An Innovative High-Strength Double-Network Hydrogel for Use as a Drilling Fluid Plugging Agent.

The problem of wellbore leakage is a key challenge in the petroleum industry, limiting drilling progress and increasing drilling costs. Plugging agents play a role in repairing leaks and fractures; however, traditional plugging materials generally have low mechanical strength, poor adaptability to permeable strata, limited water absorption and expansion capabilities, and poor temperature and salt resistance. To address these limitations, a pioneering polyacrylic acid-polyacrylamide (PAA/PAM) double-network hydrogel was synthesized through aqueous solution polymerization in this study. Its strength, water absorption, expansion, temperature resistance, salt resistance, and plugging effectiveness were comprehensively evaluated. The results demonstrate that good mechanical performance is exhibited by the synthesized hydrogel, capable of withstanding a maximum stress of approximately 3.5 MPa at a 90% strain. Excellent water absorption and expansion are observed in the synthesized double-network hydrogel, with a maximum expansion of 6 times within 30 min and 8 times after 2 h. Test results show that the hydrogel had good temperature resistance and salt resistance, maintaining a strength grade E within the experimental range. The simulated evaluation of the plugging experiment indicates that, under conditions of 130 °C and 6 MPa, the leakage rate of the drilling fluid is maintained below 5 mL/min when the double-network hydrogel is utilized. From the above experimental results, it can be illustrated that excellent mechanical properties, impressive water absorption, and expansion capabilities are exhibited by the synthesized double-network hydrogel. Furthermore, the high-temperature resistance and salt resistance of the double-network hydrogel were also demonstrated. Therefore, In comparison to traditional plugging materials, significant promise is held by this newly synthesized double-network hydrogel material as a plugging agent in drilling fluids.

Mechanisms of antiviral action and toxicities of ipecac alkaloids: Emetine and dehydroemetine exhibit anti-coronaviral activities at non-cardiotoxic concentrations.

The emergence of highly infectious pathogens with their potential for triggering global pandemics necessitate the development of effective treatment strategies, including broad-spectrum antiviral therapies to safeguard human health. This study investigates the antiviral activity of emetine, dehydroemetine (DHE), and congeneric compounds against SARS-CoV-2 and HCoV-OC43, and evaluates their impact on the host cell. Concurrently, we assess the potential cardiotoxicity of these ipecac alkaloids. Significantly, our data reveal that emetine and the (-)-R,S isomer of 2,3-dehydroemetine (designated in this paper as DHE4) reduce viral growth at nanomolar concentrations (i.e., IC50 ∼ 50-100 nM), paralleling those required for inhibition of protein synthesis, while calcium channel blocking activity occurs at elevated concentrations (i.e., IC50 ∼ 40-60 µM). Our findings suggest that the antiviral mechanisms primarily involve disruption of host cell protein synthesis and is demonstrably stereoisomer specific. The prospect of a therapeutic window in which emetine or DHE4 inhibit viral propagation without cardiotoxicity renders these alkaloids viable candidates in strategies worthy of clinical investigation.

Use of the Scissor-Type Knife During the Peroral Endoscopy Myotomy Procedure for the Treatment of Achalasia.

Peroral endoscopic myotomy (POEM) is one of the first-line treatment modalities along with pneumatic dilation and Heller myotomy for patients with achalasia. Endoscopists, especially trainees during the learning phase, commonly face difficulty in tissue plane dissection and selective myotomy while working near the esophagogastric junction, with increased risks of inadvertent injury, unexpected bleeding, and inadequate myotomy. To minimize the technical difficulty and improve the safety of POEM, we describe a protocol for using a scissor-type knife for the main steps of POEM, including mucosal incision, submucosal tunneling, myotomy, and hemostasis. The standard techniques used with the scissor-type knife involve grasping the target tissue, and then dissection or coagulation. The confirmation of the cutting line after grasping improves the accuracy and reliability of dissection, which is particularly useful for the selective myotomy of the internal circular muscle. Meanwhile, the scissor-type knife provides enhanced hemostatic capability and enables hemostasis and pre-coagulation without the device exchange for hemostatic forceps. Evaluation of the clinical outcomes in three patients who successfully received POEM using the scissor-type knife revealed no perioperative adverse events. At the 3-month follow-up, all patients achieved clinical success with postoperative Eckardt scores ranging from 0 to 1. In conclusion, the use of a scissor-type knife could minimize the technical difficulty and improve the safety of the POEM procedures, which may be suitable for trainees during the learning phase.

