A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes.

Antibiotics are indispensable to infection management. However, use of antibiotics can cause gut microbiota dysbiosis, which has been linked to cognitive impairment by disrupting communication between the gut microbiota and the brain. We conducted a systematic review and meta-analysis on the effects of long-term antibiotic use on cognitive outcomes. We have searched PubMed, Web of Science, Embase, Cochrane Library and Scopus for English publications before March 2023 following the PRISMA guidelines. Screening, data extraction, and quality assessment were performed in duplicate. 960 articles were screened and 16 studies which evaluated the effect of any antibiotic compared to no antibiotics or placebo were included. Case-reports, in vitro and animal studies were excluded. We found that antibiotic use was associated with worse cognitive outcomes with a pooled effect estimate of - 0.11 (95% CI - 0.15, - 0.07, Z = 5.45; P < 0.00001). Subgroup analyses performed on adult vs pediatric patients showed a similar association of antibiotic on cognition in both subgroups. Antibiotic treatment was not associated with worse cognition on subjects with existing cognitive impairment. On the other hand, antibiotic treatment on subjects with no prior cognitive impairment was associated with worse cognitive performance later in life. This calls for future well-designed and well-powered studies to investigate the impact of antibiotics on cognitive performance.

All-printed multiplexed electrocatalytic biosensors with rationally designed nanoparticle inks.

Inkjet printing, capable of rapid and template-free fabrication with high resolution and low material waste, is a promising method to construct electrochemical biosensor devices. However, the construction of fully inkjet-printed electrochemical biosensor remains a challenge owing to the lack of appropriate inks, especially the sensing inks of bioactive materials. Herein, we demonstrate a fully inkjet-printed, integrated and multiplexed electrochemical biosensor by combining rationally designed nanoparticle Inks. The stable gold (Au) nanoparticles ink with lower sintering temperature is prepared by using L-cysteine as stabilizer, and it is used to print the interconnects, the counter electrodes, and the working electrodes. The SU-8 ink is used to serve as dielectric layer for the biosensor, whereas the silver electrode is printed on the Au electrode by using commercially silver nanoparticles ink before it is chlorinated to prepare Ag/AgCl reference electrode. Moreover, we synthesize an inkjet-printable and electroactive ink, by the 'one-pot method', which is composed of conductive poly 6-aminoindole (PIn-6-NH2) and gold-palladium (Au-Pd) alloy nanoparticle (Au-Pd@PIn-6-NH2) to enhance the sensing performance of gold electrode towards hydrogen peroxide (H2O2). Especially, the amino groups in PIn-6-NH2can be further used to immobilizing glucose oxidase (GOx) and lactic acid oxidase (LOx) by glutaraldehyde to prepare printable sensing ink for the detection of glucose and lactate. The fully inkjet-printed electrochemical biosensor enabled by advanced inks can simultaneously detect glucose and lactate with good sensitivity and selectivity, as well as facile and scalable fabrication, showing great promise for metabolic monitoring.

Impacts of the zero mark-up policy on hospitalization expenses of T2DM and cholecystolithiasis inpatients in SC province, western China: an interrupted time series analysis.

