A novel gelatin composite film with melt extrusion for walnut oil packaging.

Gelatin have excellent film-forming and barrier properties, but its lack of biological activity limits its application in packaging. In this study, fish gelatin incorporated with apple polyphenol/cumin essential oil composite films were successfully prepared by melt extrusion. The cross-linking existed in gelatin and apple polyphenol improved the thermal stability and oxidation resistance of the film. The synergistic effect of apple polyphenols and cumin essential oil decreased the sensitivity of the film to water, especially the water solubility decreased from 41.60 % to 26.07 %. The plasticization of essential oil nearly doubled the elongation at break while maintaining the tensile strength of the film (11.45 MPa). Furthermore, the FG-CEO-AP film can inhibit peroxide value to extend the shelf life about 20 days in the walnut oil preservation. In summary, the apple polyphenol/cumin essential oil of FG film exhibits excellent comprehensive properties and high preparation efficiency for utilization as an active packaging material.

Growth defect of domain III glycoprotein B mutants of human cytomegalovirus reverted by compensatory mutations co-localizing in post-fusion conformation.

Cell entry is a crucial step for a virus to infect a host cell. Human cytomegalovirus utilizes glycoprotein B (gB) to fuse the viral and host cell membranes upon receptor binding of gH/gL-containing complexes. Fusion is mediated by major conformational changes of gB from a metastable pre-fusion to a stable post-fusion state whereby the central trimeric coiled-coils, formed by domain (Dom)III α helices, remain structurally nearly unchanged. To better understand the role of the stable core, we individually introduced three potentially helix-breaking or one disulfide bond-breaking mutation in the DIII α3 to study different aspects of the viral behavior upon long-term culturing. Two of the three helix-breaking mutations, gB_Y494P and gB_I495P, were lethal for the virus in either fibroblasts or epithelial cells. The third substitution, gB_G493P, on the other hand, displayed a delayed replication and spread, which was more pronounced in epithelial cells, hinting at an impaired fusion. Interestingly, the disulfide bond-breaker mutation, gB_C507S, performed strikingly differently in the two cell types - lethal in epithelial cells and an atypical phenotype in fibroblasts, respectively. Replication curve analyses paired with the infection efficiency, the spread morphology, and the cell-cell fusogenicity suggest a dysregulated fusion process, which could be reverted by second-site mutations mapping predominantly to gB DomV. Our findings underline the functional importance of a stable DomIII core for a well-regulated DomV rearrangement during fusion.IMPORTANCEHuman cytomegalovirus (HCMV) can establish a lifelong infection. In most people, the infection follows an asymptomatic course; however, it is a major cause of morbidity and mortality in immunocompromised patients or neonates. HCMV has a very broad cell tropism, ranging from fibroblasts to epi- and endothelial cells. The virus uses different entry pathways utilizing the core fusion machinery consisting of glycoprotein complexes gH/gL and glycoprotein B (gB). The fusion protein gB undergoes fundamental rearrangements from a metastable pre-fusion to a stable post-fusion conformation. Here, we characterized the viral behavior after the introduction of four single-point mutations in the gB central core. These led to various cell type-specific atypical phenotypes and the emergence of compensatory mutations, demonstrating an important interaction between domains III and V. We provide a new basis for the development of a structurally and functionally altered gB, which can further serve as a tool for drug and vaccine development.

The Autonomous Fusion Activity of Human Cytomegalovirus Glycoprotein B Is Regulated by Its Carboxy-Terminal Domain.

The human cytomegalovirus (HCMV) glycoprotein B (gB) is the viral fusogen required for entry into cells and for direct cell-to-cell spread of the virus. We have previously demonstrated that the exchange of the carboxy-terminal domain (CTD) of gB for the CTD of the structurally related fusion protein G of the vesicular stomatitis virus (VSV-G) resulted in an intrinsically fusion-active gB variant (gB/VSV-G). In this present study, we employed a dual split protein (DSP)-based cell fusion assay to further characterize the determinants of fusion activity in the CTD of gB. We generated a comprehensive library of gB CTD truncation mutants and identified two mutants, gB-787 and gB-807, which were fusion-competent and induced the formation of multinucleated cell syncytia in the absence of other HCMV proteins. Structural modeling coupled with site-directed mutagenesis revealed that gB fusion activity is primarily mediated by the CTD helix 2, and secondarily by the recruitment of cellular SH2/WW-domain-containing proteins. The fusion activity of gB-807 was inhibited by gB-specific monoclonal antibodies (MAbs) targeting the antigenic domains AD-1 to AD-5 within the ectodomain and not restricted to MAbs directed against AD-4 and AD-5 as observed for gB/VSV-G. This finding suggested a differential regulation of the fusion-active conformational state of both gB variants. Collectively, our findings underscore a pivotal role of the CTD in regulating the fusogenicity of HCMV gB, with important implications for understanding the conformations of gB that facilitate membrane fusion, including antigenic structures that could be targeted by antibodies to block this essential step in HCMV infection.

