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The intracellular distribution and transportation process are essential for maintaining PD-L1 (programmed death-ligand 1) expression, and intervening in this cellular process may provide promising therapeutic strategies. Here, through a cell-based high content screening, it is found that the ABCB1 (ATP binding cassette subfamily B member 1) modulator zosuquidar dramatically suppresses PD-L1 expression by triggering its autophagic degradation. Mechanistically, ABCB1 interacts with PD-L1 and impairs COP II-mediated PD-L1 transport from ER (endoplasmic reticulum) to Golgi apparatus. The treatment of zosuquidar enhances ABCB1-PD-L1 interaction and leads the ER retention of PD-L1, which is subsequently degraded in the SQSTM1-dependent selective autophagy pathway. In CT26 mouse model and a humanized xenograft mouse model, zosuquidar significantly suppresses tumor growth and accompanies by increased infiltration of cytotoxic T cells. In summary, this study indicates that ABCB1 serves as a negative regulator of PD-L1, and zosuquidar may act as a potential immunotherapy agent by triggering PD-L1 degradation in the early secretory pathway., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Rapeseed oil is a widely consumed edible oil that contains varieties of beneficial micronutrients such as tocopherols and phytosterols; however, the high acid value due to increased free fatty acid can imperil the oil quality and safety. This paper proposed the enzymatic deacidification for high-acid rapeseed oil and simultaneous production of functional diacylglycerols (DAGs) catalyzed by self-made immobilized lipase CALB@MCM-41-C 8 . The results indicate that the carrier of molecular sieve MCM-41 exhibited a sufficient surface area of 1439.9 m 2 /g and a proper pore size of 3.5 nm, promoting the immobilization of lipase CLAB. Under the optimal reaction conditions, the acid value of rapeseed oil was largely decreased from 15.3 mg KOH/g to 1.7 mg KOH/g within 3 h, while DAG content was increased from 1.2% to 40.2%. The antioxidant stability of rapeseed oil was also increased from 4.3 h to 7.6 h after enzymatic deacidification. Besides, the deacidified rapeseed oil exhibited fatty, bitter almond aromas, compared to the picked-vegetable, spicy, and pungent aromas for high-acid oil. Finally, the catalytic stability and applicability of CALB@MCM-41-C 8 was validated, thus demonstrating the great potential of CALB@MCM-41-C 8 in green refining of edible oils and sustainable synthesis of functional lipids.

Background: Fluoroquinolones (FQs) are widely used in livestock and poultry industry because of their satisfactory effects in preventing and treating bacterial infection. However, due to irrational use and poor biodegradability, FQs can easily remain in food animals and further enter the human body through the food chain. Therefore, accurate and sensitive detection of FQs residues in animal-origin food is significant. The traditional methods commonly used for FQs detection have some limitations. Ratiometric fluorescence detection technology has the advantages of fast, sensitive, self-correcting, and easy visualization. However, the reports on the use of ratiometric fluorescence probes for FQs detection are limited., Results: In this work, a novel probe was proposed for ratiometric fluorescent analysis of FQs. In this probe, the fluorescence of dithioerythritol stabilized copper nanoclusters (DTE-Cu NCs) was significantly enhanced due to the Tb 3+ triggered aggregation-induced emission effect. FQs bound Tb 3+ in Tb 3+ /DTE-Cu NCs through carboxyl and carbonyl groups, so that Tb 3+ was effectively sensitized to emit green fluorescence. However, the red fluorescence of DTE-Cu NCs was not interfered. The fluorescence of the probe transformed from red to green with the increase of FQs concentration. Using norfloxacin (NOR), difloxacin (DIF), and enrofloxacin (ENR) as FQs simulants, this probe showed a sensitive linear response ranged from 0.025 to 22.5 μM, with the limits of detection of 9.6 nM, 9.3 nM, and 7.7 nM. The application potential for FQs detection was verified via a standard addition assay of egg samples with the recovery rate of 90.4 %-114.7 %., Significant: The fluorescence probe based on Tb 3+ /DTE-Cu NCs is expected to realize the ratiometric fluorescence sensitive detection of FQs. The establishment of this simple, effective, and rapid detection platform opens up a new way for the detection of FQs residues in animal-origin foods, and also provides a new idea for the design of rapid detection platforms for other hazard factors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Consumer preferences for walnut products are largely determined by the flavors released during mastication. In this study, a peeled walnut kernel (PWK) model was established with oral parameters decoupled using a Hutchings 3D model. The model explored in vitro variations using head-space solid-phase microextraction-gas chromatography-mass spectrometry and intelligent sensory techniques. The fracture strength, hardness, particle size, adhesiveness, springiness, gumminess, and chewiness were significantly reduced during mastication. We identified 61 volatile compounds and found that 2,5-dimethyl-3-ethylpyrazine is a key component, releasing predominantly baking and milky notes. Glutamic acid, alanine, arginine, and sucrose were identified as the key compounds in taste perception. The method can help establish a mastication model for nuts and facilitate breakthroughs in the development of walnut products and processing methods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Here, the influence and potential mechanism by which cellulose nanocrystals (CNC) collaborated with Ca 2+ enhancing the heat-induced gelation of pea protein isolate (PPI) were investigated. It was found that the combination of 0.45% CNC and 15 mM Ca 2+ synergistically increased the gel strength (from 14.18 to 65.42 g) and viscoelasticity of PPI while decreased the water holding capacity. The improved particle size, turbidity, and thermostability as well as the reduced solubility, crystallinity, and gel porosity were observed in CNC/CaCl 2 composite system. CNC fragments bind to specific amino acids in 11S legumin and 7S vicilin mainly through hydrogen bonding and van der Waals forces. Moreover, changes in the protein secondary structure and enhancement of the molecular interaction induced by CNC and Ca 2+ could favor the robust gel network. The results will provide a new perspective on the functional regulation of pea protein and the creation of pea protein gel-based food., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Understanding of nitrous acid (HONO) production is crucial to photochemical studies, especially in polluted environments like eastern China. In-situ measurements of gaseous and particulate compositions were conducted at a rural coastal site during the 2018 spring Ozone Photochemistry and Export from China Experiment (OPECE). This data set was applied to investigate the recycling of reactive nitrogen through daytime heterogeneous HONO production. Although HONO levels increase during agricultural burning, analysis of the observation data does not indicate more efficient HONO production by agricultural burning aerosols than other anthropogenic aerosols. Box and 1-D modeling analyses reveal the intrinsic relationships between nitrogen dioxide (NO 2 ), particulate nitrate (pNO 3 ), and nitric acid (HNO 3 ), resulting in comparable agreement between observed and simulated HONO concentrations with any one of the three heterogeneous HONO production mechanisms, photosensitized NO 2 conversion on aerosols, photolysis of pNO 3 , and conversion from HNO 3 . This finding underscores the uncertainties in the mechanistic understanding and quantitative parametrizations of daytime heterogeneous HONO production pathways. Furthermore, the implications for reactive nitrogen recycling, ozone (O 3 ) production, and O 3 control strategies vary greatly depending on the HONO production mechanism. On a regional scale, the conversion of HONO from pNO 3 can drastically enhance O 3 production, while the conversion from NO 2 can reduce O 3 sensitivity to NOx changes in polluted eastern China.

