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Bone defects in diabetes mellitus (DM) remain a major challenge for clinical treatment. Fluctuating glucose levels in DM patients lead to excessive production of reactive oxygen species (ROS), which disrupt bone repair homeostasis. Bone filler materials have been widely used in the clinical treatment of DM-related bone defects, but overall they lack efficacy in improving the bone microenvironment and inducing osteogenesis. We utilized a gelatine methacrylate (GelMA) hydrogel with excellent biological properties in combination with molybdenum (Mo)-based polyoxometalate nanoclusters (POM) to scavenge ROS and promote osteoblast proliferation and osteogenic differentiation through the slow-release effect of POM, providing a feasible strategy for the application of biologically useful bone fillers in bone regeneration. We synthesized an injectable hydrogel by gelatine methacrylate (GelMA) and POM. The antioxidant capacity and biological properties of the synthesized GelMA/POM hydrogel were tested. In vitro, studies showed that hydrogels can inhibit excessive reactive oxygen species (ROS) and reduce oxidative stress in cells through the beneficial effects of pH-sensitive POM. Osteogenic differentiation assays showed that GelMA/POM had good osteogenic properties with upregulated expression of osteogenic genes (BMP2, RUNX2, Osterix, ALP). Furthermore, RNA-sequencing revealed that activation of the PI3K/Akt signalling pathway in MC3T3-E1 cells with GelMA/POM may be a potential mechanism to promote osteogenesis. In an in vivo study, radiological and histological analyses showed enhanced bone regeneration in diabetic mice, after the application of GelMA/POM. In summary, GelMA/POM hydrogels can enhance bone regeneration by directly scavenging ROS and activating the PI3K/Akt signalling pathway.

Liao X, Shen M, Li T, et al. Int J Nanomedicine. 2023;18:5925-5942. The authors wish to advise, following publication of the article they identified errors were made during the collection and organization of data for Figures 3 and 4 on pages 5934 and 5935, respectively. The correct Figures 3 and 4 are as follows. Figure 3 Antioxidant properties of POM or hydrogel. (A) DCFH-DA assay showing intracellular ROS of MC3T3-E1 after incubation with POM in the presence of H2O2 (100 μM). (B) Quantification analysis of DCFH-DA staining (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (C) Cell capacity of migration (scratch test). (D) Quantitative analysis of percent migration in scratch assay. (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (E) Live/dead staining showing MC3T3-E1 cell viability after culturing on hydrogel in the presence of H2O2. (F) Quantification analysis of live cells. (*And #Indicate p < 0.05 in comparison with the H2O2 group and GelMA group, respectively.) (G) LSCM images showing MC3T3-E1 cultured on different hydrogels following H2O2 treatment. (n = 3, each group). (H2O2, cells cultured on the tissue culture plate with H2O2). Scale bar: 200 μm (A), 200 μm (C), 100 μm (E) and 100 μm (G). Figure 4 The osteogenesis properties of GelMA/POM hydrogel in vitro. In vitro assay of effects of hydrogel on ALP activity and extracellular calcium nodule production during osteogenesis differentiation of MC3T3-E1. (A) Alizarin red S staining. (B) Quantitative analysis of mineralized nodules. (C) Alkaline phosphatase activity. (D) Alkaline phosphatase staining. (*, # And a indicate p < 0.05 in comparison with the Control group, H2O2 group and GelMA group, respectively). (Control, cells cultured without H2O2). (n = 3, each group). Scale bar: 200 μm (A) and 200 μm (D). The authors advise these corrections do not significantly impact the overall findings and conclusions of the article or alter the interpretations or validity of the research. The authors apologize for any confusion these errors may have caused and appreciate the opportunity to rectify them.

