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Peanut protein isolate (PPI) solutions were modified by dielectric barrier discharge (DBD) cold plasma (CP) treatment. Effects of CP treatment on the solubility, emulsion stability, and water holding capacity (WHC) of peanut protein were studied. The results showed a significant improvement in solubility, emulsion stability, and WHC following CP treatment. CP treatment resulted in the unfolding of PPI structure, thereby increasing the β-sheet and random coil content and decreasing the α-helix and β-turn content, as analyzed by Fourier-transform infrared spectroscopy. Low-field nuclear magnetic resonance showed an increase in the peak area of T 21 relaxation time by CP treatment and the change in T 21 peak area was in agreement with the result of WHC. This study demonstrated that CP may be successfully applied as a method to modify the functionality of PPI.

Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression. EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540. Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1–31·8; 149 [52%] of 284 died) versus 13·3 months (10·5–16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46–0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2–8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3–6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42–0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1–9·3) and overall survival of 15·1 months (11·3–18·7). The most common grade 3–4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer. Regeneron Pharmaceuticals and Sanofi.

Understanding the functions of proteins is of great importance for deciphering the mechanisms of life activities. To date, there have been over 200 million known proteins, but only 0.2% of them have well-annotated functional terms. By measuring the contacts among residues, proteins can be described as graphs so that the graph leaning approaches can be applied to learn protein representations. However, existing graph-based methods put efforts in enriching the residue node information and did not fully exploit the edge information, which leads to suboptimal representations considering the strong association of residue contacts to protein structures and to the functions. In this article, we propose SuperEdgeGO, which introduces the supervision of edges in protein graphs to learn a better graph representation for protein function prediction. Different from common graph convolution methods that uses edge information in a plain or unsupervised way, we introduce a supervised attention to encode the residue contacts explicitly into the protein representation. Comprehensive experiments demonstrate that SuperEdgeGO achieves state-of-the-art performance on all three categories of protein functions. Additional ablation analysis further proves the effectiveness of the devised edge supervision strategy. The implementation of edge supervision in SuperEdgeGO resulted in enhanced graph representations for protein function prediction, as demonstrated by its superior performance across all the evaluated categories. This superior performance was confirmed through ablation analysis, which validated the effectiveness of the edge supervision strategy. This strategy has a broad application prospect in the study of protein function and related fields.

The development of highly efficacious materials for the removal of toxic heavy metal-based oxo-anions is of utmost importance. Herein, an ionic porous organic polymer (designated as HB-IPOP) was synthesized through a quaternization reaction between hexa(imidazole-1-yl)benzene and 5,5′-Bis(bromomethyl)-2,2′-bipyridine. HB-IPOP exhibited high saturation uptake capacities, specifically 292 mg·g−1 for Cr2O72− and 531 mg·g−1 for ReO4−, and demonstrated exceptional selectivity for both Cr2O72− and ReO4−. Additionally, HB-IPOP demonstrates high recyclability, allowing its reuse over at least five cycles. DFT calculations confirmed that the superior interaction sites and binding energies of HB-IPOP with Cr2O72− and ReO4− outperform the affinities of other competing anions. This theoretical validation aligns with the experimentally observed high capacity and selectivity of HB-IPOP for these oxo-anions. Hence, HB-IPOP emerges as a promising candidate to replace current adsorbent materials in the effective removal of Cr2O72− and TcO4− anions from water.