In this study, the polyvinylpyrrolidone-alizarin nanoparticles (PVP-AZ NPs) with favorable water dispersion and the carbon quantum dots (RQDs) with aggregate induced emission effect were synthesized to construct an eco-friendly film for food freshness monitoring. The introduction of PVP-AZ NPs and RQDs enhanced the network structure and thermal stability of the cassava starch/polyvinyl alcohol film, and reduced its crystallinity and light transmittance via non-covalent binding with the film-forming matrix. The developed film exhibited visually recognizable colorimetric and fluorescent responses to ammonia at 0.025-25 mg/mL, and it can be reused at least 6 times. Practical application experiment proved that the film, as an indicator label, can achieve accurate, real-time, and visual dynamic monitoring of the freshness of shrimp stored at 25 °C, 4 °C, and - 20 °C under daylight (orange yellow to purple) and UV light (red to blue). The integration of multivariate detection technology can eliminate the interference of external factors by self-correction to improve sensitivity and reliability, which provides a reference for the development of other food quality and safety monitoring platforms., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A novel approach to ultrasound-assisted Pickering interfacial biocatalysis (PIB) has been proposed and implemented for the efficient enzymatic transesterification production of vitamin A fatty acid esters. This is the first instance of exploiting the synergistic effect of ultrasound and the bifunctional modification of enzyme supports to accelerate biocatalytic performance in PIB systems. The optimal conditions were determined to be ultrasound power of 70 W, on/off time of 5 s/5 s, substrate molar ratio of 1:1, enzyme addition of 2 %, and a volume ratio of n-hexane to PBS of 3:1, a temperature of 40 °C, and a time of 30 min. The application of ultrasound technology not only improved lipase activity but also allowed for a reduction in emulsion droplet size to enhance interfacial mass transfer.Bifunctional modification of silica-based supports enhanced stability of immobilized enzymes by increasing hydrogen bonding while maintaining the active interface microenvironment. Compared with a non-ultrasound-assisted PIB system stabilized by mono-modified immobilized enzyme particles, the catalytic efficacy (CE) of the novel system reached 8.18 mmol g -1 min -1 , which was enhanced by 3.33-fold, while the interfacial area was found to have increased by 17.5-fold. The results facilitated the conversion of vitamin A palmitate (VAP), vitamin A oleate (VAO), vitamin A linoleate (VAL), and vitamin A linolenate (VALn), with conversion rates of approximately 98.2 %, 97.4 %, 96.1 %, and 94.7 %, respectively. This represents the most efficient example that has been reported to our knowledge. Furthermore, the system demonstrated improved reusability, with a conversion rate of 62.1 % maintained even after 10 cycles. The findings presented in this paper provide valuable insights into an efficient and conveniently promising protocol for the development of PIB systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

In this study, the β-cyclodextrin encapsulated betanin (BET@β-CD) with improved thermal stability and retention as well as the berberine (BBR) with aggregate induced luminescence effect were incorporated into corn amylose (CA) biomatrix to develop colorimetric/fluorescent dual-channel smart film. Results shown that the added functional components were uniformly distributed in the film matrix. The high tensile strength (78.87%), low water solubility (31.15%) and water vapor permeability (1.24 × 10 -10  g Pa -1  s -1  m -1 ) of the film predicted its acceptable stability. It was worth mentioning that the film displayed excellent responsiveness to volatile ammonia (0.025-25 mg/mL) with at least 4 times recyclability. Application experiment demonstrated that the film can achieve macroscopic dynamic monitoring of the freshness of shrimps stored at 25 °C, 4 °C, -20 °C under daylight (red to yellow) and UV light (yellow-green to blue-green). Thus, the study suggests an attractive and effective strategy for constructing dual-mode smart packaging materials for food freshness detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Despite considerable research efforts, lipase catalysis in a fluid milk system with aqueous multi-component mixtures containing multiple microphases, remains challenging. Pickering interfacial biocatalysis (PIB) platforms are typically fabricated with organic solvents/lipids and water. Whether a PIB with excellent catalytic performance can be constructed in complex milk mixtures remains unknown. Here, we challenged PIB with skim milk, and a small amount of flaxseed oil, and phytosterols as a model system for transesterification and lipolysis to enhance quality and flavor. The amino-modified mesoporous silica spheres (MSS-N) were employed as an emulsifier and carrier of lipase AYS (AYS@MSS-N). The conversion of phytosterol esters reached 75.5% at 1.5 h and prepared phytosterol ester-fortified milk with a content of 1.0 g/100 mL. The relative conversion rate remained above 70% after 6 cycles. In addition, the fortified milk showed an intensified and favorable effect on sensory traits through volatile flavor composition analysis. The findings provide a versatile alternative for PIB applications in complex environments, i.e., milk, which might inspire a new bioprocess strategy for dairy products., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia., Methods: Between 1 st August 2019 and 28 th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks., Results: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events., Conclusions: The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.

In this study, based on aggregation-induced emission (AIE) effect and antenna effect, a novel portable fluorescent responsive membrane was constructed with red carbon dots (R-CDs) as reference signal and terbium coordination polymer (Tb-AMP CPs) as response signal for visual, instrument-free, and sensitive detection of fluoroquinolones (FQs). Specifically, the fluorescent responsive membrane (R-T membrane) was prepared by physically depositing R-CDs with AIE property and Tb-AMP CPs on the surface of polyvinylidene fluoride filter membranes at ambient temperature. In the presence of FQs, Tb 3+ in the Tb-AMP CPs of the prepared membrane coordinated with the β-diketone structure of FQs, which turned on the yellow-green fluorescence through the "antenna effect". As the concentration of FQs increased, the R-T membrane achieved a fluorescent color transition from bright pink to yellow-green. Its visual detection sensitivity for three FQs, including ciprofloxacin, difloxacin, and enrofloxacin, was 0.01 μM, and the detection limits were 7.4 nM, 7.8 nM, and 9.2 nM, respectively, by analyzing the color parameter green. In the residue analysis of FQs in real samples, the constructed membrane also exhibited remarkable anti-interference and reliability, which is of great significance for ensuring the safety of animal-derived food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Preeclampsia is a disease with an unknown pathogenesis and is one of the leading causes of maternal and perinatal morbidity. At present, early identification of high-risk groups for preeclampsia and timely intervention with aspirin is an effective preventive method against preeclampsia. This study aims to develop a robust and effective preeclampsia prediction model with good performance by machine learning algorithms based on maternal characteristics, biophysical and biochemical markers at 11-13 +  6 weeks' gestation, providing an effective tool for early screening and prediction of preeclampsia., Methods: This study included 5116 singleton pregnant women who underwent PE screening and fetal aneuploidy from a prospective cohort longitudinal study in China. Maternal characteristics (such as maternal age, height, pre-pregnancy weight), past medical history, mean arterial pressure, uterine artery pulsatility index, pregnancy-associated plasma protein A, and placental growth factor were collected as the covariates for the preeclampsia prediction model. Five classification algorithms including Logistic Regression, Extra Trees Classifier, Voting Classifier, Gaussian Process Classifier and Stacking Classifier were applied for the prediction model development. Five-fold cross-validation with an 8:2 train-test split was applied for model validation., Results: We ultimately included 49 cases of preterm preeclampsia and 161 cases of term preeclampsia from the 4644 pregnant women data in the final analysis. Compared with other prediction algorithms, the AUC and detection rate at 10% FPR of the Voting Classifier algorithm showed better performance in the prediction of preterm preeclampsia (AUC=0.884, DR at 10%FPR=0.625) under all covariates included. However, its performance was similar to that of other model algorithms in all PE and term PE prediction. In the prediction of all preeclampsia, the contribution of PLGF was higher than PAPP-A (11.9% VS 8.7%), while the situation was opposite in the prediction of preterm preeclampsia (7.2% VS 16.5%). The performance for preeclampsia or preterm preeclampsia using machine learning algorithms was similar to that achieved by the fetal medicine foundation competing risk model under the same predictive factors (AUCs of 0.797 and 0.856 for PE and preterm PE, respectively)., Conclusions: Our models provide an accessible tool for large-scale population screening and prediction of preeclampsia, which helps reduce the disease burden and improve maternal and fetal outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Xu, Wang, Wang, Tang, Duan, Zhao, Zheng and Hu.)

