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Abstract Integration of functional fillers into liquid metals (LM) induces rheology modification, enabling the free-form shaping of LM at the micrometer scale. However, integrating non-chemically modified low-dimensional materials with LM to form stable and uniform dispersions remain a great challenge. Herein, we propose a solvent-assisted dispersion (SAD) method that utilizes the fragmentation and reintegration of LM in volatile solvents to engulf and disperse fillers. This method successfully integrates MXene uniformly into LM, achieving better internal connectivity than the conventional dry powder mixing (DPM) method. Consequently, the MXene/LM (MLM) coating exhibits high electromagnetic interference (EMI) shielding performance (105 dB at 20 μm, which is 1.6 times that of coatings prepared by DPM). Moreover, the rheological characteristic of MLM render it malleable and facilitates direct printing and adaptation to diverse structures. This study offers a convenient method for assembling LM with low-dimensional materials, paving the way for the development of multifunctional soft devices.

BackgroundMalnutrition often occurs in patients with colorectal cancer. This study aims to develop a predictive model based on GLIM criteria for patients with colorectal cancer who underwent radical surgery.MethodsFrom December 2015 to May 2021, patients with colorectal cancer who underwent radical surgery at our center were recruited for this study. We prospectively collected data on GLIM-defined malnutrition and other clinicopathological characteristics. Using Cox regeneration, we developed a novel nomogram for prognostic prediction, which was validated and compared to traditional nutritional factors for predictive accuracy.ResultsAmong the 983 patients enrolled in this study, malnutrition was identified in 233 (23.70%) patients. Multivariate analysis indicated that GLIM-defined malnutrition is the independent risk factor for overall survival (HR = 1.793, 95% CI = 1.390–2.313 for moderate malnutrition and HR = 3.485, 95% CI = 2.087–5.818 for severe malnutrition). The novel nomogram based on the GLIM criteria demonstrated a better performance than existing criteria, with AUC of 0.729, 0.703, and 0.683 for 1-year, 3-year, and 5-year OS, respectively, in the validation cohort. In addition, the risk score determined by this system exhibited significantly poorer short-term and long-term clinical outcomes in high-risk groups in both malnourished and well-nourished patients.ConclusionCombining handgrip strength, serum albumin level, and TNM stage would help improve the predictive effect of GLIM criteria for colorectal cancer patients post-radical surgery and benefit the individual prognostic prediction of colorectal cancer.

BackgroundPrevious studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD).MethodsSummary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we applied multiple robust analytical methods, with the inverse variance weighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions.ResultsA potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 – 1.49, P < 0.001), which was further confirmed by meta-analysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 – 1.50, P < 0.001), and this was also confirmed by meta-analysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them.ConclusionOur study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work.

Abstract Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.

IntroductionBispecific antibodies (BsAbs) can simultaneously target two epitopes of different antigenic targets, bringing possibilities for diversity in antibody drug design and are promising tools for the treatment of cancers and other diseases. T-cell engaging bsAb is an important application of the bispecific antibody, which could promote T cell-mediated tumor cell killing by targeting tumor-associated antigen (TAA) and CD3 at the same time.MethodsThis study comprised antibodies purification, Elisa assay for antigen binding, cytotoxicity assays, T cell activation by flow cytometry in vitro and xenogenic tumor model in vivo.ResultsWe present a novel bsAb platform named PHE-Ig technique to promote cognate heavy chain (HC)-light chain (LC) pairing by replacing the CH1/CL regions of different monoclonal antibodies (mAbs) with the natural A and B chains of PHE1 fragment of Integrin β2 based on the knob-in-hole (KIH) technology. We had also verified that PHE-Ig technology can be effectively used as a platform to synthesize different desired bsAbs for T-cell immunotherapy. Especially, BCMA×CD3 PHE-Ig bsAbs exhibited robust anti-multiple myeloma (MM) activity in vitro and in vivo.DiscussionMoreover, PHE1 domain was further shortened with D14G and R41S mutations, named PHE-S, and the PHE-S-based BCMA×CD3 bsAbs also showed anti BCMA+ tumor effect in vitro and in vivo, bringing more possibilities for the development and optimization of different bsAbs. To sum up, PHE1-based IgG-like antibody platform for bsAb construction provides a novel strategy for enhanced T-cell immunotherapy.

