Search

Abstract The ability to synthesize compositionally complex nanostructures rapidly is a key to high‐throughput functional materials discovery. In addition to being time‐consuming, a majority of conventional materials synthesis processes closely follow thermodynamics equilibria, which limit the discovery of new classes of metastable phases such as high entropy oxides (HEO). Herein, a photonic flash synthesis of HEO nanoparticles at timescales of milliseconds is demonstrated. By leveraging the abrupt heating and cooling cycles induced by a high‐power‐density xenon pulsed light, mixed transition metal salt precursors undergo rapid chemical transformations. Hence, nanoparticles form within milliseconds with a strong affinity to bind to the carbon substrate. Oxygen evolution reaction (OER) activity measurements of the synthesized nanoparticles demonstrate two orders of magnitude prolonged stability at high current densities, without noticeable decay in performance, compared to commercial IrO2 catalyst. This superior catalytic activity originates from the synergistic effect of different alloying elements mixed at a high entropic state. It is found that Cr addition influences surface activity the most by promoting higher oxidation states, favoring optimal interaction with OER intermediates. The proposed high‐throughput method opens new pathways toward developing next‐generation functional materials for various electronics, sensing, and environmental applications, in addition to renewable energy conversion.

Air pollution has been linked to respiratory diseases, and urban air pollution can be attributed to a number of emission sources. The emitted particles and gases are the primary components of air pollution that enter the lungs during respiration. Particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) can deposit deep into the respiratory tract via inhalation and has been proposed as a causative agent for adverse respiratory health. In addition, the lung contains a diverse microbial community (microbiome) that maintains normal homeostasis and is significantly altered in a variety of pulmonary disorders. Air pollution, specifically PM2.5, has previously been shown to significantly alter the composition of the lower airway microbiome, which has been linked to decreased lung function in chronic obstructive pulmonary disease (COPD) patients. Surprisingly, the intestinal microbiome has also been implicated in the modulation of pulmonary inflammatory diseases. Therefore, dysbiosis of the lung and intestinal microbiomes pose significant negative effects on human health.This dataset describes the microbial community profiles of the lungs and intestines of ageing rats exposed to ambient unconcentrated traffic-related air pollution for three months. The whole-body exposure system was equipped with and without high efficiency particulate air (HEPA) filtration (gaseous vs. PM2.5 pollution). The data can provide valuable information on lung and intestinal microbiome changes, including that which was only found after traffic-related air pollution exposure.

Objective To investigate the predictive function of miR-200c level in peripheral blood on acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation. Methods Fifty-one patients who received allo-HSCT in hematology department of our hospital from January 2014 to October 2018 were selected as the research subjects. According to the principle of whether agVHD occurred after transplantation, 33 patients were in the experimental group (with aGVHD) and 18 patients were in the control group (without aGVHD). RT-qPCR was used to detect miR-200c in two groups and the differences in miR-200c expression between the two groups were analyzed. Results The transplantation was successful in both groups, and the hematopoietic function was restored. The recovery time was 18 days, among which 33 patients developed aGVHD and 18 patients did not develop aGVHD, with an incidence of 64.71%. The expression of miR-200c in experimental group was lower than that in control group before transplantation and 7, 14, and 72 d after transplantation (P＜0.05). MiR-200c in peripheral blood after the occurrence of aGVHD was significantly lower than that before the occurrence(P＜0.001). Compared with aGVHD Ⅱ, the expression of miR-200c in peripheral blood of aGVHD Ⅱ patients was down-regulated (P＜0.05); as compared with aGVHD Ⅲ patients, the expression of miR-200c in peripheral blood of aGVHD Ⅲ patients was down-regulated (P＜0.001); the 2-year survival rate in the high expression group of miR-200c was higher than that in the low expression group (P＜0.05). Conclusions The reduced level of miR-200c is associated with the occurrence of aGVHD after allogeneic hematopoietic stem cell transplantation. With the increase of the severity of aGVHD the expression level of miR-200c is decreased, and the survival rate of patients with low miR-200c expression is low, so the expression of miR-200 is a potential marker for early diagnosis and prediction of aGVHD.

