Ultra-Strong Janus Covalent Organic Framework Membrane with Smart Response to Organic Vapor.

Vapor-driven smart Janus materials have made significant advancements in intelligent monitoring, control, and interaction, etc. Nevertheless, the development of ultrafast response single-layer Janus membrane, along with a deep exploration of the smart response mechanisms, remains a long-term endeavor. Here, the successful synthesis of a high-crystallinity single-layer Covalent organic framework (COF) Janus membrane is reported by morphology control. This kind of membrane displays superior mechanical properties and specific surface area, along with excellent responsiveness to CH2Cl2 vapor. The analysis of the underlying mechanisms reveals that the vapor-induced breathing effect of the COF and the stress mismatch of the Janus structure play a crucial role in its smart deformation performance. It is believed that this COF Janus membrane holds promise for complex tasks in various fields.

Dynamic Insights into the Growth Mechanisms of 2D Covalent Organic Frameworks on Graphene Surfaces.

Producing high-quality two-dimensional (2D) covalent organic frameworks (COFs) is crucial for industrial applications. However, this remains significantly challenging with current synthetic techniques. A deep understanding of the intermolecular interactions, reaction temperature, and oligomers is essential to facilitate the growth of highly crystalline COF films. Herein, molecular dynamics simulations were employed to explore the growth of 2D COFs from monomer assemblies on graphene. Our results showed that chain growth reactions dominated the COF surface growth and that van der Waals (vdW) interactions were important in enhancing the crystallinity through monomer preorganization. Moreover, appropriately tuning the reaction temperature improved the COF crystallinity and minimized the effects of amorphous oligomers. Additionally, the strength of the interface between the COF and the graphene substrate indicated that the adhesion force was proportional to the crystallinity of the COF. This work reveals the mechanisms for nucleation and growth of COFs on surfaces and provides theoretical guidance for fabricating high-quality 2D polymer-based crystalline nanomaterials.

High-Strength Polycrystalline Covalent Organic Framework with Abnormal Thermal Transport Insensitive to Grain Boundary.

Grain boundaries (GBs) in two-dimensional (2D) covalent organic frameworks (COFs) unavoidably form during the fabrication process, playing pivotal roles in the physical characteristics of COFs. Herein, molecular dynamics simulations were employed to elucidate the fracture failure and thermal transport mechanisms of polycrystalline COFs (p-COFs). The results revealed that the tilt angle of GBs significantly influences out-of-plane wrinkles and residual stress in monolayer p-COFs. The tensile strength of p-COFs can be enhanced and weakened with the tilt angle, which exhibits an inverse relationship with the defect density. The crack always originates from weaker heptagon rings during uniaxial tension. Notably, the thermal transport in p-COFs is insensitive to the GBs due to the variation of minor polymer chain length at defects, which is abnormal for other 2D crystalline materials. This study contributes insights into the impact of GBs in p-COFs and offers theoretical guidance for structural design and practical applications of advanced COFs.

Clinical characteristics and prognostic analysis of postoperative recurrence or metastasis of low-risk gastrointestinal stromal tumors.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. This study aimed to investigate the clinical characteristics and prognosis of postoperative recurrence or metastasis in patients with low-risk stromal tumors, in order to take individualized postoperative management and treatment for patients with low-risk GISTs with relatively high recurrence. METHODS: We retrospectively analyzed the clinicopathological and follow-up data of patients with GISTs who underwent surgical resection in Nanjing Drum Tower Hospital from March 2010 to December 2021. A total of 282 patients with low-risk GISTs were included, none of whom were treated with imatinib. Univariate and multivariate Cox analysis and survival curves were used to explore the relationship between clinical features and recurrence or metastasis in patients with low-risk GISTs. RESULTS: Of the 282 patients with low-risk GISTs who met inclusion criteria, 14 (4.96%) had recurrence or metastasis. There was a correlation between tumor size, primary site, resection type, Ki67 index, neutrophil lymphocyte ratio (NLR) and CD34 expression and postoperative recurrence or metastasis of GISTs (P < 0.05). Subsequently, multifactorial analysis showed that tumor primary site, tumor size, and Ki67 index were independent risk factors affecting postoperative recurrent or metastasis in patients with low-risk GISTs (P < 0.05). Ultimately, According to Kaplan-Meier analysis, non-gastric primary tumors, larger tumors, and high Ki67 index were significantly associated with poor progression-free survival ( PFS ). CONCLUSIONS: Tumor location, tumor size and Ki-67 were independent risk factors for postoperative recurrence and metastasis in patients with low-risk GISTs. Based on the 2008 modified NIH recurrence risk grading system, combined with the above three factors, it can be used to evaluate the prognosis of patients with low-risk GISTs and provide personalized postoperative review and follow-up management recommendations.