Abiotic stresses are major environmental conditions that reduce plant growth, productivity and quality. Protein-protein interaction (PPI) approaches can be used to screen stress-responsive proteins and reveal the mechanisms of protein response to various abiotic stresses. Biotin-based proximity labeling (PL) is a recently developed technique to label proximal proteins of a target protein. TurboID, a biotin ligase produced by directed evolution, has the advantages of non-toxicity, time-saving and high catalytic efficiency compared to other classic protein-labeling enzymes. TurboID-based PL has been successfully applied in animal, microorganism and plant systems, particularly to screen transient or weak protein interactions, and detect spatially or temporally restricted local proteomes in living cells. This review concludes classic PPI approaches in plant response to abiotic stresses and their limitations for identifying complex network of regulatory proteins of plant abiotic stresses, and introduces the working mechanism of TurboID-based PL, as well as its feasibility and advantages in plant abiotic stress research. We hope the information summarized in this article can serve as technical references for further understanding the regulation of plant adaptation to abiotic stress at the protein level.

Purpose To investigate the relationship between baseline optical coherence tomography (OCT) features of wet age-related macular degeneration (wAMD) and prognosis, and evaluate anti-VEGF treatment effects under varying baseline OCT conditions. Methods This retrospective study included patients diagnosed with wAMD who underwent monthly anti-VEGF therapy for 1–3 months. Baseline, one-month, and three-month OCTs recorded morphological features. Treatment effectiveness was defined as central retinal thickness (CRT) reduction ≥ 25%, or absence of subretinal fluid (SRF) and intraretinal fluids (IRF) post-treatment. Results Data from 251 eyes were analyzed. After one injection, effective responders had smaller baseline lesion sizes (11.01 ± 9.93 vs. 12.53 ± 8.80, P  = 0.046), lower PED height (124.10 ± 232.55 vs. 216.06 ± 248.66, P  < 0.001), and larger baseline IRF (86.52 ± 154.74 vs. 31.26 ± 81.14, P  = 0.002) compared to non-responders. After three injections, effective responders continued to show larger baseline IRF (65.94 ± 135.20 vs. 20.28 ± 61.93, P  = 0.015). Multivariate analysis indicated greater CRT reductions at one and three months were associated with larger baseline CRT ( P  < 0.001), larger baseline IRF ( P  < 0.001 and P  = 0.012), and absence of retinal hemorrhage ( P  = 0.003). Conclusions Baseline OCT features significantly influence treatment responsiveness in wAMD. Tailoring anti-VEGF regimens based on these features may improve outcomes.

Background To date, the mechanisms underlying the relationship between sensory impairment and new-onset arthritis remain inadequately understood. This study aims to investigate the mediating role of depressive symptoms in the longitudinal association between sensory impairment and new-onset arthritis, specifically focusing on visual impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI). Objectives This study aimed to elucidate the associative dynamics between various sensory impairments and the risk of developing new-onset arthritis, with a specific focus on the mediating influence of depressive symptoms. By understanding these interconnections, we seek to provide insights that could inform targeted interventions aimed at mitigating arthritis onset in older adults. Methods Utilizing data derived from the 2011 China Health and Retirement Longitudinal Study (CHARLS), a cohort of 8,415 participants aged 45 years and older was analyzed. Participants were categorized based on their sensory status into four groups: no impairment, VI only, HI only, and DSI. A multivariate logistic regression analysis was employed to assess the association between sensory impairments and the incidence of arthritis over a four-year follow-up period, supplemented by subgroup analyses and mediation analysis to explore the mediating role of depressive symptoms. Results Among 8,415 participants who were free of arthritis at baseline (2011), 1,554 developed arthritis by 2015. In fully adjusted models, visual impairment (VI), hearing impairment (HI), and dual sensory impairment (DSI) were each found to be associated with higher odds of incident arthritis (VI: aOR = 1.32; HI: aOR = 1.39; DSI: aOR = 1.34). In a four-category analysis, using individuals with no sensory impairment as the reference group, the results indicated that VI only (aOR = 1.29, 95% CI 1.07–1.56), HI only (aOR = 1.60, 95% CI 1.21–2.12), and DSI (aOR = 1.65, 95% CI 1.38–1.96) were associated with elevated risks. Mediation analysis revealed that depressive symptoms partially explained these associations, accounting for 18.28% of the VI–arthritis association, 12.70% for HI, and 15.69% for DSI. The findings were consistent across secondary analyses. Conclusion The findings of this study highlight that sensory impairments are significantly associated with an increased risk of arthritis among older Chinese adults, with depressive symptoms serving as a partial mediator. These results underscore the importance of integrating mental health management into the care strategies for individuals with sensory disabilities. Future research should explore intervention strategies aimed at addressing both sensory impairments and mental health to further reduce the incidence of arthritis in this vulnerable demographic.

