Phytic Acid-Functional Cellulose Nanocrystals and Their Application in Self-Healing Nanocomposite Hydrogels.

Cellulose nanocrystals (CNCs) have garnered significant attention as a modifiable substrate because of their exceptional performances, including remarkable degradability, high tensile strength, high elastic modulus, and biocompatibility. In this article, the successful adsorption of phytic acid (PA) onto the surface of cellulose nanocrystals @polydopamine (CNC@PDA) was achieved. Taking inspiration from mussels, a dopamine self-polymerization reaction was employed to coat the surface of CNCs with PDA. Utilizing Pickering emulsion, the CNC@PDA-PA nanomaterial was obtained by grafting PA onto CNC@PDA. An environmentally friendly hydrogel was prepared through various reversible interactions using poly(acrylic acid) (PAA) and Fe3+ as raw materials with the assistance of CNC@PDA-PA. By multiple hydrogen bonding and metal-ligand coordination, nanocomposite hydrogels exhibit remarkable mechanical properties (the tensile strength and strain were 1.82 MPa and 442.1%, respectively) in addition to spectacular healing abilities (96.6% after 5 h). The study aimed to develop an innovative approach for fabricating nanocomposite hydrogels with exceptional self-healing capabilities.

Disruption of the gastric epithelial barrier in Correa's cascade: Clinical evidence via confocal endomicroscopy.

BACKGROUND: Gastric epithelial barrier disruption constitutes a crucial step in gastric cancer (GC). We investigated these disruptions during the Correa's cascade timeline to correlate epithelial barrier dysfunction. MATERIALS AND METHODS: This study was conducted as a single-center, non-randomized clinical trial in China from May 2019 to October 2022. Patients with chronic atrophic gastritis (CAG), gastric intestinal metaplasia (GIM), low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and intramucosal carcinoma underwent probe-based confocal laser endomicroscopy (pCLE). The pCLE scoring system was used to assess gastric epithelial barrier disruption semi-quantitatively. RESULTS: We enrolled 95 patients who underwent a pCLE examination. The control group consisted of 15 individuals, and the experimental group included 17 patients with CAG, 27 patients with GIM, 20 patients with LGIN, and 16 patients with early gastric cancer (EGC). Apart from CAG, which showed no significant difference compared to the control group, a significantly higher incidence of gastric epithelial barrier damage was found in the GIM, LGIN, and EGC groups compared to the control group (Kruskal-Wallis H test = 69.295, p < 0.001). There is no difference in LGIN patients between GIM and LGIN areas, and there is no difference between the two groups compared with the EGC group. The intestinal metaplasia area in LGIN patients causes more severe gastric epithelial damage compared to that in non-LGIN patients. Additionally, compared to control group, a significant difference (p < 0.001) was noted between individuals with Helicobacter pylori-positive atrophic gastritis and those with IM, whereas no significant difference (p > 0.05) was observed among individuals with H. pylori-negative atrophic gastritis. CONCLUSIONS: The gastric epithelial barrier remains dysfunctional from the initiation of H. pylori infection to GC progression. Beyond the "point of no return," subsequent carcinogenesis processes may be attributed to other mechanisms.

Structural Element of Vitamin U-Mimicking Antibacterial Polypeptide with Ultrahigh Selectivity for Effectively Treating MRSA Infections.

Antimicrobial peptides (AMPs) exhibit mighty antibacterial properties without inducing drug resistance. Achieving much higher selectivity of AMPs towards bacteria and normal cells has always been a continuous goal to be pursued. Herein, a series of sulfonium-based polypeptides with different degrees of branching and polymerization were synthesized by mimicking the structure of vitamin U. The polypeptide, G2 -PM-1H+ , shows both potent antibacterial activity and the highest selectivity index of 16000 among the reported AMPs or peptoids (e.g., the known index of 9600 for recorded peptoid in "Angew. Chem. Int. Ed., 2020, 59, 6412."), which can be attributed to the high positive charge density of sulfonium and the regulation of hydrophobic chains in the structure. The antibacterial mechanisms of G2 -PM-1H+ are primarily ascribed to the interaction with the membrane, production of reactive oxygen species (ROS), and disfunction of ribosomes. Meanwhile, altering the degree of alkylation leads to selective antibacteria against either gram-positive or gram-negative bacteria in a mixed-bacteria model. Additionally, both in vitro and in vivo experiments demonstrated that G2 -PM-1H+ exhibited superior efficacy against methicillin-resistant Staphylococcus aureus (MRSA) compared to vancomycin. Together, these results show that G2 -PM-1H+ possesses high biocompatibility and is a potential pharmaceutical candidate in combating bacteria significantly threatening human health.

Multi-Axial Self-Driven X-Ray Detection by a Two-Dimensional Biaxial Hybrid Organic-Inorganic Perovskite Ferroelectric.

