Oligomeric proanthocyanidins ameliorates osteoclastogenesis through reducing OPG/RANKL ratio in chicken's embryos.

Skeletal disorders can seriously threaten the health and the performance of poultry, such as tibial dyschondroplasia (TD) and osteoporosis (OP). Oligomeric proanthocyanidins (OPC) are naturally occurring polyphenolic flavonoid compounds that can be used as potential substances to improve the bone health and the growth performance of poultry. Eighty 7-day-old green-eggshell yellow feather layer chickens were randomly divided into 4 groups: basal diet and basal diet supplementation with 25, 50, and 100 mg/kg OPC. The results have indicated that the growth performance and bone parameters of chickens were significantly improved supplementation with OPC in vivo, including the bone volume (BV), the bone mineral density (BMD) and the activities of antioxidative enzymes, but ratio of osteoprotegerin (OPG)/receptor activator of NF-κB (RANK) ligand (RANKL) was decreased. Furthermore, primary bone marrow mesenchymal stem cells (BMSCs) and bone marrow monocytes/macrophages (BMMs) were successfully isolated from femur and tibia of chickens, and co-cultured to differentiate into osteoclasts in vitro. The osteogenic differentiation derived from BMSCs was promoted treatment with high concentrations of OPC (10, 20, and 40 µmol/L) groups in vitro, but emerging the inhibition of osteoclastogenesis by increasing the ratio of OPG/RANKL. In contrary, the osteogenic differentiation was also promoted treatment with low concentrations of OPC (2.5, 5, and 10 µmol/L) groups, but osteoclastogenesis was enhanced by decreasing the ratio of OPG/RANKL in vitro. In addition, OPG inhibits the differentiation and activity of osteoclasts by increasing the autophagy in vitro. Dietary supplementation of OPC can improve the growth performance of bone and alter the balance of osteoblasts and osteoclasts, thereby improving the bone health of chickens.

Case report: A novel splice-site mutation of MTX2 gene caused mandibuloacral dysplasia progeroid syndrome: the first report from China and literature review.

Background: Mandibuloacral dysplasia (MAD) syndrome is a rare genetic disease. Several progeroid syndromes including mandibuloacral dysplasia type A (MADA), mandibuloacral dysplasia type B(MADB), Hutchinson-Gilford progeria (HGPS) and mandibular hypoplasia, deafness, and lipodystrophy syndrome (MDPL) have been reported previously. A novel MAD progeroid syndrome (MADaM) has recently been reported. So far, 7 cases of MADaM diagnosed with molecular diagnostics have been reported in worldwide. In the Chinese population, cases of MAD associated with the MTX2 variant have never been reported. Methods: The clinical symptoms and the genetic analysis were identified and investigated in patients presented with the disease. In addition, we analyzed and compared 7 MADaM cases reported worldwide and summarized the progeroid syndromes reported in the Chinese population to date. Results: The present study reports a case of a novel homozygous mutation c.378 + 1G > A in the MTX2 gene, which has not been previously reported in the literature. Patients present with early onset and severe symptoms and soon after birth are found to have growth retardation. In addition to the progeroid features, skeletal deformities, generalized lipodystrophy reported previously, and other multisystem involvement, e.g. hepatosplenic, renal, and cardiovascular system, this case was also reported to have combined hypogammaglobulinemia. She has since been admitted to the hospital several times for infections. Among 22 previously reported progeroid syndromes, 16/22 were MADA or HGPS caused by LMNA gene mutations, and the homozygous c.1579C > T (p.R527C) mutation may be a hot spot mutation for MAD in the Chinese population. MAD and HGPS mostly present in infancy with skin abnormalities or alopecia, MDPL mostly presents in school age with growth retardation as the first manifestation, and is often combined with an endocrine metabolism disorder after several decades. Conclusion: This is the first case of MAD syndrome caused by mutations in MTX2 gene reported in the Chinese population. MTX2 gene c.378 + 1G > A homozygous mutation has not been previously reported and the report of this patient expands the spectrum of MTX2 mutations. In addition, we summarized the genotypes and clinical characteristics of patients with progeroid syndromes in China.