Abstract Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor and is associated with a poor prognosis. Treatment strategies for PDAC are largely ineffective primarily because of delay in its diagnosis and limited efficacy of systematic treatment. S100A2 is associated with the proliferation, migration, and differentiation of several tumors; however, its effects on PDAC and the associated molecular mechanisms remain to be explored. We studied the mechanisms underlying the effect of S100A2 on epithelial–mesenchymal transition (EMT) and metastasis in PDAC cells. We found that the level of S100A2 remarkably increased and was associated with poor PDAC prognosis. The overexpression of S100A2 in PANC-1 cells also induced EMT, in addition to increasing the invasion and migration of PDAC cells, whereas the knockdown of S100A2 markedly inhibited cell metastasis. Furthermore, S100A2 was found to enhance metastatic abilities in vivo. The overexpression of S100A2 increased SMAD4 expression, whereas the knockdown of S100A2 reduced SMAD4 expression. SMAD4 overexpression could effectively rescue the effects of S100A2 knockdown on EMT. S100A2 mechanistically activated the transforming growth factor (TGF)-β/Smad2/3 signaling pathway, upregulated SMAD4 expression, induced EMT, and increased PANC-1 cell metastasis. In conclusion, the S100A2/SMAD4 axis modulates EMT to accelerate PDAC development. Our results supplement and enrich the understanding of the pathogenesis underlying PDAC and provide a new theoretical basis and strategy targeting S100A2 for the diagnosis and treatment of PDAC.

Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, yet the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/plateletspecific knockout of PALLD in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain (DBD) and Src homology 2 (SH2) domain via Immunoglobulin domain 3 (Ig3). Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.

Breakthrough treatment for refractory and relapsed immune thrombocytopenia (ITP) patients is urgently needed. Autoantibody-mediated platelet clearance and megakaryocyte dysfunction are important pathogenic mediators of ITP. Glycoprotein (GP) Ibα is a significant autoantigen found in ITP patients and is associated with poor response to standard immunosuppressive treatments. Here, we engineered human T cells to express a chimeric autoantibody receptor (CAAR) with GPIbα constructed into the ligand-binding domain fused to the CD8 transmembrane domain and CD3ζ-4-1BB signaling domains. We performed cytotoxicity assays to assess GPIbα CAAR-T-cell selective cytolysis of cells expressing anti-GPIbα B-cell receptors (BCRs) in vitro. Furthermore, we demonstrated the potential of GPIbα CAAR-T cells to persist and precisely eliminate GPIbα-specific B cells in vivo. In summary, we present a proof of concept for CAAR-T-cell therapy to eradicate autoimmune B cells while sparing healthy B cells with GPIbα CAAR-T cells that function like a Trojan horse. GPIbα CAAR-Tcell therapy is a promising treatment for refractory and relapsed ITP patients.

BackgroundPrevious studies have shown a coexistence phenomenon between systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), but the causal relationship between them is still unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis using publicly available summary statistics data to evaluate whether there was a causal relationship between the two diseases.MethodsSummary statistics for SLE and IBD were downloaded from the Open Genome-Wide Association Study and the International Inflammatory Bowel Disease Genetics Consortium. European and East Asian populations were included in this MR work. We adopted a series of methods to select instrumental variables that are closely related to SLE and IBD. To make the conclusion more reliable, we applied a variety of different analysis methods, among which the inverse variance–weighted (IVW) method was the main method. In addition, heterogeneity, pleiotropy, and sensitivity were assessed to make the conclusions more convincing.ResultsIn the European population, a negative causal relationship was observed between SLE and overall IBD (OR = 0.94; 95% CI = 0.90, 0.98; P < 0.004) and ulcerative colitis (UC) (OR = 0.93; 95% CI = 0.88, 0.98; P = 0.006). After removing outliers with Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), the results remained consistent with IVW. However, there was no causal relationship between SLE and Crohn’s disease. In the East Asian population, no causal relationship was found between SLE and IBD.ConclusionOur results found that genetic susceptibility to SLE was associated with lower overall IBD risk and UC risk in European populations. In contrast, no association between SLE and IBD was found in East Asian populations. This work might enrich the previous research results, and it may provide some references for research in the future.

