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.

Fabrication of anti-freezing and self-healing nanocomposite hydrogels based on phytic acid and cellulose nanocrystals for high strain sensing applications.

For hydrogel-based flexible sensors, it is a challenge to enhance the stability at sub-zero temperatures while maintaining good self-healing properties. Herein, an anti-freezing nanocomposite hydrogel with self-healing properties and conductivity was designed by introducing cellulose nanocrystals (CNCs) and phytic acid (PA). The CNCs were grafted with polypyrrole (PPy) by chemical oxidation, which were used as the nanoparticle reinforcement phase to reinforce the mechanical strength of hydrogels (851.8%). PA as a biomass material could form strong hydrogen bond interactions with H2O molecules, endowing hydrogels with prominent anti-freezing properties. Based on the non-covalent interactions, the self-healing rate of the hydrogels reached 92.9% at -15 °C as the content of PA was 40.0 wt%. Hydrogel-based strain sensors displayed high sensitivity (GF = 0.75), rapid response time (350 ms), good conductivity (3.1 S m-1) and stability at -15 °C. Various human movements could be detected by using them, including small (smile and frown) and large changes (elbow and knee bending). This work provides a promising method for the development of flexible wearable sensors that work stably in frigid environments.

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.

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.

Ultrasound Triggered Tumor Metabolism Suppressor Induces Tumor Starvation for Enhanced Sonodynamic Immunotherapy of Breast Cancer.

Introduction: Sonodynamic therapy (SDT) as an emerging tumor treatment gained wide attention. However, tumor vascular destruction and oxygen depletion in SDT process may lead to further hypoxia. This may lead to enhanced glycolysis, lactate accumulation, and immunosuppression. Methods: A glycolysis inhibitor (3PO) loaded and PEG modified black phosphorus nanosheets (BO) is constructed for potent starvation therapy and efficient immune activation. Results: Under ultrasound irradiation, the BO can produce ROS to destroy tumors and tumor blood vessels and lead to further hypoxia and nutrients block. Then, the released 3PO inhibits tumor glycolysis and prevents the hypoxia-induced glycolysis and lactate accumulation. Both SDT and 3PO can cut off the source of lactic acid, as well as achieve antitumor starvation therapy through the blockade of the adenosine triphosphate (ATP) supply. In addition, the combination of starvation treatment and SDT further facilitates dendritic cells (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity and inhibition of abscopal tumor growth. Conclusion: This is the first time that combines SDT with inhibition of glycolysis, achieving admirable tumor treatment and decreasing adverse events caused by SDT process and that has caused good immune activation. Our system provides a new idea for the future design of anti-tumor nanomedicines.

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.

Injectable thermo-sensitive hydrogel loaded hollow copper sulfide nanoparticles for ROS burst in TME and effective tumor treatment.

Introduction: Lung cancer the most prevalent cause of cancer-related deaths, and current therapies lack sufficient specificity and efficacy. This study developed an injectable thermosensitive hydrogel harboring hollow copper sulfide nanoparticles and ß-lapachone (Lap) (CLH) for lung tumor treatment. Methods: The hydrogel-encapsulated CLH system can remotely control the release of copper ions (Cu2+) and drugs using photothermal effects for non-invasive controlled-release drug delivery in tumor therapy. The released Cu2+ consumes the overexpressed GSH in TME and the generated Cu+ further exploits the TME characteristics to initiate nanocatalytic reactions for generating highly toxic hydroxyl radicals. In addition, in cancer cells overexpressing Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase 1 (NQO1), Lap can catalyze the generation of hydrogen peroxide (H2O2) through futile redox cycles. H2O2 is further converted into highly toxic hydroxyl radicals via the Fenton-like reaction, leading to a burst of reactive oxygen species in TME, which further enhances the therapeutic effect of chemokines. Results: Analysis of the antitumor efficacy in a subcutaneous A549 lung tumor model mice showed a significant delay in tumor growth and no systemic toxicity was detected. Discussion: In conclusion, we have established a CLH nanodrug platform that enables efficient lung tumor therapy through combined photothermal/chemodynamic therapy (CDT) treatment and self-supplying H2O2 to achieve cascade catalysis, leading to explosive amplification of oxidative stress.

