Modified Y-V plasty based on MRU evaluation for iatrogenic bladder outlet obliteration: a multicentre experience in China.

PURPOSE: To compare the diagnostic ability of traditional radiographic urethrography and magnetic resonance urethrography (MRU) for iatrogenic bladder outlet obliteration (BOO), and explore the efficacy and complications of laparoscopic modified Y-V plasty for patients selected based on MRU evaluation. METHODS: 31 patients with obliteration segments ≤ 2 cm and no false passages or diverticula based on MRU evaluation from eight centers in China were included. Obliteration segments were measured preoperatively by MRU and conventional RUG/VCUG and compared with intra-operative measurements. Surgical effects were evaluated by uroflow rates, urethrography, or cystoscopy at 1, 3, 6, and 12 months post-operation and then every 12 months. Postoperative urinary continence was assessed by 24-h urine leakage (g/day). RESULTS: The results showed that MRU measured the length of obliteration more accurately than RUG/VCUG (MRU 0.91 ± 0.23 cm, RUG/VCUG 1.72 ± 1.08 cm, Actual length 0.96 ± 0.36 cm, p < 0.001), and clearly detected false passages and diverticula. Laparoscopic Y-V plasty was modified by incisions at 5 and 7 o'clock positions and double-layer suture with barbed sutures. All operations were successfully completed within a median time of 75 (62-192) minutes and without any complications. Urethral patency and urinary continence rates were 90.3% (28/31) and 87.1% (27/31), respectively. Three recurrences were cured by direct visual internal urethrotomy. Four patients had stress urinary incontinence after catheter removal 14 days post-operation, with urine leakage of 80-120 g/day, not relieved during follow-up. CONCLUSIONS: Laparoscopic modified Y-V plasty based on MRU evaluation is a promising approach for iatrogenic BOO, with a high patency rate and a low incontinence rate.

Tumor microenvironment characterization identifies two lung adenocarcinoma subtypes with specific immune and metabolic state.

The tumor microenvironment (TME) is a vital component of tumor tissue. Increasing evidence suggests their significance in predicting outcomes and guiding therapies. However, no studies have reported a systematic analysis of the clinicopathologic significance of TME in lung adenocarcinoma (LUAD). Here, we inferred tumor stromal cells in 1184 LUAD patients using computational algorithms based on bulk tumor expression data, and evaluated the clinicopathologic significance of stromal cells. We found LUAD patients showed heterogeneous abundance in stromal cells. Infiltration of stromal cells was influenced by clinicopathologic features, such as age, gender, smoking, and TNM stage. By clustering stromal cells, we identified 2 clinically and molecularly distinct LUAD subtypes with immune active and immune repressed features. The immune active subtype is characterized by repressed metabolism and repressed proliferation of tumor cells, while the immune repressed subtype is characterized by active metabolism and active proliferation of tumor cells. Differentially expressed gene analysis of the two LUAD subtypes identified an immune activation signature. To diagnose TME subtypes practically, we constructed a TME score using principal component analysis based on the immune activation signature. The TME score predicted TME subtypes effectively in 3 independent datasets with areas under the receiver operating characteristic curves of 0.960, 0.812, and 0.819, respectively. In conclusion, we proposed 2 clinically and molecularly distinct LUAD subtypes based on tumor microenvironment that could be valuable in predicting clinical outcome and guiding immunotherapy.

Utility of isocitrate dehydrogenase 1 as a serum protein biomarker for the early detection of non-small-cell lung cancer: A multicenter in vitro diagnostic clinical trial.

We aimed to verify the expression status and diagnostic significance of isocitrate dehydrogenase 1 (IDH1) in non-small-cell lung cancer (NSCLC), especially during early stages. Serum IDH1 levels were measured by ELISA. A total of 1223 participants (660 patients with NSCLC, 276 healthy controls [HCs], 95 patients with benign pulmonary conditions [BPCs], 135 patients with other cancers [OCs], and 57 samples with interfering factors) were divided into a training cohort and a validation cohort according to 3 testing centers. The IDH1 concentrations in the NSCLC group were obviously higher than those in the control groups (P < .001). Area under the receiver operating characteristic curves (AUCs) for discriminating NSCLC patients from controls (HC, BPC, and OC) were 0.870 and 0.745 (sensitivity, 63.3% and 55.0%; specificity, 86.8% and 86.3%) in the training cohort and validation cohort, respectively. The AUCs for discriminating stage 0-IA lung cancer patients from HCs were 0.907 and 0.788 (sensitivity, 58.6% and 59.1%; specificity, 92.9% and 89.3%) in 2 cohorts, respectively. Isocitrate dehydrogenase 1 showed specificity for NSCLC and had no diagnostic value for other common cancers. Furthermore, IDH1 was significantly reduced in postoperative serum. Isocitrate dehydrogenase 1 shows clinical utility as a serum protein biomarker for the early diagnosis of NSCLC.

