Double-Negative Results Matter: A Reevaluation of Sensitivities for Detecting SARS-CoV-2 Infection Using Saliva Versus Nasopharyngeal Swabs.

In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.

Exploring the role of ITGB6: fibrosis, cancer, and other diseases.

Integrin ß6 (ITGB6), a member of the integrin family of proteins, is only present in epithelial tissues and frequently associates with integrin subunit αv to form transmembrane heterodimers named integrin αvß6. Importantly, ITGB6 determines αvß6 expression and availability. In addition to being engaged in organ fibrosis, ITGB6 is also directly linked to the emergence of cancer, periodontitis, and several potential genetic diseases. Therefore, it is of great significance to study the molecular-biological mechanism of ITGB6, which could provide novel insights for future clinical diagnosis and therapy. This review introduces the structure, distribution, and biological function of ITGB6. This review also expounds on ITGB6-related diseases, detailing the known biological effects of ITGB6.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Interpenetrating Polymer Network HA/Alg-RGD Hydrogel: An Equilibrium of Macroscopic Stability and Microscopic Adaptability for 3D Cell Growth and Vascularization.

Two-dimensional (2D) cell culture methods dominate the current research. However, the inherent responsiveness of cells to their native three-dimensional (3D) microenvironment necessitates a paradigm shift toward the development of advanced hydrogels that faithfully mimic the intricacies of the extracellular matrix (ECM) and enable continuous cell-ECM interactions. To address the constraints of traditional static hydrogel networks that impede effective cell-matrix and cell-cell interactions, and to tackle the inherent stability issues associated with dynamically cross-linked hydrogels, which have become a pressing concern. Herein, we present an interpenetrating polymer network (IPN) hydrogel (HA/Alg-RGD hydrogel) that combines a physically cross-linked network between alginate and calcium ions (Alg-Ca2+) for the enhanced cell growth adaptability with a chemically cross-linked hyaluronic acid (HA) network to ensure macroscopic stability during cell culture. The incorporation of arginine-glycine-aspartic peptide modified alginate (Alg-RGD) further facilitates cell adhesion and improves the cell-hydrogel interaction. Notably, this IPN hydrogel demonstrates mechanical stability and enables cell spreading and growth within its structural framework. Leveraging the reversible characteristics of the ionically cross-linked Alg-Ca2+ network within IPN hydrogels, we demonstrate the feasibility of the gelatin sacrificial solution for 3D printing purposes within the hydrogel matrix. Subsequent UV-induced covalent cross-linking enables the fabrication of vascularized microfluidic channels within the resulting construct. Our results demonstrate endothelial cell spreading and spontaneous cell sprouting within the hydrogel matrix, thus highlighting the efficacy of this IPN hydrogel system in facilitating 3D cell growth. Additionally, our study emphasizes the potential of 3D printed constructs as a promising approach for vascularization in tissue engineering. The importance of RGD peptides in promoting favorable cell-hydrogel scaffold interactions is also highlighted, emphasizing their critical role in optimizing biomaterial-cell interfaces.

New Perspective on the Mobilization of Microplastics through Capillary Fringe Fluctuation in a Tidal Aquifer Environment.

The presence of plastic fragments in the environment is a growing global concern. In this study, we explored the effects of dynamic fluctuations of capillary fringe on the transport of microplastics (MPs) in the substrate combining various environmental and MP properties. Both experimental and Hydrus-2D modeling results confirmed that increasing cycles of water table fluctuation led to the rise of capillary fringe. An increase in the cycles of water table fluctuations did not significantly change the overall MP retention percentages in 0.5 mm substrate but altered the MP distribution along the column. In 1 and 2 mm substrate, the increase in cycle numbers enhanced the MP transport from substrate to the water below. In terms of the size of the MPs, more 20-25 µm polyethylene (PE2) were retained in the substrate compared to 4-6 µm polyethylene (PE1) under the same number of fluctuation cycles. High-density polytetrafluoroethylene (PTFE, 5-6 µm) exhibited higher retention percentages compared to PE1 particles. Ultraviolet aging for 60 days enhanced PE1 transport along the column, while 60 days of seawater aging did not affect PE1 transport greatly. For PTFE, ultraviolet and seawater aging enhanced its retention in the substrate. The retention percentages of both PE1 and PTFE in the column increased with the elevated ionic strength and the decrease of fluctuation velocity. This work highlights that capillary fringe fluctuation can serve as a pathway to relocate MPs to the tidal aquifer.