Effect of radiation sterilisation on the structure and antibacterial properties of antimicrobial peptides.

Antimicrobial peptides (AMPs) have recently been exploited to fabricate anti-infective medical devices due to their biocompatibility and ability to combat multidrug-resistant bacteria. Modern medical devices should be thoroughly sterilised before use to avoid cross-infection and disease transmission, consequently it is essential to evaluate whether AMPs withstand the sterilisation process or not. In this study, the effect of radiation sterilisation on the structure and properties of AMPs was explored. Fourteen AMPs formed from different monomers with different topologies were synthesised by ring-opening polymerisation of N-carboxyanhydrides. The results of solubility testing showed that the star-shaped AMPs changed from water-soluble to water-insoluble after irradiation, while the solubility of linear AMPs remained unchanged. Matrix-assisted laser desorption/ionisation time of flight mass spectrometry showed that the molecular weight of the linear AMPs underwent minimal changes after irradiation. The results of minimum inhibitory concentration assay also illustrated that radiation sterilisation had little effect on the antibacterial properties of the linear AMPs. Therefore, radiation sterilisation may be a feasible method for the sterilisation of AMPs, which have promising commercial applications in medical devices.

Molecular subtypes predict the preferential site of distant metastasis in advanced breast cancer: a nationwide retrospective study.

Objective: This study aimed to explore possible associations between molecular subtypes and site of distant metastasis in advanced breast cancer (ABC). Methods: 3577 ABC patients were selected from 21 hospitals of seven geographic regions in China from 2012-2014. A questionnaire was designed to collect medical information regarding demographic characteristics, risk factors, molecular subtype, recurrence/metastasis information, and disease-free survival (DFS). The cancers were classified into Luminal A, Luminal B, HER2-enriched and Triple Negative subtypes. Chi-square test and multivariate Cox proportional hazard models were performed to explore the associations between molecular subtypes and distant metastasis sites. Results: A total of 2393 cases with molecular subtypes information were finally examined. Patients with Luminal A (51.1%) and Luminal B (44.7%) were most prone to bone metastasis, whereas liver metastasis was more frequently observed in HER2-enriched ABC patients (29.1%).The cumulative recurrence and metastasis rates of ABC patients at 36 months of DFS were the most significant within molecular types, of which Triple Negative was the highest (82.7%), while that of Luminal A was the lowest (58.4%). In the adjusted Cox regression analysis, Luminal B, HER2-enriched and Triple Negative subtypes increased the risk of visceral metastasis by 23%, 46% and 87% respectively. In addition, Triple Negative patients had a higher probability of brain metastasis (HR 3.07, 95% CI: 1.04-9.07). Conclusion: Molecular subtypes can predict the preferential sites of distant metastasis, emphasizing that these associations were of great help in choices for surveillance, developing appropriate screening and cancer management strategies for follow-up and personalized therapy in ABC patients.

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.

Age at initial diagnosis and prognosis of breast cancer: a nationwide multicenter retrospective study in China.