Aims To compare the prevalence, incidence, and factors of diabetic retinopathy (DR) and macular edema (DME) in patients with early‐onset (EOD) and late‐onset diabetes (LOD). Methods Participants with type 2 diabetes mellitus (T2DM) were recruited from a community‐based study conducted in southern urban China. Participants were followed up for 2 years. The prevalence and incidence of DR and DME were compared between EOD (≤40 years) and LOD (>40 years) groups, and potential factors were evaluated using multivariate logistic regression. Results Among 2,703 participants, 173 (6.4%) with EOD had a higher prevalence of DR than 2,530 (93.6%) with LOD (27.8% vs 15.5%, P < 0.001). Participants with EOD had a higher incidence of DR, although this difference was not statistically significant (EOD: 8.1% vs LOD: 3.6%, P = 0.12). Insulin use and higher HbA1c levels were significantly associated with DR in both EOD and LOD groups (both P < 0.05). Additionally, longer diabetes duration, higher systolic blood pressure, and the presence of albuminuria independently associated with the presence of any DR in LOD patients (all P < 0.05). For DME, HbA1c level was a significant association in EOD, while in LOD, age, BMI, insulin use, and albuminuria were significant factors (all P < 0.05). Conclusions A higher prevalence of DR was observed among patients with early‐onset T2DM in urban southern China. Timely diagnosis of DR and regular eye care services are needed for early‐onset T2DM. The prevalence and incidence of diabetic retinopathy in early‐onset type 2 diabetes are higher than those in late‐onset diabetes in southern urban China. Higher HbA1c showed a strong association with the prevalence of DR and DME, regardless of EOD and LOD. Early‐onset T2DM needs to pay more attention to long‐term glycemic control, especially in insulin management compared to late‐onset T2DM.

Ovarian cancer is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Deubiquitinating enzymes (DUBs) have emerged as critical regulators of protein ubiquitination and proteasomal degradation, influencing various cellular processes relevant to cancer pathogenesis. In this study, the research progress between ovarian cancer and DUBs was mapped and visualized using bibliometrics, and the expression patterns and biological roles of DUBs in ovarian cancer were summarized. Studies related to DUBs in ovarian cancer were extracted from the Web of Science Core Collection (WoSCC) database. VOSviewer 1.6.20, CiteSpace 6.3.R1, and R4.3.3 were used for bibliometric analysis and visualization. For analysis 243 articles were included in this study. The number of publications on DUBs in ovarian cancer has gradually increased each year. China, the United States, and the United Kingdom are at the center of this field of research. The Johns Hopkins University, Genentech, and Roche Holding are the main research institutions. David Komander, Zhihua Liu, and Richard Roden are the top authors in this field. The top five journals with the largest publication volumes in this field are , , , , and . Keyword burst analysis identified five research areas: \"deubiquitinating enzyme,\" \"expression,\" \"activation,\" \"degradation,\" and \"ubiquitin.\" In addition, we summarized the expression profiles and biological roles of DUBs in ovarian cancer, highlighting their roles in tumor initiation, growth, chemoresistance, and metastasis. An overview of the research progress is provided in this study on DUBs in ovarian cancer over the last three decades. It offers insight into the most cited papers and authors, core journals, and identified new trends.

Remorin genes encode plant-specific and plasma-membrane-associated proteins that play important roles in several plant physiological processes and adaptations to environmental adaptations. However, little is known regarding the remorin gene family in foxtail millet (Setaria italica), a traditional drought-resistant crop that grows in China. In this study, 21 remorin genes in the foxtail millet genome were identified, renamed according to their chromosomal distribution, and classified into four main groups based on their phylogenetic relationships and structural features. Additionally, we found that SiREM gene family expansion was primarily because of whole- genome duplication and segmental duplication events. Evolutionary changes in the remorin family in Poaceae crops were clarified via synteny analyses. Gene expression analyses through RT-PCR and qRT-PCR indicated that SiREM genes influenced millet growth and development, particularly SiREM1, 4, 11, and 12. Concurrently, SiREM genes expression showed inconsistent response to phytohormone treatments and abiotic stresses, suggesting that they are regulated by different signaling pathways. This systematic reanalysis remorin gene family in the foxtail millet provides fundamental information about the biological functions associated with growth, development, and stress tolerance and evolutionary characteristics, thus helping in elucidating the molecular mechanism and improving the agricultural traits of this crop in the future.

