The occurrence, role, and management strategies for phytic acid in foods.

Phytic acid, a naturally occurring compound predominantly found in cereals and legumes, is the focus of this review. This review investigates its distribution across various food sources, elucidating its dual roles in foods. It also provides new insights into the change in phytic acid level during food storage and the evolving trends in phytic acid management. Although phytic acid can function as a potent color stabilizer, flavor enhancer, and preservative, its antinutritional effects in foods restrict its applications. In terms of management strategies, numerous treatments for degrading phytic acid have been reported, each with varying degradation efficacies and distinct mechanisms of action. These treatments encompass traditional methods, biological approaches, and emerging technologies. Traditional processing techniques such as soaking, milling, dehulling, heating, and germination appear to effectively reduce phytic acid levels in processed foods. Additionally, fermentation and phytase hydrolysis demonstrated significant potential for managing phytic acid in food processing. In the future, genetic modification, due to its high efficiency and minimal environmental impact, should be prioritized to downregulate the biosynthesis of phytic acid. The review also delves into the biosynthesis and metabolism of phytic acid and elaborates on the mitigation mechanism of phytic acid using biotechnology. The challenges in the application of phytic acid in the food industry were also discussed. This study contributes to a better understanding of the roles phytic acid plays in food and the sustainability and safety of the food industry.

A Low-Cost Handheld Centrifugal Microfluidic System for Multiplexed Visual Detection Based on Isothermal Amplification.

A low-cost, handheld centrifugal microfluidic system for multiplexed visual detection based on recombinase polymerase amplification (RPA) was developed. A concise centrifugal microfluidic chip featuring four reaction units was developed to run multiplexed RPA amplification in parallel. Additionally, a significantly shrunk-size and cost-effective handheld companion device was developed, incorporating heating, optical, rotation, and sensing modules, to perform multiplexed amplification and visual detection. After one-time sample loading, the metered sample was equally distributed into four separate reactors with high-speed centrifugation. Non-contact heating was adopted for isothermal amplification. A tiny DC motor on top of the chip was used to drive steel beads inside reactors for active mixing. Another small DC motor, which was controlled by an elaborate locking strategy based on magnetic sensing, was adopted for centrifugation and positioning. Visual fluorescence detection was optimized from different sides, including material, surface properties, excitation light, and optical filters. With fluorescence intensity-based visual detection, the detection results could be directly observed through the eyes or with a smartphone. As a proof of concept, the handheld device could detect multiple targets, e.g., different genes of African swine fever virus (ASFV) with the comparable LOD (limit of detection) of 75 copies/test compared to the tube-based RPA.

Enhancing the high-temperature energy storage properties of PEI dielectrics by constructing trap-rich covalently cross-linked networks via POSS-functionalized BNNS.

Polymer films are ideal dielectric materials for energy storage capacitors due to their light weight and flexibility, but lower energy density and poor heat resistance greatly limit their application in high-temperature energy storage. Unlike the traditional method of solely adding wide-bandgap inorganic fillers to enhance energy density, in this study we constructed trap-rich hybrid covalently cross-linked networks in polyetherimide (PEI) via reactive polyhedral oligomeric silsesquioxane (POSS)-functionalized boron nitride nanosheets (BNNS@POSS), which not only serve as interfacial layers for dielectric transitions and insulating barriers but also create deeper traps and higher energy barriers in the region of cross-linked chains. This strategy based on the co-modulation of interfaces and traps achieved the compatibility of high polarization and high breakdown strength and improved energy storage performance. Therefore, the composite film BNNS@POSS/PEI with the addition of 5 wt% BNNS@POSS achieved a maximum discharge energy density and charge-discharge efficiency at 150 °C of 6.16 J cm-3 and 89.92%, and maintained high values at 200 °C of 4.12 J cm-3 and 88.38%, respectively. Moreover, the glass transition temperature (Tg) of the composite dielectrics increased by 20.2 °C. This work provides a promising candidate material and development directions for research in the field of high-temperature energy storage capacitors.

Natural products as glycolytic inhibitors for cervical cancer treatment: A comprehensive review.

