Search

Heterogeneous organ‐specific responses to immunotherapy exist in lung cancer. Dissecting tumor microenvironment (TME) can provide new insights into the mechanisms of divergent responses, the process of which remains poor, partly due to the challenges associated with single‐cell profiling using formalin‐fixed paraffin‐embedded (FFPE) materials. In this study, single‐cell nuclei RNA sequencing and imaging mass cytometry (IMC) are used to dissect organ‐specific cellular and spatial TME based on FFPE samples from paired primary lung adenocarcinoma (LUAD) and metastases. Single‐cell analyses of 84 294 cells from sequencing and 250 600 cells from IMC reveal divergent organ‐specific immune niches. For sites of LUAD responding well to immunotherapy, including primary LUAD and adrenal gland metastases, a significant enrichment of B, plasma, and T cells is detected. Spatially resolved maps reveal cellular neighborhoods recapitulating functional units of the tumor ecosystem and the spatial proximity of B and CD4+ T cells at immunogenic sites. Various organ‐specific densities of tertiary lymphoid structures are observed. Immunosuppressive sites, including brain and liver metastases, are deposited with collagen I, and T cells at these sites highly express TIM‐3. This study originally deciphers the single‐cell landscape of the organ‐specific TME at both cellular and spatial levels for LUAD, indicating the necessity for organ‐specific treatment approaches. [ABSTRACT FROM AUTHOR]

The heterogeneity of macrophages influences the response to immune checkpoint inhibitor (ICI) therapy. However, few studies explore the impact of APOE+ macrophages on ICI therapy using single‐cell RNA sequencing (scRNA‐seq) and machine learning methods. The scRNA‐seq and bulk RNA‐seq data are Integrated to construct an M.Sig model for predicting ICI response based on the distinct molecular signatures of macrophage and machine learning algorithms. Comprehensive single‐cell analysis as well as in vivo and in vitro experiments are applied to explore the potential mechanisms of the APOE+ macrophage in affecting ICI response. The M.Sig model shows clear advantages in predicting the efficacy and prognosis of ICI therapy in pan‐cancer patients. The proportion of APOE+ macrophages is higher in ICI non‐responders of triple‐negative breast cancer compared with responders, and the interaction and longer distance between APOE+ macrophages and CD8+ exhausted T (Tex) cells affecting ICI response is confirmed by multiplex immunohistochemistry. In a 4T1 tumor‐bearing mice model, the APOE inhibitor combined with ICI treatment shows the best efficacy. The M.Sig model using real‐world immunotherapy data accurately predicts the ICI response of pan‐cancer, which may be associated with the interaction between APOE+ macrophages and CD8+ Tex cells. [ABSTRACT FROM AUTHOR]

In this study, a series of H‐bonded arylamide foldamers bearing benzoselenadiazole ends with solvent‐responsive properties have been synthesized. In dichloromethane or dimethyl sulfoxide solvents, the molecules exhibit meniscus or linear structures, respectively, which can be attributed to the unique intramolecular hydrogen bonding behavior evidenced by 1D 1H NMR and 2D NOESY spectra. UV‐vis spectroscopy experiments show that the absorption wavelength of H‐bonded arylamide foldamers are significantly red‐shifted due to the presence of benzoselenadiazole group. In addition, the crystal structures reveal that effective intermolecular dual Se ⋅ ⋅ ⋅ N interactions between benzoselenadiazole groups induce further assembly of the monomers. Remarkably, supramolecular linear and double helices structures are constructed under the synergistic induction of intramolecular hydrogen bonding and intermolecular chalcogen bonding. Additionally, 2D DOSY diffusion spectra and theoretical modelling based on density functional theory (DFT) are performed to explore the persistence of intermolecular Se ⋅ ⋅ ⋅ N interactions beyond the crystalline state. [ABSTRACT FROM AUTHOR]

Contact resistance has become one of the main bottlenecks that hinder further improvement of mobility and integration density of organic field‐effect transistors (OFETs). Much progress has been made in reducing contact resistance by modifying the electrode/semiconductor interface and decreasing the crystal thickness, however, the development of new organic semiconductor materials with low contact resistance still faces many challenges. Here, 2,6‐bis‐phenylethynyl‐anthracene (BPEA) is found, which is a material that combines high mobility with low contact resistance. Single‐crystal BEPA OFETs with a thickness of ≈20 nm demonstrated high mobility of 4.52 cm2 V−1 s−1, contact resistance as low as 335 Ω cm, and band‐like charge transport behavior. The calculated compatibility of the EHOMO of BPEA with the work function of the Au electrode, and the decreased |EHOMO‐ΦAu| with the increase of external electric field intensity from source to gate both contributed to the efficient charge injection and small contact resistance. More intriguingly, p‐type BPEA as a buffer layer can effectively reduce the contact resistance, improve the mobility, and meanwhile inhibit the double‐slope electrical behavior of p‐channel 2,6‐diphenyl anthracene (DPA) single‐crystal OFETs. [ABSTRACT FROM AUTHOR]

The recycling of subcontinental lithospheric mantle back into the asthenosphere during continental breakup is potentially a major but underappreciated process in plate tectonics. Here, we report major and trace elements for detrital peridotite minerals in carbonate breccias dredged from the Marion Rise, Southwest Indian Ridge. With an emphasis on the trace elements of the relatively abundant orthopyroxene detrital grains, the results show that a portion of pyroxene grains was likely derived from a mantle source that experienced hydrous melting and slab‐derived melt metasomatism above a subduction zone. This finding provides a novel view into the mantle geochemistry at midocean ridges, as well as evidence that Marion Rise is at least partially supported by chemically buoyant recycled refractory mantle wedge material. [ABSTRACT FROM AUTHOR]

The underactuated autonomous underwater vehicle (AUV) depth‐tracking approach is presented in this research along with comparative field experiments. First, a model‐free ADRC‐SMC pitch autopilot method is proposed to eliminate dynamics‐related disturbances. The active disturbance rejection control (ADRC) framework is adopted to compensate the complicated and unknown pitch dynamics into an approximate integral series type. Sliding mode control (SMC) feedback law is designed to further compensate for dynamic feedback linearization inaccuracy of the ADRC framework. Second, the disturbance rejection double‐loop depth‐tracking approach is suggested in conjunction with adaptive line‐of‐sight (ALOS), which converts depth tracking into pitch tracking. The ALOS not only estimates the actual angle of attack but also compensates the pitch‐tracking inaccuracy from the ADRC‐SMC in the inner loop. Then, the uniformly semiglobally exponential stability of the closed‐loop depth controller is proved after a detailed analysis of the stability from the inner loop to the outer loop. Finally, comparative field experiments are conducted to verify the proposed method. The effectiveness and strong disturbance rejection capabilities of the ADRC‐SMC pitch autopilot method and the suggested depth‐tracking approach are demonstrated by experimental results. [ABSTRACT FROM AUTHOR]

