Search

A crystal plasticity model based on Electron Backscatter Diffraction (EBSD) experimental data has been developed to simulate the tensile behavior of additively manufactured TiAl alloys at various temperatures. To accurately capture the activity of different slip systems and their contribution to the material's plasticity, multiple slip systems across different phases are considered. The validity of the model is verified by comparing the simulation results, such as microscopic properties, with experimental and test data. Additionally, a continuous damage model is incorporated to analyze the damage behavior of additively manufactured TiAl alloys at different temperatures. Compared to experimental data, the crystal plasticity model incorporating damage effectively simulates the tensile failure behavior of TiAl alloys across a range of temperatures.

γ−TiAl alloy, with its high specific strength and creep resistance, is ideal for aerospace engines and gas turbines, but its brittleness poses significant manufacturing and processing challenges. To address these issues, this study employs a crystal plasticity finite element method incorporating dislocation and twinning to analyze the brittle-to-ductile transition behavior of γ−TiAl alloy at different temperatures. Additionally, the Bayesian optimization methods are employed to efficiently and accurately obtain parameters related to numerical calculations of crystal plasticity. The results indicate that at room temperature, the high activation resistance of the slip systems in the α2 phase leads to limited slip activity, resulting in poor plasticity. However, at 750 °C and 850 °C, the strength of the slip systems decreases significantly, allowing more α2 phase lamellae in the γ-TiAl alloy to undergo greater plastic deformation. This enhancement in the plastic deformation capacity of the α2phase lamellae reduce the overall deformation incompatibility in the TiAl alloy, thereby improving the overall ductile of the γ-TiAl alloy.

Abstract Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE); even combining IR with immune checkpoint inhibitors has shown only anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug, disulfiram (DSF), complexed with copper (DSF/Cu) to induce tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine. We determined the anticancer response by primary tumor rejection and assessed systemic immune responses by tumor rechallenge and the occurrence of AEs relative to spontaneous lung metastasis. In addition, we analyzed immune cell subsets and quantified proinflammatory and immunosuppressive chemokines/cytokines in the tumor microenvironment (TME) and blood of the vaccinated mice. Immune cell depletion was investigated for its effects on the vaccine-induced anticancer response. The results showed that DSF/Cu and IR induced more potent ICD under hypoxia than normoxia in vitro. Low-dose intratumoral (i.t.) injection of DSF/Cu and IR(12Gy) demonstrated strong anti-primary and -rechallenged tumor effects and robust AEs in mouse models. These vaccinations also increased CD8+ and CD4+ cell numbers while decreasing Tregs and myeloid-derived suppressor cells in the 4T1 model, and increased CD8+, dendritic cells (DC), and decreased Treg cell numbers in the MCa-M3C model. Depleting both CD8+ and CD4+ cells abolished the vaccine’s anticancer response. Moreover, vaccinated tumor-bearing mice exhibited increased TNFα levels and reduced levels of immunosuppressive chemokines/cytokines. In conclusion, our novel approach generated an anticancer immune response that results in a lack of or low tumor incidence post-rechallenge and robust AEs, i.e., absence of or decreased spontaneous lung metastasis in tumor-bearing mice. This approach is readily translatable to clinical settings and may increase IR-induced AEs in cancer patients.

Abstract In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in 20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.

Abstract The key to designing photocatalysts is to orient the migration of photogenerated electrons to the target active sites rather than dissipate at inert sites. Herein, we demonstrate that the doping of phosphorus (P) significantly enriches photogenerated electrons at Ni active sites and enhances the performance for CO2 reduction into syngas. During photocatalytic CO2 reduction, Ni single‐atom‐anchored P‐modulated carbon nitride showed an impressive syngas yield rate of 85 μmol gcat−1 h−1 and continuously adjustable CO/H2 ratios ranging from 5:1 to 1:2, which exceeded those of most of the reported carbon nitride‐based single‐atom catalysts. Mechanistic studies reveal that P doping improves the conductivity of catalysts, which promotes photogenerated electron transfer to the Ni active sites rather than dissipate randomly at low‐activity nonmetallic sites, facilitating the CO2‐to‐syngas photoreduction process.

