility of native and treated potato starch with electron beam and X-ray was analyzed. Two irradiations caused the destruction of internal structure, the disappearance of growth rings and increase of pores. Irradiation degraded starch to produce short chains and to decrease molecular weight. Irradiation increased double helical content and the thickness and peak area of lamellar structure, resulting in the reorganization of amylopectin and increase of structure order degree. The protected glycosidic linkages increased starch resistance to hydrolase attack, thereby enhancing the anti-digestibility of irradiated starch. Pearson correlation matrix also verified the above-mentioned results. Moreover, X-ray more increased the anti-digestibility of starch by enhancing ability to change fine structure.

Calcium-mediated modulation of Pseudomonas fluorescens biofilm formation.

Biofilm formation is usually affected by many environmental factors, including divalent cations. The purpose of the current work was to analyze how calcium (Ca2+) affects the biofilm formation of dairy Pseudomonas fluorescens isolates by investigating their growth, swarming motility, biofilm-forming capacity, extracellular polymeric substance production, and biofilm structures. Moreover, the regulation mechanism of Ca2+ involved in its biofilm formation was explored through RNA-sequencing analysis. This work revealed that supplementation of 5, 10, 15, and 20 mM Ca2+ significantly reduced the swarming motility of P. fluorescens strains (P.F2, P.F4, and P.F17), but the biofilm-forming ability and polysaccharide production were increased after the supplementation of 5 and 10 mM Ca2+. By the supplementation of Ca2+, complex structures with more cell clusters glued together in P. fluorescens P.F4 biofilms were confirmed by scanning electron microscopy, and increased biomass and coverage of P. fluorescens P.F4 biofilms were observed by confocal laser scanning microscopy. In addition, RNA-sequencing results showed that P. fluorescens P.F4 showed a transcriptional response to the supplementation of 10 mM Ca2+, and a total of 137 genes were significantly expressed. The differential genes were represented in 4 upregulated Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (nonribosomal peptide structures, quorum sensing, biosynthesis of siderophore group nonribosomal peptides, and phenylalanine metabolism), and 4 downregulated KEGG pathways (flagellar assembly, amino sugar and nucleotide sugar metabolism, nitrotoluene degradation, and cationic antimicrobial peptide resistance). The results indicate that Ca2+ might serve as an enhancer to substantially trigger the biofilm formation of dairy P. fluorescens isolates in the dairy industry.

Advances in drug structure-activity-relationships for the development of selenium-based compounds against HIV.

INTRODUCTION: Selenium possesses numerous advantageous properties in the field of medicine, and a variety of selenium-containing compounds have been documented to exhibit anti-HIV activity. This paper aims to categorize these compounds and conduct SAR analysis to offer guidance for drug design and optimization. AREAS COVERED: The authors present a comprehensive review of the reported SAR analysis conducted on selenium-based compounds against HIV, accompanied by a concise discussion regarding the pivotal role of selenium in drug development. EXPERT OPINION: In addition to the conventional bioisosterism strategy, advanced strategies such as covalent inhibition, fragment-based growth and drug repositioning can also be incorporated into research on selenium-containing anti-HIV drugs. Ebselen, which acts as an HIV capsid inhibitor, serves as a valuable probe compound for the discovery of novel HIV integrase inhibitors. Furthermore, it is crucial not to underestimate the potential toxicity associated with organic selenium compounds despite no reported instances of severe toxicity.