Scheduling workload is a demand response strategy for data centers to reshape electricity usage, which provides an opportunity for them to utilize renewable energy. Enhancing the flexibility of workload scheduling would promote the data center to integrate renewable energy. Considering that the improvement of flexibility in workload scheduling is tightly related to the Quality of Service (QoS) required by IT consumers (ITCs), it becomes desirable for the data center to collaborate with them to further facilitate renewable energy integration in demand response programs. This paper proposes a QoS‐based bi‐level demand response model for the data center, where game theory is adopted to resolve the conflict of interest in the collaboration between the data center and ITCs. At the upper level, the data center is a leader who provides differential monetary incentives to ITCs while dispatching workload to integrate renewable energy. At the lower level, ITCs act as followers who adjust the workload's QoS to enhance the flexibility of workload scheduling. Simulation results show that the proposed model can decrease the operating cost of the data center while increasing the utilization of renewable energy. © 2024 Institute of Electrical Engineer of Japan and Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Chemodynamic therapy (CDT) has great potential in cancer treatment, but its efficacy is limited due to non‐specificity, insufficient hydrogen peroxide (H2O2), and excessive glutathione (GSH) within the tumor microenvironment (TME). Here, an intelligent nanoplatform (Fe3O4@MnO2@NO@Au NPs, abbreviated as CD44FMNA) is reported for the treatment of breast cancer, which is constructed with Fe3O4 nanoparticles (NPs) as the core coated with manganese dioxide (MnO2) nanoshells encapsulating NO donors and gold nanoparticles (Au NPs) within the pores of MnO2, followed by the conjugation of targeting ligand anti‐CD44 mAb. The fabricated CD44FMNA initially remains inactive in normal cells, but after CD44 receptor ‐mediated MDA‐MB‐231 cell‐specific endocytosis, acidic TME can induce the decomposition of the MnO2 shell to release NO donors, thereby dually depleting the existing GSH in cells and enhancing the Fenton‐like reaction in a cascade manner. The generation of hydroxyl radicals (·OH) and the dual depletion of GSH can significantly weaken the GSH‐related antioxidant defense system (ADS) within MDA‐MB‐231 cells, accelerating apoptosis and cell death via the mitochondrial pathway. In addition, in vivo studies demonstrate that CD44FMNA can effectively inhibit tumor growth with good biosafety. Therefore, this nanoplatform may provide an effective therapy for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Disulfides in peptides and proteins are essential for maintaining a properly folded structure. Their oxidative folding is invariably performed in an aqueous‐buffered solution. However, this process is often slow and can lead to misfolded products. Here, we report a novel concept and strategy that is bio‐inspired to mimic protein disulfide isomerase (PDI) by accelerating disulfide exchange rates many thousand‐fold. The proposed strategy termed organic oxidative folding is performed under organic solvents to yield correctly folded cysteine‐rich microproteins instantaneously without observable misfolded or dead‐end products. Compared to conventional aqueous oxidative folding strategies, enormously large rate accelerations up to 113,200‐fold were observed. The feasibility and generality of the organic oxidative folding strategy was successfully demonstrated on 15 cysteine‐rich microproteins of different hydrophobicity, lengths (14 to 58 residues), and numbers of disulfides (2 to 5 disulfides), producing the native products in a second and in high yield. [ABSTRACT FROM AUTHOR]

Objectives: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are prevalent functional gastrointestinal disorders (FGIDs). In this study we aimed to explore the causal association between physical activity or sedentary behavior and the risk of FD and IBS. Methods: Mendelian randomization (MR) analysis was employed. Candidate genetic instruments for physical activity and sedentary behavior were retrieved from the latest published Genome‐Wide Association Study (GWAS), which included up to 703 901 participants. Summary‐level GWAS data for FD (8 875 cases and 320 387 controls) and IBS (9 323 cases and 301 931 controls) were obtained from the FinnGen study. The causal effects were mainly estimated by inverse variance weighted (IVW) method. Sensitivity analyses were implemented with Cochran's Q test, MR‐Egger intercept test, leave‐one‐out analysis, and the funnel plot. Results: No significant association of moderate‐to‐vigorous intensity physical activity (MVPA), leisure screen time (LST), sedentary behavior at work (SDW), and sedentary commuting (SDC) with the risk of FD was found. However, there was a suggestive correlation between MVPA and the decreased risk of FD (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.39–0.99, P = 0.047). Genetically predicted MVPA decreased the risk of IBS (OR 0.58, 95% CI 0.40–0.84, P = 0.004), while increased LST was positively associated with IBS risk (OR 1.33, 95% CI 1.15–1.53, P < 0.001). No causal effects of SDW or SDC on IBS risk were observed. Conclusion: MVPA and LST are causally linked to the development of IBS, which will facilitate primary prevention of IBS. [ABSTRACT FROM AUTHOR]

Cancer has been the most deadly disease, and 13 million cancer casualties are estimated to occur each year by 2030. Gold nanoparticles (AuNPs)‐based photothermal therapy (PTT) has attracted great interest due to its high spatiotemporal controllability and noninvasiveness. Due to the trade‐off between particle size and photothermal efficiency of AuNPs, rational design is needed to realize aggregation of AuNPs into larger particles with desirable NIR adsorption in tumor site. Exploiting the bioorthogonal "Click and Release" (BCR) reaction between iminosydnone and cycloalkyne, aggregation of AuNPs can be achieved and attractively accompanied by the release of chemotherapeutic drug purposed to photothermal synergizing. We synthesize iminosydnone‐lonidamine (ImLND) as a prodrug and choose dibenzocyclooctyne (DBCO) as the trigger of BCR reaction. A PEGylated AuNPs‐based two‐component nanoplatform consisting of prodrug‐loaded AuNPs‐ImLND and tumor‐targeting peptide RGD‐conjugated AuNPs‐DBCO‐RGD is designed. In the therapeutic regimen, AuNPs‐DBCO‐RGD are intravenously injected first for tumor‐specific enrichment and retention. Once the arrival of AuNPs‐ImLND injected later at tumor site, highly photothermally active nanoaggregates of AuNPs are formed via the BCR reaction between ImLND and DBCO. The simultaneous release of lonidamine further enhanced the therapeutic performance by sensitizing cancer cells to PTT. [ABSTRACT FROM AUTHOR]