Predictive value of single high-sensitivity cardiac troponin Ⅰ level on the 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome / 中华检验医学杂志

Objective:To explore the predictive value of single high-sensitivity cardiac troponin I (hs-cTnI) concentration of 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome (ACS).Methods:This is a multicenter, prospective and observational clinical study. Patients with suspected ACS who were admitted into the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were enrolled. hs-cTnI result at the time of visit was obtained from patients with suspected ACS. Patients were followed up for 30 days and patients were divided into no events group and events group according to the presence or absence of 30-day cardiovascular adverse events (acute myocardial infarction (including index), unplanned revascularization and cardiovascular death). The predictive value of single Hs-cTnI at different concentration thresholds on the adverse event was evaluated in terms of sensitivity, negative predictive value (NPV) and 95% confidence interval ( CI). The best threshold was defined as: missed diagnosis rate <2% and NPV >99%. Patients were sub-grouped according to the confounders of hs-cTnI (sex, age, chest pain duration, estimated glomerular filtration rate), and Chi-square test was used to compare sensitivity and NPV among various subgroups. Results:A total of 1 461 patients were included. Among them, 387 patients (26.5%) had 30-day adverse cardiovascular events and 1 074 patients (73.5%) had no adverse cardiovascular events. Mean age was (62±12) years old and 905 were males (61.9%). When the concentration of hs-cTnI was less than 2 ng/L (limit of detection), the missed diagnosis rate of 30-day cardiovascular adverse events was 0.8% (3/387), the sensitivity was 99.2% (95% CI 97.6%-99.8%), and NPV was 98.7% (95% CI 96.0%-99.7%). When hs-cTnI concentration was less than 6 ng/L, the missed diagnosis rate was 1.8%, the sensitivity was 98.2% (95% CI 96.1%-99.2%), and NPV was 99.0% (95% CI 97.9%-99.6%). Subgroup analysis showed that the sensitivity and NPV of single hs-cTnI concentration <6 ng/L for 30-day cardiovascular adverse events were lower in patients with chest pain less than 3 h than those with chest pain time>3 hours ( P<0.05). Conclusions:Single hs-cTnI concentration less than 6 ng/L can predict the risk of 30-day cardiovascular adverse events in suspected ACS patients, but continuous monitoring is recommended for patients with chest pain onset≤3 hours.

Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder / 中华病理学杂志

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

Occurrence, source tracking and removal of antibiotics in recirculating aquaculture systems (RAS) in southern China.

