The functional role of circRNA CHRC through miR-431-5p/KLF15 signaling axis in the progression of heart failure.

Pathological myocardial hypertrophy is a common early clinical manifestation of heart failure, with non-coding RNAs exerting regulatory influence. However, the molecular function of circular RNAs (circRNAs) in the progression from cardiac hypertrophy to heart failure remains unclear. To uncover functional circRNAs and identify the core circRNA signaling pathway in heart failure, we construct a global triple network (microRNA, circRNA, and mRNA) based on the competitive endogenous RNA (ceRNA) theory. We observe that circRNA CHRC, within the ceRNA network, is down-regulated in both transverse aortic constriction (TAC) mice and Ang-II-treated primary mouse cardiomyocytes. Silencing circRNA CHRC increases cross-sectional cell area, atrial natriuretic peptide, and ß-myosin heavy chain levels in primary mouse cardiomyocytes. Further screening reveals that circRNA CHRC targets the miR-431-5p/KLF15 axis implicated in heart failure progression in vivo and in vitro. Immunoprecipitation with anti-Ago2-RNA confirms the interaction between circRNA CHRC and miR-431-5p, while miR-431-5p mimics reverse Klf15 activation caused by circRNA CHRC over-expression. In summary, circRNA CHRC attenuates cardiac hypertrophy via sponging miR-431-5p to maintain the normal level of Klf15 expression.

Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy.

Photothermal therapy (PTT) of nanomaterials is an emerging novel therapeutic strategy for breast cancer. However, there exists an urgent need for appropriate strategies to enhance the antitumor efficacy of PTT and minimize damage to surrounding normal tissues. Piezo1 might be a promising novel photothermal therapeutic target for breast cancer. This study aims to explore the potential role of Piezo1 activation in the hyperthermia therapy of breast cancer cells and investigate the underlying mechanisms. Results showed that the specific agonist of Piezo1 ion channel (Yoda1) aggravated the cell death of breast cancer cells triggered by heat stress in vitro. Reactive oxygen species (ROS) production was significantly increased following heat stress, and Yoda1 exacerbated the rise in ROS release. GSK2795039, an inhibitor of NADPH oxidase 2 (NOX2), reversed the Yoda1-mediated aggravation of cellular injury and ROS generation after heat stress. The in vivo experiments demonstrate the well photothermal conversion efficiency of TiCN under the 1,064 nm laser irradiation, and Yoda1 increases the sensitivity of breast tumors to PTT in the presence of TiCN. Our study reveals that Piezo1 activation might serve as a photothermal sensitizer for PTT, which may develop as a promising therapeutic strategy for breast cancer.

α-Cyanostilbene-based Molecule with the Synergistical Mechanisms of AIE, ESIPT and TICT: A New Schiff Base Probe for Selective Detection of Fe3+ and Reversible Response to HCl/NH3 Vapor.

We designed and synthesized a new Schiff base probe, which incorporated the salicylaldehyde-analogue α-cyanostilbene and benzophenone hydrazone by the imine linkage. Its chemical structure was verified by FT-IR, MALDI-TOF-MS, HR-MS and 1H/13C NMR technologies. It could exhibit a red fluorescence based on the synergistical effects of aggregation-induce emission (AIE), excited-state intramolecular proton transfer (ESIPT) and twisted intramolecular charge-transfer (TICT) in the aggregation or solid states. Interestingly, the TLC-based test strip loaded with the target compound showed the reversible fluorescence response to amine/acid vapor and on-site visual fluorescence quenching response to Fe3+. In THF/water mixtures (fw = 90%, 10 µM, pH = 7.4), the detection limit (DL) and the binding constant (Ka) of the developed probe towards Fe3+ were evaluated as 5.50 × 10- 8 M and 1.69 × 105, respectively. The developed probe was successfully applied for the detection of Fe3+ with practical, reliable, and satisfying results.

