Drug-coated balloon angioplasty with rescue stenting versus intended stenting for the treatment of patients with de novo coronary artery lesions (REC-CAGEFREE I): an open-label, randomised, non-inferiority trial.

BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

In vitro evaluation of the biocompatibility and bioactivity of a SLM-fabricated NiTi alloy with superior tensile property.

Because nickel-titanium (NiTi) alloys have unique functions, such as superelasticity, shape memory, and hysteresis similar to bone in the loading-unloading cycles of their recoverable deformations. They likely offer good bone integration, a low loosening rate, individual customization, and ease of insertion. Due to the poor processability of NITI, traditional methods cannot manufacture NiTi products with complex shapes. Orthopedic NiTi implants need to show an adequate fracture elongation of at least 8%. Additive manufacturing can be used to prepare NiTi implants with complex structures and tunable porosity. However, as previously reported, additively manufactured NiTi alloys could only exhibit a maximum tensile fracture strain of 7%. In new reports, a selective laser melting (SLM)-NiTi alloy has shown greater tensile strain (15.6%). Nevertheless, due to the unique microstructure of additive manufacturing NiTi that differs from traditional NITI, the biocompatibility of SLM-NITI manufactured by this new process requires further evaluation In this study, the effects of the improved NiTi alloy on bone marrow mesenchymal stem cell (BMSC) proliferation, adhesion, and cell viability were investigated via in vitro studies. A commercial Ti-6Al-4V alloy was studied side-by-side for comparison. Like the Ti-6Al-4V alloy, the SLM-NiTi alloy exhibited low cytotoxicity toward BMSCs and similar effect on cell adhesion or cell viability. This study demonstrates that the new SLM-NiTi alloy, which has exhibited improved mechanical properties, also displays excellent biocompatibility. Therefore, this alloy may be a superior implant material in biomedical implantation.

Molecular weaving.

Historically, the interlacing of strands at the molecular level has mainly been limited to coordination polymers and DNA. Despite being proposed on a number of occasions, the direct, bottom-up assembly of molecular building blocks into woven organic polymers remained an aspirational, but elusive, target for several decades. However, recent successes in two-dimensional and three-dimensional molecular-level weaving now offer new opportunities and research directions at the interface of polymer science and molecular nanotopology. This Perspective provides an overview of the features and potential of the periodic nanoscale weaving of polymer chains, distinguishing it from randomly entangled polymer networks and rigid crystalline frameworks. We review the background and experimental progress so far, and conclude by considering the potential of molecular weaving and outline some of the current and future challenges in this emerging field.

Nucleolin Promotes IRES-Driven Translation of Foot-and-Mouth Disease Virus by Supporting the Assembly of Translation Initiation Complexes.

Nucleolin (NCL), a stress-responsive RNA-binding protein, has been implicated in the translation of internal ribosome entry site (IRES)-containing mRNAs, which encode proteins involved in cell proliferation, carcinogenesis, and viral infection (type I IRESs). However, the details of the mechanisms by which NCL participates in IRES-driven translation have not hitherto been described. Here, we identified NCL as a protein that interacts with the IRES of foot-and-mouth disease virus (FMDV), which is a type II IRES. We also mapped the interactive regions within FMDV IRES and NCL in vitro. We found that NCL serves as a substantial regulator of FMDV IRES-driven translation but not of bulk cellular or vesicular stomatitis virus cap-dependent translation. NCL also modulates the translation of and infection by Seneca Valley virus (type III-like IRES) and classical swine fever virus (type III IRES), which suggests that its function is conserved in unrelated IRES-containing viruses. We also show that NCL affects viral replication by directly regulating the production of viral proteins and indirectly regulating FMDV RNA synthesis. Importantly, we observed that the cytoplasmic relocalization of NCL during FMDV infection is a substantial step for viral IRES-driven translation and that NCL specifically promotes the initiation phase of the translation process by recruiting translation initiation complexes to viral IRES. Finally, the functional importance of NCL in FMDV pathogenicity was confirmed in vivo. Taken together, our findings demonstrate a specific function for NCL in selective mRNA translation and identify a target for the development of a broad-spectrum class of antiviral interventions. IMPORTANCE FMDV usurps the cellular translation machinery to initiate viral protein synthesis via a mechanism driven by IRES elements. It allows the virus to shut down bulk cellular translation, while providing an advantage for its own gene expression. With limited coding capacity in its own genome, FMDV has evolved a mechanism to hijack host proteins to promote the recruitment of the host translation machinery, a process that is still not well understood. Here, we identified nucleolin (NCL) as a positive regulator of the IRES-driven translation of FMDV. Our study supports a model in which NCL relocalizes from the nucleus to the cytoplasm during the course of FMDV infection, where the cytoplasmic NCL promotes FMDV IRES-driven translation by bridging the translation initiation complexes with viral IRES. Our study demonstrates a previously uncharacterized role of NCL in the translation initiation of IRES-containing viruses, with important implications for the development of broad antiviral interventions.

