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ABSTRACTThe antipsychotic drug pimozide has been demonstrated to inhibit cancer. However, the precise anti-cancer mechanism of pimozide remains unclear. The purpose of this study was to investigate the effects of pimozide on human MCF-7 and MDA-MB-231 breast cancer cell lines, and the potential involvement in the RAF/ERK signaling. The effects of pimozide on cells were examined by 4,5-dimethylthiazol-2-yl-3,5-diphenylformazan, wound healing, colony formation, transwell assays, and caspase activity assay. Flow cytometry and acridine orange and ethidium bromide staining were performed to assess changes in cells. Transmission electron microscopy and monodansylcadaverine staining were used to observe autophagosomes. The cyclic adenosine monophosphate was evaluated using the FRET system. Immunohistochemistry, immunofluorescence, RNA interference, and western blot investigated the expression of proteins. Mechanistically, we focus on the RAF1/ERK signaling. We detected pimozide was docked to RAF1 by Schrodinger software. Pimozide down-regulated the phosphorylation of RAF1, ERK 1/2, Bcl-2, and Bcl-xl, up-regulated Bax, and cleaved caspase-9 to induce apoptosis. Pimozide might promote autophagy by up-regulating cAMP. The enhancement of autophagy increased the conversion of LC3-I to LC3-II and down-regulated p62 expression. But mTOR signaling was not involved in promoting autophagy. The knockdown of RAF1 expression induced autophagy and apoptosis in breast cancer cells, consistent with the results of pimozide or sorafenib alone. Blocked autophagy by chloroquine resulted in the impairment of pimozide-induced apoptosis. These data showed that pimozide inhibits breast cancer by regulating the RAF/ERK signaling pathway and might activate cAMP-induced autophagy to promote apoptosis and it may be a potential drug for breast cancer treatment.

Huangjiu is known for its unique aroma, primarily attributed to its high concentration of β-phenylethanol (ranging from 40 to 130 mg/L). Phenylalanine aminotransferase Aro9p and phenylpyruvate decarboxylase Aro10p are key enzymes in the β-phenylethanol synthetic pathway of Saccharomyces cerevisiae HJ. This study examined the enzymatic properties of these two enzymes derived from S. cerevisiae HJ and S288C. After substrate docking, Aro9pHJ (−24.05 kJ/mol) and Aro10pHJ (−14.33 kJ/mol) exhibited lower binding free energies compared to Aro9pS288C (−21.93 kJ/mol) and Aro10pS288C (−12.84 kJ/mol). ARO9 and ARO10 genes were heterologously expressed in E. coli BL21. Aro9p, which was purified via affinity chromatography, showed inhibition by l-phenylalanine (L-PHE), but the reaction rate Vmax(Aro9pHJ: 23.89 μmol·(min∙g)−1) > Aro9pS288C: 21.3 μmol·(min∙g)−1) and inhibition constant Ki values (Aro9pHJ: 0.28 mol L−1>Aro9pS288C 0.26 mol L−1) indicated that Aro9p from S. cerevisiae HJ was more tolerant to substrate stress during Huangjiu fermentation. In the presence of the same substrate phenylpyruvate (PPY), Aro10pHJ exhibited a stronger affinity than Aro10pS288C. Furthermore, Aro9pHJ and Aro10pHJ were slightly more tolerant to the final metabolites β-phenylethanol and ethanol, respectively, compared to those from S288C. The study suggests that the mutations in Aro9pHJ and Aro10pHJ may contribute to the increased β-phenylethanol concentration in Huangjiu. This is the first study investigating enzyme tolerance mechanisms in terms of substrate and product, providing a theoretical basis for the regulation of the β-phenylethanol metabolic pathway.

ABSTRACTThe effects of microbial contamination on the rancidity of Huangjiu (Chinese rice wine) during pottery jar storage were studied. With the increase in the rancidity of Huangjiu, the alcohol content decreased, while the conductivity increased significantly. The sour taste and umami taste of Huangjiu increased, leading to flavor deterioration. Meanwhile, the increase in biogenic amine content makes Huangjiu unfit for drinking. The changes in components showed that the degree of rancidity was related to the metabolism of organic acids and amino acids caused by contaminated microorganisms. According to the analysis of microbial community structure, more microorganisms were found in the severe rancid Huangjiu. This indicated that with the aggravation of the degree of rancidity, the community structure of the contaminated microorganisms becomes complex, and potentially pathogenic microorganisms such as Arcobacter species were detected. Therefore, the change of components of Huangjiu will also affect the community structure of contaminated microorganisms.

