Artificial intelligence assisted automatic screening of opportunistic osteoporosis in computed tomography images from different scanners.

OBJECTIVES: It is feasible to evaluate bone mineral density (BMD) and detect osteoporosis through an artificial intelligence (AI)-assisted system by using quantitative computed tomography (QCT) as a reference without additional radiation exposure or cost. METHODS: A deep-learning model developed based on 3312 low-dose chest computed tomography (LDCT) scans (trained with 2337 and tested with 975) achieved a mean dice similarity coefficient of 95.8% for T1-T12, L1, and L2 vertebral body (VB) segmentation on test data. We performed a model evaluation based on 4401 LDCT scans (obtained from scanners of 3 different manufacturers as external validation data). The BMD values of all individuals were extracted from three consecutive VBs: T12 to L2. Line regression and Bland‒Altman analyses were used to evaluate the overall detection performance. Sensitivity and specificity were used to evaluate the diagnostic performance for normal, osteopenia, and osteoporosis patients. RESULTS: Compared with the QCT results as the diagnostic standard, the BMD assessed had a mean error of (- 0.28, 2.37) mg/cm3. Overall, the sensitivity of a normal diagnosis was greater than that of a diagnosis of osteopenia or osteoporosis. For the diagnosis of osteoporosis, the model achieved a sensitivity > 86% and a specificity > 98%. CONCLUSION: The developed tool is clinically applicable and helpful for the positioning and analysis of VBs, the measurement of BMD, and the screening of osteopenia and osteoporosis. CLINICAL RELEVANCE STATEMENT: The developed system achieved high accuracy for automatic opportunistic osteoporosis screening using low-dose chest CT scans and performed well on CT images collected from different scanners. KEY POINTS: Osteoporosis is a prevalent but underdiagnosed condition that can increase the risk of fractures. This system could automatically and opportunistically screen for osteoporosis using low-dose chest CT scans obtained for lung cancer screening. The developed system performed well on CT images collected from different scanners and did not differ with patient age or sex.

eIF6 Promotes Gastric Cancer Proliferation and Invasion by Regulating Cell Cycle.

OBJECTIVE: To investigate the role and function of eIF6 in gastric cancer (GC). METHODS: The expression level of eIF6 in GC tissues and normal tissues was detected in different high-throughput sequencing cohorts. Survival analysis, gene differential analysis, and enrichment analysis were performed in the TCGA cohort. Biological networks centered on eIF6 were constructed through two different databases. Immunohistochemistry (IHC) and Western blot were used to detect protein expression of eIF6, and qRT-PCR was used to detect eIF6 mRNA expression. The correlation between the expression of eIF6 in GC tissues and clinicopathological parameters of GC was analyzed. siRNA knockout of eIF6 was used to study the proliferation, migration, and invasion. The effects of eIF6 on cell cycle and Cyclin B1 were detected by flow cytometry and Western blot. RESULTS: eIF6 was significantly overexpressed in GC tissues and predicted poor prognosis. In addition, 113 differentially expressed genes were detected in cancer-related biological pathways and functions by differential analysis. Biological networks revealed interactions of genes and proteins with eIF6. The expression intensity of eIF6 in cancer tissues was higher than that in adjacent tissues (P = 0.0001), confirming the up-regulation of eIF6 expression in GC tissues. The expression level of eIF6 was statistically significant with pTNM stage (P = 0.006). siRNA knockout of eIF6 significantly reduced the proliferation, colony formation, migration, and invasion ability of GC cells. Silencing of eIF6 also inhibited the cell cycle of GC cells in G2/M phase and decreased the expression level of CyclinB1. CONCLUSION: Our study suggests that eIF6 is up-regulated in GC and may promote the proliferation, migration, and invasion of GC by regulating cell cycle.

Alantolactone enhances the sensitivity of melanoma to MAPK pathway inhibitors by targeting inhibition of STAT3 activation and down-regulating stem cell markers.

Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.

