Cronkhite‒Canada syndrome as inflammatory hamartomatous polyposis: new evidence from whole transcriptome sequencing of colonic polyps.

BACKGROUND: Cronkhite-Canada syndrome (CCS) is a rare, nonhereditary disease characterized by diffuse gastrointestinal polyposis and ectodermal abnormalities. Although it has been proposed to be a chronic inflammatory condition, direct evidence of its pathogenesis is lacking. This study aims to investigate the pathophysiology of CCS by analyzing transcriptomic changes in the colonic microenvironment. METHODS: Next-generation sequencing-based genome-wide transcriptional profiling was performed on colonic hamartomatous polyps from four CCS patients and normal colonic mucosa from four healthy volunteers. Analyses of differential expression and multiple enrichment analyses were conducted from the molecular level to the cellular level. Quantitative real-time PCR (qRT-PCR) was carried out to validate the sequencing accuracy in samples from six CCS patients and six healthy volunteers. RESULTS: A total of 543 differentially expressed genes were identified, including an abundance of CC- and CXC-chemokines. Innate immune response-related pathways and processes, such as leukocyte chemotaxis, cytokine production, IL-17, TNF, IL-1 and NF-kB signaling pathways, were prominently enhanced in CCS colonic polyps. Upregulation of wound healing, epithelial-mesenchymal transition, Wnt, and PI3K-Akt signaling pathways were also observed. Enrichment analyses at different levels identified extracellular structure disorganization, dysfunction of the gut mucosal barrier, and increased angiogenesis. Validation by qRT-PCR confirmed increased expression of the LCN2, IL1B, CXCL1, and CXCL3 genes in CCS colonic polyps. CONCLUSIONS: This case-control whole transcriptome analysis of active CCS colonic hamartomatous polyps revealed intricate molecular pathways, emphasizing the role of the innate immune response, extracellular matrix disorganization, inflammatory cell infiltration, increased angiogenesis, and potential epithelial to mesenchymal transition. These findings supports CCS as a chronic inflammatory condition and sheds light on potential therapeutic targets, paving the way for more effective and personalized management of CCS in the future.

Modified melamine-based porous organic polymers with imidazolium ionic liquids as efficient heterogeneous catalysts for CO2 cycloaddition.

The chemical conversion of carbon dioxide (CO2) into highly value-added products not only alleviates the environmental issues caused by global warming but also makes an impact on economic benefits in the world. The synthesis of cyclic carbonates by the cycloaddition of CO2 with epoxides is one of the most attractive methods for CO2 conversion. However, the development of green and highly efficient heterogeneous catalysts is considered to be a great challenge in catalysis. In this work, alkenyl-modified melamine-based porous organic polymer (MPOP-4A) was firstly synthesized by a one-pot polycondensation method, and it was again modified with imidazolium-based ionic liquids to obtain final modified catalyst (MPOP-4A-IL). Various analytical techniques were used to confirm structure and chemical composition of the prepared materials. The MPOP-4A-IL catalyst synthesized by the post-modification strategy with imidazolium-based ionic liquids exhibited enhanced catalytic activity for CO2 cycloaddition reaction. The enhanced catalytic performance could be attributed to the presence of abundant active sites in their structure such as hydrogen bond donors (HBD), nitrogen (N) sites, and nucleophilic groups for an effective chemical reaction. The MPOP-4A-IL catalyst was found to be metal-free, easy to recycle and reuse, and has good versatility for a series of different epoxides. The interaction of MPOP-4A-IL catalyst with epoxide and CO2 was further verified by density functional theory (DFT) calculations, and the possible mechanism of the CO2 cycloaddition reaction was proposed.

One-step synthesis of nitrogen-rich organic polymers for efficient catalysis of CO2 cycloaddition.

Nitrogen-rich organic polymer poly(chloride triazole) (PCTs) was synthesized by a one-step method as metal-halogen-free heterogeneous catalyst for the solvent-free CO2 cycloaddition. PCTs had abundant nitrogen sites and hydrogen bond donors, exhibited great activity for the cycloaddition of CO2 and epichlorohydrin, and achieved 99.6% yield of chloropropene carbonate under the conditions of 110 ℃, 6 h, and 0.5 MPa CO2. The activation of epoxides and CO2 by hydrogen bond donor and nitrogen sites was further explained by density functional theory (DFT) calculations. In summary, this study showed that nitrogen-rich organic polymer is a versatile platform for CO2 cycloaddition, and this paper provides a reference for the design of CO2 cycloaddition catalysts.

