Carcinogenic assessment of cobalt-containing alloys in medical devices or cobalt in occupational settings: A systematic review and meta-analysis of overall cancer risk from published epidemiologic studies.

In 2020, the European Commission up-classified pure cobalt metal to a Category 1B hazard, based primarily on data from rodent inhalation carcinogenicity studies of metallic cobalt. The European Commission review did not evaluate cobalt-containing alloys in medical devices, which have very different properties vs. pure cobalt metal and did not include a systematic epidemiologic review. We performed a systematic review and meta-analysis of published, peer-reviewed epidemiologic studies evaluating the association between overall cancer risk and exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings. Study-specific estimates were pooled using random-effects models. Analyses included 20 papers on orthopedic implants and 10 occupational cohort papers (~1 million individuals). The meta-analysis summary estimates (95% confidence intervals) for overall cancer risk were 1.00 (0.96-1.04) overall and 0.97 (0.94-1.00) among high-quality studies. Results were also similar in analyses stratified by type of exposure/data sources (occupational cohort, implant registry or database), comparators (general or implant population), cancer incidence or mortality, follow-up duration (latency period), and study precision. In conclusion, meta-analysis found no association between exposure to orthopedic implants containing cobalt alloys or cobalt particulates in occupational settings and overall cancer risk, including an analysis of studies directly comparing metal-on-metal vs. non-metal-on-metal implants.

Nanocatalyst doped bacterial cellulose-based thermosensitive nanogel with biocatalytic function for antibacterial application.

Reactive oxygen species (ROS) for treating bacterial infection is an alternative strategy to overcome the drawbacks such as bacterial resistance of commonly used antibiotics. Nanocatalysts have been proved highly effective in regulating intracellular ROS level due to their intrinsic enzymes-mimicking ability. Herein, we prepared a carbon-based nanozyme doped with copper atoms with peroxidase mimetic activity to catalyze the decomposition of bio-safety dosage of H2O2 to highly reactive OH radicals for antibacterial treatment. Furthermore, we designed the thermo-responsive nanogels consisting of bacterial cellulose nanowhiskers as the carrier of the nanozyme. The obtained nanogels displayed remarkable intelligent response to temperature change with sol-gel transition temperature of ~33 °C and in situ gel forming ability. Moreover, the nanogels exhibited excellent biocompatibility in vitro, along with remarkable antibacterial efficacy which could inactivate 6.36 log of S. aureus and 6.01 log of E. coli in 3 h, respectively. The findings provide a novel strategy for advancing the development of nanocatalysts-based responsive biomaterials for treating bacterial infections.

Glucose-responsive biomimetic nanoreactor in bacterial cellulose hydrogel for antibacterial and hemostatic therapies.

Anti-infections therapy accompanied with effective hemorrhage control is highly urgent in clinics. Herein, a biomimetic nanoreactor encapsulated self-healing hydrogel with glucose-responsive catalytic activity was constructed for synergetic antibacterial defense and hemostasis. A metal-organic frameworks (MOF)-based nanocatalyst loaded with glucose oxidase (GOx) was fabricated and encapsulated in the bacterial cellulose (BC) reinforced hydrogel, while the sustained release of GOx could catalyze the decomposition of glucose for triggering the MOF-mediated catalytic activity to in situ generate OH for bacteria killing. Importantly, this nanozyme-based hydrogel exhibited excellent hemostatic property owing to the enhanced absorption capacity, which provides the essential glucose from blood for triggering the glucose-responsive antibacterial activity simultaneously. Antibacterial tests revealed that the hydrogel exhibited significant antibacterial efficacy and biofilm inhibition ability in the presence of normal blood level of glucose. Such design of biocatalytic hydrogel for synergistic hemostatic and antibacterial application brings new insight for nanozyme-based biomedical therapies.

Qing Zao Fang (QZF) Alleviates the Inflammatory Microenvironment of the Submandibular Gland in Sjögren's Syndrome Based on the PI3K/Akt/HIF-1α/VEGF Signaling Pathway.

