UHMK1 promotes gastric cancer progression through reprogramming nucleotide metabolism.

UHMK1 is a nuclear serine/threonine kinase recently implicated in carcinogenesis. However, the functions and action mechanisms of UHMK1 in the pathogenesis of human gastric cancer (GC) are unclear. Here, we observed that UHMK1 was markedly upregulated in GC. UHMK1 silencing strongly inhibited GC aggressiveness. Interestingly, UHMK1-induced GC progression was mediated primarily via enhancing de novo purine synthesis because inhibiting purine synthesis reversed the effects of UHMK1 overexpression. Mechanistically, UHMK1 activated ATF4, an important transcription factor in nucleotide synthesis, by phosphorylating NCOA3 at Ser (S) 1062 and Thr (T) 1067. This event significantly enhanced the binding of NCOA3 to ATF4 and the expression of purine metabolism-associated target genes. Conversely, deficient phosphorylation of NCOA3 at S1062/T1067 significantly abrogated the function of UHMK1 in GC development. Clinically, Helicobacter pylori and GC-associated UHMK1 mutation induced NCOA3-S1062/T1067 phosphorylation and enhanced the activity of ATF4 and UHMK1. Importantly, the level of UHMK1 was significantly correlated with the level of phospho-NCOA3 (S1062/T1067) in human GC specimens. Collectively, these results show that the UHMK1-activated de novo purine synthesis pathway significantly promotes GC development.

[Association between serum uric acid and airflow obstruction based on the health-checkup population].

OBJECTIVE: To investigate the association between serum uric acid, pulmonary function and airflow obstruction in Chinese Taiwan healthy subjects. METHODS: All the cross-sectional analysis was performed in the population over 40 years old using the physical examination data of Chinese Taiwan MJ Health Resource Center between 1996 and 2016 stratification by gender. The correlation analyses between serum uric acid were done and multivariate Logistic regression analysis was used to explore the effect of serum uric acid on airflow obstruction. RESULTS: A total of 35 465 people were included in the study, including 16 411 men and 19 054 women. Among them, the serum uric acid concentration of men was higher than that of women, and the serum uric acid concentration of the people with airflow obstruction was higher than that of the people without airflow obstruction. There was a negative correlation between serum uric acid level and the forced expiratory volume in one second (FEV1) and the force vital capacity (FVC) in women (P < 0.05), but in men the correlation didn' t exist (P>0.05). After adjusting for age, education, smoking status, drinking status, work strength, body mass index, history of cough, history of hypertension, history of diabetes, history of dyslipidemia, white blood cells and blood albumin, the airflow obstruction in women was more likely to exist with the serum uric acid elevated (OR=1. 12, 95%CI: 1.02-1.22, P < 0.05). The results showed that women with hyperuricemia were more likely to have airflow obstruction than those without hyperuricemia (OR=1.36, 95%CI: 1.06-1.75, P < 0.05). There was no correlation between serum uric acid concentration and airflow obstruction in men (OR=1.04, 95%CI: 0.96-1.13, P>0.05), also the hyperuricemia and airflow obstruction (OR=1.12, 95%CI: 0.89-1.39, P>0.05). CONCLUSION: There is a negative correlation between serum uric acid and FEV1 and FVC in relatively healthy women, and there is an association between elevated serum uric acid and airflow obstruction in women, but not in men. Further prospective studies are needed to explore whether high serum uric acid level can increase the risk of airflow obstruction.

Effectiveness of COVID-19 vaccines against SARS-CoV-2 variants of concern: a systematic review and meta-analysis.