Introduction: The aim of this study was to assess the short- and long-term outcome of selective reduction by fetoscopy-guided bipolar cord coagulation in monochronic twin pregnancies., Methods: Retrospective analysis was conducted of a consecutive cohort of all monochorionic twin pregnancies treated with fetoscopy-guided bipolar cord coagulation between December 2015 and December 2022 in a single center in China., Results: A total of 43 monochronic twin pregnancies undergoing fetoscopy-guided bipolar cord coagulation were analyzed. There were 5 intrauterine deaths with an 88.4% (38/43) survival rate overall. The preterm premature rupture of the membranes rate was 13.2%, and the preterm birth before 37 and 32 weeks was 42.1% and 13.1%, respectively. An uptrend in the survival rate (78.9 vs. 95.8%, p = 0.086) and a downtrend of procedure time (30 vs. 16.5 min, p = 0.036) were observed over time (period 1 from December 2015 to December 2019 verses period 2 from January 2020 to December 2022). Long-term outcome was assessed in 94.6% (35/37) of survivors, and 91.4% (32/35) had normal neurodevelopmental outcome., Conclusion: Fetoscopy-guided bipolar cord coagulation for fetal reduction in complicated monochorionic twin pregnancies could achieve a favorable short- and long-term outcome, especially in experienced hands., (© 2024 S. Karger AG, Basel.)

The differences in the gelling properties of soy protein isolate (SPI) and soy protein isolate amyloid fibrils (SAFs) as well as the role of cellulose nanocrystals (CNC) in regulating their gel behaviors were investigated in this study. The binding of CNC to β-conglycinin (7S), glycinin (11S), and SAFs was predominantly driven by non-covalent interactions. CNC addition reduced the particle size, turbidity, subunit segments, and crystallinity of SPI and SAFs, promoted the conversion of α-helix to β-sheet, improved the thermal stability, exposed more tyrosine and tryptophan residues, and enhanced the intermolecular interactions. A more regular and ordered lamellar network structure was formed in the SAFs-CNC composite gel, which could be conducive to the improvement of gel quality. This study would provide theoretical reference for the understanding of the regulatory mechanism of protein amyloid fibrils gelation as well as the high-value utilization of SAFs-CNC complex as a functional protein-based material or food ingredient in food field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To evaluate monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies conceived by assisted reproductive technology (ART) and conceived naturally., Methods: We retrospectively analyzed the data on twin pregnancies conceived by ART from January 2015 to January 2022,and compared pregnancy outcomes of MCDA and DCDA twins conceived by ART with those of MCDA and DCDA twins conceived naturally, pregnancy outcomes between MCDA and DCDA twins conceived by ART, and pregnancy outcomes of DCT and TCT pregnancies reduced to DCDA pregnancies with those of DCDA pregnancies conceived naturally., Result: MCDA pregnancies conceived by ART accounted for 4.21% of the total pregnancies conceived by ART and 43.81% of the total MCDA pregnancies. DCDA pregnancies conceived by ART accounted for 95.79% of the total pregnancies conceived by ART and 93.26% of the total DCDA pregnancies. Women with MCDA pregnancies conceived by ART had a higher premature delivery rate, lower neonatal weights, a higher placenta previa rate, and a lower twin survival rate than those with MCDA pregnancies conceived naturally (all p < 0.05). Women with DCDA pregnancies conceived naturally had lower rates of preterm birth, higher neonatal weights, and higher twin survival rates than women with DCDA pregnancies conceived by ART and those with DCT and TCT pregnancies reduced to DCDA pregnancies (all p < 0.05)., Conclusion: Our study confirms that the pregnancy outcomes of MCDA pregnancies conceived by ART are worse than those of MCDA pregnancies conceived naturally. Similarly, the pregnancy outcomes of naturally-conceived DCDA pregnancies are better than those of DCDA pregnancies conceived by ART and DCT and TCT pregnancies reduced to DCDA pregnancies., (© 2024. The Author(s).)

Adenosine (Ado) is significantly elevated in the tumor microenvironment (TME) compared to normal tissues. It binds to adenosine receptors (AdoRs), suppressing tumor antigen presentation and immune cell activation, thereby inhibiting tumor adaptive immunity. Ado downregulates major histocompatibility complex II (MHC II) and co-stimulatory factors on dendritic cells (DCs) and macrophages, inhibiting antigen presentation. It suppresses anti-tumor cytokine secretion and T cell activation by disrupting T cell receptor (TCR) binding and signal transduction. Ado also inhibits chemokine secretion and KCa3.1 channel activity, impeding effector T cell trafficking and infiltration into the tumor site. Furthermore, Ado diminishes T cell cytotoxicity against tumor cells by promoting immune-suppressive cytokine secretion, upregulating immune checkpoint proteins, and enhancing immune-suppressive cell activity. Reducing Ado production in the TME can significantly enhance anti-tumor immune responses and improve the efficacy of other immunotherapies. Preclinical and clinical development of inhibitors targeting Ado generation or AdoRs is underway. Therefore, this article will summarize and analyze the inhibitory effects and molecular mechanisms of Ado on tumor adaptive immunity, as well as provide an overview of the latest advancements in targeting Ado pathways in anti-tumor immune responses., (© 2024 The Authors.)