Cervical cancer, a prevalent gynaecological malignancy, presents challenges in late-stage treatment efficacy. Aerobic glycolysis, a prominent metabolic trait in cervical cancer, emerges as a promising target for novel drug discovery. Natural products, originating from traditional medicine, represent a significant therapeutic avenue and primary source for new drug development. This review explores the regulatory mechanisms of glycolysis in cervical cancer and summarises natural compounds that inhibit aerobic glycolysis as a therapeutic strategy. The glycolytic phenotype in cervical cancer is regulated by classical molecules such as HIF-1, HPV virulence factors and specificity protein 1, which facilitate the Warburg effect in cervical cancer. Various natural products, such as artemisinin, shikonin and kaempferol, exert inhibitory effects by downregulating key glycolytic enzymes through signalling pathways such as PI3K/AKT/HIF-1α and JAK2/STAT3. Despite challenges related to drug metabolism and toxicity, these natural compounds provide novel insights and promising avenues for cervical cancer treatment.

Squalene epoxidase promotes the chemoresistance of colorectal cancer via (S)-2,3-epoxysqualene-activated NF-κB.

BACKGROUND: While de novo cholesterol biosynthesis plays a crucial role in chemotherapy resistance of colorectal cancer (CRC), the underlying molecular mechanism remains poorly understood. METHODS: We conducted cell proliferation assays on CRC cells with or without depletion of squalene epoxidase (SQLE), with or without 5-fluorouracil (5-FU) treatment. Additionally, a xenograft mouse model was utilized to explore the impact of SQLE on the chemosensitivity of CRC to 5-FU. RNA-sequencing analysis and immunoblotting analysis were performed to clarify the mechanism. We further explore the effect of SQLE depletion on the ubiquitin of NF-κB inhibitor alpha (IκBα) and (S)-2,3-epoxysqualene on the binding of IκBα to beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC) by using immunoprecipitation assay. In addition, a cohort of 272 CRC patients were selected for our clinical analyses. RESULTS: Mechanistically, (S)-2,3-epoxysqualene promotes IκBα degradation and subsequent NF-κB activation by enhancing the interaction between BTRC and IκBα. Activated NF-κB upregulates the expression of baculoviral IAP repeat containing 3 (BIRC3), sustains tumor cell survival after 5-FU treatment and promotes 5-FU resistance of CRC in vivo. Notably, the treatment of terbinafine, an inhibitor of SQLE commonly used as antifungal drug in clinic, enhances the sensitivity of CRC to 5-FU in vivo. Additionally, the expression of SQLE is associated with the prognosis of human CRC patients with 5-FU-based chemotherapy. CONCLUSIONS: Thus, our finding not only demonstrates a new role of SQLE in chemoresistance of CRC, but also reveals a novel mechanism of (S)-2,3-epoxysqualene-dependent NF-κB activation, implicating the combined potential of terbinafine for 5-FU-based CRC treatment.

NET-targeted nanoparticles for antithrombotic therapy in pregnancy.

Pulmonary embolism caused by deep vein thrombosis (DVT) is a major contributor to maternal morbidity and mortality. There is still an unmet need for safe and effective treatment options for DVT during pregnancy. Recent research has shown that neutrophil extracellular trap (NET) formation plays a very vital role in thrombosis. We created nanoparticles surface-modified by neutrophil elastase (NE)-binding peptide that can target activated neutrophils specifically in vitro and in vivo. Prussian blue nanoparticles (PB NPs) designed in the core scavenges abnormally elevated reactive oxygen species (ROS) in the vascular microenvironment and acts as a photothermal agent to mediate photothermal therapy (PTT) to damage fibrin network structure. Based on the data we have included, this noninvasive therapeutic approach is considered safe for both mothers and the fetus. Furthermore, our findings indicate that this therapeutic approach has a significant alleviation effect on intrauterine growth restriction caused by maternal thrombosis.

Platelet membrane encapsulated curcumin nanomaterial-mediated specific thrombolysis and anti-thrombotic treatment among pregnant women.