Tumor Microenvironment-Responsive Polymer-Based RNA Delivery Systems for Cancer Treatment.

Ribonucleic acid (RNA) therapeutics offer a broad prospect in cancer treatment. However, their successful application requires overcoming various physiological barriers to effectively deliver RNAs to the target sites. Currently, a number of RNA delivery systems based on polymeric nanoparticles are developed to overcome these barriers in RNA delivery. This work provides an overview of the existing RNA therapeutics for cancer gene therapy, and particularly summarizes those that are entering the clinical phase. This work then discusses the core features and latest research developments of tumor microenvironment-responsive polymer-based RNA delivery carriers which are designed based on the pathological characteristics of the tumor microenvironment. Finally, this work also proposes opportunities for the transformation of RNA therapies into cancer immunotherapy methods in clinical applications.

Intraoperative central venous pressure during cardiopulmonary bypass is an alternative indicator for early prediction of acute kidney injury in adult cardiac surgery.

BACKGROUND: The relationship between venous congestion in cardiopulmonary bypass (CPB) and acute kidney injury (AKI) in cardiac surgery has not utterly substantiated. This study aimed at investigate the relationship between CVP in CPB and the occurrence of AKI. METHODS: We retrospectively reviewed 2048 consecutive patients with cardiovascular disease undergoing cardiac procedure with CPB from January 2018 to December 2022. We used the median CVP value obtained during CPB for our analysis and patients were grouped according to this parameter. The primary outcomes were AKI and renal replacement therapy(RRT). Multivariable logistic regression was used to explore the association between CVP and AKI. RESULTS: A total of 2048 patients were enrolled in our study and divided into high CVP group (CVP ≥ 6.5 mmHg) and low CVP group (CVP < 6.5 mmHg) according to the median CVP value. Patients in high CVP group had the high AKI and RRT rate when compared to the low CVPgroup[(367/912,40.24%)vs.(408/1136,35.92%),P = 0.045;(16/912,1.75%vs.9/1136;0.79%), P = 0.049]. Multivariate logistic regression analysis displayed CVP played an indispensable part in development of renal failure in surgical. CONCLUSIONS: Elevated CVP(≥ 6.5mmH2OmmHg) in CPB during cardiac operation is associated with an increased risk of AKI in cardiovascular surgery patients. Clinical attention should be paid to the potential role of CVP in predicting the occurrence of AKI.

Genetic alterations of GI-NECs involving three main signaling pathways.

BACKGROUND: Gastrointestinal (GI)-neuroendocrine neoplasms (NENs) are subclassified in neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). The genetic characteristics of GI-NEN has been a hot issue in recent years, but more studies are needed to provide further details. This study aims to provide additional data about genomic characteristics of GI-NENs and the genetic differences between NETs and NECs. PATIENTS AND METHODS: Thirteen samples were selected for next-generation sequencing (NGS) analysis with a 425-gene panel. Microsatellite instability (MSI) and tumor mutational burden (TMB) were calculated as well as immunohistochemistry (IHC) was used to test for protein expression. RESULTS: Genetic alterations were very common in NECs, but rare in NETs. The average TMB of NETs and NECs was 2.3 and 6.9, respectively. The TMB of NECs was significantly higher compared to NETs. The TP53 mutation rate was significantly higher in NECs than in NETs (100% vs. 20%), other mutations involved MTOR (n = 2, 15.4%), DDR2 (n = 3, 23.1%), ERBB4 (n = 1, 7.7%), BRCA1 (n = 1, 7.7%), BRCA2 (n = 1, 7.7%), ATM (n = 1, 7.7%), and SMAD4 (n = 1, 7.7%). Deep loss of SMAD4 (1/3, 33.3%), SDHB (1/3, 33.3%), RB1 (1/3, 33.3%), and BRCA2 (1/3, 33.3%), high-level amplification of CRKL (1/3, 33.3%), CCNE1(1/3, 33.3%), and MCL1(1/3, 33.3%) were found in NECs. The integrated analysis found these genetic alterations frequently involve DNA repair and cell cycle, PI3K/AKT/mTOR and TGF-ß/SMAD4 signaling pathways. CONCLUSION: Genetic alterations were very common in NECs and rare in NETs, and frequently involved three main signaling pathways. NEC patients harboring these genetic alterations may benefit from targeted therapy and PD-1/PD-L1 immunotherapy.

