Nickel-Catalyzed Enantioconvergent Allenylic Amination of Allenols Activated by Hydrogen-Bonding Interaction with Methanol.

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel-catalyzed enantioconvergent allenylic amination of methanol-activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram-scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel-catalyzed reaction, facilitating the oxidative addition of the C-O bond of allenols through hydrogen-bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3-alkadienylnickel intermediates.

Functional Materials for Water Restoration: A "Fish Cage" for Efficient Capture of Pb(II) Ions.

In this work, a "fish cage" material for trapping Pb(II) ions has been successfully obtained, which is a novel clathrate functionalized metal-oganic framework (Cage-MOF) by introducing free adsorption sites (SO42-). The three-dimensional (3D) cage structure of Cage-MOF gives it a larger contact area and can capture "swimming fish" (Pb(II)) like a "fishing cage" in a water solution. This is the first high-efficiency adsorption material obtained by introducing free coordination groups. Cage-MOF not only has excellent water stability but also improves the selectivity and affinity for Pb(II) ions in water because of the presence of sulfate adsorption sites, and its adsorption capacity is as high as 806 mg/g. This work shows a novel and effective idea for the synthesis of water restoration materials.

Case-Control Study on the Interaction Effects of rs10757278 Polymorphisms at 9p21 Locus and Traditional Risk Factors on Coronary Heart Disease in Xinjiang, China.

OBJECTIVE: To study the interaction effects of rs10757278 polymorphisms at 9p21 locus and traditional risk factors on coronary heart disease (CHD) in Xinjiang, China. METHODS: This case-control study consecutively enrolled 310 unrelated consecutive CHD patients aged 18-70 years old. All study participants were recruited between January and December 2017 from The Heart Center of The First Affiliated Hospital of Xinjiang Medical University. CHD patients were confirmed by coronary angiography (≥50% diameter stenosis in at least one of the major coronary arteries) according to the American Heart Association criteria for the confirmation of CHD. Healthy subjects were randomly selected from the occupational population, who received physical examination in our hospital and matched to cases on the basis of age (±3 years) and sex, those without medical history of cardiovascular diseases, and 536 subjects were selected as the control group after medical history inquiry, physical examination, cardiac ultrasound, electrocardiogram, and other blood biochemical examinations in the hospital. The occupational stress was evaluated by an effort-reward imbalance questionnaire. An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted. RESULTS: Both the case and the control groups showed significant difference in smoking, drinking, physical activity, hypertension, diabetes mellitus, family history of CHD, and body mass index (BMI) (all P < 0.05); prevalence of CHD was not related to occupational stress. There was no significant difference in occupational stress level between the 2 groups (P > 0.05); Differences in rs10757278 genotype between the case group and the control groups were statistically significant; binary logistic regression analysis was used to evaluate the risk factors of CHD. After adjustment for age and sex, significant increased risk effects for CHD were found to be associated with smoking [odds ratio (OR) = 2.311; 95% confidence interval (CI): 1.04-2.499; P < 0.001], physical exercise (OR = 1.365; 95% CI: 1.137-1.639; P < 0.001), hypertension (OR = 4.627; 95% CI: 2.165-10.764; P < 0.001), family history of CHD (OR = 4.103; 95% CI: 3.169-6.892; P < 0.001), BMI (OR = 2.484; 95% CI: 2.036-3.03; P < 0.001), and GG genotype at rs10757278 (OR = 1.978; 95% CI: 1.413-2.769; P < 0.001); We noted that a significant interaction association between GG genotype at rs10757278 and CHD differs across categories of smoking, hypertension, family history of CHD, and BMI. CONCLUSION: GG genotype at rs10757278 may be a risk factor for CHD. And there are interaction effects between GG genotype of rs10757278 in region 9p21 gene and traditional risk factors.

Incidence and Nutritional Management of Chylothorax after Surgery for Congenital Heart Diseases in Children.