This article discusses the role of small quantities of cartilage sodium channels in osteoarthritis (OA). The researchers found that the sodium channel Nav1.7 is present and elevated in human OA chondrocytes, and its deletion or blockade can attenuate the progression of OA and alleviate OA pain. The study also highlights the need for further investigation into the molecular mechanisms underlying the role of Nav1.7 in OA progression. The authors suggest that targeting Nav1.7 could be a potential therapeutic approach for treating OA. [Extracted from the article]

Objective: We aimed to explore the geographic differences in psychological symptoms, sleep quality, and quality of life (QoL) among adult patients with inflammatory bowel disease (IBD). Methods: A unified questionnaire was developed to collect data on psychological status and QoL of IBD patients from 42 hospitals across 22 provinces, municipalities, and autonomous regions in China's mainland from September 2021 to May 2022. Results: A total of 2478 patients with IBD were surveyed. The proportions of patients with anxiety (28.5% vs 23.1%), depression (32.3% vs 27.8%), and poor QoL (44.8% vs 32.2%) were significantly higher in patients from the northern region compared to the southern region (all P < 0.05). In the western region, the proportions of patients with anxiety (31.9% vs 23.0%), depression (37.7% vs 26.7%), sleep disturbances (64.5% vs 58.5%), and poor QoL (44.9% vs 34.8%) were significantly higher than in the eastern and central regions (all P < 0.01). Patients from inland regions had significantly higher rates of anxiety (27.1% vs 23.3%), depression (32.5% vs 26.0%), sleep disturbance (62.0% vs 57.7%), and poor QoL (43.5% vs 29.9%) compared to those from coastal regions (all P < 0.05). In economically underdeveloped areas, the proportions of patients with depression (33.1% vs 28.5%) and poor QoL (52.0% vs 32.4%) were significantly higher than in economically (relatively) developed areas (both P < 0.05). Conclusion: There are significant geographic differences in psychological symptoms, sleep quality, and QoL among Chinese patients with IBD, which might provide valuable insights for global IBD research and clinical practice. [ABSTRACT FROM AUTHOR]

Highly sensitive and wearable gas sensors are highly demanded on account of their widespread application in health and environmental monitoring. However, the sensing performance of conventional room‐temperature gas sensors are prone to fluctuate or even fail under changing humidity, temperature or putting into water, thus severely limiting their practical applications. Herein, a porous elastomer‐encapsulated hydrogel‐based oxygen sensor is designed with impressive room‐temperature sensing performance under various environmental conditions, including high precision (at ppm level), wide detection range (from 5 ppm to 90% O2), excellent repeatability, selectivity, long‐term stability, breathability, and waterproofing. The hydrophobic elastomer film prevents the water molecules from intruding and evaporating to a great extent, making the device resistant to humidity interference and applicable to underwater operation. Benefiting from the intrinsic stretchability of both hydrogel and elastomer films and their strong interfacial bonding, the final device can be stretched up to 100% strain. By integrating the sensor with a wireless circuit module, a wearable/portable oxygen sensing system for real‐time monitoring of health and environment is demonstrated, realizing timely and convenient assessment of respiratory rate, tissue oxygen, ambient oxygen, and dissolved oxygen. [ABSTRACT FROM AUTHOR]

Subduction initiation in oceans is key to understanding regional and global plate tectonics and ocean basin dynamics; however, its genetic mechanism is still enigmatic. The most famous model that predicts intraoceanic subduction initiation along transform faults or fracture zones (i.e., the Subduction Initiation Rule) has been widely used to explain arc‐like geochemical signatures within the Neo‐Tethyan ophiolites, but fails to account for the speculation and/or calculation of a sub‐parallel relationship between the Jurassic subduction zones and paleo ridges of the western Neo‐Tethys. Here, we propose a ridge‐parallel detachment fault‐hosted subduction re‐initiation model for the Jurassic western Neo‐Tethys. Based on field geological and geochemical evidence, we show that the Refahiye ophiolite in the İzmir–Ankara–Erzincan suture of northern Turkey has diagnostic characteristics indicative of (ultra)slow seafloor spreading. An (ultra)slow‐spreading nature also characterizes many Neo‐Tethyan ophiolites from the Alps to Southeast Asia, either at mid‐ocean ridges or in suprasubduction zones. Due to its extremely weak nature, detachment faults were probably a key candidate for the Jurassic intraoceanic subduction re‐initiation of the western Neo‐Tethys in response to far‐field compression after its long‐lived northward subduction. This model is applicable to both the Jurassic and Early Cretaceous ophiolites, but is questionable for the Late Cretaceous ophiolites. Its utility deponds on the kinematics of ancient plate boundaries and compositions of ophiolites. The detachment fault‐hosted subduction re‐initiation model can explain the arc‐like geochemical features of the Jurassic western Neo‐Tethyan ophiolites, but its effect on the structure and component of ophiolites is diverse. Plain Language Summary: Subduction of oceans is key to understanding regional and global plate tectonics. However, where and how ocean subduction initiates (i.e., subduction initiation) is still enigmatic, in particular for those vanished oceans in Earth's geologic history. In this study, we propose a new model of ridge‐parallel detachment fault‐hosted subduction re‐initiation for the western Neo‐Tethys Ocean in the Jurassic. Based on this study and a global compilation, we show that the ophiolites along the Neo‐Tethyan orogenic belt commonly contain slow‐ and ultraslow‐spreading oceanic lithospheres, either formed at mid‐ocean ridges or in suprasubduction zones. As for the western Neo‐Tethys, detachment faults adjacent to the paleoridges may have served as key candidates for subduction re‐initiation after the long‐lived northward subduction in the early stage, rather than along transform faults or fracture zones as previously suggested. This new model provides alternative explanations for the geochemical and structural diversities of the western Neo‐Tethyan ophiolites, and its utility in global ophiolites needs further examination. Key Points: The Neo‐Tethyan Refahiye ophiolite in northern Turkey formed at an (ultra)slow‐spreading ocean basin, probably at mid‐ocean ridgesDetachment fault is a key candidate for the Jurassic subduction re‐initiation of the western Neo‐Tethys OceanThe utility and diversity of detachment fault‐hosted subduction re‐initiation is discussed for the origin of Neo‐Tethyan ophiolites [ABSTRACT FROM AUTHOR]