Background: Since 2009, a series of ambitious health system reforms have been launched in China, including the zero mark-up drug policy (ZMDP); the policy was intended to reduce substantial medicine expenses for patients by abolishing the 15% mark-up on drugs. This study aims to evaluate the impacts of ZMDP on medical expenditures from the perspective of disease burden disparities in western China. Method: Two typical diseases including Type 2 diabetes mellitus (T2DM) in internal medicine and cholecystolithiasis (CS) in surgery were selected from medical records in a large tertiary level-A hospital in SC Province. The monthly average medical expenses of patients from May 2015 to August 2018 were extracted to construct an interrupted time series (ITS) model to evaluate the impact of policy implementation on the economic burden. Results: A total of 5,764 cases were enrolled in our study. The medicine expenses for T2DM patients maintained a negative trend both before and after the intervention of ZMDP. It had declined by 74.3 CNY (P < 0.001) per month on average in the pre-policy period and subsequently dropped to 704.4 CNY (P = 0.028) immediately after the policy. The level change of hospitalization expenses was insignificant (P = 0.197), with a reduction of 677.7 CNY after the policy, while the post-policy long-term trend was significantly increased by 97.7 CNY (P = 0.035) per month contrasted with the pre-policy period. In addition, the anesthesia expenses of T2DM patients had a significant increase in the level under the impact of the policy. In comparison, the medicine expenses of CS patients significantly decreased by 1,014.2 CNY (P < 0.001) after the policy, while the total hospitalization expenses had no significant change in level and slope under the influence of ZMDP. Furthermore, the expenses of surgery and anesthesia for CS patients significantly increased by 320.9 CNY and 331.4 CNY immediately after the policy intervention. Conclusion: Our study indicated that the ZMDP has been an effective intervention to reduce the excessive medicine expenses for both researched medical and surgical diseases, but failed to show any long-term advantage. Moreover, the policy has no significant impact on relieving the overall hospitalization burden for either condition.

PEDOT:PSS hydrogels with high conductivity and biocompatibility for in situ cell sensing.

Conducting polymer hydrogels, especially poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) hydrogels, show great promise in soft bioelectronics due to their high conductivity and the ability of electrical coupling with tissues for sensing and stimulation. However, it is challenging to solve the problem of poor biocompatibility of PEDOT:PSS hydrogels due to the existing harsh preparation methods with the use of toxic and harmful reagents. Herein, we report the synthesis of PEDOT:PSS hydrogels with positively charged conductive polymers as a cross-linker and the application of PEDOT:PSS hydrogels as in situ electrochemical sensors for living cells. The conductivities of PEDOT:PSS hydrogels prepared using this method without any toxic or harmful reagents can reach up to 3265 S m-1. The facile synthesis approach with a simple mixture of PEDOT:PSS aqueous solution and the monomers of conductive polymers at room temperature also enables the printability of PEDOT:PSS hydrogels to fabricate patterned electrodes. Moreover, all the proposed PEDOT:PSS hydrogels demonstrated good biocompatibility. The in situ electrochemical detection of dopamine secreted from PC12 cells cultured within PEDOT:PSS hydrogels suggests that our PEDOT:PSS hydrogels with high conductivity and biocompatibility offer great potential for the integration of biosensors within 3D cell culture.

Identification of cancer-related genes FGFR2 and CEBPB in choledochal cyst via RNA sequencing of patient-derived liver organoids.

BACKGROUND: Choledochal cysts (CC) are congenital bile duct anomalies with 6-30% risk for developing bile duct cancer. However, the molecular mechanisms underlying cancer risk of CC are unknown. We sought to identify the gene expression changes underlying the cancer risk of CC patients. METHODS: Liver organoids (n = 51) were generated from liver/bile duct biopsies of CC (n = 7; type I) and hepatoblastoma (n = 5; HB: non-tumor & tumor) for RNA sequencing. Bioinformatics analysis was conducted to identify differentially expressed cancer-related genes in CC and controls. We compared CC with non-cancerous and cancerous controls, normal adjacent non-tumor region of hepatoblastoma (HB) liver as non-cancerous control and tumor region as non-CC cancer control (HB-tumor). Reverse transcription real-time quantitative PCR (RT-qPCR) verification and immunohistochemistry of selected genes was conducted in additional CC and HB liver biopsies. FINDINGS: HB non-tumor and HB tumor organoids displayed distinct gene expression profiles. Expression profiling separated CC organoids into two clusters, one overlapping with HB non-tumor and the other one with HB tumor organoids. Genes selected based on their log2FoldChange values for RT-qPCR verification in 31 CC and 11 HB non-tumor liver tissues revealed significantly elevated expression of FGFR2 in 7 and CEBPB in 2 CC liver tissues (CC vs HB: 4.082 vs. 0.7671, p<0.01; 2.506 vs. 1.210, p<0.01). Distinctive positive staining in bile ducts were seen in CC, HB tumor and non-tumor liver tissues for FGFR2 and CEBPB. Percentages of CEBPB-immuno-positive or FGFR2-immuno-positive bile duct cells in CC and HB-tumor liver were higher than that in HB non-tumor liver. INTERPRETATION: The study identified dysregulated genes related to cancer pathways in CC patients suggesting cancer risk. The findings suggest that the elevated expression of FGFR2 and CEBPB in liver may contribute to cancer development in CC patients.