Polystyrene exacerbates cadmium-induced mitochondrial damage to lung by blocking autophagy in mice.

Cadmium (Cd) is an environmental heavy metal, and its accumulation is harmful to animal and human health. The cytotoxicity of Cd includes oxidative stress, apoptosis, and mitochondrial histopathological changes. Furthermore, polystyrene (PS) is a kind of microplastic piece derived from biotic and abiotic weathering courses, and has toxicity in various aspects. However, the potential mechanism of action of Cd co-treated with PS is still poorly unclear. The objective of this study was to investigate the effects of PS on Cd-induced histopathological injury of mitochondria in the lung of mice. In this study, the results have showed that Cd could induce the activity of oxidative enzymes of the lung cells in mice, increasing the content of partial microelement and the phosphorylation of inflammatory factor NF-κB p65. Cd further destroys the integrity of mitochondria by increasing the expression of apoptotic protein and blocking the autophagy. In addition, PS solely group aggravated the lung damage in mice, especially mitochondrial toxicity, and played a synergistic effect with Cd in lung injury. However, how PS can augment mitochondrial damage and synergism with Cd in lung of mice requiring further exploration. Therefore, PS was able to exacerbate Cd-induced mitochondrial damage to the lung in mice by blocking autophagy, and was associated with the apoptosis.

Solid-gas carbonate formation during dust events on Mars.

Electrostatic discharge experiments under simulated martian atmospheric conditions indicate that atmospheric CO2 has been sequestered into carbonate by the Mars dust activities during the Amazonia era.

Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

Characterization of cancer-related fibroblasts (CAF) in hepatocellular carcinoma and construction of CAF-based risk signature based on single-cell RNA-seq and bulk RNA-seq data.

Background: Cancer-associated fibroblasts (CAFs) are involved in tumor growth, angiogenesis, metastasis, and resistance to therapy. We sought to explore the CAFs characteristics in hepatocellular carcinoma (HCC) and establish a CAF-based risk signature for predicting the prognosis of HCC patients. Methods: The signal-cell RNA sequencing (scRNA-seq) data was obtained from the GEO database. Bulk RNA-seq data and microarray data of HCC were obtained from the TCGA and GEO databases respectively. Seurat R package was applied to process scRNA-seq data and identify CAF clusters according to the CAF markers. Differential expression analysis was performed to screen differentially expressed genes (DEGs) between normal and tumor samples in TCGA dataset. Then Pearson correlation analysis was used to determine the DEGs associated with CAF clusters, followed by the univariate Cox regression analysis to identify CAF-related prognostic genes. Lasso regression was implemented to construct a risk signature based on CAF-related prognostic genes. Finally, a nomogram model based on the risk signature and clinicopathological characteristics was developed. Results: Based on scRNA-seq data, we identified 4 CAF clusters in HCC, 3 of which were associated with prognosis in HCC. A total of 423 genes were identified from 2811 DEGs to be significantly correlated with CAF clusters, and were narrowed down to generate a risk signature with 6 genes. These six genes were primarily connected with 39 pathways, such as angiogenesis, apoptosis, and hypoxia. Meanwhile, the risk signature was significantly associated with stromal and immune scores, as well as some immune cells. Multivariate analysis revealed that risk signature was an independent prognostic factor for HCC, and its value in predicting immunotherapeutic outcomes was confirmed. A novel nomogram integrating the stage and CAF-based risk signature was constructed, which exhibited favorable predictability and reliability in the prognosis prediction of HCC. Conclusion: CAF-based risk signatures can effectively predict the prognosis of HCC, and comprehensive characterization of the CAF signature of HCC may help to interpret the response of HCC to immunotherapy and provide new strategies for cancer treatment.

Single-cell dissection of remodeled inflammatory ecosystem in primary and metastatic gallbladder carcinoma.