With the continuous development of the internet of things (IoT), federated learning is being widely applied. This technology keeps data locally to protect data security. However, during the process of uploading gradients from local clients, there is a possibility of leaking sensitive information such as identities. To address this issue, this paper presents a secure and efficient anonymous federated learning framework. In our proposed, we first design a lightweight key‐sharing protocol based on elliptic curve cryptography (ECC) to generate shared keys and ensure secure communication. We then describe the improved process of federated learning, where clients communicate with the cloud server using pseudonyms to achieve anonymity. The security of our protocol is analyzed from both formal and informal perspectives, demonstrating that our proposed protocol satisfies "session key security." We also employ the formal verification tool ProVerif to validate the security of the protocol in terms of mutual authentication and key configuration in the Dolve–Yao threat model. Finally, the computational and communication costs of the proposed anonymous federated learning framework are evaluated, showing that both the computational and communication expenses are relatively low. A comparison was made between the proposed federated learning process and three other federated learning processes, demonstrating the clear advantages of our proposed. [ABSTRACT FROM AUTHOR]

Biomass‐based hydrogel is a promising flame‐retardant material and has a high potential for applications in transportation, aerospace, building and electrical engineering, and electronics. However, rapid vat photopolymerization (VP) 3D printing of biomass‐based hydrogels, especially that of all‐natural ones, is still rare. Herein, a new class of VP 3D‐printed hydrogels with strong covalent networks, fabricating using fully biomass materials and a commercial liquid crystal display (LCD) printer assembled with low‐intensity visible light is presented. Encouragingly, the highly ordered layer‐by‐layer packing structures provided by VP 3D printing technology endow these hydrogels with remarkable flame retardancy, exceptional temperature resistance, advantageous combustion behaviors, and favorable mechanical strength, in particular, giving them a better limit oxygen index (83.5%) than various biomass‐based hydrogels. The proposed approach enables the green design as well as the precise and efficient preparation for flame‐retardant materials, paving the way for the future flame‐retardant materials toward attaining green sustainability. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT) ablates tumors by thermal effects of photothermal agents (PTAs), and attracts wide attention due to the non‐invasive characteristic. The ideal PTAs are expected to have high photothermal conversion effect under NIR irradiation, as well as targeting abilities and good biocompatibility satisfying the need of application in vivo. Nanoparticles (NPs) are commonly used as anti‐tumor materials, and plenty of researches on therapeutical NPs for PTT treatment have been developed. Among various building blocks for photothermal NPs, polymer materials for biomedical applications have great advantages due to their negligible toxicity, flexibility for functional modification, and ability to integrate multiple therapeutic strategies. This review focuses on the polymer materials utilized in photothermal NP designing, including their application as excellent carriers and powerful PTAs with great PTT effects. Furthermore, the synergy therapy based on polymeric nanoplatform for enhancing PTT therapeutic efficiency will be introduced. [ABSTRACT FROM AUTHOR]

Processes of magma generation and transportation in global mid‐ocean ridges are key to understanding lithospheric architecture at divergent plate boundaries. These magma dynamics are dependent on spreading rate and melt flux, where the SW Indian Ridge represents an end‐member. The vertical extent of ridge magmatic systems and the depth of axial magma chambers (AMCs) are greatly debated, in particular at ultraslow‐spreading ridges. Here we present detailed mineralogical studies of high‐Mg and low‐Mg basalts from a single dredge on Southwest Indian Ridge (SWIR) at 45°E. High‐Mg basalts (MgO = ∼7.1 wt.%) contain high Mg# olivine (Ol, Fo = 85–89) and high‐An plagioclase (Pl, An = 66–83) as phenocrysts, whereas low‐Mg basalts contain low‐Mg# Ol and low‐An Pl (Fo = 75–78, An = 50–62) as phenocrysts or glomerocrysts. One low‐Mg basalt also contains normally zoned Ol and Pl, the core and rim of which are compositionally similar to those in high‐Mg and low‐Mg basalts, respectively. Mineral barometers and MELTS simulation indicate that the high‐Mg melts started to crystallize at ∼32 ± 7.8 km, close to the base of the lithosphere. The low‐Mg melts may have evolved from the high‐Mg melts in an AMC at a depth of ∼13 ± 7.8 km. Such great depths of magma crystallization and the AMC are likely the result of enhanced conductive cooling at ultraslow‐spreading ridges. Combined with diffusion chronometers, the basaltic melts could have ascended from the AMC to seafloor within 2 weeks to 3 months at average rates of ∼0.002–0.01 m/s, which are the slowest reported to date among global ridge systems and may characterize mantle melt transport at the slow end of the ridge spreading spectrum. Plain Language Summary: Mid‐ocean ridges are divergent plate boundaries where asthenospheric mantle undergoes decompressional melting to form basaltic melts and lithospheric mantle. The southwest Indian ridge (SWIR) represents the slowest spreading class of ocean ridges. It is characterized by intermittent volcanism resulting in thin or missing oceanic crust. To better understand the magma dynamics of such specific ridges and their correlation with the spreading rates, we calculated the depth of mineral crystallization in high‐Mg and low‐Mg basalts collected together and constrained the residence time of individual crystals in the melt through Fe‐Mg diffusion profiles. We show that the high‐Mg melts started crystallization close to the base of the tectonic plate, and likely partially crystallized in a deep magma chamber in the mantle to form low‐Mg magmas prior to eruption to the seafloor. This study determined that the rate at which the melts flowed up through the mantle to the crust was the slowest yet found for any ocean ridges. The mineral dynamics of the ultraslow‐spreading SWIR therefore illustrate the critical role of the velocity at which the tectonic plates separate on the formation of magmas at mid‐ocean ridges. Key Points: Deep crystallization depths (∼32 ± 7.8 km) and a deep axial magma chamber (AMC) (∼13 ± 7.8 km) may exist under the ultraslow‐spreading Southwest Indian Ridge (SWIR)The ascent rate from the AMC to seafloor of the SWIR is ∼0.002–0.01 m/s, which is the slowest in global mid‐ocean ridge systemsMagma ascent rates correlate positively with the spreading rates in the global mid‐ocean ridge systems [ABSTRACT FROM AUTHOR]