Lilly's Technique for Delayed Hemorrhage After Choledochal Cyst Radical Surgery.

Background: Choledochal cysts (CCs) are characterized by dilations of the extra- and/or intrahepatic bile ducts. Surgery (cyst excision and Roux-en-Y hepaticojejunostomy) remains the gold standard for treatment. However, delayed hemorrhage can occur postoperatively, and although rare, it can be life-threatening. This study aimed to determine the risk factors and corresponding prevention of delayed hemorrhage after radical CC surgery, and to apply a technique to lower its incidence. Materials and Methods: This retrospective study enrolled 267 patients who received CC surgery between June 2016 and December 2020 at Shenzhen Children's Hospital. Univariate and multivariate logistic regression analyses were performed to identify risk factors for delayed hemorrhage. Results: Eleven (4.1%) patients had delayed hemorrhage after laparoscopic radical surgery. The most common hemorrhage site was the dissected surface between the cyst and adjacent structures with chronic severe adhesions, postoperatively. The occurrence of recurrent CC-associated complication and excessive total blood loss during surgery were risk factors for delayed hemorrhage after CC radical surgery. Length of disease course, operation when cholangitis/pancreatitis still existed, cyst diameter, and application of trypsin inhibitor after the surgery were not significantly different between the two groups. Conclusion: For patients without adhesions, complete cyst resection is the gold standard. However, for those with intensive adhesions, in cases of delayed hemorrhage on the dissection surface and malignancy transformation risk, the Lilly's technique with Roux-en-Y hepaticojejunostomy could be an alternative.

FIB-4 and APRI scores for progressive liver fibrosis diagnosis in children with biliary atresia.

Introduction: Finding non-invasive methods to predict the degree of liver fibrosis is very important in managing children with biliary atresia. Therefore, we explored the predictive value of APRI, FIB-4, and serological markers for liver fibrosis in children with biliary atresia. Methods: This study retrospectively reviewed data from children diagnosed with BA between March and December 2022. Liver tissue pathology specimens were obtained during surgery. The serum markers were measured within 2 days before the Kasai procedure or liver transplantation. The aspartate aminotransferase-to-platelet ratio index (APRI) and the four-factor-based fibrosis index (FIB-4) were calculated. The outcome was the diagnosis of progressive liver fibrosis. Results: This study reviewed the data from 41 children with biliary atresia. APRI had 52% sensitivity and 83% specificity for progressive liver fibrosis, while FIB-4 had 83% sensitivity and 67% specificity. Their areas under the curve were not significantly different from those of conventional markers. Conclusion: Although they were not better than conventional markers, APRI and FIB-4 can be used as follow-up markers for progressive liver fibrosis in patients with biliary atresia, but their predictive value was moderate. Additional studies are necessary to determine whether they could be combined with other markers to improve their predictive value.

Interaction between human leukocyte antigen (HLA-C) and killer cell Ig-like receptors (KIR2DL) inhibits the cytotoxicity of natural killer cells in patients with hepatoblastoma.