BACKGROUND: It was urgent and necessary to synthesize the evidence for vaccine effectiveness (VE) against SARS-CoV-2 variants of concern (VOC). We conducted a systematic review and meta-analysis to provide a comprehensive overview of the effectiveness profile of COVID-19 vaccines against VOC. METHODS: Published randomized controlled trials (RCTs), cohort studies, and case-control studies that evaluated the VE against VOC (Alpha, Beta, Gamma, Delta, or Omicron) were searched until 4 March 2022. Pooled estimates and 95% confidence intervals (CIs) were calculated using random-effects meta-analysis. VE was defined as (1-estimate). RESULTS: Eleven RCTs (161,388 participants), 20 cohort studies (52,782,321 participants), and 26 case-control studies (2,584,732 cases) were included. Eleven COVID-19 vaccines (mRNA-1273, BNT162b2, ChAdOx1, Ad26.COV2.S, NVX-CoV2373, BBV152, CoronaVac, BBIBP-CorV, SCB-2019, CVnCoV, and HB02) were included in this analysis. Full vaccination was effective against Alpha, Beta, Gamma, Delta, and Omicron variants, with VE of 88.0% (95% CI, 83.0-91.5), 73.0% (95% CI, 64.3-79.5), 63.0% (95% CI, 47.9-73.7), 77.8% (95% CI, 72.7-82.0), and 55.9% (95% CI, 40.9-67.0), respectively. Booster vaccination was more effective against Delta and Omicron variants, with VE of 95.5% (95% CI, 94.2-96.5) and 80.8% (95% CI, 58.6-91.1), respectively. mRNA vaccines (mRNA-1273/BNT162b2) seemed to have higher VE against VOC over others; significant interactions (pinteraction < 0.10) were observed between VE and vaccine type (mRNA vaccines vs. not mRNA vaccines). CONCLUSIONS: Full vaccination of COVID-19 vaccines is highly effective against Alpha variant, and moderate effective against Beta, Gamma, and Delta variants. Booster vaccination is more effective against Delta and Omicron variants. mRNA vaccines seem to have higher VE against Alpha, Beta, Gamma, and Delta variants over others.

Long-term exposure to air pollution, habitual physical activity and risk of non-alcoholic fatty liver disease: A prospective cohort study.

BACKGROUND: Emerging studies suggest a positive association between air pollution exposure and risk of non-alcoholic fatty liver disease (NAFLD), however, the combined effects of long-term exposure to air pollution, physical activity (PA), and risk of NAFLD is unclear. METHODS: We included 58,026 Taiwan residents who received a standard medical screening program between 2001 and 2016. Levels of fine particulate matter (PM2.5) at each participant's residential address were estimated using multiple satellite-based aerosol optical depth data combined with a chemical transport model. PA volume was calculated as hours of metabolic equivalent tasks per week (MET-h/week) based on a standard self-administered questionnaire. Incident NAFLD was defined as the first occurrence of a fatty liver index (FLI) value > 30 or a hepatic steatosis index (HSI) value > 36 in participants without NAFLD at the baseline. Time-varying Cox regression was used to evaluate the combined effects of PA and PM2.5. RESULTS: Exposure to PM2.5 was positively associated with NAFLD. A 1 µg/m3 increase in PM2.5 above 23.5 µg/m3 was associated with a hazard ratio (HR) of 1.06 (95% CI: 1.04, 1.09) and 1.05 (95% CI: 1.03, 1.07) for NAFLD identified by FLI and HSI, respectively. Performing PA was inversely associated with NAFLD. Compared with participants in high PM2.5 [≥ 27.5 µg/m3]-very low PA [< 3.75 MET-h/week] group, low PM2.5 [< 23.5 µg/m3]-very high PA [≥ 25.50 MET-h/week] group had a 57% (95% CI: 50%, 63%) and 42% (95% CI: 33%, 50%) lower risk of NAFLD defined by FLI and HSI, respectively. We found no evidence of any additive or multiplicative interaction between PA and PM2.5. CONCLUSION: Long-term PM2.5 exposure was positively associated with NAFLD, whereas performing PA was inversely associated with NAFLD. The benefits of PA on NAFLD remained stable in participants exposed to various PM2.5 levels.

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Loss Activates Purine Metabolism and Promotes Hepatocellular Carcinoma Progression.