Overlooked Role of Bulk Nanobubbles in the Alteration and Motion of Microplastics in the Ocean Environment.

The increasing enrichment of microplastics (MPs) in the shoreline environment poses both ecological and social-economic risks. The alteration and motion of MPs in the ocean under the effect of bulk nanobubbles (NBs) have been less extensively studied. In this study, we explored the behavior and movement of various MPs in the presence of bulk NBs. The role of salinity and external energy in the interactions between NBs and MPs was evaluated, and the mechanism underlying these interactions was analyzed. In the presence of NBs, the binding of MPs and NBs resulted in an increase in the measured average particle size and concentration. Meanwhile, NBs reduced the aggregation between MPs, while the NBs present combined with MPs to make them more stable in suspensions. The velocity of motion of MPs driven by NBs varies under different salinity conditions. The increase in ionic strength reduced the energy barrier between particles and promoted their aggregation. Thus, the binding of NBs and MPs became more stable, which in turn affected the movement of MPs in suspensions. Polyethylene (PE1) with small particle size was mainly affected by Brownian motion, and its rising was limited; therefore, polyethylene (PE2) with large particle size rose faster than PE1 in suspension, especially in the presence of NBs. The rising velocity of poly(tetrafluoroethylene) (PTFE) was higher than that of PE1 and PE2. However, when NBs were present, the trend of the change in velocity was the opposite compared to the absence of NBs for PTFE. Moreover, various types of MPs were found to be affected distinctly by external energy. The presence of NBs had a clear effect on PE under shaking conditions, whereas the effect on PTFE was less obvious.

Understanding metabolic alterations after SARS-CoV-2 infection: insights from the patients' oral microenvironmental metabolites.

BACKGROUND: Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection. METHODS: Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students' t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application. RESULTS: PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body's metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites. CONCLUSIONS: This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.

Lamprey-Teeth-Inspired Oriented Antibacterial Sericin Microneedles for Infected Wound Healing Improvement.

The therapeutic efficacy of wound infections caused by bacteria is challenged by limited wound repairs and a high risk of inflammation. Microneedles have been generated for wound healing since they are able to efficiently pierce the epidermis and deliver drugs. However, regular microneedles cannot provide oriented traction to "shrink" the wound area, and most microneedles are made of inert polymers, which mainly serve as a support but rarely participate in the following physiological processes. Herein, inspired by lamprey teeth, we designed oriented antibacterial sericin microneedles with dually functionalized needles to provide penetration and directional traction. Sericin, derived from silkworm cocoons, was employed to fabricate microneedle tips, significantly improving skin repair via hair follicle regeneration and angiogenesis. Besides, zinc oxide nanoparticles were integrated as an antibacterial module, endowing the OASM with high bacterial suppression. It is believed that the synergy of these systems may effectively heal infected wounds, suggesting its clinically translational potential.

Application of VSD technique in adults with chronic osteomyelitis of the extremities combined with soft tissue defects.

To investigate the clinical application of vacuum sealing drainage (VSD) in chronic osteomyelitis of the extremities combined with soft tissue defects in adults. This study retrospectively included 32 adult patients with clearly diagnosed chronic osteomyelitis of the extremities combined with local soft tissue defects, and the trauma was covered by VSD after debridement, osteotomy, and vancomycin-laden bone cement filling of the occupancy, and the trauma was covered by selecting a suitable flap transfer repair according to the site and extent of the soft tissue defect after the trauma condition was suitable, and the secondary trauma was taken from the abdominal full-thickness skin free skin slice graft, according to whether the skin graft area was performed. The skin flap hematoma and infection rate, as well as the skin flap survival rate and implant fixation time were compared and analysed between the two groups. The primary outcome is the implant fixation time, and the secondary outcome is the skin fragment survival rate. In 32 patients, VSD was performed on the bone cement surface to cover the trauma, and 33.2 to 39.8 kPa continuous vacuum sealing drainage was set. The average VSD time duration before soft tissue coverage was 47.87 ± 23.14 days, and the average number of VSD use was 7.18 ± 3.23. The use of VSD before soft tissue coverage did not cause complications such as negative pressure could not be maintained, vacuum sealing drainage was not smooth, skin blistering, trauma. Among the 32 patients, 12 cases of soft tissue coverage were followed by trauma free skin grafting with packing + VSD, and 20 cases were fixed with packing alone, and the duration of continuous packing and fixation of free skin pieces in the VSD group was significantly less than that in the control group (P = .006). The survival rate was significantly higher than that of the control group (P = .019). VSD in adult patients with chronic osteomyelitis of the extremities combined with soft tissue defects can effectively improve the trauma condition, provide the possibility of second-stage soft tissue coverage, and significantly shorten the preparation time for soft tissue coverage. In addition, when soft tissue coverage trauma is performed, VSD combined with skin graft packing technique can significantly improve the survival rate of skin pieces, shorten the time of skin graft fixation.