Construction of a Pyroptosis-Related Signature for Prognostic Prediction and Characterization of Immune Microenvironment in Acute Myelogenous Leukemia.

Background: Acute myelogenous leukemia (AML) is a common and fatal disease in hematology with frequent relapses and a poor prognosis. Pyroptosis, a programmed cell death mediated by inflammasomes, has been shown to be associated with leukemia recently. However, the role of pyroptosis for diagnosis and prognosis in AML remained less understood. Methods: We downloaded three public datasets and constructed a signature of TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model to predict the overall survival of AML patients. Samples from the GEO database were treated as a validation cohort. Gone through LASSO-Cox regression analysis, an 8-PRG-related signature was developed. Used the median score from the signature, we classified patients in two subgroups. Subsequently, we employed univariate COX, multivariate Cox regression, ROC analysis and constructed a nomogram, Finally, differential analysis, GO and KEGG functional analysis, ESTIMATE algorithm and CIBERSORT algorithm were used to explore the difference between two groups. Results: The expression levels of 90.9% pyroptosis-related genes (PRGs) had significant difference compared AML with normal tissues. The results of univariate COX regression analysis demonstrated 10 differentially expressed genes (DEGs) were associated with patients' OS (p < 0.05). Then, we found OS of patients in the low-risk group was more likely to be lengthened compared with their high-risk counterparts (P < 0.05 both in the TCGA and GEO cohort). After controlling clinical factors, the risk score could still remain an independent predictive element (HR > 1, P < 0.001) of OS in multivariate Cox regression analysis. Furthermore, a nomogram with prognostic value for AML was thus established. Time-dependent ROC analysis proved the predictive power of the signature. Functional analysis suggested that DEGs were mainly concentrated in immune-related pathways, such as humoral immune response and T cell proliferation. TME scores and risk scores were strongly correlated and immune status differed between the risk subgroups. Conclusion: A novel PRG-related signature was established to forecast the prognosis in AML, and pyroptosis may be a potential therapeutic target for AML.

Research progress of smart response composite hydrogels based on nanocellulose.

In recent years, smart-responsive nanocellulose composite hydrogels have attracted extensive attention due to their unique porous substrate, hydrophilic properties, biocompatibility and stimulus responsiveness. At present, the research on smart response nanocellulose composite hydrogel mainly focuses on the selection of composite materials and the construction of internal chemical bonds. The common composite materials and connection methods used for preparation of smart response nanocellulose composite hydrogels are compared according to the different types of response sources such as temperature, pH and so on. The response mechanisms and the application prospects of different response types of nanocellulose composite hydrogels are summarized, and the transformation of internal ions, functional groups and chemical bonds, as well as the changes in mechanical properties such as modulus and strength are discussed. Finally, the shortcomings and application prospects of nanocellulose smart response composite hydrogels are summarized and prospected.

CCT8 recovers WTp53-suppressed cell cycle evolution and EMT to promote colorectal cancer progression.

LIM and SH3 protein 1 (LASP1) is a metastasis-related protein reported to enhance tumor progression in colorectal cancer (CRC). However, the underlying mechanism is still elusive. The chaperonin protein containing TCP1 (CCT) is a cellular molecular chaperone complex, which is necessary for the correct folding of many proteins. It contains eight subunits, CCT1-8. CCT8 is overexpressed in many cancers, however, studies on CCT8 are limited and its role on CRC development and progression remains elusive. In this study, we confirmed that CCT8 and LASP1 can interact with each other and express positively in CRC cells. CCT8 could recover the ability of LASP1 to promote the invasion of CRC; CCT8 could significantly promote the proliferation, invasion, and metastasis of colorectal cells in vivo and in vitro. Mechanically, CCT8 inhibited the entry of WTp53 into the nucleus, and there was a negative correlation between the expression of CCT8 and the nuclear expression of WTp53 in clinical colorectal tissues. CCT8 promoted the cell cycle evolution and EMT progression of CRC by inhibiting the entry of WTp53 into the nucleus. Clinically, CCT8 was highly expressed in CRC. More importantly, the overall survival of CRC patients with high expression of CCT8 was worse than that of patients with low expression of CCT8. These findings indicate that as LASP1-modulated proteins, CCT8 plays a key role in promoting the progression of colorectal cancer, which provides a potential target for clinical intervention in patients with colorectal cancer.

High-performance Fe-doped ZIF-8 adsorbent for capturing tetracycline from aqueous solution.