Survival-associated alternative splicing signatures in esophageal carcinoma.

Alternative splicing (AS), a major mechanism for the enhancement of transcriptome and proteome diversity, has been widely demonstrated to be involved in the full spectrum of oncogenic processes. High-throughput sequencing technology and the rapid accumulation of clinical data sets have provided an opportunity to systemically analyze the association between messenger RNA AS variants and patient clinical outcomes. Here, we compared differentially spliced AS transcripts between esophageal carcinoma (ESCA) and non-tumor tissues, profiled genome-wide survival-associated AS events in 87 patients with esophageal adenocarcinoma (EAC) and 79 patients with esophageal squamous cell carcinoma (ESCC) using The Cancer Genome Atlas (TCGA) RNA-seq data set, and constructed predictive models as well as splicing regulation networks by integrated bioinformatic analysis. A total of 2326 AS events in 1738 genes and 1812 AS events in 1360 genes were determined to be significantly associated with overall survival (OS) of patients in the EAC and ESCC cohorts, respectively, including some essential participants in the oncogenic process. The predictive model of each splice type performed reasonably well in distinguishing good and poor outcomes of patients with esophageal cancer, and values for the area under curve reached 0.942 and 0.815 in the EAC exon skip predictive model and the ESCC alternate acceptor site predictive model, respectively. The splicing regulation networks revealed an interesting correlation between survival-associated splicing factors and prognostic AS genes. In summary, we created prognostic models for patients with esophageal cancer based on AS signatures and constructed novel splicing correlation networks.

Translational value of IDH1 and DNA methylation biomarkers in diagnosing lung cancers: a novel diagnostic panel of stage and histology-specificity.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide, and the timely and serial assessment of low-dose computed tomography (LDCT) in high-risk populations remains a challenge. Furthermore, testing a single biomarker for the diagnosis of lung cancers is of relatively low effectiveness. Thus, a stronger diagnostic combination of blood biomarkers is needed to improve the diagnosis of non-small cell lung cancer (NSCLC). METHODS: The blood levels of individual biomarkers [IDH1, DNA methylation of short stature homeobox 2 gene (SHOX2), and prostaglandin E receptor 4 gene (PTGER4)] were measured and statistically analyzed in samples from healthy controls and patients with lung cancer. In total, 221 candidates were enrolled and randomly assigned into two groups for the training and validation of a diagnostic panel. Additionally, a subgroup analysis was performed in the whole cohort. RESULTS: A newly combined 3-marker diagnostic model for lung cancers was established and validated with area under the receiver operating characteristic (ROC) curve (AUC) values ranging from 0.835 to 0.905 in independent groups showing significantly stronger diagnostic value compared with a single tested biomarker. The sensitivity of the diagnostic model was as high as 86.1% and 80.0% in the training and validation sets, respectively. Although no apparent differences were found between the 3-marker and 2-marker models, the high clinical T-stage and histological type specificity of IDH1 and two other methylated DNA biomarkers were demonstrated in the subgroup analysis. CONCLUSIONS: The combination of single biomarkers with high stage-specificity and histological type specificity (SHOX2 and PTGER4 DNA methylation and IDH1) showed better diagnostic performance in the detection of lung cancers compared with single marker assessment. A greater clinical utility of the panel may be developed by adding demographic/epidemiologic characteristics.

Synthesis of Thermo-, Oxidation-, pH-, and CO2 -Responsive Polymers via the Combination of Aza-Michael and Thiol-Michael Reactions in One Pot.