Gallbladder carcinoma (GBC) is the most common biliary tract malignancy with the lowest survival rate, primarily arising from chronic inflammation. To better characterize the progression from inflammation to cancer to metastasis, we performed single-cell RNA sequencing across samples of 6 chronic cholecystitis, 12 treatment-naive GBCs, and 6 matched metastases. Benign epithelial cells from inflamed gallbladders displayed resting, immune-regulating, and gastrointestinal metaplastic phenotypes. A small amount of PLA2G2A+ epithelial cells with copy number variation were identified from a histologically benign sample. We validated significant overexpression of PLA2G2A across in situ GBCs, together with increased proliferation and cancer stemness in PLA2G2A-overexpressing GBC cells, indicating an important role for PLA2G2A during early carcinogenesis. Malignant epithelial cells displayed pervasive cancer hallmarks and cellular plasticity, differentiating into metaplastic, inflammatory, and mesenchymal subtypes with distinct transcriptomic, genomic, and prognostic patterns. Chronic cholecystitis led to an adapted microenvironment characterized by MDSC-like macrophages, CD8+ TRM cells, and CCL2+ immunity-regulating fibroblasts. By contrast, GBC instigated an aggressive and immunosuppressive microenvironment, featured by tumor-associated macrophages, Treg cells, CD8+ TEX cells, and STMN1+ tumor-promoting fibroblasts. Single-cell and bulk RNA-seq profiles consistently showed a more suppressive immune milieu for GBCs with inflammatory epithelial signatures, coupled with strengthened epithelial-immune crosstalk. We further pinpointed a subset of senescence-like fibroblasts (FN1+TGM2+) preferentially enriched in metastatic lesions, which promoted GBC migration and invasion via their secretory phenotype. Collectively, this study provides comprehensive insights into epithelial and microenvironmental reprogramming throughout cholecystitis-propelled carcinogenesis and metastasis, laying a new foundation for the precision therapy of GBC.

A Review of Signaling Transduction Mechanisms in Osteoclastogenesis Regulation by Autophagy, Inflammation, and Immunity.

Osteoclastogenesis is an ongoing rigorous course that includes osteoclast precursors fusion and bone resorption executed by degradative enzymes. Osteoclastogenesis is controlled by endogenous signaling and/or regulators or affected by exogenous conditions and can also be controlled both internally and externally. More evidence indicates that autophagy, inflammation, and immunity are closely related to osteoclastogenesis and involve multiple intracellular organelles (e.g., lysosomes and autophagosomes) and certain inflammatory or immunological factors. Based on the literature on osteoclastogenesis induced by different regulatory aspects, emerging basic cross-studies have reported the emerging disquisitive orientation for osteoclast differentiation and function. In this review, we summarize the partial potential therapeutic targets for osteoclast differentiation and function, including the signaling pathways and various cellular processes.

Hybrid Hydrogels from Nongelling Polymers Using a Fibrous Peptide Hydrogelator at Low Concentrations.

Nature-made hydrogels typically combine a wide range of multiscale fibers into biological composite networks, which offer an adaptive property. Inspired by nature, we report a facile approach to construct hybrid hydrogels from a range of natural or commercially available synthetic nongelling polymers (e.g., poly(ethylene glycol), poly(acrylic acid), carboxylated cellulose nanocrystal, and sodium alginate) at a concentration as low as 0.53 wt % using a nonionic fibrous peptide hydrogelator. Through simply mixing the peptide hydrogelator with a polymer aqueous solution, stable hybrid hydrogels can be formed with the concentration of hydrogelator at ∼0.05 wt %. The gel strength of the resulting hydrogels can be effectively modulated by the concentration, molecular weight, and terminal group of the polymer. We further demonstrate that the molecular interactions between the peptide hydrogelator and the polymer are very crucial for the formation of hybrid hydrogel, which synergically induce the gelation at considerably low concentrations. A peptide hydrogelator can be easily obtained by aminolysis of alkyl-oilgo(γ-benzyl-l-glutamate) samples. Live/Dead assays indicate low cytotoxicity of the hybrid hydrogel toward HeLa cells. Combining the low-cost, scalable synthesis, and biocompatibility, the prepared peptide hydrogelator presents a potential candidate to expand the scope of polymer hydrogels for biomedical applications and also shows considerable commercial significance.