Abstract Targeted spatial transcriptomics hold particular promise in analyzing complex tissues. Most such methods, however, measure only a limited panel of transcripts, which need to be selected in advance to inform on the cell types or processes being studied. A limitation of existing gene selection methods is their reliance on scRNA-seq data, ignoring platform effects between technologies. Here we describe gpsFISH, a computational method performing gene selection through optimizing detection of known cell types. By modeling and adjusting for platform effects, gpsFISH outperforms other methods. Furthermore, gpsFISH can incorporate cell type hierarchies and custom gene preferences to accommodate diverse design requirements.

Abstract Background Despite therapeutic advances, once a cancer has metastasized to the bone, it represents a highly morbid and lethal disease. One third of patients with advanced clear cell renal cell carcinoma (ccRCC) present with bone metastasis at the time of diagnosis. However, the bone metastatic niche in humans, including the immune and stromal microenvironments, has not been well-defined, hindering progress towards identification of therapeutic targets. Methods We collected fresh patient samples and performed single-cell transcriptomic profiling of solid metastatic tissue (Bone Met), liquid bone marrow at the vertebral level of spinal cord compression (Involved), and liquid bone marrow from a different vertebral body distant from the tumor site but within the surgical field (Distal), as well as bone marrow from patients undergoing hip replacement surgery (Benign). In addition, we incorporated single-cell data from primary ccRCC tumors (ccRCC Primary) for comparative analysis. Results The bone marrow of metastatic patients is immune-suppressive, featuring increased, exhausted CD8 + cytotoxic T cells, T regulatory cells, and tumor-associated macrophages (TAM) with distinct transcriptional states in metastatic lesions. Bone marrow stroma from tumor samples demonstrated a tumor-associated mesenchymal stromal cell population (TA-MSC) that appears to be supportive of epithelial-to mesenchymal transition (EMT), bone remodeling, and a cancer-associated fibroblast (CAFs) phenotype. This stromal subset is associated with poor progression-free and overall survival and also markedly upregulates bone remodeling through the dysregulation of RANK/RANKL/OPG signaling activity in bone cells, ultimately leading to bone resorption. Conclusions These results provide a comprehensive analysis of the bone marrow niche in the setting of human metastatic cancer and highlight potential therapeutic targets for both cell populations and communication channels.

Cyclone separators are commonly employed in the mining, metallurgy and chemical industries due to their simple structure, easy maintenance and high recovery efficiency. However, with the wide application of cyclone separators, many problems have become exposed in their practical operation, restricting their development. Among these, wall erosion is becoming a significant problem. In this study, to resolve the problem of severe erosion on the walls, the Eulerian–Lagrangian framework was employed to investigate a cyclone separator with a draft plate at the inlet and to evaluate the effect of a draft plate with angles of 0°, 45° and 90° on the degree of erosion and the stabilization of flow fields. Moreover, after verifying the reliability of the numerical model via data from experiments, the characteristics of gas–solid flow were analyzed and the effects of the new structure on the degree of wear were investigated. The results demonstrated that unfavorable phenomena such as secondary flow and wall erosion generated during the operation could be mitigated by the draft plate. When the plate angle was 90°, the wall erosion was the lightest and the range of influence of the secondary flow was the smallest. When the plate angle was 45°, the comprehensive performance was the best, and there was a better balance between the energy loss and the degree of wall erosion. Therefore, the presence of the draft plate has a significant impact on the interaction of gas–solid phases in a cyclone separator.

Abstract The poor efficacy of chimeric antigen receptor T-cell therapy (CAR T) for solid tumors is due to insufficient CAR T cell tumor infiltration, in vivo expansion, persistence, and effector function, as well as exhaustion, intrinsic target antigen heterogeneity or antigen loss of target cancer cells, and immunosuppressive tumor microenvironment (TME). Here we describe a broadly applicable nongenetic approach that simultaneously addresses the multiple challenges of CAR T as a therapy for solid tumors. The approach reprograms CAR T cells by exposing them to stressed target cancer cells which have been exposed to the cell stress inducer disulfiram (DSF) and copper (Cu)(DSF/Cu) plus ionizing irradiation (IR). The reprogrammed CAR T cells acquire early memory-like characteristics, potent cytotoxicity, enhanced in vivo expansion, persistence, and decreased exhaustion. Tumors stressed by DSF/Cu and IR also reprogram and reverse the immunosuppressive TME in humanized mice. The reprogrammed CAR T cells, derived from peripheral blood mononuclear cells of healthy donors or metastatic female breast cancer patients, induce robust, sustained memory and curative anti-solid tumor responses in multiple xenograft mouse models, establishing proof of concept for empowering CAR T by stressing tumor as a promising therapy for solid tumors.

