Periodontium-Mimicking, Multifunctional Biomass-Based Hydrogel Promotes Full-Course Socket Healing.

Preserving stable tooth-periodontal tissue integration is vital for maintaining alveolar bone stability under physiological conditions. However, tooth extraction compromises this integration and impedes socket healing. Therefore, it becomes crucial to provide early stage coverage of the socket to promote optimal healing. Drawing inspiration from the periodontium, we have developed a quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel, termed the quaternized methacryloyl chitosan/dopamine-grafted oxidized sodium alginate hydrogel (QDL hydrogel). Through blue-light-induced cross-linking, the QDL hydrogel serves as a comprehensive wound dressing for socket healing. The QDL hydrogel exhibits remarkable efficacy in closing irregular tooth extraction wounds. Its favorable mechanical properties, flexible formability, and strong adhesion are achieved through modifications of chitosan and sodium alginate derived from biomass sources. Moreover, the QDL hydrogel demonstrates a superior hemostatic ability, facilitating swift blood clot formation. Additionally, the inherent antibacterial properties of the QDL hydrogel effectively inhibit oral microorganisms. Furthermore, the QDL hydrogel promotes angiogenesis, which facilitates the nutrient supply for subsequent tissue regeneration. Notably, the hydrogel accelerates socket healing by upregulating the expression of genes associated with wound healing. In conclusion, the periodontium-mimicking multifunctional hydrogel exhibits significant potential as a clinical tooth extraction wound dressing.

Simultaneous Rosiglitazone Release and Low-Density Lipoprotein Removal by Chondroitin Sodium Sulfate/Cyclodextrin/Poly(acrylic acid) Composite Adsorbents for Atherosclerosis Therapy.

Atherosclerosis (AS) is characterized by the accumulation of substantial low-density lipoprotein (LDL) and inflammatory response. Hemoperfusion is commonly employed for the selective removal of LDL from the body. However, conventional hemoperfusion merely focuses on LDL removal and does not address the symptom of plaque associated with AS. Based on the LDL binding properties of acrylated chondroitin sodium sulfate (CSA), acrylated beta-cyclodextrin (CD) and acrylic acid (AA), along with the anti-inflammatory property of rosiglitazone (R), the fabricated AA-CSA-CD-R microspheres could simultaneously release R and facilitate LDL removal for hemoperfusion. The AA and CSA offer electrostatic adsorption sites for LDL, while the CD provides hydrophobic adsorption sites for LDL and weak binding sites for R. According to the Sips model, the maximum static LDL adsorption capacity of AA-CSA-CD-R is determined to be 614.73 mg/g. In dynamic simulated perfusion experiments, AA-CSA-CD-R exhibits an initial cycle LDL adsorption capacity of 150.97 mg/g. The study suggests that the weakened inflammatory response favors plaque stabilization. The anti-inflammatory property of the microspheres is verified through an inflammation model, wherein the microsphere extracts are cocultured with mouse macrophages. Both qualitative analysis of iNOS\TNF-α and quantitative analysis of IL-6\TNF-α collectively demonstrate the remarkable anti-inflammatory effect of the microspheres. Therefore, the current study presents a novel blood purification treatment of eliminating pathogenic factors and introducing therapeutic factors to stabilize AS plaque.

Monocytic myeloid-derived suppressor cells as an immune indicator of early diagnosis and prognosis in patients with sepsis.