Methyl α-D-galactopyranosyl-(1→3)-ß-D-galactopyranoside and methyl ß-D-galactopyranosyl-(1→3)-ß-D-galactopyranoside: Glycosidic linkage conformation determined from MA'AT analysis.

MA'AT analysis has been applied to two biologically-important O-glycosidic linkages in two disaccharides, α-D-Galp-(1→3)-ß-D-GalpOMe (3) and ß-D-Galp-(1→3)-ß-D-GalpOMe (4). Using density functional theory (DFT) to obtain parameterized equations relating a group of trans-O-glycosidic NMR spin-couplings to either phi (ϕ') or psi (ψ'), and experimental 3 JCOCH , 2 JCOC , and 3 JCOCC spin-couplings measured in aqueous solution in 13 C-labeled isotopomers, probability distributions of ϕ' and ψ' in each linkage were determined and compared to those determined by aqueous 1-µs molecular dynamics (MD) simulation. Good agreement was found between the MA'AT and single-state MD conformational models of these linkages for the most part, with modest (approximately <15°) differences in the mean values of ϕ' and ψ', although the envelope of allowed angles (encoded in circular standard deviations or CSDs) is consistently larger for ϕ' determined from MA'AT analysis than from MD for both linkages. The MA'AT model of the α-Galp-(1→3)-ß-Galp linkage agrees well with those determined previously using conventional NMR methods (3 JCOCH values and/or 1 H-1 H NOEs), but some discrepancy was observed for the ß-Galp-(1→3)-ß-Galp linkage, which may arise from errors in the conventions used to describe the linkage torsion angles. Statistical analyses of X-ray crystal structures show ranges of ϕ' and ψ' for both linkages that include the mean angles determined from MA'AT analyses, although both angles adopt a wide range of values in the crystalline state, with ϕ' in ß-Galp-(1→3)-ß-Galp linkages showing greater-than-expected conformational variability.

Purification and Properties of a Plasmin-like Marine Protease from Clamworm (Perinereis aibuhitensis).

Marine organisms are a rich source of enzymes that exhibit excellent biological activity and a wide range of applications. However, there has been limited research on the proteases found in marine mudflat organisms. Based on this background, the marine fibrinolytic enzyme FELP, which was isolated and purified from clamworm (Perinereis aibuhitensis), has exhibited excellent fibrinolytic activity. We demonstrated the FELP with a purification of 10.61-fold by precipitation with ammonium sulfate, ion-exchange chromatography, and gel-filtration chromatography. SDS-PAGE, fibrin plate method, and LC-MS/MS indicated that the molecular weight of FELP is 28.9 kDa and identified FELP as a fibrinolytic enzyme-like protease. FELP displayed the maximum fibrinolytic activity at pH 9 (407 ± 16 mm2) and 50 °C (724 ± 27 mm2) and had excellent stability at pH 7-11 (50%) or 30-60 °C (60%), respectively. The three-dimensional structure of some amino acid residues of FELP was predicted with the SWISS-MODEL. The fibrinolytic and fibrinogenolytic assays showed that the enzyme possessed direct fibrinolytic activity and indirect fibrinolysis via the activation of plasminogen; it could preferentially degrade Aα-chains of fibrinogen, followed by Bß- and γ-chains. Overall, the fibrinolytic enzyme was successfully purified from Perinereis aibuhitensis, a marine Annelida (phylum), with favorable stability that has strong fibrinolysis activity in vitro. Therefore, FELP appears to be a potent fibrinolytic enzyme with an application that deserves further investigation.

Difluoromethylated Difunctionalization of Alkenes under Visible Light.

Difluoromethylated compounds usually act as bioisosteres for alcohol functional groups and show unique physicochemical and biological properties. The cyano-difluoromethylation of alkenes using 5-((difluoromethyl)sulfonyl)-1-phenyl-1H-tetrazole as a CF2H radical difluoromethyl precursor was developed to afford nitriles including a CF2H group. A low-cost, stable, easily handled 5-((difluoromethyl)sulfonyl)-1-methyl-1H-tetrazole (DFSMT) was synthesized and applied as the radical CF2H reagent. Using DFSMT as the radical CF2H precursor, the oxyl-difluoromethylation of alkenes was developed to obtain difluoromethylated ether products. All of the reactions showed good functional group tolerability. Initial mechanistic experiments indicated that the CF2H radical was involved as the key active intermediate.