Metal halide perovskite ferroelectrics combining spontaneous polarization and excellent semiconducting properties is an ideal platform for enabling self-driven X-ray detection. However, achievements to date have been only based on uniaxiality, which increases the complexity of device fabrication. Multi-axial ferroelectric materials have multiple equivalent polarization directions, making them potentially amenable to multi-axial self-driven X-ray detection, but the report on these types of materials is still a huge blank. Herein, a high-quality (BA)2(EA)2Pb3I10 (1) biaxial ferroelectric single crystal was successfully grown, which exhibited significant spontaneous polarization along the c-axis and b-axis. Under X-ray irradiation, bulk photovoltaic effect (BPVE) was exhibited along both the c-axis and b-axis, with open circuit voltages (Voc) of 0.23 V and 0.22 V, respectively. Then, the BPVE revealed along the inversion of polarized direction with the polarized electric fields. Intriguingly, due to the BPVE of 1, 1 achieved multi-axial self-driven X-ray detection for the first time (c-axis and b-axis) with relatively high sensitivities and ultralow detection limits (17.2 nGyair s-1 and 19.4 nGyair s-1, respectively). This work provides a reference for the subsequent use of multi-axial ferroelectricity for multi-axial self-driven optoelectronic detection.

Analysis of m7G-Related signatures in the tumour immune microenvironment and identification of clinical prognostic regulators in breast cancer.

BACKGROUND: Breast cancer is a malignant tumour that seriously threatens women's life and health and exhibits high inter-individual heterogeneity, emphasising the need for more in-depth research on its pathogenesis. While internal 7-methylguanosine (m7G) modifications affect RNA processing and function and are believed to be involved in human diseases, little is currently known about the role of m7G modification in breast cancer. METHODS AND RESULTS: We elucidated the expression, copy number variation incidence and prognostic value of 24 m7G-related genes (m7GRGs) in breast cancer. Subsequently, based on the expression of these 24 m7GRGs, consensus clustering was used to divide tumour samples from the TCGA-BRCA dataset into four subtypes based on significant differences in their immune cell infiltration and stromal scores. Differentially expressed genes between subtypes were mainly enriched in immune-related pathways such as 'Ribosome', 'TNF signalling pathway' and 'Salmonella infection'. Support vector machines and multivariate Cox regression analysis were applied based on these 24 m7GRGs, and four m7GRGs-AGO2, EIF4E3, DPCS and EIF4E-were identified for constructing the prediction model. An ROC curve indicated that a nomogram model based on the risk model and clinical factors had strong ability to predict the prognosis of breast cancer. The prognoses of patients in the high- and low-TMB groups were significantly different (p = 0.03). Moreover, the four-gene signature was able to predict the response to chemotherapy. CONCLUSIONS: In conclusion, we identified four different subtypes of breast cancer with significant differences in the immune microenvironment and pathways. We elucidated prognostic biomarkers associated with breast cancer and constructed a prognostic model involving four m7GRGs. In addition, we predicted the candidate drugs related to breast cancer based on the prognosis model.

Soy Protein Isolate/Genipin-Based Nanoparticles for the Stabilization of Pickering Emulsion to Design Self-Healing Guar Gum-Based Hydrogels.

Nowadays, stretchable self-healing hydrogels designed by biomass-based materials have gathered remarkable attention in numerous frontier fields such as wound healing, health monitoring issues, and electronic skin. In this study, soy protein isolate (SPI), a common plant protein, was cross-linked to nanoparticles (SPI NPs) by Genipin, (Gen) which was attracted from the native Geniposide. Oil-in-water (O/W) Pickering emulsion was formed by SPI NPs wrapping the linseed oil, and further implanted into poly(acrylic acid)/guar gum (PAA/GG)-based self-healing hydrogels by multiple reversible weak interactions. With the addition of Pickering emulsion, the hydrogels have achieved a remarkable self-healing ability (self-healing efficiency could reach 91.6% within 10 h) and mechanical properties (tensile strength of 0.89 MPa and strain of 853.2%). Therefore, these hydrogels with good reliable durability have outstanding application prospects in sustainable materials.

Regioselective and Diastereoselective Halofunctionalization of Alkenes Promoted by Organophotocatalytic Solar Catalysis.

A visible-light metal-free photocatalytic regioselective and enantioselective alkene halofunctionalization reaction under mild conditions is reported. Various terminal and internal alkenes were transformed to their α-halogenated and α,ß-dibrominated derivatives in good to excellent yields within reaction time as short as 5 min. Water can be used as the "green" nucleophile and solvent in the halohydroxylation and halo-oxidation reactions. Different types of products can be obtained by adjusting the reaction conditions. In addition, sunlight is proved to produce products with similar yields, representing a practical example of solar synthesis and providing an opportunity for solar energy utilization.

Coexistence of early gastric cancer and benign submucosal lesions mimic invasive cancer: a retrospective multicenter experience.

