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ATP (adenosine triphosphate) and HMGB1 (high mobility group box 1 protein) are key players in treatments that induce immunogenic cell death (ICD). However, conventional therapies, including radiotherapy, are often insufficient to induce ICD. In this study, we explore a strategy using nanoparticle-loaded macrophages as a source of ATP and HMGB1 to complement radiation-induced intrinsic and adaptive immune responses. To this end, we tested three inorganic particles, namely, iron oxide nanoparticles (ION), aluminum oxide nanoparticles (AON), and zinc oxide nanoparticles (ZON), in vitrowith bone marrow-derived dendritic cells (BMDCs) and then in vivoin syngeneic tumor models. Our results showed that ION was the most effective of the three nanoparticles in promoting the secretion of ATP and HMGB1 from macrophages without negatively affecting macrophage survival. Secretions from ION-loaded macrophages can activate BMDCs. Intratumoral injection of ION-loaded macrophages significantly enhanced tumor infiltration and activation of dendritic cells and cytotoxic T cells. Moreover, exogenous ION macrophages can enhance the efficacy of radiotherapy. In addition, direct injection of ION can also enhance the efficacy of radiotherapy, which is attributed to ION uptake by and stimulation of endogenous macrophages. Instead of directly targeting cancer cells, our strategy targets macrophages and uses them as a secretory source of ATP and HMGB1 to enhance radiation-induced ICD. Our research introduces a new nanoparticle-based immunomodulatory approach that may have applications in radiotherapy and beyond.

Among various mRNA carrier systems, lipid nanoparticles (LNPs) stand out as the most clinically advanced. While current clinical trials of mRNA/LNP therapeutics mainly address liver diseases, the potential of mRNA therapy extends far beyond─yet to be unraveled. To fully unlock the promises of mRNA therapy, there is an urgent need to develop safe and effective LNP systems that can target extrahepatic organs. Here, we report on the development of sulfonium lipid nanoparticles (sLNPs) for systemic mRNA delivery to the lungs. sLNP effectively and specifically delivered mRNA to the lungs following intravenous administration in mice. No evidence of lung and systemic inflammation or toxicity in major organs was induced by sLNP. Our findings demonstrated that the newly developed lung-specific sLNP platform is both safe and efficacious. It holds great promise for advancing the development of new mRNA-based therapies for the treatment of lung-associated diseases and conditions.

IMPORTANCE: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). OBJECTIVE: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. DESIGN, SETTING, AND PARTICIPANTS: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. INTERVENTION: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. RESULTS: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy–General and Functional Assessment of Cancer Therapy–Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. CONCLUSIONS AND RELEVANCE: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03521570

Uveal melanoma (UM) is the most common primary ocular malignancy in adults and has high mortality. Recurrence, metastasis, and therapeutic resistance are frequently observed in UM, but no beneficial systemic therapy is available, presenting an urgent need for developing effective therapeutic drugs. Verteporfin (VP) is a photosensitizer and a Yes-Associated Protein (YAP) inhibitor that has been used in clinical practice. However, VP’s lack of tumor targetability, poor biocompatibility, and relatively low treatment efficacy hamper its application in UM management. Herein, we developed a biocompatible CD44-targeting hyaluronic acid nanoparticle (HANP) carrying VP (HANP/VP) to improve UM treatment efficacy. We found that HANP/VP showed a stronger inhibitory effect on cell proliferation than that of free VP in UM cells. Systemic delivery of HANP/VP led to targeted accumulation in the UM-tumor-bearing mouse model. Notably, HANP/VP mediated photodynamic therapy (PDT) significantly inhibited UM tumor growth after laser irradiation compared with no treatment or free VP treatment. Consistently, in HANP/VP treated tumors after laser irradiation, the tumor proliferation and YAP expression level were decreased, while the apoptotic tumor cell and CD8+ immune cell levels were elevated, contributing to effective tumor growth inhibition. Overall, the results of this preclinical study showed that HANP/VP is an effective nanomedicine for tumor treatment through PDT and inhibition of YAP in the UM tumor mouse model. Combining phototherapy and molecular-targeted therapy offers a promising approach for aggressive UM management.