Ultrastretchable Helical Carbon Nanotube-Woven Film.

Helical carbon nanotube (HCNT) is regarded as one of the most promising nanomaterials due to its excellent tensile strength and superhigh stretchability. Here, a novel HCNT-woven film (HWF) is proposed, and its in-plane and out-of-plane mechanical properties are systematically investigated via molecular dynamics (MD) simulation. The MD results show that HWF possesses highly stretchable capability resulting from sliding and straightening of CNT segments, and the maximum tensile strain can reach 2113%. Furthermore, the HWF presents an obvious tensile mechanical anisotropy. The torsion failure is the main fracture mode when the HWF is stretched along the longitudinal direction. However, when the HWF is stretched along the transverse direction, the fracture is mainly caused by intertube compression. On the other hand, the HWF can dissipate large amount of kinetic energy of projectile via sliding and fracture of HCNTs, leading to high specific penetration energy. This work provides a theoretical guidance for designing and fabricating next-generation superstrong two-dimensional CNT-based nanomaterials.

A single carbon nanotube-entangled high-performance buckypaper with tunable fracture mode.

It is well known that the traditional buckypaper (BP) is composed of a certain number of short carbon nanotubes (CNTs) intertwined with each other and sliding always happens when the BP is under tensile and impact loading, which results in inferior mechanical properties compared to single CNTs. In this work, a highly-entangled single-wire BP (SWBP) structure is constructed by a modified self-avoiding random walk approach. The in-plane mechanical properties and impacting behaviors of the SWBPs with different entanglement degrees and interface frictions are systematically investigated via newly developed coarse-grained molecular dynamics (CGMD) simulation. A coarse-grained method can effectively reflect the inter-tube van der Waals (vdW) interactions and the mechanical behaviors of CNTs, including tension, bending and adhesion. In this work, from the tensile simulations of the SWBP, the results showed that the self-locking mechanism between entangled CNTs could significantly enhance the tensile resistance of the film. Besides, the mechanical properties of the SWBP are highly dependent on the entanglement degree and the interface friction between CNTs. Furthermore, two distinct fracture modes, ductile fracture and brittle fracture, are revealed, which can be efficiently controlled by changing the related friction between CNTs. From the impacting simulations, it is found that the impacting performance can be effectively tuned by adjusting the entanglement degree of the film. In addition, the kinetic energy of the projectile could be rapidly dissipated through the stretching and bending of CNTs in the SWBP. This work provides an in-depth understanding of the effect of interface friction and entanglement degree on the mechanical properties of the buckypaper and provides a reference for the preparation of strong CNT-based micromaterials.

Role of interleukin 6 and its soluble receptor on the diffusion barrier dysfunction of alveolar tissue.

During respiratory infection, barrier dysfunction in alveolar tissue can result from "cytokine storm" caused by overly reactive immune response. Particularly, interleukin 6 (IL-6) is implicated as a key biomarker of cytokine storm responsible for and further progression to pulmonary edema. In this study, alveolar-like tissue was reconstructed in a microfluidic device with: (1) human microvascular lung endothelial cells (HULEC-5a) cultured under flow-induced shear stress and (2) human epithelial cells (Calu-3) cultured at air-liquid interface. The effects of IL-6 and the soluble form of its receptor (sIL-6R) on the permeability, electrical resistance, and morphology of the endothelial and epithelial layers were evaluated. The diffusion barrier properties of both the endothelial and epithelial layers were significantly degraded only when IL-6 treatment was combined with sIL-6R. As suggested by recent review and clinical studies, our results provide unequivocal evidence that the barrier dysfunction occurs through trans-signaling in which IL-6 and sIL-6R form a complex and then bind to the surface of endothelial and epithelial cells, but not by classical signaling in which IL-6 binds to membrane-expressed IL-6 receptor. This finding suggests that the role of both IL-6 and sIL-6R should be considered as important biomarkers in developing strategies for treating cytokine storm.

Comparison of clinical outcomes and prognosis between surgery and endoscopic submucosal dissection in patients with synchronous multifocal early gastric cancer.

