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Current cancer immunotherapy predominately focuses on eliciting type 1 immune responses fighting cancer; however, long-term complete remission remains uncommon1,2. A pivotal question arises as to whether type 2 immunity can be orchestrated alongside type 1-centric immunotherapy to achieve enduring response against cancer3,4. Here we show that an interleukin-4 fusion protein (Fc–IL-4), a typical type 2 cytokine, directly acts on CD8+ T cells and enriches functional terminally exhausted CD8+ T (CD8+ TTE) cells in the tumour. Consequently, Fc–IL-4 enhances antitumour efficacy of type 1 immunity-centric adoptive T cell transfer or immune checkpoint blockade therapies and induces durable remission across several syngeneic and xenograft tumour models. Mechanistically, we discovered that Fc–IL-4 signals through both signal transducer and activator of transcription 6 (STAT6) and mammalian target of rapamycin (mTOR) pathways, augmenting the glycolytic metabolism and the nicotinamide adenine dinucleotide (NAD) concentration of CD8+ TTE cells in a lactate dehydrogenase A-dependent manner. The metabolic modulation mediated by Fc–IL-4 is indispensable for reinvigorating intratumoural CD8+ TTE cells. These findings underscore Fc–IL-4 as a potent type 2 cytokine-based immunotherapy that synergizes effectively with type 1 immunity to elicit long-lasting responses against cancer. Our study not only sheds light on the synergy between these two types of immune responses, but also unveils an innovative strategy for advancing next-generation cancer immunotherapy by integrating type 2 immune factors.Fc–IL-4, a typical type 2 cytokine, reinvigorates exhausted CD8+ T cells in tumours, underscoring this fusion protein as a potent immunotherapy that synergizes effectively with type 1 immunity against cancer. [ABSTRACT FROM AUTHOR]

Aluminum electrolysis is a typical industry with high energy consumption, and the energy saving of aluminum electrolysis cells is conducive to the sustainable development of the ecological environment. The current density distribution on the steel claws of conventional aluminum electrolysis cells is uneven, resulting in a large amount of power loss. Therefore, a new type of current-equalized steel claw (CESC) is designed in this paper. The ANSYS simulation study shows that the CESC can achieve a more uniform current density distribution and reduce the voltage drop by about 36 mV compared with the traditional steel claw (TSC). In addition, the use of CESC optimizes the temperature distribution of the steel claws and reduces the risk of cracking and deformation. The results of the industrial application tests are highly consistent with the simulation results, confirming the accuracy of the simulation results. The economic benefit analysis shows that using CESC saves 114.1 kWh of electricity per ton of aluminum produced. If this technology can be promoted throughout China, it is expected to save up to 4.75 billion kWh of electricity annually. The development of CESC is promising and of great significance for improving the overall technical level of the aluminum electrolysis industry. [ABSTRACT FROM AUTHOR]

Biogas steam reforming is one important way for hydrogen production, and the development of efficient and stable catalysts is the key for its large-scale application. Based on this, a series of Ni-based catalysts based on ZrO2-Al2O3 composite support were prepared by continuous impregnation method, and the catalytic performances for hydrogen production by biogas steam reforming were tested. The texture properties and crystal phase compositions of catalysts were analyzed by characterization methods such as N2 adsorption/desorption and XRD. The influence mechanisms of the physical structure and chemical properties of catalysts on their catalytic performances of biogas steam reforming for hydrogen production were studied. The effects of calcination temperatures and metal promotor Fe on the catalytic performances of catalysts were also discussed. The results show that Ni/ZrO2-Al2O3 exhibits outstanding catalytic performance for hydrogen production at 700 and gas volume space velocity of 12000 h-1, with CH4 conversion rate of 89.94% and H2 yield of 81.49%. Compared with Al2O3 support, ZrO2-Al2O3 composite support increases the specific surface area of catalysts, promotes the high dispersion of small particle size Ni on the surface of the support, and thus improves the catalytic performances of catalysts in biogas steam reforming for hydrogen production. The calcination temperature can regulate the specific surface area and pore volume of catalysts. The specific surface area and pore volume of Ni/ZrO2-Al2O3 calcined at 550 are larger than those of Ni/ZrO2-Al2O3 calcined at 700 . The coupled modification of Fe and ZrO2 improves the reduction performance of catalysts, and more highly active Ni0 is formed, which is conducive to the occurrence of methane dry reforming for hydrogen production, and the nH2 /nCO in the gas product is also modified. [ABSTRACT FROM AUTHOR]