This study aimed to investigate the multiscale structure, physicochemical properties, and in vitro digestibility of black rice starch (BRS) and gallic acid (GA) complexes prepared using varying ultrasound powers. The findings revealed that ultrasonic treatment disrupted BRS granules while enhancing the composite degree with GA. The starch granules enlarged and aggregated into complexes with uneven surfaces. Moreover, the crystallinity of the BRS-GA complexes increased to 22.73 % and formed V6-I-type complexes through non-covalent bonds. The increased short-range ordering of the complexes and nuclear magnetic resonance hydrogen ( 1 H NMR) further indicated that the BRS and GA molecules interacted mainly through non-covalent bonds such as hydrogen bonds. Additionally, ultrasound reduced the viscoelasticity of the complexes while minimizing the mass loss of the complexes at the same temperature. In vitro digestion results demonstrated an increase in resistant starch content up to 37.60 % for the BRS-GA complexes. Therefore, ultrasound contributes to the formation of V-typed complexes of BRS and GA, which proves the feasibility of using ultrasound alone for the preparation of starch and polyphenol complexes while providing a basis for the multiscale structure and digestibility of polyphenol and starch complexes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present study focused on the extraction of water-soluble dietary fiber (CSDF) and water-insoluble dietary fiber (CIDF) from celery. It investigated their effects on glutinous rice starch's (GRS) physicochemical, structural, and digestive properties. The results showed that as the addition of the two dietary fibers increased, they compounded with GRS to varying degrees, with the complexing index reaching 69.41 % and 60.81 %, respectively. The rheological results indicated that the two dietary fibers reduced the viscosity of GRS during pasting and inhibited the short-term regrowth of starch. The FTIR and XRD results revealed that the two fibers interacted with GRS through hydrogen bonding, effectively inhibiting starch retrogradation. Furthermore, both fibers increased the pasting temperature of GRS, thus delaying its pasting and exhibiting better thermal stability. Regarding digestibility, the starch gels containing dietary fibers exhibited significantly reduced digestibility, with RS significantly increased by 8.15 % and 8.95 %, respectively. This study provides insights into the interaction between two dietary fibers and GRS during processing. It enriches the theoretical model of dietary fiber-starch interaction and provides a reference for the application development of starch-based functional foods., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This study aimed to develop and validate a nomogram for predicting overall survival (OS) in patients undergoing surgery for right-sided colon cancer (RCC)., Methods: We collected 25,203 patients with RCC from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided them into 7:3 training and internal validation set. Utilizing the Cox proportional hazards regression model, we constructed a nomogram based on prognostic risk factors. Furthermore, for external validation, we retrospectively followed up with 228 patients from Jiaxing First Hospital and assessed and calibrated the nomogram using the C-index and calibration curves., Results: After identifying independent prognostic factors through univariate and multivariate analyses, a nomogram was developed. The c-index values of this nomogram differed as follows: 0.851 (95% CI: 0.845-0.857) in the training set, 0.860 (95% CI: 0.850-0.870) in the internal validation set, and 0.834 (95% CI: 0.780-0.888) in the external validation set, indicating the model's strong discriminative ability. Calibration curves for 1-year, 3-year, and 5-year overall survival (OS) probabilities exhibited a high level of consistency between predicted and actual survival rates. Furthermore, Decision Curve Analysis (DCA) demonstrated that the new model consistently outperformed the TNM staging system in terms of net benefit., Conclusion: We developed and validated a survival prediction model for patients with RCC. This novel nomogram outperforms the traditional TNM staging system and can guide clinical practitioners in making optimal clinical decisions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Qin, Yu, Dong, Zheng, Wang and Shen.)

The endocytic trafficking pathway is a highly organized cellular program responsible for the regulation of membrane components and uptake of extracellular substances. Molecules internalized into the cell through endocytosis will be sorted for degradation or recycled back to membrane, which is determined by a series of sorting events. Many receptors, enzymes, and transporters on the membrane are strictly regulated by endocytic trafficking process, and thus the endocytic pathway has a profound effect on cellular homeostasis. However, the endocytic trafficking process is typically dysregulated in cancers, which leads to the aberrant retention of receptor tyrosine kinases and immunosuppressive molecules on cell membrane, the loss of adhesion protein, as well as excessive uptake of nutrients. Therefore, hijacking endocytic trafficking pathway is an important approach for tumor cells to obtain advantages of proliferation and invasion, and to evade immune attack. Here, we summarize how dysregulated endocytic trafficking process triggers tumorigenesis and progression from the perspective of several typical cancer hallmarks. The impact of endocytic trafficking pathway to cancer therapy efficacy is also discussed., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diminished or lost Major Histocompatibility Complex class I (MHC-I) expression is frequently observed in tumors, which obstructs the immune recognition of tumor cells by cytotoxic T cells. Restoring MHC-I expression by promoting its transcription and improving protein stability have been promising strategies for reestablishing anti-tumor immune responses. Here, through cell-based screening models, we found that cediranib significantly upregulated MHC-I expression in tumor cells. This finding was confirmed in various non-small cell lung cancer (NSCLC) cell lines and primary patient-derived lung cancer cells. Furthermore, we discovered cediranib achieved MHC-I upregulation through transcriptional regulation. interferon regulatory factor 1 (IRF-1) was required for cediranib induced MHC-I transcription and the absence of IRF-1 eliminated this effect. Continuing our research, we found cediranib triggered STAT1 phosphorylation and promoted IRF-1 transcription subsequently, thus enhancing downstream MHC-I transcription. In vivo study, we further confirmed that cediranib increased MHC-I expression, enhanced CD8 + T cell infiltration, and improved the efficacy of anti-PD-L1 therapy. Collectively, our study demonstrated that cediranib could elevate MHC-I expression and enhance responsiveness to immune therapy, thereby providing a theoretical foundation for its potential clinical trials in combination with immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ammonia control has attracted attention due to the possibility for fine particles (PM 2.5 ) mitigation. Based on past decade ammonia emissions assessments and future predictions, this study seasonally evaluated the ammonia emissions reduction potential in 2025 and 2030 in Wuhan, a Central China megacity, according to the short-term and long-term predictable policies. Furthermore, combined with the reduction potential, PM 2.5 components observation and thermodynamic model, the effectiveness of implementing ammonia emission control to reduce PM 2.5 by 2025 and 2030 was explored seasonally. Results indicated that the total ammonia emissions are expected to decrease by 19.6-33.9% in 2025 and 2030 under positive reduction scenarios, or increase by 8.9-11.7% in the absence of any intervention. Livestock holds the largest potential for reducing ammonia emissions accounting for 46.4-52.5% of the total. Improvement of human excrement management in rural regions also contributes a 35-37% potential. Despite the implementation of exhaust requirements, ammonia emissions from vehicles in 2030 are expected to continue to increase by 55.3% and 23.5% under the regular (S1) and enhanced (S2) reduction strategy scenarios, respectively. Seasonally, the most potential source of ammonia reduction in spring, summer and fall remains livestock. While in winter, non-agricultural sources dominate the reduction potential. Further results indicated that by ammonia control is expected to decrease PM 2.5 concentration up to 5% (less than 1 μg m -3 ) in 2025-2030. Despite the better effectiveness in winter, ammonia control won't be an effective way to reduce PM 2.5 in Central China in future, from the management policies and areal ammonia-rich conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this work, a bimetallic organic framework (Cu/UiO-66) based "turn on" fluorescent aptamer probe was designed for the high-efficiency detection of zearalenone (ZEN). In the probe, the 6-carboxyfluorescein-labeled aptamer (FAM-Apt) was used as the recognition element, and the electrostatic interaction, coordination effect, and photoinduced electron transfer effect between FAM-Apt and Cu/UiO-66 caused fluorescence quenching. When ZEN existed, FAM-Apt recognized ZEN specifically, causing FAM-Apt to separate from the surface of Cu/UiO-66 and recovery of fluorescence. Under the optimal conditions, the probe had a linear detection range of 0.5 ng/mL-60 ng/mL, and the detection limit was 0.048 ng/mL. The application potential of the probe was verified by real detection of various cereals and their products, with a standard recovery from 83.67 %-106.8 %. The development of this efficient, rapid, and sensitive ZEN detection method provides a new platform for the quality control of cereals and their products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Cyclin-dependent kinases (CDKs) play an important role in the regulation of cell proliferation, and many CDK inhibitors were developed. However, pan-CDK inhibitors failed to be approved due to intolerant toxicity or low efficacy and the use of selective CDK4/6 inhibitors is limited by resistance. Protein degraders have the potential to increase selectivity, efficacy and overcome resistance, which provides a novel strategy for regulating CDKs. In this review, we summarized the function of CDKs in regulating the cell cycle and transcription, and introduced the representative CDK inhibitors. Then we made a detailed introduction about four types of CDKs degraders, including their action mechanisms, research status and application prospects, which could help the development of novel CDKs degraders.