Diabetic oxidative stress-induced telomere damage aggravates periodontal bone loss in periodontitis.

Periodontitis, one of the most common oral complications of diabetes mellitus (DM), causes a reduction in alveolar bone height and loss of alveolar bone mass. It has been shown that DM aggravates the progression of periodontitis, but the mechanism remains inconclusive. The hyperglycemic environment of DM has been proven to generate reactive oxygen species (ROS). Since telomeres, guanine-rich repeats, are highly susceptible to oxidative attack, we speculate that the excessive accumulation of ROS in DM could induce telomere damage resulting in dysfunction of periodontal ligament cells, especially periodontal ligament stem cells (PDLSCs), which reduces the ability of tissue repair and reconstruction in diabetic periodontitis. In this study, our current data revealed that oxidative telomere damage occurred in the periodontal ligaments of diabetic mice. And Micro-CT scans showed reduced alveolar bone height and impaired alveolar bone mass in a diabetic periodontitis model. Next, cultured mouse PDLSCs (mPDLSCs) were treated with the oxidant tert-butyl hydroperoxide (t-BHP) in vitro, as we expected telomere damage was observed and resulted in cellular senescence and dysfunction. Taken together, oxidative stress in DM causes telomere dysfunction and PDLSCs senescence, which influences periodontal bone tissue regeneration and reconstruction and ultimately exacerbates bone loss in periodontitis.

Cell pyroptosis in picornavirus and its potential for treating viral infection.

Cell pyroptosis has received increased attention due to the associations between innate immunity and disease, and it has become a major focal point recently due to in-depth studies of cancer. With increased research on pyroptosis, scientists have discovered that it has an essential role in viral infections, especially in the occurrence and development of some picornavirus infections. Many picornaviruses, including Coxsackievirus, a71 enterovirus, human rhinovirus, encephalomyocarditis virus, and foot-and-mouth disease virus induce pyroptosis to varying degrees. This review summarized the mechanisms by which these viruses induce cell pyroptosis, which can be an effective defense against pathogen infection. However, excessive inflammasome activation or pyroptosis also can damage the host's health or aggravate disease progression. Careful approaches that acknowledge this dual effect will aid in the exploration of picornavirus infections and the mechanisms that produce the inflammatory response. This information will promote the development of drugs that can inhibit cell pyroptosis and provide new avenues for future clinical treatment.

Transport of Microplastics in Shore Substrates over Tidal Cycles: Roles of Polymer Characteristics and Environmental Factors.

Tidal zones providing habitats are particularly vulnerable to microplastic (MP) pollution. In this study, the effects of tidal cycles on the transport of MPs (4-6 µm polyethylene, PE1; 125 µm polyethylene, PE2; and 5-6 µm polytetrafluoroethylene, PFTE) in porous media combined with various environmental and MPs properties were systemically investigated. The results indicated that smaller substrate sizes exhibited higher retention percentages compared to those of larger substrate sizes under different tidal cycles. In terms of the size of MPs, a larger size (same density) was found to result in enhanced retention of MPs in the column. As the number of tidal cycles increased, although the transport of MPs from the substrate to the water phase was enhanced, PE1 was washed out more with the change in water level, compared to PTFE. Additionally, more MPs were retained in the column with the increase of salinity and the decrease of flow velocity under the same tidal cycles. Ultraviolet and seawater aged PE1 showed enhanced transport, while aged PTFE showed enhanced retention under the same tidal cycles. These results can help understand the MP behaviors in the shoreline environment and provide support for future cleanup and sampling in tidal zones.