The current treatment for venous thrombosis during pregnancy is ineffective, primarily, due to the unique physiology of pregnant women. Most clinical medications have fetal side effects when they circulate in the body. We first synthesized nanomaterials (Cur-PFP@PC) using poly lactic-co-glycolic acid (PLGA) as the base material, with curcumin (Cur) and perfluoropentane (PFP) as core components. Subsequently, we encapsulated Cur-PFP@PC into the platelet membrane to synthesize P-Cur-PFP@PC. Under ultrasound guidance, in combination with low-intensity focused ultrasound (LIFU), PFP underwent a phase change, resulting in thrombolysis. The generated microbubbles enhanced the signal impact of ultrasound, and P-Cur-PFP@PC showed better performance than Cur-PFP@PC. P-Cur-PFP@PC can target thrombosis treatment, achieve visually and precisely controlled drug release, and repair damaged blood vessels, thus avoiding the adverse effects associated with traditional long-term drug administration.

Histone H3K27 demethylase SlJMJ3 modulates fruit ripening in tomato.

The histone lysine (K) demethylase 4 (KDM4/JHDM3) subfamily of jumonji domain-containing demethylases (JMJs) has been implicated in various aspects of plant development. However, their involvement in regulating the ripening of fleshy fruits remains unclear. In this study, we identified SlJMJ3, a member of the KDM4/JHDM3 family, as an H3K27me3 demethylase in tomato (Solanum lycopersicum) that plays an important role in fruit ripening regulation. Overexpression of SlJMJ3 leads to accelerated fruit ripening, whereas loss of function of SlJMJ3 delays this process. Furthermore, we determined that SlJMJ3 exerts its regulatory function by modulating the expression of multiple ripening-related genes involved in ethylene biosynthesis and response, carotenoid metabolism, cell wall modification, transcriptional control, and DNA methylation modification. SlJMJ3 binds directly to the promoters of ripening-related genes harboring the CTCTGYTY motif and activates their expression. Additionally, SlJMJ3 reduces the levels of H3K27me3 at its target genes, thereby upregulating their expression. In summary, our findings highlight the role of SlJMJ3 in the regulation of fruit ripening in tomato. By removing the methyl group from trimethylated histone H3 lysine 27 at ripening-related genes, SlJMJ3 acts as an epigenetic regulator that orchestrates the complex molecular processes underlying fruit ripening.

Enabling Rapid and Stable Sodium Storage via a P2-Type Layered Cathode with High-Voltage Zero-Phase Transition Behavior.

Currently, a major target in the development of Na-ion batteries is the concurrent attainment of high-rate capacity and long cycling stability. Herein, an advanced Na-ion battery with high-rate capability and long cycle stability based on Li/Ti co-doped P2-type Na0.67Mn0.67Ni0.33O2, a host material with high-voltage zero-phase transition behavior and fast Na+ migration/conductivity during dynamic de-embedding process, is constructed. Experimental results and theoretical calculations reveal that the two-element doping strategy promotes a mutually reinforcing effect, which greatly facilitates the transfer capability of Na+. The cation Ti4+ doping is a dominant high voltage, significantly elevating the operation voltage to 4.4 V. Meanwhile, doping Li+ shows the function in charge transfer, improving the rate performance and prolonging cycling lifespan. Consequently, the designed P2-Na0.75Mn0.54Ni0.27Li0.14Ti0.05O2 cathode material exhibits discharge capacities of 129, 104, and 85 mAh g- 1 under high voltage of 4.4 V at 1, 10, and 20 C, respectively. More importantly, the full-cell delivers a high initial capacity of 198 mAh g-1 at 0.1 C (17.3 mA g-1) and a capacity retention of 73% at 5 C (865 mA g-1) after 1000 cycles, which is seldom witnessed in previous reports, emphasizing their potential applications in advanced energy storage.

ATP homeostasis and signaling in plants.