Hepatic venous pressure gradient (HVPG) is the gold standard for evaluating clinically significant portal hypertension (CSPH). However, reliable noninvasive methods are limited. Our study aims to investigate the diagnostic value of serum Golgi protein 73 (GP73) for CSPH in patients with compensated cirrhosis. The study enrolled 262 consecutive patients with compensated cirrhosis from three centers in China from February 2021 to September 2023, who underwent both serum GP73 tests and HVPG measurements. CSPH was defined as HVPG ≥ 10 mmHg. Diagnostic accuracy was evaluated using the areas under the receiver operating characteristic curve (AUC). The prevalence of CSPH was 56.9% (n = 149). There were significant differences between the CSPH and non‐CSPH groups in the median serum GP73 level (126.8 vs. 73.1 ng/mL, p < 0.001). GP73 level showed a significant positive linear correlation with HVPG (r = 0.459, p < 0.001). The AUC for the diagnosis of CSPH using serum GP73 alone was 0.75 (95% confidence interval [CI] 0.68–0.81). Multivariate logistic regression analysis determined that the levels of GP73, platelets and international normalized ratio were independently associated with CSPH. The combination of these three markers was termed "IP73" score with an AUC value of 0.85 (95% CI 0.80–0.89) for CSPH. Using 0 as a cut‐off value, the specificity and sensitivity of IP73 score were 77.9% and 81.9%, respectively. The IP73 score offers a novel, simple and noninvasive method of assessing CSPH in patients with compensated cirrhosis. A cut‐off value of the IP73 score at 0 can distinguish patients with or without CSPH. [ABSTRACT FROM AUTHOR]

An oxidant‐free photocatalytic [2+2+m] cyclization of 2‐cyanoaryl acrylamides with 2‐bromocarbonyls is reported, enabling the assembly of biologically important N‐heterocycle‐fused quinolinones including benzo[1,6]naphthyridinones and pyrrolo[3,2‐c]‐quinolines. This photocatalytic protocol proceeds through a radical relay pathway including alkene difunctionalization along with an intramolecular cyano insertion and subsequent site‐specific functionalization of inert C(sp3)−H bond enabled by cyano‐derived iminyl radical‐mediated 1,n‐hydrogen atom transfer. Notably, this transformation selectively formed two distinct C−C bonds, one C−N bond, and one quaternary carbon center in a one‐pot procedure. [ABSTRACT FROM AUTHOR]

A11 dopaminergic neurons regulate somatosensory transduction by projecting from the diencephalon to the spinal cord, but the function of this descending projection in itch remained elusive. Here, we report that dopaminergic projection neurons from the A11 nucleus to the spinal dorsal horn (dopaminergicA11‐SDH) are activated by pruritogens. Inhibition of these neurons alleviates itch‐induced scratching behaviors. Furthermore, chemogenetic inhibition of spinal dopamine receptor D1‐expressing (DRD1+) neurons decreases acute or chronic itch‐induced scratching. Mechanistically, spinal DRD1+ neurons are excitatory and mostly co‐localize with gastrin‐releasing peptide (GRP), an endogenous neuropeptide for itch. In addition, DRD1+ neurons form synapses with GRP receptor‐expressing (GRPR+) neurons and activate these neurons via AMPA receptor (AMPAR). Finally, spontaneous itch and enhanced acute itch induced by activating spinal DRD1+ neurons are relieved by antagonists against AMPAR and GRPR. Thus, the descending dopaminergic pathway facilitates spinal itch transmission via activating DRD1+ neurons and releasing glutamate and GRP, which directly augments GRPR signaling. Interruption of this descending pathway may be used to treat chronic itch. Synopsis: Dopaminergic neurons projecting from the A11 nucleus to the spinal dorsal horn (SDH) activate spinal DRD1+ neurons to facilitate spinal itch processing. DRD1+ neurons release glutamate and GRP to activate GRPR+ neurons. A11 dopaminergic neurons facilitate spinal itch processing.DopaminergicA11‐SDH projection acts on DRD1+ neurons to enhance itch transmission.DRD1+ neurons form monosynaptic connections with GRPR+ neurons in the SDH. [ABSTRACT FROM AUTHOR]

Nicotine lactate, nicotine tartrate, nicotine benzoate, and freebase nicotine (FBN) are four forms of nicotine salt systems that are present in tobacco products. However, few in vivo studies have compared their pharmacological (pK) efficacies, which are important for understanding their roles in the addiction and abuse of tobacco and nicotine products. In this work, the pK of the above nicotine salt systems was studied by subcutaneously injecting their aqueous solutions in rats and obtaining blood samples from the jugular vein. Nicotine levels in the blood were analyzed by LC–MS/MS. The results demonstrated that rapid nicotine absorption occurred in all nicotine systems. Of them, NB had the smallest Tmax, while FBN had the largest Tmax. The nicotine metabolic rate and clearance decreased for FBN, indicating that nicotine retention in the body was higher than for the other three salt‐based systems. Compared with nicotine salts, FBN could reach and maintain a higher concentration in the animal model. Additionally, as the benzoic acid ratios increased, the Cmax of the nicotine benzoate (NB) in the plasma decreased. This indicates that the lower the pH, the lower the Cmax. When different concentrations of NB were used, the higher the NB concentration, the greater the Cmax and AUC(0‐t). These results demonstrate that nicotine adsorption by NB in the animal model depended on both pH and concentration. This baseline information could be used to explain different clinical pharmacological observations in humans, though this study only considered the effects of nicotine on pharmacokinetics in vivo. [ABSTRACT FROM AUTHOR]