BACKGROUND: Synchronous multiple early gastric cancer (SMEGC) refers to the simultaneous occurrence of two or more malignant cancer lesions in the stomach. For patients with multiple early gastric carcinomas, the choice of appropriate treatment remains controversial. This study is dedicated to comparing the clinical outcomes and prognosis of patients with SMEGC who underwent endoscopic submucosal dissection (ESD) or gastrectomy. METHODS: A total of 180 patients with more than one malignant cancer lesion in the stomach who had received gastrectomy or ESD between 2012 and 2021 were retrospectively evaluated to determine their clinical outcomes and prognosis. Univariate and multivariate logistic regression were utilized to identify risk factors for tumor recurrence. RESULTS: Over the 57.5 months median follow-up period for the 140 enrolled cases, tumor recurrence occurred in 8 (12%) in the ESD group but only 1 (1%) in the surgery group. Relapse-free survival (RFS) was higher in the surgery group (p = 0.023) in all cases; however, there was no significant difference in Overall survival (OS, p = 0.772). Complications were significantly higher in the surgery group than in the ESD group, but fewer in the radical distal gastrectomy group. Multivariate regression analysis revealed that ESD(p = 0.034), the main lesion size > 2 cm(p = 0.019), and undifferentiated tumor(p = 0.022) were independent risk factors for tumor recurrence. CONCLUSIONS: For the treatment of simultaneous multifocal early gastric cancer, ESD has a good short-term effect and higher quality of life. However, ESD has a higher risk of recurrence than surgery. And we found that the partial gastrectomy appears to be considered as adequate treatment for some SMEGC patients.

High Impact Resistance of 2D MXene with Multiple Fracture Modes.

Two-dimensional (2D) transition metal carbides/nitrides (MXenes) are promising nanomaterials due to their remarkable mechanical and electrical properties. However, the out-of-plane mechanical properties of MXene under impact loading remain unclear. Here, particular impact-resistant fracture behaviors and energy dissipation mechanisms of MXene were systemically investigated via molecular dynamics (MD) simulation. Specifically, it was found that the specific penetration energy of MXene exceeds most conventional impact-resistant materials, such as aluminum and polycarbonate. Two kinds of novel energy dissipation mechanisms, including radial fracture and crushed fracture under different impact velocities, are revealed. In addition, the sandwiched atomic-layer structure of MXene can deflect cracks and restrain their propagation to some extent, enabling the cracked MXene to retain remarkable resistance. This work provides in-depth insights into the impact-resistance of MXene, laying a foundation for its future applications.

Controlling Nutritional Status (CONUT) score as a prognostic marker for gastrointestinal stromal tumours.

BACKGROUND: The Controlling Nutritional Status (CONUT) score, regarded as the effective indicator of patient nutrition, has been demonstrated to be related to prognosis of numerous tumours. Nevertheless, the significance of CONUT for gastrointestinal stromal tumour (GIST) remains unclear. This study intended to clarify the association between CONUT and the prognosis of GISTs. METHODS: Three hundred and fifty-five patients with GISTs undergoing surgical resection at our center were retrospectively assessed. Receiver operating characteristic curve analysis was used to help determine the cut-off value of CONUT score. Relapse-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier curve analysis. Prognostic factors for RFS and OS were examined by Cox proportional hazards models. RESULTS: A total of 355 patients were enrolled in this study. Areas under the curve (AUC) were 0.638 for CONUT score, and the cut-off value of CONUT was shown to be three. Kaplan-Meier curve analysis showed that high CONUT score was linked to poorer RFS and OS. Univariate and multivariate analyses ultimately revealed that CONUT was a risk factor for RFS and OS, independent of demographics and clinicopathological tumour characteristics. CONCLUSIONS: CONUT score was an effective and novel predictor for prognosis of GIST patients treated with surgery, indicating its potential as a prognostic marker in the overall management.

Prognostic analysis of 2-5 cm diameter gastric stromal tumors with exogenous or endogenous growth.