A Review: PI3K/AKT/mTOR Signaling Pathway and Its Regulated Eukaryotic Translation Initiation Factors May Be a Potential Therapeutic Target in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a malignant tumor developing from the esophageal squamous epithelium, and is the most common histological subtype of esophageal cancer (EC). EC ranks 10th in morbidity and sixth in mortality worldwide. The morbidity and mortality rates in China are both higher than the world average. Current treatments of ESCC are surgical treatment, radiotherapy, and chemotherapy. Neoadjuvant chemoradiotherapy plus surgical resection is recommended for advanced patients. However, it does not work in the significant promotion of overall survival (OS) after such therapy. Research on targeted therapy in ESCC mainly focus on EGFR and PD-1, but neither of the targeted drugs can significantly improve the 3-year and 5-year survival rates of disease. Phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is an important survival pathway in tumor cells, associated with its aggressive growth and malignant progression. Specifically, proliferation, apoptosis, autophagy, and so on. Related genetic alterations of this pathway have been investigated in ESCC, such as PI3K, AKT and mTOR-rpS6K. Therefore, the PI3K/AKT/mTOR pathway seems to have the capability to serve as research hotspot in the future. Currently, various inhibitors are being tested in cells, animals, and clinical trials, which targeting at different parts of this pathway. In this work, we reviewed the research progress on the PI3K/AKT/mTOR pathway how to influence biological behaviors in ESCC, and discussed the interaction between signals downstream of this pathway, especially eukaryotic translation initiation factors (eIFs) and the development and progression of ESCC, to provide reference for the identification of new therapeutic targets in ESCC.

Morusin enhances the antitumor activity of MAPK pathway inhibitors in BRAF-mutant melanoma by inhibiting the feedback activation of STAT3.

BACKGROUND: BRAF and MEK inhibitors significantly prolonged the progression-free survival of patients with BRAF mutant melanoma, but their long-term efficacy was limited by drug resistance. Our previous studies found that targeted inhibition of the mitogen-activated protein kinases (MAPK) pathway promotes the activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in BRAF-mutant melanoma cells. Whether dual inhibition of MAPK and JAK2/STAT3 pathways can reverse drug resistance in melanoma remains unclear. METHODS: This study verified whether morusin could enhance the inhibitory effect of MAPK pathway inhibitors on BRAF mutant melanoma by inhibiting the feedback activation of STAT3 at the cellular and animal levels. RESULTS: We demonstrated that morusin could enhance the inhibitory effect of MAPK pathway inhibitors on BRAF mutant melanoma cells by inhibiting the feedback activation of the STAT3/SOX2 pathway. Moreover, our study showed morusin combined with MAPK pathway inhibitors specifically inhibited BRAF-mutant melanoma cells to a greater extent than wild-type cells. Our results also showed that the combination of morusin and BRAF inhibitors could jointly inhibit BRAF mutant melanoma in vivo. Finally, our experiment also revealed that the combination therapy of morusin and MAPK pathway inhibitors jointly inhibited drug-resistant melanoma in vitro and in vivo. CONCLUSION: Our results suggested that the combination of morusin and MAPK pathway inhibitors may be a more effective treatment strategy for BRAF-mutant melanoma than MAPK pathway inhibitors alone.

Encapsulation of Enzymes in Metal-Phenolic Network Capsules for the Trigger of Intracellular Cascade Reactions.

