Synergistic effect of two bacterial strains promoting anaerobic digestion of rice straw to produce methane.

A large amount of agricultural waste causes global environmental pollution. Biogas production by microbial pretreatment is an important way to utilize agricultural waste resources. In this study, Sporocytophaga CG-1 (A, cellulolytic strain) was co-cultured with Bacillus clausii HP-1 (B, non-cellulolytic strain) to analyze the effect of pretreatment of rice straw on methanogenic capacity of anaerobic digestion (AD). The results showed that weight loss rate of filter paper of co-culture combination is 53.38%, which is 29.37% higher than that of A. The synergistic effect of B on A can promote its degradation of cellulose. The cumulative methane production rate of the co-culture combination was the highest (93.04 mL/g VS substrate), which was significantly higher than that of A, B and the control group (82.38, 67.28 and 67.70 mL/g VS substrate). Auxiliary bacteria can improve cellulose degradation rate by promoting secondary product metabolism. These results provide data support for the application of co-culture strategies in the field of anaerobic digestion practices.

Preparation of open tubular capillary column covalently coated with polystyrene sulfonate with 4,4'-Azobis(4-cyanopentanoyl chloride) as polymerization initiator for electrochromatographic separation of alkaloids, sulfonamides, and peptides.

An open tubular capillary electrochromatography column covalently bonded with polystyrene sulfonate was prepared via in situ polymerization using functionalized Azo-initiator 4,4'-Azobis(4-cyanopentanoyl chloride). Scanning electron, fluorescence, and atomic force microscopy techniques showed the formation of a relatively rough layer of polymer. In addition, -CN and C = O stretching vibrations from infrared spectroscopy proved the successful immobilization of the azo-initiator through covalent bonding and X-ray photoelectron spectroscopy confirmed the elemental composition of the formed polymer layer. The prepared column was found to be appropriate for small and medium-sized molecules separation. Compared to bare fused silica capillary column higher selectivity and resolution were obtained for the separation of alkaloids, sulfonamides, and peptides as a result of the electrostatic and pi-pi stacking interactions between the small organic molecules and the coated column without compromising the electroosmotic flow mobility. Separation efficiency was also increased compared to the bare capillary for the separation of alkaloids (about 1.5 times). Moreover, intraday, inter-day, intra-batch, and inter-batch relative standard deviation values of retention time and peak area of peptides were within 2% and 10%, respectively, indicating good repeatability of the column preparation procedure. The developed method for the covalent bonding of polymers through a functionalized azo-initiator could represent a promising stable method for the preparation of an open tubular column.

Polymeric sheet actuators with programmable bioinstructivity.

Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSCs). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSCs are interconnected via intracellular Ca2+ Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.

Long-circulating doxorubicin and Schizandrin A liposome with drug-resistant liver cancer activity: in vitro and in vivo evaluation.

Co-loading doxorubicin (DOX) and Schizandrin A (SchA) long-circulating liposome (SchA-DOX-Lip) have been confirmed to have good antitumor activity in vitro. However, in vivo pharmacodynamics, targeting, safety, and mechanism of action of SchA-DOX-Lip still need to be further verified. We investigated the tumor inhibition effect, targeting, safety evaluation, and regulation of tumor apoptosis-related proteins of the SchA-DOX-Lip. MTT assay was used to investigate the inhibitory effect of SchA-DOX-Lip on CBRH7919 cells. The drug uptake of CBRH7919 cells was observed by inverted fluorescence microscope. The tumor-bearing nude mice models of CBRH7919 were established, and the anti-tumor effect of SchA-DOX-Lip in vivo was evaluated by tumor biological observation, H&E staining, and TUNEL staining. The distribution and targeting of SchA-DOX-Lip in nude mice models were investigated by small animal imaging and tissue distribution experiment of CBRH7919. The biosafety of SchA-DOX-Lip was evaluated by blood routine parameters, biochemical indexes, and H&E staining. The expression of tumor-associated apoptotic proteins (Bcl-2, Bax, and Caspase-3) was detected by immunohistochemistry anvd western blotting. The results showed that SchA-DOX-Lip had cytotoxicity to CBRH7919 cells which effectively inhibited the proliferation of CBRH7919 cells, improved the uptake of drugs by CBRH7919 cells and the targeting effect of drugs on tumor site. H&E staining and biochemical detection results showed that SchA-DOX-Lip had high biosafety and did not cause serious damage to normal tissues. Western-blotting and TUNEL staining results showed that SchA-DOX-Lip could improve the regulatory effect of drugs on tumor apoptosis proteins. It was demonstrated that SchA-DOX-Lip had high safety and strong tumor inhibition effects, providing a new method for the clinical treatment of hepatocellular carcinoma (HCC).