BackgroundLower extremity deep vein thrombosis (DVT) is one of the major postoperative complications in patients with ruptured intracranial aneurysms (RIA) who underwent endovascular treatment (EVT). However, patient-specific predictive models are still lacking. This study aimed to construct and validate a nomogram model for estimating the risk of lower extremity DVT for RIA patients who underwent EVT.MethodsThis cohort study enrolled 471 RIA patients who received EVT in our institution between 1 January 2020 to 4 February 2022. Perioperative information on participants is collected to develop and validate a nomogram for predicting lower extremity DVT in RIA patients after EVT. Predictive accuracy, discriminatory capability, and clinical effectiveness were evaluated by concordance index (C-index), calibration curves, and decision curve analysis.ResultMultivariate logistic regression analysis showed that age, albumin, D-dimer, GCS score, middle cerebral artery aneurysm, and delayed cerebral ischemia were independent predictors for lower extremity DVT. The nomogram for assessing individual risk of lower extremity DVT indicated good predictive accuracy in the primary cohort (c-index, 0.92) and the validation cohort (c-index, 0.85), with a wide threshold probability range (4–82%) and superior net benefit.ConclusionThe present study provided a reliable and convenient nomogram model developed with six optimal predictors to assess postoperative lower extremity DVT in RIA patients, which may benefit to strengthen the awareness of lower extremity DVT control and supply appropriate resources to forecast patients at high risk of RIA-related lower extremity DVT.

Abstract Demand for lightweight and efficient electromagnetic wave (EW) absorbers continues to increase with technological advances in highly integrated electronics and military applications. Although MXene‐based EW absorbers have been extensively developed, more efficient electromagnetic coupling and thinner thickness are still essential. Recently, ordered heterogeneous materials have emerged as a novel design concept to address the bottleneck faced by current material development. Herein, an ordered heterostructured engineering to assemble Ti3CNTx MXenes/Aramid nanofibers/FeCo@SiO2 nanobundles (FS) aerogel (AMFS‐O) is proposed, where the commonly disordered magnetic composition is transformed to ordered FS arrays that provide more powerful magnetic loss capacity. Experiments and simulations reveal that the anisotropy magnetic networks enhance the response to the magnetic field vector of EW, which effectively improves the impedance matching and makes the reflection loss (RL) peaks shift to lower frequencies, leading to the thinner matching thickness. Furthermore, the temperature stability and excellent compressibility of AMFS‐O expand functionalized applications. The synthesized AMFS‐O achieves full‐wave absorption in X and Ku‐band (8.2–18.0 GHz) at 3.0 mm with a RLmin of −41 dB and a low density of 0.008 g cm−3. These results suggest that ordered heterostructured engineering is an effective strategy for designing high‐performance multifunctional EW absorbers.

Abstract The rational construction of microstructure and composition with enhanced Maxwell-Wagner-Sillars effect (MWSE) is still a challenging direction for reinforcing electromagnetic wave (EMW) absorption performance, and the related EMW attenuation mechanism has rarely been elucidated. Herein, MWSE boosted β-chitin/carbon nano-onions/Ni–P composites is prepared according to the heterointerface engineering strategy via facile layer-by-layer electrostatic assembly and electroless plating techniques. The heterogeneous interface is reinforced from the aspect of porous skeleton, nanomaterials and multilayer construction. The composites exhibit competitive EMW response mechanism between the conductive loss and the polarization/magnetic loss, as describing like the story of “The Hare and the Tortoise”. As a result, the composites not only achieve a minimum reflection loss (RLmin) of − 50.83 dB and an effective bandwidth of 6.8 GHz, but also present remarkable EMW interference shielding effectiveness of 66.66 dB. In addition, diverse functions such as good thermal insulation, infrared shielding and photothermal performance were also achieved in the hybrid composites as a result of intrinsic morphology and chemicophysics properties. Therefore, we believe that the boosted MWSE open up a novel orientation toward developing multifunctional composites with high-efficient EMW response and thermal management.