The combination of efficient and harmonious aza-Michael and thiol-Michael reactions in one pot is first reported for the convenient synthesis of thermo-, oxidation-, pH-, and CO2 -responsive polymers. The simultaneous two-type Michael reactions are proved to proceed smoothly without additional catalyst. The dithiol and diamine are involved in the copolymerization competitively and thus in a random distribution. A wide range of commercially available starting materials are utilized for the simultaneous two-type Michael reactions in one pot to obtain various responsive polymers with different structures. The cloud point of the thermo-responsive polymers is easily tuned by adjusting the copolymerization ratio of monomers or using monomers with different structures. Besides, the oxidation- and pH-/CO2 - responsiveness are also demonstrated.

MicroRNA-30e-5p suppresses non-small cell lung cancer tumorigenesis by regulating USP22-mediated Sirt1/JAK/STAT3 signaling.

MicroRNA-30e-5p (miR-30e-5p) is a tumor suppressor that is known to be downregulated in non-small cell lung cancer (NSCLC). However, how miR-30e-5p inhibits NSCLC tumorigenesis is not known. Ubiquitin-specific peptidase 22 (USP22) is upregulated in NSCLC and promotes tumorigenesis via a Sirt1-JAK-STAT3 pathway. In this study, we investigated whether miR-30e-5p inhibits tumor growth by targeting USP22 in NSCLC. Our results reveal that miR-30e-5p expression was correlated negatively with USP22 in NSCLC tissues. Luciferase reporter assays showed that miR-30e-5p negatively regulated USP22 expression by binding to a specific sequence in the 3'UTR. MiR-30e-5p overexpression and USP22 knockdown significantly inhibited tumor growth in vivo and induced cell cycle arrest and apoptosis in NSCLC cells in vitro. The effects of miR-30e-5p inhibition were prevented by USP22 knockdown. MiR-30e-5p inhibited SIRT1 expression and increased expression of p53 and the phosphorylated form of STAT3 (pSTAT3). Furthermore, miR-30e-5p prevented USP22-mediated regulation of SIRT1, pSTAT3, and p53 expression. Taken together, these findings suggest that miR-30e-5p suppresses NSCLC tumorigenesis by downregulatingUSP22-mediated Sirt1/JAK/STAT3 signaling. Our study has identified miR-30e-5p as a potential therapeutic target for the treatment of NSCLC.

RNA editing is induced by type I interferon in esophageal squamous cell carcinoma.

In recent years, abnormal RNA editing has been shown to play an important role in the development of esophageal squamous cell carcinoma, as such abnormal editing is catalyzed by ADAR (adenosine deaminases acting on RNA). However, the regulatory mechanism of ADAR1 in esophageal squamous cell carcinomas remains largely unknown. In this study, we investigated ADAR1 expression and its association with RNA editing in esophageal squamous cell carcinomas. RNA sequencing applied to esophageal squamous cell carcinoma clinical samples showed that ADAR1 expression was correlated with the expression of STAT1, STAT2, and IRF9. In vitro experiments showed that the abundance of ADAR1 protein was associated with the induced activation of the JAK/STAT pathway by type I interferon. RNA sequencing results showed that treatment with type I interferon caused an increase in the number and degree of RNA editing in esophageal squamous cell carcinoma cell lines. In conclusion, the activation of the JAK/STAT pathway is a regulatory mechanism of ADAR1 expression and causes abnormal RNA editing profile in esophageal squamous cell carcinoma. This mechanism may serve as a new target for esophageal squamous cell carcinoma therapy.

Synthesis of Photocrosslinkable and Amine Containing Multifunctional Nanoparticles via Polymerization-Induced Self-Assembly.

Photo-crosslinkable and amine-containing block copolymer nanoparticles are synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly of a multifunctional core-forming monomer, 2-((3-(4-(diethylamino)phenyl)acryloyl)oxy)ethyl methacrylate (DEMA), using poly(2-hydroxypropyl methacrylate) macromolecular chain transfer agent as a steric stabilizer in methanol at 65 °C. By tuning the chain length of PDEMA, a range of nanoparticle morphologies (sphere, worm, and vesicle) can be obtained. Since cinnamate groups can easily undergo a [2 + 2] cycloaddition of the carbon-carbon double bonds upon UV irradiation, the as-prepared block copolymer nanoparticles are readily stabilized by photo-crosslinking to produce anisotropic nanoparticles. The crosslinked block copolymer nanoparticles can be used as templates for in situ formation polymer/gold hybrid nanoparticles.