Sugarcane-Seed-Cutting System Based on Machine Vision in Pre-Seed Mode.

China is the world's third-largest producer of sugarcane, slightly behind Brazil and India. As an important cash crop in China, sugarcane has always been the main source of sugar, the basic strategic material. The planting method of sugarcane used in China is mainly the pre-cutting planting mode. However, there are many problems with this technology, which has a great impact on the planting quality of sugarcane. Aiming at a series of problems, such as low cutting efficiency and poor quality in the pre-cutting planting mode of sugarcane, a sugarcane-seed-cutting device was proposed, and a sugarcane-seed-cutting system based on automatic identification technology was designed. The system consists of a sugarcane-cutting platform, a seed-cutting device, a visual inspection system, and a control system. Among them, the visual inspection system adopts the YOLO V5 network model to identify and detect the eustipes of sugarcane, and the seed-cutting device is composed of a self-tensioning conveying mechanism, a reciprocating crank slider transmission mechanism, and a high-speed rotary cutting mechanism so that the cutting device can complete the cutting of sugarcane seeds of different diameters. The test shows that the recognition rate of sugarcane seed cutting is no less than 94.3%, the accuracy rate is between 94.3% and 100%, and the average accuracy is 98.2%. The bud injury rate is no higher than 3.8%, while the average cutting time of a single seed is about 0.7 s, which proves that the cutting system has a high cutting rate, recognition rate, and low injury rate. The findings of this paper have important application values for promoting the development of sugarcane pre-cutting planting mode and sugarcane planting technology.

Isolation and Characterization of a Novel Laccase for Lignin Degradation, LacZ1.

Lignin is a complex natural organic polymer and is one of the primary components of lignocellulose. The efficient utilization of lignocellulose is limited because it is difficult to degrade lignin. In this study, we screened a lacz1 gene fragment encoding laccase from the macrotranscriptome data of a microbial consortium WSC-6, which can efficiently degrade lignocellulose. The reverse transcription-quantitative PCR (RT-qPCR) results demonstrated that the expression level of the lacz1 gene during the peak period of lignocellulose degradation by WSC-6 increased by 30.63 times compared to the initial degradation period. Phylogenetic tree analysis demonstrated that the complete lacz1 gene is derived from a Bacillus sp. and encoded laccase. The corresponding protein, LacZ1, was expressed and purified by Ni-chelating affinity chromatography. The optimum temperature was 75°C, the optimum pH was 4.5, and the highest enzyme activity reached 16.39 U/mg. We found that Cu2+ was an important cofactor needed for LacZ1 to have enzyme activity. The molecular weight distribution of lignin was determined by gel permeation chromatography (GPC), and changes in the lignin structure were determined by 1H nuclear magnetic resonance (1H NMR) spectra. The degradation products of lignin by LacZ1 were determined by gas chromatography and mass spectrometry (GC-MS), and three lignin degradation pathways (the gentian acid pathway, benzoic acid pathway, and protocatechuic acid pathway) were proposed. This study provides insight into the degradation of lignin and new insights into high-temperature bacterial laccase. IMPORTANCE Lignin is a natural aromatic polymer that is not easily degraded, hindering the efficient use of lignocellulose-rich biomass resources, such as straw. Biodegradation is a method of decomposing lignin that has recently received increasing attention. In this study, we screened a gene encoding laccase from the lignocellulose-degrading microbial consortium WSC-6, purified the corresponding protein LacZ1, characterized the enzymatic properties of laccase LacZ1, and speculated that the degradation pathway of LacZ1 degrades lignin. This study identified a new, high-temperature bacterial laccase that can degrade lignin, providing insight into lignin degradation by this laccase.

ICG/l-Arginine Encapsulated PLGA Nanoparticle-Thermosensitive Hydrogel Hybrid Delivery System for Cascade Cancer Photodynamic-NO Therapy with Promoted Collagen Depletion in Tumor Tissues.