Abstract Nonlinear light–matter interaction, as the core of ultrafast optics, bulk photovoltaics, nonlinear optical sensing and imaging, and efficient generation of entangled photons, has been traditionally studied by first-principles theoretical methods with the sum-over-states approach. However, this indirect method often suffers from the divergence at band degeneracy and optical zeros as well as convergence issues and high computation costs when summing over the states. Here, using shift vector and shift current conductivity tensor as an example, we present a gauge-invariant generalized approach for efficient and direct calculations of nonlinear optical responses by representing interband Berry curvature, quantum metric, and shift vector in a generalized Wilson loop. This generalized Wilson loop method avoids the above cumbersome challenges and allows for easy implementation and efficient calculations. More importantly, the Wilson loop representation provides a succinct geometric interpretation of nonlinear optical processes and responses based on quantum geometric tensors and quantum geometric potentials and can be readily applied to studying other excited-state responses.

Abstract Miniature pigs are an ideal animal model for translational research to evaluate stem cell therapies and regenerative applications. While the derivation of induced pluripotent stem cells (iPSCs) from miniature pigs has been demonstrated, there is still a lack of a reliable method to generate and maintain miniature pig iPSCs. In this study, we derived iPSCs from fibroblasts of Wisconsin miniature swine (WMS), Yucatan miniature swine (YMS), and Göttingen minipigs (GM) using our culture medium. By comparing cells of the different pig breeds, we found that YMS fibroblasts were more efficiently reprogrammed into iPSCs, forming colonies with well-defined borders, than WMS and GM fibroblasts. We also demonstrated that YMS iPSC lines with a normal pig karyotype gave rise to cells of the three germ layers in vitro and in vivo. Mesenchymal stromal cells expressing phenotypic characteristics were derived from established iPSC lines as an example of potential applications. In addition, we found that the expression level of the switch/sucrose nonfermentable component BAF60A regulated by STAT3 signaling determined the efficiency of pig iPSC generation. The findings of this study provide insight into the underlying mechanism controlling the reprogramming efficiency of miniature pig cells to develop a viable strategy to enhance the generation of iPSCs for biomedical research.

Abstract The nonlinear optical (NLO) responses of topological materials are under active research. Most previous works studied the surface and bulk NLO responses separately. Here we develop a generic Green’s function framework to investigate the surface and bulk NLO responses together. We reveal that the topological surface can behave disparately from the bulk under light illumination. Remarkably, the photocurrents on the surface can flow in opposite directions to those in the bulk interior, and the light-induced spin current on the surface can be orders of magnitude stronger than its bulk counterpart on a per-volume basis. We also study the responses under inhomogeneous field and higher-order NLO effect, which are all distinct on the surface. These anomalous surface responses suggest that light can be a valuable tool for probing the surface states of topological materials. Besides, the surface effects should be prudently considered when investigating the optical properties of topological materials.

Cargo transport from the ER to the Golgi is highly selective. Here the authors identify three secretory pathway localized proteins that regulate ER sorting of receptor kinases in Arabidopsis and are required to support pollen tube growth.

Abstract Background Disease situations are more aggressive in patients with childhood-onset systemic lupus erythematosus (cSLE) than in those with adult-onset SLE (aSLE). However, information on pregnant women with cSLE and its association with pregnancy outcomes is limited. This study aimed to compare pregnancies in patients with cSLE vs. aSLE, and further analyse the characteristics of cSLE in pregnant women and explore its association with adverse pregnancy outcomes. Methods Altogether, data of 167 pregnancies from 150 women, including 22 pregnancies with cSLE and 145 pregnancies with aSLE, were retrospectively analysed. Characteristics and disease activity were compared between the cSLE and aSLE groups during pregnancy. Associations between cSLE and the risk of active SLE (SLEPDAI > 4), active lupus nephritis (LN), and adverse pregnancy outcomes were analysed using logistic regression. Results The cSLE group had a higher incidence of active SLE (12/22 vs. 30/145, P = 0.001) and active LN (11/22 vs. 26/145, P = 0.001) than the aSLE group. In the multivariable analysis, cSLE was a risk factor for active SLE and active LN during pregnancy, with ORs of 4.742 (95%CI 1.678–13.405, P = 0.003) and 4.652 (95%CI 1.630–13.279, P = 0.004), respectively. No significant association between cSLE and the risk of composite adverse gestational outcomes was identified after sequentially adjusting pre-pregnancy characteristics and pregnancy factors (P > 0.05). Conclusion Disease activity of women with cSLE in pregnancy was more aggressive than that of women with aSLE, which was similar to the characteristics of non-pregnant women with SLE. cSLE might have indirect effects on the risk of adverse pregnancy outcomes through LN and active disease. Therefore, closely monitoring patients with cSLE during pregnancy is crucial.