The recirculating aquaculture system (RAS) has attracted much attention in China as a way to rapidly transform and upgrade aquaculture ponds to realize zero-emissions of pollutants in aquaculture tail water. Tail water purification ponds (TWPPs) play an important role in the treatment of aquaculture wastewater. However, until now, there have been few reports on the occurrence of antibiotics in RAS and the removal of antibiotics from the TWPPs of RAS. Therefore, this study focused on the occurrence of antibiotics in a typical ecological RAS. For comparison, the same measurements were simultaneously carried out in nearby open aquaculture ponds and rivers. The pollution level and spatial distribution of antibiotics in the RAS and the removal of antibiotics in the TWPPs were explored. The results showed that (1) eleven and twelve antibiotics were detected in water and sediment samples in the RAS, respectively, but no antibiotics were found in fish muscles and feed. Erythromycin (ERY), lincomycin (LIN), and ciprofloxacin (CFX) were the three main types of antibiotics found in water and sediment samples. (2) The TWPPs of the RAS can effectively remove antibiotics in aquaculture water. The antibiotic concentration in recirculating aquaculture ponds of the RAS was as high as 180 ng/L. After treatments in the TWPPs, the antibiotic concentration of aquaculture water decreased to 81.6 ng/L (3) The antibiotic concentrations in recirculating aquaculture ponds (25.2-180 ng/L) were lower than those in the nearby open aquaculture ponds (126-267.3 ng/L), and the concentration of antibiotics in the sediments of recirculating aquaculture ponds was up to 22.9 ng/g, while that in TWPPs was as high as 56.1 ng/g. In conclusion, the antibiotic residues in the RAS were low after antibiotics were banned in feed in China, and the removal of antibiotics in the TWPPs was more pronounced. Furthermore, cross-contamination was found between the RAS, surrounding open aquaculture ponds and the river, and the water supply of the RAS was likely to be the main contributor of antibiotics in the aquaculture environments. This study can help the government formulate discharge standards for antibiotics in aquaculture and also provide a reference for the transformation and upgrading of aquaculture ponds to achieve a zero-emission aquaculture mode.

Therapeutic effect and mechanism of Anemarrhenae Rhizoma on Alzheimer's disease based on multi-platform metabolomics analyses.

Anemarrhenae Rhizoma (AR) has multiple pharmacological activities to prevent and treat Alzheimer's disease (AD). However, the effect and its molecular mechanism are not elucidated clear. This study aims to evaluate AR's therapeutic effect and mechanism on AD model rats induced by D-galactose and AlCl3 with serum metabolomics. Behavior study, histopathological observations, and biochemical analyses were applied in the AD model assessment. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-QTOF/MS) were combined with multivariate statistical analysis to identify potential biomarkers of AD and evaluate the therapeutic effect of AR on AD from the perspective of metabolomics. A total of 49 biomarkers associated with the AD model were identified by metabolomics, and pathway analysis was performed to obtain the metabolic pathways closely related to the model. With the pre-treatment of AR, 32 metabolites in the serum of AD model rats were significantly affected by AR compared with the AD model group. The regulated metabolites affected by AR were involved in the pathway of arginine biosynthesis, arginine and proline metabolism, ether lipid metabolism, glutathione metabolism, primary bile acid biosynthesis, and steroid biosynthesis. These multi-platform metabolomics analyses were in accord with the results of behavior study, histopathological observations, and biochemical analyses. This study explored the therapeutic mechanism of AR based on multi-platform metabolomics analyses and provided a scientific basis for the application of AR in the prevention and treatment of AD.

Cost-efficient snare-assisted peroral endoscopic myotomy in comparison of conventional endoscopic knife for treatment of achalasia: results of a randomized controlled trial.

BACKGROUND: To date, the ideal endoscopic knife for peroral endoscopic myotomy (POEM) with good performance and cost-effectiveness is still under investigation. The present study was aimed to evaluate the efficacy, safety, and cost-effectiveness of snare-assisted POEM, compared with the conventional endoscopic knife approach. METHODS: From May 2017 to December 2018, patients with achalasia presenting for POEM without previous endoscopic or surgical therapy were prospectively recruited in this randomized controlled trial. Patients were randomly allocated to receive POEM using either the snare (snare group) or HookKnife (conventional group). The primary outcome was clinical success (Eckardt score ≤ 3) at 12-month follow-up, powered for noninferiority with a margin of -15%. The secondary outcomes included adverse events (AEs), procedure-related parameters, clinical outcomes, and cost-effectiveness. RESULTS: A total of 75 patients with similar baseline characteristics between the snare (N = 37) and conventional (N = 38) groups were included. Clinical success at 12-month follow-up was achieved in 94.6% of patients in the snare group and 92.1% of patients in the conventional group (difference, 2.5% [95% CI, -8.7% to 13.7%]; P < 0.001 for noninferiority). No severe AEs occurred in both groups. The use of snare is associated with comparable procedure time (40.6 minutes vs. 42.5 minutes, P = 0.337), a lower frequency of hemostatic forceps use (27.0% vs. 68.4%, P < 0.001), and lower hospital costs ($4271.1 vs. $5327.3, P < 0.001). The cost-effectiveness plane revealed that 96.9% of snare-assisted POEM procedures offered more cost-savings and health utility benefits. CONCLUSIONS: The snare-assisted POEM was noninferior to the conventional endoscopic knife approach in terms of clinical efficacy, with comparable safety outcomes and cost-effective benefits.