Abstract Different microorganisms can produce different proteases, which can adapt to different industrial requirements such as pH, temperature, and pressure. Salt-tolerant proteases (STPs) from microorganisms exhibit higher salt tolerance, wider adaptability, and more efficient catalytic ability under extreme conditions compared to conventional proteases. These unique enzymes hold great promise for applications in various industries including food, medicine, environmental protection, agriculture, detergents, dyes, and others. Scientific studies on microbial-derived STPs have been widely reported, but there has been little systematic review of microbial-derived STPs and their application in high-salt conventional soybean fermentable foods. This review presents the STP-producing microbial species and their selection methods, and summarizes and analyzes the salt tolerance mechanisms of the microorganisms. It also outlines various techniques for the isolation and purification of STPs from microorganisms and discusses the salt tolerance mechanisms of STPs. Furthermore, this review demonstrates the contribution of modern biotechnology in the screening of novel microbial-derived STPs and their improvement in salt tolerance. It highlights the potential applications and commercial value of salt-tolerant microorganisms and STPs in high-salt traditional soy fermented foods. The review ends with concluding remarks on the challenges and future directions for microbial-derived STPs. This review provides valuable insights into the separation, purification, performance enhancement, and application of microbial-derived STPs in traditional fermented foods. Graphical Abstract

Abstract Identification of the core functional microorganisms in food fermentations is necessary to understand the ecological and functional processes for making those foods. Wheat qu, which provides liquefaction and saccharifying power, and affects the flavor quality, is a key ingredient in ancient alcoholic huangjiu fermentation, while core microbiota of them still remains indistinct. In this study, metagenomics, metabolomics, microbial isolation and co-fermentation were used to investigate huangjiu. Although Aspergillus is usually regarded as core microorganism in wheat qu to initiate huangjiu fermentations, our metagenomic analysis showed that bacteria Saccharopolyspora are predominant in wheat qu and responsible for breakdown of starch and cellulose. Metabolic network and correlation analysis showed that Saccharopolyspora rectivirgula, Saccharopolyspora erythraea, and Saccharopolyspora hirsuta made the greatest contributions to huangjiu’s metabolites, consisting of alcohols (phenylethanol, isoamylol and isobutanol), esters, amino acids (Pro, Arg, Glu and Ala) and organic acids (lactate, tartrate, acetate and citrate). S. hirsuta J2 isolated from wheat qu had the highest amylase, glucoamylase and protease activities. Co-fermentations of S. hirsuta J2 with S. cerevisiae HJ resulted in a higher fermentation rate and alcohol content, and huangjiu flavors were more similar to that of traditional huangjiu compared to co-fermentations of Aspergillus or Lactiplantibacillus with S. cerevisiae HJ. Genome of S. hirsuta J2 contained genes encoding biogenic amine degradation enzymes. By S. hirsuta J2 inoculation, biogenic amine content was reduced by 45%, 43% and 62% in huangjiu, sausage and soy sauce, respectively. These findings show the utility of Saccharopolyspora as a key functional organism in fermented food products.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Abstract Background There is growing interest regarding vitamin D and its potential role in gestational diabetes mellitus (GDM). We aimed to assess maternal vitamin D status in early pregnancy and its relationships with the risk of GDM in a Chinese population in Shanghai. Methods The retrospective cohort study included a total of 7816 pregnant women who underwent a 75-g oral glucose tolerance test (OGTT) during 24–28 weeks of gestation. Participants’ demographic information including maternal age, prepregnancy body mass index (BMI), gestational age, parity, season of blood collection, serum 25-hydroxy vitamin D [25(OH)D] data and other blood biomarker data at 6 to 14 weeks of gestation were retrospectivly extracted from the medical records in the hospital information system. Results In the cohort, the prevalence of GDM was 8.6% and the prevalence of vitamin D deficiency and insufficiency in early pregnancy was 53.1 and 38.5%, respectively. The mean value of the serum 25(OH)D concentration was 19.6±7.5 ng/mL. The restricted cubic splines model showed an inverted J-shaped relationship in which the risk of GDM decreased when the 25(OH)D concentrations were ≥ 20 ng/mL. Logistic model analysis showed that 25(OH)D concentrations ≥ 30 ng/mL significantly decreased the risk of GDM (odds ratio = 0.63, 95% confidence interval: 0.45-0.89; P = 0.010) compared with 25(OH)D concentrations < 20 ng/ml. Conclusions In early pregnancy, vitamin D deficiency and insufficiency were very common, and a high level of vitamin D showed protective effects against the incidence risk of GDM.