Ribosomal Protein L13 Promotes IRES-Driven Translation of Foot-and-Mouth Disease Virus in a Helicase DDX3-Dependent Manner.

Internal ribosome entry site (IRES)-driven translation is a common strategy among positive-sense, single-stranded RNA viruses for bypassing the host cell requirement of a 5' cap structure. In the current study, we identified the ribosomal protein L13 (RPL13) as a critical regulator of IRES-driven translation of foot-and-mouth disease virus (FMDV) but found that it is not essential for cellular global translation. RPL13 is also a determinant for translation and infection of Seneca Valley virus (SVV) and classical swine fever virus (CSFV), and this suggests that its function may also be conserved in unrelated IRES-containing viruses. We further showed that depletion of DEAD box helicase DDX3 disrupts binding of RPL13 to the FMDV IRES, whereas the reduction in RPL13 expression impairs the ability of DDX3 to promote IRES-driven translation directly. DDX3 cooperates with RPL13 to support the assembly of 80S ribosomes for optimal translation initiation of viral mRNA. Finally, we demonstrated that DDX3 affects the recruitment of the eukaryotic initiation factor eIF3 subunits e and j to the viral IRES. This work provides the first connection between DDX3 and eIF3e/j and recognition of the role of RPL13 in modulating viral IRES-dependent translation. This previously uncharacterized process may be involved in selective mRNA translation.IMPORTANCE Accumulating evidence has unveiled the roles of ribosomal proteins (RPs) belonging to the large 60S subunit in regulating selective translation of specific mRNAs. The translation specificity of the large-subunit RPs in this process is thought provoking, given the role they play canonically in catalyzing peptide bond formation. Here, we have identified the ribosomal protein L13 (RPL13) as a critical regulator of IRES-driven translation during FMDV infection. Our study supports a model whereby the FMDV IRESs recruit helicase DDX3 recognizing RPL13 to facilitate IRES-driven translation, with the assistance of eIF3e and eIF3j. A better understanding of these specific interactions surrounding IRES-mediated translation initiation could have important implications for the selective translation of viral mRNA and thus for the development of effective prevention of viral infection.

Sec62 Suppresses Foot-and-Mouth Disease Virus Proliferation by Promotion of IRE1α-RIG-I Antiviral Signaling.