Serum uric acid, body mass index, and cardiovascular diseases: A multiple two-step Mendelian randomization study.

BACKGROUND AND AIMS: A number of health issues, including high serum uric acid (SUA) and cardiovascular disease (CVD), have been linked to obesity based on observational evidence, though it's currently unclear how these issues are causally related. In order to determine whether obesity mediates this association, we set out to investigate the causal relationship between SUA, obesity, and CVD. METHODS AND RESULTS: From publicly available genome-wide association studies, we acquired instrumental variables that had a strong correlation to SUA and body mass index (BMI). We employed multiple two-step Mendelian randomization (MR) analyses, using genetic and clinical data from various publicly available biological databases. The mediating role of BMI was examined through mediation analysis. SUA was genetically correlated with BMI [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. There was a positive causal effect of SUA on AF [OR = 0.892, 95% CI: 0.804-0.990, P = 0.032], CAD [OR = 0.942, 95% CI: 0.890-0.997, P = 0.037], and EHT [OR = 1.080, 95% CI: 1.024-1.139, P = 0.005]. Among them, BMI mediated the effects of SUA on AF (42.2%; 95% CI, 35.3%-51.9%), CAD (76.3%; 95% CI, 63.4%-92.0%), and EHT (10.0%; 95% CI, 0%-20.0%). CONCLUSION: Our research revealed a causal relationship between high SUA exposure and an increased risk of obesity. Additionally, a high SUA level was linked to an increased risk of various CVDs. Given that individuals with high SUA are more likely to be susceptible to AF, CAD, and EHT, attention must be given to their weight status.

The lipid-amylose complexes enhance resistant starch content in candelilla wax-based oleogels cookies.

The substitution of margarine with candelilla wax (CW)-based oleogel is currently a prominent focus of research in the bakery industry. However, the use of CW-based oleogel in cookies increased starch digestibility, potentially posing a risk to human health. Thus, the anti-enzymatic mechanism of lipid-amylose complexes was used to evaluate the influence of olive diacylglycerol stearin (ODS) on starch digestibility in CW-based oleogel cookies. The in vitro digestibility analysis demonstrated that the DCW/ODS-35 cookie exhibited a increase of 27.72 % in slowly digestible starch (SDS) and resistant starch (RS) contents, compared to cookie formulated with margarine. The in-vivo glycemic index analysis revealed that the DCW/ODS-35 cookie had a medium glycemic index of 68. XRD pattern suggested that the presence of ODS in oleogels facilitated the formation of lipid-amylose complexes. The DSC analysis revealed that the addition of ODS resulted in the gelatinization enthalpy of DCW-based cookies increased from 389.9 to 3314.9 J/g. The FTIR spectra indicated that the combination of ODS could promote a short-range ordered structure in DCW-based cookies. Overall, these findings demonstrated that the utilization of DCW-based oleogel presented a viable alternative to commercial margarine in the development of CW-based cookies with reduced starch digestibility.

Microplastics and arsenic speciation in edible bivalves from the coast of China: Distribution, bioavailability, and human health risk.

Bivalves, such as oysters and mussels, are exposed to environmental pollutants, like microplastics (MPs) and arsenic (As). This study investigated co-existence and interaction of MPs and As (total As and As species) in two bivalve species from the Chinese coastline. Smaller MPs (20-100 µm) averaged 30.98 items/g, while larger MPs (100-500 µm) averaged 2.98 items/g. Oysters contained more MPs (57.97 items/g) in comparison to mussels (11.10 items/g). In Contrast, mussels had a higher As concentrations (8.36-23.65 mg/kg) than oysters (4.97-11.02 mg/kg). The size and composition of MPs influenced As uptake and speciation in bivalves, with inorganic arsenic (iAs) and methylated arsenic (MMA and DMA) correlating with larger-sized MPs. Polyethylene (PE) may interact with the formation of arsenobetaine (AsB) in oyster. This study provides valuable insights into the interaction of MPs and As in marine ecosystems and highlights their implications for food safety.

