Effect of cooking methods on volatile compounds and texture properties in maize porridge.

To investigate the optimal processing of maize porridge, the volatile compounds and texture under different cooking methods and time have been studied. A total of 51 volatile compounds were identified in maize porridge. Notably, the major volatiles, aldehydes and esters exhibited a relatively high content in electric pressure cooker (EPC), and esters tend to significantly increase after cooking. Among aldehydes, nonanal and hexanal played a great role in flavor due to their relatively high content. Volatile compounds of maize porridge in different cooking methods could be clearly distinguished by multiple chemometrics. Furthermore, texture analysis revealed that almost all the indicators in the EPC can reach the lowest value at 60 min. To summarize, different cooking methods had a more significant influence on the volatile compounds and texture compared to time. This study helps to improve the sensory attributes of maize porridge, and thus contributes to healthier and more sustainable production.

Modeling and Prediction of Thermal Deformation Errors in Fiber Optic Gyroscopes Based on the TD-Model.

For a fiber optic gyroscope, thermal deformation of the fiber coil can introduce additional thermal-induced phase errors, commonly referred to as thermal errors. Implementing effective thermal error compensation techniques is crucial to addressing this issue. These techniques operate based on the real-time sensing of thermal errors and subsequent correction within the output signal. Given the challenge of directly isolating thermal errors from the gyroscope's output signal, predicting thermal errors based on temperature becomes necessary. To establish a mathematical model correlating the temperature and thermal errors, this study measured synchronized data of phase errors and angular velocity for the fiber coil under various temperature conditions, aiming to model it using data-driven methods. However, due to the difficulty of conducting tests and the limited number of data samples, direct engagement in data-driven modeling poses a risk of severe overfitting. To overcome this challenge, we propose a modeling algorithm that effectively integrates theoretical models with data, referred to as the TD-model in this paper. Initially, a theoretical analysis of the phase errors caused by thermal deformation of the fiber coil is performed. Subsequently, critical parameters, such as the thermal expansion coefficient, are determined, leading to the establishment of a theoretical model. Finally, the theoretical analysis model is incorporated as a regularization term and combined with the test data to jointly participate in the regression of model coefficients. Through experimental comparative analysis, it is shown that, relative to ordinary regression models, the TD-model effectively mitigates overfitting caused by the limited number of samples, resulting in a substantial 58% improvement in predictive accuracy.

BCL2 Inhibition Reveals a Dendritic Cell-Specific Immune Checkpoint That Controls Tumor Immunosurveillance.

We developed a phenotypic screening platform for the functional exploration of dendritic cells (DC). Here, we report a genome-wide CRISPR screen that revealed BCL2 as an endogenous inhibitor of DC function. Knockout of BCL2 enhanced DC antigen presentation and activation as well as the capacity of DCs to control tumors and to synergize with PD-1 blockade. The pharmacologic BCL2 inhibitors venetoclax and navitoclax phenocopied these effects and caused a cDC1-dependent regression of orthotopic lung cancers and fibrosarcomas. Thus, solid tumors failed to respond to BCL2 inhibition in mice constitutively devoid of cDC1, and this was reversed by the infusion of DCs. Moreover, cDC1 depletion reduced the therapeutic efficacy of BCL2 inhibitors alone or in combination with PD-1 blockade and treatment with venetoclax caused cDC1 activation, both in mice and in patients. In conclusion, genetic and pharmacologic BCL2 inhibition unveils a DC-specific immune checkpoint that restrains tumor immunosurveillance. SIGNIFICANCE: BCL2 inhibition improves the capacity of DCs to stimulate anticancer immunity and restrain cancer growth in an immunocompetent context but not in mice lacking cDC1 or mature T cells. This study indicates that BCL2 blockade can be used to sensitize solid cancers to PD-1/PD-L1-targeting immunotherapy. This article is featured in Selected Articles from This Issue, p. 2293.