Injectable thermo-sensitive and wide-crack self-healing hydrogel loaded with antibacterial anti-inflammatory dipotassium glycyrrhizate for full-thickness skin wound repair.

Severe skin injuries are hard to repair and susceptible to bacterial infection. Development of a versatile antimicrobial anti-inflammatory hydrogel dressing that eliminates concern over antibiotic resistance is urgently needed but remains an elusive goal. Our research, described herein, the design and fabrication of a new family of supramolecular hydrogels based on hydroxypropyl chitosan (HPCS) and poly(N-isopropylacrylamide) (PNIPAM) may prove to be that goal. Employing the reversible cross-linking by ß-cyclodextrin (ß-CD) and adamantyl (AD) pre-assembly, the hydrogels can be formed in a facile one-pot method. Additionally, the structure and performance of the hydrogels can be controlled by a simple adjustment of the AD content. The obtained hydrogels exhibit an abundance of desired properties; they are injectable, thermosensitive, highly ductile, self-healable (will self-heal recurring damage to the hydrogel bandage of up to several millimeters wide), biocompatible, and have antimicrobial activity against Staphylococcus aureus when infused with dipotassium glycyrrhizinate (DG). Using a mouse full-thickness skin defect model, in vivo wound healing evaluations revealed that the DG-loaded hydrogels (HP-3/DG10) applied to the wound resulted in rapid wound closure. The hydrogels promoted efficient tissue remolding, collagen deposition, decreased inflammation and performed better than the control groups of commercial TegadermTM film and 3M dressing. Given their multifunctionality and in vivo efficacy, the DG-loaded HP hydrogels hold great potential as a wound dressing for full-thickness skin repair. STATEMENT OF SIGNIFICANCE: Injectable hydrogels are receiving increasing attention as an ideal wound dressing. To the best of our knowledge, however, injectable and wide-crack self-healing hydrogel dressings have been hardly studied. A versatile antimicrobial hydrogel without drug resistance or cytotoxicity is also highly required. Therefore, in the present study, we constructed injectable thermosensitive and wide-crack self-healing hydrogels with antibacterial and anti-inflammatory properties. These hydrogels were developed through novel strategies of the wide-crack self-healing design and the loading of the bioactive antibacterial and anti-inflammatory agent dipotassium glycyrrhizinate. The simple preparation method and multifunctionality of the studied hydrogel composites may provide important insights for the development of future biomaterials for wound dressings and other biomedical applications.

Severe bleeding following off-pump coronary artery bypass grafting: predictive factors and risk model.