Background: Hepatoblastoma (HB) is the most common liver malignancy in childhood with poor prognosis and lack of effective therapeutic targets. Single-cell transcriptome sequencing technology has been widely used in the study of malignant tumors, which can understand the tumor microenvironment and tumor heterogeneity. Materials and methods: Two children with HB and a healthy child were selected as the research subjects. Peripheral blood and tumor tissue were collected for single-cell transcriptome sequencing, and the sequencing data were compared and analyzed to describe the differences in the immune microenvironment between children with HB and normal children. Results: There were significant differences in the number and gene expression levels of natural killer cells (NK cells) between children with HB and normal children. More natural killer cells were seen in children with HB compared to normal control. KIR2DL were highly expressed in children with HB. Conclusion: Single-cell transcriptome sequencing of peripheral blood mononuclear cells (PBMC) and tumor tissue from children with HB revealed that KIR2DL was significantly up-regulated in NK cells from children with HB. HLA-C molecules on the surface of tumor cells interact with inhibitory receptor KIR2DL on the surface of NK cells, inhibiting the cytotoxicity of NK cells, resulting in immune escape of tumors. Inhibitors of related immune checkpoints to block the interaction between HLA-C and KIR2DL and enhance the cytotoxicity of NK cells, which may be a new strategy for HB treatment.

mRNA and lncRNA expression profiles of liver tissues in children with biliary atresia.

Progressive liver fibrosis is the most common phenotype in biliary atresia (BA). A number of pathways contribute to the fibrosis process so comprehensive understanding the mechanisms of liver fibrosis in BA will pave the way to improve patient's outcome after operation. In this study, the differentially expressed profiles of mRNAs and long non-coding RNAs from BA and choledochal cyst (CC) liver tissues were investigated and analyzed, which may provide potential clues to clarify hepatofibrosis mechanism in BA. A total of two BA and two CC liver tissue specimens were collected, the expression level of mRNAs and lncRNAs was detected by RNA sequencing. Differentially expressed mRNAs (DEmRNAs) were functionally annotated and protein-protein interaction networks (PPI) was established to predict the biological roles and interactive relationships. Differentially expressed lncRNAs (DElncRNAs) nearby targeted DEmRNA network and DElncRNA-DEmRNA co-expression network were constructed to further explore the roles of DElncRNAs in BA pathogenesis. The expression profiles of significant DEmRNAs were validated in Gene Expression Omnibus database. A total of 2,086 DEmRNAs and 184 DElncRNAs between BA and CC liver tissues were obtained. DEmRNAs were enriched in 521 Gene Ontology terms and 71 Kyoto Encyclopedia of Genes and Genomes terms which were mainly biological processes and metabolic pathways related to immune response and inflammatory response. A total of five hub proteins (TYRO protein tyrosine kinase binding protein, C-X-C motif chemokine ligand 8, pleckstrin, Toll-like receptor 8 and C-C motif chemokine receptor 5) were found in the PPI networks. A total of 31 DElncRNA-nearby-targeted DEmRNA pairs and 2,337 DElncRNA-DEmRNA co-expression pairs were obtained. The expression of DEmRNAs obtained from RNA sequencing were verified in GSE46960 dataset, generally. The present study identified key genes and lncRNAs participated in BA associated liver fibrosis, which may present a new avenue for understanding the patho-mechanism for hepatic fibrosis in BA.

Plasma amyloid-beta levels correlated with impaired hepatic functions: An adjuvant biomarker for the diagnosis of biliary atresia.

