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Magnesium (Mg) and Mg alloys are considered as potential candidates for biomedical applications because of their high specific strength, low density, and elastic modulus, degradability, good biocompatibility and biomechanical compatibility. However, the rapid corrosion rate of Mg alloys results in premature loss of mechanical integrity, limiting their clinical application in load-bearing parts. Besides, the low strength of Mg alloys restricts their further application. Thus, it is essential to understand the characteristics and influencing factors of mechanical and corrosion behavior, as well as the methods to improve the mechanical performances and corrosion resistance of Mg alloys. This paper reviews the recent progress in elucidating the corrosion mechanism, optimizing the composition, and microstructure, enhancing the mechanical performances, and controlling the degradation rate of Mg alloys. In particular, the research progress of surface modification technology of Mg alloys is emphasized. Finally, the development direction of biomedical Mg alloys in the future is prospected.

Thousands of different nanoparticles (NPs) involve in our daily life with various origins from food, cosmetics, drugs, etc. It is believed that decreasing the size of materials up to nanometer levels can facilitate their unfavorable absorption since they can pass the natural barriers of live tissues and organs even, they can go across the relatively impermeable membranes. The interaction of these NPs with the biological environment disturbs the natural functions of cells and its components and cause health issues. In the lack of the detailed and comprehensive standard protocols about the toxicity of NPs materials, their control, and effects, this review study focuses on the current research literature about the related factors in toxicity of NPs such as size, concentration, etc. with an emphasis on metal and metal oxide nanoparticles. The goal of the study is to highlight their potential hazard and the advancement of green non-cytotoxic nanomaterials with safe threshold dose levels to resolve the toxicity issues. This study supports the NPs design along with minimizing the adverse effects of nanoparticles especially those used in biological treatments.Thousands of different nanoparticles (NPs) involve in our daily life with various origins from food, cosmetics, drugs, etc. It is believed that decreasing the size of materials up to nanometer levels can facilitate their unfavorable absorption since they can pass the natural barriers of live tissues and organs even, they can go across the relatively impermeable membranes. The interaction of these NPs with the biological environment disturbs the natural functions of cells and its components and cause health issues. In the lack of the detailed and comprehensive standard protocols about the toxicity of NPs materials, their control, and effects, this review study focuses on the current research literature about the related factors in toxicity of NPs such as size, concentration, etc. with an emphasis on metal and metal oxide nanoparticles. The goal of the study is to highlight their potential hazard and the advancement of green non-cytotoxic nanomaterials with safe threshold dose levels to resolve the toxicity issues. This study supports the NPs design along with minimizing the adverse effects of nanoparticles especially those used in biological treatments.

Depending on the requirements of specific applications, implanted materials including metals, ceramics, and polymers have been used in various disciplines of medicine. Titanium and its alloys as implant materials play a critical role in the orthopedic and dental procedures. However, they still require the utilization of surface modification technologies to not only achieve the robust osteointegration but also to increase the antibacterial properties, which can avoid the implant-related infections. This article aims to provide a summary of the latest advances in surface modification techniques, of titanium and its alloys, specifically in biomedical applications. These surface techniques include plasma spray, physical vapor deposition, sol-gel, micro-arc oxidation, etc. Moreover, the microstructure evolution is comprehensively discussed, which is followed by enhanced mechanical properties, osseointegration, antibacterial properties, and clinical outcomes. Future researches should focus on the combination of multiple methods or improving the structure and composition of the composite coating to further enhance the coating performance.Depending on the requirements of specific applications, implanted materials including metals, ceramics, and polymers have been used in various disciplines of medicine. Titanium and its alloys as implant materials play a critical role in the orthopedic and dental procedures. However, they still require the utilization of surface modification technologies to not only achieve the robust osteointegration but also to increase the antibacterial properties, which can avoid the implant-related infections. This article aims to provide a summary of the latest advances in surface modification techniques, of titanium and its alloys, specifically in biomedical applications. These surface techniques include plasma spray, physical vapor deposition, sol-gel, micro-arc oxidation, etc. Moreover, the microstructure evolution is comprehensively discussed, which is followed by enhanced mechanical properties, osseointegration, antibacterial properties, and clinical outcomes. Future researches should focus on the combination of multiple methods or improving the structure and composition of the composite coating to further enhance the coating performance.