MiR-196a2 rs11614913 T>C Polymorphism is Associated with an Increased Risk of Tetralogy of Fallot in a Chinese Population.

BACKGROUND: MicroRNAs (miRNAs) are a family of endogenous, small, noncoding single-stranded RNAs that act as post-transcriptional gene regulatory elements. MiRNA polymorphisms may be associated with susceptibility to congenital heart disease (CHD). The aim of this study was to evaluate the impact of miRNA single nucleotide polymorphisms (SNPs) on CHD susceptibility. METHODS: We genotyped two functional SNPs, miR-196a2 rs11614913 and miR-146a rs2910164, in a case-control cohort of 173 Chinese patients with tetralogy of Fallot (TOF) and 207 non-CHD controls. RESULTS: When the miR-196a2 rs11614913 TT homozygote genotype was used as the reference group, the TC genotype was not associated with an increased risk of TOF. The CC genotype was associated with a borderline significantly increased risk for TOF. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significantly increased risk of TOF (OR = 1.96, 95% CI = 1.18-3.25, p = 0.01). The miR-146a rs2910164 C>G polymorphism was not associated with developing TOF. CONCLUSIONS: Our findings suggested that the miR-196a2 rs11614913 T>C polymorphism may play a role in the development of TOF. Future larger studies that include populations of other ethnicities are required to confirm these findings. KEY WORDS: Congenital heart disease; MiRNA; Molecular epidemiology; Polymorphisms; Tetralogy of Fallot.

The early and mid-term results of mitral valve repair for mitral regurgitation in children.

PURPOSE: To review the surgical techniques and mid-term results of mitral valve repair in children with moderate or severe mitral regurgitation (MR). METHODS: One hundred and seven children with moderate or severe MR, aged 19.6 ± 8.5 months, were enrolled in this study. The surgical techniques used for mitral valve repair varied according to the mitral valve morphology, and included annuloplasty, annuloplasty ring, cleft closure, reconstruction of the posterior leaflet, etc. The concomitant cardiac anomalies were treated simultaneously. The results of repair were evaluated by transesophageal echocardiography performed during the operation and by serial transthoracic echocardiography performed during the follow-up. RESULTS: One hundred and six cases had no more than mild regurgitation intraoperatively, whereas only one case had moderate regurgitation. This patient underwent redo repair immediately, and the subsequent regurgitation was trivial. The in-hospital mortality rate was 0.9 % (1/107). The average follow-up was 46.5 ± 8.2 months. One patient died of heart failure 10 months postoperatively. The freedom from moderate or severe regurgitation after mitral valve repair was 92.3 ± 3.3 %. CONCLUSION: Pediatric patients with moderate or severe MR require early surgical treatment. The early and mid-term results of mitral valve repair in pediatric patients were satisfactory.

Synergistic effects of Ω-3 polyunsaturated fatty acid supplementation and programmed cell death protein 1 blockade on tumor growth and immune modulation in a xenograft model of esophageal cancer.

BACKGROUND: Esophageal cancer, especially esophageal squamous cell carcinoma (ESCC), remains a significant global health challenge with limited survival rates. This study aimed to elucidate the combined effects of immune-modulating nutrition (IMN) with Ω-3 polyunsaturated fatty acid (PUFA) supplementation and anti-programmed cell death protein 1 (PD-1) treatment on tumor growth and immune responses in a xenograft model of ESCC. METHODS: A total of 36 C57BL/6 mice were used to construct a xenograft model using the mouse esophageal cancer cell line AKR. Mice were subjected to treatment with anti- PD-1 antibody combined with either Ω-3 PUFA-rich or Ω-3 PUFA-deficient nutrition. Tumor growth, immune markers, cytokine profiles, and metabolic changes were evaluated. RESULTS: The combination of anti-PD-1 and Ω-3 PUFA supplementation significantly inhibited tumor growth more effectively than anti-PD-1 treatment alone. Enhanced expression of immune markers PD-L1 and CD3 was observed in Ω-3 PUFA-fed mice. Additionally, compared with anti-PD-1 therapy and anti-PD-1 plus Ω-3 PUFA-deficient nutrition, Ω-3 PUFAs intensified alterations in key chemokines and cytokines, including elevated IL-12, IFN-γ, and GM-CSF levels, and reduced CXCL12 levels. However, Ω-3 PUFAs did not significantly alter the glycolysis and tryptophan metabolic program induced by anti-PD-1. CONCLUSION: Our findings indicated the potential synergetic therapeutic benefits of combining anti-PD-1 treatment with Ω-3 PUFA supplementation in ESCC, which offered promising avenue for further research.