Preparation of Sustainable Ni/SiO2 Catalysts from Rice Husk by Different Methods for CO2 Methanation.

Silicon dioxide (SiO2) from rice husk can be extracted and be used as support for Ni-based catalysts. The impregnation method (IM) is usually used for preparing Ni/SiO2 catalysts, but its catalytic activity in CO2 hydrogenation to CH4 remains unsatisfactory. In this work, we explored alternative preparation methods, using ammonia evaporation method (AEM) and hydrothermal method (HM) to prepare the catalysts. The results showed that the catalysts prepared by AEM and HM were significantly superior to that prepared by IM. Notably, the catalyst synthesized by AEM from sustainable silica exhibited the best performance, achieving 81.69% CO2 conversion and over 99% methane selectivity at low reaction temperature of 300 °C. The characterization techniques indicate that the Ni/SiO2-AEM catalyst can form nickel phyllosilicate with lamellar structure, leading to better Ni dispersion and higher specific surface area. Furthermore, the results of in-situ DRIFTS have revealed the potential catalytic mechanism over Ni/SiO2 catalysts, indicating that it involves pathways with both the CO* and HCOO* as the key intermediates.

Endovascular treatment of ruptured basilar artery trunk aneurysms: complications and long-term outcomes.

OBJECT: Treatment of ruptured basilar artery trunk (BAT) aneurysms is challenging, and is associated with high complication and mortality rates. Herein, we analyzed the complications, long-term outcomes, and outcome predictors of endovascular treatment for ruptured BAT aneurysms. METHODS: Between January 2011 and July 2023, 36 patients with 36 ruptured BAT aneurysms underwent endovascular treatment at our institution. The postprocedural complications and clinical and angiographic outcomes were subsequently reviewed, and the risk factors for postprocedural complications were evaluated. RESULTS: All 36 aneurysms in 36 patients were treated successfully. The median clinical follow-up time was 47.0 (IQR: 10.5, 84.5) months. Overall, complications occurred in 10 (27.8%) patients, including 3 (8.3%) deaths. Ischemic events occurred in seven (19.4%) patients, while three (8.3%) patients had shunt-dependent hydrocephalus, of whom one (2.8%) patient had both shunt-dependent hydrocephalus and ischemic events. The cumulative survival rates at 3 and 5 years were 94.1% and 87.8%, respectively. The cumulative 3- and 5-year complication-free survival rates were 75.0% and 70.0%, respectively. Multivariate Cox regression analysis revealed that diabetes mellitus (HR:8.76, 95%CI:2.35-32.69, p=0.001), and Glasgow coma scale score ≤ 12 before the procedure (HR:5.04, 95%CI:1.40-18.12, p=0.013) were associated with overall postprocedural complications. The complete aneurysm occlusion rate was 61.5% at a median angiography follow-up time of 6.0 (IQR: 5.0, 6.0) months. CONCLUSIONS: Endovascular treatment is a safe and feasible option for treating ruptured BAT aneurysms. The rate of favorable outcomes at the final follow-up was satisfactory. However, postprocedural complications, particularly ischemic events, should be carefully considered.

Fate of emerging antibiotics in soil-plant systems: A case on fluoroquinolones.

Fluoroquinolones (FQs), a class of broad-spectrum antibiotics widely used to treat human and animal diseases globally, have limited adsorption and are often excreted unchanged or as metabolites. These compounds enter the soil environment through feces, urban wastewater, or discharge of biological solids. The fluorine atoms in FQs impart high electronegativity, chemical stability, and resistance to microbial degradation, allowing them to potentially enter food chains. The persistence of FQs in soils raises questions about their impacts on plant growth, an aspect not yet conclusively determined. We reviewed whether, like other organic compounds, FQs are actively absorbed by plants, resulting in bioaccumulation and posing threats to human health. The influx of FQs has led to antibiotic resistance in soil microbes by exerting selective pressure and contributing to multidrug-resistant bacteria. Therefore, the environmental risks of FQs warrant further attention. This work provides a comprehensive review of the fate and behavior of FQs at the plant-environment interface, their migration and transport from the environment into plants, and associated toxicity. Current limitations in research are discussed and prospects for future investigations outlined. Thus, understanding antibiotic behavior in plants and translocation within tissues is not only crucial for ecosystem health (plant health), but also assessing potential human health risks. In addition, it can offer insights into the fate of emerging soil pollutants in plant-soil systems.