Background: Several studies have indicated possible associations between age and the prognosis of breast cancer (BC), but limited data are available from hospital-based multicenter studies in China. This study aimed to explore the associations between age at initial diagnosis of BC and the risk of recurrence or metastasis among Chinese women with newly diagnosed advanced breast cancer (ABC) and provide treatment decision support for BC patients of different ages to medical workers. Methods: The medical records of patients newly diagnosed with ABC were obtained from 21 hospitals in seven geographic regions in China from 2012 to 2014. Patients' general information, clinicopathological features at first diagnosis, treatment information, and prognosis were retrospectively collected based on the self-designed case report form (CRF). Cox proportional hazards regression models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for the associations between age groups and the risk of recurrence and metastasis. Results: A total of 1,852 cases were included in the final analysis. Age at initial diagnosis was shown to be significantly related to hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtypes, and the number of lymph node metastasis (all P<0.05). Patients aged <35 years were more likely to have bone metastasis (45.6%). Patients aged ≥65 years had a lower percentage of receiving surgery (87.1%), adjuvant chemotherapy (61.3%), adjuvant radiotherapy (35.5%), and adjuvant endocrine therapy (30.6%) than the other groups (all P<0.05). Compared with patients aged <35 years, the risk of recurrence or metastasis in those aged 55-64 years was significantly higher (HRage 55-64 =1.24, 95% CI: 1.04-1.47), and the risk of bone metastasis and lung metastasis in those aged 35-44 years was lower (HRbone metastasis =0.74, 95% CI: 0.59-0.93; HRlung metastasis =0.70, 95% CI: 0.53-0.93). After adjusting for stage, grade, and molecular subtype, surgery, neoadjuvant chemotherapy, adjuvant chemotherapy, adjuvant radiotherapy, adjuvant endocrine therapy, and family history of BC, patients aged 35-44 years still had a significantly reduced risk of bone metastasis and lung metastasis by 31% and 52%, respectively (HRbone metastasis =0.69, 95% CI: 0.48-0.98; HRlung metastasis =0.48, 95% CI: 0.31-0.74). Conclusions: Age at initial diagnosis is related to the clinicopathological characteristics and treatment pattern. Although the risk of site-specific metastasis varies by age, age is not an independent factor influencing the risk of total recurrence and metastasis. In accordance with current clinical practice guidelines for BC, however, precise treatment shall be chosen personally for patients whose ages at initial diagnosis are different.

Fabrication of Janus-type nanocomposites from cellulose nanocrystals for self-healing hydrogels' flexible sensors.

Janus bio-nanomaterials have great application potential in functional solid surfactants, probes and flexible sensors. In this manuscript, the sustainable Janus cellulose nanocrystals-type (CNCs-type) nanomaterials were prepared by Pickering emulsion template method. The asymmetric functionalism of Janus nanorods was realized by asymmetrically grafting polypyrrole (PPy) and polydopamine (PDA) onto different sides of CNCs (Janus CNCs-PPy /PDA (JCNs)). JCNs was successfully applied to self-healing nanocomposite hydrogels and further applied to the development of flexible sensors. The self-healing efficiency of nanocomposite hydrogels was 87.2%, and the stress and strain reached 3.50 MPa and 453.45%, respectively. It is worth noting that flexible sensors have been widely used in the field of wearable electronic sensing for real-time monitoring of human movement due to their high sensitivity (gauge factor (GF) = 9.9) and fast response time (260 ms).

Janus-like Bx C/C Quantum Sheets with Z-Scheme Mechanism Strengthen Tumor Photothermal-Immunotherapy in NIR-II Biowindow.

Carbon dots (CDs) are one of the most popular photothermal agents (PTAs) as a noninvasive strategy for tumor treatment. However, because of the inherent dominant fluorescent emission, the CDs-based PTAs hardly achieve a single photothermal conversion, which causes low photothermal conversion efficiency and poor photothermal performance. In this regard, finding a new CDs-based material system to greatly restrain its fluorescence to enhance its photothermal conversion efficiency is highly required, however, it is still a grand challenge. Herein, a kind of Z-scheme CDs-based PTAs consisting of 2D ultrathin nonmetallic Bx C/C Janus quantum sheets (Bx C/C JQSs) is reported to greatly enhance the photothermal conversion efficiency. It is demonstrated that the heterogeneous growth of Z-scheme Bx C/C JQSs enables the NIR-driven quick injection of hot electrons from C into the conjugated Bx C, realizing a single conversion of light to heat, and resulting in a high photothermal conversion of 60.0% in NIR-II. Furthermore, these new Z-scheme Bx C/C-polyethylene glycol JQSs display outstanding biocompatibility and show effective tumor elimination outcome both in vitro and in vivo through the synergistic photothermal-immunotherapy in the NIR-II biowindow with undetectable harm to normal tissues.

Preparation of antibacterial polypeptides with different topologies and their antibacterial properties.