Calcium nanoparticles have been investigated for applications, such as drug and gene delivery. Additionally, Ca2+serves as a crucial second messenger in the activation of immune cells. However, few studies have systematically studied the effects of calcium nanoparticles on the calcium levels and functions within immune cells. In this study, we explore the potential of calcium nanoparticles as a vehicle to deliver calcium into the cytosol of dendritic cells (DCs) and influence their functions. We synthesized calcium hydroxide nanoparticles, coated them with a layer of silica to prevent rapid degradation, and further conjugated them with anti-CD205 antibodies to achieve targeted delivery to DCs. Our results indicate that these nanoparticles can efficiently enter DCs and release calcium ions in a controlled manner. This elevation in cytosolic calcium activates both the NFAT and NF-κB pathways, in turn promoting the expression of costimulatory molecules, antigen-presenting molecules, and pro-inflammatory cytokines. In mouse tumor models, the calcium nanoparticles enhanced the antitumor immune response and augmented the efficacy of both radiotherapy and chemotherapy without introducing additional toxicity. Our study introduces a safe nanoparticle immunomodulator with potential widespread applications in cancer therapy.

Electrocarboxylation of the C(sp3)–O bond in 1,3-oxazolidin-2-ones with CO2to achieve β-amino acids is developed. The C–O bond in substrates can be selectively cleaved via the single electron transfer on the surface of a cathode or through a CO2•–intermediate under additive-free conditions. A great diversity of β-amino acids can be obtained in a moderate to excellent yield and readily converted to various biologically active compounds.

Anti-programmed cell death protein 1 (PD-1) therapy is a standard of care in recurrent metastatic head and neck squamous cell carcinoma (RMHNSCC). Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors, have immunomodulatory properties and have offered promising results when combined with anti-PD-1 agents. We conducted a phase 2, multicenter, single-arm trial of pembrolizumab and cabozantinib in patients with RMHNSCC who had Response Evaluation Criteria in Solid Tumors v.1.1 measurable disease and no contraindications to either agent. We assessed the primary end points of tolerability and overall response rate to the combination with secondary end points of progression-free survival and overall survival and performed correlative studies with PDL-1 and combined positive score, CD8+T cell infiltration and tumor mutational burden. A total of 50 patients were screened and 36 were enrolled with 33 evaluable for response. The primary end point was met, with 17 out of 33 patients having a partial response (52%) and 13 (39%) stable disease with an overall clinical benefit rate of 91%. Median and 1-year overall survival were 22.3 months (95% confidence interval (CI) = 11.7–32.9) and 68.4% (95% CI = 45.1%–83.5%), respectively. Median and 1-year progression-free survival were 14.6 months (95% CI = 8.2–19.6) and 54% (95% CI = 31.5%–72%), respectively. Grade 3 or higher treatment-related adverse events included increased aspartate aminotransferase (n= 2, 5.6%). In 16 patients (44.4%), the dose of cabozantinib was reduced to 20 mg daily. The overall response rate correlated positively with baseline CD8+T cell infiltration. There was no observed correlation between tumor mutational burden and clinical outcome. Pembrolizumab and cabozantinib were well tolerated and showed promising clinical activity in patients with RMHNSCC. Further investigation of similar combinations are needed in RMHNSCC. The trial is registered at ClinicalTrials.gov under registration no. NCT03468218.

In this paper, we perform molecular dynamics simulations to investigate the performance of multilayer graphene slit membranes. Graphene slit membranes at a critical slit size have been found to be promising desalination membranes. In this contribution, it is shown that multilayer slit membranes have the potential to provide significantly better permeability while retaining outstanding salt rejection. Improved permeability of the membrane is achieved by using slits of widths larger than the critical slit size required to reject salt through size exclusion, and desalination of sea water is performed by increased resistance to salt passage through the multilayering. To facilitate the design process of future multilayer membranes, we analyze the flow resistance of the membrane as a combination of electrical resistors in series and show that this analogy works for membranes where the layers possess the same slit size, as well as membranes with layers of different slit sizes. Comparing with single layer graphene membranes, it was shown that it is possible to obtain 55% improvement in permeability without loss in salt rejection capabilities through multilayering. This opens up possibilities for membrane designers to be free from the restrictions of using a single layer graphene slit membrane with a fixed slit width.