Long-Chain Saturated Fatty Acids in Olive Diacylglycerol Stearin Enhances Resistant Starch Content of Candelilla Wax Oleogel Cookies.

The purpose of this study was to substitute shortening with olive diacylglycerol oil/candelilla wax (OCW)-olive diacylglycerol stearin (ODS) oleogels and evaluate their impact on starch digestibility in cookies. The in vitro digestibility study confirmed that the OCW/ODS-based cookies exhibited a notable enhancement of 14.6% in slowly digestible starch (SDS) and an increase of 3.14% in resistant starch (RS) values when contrasted with shortening cookies. The XRD pattern indicated that the existence of ODS may improve the formation of complexes between lipids and amylose. The DSC analysis demonstrated that the incorporation of ODS led to a remarkable rise in enthalpy alteration, escalating from 0.90 to 437.70 J/g, suggesting an improved ability to resist gelatinization. The FTIR spectra suggested that the incorporation of ODS might strengthen interactions between the hydrogen bonds and form the short-range ordered structure in OCW/ODS-based cookies. Overall, these results indicated that incorporating OCW/ODS-based oleogels could serve as a feasible substitute for conventional shortening in cookies with decreased starch digestibility.

MAFLD-related hepatocellular carcinoma: Exploring the potent combination of immunotherapy and molecular targeted therapy.

Hepatocellular carcinoma (HCC) is a common cause of cancer-related mortality and morbidity globally, and with the prevalence of metabolic-related diseases, the incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) related hepatocellular carcinoma (MAFLD-HCC) continues to rise with the limited efficacy of conventional treatments, which has created a major challenge for HCC surveillance. Immune checkpoint inhibitors (ICIs) and molecularly targeted drugs offer new hope for advanced MAFLD-HCC, but the evidence for the use of both types of therapy in this type of tumour is still insufficient. Theoretically, the combination of immunotherapy, which awakens the body's anti-tumour immunity, and targeted therapies, which directly block key molecular events driving malignant progression in HCC, is expected to produce synergistic effects. In this review, we will discuss the progress of immunotherapy and molecular targeted therapy in MAFLD-HCC and look forward to the opportunities and challenges of the combination therapy.

Security in Transformer Visual Trackers: A Case Study on the Adversarial Robustness of Two Models.

Visual object tracking is an important technology in camera-based sensor networks, which has a wide range of practicability in auto-drive systems. A transformer is a deep learning model that adopts the mechanism of self-attention, and it differentially weights the significance of each part of the input data. It has been widely applied in the field of visual tracking. Unfortunately, the security of the transformer model is unclear. It causes such transformer-based applications to be exposed to security threats. In this work, the security of the transformer model was investigated with an important component of autonomous driving, i.e., visual tracking. Such deep-learning-based visual tracking is vulnerable to adversarial attacks, and thus, adversarial attacks were implemented as the security threats to conduct the investigation. First, adversarial examples were generated on top of video sequences to degrade the tracking performance, and the frame-by-frame temporal motion was taken into consideration when generating perturbations over the depicted tracking results. Then, the influence of perturbations on performance was sequentially investigated and analyzed. Finally, numerous experiments on OTB100, VOT2018, and GOT-10k data sets demonstrated that the executed adversarial examples were effective on the performance drops of the transformer-based visual tracking. White-box attacks showed the highest effectiveness, where the attack success rates exceeded 90% against transformer-based trackers.

Enhancement of resistant starch content in ethyl cellulose-based oleogels cakes with the incorporation of glycerol monostearate.

