Porous aromatic frameworks (PAFs) with rich metal coordination sites are highly effective support materials for gold nanoparticles (AuNPs), which would not only prevent AuNPs agglomeration but also facilitate mass transfer during the catalytic process. In this work, PAF-160, -161, and -162 bearing diphosphine units are synthesized via the Friedel–Crafts alkylation reaction to act as efficient platforms for AuNPs immobilization. These PAFs possess high surface areas (up to 655 m2 g–1) together with excellent stabilities, and the different linkage lengths between P centers allow more scattered and accessible sites for gold coordination. In the resultant Au-PAFs, AuNPs with uniform sizes are stabilized dispersedly. The catalytic performances of these Au-PAFs are monitored by the reduction of 4-nitrophenol (4-NP), and all materials exhibit excellent catalytic activities on the reduction of 4-NP, especially Au-PAF-162 with the apparent rate constant (kapp) up to 0.019 s–1. Additionally, the reductions of various nitroarenes with different functional groups are explored and all Au-PAFs can convert most nitroaromatic derivatives to the corresponding arylamines with high conversions of 99%, in which the reaction mechanism is also proposed. Furthermore, a continuous catalytic device with Au-PAF-160 catalyst is explored, and Au-PAF-160 can convert 1-chloro-4-nitrobenzene, 2,6-dichoronitrobenzene and 1-chloro-2,4-dinitrobenzene into the corresponding amines in sequence in the continuous flow catalytic experiments. This work has enriched the variety of porous materials for noble metal immobilization and promotes their applications in heterogeneous catalysis.
Abstract KRAS G12C inhibitors have demonstrated encouraging clinical benefit in patients with solid tumors harboring KRAS G12C mutation. However, the overall response rate and duration of response remain to be improved. Though combining KRAS G12C inhibitors with anti-PD-1 antibodies showed enhanced preclinical efficacy, clinical benefit for this regimen was compromised by treatment-related toxicities. While the mechanisms underlining these toxicities are being actively investigated, combination strategies incorporating other immunotherapies into KRAS G12C inhibition may provide an alternative to anti-PD-1 combination. We have discovered a new bispecific antibody (BsAb), D3L-002, targeting the TIGIT and PVRIG immune checkpoint molecules that are expressed on activated T and NK cells and mediate inhibitory signaling to counteract the immune stimulatory DNAM-1 pathway. To assess the combination effect of D3L-002 with KRAS G12C inhibitors, the anti-tumor efficacies of KRAS G12C inhibitor D3S-001, a murine surrogate anti-TIGITxPVRIG BsAb (mTxP BsAb), a murine anti-PD-1 antibody (mPD-1 Ab), the combination of D3S-001 with mTxP BsAb and with mPD-1 Ab were evaluated in CT-26 KRAS G12C syngeneic mouse tumor models. Tumor microenvironment (TME) profiling was analyzed by flow cytometry, immunohistology and single cell sequencing. In this study, D3S-001 monotherapy inhibited tumor growth with a 50% complete remission (CR) rate. While mTxP BsAb alone was not effective in this immune “cold” model, combination of D3S-001 with mTxP BsAb resulted in a 70% CR rate, comparable to that of the combination of D3S-001 with the mPD-1 Ab. TME profiling indicated that D3S-001 remodeled the TME from “cold” to “hot” by reducing M2 macrophages and MDSCs while increasing T cells in the tumor. Interestingly, D3S-001 treatment led to increased expression of DNAM-1 on T cells, which has been implicated in augmenting T cell sensitivity towards environmental stimulation. The expression of TIGIT and PD-1 was also upregulated on T cells after D3S-001 treatment, correlating with enhanced T cell activation and anti-tumor efficacy in the combination group of mTxP BsAb and D3S-001 or mPD-1 Ab and D3S-001, respectively. In single cell analysis, mTxP BsAb demonstrated a distinctive effect in regulating immune suppressive Treg population from that of the mPD-1 Ab. While Treg population was increased in D3S-001 or the combination of D3S-001 with mPD-1 Ab group, it was decreased in mTxP BsAb monotherapy or D3S-001 and mTxP BsAb combination group. Collectively, these data showed that D3S-L002’s surrogate mTxP BsAb synergized with D3S-001 in achieving enhanced and durable anti-tumor effect in KRAS G12C-mutant tumors. The combination treatment transformed TME from “cold” to “hot” and inhibited Treg population. These results provide a strong rationale for combining D3L-002 with D3S-001 in clinic trials, which may lead to an alternative treatment option, with differentiated mechanisms and potentially better tolerability, from current strategy in combining anti-PD-1 antibodies with KRAS G12C inhibitors. Citation Format: George Chen, Jing Zhang, Haopeng Rui, Xiaofeng Yang, Tienan Wang. Combination of D3L-002, an anti-TIGIT/PVRIG bispecific antibody, with D3S-001, a KRAS G12C inhibitor, transformed tumor microenvironment from “cold” to “hot” and achieved durable tumor remission in preclinical models [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C064.