Characteristic volatiles fingerprints in olive vegetable stored at different conditions by HS-GC-IMS.

The olive vegetable is popular food owing to its unique flavor. This study innovatively used headspace-gas chromatography-ion mobility spectrometry to evaluate olive vegetables' volatiles under different conditions. A total of 57 volatile compounds were determined from olive vegetables, including 30 aldehydes, 8 ketones, 5 alcohols, 2 esters, 8 hydrocarbons, 1 furans, 3 sulfur compounds. The PCA distinguished the olive vegetable stored at different conditions by volatiles. The gallery plot showed that olive vegetables stored at 4 °C for 21 d produced more limonene, which had a desirable fruity odor. The (E)-2-octenal, (E)-2-pentenal, (E,E)-2,4-heptadienal, 5-methylfurfural, and heptanal in fresh olive vegetables were lowest and increased with storage time. Furthermore, the change of volatiles was the least when the olive vegetable was stored at 0 °C. This study can provide theoretical bases for improving the flavor quality of olive vegetables and developing traditional food for standardized industrial production.

Anticancer effects of ikarugamycin and astemizole identified in a screen for stimulators of cellular immune responses.

BACKGROUND: Most immunotherapies approved for clinical use rely on the use of recombinant proteins and cell-based approaches, rendering their manufacturing expensive and logistics onerous. The identification of novel small molecule immunotherapeutic agents might overcome such limitations. METHOD: For immunopharmacological screening campaigns, we built an artificial miniature immune system in which dendritic cells (DCs) derived from immature precursors present MHC (major histocompatibility complex) class I-restricted antigen to a T-cell hybridoma that then secretes interleukin-2 (IL-2). RESULTS: The screening of three drug libraries relevant to known signaling pathways, FDA (Food and Drug Administration)-approved drugs and neuroendocrine factors yielded two major hits, astemizole and ikarugamycin. Mechanistically, ikarugamycin turned out to act on DCs to inhibit hexokinase 2, hence stimulating their antigen presenting potential. In contrast, astemizole acts as a histamine H1 receptor (H1R1) antagonist to activate T cells in a non-specific, DC-independent fashion. Astemizole induced the production of IL-2 and interferon-γ (IFN-γ) by CD4+ and CD8+ T cells both in vitro and in vivo. Both ikarugamycin and astemizole improved the anticancer activity of the immunogenic chemotherapeutic agent oxaliplatin in a T cell-dependent fashion. Of note, astemizole enhanced the CD8+/Foxp3+ ratio in the tumor immune infiltrate as well as IFN-γ production by local CD8+ T lymphocytes. In patients with cancer, high H1R1 expression correlated with low infiltration by TH1 cells, as well as with signs of T-cell exhaustion. The combination of astemizole and oxaliplatin was able to cure the majority of mice bearing orthotopic non-small cell lung cancers (NSCLC), then inducing a state of protective long-term immune memory. The NSCLC-eradicating effect of astemizole plus oxaliplatin was lost on depletion of either CD4+ or CD8+ T cells, as well as on neutralization of IFN-γ. CONCLUSIONS: These findings underscore the potential utility of this screening system for the identification of immunostimulatory drugs with anticancer effects.

Bile acids regulate MAdCAM-1 expression to link the gut microbiota to cancer immunosurveillance.

In a recent paper in Science, Fidelle et al. unravel a gut immune checkpoint that is subverted by antibiotic treatment. Post-antibiotic dysbiosis of the ileum causes an increase in bile acids that downregulate MAdCAM-1, thereby triggering the exodus of immunosuppressive T cells from gut-associated lymphoid tissues toward tumors.

A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers.