The objective of this work was to completely replace margarine with peanut diacylglycerol oil/ethyl cellulose-glycerol monostearate oleogel (DEC/GMS) oleogel, and evaluate its effect on starch digestibility of cakes. The in vitro digestibility analysis demonstrated that the DEC/GMS-6 cake exhibited a 26.36% increase in slowly digestible starch (SDS) and resistant starch (RS) contents, compared to cakes formulated with margarine. The increased SDS and RS contents might mainly be due to the hydrophobic nature of OSA-wheat flour, which could promote the formation of lipid-amylose complexes with GMS and peanut diacylglycerol oil. XRD pattern suggested that the presence of GMS in DEC-based oleogels facilitated the formation of lipid-amylose complexes. The DSC analysis revealed that the addition of GMS resulted in a significant increase in gelatinization enthalpy, rising from 249.7 to 551.9 J/g, which indicates an improved resistance to gelatinization. The FTIR spectra indicated that the combination of GMS could enhance the hydrogen bonding forces and short-range ordered structure in DEC-based cakes. The rheological analysis revealed that an increase in GMS concentration resulted in enhanced viscoelasticity of DEC-based cake compared to TEC-based cakes. The DEC-based cakes exhibited a more satisfactory texture profile and higher overall acceptability than those of TEC-based cakes. Overall, these findings demonstrated that the utilization of DEC-based oleogel presented a viable alternative to commercial margarine in the development of cakes with reduced starch digestibility.

An esophagectomy surgical Apgar score-based nomogram-a risk-based postoperative triage system: a phase II randomised trial.

Background: The esophagectomy surgical Apgar score (eSAS) has been found to be a predictor of postoperative complications in esophagectomy. In our previous study, we built a graphic nomogram based on eSAS and demonstrated that it can effectively predict the risk of major morbidity after esophagectomy. In this study, we aimed to assess the benefits of using an eSAS-based nomogram model as a postoperative risk-based triage system for patients undergoing esophagectomy. Methods: We enrolled 119 patients diagnosed with esophageal carcinoma and randomly assigned them to a nomogram group (NG) or control group (CG) from January 2019 to December 2020. Patients in the NG were assigned to a low-risk group and high-risk group based on the nomogram. Patients in the high-risk group were admitted to the intensive care unit (ICU) after esophagectomy. Risk estimation in the CG patients was based on the surgeon's clinical experience. Thirty-day major complications, postoperative hospital stay, hospital costs, and quality of life (QOL) during the follow-up were compared between the two groups. Results: Baseline clinicopathological characteristics were comparable between the NG (n=58) and CG (n=61). All patients underwent esophagectomy. Postoperative complications were significantly higher in the CG (30, 49.2%) than in the NG (14, 24.1%) (P=0.008), with pneumonia being the most common (CG: 23, 37.7%; NG: 12, 20.7%; P=0.042). There was no significant difference in anastomotic leakage (NG: 1, 1.7%; CG: 6, 9.8%; P=0.12). Postoperative median hospital stay was shorter in the NG (14 days) than in the CG (16 days) (P=0.041). Hospital costs (NG: ¥60,045.1; CG: ¥63,961.5; P=0.21) and postoperative QOL did not differ significantly between groups. Conclusions: An eSAS-based nomogram as a triage system can reduce the overall occurrence of postoperative complications and shorten postoperative hospital stay without increasing hospital costs. Trial Registration: Chinese Clinical Trial Registry ChiCTR1900021636.

Highly pathogenic PRRSV upregulates IL-13 production through nonstructural protein 9-mediated inhibition of N6-methyladenosine demethylase FTO.

Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances m6A-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an m6A demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production via attenuation of FTO expression. These insights delineate PRRSV nsp9's role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.

LiverRisk score: An accurate, cost-effective tool to predict fibrosis, liver-related, and diabetes-related mortality in the general population.

BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

The causal relationship between severe mental illness and risk of lung carcinoma.

Observational studies have suggested a link between severe mental illness (SMI) and risk of lung carcinoma (LC); however, causality has not been established. In this study, we conducted a two-sample, two-step Mendelian randomization (MR) investigation to uncover the etiological influence of SMI on LC risk and quantify the mediating effects of known modifiable risk factors. We obtained summary-level datasets for schizophrenia, major depressive disorder (MDD), and bipolar disorder (BD) from the Psychiatric Genomics Consortium (PGC). Data on single nucleotide polymorphisms (SNPs) associated with lung carcinoma (LC) were sourced from a recent large meta-analysis by McKay et al. We employed two-sample MR and two-step MR utilizing the inverse variance weighted method for causal estimation. Sensitivity tests were conducted to validate causal relationships. In two-sample MR, we identified schizophrenia as a risk factor for LC (OR = 1.06, 95% CI 1.02-1.11, P = 3.48E-03), while MDD (OR = 1.18, 95% CI 0.98-1.42, P = .07) and BD (OR = 1.07, 95% CI 0.99-1.15, P = .09) showed no significant association with LC. In the two-step MR, smoking accounted for 24.66% of the schizophrenia-LC risk association, and alcohol consumption explained 7.59% of the effect. Schizophrenia is a risk factor for lung carcinoma, and smoking and alcohol consumption are the mediating factors in this causal relationship. LC screening should be emphasized in individuals with schizophrenia, particularly in those who smoke and consume alcohol regularly.