Abstract Protein arginine methyltransferase 5 (PRMT5) is a major type II enzyme responsible for symmetric dimethylation of arginine (SDMA), and plays predominantly roles in human cancers, including in ovarian cancer. However, the exactly roles and underlying mechanisms of PRMT5 contributing to the progression of ovarian cancer mediated by reprogramming cell metabolism remain largely elusive. Here, we report that PRMT5 is highly expressed and correlates with poor survival in ovarian cancer. Knockdown or pharmaceutical inhibition of PRMT5 is sufficient to decrease glycolysis flux, attenuate tumor growth, and enhance the antitumor effect of Taxol. Mechanistically, we find that PRMT5 symmetrically dimethylates alpha‐enolase (ENO1) at arginine 9 to promotes active ENO1 dimer formation, which increases glycolysis flux and accelerates tumor growth. Moreover, PRMT5 signals high glucose to increase the methylation modification of ENO1. Together, our data reveal a novel role of PRMT5 in promoting ovarian cancer growth by controlling glycolysis flux mediated by methylating ENO1, and highlights that PRMT5 may represent a promising therapeutic target for treating ovarian cancer.

Luxiang-flavor Baijiu is the mainstream of Baijiu production and consumption in China, and the microbial composition has a great influence on the flavor and quality of Baijiu. In this study, we combined multi-omics sequencing technology to explore the microbial composition, dynamics and metabolite changes of Luxiang-flavor Jiupei during long fermentation periods. The results showed that based on the interaction between environmental constraints and microorganisms, Jiupei microorganisms formed different ecological niches and functional differentiation, which led to the formation of Jiupei stable core microorganisms. The bacteria were mainly Lactobacillus and Acetobacter, and the fungi were mainly Kazachstani and Issatchenkia. Most bacteria were negatively correlated with temperature, alcohol and acidity, and for the fungi, starch content, reducing sugar content and temperature had the most significant effects on community succession. Macroproteomic analysis revealed that Lactobacillus jinshani had the highest relative content; microbial composition, growth changes and functions were more similar in the pre-fermentation period (0–18 days); microorganisms stabilized in the late fermentation period (24–220 days). The metabolome analysis revealed that the metabolites of the Jiupei changed rapidly from 18 to 32 days of fermentation, with a significant increase in the relative content of amino acids, peptides and analogs and a significant decrease in the relative content of sugars; the metabolites of the Jiupei changed slowly from 32 to 220 days of fermentation, with a stabilization of the content of amino acids, peptides and analogs. This work provides insights into the microbial succession and microbial drivers during the long-term fermentation of Jiupei, which have potential implications for optimizing production and improving the flavor of Baijiu.

Huangjiu is rich in low-molecular-weight peptides and has an umami taste. In order for its umami peptides to be discovered, huangjiu was subjected to ultrafiltration, ethanol precipitation, and macroporous resin purification processes. The target fractions were gathered according to sensory evaluation. Subsequently, we used peptidomics to identify the sum of 4158 peptides in most umami fractions. Finally, six novel umami peptides (DTYNPR, TYNPR, SYNPR, RFRQGD, NFHHGD, and FHHGD) and five umami-enhancing peptides (TYNPR, SYNPR, NFHHGD, FHHGD, and TVDGPSH) were filtered via virtual screening, molecular docking, and sensory verification. Moreover, the structure–activity relationship was discussed using computational approaches. Docking analysis showed that all umami peptides tend to bind with T1R1 through hydrogen bonds and hydrophobic forces, which involve key residues HIS71, ASP147, ARG151, TYR220, SER276, and ALA302. The active site calculation revealed that the positions of the key umami residues D and R in the terminal may cause taste differences in identified peptides.