The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

The fibroblast growth factor 19 gene FGF19has previously been reported to be amplified in several cancer types and encodes for a key autocrine signaler known to promote tumorigenic growth. Thus, it is imperative to understand which cancers are oncogenically addicted to FGF19amplification as well as the role it serves in these cancer types. We report for the first time high FGF19amplification in head and neck squamous cell carcinomas (HNSCC), which is associated with increased autocrine secretion of FGF19 and poor patient outcome in HNSCC. FGF19amplification corresponded with constitutive activation of FGF receptor 4 (FGFR4)-dependent ERK/AKT–p70S6K–S6 signaling activation in HNSCC cells, and addition of human recombinant FGF19 could promote cell proliferation and soft agar colony formation in HNSCC cells with low FGF19expression through activation of FGFR4 and downstream signaling cascades. In contrast, FGF19knockout counteracts the observed effects in HNSCC cells carrying high endogenous FGF19, with knockout of FGF19significantly suppressing tumor growth in an orthotopic mouse model of HNSCC. Collectively, this study demonstrates that FGF19 gene amplification corresponds with an increased dependency upon FGF19/FGFR4 autocrine signaling in HNSCC, revealing a therapeutic target for this cancer type.

Coordination between the amplification of the fibroblast growth factor FGF19, overexpression of its corresponding receptor FGFR4, and hyperactivation of the downstream transmembrane enzyme β-klotho has been found to play pivotal roles in mediating tumor development and progression. Aberrant FGF19-FGFR4 signaling has been implicated in driving specific tumorigenic events including cancer cell proliferation, apoptosis resistance, and metastasis by activating a myriad of downstream signaling cascades. As an attractive target, several strategies implemented to disrupt the FGF19-FGFR4 axis have been developed in recent years, and FGF19-FGFR4 binding inhibitors are being intensely evaluated for their clinical use in treating FGF19-FGFR4 implicated cancers. Based on the established work, this review aims to detail how the FGF19-FGFR4 signaling pathway plays a vital role in cancer progression and why disrupting communication between FGF19 and FGFR4 serves as a promising therapeutic strategy for disrupting cancer progression.

The conversion study on the environmental quality criteria between water/air and soil is the need to carry out research on soil-environmental quality standards in an all-round way, and also the demand for solving emerging problems in this field using the system dynamic and the overall view. Carrying out this study is of practical significance and theoretical values in the face of formulation and revision of soil-environmental quality standards in China. Firstly, the theoretical basis and relative models of soil-water and soil-air systems were expounded, respectively. And on this basis, a preliminary conceptual model about the conversion was constructed. After that, the current worldwide environmental quality criteria/standards for soil, water and air media were introduced based on their types, concerned pollutants and hierarchical classification, and their variation were also analyzed briefly. Particularlly, the key points for the conversion of environmental quality criteria between soil and water and/or between soil and air were discussed, respectively, while combined with the relative researching results. Finally, this conversion study was commented and prospected.

The DNA binding protein and chromatin structural regulator DEK regulate many cellular processes. These include proliferation, differentiation, apoptosis, senescence, DNA repairing and the maintenance of stem cell phenotype. DEK is increasingly recognized as a crucial player in many steps of cancer initiation and progression, and is precisely regulated by abundant promoting and inhibiting factors directly or indirectly. DEK may serve as an architectural modulating protein to regulate the expression and function of multiple human genes in cancer cells. In this article we have reviewed the specificities and complexities of DEK in the regulation of transcription factors and global chromatin, including its biologic roles in malignant cells, and summarized the current research. The possible use of DEK as a diagnostic marker and drug target in the prevention or treatment of tumors is also discussed.