Efficient removal of antibiotics from aqueous solution is of fundamental importance due to the increasingly severe antibiotic-related pollution. Herein, a high-performance Fe-ZIF-8-500 adsorbent was synthesized by Fe-doping strategy and subsequent activation with high-temperature. In order to evaluate the feasibility of Fe-ZIF-8-500 as an adsorbent for tetracycline (TC) removal, the adsorption properties of Fe-ZIF-8-500 were systematically explored. The results showed that the Fe-ZIF-8-500 exhibited ultrahigh adsorption capacity for TC with a record-high value of 867 mg g-1. Additionally, the adsorption kinetics and isotherms for TC onto the Fe-ZIF-8-500 can be well-fitted by the pseudo-second-order kinetics model and the Freundlich model, respectively. The ultrahigh adsorption capacity of Fe-ZIF-8-500 can be explained by the synergistic effect of multi-affinities, i.e., surface complexation, electrostatic attraction, π-π interaction and hydrogen bonding. After being used for four cycles the adsorption capacity of Fe-ZIF-8-500 remains a high level, demonstrating its outstanding reusability. The ultrahigh adsorption capacity, excellent reusability, satisfactory water stability and easy-preparation nature of Fe-ZIF-8-500 highlight its bright prospect for removing tetracycline pollutant from wastewater.

[Preparation and applications of the polymeric micelle/hydrogel nanocomposites as biomaterials].

Polymeric hydrogels have been widely researched as drug delivery systems, wound dressings and tissue engineering scaffolds due to their unique properties such as good biocompatibility, shaping ability and similar properties to extracellular matrix. However, further development of conventional hydrogels for biomedical applications is still limited by their poor mechanical properties and self-healing properties. Currently, nanocomposite hydrogels with excellent properties and customized functions can be obtained by introducing nanoparticles into their network, and different types of nanoparticles, including carbon-based, polymer-based, inorganic-based and metal-based nanoparticle, are commonly used. Nanocomposite hydrogels incorporated with polymeric micelles can not only enhance the mechanical properties, self-healing properties and chemical properties of hydrogels, but also improve the in vivo stability of micelles. Therefore, micelle-hydrogel nanocomposites have been recently considered as promising biomaterials. In this paper, the structure, properties and methods for preparation of the micelle-hydrogel nanocomposite systems are introduced, and their applications in drug delivery, wound treatment and tissue engineering are reviewed, aiming to provide reference for further development and application of the nanocomposites.

Dextran hydrogels via disulfide-containing Schiff base formation: Synthesis, stimuli-sensitive degradation and release behaviors.

Dextran hydrogels (Dex-SS) containing both disulfide and Schiff base bonds were developed via facile method based on the dextran oxidation and subsequent formation of Schiff base linkages between polyaldehyde dextran and cystamine, denoted as the disulfide-containing Schiff base reactions. Results of rheology, swelling and 13C CP/MAS NMR study indicated that cross-linking degree of Dex-SS hydrogels depended strongly on the molar ratio of -CHO/-NH2. Acidic and reductive (GSH) environment sensitive degradation behaviors of Dex-SS hydrogels were then evidenced by SEM, rheology study and Ellman's assay. Moreover, doxorubicin (DOX) was loaded into the hydrogel matrix and pH/GSH-responsive release behaviors were demonstrated. Cytocompatibility of Dex-SS hydrogel and effective cell uptake of released DOX was finally proved by transwell assay with HepG2 cells. Take advantages of the abundance of vicinal hydroxyl on a variety of polysaccharides, the disulfide-containing Schiff base reactions is considered as versatile method to develop stimuli-sensitive hydrogels for local drug delivery.

Prognosis prediction model for a special entity of gastric cancer, linitis plastica.