Antibiotics (ABX) compromise the efficacy of programmed cell death protein 1 (PD-1) blockade in cancer patients, but the mechanisms underlying their immunosuppressive effects remain unknown. By inducing the down-regulation of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in the ileum, post-ABX gut recolonization by Enterocloster species drove the emigration of enterotropic α4ß7+CD4+ regulatory T 17 cells into the tumor. These deleterious ABX effects were mimicked by oral gavage of Enterocloster species, by genetic deficiency, or by antibody-mediated neutralization of MAdCAM-1 and its receptor, α4ß7 integrin. By contrast, fecal microbiota transplantation or interleukin-17A neutralization prevented ABX-induced immunosuppression. In independent lung, kidney, and bladder cancer patient cohorts, low serum levels of soluble MAdCAM-1 had a negative prognostic impact. Thus, the MAdCAM-1-α4ß7 axis constitutes an actionable gut immune checkpoint in cancer immunosurveillance.

Macrolide antibiotics activate the integrated stress response and promote tumor proliferation.

Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibiotics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users compared to non-users. Further experiments showed that macrolides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibiotic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects.

Comparative study on quality characteristics of Bischofia polycarpa seed oil by different solvents: Lipid composition, phytochemicals, and antioxidant activity.

Bischofia polycarpa seed oil is rich in nutrition and positively affects on human health. We analyzed and compared the chemical compositions, antioxidant activities, and quality characteristics of Bischofia polycarpa seed oils using different solvents and cold-pressing. Hx: Iso (n-hexane/isopropanol, 3:2 v/v) had the highest lipid yield (35.13 %), while Folch (chloroform/methanol, 2:1 v/v) had the highest linolenic acid (50.79 %), LnLnLn (43.42 %), and LnLnL (23.43 %). Tocopherols (2108.99 mg/kg) were extracted most efficiently with Folch, whereas phytosterols (3852.97 mg/kg) and squalene (55.21 mg/kg) were extracted most efficiently with petroleum ether. Although the lower phytosterol was obtained using isopropanol, the polyphenol content (271.34 mg GAE/kg) was significantly higher than other solvents, showing the best antioxidant ability. Additionally, polyphenols were observed to be the most significant factor predicting antioxidant activity from the correlation analysis. The above information can provide a useful reference for manufacturers to obtain satisfactory Bischofia polycarpa seed oil.

Quadriwave lateral shearing interferometry based on double birefringent crystals of beam displacer.

A quadriwave lateral shearing interferometry (QWLSI) is proposed based on double birefringent crystals of a beam displacer (DBCs-BD). The DBCs-BD is formed by adopting two birefringent crystals of a polarization beam displacer (PBD), which can generate the lateral shearing interference waves of four beams of overlapped replicas in the DBCs-BD orthogonal directions. When the replica waves are overlapped incident to the analyzer, and the direction of the transmission axis is set as 45° or 135°, the QWLSI's polarization interferogram can be obtained. The high-precision phase can be obtained by simple spectrum denoising and performing the Fourier transform of the resulting interferogram. We deduce the principle of QWLSI in detail, and the wavefront distribution can be achieved by the phase calculation. The experiment shows that the DBCs-BD-QWLSI exhibits feasibility and high precision.

Characteristic volatile compounds, fatty acids and minor bioactive components in oils from green plum seed by HS-GC-IMS, GC-MS and HPLC.

Green plum is popular due to its tasty flavor and nutritional benefits. This study investigated the volatiles of oils extracted from the green plum seed using the headspace-gas chromatography-ion mobility spectrometry. A total of 42 volatiles were identified in the oil of green plum seed kernel and shell. By principal component analysis, a distinct separation between the seed kernel oil and shell oil was observed. The gallery plot showed that seed kernel oil had more desirable flavor compounds, such as ethyl acetate, 1-pentanol, 2-pentylfuran, and 2-heptanone. However, seed shell oil contained more alkenals with a fatty odor and acetic acid with a pungent odor. The green plum seed oils were rich in oleic acid (>45 g/100 g), linoleic acid (>35 g/100 g), and minor bioactive components, i.e., tocopherol, phytosterol, and squalene. The shell oil had more total tocopherol (95.35 mg/kg) and ß-Sitosterol (80.70 %) compared to kernel oil. Therefore, green plum seed oil can be sustainably used as an edible oil.