The development of alternative energy resources is of great significance to alleviate the global energy issue. The direct methanol fuel cell (DMFC) is gradually becoming one of the most promising portable energy technologies due to the merits of low operating temperature, high energy density, and low pollutant emission. Currently, its commercialization process mainly depends on the kinetics of the anodic methanol oxidation reaction (MOR). Noble metals have been widely studied as the most commonly used anode catalysts. However, high prices and limited reserves have severely hindered their further development. In addition, the active surface of Pt is susceptible to the poison of COads intermediate products, leading to the rapid loss of the catalytic activity due to blocked Pt sites. Considering the above problems, the design and development of low Pt or non-Pt nanocatalysts with an excellent antipoisoning ability have become very important. Transition metals have been widely used as promising substitutes for noble metal catalysts because of their abundant reserves, low price, and high catalytic activity. Among the transition metals studied, Ni, Cu, and Co have attracted sustained attention because of their high corrosion resistance. Owing to the ligand effect and synergistic effect, the addition of transition metals can effectively weaken the adsorption of COads intermediates on Pt sites. At the same time, non-noble transition metals are easy to form MOOH active species, which promote the oxidation of COads intermediates. Besides, methanol electrooxidation performance is closely related to the shape, structure, and composition of transition metals. From the principle of DMFC anode electrocatalysis, this review summarized the research progress of transition metal-based catalysts (transition metal-noble metal catalysts, transition metal catalysts, and self-supporting catalysts) in MOR. More importantly, the effects of the nanocatalyst composition, porous structure, high-index surface, crystal defects, and vertex enhancement on its electrochemical properties were emphasized. Finally, opportunities and challenges faced by transition metal-based electrocatalysts in DMFC were discussed.

Background/Purpose: Viruses-bacteria synergistic interaction is associated with destructive periodontal diseases. However, the underlying mechanism for tissue destruction is not fully elucidated. In this study, lipopolysaccharide from Porphyromonas gingivalis (Pg-LPS) and polyinosinic-polycytidylic acid (poly I:C) were used to simulate bacteria and viruses, respectively. The possible combined effects of both molecular patterns on secretion of interleukin (IL)-6 and prostaglandin E2 (PGE2) from osteoblasts were determined. The effects of povidone-iodine (PVP-I) on the secretion of IL-6 and PGE2 were also examined. Methods: Viability of treated osteoblastic cells (MG63) was examined by detection the mitochondrial dehydrogenase activity. Secretion of IL-6 and PGE2 was detected using the enzyme-linked immunosorbent assay (ELISA). Mitogen-activated protein kinases (MAPKs) and cyclooxygenase-2 (COX-2) were determined using the Western blotting analysis. Results: Pg-LPS or poly I:C significantly enhanced the production of IL-6 and PGE2 in MG63 cells. The additive/synergistic effects of Pg-LPS/poly I:C on production of IL-6 and PGE2 were evident. The levels of phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) and expression of COX-2 protein were enhanced by Pg-LPS and/or poly I:C. On the other hand, the level of phosphorylation of extracellular signal-regulated kinase (ERK) was reduced by Pg-LPS and/or poly I:C. The stimulatory secretion of PGE2 by poly I:C was significantly reduced by PVP-I. Conclusion: Concomitant infection of viruses and bacteria may be potentially harmful to the tooth supporting tissues by production of proinflammatory mediators. The results suggest the potential anti-inflammatory effect of PVP-I on bacterial or viral infection.