针对市场在售的调和油、玉米油、大豆油、花生油和菜籽油等食用植物油,随机购买20种共290份食用植物油样品。采用液相色谱法测定AFB1、AFB2、AFG1、AFG2以及OTA、OTB真菌毒素的含量，对食用植物油中黄曲霉毒素和赭曲霉毒素的污染水平和分布特征进行分析。结果表明：20种290份食用植物油样品中，有16种共67份样品存在不同程度的真菌毒素污染，总污染率达到23.1%，不同种类食用植物油污染呈现“多种类、共分布”的特点，其中AFG1污染率（14.8%）最高，其次为OTA（13.4%）。绝大多数阳性样本受1～4种真菌毒素污染，仅有少数阳性样本受真菌毒素污染数量达到5种。总体上食用植物油样品受到多种真菌毒素的混合污染情况比较严重，应引起一定的重视。 A total of 290 samples from 20 kinds of edible vegetable oils such as blended oil, corn oil, soybean oil, peanut oil, and rapeseed oil on the market were randomly purchased. Then, the contents of AFB1, AFB2, AFG1, AFG2, OTA and OTB were accurately determined by HPLC to investigate the pollution levels and distribution characteristics of aflatoxins and ochratoxins in edible vegetable oils. The results showed that among the 20 kinds of 290 edible vegetable oil samples, 16 kinds of 67 samples suffered from different degrees of mycotoxin contamination, and the total pollution rate reached 23.1%. The pollution of different kinds of edible vegetable oils presented the characteristics of multi-species and co-distribution. AFG1 had the highest pollution rate (14.8%), followed by OTA (13.4%). Besides, the vast majority of positive samples were contaminated by 1-4 kinds of mycotoxins, only a few positive samples were contaminated with 5 kinds of mycotoxins. Overall, the problem that the edible vegetable oil samples are polluted by multiple mycotoxins is serious and should be paid attention to.

ObjectiveTo compare our initial perioperative and postoperative outcomes of the modified anterior approach (MA) with Retzius space preservation robot-assisted radical prostatectomy (RARP) with the standard anterior approach (SA) RARP.Materials and methodsA retrospective analysis was performed on 116 patients with RARP completed by the same surgeon between September 2019 and March 2022. They were divided into SA-RARP group (77 cases) and MA-RARP group (39 cases). Propensity score matching was performed using eight preoperative variables, including age, BMI, preoperative PSA, biopsy Gleason score, prostate volume, D’Amico risk classification, SHIM, and clinical T stage. Functional outcome was assessed by urine pad count and SHIM after surgery, and oncological outcome was assessed by statistics of postoperative pathological findings as well as follow-up postoperative PSA. The median follow-up was 13 months and 17 months for MA-RARP and SA-RARP groups respectively.ResultsPropensity score matching was performed 1:1, and baseline data were comparable between the two groups after matching. Comparison of postoperative data: MA-RARP group had less mean EBL than SA-RARP group (200 vs 150 ml, p = 0.033). PSM did not differ between groups (p = 1). In terms of urinary control recovery, the MA-RARP group showed significant advantages in urinary control recovery at 24 h, 2 weeks, 1 month and 3 months after catheter removal, respectively (48.6% vs 5.7%, p < 0.001; 80% vs 22.9%, p < 0.001; 94.3% vs 51.4%, p < 0.001; 100% vs 74.3%, p = 0.002). This advantage gradually disappeared 6 months or more after surgery. The median time to recovery of sexual function was shorter in the MA-RARP group (165 vs 255 d, p = 0.001).ConclusionMA-RARP is safe and reliable, and can achieve better early urinary control function and sexual function recovery while achieving the primary tumor control goal.