In this study, type III resistant starch (RS3) was prepared from high amylose maize starch (HAMS) using hydrothermal (RS-H), hydrothermal combined ultrasonication (RS-HU), hydrothermal-alkali (RS-HA), and hydrothermal-alkali combined ultrasonication (RS-HAU). The role of the preparation methods and the mechanism of RS3 formation were analyzed by studying the multiscale structure and digestibility of the starch. The SEM, NMR, and GPC results showed that hydrothermal-alkali combined with ultrasonication could destroy the granule structure and α-1,6 glycosidic bond of HAMS and reduce the molecular weight of HAMS from 195.306 kDa to 157.115 kDa. The other methods had a weaker degree of effect on the structure of HAMS, especially hydrothermal and hydrothermal combined ultrasonication. The multiscale structural results showed that the relative crystallinity, short-range orderliness, and thermal stability of RS-HAU were significantly higher compared with native HAMS. In terms of digestion, RS-HAU had the highest RS content of 69.40 %. In summary, HAMS can generate many short-chain amylose due to structural damage, which rearrange to form digestion-resistant crystals. With correlation analysis, we revealed the relationship between the multiscale structure and the RS content, which can be used to guide the preparation of RS3., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Currently, the effect of varieties on the flavor and stability of flaxseed milk remains unknown. Therefore, this study was conducted to investigate the effects of different varieties on the stability, sensory, and aromas of flaxseed milk. 51 volatile compounds were identified in flaxseed milk using Stir Bar Sorptive Extraction-Gas Chromatography-Olfactometry-Mass Spectrometry (SBSE-GC-O-MS). Among them, 1-octen-3-ol, 2-methoxy-4-vinylphenol, and 2,3,5-trimethylpyrazine contributed higher relative odor active values (ROAV), resulted in the fruity, roasted, sweet, and cucumber in flaxseed milk. Isovaleraldehyde (green notes) was not detected in XHZM. However, other compounds such as 1-nonanol (floral), γ-nonanolactone and γ-octanoic lactone (coconut milk) had higher concentrations, causing a better sensory evaluation. Additionally, its stability was relatively good. The orthogonal partial least-squares regression (OPLS) model and VIP values showed that eight compounds were responsible for the sensory differences from different varietals. The study provided references to selection and understanding flavor composition basis of flaxseed milk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Accelerated eutrophication in lakes reduces the number of submerged macrophytes and alters the residues of glyphosate and its degradation products. However, the effects of submerged macrophytes on the fate of glyphosate remain unclear. We investigated eight lakes with varying trophic levels along the middle and lower reaches of the Yangtze River in China, of which five lakes contained either glyphosate or aminomethylphosphate (AMPA). Glyphosate and AMPA residues were significantly positively correlated with the trophic levels of lakes (P < 0.01). In lakes, glyphosate is degraded through the AMPA and sarcosine pathways. Eight shared glyphosate-degrading enzymes and genes were observed in different lake sediments, corresponding to 44 degrading microorganisms. Glyphosate concentrations in sediments were significantly higher in lakes with lower abundances of soxA (sarcosine oxidase) and soxB (sarcosine oxidase) (P < 0.05). In the presence of submerged macrophytes, oxalic and malonic acids secreted by the roots of submerged macrophytes increased the abundance of glyphosate-degrading microorganisms containing soxA or soxB (P < 0.05). These results revealed that a decrease in the number of submerged macrophytes in eutrophic lakes may inhibit glyphosate degradation via the sarcosine pathway, leading to a decrease in glyphosate degradation and an increase in glyphosate residues., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is a prevalent and lethal malignancy worldwide. The MET gene, which encodes receptor tyrosine kinase c-Met, is aberrantly activated in various solid tumors, including non-small cell lung cancer and HCC. In this study, we identified a novel c-Met inhibitor 54 by virtual screening and structural optimization. Compound 54 showed potent c-Met inhibition with an IC 50 value of 0.45 ± 0.06 nM. It also exhibited high selectivity among 370 kinases and potent anti-proliferative activity against MET-amplified HCC cells. Moreover, compound 54 displayed significant anti-tumor efficacy in vivo, making it a potential candidate for HCC treatment in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Radix Cynanchi bungei (RCb) contains 40-70 % starch, yet little is known about the structure and properties of RCb starch. In this study, the multiscale structure of two cultivars of RCb starch (YW201501 and BW201001) were characterized, and the effects of starch structure on its physicochemical properties were investigated. The differences in physicochemical properties of RCb starch were influenced by its multiscale structure. The starch granules were round and irregular polygon, with sizes ranging between 2 and 14 μm. YW201501 had a higher amylose (21.81 %) and lipid (0.96 %) content, molecular weight (59.5 × 10 6  g/mol), and A chain proportion (27.5 %), and a lower average granule size (6.14 μm), amylopectin average chain length (19.7), and B3 chain proportion (10.3 %). Both starches were B-type crystalline, with higher crystallinity (26.3 %) and R 1047/1022 (0.74) for YW201501, resulting in large gelatinization enthalpy. In addition, the higher peak viscosity and larger retrogradation degree of YW201501 were correlated to its higher amylose content. In vitro digestibility revealed that the low rapidly digestible starch and high resistant starch of BW201001 were related to the fine structure of starch. YW201501 and BW201001 had a medium glycemic index (62.6-66.0) with potential for processing into healthy starchy foods., Competing Interests: Declaration of competing interest Authors declared that there are no conflicts of interest to this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

In view of the potential hazards of organophosphorus pesticides (OPs), this paper constructed a ratiometric fluorescent probe utilizing a functionalized metal-organic framework to detect OPs. Ru(bpy) 3 Cl 2 was encapsulated inside UiO-66 as a reference signal, and MnO 2 nanosheets (MnO 2 NSs) were grown on the surface to obtain Ru@UiO-66@MnO 2 NSs. Acetylcholinesterase catalyzed the decomposition of acetylcholine into reductive thiocholine, which consumed MnO 2 NSs, thus restoring the Ru@UiO-66 fluorescence. Due to the enzymatic inhibition of OPs and the redox reaction between MnO 2 NSs and thiamine, this probe emitted blue fluorescence in the presence of OPs. The probe achieved linear responses to dichlorvos and chlorpyrifos with LODs of 9.99 × 10 -6 μg mL -1 and 9.99 × 10 -5 μg mL -1 . The probe exhibited a satisfactory recovery rate for OPs in green tea. Furthermore, a hydrogel detection platform was developed by embedding the probe into sodium alginate. Overall, this work provides a visual approach to detect OPs in agricultural products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prostate cancer (PCa) seriously threatens male health, and targeting dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) has been verified to reduce PCa burden, while the research progress on the DYRK2 inhibitors was relatively slow. In this work, we discovered DYRK2 inhibitor 12 (IC 50 = 9681 nM) through virtual screening. Subsequently, we performed systematic structural optimization to obtain 54 (IC 50 = 14 nM). Compound 54 exhibited high selectivity among 215 kinases and significantly suppressed the proliferation and metastasis of PCa cells in vitro . Moreover, compound 54 displayed high safety, favorable bioavailability, and potent tumor growth inhibitory activity in vivo , which could be used as a potential candidate in the discovery of novel anti-PCa drugs.