Nanoengineered capsules encapsulated with functional cargos (e.g., enzymes) are of interest for various applications including catalysis, bioreactions, sensing, and drug delivery. Herein, we report a facile strategy to engineer enzyme-encapsulated metal-phenolic network (MPN) capsules using enzyme-loaded zeolitic imidazolate framework nanoparticles (ZIF-8 NPs) as templates, which can be removed in a mild condition (e.g., ethylenediaminetetraacetic acid (EDTA) solution). The capsule size (from 250 nm to 1 µm) and thickness (from 9.8 to 33.7 nm) are well controlled via varying the template size and coating time, respectively. Importantly, MPN capsules encapsulated with enzymes (i.e., glucose oxidase) can trigger the intracellular cascade reaction via the exhaustion of glucose to produce H2O2 and subsequently generate toxic hydroxyl radicals (•OH) based on the Fenton reaction via the reaction between H2O2 and iron ions in MPN coatings. The intracellular cascade reaction for the generation of •OH is efficient to inhibit cancer cell viability, which is promising for the application in chemodynamic therapy.

New strain of Pediococcus pentosaceus alleviates ethanol-induced liver injury by modulating the gut microbiota and short-chain fatty acid metabolism.

BACKGROUND: Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease (ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective microbe-based therapy is lacking. Pediococcus pentosaceus (P. pentosaceus) CGMCC 7049 is a newly isolated strain of probiotic that has been shown to be resistant to ethanol and bile salts. However, further studies are needed to determine whether P. pentosaceus exerts a protective effect on ALD and to elucidate the potential mechanism. AIM: To evaluate the protective effect of the probiotic P. pentosaceus on ethanol-induced liver injury in mice. METHODS: A new ethanol-resistant strain of P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge model of experimental ALD was established to evaluate the protective effects. Twenty-eight C57BL/6 mice were randomly divided into three groups: The control group received a pair-fed control diet and oral gavage with sterile phosphate buffered saline, the EtOH group received a ten-day Lieber-DeCarli diet containing 5% ethanol and oral gavage with phosphate buffered saline, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet but was treated with P. pentosaceus. One dose of isocaloric maltose dextrin or ethanol was administered by oral gavage on day 11, and the mice were sacrificed nine hours later. Blood and tissue samples (liver and gut) were harvested to evaluate gut barrier function and liver injury-related parameters. Fresh cecal contents were collected, gas chromatography-mass spectrometry was used to measure short-chain fatty acid (SCFA) concentrations, and the microbiota composition was analyzed using 16S rRNA gene sequencing. RESULTS: The P. pentosaceus treatment improved ethanol-induced liver injury, with lower alanine aminotransferase, aspartate transaminase and triglyceride levels and decreased neutrophil infiltration. These changes were accompanied by decreased levels of endotoxin and inflammatory cytokines, including interleukin-5, tumor necrosis factor-α, granulocyte colony-stimulating factor, keratinocyte-derived protein chemokine, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Ethanol feeding resulted in intestinal dysbiosis and gut barrier disruption, increased relative abundance of potentially pathogenic Escherichia and Staphylococcus, and the depletion of SCFA-producing bacteria, such as Prevotella, Faecalibacterium, and Clostridium. In contrast, P. pentosaceus administration increased the microbial diversity, restored the relative abundance of Lactobacillus, Pediococcus, Prevotella, Clostridium and Akkermansia and increased propionic acid and butyric acid production by modifying SCFA-producing bacteria. Furthermore, the levels of the tight junction protein ZO-1, mucin proteins (mucin [MUC]-1, MUC-2 and MUC-4) and the antimicrobial peptide Reg3ß were increased after probiotic supplementation. CONCLUSION: Based on these results, the new strain of P. pentosaceus alleviated ethanol-induced liver injury by reversing gut microbiota dysbiosis, regulating intestinal SCFA metabolism, improving intestinal barrier function, and reducing circulating levels of endotoxin and proinflammatory cytokines and chemokines. Thus, this strain is a potential probiotic treatment for ALD.

KRAS SNPs are related to colorectal cancer susceptibility and survival in Chinese people.