Alcohol significantly contributes to pancreatitis, causing high global mortality and health burden. This study examines trends in alcohol-attributable pancreatitis (AAP) from 1990 to 2021 using Global Burden of Disease (GBD) 2021 data, focusing on demographic, temporal, and regional variations to inform policymaking. AAP-related deaths and disability-adjusted life years (DALYs) were analyzed across 204 countries from 1990 to 2021, stratified by Sociodemographic Index (SDI), gender, and age groups. An age-period-cohort model assessed age-standardized DALY rates (ASDR), and decomposition analysis quantified impacts of population growth, aging, and epidemiological changes. AAP-related DALYs rose from 401,700 in 1990 to 699,300 in 2021, though ASDR and ASMR showed declines globally. Burden increased notably in low and lower-middle SDI regions, especially among those under 40, while high SDI regions achieved better control. Males faced a disproportionately high burden due to alcohol consumption patterns, although some regions saw rising female burdens. Low-SDI areas suffered from limited healthcare, increasing alcohol use, and weak policies, with younger populations contributing significantly to rising burdens. Projections estimate 1.146 million DALYs annually by 2050, with males comprising over 90%. A GBD-AAP visualization platform was developed to present burden data and trends. AAP exhibits significant regional and gender disparities. Targeted measures, including alcohol regulation, resource allocation, and public health education, are critical in low-SDI regions and among young males to mitigate AAP burden. The GBD-AAP platform offers valuable tool for targeted interventions. •Young populations, particularly in lower SDI regions, showed rising AAP burden.•SDI and ASDR had a positive correlation in low SDI regions, and negative in high SDI.•Policies targeting alcohol consumption and healthcare access are critical for AAP control.•Tailored interventions are necessary across SDI levels to address global AAP challenges.•We have developed a visualization platform, GBD-AAP, to present burden data and predict trends.

With the continuous progress and development in biomedicine, metallic biomedical materials have attracted significant attention from researchers. Due to the low compatibility of traditional metal implant materials with the human body, it is urgent to develop new biomaterials with excellent mechanical properties and appropriate biocompatibility to solve the adverse reactions caused by long-term implantation. High entropy alloys (HEAs) are nearly equimolar alloys of five or more elements, with huge compositional design space and excellent mechanical properties. In contrast, biological high-entropy alloys (Bio-HEAs) are expected to be a new bio-alloy for biomedicine due to their excellent biocompatibility and tunable mechanical properties. This review summarizes the composition system of Bio-HEAs in recent years, introduces their biocompatibility and mechanical properties of human bone adaptation, and finally puts forward the following suggestions for the development direction of Bio-HEAs: to improve the theory and simulation studies of Bio-HEAs composition design, to quantify the influence of composition, process, post-treatment on the performance of Bio-HEAs, to focus on the loss of Bio-HEAs under actual service conditions, and it is hoped that the clinical application of the new medical alloy Bio-HEAs can be realized as soon as possible.

As the unique cell type in articular cartilage, chondrocyte senescence is a crucial cellular event contributing to osteoarthritis development. Here we show that clathrin-mediated endocytosis and activation of Notch signaling promotes chondrocyte senescence and osteoarthritis development, which is negatively regulated by myosin light chain 3. Myosin light chain 3 (MYL3) protein levels decline sharply in senescent chondrocytes of cartilages from model mice and osteoarthritis (OA) patients. Conditional deletion of Myl3 in chondrocytes significantly promoted, whereas intra-articular injection of adeno-associated virus overexpressing MYL3 delayed, OA progression in male mice. MYL3 deficiency led to enhanced clathrin-mediated endocytosis by promoting the interaction between myosin VI and clathrin, further inducing the internalization of Notch and resulting in activation of Notch signaling in chondrocytes. Pharmacologic blockade of clathrin-mediated endocytosis-Notch signaling prevented MYL3 loss-induced chondrocyte senescence and alleviated OA progression in male mice. Our results establish a previously unknown mechanism essential for cellular senescence and provide a potential therapeutic direction for OA. Age is the greatest risk factor for osteoarthritis (OA) and chondrocyte senescence is an important cellular event that contributes to OA development. This study shows that clathrin-mediated endocytosis and activation of Notch signaling promotes articular chondrocyte senescence and OA development, which is negatively regulated by myosin light chain 3 (MYL3).

Design an implant similar to the human bone is one of the critical problems in bone tissue engineering. Metal porous scaffolds have good prospects in bone tissue replacement due to their matching elastic modulus, better strength, and biocompatibility. However, traditional processing methods are challenging to fabricate scaffolds with a porous structure, limiting the development of porous scaffolds. With the advancement of additive manufacturing (AM) and computer-aided technologies, the development of porous metal scaffolds also ushers in unprecedented opportunities. In recent years, many new metal materials and innovative design methods are used to fabricate porous scaffolds with excellent mechanical properties and biocompatibility. This article reviews the research progress of porous metal scaffolds, and introduces the AM technologies used in porous metal scaffolds. Then the applications of different metal materials in bone scaffolds are summarized, and the advantages and limitations of various scaffold design methods are discussed. Finally, we look forward to the development prospects of AM in porous metal scaffolds.