Chimeric transcripts observed in non-canonical FGFR2 fusions with partner genes' breakpoint located in intergenic region in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is a fatal bile duct cancer with dismal prognosis and limited therapeutic options. FGFR family fusion have been identified in many diseases, and FGFR2 fusion is a validated oncogenic driver in ICC. At present, a variety of fusion forms have been reported, including gene-gene, gene-intergenic, and intergenic-intergenic fusion. Here, by performing RNA- and DNA-sequencing analysis, FGFR2 fusions were found in 10.1% of ICC, including 4 gene-intergenic fusions. We confirmed that the non-canonical rearrangements can generate chimeric transcripts, and used conventional splicing mechanism to explain the event. Our study provides possible target therapy for these 4 patients and possibility analysis scheme for similar situation.

Preparation of a Novel Type of Zwitterionic Polymer and the Antifouling PDMS Coating.

As awareness of environmental protection increases, environmentally friendly coatings have been receiving great interest. Zwitterionic polymers are considered promising candidates due to their biocompatibility and excellent antifouling properties. In this paper, a type of polypeptoid containing zwitterions on the side chain was synthesized via ring-opening polymerization (ROP) and post-modification. This obtained polypeptoid was subsequently grafted onto the surface of polydimethylsiloxane (PDMS) via plasma and UV-induced surface polymerization. Surface morphology and protein adsorption tests of the resulting coating were systematically carried out. The results show that the modified coating has excellent antifouling properties and thus has great potential for environmentally friendly coating applications.

Comprehensive Evaluation and Application of a Novel Method to Isolate Cell-Free DNA Derived From Bile of Biliary Tract Cancer Patients.

Cell-free DNA (cfDNA) exists in various types of bodily fluids, including plasma, urine, bile, and others. Bile cfDNA could serve as a promising liquid biopsy for biliary tract cancer (BTC) patients, as bile directly contacts tumors in the biliary tract system. However, there is no commercial kit or widely acknowledged method for bile cfDNA extraction. In this study, we established a silica-membrane-based method, namely 3D-BCF, for bile cfDNA isolation, exhibiting effective recovery of DNA fragments in the spike-in assay. We then compared the 3D-BCF method with four other commercial kits: the BIOG cfDNA Easy Kit (BIOG), QIAamp DNA Mini Kit (Qiagen), MagMAXTM Cell-Free DNA Isolation Kit (Thermo Fisher), and NORGEN Urine Cell-Free Circulating DNA Purification Mini Kit (Norgen Biotek). The proposed 3D-BCF method exhibited the highest cfDNA isolation efficiency (p < 0.0001) from patient bile samples, and bile cfDNA of short, medium or long fragments could all be extracted effectively. To test whether the extracted bile cfDNA from patients carries tumor-related genomic information, we performed next-generation sequencing on the cfDNA and verified the gene-mutation results by polymerase chain reaction (PCR)-Sanger chromatograms and copy-number-variation (CNV) detection by fluorescence in situ hybridization (FISH) of tumor tissues. The 3D-BCF method could efficiently extract cfDNA from bile samples, providing technical support for bile cfDNA as a promising liquid biopsy for BTC patient diagnosis and prognosis.

Tunable Aggregation-Induced Emission Fluorophore with the Assistance of the Self-Assembly of Block Copolymers by Controlling the Morphology and Secondary Conformation for Bioimaging.