Candida albicans CHK1 gene regulates its cross-kingdom interactions with Streptococcus mutans to promote caries.

The cross-kingdom interactions between Candida albicans and Streptococcus mutans have played important roles in early childhood caries (ECC). However, the key pathways of C. albicans promoting the cariogenicity of S. mutans are still unclear. Here, we found that C. albicans CHK1 gene was highly upregulated in their dual-species biofilms. C. albicans chk1Δ/Δ significantly reduced the synergistical growth promotion, biofilm formation, and exopolysaccharides (EPS) production of S. mutans, the key cariogenic agent, compared to C. albicans wild type (WT) and CHK1 complementary strains. C. albicans WT upregulated the expressions of S. mutans EPS biosynthesis genes gtfB, gtfC, and gtfD, and their regulatory genes vicR and vicK, but chk1Δ/Δ had no effects. Both C. albicans WT and chk1Δ/Δ failed to promote the biofilm formation and EPS production of S. mutans ΔvicK and antisense-vicR strains, indicating that C. albicans CHK1 upregulated S. mutans vicR and vicK to increase the EPS biosynthesis gene expression, then enhanced the EPS production and biofilm formation to promote the cariogenicity. In rat caries model, the coinfection with chk1Δ/Δ and S. mutans decreased the colonization of S. mutans and developed less caries especially the severe caries compared to that from the combinations of S. mutans with C. albicans WT, indicating the essential role of C. albicans CHK1 gene in the development of dental caries. Our study for the first time demonstrated the key roles of C. albicans CHK1 gene in dental caries and suggested that it may be a practical target to reduce or treat ECC. KEY POINTS: • C. albicans CHK1 gene is important for its interaction with S. mutans. • CHK1 regulates S. mutans two-component system to promote its cariogenicity. • CHK1 gene regulates the cariogenicity of S. mutans in rat dental caries.

A novel bone cement injector augments Chinese osteoporotic lumbar pedicle screw channel: a biomechanical investigation.

BACKGROUND: The study aimed to (1) create a series of pedicle injectors with different number of holes on the sheath especially for the Chinese elderly patients and (2) further investigate the effects of the injectors on the augmentation of pedicle screw among osteoporotic lumbar pedicle channel. METHODS: This study used the biomechanical test module of polyurethane (Pacific Research Laboratory Corp, USA) to simulate the mechanical properties of human osteoporotic cancellous bone. The bone cement injectors were invented based on anatomical parameters of lumbar pedicle in Chinese elderly patients. Mechanical test experiments were performed on the bone cement injectors according to the three groups, namely, a local augmentation group, a full-length augmentation group, and a control group. The local augmentation group included three subgroups including 4-hole group, 6-hole group, and 8-hole group. All holes were laterally placed. The full-length augmentation group was a straight-hole injector. The control group was defined that pedicle screws were inserted without any cement augmentation. Six screws were inserted in each group and the maximum insertion torque was recorded. After 24 h of injecting acrylic bone cement, routine X-ray and CT examinations were performed to evaluate the distribution of bone cement. The axial pull-out force of screws was tested with the help of the material testing system 858 (MTS-858) mechanical tester. RESULTS: The bone cement injectors were consisted of the sheaths and the steel rods and the sheaths had different number of lateral holes. The control group had the lowest maximum insertion torque as compared with the 4-hole, 6-hole, 8-hole, and straight pore groups (P < 0.01), but the differences between the 4-hole, 6-hole, 8-hole, and straight pore groups were no statistical significance. The control group had the lowest maximum axial pull-out force as compared with the other four groups (P < 0.01). Subgroup analysis showed the 8-hole group (161.35 ± 27.17 N) had the lower maximum axial pull-out force as compared with the 4-hole group (217.29 ± 49.68 N), 6-hole group (228.39 ± 57.83 N), and straight pore group (237.55 ± 35.96 N) (P < 0.01). Bone cement was mainly distributed in 1/3 of the distal end of the screw among the 4-hole group, in the middle 1/3 and distal end of the screw among the 6-hole group, in the proximal 1/3 of the screw among the 8-hole group, and along the long axis of the whole screw body in the straight pore group. It might indicate that the 8-hole and straight-hole groups were more vulnerable to spinal canal cement leakage. After pullout, bone cement was also closely connected with the screw without any looseness or fragmentation. CONCLUSIONS: The bone cement injectors with different number of holes can be used to augment the pedicle screw channel. The pedicle screw augmented by the 4-hole or 6-hole sheath may have similar effects to the straight pore injector. However, the 8-hole injector may result in relatively lower pull-out strength and the straight pore injector has the risks of cement leakage as well as cement solidarization near the screw head.

