Rewiring metabolic flux to simultaneously improve malate production and eliminate by-product succinate accumulation by Myceliophthora thermophila.

Although a high titre of malic acid is achieved by filamentous fungi, by-product succinic acid accumulation leads to a low yield of malic acid and is unfavourable for downstream processing. Herein, we conducted a series of metabolic rewiring strategies in a previously constructed Myceliophthora thermophila to successfully improve malate production and abolish succinic acid accumulation. First, a pyruvate carboxylase CgPYC variant with increased activity was obtained using a high-throughput system and introduced to improve malic acid synthesis. Subsequently, shifting metabolic flux to malate synthesis from mitochondrial metabolism by deleing mitochondrial carriers of pyruvate and malate, led to a 53.7% reduction in succinic acid accumulation. The acceleration of importing cytosolic succinic acid into the mitochondria for consumption further decreased succinic acid formation by 53.3%, to 2.12 g/L. Finally, the importer of succinic acid was discovered and used to eliminate by-product accumulation. In total, malic acid production was increased by 26.5%, relative to the start strain JG424, to 85.23 g/L and 89.02 g/L on glucose and Avicel, respectively, in the flasks. In a 5-L fermenter, the titre of malic acid reached 182.7 g/L using glucose and 115.8 g/L using raw corncob, without any by-product accumulation. This study would accelerate the industrial production of biobased malic acid from renewable plant biomass.

Developing Liver Microphysiological Systems for Biomedical Applications.

Microphysiological systems (MPSs), also known as organ chips, are micro-units that integrate cells with diverse physical and biochemical environmental cues. In the field of liver MPSs, cellular components have advanced from simple planar cell cultures to more sophisticated 3D formations such as spheroids and organoids. Additionally, progress in microfluidic devices, bioprinting, engineering of matrix materials, and interdisciplinary technologies have significant promise for producing MPSs with biomimetic structures and functions. This review provides a comprehensive summary of biomimetic liver MPSs including their clinical applications and future developmental potential. First, the key components of liver MPSs, including the principal cell types and engineered structures utilized for cell cultivation, are briefly introduced. Subsequently, the biomedical applications of liver MPSs, including the creation of disease models, drug absorption, distribution, metabolism, excretion, and toxicity, are discussed. Finally, the challenges encountered by MPSs are summarized, and future research directions for their development are proposed.

Bi2O3/Gd2O3 Meta-Aerogel with Leaf-Inspired Nanotrap Array Enables Efficient X-Ray Absorption.

The increasing utilization of X-rays has generated a growing need for efficient shielding materials. However, the existing Pb-based materials suffer from a narrow X-ray absorbing range, high weight, and rigidity. Inspired by the natural leaf, which can efficiently absorb light through chlorophyll and carotenoids in confined cells, we engineer ultralight and superelastic nanofibrous Bi2O3/Gd2O3 meta-aerogels (BGAs) with X-ray nanotrap arrays by manipulating the 3D confined assembly of 1D Bi2O3 and Gd2O3 nanofibers. The BGAs can synergistically absorb X-ray photons from complementary energy ranges into the nanotraps and induce cyclic collisions with Bi2O3 and Gd2O3 nanofibers, maximizing the effective X-ray attenuation. The meta-aerogel exhibits the integrated performance of efficient X-ray shielding efficiency (60-83%, 16-90 keV), ultralow density (10 mg cm-3), and superelasticity. The production of these meta-aerogels presents an avenue for the development of next-generation X-ray protective materials and the resolution of X-ray imaging systems.

Dietary fat and fatty acid consumptions and the odds of asthenozoospermia: a case-control study in China.