Concurrent vs Staged Hybrid Ablation for Long-Standing Persistent Atrial Fibrillation: A Propensity-Matched Cohort Study.

BACKGROUND: Long-term success rates of catheter ablation (CA) for long-standing persistent atrial fibrillation (LSPAF) are less than satisfactory. Further improvement of ablation methods is crucial for enhancing the treatment of LSPAF. OBJECTIVES: This study sought to compare the outcomes of concurrent vs staged minimally invasive surgical-catheter hybrid ablation for LSPAF. METHODS: From December 2015 to December 2021, 104 matched patients (concurrent and staged, 1:1) were included in study. In the concurrent group, both left unilateral thoracoscopic epicardial ablation (EA) and CA were performed simultaneously in one procedure. In the staged group, EA was performed at the first hospitalization. If the patients experienced atrial fibrillation (AF) recurrence, CA was performed between 3 months and 1 year after EA. RESULTS: In the concurrent group, 4 patients were restored to sinus rhythm after EA, and 41 were patients restored to sinus rhythm during CA; 86.5% (45 of 52) achieved intraprocedural AF termination during concurrent hybrid ablation. In the staged group, all 52 patients underwent staged CA because of the recurrence of AF or atrial tachycardia (AT). Forty-seven (90.4%) patients achieved intraprocedural AF or AT termination during CA. Freedom from AF or AT off antiarrhythmic drugs at 2 years after hybrid ablation was 79.9% ± 5.7% in the concurrent group and 86.0% ± 4.9% in the staged group (P = 0.390). Failure of intraprocedural AF termination (HR: 14.378) was an independent risk factor for AF recurrence after hybrid ablation. CONCLUSIONS: Both concurrent and staged hybrid ablation could be safely and effectively applied to treat LSPAF. Improving the intraprocedural AF termination rate predicted better outcomes.

A Novel System for Transcatheter Aortic Valve Implantation: First-in-Man Study.

Transcatheter aortic valve implantation (TAVI) has become a therapeutic treatment for severe symptomatic patients with aortic stenosis. This study aimed to test a novel transcatheter aortic self-expandable bioprosthesis-the ScienCrown system (Lepu Medtech Inc., Beijing, China)-and evaluate the safety of the new device during TAVI. ScienCrown aortic valve implantation was performed on 10 patients. Clinical assessment was performed at baseline, post procedure, and after 1 year. Clinical outcomes and adverse events were assessed according to Valvular Academic Research Consortium-3 criteria. The mean age was 75.30 ± 4.78 years with a mean Society of Thoracic Surgeons score of 4.64 ± 3.23%. Device success was achieved in all patients (80% transfemoral, 20% transapical). After 1 year, there were no deaths, disabling strokes, myocardial infarctions, conversions to surgery, or major procedure-related complications. New pacemaker implantation was required in one patient (10%). ScienCrown implantation resulted in a reduction in mean valve gradient (63.00 ± 18.84 to 9.67 ± 4.97 mm Hg, p <0.001) and an increase in effective orifice area (0.57 ± 0.20 to 2.57 ± 0.59 cm2, p <0.001) at 1 year. Paravalvular leak was absent in 9 patients (90%), and there was a trace in one patient (10%). All patients were in New York Heart Association class I to II at a mean follow-up of 1 year. The experience showed that ScienCrown transcatheter aortic valve system was safely and successfully implanted for treatment of severe symptomatic aortic stenosis. The newer-generation device affords a stable implantation while providing optimal hemodynamic performance.

The role of aquaporin 1 activated by cGMP in myocardial edema caused by cardiopulmonary bypass in sheep.