Genetic loss of Nrf1 and Nrf2 leads to distinct metabolism reprogramming of HepG2 cells by opposing regulation of the PI3K-AKT-mTOR signalling pathway.

As a vital hallmarker of cancer, the metabolic reprogramming has been shown to play a pivotal role in tumour occurrence, metastasis and drug resistance. Amongst a vast variety of signalling molecules and metabolic enzymes involved in the regulation of cancer metabolism, two key transcription factors Nrf1 and Nrf2 are required for redox signal transduction and metabolic homeostasis. However, the regulatory effects of Nrf1 and Nrf2 (both encoded by Nfe2l1 and Nfe2l2, respectively) on the metabolic reprogramming of hepatocellular carcinoma cells have been not well understood to date. Here, we found that the genetic deletion of Nrf1 and Nrf2 from HepG2 cells resulted in distinct metabolic reprogramming. Loss of Nrf1α led to enhanced glycolysis, reduced mitochondrial oxygen consumption, enhanced gluconeogenesis and activation of the pentose phosphate pathway in the hepatocellular carcinoma cells. By striking contrast, loss of Nrf2 attenuated the glycolysis and gluconeogenesis pathways, but with not any significant effects on the pentose phosphate pathway. Moreover, knockout of Nrf1α also caused fat deposition and increased amino acid synthesis and transport, especially serine synthesis, whilst Nrf2 deficiency did not cause fat deposition, but attenuated amino acid synthesis and transport. Further experiments revealed that such distinctive metabolic programming of between Nrf1α-/- and Nrf2-/- resulted from substantial activation of the PI3K-AKT-mTOR signalling pathway upon the loss of Nrf1, leading to increased expression of critical genes for the glucose uptake, glycolysis, the pentose phosphate pathway, and the de novo lipid synthesis, whereas deficiency of Nrf2 resulted in the opposite phenomenon by inhibiting the PI3K-AKT-mTOR pathway. Altogether, these provide a novel insight into the cancer metabolic reprogramming and guide the exploration of a new strategy for targeted cancer therapy.

Molecular origin and biological effects of exercise mimetics.

With the rapid development of sports science and molecular biology technology, academia refers to molecules or microorganisms that mimic or enhance the beneficial effects of exercise on the body, called "exercise mimetics." This review aims to clarify the concept and development history of exercise mimetics, and to define the concept of exercise mimetics by summarizing its characteristics and functions. Candidate molecules and drug targets for exercise mimetics are summarized, and the relationship between exercise mimetics and exercise is explained, as well as the targeting system and function of exercise mimetics. The main targeting systems for exercise mimetics are the exercise system, circulatory system, endocrine system, endocrine system, and nervous system, while the immune system is potential targeting systems. Finally, future research directions for exercise mimetics are discussed.

Efficacy and safety of ripretinib vs. sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib: A phase 2, multicenter, randomized, open-label study in China.

AIM: A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. METHODS: This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). RESULTS: Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). CONCLUSIONS: Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation.

Wild Rosa roxburghii Tratt Juices Grown at Different Altitudes Regulate Blood Glucose in Type 1 Diabetic Mice via the PI3K/Akt Pathway.