BACKGROUND: Chylothorax is caused by thoracic lymphatic system injury that leads to lymph extravasates in the thoracic cavity. Cardiac surgery was the most common cause. Reports comparing therapeutic effects between enteral nutrition (EN) with medium-chain triglycerides (MCT) and total parenteral nutrition (TPN) are few and inconsistent. Our study aimed to analyze the incidence of chylothorax in children in our hospital and optimum nutritional management modalities. METHODS: We retrospectively reviewed the medical records of children admitted to our hospital with a diagnosis of chylothorax from 2014 to 2018. We analyzed the incidence of chylothorax, therapeutic effectiveness, and cost effectiveness of EN with MCT or TPN. RESULTS: 136 patients with chylothorax after surgery for congenital heart disease (CHD) were identified from 172 patients with chylothorax (79.07%); chylothorax occurred in 5.62% of all 2420 congenital heart disease surgeries that were performed during that period. Tetralogy of Fallot (TOF), ventricular septal defect (VSD), and double-outlet right ventricle (DORV) were the most common primary diagnoses. Fontan surgery, TOF repair, and VSD repair were the most common primary procedures. We enrolled 45 patients with cured chylothorax. Nutrition support costs in the EN with MCT group (n = 28) were significantly lower than in the TPN group (n = 17) (P = .000). Time to resolution and time to removal of the drainage tube were shorter in EN with MCT versus TPN (P = .003), and the length of hospital stay was shorter (P = .032). There were no significant differences between the 2 groups in time from admission to surgery, postoperative days before diagnosing chylothorax, or length of PICU stay (P > .05). CONCLUSIONS: The therapeutic effects of EN with MCT were significantly better than those of TPN, with lower costs. Therefore, we suggest that EN with MCT be chosen first to treat chylothorax caused by surgery with mild chest drainage volume when gastrointestinal tract function is allowed.

Upregulation of long noncoding RNA XIST is associated with poor prognosis in human cancers.

Growing evidence from recent studies has shown that the X-inactive specific transcript (XIST), a well-known long noncoding RNA involved in early embryonic development, is aberrantly regulated in various human cancers. However, the prognostic value of XIST in cancers remains uncharacterized. In this study, we searched PubMed, Web of Science, and Embase to collect all relevant studies, and a meta-analysis was performed to explore the association of XIST expression with overall survival (OS) and clinicopathological parameters. We demonstrated that high XIST expression was associated with poor OS (hazard ratio = 1.76; 95% confidence intervals [CI], 1.56-1.98; p < 0.001). In addition, increased XIST expression was found to be associated with lymph node metastasis (odds ratio [OR] = 2.06; 95% CI, 1.46-1.90; p < 0.001), distant metastasis (OR = 2.93; 95% CI, 2.00-4.28; p < 0.001), tumor size (OR = 2.66; 95% CI, 1.86-3.81; p < 0.001), poor differentiation (OR = 1.45; 95% CI, 1.00-2.10; p = 0.049), and advanced tumor stage (OR = 3.35; 95% CI, 2.25-5.00; p < 0.001), but not with age (OR = 0.82; 95% CI, 0.59-1.15; p = 0.251) or gender (OR = 0.92; 95% CI, 0.70-1.19; p = 0.512). Our meta-analysis showed that XIST may be a useful common biomarker for predicting prognosis in patients with cancer.

Pooling analysis reveals that galectin-1 is a reliable prognostic biomarker in various cancers.

Galectin-1 is reported to be upregulated in various human cancers. However, the relationship between galectin-1 expression and cancer prognosis has not been systematically assessed. In this study, we searched PubMed, Web of Science, and Embase to collect all relevant studies and a meta-analysis was performed. We found that increased galectin-1 expression was associated with tumor size (odds ratio [OR] = 1.75; 95% confidence interval [CI]: 1.06-2.89; p = 0.029), clinical stage (OR = 3.89; 95% CI: 2.40-6.31; p < 0.001), and poorer differentiation (OR = 1.39; 95% CI: 1.14-1.69; p = 0.001), but not with age (OR = 1.07; 95% CI: 0.82-1.39; p = 0.597), sex (OR = 0.89; 95% CI: 0.74-1.07; p = 0.202), or lymph node metastasis (OR = 2.57; 95% CI: 0.98-6.78; p = 0.056). In addition, we found that high galectin-1 expression levels were associated with poor overall survival (HR = 2.12; 95% CI: 1.71-2.64; p < 0.001). The results were further validated using The Cancer Genome Atlas data set. Moreover, high galectin-1 expression was significantly associated with disease-free survival (hazard ratio [HR] = 1.60; 95% CI: 1.17-2.19; p = 0.003), progression-free survival (HR = 1.93; 95% CI: 1.65-2.25; p < 0.001), and cancer-specific survival (HR = 1.82; 95% CI: 1.30-2.55; p < 0.001). Our meta-analysis demonstrated that galectin-1 might be a useful common biomarker for predicting prognosis in patients with cancer.

