Selective lignin arylation for biomass fractionation and benign bisphenols.

Lignocellulose is mainly composed of hydrophobic lignin and hydrophilic polysaccharide polymers, contributing to an indispensable carbon resource for green biorefineries1,2. When chemically treated, lignin is compromised owing to detrimental intra- and intermolecular crosslinking that hampers downstream process3,4. The current valorization paradigms aim to avoid the formation of new C-C bonds, referred to as condensation, by blocking or stabilizing the vulnerable moieties of lignin5-7. Although there have been efforts to enhance biomass utilization through the incorporation of phenolic additives8,9, exploiting lignin's proclivity towards condensation remains unproven for valorizing both lignin and carbohydrates to high-value products. Here we leverage the proclivity by directing the C-C bond formation in a catalytic arylation pathway using lignin-derived phenols with high nucleophilicity. The selectively condensed lignin, isolated in near-quantitative yields while preserving its prominent cleavable ß-ether units, can be unlocked in a tandem catalytic process involving aryl migration and transfer hydrogenation. Lignin in wood is thereby converted to benign bisphenols (34-48 wt%) that represent performance-advantaged replacements for their fossil-based counterparts. Delignified pulp from cellulose and xylose from xylan are co-produced for textile fibres and renewable chemicals. This condensation-driven strategy represents a key advancement complementary to other promising monophenol-oriented approaches targeting valuable platform chemicals and materials, thereby contributing to holistic biomass valorization.

CCR2 is a potential therapeutic target in peri-implantitis.

AIM: CCR2 (C-C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri-implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri-implantitis and the treatment effects of cenicriviroc (CVC) on peri-implant inflammation and bone resorption. MATERIALS AND METHODS: The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri-implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri-implantitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC on peri-implantitis was evaluated using systemic and local dosage forms. RESULTS: Human peri-implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri-implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro-inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri-implantitis. CONCLUSIONS: CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.

Long-term follow-up after the treatment of impacted canines in the maxilla causing severe root resorption of the lateral incisors: two case reports.

BACKGROUND: Root resorption of adjacent teeth due to impacted canines is common, and orthodontic treatment often leads to secondary resorption or even loss of adjacent roots. Clinical reports of long-term stability after treatment are rare. CASE PRESENTATION: This study reports two cases of maxillary impacted canines resulting in severe root resorption of the adjacent lateral incisors. Surgical exposure, orthodontic retraction, and alignment of the impacted canines were successful in both cases, and the resorbed lateral incisors were stable with no significant loosening and normal pulp vitality after treatment and at the 5- and 10-year follow-up appointments. CONCLUSIONS: Light orthodontic force may be used to move adjacent teeth with root resorption due to tooth obstruction. The path and direction in which the teeth are moved must be specifically designed so that the adjacent roots are not resorbed and so long-term stability can be achieved.

CCL2 is a key regulator and therapeutic target for periodontitis.

AIM: Our previous study revealed that the C-C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C-C motif chemokine ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. MATERIALS AND METHODS: The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, bead-based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. RESULTS: Among different ligands of CCR2, only CCL2 was significantly up-regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild-type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno-associated virus-2 vectors overexpressing CCL2 in Ccl2-/- mice gingiva reversed the attenuation of periodontitis in a CCR2-dependent manner. In ligation-induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß. CONCLUSIONS: CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.

Ultrathin Supratrochlear Artery Cutaneous Branch Flaps for Large Defects Around Eyebrows.

BACKGROUND: The key point of repairing large defects around eyebrows is to keep the eyebrow undistorted. The limited skin elevates the application difficulty of conventional methods such as direct suture or local flap. Forehead pedicle flaps do well in tension control. However, most of them are too thick for defects because the frontalis muscle must be included. Recently, 1 stable supratrochlear artery cutaneous branch was found, which provides an opportunity to make an ultrathin forehead flap with a good blood supply. This study aims to investigate whether the supratrochlear artery cutaneous branch flap could perform good esthetic reconstruction for defects around the eyebrow. METHODS: The authors retrospectively included 15 patients whose defect around the eyebrows was repaired by the supratrochlear artery cutaneous branch flap from June 2017 to June 2020. The authors followed up about their flap color and texture, scar, abnormal sensation, any complication, recurrence, and patient satisfaction for at least 6 months online or face-to-face. RESULTS: All of the flaps survived, without distortion of the eyebrows or inner canthi. Similar flap color, texture, and thickness with the nearby skin were obtained, except 2 patients reported pigmentation. Donor and receptor scars were acceptable. There was no recurrence or other complications. All of the patients were satisfied with the surgery effect. CONCLUSIONS: The supratrochlear artery cutaneous branch flap is a valuable alternative method to repair large defects around the eyebrows. It can avoid facial distortion and achieve good esthetic outcomes in single-stage surgery.