ObjectiveNeutrophils are prominent components of solid tumours and exhibit distinct phenotypes in different tumour microenvironments. However, the nature, regulation, function and clinical relevance of neutrophils in human gastric cancer (GC) are presently unknown.DesignFlow cytometry analyses were performed to examine levels and phenotype of neutrophils in samples from 105 patients with GC. Kaplan-Meier plots for overall survival were performed using the log-rank test. Neutrophils and T cells were isolated, stimulated and/or cultured for in vitro and in vivo regulation and function assays.ResultsPatients with GC showed a significantly higher neutrophil infiltration in tumours. These tumour-infiltrating neutrophils showed an activated CD54+phenotype and expressed high level immunosuppressive molecule programmed death-ligand 1 (PD-L1). Neutrophils activated by tumours prolonged their lifespan and strongly expressed PD-L1 proteins with similar phenotype to their status in GC, and significant correlations were found between the levels of PD-L1 and CD54 on tumour-infiltrating neutrophils. Moreover, these PD-L1+neutrophils in tumours were associated with disease progression and reduced GC patient survival. Tumour-derived GM-CSF activated neutrophils and induced neutrophil PD-L1 expression via Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signalling pathway. The activated PD-L1+neutrophils effectively suppressed normal T-cell immunity in vitro and contributed to the growth and progression of human GC in vivo; the effect could be reversed by blocking PD-L1 on these neutrophils.ConclusionsOur results illuminate a novel mechanism of PD-L1 expression on tumour-activated neutrophils in GC, and also provide functional evidence for these novel GM-CSF-PD-L1 pathways to prevent, and to treat this immune tolerance feature of GC.

Co-primary spectrum sharing for multiple operators has been utilized to fully explore the spectrum resources and thus improve the spectrum efficiency. The inter-operator interference (IOI) problem should be seriously considered in order to achieve the mentioned target, especially under the scenario of the ultra-dense network (UDN) in the fifth generation (5G) wireless systems. To solve this problem, we propose an asymmetrical power levels based soft IOI coordination mechanism. The shared spectrum pool is consisted of three separated parts, where each part can be dynamically adjusted according to the minimal spectrum demand from each operator. Furthermore, different power masks are configured to different parts for each operator. The simulation results show that the proposed mechanism can improve the network spectrum efficiency significantly.

Possessing exceptional properties, graphene has garnered immense interest in the research community for a wide array of potential applications. The mechanical properties play an important role in the success of the potential applications and thus a thorough understanding is cardinal. Computational modeling and simulation is an important tool in the design process due to the low costs compared to the experimental means. This review aims to consolidate the findings of works of computational modeling and simulation of graphene, with focus on models at the continuum and molecular levels. The review shows intrinsic differences in focus of the applications and types of graphene investigated by the different scale models, thus highlighting the advantages and shortcomings of each type of modeling approach.

The southern section of Gouzhigou tunnel, which is in the pipeline project of the natural gas transmission from the western to the eastern region, is located in the medium mountain canyon area in the northern Tianshan fold belt, Xinjiang. The physical geography and geological environment conditions at the tunnel project area are complex. After a field survey, the geological hidden trouble in the project area mainly are unstable rock and collapses at the cave entrance, unstable slopes, abandoned slag slopes and the stability of surrounding rocks. In this paper, the distribution, size and characteristics of the geological hazards are described. The risks of the hazards and the impacts of the tunnel construction safety are analyzed. At last based on the evaluation results of geological security, prevention measures are put forward to remove or weaken the geologic hidden trouble.

Chip mounters are the important equipment on Surface Mounting Technology (SMT) production line, and with continuous improvement of the requirement on the mounting speed and mounting accuracy of micro-electronic components, high-speed and high-precision chip mounters have become important goals pursued by many companies and manufacturers of SMT equipment. As there is great difference in the shape, size, shape and number of pins of the components to be mounted by chip mounters, higher technical requirements on the mounting components identification and visual system must be put forward. The traditional mounter vision system controls and handles the light source system and the image acquisition system by personal computer (PC). However, in the practical application, the visual system has disadvantages such as large volume and high cost, which will lead to the shortcomings of bulky volume of the production equipment, inconvenient assembling, expensive price, difficult upgrading, etc. In this paper, to overcome these deficiencies of mounter vision system, based on the advantages of embedded system such as small size, fast response, reliable operation and relatively low prices, etc., the application of Advanced RISC Machines (ARM) embedded system in SMT machine vision system is researched, and the whole system and the module design is done with the modular design thought, which is conductive to the development and later maintenance, updating, and upgrade of the system.