Saccharopolyspora is an important microorganism in the fermentation process of wheat qu and huangjiu, yet the mechanisms by which it performs specific functions in huangjiu remain unclear. A strain with high amylase and glucoamylase activities was isolated from wheat qu and identified as Saccharopolyspora rosea (S. rosea) A22. We initially reported the whole genome sequence of S. rosea A22, which comprised a circular chromosome 6,562,638 bp in size with a GC content of 71.71%, and 6,118 protein-coding genes. A functional genomic analysis highlighted regulatory genes involved in adaptive mechanisms to harsh conditions, and in vitro experiments revealed that the growth of S. rosea A22 could be regulated in response to the stress condition. Based on whole-genome sequencing, the first genome-scale metabolic model of S. rosea A22 named iSR1310 was constructed to predict the growth ability on different media with 91% accuracy. Finally, S. rosea A22 was applied to huangjiu fermentation by inoculating raw wheat qu, and the results showed that the total higher alcohol content was reduced by 12.64% compared with the control group. This study has elucidated the tolerance mechanisms and enzyme-producing properties of S. rosea A22 at the genetic level, providing new insights into its application to huangjiu.

Fermentation is an ancient food preservation and processing technology with a long history of thousands of years, that is still practiced all over the world. Fermented foods are usually defined as foods or beverages made by controlling the growth of microorganisms and the transformation of raw and auxiliary food components, which provide the human body with many beneficial nutrients or health factors. As fungus widely used in traditional Chinese fermented foods, molds and yeasts play an irreplaceable role in the formation of flavor substances and the production of functional components in fermented foods. The research progress of molds and yeasts in traditional Chinese fermented foods from traditional to modern is reviewed, including the research on the diversity, and population structure of molds and yeasts in fermented foods. The interaction between fermenting mold and yeast and the latest research results and application development prospects of related industries were discussed.

Huangjiu is one of the oldest alcoholic beverages in the world. It is usually made by fermenting grains, and Qu is used as a saccharifying and fermenting agent. In this study, we identified differential carbonyl compounds in Huangjiu with varying sugar contents from different regions. First, we developed and validated a detection method for volatile carbonyl compounds in Huangjiu, and for optimal extraction, 5 mL of Huangjiu and 1.3 g/L of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride (PFBHA) were incubated at 45 °C for 5 min before extracting the volatile carbonyl compounds at 45 °C for 35 min. Second, the targeted quantitative analysis of 50 carbonyl compounds in Huangjiu showed high levels of Strecker aldehydes and furans. Finally, orthogonal projections to latent structures discriminant analysis (OPLS-DA) was used to differentiate between Huangjiu with different sugar contents, raw materials, and region of origin. A total of 19 differential carbonyl compounds (VIP > 1, p < 0.05) were found in Huangjiu with different sugar contents (semidry and semisweet Huangjiu), and 20 differential carbonyl compounds (VIP > 1, p < 0.05) were found in different raw materials for Huangjiu production (rice and nonrice Huangjiu). A total of twenty-two and eight differential carbonyl compounds, with VIP > 1 and p < 0.05, were identified in semidry and semisweet Huangjiu from different regions (Zhejiang, Jiangsu, Shanghai, and Fujian), respectively.

Aging is a time-consuming step in the manufacturing of fermented alcoholic beverages. Natural-aging huangjiu sealed in pottery jars was taken as an example to investigate the changes of physiochemical indexes during aging and to quantify intercorrelations between aging-related factors and metabolites through machine learning methods. Machine learning models provided significant predictions for 86% of metabolites. Physiochemical indexes well reflected the metabolic profile, and total acid was the most important index that needed to be controlled. For aging-related factors, several aging biomarkers of huangjiu were also well predicted. Feature attribution analysis showed aging year was the most powerful predictive factor, and several microbial species were significantly associated with aging biomarkers. Some of the correlations, mostly connected to environmental microorganisms, were newly found, showing considerable microbial influence on aging. Overall, our results reveal the potential determinants that affect the metabolic profile of aged huangjiu, paving the way for a systematical understanding of changes in metabolites of fermented alcoholic beverages.

Abstract Monacolin K (MK) is a secondary metabolite synthesized by polyketide synthases of Monascus spp. In this study, the combined supplementation of three medicines, including Citri Reticulatae Pericarpium (CRP), Fructus crataegi (FC), and Radix Angelicae Dahuricae (RAD), were mixed with nonglutinous rice and were optimized by response surface methodology to enhance the production of MK in fermented red mold rice (RMR). Under the optimum condition, MK production achieved 3.60 mg/g, which was 41.18% higher than RMR without medicines. The improved MK production was mainly caused by the up‐regulated transcription level of mokA, mokB, mokF, mokH, mokI, and mplaeA. Meanwhile, the inhibitory effect of Poria cocos (PC) on MK production (only 0.436 mg/g) was caused by significantly down‐regulated transcription of six tested genes. Therefore, this study is beneficial for better understanding of the possible mechanism of enhanced MK production by optimization of fermentation conditions.