STUDY QUESTION: Are dietary fat and fatty acid (FA) intakes related to the odds of asthenozoospermia? SUMMARY ANSWER: Plant-based fat consumption was associated with decreased asthenozoospermia odds, while the consumption of animal-based monounsaturated fatty acid (MUFA) was positively related to asthenozoospermia odds. WHAT IS KNOWN ALREADY: Dietary fat and FA are significant ingredients of a daily diet, which have been demonstrated to be correlated to the reproductive health of men. However, to date, evidence on fat and FA associations with the odds of asthenozoospermia is unclear. STUDY DESIGN SIZE DURATION: The hospital-based case-control study was performed in an infertility clinic from June 2020 to December 2020. Briefly, 549 asthenozoospermia cases and 581 controls with normozoospermia were available for final analyses. PARTICIPANTS/MATERIALS SETTING METHODS: We collected dietary data through a verified food frequency questionnaire of 110 food items. Asthenozoospermia cases were ascertained according to the World Health Organization guidelines. To investigate the correlations of dietary fat and FA consumptions with the odds of asthenozoospermia, we calculated the odds ratios (ORs) and corresponding 95% CIs through unconditional logistic regression models. MAIN RESULTS AND THE ROLE OF CHANCE: Relative to the lowest tertile of consumption, the highest tertile of plant-based fat intake was inversely correlated to the odds of asthenozoospermia (OR = 0.68, 95% CI = 0.50-0.91), with a significant dose-response relation (OR = 0.85, 95% CI = 0.75-0.97, per standard deviation increment). Inversely, animal-based MUFA intake (OR = 1.49, 95% CI = 1.04-2.14) was significantly correlated to increased odds of asthenozoospermia, and an evident dose-response relation was also detected (OR = 1.24, 95% CI = 1.05-1.45, per standard deviation increment). Subgroup analyses showed similar patterns of associations to those of the primary results. Moreover, we observed significant interactions on both multiplicative and additive scales between animal-based MUFA and cigarette smoking. LIMITATIONS REASONS FOR CAUTION: Selection bias and recall bias were unavoidable in any of the observational studies. As we failed to obtain the information of trans-fatty acid (TFA) consumption, the relation of TFA intake and asthenozoospermia odds was unclear. WIDER IMPLICATIONS OF THE FINDINGS: This study indicated that different sources of fat and FAs might exert different effects on the etiology of asthenozoospermia, and cigarette smoking could exacerbate the adverse effect of high animal-based MUFA intake on asthenozoospermia. Our findings provide novel evidence pertaining to the fields of prevention of asthenozoospermia through decreasing animal-derived fat and FA consumptions and smoking cessation. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the JieBangGuaShuai Project of Liaoning Province, Natural Science Foundation of Liaoning Province, Clinical Research Cultivation Project of Shengjing Hospital, and Outstanding Scientific Fund of Shengjing Hospital. All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Phytochemical consumption and the risk of teratozoospermia: findings from a hospital-based case-control study in China.

STUDY QUESTION: Are dietary phytochemicals associated with the risk of teratozoospermia? SUMMARY ANSWER: Dietary intake of carotene, including total carotene, α-carotene, ß-carotene as well as retinol equivalent, and lutein + zeaxanthin, were inversely correlated with the risk of teratozoospermia. WHAT IS KNOWN ALREADY: Phytochemicals are natural plant derived bioactive compounds, which have been reported to be potentially associated with male reproductive health. To date, no study has investigated the association between phytochemical intake and the risk of teratozoospermia. STUDY DESIGN SIZE DURATION: This hospital-based case-control study, which included 146 newly diagnosed teratozoospermia cases and 581 controls with normozoospermia from infertile couples, was conducted in a hospital-based infertility clinic in China, from June 2020 to December 2020. PARTICIPANTS/MATERIALS SETTING METHODS: Dietary information was collected using a validated semi-quantitative 110-item food frequency questionnaire. Unconditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between phytochemical (i.e. phytosterol, carotene, flavonoid, isoflavone, anthocyanidin, lutein + zeaxanthin, and resveratrol) intake and the risk of teratozoospermia. MAIN RESULTS AND THE ROLE OF CHANCE: We observed a decreased risk of teratozoospermia for the highest compared with the lowest tertile consumption of total carotene (OR = 0.40, 95% CI = 0.21-0.77), α-carotene (OR = 0.53, 95% CI = 0.30-0.93), ß-carotene (OR = 0.47, 95% CI = 0.25-0.88), retinol equivalent (OR = 0.47, 95% CI = 0.24-0.90), and lutein + zeaxanthin (OR = 0.35, 95% CI = 0.19-0.66), with all of the associations showing evident linear trends (all P trend <0.05). In addition, significant dose-response associations were observed between campestanol and α-carotene consumption and the risk of teratozoospermia. Moreover, there was a significant multiplicative interaction between BMI and lutein + zeaxanthin intake (P interaction <0.05). LIMITATIONS REASONS FOR CAUTION: The cases and controls were not a random sample of the entire target population, which could lead to admission rate bias. Nevertheless, the controls were enrolled from the same infertility clinic, which could reduce the bias caused by selection and increase the comparability. Furthermore, our study only included a Chinese population, therefore caution is required regarding generalization of our findings to other populations. WIDER IMPLICATIONS OF THE FINDINGS: Dietary phytochemicals, namely carotene, lutein, and zeaxanthin, might exert a positive effect on teratozoospermia. These phytochemicals are common in the daily diet and dietary supplements, and thus may provide a preventive intervention for teratozoospermia. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Natural Science Foundation of Liaoning Province (No. 2022-MS-219 to X.B.W.), Outstanding Scientific Fund of Shengjing Hospital (No. M1150 to Q.J.W.), Clinical Research Cultivation Project of Shengjing Hospital (No. M0071 to B.C.P.), and JieBangGuaShuai Project of Liaoning Province (No. 2021JH1/1040050 to Y.H.Z.). All authors declared that there was no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