Effects of post-treatment on metal-ceramic bond properties of selective laser melted Co-Cr dental alloy. Part 1: Annealing temperature.

STATEMENT OF PROBLEM: Dental cobalt-chromium (Co-Cr) alloy manufactured by selective laser melting (SLM) is not recommended for clinical applications before annealing because of excessive residual stress. However, limited information is available regarding the relationship between annealing temperature and the metal-ceramic bond properties of SLM Co-Cr alloys. PURPOSE: The purpose of this in vitro study was to investigate the effects of annealing temperature on the metal-ceramic bond properties of SLM Co-Cr alloys. MATERIAL AND METHODS: Four groups with different annealing temperatures (850 °C; 950 °C; 1050 °C; 1150 °C) were prepared by using SLM techniques. Bond strengths were measured by using a 3-point bend test; subsequently, debonded surface morphologies and elements were assessed by using a scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy (EDS). The area fraction of adherence porcelain (AFAP) value was introduced to analyze fracture characteristics. Microstructural and interfacial characteristics were characterized by SEM/EDS and X-ray diffraction analysis. The coefficient of thermal expansion (CTE) test was used to analyze thermal matching. A 1-way ANOVA and the Tukey honestly significant difference tests were used to analyze bond strengths and AFAP values statistically (α=.05). RESULTS: The mean ±standard deviation values of the metal-ceramic bond strengths were 40.68 ±4.34 MPa for the 850 °C group, 37.54 ±5.34 MPa for the 950 °C group, 45.97 ±2.18 MPa for the 1050 °C group, and 50.79 ±1.79 MPa for the 1150 °C group. Significant differences (P<.05) were observed among all groups. Debonded surfaces and AFAP analysis displayed a mixed fracture mode of adhesive and cohesive fracture, and 1150 °C-annealing specimens exhibited better fracture characteristics close to cohesive fractures. As the temperature increased, native oxide film thicknesses remained unchanged; the 850 °C group had the thinnest diffusion layer, while the other 3 groups had similar thicknesses. Although the 1050 °C and 1150 °C groups displayed higher CTE values, their microstructures were more conducive to atomic diffusion and improved chemical bonding. Microstructure analysis found that ε phase and second-phase precipitates jointly affected metal-ceramic bond strength. CONCLUSIONS: Annealing temperatures affected the metal-ceramic bond strengths of SLM Co-Cr porcelain specimens. 1150 °C annealing SLM Co-Cr specimens displayed higher bond strengths and improved fracture and interface characteristics among the 4 groups.

Effects of posttreatment on the metal-ceramic bond properties of selective-laser-melted Co-Cr dental alloy-Part 2: Heat treatment after porcelain firing.