Aiming at the shortcomings of A* algorithm in the path planning process of electric disinfection vehicles, such as long planned paths, low one-way search efficiency, and unsmooth inflection points, an improved two-way A* search algorithm is proposed from the heuristic function and search direction. First, the cosine factor is introduced into the heuristic function of the A* algorithm to optimize the direction of the path search. Second, the search neighborhood is expanded, and the 24-neighbor search is used to obtain a better path. Finally, the one-way search from the start point to the end point is changed to a two-way simultaneous search. The experimental results show that the path distance planned by the improved A* algorithm is shortened by 9.13%, the time is shortened by 38.21%, and the inflection point is reduced by an average of 30.34%.

Among various data analysis methods, classifier ensemble (data classification) and community network detection (data clustering) have aroused the interest of many scholars. The maximum operator, as the fusion function, was always used to fuse the results of the base algorithms in the classifier ensemble and the membership degree of nodes to classes in the fuzzy community. It is vital to use generalized fusion functions in ensemble and community applications. Since the Pseudo overlap function and the Choquet-like integrals are two new fusion functions, they can be combined as a more generalized fusion function. Along this line, this paper presents new classifier ensemble and fuzzy community detection methods using a pseudo overlap pair (POP) Choquet-like integral (expressed as a fraction). First, the pseudo overlap function pair is proposed to replace the product operator of the Choquet integral. Then, the POP Choquet-like integrals are defined to perform the combinatorial step of ensembles of classifiers and to generalize the GN modularity for the fuzzy community network. Finally, two new algorithms are designed for experiments, and some computational experiments with other algorithms show the importance of POP Choquet-like integrals. All of the experimental results show that our algorithms are practical.

Panax ginseng and Panax notoginseng, two well-known herbs with enormous medical value in Asian countries, have a long usage history in China for the therapy of some diseases, such as stroke. Ginsenoside Rb1 is one of most important active ingredients in Panax ginseng and Panax notoginseng. In the last two decades, more attention has focused on ginsenoside Rb1 as an antioxidative, anti-apoptotic and anti-inflammatory agent that can protect the nervous system. In the review, we summarize the neuroprotective roles of ginsenoside Rb1 and its potential mechanisms in central nervous system diseases (CNSDs), including neurodegenerative diseases, cerebral ischemia injury, depression and spinal cord injury. In conclusion, ginsenoside Rb1 has a potential neuroprotection due to its inhibition of oxidative stress, apoptosis, neuroinflammation and autophagy in CNSDs and may be a promising candidate agent for clinical therapy of CNSDs in the future.

In this article, we present an experimental study on the impact of post-metallization annealing conditions on the negative-bias temperature instability (NBTI) of Si p-channel fin field-effect transistors (p-FinFETs) with atomic layer deposition tungsten (ALD W) as the gate-filling metal. The effects of annealing conditions on the tensile stress of the W film, impurity element concentration in the gate stack, fresh interface quality, threshold voltage shift ( ${\Delta }$ V $_{T}$ ), pre-existing traps ( ${\Delta } {N} _{\mathrm {HT}}$ ), generated traps, and their relative contributions were studied. The time exponents of ${\Delta }$ V $_{T}$ , the impacts of stress bias and temperature on NBTI degradation, and the recovery kinetics of the generated traps were analyzed. For devices with a B2H6-based W-filling metal, a 34% reduction in the fresh interface states, reduced ${\Delta }$ V $_{T}$ , and a 29% improvement in the operation overdrive voltage could be achieved by optimizing the annealing conditions. The NBTI is alleviated mainly because of the reduction in the generated traps, while the energy distribution of ${\Delta } {N} _{\mathrm {HT}}$ is insensitive to the annealing conditions. Furthermore, the relative contribution of the generated bulk insulator traps to the total number of generated traps could be reduced by optimizing the annealing conditions.