BACKGROUND: Immunosuppression is a leading cause of septic death. Therefore, it is necessary to search for biomarkers that can evaluate the immune status of patients with sepsis. We assessed the diagnostic and prognostic value of low-density neutrophils (LDNs) and myeloid-derived suppressor cells (MDSCs) subsets in the peripheral blood mononuclear cells (PBMCs) of patients with sepsis. METHODS: LDNs and MDSC subsets were compared among 52 inpatients with sepsis, 33 inpatients with infection, and 32 healthy controls to investigate their potential as immune indicators of sepsis. The percentages of LDNs, monocytic MDSCs (M-MDSCs), and polymorphonuclear MDSCs (PMN-MDSCs) in PBMCs were analyzed. Sequential organ failure assessment (SOFA) scores, C-reactive protein (CRP), and procalcitonin (PCT) levels were measured concurrently. RESULTS: The percentages of LDNs and MDSC subsets were significantly increased in infection and sepsis as compared to control. MDSCs performed similarly to CRP and PCT in diagnosing infection or sepsis. LDNs and MDSC subsets positively correlated with PCT and CRP levels and showed an upward trend with the number of dysfunctional organs and SOFA score. Non-survivors had elevated M-MDSCs compared with that of patients who survived sepsis within 28 days after enrollment. CONCLUSIONS: MDSCs show potential as a diagnostic biomarker comparable to CRP and PCT, in infection and sepsis, even in distinguishing sepsis from infection. M-MDSCs show potential as a prognostic biomarker of sepsis and may be useful to predict 28-day hospital mortality in patients with sepsis.

Targeting circulating high mobility group box-1 and histones by extracorporeal blood purification as an immunomodulation strategy against critical illnesses.

Both high mobility group box-1 (HMGB1) and histones are major damage-associated molecular patterns (DAPMs) that mediate lethal systemic inflammation, activation of the complement and coagulation system, endothelial injury and multiple organ dysfunction syndrome in critical illnesses. Although accumulating evidence collectively shows that targeting HMGB1 or histones by their specific antibodies or inhibitors could significantly mitigate aberrant immune responses in multiple critically ill animal models, routine clinical use of such agents is still not recommended by any guideline. In contrast, extracorporeal blood purification, which has been widely used to replace dysfunctional organs and remove exogenous or endogenous toxins in intensive care units, may also exert an immunomodulatory effect by eliminating inflammatory mediators such as cytokines, endotoxin, HMGB1 and histones in patients with critical illnesses. In this review, we summarize the multiple immunopathological roles of HMGB1 and histones in mediating inflammation, immune thrombosis and organ dysfunction and discuss the rationale for the removal of these DAMPs using various hemofilters. The latest preclinical and clinical evidence for the use of extracorporeal blood purification to improve the clinical outcome of critically ill patients by targeting circulating HMGB1 and histones is also gathered.

Anlotinib Attenuates Liver Fibrosis by Regulating the Transforming Growth Factor ß1/Smad3 Signaling Pathway.

BACKGROUND: Hepatic stellate cell hyperactivation is a central link in liver fibrosis development, transforming growth factor ß1 (TGF-ß1) is a key activator of HSCs. AIMS: This study investigated whether anlotinib attenuates CCl4 induced liver fibrosis in mice and explored its antifibrotic mechanism. METHODS: We used the human hepatic stellate cell line LX-2 for in vitro assays and used TGF-ß1 to induce hepatic fibrosis in LX-2 cells. We analyzed cytotoxicity using a cell-counting kit-8 and transwell chambers to detect the migratory ability of LX-2 cells. Western blotting was used to detect the protein levels of collagen type I, α-smooth muscle actin, and p-Smad3. In addition, mice with CCl4-induced hepatic fibrosis were used as in vivo models. Histopathological examination was performed using H&E staining, Masson's trichrome staining, and immunohistochemistry. RESULTS: Anlotinib significantly reversed TGF-ß1-induced protein levels of Col I, α-SMA and p-Smad3 and inhibits migratory and proliferative abilities in vitro using LX-2 cells. CCl4 cause F4 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 12 to 14 (Ishak), a mean ALT measurement of 130 U/L and a mean measurement AST value of 119 U/L in mice. However, the CCl4-induced changes were markedly attenuated by anlotinib treatment, which returned to F2 grade (Ishak) hepatic fibrosis, liver inflammatory scores ranged from 4 to 6 (Ishak), a mean ALT measurement of 40 U/L and a mean measurement AST value of 56 U/L in mice. CONCLUSIONS: Our results suggest that anlotinib-mediated suppression of liver fibrosis is related to the inhibition of TGF-ß1 signaling pathway. Hepatic stellate cell hyper activation is a central link in liver fibrosis development, transforming growth factor ß1 is a key activator of HSCs. Anlotinib is a multi-targeted tyrosine kinase inhibitor that has similar targets to nintedanib, a clinically used anti-pulmonary fibrosis drug. Our study demonstrates an FDA-approved drug-anlotinib-that could prevent liver fibrosis and inflammation. Experiments in cell cultures and mice show that anlotinib can inhibit the activation of hepatic stellate cells by down-regulating the TGFß1/smad3 pathway, thereby reversing liver fibrosis. In animal experiments, anlotinib showed protective effects on the CCl4-induced liver damage, including ameliorating liver inflammation, reversing liver fibrosis and reducing liver enzymes. This is a very good signal, anlotinib may be useful for halting or reversing the progression of liver fibrosis and could be employed in the development of novel therapeutic drugs for the management of chronic liver diseases.