SERS-based biosensor for detection of f-PSA%: Implications for the diagnosis of prostate cancer.

In diagnosing prostate cancer and distinguishing it from other prostate diseases, the ratio of the concentration of free prostate-specific antigen (f-PSA) to total prostate-specific antigen (t-PSA), i.e., (f-PSA%) is more accurate than the concentration of t-PSA alone. Immunoassay based on surface-enhanced Raman scattering (SERS) frequency shift has been proven to be particularly suitable for detecting large biomolecules with high reproducibility. Along similar lines, the present study developed a SERS-based biosensor that simultaneously detects t-PSA and f-PSA. The 4-mercaptobenzoic acid (MBA) on the immunocapture substrate is coupled to the t-PSA antibody through the carboxyl group, and the combination of t-PSA induces the Raman frequency shifts of MBA. The immunocolloidal gold attached with f-PSA antibodies selectively capture the f-PSA that immobilized on the MBA-modified SERS substrates, allowing for f-PSA quantification according to the SERS intensities of the 5, 5'-Dithiobis (succinimidyl-2-nitrobenzoate) (DSNB) probe. The results show that f-PSA and t-PSA have good linear response in the concentration scale of 0.1-20 ng/mL, and 1-200 ng/mL, respectively. The biosensor combines Raman frequency shifts and intensities, which greatly simplifies traditional procedures for f-PSA% detection. All the results demonstrated the great potential of the proposed biosensor in highly reproducible and accurate diagnosis of prostate cancers.

PM2.5 exposure and its interaction of oxidative balance score on ovarian cancer survival: A prospective cohort study.

Recent evidence advises particles with a diameter of 2.5 µm or less (PM2.5) might be a prognostic factor for ovarian cancer (OC) survival. The oxidative balance score (OBS) incorporates diet-lifestyle factors to estimate individuals' anti-oxidant exposure status which may be relevant to cancer prognosis. We aimed to investigate the roles of PM2.5, and OBS and their interaction in OC prognosis. 663 patients with OC were enrolled in the current study. Satellite-derived annual average exposures to PM2.5 based on patients' residential locations. The OBS was calculated based on 16 different diet-lifestyle components derived using an acknowledged self-reported questionnaire. The Cox regression model was performed to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for overall survival (OS). We also assessed the effect of modification between PM2.5 and OS by OBS via interaction terms. During a median follow-up of 37.57 (interquartile:35.27-40.17) months, 123 patients died. Compared to low-concentration PM2.5 exposure, high PM2.5 during 1 year before diagnosis was associated with worse OC survival (HR= 1.19, 95% CI = 1.01-1.42). We observed an improved OS with the highest compared with the lowest OBS (HR = 0.46, 95% CI = 0.27-0.79, P for trend < 0.05). Notably, we also found an additive interaction between low OBS and high exposure to PM2.5, with the corresponding associations of PM2.5 being more pronounced among participants with lower OBS (HR = 1.42, 95% CI = 1.09-1.86). PM2.5 may blunt OC survival, but high OBS represented an antioxidative performance that could alleviate the adverse association of PM2.5 and OS.