To explore hypoglycemic effect of wild Rosa roxburghii tratt (RRT) juice at different altitudes on type 1 diabetes mellitus (T1DM). The T1DM mouse model was induced by streptozotocin (STZ), and the experiment included a normal group (NC), model group (MC), wild RRT juice groups high (HF), medium (MF), low altitude (DF) and cultivated control group (PC). During experiment, food intake, water intake, body weight, and fasting blood glucose were measured. After 28 days of administration, glucose tolerance, glycogen level, lipid profiles, and antioxidation levels in serum and liver were measured, and histomorphological changes of liver and kidney were observed by hematoxylin and eosin staining. The results showed that wild RRT juice reduced blood glucose level, alleviated liver and kidney tissue damage, improved glucose and lipid metabolism disorders and attenuated oxidative damage in T1DM mice. Western blot showed that wild RRT juice at grown at different altitudes significantly increased protein abundance of PI3K, Akt, and GLUT2 in liver of T1DM mice. In conclusion, wild RRT juice from different altitudes improved glucose and lipid metabolism disorders and oxidative damage in T1DM mice, which may be attributed to activation of PI3K/Akt pathway. Overall effect: MF > PC > HF > DF.

Benzannulation with Et3N as 1,3-Diene Variants.

With triethylamine as a 1,3-diene variant, a simple and practical process for the synthesis of phthalimides has been developed from readily available maleimide. The transformation can be performed in the absence of a metal catalyst with high levels of functional group tolerance. Various phthalimide compounds were constructed in moderate to good yields under mild conditions. Mechanism research indicates that oxygen and acid also play crucial roles in this reaction.

Genomic insights into Aspergillus sydowii 29R-4-F02: unraveling adaptive mechanisms in subseafloor coal-bearing sediment environments.

Introduction: Aspergillussydowii is an important filamentous fungus that inhabits diverse environments. However, investigations on the biology and genetics of A. sydowii in subseafloor sediments remain limited. Methods: Here, we performed de novo sequencing and assembly of the A. sydowii 29R-4-F02 genome, an isolate obtained from approximately 2.4 km deep, 20-million-year-old coal-bearing sediments beneath the seafloor by employing the Nanopore sequencing platform. Results and Discussion: The generated genome was 37.19 Mb with GC content of 50.05%. The final assembly consisted of 11 contigs with N50 of 4.6 Mb, encoding 12,488 putative genes. Notably, the subseafloor strain 29R-4-F02 showed a higher number of carbohydrate-active enzymes (CAZymes) and distinct genes related to vesicular fusion and autophagy compared to the terrestrial strain CBS593.65. Furthermore, 257 positively selected genes, including those involved in DNA repair and CAZymes were identified in subseafloor strain 29R-4-F02. These findings suggest that A. sydowii possesses a unique genetic repertoire enabling its survival in the extreme subseafloor environments over tens of millions of years.

Cytosporin Derivatives from Arctic-Derived Fungus Eutypella sp. D-1 via the OSMAC Approach.

A chemical investigation of the Arctic-derived fungus Eutypella sp. D-1 based on the OSMAC (one strain many compounds) approach resulted in the isolation of five cytosporin polyketides (compounds 1-3 and 11-12) from rice medium and eight cytosporins (compounds 2 and 4-11) from solid defined medium. The structures of the seven new compounds, eutypelleudesmane A (1), cytosporin Y (2), cytosporin Z (3), cytosporin Y1 (4), cytosporin Y2 (5), cytosporin Y3 (6), and cytosporin E1 (7), were elucidated by analyzing their detailed spectroscopic data. Structurally, cytosporin Y1 (4) may be a key intermediate in the biosynthesis of the isolated cytosporins, rather than an end product. Compound 1 contained a unique skeleton formed by the ester linkage of two moieties, cytosporin F (12) and the eudesmane-type sesquiterpene dihydroalanto glycol. Additionally, the occurrence of cyclic carbonate moieties in compounds 6 and 7 was found to be rare in nature. The antibacterial, immunosuppressive, and cytotoxic activities of all compounds derived from Eutypella sp. D-1 were evaluated. Unfortunately, only compounds 3, 6, 8, and 10-11 displayed immunosuppressive activity, with inhibitory rates of 62.9%, 59.5%, 67.8%, 55.8%, and 68.7%, respectively, at a concentration of 5 µg/mL.

The impact of aerobic exercise training on cognitive function and gut microbiota in methamphetamine-dependent individuals in the community.