BACKGROUND/AIMS: Most cardiac procedures involve the use of cardiopulmonary bypass (CPB), which pumps oxygenated blood to the body while the heart and lungs are isolated. CPB can cause profound alterations V in the homeostasis of physiological fluids, which often results in myocardial edema. In our study, we used sheep CPB model of in vivo and in vitro to assess the relationship between cGMP and AQP1 during CPB. METHODS: ODQ, a specific inhibitor of soluble guanylate cyclase (sGC), was used to treat the CPB animals or cardiomyocytes. Left ventricular function of each group was determined by pressure-volume system. Water content of myocardial tissue was assessed by dry-wet weight, and cardiomyocytes water permeability was also calculated. The concentration of cGMP was determined by Radioimmunoassay (RIA). mRNA and protein expression of AQP1 were detected by real-time PCR and western blot, respectively. RESULTS: The relative expression level of AQP1 mRNA and protein at each time point (0, 6, 12, 24 or 48 h) after CPB was significantly increased (1.18-fold at 12 h, 1.77-fold at 24 h and 2.18-fold at 48h) compared with each sham group, the protein expression of AQP1 also showed a rising trend after CPB. The degree of myocardial edema (75.1% at 12 h, 79.3% at 24 h and 81.0% at 48h) increased following the CPB surgery. The mRNA expression level of AQP1 was significantly decreased by 39.7% (p<0.01) upon treatment with ODQ compared with the CPB-only group, and inhibition of cGMP pathway also can significantly decrease the degree of myocardial edema (84.7% in control group, while 75.2% in ODQ group) and improve cardiac function in sheep after CPB. Results of in vitro experiments showed the same changing trends as in vivo. CONCLUSION: cGMP pathway controls water channels and then affects water intake during CPB through an AQP1-mediated pathway.

Enhanced charge separation in La2NiO4 nanoplates by coupled piezocatalysis and photocatalysis for efficient H2 evolution.

Photocatalytic hydrogen evolution is one promising method for solar energy conversion, but the rapid charge recombination limits its efficiency. To this end, in this work, grain size, and hence the charge carrier migration path, is reduced by lowering the synthesis temperature of two-dimensional visible light-responsive La2NiO4 perovskite. Interestingly, the hydrogen yield for the piezoelectric response of La2NiO4 under only 40 kHz ultrasonic vibration is as high as 680 µmol h-1 g-1, which is 80 times that under only 600 mW cm-2 visible light irradiation. More surprisingly, the hydrogen production rate under both light illumination and ultrasonic vibration is 129 times higher than under visible light irradiation alone. Clearly, a synergistic effect exists between piezocatalysis and photocatalysis. The hydrogen production activity of the samples with water splitting can reach 1097 µmol h-1 g-1 without any sacrificial reagent or co-catalyst, when the light intensity reaches about 1000 mW cm-2, which is a much higher hydrogen evolution rate by piezo-photocatalysis than is achieved by either piezocatalysis or photocatalysis individually. Further analysis indicates that the internal electric field generated by deformation of the La2NiO4 edge under piezoelectric action facilitates the directional separation and migration of photogenerated charges, which in turn significantly enhances the efficiency of use of photogenerated charges for hydrogen production. The investigation here provides a novel approach to design a new reaction system for hydrogen production by coupling multiple external physical fields.

Designing High Interfacial Conduction beyond Bulk via Engineering the Semiconductor-Ionic Heterostructure CeO2-δ/BaZr0.8Y0.2O3 for Superior Proton Conductive Fuel Cell and Water Electrolysis Applications.

Proton ceramic fuel cells (PCFCs) are an emerging clean energy technology; however, a key challenge persists in improving the electrolyte proton conductivity, e.g., around 10-3-10-2 S cm-1 at 600 °C for the well-known BaZr0.8Y0.2O3 (BZY), that is far below the required 0.1 S cm-1. Herein, we report an approach for tuning BZY from low bulk to high interfacial conduction by introducing a semiconductor CeO2-δ forming a semiconductor-ionic heterostructure CeO2-δ/BZY. The interfacial conduction was identified by a significantly higher conductivity obtained from the BZY grain boundary than that of the bulk and a further improvement from the CeO2-δ/BZY which achieved a remarkably high proton conductivity of 0.23 S cm-1. This enabled a high peak power of 845 mW cm-2 at 520 °C from a PCFC using the CeO2-δ/BZY as the electrolyte, in strong contrast to the BZY bulk conduction electrolyte with only 229 mW cm-2. Furthermore, the CeO2-δ/BZY fuel cell was operated under water electrolysis mode, exhibiting a very high current density output of 3.2 A cm-2 corresponding to a high H2 production rate, under 2.0 V at 520 °C. The band structure and a built-in-field-assisted proton transport mechanism have been proposed and explained. This work demonstrates an efficient way of tuning the electrolyte from low bulk to high interfacial proton conduction to attain sufficient conductivity required for PCFCs, electrolyzers, and other advanced electrochemical energy technologies.