VHL suppresses autophagy and tumor growth through PHD1-dependent Beclin1 hydroxylation.

The Von Hippel-Lindau (VHL) protein, which is frequently mutated in clear-cell renal cell carcinoma (ccRCC), is a master regulator of hypoxia-inducible factor (HIF) that is involved in oxidative stresses. However, whether VHL possesses HIF-independent tumor-suppressing activity remains largely unclear. Here, we demonstrate that VHL suppresses nutrient stress-induced autophagy, and its deficiency in sporadic ccRCC specimens is linked to substantially elevated levels of autophagy and correlates with poorer patient prognosis. Mechanistically, VHL directly binds to the autophagy regulator Beclin1, after its PHD1-mediated hydroxylation on Pro54. This binding inhibits the association of Beclin1-VPS34 complexes with ATG14L, thereby inhibiting autophagy initiation in response to nutrient deficiency. Expression of non-hydroxylatable Beclin1 P54A abrogates VHL-mediated autophagy inhibition and significantly reduces the tumor-suppressing effect of VHL. In addition, Beclin1 P54-OH levels are inversely correlated with autophagy levels in wild-type VHL-expressing human ccRCC specimens, and with poor patient prognosis. Furthermore, combined treatment of VHL-deficient mouse tumors with autophagy inhibitors and HIF2α inhibitors suppresses tumor growth. These findings reveal an unexpected mechanism by which VHL suppresses tumor growth, and suggest a potential treatment for ccRCC through combined inhibition of both autophagy and HIF2α.

Exploring Diacylglycerol Oil-Based Oleogels as Effective Stabilizers in Peanut Butter: Performance, Structural Insights, and Sensory Evaluation.

In the pursuit of reducing oil separation in peanut butter, oleogels synthesized from diacylglycerol (DAG)-rich peanut oils, using glycerol monostearate (GMS) as the gelator, were examined as alternative stabilizers. In comparison to triacylglycerol (TAG)-rich peanut oils, the DAG oil-based oleogels exhibited better oil-binding capacities across increasing GMS concentrations. Intriguingly, thermal and rheological assessments pointed to a weaker network structure in DAG oil oleogels, as evidenced by their lower crystallization temperatures and reduced viscoelastic parameters (G' and G''). Insight from infrared spectroscopy revealed that this could stem from heightened intermolecular hydrogen bonding between the DAG oil and the gelator. When applied to peanut butter, DAG oil oleogels demonstrated efficacy in minimizing oil separation. Extended storage trials affirmed the long-term stability of peanut butter formulations incorporating these oleogels. Furthermore, sensory evaluations by panelists underscored favorable impressions, suggesting potential consumer acceptance. Overall, this study illuminates the promising role of DAG oleogels as effective, alternative stabilizers in peanut butter formulations.

Catalytic CO Oxidation on the Cu+-Ov-Ce3+ Interface Constructed by an Electrospinning Method for Enhanced CO Adsorption at Low Temperature.

It is crucial to eliminate CO emissions using non-noble catalysts. Cu-based catalysts have been widely applied in CO oxidation, but their activity and stability at low temperatures are still challenging. This study reports the preparation and application of an efficient copper-doped ceria electrospun fiber catalyst prepared by a facile electrospinning method. The obtained 10Cu-Ce fiber catalyst achieved complete CO oxidation at a temperature as low as 90 °C. However, a reference 10Cu/Ce catalyst prepared by the impregnation method needed 110 °C to achieve complete CO oxidation under identical reaction conditions. Asymmetric oxygen vacancies (ASOV) at the interface between copper and cerium were constructed, to effectively absorb gas molecules involved in the reaction, leading to the enhanced oxidation of CO. The exceptional ability of the 10Cu-Ce catalyst to adsorb CO is attributed to its unique structure and surface interaction phase Cu+-Ov-Ce3+, as demonstrated by a series of characterizations and DFT calculations. This novel approach of using electrospinning offers a promising technique for developing low-temperature and non-noble metal-based catalysts.