Antimicrobial peptides (AMPs) are attractive antimicrobial agents used to combat bacterial infections, and have been advanced to be one of the most promising alternatives to conventional antibiotics. They stand out for their attractive broad-spectrum activity, unmatched antibacterial mechanism that is not prone to develop drug resistance and diversified topologies, which can be fabricated with manifold amino acid blocks. In this study, using n-hexylamine and amine-terminated polyamidoamine dendrimers (Gx-PAMAM, x = 1-2) as initiators, a series of AMPs with linear and star-shaped topological structures were constructed via the controllable ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs). The antibacterial performances of the tailored linear and star-shaped AMPs were comprehensively evaluated in both solution states and surface-bonded states. The results indicated that the star-shaped AMPs exhibited enhanced bactericidal activity against Gram-negative E. coli and similar bactericidal activity against Gram-positive S. aureus when compared with the linear AMPs. It is worth mentioning that star-shaped AMPs demonstrated a significantly faster bactericidal efficiency (completely killed bacteria within 5 min at a concentration of 2 × MIC for S. aureus) than their linear analogues (took 15 min to achieve the same effect). However, when the AMPs were immobilized to the surface, they similarly exhibited superior antibacterial activity and fast bactericidal efficiency towards S. aureus and E. coli in the case of the same surface grafting amount. In addition, both the surfaces grafted with AMPs of different topologies demonstrated favorable biocompatibility in vitro.

Surface modification of cellulose nanocrystals via SI-AGET ATRP and application in waterborne coating for removing of formaldehyde.

The hazardous indoor air pollutants of formaldehyde (HCHO) are harmful for human health. Nowadays, it is important to design and fabricate green and efficient HCHO removal materials for HCHO removal from polluted indoor air. In this manuscript, cellulose nanocrystals (CNCs) as green nanomaterials were successfully surface-initiated by 2-(methacryloyloxy)ethyl acetoacetate (MEAA) as functional monomer via surface-initiated Activator Generated by Electron Transfer Atom Transfer Radical Polymerization (SI-AGET ATRP) for the application in removal of HCHO. The employment of CNCs/Poly(2-(methacryloyloxy)ethyl acetoacetate) (CNCs@PMEAA) as nanocomposites were further implanted self-healing waterborne coating for an effective way to remove HCHO. From the result, the HCHO removal efficiency reached 97.5% of CNCs@PMEAA-type coating within 300 min at room temperature, which was much higher than that of the conventional coating (82.8%). This study provides some promising green methods for designing nanocomposite's waterborne coating to remove HCHO at room temperature.

Comparisons of Treatment for HER2-Positive Breast Cancer between Chinese and International Practice: A Nationwide Multicenter Epidemiological Study from China.

OBJECTIVE: To better understand the status of medical treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer and the differences between the Chinese and the international clinical practice. METHODS: This was a retrospective, nationwide, multicenter, epidemiological study of advanced breast cancer patients from China. Between January 01, 2012, and December 31, 2014, a total of 3649 patients, covering 7 geographic regions and 21 institutions, participated in this series of studies. HER2-positive breast cancer was selected among the group and adopted into this study. In comparison, we summarized the demographics and clinical characteristics of HER2-positive breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: A total of 918 patients diagnosed as HER2-positive breast cancer patients were included. The median age at diagnosis was 46 years (ranging, 23 to 78) with a single-peak incidence. The proportions of stages II-IV at diagnosis and distance metastasis in viscera were more than half of the participants. In comparison, the prevalence of estrogen or progesterone receptor-positive expression and luminalB subtype was relatively lower than that of the United States. The receipt of chemotherapy was fairly higher, while the usage of targeted therapy was seriously insufficient. Tumor size was in significantly positive associations with the duration of targeted therapy (Kendall's correlation coefficient = 0.3, P < 0.0001), while no prohibitive variables among clinical characteristics were detected. CONCLUSION: Our study suggested that HER2-positive breast cancer patients were characterized as a younger trend, a lower prevalence of hormonal receptor (HR)-positive expression, and less accessible to anti-HER2 targeted therapy with insufficient duration over the past few years in China. Concerted efforts should be exerted for promising survival benefits in the future. The trial registration number is https://clinicaltrials.gov/ct2/show/NCT03047889.

Stretchable, rapid self-healing guar gum-poly(acrylic acid) hydrogels as wearable strain sensors for human motion detection based on Janus graphene oxide.