Huangjiu lees (HL) is a byproduct in Chinese Huangjiu production with various nutrient and biological functional components. Without efficient treatment, it could cause environmental issues and bioresource wasting. Existing dominant recovery approaches focus on large-scale disposal, but they ignore the application of high-value components. This study discusses the advantages and limitations of existing resourcing approaches, such as feed, food and biogas biological production, considering the efficiency and value of HL resourcing. The extraction of functional components as a suggestion for HL cascade utilization is pointed out. This study is expected to promote the application of HL resourcing.

Vinegar residue (VR) is a typical organic solid waste in Chinese cereal vinegar production. It is characterized by high yield, high moisture and low pH and is rich in lignocellulose and other organic matter. To avoid the environmental pollution caused by VR, it should be properly treated. The industry’s existing treatment processes, landfills and incineration, cause secondary pollution and waste of resources. Therefore, there is an urgent demand for environmentally friendly and cost-effective resource recovery technologies for VR. To date, a considerable amount of research has been performed in the area of resource recovery technologies for VR. This review summarizes the reported resource recovery technologies, mainly anaerobic digestion, feed production, fertilizer production, high-value product production and soil/water remediation. The principles, advantages and challenges of these technologies are highlighted. Finally, as a future perspective, a cascade and full utilization model for VR is proposed by considering the inherent drawbacks and economic-environmental feasibility of these technologies.

Energy metabolism programming is a hallmark of cancer, and serves as a potent target of cancer therapy. Valproic acid (VPA), a broad Class I histone deacetylases (HDACs) inhibitor, has been used as a therapeutic agent for cancer. However, the detail mechanism about the potential role of VPA on the Warburg effect in breast cancer remains unclear. In this study, we highlight that VPA significantly attenuates the Warburg effect by decreasing the expression of pyruvate kinase M2 isoform (PKM2), leading to inhibited cell proliferation and reduced colony formation in breast cancer MCF-7 and MDA-MB-231 cells. Mechanistically, Warburg effect suppression triggered by VPA was mediated by inactivation of ERK1/2 phosphorylation through reduced HDAC1 expression, resulting in suppressing breast cancer growth. In summary, we uncover a novel mechanism of VPA in regulating the Warburg effect which is essential for developing the effective approach in breast cancer therapy.

Hyperlipidemia is a chronic disorder that is difficult to cure and usually treated with long-term lipid-reducing drugs. Recent trends have led to the use of diet therapies or food-derived strategies in the treatment of such long-term diseases. The Chinese rice wine (huangjiu) contains a wide range of bioactive peptides that are produced during the multi-species fermentation process. To clarify the regulation effects of lipid metabolism and gut microbiota by huangjiu bioactive peptides, three huangjiu peptides were isolated, purified and characterized by hyper-filtration, macroporous resin, gel filtration separation and structural identification. Meanwhile, a mouse model of high-fat diet-induced hyperlipidemia was established to study the effects of huangjiu peptides on serum biomarker, hepatic metabolism and gut microbiota dysbiosis. Experimental results showed that huangjiu peptides T1 and T2 (HpT1, HpT2) treatment alleviated the increase in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol levels and aberrant hepatic lipid accumulation in the high-fat diet-induced hyperlipidemia mice. Furthermore, HpT2 and HpT1 restored the α-diversity and structure of gut microbial community after hyperlipidemia-induced microbiota disturbance compared with simvastatin and HpT3. The administration of HpT2 and HpT1 regulated the microbiota-mediated gut ecology through alterations of characteristic taxa including Lactobacillus, Ileibacterium, Faecalibaculum and Alloprevotella by linear discriminant analysis effect size analysis. Collectively, our results offer new insights into the abilities of food-derived peptides on alleviation of high-fat diet-induced hyperlipidemia, hepatic steatosis and gut dysbiosis in mice.