Abstract Background The growth and development of muscle stem cells (MuSCs) are significant events known to affect muscle plasticity, disease, meat production, and meat quality, which involves the types and functions of mRNA and non-coding RNA. Here, MuSCs were cultured from Guangxi fetal cattle. RNA sequencing was used to analyze the RNA expression of mRNA and non-coding RNAs during the cell proliferation and differentiation phases. Results Two thousand one hundred forty-eight mRNAs and 888 non-coding RNAs were differentially expressed between cell proliferation and differentiation phases, including 113 miRNAs, 662 lncRNAs, and 113 circRNAs. RT-qPCR verified the differential expression levels of mRNAs and non-coding RNAs, and the differentially expressed circUBE2Q2 was subsequently characterized. Expression profile analysis revealed that circUBE2Q2 was abundant in muscle tissues and intramuscular fat. The expression of cricUBE2Q2 was also significantly upregulated during MuSCs myogenic differentiation and SVFs adipogenic differentiation and decreased with age in cattle muscle tissue. Finally, the molecular mechanism of circUBE2Q2 regulating MuSCs function that affects skeletal muscle development was investigated. The results showed that circUBE2Q2 could serve as a sponge for miR-133a, significantly promoting differentiation and apoptosis of cultured MuSCs, and inhibiting proliferation of MuSCs. Conclusions CircUBE2Q2 is associated with muscle growth and development and induces MuSCs myogenic differentiation through sponging miR-133a. This study will provide new clues for the mechanisms by which mRNAs and non-coding RNAs regulate skeletal muscle growth and development, affecting muscle quality and diseases.

Abstract Background With the advantages of better cosmetic incision and faster recovery, uniportal video-assisted thoracoscopic surgery (UP-VATS) has developed rapidly worldwide in recent decades, and indications for UP-VATS have been further expanded to those for conventional VATS. Complex segmentectomy that makes several or intricate intersegmental planes, with more complex procedures, continues to be difficult in minimally invasive techniques. However, there are few reports on UP-VATS complex segmentectomy. In this report, we describe the perioperative clinical data and operative techniques and present our early results of UP-VATS complex segmentectomy in our hospital. Methods The records of a total of 30 patients who underwent UP-VATS complex segmentectomy by a single surgeon between January 2021 and June 2021 were retrospectively reviewed. We defined cases as complex segmentectomy if they required resection of segments 9 and 10, combined segmentectomy, segmentectomy + subsegmentectomy, subsegmentectomy, or combined subsegmentectomy. Results The mean age was 52.8 ± 9.9 years old; the mean nodule size was 0.84 ± 0.36 cm; the mean margin width was 2.307 ± 0.309 cm; the median operative time was 229.0 ± 58.06 min; the mean operative hemorrhage was 56.60 ± 17.95 mL; 5.58 ± 1.74 lymph nodes dissected had not metastasized; the mean duration of postoperative chest tube drainage was 4.7 ± 1.4 days; and the mean postoperative hospital stay was 6.5 ± 3.0 days. Although 1 patient experienced a prolonged air leak, the other 29 recovered uneventfully. Another patient failed to reach the 2-cm safe margins and subsequently underwent completion lobectomy. Conclusions UP-VATS complex segmentectomy is a safe and effective procedure in the treatment of lung cancers, sparing more pulmonary parenchyma and ensuring safe margins, with the disadvantage being the lengthy operative times during early skill acquisition.

The accurate measurement of coal seam gas content is essential for several aspects of deep coal mining, including disaster management, resource allocation and sustainability. However, obtaining in-situ coal samples while preserving gas content under challenging conditions, such as high stress, temperature fluctuations, and drilling fluid environments, remains a significant challenge. To overcome this difficulty, we present an innovative insitu pressure- and gas-preserved coring tool specifically designed for deep coal mining applications. This device enables the collection of coal seam samples under in-situ conditions while ensuring that both pressure and gas content are preserved, thereby preventing gas escape during sample transfer and providing more accurate parameters for evaluating coal and natural gas reserves. In the demanding environment of deep coal seams, the performance of the pressure-preserved chamber of the corer relies on the reliability of its remote triggering mechanism. The presence of drilling fluid introduces medium resistance, which can impair the triggering process--an issue largely overlooked in previous research. Herein, we propose a robust method to calculate remote triggering forces within liquid media and optimize its key parameters to improve operational stability. Laboratory tests and field validations in coal mining environments are conducted, which confirm the effectiveness of the optimized design and demonstrate the tool's practical applicability. This study offers valuable insights into addressing key challenges in deep coal reservoir exploration and gas resource preservation. [ABSTRACT FROM AUTHOR]