Photodynamic therapy (PDT) is promising for clinical cancer therapy; however, the efficacy was limited as an individual treatment regimen. Here, an approach synergistically combining PDT and nitric oxide (NO) gas therapy along with destruction of the tumor extracellular matrix (ECM) was presented to eliminate cancer. Specifically, the NO donor l-arginine (l-Arg) and the photosensitizer indocyanine green (ICG) were co-encapsulated in poly(lactic-glycolic acid) (PLGA) nanoparticles and then loaded into the poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) hydrogel to develop an injectable, thermosensitive dual drug delivery system (PLGA@ICG@l-Arg/Gel). Significantly, reactive oxygen species (ROS) produced by PLGA@ICG@l-Arg/Gel under near-infrared (NIR) light irradiation could not only result in the apoptosis of cancer cells but also oxidize l-Arg to generate NO, which could suppress the proliferation of cancer cells. Moreover, ROS could further oxidize NO to generate peroxynitrite anions (ONOO-). ONOO- could activate matrix metalloproteinases (MMPs), which notably degraded collagen in ECM so as to damage the tumor microenvironment. PLGA@ICG@l-Arg/Gel significantly increased the antitumor efficacy against highly malignant 4T1 tumors in mice. Taken together, PLGA@ICG@l-Arg/Gel is a multifunctional platform that provides a novel strategy for cancer treatment with cascade amplification of the ROS oxidation effect, which holds great potential in clinical translation.

An injectable thermosensitive hydrogel self-supported by nanoparticles of PEGylated amino-modified PCL for enhanced local tumor chemotherapy.

We synthesized amino-modified poly(ε-caprolactone) PCN-b-PEG-b-PCN (PECN) triblock copolymers and studied the contribution of the introduced amino groups to the drug delivery efficiency of PECN nanoparticles (NPs) and their injectable thermosensitive hydrogels. PECN15 with an optimal amino group content was obtained. Firstly, the hydrophobic drug paclitaxel (PTX) was loaded into PECN15 up to 5.91% and formed PTX/PECN NPs 90 nm in size and with a slightly positive charge (7.3 mV). Furthermore, the injectable PTX/PECN NPs aqueous solution (25 wt%) at ambient temperature could undergo fast gelation at 37 °C and sustainedly release PTX/PECN NPs in 10 days. More importantly, compared with our previously reported PECT NPs, the PECN NPs without an increase in toxicity could improve the cell uptake and enhance intracellular drug release by responding to the acidic environment of the endosome. Thus, the PTX/PECN NPs presented a lower IC50 of 3.14 µg mL-1 than that of the PTX/PECT NPs (7.67 µg mL-1) and free PTX (4.65 µg mL-1). Moreover, through peritumoral injection, the PTX/PECNGel showed 94.27% inhibition rate of tumor growth on day 19, higher than PTX/PECTGel (72.28%) and Taxol® (47.03%). Therefore, the PECN NPs hydrogel provided a more effective injectable platform to enhance local cancer chemotherapy, and also provided the possibility of further functionalization by the reactive amino groups.

3D printing of implantable elastic PLCL copolymer scaffolds.

Poly(l-lactic acid) (PLLA) scaffolds have been used in regenerative medicine, however, they commonly suffer from low flexibility, restricting their application in the repair and reconstruction of soft tissues. In this study, poly(l-lactide-co-ε-caprolactone) (PLCL) copolymers were examined to modulate the elasticity of PLLA with the random presence of CL units in PLLA. Thermodynamic analysis revealed that the introduction of PCL could significantly decrease the melting point and glass transition temperature of PLLA, benefiting the extrusion and printing of PLCL. Diverse scaffolds with designed architectures including porous cubes with or without large holes, cambered plates with holes and round tubes could be easily constructed by 3D printing. In the process of elastic deformation, the maximum elastic stress of the copolymer scaffold was obviously increased from 19.6 to 31.5 MPa when the relative content of PCL was increased to 70%, while the elongation at break was evidently increased from 388% to about 1974%. The Young's modulus of PLCL was also significantly decreased (P < 0.05) in comparison with that of PLLA. PLCL scaffolds have good platelet and endotheliocyte adhesion ability and no obvious hemolysis was observed. In vivo subcutaneous implantation of PLCL scaffolds demonstrated superior biocompatibility. Collectively, this work highlights that copolymerization of PCL segments into PLLA is an effective approach to tune the 3D printability and the stiffness and elasticity of PLLA scaffolds. PLCL scaffolds hold great promise for the regeneration of soft tissues including but not limited to cartilage, myocardium, muscle, tendon and nervous tissues.