Prediction of musculoskeletal pain after the first intravenous zoledronic acid injection in patients with primary osteoporosis: development and evaluation of a new nomogram.

OBJECTIVE: To construct a new prediction nomogram to predict the risk of musculoskeletal pain in patients with primary osteoporosis who receive zoledronic acid intravenously for the first time. METHOD: Clinical data of 368 patients with primary osteoporosis who received the first intravenous injection of zoledronic acid in our hospital from December 2019 to December 2022 were studied. Patients were divided into a musculoskeletal pain group (n = 258) and a non-musculoskeletal pain group (n = 110) based on the presence or absence of musculoskeletal pain 3 days after injection. Statistically significant predictors were screened by logistic regression analysis and the minimum absolute contraction and selection operator (LASSO) to construct a nomogram. The nomogram was evaluated by the receiver operating characteristic (ROC) curve, the calibration curve, the C-index, and the decision curve analysis (DCA) and verified in a validation cohort. RESULTS: The independent predictors of the nomogram were age, serum 25-hydroxyvitamin D, NSAIDs, prior Vitamin D intake, and BMI. The area under the ROC curve (AUC) was 0.980 (95% CI, 0.915-0.987), showing excellent predictive performance. The nomogram c index was 0.980, and the nomogram c index for internal verification remained high at 0.979. Moreover, calibration curves show that the nomogram has good consistency. Finally, the DCA showed that the net benefit of the nomogram was 0.20-0.49. CONCLUSION: Musculoskeletal pain is a common symptom of APR in OP patients treated with intravenous zoledronic acid. Risk factors for musculoskeletal pain after zoledronic acid injection in OP patients were: non-use of NSAIDs, youth (<80 years old), serum 25 (OH) D<30ng /mL, no prior intake of vitamin D, BMI<24 kg /m2. A nomogram constructed from the above predictors can be used to predict musculoskeletal pain after the first zoledronic acid injection.

Regional joint PM2.5-O3 control policy benefits further air quality improvement and human health protection in Beijing-Tianjin-Hebei and its surrounding areas.

Beijing-Tianjin-Hebei and its surrounding areas (hereinafter referred to as "2+26" cities) are one of the most severe air pollution areas in China. The fine particulate matter (PM2.5) and surface ozone (O3) pollution have aroused a significant concern on the national scale. In this study, we analyzed the pollution characteristics of PM2.5 and O3 in "2+26" cities, and then estimated the health burden and economic loss before and after the implementation of the joint PM2.5-O3 control policy. During 2017-2019, PM2.5 concentration reduced by 19% while the maximum daily 8 hr average (MDA8) O3 stayed stable in "2+26" cities. Spatially, PM2.5 pollution in the south-central area and O3 pollution in the central region were more severe than anywhere else. With the reduction in PM2.5 concentration, premature deaths from PM2.5 decreased by 18% from 2017 to 2019. In contrast, premature deaths from O3 increased by 5%. Noticeably, the huge potential health benefits can be gained after the implementation of a joint PM2.5-O3 control policy. The premature deaths attributed to PM2.5 and O3 would be reduced by 91.6% and 89.1%, and the avoidable economic loss would be 60.8 billion Chinese Yuan (CNY), and 68.4 billion CNY in 2035 compared with that in 2019, respectively. Therefore, it is of significance to implement the joint PM2.5-O3 control policy for improving public health and economic development.