Using pressure-preserved coring technique to determine in-situ gas content provides a more precise assessment of gas resource reserves and safeguard of mining safety in coal seams. How coring technique and depth affect the determination of gas content is unclear due to borehole zoning rupture caused by roadway excavation and drilling disturbance. To this end, a proposed coupling model of stress distribution and gas migration was simulated and validated by FLAC3D and COMSOL Multiphysics considering superposition effects of roadway excavation and drilling disturbance. The findings indicate that the roadway surrounding rock displays distinct zoning features including stress relief zone, stress concentration zone that is composed of plastic zone, elastic zone, and original stress zone; and the broken situations depending on the borehole peeping are consistent with the corresponding simulation results. On this basis, this study proposes a set of drilling coring depth calculation and prediction model for the gas desorption affected area under engineering disturbance. Optimal depth of coring drilling is not only approach to the in-situ coal bulk, but also can get the balance of the drilling workload and cost controlling. According to the typical mine site geological conditions and the numerical simulation results in this study, if the roadway excavation time is ~1 year, it is recommended that the pressure-preserved coring depth should be greater than 17 m. [ABSTRACT FROM AUTHOR]

The pressure-preserving controller is the core part of deep in-situ pressure-preserving coring (IPPCoring) system, and its pressure-preserving capability is the key to IPP-Coring technology. To achieve a good understanding of the influence of mechanical properties of materials on the ultimate pressurebearing capability (UPB-Capability) of the pressure-preserving controller, the IPP-Coring experimental platform was developed to test the UPB-Capability of pressure-preserving controllers of four different materials. The experimental results show that the UPB-Capability of pressure-preserving controllers with different material varies greatly. A numerical model of the pressure-preserving controller was developed to study the influences of mechanical parameters of materials on the UPB-Capability of the pressurepreserving controller after the accuracy of the numerical model is verified by experiments. The results indicate that the yield strength (YS) and Poisson's ratio (PR) of the material have little effect on the UPBCapability of the pressure-preserving controller, whereas the elastic modulus (EM) of the material has a significant effect. A generalized model of the UPB-Capability of the pressure-preserving controller is developed to reveal the mechanism of the influence of material properties on the UPB-Capability of the pressure-preserving controllers. Considering these results, the future optimization direction of the pressure-preserving controller and material selection scheme in practical engineering applications of the pressure-preserving controller are suggested. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress has been associated with the dysfunction of intestinal barrier in humans and animals. We have previously shown that oral administration of glycine to suckling-piglets improves ER stress-related intestinal mucosal barrier impairment and jejunal epithelial apoptosis. However, the underlying mechanism remains unknown. In this study, the protective effect and the mechanism of glycine on apoptosis and dysfunction in intestinal barrier induced by brefeldin A (BFA), an ER stress inducer, was explored in porcine intestinal epithelial cells (IPEC-1). The results showed that BFA treatment led to enhanced apoptosis and upregulation of proteins involved in ER stress signaling, including inositol-requiring enzyme 1α (IRE1α), activating transcription factor 6α (ATF6α), c-Jun N-terminal kinase (JNK), and C/EBP-homologous protein (CHOP). In addition, BFA induced a dysfunction in intestinal epithelial barrier, as evidenced by the increased paracellular permeability, decreased transepithelial electrical resistance (TEER), and reduced abundance of tight junction proteins (occludin, claudin-1, zonula occludens [ZO]-1, and ZO-2). These alterations triggered by BFA were significantly abolished by glycine treatment (P

Understanding deformation of Mg along the c-axis is important for wrought processing of Mg. Here the authors report deformation graining in submicron single crystal Mg where the initial single crystal evolves into ultrafine grains that rejuvenates dislocation activities, enabling large plasticity.

Abstract Synthetic biology has been represented by the creation of artificial life forms at the genomic scale. In this work, a CRISPR‐based chromosome‐doubling technique is designed to first construct an artificial diploid Escherichia coli cell. The stable single‐cell diploid E. coli is isolated by both maximal dilution plating and flow cytometry, and confirmed with quantitative PCR, fluorescent in situ hybridization, and third‐generation genome sequencing. The diploid E. coli has a greatly reduced growth rate and elongated cells at 4–5 µm. It is robust against radiation, and the survival rate after exposure to UV increased 40‐fold relative to WT. As a novel life form, the artificial diploid E. coli is an ideal substrate for research fundamental questions in life science concerning polyploidy. And this technique may be applied to other bacteria.