Role of adenosine A2a receptor in cancers and autoimmune diseases.

Adenosine receptors are P1 class of purinergic receptors that belong to G protein-coupled receptors. There are 4 subtypes of adenosine receptors, namely A1, A2A, A2B, and A3. A2AR has a high affinity for the ligand adenosine. Under pathological conditions or external stimuli, ATP is sequentially hydrolyzed to adenosine by CD39 and CD73. The combination of adenosine and A2AR can increase the concentration of cAMP and activate a series of downstream signaling pathways, and further playing the role of immunosuppression and promotion of tumor invasion. A2AR is expressed to some extent on various immune cells, where it is abnormally expressed on immune cells in cancers and autoimmune diseases. A2AR expression also correlates with disease progression. Inhibitors and agonists of A2AR may be potential new strategies for treatment of cancers and autoimmune diseases. We herein briefly reviewed the expression and distribution of A2AR, adenosine/A2AR signaling pathway, expression, and potential as a therapeutic target.

The association of macronutrient quality and its interactions with energy intake with survival among patients with ovarian cancer: results from a prospective cohort study.

BACKGROUND: Emerging evidence supports shifting the focus from the quantity of macronutrients to quality to obtain greater benefits for the prognosis of ovarian cancer (OC). Additionally, despite the high relevance between macronutrient quality and quantity, the interaction of these parameters on OC survival remains unknown. OBJECTIVE: A multidimensional macronutrient quality index (MQI) was applied to investigate the association between overall macronutrient quality and the survival of patients with OC. METHODS: A prospective cohort study was conducted with 701 females diagnosed with OC who were enrolled from 2015 to 2020. Dietary intake information was obtained from a validated food frequency questionnaire. The MQI was calculated based on 3 quality indices: carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Cox proportional hazards regression was conducted to calculate HRs and 95% CIs. Furthermore, we evaluated whether energy intake status (total energy intake and energy balance) modified the association between MQI and OC survival. RESULTS: During a median follow-up period of 38 (interquartile: 35-40) mo, 130 deaths occurred. The prediagnosis high MQI scores were associated with substantially improved survival among females with OC (HRtertile 3 vs. tertile 1 = 0.50, 95% CI: 0.33, 0.77). For sub-indices of the MQI, higher CQI (HR = 0.60, 95% CI: 0.36, 0.99), higher FQI (HR = 0.55, 95% CI: 0.34, 0.87), and higher PQI (HR = 0.58, 95% CI: 0.35, 0.94) scores were all associated with better survival. Notably, significant interactions were observed for the MQI score with total energy intake and energy balance as well as the quantity and quality of carbohydrates on survival. CONCLUSIONS: Intake of high-quality macronutrients before diagnosis was associated with improved survival among females with OC, especially for those with energy imbalance.

Purine Intake and All-Cause Mortality in Ovarian Cancer: Results from a Prospective Cohort Study.

BACKGROUND: Current biological evidence suggests that purine involvement in purine metabolism may contribute to the development and progression of ovarian cancer (OC), but the epidemiological association is currently unknown. METHODS: A total of 703 newly diagnosed patients with OC aged 18-79 years were included in this prospective cohort study. Utilizing a verified food-frequency questionnaire, the participants' dietary consumption was gathered. Using medical records and ongoing follow-up, the deaths up until 31 March 2021 were determined. To assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of purine intake with OC mortality, Cox proportional-hazard models were utilized. RESULTS: During the median follow-up of 31 months (interquartile: 20-47 months), 130 deaths occurred. We observed an improved survival for the highest tercile of total purine intake compared with the lowest tercile (HR = 0.39, 95% CI = 0.19-0.80; p trend < 0.05), and this protective association was mainly attributed to xanthine intake (HR = 0.52, 95% CI = 0.29-0.94, p trend < 0.05). Additionally, we observed a curving relationship in which OC mortality decreased with total purine intake, and the magnitude of the decrease was negatively correlated with intake (p non-linear < 0.05). Significant inverse associations were also observed in subgroup analyses and sensitivity analyses according to demographic and clinical characteristics. Moreover, we observed that xanthine intake and hypoxanthine intake had a multiplicative interaction with ER and PR expression (p < 0.05), respectively. CONCLUSION: A high total purine and xanthine intake was linked to a lower risk of OC mortality. Further clarification of these findings is warranted.