BACKGROUND: Gastric linitis plastica (GLP) is characteristic by its poor prognosis and highly aggressive characteristics compared with other types of gastric cancer (GC). However, the guidelines have not yet been distinguished between GLP and non-GLP. METHODS: A total of 342 eligible patients with GLP identified in the Surveillance, Epidemiology, and End Results (SEER) dataset were randomly divided into training set (n=298) and validation set (n=153). A nomogram would be developed with the constructed predicting model based on the training cohort's data, and the validation cohort would be used to validate the model. Principal component analysis (PCA) was used to evaluate the differences between groups. Cox regression and LASSO (least absolute shrinkage and selection operator) were used to construct the models. Calibration curve, time-dependent receiver operating characteristic (ROC) curve, concordance index (C-index) and decision curve analysis (DCA) were used to evaluate the predicting performance. Restricted mean survival time (RMST) was used to analyze the curative effect of adjuvant therapy. RESULTS: For patients in training cohort, univariable and multivariable Cox analyses showed that age, examined lymph nodes (LN.E), positive lymph nodes (LN.P), lesion size, combined resection, and radiotherapy are independent prognostic factors for overall survival (OS), while chemotherapy can not meet the proportional hazards (PHs) assumption; age, race, lesion size, LN.E, LN.P, combined resection and marital status are independent prognostic factors for cancer-specific survival (CSS). The C-index of the nomogram was 0.678 [95% confidence interval (CI), 0.660-0.696] and 0.673 (95% CI, 0.630-0.716) in the training and validation cohort, respectively. Meanwhile, the C-index of the CSS nomogram was 0.671 (95% CI, 0.653-0.699) and 0.650 (95% CI, 0.601-0.691) in the training and validation cohort for CSS, respectively. Furthermore, the nomogram was well calibrated with satisfactory consistency. RMST analysis further determined that chemotherapy and radiotherapy might be beneficial for improving 1- and 3-year OS and CSS, but not the 5-year CSS. CONCLUSIONS: We developed nomograms to help predict individualized prognosis for GLP patients. The new model might help guide treatment strategies for patients with GLP.

LIMK1 nuclear translocation promotes hepatocellular carcinoma progression by increasing p-ERK nuclear shuttling and by activating c-Myc signalling upon EGF stimulation.

LIM kinase 1 (LIMK1) is a serine/threonine and tyrosine kinase that is predominantly located in the cytoplasm. In our study, nuclear translocation of LIMK1 in clinical hepatocellular carcinoma (HCC) samples was demonstrated for the first time, especially in samples from those with intravascular tumour thrombus. LIMK1 was overexpressed in HCC tissues, and nuclear LIMK1 expression was associated with poor prognosis in HCC patients. Although the effects of cytoplasmic LIMK1 on cofilin phosphorylation and actin filament dynamics have been well studied, the function of nuclear LIMK1 is still unclear. Gain- and loss-of-function experiments were performed both in vitro and in vivo and demonstrated a correlation between nuclear LIMK1 and the enhanced aggressive phenotype of HCC. EGF could drive the nuclear translocation of LIMK1 by activating the interaction of p-ERK and LIMK1 and facilitating their roles in nuclear shuttling. Moreover, nuclear LIMK1 could directly bind to the promoter region of c-Myc and stimulate c-Myc transcription. Although the EGFR monoclonal antibody cetuximab has a poor therapeutic effect on advanced HCC patients, in vivo animal study showed that cetuximab achieved a significant inhibitory effect on the progression of nuclear LIMK1-overexpressing HCC cells. In addition, recent data have demonstrated the potential of cetuximab in combination therapy for HCC patients with LIMK1 nuclear translocation.

Distinguish the Role of Radiotherapy From Chemoradiotherapy for Gastric Cancer With Behavior of Metastasis-Indolent in Lymph Node.

BACKGROUND: Although the landmark INT-0116 trial and National Comprehensive Cancer Network (NCCN) guidelines recommended pT3-4Nx gastric cancer (GC) patients to receive chemoradiotherapy, the role of radiotherapy has not been distinguished from chemoradiotherapy. METHODS: GC with behavior of metastasis-indolent in lymph node (MILN) being confirmed with more than 15 examined LNs after gastrectomy were identified using the Surveillance, Epidemiology and End Result (SEER) database. The cancer-specific survival (CSS) of subgroups for radiotherapy, chemotherapy, chemoradiotherapy and non-adjuvant-treatment were compared. Propensity score matching (PSM) was performed between radiotherapy and non-radiotherapy subgroups to further distinguish the role of radiotherapy from chemoradiotherapy. Cox regression was performed to identify whether radiotherapy or chemotherapy could independently improve prognosis. RESULTS: We identified 690 MILN GC patients in SEER database. 5-year CSS was 71.9% in radiotherapy subgroup and 75.1% in non-radiotherapy subgroup(HR = 1.013, 95% CI = 0.714-1.438, p = 0.940), 75.6% in chemotherapy subgroup and 68.5% in non-chemotherapy subgroup(HR = 0.616, 95% CI = 0.430-0.884, p = 0.008), 52.5% in radiotherapy-alone subgroup and 71.9% in non-adjuvant treatment group (HR = 1.604, 95% CI = 0.575-4.471, p = 0.360), 72.9% in chemoradiotherapy subgroup and 79.5% in chemotherapy-alone subgroup (HR = 1.365, 95% CI = 0.859-2.172, p = 0.185), respectively. Further, PSM markedly improved balance of variables between radiotherapy subgroup and non-radiotherapy subgroup. After PSM, the role of the variables of radiotherapy and chemotherapy in contributing to improving CSS are consistent with that before PSM. Cox regression showed chemotherapy, tumor size, tumor invasiveness and Lauren classification were independent prognostic factors, but not including radiotherapy. CONCLUSIONS: Chemoradiotherapy confers superior prognosis to MILN GC patients compared with surgery alone might only be attributed to chemotherapy rather than radiotherapy.