Foot-and-mouth disease virus (FMDV) is highly infectious and causes a major plague in animal farming. Unfolded protein response is one of the major cellular responses to pathogenic infections, which performs a crucial role in cell survival, apoptosis, and antiviral innate immune response. In this study, we showed that FMDV infection activated two unfolded protein response branches (PERK-eIF2α and ATF6 signaling) in both baby hamster kidney cells (BHK-21) and porcine kidney (PK-15) cells, whereas it suppressed the IRE1α-XBP1 signaling by decreasing IRE1α level. Further study revealed IRE1α signaling as an important antiviral innate immune mechanism against FMDV. Sec62, the transport protein, was greatly decreased at the late stages of FMDV infection. By overexpression and knockdown study, we also found that the expression of Sec62 was positively involved in the levels of IRE1α and RIG-I and subsequent activation of downstream antiviral signaling pathways in FMDV-infected PK-15 cells. Taken together, our study demonstrates that Sec62 is an important antiviral factor that upregulates IRE1α-RIG-I-dependent antiviral innate immune responses, and FMDV evades antiviral host defense mechanism by downregulating Sec62-IRE1α/RIG-I.

Bi-functional gold nanocages enhance specific immunological responses of foot-and-mouth disease virus-like particles vaccine as a carrier and adjuvant.

Virus-like particle (VLP) vaccines have become one of the dominant vaccine candidates for foot-and-mouth disease (FMD). To further enhance the immunogenicity of VLP vaccines, gold nanocages (AuNCs) were selected as an adjuvant for the vaccine. Our experiments demonstrated that AuNCs had little biotoxicity in vivo and in vitro and improved the uptake of VLP in BHK-21 and RAW264.7 cell lines. The VLP-AuNCs activated DCs mainly through toll-like receptor 4 (TLR4) and promoted the secretion of IL-6, IL-1ß, and TNF-α. The conjugation of VLP and AuNCs triggered a strong immune response against FMD virus (FMDV) in mice and guinea pigs. The VLP-AuNCs significantly enhanced the proliferation of CD8+ T cells (P < 0.05) and the secretion of cellular immune-related cytokines (IFN-γ, P < 0.05; IL-12p70, P < 0.01) compared with VLP. The present study demonstrated that AuNCs, as a great potential adjuvant for FMDV VLP vaccines, significantly enhance the immune response.

NLRP3 inflammasome activation by Foot-and-mouth disease virus infection mainly induced by viral RNA and non-structural protein 2B.

Foot-and-mouth disease virus (FMDV) is a positive-strand RNA virus of the family Picornaviridae. Early studies show that some viruses of Picornaviridae, such as EMCV and EV71, induce NLRP3 inflammasome activation. Our current study demonstrates that FMDV induces the secretion of caspase-1 and interleukin 1 beta (IL-1ß), as well as activates the NLRP3 inflammasome in a dose- and time-dependent manner. Meanwhile, NLRP3 inflammasome can suppress FMDV replication during virus infection. Both FMDV RNA and viroporin 2B stimulate NLRP3 inflammasome activation. FMDV RNA triggers NLRP3 inflammasome through p-NF-κB/p65 pathway not dependent on RIG-I inflammasome. FMDV 2B activates NLRP3 inflammasome through elevation of intracellular ion, but not dependent on mitochondrial reactive oxygen species (ROS) and lysosomal cathepsin B. It further demonstrates that 2B viroporin activates NLRP3 inflammasome and induces IL-1ß in mice, which enhances the specific immune response against FMDV as an ideal self-adjuvant for FMD VLPs vaccine in guinea pigs. The results reveal a series of regulations between NLRP3 inflammasome complex and FMDV. Amino acids 140-145 of 2B is essential for forming an ion channel. By mutating the amino acid and changing the hydrophobic properties, the helical transmembrane region of the viroporin 2B is altered, so that the 2B is insufficient to trigger the activation of NLRP3 inflammasome. This study demonstrates the functions of FMDV RNA and 2B viroporin activate NLRP3 inflammasome and provides some useful information for the development of FMD vaccine self-adjuvant, which is also helpful for the establishment of effective prevention strategies by targeting NLRP3 inflammasome.