Expansins are cell wall (CW) proteins that mediate the CW loosening and regulate salt tolerance in a positive or negative way. However, the role of Populus trichocarpa expansin A6 (PtEXPA6) in salt tolerance and the relevance to cell wall loosening is still unclear in poplars. PtEXPA6 gene was transferred into the hybrid species, Populus alba × P. tremula var. glandulosa (84K) and Populus tremula × P. alba INRA '717-1B4' (717-1B4). Under salt stress, the stem growth, gas exchange, chlorophyll fluorescence, activity and transcription of antioxidant enzymes, Na+ content, and Na+ flux of root xylem and petiole vascular bundle were investigated in wild-type and transgenic poplars. The correlation analysis and principal component analysis (PCA) were used to analyze the correlations among the characteristics and principal components. Our results show that the transcription of PtEXPA6 was downregulated upon a prolonged duration of salt stress (48 h) after a transient increase induced by NaCl (100 mM). The PtEXPA6-transgenic poplars of 84K and 717-1B4 showed a greater reduction (42–65%) in stem height and diameter growth after 15 days of NaCl treatment compared with wild-type (WT) poplars (11–41%). The Na+ accumulation in roots, stems, and leaves was 14–83% higher in the transgenic lines than in the WT. The Na+ buildup in the transgenic poplars affects photosynthesis; the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT); and the transcription of PODa2, SOD [Cu-Zn], and CAT1. Transient flux kinetics showed that the Na+ efflux of root xylem and leaf petiole vascular bundle were 1.9–3.5-fold greater in the PtEXPA6-transgenic poplars than in the WT poplars. PtEXPA6 overexpression increased root contractility and extensibility by 33% and 32%, indicating that PtEXPA6 increased the CW loosening in the transgenic poplars of 84K and 717-1B4. Noteworthily, the PtEXPA6-promoted CW loosening was shown to facilitate Na+ efflux of root xylem and petiole vascular bundle in the transgenic poplars. We conclude that the overexpression of PtEXPA6 leads to CW loosening that facilitates the radial translocation of Na+ into the root xylem and the subsequent Na+ translocation from roots to leaves, resulting in an excessive Na+ accumulation and consequently, reducing salt tolerance in transgenic poplars. Therefore, the downregulation of PtEXPA6 in NaCl-treated Populus trichocarpa favors the maintenance of ionic and reactive oxygen species (ROS) homeostasis under long-term salt stress. [ABSTRACT FROM AUTHOR]

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy. Despite previous suggestion of pathogenicity, variant classification in public databases is still conflicting, needing additional evidence. Methods: Maximum likelihood penetrance of breast/ovarian and other cancer types was estimated using full pedigree data from 53 informative Italian families. The effect of the variant on BRCA1‐ABRAXAS1 interaction was assessed using a GFP‐fragment reassembly‐based PPI assay. Results were combined with additional data from multiple sources to classify the variant according to ACMG/AMP classification rules specified for BRCA1/2. Results: Variant‐carriers displayed increased risk for ovarian cancer (HR = 33.0, 95% CI = 7.0–155.0; cumulative risk at age 70 = 27.6%, 95% CI = 12.6–40.0%) but not for breast cancer (HR = 0.7, 95% CI = 0.2–2.2). An increased risk of uterine cancer (HR = 8.0, 95% CI = 1.03–61.6) emerged, warranting further evaluation. Likelihood‐ratio in favor of pathogenicity was 98898642.82 under assumption of standard BRCA1 breast and ovarian penetrance, and 104240832.84 after excluding breast cancer diagnoses (based on penetrance results). Functional analysis demonstrated that the variant abrogates the BRCA1‐ABRAXAS1 binding, supporting the PS3 code assignment within the ACMG/AMP rule‐based model. Collectively, these findings allowed to classify the variant as pathogenic. Conclusion: Pathogenicity of BRCA1:c.5017_5019del(p.His1673del) has been confirmed; however, breast cancer risk in Italian families is not increased, unlike in families from other countries and in carriers of most BRCA1 pathogenic variants. The knowledge of atypical risk profiles for this and other variants will pave the way for personalized management based on specific genotype. [ABSTRACT FROM AUTHOR]