Optimization of wavefront reconstruction accuracy for conjugate shift differential absolute testing.

The conjugate shift differential method, based on Fourier transforms, is critical for surface error testing of high-precision optical elements. However, this common approach is also prone to periodic spectrum loss. As such, this paper proposes conjugate double shift differential (CDSD) absolute testing, which can effectively compensate for spectrum loss and achieve accurate wavefront reconstructions. Spectrum loss in the single shift differential method is analyzed through a study of the Fourier reconstruction process. A calculation model for the proposed CDSD method is then established and constraint conditions for shift quantities are provided by analyzing double shear effects observed in transverse shear interference. Finally, the reconstruction accuracies of various spectrum compensation methods are compared. Results showed that spectrum loss became more evident with increasing shift amounts. However, the CDSD method produced the smallest measurement error compared with conventional direct zero filling and adjacent point averaging, suggesting our approach could effectively improve absolute shape measurement accuracy for planar optical elements.

Improving the phase reconstruction accuracy of simultaneous phase-shifted lateral shearing interferometry using a polarization redundant sub-region interpolation method.

In a simultaneous phase-shifted lateral shearing interferometry, a division of focal plane polarization camera is generally used as the phase-shifting device. However, acquiring simultaneous phase-shift interferograms in a single frame suffers from a lack of spatial resolution, significantly affecting the phase reconstruction accuracy. A polarization redundant sub-region interpolation (PRSI) method is proposed to solve this problem. This interpolation method distinguishes smooth regions from stripe fringe regions by calculating the polarization redundancy error of the synchronous phase shift interferogram. After sub-regional processing, resolution reconstruction is performed in the smoothed area using a fast convolutional bilinear interpolation method. In the streak detail region, the resolution reconstruction is performed based on the strength of the correlation between the orthogonal and non-orthogonal polarization channels crossing the streak region. The PRSI method can quickly reconstruct the lost pixels and accurately recover the stripe detail information. Experiment results show that the proposed interpolation method outperforms the existing dominant methods in terms of visual reconstruction effect and quantitative index of phase reconstruction.

First-Principles-Based Quantum Transport Simulations of High-Performance and Low-Power MOSFETs Based on Monolayer Ga2O3.

The electronic properties of monolayer (ML) Ga2O3 and transport properties of ML Ga2O3-based n-type metal-oxide-semiconductor field-effect transistors (MOSFETs) are investigated by first-principles calculations under the framework of density functional theory (DFT) coupled with the nonequilibrium Green's function (NEGF) formalism. The results show that ML Ga2O3 has a quasi-direct band gap of 4.92 eV, and the x- and y-directed electron mobilities are 1210 and 816 cm2 V-1 s-1 at 300 K, respectively, under the full consideration of phonon scattering. The electron-phonon scattering mechanism shows a temperature-dependent behavior, with the acoustic modes dominating below 300 K and optical modes dominating above 300 K. At a gate length of Lg = 5 nm, the on-current of ML Ga2O3 n-MOSFET for high-performance (HP) application is 2890 µA/µm, which is more than those of the most reported two-dimensional (2D) materials. The delay time as well as the power delay product of ML Ga2O3 MOSFETs can meet the demands of the latest International Technology Roadmap for Semiconductors (ITRS) for HP and low-power (LP) applications until Lg is less than 4 and 5 nm, respectively. Through underlap structure and doping optimization strategies, ML Ga2O3 n-MOSFET can further fulfill the ITRS requirements for 1 nm. At last, we compare the performance of the 32-bit arithmetic logic unit (ALU) built on ML Ga2O3 MOSFETs with the recently reported beyond-CMOS devices. Our results indicate that ML Ga2O3 can serve as a promising channel material in the post-silicon era.