Abstract The dysbiosis of the gut microbiome is one of the pathogenic factors of nonalcoholic fatty liver disease (NAFLD) and also affects the treatment and intervention of NAFLD. Among gut microbiomes, keystone species that regulate the integrity and stability of an ecological community have become the potential intervention targets for NAFLD. Here, we collected stool samples from 22 patients with nonalcoholic steatohepatitis (NASH), 25 obese patients, and 16 healthy individuals from New York for 16S rRNA gene sequencing. An algorithm was implemented to identify keystone species based on causal inference theories and dynamic intervention simulation. External validation was performed in an independent cohort from California. Eight keystone species in the gut of NAFLD, represented by Porphyromonas loveana, Alistipes indistinctus, and Dialister pneumosintes, were identified, which could efficiently restore the microbial composition of the NAFLD toward a normal gut microbiome with 92.3% recovery. These keystone species regulate intestinal amino acid metabolism and acid–base environment to promote the growth of the butyrate‐producing Lachnospiraceae and Ruminococcaceae species that are significantly reduced in NAFLD patients. Our findings demonstrate the importance of keystone species in restoring the microbial composition toward a normal gut microbiome, suggesting a novel potential microbial treatment for NAFLD.

ObjectivePrimary adrenal malignant tumor is rare. The factors affecting the prognosis remain poorly defined. This study targeted to construct and corroborate a model for predicting the overall survival of adrenal malignant tumor patients.MethodsWe investigated the SEER database for patients with primary adrenal malignant tumor. 1,080 patients were divided into a construction cohort (n = 756) and a validation cohort (n = 324), randomly. The prognostic factors for overall survival were evaluated using univariate and multivariate Cox analyses. The nomogram was constructed and then validated with C-index, calibration curve, time-dependent ROC curve, and decision curve analysis in both cohorts. Then we divided the patients into 3 different risk groups according to the total points of the nomogram and analyzed their survival status by Kaplan-Meier curve with log-rank test.ResultsThe baseline characteristics of these two cohorts were not statistically different (P > 0.05). Using univariate and multivariate Cox analyses, 5 variables, including age, tumor size, histological type, tumor stage, and surgery of primary site, were distinguished as prognostic factors (P

In the current work, a multiscale model was developed coupling a macro-model with the macromechanical physically based yield strength and a crystal plasticity model with micromechanical properties and realistic grain orientation based on the representative volume element. The simulation results show that the effect of microstructure on the macromechanical properties can be considered in the macro constitutive model due to a good consistency between experimental and computed results; whereas solid strengthening, grain boundaries, and dislocation density played a more crucial role than others. Besides coupling simulation and microstructure by EBSD, the microstructure evolution can be well explained by the micromechanical model. Strain is related to the grain orientation, leading to inhomogeneous deformation, forming the various Schmid factor and slip systems. A plastic strain occurs close to the grain boundaries and declines into the grain, resulting in higher kernel average misorientation (KAM) and geometry necessary dislocations (GNDs) in the grain boundaries. The higher the loading, the higher the local strain. Shear bands with around 45 degrees can be formed, resulting in crack initiation and tensile shear failure. This work has developed the guidance of structural integrity assessment and prediction of mechanical properties for the engineering material and components.

Abstract Associations between gut microbiota and colorectal cancer (CRC) have been widely investigated. However, the replicable markers for early-stage adenoma diagnosis across multiple populations remain elusive. Here, we perform an integrated analysis on 1056 public fecal samples, to identify adenoma-associated microbial markers for early detection of CRC. After adjusting for potential confounders, Random Forest classifiers are constructed with 11 markers to discriminate adenoma from control (area under the ROC curve (AUC) = 0.80), and 26 markers to discriminate adenoma from CRC (AUC = 0.89), respectively. Moreover, we validate the classifiers in two independent cohorts achieving AUCs of 0.78 and 0.84, respectively. Functional analysis reveals that the altered microbiome is characterized with increased ADP-l-glycero-beta-d-manno-heptose biosynthesis in adenoma and elevated menaquinone-10 biosynthesis in CRC. These findings are validated in a newly-collected cohort of 43 samples using quantitative real-time PCR. This work proves the validity of adenoma-specific markers across multi-populations, which would contribute to the early diagnosis and treatment of CRC.