ATP is the primary form of energy for plants, and a shortage of cellular ATP is generally acknowledged to pose a threat to plant growth and development, stress resistance, and crop quality. The overall metabolic processes that contribute to the ATP pool, from production, dissipation, and transport to elimination, have been studied extensively. Considerable evidence has revealed that in addition to its role in energy supply, ATP also acts as a regulatory signaling molecule to activate global metabolic responses. Identification of the eATP receptor DORN1 contributed to a better understanding of how plants cope with disruption of ATP homeostasis and of the key points at which ATP signaling pathways intersect in cells or whole organisms. The functions of SnRK1α, the master regulator of the energy management network, in restoring the equilibrium of the ATP pool have been demonstrated, and the vast and complex metabolic network mediated by SnRK1α to adapt to fluctuating environments has been characterized. This paper reviews recent advances in understanding the regulatory control of the cellular ATP pool and discusses possible interactions among key regulators of ATP-pool homeostasis and crosstalk between iATP/eATP signaling pathways. Perception of ATP deficit and modulation of cellular ATP homeostasis mediated by SnRK1α in plants are discussed at the physiological and molecular levels. Finally, we suggest future research directions for modulation of plant cellular ATP homeostasis.

Exposure to particulate matter may affect semen quality via trace metals: Evidence from a retrospective cohort study on fertile males.

Particulate matter (PM) exposure may be associated with male semen quality. Besides, PM exposure induces up and down levels of trace metals in tissues or organs. The levels of trace metals in semen are critical for adverse male semen quality. This study aims to evaluate the concentrations of seminal-level trace metals in fertile men and assess its associations with PM exposure and to explore the mediation role of trace metals in seminal plasma plays in the relationship between PM exposure and semen quality. Total 1225 fertile men who participated in a cohort study from 2014 to 2016 were finally recruited. Multivariate linear regression was applied to explore associations between each two of PM exposure, trace metals and semen parameters. 1-year PM2.5 and PM10 exposure levels were positively associated with arsenic (As), mercury (Hg), lanthanum (La), praseodymium (Pr), neodymium (Nd) but negatively associated with vanadium (V), magnesium (Mg), strontium (Sr), barium (Ba) in semen. It was also found that most of the elements were associated with total sperm number, followed by sperm concentration. Redundancy analysis (RDA) also determined several strong positive correlations or negative correlations between 1-year PM exposure and trace metals. Mediation analysis found that trace metals had a potentially compensatory or synergetic indirect effect on the total effect of the association between 1-year PM exposure and semen quality. The retrospective cohort study provides long-term PM exposure that may cause abnormal semen quality by affecting seminal plasma element levels.

In Vivo Transcranial Acoustoelectric Brain Imaging of Different Deep Brain Stimulation Currents.

Deep brain stimulation (DBS) is an effective treatment for neurologic disease and its clinical effect is highly dependent on the DBS leads localization and current stimulating state. However, standard human brain imaging modalities could not provide direct feedback on DBS currents spatial distribution and dynamic changes. Acoustoelectric brain imaging (AEBI) is an emerging neuroimaging method that can directly map current density distribution. Here, we investigate in vivo AEBI of different DBS currents to explore the potential of DBS visualization using AEBI. According to the typical DBS stimulus parameters, four types of DBS currents, including time pattern, waveform, frequency, and amplitude are designed to implement AEBI experiments in living rat brains. Based on acoustoelectric (AE) signals, the AEBI images of each type DBS current are explored and the resolution is quantitatively analyzed for performance evaluation. Furtherly, the AE signals are decoded to characterize DBS currents from multiple perspectives, including time-frequency domain, spatial distribution, and amplitude comparation. The results show that in vivo transcranial AEBI can accurately locate the DBS contact position with a millimeter spatial resolution (< 2 mm) and millisecond temporal resolution (< 10 ms). Besides, the decoded AE signal at DBS contact position is capable of describing the corresponding DBS current characteristics and identifying current pattern changes. This study first validates that AEBI can localize in vivo DBS contact and characterize different DBS currents. AEBI is expected to develop into a noninvasive DBS real-time monitoring technology with high spatiotemporal resolution.

Marginal versus conditional rate estimation for count and recurrent event data with an estimand framework.

Count and recurrent event endpoints are common key efficacy endpoints in clinical research. For example, in clinical research of pulmonary diseases such as chronic obstructive pulmonary disease (COPD) or asthma, the reduction of the occurrence of a recurrent event, pulmonary exacerbation (PEx) caused by acute respiratory symptoms, is often used to measure the treatment effect. The occurrence of PEx is often analyzed with nonlinear models, such as Poisson regression or Negative Binomial regression. It is observed that model-estimated within-group PEx rates are often lower than the descriptive statistics of within-group PEx rates. Motivated by this observation, we explore their relationship mathematically and demonstrate that it is due to the difference between conditional PEx rates and population-level PEx rates (marginal rates). Our findings corroborate the recent FDA guidance (2023) [1], which discusses considerations for covariate adjustment in nonlinear models, and that conditional or subgroup treatment effects with covariate adjustment may differ from marginal treatment effects. In this article, we demonstrate how covariate adjustment impacts the estimation of event rates and rate ratios with both closed form and simulation studies. Additionally, following the ICH E9 addendum on the estimand framework [2], we discuss the estimand framework for count and recurrent event data.