Inhibition of yes-associated protein down-regulates PD-L1 (CD274) expression in human malignant pleural mesothelioma.

Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells. In H2052 and 211H cells, PD-L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD-L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD-L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD-L1 enhancer region encompassing 2 putative YAP-TEAD-binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD-L1 concurrently expressed in immunohistochemistry stain (n = 70, P < .05, chi-square). We conclude that PD-L1 is correlated with YAP expression, and inhibition of YAP down-regulates PD-L1 expression in human MPM. Further study of how YAP regulates PD-L1 in MPM is warranted.

Comparative Transcriptomic Analysis of Embryo Implantation in Mice and Rats.

BACKGROUND/AIMS: Embryo implantation is an essential process for eutherian pregnancy, but this process varies across eutherians. The genomic mechanisms that led to the emergence and diversification of embryo implantation are largely unknown. METHODS: In this study, we analyzed transcriptomic changes during embryo implantation in mice and rats by using RNA-seq. Bioinformatics and evolutionary analyses were performed to characterize implantation-associated genes in these two species. RESULTS: We identified a total of 518 differentially expressed genes in mouse uterus during implantation, of which 253 genes were up-regulated and 265 genes were down-regulated at the implantation sites compared with the inter-implantation sites. In rat uterus, there were 374 differentially expressed genes, of which 284 genes were up-regulated and 90 genes were down-regulated. A cross-species comparison revealed that 92 up-regulated genes and 20 down-regulated genes were shared. The differences and similarities between mice and rats were investigated further at the gene ontology, pathway, network, and causal transcription factor levels. Additionally, we found that embryo implantation might have evolved through the recruitment of ancient genes into uterine expression. The evolutionary rates of the differentially expressed genes in mouse and rat uterus were significantly lower than those of the non-changed genes, indicating that implantation-related genes are evolutionary conserved due to high selection pressure. CONCLUSION: Our study provides insights into the molecular mechanisms involved in the evolution of embryo implantation.

Assessment of Embryo-Induced Transcriptomic Changes in Hamster Uterus Using RNA-Seq.

BACKGROUND/AIMS: The mouse is widely used as an animal model for studying human embryo implantation. However, the mouse is unique in that both ovarian progesterone and estrogen are critical to implantation, whereas in the majority of species (e.g. human and hamster) implantation can occur in the presence of progesterone alone. METHODS: In this study, we analyzed embryo-induced transcriptomic changes in the hamster uterus during embryo implantation by using RNA-seq. Differentially expressed genes were characterized by bioinformatic analysis. RESULTS: We identified a total of 781 differentially expressed genes, of which 367 genes were up-regulated and 414 genes were down-regulated at the implantation site compared to the inter-implantation site. Functional clustering and gene network analysis highlighted the cell cycle process in uterus upon embryo implantation. By examining of the promoter regions of differentially expressed genes, we identified 7 causal transcription factors. Additionally, through connectivity map (CMap) analysis, multiple compounds were identified to have potential anti-implantation effects due to their ability to reverse embryo-induced transcriptomic changes. CONCLUSION: Our study provides a valuable resource for in-depth understanding of the mechanism underlying embryo implantation.

Comparative Study on Temperature-Dependent CO2 Sorption Behaviors of Two Isostructural N-Oxide-Functionalized 3D Dynamic Microporous MOFs.

