Apple grading method based on neural network with ordered partitions and evidential ensemble learning

In order to improve the performance of the automatic apple grading and sorting system,in this paper,an ensemble model of ordinal classification based on neural network with ordered partitions and Dempster–Shafer theory is proposed.As a non-destructive grading method,apples are graded into three grades based on the Soluble Solids Content value,with features extracted from the preprocessed near-infrared spectrum of apple serving as model inputs.Considering the uncertainty in grading labels,mass generation approach and evidential encoding scheme for ordinal label are proposed,with uncertainty handled within the framework of Dempster–Shafer theory.Constructing neural network with ordered partitions as the base learner,the learning procedure of the Bagging-based ensemble model is detailed.Experiments on Yantai Red Fuji apples demonstrate the satisfactory grading performances of proposed evidential ensemble model for ordinal classification.

Immunomodulatory biomaterials against bacterial infections:Progress,challenges,and future perspectives

Bacterial infectious diseases are one of the leading causes of death worldwide.Even with the use of multiple antibiotic treatment strategies,4.95 million people died from drug-resistant bacterial infections in 2019.By 2050,the number of deaths will reach 10 milion annually.The increasing mortality may be partly due to bacterial heterogeneity in the infection microenvironment,such as drug-resistant bacteria,biofilms,persister cells,intracellular bacteria,and small colony variants.In addition,the complexity of the immune microenvironment at different stages of infection makes biomaterials with direct antimicrobial activity unsatisfactory for the longterm treatment of chronic bacterial infections.The increasing mortality may be partly attributed to the biomaterials failing to modulate the active antimicrobial action of immune cells.Therefore,there is an urgent need for effective alternatives to treat bacterial infections.Accordingly,the development of immunomodulatory antimicrobial biomaterials has recently received considerable interest;however,a comprehensive review of their research progress is lacking.In this review,we focus mainly on the research progress and future perspectives of immunomodulatory antimicrobial biomaterials used at different stages of infection.First,we describe the characteristics of the immune microenvironment in the acute and chronic phases of bacterial infections.Then,we highlight the immunomodulatory strategies for antimicrobial biomaterials at different stages of infection and their corresponding advantages and disadvantages.Moreover,we discuss biomaterial-mediated bacterial vaccines'potential applications and challenges for activating innate and adaptive immune memory.This review will serve as a reference for future studies to develop next-generation immunomodulatory biomaterials and accelerate their translation into clinical practice.

Biodegradable Zn-Sr alloy for bone regeneration in rat femoral condyle defect model: In vitro and in vivo studies

Bone defects are commonly caused by severe trauma,malignant tumors,or congenital diseases and remain among the toughest clinical problems faced by orthopedic surgeons,especially when of critical size.Biodegradable zinc-based metals have recently gained popularity for their desirable biocompatibility,suitable degradation rate,and favorable osteogenesis-promoting properties.The biphasic activity of Sr promotes osteogenesis and inhibits osteoclastogenesis,which imparts Zn-Sr alloys with the ideal theoretical osteogenic properties.Herein,a biodegradable Zn-Sr binary alloy system was fabricated.The cytocompatibility and osteogenesis of the Zn-Sr alloys were significantly better than those of pure Zn in MC3T3-E1 cells.RNA-sequencing illustrated that the Zn-0.8Sr alloy promoted osteogenesis by activating the wnt/β-catenin,PI3K/Akt,and MAPK/Erk signaling pathways.Furthermore,rat femoral condyle defects were repaired using Zn-0.8Sr alloy scaffolds,with pure Ti as a control.The scaffold-bone integration and bone ingrowth confirmed the favorable in vivo repair properties of the Zn-Sr alloy,which was verified to offer satisfactory biosafety based on the hematoxylin-eosin(H&E)staining and ion concentration testing of important organs.The Zn-0.8Sr alloy was identified as an ideal bone repair material candidate,especially for application in critical-sized defects on load-bearing sites due to its favorable biocompatibility and osteogenic properties in vitro and in vivo.

Serum zinc levels and multiple health outcomes: Implications for zinc-based biomaterials

Background:Zinc-based biomaterials,including biodegradable metal,nanoparticles,and coatings used in medical implants release zinc ions that may increase the whole-body and serum zinc concentrations.The impact of serum zinc concentrations on major health outcomes can provide insights for device design and clinical transformation of zinc-based biomaterials.Methods:This nationally representative cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey(NHANES,2011-2014)including 3607 participants.Using unadjusted and multivariate-adjusted logistic regression analyses,two-piecewise linear regression model with a smoothing function and threshold level analysis,we evaluated the associations between elevated serum zinc levels and major health outcomes.Results:Elevated serum zinc levels were significantly associated with an increase in total spine and total femur bone mineral density(BMD).Every 10μg/dL increase was associated with a 1.12-fold increase in diabetes mellitus(DM)and 1.23-fold and 1.29-fold increase in cardiovascular diseases(CVD)and coronary heart disease(CHD),in participants with serum zinc levels≥100μg/dL.It had no significant linear or nonlinear associations with risk of fractures,congestive heart failure,heart attack,thyroid disease,arthritis,osteoarthritis,rheumatoid arthritis,dyslipidemia and cancer.Conclusion:Serum zinc levels are significantly associated with increased BMD in the total spine and total femur,and risk of DM,and CVD/CHD among participants with serum zinc levels≥100μg/dL.