Long noncoding RNA SNHG9 facilitates growth of glioma stem-like cells via miR-326/SOX9 axis.

BACKGROUND: Glioma stem-like cells (GSCs) are greatly responsible for the progression of glioma. Long noncoding RNAs (lncRNAs) play an important role in glioma tumor progression. This study aims to explore the role and underlying mechanism of lncRNA SNHG9 in regulating GSC cell growth. METHODS: GSCs were obtained from glioma cells (U87 and U251) and referred to as GSC-87 and GSC-251, respectively. The interactions between miR-326 and SNHG9 or SOX9 were analyzed using luciferase reporter assay. Cell growth of GSCs was evaluated by EdU assay and sphere formation assay. RESULTS: SNHG9 expression was significantly higher in GSC-87 and GSC-251 cells than in U87 and U251 cells. SNHG9 overexpression promoted GSC cell growth, whereas SNHG9 knockdown inhibited GSC cell growth. Mechanistically, SNHG9 acted as a competitive endogenous RNA of miR-326 to elevate the expression of SOX9, a direct target of miR-326. Moreover, transfection with miR-326 inhibitor counteracted SNHG9 knockdown-mediated inhibition of GSC cell growth. CONCLUSIONS: SNHG9 facilitates growth of GSCs via the miR-326/SOX9 axis. This study provides a promising therapeutic target for glioma treatment.

Ultraporous Polyquaternium-Carboxylated Chitosan Composite Hydrogel Spheres with Anticoagulant, Antibacterial, and Rapid Endotoxin Removal Profiles for Sepsis Treatment.

Hemoperfusion is an important method to remove endotoxins and save the lives of patients with sepsis. However, the current adsorbents for hemoperfusion have disadvantages of insufficient endotoxin adsorption capacity, poor blood compatibility, and so on. Herein, we proposed a novel emulsion templating (ET) method to prepare ultraporous and double-network carboxylated chitosan (CCS)-poly(diallyl dimethylammonium chloride) (PDDA) hydrogel spheres (ET-CCSPD), bearing both negative and positive charges. CCS was introduced to balance the strong positive charges of PDDA to improve hemocompatibility, and emulsion templates endowed the adsorbent with an ultraporous structure for enhanced adsorption efficacy. The ET-CCSPDs neither damaged blood cells nor activated complement responses. In addition, the activated partial thromboplastin time (APTT) was prolonged to 8.5 times, which was beneficial for reducing the injection of anticoagulant in patients. The ET-CCSPDs had excellent scavenging performance against bacteria and endotoxin, with removal ratios of 96.7% for E. coli and 99.8% for S. aureus, respectively, and the static removal ratio of endotoxin in plasma was as high as 99.1% (C0 = 5.50 EU/mL, critical illness level). An adsorption cartridge filled with the ET-CCSPDs could remove 84.7% of endotoxin within 1 h (C0 = 100 EU/mL in PBS). Interestingly, the ET-CCSPDs had a good inhibitory effect on the cytokines produced by endotoxin-mediated septic blood. By developing the ET method to prepare ultraporous and double-network adsorbents, the problems of low adsorption efficiency and poor blood compatibility of traditional endotoxin adsorbents have been solved, thus opening a new route to fabricate absorbents for blood purification.

Improved Cooling Performance of Hydrogel Wound Dressings via Integrating Thermal Conductivity and Heat Storage Capacity for Burn Therapy.