Effectiveness of application of carbon-fibre polymer-fabric resistive heating compared with forced-air warming to prevent unintentional intraoperative hypothermia in patients undergoing elective abdominal operations: A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Unintentional intraoperative hypothermia was regarded as a common intraoperative symptom with serious complications. The active warming strategies of forced-air warming (FAW) and carbon-fibre polymer-fabric resistive heating were considered to be effective interventions for preventing hypothermia. However, the effectiveness of them was not reported consistently. AIM: To evaluate the effectiveness of carbon-fibre polymer-fabric resistive heating compared with FAW in preventing hypothermia in patients undergoing elective surgeries. DESIGN: Systematic review and meta-analysis. METHODS: A rigorous systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting checklist. Searching strategy was undertaken on the electronic databases of Cumulative Index to Nursing and Allied Health Literature, MEDLINE, PubMed, EMBASE and Medical Literature Retrieval Service. The assessment of study quality was performed through risk of bias of Cochrane handbook of systematic review of interventions. Data synthesis was conducted through meta-analysis with sensitive analysis. The quality of evidence was graded using Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: A total of five randomised controlled trials with 282 patients undergoing elective surgeries were included in the quantitative synthesis. Four studies concluded that FAW was as effective as carbon-fibre polymer-fabric resistive heating in preventing hypothermia. However, one study yielded a different conclusion that the efficacy of FAW was superior to carbon-fibre polymer-fabric resistive heating with small incidence of hypothermia. Meta-analysis found that FAW was more effective than carbon-fibre polymer-fabric resistive heating in preventing hypothermia. CONCLUSIONS: In the elective abdominal surgery, carbon-fibre polymer-fabric resistive heating was less effective than FAW on the prevention of hypothermia. However, hypothermia still occurred in the FAW group. It was more objective to assess the efficacy of warming technology combining the incidence of hypothermia and the core body temperature together, which was suggested for further research.

A Network Meta-analysis of Randomized Controlled Trials Comparing Treatment Modalities for Infrapopliteal Lesions in Critical Limb Ischemia.

BACKGROUND: We aimed to conduct a network meta-analysis of randomized controlled trials comparing treatment modalities for infrapopliteal lesions in critical limb ischemia. METHODS: Five treatments for infrapopliteal lesions in critical limb ischemia were recognized. We compared primary patency, target lesion revascularization (TLR), major amputation at the 12-month follow-up, and technical success rate of the treatment modalities. RESULTS: Altogether, 11 studies (22 study arms; 1,330 patients) were considered eligible. The drug-eluting balloon (DEB) significantly increased primary patency compared with balloon angioplasty (BA; odds ratio [OR] 9.02, 95% confidence interval [CI] 3.18-25.55), the bare metal stent (BMS; OR 14.39, 95% CI 4.33-47.87), and the drug-eluting stent (DES; OR 3.70, 95% CI 1.20-11.11). The DES significantly increased primary patency compared with BA (OR 2.42, 95% CI 1.57-3.74) and BMS (OR 3.86, 95% CI 2.24-6.65). DES significantly increased the technical success rate compared with BA (OR 11.78, 95% CI 1.42-97.59). According to the value of the surface under the cumulative ranking curve (SUCRA), DEB was considered the best treatment in terms of primary patency (SUCRA = 99.7) and TLR (SUCRA = 70.7), and DES was considered the best treatment in terms of technical success rate (SUCRA = 90.6) and major amputation (SUCRA = 85.9). CONCLUSIONS: DEB has shown encouraging results in terms of primary patency for infrapopliteal lesions in critical limb ischemia; furthermore, DEB may be better than other treatments in terms of TLR. DES may be better than other treatments in terms of technical success and major amputation. In contrast, BA and BMS seem to be less effective treatment options.

Safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer drug-eluting stents: a meta-analysis of randomized trials.