Sjögren's syndrome (SS) which could lead to a disorder of our immune system is a chronic autoimmune disease characterized by invading exocrine glands such as salivary glands and lacrimal glands and other exocrine glands. Its common symptom is dry mouth and dry eyes, often accompanied by a large number of lymphocyte infiltrations and can involve other organs to cause complex clinical manifestations. In this study, we aimed at investigating the effect of QZF in SS, identifying the molecular mechanism in modulating autoimmune response, and determining the important roles of these factors' function as a modulator in the pathogenesis of SS. The NOD mice were utilized to establish the rats' model of Sjögren's syndrome. After 10 weeks' hydroxychloroquine and QZF in different dose interference, submandibular gland tissue was collected. The therapeutic effect of QZF on SS rats was identified, and the results suggest the comparable potential to hydroxychloroquine. In submandibular gland tissue, interleukin- (IL-) 17 was significantly lower in high-dose QZF than that in SS rats and the focal lymphocytes were highly attenuated. Moreover, we found that PI3K/Akt signals were activated and the downstream HIF-1α/VEGF signals were enhanced in SS rats whose protein expression could be inhibited by QZF treatment. In addition, QZF could modulate autophagy in submandibular gland tissue and then inhibit the inflammation response and therefore facilitate the tissue repair.

Facile isolation of cellulose nanofibrils from agro-processing residues and its improved stabilization effect on gelatin emulsion.

In this study, the pineapple peel cellulose nanofibrils (PCNFs) were facilely isolated by a dilute alkali assisted ball milling technique, then used to adjust the stabilization of low internal phase oil-in-water emulsions (oil phase 30 vol%) stabilized by gelatin (GLT, 1 wt%). The ball milling with the aid of NaOH solution (3 wt%) efficiently promoted the purification and defibrillation of cellulose through a one-pot approach, showing an average length of 0.77 µm and crystallinity index of 43.5 %. With the increase of PCNFs concentration (0-1.0 wt%), the emulsions showed an increased droplet size (51.2-76.9 µm) and a gradually decreasing bottom water layer. The apparent viscosity, storage modulus (G') and loss modulus (G") of emulsions evidently increased with increasing PCNFs addition. The result of confocal laser scanning microscopy (CLSM) confirmed the stabilization mechanism of GLT/PCNFs emulsions, involving the interface adsorption by GLT and the formation of viscoelastic network structure by PCNFs. The environmental stabilities of GLT emulsion could be improved by introducing PCNFs, except for at high ionic strength (> 100 mM). Notably, PCNFs effectively avoided the adverse effect of GLT isoelectric point (pH 5) on the stability of emulsion.

Prodrug inspired bi-layered electrospun membrane with properties of enhanced tissue integration for guided tissue regeneration.

Guided tissue regeneration (GTR) membranes play a vital role in periodontal surgery. Recently a series of composite electrospun membranes have been fabricated to improve the unexpected biodegradation of collagen-based GTR membranes. However, their tissue integrity needs to be studied in depth. In this study, a bi-layered electrospun membrane (BEM) inspired by "prodrug" was fabricated, which contained a dense-layer (BEM-DL) and a potential loose-layer (BEM-LL). The nanofibers of BEM-DL were composed of poly(l-lactic-co-glycolic acid) and tilapia skin collagen (TSC). Whereas the BEM-LL consisted of two types of nanofibers, one was the same as BEM-DL and the other was made from TSC. The morphology, degradation in vitro, cytocompatibility and biocompatibility in rats were investigated with a poly(lactic-co-glycolic acid) electrospun membrane (PLGA) as the negative control. The pore size of BEM-LL soaked for 7 days became larger than the original sample (164.8 ± 90.9 and 52.5 ± 21.0 µm2 , respectively), which was significantly higher (p < .05) than that of BEM-DL and PLGA. The BEM-LL displayed a larger weight loss rate of 82.3 ± 3.6% than the BEM-DL of 46.0 ± 2.8% at day 7 because of the rapid degradation of TSC fibers. The cytocompatibility test demonstrated that L929 cells were only spread on the surface of the BEM-DL while MC3T3-E1 cells grew into the BEM-LL layer. The subcutaneous implantation test further proved that BEM-DL performed as a cellular barrier, whereas BEM-LL was conducive to cell infiltration as deep as 200 µm with reduced fibrous encapsulation. Herein, the BEM inspired by "prodrug" is a promising GTR membrane with a property of enhanced tissue integration.

Enhanced Interface Properties and Stability of Lignocellulose Nanocrystals Stabilized Pickering Emulsions: The Leading Role of Tannic Acid.