The European sunflower moth, Homoesoma nebulellum (Denis et Schiffermüller), emerged as a major new pest in Bayannur, China, in 2006. Insecticidal control with a single application is problematic because timing is critical, and multiple applications increase production and environmental costs. Management of H. nebulellum by planting date adjustment can be effective, but the optimal time window for late planting is unknown. Natural levels of H. nebulellum infestation were compared among sunflowers planted on five dates from April 25 to June 5 in two years, and the relationship between timing of adult abundance and flowering assessed. Delaying planting of sunflower from the traditional planting period of April 25 -May 5 to May 15 -June 5 significantly decreased damage by H. nebulellum. Seed infestation rate was 30-40 times higher, and number of larvae/head 75-100 times higher in the earliest two plantings than in the latest two. Within two years of implementing delayed planting in Bayannur city, infestation area decreased from 72% in 2006 to 1.5% in 2008, and production losses decreased from 4.5 ton/ha in 2006 to 0.36 ton/ha in 2008, a 97% decrease compared to 2006. Moreover, the infestation area caused by H. nebulellum was continuously controlled below 5.3% of the planting area since 2008. We found the overlap between the first two days of flowering and peak adult presence was the key factor influencing level of damage caused by H. nebulellum. Because the number of eggs laid in the first two days of flowering accounted for 68% of the total, and sunflower seed infestation rate was positively correlated with the number of trapped adults weighted by proportion of daily oviposition. Oviposition of the majority of eggs in the first two days of flowering suggests an evolutionary mechanism whereby females choose host plants most conducive to larval development, consistent with the preference-performance hypothesis.

Skeletal muscles are impressive as they can achieve reversible, macroscopic, anisotropic motion in soft materials. Here the authors show a bottom-up design of macroscopic hydrogel tubes containing supramolecular nanofibers that can undergo anisotropic actuation by thermal stimuli.

The present study focused on isolating an efficient enzyme production microorganism for ferulic acid (FA) production from wheat bran. A wild-type cellulase-, xylanase-, and feruloyl esterase-producing strain was isolated and identified as Penicillium oxalicum M1816. The genome was sequenced and assembled into 30.5 Mb containing 8301 predicted protein-coding genes. In total, 553 genes were associated with carbohydrate metabolism. Genomic CAZymes analysis indicated that P. oxalicum M1816, comprising 39 cellulolytic enzymes and 111 hemicellulases (including 5 feruloyl esterase genes), may play a vital role in wheat bran degradation and FA production. The crude enzyme of strain M1816 could release 1.85 ± 0.08 mg·g−1 FA from de-starched wheat bran (DSWB) at 12 h, which was significantly higher than other commercial enzymes. Meanwhile, when the strain M1816 was cultured in medium supplemented with DSWB, up to 92.89% of the total alkali-extractable FA was released. The process parameters of solid-state fermentation were optimized to enhance enzyme production. The optimized wheat bran Qu of P. oxalicum M1816 was applied to huangjiu fermentation, and the FA content was increased 12.4-fold compared to the control group. These results suggest that P. oxalicum M1816 is a good candidate for the development of fermented foods bio-fortified with FA.

Abstract Background Accumulated evidence has demonstrated that Mammalian hepatitis B X-interacting protein (HBXIP) has broad roles in cancer. Although HBXIP is associated with a variety of cancers, the HBXIP protein expression level and its clinical significance in ovarian cancer have not yet been determined. The aim of this study is to investigate the association between HBXIP expression and the clinicopathological features of ovarian cancer patients to determine whether HBXIP may be correlated with a poor prognosis in ovarian cancer patients. Methods HBXIP protein expression was assessed in a well-characterized series of ovarian cancer tissue samples (n = 120) with long-term follow-up, using immunohistochemistry to determine the location pattern and expression of HBXIP in ovarian cancer. The localization of HBXIP was detected in SKOV-3 ovarian cancer cells using immunofluorescence (IF) staining. The relationship between high HBXIP expression and the clinicopathological features of ovarian cancer patients was analyzed by Chi-square and Fisher’s exact test. Overall survival (OS) rates of all the ovarian cancer patients were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Results IF staining revealed strongly positive signals for HBXIP in both cytoplasm and nucleus, but mainly in the cytoplasm of SKOV-3 ovarian cancer cells. High HBXIP expression was predominantly observed in ovarian cancer tissues but not the adjacent non-tumor ovarian tissues. The strongly positive rate of HBXIP expression was 60.0% (72/120) in ovarian cancer and was significantly higher than in adjacent non-tumor tissues (17.4%, 4/23) (P = 0.000). High HBXIP expression was positively correlated with the occurrence of lymph node metastases (P = 0.025), histological grade (P = 0.036) and clinical stage (P = 0.003). The patients with high HBXIP expression had lower overall survival (OS) rates. Moreover, multivariate analysis indicated that HBXIP, in addition to the clinical stage, was a significant independent prognostic factor in patients with ovarian cancer. Conclusions High-level expression of HBXIP is associated with the progression of ovarian cancer and may be an effective biomarker for poor prognostic evaluation as well as a potential molecular therapy target for ovarian cancer patients.