BACKGROUND: The Orsiro biodegradable polymer sirolimus-eluting stent (O-SES) is a new-generation biodegradable polymer drug-eluting stent with the thinnest strut thickness to date developed to improve the percutaneous treatment of patients with coronary artery disease. We perform a meta-analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of an ultra-thin, Orsiro biodegradable polymer sirolimus-eluting stent (O-SES) compared with durable polymer drug-eluting stents (DP-DESs). METHODS: Medline, Embase, and CENTRAL databases were searched for randomized controlled trials comparing the safety and efficacy of O-SES versus DP-DES. Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. We used the Mantel-Haenszel method to calculate risk ratio (RR) by means of a random-effects model. RESULTS: Six RCTs with a total of 6949 patients were selected. All included trials were rated as low risk of bias. The O-SES significantly reduced the risk of myocardial infarction (RR 0.78, 95% confidence interval [CI] 0.62-0.98; I2 = 0%; 10 fewer per 1000 [from 1 fewer to 18 fewer]; high quality) compared with the DP-DES. There was no significant difference between O-SES and DP-DES in the prevention of stent thrombosis (RR: 0.75; 95% CI: 0.52-1.08), cardiac death (RR: 0.93; 95% CI: 0.63-1.36), target lesion revascularization (RR 1.10, 95% CI 0.86-1.42) and target vessel revascularization (RR 0.97, 95% CI 0.78-1.21). CONCLUSION: Among patients undergoing percutaneous coronary intervention, O-SES resulted in significantly lower rates of myocardial infarction than DP-DES and had a trend toward reduction in stent thrombosis.

Transcriptomic analysis identifies diagnostic genes in polycystic ovary syndrome and periodontitis.

PURPOSE: To investigate underlying co-mechanisms of PCOS and periodontitis through transcriptomic approach. METHODS: PCOS and periodontitis gene expression data were downloaded from the GEO database to identify differentially expressed genes. GO and KEGG pathway enrichment analysis and random forest algorithm were used to screen hub genes. GSEA analyzed the functions of hub genes. Correlations between hub genes and immune infiltration in two diseases were examined, constructing a TF-ceRNA regulatory network. Clinical samples were gathered from PCOS and periodontitis patients and RT-qPCR was performed to verify the connection. RESULTS: There were 1661 DEGs in PCOS and 701 DEGs in periodontitis. 66 intersected genes were involved and were enriched in immune and inflammation-related biological pathways. 40 common genes were selected from the PPI network. RF algorithm demonstrated that ACSL5, NLRP12, CCRL2, and CEACAM3 were hub genes, and GSEA results revealed their close relationship with antigen processing and presentation, and chemokine signaling pathway. RT-qPCR results confirmed the upregulated gene expression in both PCOS and periodontitis. CONCLUSION: The 4 hub genes ACSL5, NLRP12, CCRL2, and CEACAM3 may be diagnostic genes for PCOS and periodontitis. The created ceRNA network could provide a molecular basis for future studies on the association between PCOS and periodontitis.

Effect of Strontium-Substituted Calcium Phosphate Coatings Prepared by One-Step Electrodeposition at Different Temperatures on Corrosion Resistance and Biocompatibility of AZ31 Magnesium Alloys.

As potential degradable biomaterials, magnesium (Mg) alloys have development prospects in the field of orthopedic load-bearing, whereas the clinical application has encountered a bottleneck due to a series of problems caused by its rapid corrosion. In this study, strontium-substituted calcium phosphate (CaP) coatings with different structures were prepared on the surface of the Mg matrix by a simple one-step electrodeposition method at different temperatures, which enhanced the poor corrosion resistance of the Mg matrix. The coated sample prepared at 65 °C reduced the corrosion current density by 3 orders of magnitude and increased the impedance by nearly 2 orders of magnitude compared with bare Mg alloy, thanks to its dense fibrous structure similar to that of natural bones. Although the coating composition varies with different preparation temperatures, CaP, as an inorganic component similar to natural bone, has good cytocompatibility. Doping the right amount of strontium, which is a trace element in human bones, is beneficial to stimulate osteoblast differentiation, inhibit the activity of osteoclasts, and induce the formation of bone tissues. This provides a new option for modifying the Mg alloy with CaP coatings as a base.