The transient swelling process of polymeric gels is studied and a finite element model is introduced to simulate the phenomena based on existing hyperelastic theory for inhomogeneous swelling of gels and analogies made to transient heat conduction analysis. Examples of free swelling of a cube and a fixed cylinder were investigated, showing the highly non-linear deformation present during transition from the initial state to equilibrium.

For the prediction of the height of the fractured zone developed in mining with fully-mechanized top-coal caving system, the traditional calculation method, if used, generally yield a value with a comparatively large error. Based on mining condition of 6206 face at Wangzhuang Coal Mine in Luan mining area, a comprehensive study is made in the paper of the characteristics of the development of the fractured zone in the medium hard overlying strata under such full-seam mining conditions by taking various means, including field measurement and numerical and physical simulation. Through comparison with the field measurement data available and regression analysis, it can be seen that the height of the fractured zone developed in the medium hard overlying strata in mining with fully-mechanized top-coal caving system is directly proportional to the total mining thickness. In comparison with the result obtained with the use of empirical formula, the method used in the paper can better bring to light the occurrence of the intensive failure of overlying strata under such a mining condition. The research-derived achievement can serve as a basis for reference for the prediction of the height of fractured zone in mining under medium hard cover by using fully-mechanized top-coal caving method, and for decision making in mining under a water body.

Abstract: Multiblock kernel principal component analysis (MBKPCA) has been proposed to isolate the faults and avoid the high computation cost. However, MBKPCA is not available for dynamic processes. To solve this problem, recursive MBKPCA is proposed for monitoring large scale processes. In this paper, we present a new recursive MBKPCA (RMBKPCA) algorithm, where the adaptive technique is adopted for dynamic characteristics. The proposed algorithm reduces the high computation cost, and is suitable for online model updating in the feature space. The proposed algorithm was applied to an industrial process for adaptive monitoring and found to efficiently capture the time-varying and nonlinear relationship in the process variables.

The mechanical behavior of capsule in microscale flow is fundamentally important in physiology, pharmaceutical or agricultural industries, fluid mechanics and physics. In the present paper, the performance of two-dimensional capsule in time-dependent microchannel flow is investigated by a numerical simulation method, which combines the finite volume method for solving the fluid problem with the front tracking technique for capturing and tracking the capsule membrane. Initially circular capsule is considered in the simulations, and the capsule is modeled as liquid medium enclosed by a thin membrane, for which linear elastic properties are taken into consideration. The membrane mechanics is adopted to calculate membrane-fluid interaction, based on which the solution of fluid problem is obtained. The capsule membrane is advected explicitly according to fluid velocity results. Results of capsule position, capsule moving velocity, capsule shape, velocity field of fluid inside and outside the membrane can be obtained from the numerical simulations. Based on these results, the effects of time-dependent background fluid on capsule behavior are studied.

A multiphysics model is presented to simulate the ionic transport interaction between the smart pH-electric-sensitive hydrogel and solution in micro-scale channel for BioMEMS application, when it is immersed into a pH buffer solution subject to externally applied electric field. It is called the multi-effect-coupling pH-electric-stimuli (MECpHe) model, and covers chemo-electro-mechanical coupled effect and the fixed charge density associated with the buffer solution pH and electric potential. The model enables us to predict the distributive diffusive ionic species concentrations and the distributive electric potential in both hydrogel and surrounding solution as well as the fixed charge density and the displacement of hydrogel, especially to study the ionic transport interaction between the soft smart hydrogel and solution in the micro-channel. By the MECpHe model, the equilibrium response of the smart hydrogels is simulated to the interaction with the solution pH and electric coupled stimuli. Influence of the several key parameters including the externally applied electric voltage and solution pH is discussed in detail on the distributions of ionic species concentrations and electric potential for the ionic transport systems in micro-scale channel.