Aim:KRAS SNPs may increase KRAS transcription and KRAS levels. SNPs of KRAS 3'UTR can affect carcinoma risk and prognosis. Materials & methods: The rs8720 and rs7960917 in KRAS 3'UTR for colorectal carcinoma (CRC) risk and survival were investigated in a case-control study. Association between SNPs and CRC risk, survival analysis were analyzed by an unconditional logistic regression model, log-rank test, Kaplan-Meier estimation, Cox regression model and one-way analysis of variance. Results & conclusion: The genotype CT of rs8720 was significantly increased risk of CRC, decreased overall survival and event-free survival, and KRAS mRNA and protein expressions were significantly increased in individuals with rs8720 CT, TT genotype. rs8720 may be an important factor in CRC development and prognosis.

Injectable and Sprayable Polyphenol-Based Hydrogels for Controlling Hemostasis.

Injectable and sprayable hydrogels have attracted considerable attention for application in the biomedical field owing to their high moldability and efficiency in encapsulating therapeutics and cells. Herein, we report the spontaneous assembly of injectable and sprayable hydrogels via a one-step mixing of solutions of tannic acid (TA) and O-carboxymethyl chitosan (CMCS) without an external stimulus. The presence of 1,4-benzenediboronic acid (BDBA) improves the mechanical properties and reduces the gelation time of the resulting hydrogels. The hydrogels assemble via hydrogen bonds between TA and CMCS as well as via dynamic boronate ester bonds between TA and BDBA, as confirmed by Fourier transform infrared spectroscopy. Balancing the interactions between the three components (CMCS/TA/BDBA) is essential for the construction of the hydrogels. The moduli of the CMCS-TA-BDBA hydrogels initially increase as the amount of BDBA increases and decrease after reaching a maximum value at a BDBA-to-TA molar ratio of 3:1. The CMCS-TA-BDBA hydrogels with interconnected porous morphologies display rapid gelation (∼10 s), biocompatibility, self-healing, injectable, and sprayable abilities. In addition, the hydrogels can be used for hemostasis. The extent of bleeding in mouse livers treated with the hydrogels could be reduced extensively from 240 (nontreated mouse livers) to 55 mg (77% reduction). The reported hydrogels coupled with the combination of functionality and biological activity make them promising hemostatic materials for biomedical applications.

Ligand-Functionalized Poly(ethylene glycol) Particles for Tumor Targeting and Intracellular Uptake.

Drug carriers typically require both stealth and targeting properties to minimize nonspecific interactions with healthy cells and increase specific interaction with diseased cells. Herein, the assembly of targeted poly(ethylene glycol) (PEG) particles functionalized with cyclic peptides containing Arg-Gly-Asp (RGD) (ligand) using a mesoporous silica templating method is reported. The influence of PEG molecular weight, ligand-to-PEG molecule ratio, and particle size on cancer cell targeting to balance stealth and targeting of the engineered PEG particles is investigated. RGD-functionalized PEG particles (PEG-RGD particles) efficiently target U-87 MG cancer cells under static and flow conditions in vitro, whereas PEG and cyclic peptides containing Arg-Asp-Gly (RDG)-functionalized PEG (PEG-RDG) particles display negligible interaction with the same cells. Increasing the ligand-to-PEG molecule ratio improves cell targeting. In addition, the targeted PEG-RGD particles improve cell uptake via receptor-mediated endocytosis, which is desirable for intracellular drug delivery. The PEG-RGD particles show improved tumor targeting (14% ID g-1) when compared with the PEG (3% ID g-1) and PEG-RDG (7% ID g-1) particles in vivo, although the PEG-RGD particles show comparatively higher spleen and liver accumulation. The targeted PEG particles represent a platform for developing particles aimed at balancing nonspecific and specific interactions in biological systems.

Advancing Metal-Phenolic Networks for Visual Information Storage.