BACKGROUND: Severe bleeding following cardiac surgery remains a troublesome complication, but to date, there is a lack of comprehensive predictive models for the risk of severe bleeding following off-pump coronary artery bypass grafting (OPCABG). This study aims to analyze relevant indicators of severe bleeding after isolated OPCABG and establish a corresponding risk assessment model. METHODS: The clinical data of 584 patients who underwent OPCABG from January 2018 to April 2020 were retrospectively analyzed. We gathered the preoperative baseline data and postoperative data immediately after intensive care unit admission and used multifactor logistic regression to screen the potential predictors of severe bleeding, upon which we established a predictive model. Using the consistency index and calibration curve, decision curve, and clinical impact curve analysis, we evaluated the performance of the model. RESULTS: This study is the first to establish a risk assessment and prediction model for severe bleeding following isolated OPCABG. Eight independent risk factors were identified: male sex, aspirin/clopidogrel withdrawal time, platelet count, fibrinogen level, C-reactive protein, serum creatinine, and total bilirubin. Among the 483 patients in the training group, 138 patients (28.6%) had severe bleeding; among the 101 patients in the verification group, 25 patients (24.8%) had severe bleeding. Receiver operating characteristic (ROC) curve analysis for the internal training group revealed a convincing performance with a concordance index (C-index) of 0.859, while the area under the ROC curve for the external validation data was 0.807. Decision curve analysis showed that the model was useful for both groups. CONCLUSIONS: Although there are some limitations, the model can effectively predict the probability of severe bleeding following isolated OPCABG and is therefore worthy of further exploration and verification.

Prognostic Analysis and Risk Factors Associated with Fetal Ventriculomegaly.

BACKGROUND: This study aimed to investigate the clinical outcome and related risk factors of fetal lateral ventriculomegaly (VM). METHODS: A retrospective analysis was performed on 255 cases diagnosed as fetal VM. Prenatal imaging examination was carried out. The pregnancy outcomes were investigated through follow-up. According to the prognosis of children, they were divided into case group and control group. Multivariate logistic regression was used to analyze the factors influencing the prognosis of hydrocephalus. RESULTS: After excluding the cases with either loss of follow-up or incomplete information, 102 cases were followed up. Twelve cases with poor prognosis were set as the case group. According to the maternal age, gestational age, gender of children, and follow-up time, 3 cases were selected from the other 90 cases for each child in the case group, respectively, and selected as the control group. Paired comparative analysis was performed on 48 cases. Using prognosis as a dependent variable, multivariate logistic regression analysis of the statistically significant factors indicated that the change speed of width ratio (CSWR) and maximum lateral ventricular width (MW) were associated with fetal prognosis. CONCLUSIONS: Our results suggested that CSWR and MW may have the value of predicting fetal prognosis.

Modulating the voltage sensor of a cardiac potassium channel shows antiarrhythmic effects.

Cardiac arrhythmias are the most common cause of sudden cardiac death worldwide. Lengthening the ventricular action potential duration (APD), either congenitally or via pathologic or pharmacologic means, predisposes to a life-threatening ventricular arrhythmia, Torsade de Pointes. IKs (KCNQ1+KCNE1), a slowly activating K+ current, plays a role in action potential repolarization. In this study, we screened a chemical library in silico by docking compounds to the voltage-sensing domain (VSD) of the IKs channel. Here, we show that C28 specifically shifted IKs VSD activation in ventricle to more negative voltages and reversed the drug-induced lengthening of APD. At the same dosage, C28 did not cause significant changes of the normal APD in either ventricle or atrium. This study provides evidence in support of a computational prediction of IKs VSD activation as a potential therapeutic approach for all forms of APD prolongation. This outcome could expand the therapeutic efficacy of a myriad of currently approved drugs that may trigger arrhythmias.

Using Thromboelastography to Predict Blood Loss After Off-Pump Coronary Artery Bypass Grafting.

OBJECTIVE: This study aims to investigate the value of thromboelastography (TEG) in predicting blood loss, and its relationship with blood transfusion demand, during the perioperative period in off-pump coronary artery bypass grafting (OPCABG). METHODS: The data of 398 patients undergoing OPCABG were retrospectively analyzed. Blood was drawn before anesthesia induction (T1) and at 10 minutes after heparin neutralization (T2) for further TEG detection. The patients were divided into two groups based on the results at T2: a TEG normal group and a TEG abnormal group. Logistic regression analysis was used to predict the related factors contributing to the significant increase in perioperative blood loss (more than 20% of the estimated blood volume). RESULTS: There were 277 (69.6%) patients in the TEG normal group and 121 (30.4%) in the TEG abnormal group. Compared with the TEG normal group, the volume of blood loss, red blood cell count, and volume of plasma transfusion in the TEG abnormal group significantly increased within 24 hours after surgery. The results of the logistic regression analysis identified the use of clopidogrel, platelet count at T2, fibrinogen level at T2, and abnormality in TEG value as independent predictors for the significant increase in perioperative blood loss (P < 0.001). CONCLUSION: The abnormality in TEG value after heparin neutralization is correlated with massive hemorrhage and blood transfusion during the perioperative period in OPCABG. TEG detection can assist in clinical treatment and reduce the volume of blood lost in a hemorrhage and the volume of blood required in a transfusion during OPCABG.