Cancer cells metabolize different energy sources to generate biomass rapidly. The purine biosynthetic pathway was recently identified as an important source of metabolic intermediates for these processes. However, very little was known about the regulatory mechanisms of purine metabolism in hepatocellular carcinoma (HCC). We explored the role of dual-specificity tyrosine (Y) phosphorylation-regulated kinase 3 (Dyrk3) in HCC metabolism. Dyrk3 was significantly down-regulated in HCC compared with normal controls. Its introduction in HCC cells markedly suppressed tumor growth and metastasis in xenograft tumor models. Mass spectrometric analysis of metabolites suggests that the effect of Dyrk3 on HCC occurred at least partially through down-regulating purine metabolism, as evidenced by the fact that inhibiting purine synthesis reverted the HCC progression mediated by the loss of Dyrk3. We further provide evidence that this action of Dyrk3 knockdown requires nuclear receptor coactivator 3 (NCOA3), which has been shown to be a coactivator of activating transcription factor 4 (ATF4) to target purine pathway genes for transcriptional activation. Mechanistically, Dyrk3 directly phosphorylated NCOA3 at Ser-1330, disrupting its binding to ATF4 and thereby causing the inhibition of ATF4 transcriptional activity. However, the phosphorylation-resistant NCOA3-S1330A mutant has the opposite effect. Interestingly, the promoter activity of Dyrk3 was negatively regulated by ATF4, indicating a double-negative feedback loop. Importantly, levels of Dyrk3 and phospho-NCOA3-S1330 inversely correlate with the expression of ATF4 in human HCC specimens. Conclusion: Our findings not only illustrate a function of Dyrk3 in reprograming HCC metabolism by negatively regulating NCOA3/ATF4 transcription factor complex but also identify NCOA3 as a phosphorylation substrate of Dyrk3, suggesting the Dyrk3/NCOA3/ATF4 axis as a potential candidate for HCC therapy.

Thermal stability and oral absorbability of astaxanthin esters from Haematococcus pluvialis in Balb/c mice.

BACKGROUND: Astaxanthin is used as a functional nutraceutical and pigment in many food products. It is mostly exists in the form of a fatty acid ester in nature. However, no detailed descriptions are available concerning the stability and oral absorbability of astaxanthin esters. In the present study, the thermal stability and absorbability of astaxanthin esters from Haematococcus pluvialis were evaluated in comparison with free-form astaxanthin. RESULTS: The thermal stability of astaxanthin esters was found to be higher than that of free-form astaxantin. After gavage with astaxanthin esters, only free-form astaxanthin was detected in the digestive tract wall, blood plasma and liver, indicating that astaxanthin esters must be hydrolyzed to free-form astaxanthin in the gut before absorption. Furthermore, there was a considerable selective accumulation of different astaxanthin isomers in Balb/c mice, which selectivity decreased in the order: 13-cis > all-trans > 9-cis. Accumulated astaxanthin was mainly distributed in the heart, liver, spleen, muscle and adipose tissue, although significant differences between tissues were observed. CONCLUSION: From the present study, it can be concluded that astaxanthin esters had a higher thermal stability and higher bioavailability than free-form astaxanthin. These results provide important evidence with respect to using astaxanthin esters as bioactive components to replace free-form astaxanthin in functional food products. © 2019 Society of Chemical Industry.

Statistical Optimization of Medium for Pullulan Production by Aureobasidium pullulans NCPS2016 Using Fructose and Soybean Meal Hydrolysates.

Pullulan, with its excellent characteristics of film-forming, water solubility, and biodegradability, is attracting more and more attention in agricultural products preservation. However, high pullulan production cost largely restricts its widely application due to its low production. In order to improve pullulan production by Aureobasidium pullulans NCPS2016, the medium was optimized using single factor experiment and response surface methodology. Based on the single factor experiments, the contents of soybean meal hydrolysates (SMHs), (NH4)2SO4, and K2HPO4·3H2O were considered to be main factors influencing the extracellular polysaccharide (EPS) production, and were further optimized by Box⁻Behnken design. The optimal content of SMHs of 7.71 g/L, (NH4)2SO4 of 0.35 g/L, and K2HPO4·3H2O of 8.83 g/L were defined. Finally, EPS production of 59.8 g/L was obtained, 39% higher in comparison with the production in the basal medium. The purified EPS produced by NCPS2016 was confirmed to be pullulan. This is the first time fructose is reported to be the optimal carbon source for pullulan production by Aureobasidium pullulans, which is of great significance for the further study of the mechanism of the synthesis of pullulan by NCPS2016. Also, the results here have laid a foundation for reducing the industrial production cost of pullulan.