Aggregation-Induced Emission-Active Fluorescent Polymer: Multi-Targeted Sensor and ROS Scavenger.

A multi-functional polymer with aggregation-induced emission (AIE)-active salicylaldehyde azine (SA) functionality and reactive oxygen species (ROS)-responsive thioether groups is readily prepared via thiol-ene click polymerization of SA derivative diacrylate monomer, poly(ethylene glycol) diacrylate, and 3,6-dioxa-1,8-octanedithiol. The obtained AIE-active polymer exhibited an unexpected strong emission in amide solvents compared to that in other common organic solvents that was dramatically decreased by adding a trace amount of water, suggesting that the polymer could be utilized as a water trace indicator in amide solvents. In the backbone, the PEG segments make the polymer well dispersed in water and the ROS-responsive thioether groups enable this polymer as a promising ROS scavenger, with embedded SA moieties as a fluorescent indicator for the hemolysis determination. Due to the ability of SA moieties to complex with Cu2+, this AIE polymer can also be utilized as a fluorescent sensor for selective Cu2+ detection in real-world water samples. Thus, this multi-functional polymer is anticipated to be well applied in biological and environmental applications.

Efficacy and safety of scleral crosslinking using poly(ethylene glycol)ether tetrasuccinimidyl glutarate for form-deprivation myopia progression in rabbits.

Myopia is becoming increasingly prevalent worldwide at an alarming rate. However, no effective treatment is available for inhibiting myopia progression. Materials chemistry advancements have made it possible to regulate mechanical properties and rate of degradation with good compatibility by developing newly crosslinking systems such as the branched polyethylene glycol (PEG) systems. Herein, we presented a PEG molecule with N-hydroxysuccinimide (NHS) ester functional groups at the chain ends as a macromolecular crosslinking agent for the treatment of myopia. We found that the scleral collagen crosslinked with the four-armed star-shaped PEG molecule with NHS ester functional group (4S-PEG) showed better biomechanical properties, increased thermal stability and higher resistance to degradation. 4S-PEG exhibited relatively low cytotoxicity for human fetal scleral fibroblasts. The retrobulbar injection of 4S-PEG at a relatively low concentration (2.5 mM) showed good effective control of the progression of form-deprivation myopia in rabbits. There were no signs of adverse effect or damage by repeated injections with 4S-PEG in rabbits. The results of this work demonstrate that 4S-PEG can serve as a robust macromolecular crosslinking agent and is expected to have promise for application in the treatment of the progression of myopia.

LAMC1 upregulation via TGFß induces inflammatory cancer-associated fibroblasts in esophageal squamous cell carcinoma via NF-κB-CXCL1-STAT3.

Cancer-associated fibroblasts (CAF) are a heterogeneous cell population within the tumor microenvironment,and play an important role in tumor development. By regulating the heterogeneity of CAF, transforming growth factor ß (TGFß) influences tumor development. Here, we explored oncogenes regulated by TGFß1 that are also involved in signaling pathways and interactions within the tumor microenvironment. We analyzed sequencing data of The Cancer Genome Atlas (TCGA) and our own previously established RNA microarray data (GSE53625), as well as esophageal squamous cell carcinoma (ESCC) cell lines with or without TGFß1 stimulation. We then focused on laminin subunit gamma 1 (LAMC1), which was overexpressed in ESCC cells, affecting patient prognosis, which could be upregulated by TGFß1 through the synergistic activation of SMAD family member 4 (SMAD4) and SP1. LAMC1 directly promoted the proliferation and migration of tumor cells, mainly via Akt-NFκB-MMP9/14 signaling. Additionally, LAMC1 promoted CXCL1 secretion, which stimulated the formation of inflammatory CAF (iCAF) through CXCR2-pSTAT3. Inflammatory CAF promoted tumor progression. In summary, we identified the dual mechanism by which the upregulation of LAMC1 by TGFß in tumor cells not only promotes ESCC proliferation and migration, but also indirectly induces carcinogenesis by stimulating CXCL1 secretion to promote the formation of iCAF. This finding suggests that LAMC1 could be a potential therapeutic target and prognostic marker for ESCC.