Titanium and its alloys have superb biocompatibility, low elastic modulus, and favorable corrosion resistance. These exceptional properties lead to its wide use as a medical implant material. Titanium itself does not have antibacterial properties, so bacteria can gather and adhere to its surface resulting in infection issues. The infection is among the main reasons for implant failure in orthopedic surgeries. Nano-modification, as one of the good options, has the potential to induce different degrees of antibacterial effect on the surface of implant materials. At the same time, the nano-modification procedure and the produced nanostructures should not adversely affect the osteogenic activity, and it should simultaneously lead to favorable antibacterial properties on the surface of the implant. This article scrutinizes and deals with the surface nano-modification of titanium implant materials from three aspects: nanostructures formation procedures, nanomaterials loading, and nano-morphology. In this regard, the research progress on the antibacterial properties of various surface nano-modification of titanium implant materials and the related procedures are introduced, and the new trends will be discussed in order to improve the related materials and methods.

Vacuolar processing enzymes (VPEs) have received considerable attention due to their caspase-1-like activity and ability to regulate programmed cell death (PCD), which plays an essential role in the development of stenospermocarpic seedless grapes ovules. To characterize VPEs and the relationship between stenospermocarpic grapes and the VPE gene family, we identified 3 Vitis vinifera VPE genes (VvβVPE, VvγVPE, and VvδVPE) from the PN40024 grape genome and cloned the full-length complementary DNAs (cDNAs) from the 'Vitis vinifera cv. Pinot Noir' and 'Vitis vinifera cv. Thompson Seedless' varietals. Each of the VPEs contained a typical catalytic dyad [His (177), Cys (219)] and substrate binding pocket [Arg (112), Arg (389), Ser (395)], except that Ser (395) in the VvγVPE protein sequence was replaced with alanine. Phylogenetic analysis of 4 Arabidopsis thaliana and 6 Vitis vinifera VPEs revealed that the 10 VPEs form 3 major branches. Furthermore, the 6 grapevine VPEs share a similar gene structure, with 9 exons and 8 introns. The 6 grapevine VPEs are located on 3 different chromosomes. We also tested the enzymatic activity of recombinant VPEs expressed in the Pichia Pastoris expression system and found that the VvVPEs exhibit cysteine peptidase activity. Tissue-specific expression analysis showed that VvδVPE is only expressed in flowers, buds and ovules, that VvγVPE is expressed in various tissues, and that VvβVPE was expressed in roots, flowers, buds and ovules. The results of quantitative real-time PCR (qRT-PCR) suggested that VvβVPE in seeded grapes increased significantly at 30 days after full-bloom (DAF), close to the timing of endosperm abortion at 32 DAF. These results suggested that VvβVPE is related to ovule abortion in seedless grapes. Our experiments provide a new perspective for understanding the mechanism of stenospermocarpic seedlessness and represent a useful reference for the further study of VPEs.

It is uncertain whether metformin use is associated with reduced risk of joint replacement in patients with type 2 diabetes mellitus. We aimed to establish whether metformin use was associated with a reduced risk of total knee replacement (TKR) or total hip replacement (THR) among these patients. We selected patients with type 2 diabetes mellitus that was diagnosed between 2000 and 2012 from the Taiwan National Health Insurance Research Database. We used prescription time-distribution matching and propensity-score matching to balance potential confounders between metformin users and nonusers. We assessed the risks of TKR or THR using Cox proportional hazards regression. We included 20 347 participants who were not treated with metformin and 20 347 who were treated with metformin, for a total of 40 694 participants (mean age 63 yr, standard deviation 11 yr; 49.8% were women) after prescription time-distribution matching. Compared with participants who did not use metformin, those who used metformin had lower risks of TKR or THR (adjusted hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.60–0.81 for TKR or THR; adjusted HR 0.71, 95% CI 0.61–0.84 for TKR; adjusted HR 0.61, 95% CI 0.41–0.92 for THR) after adjustment for covariates. Propensity-score matching analyses (10 163 participants not treated with metformin v. 10 163 treated with metformin) and sensitivity analyses using inverse probability of treatment weighting and competing risk regression showed similar results. Metformin use in patients with type 2 diabetes mellitus was associated with a significantly reduced risk of total joint replacement. Randomized controlled clinical trials in patients with osteoarthritis are warranted to determine whether metformin is effective in decreasing the need for joint replacement.