Aggregation-induced emission (AIE) luminogens with highly tunable properties show great potential for many applications. In this study, we synthesized a new family of AIE-type poly(ethylene glycol)-block-poly(9-anthrylmethyl lysine) (PEG-b-PLys-An) diblock copolymers by taking advantage of amphiphilic self-assembly and rigid helical backbones. These copolymers can self-assemble into various assemblies through nanoprecipitation methods. The micelles using N,N-dimethylformamide (DMF) as a cosolvent present brighter fluorescence than the vesicles prepared from tetrahydrofuran (THF). We demonstrate that the decreased solubility of copolymers in DMF results in the formation of more compact micelles with more excimer formation during the self-assembly process, while better solvent THF favors the formation of vesicles with stretched core chains. In addition, the secondary conformation of the polypeptide block shows pronounced effects on the fluorescence property. We further show the internalization of the assemblies using two types of cells by cellular uptake experiments. By the delicate design of the block copolymer, we successfully prepare the morphology- and conformation-dependent AIE materials for potential biomedical applications.

Urgent Endoscopy Improves Hemostasis in Patients With Upper Gastrointestinal Bleeding Following Biliary-pancreatic Surgery: A Retrospective Analysis.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a lethal complication of biliary-pancreatic surgery (BPS). The role of endoscopic intervention has not been fully defined in such a critical condition. The aim of this study was to assess the efficacy and safety of endoscopic hemostasis in a retrospective cohort. MATERIALS AND METHODS: Consecutive patients with acute UGIB after BPS who received interventional endoscopy between January 2007 and August 2020 were included in this study. The clinical characteristics were collected and analyzed to screen for predictive factors significantly associated with successful hemostasis. RESULTS: Among 37,772 patients who underwent BPS, 26 patients (0.069%) developed acute UGIB. The sites and causes of hemorrhage were as follows: gastroenteric anastomoe (n=17), gastric stump (n=2), jejunal anastomose (n=1), duodenal bulb ulcer (n=2), pancreatojejunal anastomosis hemorrhage (n=1), cholangiojejunal anastomose (n=1), gastroenteric anastomose and gastric stump hemorrhage (n=1), and Dieulafoy lesion (n=1). Successful endoscopic hemostasis was achieved in 19 (73.1%) of the 26 UGIB patients. In the 7 patients who failed endotherapy, 1 patient received a successful radiologic intervention, 6 patients underwent reoperation and achieved hemostasis in 4, and the other 2 patients died after reoperation. Logistic regression analysis showed that presentation-to-endoscopy time (≤12 h) was the only independent predictive factor associated with successful endoscopic hemostasis. CONCLUSIONS: Endoscopic hemostasis is relatively safe and effective in controlling UIGB after BPS. Prompt intervention (≤12 h) could improve the success rate of endoscopic hemostasis.

Taxifolin Protects Dental Pulp Stem Cells under Hypoxia and Inflammation Conditions.

BACKGROUND: Dental pulp stem cells (DPSCs) are a unique source for future clinical application in dentistry such as periodontology or endodontics. However, DPSCs are prone to apoptosis under abnormal conditions. Taxifolin is a natural flavonoid and possesses many pharmacological activities including anti-hypoxic and anti-inflammatory. We aimed to elucidate the mechanisms of taxifolin protects DPSC under hypoxia and inflammatory conditions. METHODS: DPSCs from human dental pulp tissue was purchased from Lonza (cat. no. PT-5025. Basel, Switzerland)) and identified by DPSC's biomarkers. DPSC differentiation in vitro following the manufacturers' instructions. ARS staining and Oil red staining verify the efficiency of differentiation in vitro after 2 weeks. The changes of various genes and proteins were identified by Q-PCR and western-blot, respectively. Cell viability was determined by the CCK-8 method, while apoptosis was determined by Annexin V/PI staining. RESULTS: DPSC differentiation in vitro shows that hypoxia and TNF-α synergistically inhibit the survival and osteogenesis of DPSCs. A final concentration of 10 µM Taxifolin can significantly reduce the apoptosis of DPSCs under inflammation and hypoxia conditions. Taxifolin substantially increases carbonic anhydrase IX (CA9) expression but not HIF1a, and inhibitions of CA9 expression nullify the protective role of taxifolin under hypoxia and inflammatory condition. CONCLUSION: Taxifolin significantly increased the expression of CA9 when it inhibits DPSC apoptosis and taxifolin synergistically to protect DPSCs against apoptosis with CA9 under hypoxia and inflammatory conditions. Taxifolin can be used as a potential drug for clinical treatment of DPSC-related diseases.