STATEMENT OF PROBLEM: The selective laser melting (SLM) technique has been a promising method of fabricating Co-Cr metal-ceramic restorations; however, the lower metal-ceramic bond properties of SLM Co-Cr restorations have become a major issue in clinical use. PURPOSE: The purpose of this in vitro study was to propose and verify a method of improving the metal-ceramic bond properties of SLM Co-Cr alloy with heat treatment after porcelain firing (PH). MATERIAL AND METHODS: Forty-eight (25×3×0.5 mm) Co-Cr specimens, divided into 6 groups (Control group [CG]; 550 °C; 650 °C; 750 °C; 850 °C; 950 °C) according to PH temperatures, were prepared by using SLM techniques. The 3-point bend tests were performed to evaluate the metal-ceramic bond strengths; subsequently, the fracture feature was assessed by using a digital camera and scanning electron microscope (SEM) coupled with an energy-dispersive X-ray spectroscopy (EDS) detector, to determine the area fraction of adherence porcelain (AFAP). The interface morphologies and element distribution were determined with SEM/EDS detectors. Phase identification and quantification were examined with an X-ray diffractometer (XRD). A 1-way ANOVA and the Tukey honestly significant difference tests were used to analyze bond strengths and AFAP values (α=.05). RESULTS: The bond strengths were 35.33 ±1.25 MPa for the CG group, 34.53 ±3.20 MPa for the 550 °C group, 38.20 ±2.60 MPa for the 650 °C group, 42.85 ±2.31 MPa for the 750 °C group, 33.28 ±3.85 MPa for the 850 °C group, and 29.09 ±2.86 MPa for the 950 °C group. Significant differences were not observed among the CG, 550 °C, and 850 °C groups (P>.05) but were found among the other groups (P<.05). Fracture and AFAP results displayed a mixed fracture mode of adhesive and cohesive fracture. The thicknesses of native oxide films across the 6 groups were relatively close as the temperature increased, but the thickness of the diffusion layer increased as well. Excessive oxidation and massive phase transformation caused holes and microcracks to appear in the 850 °C and 950 °C groups, reducing bond strengths. XRD analysis evidenced that the phase transformation of γ→ε occurred at the interface during PH treating. CONCLUSIONS: PH treatment significantly affected the metal-ceramic bond properties of SLM Co-Cr porcelain specimens. The 750 °C-PH-treated specimens displayed higher mean bond strengths and improved fracture characteristics among the 6 groups.

Three dimensional evaluation of the skeletal and temporomandibular joint changes following stabilization splint therapy in patients with temporomandibular joint disorders and mandibular deviation: a retrospective study.

BACKGROUND: Three-dimensional (3D) detailed evaluations of the mandibular mediolateral position, mandibular condylar position, and temporomandibular joint (TMJ) spaces following stabilization splints (SS) therapy in patients with temporomandibular joint disorders (TMD) and mandibular deviation (MD) have not been reported in the available literature. Accordingly, this study aimed to three-dimensionally analyze the skeletal and bony temporomandibular joint changes following stabilization splint therapy in adult patients with temporomandibular joint disorders and mandibular deviation. METHODS: This study is a retrospective clinical study that enrolled 26 adult patients with TMD and MD with a mean age of 24.86 years. The Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) was used to diagnose TMD. SS was adjusted weekly until occlusal contact stabilization occurred, and then adjusted monthly, patients were instructed to wear it at night for at least 10 h. The SS was removed after the elimination of TMD symptoms (TMJ/muscle pain on palpation, muscle spasm, and clicking) and having both condyles completely seated in a musculoskeletally stable position. Pre- and post-therapeutic Cone Beam Computed Tomography (CBCT) was analyzed. Mandibular mediolateral position, TMJ spaces, and mandibular condyle position were analyzed three-dimensionally using Mimics 21.0 software. Paired t-test or Wilcoxon rank-sum test was performed, and the significance level was considered at P < 0.05. RESULTS: The treatment period with SS therapy was 10.07 ± 3.1 months. The deviated chin was improved in 69.23% of the sample; the range of improvement was > 0 mm ≤ 3.9 mm. The mandibular rotation was significantly decreased from 3.58 ± 2.02° to 3.17 ± 1.60. The deviated side's superior and posterior joint TMJ spaces were significantly increased from 2.49 ± 0.88 mm and 1.25 ± 0.79 mm to 2.98 ± 1.02 mm and 1.86 ± 0.72 mm, respectively. The value of the difference from the bilateral condyle head position to the X and Z axes significantly decreased from 2.50 ± 1.56 mm and 2.30 ± 1.57 mm to 1.64 ± 1.58 mm and 1.82 ± 1.11 mm, respectively. CONCLUSION: The main positional effect of the stabilization splint treatment in TMD patients with MD includes considerable correction of mandibular deviation, improving facial asymmetry, and moving the condyle into a stable condylar position; these were done by promoting the mandible to rotate around the Z (roll) and Y (yaw) axes and by forward, downward, and outward condylar movement on the deviated side, respectively.

Activity-Based Protein Profiling Probe for the Detection of Enzymes Catalyzing Polysorbate Degradation.