Copper chaperone for superoxide dismutase (CCS) is a critical component of oxidation–reduction system and functions as a potential tumor promoter in several cancers. However, the function and clinical significance of CCS in breast cancer remain unclear. Here, we found CCS was highly expressed in breast cancer, where it promoted breast cancer cell proliferation and migration. Suppression of CCS expression was sufficient to attenuate the phosphorylation level of ERK1/2 and increase the accumulation of reactive oxygen species (ROS). Mechanistically, we found that knockdown of CCS decreases the activity of ERK1/2 mediated by the accumulation of ROS, which leads to the inhibition of cell proliferation and migration. In summary, these results indicated that CCS promotes the growth and migration of breast cancer cells via regulating the ERK1/2 activity mediated by ROS.

Emerging evidence has demonstrated that the high expression of HBXIP has been correlated with many cancers. With evaluation of the functional role of HBXIP in non-small-cell lung cancer, the primary aim of this study is to investigate the correlation between HBXIP expression and the prognosis of non-small-cell lung cancer patients. The protein levels of HBXIP were detected using western blotting in non-small-cell lung cancer cells. Cell proliferation and migration assays were measured to evaluate the function of HBXIP in non-small-cell lung cancer cells. A total of 120 non-small-cell lung cancer patients with strict follow-up and 60 adjacent non-tumor lung tissues were selected for immunohistochemical staining of the HBXIP protein. The localization of the HBXIP protein was detected in A549 non-small-cell lung cancer cells using immunofluorescence staining. The correlation between HBXIP expression and the clinicopathological features of non-small-cell lung cancer patients was analyzed by a chi-squared and Fisher’s exact test. The overall survival rates of all of the non-small-cell lung cancer patients were calculated using the Kaplan–Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model. In function, we showed that suppression of HBXIP decreased A549 cell proliferation and migration. HBXIP protein showed a mainly cytoplasmic staining pattern in non-small-cell lung cancer using immunohistochemical staining in paraffin-embedded non-small-cell lung cancer tissues and immunofluorescence staining in A549 cells. The HBXIP protein had strong positive staining in the non-small-cell lung cancer tissues, which was significantly higher than the percentage of adjacent non-tumor tissues. The overexpression of HBXIP was closely correlated with histological grade, clinical stage, lymph node metastasis, and lower overall survival rates of patients with non-small-cell lung cancer. Moreover, multivariate analysis suggested that HBXIP emerged as a significant independent prognostic factor along with clinical stage in patients with non-small-cell lung cancer. In conclusion, a high level of expression of HBXIP is associated with the progression of non-small-cell lung cancer and may be a useful biomarker for poor prognostic evaluation and a potential molecular therapy target for patients with non-small-cell lung cancer.

Cisplatin (DDP) is currently one of the most commonly used chemotherapeutic drugs for treating ovarian and lung cancer. However, resistance to cisplatin is common and it often leads to therapy failure. In addition, the precise mechanism of cisplatin resistance is still in its infancy. In this study, we demonstrated that the oxidative pentose phosphate pathway enzyme 6-phosphogluconate dehydrogenase (6PGD) promotes cisplatin resistance. We showed that cisplatin-resistant cancer cells (C13∗ and A549DDP), had higher levels of 6PGD compared to their cisplatin-sensitive counterparts (OV2008 and A549). Furthermore, ovarian and lung cancer patients with higher 6PGD levels have worse survival outcomes relative to patients with lower 6PGD expression. Interestingly, we found that the upregulation of 6PGD in cisplatin-resistant cells was due to the decreased expression of miR-206 and miR-613, which we found to target this enzyme. We further demonstrate that suppressing 6PGD using shRNA, inhibitor or miR-206/miR-613, either as single agents or in combination, could sensitize cisplatin-resistant cancer cells to cisplatin treatment and thereby improving the therapeutic efficacy of cisplatin. Taken together, our results suggest that 6PGD serves as a novel potential target to overcome cisplatin resistance.