TMEM106C contributes to the malignant characteristics and poor prognosis of hepatocellular carcinoma.

Transmembrane protein (TMEM) is a kind of integral membrane protein that spans biological membranes. The functions of most members of the TMEM family are unknown. Here, we conducted bioinformatic analysis and biological validation to investigate the role of TMEM106C in HCC. First, GEPIA and OncomineTM were used to analyze TMEM106C expression, which was verified by real-time PCR and western blot analyses. Then, the biological functions of TMEM106C were explored by CCK8 and transwell assays. The prognostic value of TMEM106C was analyzed by UALCAN. LinkedOmics was used to analyze TMEM106C pathways generated by Gene Ontology. A protein-protein interaction network (PPI) was constructed by GeneMANIA. We demonstrated that TMEM106C was overexpressed in HCC and that inhibition of TMEM106C significantly suppressed the proliferation and metastasis of HCC through targeting CENPM and DLC-1. Upregulation of TMEM106C was closely correlated with sex, tumor stage, tumor grade and prognosis. Overexpression of TMEM106C was linked to functional networks involving organelle fission and cell cycle signaling pathways through the regulation of CDK kinases, E2F1 transcription factors and miRNAs. Our data demonstrated that TMEM106C contributes to malignant characteristics and poor prognosis in HCC, which may serve as a prognostic biomarker and potential therapeutic target.

Non-invasive detection of biliary tract cancer by low-coverage whole genome sequencing from plasma cell-free DNA: A prospective cohort study.

BACKGROUND: The diagnosis of biliary tract cancer (BTC) is challenging in clinical practice. We performed a prospective study to evaluate the value of plasma copy number variation (CNV) assays in diagnosing BTC. METHODS: 47 treatment-naïve patients with suspicious biliary lesions were recruited. Plasma samples were collected at admission. Cell-free DNA was analyzed by low coverage whole genome sequencing, followed by CNV analyses via a customized bioinformatics workflow, namely the ultrasensitive chromosomal aneuploidy detector. RESULTS: 29 patients were pathologically diagnosed as BTC, including 8 gallbladder cancers (GBCs) and 21 cholangiocarcinomas (CCs). Cancer patients had more CNV signals as compared with benign patients (26/29 vs. 2/18, P < 0.001). The most frequent copy number gains were chr3q (7/29) and chr8q (6/29). The most frequent copy number losses were chr7p (6/29), chr17p (6/29), and chr19p (6/29). The sensitivity and specificity of plasma CNV assays in diagnosing BTC were 89.7% and 88.9%, respectively. For CA 19-9 (cutoff: 37 U/ml), the sensitivity was 58.6% and the specificity was 72.2%. The diagnostic accuracy of CNV assays significantly outperformed CA 19-9 (AUC 0.91 vs. 0.62, P = 0.004). Compared with CA 19-9 alone, the adding of CNV profiles to CA 19-9 increased the sensitivity in diagnosing GBC (75.0% vs. 25.0%) and CC (100% vs. 52.4%). Higher CNV burden was also associated with decreased overall survival (Hazard ratio = 4.32, 95% CI 2.06-9.08, P = 0.033). DISCUSSION: Our results suggest that BTC harbors rich plasma CNV signals, and their assays might be useful for diagnosing BTC.

Hierarchical supramolecular assembly of a single peptoid polymer into a planar nanobrush with two distinct molecular packing motifs.