Engineering Dendritic-Cell-Based Vaccines and PD-1 Blockade in Self-Assembled Peptide Nanofibrous Hydrogel to Amplify Antitumor T-Cell Immunity.

Dendritic cells (DCs) are increasingly used in cancer vaccines due to their ability to regulate T-cell immunity. Major limitations associated with the present DC adoptive transfer immunotherapy are low cell viability and transient duration of transplanted DCs at the vaccination site and the lack of recruitment of host DCs, leading to unsatisfactory T-cell immune response. Here, we developed a novel vaccine nodule comprising a simple physical mixture of the peptide nanofibrous hydrogel, anti-PD-1 antibodies, DCs, and tumor antigens. Upon subcutaneous injection, the vaccine nodule maintained the viability and biological function including the antigen uptake and maturation of encapsulated DCs and simultaneously recruited a number of host DCs and promoted the drainage of activated DCs to lymph nodes, resulting in enhanced proliferation of antigen-specific splenocytes and provoking potent cellular immune responses. Compared with adoptive transfer of DCs and subcutaneous administration of antigen vaccine, such a vaccine nodule shows superior antitumor immunotherapy efficiency in both prophylactic and therapeutic tumor models including delayed tumor growth and prolonged mice survival due to effective stimulation of antitumor T-cell immunity and increased infiltration of activated CD8+ effector T-cells in the tumor. Our findings provide a simple and robust vaccination strategy for DC-based vaccines and also a unique vaccine product for stimulating and enhancing T-cell immunity, holding great promise for immunotherapy against cancer and infectious diseases.

Cooperation of Escherichia coli Hfq hexamers in DsrA binding.

Hfq is a bacterial post-transcriptional regulator. It facilitates base-pairing between sRNA and target mRNA. Hfq mediates DsrA-dependent translational activation of rpoS mRNA at low temperatures. rpoS encodes the stationary-phase σ factor σ(S), which is the central regulator in general stress response. However, structural information on Hfq-DsrA interaction is not yet available. Although Hfq is reported to hydrolyze ATP, the ATP-binding site is still unknown. Here, we report a ternary crystal complex structure of Escherichia coli Hfq bound to a major Hfq recognition region on DsrA (AU(6)A) together with ADP, and a crystal complex structure of Hfq bound to ADP. AU(6)A binds to the proximal and distal sides of two Hfq hexamers. ADP binds to a purine-selective site on the distal side and contacts conserved arginine or glutamine residues on the proximal side of another hexamer. This binding mode is different from previously postulated. The cooperation of two different Hfq hexamers upon nucleic acid binding in solution is verified by fluorescence polarization and solution nuclear magnetic resonance (NMR) experiments using fragments of Hfq and DsrA. Fluorescence resonance energy transfer conducted with full-length Hfq and DsrA also supports cooperation of Hfq hexamers upon DsrA binding. The implications of Hfq hexamer cooperation have been discussed.

A novel totally biodegradable device for effective atrial septal defect closure: A 2-year study in sheep.

OBJECTIVE: To evaluate the feasibility, efficacy, and safety of a fully biodegradable poly lactic acid (PLA)-based occluder for atrial septal defect (ASD) closure in an animal model. METHODS: ASDs, approximately 12-mm in diameter, were generated in sheep (n = 18) by needle puncture and balloon dilatation. For ASD closure, occluders were implanted by percutaneous transcatheter approach under echocardiographic guidance. Outcomes were evaluated by transthoracic echocardiography, electrocardiography, blood testing, and histology within the follow-up period ranging from 1 month to 2 years. RESULTS: All occluders were successfully implanted. During follow-up, no animal died; rectal temperatures, blood test results, and electrocardiograms were within normal ranges; and transthoracic echocardiograms, macroscopic studies, and histopathological and electron microscopic examination demonstrated that the occluders were well positioned, with no shifting, residual shunts, severe inflammation, thrombus formation, atrioventricular valve insufficiency, cardiac erosion or arrhythmias. The occluders gradually embedded into the endocardial tissue of the hosts with complete endothelialization and disk absorption at 12 months, and a distinct molecular weight decrease of the framework (to 9% of initial) at 24 months after implantation. CONCLUSIONS: In a sheep model, the use of totally biodegradable occluders appears feasible, efficacious and safe for ASD closure. Studies in humans are ongoing.