A facile method for in situ fabrication of silica/cellulose aerogels and their application in CO2 capture.

Old corrugated containers-based cellulose and fly ash-based fresh wet silica gel were used as raw materials for in situ synthesis of a series of silica/cellulose aerogels in NaOH/urea solution. At a silicon to cellulose ratio of less than 2.5:1, the skeleton structure of the synthesized composite material was dominated by fibrils decorated with spherical silica nanoparticles. At a silicon to cellulose ratio of higher than 2.5:1, the skeleton structure of the composite material was dominated by spherical silica particles interspersed with cellulose. The synthesized composite material was applied to capture CO2 at ambient temperature and pressure. We observed that with increasing silicon content, the CO2 adsorption capacity of the composite material decreased (regardless of its dominant structure), while its selectivity for CO2/N2 increased. This work presents a facile method for the synthesis of adsorption material that has high capacity and selectivity for CO2.

CO2 capture performance and characterization of cellulose aerogels synthesized from old corrugated containers.

Old corrugated containers with low recyclability were used as raw materials to synthesize a series of aerogels with varying cellulose concentrations in NaOH/urea solution via a freeze-drying process. The resulting aerogels had a rich porous structure with specific surface areas in the range of 132.72-245.19 m2.g-1 and mesopore volumes in the range of 0.73-1.53 cm3.g-1, and were tested for CO2 sorption at ambient temperature and pressure, displaying excellent CO2 adsorption capacities in the range of 1.96-11.78 mmol.g-1. Furthermore, the CO2/N2 selectivity of aerogels decreased with decreasing specific surface area, which was mainly caused by the decrease in CO2 capture. In addition, the CO2 sorption capacity of the sample with 2% cellulose content, CA-2, exceeded the values reported so far for many other sorbents with higher specific surface areas, and showed reasonable cyclic stability for CO2 capture. Therefore, this adsorbent represents an attractive prospect for CO2 uptake at room temperature.

Cellulosic Cr(salen) complex as an efficient and recyclable catalyst for copolymerization of SO2 with epoxide.

The search for green catalytic processes for the synthesis of useful polymers and incorporating the waste SO2 in highly-selective pathways become extremely important in the coming years. Herein, cellulose was modified by ethylenediamine, and then synthesized Schiff base with 3,5-di-tert-butyl-2-hydroxybenzaldehyde to immobilize chromium chloride and formed a novel heterogeneous cellulosic Cr(salen)-type catalyst for the first time. The cellulosic Cr(salen)-type catalyst shows high efficiency and recyclability in copolymerization of cyclohexene oxide with SO2. The influence factors such as the molar ratio of the catalyst and cyclohexene oxide, reaction temperature, and reaction time were researched in detail to study the optimal conditions. The copolymer product was characterized by FTIR and 1H NMR for confirming the structure. The possible copolymer mechanism is given, and we believed that the novel cellulosic Cr(salen)-type complex will be used as an efficient catalyst in other chemical reactions.

Study of CO2 cyclic absorption stability of CaO-based sorbents derived from lime mud purified by sucrose method.

Using lime mud (LM) purified by sucrose method, derived from paper-making industry, as calcium precursor, and using mineral rejects-bauxite-tailings (BTs) from aluminum production as dopant, the CaO-based sorbents for high-temperature CO2 capture were prepared. Effects of BTs content, precalcining time, and temperature on CO2 cyclic absorption stability were illustrated. The cyclic carbonation behavior was investigated in a thermogravimetric analyzer (TGA). Phase composition and morphologies were analyzed by XRD and SEM. The results reflected that the as-synthesized CaO-based sorbent doped with 10 wt% BTs showed a superior CO2 cyclic absorption-desorption conversion during multiple cycles, with conversion being >38 % after 50 cycles. Occurrence of Ca12Al14O33 phase during precalcination was probably responsible for the excellent CO2 cyclic stability.