The effect of Young's modulus on the behavior of pH-sensitive hydrogels is studied when subjected to coupled stimuli of solution pH and externally applied electric field. The study is the first instance for coupled stimuli numerical analysis of the hydrogels, in which a multieffect‐coupling pH‐stimulus (MECpH) model is presented. The model considers ionic diffusion, electric potential, and large mechanical deformation. A correlation between diffusive hydrogen ion and charge groups fixed onto the hydrogel polymeric chains by the Langmuir absorption isotherm is incorporated into the model. To validate the model, the computed results by the meshless Hermite‐Cloud technique are compared well with experimental data available from the literature. Then several case studies are conducted for the swelling hydrogel immersed in buffered solution subject to applied electric voltage, especially for the Young modulus effects on the volume variations of the hydrogels.

Mo-incorporated SBA-1 mesoporous molecular sieves have been synthesized under acidic conditions using cetyltriethylammonium bromide as a surfactant and used as catalysts for partial oxidation of methane with oxygen as an oxidant. In the partial oxidation of methane the catalytic performance of Mo–SBA-1 materials directly synthesized from the Mo-containing gel were superior to those of Mo-impregnated pure siliceous SBA-1 and amorphous silica.

It has been shown that the nanoplastic particles present in graphene membranes have a high tendency to cause fouling in them due to the high affinity between graphene and nanoplastic molecules. This poses a significant challenge for the use of graphene membranes for desalination. In this paper, we introduce a double-layer graphene slit membrane as a viable solution to significantly reduce fouling caused by the presence of nanoplastic particles in graphene membranes. The molecular dynamics (MD) simulations performed in this work show that when fouling occurs in a single-layer membrane, the presence of nanoplastics reduces the average permeability by close to 40%, from 1877 LMBH to 1148 LMBH, with a large standard deviation of 26% between runs. With the addition of the secondary membrane, the average permeability increases by 17%, with a significantly reduced standard deviation of 7%. These suggest that the secondary layer acts as a sacrificial shield, attracting the nanoplastic contaminants and preventing them from coming into close proximity with the primary membrane, thus preventing fouling at the primary rejection layer. Furthermore, due to the affinity of the nanoplastic particles with the secondary graphene membrane, this membrane design points toward an effective and efficient way of extracting nanoplastic particles for further analysis or processing.

Controlled ring-opening copolymerization involving epoxides represents a valuable strategy for the synthesis of oxygenated polymers with unique biodegradability and biocompatibility. In this study, simple trivalent metal complexes, salenM(III)X (salen = N,N′-bis(salicylidine) diamine derivatives, M = Al, Cr, and Co), are employed for copolymerizing p-tosyl isocyanate (TSI) with epoxides, generating perfectly alternating polyurethanes with various structures and tunable properties. The trivalent cobalt acetate complex of N,N′-bis(salicylidine)-o-phenylenediamine bearing 3- and 3′-, 5- and 5′-tert-butyl groups exhibited the highest activity of up to 41,400 h–1under mild conditions. This single-site catalyst also showed excellent activity and selectivity for copolymer formation even at an extremely low loading of 0.002 mol % without any cocatalyst activator and operated efficiently for various terminal epoxides, affording completely alternating polyurethanes with high molecular weights and narrow polydispersities. Also, this catalyst was tolerant of large quantities of chain transfer agents, thereby allowing control of the molecular weight. Notably, the ring opening of terminal epoxides predominantly occurring at the methylene C–O bond resulted in the formation of stereoregular polyurethanes with more than 96% head-to-tail content.