Burn injury has become a crucial public health issue worldwide. It is necessary to explore new methods to reduce heat damage and improve healing efficiency during burn injury treatment. In this study, a kind of hydrogel combining heat storage capacity and thermal conductivity was fabricated via a one-pot method for burn therapy. The novel hydrogel was easily prepared by in situ cross-linking polymerization, using poly(ethylene glycol) (PEG) derivatives, oligo(ethylene glycol) methacrylate and 2-(2-methoxyethoxy) ethyl methacrylate, as thermally responsive base materials and hydroxylated multiwall carbon nanotubes (CNT-OH) as thermally conductive fillers. By dispersing CNT-OH, a thermally conductive network was formed in the hydrogel, leading to an increase in the thermal conductivity. The cooling performance, thermal conductivity, heat storage property, swelling performance, rheological and mechanical properties, biocompatibility, in vivo cooling effect, and wound healing properties of the prepared hydrogel were systematically investigated. The hydrogel consisted of thermally responsive PEG derivatives, and CNT-OH performed a function of rapid heat absorption, further reduced thermal damage, and promoted wound healing. The improved cooling performance of the hydrogel was ascribed to the improved thermal conductivity, enhanced heat storage capacity, and good adhesive ability. Thus, the hydrogel has great potential to be practically applied in burn therapy, laser treatment, cooling fabrics, heat-protective clothing, and other emergency scenarios.

Synergetic Dielectric and Magnetic Losses of a Core-Shell Co/MnO/C Nanocomplex toward Highly Efficient Microwave Absorption.

High-performance microwave-absorbing materials (MAMs) derived from metal-organic frameworks (MOFs) have attracted considerable attention due to their tunable chemical composition and microstructure. In this contribution, a core-shell-structured Co/MnO/C nanocomplex was prepared using a CoMn-MIL MOF by a facile hydrothermal synthesis and subsequent pyrolysis process. The optimal microwave absorption (MA) property of the as-prepared Co/MnO/C nanocomplex was achieved by the regulation of the Co2+/Mn2+ molar ratio. The minimum reflection loss (RLmin) of the Co/MnO/C-31 nanocomplex was low to -55.0 dB at 16.2 GHz with a thickness of 1.49 mm, and the effective absorption bandwidth (EAB) was high to 5.95 GHz (12.05-18 GHz) at a thickness of 1.8 mm. The mixed-metal nanocomplex with the core-shell structure exhibited outstanding MA performance, corresponding to the synergetic effect of the magnetic and dielectric loss. It provides a high efficiency strategy for rendering low reflection loss and broad EAB to high-performance MAMs.

Optimal encephalitis/meningitis roadmap via precise diagnosis and treatment (IMPROVE): a study protocol for a randomized controlled trial.

BACKGROUND: Encephalitis/meningitis brings a heavy disease burden, and the origin of disease remains unknown in 30-40% of patients. It is greatly significant that combinations of nucleic acid amplification and autoimmune antibody testing improves the diagnosis and treatment of encephalitis/meningitis. Moreover, though several diagnostic methods are in clinical use, a recognized and unified diagnosis and treatment process for encephalitis management remains unclear. METHODS: IMPROVE is a multicenter, open label, randomized controlled clinical trial that aims to evaluate the diagnostic performance, applications, and impact on patient outcomes of a new diagnostic algorithm that combines metagenomic next-generation sequencing (mNGS), multiplex polymerase chain reaction (PCR) and autoimmune antibody testing. The enrolled patients will be grouped into two parallel groups, multiplex PCR test plus autoimmune antibody group (Group I) or the mNGS plus autoimmune antibody group (Group II) with a patient ratio of 1:1. Both groups will be followed up for 12 months. The primary outcomes include the initial time of targeted treatment and the modified Rankin scale score on the 30th day of the trial. The secondary outcomes are the cerebrospinal fluid index remission rate on the 14th day, mortality rate on the 30th day, and an evaluation of diagnostic efficacy. The two groups are predicted to comprise of 484 people in total. DISCUSSION: To optimize the roadmap of encephalitis/meningitis, precise diagnosis, and treatment are of great significance. The effect of rapid diagnosis undoubtedly depends on the progression of new diagnostic tests, such as the new multiplex PCR, mNGS, and examination of broad-spectrum autoimmune encephalitis antibodies. This randomized-controlled study could allow us to obtain an accurate atlas of the precise diagnostic ability of these tests and their effect on the treatment and prognosis of patients. Trial registration ClinicalTrial.gov, NCT04946682. Registered 29 June 2021, 'Retrospectively registered', https://clinicaltrials.gov/ct2/show/NCT04946682?term=NCT04946682&draw=2&rank=1.