Application of mesenchymal stem cells combined with nano-polypeptide hydrogel in tissue engineering blood vessel.

At present, the vascular grafts used in clinic are mainly autologous blood vessels, but they often face the dilemma of no blood vessels available due to limited sources. However, synthetic blood vessels made of polytetrafluoroethylene (ePTFE), which is commonly used in clinic, are prone to thrombosis and intimal hyperplasia, and the long-term patency rate is poor, so its effectiveness is severely limited, which is far from meeting the clinical needs. With the development of nano-materials, stem cells and 3D bio-printing technology, people began to explore the preparation of new endothelialized vascular grafts through this technology. Nano-peptide materials have excellent biocompatibility, can be compounded with different bioactive molecules, and have unique advantages in cultivating stem cells. It has been reported that self-assembled nano-polypeptide hydrogel was successfully constructed, mesenchymal stem cells were correctly isolated and cultured, and their transformation into blood vessels was studied. It was confirmed that the 3D bio-printed nano-polypeptide hydrogel tissue ADMSCs still had strong vascular endothelial differentiation ability. The application of mesenchymal stem cells and nano-polypeptide hydrogel in tissue engineering blood vessels has gradually become a research hotspot, and it is expected to develop a new type of transplanted blood vessel that meets the physiological functions of human body in terms of vascular endothelialization, cell compatibility and histocompatibility, so as to realize the customized and personalized printing of the endothelialized transplanted blood vessel according to the shape of the target blood vessel, which has attractive prospects and far-reaching social and economic benefits.

Advantages of Self-assembled Nano Peptide Hydrogels in Biological Tissue Engineering.

With the development of tissue engineering research, biological scaffolds have been widely studied and applied in the field of regenerative medicine. Self-assembling nanopeptide hydrogels have good biocompatibility, and their seed cells can be used for their biological activities and have no toxic side effects. The products can be absorbed and degraded by the organism and have great advantages in tissue engineering and regenerative medicine. Studies have shown that the self-assembled nano peptide hydrogel and adipose-derived mesenchymal stem cells (ADMSCs) mixed solution are "biological ink". 3D related biological printing technology can be used to print related tissue models and induce ADMSCs to differentiate into blood vessels. It is further illustrated that the use of self-assembled nano peptide hydrogel scaffolds to load stem cells has a good application prospect in stem cell transplantation and 3D biological printing.

Everolimus and plicamycin specifically target chemoresistant colorectal cancer cells of the CMS4 subtype.

Colorectal cancers (CRC) can be classified into four consensus molecular subtypes (CMS), among which CMS1 has the best prognosis, contrasting with CMS4 that has the worst outcome. CMS4 CRC is notoriously resistant against therapeutic interventions, as demonstrated by preclinical studies and retrospective clinical observations. Here, we report the finding that two clinically employed agents, everolimus (EVE) and plicamycin (PLI), efficiently target the prototypic CMS4 cell line MDST8. As compared to the prototypic CMS1 cell line LoVo, MDST8 cells treated with EVE or PLI demonstrated stronger cytostatic and cytotoxic effects, increased signs of apoptosis and autophagy, as well as a more pronounced inhibition of DNA-to-RNA transcription and RNA-to-protein translation. Moreover, nontoxic doses of EVE and PLI induced the shrinkage of MDST8 tumors in mice, yet had only minor tumor growth-reducing effects on LoVo tumors. Altogether, these results suggest that EVE and PLI should be evaluated for their clinical activity against CMS4 CRC.

Study on a 3D-Bioprinted Tissue Model of Self-Assembled Nanopeptide Hydrogels Combined With Adipose-Derived Mesenchymal Stem Cells.