In the present study, we demonstrated that the presence of cysteine could remarkably enhance the degradation of atrazine by Fe 3 O 4 /persulfate system. The results of electron paramagnetic resonance (EPR) spectra confirmed the combination of cysteine and Fe 3 O 4 exhibited much higher activity on activation of persulfate to generate more SO 4 •- and •OH than Fe 3 O 4 alone. At pH of 3.0, SO 4 •- and •OH contributed to about 58.2 % and 41.8 % of atrazine removal respectively, while •OH gradually dominated the oxidation of atrazine from neutral condition to alkaline condition. The co-existing Cl - and HCO 3 - could quench SO 4 •- , resulting in the inhibition of atrazine degradation. The presence of low natural organic matters (NOM) concentration (0-2 mg L -1 ) could enhance the atrazine removal, and high concentration (>5 mg L -1 ) of NOM restrained the atrazine degradation. During the Cysteine/Fe 3 O 4 /Persulfate process, cysteine served as a complexing reagent and reductant. Through acidolysis and complexation, Fe 3 O 4 could release dissolved and surface bound Fe 2+ , both of which contributed to the activation of persulfate together. Meanwhile, cysteine was not rapidly consumed due to a regeneration process, which was beneficial for maintaining Fe 2+ /Fe 3+ cycle and constantly accelerating the activation of persulfate for atrazine degradation. The reused Fe 3 O 4 and cysteine in the Cysteine/Fe 3 O 4 /Persulfate process exhibited high stability for the atrazine degradation after three cycles. The degradation pathway of atrazine included alkylic-oxidation, dealkylation, dechlorination-hydroxylation processes. The present study indicates the novel Cysteine/Fe 3 O 4 /Persulfate process might be a high potential for treatment of organic polluted water., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Outdoor air pollution causes millions of premature deaths annually worldwide. Sulfate is a major component of particulate pollution. Winter sulfate observations in China show both high concentrations and an accumulation mode with a modal size >1 μm. However, we find that this observed size distribution cannot be simulated using classical gaseous and aqueous phase formation (CSF) or proposed aerosol-processing formation (APF) mechanisms. Specifically, the CSF simulation underestimates sulfate concentrations by 76% over megacities in China and predicts particle size distributions with a modal size of ∼0.35 μm, significantly smaller than observations. Although incorporating the APF mechanism in the atmospheric chemical model notably improves sulfate concentration simulation with reasonable parameters, the simulated sulfate particle size distribution remains similar to that using the CSF mechanism. We further conduct theoretical analyses and show that particles with diameters <0.3 μm grow rapidly (2-3 s) to 1 μm through the condensation of sulfuric acid in fresh high-temperature exhaust plumes, referred to as in-source formation (ISF). An ISF sulfate source equivalent to 15% of sulfur emissions from fossil fuel combustion largely explains both observed size distributions and mass concentrations of sulfate particles. The findings imply that ISF is a major source of wintertime micron-sized sulfate in China and underscore the importance of considering the size distribution of aerosols for accurately assessing the impacts of inorganic aerosols on radiative forcing and human health.

Background: In recent years, light therapy has been tried for the treatment of depression and sleep in pregnancy or postnatal period women, but the results have been inconclusive. This meta-analysis is the first to systematically review the effects of light therapy on depression and sleep disturbances in women during pregnancy and the postnatal period., Methods: We searched for randomized controlled studies in PubMed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, and Chinese Biomedical Database up to January 2023. The standardized mean difference (SMD) was used to assess the efficacy of the outcome indicators., Results: Eight studies were eventually included in the analysis. The results showed that light therapy was more effective than the placebo group in terms of depression (SMD = .34, CI = .08-.61) and sleep (SMD = .64,95%CI = .28-1.00). Subgroup analysis could not explain the significant heterogeneity. There were no serious adverse effects in either the light therapy or placebo groups., Conclusions: Light therapy could be considered an effective treatment for depression and sleep disturbances in women during pregnancy and the postnatal period. However, future high-quality trials with larger sample sizes are still needed., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Recent studies have pointed to the role of Krüpple-like factor 12 (KLF12) in cancer-associated processes, including cancer proliferation, apoptosis, and metastasis. However, the role of KLF12 in tumor immunity remains obscure. Here, we found that KLF12 expression was significantly higher in non-small cell lung cancer (NSCLC) cells with higher programmed death-ligand 1 (PD-L1) expression. Additionally, a positive correlation between KLF12 and PD-L1 was observed in clinical patient tumor tissues. By chromatin immunoprecipitation (ChIP) analysis, KLF12 was identified to bind to the CACCC motif of the PD-L1 promoter. Overexpression of KLF12 promoted PD-L1 transcription, whereas silencing of KLF12 inhibited PD-L1 transcription. Furthermore, signal transducer and activator of transcription 1 (STAT1)- and STAT3-triggered PD-L1 transcription was abolished in the absence of KLF12, and KLF12 knockdown weakened the binding of STAT1 and STAT3 to the PD-L1 promoter. Mechanistically, KLF12 physically interacted with P300, a histone acetyltransferase. In addition, KLF12 silencing reduced P300 binding to the PD-L1 promoter, which subsequently caused decreased acetylation of histone H3. PD-L1 transcription driven by KLF12 overexpression was eliminated by EP300 silencing. In immunocompetent mice, KLF12 knockout inhibited tumor growth and promoted infiltration of CD8 + T cells. However, this phenomenon was not observed in immunodeficient mice. Overall, this study reveals KLF12-mediated transcriptional regulation of PD-L1 in NSCLC; targeting KLF12 may be a potential therapeutic strategy for NSCLC., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: The brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia., Methods: In this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence-based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms., Results: Here, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms., Conclusions: These findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia., (© 2023. The Author(s).)

Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Immunotherapy targeting the programmed death protein 1(PD-1) and its ligand (PD-L1), is a promising treatment option for many cancers, but has exhibited poor therapeutic efficacy in CRC. This study aimed to identify and validate the prognostic value of immune-related genes and PD-1-associated genes for immunotherapy treatment of CRC., Methods: An extensive analysis of prognostic immune-related DEGs and PD-1-related genes has highlighted CDKN2A as a vital overlapping gene. To further explore its expression in CRC and its prognostic value, we conducted qRT-PCR, Western blot experiments, and consulted various databases. Subsequently, we conducted gene expression analysis, survival and prognostic analysis, enrichment analysis, immune infiltration assessment, and TIDE analysis to assess the significance of CDKN2A., Results: In CRC, CDKN2A was highly expressed compared to normal tissue. It was found that CDKN2A expression was related to clinicopathological features such as inflammation and tumor stage. Furthermore, a significant correlation was identified between CDKN2A and immune infiltration, specifically involving CD4 T cells, CD8 T cells, and macrophages. The analysis of the GSEA of CRC samples with high CDKN2A expression identified enrichment of genes involved in MYC target-v2 and metabolism pathways. Furthermore, UBE2I, CDK4, CDK6, TP53, and CCND1 were found to be significantly coexpressed with CDKN2A, suggesting a potential role that these gene play in CRC and immunotherapy., Conclusions: Our study revealed that high CDKN2A expression in CRC is a potentially valuable prognostic biomarker, which may guide PD-1-mediated immunotherapy., (© 2023. The Author(s).)