Public administration is a discipline with considerable history, and is also a diverse, interdisciplinary field in social science. To analyze its evolution, discover the present research foci, and predict future development trends, this study applied scientometrics visualization technology to evaluate over 72,000 scientific articles from the 1920s to 2020s. This research referred to the SSCI and JCR databases to gather scientific data of the discipline and the journals' impact factor. Consequently, paper citations, cited journals, journal co‐citations, author co‐citations, authoritative papers, top countries, productive institutes, average references, and research collaboration trends were analyzed on the bases of the published literature. This study found top productive journals in the discipline, discovered productive countries and institutes, present the research foci, and predicted future development trends. Through this study, scientific production, international cooperation, and knowledge evolution mode of public administration research offers a clear knowledge map of the public administration discipline. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is often diagnosed in the advanced stages with a poor prognosis. Thymoquinone (TQ) is known for its antitumor activity; however, the specific mechanism in GC remains unknown. In our study, TQ inhibited GC cell proliferation and induced apoptosis and autophagy in a concentration‐dependent manner. Transmission electron microscopy showed increased autophagosome formation in GC cells treated with TQ. Meanwhile, the LC3B puncta and LC3BII protein levels were significantly increased in GC cells, while p62 expression was significantly decreased. The autophagy inhibitor, Bafilomycin A1 enhanced TQ‐inhibited proliferation and TQ‐induced apoptosis, suggesting that TQ‐induced autophagy has a protective effect on GC cells. Furthermore, TQ decreased the phosphorylation levels of phosphatidylinositol‐4,5‐bisphosphate 3 kinase (PI3K), protein kinase B (Akt), and mechanistic target of rapamycin (mTOR). The PI3K agonist partially rescued TQ‐induced autophagy and apoptosis. Finally, in vivo experiments showed that TQ could inhibit tumor growth and promote apoptosis and autophagy. This study provides new insights into the specific mechanism for the anti‐GC effect of TQ. TQ inhibits the proliferation of GC cells and induces apoptosis and protective autophagy by inhibiting the PI3K/Akt/mTOR pathway. The results suggest that the combination of TQ and autophagy inhibitors might be a potential chemotherapeutic strategy for GC. [ABSTRACT FROM AUTHOR]

Peptide asparaginyl ligases (PALs) are precision tools for peptide cyclization, cell‐surface labelling, protein semisynthesis and protein conjugation. PALs are expressed as inactive proenzymes requiring low pH activation. During activation, a large portion of the cap domain of the proenzyme that covers the substrate binding site is proteolytically removed, exposing the active site to solvent and releasing a population of heterogenous active enzymes. The availability of a readily active ligase not requiring acid activation and subsequent purification of active forms would facilitate manufacturing and streamline applications. Here, we engineered the OaAEP1b‐C247A hyperactive ligase via serial truncations along the linker connecting the cap and core domain of the proenzyme. The recombinant expression of the truncated constructs was carried out in Escherichia coli. Following a solubilization/refolding protocol, one truncated construct termed 'OaAEP1b‐C247A‐∆351' could be overexpressed in the insoluble fraction, purified, and displayed a level of ligase activity comparable to the acid‐activated OaAEP1b‐C247A enzyme. This constitutively active protein can be stored for up to 2 years at −80 °C and readily used for peptide cyclization and protein conjugation. We were able to express and purify a stable constitutively active asparaginyl ligase that can be stored for months without significant activity loss. The removal of the low pH proenzyme activation step eliminates the heterogeneity introduced by this procedure. The yield of purified recombinant active ligase that can be routinely obtained per 100 mL of E. coli cell culture is about 0.9 mg. This recombinant active ligase can be used to carry out protein conjugation. [ABSTRACT FROM AUTHOR]

Amorphous oxide semiconductor thin‐film transistors (AOS TFTs) are ever‐increasingly utilized in displays. However, to bring high mobility and excellent stability together is a daunting challenge. Here, the carrier transport/relaxation bilayer stacked AOS TFTs are investigated to solve the mobility‐stability conflict. The charge transport layer (CTL) is made of amorphous In‐rich InSnZnO, which favors big average effective coordination number for all cations and more edge‐shared structures for better charge transport. Praseodymium‐doped InSnZnO is used as the charge relaxation layer (CRL), which substantially shortens the photoelectron lifetime as revealed by femtosecond transient absorption spectroscopy. The CTL and CRL with the thickness suitable for industrial production respectively afford minute potential barrier fluctuation for charge transport and fast relaxation for photo‐generated carriers, resulting in transistors with an ultrahigh mobility (75.5 cm2 V−1 s−1) and small negative‐bias‐illumination‐stress/positive‐bias‐temperature‐stress voltage shifts (−1.64/0.76 V). The design concept provides a promising route to address the mobility‐stability conflict for high‐end displays. [ABSTRACT FROM AUTHOR]

Summary: Peptide asparaginyl ligases (PALs) are useful tools for precision modifications of proteins and live‐cell surfaces by ligating peptides after Asn/Asp (Asx). They share high sequence and structural similarity to plant legumains that are generally known as asparaginyl endopeptidases (AEPs), thus making it challenging to identify PALs from AEPs. In this study, we investigate 875 plant species from algae to seed plants with available sequence data in public databases to identify new PALs.We conducted evolutionary trace analysis on 1500 plant legumains, including eight known PALs, to identify key residues that could differentiate ligases and proteases, followed by recombinant expression and functional validation of 16 novel legumains.Previously, we showed that the substrate‐binding sequences flanking the catalytic site can strongly influence the enzymatic direction of a legumain and which we named as ligase‐activity determinants (LADs). Here, we show that two conserved substrate‐binding Gly residues of LADs are critical, but negative determinants for ligase activity.Our results suggest that specific glycine residues are molecular determinants to identify PALs and AEPs as two different legumain subfamilies, accounting for c. 1% and 88%, respectively. [ABSTRACT FROM AUTHOR]

Flexible gas sensors play an indispensable role in diverse applications spanning from environmental monitoring to portable medical electronics. Full wearable gas monitoring system requires the collaborative support of high‐performance sensors and miniaturized circuit module, whereas the realization of low power consumption and sustainable measurement is challenging. Here, a self‐powered and reusable all‐in‐one NO2 sensor is proposed by structurally and functionally coupling the sensor to the battery, with ultrahigh sensitivity (1.92%/ppb), linearity (R2 = 0.999), ultralow theoretical detection limit (0.1 ppb), and humidity immunity. This can be attributed to the regulation of the gas reaction route at the molecular level. The addition of amphiphilic zinc trifluoromethanesulfonate (Zn(OTf)2) enables the H2O‐poor inner Helmholtz layer to be constructed at the electrode–gel interface, thereby facilitating the direct charge transfer process of NO2 here. The device is then combined with a well‐designed miniaturized low‐power circuit module with signal conditioning, processing and wireless transmission functions, which can be used as wearable electronics to realize early and remote warning of gas leakage. This study demonstrates a promising way to design a self‐powered, sustainable, and flexible gas sensor with high performance and its corresponding wireless sensing system, providing new insight into the all‐in‐one system of gas detection. [ABSTRACT FROM AUTHOR]