By functionalization of the achiral carboxylate-based pyridine-N ligand 2,2'-bipyridine-3,3'-dicarboxylate (H2bpda) with N-oxide groups, the axially chiral ligand 2,2'-bipyridine-3,3'-dicarboxylate 1,1'-dioxide (H2bpdado) has been obtained. On the basis of H2bpdado and auxiliary N-donor ligands, two isostructural 3D dynamic porous Cu(II) metal-organic frameworks (MOFs), {[Cu0.5(bpdado)0.5(L)0.5]·3H2O}n (L = 1,2-bis(4-pyridyl)ethane (bpa), trans-1,2-bis(4-pyridyl)ethene (bpe) for 1 and 2, respectively), have been synthesized, which contain N-oxide "open donor sites" (ODSs) and carboxyl sites on the pore surfaces. The modification of pyridine-N into the N-oxide group not only transforms the nonporous structure into a porous framework but also endows the N-oxide group with unique charge-separated plus electron-rich character, which may provide an enhanced affinity toward CO2 molecules. Interestingly, both 1 and 2 present reversible structural transformation upon dehydration and rehydration. The adsorption properties of 1 and 2 have been investigated by N2, H2, CH4, and CO2 gases, and they reveal evident adsorption for CO2 and CH4. Both MOFs have high CO2 uptake, CO2 sorption affinity, and sorption selectivities of CO2 over CH4 and N2. Remarkably, 1' and 2' exhibit intriguingly comparable temperature-dependent CO2 sorption behaviors that can probably be attributed to the difference in bpa and bpe. First, at 195 K, 1' and 2' exhibit stepwise adsorption and hysteretic desorption behavior for CO2, but in the second step, the isotherms of 2' display a starting pressure greater than that of 1'. Then, at 298 K, their CO2 isotherms all show nonclassical type I adsorption, while peculiarly, at 273 K, the CO2 isotherm of 1' still exhibits uncommon stepwise adsorption but that of 2' does not. Thus, these temperature-dependent CO2 sorption behaviors indicate that there exist different threshold temperatures and pressures of channel expansion for 1' and 2'.

Integration of Transcriptomic and Metabolomic Data Reveals Enhanced Steroid Hormone Biosynthesis in Mouse Uterus During Decidualization.

It has been long recognized that decidualization is accompanied by significant changes in metabolic pathways. In the present study, we used the GC-TOF-MS approach to investigate the global metabolite profile changes associated with decidualization of mouse uterus on day 8 of pregnancy. We identified a total of 20 differentially accumulated metabolites, of which nine metabolites were down-regulated and 11 metabolites were up-regulated. As expected, seven differentially accumulated metabolites were involved in carbohydrate metabolism. We observed statistically significant changes in polyamines, putrescine and spermidine. Interestingly, the pantothenic acid, also known as vitamin B5 , was up-regulated. Finally, by integrating with transcriptomic data obtained by RNA-seq, we revealed enhanced steroid hormone biosynthesis during decidualization. Our study contributes to an increase in the knowledge on the molecular mechanisms of decidualization.

Targeting YAP in malignant pleural mesothelioma.

Malignant mesothelioma is an aggressive cancer that is resistant to current therapy. The poor prognosis of mesothelioma has been associated with elevated Yes-associated protein (YAP) activity. In this study, we evaluated the effect of targeting YAP in mesothelioma. First, we comprehensively studied YAP activity in five mesothelioma cell lines (211H, H2052, H290, MS-1 and H2452) and one normal mesothelial cell line (LP9). We found decreased phospho-YAP to YAP protein ratio and consistently increased GTIIC reporter activity in 211H, H2052 and H290 compared to LP9. The same three cell lines (IC50 s < 1 µM) were more sensitive than LP9 (IC50 = 3.5 µM) to the YAP/TEAD inhibitor verteporfin. We also found that verteporfin significantly reduced YAP protein level, mRNA levels of YAP downstream genes and GTIIC reporter activity in the same three cell lines, indicating inhibition of YAP signaling by verteporfin. Verteporfin also impaired invasion and tumoursphere formation ability of H2052 and H290. To validate the effect of specific targeting YAP in mesothelioma cells, we down-regulated YAP by siRNA. We found siYAP significantly decreased YAP transcriptional activity and impaired invasion and tumoursphere formation ability of H2052 and H290. Furthermore, forced overexpression of YAP rescued GTIIC reporter activity and cell viability after siYAP targeting 3'UTR of YAP. Finally, we found concurrent immunohistochemistry staining of ROCK2 and YAP (P < 0.05). Inhibition of ROCK2 decreased GTIIC reporter activity in H2052 and 211H suggesting that Rho/ROCK signaling also contributed to YAP activation in mesothelioma cells. Our results indicate that YAP may be a potential therapeutic target in mesothelioma.