Tuberculosis (TB) is one of the most threatening diseases for humans, however, the drug treatment strategy for TB has been stagnant and inadequate, which could not meet current treatment needs. TB is caused by Mycobacterial tuberculosis, which has a unique cell wall that plays a crucial role in its growth, virulence, and drug resistance. Polyketide synthase 13 (Pks13) is an essential enzyme that catalyzes the biosynthesis of the cell wall and its critical role is only found in Mycobacteria. Therefore, Pks13 is a promising target for developing novel anti-TB drugs. In this review, we first introduced the mechanism of targeting Pks13 for TB treatment. Subsequently, we focused on summarizing the recent advance of Pks13 inhibitors, including the challenges encountered during their discovery and the rational design strategies employed to overcome these obstacles, which could be helpful for the development of novel Pks13 inhibitors in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

The current serious environmental problems have greatly encouraged the design and development of food packaging materials with environmental protection, green, and safety. This study aims to explore the synergistic effect and corresponding mechanism of cellulose nanocrystals (CNC) and CaCl 2 to enhance the film-forming properties of pea protein isolate (PPI). The combination of 0.5 % CNC and 4.5 mM CaCl 2 resulted in a 76.6 % increase in tensile strength when compared with pure PPI-based film. Meanwhile, this combination effectively improved the barrier performance, surface hydrophobicity, water resistance, and biodegradability of PPI-based film. The greater crystallinity, viscoelasticity, lower water mobility, and improved protein spatial conformation were also observed in CNC/CaCl 2 composite film. Compared with the control, the main degradation temperature of composite film was increased from 326.23 °C to 335.43 °C. The CNC chains bonded with amino acid residue of pea protein at specific sites via non-covalent forces (e.g., hydrogen bonds, Van der Waals forces). Meanwhile, Ca 2+ promoted the ordered protein aggregation at suitable rate and degree, accompanied by the formation of more disulfide bonds. Furthermore, proper Ca 2+ could strengthen the cross-linking and interaction between CNC and protein, thereby establishing a stable network structure. The prepared composite films are expected to be used for strawberry preservation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Tumors in which the microenvironment is characterized by lack of immune cell infiltration are referred as "cold tumors" and typically exhibit low responsiveness to immune therapy. Targeting the factors contributing to "cold tumors" formation and converting them into "hot tumors" is a novel strategy for improving the efficacy of immunotherapy. Adenosine, a hydrolysis product of ATP, accumulates with a significantly higher concentration in the tumor microenvironments compared with normal tissue and exerts inhibitory effects on tumor-specific adaptive immunity. Tumor cells, dendritic cells, macrophages, and T cells express abundant adenosine receptors on their surfaces. The binding of adenosine to these receptors initiates downstream signaling pathways that suppress tumor antigen presentation and immune cell activation, consequently dampening adaptive immune responses against tumors. Adenosine down-regulates the expression of major histocompatibility complex Ⅱ and co-stimulatory factors on dendritic cells and macrophages, thereby inhibiting antigen presentation to T cells. Adenosine also inhibits ligand-receptor binding and transmembrane signaling on T cells, concomitantly suppressing the secretion of anti-tumor cytokines and impairing T cell activation. Furthermore, adenosine hinders effector T cell trafficking to tumor sites and infiltration by inhibiting chemokine secretion and KCa3.1 channels. Additionally, adenosine promotes the secretion of immunosuppressive cytokines, increases immune checkpoint protein expression, and enhances the activity of immunosuppressive cells, collectively curbing cytotoxic T cell-mediated tumor cell killing. Given the immunosuppressive role of adenosine in adaptive antitumor immunity, several inhibitors targeting adenosine generation or adenosine receptor blockade are currently in preclinical or clinical development with the aim of enhancing the effectiveness of immunotherapies. This review provides an overview of the inhibitory effects of adenosine on adaptive antitumor immunity, elucidate the molecular mechanisms involved, and summarizes the latest advances in application of adenosine inhibition strategies for antitumor immunotherapy.

Increasing evidence demonstrated that pyroptosis and subsequent inflammation played an important role in the pathological process of non-alcoholic steatohepatitis (NASH). Plant sterol ester of α-linolenic acid (PS-ALA) was beneficial for non-alcoholic fatty liver disease, but the underlying mechanisms are still not fully understood. This study aims to investigate whether PS-ALA can protect against proptosis via regulating SIRT1. Thirty male C57BL/6J mice were fed a normal diet, a high-fat and high-cholesterol diet (HFCD), or a HFCD supplemented with either 1.3%ALA, 2%PS, or 3.3% PS-ALA for 24 weeks. Hepatocytes were treated with oleic acid and cholesterol (OA/Cho) with or without PS-ALA. We found that PS-ALA ameliorated NASH in HFCD-fed mice. In addition, PS-ALA decreased the expression of NLRP3 and ASC and reduced the co-localization of NLRP3 and cleave-Caspase-1. Also, PS-ALA protected against pyroptosis as evidenced by decreased co-localization of GSDMD and propidium iodide (PI) positive cells. Mechanistically, we revealed that the inhibitory action of PS-ALA on the pyroptosis was mediated by SIRT1. This was demonstrated by the fact that silencing SIRT1 with small interfering RNA or inhibition of SIRT1 with its inhibitor abolished the inhibition effect of PS-ALA on the expression of NLRP3 and GSDMD cleavage. Collectively, the data from the present study reveals a novel mechanism that PS-ALA inhibits pyroptosis and it triggered inflammation via stimulating SIRT1, which provides new insights into the beneficial effect of PS-ALA on NASH., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Enzymatic hydrolysis is a promising approach for protein and food processing. However, the efficiency of this approach is constrained by the self-hydrolysis, self-agglomeration of free enzymes and the limited applicability resulted from enzymes' selectivityt. Here, novel organic-inorganic hybrid nanoflowers (AY-10@AXH-HNFs) were prepared by coordinating Cu 2+ with both endopeptidase of PROTIN SD-AY10 and exopeptidase of Prote AXH. The results indicate that the AY-10@AXH-HNFs exhibited 4.1 and 9.6 times higher catalytic activity than free Prote AXH and PROTIN SD-AY10, respectively, for the enzymatic hydrolysis of N-benzoyl-L-arginine ethyl ester (BAEE). The kinetic parameters of K m , V max and K cat /K m by AY-10@AXH-HNFs were determined to be 0.6 mg/mL, 6.8 mL·min/mg and 6.1 mL/(min·mg), respectively, surpassing the values obtained from free endopeptidase and exopeptidase. Furthermore, the ability of AY-10@AXH-HNFs to retain 41 % of their initial catalytic activity after undergoing 5 cycles of repeated use confirmed their stability and reusability. This study introduces a novel approach of co-immobilizing endopeptidase and exopeptidase on nanoflowers, resulting in significantly enhanced stability and reusability of the protease in catalytic applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This work focused on the pathways by which NCC regulated the digestibility of corn starch. The addition of NCC changed the viscosity of the starch during pasting, improved the rheological properties and short-range order of the starch gel, and finally formed a compact, ordered, and stable gel structure. In this respect, NCC affected the digestion process by changing the properties of the substrate, which reduced the degree and rate of starch digestion. Moreover, NCC induced changes in the intrinsic fluorescence, secondary conformation, and hydrophobicity of α-amylase, which lowered its activity. Molecular simulation analyses suggested that NCC bonded with amino acid residues (Trp 58, Trp 59, and Tyr 62) at the active site entrance via hydrogen bonding and van der Waals forces. In conclusion, NCC decreased CS digestibility by modifying the gelatinization and structural properties of starch and inhibiting α-amylase activity. This study provides new insights into the mechanisms by which NCC regulates starch digestibility, which could be beneficial for the development of functional foods to tackle type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