Effect of forest thinning and wood quality on the short-term wood decomposition rate in a Pinus tabuliformis plantation.

The effects of forest thinning and wood quality on wood decomposition in the mineral soil were investigated in a Chinese pine (Pinus tabuliformis Carriére) plantation in northern China by measuring mass loss and changes in wood properties (carbohydrates, lignin and nitrogen (N) concentrations) in wood stakes of two tree species-loblolly pine (Pinus taeda L.) and trembling aspen (Populus tremuloides Michx.). Stakes were inserted to a 20 cm soil depth in stands with three thinning levels (low, moderate, and heavy) and an unharvested control and removed after 1 year. There were significant differences in stake mass loss among the treatments. The species effect on the stake mass loss was marginally significant. Wood N content of both species increased during decomposition in all thinning treatments, and was only correlated with aspen mass loss. Wood properties of stakes placed in each stand before insertion (t = 0) were similar, except for pine lignin concentration and aspen lignin: N ratio, but neither had any effect on thinning treatment results. Lignin concentration increased and carbohydrate concentration decreased in both aspen and pine wood stakes during decomposition across all thinning treatments, which suggests that brown-rot fungi are dominant wood-decomposers on our study site. We conclude that thinning has a significant influence on the wood decomposition in the mineral soil of this Chinese pine plantation.

A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy.

In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3+CD8+T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8+ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.

Polydepsipeptide Block-Stabilized Polyplexes for Efficient Transfection of Primary Human Cells.

The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an Mn ∼ 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60-150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells.

Novel application method of talcum powder to prevent sticking tendency and modify release of esomeprazole magnesium enteric-coated pellets.

Actually, reflecting drug release from polymer-coated pellets remains a challenge. In this study, sticking of pellets caused by Eudragit®L30D-55 was observed during the release process, leading to change in drug release. Talcum powder (talc) was used in esomeprazole magnesium pellets to prevent sticking and modify release of pellets. Three methods including talc incorporated in enteric layer, physically mixed and coating resulted pellets were employed to prevent the sticking. The release of pellets was modified by addition talc into subcoat. The dispersion coefficient (Fd) and release profiles were determined in phosphate buffer solution (pH 6.8 and 6.0) and distilled water. It was found that the first manner made Fd increase to about 0.75, but the latter two methods could completely prevent sticking. Also, the second manner was more simple and readily scaled up. In addition, talc in subcoat significantly slowed the drug release in water, but the slowing release effect is less pronounced at pH 6.0 and 6.8. These different effects of talc were attributed to a different release mechanism in three media. The release profiles in water were fitted to Nuttanan model, and the K designated as "diffusive resistance constant" was linearly increased with talc levels in subcoat (R(2)=0.9874).

[Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients].

OBJECTIVE: To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy. METHODS: Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers (PCR-SSP). The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared. RESULTS: Different treatment responses of Peg-IFNalpha were observed in CHB patients of two different CM constitutions. The ratio of CR + PR was 61.0% (36/59) in YDS group, obviously lower than that in NYDS group [78.7% (48/61), P < 0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1 * 0501 than those with no-response [14.8% (8/54) vs. 30.6% (22/72)] with statistical difference (P < 0.05). Patients with CR had a higher allele frequency of HLA-DQA1 * 0601 than those with no-response [18.5% (10/54) vs. 5.6% (4/72)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0301 was lower in YDS group than in non-YDS group [2. 5% (3/118) vs. 9.8% (12/122)] with statistical difference (P < 0.05). The allele frequency of HLA-DQA1 * 0501 was higher in YDS group than in non-YDS group [33.9% (40/118) vs. 18.9% (23/122)] with statistical difference (P < 0.05). Yet statistical significance was lost after adjustment (Pc > 0.05 for both). CONCLUSIONS: Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.