OBJECTIVE: This study aimed to investigate the impact and mechanism of gut microbiota on the enhancement of cognitive function in methamphetamine (MA)-dependent individuals during aerobic exercise training. METHODS: A total of sixty-four MA-dependent individuals were randomly assigned to either an aerobic exercise training group (DK, n = 32) or a conventional rehabilitation group (CK, n = 32). After an eight-week intervention, the participants' working memory and inhibition ability were assessed using the Stroop paradigm and Go/NoGo paradigm, respectively. Gut microbiota composition was analyzed using high-throughput sequencing. RESULTS: 1) Eight weeks of aerobic exercise training significantly improved the working memory and inhibition ability of MA-dependent individuals (P < 0.05). 2) Following the intervention, the DK group exhibited significantly higher levels of Lactobacillus, Lactococcus lactis, Prevotellaceae, and Ruminococcaceae compared to the CK group. Conversely, the DK group demonstrated significantly lower levels of Desulfovibrio and Akkermansia compared to the CK group. Furthermore, the DK group showed significantly increased metabolic pathways associated with d-Glutaralate and d-Galactate Degradation, as well as the Alanine, aspartate, and glutamate metabolism pathway, compared to the control group. 3) Cognitive function related to MA addiction positively correlated with Bifidobacterium, Dialister, and Adlercreutzia, while negatively correlated with Enterobacteria, Bacillus cereus, Catabacter, and Akkermansia. CONCLUSION: Aerobic exercise training enhances working memory and inhibition ability in MA-dependent individuals, thereby mitigating the detrimental effects of MA addiction on cognitive function. Additionally, analysis of gut microbiota suggests that the modulation of gut microbiota and associated metabolic pathways play a role in regulating the improvement of cognitive function in MA-dependent individuals through exercise.

Annulation of α-bromocinnamaldehydes to access 3-formyl-imidazo[1,2-α]pyridines and pyrimidines under transition metal-free conditions.

An environmentally friendly and transition metal-free method for the annulation of α-bromocinnamaldehydes was established. 3-Formyl-imidazo[1,2-α]pyridines and pyrimidines were obtained in moderate to excellent yields. This approach features easily available starting materials, transition metal-free conditions, good functional group tolerance and operational simplicity.

Effect of Probiotic Yogurt Supplementation(Bifidobacterium animalis ssp. lactis BB-12) on Gut Microbiota of Female Taekwondo Athletes and Its Relationship with Exercise-Related Psychological Fatigue.

OBJECTIVE: The gut microbiota plays a critical role in regulating human health and athletic performance. Probiotic supplementation has been shown to modulate gut microbiota composition and improve exercise performance. This study aimed to investigate the effect of probiotic yogurt supplementation on gut microbiota and its relationship with exercise-related psychological fatigue in female taekwondo athletes. METHODS: Twenty female taekwondo athletes were randomly assigned to either a dietary intervention group (DK) or a control group (CK). The athletes' exercise-related psychological fatigue was measured using the Athlete Burnout Questionnaire (ABQ) before and after an 8-week intervention. High-throughput sequencing was used to profile the gut microbiota, and functional prediction of the microbial community was performed. The effect of the dietary intervention on the athletes' exercise-related psychological fatigue clearance rate and its relationship with the gut microbiota were explored. RESULTS: (1) The probiotic supplementation of Bifidobacterium animalis ssp. lactis BB-12 for 8 weeks significantly increased the ABQ scores of the DK group compared to the CK group (p < 0.05). (2) The abundances of Bifidobacterium, Bacteroides, Lachnospiraceae, family _Lactobacillaceae, and genus _Lactobacillus were significantly higher in the DK group than in the CK group after probiotic supplementation, while Escherichia coli was significantly lower in the DK group than in the CK group. (3) The ABQa scores were positively correlated with Proteus; ABQb scores were positively correlated with Streptococcus and Enterococcus; and ABQc scores were positively correlated with Klebsiella, Bacteroides, and Streptomyces. (4) The DK group had significantly higher levels of L-arginine biosynthesis I (via L-ornithine), fatty acid biosynthesis and oxidation, and L-isoleucine biosynthesis III pathways compared to the CK group. Tyrosine degradation I (via 2,3-dihydroxyphenylpropionate) was significantly lower in the DK group than in the CK group. CONCLUSIONS: Probiotic yogurt supplementation of Bifidobacterium animalis ssp. lactis can promote the clearance of exercise-related psychological fatigue in female taekwondo athletes by upregulating beneficial gut microbiota, inhibiting harmful gut microbiota, and regulating relevant metabolic pathways.