Objective: This study aimed to observe the cell growth status and multidirectional differentiation ability in a 3D-bioprinted tissue model of self-assembled nanopeptides and human adipose-derived mesenchymal stem cells (Ad-MSCs). Methods: Primary Ad-MSCs were isolated, cultured, and identified by flow cytometry. Tissue models were printed via 3D bioprinting technology using a "biological ink" consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs. Ad-MSCs were induced into osteogenic, adipogenic, and endothelial differentiation and compared with the control groups by staining. Results: The nanopeptide fiber was 10-30 nm in diameter and 200-500 nm in length under the atomic-force microscope. It had the characteristics of nano-scale materials. Flow cytometry showed that the isolated and cultured cells were positive for CD29 (98.51%), CD90 (97.87%), and CD166 (98.32%) but did not express CD31 (1.58%), CD34 (2.42%), CD45 (2.95%), or human leukocyte antigen (HLA)-DR (0.53%), consistent with the immunophenotype of Ad-MSCs. Then, a tissue model was printed using the biological ink, followed by induction of differentiation of Ad-MSCs within the tissue model. Alizarin red S staining showed the formation of calcium nodules in the osteogenesis induction experimental group, and oil red O stained lipid droplets in Ad-MSCs in the adipogenesis induction experimental group, whereas the two control groups were not stained. Conclusion: Ad-MSCs from primary cultures have the characteristics of stem cells. Self-assembled nanopeptide hydrogel is a good tissue engineering material that can serve as an extracellular matrix. Ad-MSCs in the 3D-printed tissue model using a biological ink consisting of a mixed solution of self-assembled nanopeptides and Ad-MSCs grew well and still had strong differentiation ability.

Autophagic flux assessment by immunoblot.

Autophagy is one of the main adaptive mechanisms to maintain cellular homeostasis in response to multiple stresses. During autophagy diverse cellular components such as damaged organelles or superfluous proteins are targeted for lysosomal degradation. Importantly, during the initiation of autophagy MAP1LC3B (better known as LC3) lipidates into the membrane of the forming phagophore, which facilitates the formation and lengthening of autophagosomes. In addition, the autophagy receptor SQSTM1 (better known as p62) selectively recruits various cargos to autophagosomes for lysosomal degradation. Both, the conversion of LC3 as well as the degradation of p62 can be assessed as means of monitoring autophagy. Here we detail a protocol for assessing these key events of the autophagic flux via immunoblot.

The excretory-secretory antigen HcADRM1 to generate protective immunity against Haemonchus contortus.

The prevention, treatment and control of Haemonchus contortus have been increasingly problematic due to its widespread occurrence and anthelmintic resistance. There are very few descriptions of recombinant antigens being protective for H. contortus, despite the success of various native antigen preparations, including Barbervax. We recently identified an H. contortus excretory­secretory antigen, H. contortus adhesion-regulating molecule 1 (HcADRM1), that served as an immunomodulator to impair host T-cell functions. Given the prophylactic potential of HcADRM1 protein as a vaccine candidate, we hereby assessed the efficacies of HcADRM1 preparations against H. contortus infection. Parasitological and immunological parameters were evaluated throughout all time points of the trials, including fecal egg counts (FEC), abomasal worm burdens, complete blood counts, cytokine production profiles and antibody responses. Active vaccination with recombinant HcADRM1 (rHcADRM1) protein induced protective immunity in inoculated goats, resulting in reductions of 48.9 and 58.6% in cumulative FEC and worm burdens. Simultaneously, passive administration of anti-HcADRM1 antibodies generated encouraging levels of protection with 46.7 and 56.2% reductions in cumulative FEC and worm burdens in challenged goats. In addition, HcADRM1 preparations-immunized goats showed significant differences in mucosal and serum antigen-specific immunoglobulin G (IgG) levels, total mucosal IgA levels, haemoglobin values and circulating interferon-γ, interleukin (IL)-4 and IL-17A production compared to control goats in both trials. The preliminary data of these laboratory trials validated the immunoprophylactic effects of rHcADRM1 protein. It can be pursued as a potential vaccine antigen to develop an effective recombinant subunit vaccine against H. contortus under field conditions.