A comprehensive field survey was conducted, and a numerical model based on the Princeton Ocean Model was established to investigate the vertical structure of current induced by surface waves and identify its effect on sand loss from a beach. Previous studies have examined wave‐induced longshore transport, whereas this study focused on cross‐shore transport caused by waves. The introduction of vertically dependent radiation stress revealed that wave‐induced vertical gyres existed with onshore and offshore flows in the upper and lower layers, respectively, besides the well‐known wave‐induced longshore flow. It was found that the vertical gyres were caused by the onshore wave force (a gradient of radiation stress) in the upper layer and the offshore wave force usually existed in the lower layer, as well as the horizontal imbalance of local wave force. The locations of wave‐induced vertical gyres were found to correspond to the location of sediment erosion, and thus the lower part of the vertical gyres drove the offshore transport of eroded sediment. Moreover, the vertical gyres were located in areas with a highly variable topographic gradient (e.g., at a bar), and their driven offshore currents (undertow/return flow) extended far beyond the surf zone. The topographic slope had a profound effect on the vertical structure. Numerical experiments showed that an extended breakwater from the eastern headland of the bay could prevent sediment from being eroded. Furthermore, the shear front at the rim of a horizontal gyre could retain suspended sediment in the center of the gyre. Rather than examining longshore flow, which has been extensively investigated, this study focused on cross‐shore flow due to waves. It was found that in addition to the longshore flow (vertically mean), a wave‐induced offshore flow component extended a long‐distance offshore. Moreover, the vertical and horizontal gyres (eddies) generated by waves greatly contributed to sand loss from a beach. Specifically, a vertical gyre eroded sediment and drove its offshore transport in the lower layer of water. Furthermore, it was determined that the vertical and horizontal gyres were both affected by highly variable topographic slopes, and that the fast‐rotating rim of a horizontal gyre ensured that suspended sediment was retained in the center of the gyre. The results suggest that a breakwater extending from the eastern headland could prevent the erosion of sediment in the bay, as simulations showed that the pattern of wave‐induced currents was mainly influenced by the length of barriers (headlands) and the bottom slope. In addition to vertically mean longshore flow, there was a prevalent wave‐induced offshore component of flowWave‐induced vertical gyres were found to erode sediment and drive its offshore transportNumerical experiments showed that a breakwater at the eastern headland of the bay could prevent the erosion of sediment In addition to vertically mean longshore flow, there was a prevalent wave‐induced offshore component of flow Wave‐induced vertical gyres were found to erode sediment and drive its offshore transport Numerical experiments showed that a breakwater at the eastern headland of the bay could prevent the erosion of sediment

Both elastic and fracture behavior of hydrogel are affected by its water content. As shown by extensive experimental data, currently prevalent models, which are primarily based on the Flory–Rehner theory (F–R theory), are unable to correctly capture the effect of water content (or conversely polymer fraction) on the elastic modulus of hydrogels. Lake–Thomas theory cannot provide correct predictions on fracture toughness with different water content conditions as well. In this work, we carry out experiments on polyacrylamide (PAAm) gel and discover scaling-laws that differ significantly in the swollen and dehydrated state in addition to contradicting F–R model. We also derive scaling laws that are consistent with our experiments. Intriguingly, we find that the application of the scaling theory to fracture problems of the hydrogel can also provide a better theoretical prediction. An intriguing implication of this result is that the study of the fracture threshold of soft matter may be replaced to some extent by merely the studying of their elastic modulus.

This paper investigates the orthotropic properties of Fused Deposition Modeling (FDM)-printed Acrylonitrile Styrene Acrylate (ASA) material with different raster configurations. The elastic properties were determined using a non-destructive ultrasonic technique. This technique allows us to deduce the orthotropic elastic constants from the material density and the velocities of the longitudinal and shear waves propagating through the material along different directions. Tensile tests were performed in addition to ultrasonic tests to obtain the yield properties of the ASA material and to validate the elastic constants determined by the ultrasonic tests, which have shown very close correspondence. Finally, numerical verification was performed by comparing the experimental results of the three-point and four-point bending tests with the finite element simulation results which have as input the material properties from the ultrasonic testing. The simulation results have shown excellent agreement with the experimental results, implying that the material properties obtained from the ultrasonic testing were highly accurate comparing to the actual orthotropic elastic properties of the 3D-printed ASA material.

This paper investigates the differences in structural response of lightweight internal structures using finite element (FE) simulation to provide quantitative comparison of the advantages of each type of structure. Various configurations, corresponding to different amounts of weight savings, were studied under distributed pressure loading and bending moment loading conditions. It was found that for configurations with less weight savings, the kagome possesses better performance than the honeycomb structure. However, as the amount of weight savings increases, the trend was observed to be reversed, with the honeycomb structure providing much better performance than the kagome structure. In general, it was shown that the honeycomb structure possesses better performance than the kagome structure under cantilever loading conditions.