BACKGROUND: There has been limited research on the prognosis differences in patients with gastric stromal tumor invasion of the plasma membrane surface. This study intended to investigate whether there is a difference in prognosis in patients with endogenous or exogenous 2-5 cm diameter GISTs. METHODS: We retrospectively analyzed the clinicopathological and follow-up data of gastric stromal tumor patients, all of whom underwent surgical resection for primary GIST at Nanjing Drum Tower Hospital from December 2010 to February 2022. We classified patients based on tumor growth patterns and then investigated the association between tumor growth patterns and clinical outcomes. Progression-free survival (PFS) and overall survival (OS) were calculated by the Kaplan‒Meier method. RESULTS: A total of 496 gastric stromal tumor patients were enrolled in this study, among which 276 patients had tumors of 2-5 cm in diameter. Of these 276 patients, 193 had exogenous tumors, and 83 had endogenous tumors. Tumor growth patterns were significantly related to age, rupture status, resection style, tumor site, tumor size, and intraoperative bleeding. According to Kaplan‒Meier curve analysis, the tumor growth pattern among patients with 2-5 cm diameter tumors was significantly correlated with worse progression-free survival (PFS). Ultimately, multivariate analyses identified the Ki-67 index (P = 0.008), surgical history (P = 0.031), and resection style (P = 0.045) as independent prognostic markers for PFS. CONCLUSIONS: Although gastric stromal tumors with a diameter of 2-5 cm are classified as low risk, the prognosis is lower for exogenous tumors than for endogenous tumors, and exogenous gastric stromal tumors have a risk of recurrence. Consequently, clinicians should be vigilant regarding the prognosis of patients with this type of tumor.

Comparative transcriptomic analysis and functional characterization reveals that the class III peroxidase gene TaPRX-2A regulates drought stress tolerance in transgenic wheat.

Drought is a major abiotic stress that reduces crop yields and quality worldwide. Although some genes involved in the response to drought stress have been identified, a more in-depth understanding of the mechanisms underlying wheat tolerance to drought is needed for the control of drought tolerance. Here, we evaluated the drought tolerance of 15 wheat cultivars and measured their physiological-biochemical parameters. Our data showed that the drought tolerance of the resistant wheat cultivars was significantly higher than that of drought-sensitive cultivars, which was associated with a greater antioxidant capacity of the former. Transcriptomic analysis revealed that different mechanisms of drought tolerance exist between the wheat cultivars Ziyou 5 and Liangxing 66. Transcriptomic analysis also revealed a large number of DEGs, including those involved in flavonoid biosynthesis, phytohormone signalling, phenolamides and antioxidants. qRT-PCR was performed, and the results showed that the expression levels of TaPRX-2A were significantly different among the various wheat cultivars under drought stress. Further study revealed that overexpression of TaPRX-2A enhanced tolerance to drought stress through the maintenance of increased antioxidase activities and reductions in ROS contents. Overexpression of TaPRX-2A also increased the expression levels of stress-related genes and ABA-related genes. Taken together, our findings show that flavonoids, phytohormones, phenolamides and antioxidants are involved in the plant response to drought stress and that TaPRX-2A is a positive regulator of this response. Our study provides insights into tolerance mechanisms and highlights the potential of TaPRX-2A overexpression in enhancing drought tolerance in crop improvement programmes.

The ubiquitin E3 ligase TRIM10 promotes STING aggregation and activation in the Golgi apparatus.

STING is an endoplasmic reticulum-resident protein regulating innate immunity. After binding with cyclic guanosine monophosphate-AMP (cGAMP), STING translocates from the endoplasmic reticulum (ER) to the Golgi apparatus to stimulate TBK1 and IRF3 activation, leading to expression of type I interferon. However, the exact mechanism concerning STING activation remains largely enigmatic. Here, we identify tripartite motif 10 (TRIM10) as a positive regulator of STING signaling. TRIM10-deficient macrophages exhibit reduced type I interferon production upon double-stranded DNA (dsDNA) or cGAMP stimulation and decreased resistance to herpes simplex virus 1 (HSV-1) infection. Additionally, TRIM10-deficient mice are more susceptible to HSV-1 infection and exhibit faster melanoma growth. Mechanistically, TRIM10 associates with STING and catalyzes K27- and K29-linked polyubiquitination of STING at K289 and K370, which promotes STING trafficking from the ER to the Golgi apparatus, formation of STING aggregates, and recruitment of TBK1 to STING, ultimately enhancing the STING-dependent type I interferon response. Our study defines TRIM10 as a critical activator in cGAS-STING-mediated antiviral and antitumor immunity.

PRRSV nonstructural protein 11 degrades swine ISG15 by its endoribonuclease activity to antagonize antiviral immune response.