Mucus-Penetrating Nanoassembly as Potential Oral Phototherapeutic Formulation against Multi-Drug Resistant Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) infection presents increasing challenges to antibiotic therapies in limited penetration through gastric mucus, multi-drug resistance (MDR), biofilm formation, and intestinal microflora dysbiosis. To address these problems, herein, a mucus-penetrating phototherapeutic nanomedicine (RLs@T780TG) against MDR H. pylori infection is engineered. The RLs@T780TG is assembled with a near-infrared photosensitizer T780T-Gu and an anionic component rhamnolipids (RLs) for deep mucus penetration and light-induced anti-H. pylori performances. With optimized suitable size, hydrophilicity and weak negative surface, the RLs@T780TG can effectively penetrate through the gastric mucus layer and target the inflammatory site. Subsequently, under irradiation, the structure of RLs@T780TG is disrupted and facilitates the T780T-Gu releasing to target the H. pylori surface and ablate multi-drug resistant (MDR) H. pylori. In vivo, RLs@T780TG phototherapy exhibits impressive eradication against H. pylori. The gastric lesions are significantly alleviated and intestinal bacteria balance is less affected than antibiotic treatment. Summarily, this work provides a potential nanomedicine design to facilitate in vivo phototherapy in treatment of H. pylori infection.

The role and outcomes of music therapy during pregnancy: a systematic review of randomized controlled trials.

INTRODUCTION: The abundant functions of music and its effects on human's mental and physical health have been verified since ancient times, but rarely received attention as an alternative obstetric intervention. OBJECTIVE: This study aims to investigate the benefits of music therapy on prenatal and delivery experiences of pregnant women. METHOD: A systematic search for articles was conducted in electronic databases including CINAHL, Web of Science, PubMed/Medline, and CNKI. A total of 240 articles were identified, and 17 studies were selected for this review. The extracted data included author, year, location, sample size, intervention phase, type of music, music therapy strategy, measuring instruments, and results. The data were organized chronologically based on the publication year of each study. RESULT: The articles indicated that music therapy has advantages in reducing pain during childbirth, lowering anxiety and stress levels in mothers, improving sleep quality, and increasing fetal movements, basal fetal heart rate, and accelerations. CONCLUSION: Based on the findings, it can be concluded that music therapy is an effective approach to enhance the experience of pregnant women during pregnancy and delivery. Therefore, its implementation in obstetrical clinical practice is highly recommended.

[Comparative study of purgative pharmacological effects and mechanisms of Moringa oleifera leaves and Rhei Radix et Rhizoma].

Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.

Effects of alkaline mineral complex supplementation on production performance, serum variables, and liver transcriptome in calves.

Calf diarrhea causes huge economic losses to livestock due to its high incidence and mortality rates. Alkaline mineral complex water is an alkaline solution containing silicon, sodium, potassium, zinc, and germanium, and has biological benefits and therapeutic effects. This study aimed to evaluate the impact of alkaline mineral complex water supplementation on the health of calves and to investigate the effect of Alkaline mineral complex water supplementation on neonatal calf serum variables and the liver transcriptome. Sixty Holstein calves (age 1.88 ± 0.85 days, weight 36.63 ± 3.34 kg) were selected and randomly divided into two groups: the T group (treatment group with alkaline mineral complex water supplemented during the experiment) and C group (control group without alkaline mineral complex water supplementation). Alkaline mineral complex water supplementation significantly increased the body weight for calves aged 60 d and average daily gain during the experimental period (1-60 d). In addition, Alkaline mineral complex water supplementation could significantly decrease the diarrhea rate for calves aged 16-30 d, enhance the T-AOC, IgG, IGF-1, and IGFBP-2 in concentrations. The results of KEGG enrichment analysis in transcriptomics indicate that Alkaline mineral complex water supplementation inhibited the target IL-1B gene of the NF-kappa B signaling pathway of liver. Alkaline mineral complex water supplementation decreased calf diarrhea and improved partial immune function, anti-inflammatory activity, antioxidant capacity, and health of calves. Alkaline mineral complex is a candidate to replace medicated feed additives. Alkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex waterAlkaline mineral complex water.

Optimization of trans-4-hydroxyproline synthesis pathway by rearrangement center carbon metabolism in Escherichia coli.