Stearic Acid Treatment Enhancing Corrosion Resistance of Biomimetic-Deposited Calcium Phosphate Dihydrate Coating on Medical Degradable Magnesium Alloy.

Magnesium (Mg) alloys, a degradable material, have been studied for medical applications due to their excellent mechanical and chemical properties. However, their applications are limited by rapid corrosion. In this work, stearic acid and sodium stearate were used to treat the silane-induced calcium phosphate dihydrate coating to improve its protection for the Mg alloy further without changing the bone-like structure of calcium phosphate. The different effects of stearic acid treatment and sodium stearate treatment were compared. Electrochemical test and immersion test results confirmed that the corrosion resistance of the stearic acid-treated composite coating was greatly enhanced with a reduced corrosion current density by 3 orders of magnitude and hydrogen evolution reduced to 1/25 after 14 days. The stearic acid-treated coating also exhibited improved in vitro biocompatibility corroborated by promoted cell viability and better cell morphology.

Modulation of the differentiation of dental pulp stem cells by different concentrations of ß-glycerophosphate.

Dentinogenesis is a necessary prerequisite for dental tissue engineering. One of the steps for dentinogenesis is to obtain large quantities of highly purified odontoblasts. Therefore, we have undertaken an experiment applying different concentrations of ß-glycerophosphate (ß-GP) to induce the differentiation of dental pulp stem cells (DPSCs) in a long-term 28-day culture. In the meanwhile, we have studied the time- and maturation-dependent expression of matrix extracellular phosphoglycoprotein (MEPE) and that of the odontoblast-like marker-dentin sialoprotein (DSP), in order to investigate an optimized mineralized condition. Western blot results revealed that the expression of DSP became lower when accompanied by the increase of the ß-GP concentration, and there was also an influence on MEPE expression when different concentrations of ß-GP were applied. Meanwhile, the mineralized groups had an inhibitory function on the expression of MEPE as compared with the control group. Above all, all experimental groups successfully generated mineralized nodules by Alizarin Red S and the 5 mM ß-GP group formed more mineralized nodules quantitated using the CPC extraction method. In conclusion, there is a significant modulation of the ß-GP during the differentiation of the DPSCs. The degree of odontoblast differentiation is ß-glycerophosphate concentration dependent. A low concentration of ß-GP (5 mM) has been shown to be the optimal concentration for stimulating the maturation of the DPSCs. Moreover, MEPE accompanied with DSP clearly demonstrates the degree of the differentiation.

Corrosion Resistance and Biocompatibility of Calcium Phosphate Coatings with a Micro-Nanofibrous Porous Structure on Biodegradable Magnesium Alloys.

Magnesium (Mg) and its alloys have exhibited great potential for orthopedic applications; however, their poor corrosion resistance and potential cytotoxicity have hindered their further clinical applications. In this study, we prepared a calcium phosphate (Ca-P) coating with a micro-nanofibrous porous structure on the Mg alloy surface by a chemical conversion method. The morphology, composition, and corrosion performance of the coatings were investigated by scanning electron microscope (SEM), energy-dispersive spectrometer (EDS), X-ray diffraction (XRD), immersion tests, and electrochemical measurements. The effects of the preparation temperature of the Ca-P coatings were analyzed, and the results confirmed that the coating obtained at 60 °C had the densest structure and the best corrosion resistance. In addition, a systematic investigation into cell viability, ALP activity, and cell morphology confirmed that the Ca-P coating had excellent biocompatibility, which could effectively promote the proliferation, differentiation, and adhesion of osteoblasts. Hence, the Ca-P coating demonstrates great potential in the field of biodegradable Mg-based orthopedic implant materials.

Promoting Lignin Valorization by Coping with Toxic C1 Byproducts.

The toxic C1 compounds methanol and formaldehyde are generated during bioconversion of lignin into value-added chemicals. These toxins can be detoxified and assimilated by methylotrophs to synthesize useful metabolites and cell biomass. We discuss the promising future of constructing integrated biosystems to use toxic C1 byproducts and promote lignin valorization.