The Preventive Effect of A Magnetic Nanoparticle-Modified Root Canal Sealer on Persistent Apical Periodontitis.

Persistent apical periodontitis is a critical challenge for endodontists. Developing root canal filling materials with continuous antibacterial effects and tightly sealed root canals are essential strategies to avoid the failure of root canal therapy and prevent persistent apical periodontitis. We modified the EndoREZ root canal sealer with the antibacterial material dimethylaminododecyl methacrylate (DMADDM) and magnetic nanoparticles (MNPs). The mechanical properties of the modified root canal sealer were tested. The biocompatibility of this sealer was verified in vitro and in vivo. Multispecies biofilms were constructed to assess the antibacterial effects of the modified root canal sealer. We applied magnetic fields and examined the extent of root canal sealer penetration in vitro and in vivo. The results showed that EndoREZ sealer containing 2.5% DMADDM and 1% MNP had biological safety and apical sealing ability. In addition, the modified sealer could increase the sealer penetration range and exert significant antibacterial effects on multispecies biofilms under an external magnetic field. According to the in vivo study, the apices of the root canals with the sealer containing 2.5% DMADDM and 1% MNP showed no significant resorption and exhibited only a slight increase in the periodontal ligament space, with a good inhibitory effect on persistent apical periodontitis.

Surgery-first treatment of a skeletal Class III malocclusion with a completely digital workflow.

Completely digital design/completely digital manufacturing (CDD/CDM) workflows have been widely used in orthodontic and orthognathic treatments. This case report introduces a CDD/CDM workflow consisting of clear aligners and virtual planning for a surgery-first approach (SFA) in a patient with a skeletal Class III malocclusion. Following a shortened treatment time of 5 months, the patient's facial appearance improved significantly, and well-balanced occlusion was obtained. SFAs with clear aligners can enable patients to achieve complete esthetic satisfaction during the therapeutic period. The CDD/CDM workflow provided accurate results, improved the clinical outcome, and reduced treatment time.

Synthetic Porous Melanin.

Commonly known as a skin pigment, melanin has a vital role in UV radiation protection, primarily acting as a radical scavenger. However, a lesser known natural property of melanin, observed in some melanized organisms, is its capacity to adsorb toxins, including metals and organic molecules. Inspired by this, we set out to generate a synthetic porous melanin that would pave the way to enhancing the natural adsorbent properties of melanin and melanin-like materials. Here, we developed a method for the synthesis of porous polydopamine-based melanin utilizing a mesoporous silica (MS) nanoparticle template and characterized its physical properties. Through the oxidative polymerization of dopamine, followed by the etching of silica, we generated synthetic porous melanin (SPM) with the highest measured surface area of any known polydopamine-based material. The prepared SPM was effective for the uptake of various gases and organophosphate toxins, with the material exhibiting high selectivity for CO2 over CH4 and high potential for ammonia capture. Given the demonstrated advantages provided by synthetic porous melanin and melanin's role as an adsorbent in nature, we anticipate the discovery of porous analogues in biological systems.

Allomelanin: A Biopolymer of Intrinsic Microporosity.