Polysorbates are nonionic surfactants that have been widely used in biotherapeutic formulations to prevent protein aggregation and denaturation. However, polysorbates are subject to degradation after prolonged storage if certain lipases are present in the biotherapeutic product. Because the degradation of polysorbates compromises the shelf life of biotherapeutics and leads to the formation of undesirable products such as protein aggregates and subvisible particles, it is important to identify the active enzymes that catalyze polysorbate hydrolysis. In this study, we developed a novel fluorophosphonate activity-based protein profiling (ABPP) probe (termed the REGN probe), which mimics the structure of polysorbate and targets lipases catalyzing polysorbate degradation. We demonstrated that the REGN probe could enrich certain lipases from Chinese hamster ovary (CHO) cell lysate by more than 100-fold compared with direct tryptic digestion. Furthermore, we found that the REGN probe had higher lipase enrichment efficiency than commercially available ABPP probes including fluorophosphonate-biotin (FP-biotin) and FP-desthiobiotin. Remarkably, the REGN probe can enrich several lipases that cannot be labeled by commercial probes, such as lysosomal acid lipase and cytosolic phospholipase A2. Additionally, we showed that lipases with abundances as low as 0.08 ppm in drug substances were detected by the REGN probe enrichment and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Collectively, we have developed a novel ABPP probe with higher enrichment efficiency and broader coverage for lipases compared with commercial probes, and this probe can be used to detect the trace level of lipases in biotherapeutic products and to facilitate their development and manufacturing.

Monitoring polysorbate hydrolysis in therapeutic proteins using an ultrasensitive extraction-free fatty acid quantitation method.

Polysorbates (PSs) are surfactants commonly added to therapeutic protein drug product formulations to protect proteins from denaturation and aggregation during storage, transportation, and delivery. However, enzymatic hydrolysis of PSs has been recognized as the primary route of PS degradation in monoclonal antibody formulations, resulting in the release of free fatty acids that drive undesired particulate formation. Here, we present a rapid lipase activity assay with optimized incubation conditions for accurate quantitation of free fatty acids without a fatty acid extraction step. This assay can detect low levels of PS degradation (0.000024% PS20 degradation) within 1 day with minimal sample preparation. The levels of released free fatty acids were found to strongly correlate with the degree of PS20 degradation. The case study described herein suggests that this approach can detect low levels of PS20 degradation caused by sub-ppm lipase levels within 1 day, compared with the duration of 14 days needed for PS degradation assays based on two-dimensional liquid chromatography-charge aerosol detection.

Identification of the specific causes of polysorbate 20 degradation in monoclonal antibody formulations containing multiple lipases.

PURPOSE: Polysorbates (PS) are excipients used in the biotech industry to stabilize monoclonal antibody (mAb) protein products. However, PS in drug product formulations can be degraded during storage and lead to particle formation because of the limited solubility of the free fatty acids released through the enzymatic hydrolysis of PS-a process driven by residual host cell proteins, especially lipases, that are co-purified with the drugs. When multiple lipases are present, it is very difficult to know the cause for PS degradation. In this study, we aim to determine the cause of PS degradation from two lipases, lysosomal acid lipase (LAL) and lipoprotein lipase (LPL). METHODS: PS degradation pattern of the drug product was compared with those induced by recombinant lipases. Correlations between the concentration of LPL or LAL and PS20 loss were compared. Specific inhibitors, LAL inhibitor lalistat2 and LPL inhibitor GSK264220A, were used to differentiate their degradation of PS in the drug products. RESULTS: The complete inhibition of PS20 degradation by lalistat2 suggested that LAL, rather than LPL, was responsible for the PS20 degradation. In addition, LAL was more strongly correlated than LPL with the percentage of PS20 degradation. No PS20 degradation was observed for several mAbs containing similar levels of LPL (0.5-1.5 ppm) in the absence of LAL, suggesting that LPL concentrations below 1.5 ppm does not degrade PS20 in drug products. CONCLUSIONS: LAL was determined to be the cause of the PS20 degradation. This study provides a practical strategy to determine the root cause of PS degradation.

Synergistic Effect of Co-Delivering Ciprofloxacin and Tetracycline Hydrochloride for Promoted Wound Healing by Utilizing Coaxial PCL/Gelatin Nanofiber Membrane.