Summary: Achieving high selectivity and activity with the oxygen reduction reaction (ORR) is significant for developing efficient energy conversion techniques and chemical production. Here, we report that selective ORRs can be achieved by tuning short-range order in amorphous and crystalline NiO nanosheets (a-NiO NSs and c-NiO NSs, respectively). X-ray absorption spectroscopy analysis reveals that the short-range order of a-NiO NSs and c-NiO NSs mainly adopt the NiO5 pyramidal and NiO6 octahedral structures, respectively. The a-NiO NSs for electrochemical H2O2 production in 0.1 M KOH exhibits both high selectivity over 90% and high activity (1 mA cm−2 at 0.66 V versus RHE), while c-NiO NSs tends to catalyze ORRs through 4-electron pathways to generate H2O. Theoretical calculations indicate that the changed short-range order of a-NiO NSs leads to alteration of Ni d-orbital states, which can regulate the adsorption orientation and strength of ∗OOH intermediates to achieve high selectivity and activity of 2-electron ORRs.

Transmembrane and ubiquitin-like domain-containing 1 (Tmub1) inhibits hepatocyte proliferation during liver regeneration, but its role in hepatocellular carcinoma (HCC) has yet to be revealed. In this study, we show that the levels of Tmub1 were significantly lower in HCC tissues and cells than they were in adjacent tissues and normal hepatic cells, and the low levels of Tmub1 indicated a poor prognosis in HCC patients. Xenograft growth assay revealed that Tmub1 represses HCC growth in vivo. In addition, Tmub1 formed a protein complex with apoptosis-associated protein tumor protein 63 (p63), especially with the ΔN isoforms (ΔNp63α, β, and γ). Further loss- and gain-of-function analyses indicated that Tmub1 promotes apoptosis of Hep3B and MHCC-LM3 cells. Tmub1 decreased the protein expression of ΔNp63, and the pro-apoptotic effect of Tmub1 can be reversed by ΔNp63 isoforms (α, β, and γ). Additionally, we report that Tmub1 promotes the ubiquitination and degradation of ΔNp63 proteins. Finally, we confirmed in HCC tissues that Tmub1 is negatively correlated with ΔNp63 and positively correlated with the level of apoptosis. Taken together, Tmub1 suppresses HCC by enhancing the ubiquitination and degradation of ΔNp63 isoforms to induce HCC cell apoptosis. These findings provide a potential strategy for the management of HCC.

Abstract Constructing nitrogen (N2) adsorption and activation sites on semiconductors is the key to achieving efficient N2 photofixation. Herein, Mn–W dual‐metal sites on WO3 are designed toward efficient N2 photoreduction via controlled Mn doping. Impressively, the optimal 2.3% Mn‐doped WO3 (Mn‐WO3) exhibits a remarkable ammonia (NH3) production rate of 425 µmol gcat.−1 h−1, representing the best catalytic performance among the ever‐reported tungsten oxide‐based photocatalysts for N2 fixation. Quasi in situ synchrotron radiation X‐ray spectroscopy directly identifies that the Mn–W dual‐metal sites can enhance the polarization of the adsorbed N2, which is beneficial to the N2 activation. Further theoretical calculations reveal that the increased polarization is originated from the electron back‐donation into the antibonding orbitals of the adsorbed N2, hence lowering the reaction energy barrier toward the N2 photofixation. The concept of dual sites construction for inert molecule activation offers a powerful platform toward rational design of highly efficient catalysts for nitrogen fixation and beyond.

Guidance systems for visually impaired persons have become a popular topic in recent years. Existing guidance systems on the market typically utilize auxiliary tools and methods such as GPS, UWB, or a simple white cane that exploits the user’s single tactile or auditory sense. These guidance methodologies can be inadequate in a complex indoor environment. This paper proposes a multi-sensory guidance system for the visually impaired that can provide tactile and auditory advice using ORB-SLAM and YOLO techniques. Based on an RGB-D camera, the local obstacle avoidance system is realized at the tactile level through point cloud filtering that can inform the user via a vibrating motor. Our proposed method can generate a dense navigation map to implement global obstacle avoidance and path planning for the user through the coordinate transformation. Real-time target detection and a voice-prompt system based on YOLO are also incorporated at the auditory level. We implemented the proposed system as a smart cane. Experiments are performed using four different test scenarios. Experimental results demonstrate that the impediments in the walking path can be reliably located and classified in real-time. Our proposed system can function as a capable auxiliary to help visually impaired people navigate securely by integrating YOLO with ORB-SLAM.