A study on regional differences in decidualization of the mouse uterus.

Although regional differences in mouse decidualization have been recognized for decades, the molecular mechanisms remain understudied. In the present study, by using RNA-seq, we compared transcriptomic differences between the anti-mesometrial (AM) region and the mesometrial (M) region of mouse uterus on day 8 of pregnancy. A total of 1423 differentially expressed genes were identified, of which 811 genes were upregulated and 612 genes were downregulated in the AM region compared to those in the M region. Gene ontology analysis showed that upregulated genes were generally involved in cell metabolism and differentiation, whereas downregulated genes were associated with lymphocyte themes and immune response. Through network analysis, we identified a total of 6 hub genes. These hub genes are likely more important than other genes due to their key positions in the network. We also examined the promoter regions of differentially expressed genes for the enrichment of transcription factor-binding sites. In the end, we demonstrated that a similar regional gene expression pattern can be observed in the artificial decidualization model. Our study contributes to an increase in the knowledge on the molecular mechanisms underlying regional decidualization in mice.

A prospective randomized single-blind control study of volume threshold for chest tube removal following lobectomy.

BACKGROUND: The aim of the current study was to assess the feasibility and safety of a new volume threshold for chest tube removal following lobectomy. METHODS: The prospective randomized single-blind control study included 90 consecutive patients who underwent lobectomy or bilobectomy for pathological conditions between March 2012 and September 2012. Eligible patients were randomized into two groups: early removal group (chest tube removal at the drainage volume of 300 ml/24 h or less) and traditional management group (chest tube removal when the drainage volume is less than 100 ml/24 h). Criteria for the early removal group were established and met prior to chest tube removal. The volume and characteristics of drainage, time of drainage tube extraction, and postoperative hospital stay were recorded. All patients received standard care while in the hospital and a follow-up visit was performed 7 days after discharge from hospital. RESULTS: In accordance with the exit criteria, 20 patients were excluded from the study. The remaining 70 patients included in the final analysis were divided into two groups: early removal group (n = 41) and traditional management group (n = 29). There was no difference between the two groups in terms of age, sex, comorbidities, and pathological evaluation of resection specimens. In eligible patients (n = 70), the mean volume of drainage 24 h after surgery was 300 ml, while the mean volume of drainage 48 h after surgery was 250 ml. The average daily drainage 48 h after surgery was significantly different than the average daily drainage 24 h after surgery (Z = -2.059, P = 0.039). The mean duration of chest tube placement was 44 h in the early removal group and 67 h in the traditional management group (P = 0.004). Patients who underwent early removal management had a shorter postoperative hospital stay compared to the traditional management group (5 vs. 6 days, P < 0.01). No statistically significant differences were observed between the rates of pleural effusion development, thoracentesis, and postoperative complications 1 week after hospital discharge. CONCLUSION: Early removal of the chest tube after lobectomy is feasible and safe and may shorten patient hospital stay and reduce morbidity without the added risk of postoperative complications.

Efficacy of EGFR tyrosine kinase inhibitors in non-small-cell lung cancer patients with/without EGFR-mutation: evidence based on recent phase III randomized trials.