The toxic metal cadmium (Cd) poses a serious threat to plant growth and human health. Populus euphratica calcium-dependent protein kinase 21 (CPK21) has previously been shown to attenuate Cd toxicity by reducing Cd accumulation, enhancing antioxidant defense and improving water balance in transgenic Arabidopsis. Here, we confirmed a protein–protein interaction between PeCPK21 and Arabidopsis nuclear transcription factor YC3 (AtNF-YC3) by yeast two-hybrid and bimolecular fluorescence complementation assays. AtNF-YC3 was induced by Cd and strongly expressed in PeCPK21-overexpressed plants. Overexpression of AtNF-YC3 in Arabidopsis reduced the Cd inhibition of root length, fresh weight and membrane stability under Cd stress conditions (100 µM, 7 d), suggesting that AtNF-YC3 appears to contribute to the improvement of Cd stress tolerance. AtNF-YC3 improved Cd tolerance by limiting Cd uptake and accumulation, activating antioxidant enzymes and reducing hydrogen peroxide (H2O2) production under Cd stress. We conclude that PeCPK21 interacts with AtNF-YC3 to limit Cd accumulation and enhance the reactive oxygen species (ROS) scavenging system and thereby positively regulate plant adaptation to Cd environments. This study highlights the interaction between PeCPK21 and AtNF-YC3 under Cd stress conditions, which can be utilized to improve Cd tolerance in higher plants. [ABSTRACT FROM AUTHOR]

The airborne transient electromagnetic method is a crucial technique for near-surface exploration in rugged terrains. In this study, we introduce a multi-input, single-output double-hidden wavelet neural network design for airborne transient electromagnetic pseudo-resistivity imaging. We construct uniform half-space, stratified stratum, and three-dimensional geoelectric models. By evaluating various performance indicators of neural networks that employ different wavelet basis functions as activation functions, we identify the most suitable wavelet basis functions. The quasi-resistivity is computed using both the wavelet neural network and the backpropagation neural network and then juxtaposed with traditional apparent resistivity. Our findings indicate that the wavelet neural network's quasi-resistivity aligns more closely with the resistivity of the real model. It is also more responsive to low resistivity anomalies than the conventional apparent resistivity translation algorithm. The wavelet approach moderates the undershoot or overshoot occurrences during abrupt stratum changes, offering a more accurate representation of subterranean electrical properties. When compared to the backpropagation neural network, the wavelet neural network provides a superior fit for the model, rendering a smoother quasi-resistivity depth curve. Therefore, it stands out as an improved method for pseudo-resistivity imaging. By processing survey data via the trained wavelet neural network, we find that the all-time apparent resistivity and quasi-resistivity align well with real-world situations. The wavelet neural network prominently showcases the low-resistance calculation results, offering a broader resistivity range. This clarity enhances anomaly detection, confirming the wavelet neural network's applicability and practicality for airborne transient electromagnetic imaging. [ABSTRACT FROM AUTHOR]

Objective: We aimed to create a question bank about clinical factors for predicting the diagnoses of psoriatic arthritis in patients with psoriasis of various ancestries and skin tones, which can be completed entirely by patients. Methods: Utah Psoriasis Initiative participants without a psoriatic arthritis diagnosis at enrollment were observed for diagnosis during the study period. We inferred ancestry from exome sequencing data and performed Cox proportional hazards regression to identify clinical predictors of psoriatic arthritis in different ancestry groups. Based on results and literature review, we developed a question bank for assessing psoriatic arthritis risk among patients with psoriasis in various ancestries. Results: Patient‐reported untreated psoriasis induration and history of fingernail psoriasis were associated with psoriatic arthritis in participants of European and non‐European ancestry. We developed the Psoriatic Arthritis Prediction and Identification Question Bank for Diverse Ancestries (PAPRIKA) version 1.0, which included questions regarding psoriasis characteristics, arthritis symptoms, comorbidities, family history, and demographics. PAPRIKA is accessible at http://bjfenglab.org/. Conclusion: The clinical features (untreated psoriasis induration and history of fingernail psoriasis) that can predict psoriatic arthritis in European individuals also work for non‐European individuals. PAPRIKA can be used to gather psoriatic arthritis predictive data from patients with psoriasis without provider assistance and is relevant for patients across ancestries. [ABSTRACT FROM AUTHOR]