The aim of this report is to present our experience on the use of the digital subtraction angiography (DSA) in selection of the vascularized greater trochanter bone grafting for the treatment of the osteonecrosis of femoral head (ONFH) in early stages. Between January 2005 and June 2007, DSA was used to evaluate the blood perfusion of the early stages ONFH in 32 patients (45 hips). There were 18 males and 14 females with an average age of 30 years old. Twenty-one hips were in ARCO stage I, and 24 in ARCO stage II. The arterial blood supply insufficiency was found in 22 hips by DSA, and the venous stasis in 23 hips. The hips with artery blood supply insufficiency received the vascularized greater trochanter bone grafting, and the hips with the venous stasis received the core decompression. All of patients were followed-up with an average of 4.8 years (ranging 2.4-6.6 years). The preoperative Harris Hip score (HHS) in the patients with arterial blood supply insufficiency was 48.18 ± 7.81 and the postoperative HHS was 93.27 ± 3.03. The preoperative HHS in the patients with venous stasis was 44.04 ± 6.40, and the postoperative HHS 92.65 ± .93. The postoperative DSA showed an improved perfusion of the femoral head in 44 hips. Our experience showed that DSA would help to select the appropriate procedure for treatment of ONFH in the early stage.
Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions induced by inflammatory responses, in which cell-free DNA (cfDNA) plays a pivotal role. This study investigated the therapeutic potential of biodegradable cationic nanoparticles (cNPs) in alleviating ALI. Using a mouse model of lipopolysaccharide-induced ALI, we examined the impact of intravenously administered cNPs. Our findings indicate that cNPs possess robust DNA binding capability, enhanced accumulation in inflamed lungs, and a favorable safety profile in vivo. Furthermore, cNPs attenuate the inflammatory response in LPS-induced ALI mice by scavenging cfDNA, mainly derived from neutrophil extracellular traps, and activating the macrophage-mediated cGAS-STING pathway. The findings suggest a potential treatment for ALI by targeting cfDNA with cNPs. This approach has demonstrated efficacy in mitigating lung injury and merits further exploration.
Purpose This paper aims to examine how the firm’s global coopetition network position impacts market share and to explore the multiple moderating effects of trade network strength and structures on the relationship between firm global coopetition network position and market share. Design/methodology/approach This paper selects global automobile manufacturing firms as samples whose classification is “Automobile” in the Factiva database from 2014 to 2018 and develops the measurement for global coopetition network and trade network by using Ucinet6. Finally, Stata was used for data analysis. Findings This paper finds that structural holes and centrality are beneficial to improve global market share. And the trade network strength and structures have positive multiple moderating effects on the relationship between the firm global coopetition network position and market share. Originality/value This paper explores industrial international competitiveness according to the intricate trade relations among countries and the impact of industrial international competitiveness on the relationship between global coopetition network position of brand firms and market share. The results of this paper expand the current literature on the relationship between characteristics of coopetition network and trade network.