Background: Biliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aß) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aß levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown. Method: Plasma samples of 11 BA and 24 controls were collected for liver function test, Aß40 and Aß42 measurement by enzyme-linked immunosorbent assay (ELISA). Pearson's chi-squared test or Mann-Whitney U test was performed to assess differences between groups. Correlation between Aß42/Aß40 and liver function parameters was performed using Pearson analysis. The area under the receiver-operative characteristic (ROC) curve (area under curve; AUC) was measured to evaluate the diagnostic power of Aß42/Aß40 for BA. Diagnostic enhancement was further evaluated by binary regression ROC analysis of Aß42/Aß40 combined with other hepatic function parameters. Results: Plasma Aß42/Aß40 was elevated in BA patients. Aß42 displayed a weak positive correlation with γ-glutamyl transpeptidase (GGT) (Pearson's correlation = 0.349), while there was no correlation for Aß40 with hepatic functions. Aß42/Aß40 was moderately correlated with GGT, total bile acid (TBA), direct bilirubin (DBIL) (Pearson's correlation = 0.533, 0.475, 0.480), and weakly correlated with total bilirubin (TBIL) (Pearson's correlation = 0.337). Aß42/Aß40 showed an acceptable predictive power for cholestasis [AUC = 0.746 (95% CI: 0.552-0.941), p < 0.05]. Diagnostic powers of Aß42/Aß40 together with hepatic function parameters for cholestasis were markedly improved compared to any indicator alone. Neither Aß42/Aß40 nor hepatic function parameters displayed sufficient power in discriminating BA from choledochal cysts (CC); however, combinations of Aß42/Aß40 + GGT along with any other hepatic function parameters could differentiate BA from CC-cholestasis (AUC = 1.000, p < 0.05) with a cut-off value as 0.02371, -0.28387, -0.34583, 0.06224, 0.01040, 0.06808, and 0.05898, respectively. Conclusion: Aß42/Aß40 is a good indicator for cholestasis, but alone is insufficient for a distinction of BA from non-BA. However, Aß42/Aß40 combined with GGT and one other hepatic function parameter displayed a high predictive power as a screening test for jaundiced neonates who are more likely to be BA, enabling them to early intraoperative cholangiography for BA confirmation and KPE to improve surgical outcomes. However, a multi-centers validation is needed before introduction into daily clinical practice.

Palladium-catalyzed allylic etherification of phenols with vinyl ethylene carbonate.

The palladium-catalyzed decarboxylative reactions of phenols and vinyl ethylene carbonate to produce allylic aryl ethers under mild conditions have been established. Adopting an inexpensive PdCl2(dppf) catalyst promotes the efficient conversion of phenols to the corresponding allylic aryl ethers via the formation of a new C-O bond in good isolated yields with complete regioselectivities, acceptable functional group tolerance and operational simplicity. The robust procedure could be completed smoothly by conducting a scaled-up reaction with comparable efficiency to afford the target product.

Pathogenesis of Choledochal Cyst: Insights from Genomics and Transcriptomics.

Choledochal cysts (CC) is characterized by extra- and/or intra-hepatic b\ile duct dilations. There are two main theories, "pancreaticobiliary maljunction" and "congenital stenosis of bile ducts" proposed for the pathogenesis of CC. Although family cases or CC associated with other anomalies have been reported, the molecular pathogenesis of CC is still poorly understood. Recent advances in transcriptomics and genomics analysis platforms have unveiled key expression signatures/genes/signaling pathways in the pathogenesis of human diseases including CC. This review summarizes insights from genomics and transcriptomics studies into the pathogenesis of CC, with the aim to improve (i) our understanding of its underlying complex pathomechanisms, and (ii) clinical management of different subtypes of CC, in particular their associated hepatic fibrotic change and their risk of malignancy transformation.

Dynamic analysis of serum MMP-7 and its relationship with disease progression in biliary atresia: a multicenter prospective study.

PURPOSE: We aimed to assess the dynamic changing trend of serum matrix metalloproteinase-7 (MMP-7) in biliary atresia (BA) patients from diagnosis to LTx to further elucidate its clinical value in diagnosis and prognoses and its relationship with disease progression. METHODS: In this multicentre prospective study, 440 cholestasis patients (direct bilirubin level of > 17 µmol/L) were enrolled. Serum MMP-7 levels were measured using an enzyme-linked immunosorbent assay at diagnosis, 1 week, 2 weeks, 1 month, 6 weeks, 2 months, 3 months, 6 months and then every 6 months post-KPE. The medical record at each follow-up visit for post-Kasai portoenterostomy patient was collected and analyzed. RESULTS: Using a cut-off value of > 26.73 ng/mL, serum MMP-7 had an AUC of 0.954 in BA neonates and 0.983 in BA infants. A genetic mutation (G137D) was associated with low MMP-7 levels in serum of BA patients. MMP-7 showed a mediation effect on the association between inflammation and liver fibrosis in BA patients. Four dynamic patterns of serum MMP-7 post-KPE were associated with prognosis. Serum MMP-7 was the only significant predictor at 6 weeks post-KPE and the most accurate predictor at 3 months post-KPE of survival with the native liver in 2 years. CONCLUSION: As one of the critical factors associated with BA occurrence and progression, serum MMP-7 can be used for early diagnosis of BA and post-KPE MMP-7 level is the earliest prognostic biomarker so far.