Advance in Gait Adaptability Training for Rehabilitation of Stroke (review) / 中国康复理论与实践

Gait adaptability refers to adjustments of gait to accomplish walking and to overcome environmental difficulties. According to the training environment, gait adaptability training in stroke rehabilitation can be divided into two categories: real environment and simulated environment. The simulated environment is divided into simple indoor and multimoding environment. Some technologies, such as virtual reality and augmented reality may provide safer and more efficient methods for gait adaptability training. Gait adaptability training can improve walking function and confidence of hemiplegic patients, and help them to return to community life and social participation.

Regulation of HCN2 Current by PI3K/Akt Signaling.

It has long been known that heart rate is regulated by the autonomic nervous system. Recently, we demonstrated that the pacemaker current, I f , is regulated by phosphoinositide 3-kinase (PI3K) signaling independently of the autonomic nervous system. Inhibition of PI3K in sinus node (SN) myocytes shifts the activation of I f by almost 16 mV in the negative direction. I f in the SN is predominantly mediated by two members of the HCN gene family, HCN4 and HCN1. Purkinje fibers also possess I f and are an important secondary pacemaker in the heart. In contrast to the SN, they express HCN2 and HCN4, while ventricular myocytes, which do not normally pace, express HCN2 alone. In the current work, we investigated PI3K regulation of HCN2 expressed in HEK293 cells. Treatment with the PI3K inhibitor PI-103 caused a negative shift in the activation voltage and a dramatic reduction in the magnitude of the HCN2 current. Similar changes were also seen in cells treated with an inhibitor of the protein kinase Akt, a downstream effector of PI3K. The effects of PI-103 were reversed by perfusion of cells with phosphatidylinositol 3,4,5-trisphosphate (the second messenger produced by PI3K) or active Akt protein. We identified serine 861 in mouse HCN2 as a putative Akt phosphorylation site. Mutation of S861 to alanine mimicked the effects of Akt inhibition on voltage dependence and current magnitude. In addition, the Akt inhibitor had no effect on the mutant channel. These results suggest that Akt phosphorylation of mHCN2 S861 accounts for virtually all of the observed actions of PI3K signaling on the HCN2 current. Unexpectedly, Akt inhibition had no effect on I f in SN myocytes. This result raises the possibility that diverse PI3K signaling pathways differentially regulate HCN-induced currents in different tissues, depending on the isoforms expressed.

Establishment of a Swine Benign Biliary Stricture Model of Endobiliary Thermal Injury With a Diathermic Sheath.

BACKGROUND: A reliable large animal model of benign biliary stricture (BBS) is essential to study endoscopic management of BBS. The aim of this study was to establish a swine BBS model of endobiliary electrothermal injury with a diathermic sheath and screen out the optimal energy dose. MATERIALS AND METHODS: Twelve swine were equally randomized into a low (20 W), a medium (30 W), and a high (40 W)-dose group. Endobiliary electrothermal injury was applied to the common bile duct using a diathermic sheath at different energy doses for 20 seconds via endoscopic retrograde cholangiopancreatography. Cholangiographic findings and liver function were evaluated weekly after thermal injury. Two animals from each group were sacrificed at 2 weeks and the other 2 sacrificed 4 weeks after thermal injury for histopathologic evaluation. RESULTS: BBS was established successfully in 10 of the 12 animals. Two of the 4 animals in low-dose group did not produce biliary stricture at 4 weeks; in medium-dose group, BBS was induced in both animals at 2 weeks without causing severe complications; and in high-dose group, BBS was produced in 4 animals at 2 weeks, causing perforation and abdominal abscess formation in 1 animal. CONCLUSIONS: A safe and reproducible swine model of BBS could be established successfully by applying endobiliary electrothermal injury with a diathermic sheath at 30 W for 20 seconds.