The treatment of displaced calcaneal fractures is controversial.Open reduction and internal fixation are widely described as the gold standard in the literature,but these technique shave many complications,including skin necrosis,internal fixation leakage and deep infection and wound healing problems.Percutaneous reduction and unilateral external fixation have received increasing attention because they can provide a good, stable reduction and reduce the soft tissue complications caused by open surgery(such as deep infection and delayed wound healing).The purpose of this retrospective study was to evaluate the reduction imaging and clinical results of calcaneus traction compressionwith orthopaedic compression reduction forceps combined with percutaneous minimally invasive external fixation for intra-articular calcaneal fractures.This was a retrospective analysis. A total of 35 patients with unilateral calcaneal fractures were divided into two groups: 1) the open reduction, internal fixation group (19 feet)and 2) the percutaneous minimally invasive, closed reduction external fixation group (16 feet).Evaluation of the reduction include dimaging measurements of the calcaneus length,width,and height,and the Bohler angle and Gissane angle before and after surgery.Clinical outcomes included the time of surgery,length of hospital stay,operation time,wound-related complications,the American Orthopaedic Foot and Ankle Society hindfoot score,the visual analogue score for pain, and the SF-36 score.The average follow-up time was 25.52 ± 1.68 months.There was no significant difference in reduction between the open group and the closed group (P > 0.05).The operation time of the open group was significantly longer than that of the closed group(P = 0.0001).The length of hospitalization and waiting time for surgery in the open reduction group were significantly longer than those in the closed reduction group (P < 0.05).Incidence-related complications in the open group and closed group were 21.1 %(4/19) and 6.3 %(1/16),respectively (P = 0.0001).The American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot scores in the open and closed groups were 81.35 ± 5.25 and 82.52 ± 4.78, respectively (P = 0.0875). The visual analogues cale (VAS) scores of the open group and the closed group were 1.81 ± 1.32 and 0.78 ± 0.91, respectively (P = 0.0412).The SF-36 scores were 80 ± 4.5 and 79 ± 4.2, respectively.Our research shows that for various types of intra-articular calcaneal fractures compared with open reduction,internal plate fixation,calcaneus traction compression with orthopaedic reduction forceps combined with percutaneous minimally invasive external fixation is a simple and effective method for treating calcaneal fractures; not only can the calcaneus be corrected, but it can also provide notable imaging and clinical results.
Abstract Geological slopes are often disturbed by external engineering, leading changes of the upper moisture content and dry density in loess-mudstone composite layer. It directly affects the shear strength of the loess-mudstone composite layer interface. In order to explore the influence of the upper loess moisture content and dry density on the shear strength of the loess-mudstone composite layer, taking the cutting slope in a test base in Shaanxi Province as the engineering background, different loess moisture contents (10%, 13%, 16%, 19%) and dry densities (1.4, 1.45, 1.5, 1.55 g/cm 3 ) are employed to investigate the shear strength of loess-mudstone composite layers. Scanning electron microscopy (SEM) is used to observe the failure interface of the loess-mudstone composite layer to analyze the failure mechanism of the samples. The results show that: (1) The shear strength of the loess-mudstone composite layer is lower than those of pure loess and mudstone samples. (2) The moisture content of loess will deteriorate the shear strength of the composite layer, and its effect is greater than that of homogeneous loess; but the dry density of loess will enhance the shear strength of the composite layer, and its effect is less than that of homogeneous loess (3) The moisture content and dry density of loess will affect the distribution of pores in the composite layer interface, changing the shear strength of the composite layer. The research can provide certain data and theoretical basis for the prevention and control of landslides at the loess-mudstone interface.
Purpose Since IT investment constitutes a significant portion of a firm’s budget, evaluating IT investment performance is important for both research and firms’ operations. In the digital era, there are significant disparities in the effects of IT investment on firm performance. Design/methodology/approach Drawing on the resource-based view and upper echelons theory, we investigate the effect of IT investment on the business performance of manufacturing firms. We also explore the moderating role of digital transformation and dual moderating effect of digital transformation and CEO age in this relationship. Findings Analyzing a sample of Chinese manufacturing firms spanning 2016–2020, we find that IT investment by Chinese manufacturing firms has a negative effect on business performance. However, this negative effect is moderated by digital transformation. Furthermore, digital transformation has a more pronounced inverse moderating influence on this negative effect for firms with older CEOs. Originality/value Hence, we reveal that the key factors for reducing the negative effect of IT investment on China’s manufacturing firms are digital transformation and the appointment of older CEOs who actively lead firms’ digital transformation.
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