Comparative Functional Genome Analysis Reveals the Habitat Adaptation and Biocontrol Characteristics of Plant Growth-Promoting Bacteria in NCBI Databases.

Plant growth-promoting bacteria (PGPB) are a group of beneficial microorganisms that include 60 bacterial genera, such as Bacillus, Pseudomonas, and Burkholderia, which widely colonize plant leaves and soil, promote plant growth, and/or inhibit pathogen infection. However, the genetic factors underpinning adaptation of PGPB to plant leaves and soil remain poorly understood. In this study, we performed a comparative functional genome analysis approach to investigate the functional genes of 195 leaf-associated (LA) and 283 soil-associated (SA) PGPB strains and their roles in adapting to their environment, using 95 strains from other-associated (OA) environmental habitats with growth-promoting or antimicrobial functions as negative controls. Comparison analysis of the enrichment of nonredundant (NR) protein sequence databases showed that cytochrome P450, DNA repair, and motor chemotaxis genes were significantly enriched in LA PGPB strains related to environmental adaptation, while cell wall-degrading enzymes, TetR transcriptional regulatory factors, and sporulation-related genes were highly enriched in SA PGPB strains. Additionally, analysis of carbohydrate-active enzymes demonstrated that glycosyltransferases (GTs) and glycoside hydrolases (GHs) were abundant families in all PGPB strains, which is in favor of plant growth, and enriched in SA PGPB strains. Except for most Bacillus strains, SA PGPB genomes contained significantly more secondary metabolism clusters than LA PGPB. Most LA PGPB contained hormone biosynthesis genes, which may contribute to plant growth promotion, while SA PGPB harbored numerous carbohydrate and antibiotic metabolism genes. In summary, this study further deepens our understanding of the habitat adaptation and biocontrol characteristics of LA and SA PGPB strains. IMPORTANCE Plant growth-promoting bacteria (PGPB) are essential for the effectiveness of biocontrol agents in plant phyllosphere and rhizosphere. However, little is known about the ecological adaptation of PGPB to different habitats. In this study, comparative functional genome analysis of leaf-associated (LA), soil-associated (SA), and other-associated (OA) PGPB strains was performed. We found that genes related to the metabolism of hormones were enriched in LA PGPB. Carbohydrate and antibiotic metabolism genes were enriched in SA PGPB, which likely facilitated their adaptation to the plant growth environment. Our findings provide genetic insights on LA and SA PGPB strains' ecological adaptation and biocontrol characteristics.

Exploring the mechanism of browning of Rosa roxburghii juice based on nontargeted metabolomics.

To explore the mechanism of Rosa roxburghii juice browning, this experiment was based on nontargeted metabolomics to study the effects of browning on the nutrition, flavor, metabolites, and metabolic pathways of R. roxburghii juice before and after storage. The results showed that the total soluble solids, superoxide dismutase (SOD), vitamin C (VC ), total phenol, and total flavonoid of R. roxburghii juice decreased significantly before and after storage. The color difference value ∆E, browning index, and flavor and taste of R. roxburghii juice changed significantly (p < 0.05). A total of 541 metabolites were detected before and after browning of R. roxburghii juice by nontargeted metabolomics, including 435 differential metabolites, of which 221 were upregulated, and 214 were downregulated. The differential metabolites were mainly amino acids and peptides, carbohydrates, and carbohydrate conjugates. There were a total of 76 metabolic pathways enriched by differential metabolites, involving mainly galactose metabolism; alanine, aspartate and glutamate metabolism; and pantothenate and CoA biosynthesis. The experimental results showed that after browning of R. roxburghii juice, VC , total phenol, total flavonoid, and SOD activity were seriously lost, and the flavor deteriorated. The contribution of differential metabolites and metabolic pathways to the browning of R. roxburghii juice was sugar metabolism > amino acid metabolism > ascorbate and aldarate metabolism > phenols.