Synthesis, stability and bioavailability of astaxanthin succinate diester.

BACKGROUND: We synthesized astaxanthin succinate diester (ASD), a novel astaxanthin (AST) derivate, with succinic anhydride and free AST. ASD was purified and characterized using silica gel column chromatography and spectrometry, respectively. RESULTS: The ASD final synthesis rate was 82.63%. A stability test revealed a high AST and ASD retention rate at pH 5.0-7.0. ASD showed better stability than did AST under acidic conditions. Both sample ions showed lower retention rates under Fe2+ and Fe3+ states. The ASD metabolic curve showed serum and liver area under the curve from 0 h to time t (AUC0-t ) values of 45.05 ± 4.58 and 120.38 ± 23.66 µg h-1  mL-1 , respectively. The long-term accumulation was significantly higher in the ASD group than in the AST group, which showed higher accumulation in the heart, muscle and spleen than in other tissues in vivo. CONCLUSION: The thermal stability and bioavailability of ASD were higher than that of the non-esterified free AST and common free AST, respectively. Additionally, AST accumulation in different tissues of the ASD group was multifold higher than that of free AST. These results prove that ASD may serve as a better source of AST for human nutrition than does free AST. © 2017 Society of Chemical Industry.

Novel zero-valent iron-assembled reactor for strengthening anammox performance under low temperature.

To further expand the application of anammox biotechnology, a novel zero-valent iron-assembled upflow anaerobic sludge bed reactor was employed to strengthen anammox performance under low temperature and shock load. Packed with sponge iron and polyester sponge, this novel reactor could speed up the recovery of anammox activity in 12 days and improve the adaptability of anammox bacteria at the temperature of 10-15 °C. The high nitrogen loading rate of 1109.2 mg N/L/day could be adapted in 27 days and the new nitrogen pathway under the effect of sponge iron was clarified by batch experiment. Moreover, the real-time quantitative PCR analysis and Illumina MiSeq sequencing verified the dominant status of Candidatus Kuenenia stuttgartiensis and planctomycete KSU-1, as well as demonstrated the positive role of sponge iron on anammox microorganisms' proliferation. The findings might be beneficial to popularize anammox-related processes in municipal and industrial wastewater engineering.

Assessment of total and organic vanadium levels and their bioaccumulation in edible sea cucumbers: tissues distribution, inter-species-specific, locational differences and seasonal variations.

The objective of this study is to investigate the levels, inter-species-specific, locational differences and seasonal variations of vanadium in sea cucumbers and to validate further several potential factors controlling the distribution of metals in sea cucumbers. Vanadium levels were evaluated in samples of edible sea cucumbers and were demonstrated exhibit differences in different seasons, species and sampling sites. High vanadium concentrations were measured in the sea cucumbers, and all of the vanadium detected was in an organic form. Mean vanadium concentrations were considerably higher in the blood (sea cucumber) than in the other studied tissues. The highest concentration of vanadium (2.56 µg g(-1)), as well as a higher degree of organic vanadium (85.5 %), was observed in the Holothuria scabra samples compared with all other samples. Vanadium levels in Apostichopus japonicus from Bohai Bay and Yellow Sea have marked seasonal variations. Average values of 1.09 µg g(-1) of total vanadium and 0.79 µg g(-1) of organic vanadium were obtained in various species of sea cucumbers. Significant positive correlations between vanadium in the seawater and V org in the sea cucumber (r = 81.67 %, p = 0.00), as well as between vanadium in the sediment and V org in the sea cucumber (r = 77.98 %, p = 0.00), were observed. Vanadium concentrations depend on the seasons (salinity, temperature), species, sampling sites and seawater environment (seawater, sediment). Given the adverse toxicological effects of inorganic vanadium and positive roles in controlling the development of diabetes in humans, a regular monitoring programme of vanadium content in edible sea cucumbers can be recommended.

Qingshengfania soli gen. nov., sp. nov., a member of the order Rhizobiales isolated from the soil of a pesticide factory.