Abstract Background Sleep disruption is a major public health issue and may increase the risk of mortality by ten-folds if an individual is sleeping less than 6 h per night. Sleep has changed dramatically during to the COVID-19 pandemic because COVID symptoms can lead to psychological distress including anxiety. Hericium erinaceus mycelium has been widely investigated in both the in vivo studies and clinical trials for its neuroprotective functions because the mycelium contains hericenones and erinacines, which synthesize the nerve growth factor and brain-derived neurotrophic factor (BDNF). Recent in vivo reports have shown showed that erinacine A-enriched Hericium erinaceus mycelium can modulate BDNF/TrkB/PI3K/Akt/GSK-3β pathways to induce an antidepressant-like effect. A large body of evidence indicates that erinacine can pass the blood-brain barrier and suggests its neuroprotective function in both peripheral and central nervous systems. Thus, Hericium erinaceus mycelium may be a dual-function supplement for sleep disruption improvement while sustaining anxiolytic effects. Method To simulate the condition of sleep disruption, the mice were subjected to the tail suspension test (TST) for 15 min every day during the same period for nine consecutive days. Two different doses (75 and 150 mg/kg) of Hericium erinaceus mycelium were administered orally 20 min prior to the TSTs before entering the light period of 12:12 h L:D cycle. All sleep-wake recording was recorded for 24 h using electroencephalogram and electromyogram. The elevated-plus-maze and open-field tests were conducted to record the behavior activities. Results Consecutive TSTs prior to the light period could cause significant sleep disturbance and anxiety behavior in the elevated-plus-maze experiments. Results showed that administration with Hericium erinaceus mycelium at 150 mg/kg ameliorated the rodent anxiety (p

BackgroundImmune checkpoint inhibitors are increasingly used in neoadjuvant therapy for locally advanced gastric cancer. However, the effect of body composition on the efficacy of neoadjuvant therapy has not been reported.MethodsThe computed tomography (CT) images and clinicopathological data of 101 patients with locally advanced gastric cancer who received neoadjuvant chemotherapy combined with immunotherapy (NCI) from 2019 to 2021 were collected. The CT image of L3 vertebral body section was selected, and the body composition before and after the neoadjuvant treatment was calculated using the SliceOmatic software, mainly including skeletal muscle index (SMI), subcutaneous adipose index (SAI), and visceral adipose index (VAI). The relationship between body composition and the efficacy and adverse events of NCI was analyzed.ResultsOf the 101 patients, 81 with evaluable data were included in the analysis. Of the included patients, 77.8% were male; the median age of all the patients was 62 years, and the median neoadjuvant therapy cycle was three. After the neoadjuvant therapy, 62.9% of the tumors were in remission (residual tumor cells ≤ 50%), and 37.1% of the tumors had no remission (residual tumor cells>50%). Moreover, 61.7% of the patients had treatment-related adverse events (TRAEs), and 18.5% had immune-related adverse events (irAEs). After neoadjuvant therapy, the body mass index (from 23 to 22.6 cm2/m2, p=0.042), SAI (from 34.7 to 32.9 cm2/m2, p=0.01) and VAI (from 32.4 to 26.8 cm2/m2, p=0.005) were significantly lower than those before treatment, while the SMI had no significant change (44.7 vs 42.5 cm2/m2, p=0.278). The multivariate logistics regression analysis revealed that low SMI (odds ratio [OR]: 3.23,95% confidence interval [CI]: 1.06–9.81, p=0.047), SMI attenuation (△SMI) ≥ 1.8(OR: 1.45,95%CI: 1.20–3.48, p=0.048), and clinical node positivity (OR: 6.99,95%CI: 2.35–20.82, p=0.001) were independent risk factors for non-remission. Additionally, high SAI is an independent risk factor for irAEs (OR: 14, 95%CI: 1.73–112.7, p=0.013).ConclusionLow SMI and △SMI≥1.8 are independent risk factors for poor tumor regression in patients with advanced gastric cancer receiving NCI. Patients with a high SAI are more likely to develop irAEs.