We report a facile inking strategy for visual information storage (e.g., writing, printing, and beyond) via surface modification of substrates with polyphenols and subsequent in situ formation of metal-phenolic networks (MPNs) on the substrates. The reported technique has several advantages compared with current printing techniques. Diverse substrates can be used to fulfill the requirements for different applications (e.g., printing, writing, painting, and stamping). A range of colors (e.g., yellow, blue, and green) can be realized using different polyphenols (e.g., tannic acid, gallic acid, and pyrogallol) and metal ions (e.g., CuII, FeIII, and TiIV). The disadvantages (e.g., ink precipitation, color fading) associated with writing or printing using traditional ink can be overcome. The obtained paintings can be easily removed by acids enabling the recycling of substrates. The reported strategy provides a new avenue for the development of portable, nontoxic, and green technologies for writing, printing, and beyond, which expands the applications of MPN-based materials.

Polyphenol-Based Particles for Theranostics.

Polyphenols, due to their high biocompatibility and wide occurrence in nature, have attracted increasing attention in the engineering of functional materials ranging from films, particles, to bulk hydrogels. Colloidal particles, such as nanogels, hollow capsules, mesoporous particles and core-shell structures, have been fabricated from polyphenols or their derivatives with a series of polymeric or biomolecular compounds through various covalent and non-covalent interactions. These particles can be designed with specific properties or functionalities, including multi-responsiveness, radical scavenging capabilities, and targeting abilities. Moreover, a range of cargos (e.g., imaging agents, anticancer drugs, therapeutic peptides or proteins, and nucleic acid fragments) can be incorporated into these particles. These cargo-loaded carriers have shown their advantages in the diagnosis and treatment of diseases, especially of cancer. In this review, we summarize the assembly of polyphenol-based particles, including polydopamine (PDA) particles, metal-phenolic network (MPN)-based particles, and polymer-phenol particles, and their potential biomedical applications in various diagnostic and therapeutic applications.

Modulating Targeting of Poly(ethylene glycol) Particles to Tumor Cells Using Bispecific Antibodies.

Low-fouling or "stealth" particles composed of poly(ethylene glycol) (PEG) display a striking ability to evade phagocytic cell uptake. However, functionalizing them for specific targeting is challenging. To address this challenge, stealth PEG particles prepared by a mesoporous silica templating method are functionalized with bispecific antibodies (BsAbs) to obtain PEG-BsAb particles via a one-step binding strategy for cell and tumor targeting. The dual specificity of the BsAbs-one arm binds to the PEG particles while the other targets a cell antigen (epidermal growth factor receptor, EGFR)-is exploited to modulate the number of targeting ligands per particle. Increasing the BsAb incubation concentration increases the amount of BsAb tethered to the PEG particles and enhances targeting and internalization into breast cancer cells overexpressing EGFR. The degree of BsAb functionalization does not significantly reduce the stealth properties of the PEG particles ex vivo, as assessed by their interactions with primary human blood granulocytes and monocytes. Although increasing the BsAb amount on PEG particles does not lead to the expected improvement in tumor accumulation in vivo, BsAb functionalization facilitates tumor cell uptake of PEG particles. This work highlights strategies to balance evading nonspecific clearance pathways, while improving tumor targeting and accumulation.

Cell-Conditioned Protein Coronas on Engineered Particles Influence Immune Responses.

A protein corona, which forms on engineered particles as soon as they are introduced into biological environments, is known to provide particles with a "biological identity". Protein coronas derived from various biological environments have been demonstrated to alter the cell internalization mechanism, to diminish targeting ability and to induce nanoparticle aggregation. So far, most of these studies have challenged engineered particles with a static biological environment. However, the extracellular environment is highly dynamic due to the process termed "cell-conditioning", in which cells deplete and secrete biomolecules. In this work, we demonstrate that protein coronas formed on engineered particles from such cell-conditioned media affect the biophysical particle properties and protein adsorption differently to protein coronas derived from an unconditioned environment. When investigating particles with protein coronas formed in various biologically relevant environments for their interaction with immune cells, we observed differences in pro-inflammatory cytokine secretion and immune cell apoptosis. We found that the particles either increased or mitigated the secretion of a specific cytokine, depending on the environment where the protein corona was formed. Our study suggests that the use of protein coronas could be useful to engineer drug carriers for elongated circulation, enhanced biocompatibility, and lower toxicity by triggering a specific immune response.