Porcine reproductive and respiratory syndrome virus (PRRSV) is an enveloped positive-stranded RNA virus which causes serious economic losses to pig industry worldwide. Type I IFN induces expression of interferon-stimulated genes 15 (ISG15) to inhibit virus replication. To survive in the host, PRRSV has evolved to antagonize the antiviral response of ISGylation. Previous studies have reported that nonstructural protein 2 of PRRSV inhibits the ISGylation and antiviral function of ISG15 depending on its ovarian tumor (OTU) domain/papain-like protease domain (PLP2). However, whether there are other PRRSV proteins inhibiting ISGylation of cellular proteins is less well understood. In this study, we first found that PRRSV Nsp11 decreased ISGylation of cellular proteins. Meanwhile, the expression level of ISG15 was significantly inhibited by Nsp11. Further mechanistic studies demonstrated that the transcription of ISG15 was reduced by endoribonuclease activity of Nsp11. Finally, we found that the Nsp11-induced degradation of ISG15 was partially relied on autophagy-lysosome system. Taken together, PRRSV Nsp11 antagonizes the antiviral response of ISG15 by its endoribonuclease activity to promote PRRSV replication. Our results reveal a novel mechanism that PRRSV inhibits ISGylation of cellular proteins and impairs host innate immune response.

3Cpro of FMDV inhibits type II interferon-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation.

Foot-and-mouth disease virus (FMDV) has developed various strategies to antagonize the host innate immunity. FMDV Lpro and 3Cpro interfere with type I IFNs through different mechanisms. The structural protein VP3 of FMDV degrades Janus kinase 1 to suppress IFN-γ signaling transduction. Whether non-structural proteins of FMDV are involved in restraining type II IFN signaling pathways is unknown. In this study, it was shown that FMDV replication was resistant to IFN-γ treatment after the infection was established and FMDV inhibited type II IFN induced expression of IFN-γ-stimulated genes (ISGs). We also showed for the first time that FMDV non-structural protein 3C antagonized IFN-γ-stimulated JAK-STAT signaling pathway by blocking STAT1 nuclear translocation. 3Cpro expression significantly reduced the ISGs transcript levels and palindromic gamma-activated sequences (GAS) promoter activity, without affecting the protein level, tyrosine phosphorylation, and homodimerization of STAT1. Finally, we provided evidence that 3C protease activity played an essential role in degrading KPNA1 and thus inhibited ISGs mRNA and GAS promoter activities. Our results reveal a novel mechanism by which an FMDV non-structural protein antagonizes host type II IFN signaling.

Multiple Impact-Resistant 2D Covalent Organic Framework.

Exploring and designing two-dimensional (2D) nanomaterials for armor-piercing protection has become a research focus. Here, by molecular dynamics simulation, we revealed that the ultralight monolayer covalent organic framework (COF), one kind of novel 2D crystalline polymer, possesses superior impact-resistant capability under high-velocity impact. The calculated specific penetration energy is much higher than that of other traditional impact-resistant materials, such as steel, poly(methyl methacrylate), Kevlar, etc. It was found that the hexagonal nanopores integrated by polymer chains have large deformation compatibility resulting from flexible torsion and stretching, which can remarkably contribute to the energy dissipation. In addition, the deformable nanopores can effectively restrain the crack propagation, enable COF to resist multiple impacts. This work uncovers the extreme dynamic responses of COF under high-velocity impact and provides theoretical guidance for designing superstrong 2D polymer-based crystalline nanomaterials.

Prognostic significance of serum CA125 in the overall management for patients with gastrointestinal stromal tumors.

BACKGROUND: Carbohydrate antigen 125 (CA125) is elevated as a tumor marker in many carcinomas, but its association with gastrointestinal stromal tumor (GIST) has received less attention. This study intends to evaluate whether CA125 level can predict tumor progression and overall survival (OS) of GIST patients. METHODS: We retrospectively analyzed the clinical data and follow-up records of GIST patients who underwent surgical resection in Nanjing Drum Tower Hospital from August 2010 to December 2020. All patients were classified according to serum CA125 level. The relationship between CA125 and clinical outcomes was then examined. RESULTS: A total of 406 GIST patients were enrolled in this study, among which 46 patients had preoperative elevated serum CA125 level and 13 patients with high CA125 level both preoperative and postoperative were observed. Preoperative CA125 concentration was significantly related to rupture status, resection style, tumor site, tumor size, mitotic index, NIH risk grade and c-kit exons. According to Kaplan-Meier curve analysis, high expression of postoperative CA125 was significantly correlated with worse progression-free survival (PFS) and OS among patients with preoperative elevated CA125 level. Ultimately, Cox proportional regression model analysis revealed that increase of preoperative and concurrent postoperative CA125 concentration was an independent predictive factor for PFS. CONCLUSIONS: The concurrent abnormality of serum CA125 before and after operation was an independent risk factor for GIST progression, suggesting its significance as a serum biomarker in the overall management of GIST patients.