In this study, high amylose maize starch(HAMS)was treated by Hydrothermal-alkali. SEM, SAXS, XRD, FTIR, LC-Raman, 13 C CP/MAS NMR, GPC and TGA were used to study the changes in the granules and structure of HAMS. The results show that the granule morphology, lamellar structure, and birefringence of HAMS remained intact at 30 °C and 45 °C. With increasing temperature, the starch granules are fragmented, and the crystallinity, DD, FWHM values, molecular weight, and thermal stability of HAMS decrease. The double helical structure dissociated, and the content of amorphous regions increased, indicating the from order to the disorder of the HAMS structure. A similar annealing behavior occurred in HAMS at 45 °C, with the rearrangement of amylose and amylopectin occurring. At 75 °C and 90 °C, the short-chain starch produced by chain breakage regroups to form an ordered double helix structure. In general, the granule structure level of HAMS was damaged to different degrees at varying temperatures. HAMS showed gelatinization behavior in alkaline solutions when the temperature is 60 °C. This study expects to provide a model for the gelatinization theory of HAMS systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Schizophrenia (SCZ) is associated with chronic low-grade inflammation, which may be involved in the underlying pathological mechanism of the disease and may influence patient prognosis. We evaluated the differences in serum cytokine and Tie-2 receptor levels between patients with first-episode SCZ and healthy controls and explored the correlation thereof with clinical symptoms., Methods: Seventy-six participants were recruited for the present study, including 40 patients with first-episode SCZ and 36 healthy controls. Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) scores, demographic data, and blood samples were collected at baseline. A hypersensitive Meso Scale Discovery (MSD) electrochemiluminescence assay system was used to measure cytokine and Tie-2 receptor levels. Spearman's correlation and stepwise linear regression were used to analyze the data., Results: Serum interleukin-1β and -4 levels were significantly increased, and Tie-2 levels were significantly decreased, in first-episode SCZ patients as compared to healthy controls. IL-1β levels were positively correlated with total BPRS scores, resistance subscores, and PANSS positive subscores. Furthermore, IL-1β levels were negatively correlated with Tie-2 receptor expression levels. Stepwise linear regression analysis demonstrated that IL-1β levels correlated positively with PANSS positive subscores and BPRS total scores. PANSS negative subscores, general psychopathology subscores, and PANSS total scores had positive effects on the Tie-2 receptor. Receiver operating characteristic (ROC) curve analysis showed that IL-1β and Tie-2 were highly sensitive and specific for predicting first-episode SCZ symptoms and achieving an area under the ROC curve of 0.8361 and 0.6462, respectively., Conclusion: Our results showed that patients with first-episode SCZ have low-grade inflammation. IL-1β and Tie-2 receptors may be important mediators between inflammation and vascular dysfunction in patients with SCZ and may underlie the increased cardiovascular disease in this population., Trial Registration: The clinical trial registration date was 06/11/2018, registration number was chiCTR1800019343., (© 2023. The Author(s).)

Alcohol solution is a cheap, simple, and effective precipitating solvent frequently used for separating debranched starch (DBS), yet little is known about the precipitation mechanism of DBS by different alcohols. This study precipitated DBS from pullulanase-hydrolyzed starch using ethanol, n-butanol, and isopentanol. The multiscale structures of DBS were characterized, including chain length, single/double helix, and crystalline. The chain conformation and precipitation mechanism of DBS in different alcohols was investigated using molecular dynamics (MD) simulation. DBS precipitated by n-butanol contained the largest proportion of short chain (DP6-24, 83.2 %), the highest V-type crystallinity (21.1 %), and the largest single-helix content (24.7 %). A single helix conformation of DBS chain was determined in alcohols, where alcohol molecules entered the helix cavity. Intra/inter-molecular hydrogen bonds stabilized the helix, with a large number of hydrogen bonds leading to strong molecular interaction and stable helical structure. The solvent accessible surface area of DBS chain decreased by 7.88-19.32 % in alcohols, and the radial distribution function revealed that the first solvent layer of DBS chain at 0.29 nm was closely related to hydrogen bonding. This study provides a basis for the choice of precipitation solvent for preparing DBS with different chain lengths and physicochemical properties., Competing Interests: Declaration of competing interest Authors declared that there are no conflicts of interest to this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Mevalonate metabolism plays an important role in regulating tumor growth and progression; however, its role in immune evasion and immune checkpoint modulation remains unclear. Here, we found that non-small cell lung cancer (NSCLC) patients with higher plasma mevalonate response better to anti-PD-(L)1 therapy, as indicated by prolonged progression-free survival and overall survival. Plasma mevalonate levels were positively correlated with programmed death ligand-1 (PD-L1) expression in tumor tissues. In NSCLC cell lines and patient-derived cells, supplementation of mevalonate significantly up-regulated the expression of PD-L1, whereas deprivation of mevalonate reduced PD-L1 expression. Mevalonate increased CD274 mRNA level but did not affect CD274 transcription. Further, we confirmed that mevalonate improved CD274 mRNA stability. Mevalonate promoted the affinity of the AU-rich element-binding protein HuR to the 3'-UTR regions of CD274 mRNA and thereby stabilized CD274 mRNA. By in vivo study, we further confirmed that mevalonate addition enhanced the anti-tumor effect of anti-PD-L1, increased the infiltration of CD8 + T cells, and improved cytotoxic function of T cells. Collectively, our findings discovered plasma mevalonate levels positively correlated with the therapeutic efficacy of anti-PD-(L)1 antibody, and provided the evidence that mevalonate supplementation could be an immunosensitizer in NSCLC., Competing Interests: The authors declare no competing interests., (© 2023 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.)

Osimertinib resistance is an unmet clinical need for the treatment of non-small cell lung cancer (NSCLC), and the main mechanism is tertiary C797S mutation of epidermal growth factor receptor (EGFR). To date, there is no inhibitor approved for the treatment of Osimertinib-resistant NSCLC. Herein, we reported a series of Osimertinib derivatives as fourth-generation inhibitors which were rationally designed. Top candidate D51 potently inhibited the EGFR L858R/T790M/C797S mutant with an IC 50 value of 14 nM and suppressed the proliferation of H1975-TM cells with an IC 50 value of 14 nM, which show over 500-fold selectivity against wild-type forms. Moreover, D51 inhibited the EGFR del19/T790M/C797S mutant and the proliferation of the PC9-TM cell line with IC 50 values of 62 and 82 nM. D51 also exhibited favorable in vivo druggability, including PK parameters, safety properties, in vivo stability, and antitumor activity.