Perovskite light‐emitting diodes (PeLEDs) emerge as a promising kind of optoelectronic devices for the next‐generation full‐color display and white‐lighting technology. However, the performance of blue PeLEDs is far from satisfactory and some significant properties still remain unknown. Herein, for the first time, the active‐matrix display potential of blue PeLEDs has been unveiled by virtue of highly efficient, bright, and color‐stable blue PeLEDs. Through a synergistic strategy of ligand‐, anti‐solvent‐, device‐, and additive engineering, the photoluminescence quantum yield of blue perovskite films is as high as 76%. Blue PeLEDs exhibit a maximum external quantum efficiency of 9.81% at 251 cd m−2, a maximum power efficiency of 9.78 lm W−1, a peak luminance of 2298 cd m−2, and stable emissions, rendering that the performance is among the best blue PeLEDs. Furthermore, the integration applications of blue PeLEDs have been studied and the first prototype active‐matrix blue PeLED pixel circuit is demonstrated. Moreover, an unprecedented endeavor for active‐matrix flexible blue PeLEDs has been taken. The findings not only provide an alternative approach to achieve high‐performance blue PeLEDs, but also unlock the significant active‐matrix property of blue PeLEDs, which may pave the pathway for PeLED‐based display technology and related integrated optoelectronics. [ABSTRACT FROM AUTHOR]

Stretchable, self‐healing, and breathable skin‐biomimetic‐sensing iontronics play an important role in human physiological signal monitoring and human–computer interaction. However, previous studies have focused on the mimicking of skin tactile sensing (pressure, strain, and temperature), and the development of more functionalities is necessary. To this end, a superior humidity‐sensitive ionic skin is developed based on a self‐healing, stretchable, breathable, and biocompatible polyvinyl alcohol–cellulose nanofibers organohydrogel film, showing a pronounced thickness‐dependent humidity‐sensing performance. The as‐prepared 62.47‐μm‐thick organohydrogel film exhibits a high response (25,000%) to 98% RH, excellent repeatability, and long‐term stability (120 days). Moreover, this ionic skin has excellent resistance to large mechanical deformation and damage, and the worn‐out material can still retain its humidity‐sensing capabilities after self‐repair. Humidity‐sensing mechanism studies show that the induced response is mainly related to the increase of proton mobility and interfacial charge transport efficiency after water adsorption. The superior humidity responsiveness is attributed to the reduced thickness and the increased specific surface area of the organohydrogel film, allowing real‐time recording of physiological signals. Notably, by combining with a self‐designed printed circuit board, a continuous and wireless respiration monitoring system is developed, presenting its great potential in wearable and biomedical electronics. [ABSTRACT FROM AUTHOR]

High‐performance bilayer In2O3/IGZO thin‐film transistors (TFTs) fabricated by pulsed laser deposition are reported. The TFTs exhibit an on/off current ratio of 109, a reversed subthreshold slope (ss) of 0.08 V dec−1, and a high saturation mobility of 47.9 cm2 V−1 s−1. The reliability of the mobility values is critically validated and assessed by four‐probe measurements, the transfer‐length method, and the temperature‐dependence. X‐ray photoelectron spectra are combined with C–V measurements to characterize the interface, and the results show that a two‐dimensional electron gas (2DEG)‐like state accumulates at the In2O3/IGZO interface. However, this state only forms in the subthreshold region and does not cause the high carrier mobility in the region above the threshold. Instead, the enhanced carrier mobility results from the intrinsic high mobility of the In2O3, the smooth surface, and the low‐defect states in the In2O3/IGZO bilayer with a good percolation transport path. [ABSTRACT FROM AUTHOR]

To explore the association between male infertility and hypertension risk, a meta‐analysis and systematic review was conducted. Observational studies were sought in Medline, PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure up to April 30, 2021. Two independent reviewers selected available studies and extracted the data. The association between male infertility and hypertension risk was estimated by calculating the relative risk (RR) and 95% confidence interval (95% CI) using Stata12.0 statistical software. A total of seven studies were included in this meta‐analysis, including 102,152 patients and 636,645 healthy individuals. The results demonstrated that male infertility was significantly associated with increased hypertension incidence (RR = 1.08; 95% CI 1.02–1.14; p = 0.004), with moderate‐quality evidence. A subgroup analysis based on region showed that a positive association was observed in Europe but not the United States or Asia. This positive association was further confirmed in a cohort study, but not in a case‐control study. After adjusting for potential confounders, male infertility was still significantly associated with hypertension risk (RR = 1.06, 95% CI 1.03–1.09). In conclusion, our findings suggest that male infertility increases the risk of hypertension incidence. However, further studies are needed to provide more conclusive evidence. [ABSTRACT FROM AUTHOR]

Data on safety and immunogenicity of coronavirus disease 2019 (COVID‐19) vaccinations in hepatocellular carcinoma (HCC) patients are limited. In this multicenter prospective study, HCC patients received two doses of inactivated whole‐virion COVID‐19 vaccines. The safety and neutralizing antibody were monitored. Totally, 74 patients were enrolled from 10 centers in China, and 37 (50.0%), 25 (33.8%), and 12 (16.2%) received the CoronaVac, BBIBP‐CorV, and WIBP‐CorV, respectively. The vaccines were well tolerated, where pain at the injection site (6.8% [5/74]) and anorexia (2.7% [2/74]) were the most frequent local and systemic adverse events. The median level of neutralizing antibody was 13.5 (interquartile range [IQR]: 6.9–23.2) AU/ml at 45 (IQR: 19–72) days after the second dose of vaccinations, and 60.8% (45/74) of patients had positive neutralizing antibody. Additionally, lower γ‐glutamyl transpeptidase level was related to positive neutralizing antibody (odds ratio = 1.022 [1.003–1.049], p = 0.049). In conclusion, this study found that inactivated COVID‐19 vaccinations are safe and the immunogenicity is acceptable or hyporesponsive in patients with HCC. Given that the potential benefits may outweigh the risks and the continuing emergences of novel severe acute respiratory syndrome coronavirus 2 variants, we suggest HCC patients to be vaccinated against COVID‐19. Future validation studies are warranted. [ABSTRACT FROM AUTHOR]