BACKGROUND: EGFR mutation might be a predictive factor for applying EGFR-tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, erlotinib and afatinib) in non-small-cell lung cancer (NSCLS) patients. Thus, it is necessary to pool previous trials to compare the effect of EGFR-TKIs versus cytotoxic chemotherapy in EGFR mutation positive (mut+) and negative (mut-) patients. MATERIAL AND METHODS: This study identified 8 first-line and 9 second-line phase III trials in databases. Hazard ratio (HR) was pooled to assess the risk of progression-free survival (PFS), and overall survival (OS), while odds ratio (OR) was pooled to assess objective response, disease control, and toxicity of EGFR-TKIs verses chemotherapy. RESULTS: In EGFR mut+ patients, EGFR-TKIs were associated with significantly lower risk of disease progression in the first-line setting, but this trend was only observed in the gefitinib group, not in the erlotinib group in the second-line setting. In EGFR mut- patients, gefitinib and erlotinib had significantly higher risk of disease progression in first-line and second-line setting, respectively. Compared with chemotherapy, the effects of EGFR-TKIs on OS in both first-line and second-line settings were not evident. Regarding toxicity, EGFR-TKIs had significantly higher risk of rash and lower hematological toxicity compared with chemotherapy. CONCLUSIONS: All of the 3 EGFR-TKIs and gefitinib alone regimens had better effects in prolonging PFS in EGFR mut+ patients in first-line and second-line setting, respectively, but chemotherapy seemed more effective in EGFR mut- patients than EGFR-TKIs. Therefore, accurate identification of EGFR mutation status is useful to decide on an appropriate regimen for treatment of NSCLC patients.

[Early removal of the chest tube after lobectomies: a prospective randomized control study].

OBJECTIVE: To evaluate the feasibility and safety of early chest tube removal after lobectomies for lung diseases. METHODS: A prospective randomized control study was performed with data collected from lobectomies between March 2012 and September 2012. Eligible patients (n = 70) were randomized into two groups; early removal group (removal of chest tube when drainage less than 300 ml/24 h, n = 41) and traditional management group (removal of chest tube when drainage less than 100 ml/24 h, n = 29). Criteria for early removal were established and met before chest tube removal. The volume and character of drainage, time of extracting drainage tube and postoperative hospital stay were measured. All patients received standard care during hospital admission and a follow-up visit was performed after 7 days of discharge from hospital. RESULTS: There were no differences between two groups with respect to age, sex, comorbidities, or pathologic evaluation of resection specimens. The median volume of drainage within 24 h after surgery was 300 ml and within 48 h was 250 ml, there was significantly different between two groups (Z = -2.059, P = 0.039). Patients undergoing early removal management had a shorter Chest tube duration (44 hours vs. 67 hours, Z = -2.914, P = 0.004) and a shorter postoperative hospital stay (5.0 days vs. 6.0 days, Z = -3.882, P = 0.000). Analysis of data showed no statistically significant differences between the rate of pleural effusions developed, thoracentesis and complications, one week after discharge from hospital. CONCLUSIONS: Compared to the traditional management group (drainage ≤ 100 ml/24 h), early removal of chest tube after lobectomy (drainage ≤ 300 ml/24 h) is feasible and safe. It could result in a shorter hospital stay, and most importantly, reduces morbidity without the added risk of complications.

A Modified Small Intestinal Submucosa Patch with Multifunction to Promote Scarless Repair and Reinvigoration of Urethra.

To reconstruct and restore the functions of the male urethra is a challenging task for urologists. The acellular matrix graft currently used in the clinics is mono-functional and may cause a series of complications including stricture, fibrosis, and stone formation. As a result, such graft materials cannot meet the increasing demand for multifunctionality in the field of urethral tissue engineering. In this context, a multifunctional urethral patch is designed for the repair of urethral defects by mixing protocatechualdehyde (PCA) with small intestinal submucosa (SIS) under an alkalin condition to allow cross linking. As shown, the PCA/SIS patch possesses excellent biocompatibility, antioxidant activity, and anti-inflammatory property. More importantly, this patch can remarkably promote the adhesion, proliferation, and directional extension of rabbit bladder epithelial mucous cells (R-EMCs) as well as rabbit bladder smooth muscle cells (R-SMCs), and upregulate the expression of cytokeratin in the EMCs and contractile protein in the SMCs in vitro. In vivo experiments also confirm that the PCA/SIS patch can significantly enhance scarless repair of urethral defects in rabbits by facilitating smooth muscle regeneration, reducing excessive collagen deposition, and accelerating re-epithelialization and neovascularization. Taken together, the newly developed multifunctional PCA/SIS patch provides a promising candidate for urethral regeneration.