Changes in clinical and CT manifestations related to liver abscesses in patients with vs. without basic diabetes mellitus before and after CT-guided interventional therapy: An observational study.

PURPOSE: To explore differences in the changes of clinical and CT manifestations related to liver abscess before and after CT-guided interventional therapy between patients with and without Diabetes Mellitus (DM). MATERIALS AND METHODS: Fifty-eight consecutive patients with liver abscesses were retrospectively enrolled in this study. All patients underwent upper abdominal contrast-enhanced CT scans before and after CT-guided interventional therapy. They were divided into two groups including the DM group (n=30) and the Non-DM group (n=28) if the liver abscess occurred in patients with and without DM, respectively. The changes in the clinical and CT manifestations related to liver abscess after CT-guided interventional therapy in both groups were statistically analyzed. RESULTS: After CT-guided interventional therapy, the length of hospital stay, white blood cell recovery time and drainage tube removal time in the DM group were longer than in the Non-DM group (all p-values < 0.05). The incidence of postoperative complications in the DM group was higher than in the Non-DM group (p < 0.05). As shown on CT, the postoperative reduced percentage of maximum diameter of abscess cavity and the reduction rate of edema band surrounding the liver abscess in the DM group were smaller than in the Non-DM group (both p-values < 0.05). The time intervals of the previous characteristic changes on CT before and after interventional therapy in the DM group were longer than in the Non-DM group (all p-values < 0.05). CONCLUSIONS: The liver abscesses patients with DM could not have a faster recovery and better therapeutic effect than those without DM after the CT-guided interventional therapy.

Upregulation of HMGB1 in tumor-associated macrophages induced by tumor cell-derived lactate further promotes colorectal cancer progression.

BACKGROUND: Lactate accumulation leads to an acidic tumor microenvironment (TME), in turn promoting colorectal cancer (CRC) progression. Tumor-associated macrophages (TAMs) are the predominant cells in TME. This study aimed to reveal the regulation mechanism of CRC cell-derived lactate on TAMs and explore the mechanism underlying lactate accumulation-induced aggravation in CRC. METHODS: Cell growth and metastasis were evaluated by colony formation, Transwell, and wound healing assays. Western blot and RT-qPCR were applied to determine the protein and mRNA expression. Flow cytometry was used to analyze the polarization state and apoptotic rate of macrophages induced in THP-1 cells. The lactate in the cell supernatant was quantified using an ELISA kit. Immunofluorescence was performed to visualize the location of High Mobility Group Box 1 (HMGB1). H&E and Ki67 staining assays were used to assess tumorigenesis in nude mice bearing ectopic tumors. RESULTS: Cell growth and metastasis were promoted in the hypoxic CRC cells. The hypoxic cell supernatant stimulated the M2-type polarization of macrophages. The lactate level increased in hypoxic cancer cells. However, the inhibition of lactate using 3-hydroxy-butyrate (3-OBA) reversed the effects of hypoxia. Also, macrophages showed no promoting effect on cancer cell growth and migration in the presence of 3-OBA. HMGB1 was secreted into the extracellular space of lactate-induced macrophages, further enhancing the malignant behaviors of cancer cells. ERK, EMT, and Wnt signaling pathways were activated in cancer cells due to HMGB1 upregulation. CONCLUSIONS: The lactate metabolized by cancer cells stimulated M2 polarization and HMGB1 secretion by macrophages, aggravating the carcinogenic behaviors of cancer cells.