Combining multiple drugs or biologically active substances for wound healing could not only resist the formation of multidrug resistant pathogens, but also achieve better therapeutic effects. Herein, the hydrophobic fluoroquinolone antibiotic ciprofloxacin (CIP) and the hydrophilic broad-spectrum antibiotic tetracycline hydrochloride (TH) were introduced into the coaxial polycaprolactone/gelatin (PCL/GEL) nanofiber mat with CIP loaded into the PCL (core layer) and TH loaded into the GEL (shell layer), developing antibacterial wound dressing with the co-delivering of the two antibiotics (PCL-CIP/GEL-TH). The nanostructure, physical properties, drug release, antibacterial property, and in vitro cytotoxicity were investigated accordingly. The results revealed that the CIP shows a long-lasting release of five days, reaching the releasing rate of 80.71%, while the cumulative drug release of TH reached 83.51% with a rapid release behavior of 12 h. The in vitro antibacterial activity demonstrated that the coaxial nanofiber mesh possesses strong antibacterial activity against E. coli and S. aureus. In addition, the coaxial mats showed superior biocompatibility toward human skin fibroblast cells (hSFCs). This study indicates that the developed PCL-CIP/GEL-TH nanofiber membranes hold enormous potential as wound dressing materials.

Dual-Functional Nanofibrous Patches for Accelerating Wound Healing.

Bacterial infections and inflammation are two main factors for delayed wound healing. Coaxial electrospinning nanofibrous patches, by co-loading and sequential co-delivering of anti-bacterial and anti-inflammation agents, are promising wound dressing for accelerating wound healing. Herein, curcumin (Cur) was loaded into the polycaprolactone (PCL) core, and broad-spectrum antibacterial tetracycline hydrochloride (TH) was loaded into gelatin (GEL) shell to prepare PCL-Cur/GEL-TH core-shell nanofiber membranes. The fibers showed a clear co-axial structure and good water absorption capacity, hydrophilicity and mechanical properties. In vitro drug release results showed sequential release of Cur and TH, in which the coaxial mat showed good antioxidant activity by DPPH test and excellent antibacterial activity was demonstrated by a disk diffusion method. The coaxial mats showed superior biocompatibility toward human immortalized keratinocytes. This study indicates a coaxial nanofiber membrane combining anti-bacterial and anti-inflammation agents has great potential as a wound dressing for promoting wound repair.

Analysis of microstructure and fatigue of cast versus selective laser-melted dental Co-Cr alloy.

STATEMENT OF PROBLEM: The forces exerted on teeth and prostheses during mastication are repeated and dynamic, resulting in fatigue damage to dental prostheses. Most fractures of dental restorations are fatigue failure. The 4-point bend fatigue behavior of Co-Cr-Mo-W alloys manufactured by investment casting (CAST) and selective laser melting (SLM) has received little attention. PURPOSE: The purpose of this in vitro study was to evaluate the 4-point bend fatigue property of dental Co-Cr alloys and determine the relationship between microstructure and the 4-point bend fatigue property of Co-Cr alloys created by traditional casting and SLM. These can guide the use of Co-Cr alloy in dentistry. MATERIAL AND METHODS: Co-Cr-Mo-W alloys were fabricated with a dimension of 45×2×2 mm by investment casting and SLM. The 3-point bend test measured the ultimate bend strength with 3 specimens in each group. The 4-point bend fatigue test evaluated the fatigue life under various stresses, with 6 specimens in each group. The specimens were mechanically ground, polished, and electrochemically etched. Scanning electron microscopy was used to identify the microstructures of both etched specimens and fracture surfaces. X-ray diffraction investigations were used to determine the phases. Significant differences in the bend strength were analyzed by using the independent samples t test (α=.05), and the fatigue test was analyzed with ANCOVA (α=.05). RESULTS: The mean ±standard deviation bend strength of SLM specimens was 1837 ±3 MPa, higher than the 1200 ±6 MPa for CAST specimens (P<.05). The maximum bend stress of the SLM specimens without fatigue failure was 735 MPa, which was statistically higher than the 394 MPa for CAST specimens (P<.05). The microstructure characteristics of the SLM alloy contributed to its excellent fatigue performance. In SLM alloy, the γ phase constituted the majority with some ε and Laves phases, while the cast alloy possessed higher ε and Laves phases. The grains of SLM alloy were equiaxed and fine, and the second phases were fine and dispersive. In contrast, the cast alloy possessed clear dendrites, and the second phases were sizable. CONCLUSIONS: The SLM dental Co-Cr-Mo-W alloy had statistically better 4-point bend fatigue properties than cast alloy, which was associated with an improved microstructure.