A Stepwise Evaluation of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure to Optimize the Indication for Urgent Liver Transplantation.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a dynamic but reversible disease. AIM: We aimed to clarify whether the change in Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) grade in HBV-ACLF patients can be used to predict prognosis, and to explore the appropriate conditions for performing urgent liver transplantation. METHODS: We assessed the COSSH-ACLF grades of HBV-ACLF patients at different time points from June 2013 to May 2019 at Huashan Hospital in Shanghai, China, and analyzed the relationship between the change in grade and patient prognosis. RESULTS: A total of 207 HBV-ACLF patients were enrolled, of which 79 underwent urgent liver transplantation. Their COSSH-ACLF grades were calculated at diagnosis, 3-7 days after diagnosis, and on the final day. Most of the final ACLF grades were consistent with their corresponding grades at days 3-7 after diagnosis (62.5%), while only 44.5% were in accordance with the initial grades at diagnosis. In patients who had a poor prognosis (initial ACLF-3 and ACLF-2 or -3 at days 3-7), the 28-day survival rate was 93.3% in those who underwent transplantation and 6.8% in those who did not (P < 0.0001). However, in patients who had a good prognosis (ACLF-0 or ACLF-1 at days 3-7), the 28-day survival rate was 100% in transplanted patients and 91.5% in non-transplanted patients (P = 0.236). CONCLUSIONS: Reevaluation of the COSSH-ACLF grade 3-7 days after diagnosis could potentially show an indication for urgent liver transplantation.

Fine mapping of the MHC region identifies major independent variants associated with Han Chinese primary biliary cholangitis.

The genetic association of primary biliary cholangitis with major histocompatibility complex (MHC) has been widely confirmed among different ethnicities. To map specific MHC region variants associated with PBC in a Han Chinese cohort, we imputed HLA antigens and amino acids (AA) in 1126 PBC cases and 1770 healthy control subjects using a Han-MHC reference database. We demonstrate that HLA-DRB1 and/or HLA-DQB1 contributed the strongest signals, and that HLA-DPB1 was a separate independent locus. Regression analyses with classical HLA alleles indicate that HLA-DQB1*03:01 or HLA-DQß1-Pro55, HLA-DPB1*17:01 or HLA-DPß1-Asp84 and HLA-DRB1*08:03 could largely explain MHC association with PBC. Forward stepwise regression analyses with HLA amino acid variants localize the major signals to HLA-DRß1-Ala74, HLA-DQß1-Pro55 and HLA-DPß1-Asp84. Electrostatic potential calculations implicated AA variations at HLA-DQß1 position 55 and HLA-DPß1 position 84 as critical to peptide binding properties. Furthermore, although several critical Han Chinese AA variants differed from those shown in European populations, the predicted effects on antigen binding are likely to be very similar or identical and underlie the major component of MHC association with PBC.

Genome-wide Association Studies of Specific Antinuclear Autoantibody Subphenotypes in Primary Biliary Cholangitis.