Hierarchical nanomaterials have received increasing interest for many applications. Here, we report a facile programmable strategy based on an embedded segmental crystallinity design to prepare unprecedented supramolecular planar nanobrush-like structures composed of two distinct molecular packing motifs, by the self-assembly of one particular diblock copolymer poly(ethylene glycol)-block-poly(N-octylglycine) in a one-pot preparation. We demonstrate that the superstructures result from the temperature-controlled hierarchical self-assembly of preformed spherical micelles by optimizing the crystallization-solvophobicity balance. Particularly remarkable is that these micelles first assemble into linear arrays at elevated temperatures, which, upon cooling, subsequently template further lateral, crystallization-driven assembly in a living manner. Addition of the diblock copolymer chains to the growing nanostructure occurs via a loosely organized micellar intermediate state, which undergoes an unfolding transition to the final crystalline state in the nanobrush. This assembly mechanism is distinct from previous crystallization-driven approaches which occur via unimer addition, and is more akin to protein crystallization. Interestingly, nanobrush formation is conserved over a variety of preparation pathways. The precise control ability over the superstructure, combined with the excellent biocompatibility of polypeptoids, offers great potential for nanomaterials inaccessible previously for a broad range of advanced applications.

Tunable LCST/UCST-Type Polypeptoids and Their Structure-Property Relationship.

Bioinspired thermoresponsive polymeric materials with tunable phase-transition behaviors are highly desirable for biomedical applications. Here, we reported a facile approach for the synthesis of both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) types of thermoresponsive polypeptoids with tunable phase-transition temperature in the range of 29--55 °C. The introduction of alkyl groups and ethylene glycol (EG) units results in a controlled phase-transition behavior under fairly mild conditions. A very sharp transition (ΔT ≤ 1.5 °C) is observed by simply adjusting pH and the alkyl chain length. In particular, the carboxyl-containing polypeptoids display designable UCST behavior, which can be finely tuned in both water and methanol. All these features make the obtained polymers beneficial for practical applications. More interestingly, we demonstrate that the hydrophilic EG group behaves as an excellent regulator to tune the UCST behavior, while the hydrophobic alkyl residues show remarkable capability to regulate the LCST behavior of the system. We hope that such systematic structure-property studies will enable the design of smart polymer materials to meet the specific needs of future applications.

Early Versus Delayed Surgical Repair and Referral for Patients With Bile Duct Injury: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study was to systematically review and meta-analyze the available evidence regarding the association between timing of repair or referral and clinical outcomes in bile duct injury (BDI). BACKGROUND: Surgical repair is recommended for patients with complex BDI following laparoscopic cholecystectomy. However, consensus on the timing of surgery or referral to a specialist is lacking. METHODS: We searched PubMed, Embase, Cochrane Library, and Scopus for eligible studies. The coprimary outcomes were repair failure in follow-up and postoperative complications. We pooled odds ratios (ORs) using random-effects models. RESULTS: We included 32 studies. The rate of repair failure was significantly higher for early versus delayed repair [OR 1.65, 95% confidence interval (CI) 1.14-2.37, P= 0.007], lower for early versus delayed referral (OR 0.28, 95% CI 0.17-0.45, P < 0.001), but did not differ substantially for on-table versus postcholecystectomy repair (OR 2.06, 95% CI 0.89-4.73, P = 0.09). Regarding postoperative complications, early referral outperformed delayed referral (OR 0.24, 95% CI 0.09-0.68, P= 0.007); however, we found no significant differences between early and delayed repair (OR 1.34, 95% CI 0.96-1.87, P= 0.08), or between on-table and postcholecystectomy repair (OR 1.13, 95% CI 0.42-3.07, P= 0.81). At the cutoff time point of 6 weeks, early repair was associated with increased rates of repair failure (OR 4.03; P < 0.001), postoperative complications (OR 2.18; P < 0.001), and biliary stricture (OR 6.23; P < 0.001). CONCLUSIONS: Among patients with BDI, early referral and delayed repair appear to confer favorable outcomes.