Recent Advances of Pyridinone in Medicinal Chemistry.

Pyridinones have been adopted as an important block in medicinal chemistry that could serve as hydrogen bond donors and acceptors. With the help of feasible synthesis routes via established condensation reactions, the physicochemical properties of such a scaffold could be manipulated by adjustment of polarity, lipophilicity, and hydrogen bonding, and eventually lead to its wide application in fragment-based drug design, biomolecular mimetics, and kinase hinge-binding motifs. In addition, most pyridinone derivatives exhibit various biological activities ranging from antitumor, antimicrobial, anti-inflammatory, and anticoagulant to cardiotonic effects. This review focuses on recent contributions of pyridinone cores to medicinal chemistry, and addresses the structural features and structure-activity relationships (SARs) of each drug-like molecule. These advancements contribute to an in-depth understanding of the potential of this biologically enriched scaffold and expedite the development of its new applications in drug discovery.

Role of long non-coding RNA-adducin 3 antisense RNA1 in liver fibrosis of biliary atresia.

Biliary atresia (BA) is a devastating liver disease in neonates. Liver fibrosis is regarded as a universal and prominent feature of BA. Studies have revealed that long non-coding RNAs (lncRNAs) regulate cellular processes during the development of liver fibrosis in BA. Long non-coding RNA-adducin 3 antisense RNA1 (lnc-ADD3-AS1) has been shown to increase susceptibility to BA. However, the role of lnc-ADD3-AS1 in liver fibrosis in BA remains unclear. Here, we investigated the role of lnc-ADD3-AS1 in the proliferation, migration, and apoptosis of the immortalized human hepatic stellate cell (HSC) line, LX-2. We successfully overexpressed and silenced lnc-ADD3-AS1 in LX-2 cells using adenovirus vectors and evaluated the proliferation of transfected cells using the Cell Counting Kit-8 (CCK8) assay. Cell apoptosis was detected using annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining and flow cytometry. We then analyzed cell migration by performing wound-scratch and transwell migration assays. Our results show that lnc-ADD3-AS1 significantly promoted LX-2 cell proliferation and attenuated apoptosis. More importantly, lncRNA-ADD3-AS1 significantly accelerated the migration of LX-2 cells. Our data indicated that lncRNA-ADD3-AS1 plays a role in the pathogenesis of liver fibrosis in patients with BA and may serve as a potential diagnostic marker for monitoring liver fibrosis in BA or as a therapeutic target for the disease.

Maternal regulation of biliary disease in neonates via gut microbial metabolites.

Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.

Template-free, controllable and scalable synthesis of poly(5-aminoindole) nanoparticles for printable electrochemical immunosensor with ultra-high sensitivity.