Lateral approach is a more aesthetical option for radical resection of BSCC: assessment of its surgical, oncological, functional, and aesthetic outcomes.

BACKGROUND: The purpose of this study was to introduce a modified lateral approach for combined radical resection of buccal squamous cell carcinoma (BSCC) and evaluate its surgical, oncological, functional, and aesthetic outcomes in comparison with the conventional lower-lip splitting approach. METHODS: This single-center study retrospectively reviewed 80 patients with BSCC, of which 37 underwent the lateral approach and 43 underwent the conventional approach. Surgical, functional, oncological, and aesthetic evaluations, as well as follow-ups, were recorded and compared. RESULTS: Compared to the conventional approach group, the lateral approach group had a longer surgical time (P = 0.000), but there was no significant difference in other surgical and oncological parameters. Moreover, the scar in the head and neck had a significantly discreet appearance in the lateral approach group, whose satisfaction was better than those in the conventional approach group (P = 0.000). Other oral function parameters, postoperative mouth-opening, and 3-year survival rate were not significantly different between the two groups. CONCLUSION: The lateral approach could provide superior aesthetic results while maintaining equal surgical, functional, and oncological outcomes compared to the conventional approach for radical resection of BSCC.

Matrix stiffness and shear stresses modulate hepatocyte functions in a fibrotic liver sinusoidal model.

Extracellular matrix (ECM) rigidity has important effects on cell behaviors and increases sharply in liver fibrosis and cirrhosis. Hepatic blood flow is essential in maintaining hepatocytes' (HCs) functions. However, it is still unclear how matrix stiffness and shear stresses orchestrate HC phenotype in concert. A fibrotic three-dimensional (3-D) liver sinusoidal model is constructed using a porous membrane sandwiched between two polydimethylsiloxane (PDMS) layers with respective flow channels. The HCs are cultured in collagen gels of various stiffnesses in the lower channel, whereas the upper channel is pre-seeded with liver sinusoidal endothelial cells (LSECs) and accessible to shear flow. The results reveal that HCs cultured within stiffer matrices exhibit reduced albumin production and cytochrome P450 (CYP450) reductase expression. Low shear stresses enhance synthetic and metabolic functions of HC, whereas high shear stresses lead to the loss of HC phenotype. Furthermore, both mechanical factors regulate HC functions by complementing each other. These observations are likely attributed to mechanically induced mass transport or key signaling molecule of hepatocyte nuclear factor 4α (HNF4α). The present study results provide an insight into understanding the mechanisms of HC dysfunction in liver fibrosis and cirrhosis, especially from the viewpoint of matrix stiffness and blood flow.NEW & NOTEWORTHY A fibrotic three-dimensional (3-D) liver sinusoidal model was constructed to mimic different stages of liver fibrosis in vivo and to explore the cooperative effects of matrix stiffness and shear stresses on hepatocyte (HC) functions. Mechanically induced alterations of mass transport mainly contributed to HC functions via typical mechanosensitive signaling.

A high performance nanocomposite based bioanode for biofuel cell and biosensor application.

Herein, to improve the current density and sensitivity for biofuel cell and glucose sensing application, a bioanode based on redox polymer (PEI-Fc) binding polydopamine (PDA) coated MWCNTs (PEI-Fc/PDA/MWCNTs) nanocomposite and glucose oxidase (GOD) was fabricated. PDA/MWCNTs nanocomposite was prepared by spontaneous self-polymerization of dopamine on MWCNTs surface and the PEI-Fc/PDA/MWCNTs nanocomposite was prepared by a simple self-assembly method. The PEI-Fc/PDA/MWCNTs nanocomposite and the resulting bioanode were fully characterized. A maximum current density of 0.73 mA cm-2 at the resulting bioanode was obtained by linear sweep voltammetry (LSV) at the scan rate of 50 mV s-1 with 20 mM glucose concentration. Moreover, a linear range up to 4 mM, a high sensitivity of 57.2 µA mM-1 cm-2, a fast response time reaching 95% of the steady current (2 s) and a low limit of detection (0.024 mM) were achieved. The amperometric method demonstrated both the sensitivity and the stability of the bioanode for glucose-sensing was improved by the employed PDA layer. Finally, the biosensor was used for glucose detection in human serum samples showing good recoveries. This study proposed an excellent functional material prepared by a facile self-assembled method for applying in biofuel cells and second-generation biosensors.