Histone deacetylase 6 (HDAC6) acts as a regulator of the nuclear factor kappa-B (NF-κB) signaling pathway by deacetylating the non-histone protein myeloid differentiation primary response 88 (MyD88) at lysine residues, which is an adapter protein for the Toll-like receptor (TLR) and interleukin (IL)-1β receptor. Over-activated immune responses, induced by infiltrated immune cells, excessively trigger the NF-κB signaling pathway in other effector cells and contribute to the development of rheumatoid arthritis (RA). It has also been reported that HDAC6 can promote the activation of the NF-κB signaling pathway. In the present study, we showed that HDAC6 protein level was increased in the synovium tissues of adjuvant-induced arthritis rats. In addition, hydrogen sulfide (H2S) donor S-propargyl-cysteine (SPRC) can inhibit HDAC6 expression and alleviate inflammatory response in vivo. In vitro study revealed that HDAC6 overexpression activated the NF-κB signaling pathway by deacetylating MyD88. Meanwhile, sodium hydrosulfide (NaHS) or HDAC6 inhibitor tubastatin A (tubA) suppressed the pro-inflammatory function of HDAC6. Furthermore, the reduced expression of HDAC6 appeared to result from transcriptional inhibition by S-sulfhydrating specificity protein 1 (Sp1), which is a transcription factor of HDAC6. Our results demonstrate that Sp1 can regulate HDAC6 expression, and S-sulfhydration of Sp1 by antioxidant molecular H2S ameliorates RA progression via the HDAC6/MyD88/NF-κB signaling pathway.

Triclosan (TCS), an antimicrobial agent widely used in personal care products and ubiquitously exists in environment, has drawn increasing concern due to its potential to exert multiple adverse effects, ranging from endocrine disruption to carcinogenesis. However, the mechanism of these adverse effects is still not fully elucidated. More and more studies have shown that chemical reactive metabolites (RMs) covalently binding to proteins is a possible reason for these adverse effects, but there is still a lack of appropriate methods to predict or evaluate these adverse effects due to the extremely low abundance of the modified proteins in complex biological samples. In this study, we attempted to address this problem and investigate the possible mechanism of TCS adverse effects by a shotgun proteomics approach based on three-dimensional-liquid chromatography-mass spectrometry (3D-LC-MS). First, the in vitro incubation with model amino acids and protein in microsomes showed that TCS could react with cysteine residue of proteins through 3 types of RMs. Then, a 3D-LC-MS approach was developed to sensitively determine the low abundant modified proteins, which resulted in the identification of 45 TCS-modified proteins, including albumin, haptoglobin and NR1I2, in rats. STRING analysis indicated that these modified proteins mainly were involved in reproductive and development system, endocrine and immune system, and carcinogenesis, which were in accord with the main reported TCS-induced adverse effects and suggested that the covalent modification of TCS RMs for proteins might affect their activities and functions, thus inducing serious adverse effects. This study provided a new insight into the mechanism of TCS adverse effects and may serve as a valuable method to predict or evaluate adverse effects of ubiquitous chemicals. Keywords: Triclosan, Adverse effects, Reactive metabolites, Covalent protein modification, In vivo, Three-dimensional-liquid chromatography-mass spectrometry

Abstract Metal‐containing polymer networks are ubiquitous in biological systems, and their unique structures enable a variety of fascinating biological behaviors. Cuticle of mussel byssal threads, containing Fe‐catecholate complexes, shows remarkably high hardness, high extensibility, and self‐healing capability. Understanding strengthening and self‐healing mechanisms is essential for elucidating animal behaviors and rationally designing mussel‐inspired materials. Here, direct evidence of Fe3+ and Fe2+ gradient distribution across the cuticle thickness is demonstrated, which shows more Fe2+ inside the inner cuticle, to support the hypothesis that the cuticle is a functionally graded material with high stiffness, extensibility, and self‐healing capacity. The mechanical tests of the mussel threads show that both strength and extensibility of the threads decrease with increasing oxygen contents, but this property degradation can be restored upon removing the oxygen. The first‐principles calculations explain the change in iron coordination, which plays a key role in strengthening, degradation, and self‐healing of the polymer networks. The oxygen absorbs on metal ions, weakening the iron‐catecholate bonds in the cuticle and collagen core, but this process can be reversed by sea water. These findings can have important implications in the design of next‐generation bioinspired robust, highly extensible materials, and catalysis.