Nutrients-Rich Food Index Scores and the Overall Survival of Ovarian Cancer Patients: Results from the Ovarian Cancer Follow-Up Study, a Prospective Cohort Study.

Background: The nutrients-rich food (NRF) index provides a score of diet quality. Although high diet quality is associated with survival of ovarian cancer (OC), the associations between NRF index scores and OC survival remain unevaluated. Methods: The prospective cohort study enrolled 703 women with newly diagnosed epithelial OC to assess the correlations between NRF index scores and overall survival (OS) in OC patients. Dietary consumption was evaluated through a food frequency questionnaire and diet quality was calculated based on NRF index scores, including three limited nutrients and six (NRF6.3), nine (NRF9.3), or eleven (NRF11.3) benefit nutrients. All-cause deaths were ascertained through medical records combined with active follow-up. Immunohistochemistry (IHC) analyses were conducted to evaluate the expression of IHC indicators (including Estrogen Receptor, Progesterone Receptor, p53, Vimentin, and Wilms' tumor 1), which were identified by two independent pathologists. The Cox proportional hazards regression models were applied for estimating the hazard ratios (HRs) and 95% confidence intervals (CIs). Moreover, we performed the penalized cubic splines model to assess the curvilinear associations of NRF index scores with OC survival. Results: During the median follow-up of 37.17 (interquartile: 24.73-50.17) months, 130 deaths were documented. Compared to the lowest tertiles, the highest tertile of index scores [NRF9.3 (HR = 0.63, 95% CI = 0.41-0.95), NRF6.3 (HR = 0.59, 95% CI = 0.39-0.89), and NRF11.3 (HR = 0.57, 95% CI = 0.38-0.87)] were correlated to better OS, showing an obvious linear trend (all p trend < 0.05). Interestingly, the curvilinear association between the NRF6.3 index score and OC survival was also observed (p non-linear < 0.05). Subgroup analyses, stratified by clinical, demographic, and IHC features, showed similar risk associations as the unstratified results. Furthermore, there were significant multiplicative interactions between NRF index scores and Progestogen Receptors as well as Wilms' tumor 1 expressions (all p interaction < 0.05). Conclusions: Higher NRF index scores were associated with an improved OS in OC patients.

Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase.

Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.

Cortical Organoid-on-a-Chip with Physiological Hypoxia for Investigating Tanshinone IIA-Induced Neural Differentiation.

Cortical organoids represent cutting-edge models for mimic human brain development during the early and even middle stage of pregnancy, while they often fail to recreate the complex microenvironmental factors, such as physiological hypoxia. Herein, to recapitulate fetal brain development, we propose a novel cortical organoid-on-a-chip with physiological hypoxia and further explore the effects of tanshinone IIA (Tan IIA) in neural differentiation. The microfluidic chip was designed with a micropillar array for the controlled and efficient generation of cortical organoids. With low oxygen, the generated cortical organoids could recapitulate key aspects of early-gestational human brain development. Compared to organoids in normoxic culturing condition, the promoted neurogenesis, synaptogenesis and neuronal maturation were observed in the present microsystem, suggesting the significance of physiological hypoxia in cortical development. Based on this model, we have found that Chinese herbal drug Tan IIA could promote neural differentiation and maturation, indicating its potential therapeutic effects on neurodevelopmental disorders as well as congenital neuropsychiatric diseases. These results indicate that the proposed biomimetic cortical organoid-on-a-chip model with physiological hypoxia can offer a promising platform to simulate prenatal environment, explore brain development, and screen natural neuroactive components.

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

Simultaneous Improvement of Final Product-Tolerance and Thermostability of GH39 Xylosidase for Prebiotic Production by Directed Evolution.