Two Gram-stain negative, coccoid to oval-shaped, non-spore-forming bacteria (LR4T and LR4-1), isolated from the soil of a pesticide factory in Nanjing, China, were investigated for their taxonomic allocation by using a polyphasic approach. Both strains grew optimally at pH 7.0, 30 °C and in the absence of NaCl. Both strains were positive for catalase and oxidase activities. Q-10 was the predominant respiratory ubiquinone. The major polar lipids were phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and two unknown aminolipids. The major fatty acids (>10 % of the total fatty acids) were C18:1ω7c/C18:1ω6c (summed feature 8) and C17:1 iso I/C17:1 anteiso B (summed feature 4). Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the two isolates formed a distinct line within a clade containing the genera Chelatococcus, Bosea, Camelimonas, Salinarimonas, Psychroglaciecola, Microvirga, Methylobacterium, Albibacter, Hansschlegelia and Methylopila in the order Rhizobiales, with the highest 16S rRNA gene sequence similarity to Chelatococcus asaccharovorans TE2T (94.12 %), followed by Bosea thiooxidans DSM 9653T (93.25 %). Strains LR4T and LR4-1 were closely related on the basis of DNA-DNA reassociation and therefore represent a single novel species. Based on phenotypic, chemotaxonomic and phylogenetic data, strains LR4T and LR4-1 represent a novel species of a new genus in the order Rhizobiales, for which the name Qingshengfania soli gen. nov., sp. nov. is proposed. The type strain of the type species is LR4T ( = CCTCC AB 2015036T = KCTC 42463T).

Intracellular ß-glucosidases CEL1a and CEL1b are essential for cellulase induction on lactose in Trichoderma reesei.

Lactose (1,4-O-ß-d-galacto-pyranosyl-d-glucose) induces cellulolytic enzymes in Trichoderma reesei and is in fact one of the most important soluble carbon sources used to produce cellulases on an industrial level. The mechanism underlying the induction is, however, not fully understood. In this study, we investigated the cellular functions of the intracellular ß-glucosidases CEL1a and CEL1b in the induction of cellulase genes by lactose in T. reesei. We demonstrated that while CEL1a and CEL1b were functionally equivalent in mediating the induction, the simultaneous absence of these intracellular ß-glucosidases abolished cbh1 gene expression on lactose. d-Galactose restored the efficient cellulase gene induction in the Δcel1a strain independently of its reductive metabolism, but not in the Δcel1a Δcel1b strain. A further comparison of the transcriptional responses of the Δcel1a Δcel1b strain complemented with wild-type CEL1a or a catalytically inactive CEL1a version and the Δcel1a strain constitutively expressing CEL1a or the Kluyveromyces lactis ß-galactosidase LAC4 showed that both the CEL1a protein and its glycoside hydrolytic activity were indispensable for cellulase induction by lactose. We also present evidence that intracellular ß-glucosidase-mediated lactose induction is further conveyed to XYR1 to ensure the efficiently induced expression of cellulase genes.

GPC1 regulated by miR-96-5p, rather than miR-182-5p, in inhibition of pancreatic carcinoma cell proliferation.

To determine the relationships between miR-96-5p/-182-5p and GPC1 in pancreatic cancer (PC), we conducted the population and in vitro studies. We followed 38 pancreatic cancer patients, measured and compared the expression of miR-96-5p/-182-5p, GPC1, characteristics and patients' survival time of different miR-96-5p/-182-5p expression levels in PC tissues. In an in vitro study, we investigated the proliferation, cycle and apotosis in cells transfected with mimics/inhibitors of the two miRNAs, and determine their effects on GPC1 by dual-luciferase assay. In the follow-up study, we found that the expressions of miR-96-5p/-182-5p were lower/higher in PC tissues; patients with lower/higher levels of miR-96-5p/-182-5p suffered poorer characteristics and decreased survival time. In the in vitro study, the expressions of miR-96-5p/-182-5p were different in cells. Proliferation of cells transfected with miR-96-5p mimics/inhibitors was lower/higher in Panc-1/BxPC-3; when transfected with miR-182-5p mimics/inhibitors, proliferation of cells were higher/lower in AsPC-1/Panc-1. In a cell cycle study, panc-1 cells transfected with miR-96-5p mimics was arrested at G0/G1; BxPC-3 cells transfected with miR-96-5p inhibitors showed a significantly decrease at G0/G1; AsPC-1 cells transfected with miR-182-5p mimics was arrested at S; Panc-1 cells transfected with miR-182-5p inhibitors showed a decrease at S. MiR-96-5p mimics increased the apoptosis rate in Panc-1 cells, and its inhibitors decreased the apoptosis rate in BxPC-3. Dual luciferase assay revealed that GPC1 was regulated by miR-96-5p, not -182-5p. We found that miR-96-5p/-182-5p as good markers for PC; miR-96-5p, rather than -182-5p, inhibits GPC1 to suppress proliferation of PC cells.