BACKGROUND: trans-4-Hydroxyproline (T-4-HYP) is a promising intermediate in the synthesis of antibiotic drugs. However, its industrial production remains challenging due to the low production efficiency of T-4-HYP. This study focused on designing the key nodes of anabolic pathway to enhance carbon flux and minimize carbon loss, thereby maximizing the production potential of microbial cell factories. RESULTS: First, a basic strain, HYP-1, was developed by releasing feedback inhibitors and expressing heterologous genes for the production of trans-4-hydroxyproline. Subsequently, the biosynthetic pathway was strengthened while branching pathways were disrupted, resulting in increased metabolic flow of α-ketoglutarate in the Tricarboxylic acid cycle. The introduction of the NOG (non-oxidative glycolysis) pathway rearranged the central carbon metabolism, redirecting glucose towards acetyl-CoA. Furthermore, the supply of NADPH was enhanced to improve the acid production capacity of the strain. Finally, the fermentation process of T-4-HYP was optimized using a continuous feeding method. The rate of sugar supplementation controlled the dissolved oxygen concentrations during fermentation, and Fe2+ was continuously fed to supplement the reduced iron for hydroxylation. These modifications ensured an effective supply of proline hydroxylase cofactors (O2 and Fe2+), enabling efficient production of T-4-HYP in the microbial cell factory system. The strain HYP-10 produced 89.4 g/L of T-4-HYP in a 5 L fermenter, with a total yield of 0.34 g/g, the highest values reported by microbial fermentation, the yield increased by 63.1% compared with the highest existing reported yield. CONCLUSION: This study presents a strategy for establishing a microbial cell factory capable of producing T-4-HYP at high levels, making it suitable for large-scale industrial production. Additionally, this study provides valuable insights into regulating synthesis of other compounds with α-ketoglutaric acid as precursor.

A uniform human multimodal dataset for emotion perception and judgment.

Face perception is a fundamental aspect of human social interaction, yet most research on this topic has focused on single modalities and specific aspects of face perception. Here, we present a comprehensive multimodal dataset for examining facial emotion perception and judgment. This dataset includes EEG data from 97 unique neurotypical participants across 8 experiments, fMRI data from 19 neurotypical participants, single-neuron data from 16 neurosurgical patients (22 sessions), eye tracking data from 24 neurotypical participants, behavioral and eye tracking data from 18 participants with ASD and 15 matched controls, and behavioral data from 3 rare patients with focal bilateral amygdala lesions. Notably, participants from all modalities performed the same task. Overall, this multimodal dataset provides a comprehensive exploration of facial emotion perception, emphasizing the importance of integrating multiple modalities to gain a holistic understanding of this complex cognitive process. This dataset serves as a key missing link between human neuroimaging and neurophysiology literature, and facilitates the study of neuropsychiatric populations.

Coffee Leaf Tea Extracts Improve Hyperuricemia Nephropathy and Its Associated Negative Effect in Gut Microbiota and Amino Acid Metabolism in Rats.

Hyperuricemia nephropathy (HN) is a metabolic disease characterized by tubular damage, tubulointerstitial fibrosis, and uric acid kidney stones and has been demonstrated to be associated with hyperuricemia. Coffee leaf tea is drunk as a functional beverage. However, its prevention effects on HN remain to be explored. This study showed that coffee leaf tea extracts (TE) contain 19 polyphenols, with a total content of 550.15 ± 27.58 mg GAE/g. TE decreased serum uric acid levels via inhibiting XOD activities and modulating the expression of urate transporters (GLUT9, OAT3, and ABCG2) in HN rats. TE prevented HN-induced liver and kidney damage and attenuated renal fibrosis. Moreover, it upregulated the abundance of SCFA-producing bacteria (Phascolarctobacterium, Alloprevotella, and Butyricicoccus) in the gut and reversed the amino acid-related metabolism disorder caused by HN. TE also decreased the circulating LPS and d-lactate levels and increased the fecal SCFA levels. This study supported the preliminary and indicative effect of coffee leaf tea in the prevention of hyperuricemia and HN.