An Amphiphilic PEGylated Peptide Dendron-Gemcitabine Prodrug-Based Nanoagent for Cancer Therapy.

An amphiphilic peptide dendrimer conjugated with gemcitabine (GEM), PEGylated dendron-Gly-Phe-Leu-Gly-GEM (PEGylated dendron-GFLG-GEM), is developed as a nano-prodrug for breast cancer therapy. The self-assembled behavior is observed under a transmission electron microscopy and dynamic light scattering. The negatively charged surface and hydrodynamic size of the amphiphilic nanosized prodrug supported that the prodrug can maintain the stability of GEM during circulation and accumulate in the tumor tissue. Drug release assays are conducted to monitor the release of GEM from this nanodrug delivery system in response to the tumor microenvironment, and these assays confirm that GEM released from the nanocarrier is identical to free GEM. The GEM prodrug can prevent proliferation of tumor cells. The therapeutic effect against breast cancer is systematically investigated using an in vivo animal model. Immunohistochemical results are aligned with the significantly enhanced anticancer efficacy of GEM released from the prodrug. This self-assembled amphiphilic drug delivery nanocarrier may broaden the application for GEM and other anticancer agents for breast cancer chemotherapy.

Chemokine C-C motif ligand 33 is a key regulator of teleost fish barbel development.

Barbels are important sensory organs in teleosts, reptiles, and amphibians. The majority of ∼4,000 catfish species, such as the channel catfish (Ictalurus punctatus), possess abundant whisker-like barbels. However, barbel-less catfish, such as the bottlenose catfish (Ageneiosus marmoratus), do exist. Barbeled catfish and barbel-less catfish are ideal natural models for determination of the genomic basis for barbel development. In this work, we generated and annotated the genome sequences of the bottlenose catfish, conducted comparative and subtractive analyses using genome and transcriptome datasets, and identified differentially expressed genes during barbel regeneration. Here, we report that chemokine C-C motif ligand 33 (ccl33), as a key regulator of barbel development and regeneration. It is present in barbeled fish but absent in barbel-less fish. The ccl33 genes are differentially expressed during barbel regeneration in a timing concordant with the timing of barbel regeneration. Knockout of ccl33 genes in the zebrafish (Danio rerio) resulted in various phenotypes, including complete loss of barbels, reduced barbel sizes, and curly barbels, suggesting that ccl33 is a key regulator of barbel development. Expression analysis indicated that paralogs of the ccl33 gene have both shared and specific expression patterns, most notably expressed highly in various parts of the head, such as the eye, brain, and mouth areas, supporting its role for barbel development.

Heteroatom-participated lignin cleavage to functionalized aromatics.

Lignin, the most abundant aromatic polymer in nature, enables sustainable supply of miscellaneous aromatics as green fuels and chemicals. Obtaining the value-added aromatics from lignin, though subjected to enormous research efforts, mainly relies on depolymerization induced by activated hydrogen species or oxygen species, delivering hydrocarbons and oxygenates. The future bio-refinery demands a broad spectrum of fine chemicals, especially those containing elements other than C, H and O. Heteroatom-containing compounds have emerged as powerful reagents to participate in the bond cleavage in lignin; meanwhile, the obtained heteroatom-containing aromatics, which could be used as dye precursors, pharmaceutical precursors, hydrogen storage materials, etc., extend the application of lignin-derived products. This tutorial review updates recent advances in the lignin C-C and C-O bond cleavages induced by heteroatoms X (N, Si, I and Li), which also lead to functionalized products containing C-X and O-X bonds. The representative reaction pathways and feasibilities in lignin models and extracts are summarized. Potential applications of functionalized monomers in synthetic transformations, pharmaceuticals, dyes and energy storage are also discussed.