Cellulose and tannin are both abundant and biodegradable biopolymers, whose integrations show great potential in the food field due to their nutritional properties and biological activity. Here, lignocellulose nanocrystals (LCNC) isolated from pineapple peel were complexed with tannic acid (TA) through hydrogen-bonding interaction to prepare the LCNC/TA complex for stabilizing Pickering emulsions. Introducing TA decreased the interfacial tension (23.8-20.1 mN/m) and water contact angle (83.2-56.2°) with the LCNC/TA ratio ranging from 1:0 to 1:0.8 (w/w) but increased the size of the LCNC/TA complex. The droplet size of emulsions decreased from 115.0 to 51.3 µm accompanied by improved rheological properties. The emulsions stabilized by the LCNC/TA complex exhibited higher storage and environmental stabilities than those stabilized by LCNC alone. Interestingly, TA effectively promoted the interfacial adsorption of LCNC to build a stronger interfacial layer. The emulsion network structure was enhanced due to the formation of hydrogen-bonding interaction between LCNC and TA in the continuous phase.

N-halamine modified multiporous bacterial cellulose with enhanced antibacterial and hemostatic properties.

Bacterial cellulose (BC) is a natural polymer with remarkable superiority for fabricating biomaterials. In this study, a multiporous bacterial cellulose (MBC) film was modified with N-isopropylacrylamide (NIPAM), and the modified MBC film was imbued with antibacterial properties after chlorination. The dried chlorinated samples showed superb antibacterial efficacy and could inactivate 6.19 log of inoculated S. aureus and 6.29 log of E. coli within 1 min of contact. After releasing active chlorine for 12 h, 3.67 log of S. aureus and 3.97 log of E. coli were inactivated within 30 min of contact. The prepared films displayed high porous and layered structures with a resultant excellent water retention which can be applied as material for wound dressings. In addition, the chlorinated films showed hemostatic ability on wound bleeding and good biocompatibility. The prepared N-halamine functionalized MBC films might have great potential applications as wound dressings.

Converting waste lignin into nano-biochar as a renewable substitute of carbon black for reinforcing styrene-butadiene rubber.

Industrial waste lignin was commonly burnt or discharged into river in the past. However, in this study, lignin has been converted into high value-added nano-biochar as a renewable reinforcing filler of styrene-butadiene rubber (SBR) by a simple high-temperature carbonization treatment. Herein, the physicochemical change in lignin before and after carbonization was investigated. It was found that lignin-derived biochar (LB) consisted of vesicle-like primary nanoparticles which were closely packed to form "high-structure" irregular fragments with a high specific surface area (83.41 m2/g). When incorporating LB into SBR, the tensile properties of LB/SBR composites were significantly improved. At the filler loading of 40 phr, the tensile strength and elongation at break of the rubber composite were improved up to 7.1-folds and 2.4-folds of pristine SBR, respectively. Compared to commercial carbon black (CB) N330, the LB showed a similar reinforcing effect on SBR. However, the analysis on the morphology, stress-strain behavior and dynamic mechanical behavior suggested distinct reinforcing mechanisms for LB- and CB-filled rubber composites, due to the difference in the surface properties and structural characteristic of fillers. This work showed the application potential of LB as a renewable substitute of CB in rubber industry and brought environmental and economic benefits for the disposal of lignin.

A novel method for removing polyethyleneimine from biopharmaceutical samples: improving assay sensitivity of residual DNA qPCR.

Polyethyleneimine (PEI) is a flocculent that is widely used in the downstream purification of monoclonal antibodies. It is an in-process residual that is carried through the drug purification process and strongly inhibits residual DNA quantitation by real-time quantitative PCR assay. Very high sample dilutions (e.g., 1:10,000) can overcome the interference of PEI, but at the cost of DNA assay sensitivity. Diluting samples poses a significant risk to the assay sensitivity needed to satisfy regulatory requirements on the quantitation of residual genomic DNA present per dose (i.e., 10 ng/dose). Removing PEI while retaining DNA, by the use of sodium dodecyl sulfate, heparin and/or sarkosyl can overcome the interference of PEI and allow a more accurate quantitation of residual DNA.

Immunogenicity and protective efficacy of a novel foot-and-mouth disease virus empty-capsid-like particle with improved acid stability.

Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects cloven-hoofed animal species. The FMDV capsid is highly acid labile and viral particles lose their immunogenicity when they disassemble at mildly acidic pHs. The viral capsid of FMDV serotype O is more sensitive than those of other serotypes, making it more difficult to acquire enough empty-capsid-like particles in the acidic insect cell environment for research. In this study, novel FMDV mutants with increased acid resistance were isolated using BHK-21 cell cultured under low-pH conditions. Amino acid substitutions Q25R, K41E, and N85A in the VP1 capsid protein and K154Q in the VP3 capsid protein were detected in all six mutants. Based on these amino acid replacements, empty-capsid-like particles of FMDV serotype O, which were resistant to the acid-induced dissociation of the capsid into pentameric subunits, were produced in insect cells. We characterized the protective immunity induced by these acid-resistant empty capsid particles. Significant humoral and cellular immune responses were elicited in mice after immunization with the acid-resistant empty capsid particles. The acid-resistant empty-capsid-like particles also induced strong neutralizing antibodies in guinea pigs and protected all the guinea pigs from FMDV challenge. Our results suggest that these acid-resistant empty-capsid-like particles have potential utility as a vaccine against serotype O FMDV infection.

Evaluation of biocompatibility and immunogenicity of micro/nanofiber materials based on tilapia skin collagen.

Type I collagen, used as a raw material, plays a pivotal role in the development of medical devices and tissue engineering. Due to the risk of zoonotic transmission and religious constraints for mammalian collagen, fish collagen gains increased attention and is widely seen as an alternative. In this study, two collagen micro/nanofiber materials, self-assembled collagen nanofiber and electrospun collagen nanofiber, were prepared by tilapia skin collagen and their biocompatibility and immunogenicity was thoroughly investigated. The result revealed that the state of tilapia skin collagen in self-assembled collagen nanofiber and electrospun collagen nanofiber was different. The circular dichroism spectrum indicated that collagen in self-assembled collagen nanofiber retained the triple helical structure of the native collagen, while collagen in electrospun collagen nanofiber was denatured into gelatin. Nevertheless, the evaluation according to ISO10993, including tests of cytotoxicity, hemolysis, skin sensitization, acute systemic toxicity, mouse immunization and lymphocyte proliferation, demonstrated good biocompatibility and low immunogenicity for both self-assembled and electrospun collagen nanofiber materials. Overall, the present study highlighted that type I collagen from tilapia skin would be a promising biomaterial for the development of regenerate medical products.

Antibacterial modification of PET with quaternary ammonium salt and silver particles via electron-beam irradiation.

Quaternary ammonium compound 2-dimethyl-2-hexadecyl-1-methacryloxyethyl ammonium bromide (DEHMA) was synthesized and grafted onto polyester (PET) fibers with acrylic acid (AA) via electron-beam (EB) irradiation process. The grafted fibers were soaked in AgNO3 solution for further improving antibacterial efficiency. SEM, FTIR, EDX, and XPS were used to characterize the treated PET samples. The antibacterial efficacy testing showed the grafted PET samples inactivated all Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli O157:H7) in 10min. After coated with silver ions, the antibacterial efficacy of the grafted PET with silver against S. aureus improved significantly. The EB irradiation process only caused a small degree of the breaking strength loss of the grafted PET fabrics which is acceptable in practical application.

Foot-and-mouth disease virus capsid protein VP2 activates the cellular EIF2S1-ATF4 pathway and induces autophagy via HSPB1.

Foot-and-mouth disease virus (FMDV) can result in economical destruction of cloven-hoofed animals. FMDV infection has been reported to induce macroautophagy/autophagy; however, the precise molecular mechanisms of autophagy induction and effect of FMDV capsid protein on autophagy remain unknown. In the present study, we report that FMDV infection induced a complete autophagy process in the natural host cells of FMDV, and inhibition of autophagy significantly decreased FMDV production, suggesting that FMDV-induced autophagy facilitates viral replication. We found that the EIF2S1-ATF4 pathway was activated and the AKT-MTOR signaling pathway was inhibited by FMDV infection. We also observed that ultraviolet (UV)-inactivated FMDV can induce autophagy. Importantly, our work provides the first piece of evidence that expression of FMDV capsid protein VP2 can induce autophagy through the EIF2S1-ATF4-AKT-MTOR cascade, and we found that VP2 interacted with HSPB1 (heat shock protein family B [small] member 1) and activated the EIF2S1-ATF4 pathway, resulting in autophagy and enhanced FMDV replication. In addition, we show that VP2 induced autophagy in a variety of mammalian cell lines and decreased aggregates of a model mutant HTT (huntingtin) polyglutamine expansion protein (HTT103Q). Overall, our results demonstrate that FMDV capsid protein VP2 induces autophagy through interaction with HSPB1 and activation of the EIF2S1-ATF4 pathway.