ABSTRACTThe potential contributions of CD8+memory stem T cells to anti-tumor immunity and immunotherapy responses in gastric cancer has not been demonstrated. We found that CD8+memory stem T cell frequencies were increased in the peripheral blood of gastric cancer patients compared to healthy donors and declined in frequency with disease progression. Despite minimal in vitrocytotoxic activity, the adoptive transfer of CD8+memory stem T cells into Rag1−/−tumor bearing mice enhanced tumor regression compared to CD8+central or effector memory T cell counterparts. This effect was associated with an increase in splenic, draining lymph node and tumor infiltrating CD8+T cell numbers and the development of an altered CD8+T cell phenotype not seen during homeostasis. GSK-3β inhibition is known to promote memory stem T cell accumulation by arresting effector T cell differentiation in vivo. Surprisingly however, GSK-3β inhibition conversely increased the cytotoxic capacity of CD8+memory stem T cells in vitro, and this was associated with the induction of effector T cell-associated effector proteins including FasL. Finally, FasL neutralization following GSK-3β inhibition directly attenuated the anti-tumoral capacity of CD8+memory stem T cells both in vitroand in vivo. Altogether, our findings identify the therapeutic potential of modulating CD8+memory stem T cells for improved anti-tumoral responses against gastric cancer.

This study investigates the distribution and propagation of potential energy in graphene under tearing loads. Before crack extension, high potential energy accumulates at the crack tip. The distributions of the high potential energy are symmetrical and asymmetrical in pristine graphene and bi-crystal graphene with misorientation angle of 21.79∘, respectively. When a C–C bond breaks during the fracture of graphene, numerous energy waves successively arise from the crack tip, i.e., the two atoms linked by the broken bond. These atoms lose one bond constraint and turn into unstable states, and they displace with high accelerations. In pristine graphene, the energy waves present as hexagonal geometries, while the waveforms near the loading areas are compressed to flatter geometries. In bi-crystal graphene, the refractions of potential energy waves are observed when the energy waves propagate to the grain boundary (GB) and interact with it, and the waveforms are changed after the wave crosses the GB. For both pristine graphene and bi-crystal graphene, wrinkles are generated when the crack tip extends to the site sufficiently close to the vertical free boundary, and the wrinkles are always nearly parallel to the horizontal free boundary and move along with the motion of the crack tip.

Mo-Containing SBA-1 mesoporous molecular sieves synthesized under strongly acidic conditions exhibited catalytic performance, superior to that of Mo-impregnated pure silica SBA-1 or silica gel, for the partial oxidation of methane with oxygen as an oxidant.

The underlying mechanisms of surface phenomena are very complex and still not entirely clear. The aim of this work attempts to reveal the important contribution of the nonlocal integral theory of elasticity to surface elasticity, which is of fundamental scientific interest. By considering a uniform and isotropic half-space medium subjected to an arbitrary uniform strain, it is shown that the bulk is homogeneous, however, the whole medium is heterogeneous due to the bond loss near the free surface. The nonlocal effect cannot be observed at all in the homogeneous bulk, but the bond loss characterized by the nonlocal integral theory can show an important contribution to the surface elasticity. This in turn allows to propose a simplified surface model to replace the complex modeling of nonlocal integral theory. The thickness of surface zone can be evaluated from the intrinsic characteristic length used in the nonlocal integral theory. According to the intrinsic correlation and using the molecular dynamics simulations, the thickness of the surface layer of silicon films is 2.6911 Å. Furthermore, with application of the simplified surface model to a thin film in tension, it has been noted that the geometric dimension of size-dependence is generally not that of traditional mechanics. For instance, in most situations, the main contribution to size-dependence has actually come from the thickness (or radius) direction of a rod-type structure, rather than its axial direction which is intuitively- and widely-used in the current practice in open literature. [ABSTRACT FROM AUTHOR]