Integrin-targeted zwitterionic polymeric nanoparticles with acid-induced disassembly property for enhanced drug accumulation and release in tumor.

Reasonably structural design of nanoparticles (NPs) to combine functions of prolonged systemic circulation, enhanced tumor targeting and specific intracellular drug release is crucial for antitumor drug delivery. Combining advantages of Arg-Gly-Asp (RGD) for active tumor targeting, zwitterionic polycarboxybetaine methacrylate (PCB) for prolonged systemic circulation, poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) for acid-triggered intracellular release, novel RGD-PCB-b-PDPA (RGD-PCD) block copolymers were prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization and followed by functionalization with RGD. Doxorubicine (DOX) was encapsulated within the RGD-PCD NPs as model medicine (RGD-PCD/DOX NPs). With ultra pH-sensitivity of PDPA, the drug release was restrained at pH 7.4 for only 24% within 36 h, which was increased to 60% at pH 6.0 within 24 h, and released more rapidly at pH 5.0 for 100% within 5 h, indicating that the RGD-PCD/DOX NPs were able to turn drug release "off" at neutral pH (e.g., systemic circulation) whereas "on" under acidic conditions (e.g., inside endo/lysosomes). Furthermore, the results of fluorescence microscopy and flow cytometry analysis demonstrated improved internalization of RGD-PCD/DOX NPs in HepG2 cells via integrin-mediated endocytosis with rapid DOX release intracellularly. Consequently, the RGD-PCD/DOX NPs showed considerable cytotoxicity against HepG2 and HeLa cells in comparison with free DOX. Importantly, the RGD-PCD/DOX NPs exhibited little protein adsorption property with excellent serum stability, which led to prolonged systemic circulation and enhanced tumor accumulation in tumor-bearing nude mice. Therefore, this multifunctional RGD-PCD NPs, which represented the flexible design approach, showed great potential for the development of novel nanocarriers in tumor-targeted drug delivery.

Bioactive microgel-coated electrospun membrane with cell-instructive interfaces and topology for abdominal wall defect repair.

Current mesh materials used for the clinical treatment of abdominal defects struggle to balance mechanical properties and bioactivity to support tissue remodeling. Therefore, a bioactive microgel-coated electrospinning membrane was designed with the superiority of cell-instructive topology in guiding cell behavior and function for abdominal wall defect reconstruction. The electrostatic spinning technique was employed to prepare a bioabsorbable PLCL fiber membrane with an effective mechanical support. Additionally, decellularized matrix (dECM)-derived bioactive microgels were further coated on the fiber membrane through co-precipitation with dopamine, which was expected to endow cell-instructive hydrophilic interfaces and topological morphologies for cell adhesion. Moreover, the introduction of the dECM into the microgel promoted the myogenic proliferation and differentiation of C2C12 cells. Subsequently, in vivo experiments using a rat abdominal wall defect model demonstrated that the bioactive microgel coating significantly contributed to the reconstruction of intact abdominal wall structures, highlighting its potential for clinical application in promoting the repair of soft tissue defects associated with abdominal wall damage. This study presented an effective mesh material for facilitating the reconstruction of abdominal wall defects and contributed novel design concepts for the surface modification of scaffolds with cell-instructive interfaces and topology.

Synergistic analysis of lignin degrading bacterial consortium and its application in rice straw fiber film.

Fiber film have received widespread attention due to its green friendliness. We can use microorganisms to degrade lignin in straw to obtain cellulose and make fiber films. Herein, a group of high-temperature (50 °C) lignin degrading bacterial consortium (LDH) was enriched and culture conditions for lignin degradation were optimized. Combined with high-throughput sequencing technology, the synergistic effect of LDH-composited bacteria was analyzed. Then LDH was used to treat rice straw for the bio-pulping experiment. The results showed that the lignin of rice straw was degraded 32.4 % by LDH at 50 °C for 10 d, and after the optimization of culture conditions, lignin degradation rate increased by 9.05 % (P < 0.001). The bacteria that compose in LDH can synergistically degrade lignin. Paenibacillus can encode all lignin-degrading enzymes present in the LDH. Preliminary tests of LDH in the pulping industry have been completed. This study is the first to use high temperature lignin degrading bacteria to fabricate fiber film.