Anti-nuclear antibodies to speckled 100 kDa (sp100) and glycoprotein 210 (gp210) are specific serologic markers of primary biliary cholangitis (PBC) of uncertain/controversial clinical or prognostic significance. To study the genetic determinants associated with sp100 and gp210 autoantibody subphenotypes, we performed a genome-wide association analysis of 930 PBC cases based on their autoantibody status, followed by a replication study in 1,252 PBC cases. We confirmed single-nucleotide polymorphisms rs492899 (P = 3.27 × 10-22 ; odds ratio [OR], 2.90; 95% confidence interval [CI], 2.34-3.66) and rs1794280 (P = 5.78 × 10-28 ; OR, 3.89; 95% CI, 3.05-4.96) in the human major histocompatibility complex (MHC) region associated with the sp100 autoantibody. However, no genetic variant was identified as being associated with the gp210 autoantibody. To further define specific classical human leukocyte antigen (HLA) alleles or amino acids associated with the sp100 autoantibody, we imputed 922 PBC cases (211 anti-sp100-positive versus 711 negative cases) using a Han Chinese MHC reference database. Conditional analysis identified that HLA-DRß1-Asn77/Arg74, DRß1-Ser37, and DPß1-Lys65 were major determinants for sp100 production. For the classical HLA alleles, the strongest association was with DRB1*03:01 (P = 1.51 × 10-9 ; OR, 2.97; 95% CI, 2.06-4.29). Regression analysis with classical HLA alleles identified DRB1*03:01, DRB1*15:01, DRB1*01, and DPB1*03:01 alleles can explain most of the HLA association with sp100 autoantibody. Conclusion: This study indicated significant genetic predisposition to the sp100 autoantibody, but not the gp210 autoantibody, subphenotype in PBC patients. Additional studies will be necessary to determine if these findings have clinical significance to PBC pathogenesis and/or therapeutics.

Layer-by-Layer Assembly for Surface Tethering of Thin-Hydrogel Films: Design Strategies and Applications.

Manipulation and engineering of the surfaces has a key role in improving the materials properties. Anchoring of thin hydrogels on the materials surface is one of the recently developed methods to achieve surfaces with high potential applications. Layer-by-layer (LBL) has been used widely as a strong strategy for immobilization of thin hydrogel films on the surface of various organic/inorganic substrates. Electrostatic LBL and covalent LBL are two main strategies used in this regard. In electrostatic LBL, negatively and positively hydrophilic polymers are sequentially assembled to create a multilayer hydrogel which subsequent covalent crosslinking of multilayers improved the stability of the inserted layers. On the other hand, covalent LBL requires hydrophilic polymers bearing reactive telechelic groups. These reactive polymers are prepared by various polymerization techniques or by post-functionalization of biopolymers. The principles of hydrogel anchoring have described along with representative examples. Besides, the potential applications of the modified surfaces in specific cases have been addressed and overviewed.

Self-Anticoagulant Nanocomposite Spheres for the Removal of Bilirubin from Whole Blood: A Step toward a Wearable Artificial Liver.

Current therapy for liver failure and concomitant hyperbilirubinemia faces the challenge of poor hemocompatibility and bleeding risks associated with the anticoagulant injection. Herein, heparin-mimetic biomacromolecule (HepMBm) with a similar degree of sulfation and anticoagulant properties to heparin was synthesized by imitating the structure of natural biomacromolecule heparin. Then HepMBm was used to prepare nanocomposite spheres based on reduced graphene oxide (rGO). The formation of a dual-network structure in the spheres endowed the spheres with improved dimensional stability. The proposed spheres exhibited outstanding blood compatibilities and excellent self-anticoagulant properties. The bilirubin adsorption experiments and whole blood bilirubin removal assay indicated that the spheres exhibited high bilirubin removal capability from whole blood (The removal ratio was 99.69%.). The spheres open new routes for a therapeutic strategy without a plasma separation system and heparin pump, which may be a step toward a lightweight wearable artificial liver.

An antiviral drug-resistant mutant of hepatitis B virus with high replication capacity in association with a large in-frame deletion in the preS1 region of viral surface gene.