Wearable strain sensors have received widespread attention in research fields due to their applications in human motion detection. In this manuscript, the fabrication of functionalized Janus graphene oxide (GO) nanosheets were used by Pickering emulsion template. Polypyrrole (PPy) and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) were asymmetrically grafted on the two sides of GO (GO@PPy/PDMAEMA Janus NS), which successfully applied to synthesize Janus NS/guar gum-poly(acrylic acid) (GG-PAA) self-healing nanocomposite hydrogels. The outstandingly improved self-healing efficiency (92.8% for 2 h) and mechanical properties (strength of 4.12 MPa and toughness of 873.8%) of nanocomposite hydrogels were mainly supported by the collaborative effect of reversible electrostatic interactions, multiple hydrogen bonds and metal-ligand coordination. Moreover, the hydrogels exhibited strain sensitivity and could be able to monitor a variety of human motions, which have outstanding application prospects in wearable flexible sensors.

Profile, treatment patterns, and influencing factors of anthracycline use in breast cancer patients in China: A nation-wide multicenter study.

BACKGROUND: Anthracycline-based chemotherapy (ABC) is one of the standard therapies against breast cancer. However, few guidelines are currently available to optimize the use of ABC. Therefore, the present analysis aimed at determining the profile and treatment patterns of ABC and the association of clinicopathological characteristics with ABC selection. METHODS: We retrospectively analyzed the data of a nation-wide multicenter epidemiological study, which collected the medical records of breast cancer patients receiving chemotherapy in different settings from seven geographic regions in China (NCT03047889). RESULTS: In total, 3393 patients were included, with 2917 treated with ABC. Among them, 553 (89.8%), 2165 (81.7%), and 814 (25.7%) were subjected to ABC as neoadjuvant, adjuvant, and advanced chemotherapy, respectively. The most frequently used regimens were anthracycline-taxane-based combinations for neo- and adjuvant chemotherapy, along with taxanes and oral fluorouracils for the palliative stages. In the overall cohort, patients aged < 40 or 40-65 (p < 0.001), in premenopause (p < 0.001), without comorbidities (p = 0.016), with invasive ductal carcinoma (p= 0.001), high lymph node involvement (p < 0.001), in the pTNM stage II, III, or IV versus stage I (p < 0.001), subjected to mastectomy (p < 0.001) or subjected to sentinel lymph node biopsy combined with axillary lymph node dissection (p = 0.044), or with a decreased disease-free survival (p < 0.001) were more likely to be recommended to ABC. CONCLUSION: Taken together, ABC remained the mainstay of breast cancer treatment, especially in neo and adjuvant therapy. ABC was mainly used as a combination therapy, and the correlation between influencing factors and ABC choice varied during different settings, indicating the preference and different perspectives of medication considered by medical oncologists regarding the use ABC in China.

Aquaporin 1 knockdown inhibits triple-negative breast cancer cell proliferation and invasion in vitro and in vivo.

Aquaporin 1 (AQP1) contributes to the progression of several cancer types, but its potential involvement in triple-negative breast cancer (TNBC) is unclear. The aim of the present study was to examine the role of AQP1 in cell proliferation and invasion in TNBC. Reverse transcription-quantitative PCR analysis and western blotting were used to detect AQP1 expression in different cell lines. A short hairpin (sh)RNA targeting AQP1 was established and transfected into MDA-MB-231 breast cancer cells. To investigate the effects of AQP1 knockdown, breast cancer cell proliferation, migration and invasion were evaluated by Cell Counting Kit-8 and Transwell assays. Furthermore, the volume and weight of tumor xenografts in mice were measured to evaluate breast cancer growth ability. The results revealed that the levels of AQP1 were higher in the MDA-MB-231 cell line compared with those in other breast cancer cell lines (MCF-7 and SK-BR-3) and a normal mammary epithelial cell line (MCF-10A). The shRNA targeting AQP1 effectively downregulated AQP1 expression at the mRNA and protein levels, and markedly suppressed TNBC cell proliferation, migration and invasion in vitro, and tumor growth in vivo. These results suggested that AQP1 may serve as a potential therapeutic target in TNBC.