Conductive polymer polyindole derivatives have good conductivities and abundant functional groups, which would offer great potential for versatile applications including biosensors, bioelectronics and energy devices. However, the polyindole derivatives are mainly synthesized by the electropolymerization method on conductive electrode surfaces, which limits large-scale synthesis and practical applications. Herein, we explore a strategy of template-free, controllable and scalable synthesis of poly-5-aminoindole (PIn-5-NH2) nanoparticles (NPs) and demonstrate the application of PIn-5-NH2 NPs in printable multiplexed electrochemical biosensors with ultra-high sensitivity. The synthesis of PIn-5-NH2 NPs is based on a self-templated method since the In-5-NH2 monomer with amphiphilic structures can form micelles by self-assembly in an aqueous solution. The diameter of PIn-5-NH2 NPs could be controlled by adjusting the synthesis conditions, such as monomer concentration, oxidant/monomer ratio and reaction time. The PIn-5-NH2 NPs possess distinct features, including good conductivity, large surface area, and abundant -NH2 functional groups for covalent binding of the antibody, and therefore offer substantial possibilities for developing an all-printable process to fabricate multiplexed electrochemical immunosensors. The printed multiplexed electrochemical immunosensors on the basis of the aqueous suspension of PIn-5-NH2 NPs linked with antibodies can simultaneously detect multiple cancer markers, and exhibit high sensitivity and good selectivity. Our facile and scalable synthesis strategy would offer great opportunities for versatile applications of PIn-5-NH2 NPs.

Highly Conductive PPy-PEDOT:PSS Hybrid Hydrogel with Superior Biocompatibility for Bioelectronics Application.

Conductive polymer hydrogels (CPHs) hold significant promise in broad applications, such as bioelectronics and energy devices. Hitherto, the development of a facile and scalable synthesis method for CPHs with high electrical conductivity and biocompatibility has still been a challenge. Herein, we demonstrate highly conductive PPy-PEDOT:PSS hybrid hydrogels which are prepared by a simple solution-mixing method. This fabrication method involves the mixing of a pyrrole monomer with a PEDOT:PSS dispersion, followed by in situ chemical oxidative polymerization to form polypyrrole (PPy). The electrostatic interaction between negatively charged PSS and positively charged conjugated PPy facilitates the formation of PPy-PEDOT:PSS hybrid hydrogels. The conductivity of the PPy-PEDOT:PSS hybrid hydrogels is 867 S m-1. The PPy-PEDOT:PSS hybrid hydrogels show excellent biocompatibility. Moreover, the PPy-PEDOT:PSS hybrid hydrogels have a hierarchical porous structure which facilitates the 3D cell culture within the hydrogels. The PPy-PEDOT:PSS hybrid hydrogels exhibit excellent in situ biomolecular detection and real-time cell proliferation monitoring performance, indicating their potential as highly sensitive electrochemical biosensors for bioelectronics applications. Our strategy for the fabrication of CPHs with the electrostatic interaction between the negatively charged conductive polymer and positively charged conductive polymer would provide new opportunities for the design of highly conductive conjugated hydrogels for bioelectronics applications and energy devices.

Biliary atresia screening in Shenzhen: implementation and achievements.

OBJECTIVE: To elaborate on the implementation and achievements of a biliary atresia (BA) screening programme in Shenzhen. METHODS: In 2015, we partnered with the government in Shenzhen and attached the stool colour card (SCC) to the health handbook for mothers and children. These handbooks have been distributed through official channels to every pregnant woman in Shenzhen since 1 January 2015. A total of 118 patients diagnosed with BA at Shenzhen Children's Hospital were enrolled and divided into two cohorts based on their date of diagnosis: cohort A before and cohort B after introduction of screening. The cohorts were compared to evaluate differences in age at diagnosis, jaundice-free rate, 2-year native liver survival rate and so on. RESULTS: After the implementation of the screening programme, the age at diagnosis decreased from 81±12 to 56±15 days old (p<0.05), the incidence of postoperative complications decreased from 58.8% to 52.6% (p<0.05), the jaundice-free rate increased from 47.1% to 54.4% (p<0.05), and the 2-year native liver survival rate increased from 44.4% to 52.6% (p<0.05). The percentage of patients who underwent surgery increased from 68.0% to 83.8% (p<0.05). CONCLUSION: In Shenzhen, our screening programme led to earlier diagnoses and better prognoses. The latter resulted in an increased willingness to undergo the Kasai procedure. Through a hospital and government collaboration, this programme exerted a considerable influence, and guardians observed benefits with only a small cost of implementation. Our results may eventually help promote the widespread use of the SCC across the whole country.