Xylosidases are widely used for the production of prebiotics and the transformation of natural active substances in the food industry. However, xylosidases with excellent thermostability and product tolerance are required for industrial applications. In this study, the thermostability and final-product tolerance of the previously reported robust xylosidase Xyl21 were further improved via directed evolution. The triple mutant variant Xyl21-A16 (K16R, L94I, and K262N) showed significantly enhanced xylose tolerance, ethanol tolerance, and thermostability with no apparent changes in the specific activity, optimum pH, and temperature compared with the wild type. Single site mutations suggested that variant Xyl21-A16 is the cumulative result of three mutated sites, which indicated that K16 and L94 play important roles in enzyme characteristics. Moreover, a comparison of the predicted protein structures of Xyl21 and its variant indicated that additional molecular interactions formed by K16R and K262N might directly improve the rigidity of the protein structure, therefore contributing to the increased thermostability and product tolerance. The variant Xyl21-A16 developed in this study has great application potential in the production of prebiotics, and also provides a useful reference for the future engineering of other xylosidases.

Detection of prostate cancer biomarkers via a SERS-based aptasensor.

The overexpression of specific biomarkers in serum is closely related to diseases, and accurate and sensitive detection of them is beneficial for the early diagnosis and treatment of cancer. In this study, we developed a novel surface-enhanced Raman spectroscopy (SERS)-based aptasensor to detect the prostate-specific antigen biomarkers, consisting of total prostate-specific antigen (PSA) and free prostate-specific antigen (f-PSA). A composite structure containing arrays of polystyrene colloidal sphere @Ag shell (PS@Ag) was fabricated as a SERS-active chip. A complementary DNA probe (SH-DNA) and PSA aptamer (Apt) were immobilised stepwise on the chip, followed by the binding of a Raman reporter methylene blue (MB) to the guanine base of the aptamer. PSA-Apt recognition causes the release of MB-Apt and a decrease in the SERS intensity of MB on the chip, which correlates with the PSA concentration. The proposed biosensor has high spectral reproducibility, selectivity, and sensitivity and successfully determines the PSA levels in serum samples collected from prostate cancer patients, demonstrating great potential for clinical diagnosis.

Phytosterol intake and overall survival in newly diagnosed ovarian cancer patients: An ambispective cohort study.

Background: Phytosterol is a bioactive compound existing in all plant foods, which might have anticancer properties. The aim of this study was to first assess the impact of the pre-diagnosis phytosterol intake on overall survival (OS) of patients with ovarian cancer (OC). Materials and methods: This ambispective cohort study recruited 703 newly diagnosed OC patients to investigate the aforementioned associations. Dietary intake was assessed using a validated 111-item food frequency questionnaire. Deaths were ascertained until March 31, 2021, through active follow-up and medical records. Cox proportional hazards regression models were applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During the median follow-up of 37.17 months, 130 deaths occurred. The median age at diagnosis of 703 OC patients was 53.00 (interquartile: 48.00-60.00) years. Of these, almost half patients (48.08%) were diagnosed in advanced International Federation of Gynecology and Obstetrics (FIGO) stage (III-IV). Additionally, more than half patients were serous carcinoma (68.14%), poorly differentiated (85.21%), and no residual lesions (78.66%). Patients consumed the highest tertile of dietary campesterol (HR = 0.54, 95% CI = 0.31-0.94, P trend < 0.05), stigmasterol (HR = 0.60, 95% CI = 0.37-0.98), and ß-sitosterol (HR = 0.63, 95% CI = 0.40-0.99) were significantly associated with better OS compared with those with the lowest tertile of intake. The curvilinear associations were observed between total phytosterols and ß-sitosterol intake and OC survival (P non-linear < 0.05). Significant associations were generally consistent across different subgroups stratified by demographical, clinical, and immunohistochemical characteristics. Moreover, there were significant interactions between phytosterol intake and age at diagnosis, body mass index, as well as expressions of Wilms' tumor-1 and Progestogen Receptor (all P interaction < 0.05). Conclusion: Pre-diagnosis higher campesterol, stigmasterol, and ß-sitosterol intake were associated with better survival among OC patients.