Zinc alloy-based bone internal fixation screw with antibacterial and anti-osteolytic properties

There is no targeted effective treatment for patients undergoing internal fixation surgery/two-stage total joint revision surgery with a high risk of postoperative infection and osteolysis,while the rate of reoperation due to infection and osteolysis remains high.In this study,we report a pioneering application of implants made of biodegradable Zn-Ag alloy with active antibacterial and anti-osteolytic properties in three classical animal models,illustrating antibacterial,anti-osteolysis,and internal fixation for fractures.The antibacterial activity of the Zn-2Ag alloy was verified in a rat femur osteomyelitis prevention model,while the anti-osteolytic properties were evaluated using a mouse cranial osteolysis model.Moreover,the Zn-2Ag based screws showed similar performance in bone fracture fixation compared to the Ti-6Al-4V counterpart.The fracture healed completely after 3 months in the rabbit femoral condyle fracture model.Furthermore,the underlying antibacterial mechanism may include inhibition of biofilm formation,autolysis-related pathways,and antibiotic resistance pathways.Osseointegration mechanisms may include inhibition of osteoclast-associated protein expression,no effect on osteogenic protein expression,and no activation of related inflammatory protein expression.The empirical findings here reveal the great potential of Zn-Ag-based alloys for degradable biomaterials in internal fixation surgery/two-stage total joint revision surgery for patients with a high risk of postoperative infection and osteolysis.

Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection

Orthopedic implants account for 99%of orthopedic surgeries,however,orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and mortality.Current antibiotic treatments still lack the capacity to target bone infection sites,thereby resulting in unsatisfactory therapeutic effects.Here,the bone infection site targeting efficacy of D6 and UBI29-41 peptides was investigated,and bone-and-bacteria dual-targeted nanoparticles(NPs)with D6 and UBI29-41 peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection site.The results of this study demonstrated that the bone-and-bacteria dual-targeted mesoporous silica NPs exhibit excellent bone and bacteria targeting efficacy,excellent biocompatibility and effective antibacterial properties in vitro.Furthermore,in a rat model of orthopedic implant-related infection with methicillin-resistant Staphylococcus aureus,the growth of bacteria was evidently inhibited without cytotoxicity,thus realizing the early treatment of implant-related infection.Hence,the bone-and-bacteria dual-targeted molecule-modified NPs may target bacteria-infected bone sites and act as ideal candidates for the therapy of orthopedic implant-related infections.

Felodipine enhances aminoglycosides efficacy against implant infections caused by methicillin-resistant Staphylococcus aureus,persisters and biofilms

Methicillin-resistant Staphylococcus aureus(MRSA),biofilms,and persisters are three major factors leading to recurrent and recalcitrant implant infections.Although antibiotics are still the primary treatment for chronic implant infections in clinical,only few drugs are effective in clearing persisters and formed biofilms.Here,felodipine,a dihydropyridine calcium channel blocker,was reported for the first time to have antibacterial effects against MRSA,biofilm,and persisters.Even after continuous exposure to sub-lethal concentrations of felodipine,bacteria are less likely to develop resistance.Besides,low doses of felodipine enhances the antibacterial activity of gentamicin by inhibiting the expression of protein associated with aminoglycoside resistance(aacA-aphD).Next,biofilm eradication test and persisters killing assay suggested felodipine has an excellent bactericidal effect against formed biofilms and persisters.Furthermore,the result of protein profiling,and quantitative metabonomics analysis indicated felodipine reduce MRSA virulence(agrABC),biofilm formation and TCA cycle.Then,molecular docking showed felodipine inhibit the growth of persisters by binding to the H pocket of ClpP protease,which could lead to substantial protein degradation.Furthermore,murine infection models suggested felodipine in combination with gentamicin alleviate bacterial burden and inflammatory response.In conclusion,low dose of felodipine might be a promising agent for biomaterial delivery to enhance aminoglycosides efficacy against implant infections caused by MRSA,biofilm,and persisters.

Enoxacin-loaded Poly(lactic-co-glycolic acid) Coating on Porous Magnesium Scaffold as a Drug Delivery System: Antibacterial Properties and Inhibition of Osteoclastic Bone Resorption

Implant-associated infection remains a difficult medical problem in orthopedic surgery. Therefore, the development of multifunctional bone implants for treating infection and regenerating lost bone tissue, which may be a result of infection, is important. In the present study, we report the fabrication of enoxacin- loaded poly （lactic-co-glycolic acid） （PLGA） coating on porous magnesium scaffold （Enox-PLGA-Mg） which combine the favorable properties of magnesium, the antibacterial property and the effect of inhibition of osteoclastic bone resorption of enoxacin. The drug loaded PLGA coating of Mg scaffold enables higher drug loading efficiency （52%-56%） than non-coating enoxacin loaded Mg scaffold （Enox-Mg） （4%-5%）. Enox- PLGA-Mg exhibits sustained drug release for more than 14 days, and this controlled release of enoxacin signifcantly inhibits bacterial adhesion and prevented biofilm formation by Staphylococcus epidermidis （ATCC35984） and Staphylococcus aureus （ATCC25923）. Biocompatibility tests with Balb/c mouse embryo fibroblasts （Balb/c 3T3 cells） indicate that PLGA-Mg has better biocompatibility than Mg. Finally, we also demonstrate that Enox-PLCA-Mg extract potently inhibited osteoclast formation in vitro. Therefore, Enox- PLCA-Mg has the potential to be used as a multifunctional controlled drug delivery system bone scaffolds to prevent and/or treat orthopedic peri-implant infections.