Melanin is a ubiquitous natural pigment found in a diverse array of organisms. Allomelanin is a class of nitrogen-free melanin often found in fungi. Herein, we find artificial allomelanin analogues exhibit high intrinsic microporosity and describe an approach for further increasing and tuning that porosity. Notably, the synthetic method involves an oxidative polymerization of 1,8-DHN in water, negating the need for multiple complex templating steps and avoiding expensive or complex chemical precursors. The well-defined morphologies of these nanomaterials were elucidated by a combination of electron microscopy and scattering methods, yielding to high-resolution 3D reconstruction based on small-angle X-ray scattering (SAXS) results. Synthetic allomelanin nanoparticles exhibit high BET areas, up to 860 m2/g, and are capable of ammonia capture up to 17.0 mmol/g at 1 bar. In addition, these nanomaterials can adsorb nerve agent simulants in solution and as a coating on fabrics with high breathability where they prevent breakthrough. We also confirmed that naturally derived fungal melanin can adsorb nerve gas simulants in solution efficiently despite lower porosity than synthetic analogues. Our approach inspires further analysis of yet to be discovered biological materials of this class where melanins with intrinsic microporosity may be linked to evolutionary advantages in relevant organisms and may in turn inspire the design of new high surface area materials.

NanoZnO-modified titanium implants for enhanced anti-bacterial activity, osteogenesis and corrosion resistance.

Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which have gained increasing attention from the viewpoints of fundamental research and practical applications. Also, numerous studies have been carried out to fine-tune the micro/nanostructures of Ti and/or incorporate chemical elements to improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) are well-known for their good antibacterial properties and low cytotoxicity along with their ability to synergize with a variety of substances, which have received increasingly widespread attention as biomodification materials for implants. In this review, we summarize recent research progress on nano-ZnO modified Ti-implants. Their preparation methods of nano-ZnO modified Ti-implants are introduced, followed by a further presentation of the antibacterial, osteogenic, and anti-corrosion properties of these implants. Finally, challenges and future opportunities for nano-ZnO modified Ti-implants are proposed.

Melanin Produced by the Fast-Growing Marine Bacterium Vibrio natriegens through Heterologous Biosynthesis: Characterization and Application.

Melanin is a pigment produced by organisms throughout all domains of life. Due to its unique physicochemical properties, biocompatibility, and biostability, there has been an increasing interest in the use of melanin for broad applications. In the vast majority of studies, melanin has been either chemically synthesized or isolated from animals, which has restricted its use to small-scale applications. Using bacteria as biocatalysts is a promising and economical alternative for the large-scale production of biomaterials. In this study, we engineered the marine bacterium Vibrio natriegens, one of the fastest-growing organisms, to synthesize melanin by expressing a heterologous tyrosinase gene and demonstrated that melanin production was much faster than in previously reported heterologous systems. The melanin of V. natriegens was characterized as a polymer derived from dihydroxyindole-2-carboxylic acid (DHICA) and, similarly to synthetic melanin, exhibited several characteristic and useful features. Electron microscopy analysis demonstrated that melanin produced from V. natriegens formed nanoparticles that were assembled as "melanin ghost" structures, and the photoprotective properties of these particles were validated by their protection of cells from UV irradiation. Using a novel electrochemical reverse engineering method, we observed that melanization conferred redox activity to V. natriegens Moreover, melanized bacteria were able to quickly adsorb the organic compound trinitrotoluene (TNT). Overall, the genetic tractability, rapid division time, and ease of culture provide a set of attractive properties that compare favorably to current E. coli production strains and warrant the further development of this chassis as a microbial factory for natural product biosynthesis.IMPORTANCE Melanins are macromolecules that are ubiquitous in nature and impart a large variety of biological functions, including structure, coloration, radiation resistance, free radical scavenging, and thermoregulation. Currently, in the majority of investigations, melanins are either chemically synthesized or extracted from animals, which presents significant challenges for large-scale production. Bacteria have been used as biocatalysts to synthesize a variety of biomaterials due to their fast growth and amenability to genetic engineering using synthetic biology tools. In this study, we engineered the extremely fast-growing bacterium V. natriegens to synthesize melanin nanoparticles by expressing a heterologous tyrosinase gene with inducible promoters. Characterization of the melanin produced from V. natriegens-produced tyrosinase revealed that it exhibited physical and chemical properties similar to those of natural and chemically synthesized melanins, including nanoparticle structure, protection against UV damage, and adsorption of toxic compounds. We anticipate that producing and controlling melanin structures at the nanoscale in this bacterial system with synthetic biology tools will enable the design and rapid production of novel biomaterials for multiple applications.