Improving Targeting of Metal-Phenolic Capsules by the Presence of Protein Coronas.

Particles adsorb proteins when they enter a physiological environment; this results in a surface coating termed a "protein corona". A protein corona can affect both the properties and functionalities of engineered particles. Here, we prepared hyaluronic acid (HA)-based capsules through the assembly of metal-phenolic networks (MPNs) and engineered their targeting ability in the absence and presence of protein coronas by varying the HA molecular weight. The targeting ability of the capsules was HA molecular weight dependent, and a high HA molecular weight (>50 kDa) was required for efficient targeting. The specific interactions between high molecular weight HA capsules and receptor-expressing cancer cells were negligibly affected by the presence of protein coronas, whereas nonspecific capsule-cell interactions were significantly reduced in the presence of a protein corona derived from human serum. Consequently, the targeting specificity of HA-based MPN capsules was enhanced due to the formation of a protein corona. This study highlights the significant and complex roles of a protein corona in biointeractions and demonstrates how protein coronas can be used to improve the targeting specificity of engineered particles.

KRAS polymorphisms are associated with survival of CRC in Chinese population.

rs12245, rs12587, rs9266, rs1137282, rs61764370, and rs712 of KRAS oncogene are characterized in the 3'UTR. The study highlights the important role of these polymorphisms playing in the susceptibility, oxaliplatin-based chemotherapy sensitivity, progression, and prognosis of CRC. Improved multiplex ligation detection reaction (iMLDR) technique is used for genotyping. An unconditional logistic regression model was used to estimate the association of certain polymorphism and CRC risk. The Kaplan-Meier method, log-rank test, and Cox regression model were used to evaluate the effects of polymorphisms on survival analysis. Results demonstrated that TT genotype and T allele of rs712 were associated with the increased risk of CRC; the patients with GG genotype and G allele of rs61764370 had a shorter survival and a higher risk of relapse or metastasis of CRC. Our studies supported the conclusions that rs61764370 and rs712 polymorphisms of the KRAS are functional and it may play an important role in the development of CRC and oxaliplatin-based chemotherapy efficiency and prognosis of CRC.

XRCC1 and ERCC1 polymorphisms are related to susceptibility and survival of colorectal cancer in the Chinese population.

Excision repair cross complementing group 1 (ERCC1) and X-ray repair cross-complementing groups 1 (XRCC1) are DNA repair enzymes. Polymorphisms in DNA repair genes may be important factors affecting cancer susceptibility, prognosis and therapy outcome. The purpose of this study was to investigate the correlation of ERCC1 and XRCC1 polymorphisms with colorectal cancer (CRC) risk, and explore the effect of polymorphisms on event-free, overall survival and oxaliplatin-based therapy in CRC patients. Genotyping was examined with the iMLDR technique. An unconditional logistic regression model was used to estimate the association of certain polymorphisms with CRC risk. The Kaplan-Meier method, log-rank test and Cox regression model were employed to evaluate the effects of polymorphisms on survival analysis. Results showed that Trp/Trp genotype of XRCC1 Arg194Trp and AA genotype of ERCC1 rs2336219 have a significantly increased risk of CRC; Trp allele of XRCC1 Arg194Trp and CC genotype of ERCC1 rs735482 were associated with lower response to oxaliplatin-based chemotherapy, a shorter survival and a higher risk of relapse or metastasis. 194Trp/280Arg/399Arg haplotype was associated with a significant resistance, and the ERCC1 protein expression was statistically higher in tumours with rs735482 CC genotype than with AA genotype. Our studies indicate that XRCC1 and ERCC1 polymorphisms probably affect susceptibility, chemotherapy response and survival of CRC patients.