OBJECTIVE: To present a study to identify the characteristics of coexisting early gastric cancer (EGC) and benign submucosal lesions, with the aim of reducing the adverse consequences of overdiagnosis and overtreatment. METHODS: In this retrospective study, we searched the endoscopic databases of three tertiary centers. We screened of patients suspected of early gastric cancer submucosal infiltration by conventional endoscopy and ultimately selected for endoscopic submucosal dissection treatment after endoscopic ultrasonography and magnifying endoscopy with narrow-band imaging examination. Patients with coexisting EGC and benign submucosal lesions in histological sections were included. Clinical data and endoscopic images were reviewed. To evaluate the precision of endoscopists' diagnoses for this type of lesion, eight endoscopists with different experiences were recruited to judge the infiltration depth of these lesions and analyze the accuracy rate. RESULTS: We screened 520 patients and retrospectively identified 18 EGC patients with an invasive cancer-like morphology. The most common lesion site was the cardia (12/18, 66.67%). The coexisting submucosal lesions could be divided into solid (5/18, 27.78%) and cystic (13/18, 72.22%). The most common type of submucosal lesion was gastritis cystica profunda (12/18, 66.67%), whereas leiomyoma was the predominant submucosal solid lesion (3/18, 16.67%). Ten (55.56%) patients < underwent endoscopic ultrasonography; submucosal lesions were definitively diagnosed in 6 patients (60.00%). The accuracy of judgement of the infiltration depth was significantly lower in cases of coexistence of EGC with benign submucosal lesions (EGC-SML) than in EGC (38.50% versus 65.60%, P = 0.0167). The rate of over-diagnosis was significantly higher within the EGC-SML group compared to the EGC group (59.17% versus 10.83%, P < 0.0001). CONCLUSIONS: We should be aware of the coexistence of EGC and benign submucosal lesions, the most common of which is early cardiac-differentiated cancer with gastritis cystica profunda.

Genome-wide association study reveals candidate genes for pollution excreta traits in pigs.

Excreta traits comprise a very important characteristic in breeding that have been neglected for a long time. With the growth of intensive pig farming, plenty of environment problems have been raised, and people have begun to pay attention to pig excreta behaviors from genetics and breeding perspectives. However, the genetic architecture of excreta traits remains unclear. To investigate the genetic architecture of excreta traits in pigs, eight excreta traits and feed conversion ratio (FCR) were analyzed in this study. We performed genome-wide association studies (GWASs) on 213 Yorkshire pigs and estimated genetic parameters for a total number of 290 pigs, comprising 213 Yorkshire, 52 Landrace and 25 Duroc. After analysis, eight and 22 genome-wide significant SNPs were detected for FCR and the eight excreta traits in single-trait GWASs separately, and 18 were detected in a multi-trait meta-analysis for excreta traits, six of which were detected in both the single-trait and the multi-trait GWAS. Eighty, 182 and 133 genes were detected within 1 Mb of the genome-wide significant SNPs for FCR, excreta traits and multi-trait meta-analysis, respectively. Five candidate genes (BCKDC, DBT, ANKRD7, SHPRH and HCRT) with biochemical and physiological effects relevant to feed efficiency and excreta traits might be interesting markers for future breeding. Meanwhile, functional enrichment analysis indicates that most of the significant pathways are associated with the glutathione catabolic process, DNA topological change and replication fork protection complex. This study reveals the architecture of excreta traits in commercial pigs and offers an opportunity for decreasing the pollution from excreta using genomic selection in pigs.

Ring finger protein 126 promotes breast cancer metastasis and serves as a potential target to improve the therapeutic sensitivity of ATR inhibitors.

BACKGROUND/AIMS: This study explores the relationship between the E3 ubiquitin ligase Ring finger protein 126 (RNF126) and early breast cancer metastasis and tests the hypothesis that RNF126 determines the efficacy of inhibitors targeting Ataxia telangiectasia mutated and Rad3-related kinase (ATR). METHODS: Various metastasis-related genes were identified by univariable Cox proportional hazards regression analysis based on the GSE11121 dataset. The RNF126-related network modules were identified by WGCNA, whereas cell viability, invasion, and migration assays were performed to evaluate the biological characteristics of breast cancer cells with or without RNF126 knockdown. MTT, immunoblotting, immunofluorescence, and DNA fiber assays were conducted to determine the efficiency of ATR inhibitor in cells with or without RNF126 knockdown. RESULTS: RNF126 was associated with early breast cancer metastasis. RNF126 promoted breast cancer cell proliferation, growth, migration, and invasion. ATR inhibitors were more effective at killing breast cancer cells with intact RNF126 due to replication stress compared with the corresponding cells with RNF126 knockdown. Cyclin-dependent kinase 2 (CDK2) was involved in regulating replication stress in breast cancer cells with intact RNF126. CONCLUSION: A high level of expression of RNF126 in early breast cancer patients without lymph node metastases may indicate a high-risk type of metastatic disease, possibly due to RNF126, which may increase breast cancer cell proliferation and invasion. RNF126-expressing breast cancer cells exhibit CDK2-mediated replication stress that makes them potential targets for ATR inhibitors.