Sec62 Regulates Endoplasmic Reticulum Stress and Autophagy Balance to Affect Foot-and-Mouth Disease Virus Replication.

Endoplasmic reticulum (ER) stress-induced autophagy is closely associated with viral infection and propagation. However, the intrinsic link between ER stress, autophagy, and viral replication during foot-and-mouth disease virus (FMDV) infection is not fully elucidated. Our previous studies demonstrated that FMDV infection activated the ER stress-associated UPR of the PERK-eIF2a and ATF6 signaling pathway, whereas the IRE1a signaling was suppressed. We found that the activated-ATF6 pathway participated in FMDV-induced autophagy and FMDV replication, while the IRE1α pathway only affected FMDV replication. Further studies indicated that Sec62 was greatly reduced in the later stages of FMDV infection and blocked the activation of the autophagy-related IRE1α-JNK pathway. Moreover, it was also found that Sec62 promoted IRE1a phosphorylation and negatively regulated FMDV proliferation. Importantly, Sec62 may interact with LC3 to regulate ER stress and autophagy balance and eventually contribute to FMDV clearance via fusing with lysosomes. Altogether, these results suggest that Sec62 is a critical molecule in maintaining and recovering ER homeostasis by activating the IRE1α-JNK pathway and delivering autophagosome into the lysosome, thus providing new insights on FMDV-host interactions and novel antiviral therapies.

Investigation of microstructure and dissimilar materials connection patterns of mantis shrimp saddle.

The microstructure and dissimilar materials connection patterns of mantis shrimp saddle were investigated. The outer layer with layered helical structure and inner layer with slablike laminae structure constructed the microstructure characteristics of saddle. The merus and membrane were characterized by layered structure. The lamina of saddle connected the corresponding lamina in merus and membrane, building the continuous and smooth coupling connection patterns. The entitative "hard-hard" and "hard-soft" transitions of dissimilar materials at micro level enhanced the steady transmit of driven force. The saddle exhibited high mechanical strength. With the increase of in-situ tensile displacement, the number of fractured fragments on saddle outer layer surface increased, which subjected to tensile load and defused the damage in the form of mineralized surface fragmentation. In the inner part of saddle, the fracture of mineralized laminae and crack deflection mechanisms bore the tensile load influence. The combination of microstructure with high mechanical strength and continues micro lamina connection endowed the concise dissimilar materials connection and efficient elastic energy storage property of saddle, which can be treated as the bionic models for design and preparation of fiber reinforced resin composite, hyperelastic material and so on.

The microstructure, mechanical properties, corrosion performance and biocompatibility of hydroxyapatite reinforced ZK61 magnesium-matrix biological composite.

Magnesium (Mg)-based composites, as biomaterials, have attracted widespread attention due to their adjustable mechanical properties like elastic modulus, ductility, ultimate tensile strength, and corrosion resistance. In this study, hydroxyapatite (HA) reinforced ZK61 Mg-matrix composites were prepared by powder metallurgy and hot extrusion methods. The influence of the content of HA (10 wt%, 20 wt%, and 30 wt%) on the microstructure, density, mechanical properties, corrosion property and biocompatibility were investigated. The results showed that the density and yield strength of the composites match those of natural bone. Moreover, the composite with 10 % HA (ZK61-10HA) exhibited the best corrosion resistance, as determined by the electrochemical measurement and immersion test in simulated body fluid (SBF) at 37 °C. In addition, the ZK61-10HA composite significantly enhanced the cell viability (≥78 %) compared with ZK61 alloy in vitro testing. It is demonstrated that the mechanical properties, corrosion resistance and biocompatibility of Mg alloy can be effectively controlled by adjusting the content of HA, which suggested that the ZK61-HA composites were promising candidates for degradable implant materials.