An innovative prognostic auxiliary for colon adenocarcinoma based on zinc finger protein genes.

Background: The carcinogenesis and progression of colon adenocarcinoma (COAD) are intensively related to the abnormal expression of the zinc finger (ZNF) protein genes. We aimed to employ these genes to provide a reliable prognosis and treatment stratification tool for COAD patients. Methods: Cox and the least absolute shrinkage and selection operator (LASSO) regression analysis were applied, utilizing The Cancer Genome Atlas (TCGA) metadata, to build a ZNF protein gene-based prognostic model. Using this model, patients in the training cohort and testing cohort (GSE17537) were labelled as either high or low risk. Kaplan-Meier (KM) survival analysis and time-dependent receiver operating characteristic (ROC) curve analysis were performed in the patients with opposite risk status to assess the predictive ability in each cohort. The potentiality of the mechanism was explored by the estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE), single-sample gene set enrichment analysis (ssGSEA), gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the degrees of expression of model genes were validated by immunohistochemistry (IHC). Results: The prognostic model consisting of INSM1, PHF21B, RNF138, SYTL4, WRNIP1, ZNF585B, and ZNF514, classified patients into opposite risk statuses. Patients in the high-risk subset had a considerably lower chance of surviving compared to those in the low-risk subset. There is a high probability that these model genes were attached to immune-related biological processes, which can be confirmed by the results of the above mechanistic methods. Moreover, patients in the low-risk subset also significantly outperformed the patients in the high-risk subset when calculating immune cells and function scores. Drug sensitivity and tumor immune dysfunction and exclusion (TIDE) analyses showed a clear difference in the immunological and chemotherapeutic efficacy predictions within the two risk groups. Additionally, the degrees of expression of model genes in high-risk and low-risk subsets presented great discrepancies. Conclusions: The signature may be applied as a predictive classifier to shepherd special medication for COAD patients.

Circulating tumor DNA as prognostic markers of relapsed breast cancer: a systematic review and meta-analysis.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50-0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04-0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73-12.17; relapse outcome: RR = 7.11, 95% CI: 3.05-16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12-3.70; post-operative: HR = 6.03, 95% CI: 1.31-27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

Effects of Fermentation with Eurotium cristatum on Sensory Properties and Flavor Compounds of Mulberry Leaf Tea.

Mulberry leaf tea (MT) is a popular Chinese food with nutrition and medicinal functions. Solid-state fermentation with Eurotium cristatum of MT (FMT) can improve their quality. Differences in chromaticity, taste properties, and flavor characteristics were analyzed to evaluate the improvements of the sensory quality of FMT. After fermentation, the color of the tea infusion changed. The E-tongue evaluation results showed a significant decrease in unpleasant taste properties such as sourness, bitterness, astringency, and aftertaste-bitterness, while umami and saltiness taste properties were enhanced post-fermentation. Aroma-active compounds in MT and FMT were identified and characterized. A total of 25 key aroma-active compounds were screened in MT, and 2-pentylfuran showed the highest relative odor activity value (ROAV). A total of 26 key aroma-active compounds were identified in FMT, and the newly formed compound 1-octen-3-one showed the highest ROAV, which contributed to FMT's unique mushroom, herbal, and earthy flavor attributes. 1-octen-3-one, (E)-2-nonenal, trimethyl-pyrazine, 2-pentylfuran, and heptanal were screened as the potential markers that contributed to flavor differences between MT and FMT. E. cristatum fermentation significantly altered the sensory properties and flavor compounds of MT. This study provides valuable insights into the sensory qualities of MT and FMT, offering a theoretical basis for the development of FMT products.