Determination of antihypertensive drugs irbesartan and doxazosin mesylate in healthcare products and urine samples using surface-enhanced Raman scattering.

In this paper, a surface-enhanced Raman scattering (SERS) strategy was constructed for the determination of antihypertensive drugs irbesartan (IRB) and doxazosin mesylate (DOX). ß-Cyclodextrin-capped silver nanoparticles (CD-AgNPs) are employed as SERS-active substrate. The introduction of ß-CD with hydrophobic cavity can capture drug molecules to form host-guest complex, making the drug molecules closer to the electromagnetic enhancement field of the AgNPs, thereby enhancing the SERS signal of drug molecules with low Raman cross-section. The vibrational modes of IRB and DOX are assigned by density functional theory calculations. The linear response from 3.0 × 10-7 to 1.0 × 10-5 mol L-1 for IRB and 3.0 × 10-7 to 2.0 × 10-5 mol L-1 for DOX and low limits of detection (LOD) 7.5 × 10-8 mol L-1 for IRB and 8.6 × 10-8 mol L-1 for DOX can be achieved. Meanwhile, this SERS approach can be applicable to determine IRB and DOX in commercial drug tablets, healthcare products, and human urine samples with recoveries of 90.8-115.7% and 90.0-113.5%, respectively, with relative standard deviation (RSD) less than 4.5%. This designed SERS strategy enables for the rapid determination of IRB and DOX in drug quality monitoring and illegal additives in healthcare products as well as clinical applications.

Improving the Specific Activity and Thermostability of Psychrophilic Xylosidase AX543 by Comparative Mutagenesis.

Improving the specific activity and thermostability of psychrophilic xylosidase is important for improving its enzymatic performance and promoting its industrial application. Herein, a psychrophilic xylosidase AX543 exhibited activity in the temperature range between 0 and 35 °C, with optimum activity at 20 °C, which is lower than that of other reported psychrophilic xylosidases. The thermostability, specific activity, and catalytic efficiency of the site-directed variants G110S, Q201R, and L2 were significantly enhanced, without affecting the optimal reaction temperature. Comparative protein structural analysis and molecular dynamics simulation indicated that these improvements might be the result of the increased hydrogen bonds interaction and improved structural rigidity. Furthermore, homologous module substitution with four segments demonstrated that the psychrophilic characteristics of AX543 are the results of the whole protein structure, and the C-terminal segment A4 appears to be more essential in determining psychrophilic characteristics, exhibiting potentiality to produce more psychrophilic xylosidases. This study provides valuable structural information on psychrophilic xylosidases and also offers attractive modification strategies to modify catalytic activity, thermostability, and optimal reaction temperature.

Crucial Residues of C-Terminal Oligopeptide C60 to Improve the Yield of Prebiotic Xylooligosaccharides by Truncated Mutation.

Increasing the yields of short xylooligosaccharides by enzymatic production is efficient to improve prebiotic effects. Previously, C-terminal oligopeptide C60 was found to accelerate short xylooligosaccharides. Herein, in order to further understand the molecular mechanism of C60, the sequence analysis firstly showed that C60 displays typical properties of a linker (rich in proline/alanine/glycine/glutamine/arginine, 8.33-20.00%). C60 shared the highest identity with the N-terminal region of esterase (98.33%) and high identity with the linker between xylanase and esterase from Prevotella sp. (56.50%), it is speculated to originate from an early linker between XynA and another domain. Besides, structure simulation showed that C60 enhances the molecular interactions between substrate and active residues to improve catalytic efficiency. Moreover, three truncated variants with different lengths of C-terminal regions were successfully generated in Escherichia coli. The specific activities of variants were 6.44-10.24 fold of that of XynA-Tr, and their optimal temperature and pH were the same as XynA-Tr. Three truncated variants released more xylooligosaccharides, especially xylobiose (46.33, 43.41, and 49.60%), than XynA-Tr (32.43%). These results are helpful to understand the molecular mechanism of C60, and also provide new insight to improve the yields of short xylooligosaccharides by molecular modification at the terminal of xylanases.