In recent years, with the development of interfacial polymerization methodologies, the successful preparation of covalent organic framework (COF) monolayers featuring ultrahigh pore density and molecule-scale thickness has become a reality. This advancement has enabled ion transport with ultrahigh flux across extremely short paths. Owing to these processes, the COF monolayers have shown wide potential applications ranging from energy conversion and artificial mechanosensing to ion sieving. To date, nanofluidic systems based on COF monolayers are homogeneous, leading to nearly symmetric ion transport properties. Studies on the ionic transport behavior within ultrathin COF heterojunctions are limited and remain challenging. Herein, using a two-step sequential self-assembly and subsequent interfacial polymerization strategy, bi-layered heterogeneous tetraphenylporphyrin-based COF membranes composed of negatively charged and positively charged monolayers were prepared. Using an electric field as a driving force, rectified ion transport was observed for the first time. Notably, this ionic current rectification property could be modulated by the salt concentration and the structural composition of the membrane, and it was universal for various COF heterojunctions with different chemical ingredients. These findings are beneficial for promoting the development of innovative nanofluidic materials and devices. In this study, bi-layered heterogeneous tetraphenylporphyrin-based COF membranes, consisting of negatively and positively charged monolayers, are fabricated using a two-step sequential self-assembly process followed by interfacial polymerization. By applying an electric field as the driving force, rectified ion transport is observed for the first time. Notably, this ionic current rectification can be modulated by adjusting the salt concentration and the structural composition of the membranes. Additionally, this phenomenon is found to be universal across various COF heterojunctions with different chemical constituents. These findings have important implications for the development of innovative nanofluidic materials and devices.

Leaf senescence is strictly regulated by multiple internal factors and external environmental signals, with the epigenetic modification being an important element among them. However, the epigenetic mechanism of leaf senescence is largely unknown in horticultural crops, especially the leaf vegetable pak choi, which easily senesces, and becomes yellow post-harvest. In this study, we found that the expression of DNA methyltransferases (BcMET1, BcSUVH4, BcDRM2, BcRDR2, and BcCMT3) of pak choi decreased during storage. The preliminary results showed that its senescence process was accompanied by DNA methylation changes. Moreover, treatment with 500 μM 5-Azacytidine (5-Aza) (DNA methylation inhibitor) can promote the senescence of pak choi leaves by (1) increasing the degradation of chlorophyll (Chl) and its derivatives, (2) increasing the activities of Mg-dechelatase (MDCase), pheophytinase (PPH) and pheophorbide a oxygenase (PAO), and (3) inducing the expression of senescence-related genes (BcSAG12, BcNYC1, BcSGR1, BcSGR2, BcPPH1, BcPPH2, BcPAO, and BcRCCR), thereby accelerating the senescence of the pak choi leaves. Further studies showed that DNA demethylation occurred in the promoter regions of BcSGR2 and BcSAG12 during storage, with the bisulfite sequencing detection showing that their degrees of methylation decreased. Therefore, our findings help us understand how epigenetic modifications affect the storage tolerance of leafy vegetables, which is highly significant for cultivating anti-senescent vegetable varieties.

Submerged entry nozzle (SEN) clogging will affect the production efficiency and product quality in the continuous casting process. In this work, the transient SEN clogging model is developed by coupling the porous media model defined by the user-defined function (UDF) and the discrete phase model (DPM). The effects of the transient SEN clogging process on the flow field, the distribution of argon gas bubbles and the fluctuation of the interface between steel and slag in the concave bottom SEN in the continuous casting slab mold with a cross-section of 1500 mm × 230 mm are studied by coupling transient SEN clogging model, DPM and volume of fluid (VOF) model. The results show that the actual morphology and thicknesses of SEN clogging are in good agreement with the numerical simulation results. The measurement result of the surface velocity is consistent with the numerical simulation result. With increasing the simulation time, the degree of SEN clogging increases. The flow velocities of molten steel flowing from the outlet of the side hole increase, because the flow space is occupied with the clogging inclusions, which leads to the increased number of argon gas bubbles near the narrow wall. The steel–slag interface fluctuation near the narrow walls also increases, resulting in the increased risk of slag entrapment.