Allergen immunotherapy (AIT) is the only treatment that can change the course of allergic diseases. However, there has not been any research on metabolic reactions in relation to AIT with single or mixed allergens. In this study, patients with allergic rhinitis caused by Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f) were treated with single-mite (Der p) and double-mite (Der p:Der f = 1:1) subcutaneous immunotherapy (SCIT), respectively. To compare the efficacy and the dynamic changes of inflammation-related single- and double-species mite subcutaneous immunotherapy (SM-SCIT and DM-SCIT), we performed visual analogue scale (VAS) score, rhinoconjunctivitis quality of life questionnaire (RQLQ) score and serum metabolomics in allergic rhinitis patients during SCIT. VAS and RQLQ score showed no significant difference in efficacy between the two treatments. A total of 57 metabolites were identified, among which downstream metabolites (5(S)-HETE (Hydroxyeicosatetraenoic acid), 8(S)-HETE, 11(S)-HETE, 15(S)-HETE and 11-hydro TXB2) in the ω-6-related arachidonic acid and linoleic acid pathway showed significant differences after approximately one year of treatment in SM-SCIT or DM-SCIT, and the changes of the above serum metabolic components were correlated with the magnitude of RQLQ improvement, respectively. Notably, 11(S)-HETE decreased more with SM-SCIT, and thus it could be used as a potential biomarker to distinguish the two treatment schemes. Both SM-SCIT and DM-SCIT have therapeutic effects on patients with allergic rhinitis, but there is no significant difference in efficacy between them. The reduction of inflammation-related metabolites proved the therapeutic effect, and potential biomarkers (arachidonic acid and its downstream metabolites) may distinguish the options of SCIT.

The root of Aconitum kusnezoffii (Caowu in Chinese, CW) is not only commonly used as a traditional Chinese medicine (TCM), but also served as a tonic in China. Due to its high toxicity, clinical poisoning cases induced by CW have frequently been reported. However, the mechanism is still unclear. In this study, Aconitum alkaloids and altered endogenous metabolites in CW poisoning patients were investigated to elucidate the possible intoxication mechanism. Eighteen alkaloids, including 6 toxic diester diterpenoid alkaloids (DDAs), were determined from the sera of patients. At the same time, 5-(diisopropylamino)amylamine (DIAAA) derivatization-ultrahigh performance liquid chromatography- quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF/MS) approach was applied in the metabolomics analysis to find much more carboxyl-containing metabolites (CCMs), which are the essential components for life and critical to elucidate the mechanism of toxicity. As a result, 32 altered metabolites after poisoning were identified. Among them, hydroxyeicosatetraenoic acids (HETEs) and some dicarboxylic acids were first found to be related to Aconitum alkaloids toxicity. Finally, biological pathway analysis indicated that the significantly changed metabolites were primarily involved in amino acid metabolism, TCA cycle, fatty acid metabolism, pyruvate metabolism, arachidonic acid metabolism, sphingolipid metabolism and so on. These results can not only provide more information on the mechanism of CW intoxication but also help the clinical diagnosis of CW poisoning.

The structural characteristics and modes of the Stewart platform driven by electric cylinders are briefly introduced. Based on Simulink, the modelling method of the platform is analysed. To obtain the coordinate transformation of Stewart platform, the rotation matrix and homogeneous transformation are resolved, and the mathematical model of the electric-driven Stewart platform is established related to the structural characteristics. The simulation model of input and output signals is constructed by using graphical user interface (GUI) module provided by Simulink. The motion simulation curves of six electric actuators under different position and posture are obtained, which gives benefit to understand and control the different motion states of the electric-driven Stewart platform.