Alterations in sperm DNA methylation may as a mediator of paternal air pollution exposure and offspring birth outcomes: Insight from a birth cohort study.

Paternal exposure to environmental risk factors influences the offspring health. This study aimed to evaluate the association between paternal air pollution exposure mediated by sperm DNA methylation and adverse birth outcomes in offspring. We recruited 1607 fertile men and their partners from 2014 to 2016 and collected semen samples to detect sperm DNA methylation. Multivariate linear regression and weighted quantile sum regression models were used to assess the associations between paternal air pollution exposure and offspring birth outcomes. A critical exposure window was identified. Reduced representation bisulfite sequencing was used to detect sperm DNA methylation. The results demonstrated that high paternal exposure to PM2.5 (ß = -211.31, 95% CI: (-386.37, -36.24)), PM10 (ß = -178.20, 95% CI: (-277.13, -79.27)), and NO2 (ß = -84.22, 95% CI: (-165.86, -2.57)) was negatively associated with offspring's birthweight, especially in boys. Additionally, an early exposure window of 15-69 days before fertilization was recognized to be the key exposure window, which increased the risk of low birth weight and small for gestational age. Furthermore, paternal co-exposure to six air pollutants contributed to lower birthweight (ß = -51.91, 95% CI: (-92.72, -11.10)) and shorter gestational age (ß = -1.72, 95% CI: (-3.26, -0.17)) and PM2.5 was the most weighted pollutant. Paternal air pollution exposure resulted in 10,328 differentially methylated regions and the IGF2R gene was the key gene involved in the epigenetic process. These differentially methylated genes were predominantly associated with protein binding, transcriptional regulation, and DNA templating. These findings indicate that spermatogenesis is a susceptible window during which paternal exposure to air pollution affects sperm DNA methylation and the birth outcomes of offspring.

Triglyceride-glucose index is a predictor of the risk of prostate cancer: a retrospective study based on a transprostatic aspiration biopsy population.

Background: Current research suggests that prostate cancer (PCa), one of the most common cancers in men, may be linked to insulin resistance (IR).Triglyceride-glucose index (TyG index) was made for a marker of insulin resistance. We investigated the relationship between the TyG index and the risk of PCa. Objective: To assess the correlation and dose-response relationship between TyG index and prostate cancer. Method: Retrospectively, 316 patients who required prostate biopsy puncture in the First Affiliated Hospital of Xinjiang Medical University from March 2017 to July 2021 were collected, and the relationship between factors such as the TyG index and prostate cancer was analyzed by Logistic regression model combined with a restricted cubic spline. Results: (1) The differences in age, initial PSA and TyG index between the two groups were statistically significant; (2) Logistic regression results showed that the risk of prostate cancer in the highest quartile of the TyG index (Q4) was 3.387 times higher than that in the lowest quartile (Q1) (OR=3.387,95% CI [1.511,7.593], P=0.003); (3) The interaction results showed a significant interaction between the TyG index Q4 group and age with the risk of developing prostate cancer (P for interaction<0.001). (4) The results of the restricted cubic spline showed a linear dose-response relationship between the TyG index and the risk of prostate cancer; (5) The Receiver operating characteristic (ROC) curve results showed that the area under the curve (AUC) of the TyG index combined with initial PSA and age was 0.840, with a sensitivity and specificity of 62.5% and 93.3%, respectively. Conclusion: TyG index and age are risk factors for prostate cancer, and the interaction between the TyG index and different risk factors may increase the risk of prostate cancer. TyG index has some predictive value for the risk of prostate cancer, and the risk of prostate cancer can be reduced by controlling the levels of blood lipids and blood glucose.