The corrosion behavior of low‐alloy steel exposed to saturated H2S solution is systematically studied using electron backscattered diffraction, scanning electron microscopy, X‐ray diffraction, X‐ray photoelectron spectroscopy, and electron probe microanalysis. The experimental results suggest that the corrosion rate decreases with prolonged immersion time because more corrosion products are formed on the steel surface. The corrosion products consist of mackinawite, greigite, and molybdenite regardless of the corrosion time. The structure of the corrosion products transforms from a single layer into two layers with increasing corrosion time. The Cr content in the corrosion products is similar to that in the steel substrate. The corrosion products are rich in molybdenum owing to the formation of molybdenite. [ABSTRACT FROM AUTHOR]

Single‐emitting‐layer white organic light‐emitting diodes (SEL‐WOLEDs) have developed rapidly in recent years due to the outstanding advantages of high efficiency, simple device structure, low cost, less phase separation, and stable emission color. Nevertheless, the relatively complicated host‐dopant system is usually essential for most previous SEL‐WOLEDs and the development of simple non‐doped SEL‐WOLEDs lags behind. Hence the straightforward synthesis of single‐white‐emitting molecules for non‐doped SEL‐WOLEDs still remains a great challengeable task. In this article, we designed and synthesized two new pyrene‐based polyaromatic hydrocarbons (PAHs) and used them as emitting layer materials in the OLED devices. When the molecules change from the mono‐fused one to bis‐fused one, the emitting light changes from greenish to white color. Further study indicated that the bis‐fused molecule PyD with more twisted and extended backbone packed in neat Cmca space group in single‐crystal system compared with P21/n for PyS, which may be favorable to form excimers in the solid state and broaden the emission spectrum in the OLEDs. As a result, a solution‐processed non‐doped single‐white‐emitting‐molecule SEL‐WOLED with high performance (e. g. a high color rendering index of 66) is reported. The findings will be beneficial not only to further development of simple WOLEDs, but also to other related organic optoelectronic technology. [ABSTRACT FROM AUTHOR]

Aims: The difference between multiple primary lung cancers (MPLC) and intrapulmonary metastasis (IM) in patients with lung cancer is vital but controversial. Moreover, the genetic and clinical significance difference between MPLC and independent primary lung cancers (IPLC) patients is unknown. Methods: This study retrospectively researched clinical and genetic data of MPLC and IPLC patients from January 2019 to May 2021 at the affiliated hospital of Qingdao University, China. Ninety‐four tissue samples from 41 early‐stage patients with MPLC, and 94 tissue samples from 94 early‐stage patients with IPLC were performed to targeted sequencing. Results: A total of 36 patients (88%) showed inconsistent driver mutations, and five MPLC patients (12%) shared single identical EGFR/BRAF/TP53 hotspot mutations in the early stage. In MPLC patients, high‐frequency mutations included EGFR (63%), TP53 (12%), BRAF (12%), KRAS (10%), ERBB2 (4%), PIK3CA (3%), and MET (3%). In IPLC patients, high‐frequency mutations included EGFR (55%), TP53(26%), KRAS (13%), MAP2K1 (5%), PIK3CA (4%), ERBB2 (4%), NF1 (4%), RET (3%), and BRAF (2%). The higher BRAF and fewer TP53 mutations may be related to the lower malignancy in MPLC patients. Conclusions: The accuracy of pathological diagnosis in patients with early‐stage MPLC does not need comprehensive molecular evaluation to supplement histology for differentiating early‐stage MPLC and IM. Meanwhile, the molecular difference between MPLC and IPLC may be helpful to study the mechanism of MPLC pathogenesis. [ABSTRACT FROM AUTHOR]

This article addresses the event‐triggered stabilization for large‐scale interconnected systems in presence of time delays. Two types of event‐triggering mechanisms (static event‐triggering mechanism and dynamic event‐triggering mechanism) are constructed. For each case, event‐triggered predictor‐based controller is designed to compensate time delays by using backstepping method. Via Lyapunov approach, constructive exponential stability conditions are established in the framework of linear matrix inequalities (LMIs). A numerical simulation example is given to demonstrate the effectiveness of the proposed methods. [ABSTRACT FROM AUTHOR]

Growth accounting has documented an important contribution of information and communication technology (ICT) capital deepening to sectoral labor productivity growth during the late 1990s, especially for the knowledge‐intensive services that are used to an important extent as intermediate inputs to other sectors. Our approach traces labor productivity growth not within sectors but within value chains of final products. A main result is that more than half of the productivity gains related to ICT capital deepening for manufactured goods are contributed by upstream industries, mostly by knowledge‐intensive services. For a number of countries, similar magnitudes of upstream contributions of ICT capital deepening are observed for ICT products and for services that are not knowledge‐intensive. The major part of these contributions is domestic rather than foreign. Moreover, the high sectoral growth in total factor productivity (TFP) in the ICT sector contributes only moderately to effective TFP growth in non‐ICT value chains. [ABSTRACT FROM AUTHOR]

Ability of IL‐17‐producing CD8+ T cells (Tc17) to transform into cytotoxic anti‐tumour effectors makes them a promising candidate for immune effector cell (IEC) therapy. However, key factors regulating Tc17 reprogramming remain poorly defined, hindering translation of Tc17‐based IEC use from bench to bedside. We probed the effects of multiple cytokines and underlying signalling pathways on Tc17 cells and identified pivotal role for IL‐4 and PI3K/AKT in promoting Tc17 transformation into cytotoxic IFN‐γ‐producing IECs, an effect dependent on Eomes expression. IL‐4 not only triggered Tc17 cytotoxicity, but also induced cell expansion, which significantly improved the antitumour potential of Tc17 cells compared to that of IFN‐γ‐producing CD8+ T cells (Tc1) in a murine model. Furthermore, IL‐4/AKT signalling drove the upregulation of the T‐cell receptor‐associated transmembrane adaptor 1 (Trat1) in Tc17 cells to promote IL‐4‐induced T‐cell receptor stabilization and Tc17 cytotoxicity. Finally, we proposed a possible procedure to expand human Tc17 from peripheral blood of cancer patients, and confirmed the function of IL‐4 in Tc17 reprogramming. Collectively, these results document a novel IL‐4/AKT/Eomes/Trat1 axis that promotes expansion and transformation of Tc17 cells into cytotoxic effectors with a therapeutic potential. IL‐4 priming of Tc17 cells should be further explored as a cell therapy engineering strategy to generate IECs to augment anti‐tumour responses. [ABSTRACT FROM AUTHOR]