We amplified a full-length hepatitis B virus (HBV) genome from the serum of a chronic hepatitis B patient who experienced virological breakthrough with high HBV DNA titer following adefovir (ADV) therapy. The PCR product was cloned and sequencing of the six clones revealed an isolate of C2 subgenotype. Mutation(s) in the polymerase gene responsible for ADV resistance included rtA181T (all clones) and rtN236T (four clones). The rtA181T mutation caused the W172* nonsense mutation in the overlapping S gene. In addition, all the clones harbored another nonsense mutation in the S gene (C69*) and a 207nt in-frame deletion in the preS1 region. These clones were converted to a 1.1mer construct for transient transfection of Huh7 cells. All the clones were deficient in hepatitis B surface antigen production. Three clones had similar levels of DNA replication. Comparison with a wild-type clone of the same genotype revealed a higher intracellular level of replicative DNA for clone c4, which was reduced by putting back the deleted 207nt, but not by co-transfection with an expression construct for the three surface proteins to rescue virion production. The HBcAg expression of the c4 and c4+207nt clones was mainly in the nucleus. Co-transfection with the L/M/S proteins expression construct did not alter the distribution of core. Clone c4 showed a significantly decreased susceptibility to ADV, a mild reduction in susceptibility to lamivudine and tenofovir, but remained sensitive to entecavir. In conclusion, this is an unusual ADV-resistant HBV isolate harboring two nonsense mutations in the S gene and a large in-frame deletion in the preS1 region, but still retains a high replication phenotype, which can provide a platform for recombinant vector construction.

Metal-Organic-Framework-Derived 2D Carbon Nanosheets for Localized Multiple Bacterial Eradication and Augmented Anti-infective Therapy.

Recently emerging graphene-based 2D nanoplatforms with multiple therapeutic modalities provide enormous opportunities to combat pathogenic bacterial infections. However, because these materials suffer from complicated synthesis, massive dosage requirements, and abundant nonlocalized heat, much more simplified, tunable, and localized eradication approaches are urgently required. Herein, we report on the fabrication of the metal-organic-framework (MOF)-derived 2D carbon nanosheets (2D-CNs) with phase-to-size transformation and localized bacterial eradication capabilities for augmented anti-infective therapy. The MOF-derived, ZnO-doped carbon on graphene (ZnO@G) is first synthesized and then anchored with phase transformable thermally responsive brushes (TRB) by in situ polymerization to yield the TRB-ZnO@G. The TRB-ZnO@G exhibits flexible 2D nanostructures, high photothermal activities, sustained Zn2+ ions release, and ON-OFF switchable phase-to-size transformation abilities. Notably, the near-infrared-triggered formation of TRB-ZnO@G-bacteria aggregations enables localized massive Zn2+ ions penetration, physical cutting, and hyperthermia killing, which synergistically enhance the disruption of bacterial membranes and intracellular substances. The obtained novel 2D-CNs not only present robust and localized multiple bacterial eradication capabilities with nearly 100% bactericidal efficiency at low concentrations but also possess rapid and safe skin wound disinfection via a short-time photothermal treatment without damaging normal skin tissues or causing accumulative toxicities, thus presenting great potential for broad-spectrum eradication of pathogenic bacteria.

Ionic-Strength Responsive Zwitterionic Copolymer Hydrogels with Tunable Swelling and Adsorption Behaviors.

In this work, we studied the swelling behavior and adsorption behavior of zwitterionic copolymer hydrogels, which were prepared via the free radical copolymerization of sulfobetaine methacrylate (SBMA) and other monomers including sodium p-styrenesulfonate (NaSS), acrylic acid, N-isopropylacrylamide, and 2-(dimethylamino) ethyl methacrylate. The PSBMA hydrogel showed increased swelling ratio with the increase of ionic strength at the same temperature, and the swelling process reflected endothermicity. Interestingly, the PSBMA-NaSS hydrogels collapsed when the ionic strength increased because the ions can weaken the repulsive interaction of the anionic groups of PNaSS. In addition, the PSBMA-NaSS showed high adsorption of methylene blue (760 mg/g). The zwitterionic hydrogels have potential to be used as an adsorbent in the field of wastewater treatment.