Astaxanthin, Haematococcus pluvialis and Haematococcus pluvialis Residue Alleviate Liver Injury in D-Galactose-induced Aging Mice through Gut-liver Axis.

Astaxanthin is a keto-based carotenoid mainly obtained from marine organisms, like Haematococcus pluvialis (H. pluvialis). Previous studies indicated the protective effects of Astaxanthin and H. pluvialis on aging related oxidative injury in liver, while the potential mechanisms are largely unknown. In addition, H. pluvialis residue is a by-product after astaxanthin extraction, which is rarely studied and utilized. The present study aimed to compare the effects of astaxanthin, H. pluvialis and H. pluvialis residue on the oxidant injury of liver in D-galactose-induced aging mice and explore the potential mechanisms through gut-liver axis. The results showed that all the three supplements prevented D-galactose-induced tissue injury, oxidative stress and chronic inflammation in liver and improved liver function. Gut microbiota analysis indicated that astaxanthin notably increased fecal levels of Bacteroidetes, unclassified_f__ Lachnospiraceae, norank_f__Lachnospiraceae, norank_f__norank_o__Clostridia_UCG-014, Prevotellaceae_ UCG-001, unclassified_f__Prevotellaceae in D-galactose-fed mice (p < 0.05). Compared to aging mice, H. pluvialis group had higher fecal levels of norank_f__Lachnospiraceae and Lachnospiraceae_UCG-006 (p < 0.05). H. pluvialis residue group displayed higher relative levels of Bacteroidetes, Streptococcus, and Rikenellaceae_RC9_gut_group (p < 0.05). Moreover, the production of fecal microbial metabolites, like SCFAs and LPS was also differently restored by the three supplements. Overall, our results suggest astaxanthin, H. pluvialis and H. pluvialis residue could prevent aging related hepatic injury through gutliver axis and provide evidence for exploiting of H. pluvialis residue as a functional ingredient for the treatment of liver diseases. Future studies are needed to further clarify the effect and mechanism of dominant components of H. pluvialis residue on liver injury, which is expected to provide a reference for the high-value utilization of H. pluvialis resources.

Comparative study of lung cancer between smokers and nonsmokers: A real-world study based on the whole population from Tianjin City, China.

INTRODUCTION: The purpose of this study was to examine the prevalence, clinical characteristics, and changing trends of non-smokers with lung cancer (LC) based on data from a population-wide cancer registry in northern China. METHODS: The study used LC incidence and follow-up data from 2010 to 2019 from the Cancer Registry System of Tianjin city, which included 82769 cases. Trends in the incidence and proportion of non-smokers with LC were examined by joinpoint regression analysis. Life table and Cox survival analyses were used to calculate the survival rates and compare the death hazard ratios (HRs) in different groups, respectively. RESULTS: Among the 82769 new diagnosis cases of LC during 2010 to 2019, there were 34589 (41.8%) current smokers, 14913 (18.0%) ex-smokers, 28123 (34.0%) non-smokers, and 5144 (6.2%) unknowns. The proportion of non-smokers changed slightly from 2010 (35.36%) to 2019 (36.87%) (annual percentage change, APC= -0.01%, p>0.05). This proportion declined in men (2010 vs 2019; 22.06% vs 20.66%) and increased in women (2010 vs 2019; 53.02% vs 62.35%), and in the 0-44 years age group it showed an upward trend from 2015 to 2019 (APC=4.82%, 95% CI: 1.8-7.9). Compared with smokers with LC, non-smokers with LC were predominantly females (64.15% vs 27.26%), had a predominantly adenocarcinoma histological subtypes (76.71% vs 42.22%), and had a 20% lower risk of death than smokers (HR=0.80; 95% CI: 0.78-0.81). CONCLUSIONS: The proportion of non-smokers with LC was relatively high in northern China, with an increasing trend in the proportion of females and younger age groups. Non-smokers with LC had different epidemiological and clinical characteristics compared with smokers with LC.

The prognostic role of circulating tumor DNA across breast cancer molecular subtypes: A systematic review and meta-analysis.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.