A PIP2 substitute mediates voltage sensor-pore coupling in KCNQ activation.

KCNQ family K+ channels (KCNQ1-5) in the heart, nerve, epithelium and ear require phosphatidylinositol 4,5-bisphosphate (PIP2) for voltage dependent activation. While membrane lipids are known to regulate voltage sensor domain (VSD) activation and pore opening in voltage dependent gating, PIP2 was found to interact with KCNQ1 and mediate VSD-pore coupling. Here, we show that a compound CP1, identified in silico based on the structures of both KCNQ1 and PIP2, can substitute for PIP2 to mediate VSD-pore coupling. Both PIP2 and CP1 interact with residues amongst a cluster of amino acids critical for VSD-pore coupling. CP1 alters KCNQ channel function due to different interactions with KCNQ compared with PIP2. We also found that CP1 returned drug-induced action potential prolongation in ventricular myocytes to normal durations. These results reveal the structural basis of PIP2 regulation of KCNQ channels and indicate a potential approach for the development of anti-arrhythmic therapy.

Repeatedly Intrinsic Self-Healing of Millimeter-Scale Wounds in Polymer through Rapid Volume Expansion Aided Host-Guest Interaction.

Implantable and wearable materials, which are usually used in/on a biological body, are mostly needed with biomimetic self-healing function. To enable repeatable large-wound self-healing and volume/structure recovery, we verified a proof-of-concept approach in this work. We design a polymer hydrogel that combines temperature responsiveness with an intrinsic self-healing ability through host-guest orthogonal self-assembly between two types of poly(N-isopropylacrylamide) (PNIPAM) oligomers. The result is thermosensitive, capable of fast self-repair of microcracks based on reversible host-guest assembly. More importantly, when a large open wound appears, the hydrogel can first close the wound via volume swelling and then completely self-repair the damage in terms of intrinsic self-healing. Meanwhile, its original volume can be easily recovered by subsequent contraction. As demonstrated by the experimental data, such millimeter-level wound self-healing and volume recovery can be repeatedly carried out in response to the short-term cooling stimulus. With low cytotoxicity and good biocompatibility, moreover, this highly intelligent hydrogel is greatly promising for practical large-wound self-healing in wound dressing, electronic skins, wearable biosensors, and humanoid robotics, which can tolerate large-scale human motions.

Assembling reduced graphene oxide with sulfur/nitrogen- "hooks" for electrochemical determination of Hg(II).

Herein the sulfur/nitrogen contained groups, serving as the "hooks" for electrochemical determination of Hg(II), were assembled on the reduced graphene oxide (hereafter SN-rGO) via a one-step facile hydrothermal method. The thiourea acts as a precursor for sulfur/nitrogen doping and partial reduction of graphene oxide. The SN-rGO was used to modify the glassy carbon electrode (GCE) for electrochemical detection of Hg(II) by square wave anodic stripping voltammetry (SWASV). The sulfur/nitrogen doping significantly improves the Hg(II) complexation by SN-rGO due to the creation of multifunctional groups on the graphene nanosheet. The SN-rGO modified electrode has excellent sensitivity (20.48 µA/µM) and limit of detection (LOD 8.93 nM) for Hg(II) detection. The newly developed Hg(II) sensing electrode possesses minimal interference for other ions typically found in natural waters. Therefore, it can be used for routine water quality monitoring. The fabrication of the SN-rGO electrode is rapid and low cost; hence, it offers a potential platform for environmental monitoring of toxic metal ions.