Purpose This study aims to investigate the factors influencing changes in the kappa angle following cataract surgery. Methods A total of 95 eyes undergoing cataract surgery were included in this study. Preoperative and postoperative ocular biometric data were collected to analyze the factors influencing changes in the kappa angle after surgery. Results This study found a significant reduction in the magnitude of the kappa angle after surgery compared to the preoperative values.(0.25 ± 0.16 vs. 0.20 ± 0.14, P  < 0.001) The preoperative kappa angle magnitude was positively correlated with pupil size ( R  = 0.282, P  = 0.006), axial length ( R  = 0.274, P  = 0.009) and BK1 orientation of the posterior corneal surface ( R  = 0.258, P  = 0.011). The postoperative kappa angle magnitude was associated with the preoperative axial length ( R  = 0.296, P  = 0.005), pupil size ( R  = 0.259, P  = 0.011), and preoperative kappa angle magnitude ( R  = 0.478, P  < 0.001). The change in kappa angle magnitude was positively correlated only with the preoperative kappa angle magnitude ( R  = 0.623, P  < 0.001). Conclusion This study suggests that larger preoperative kappa angles may undergo greater reduction after cataract surgery, potentially explaining why some patients with large kappa angles do not develop significant optical discomfort following multifocal IOL implantation.

• Plant organs often grow into a genetically determined size and shape. How organ growth is finely regulated to achieve a well defined pattern is a fascinating, but largely unresolved, question in plant research. • We utilised the Arabidopsis petal to study the genetic control of plant organ growth, and identify two closely related U-box E3 ligases PUB25 and PUB26 as important growth regulators by screening the targets of the petal-specific growth-promoting transcription factor RABBIT EARS (RBE). • We showed that PUB25 is directly controlled by RBE in petal development in a spatial- and temporal-specific manner and acts as a major target to mediate RBE’s function in petal growth. We also showed that PUB25 and PUB26 repress petal growth by restricting the period of cell proliferation, and their regulation appears to be independent of other plant E3 ligase genes implicated in growth control. • PUB25 and PUB26 are among the first U-box E3 ligases shown to function in plant growth control. Furthermore, as they were also found to play a vital role in plant stress responses, PUB25 and PUB26 may act as a key hub to integrate developmental and environmental signals for balancing growth and defence in plants.

Background The relationship between gout pathogenesis and inflammatory cytokine alterations remains uncertain, with inconsistent findings across studies. This study evaluated the causal links between gout and 41 inflammatory cytokines using Mendelian randomization (MR). Methods Gout-related genetic variants were examined in two large public databases: the Finnish database with 8489 gout patients and 240,862 European ancestry controls and the Genome-Wide Association Studies (GWAS) catalog dataset with 375 gout cases and 455,973 European ancestry controls. Cytokine levels in 8293 healthy participants from the GWAS were analyzed. Moreover, univariate MR analysis, primarily the inverse variance weighting method, was applied to examine the causal association between these factors. The findings were further validated using four additional MR methods based on different modeling assumptions, and their robustness was examined through sensitivity analysis using the MR leave-one-out analysis, Cochran’s Q test, MR-Egger intercept test, and linkage disequilibrium score regression analysis. Results Following Bonferroni correction, this study unveiled a potential connection between macrophage inflammatory protein-1 beta (MIP 1B) and the risk of gout (OR: 1.08, 95%CI: 1.03-1.13, p = 9.61 × 10-4). Additionally, growth-regulated oncogene alpha (GROA) and macrophage migration inhibitory factor (MIF) were implicated in downstream gout development (OR: 1.04, 95%CI: 1.01-1.08, p = 0.02; OR = 1.04, 95%CI: 1.01-1.07, p = 0.0079). Sensitivity analyses confirmed the findings’ reliability and consistency. Conclusion Our study suggests that MIP 1B may be a risk factor for gout, and inflammatory cytokines such as GROA and MIF are involved in the progression of gout. This supports a causal relationship between inflammatory cytokines and gout.

Summary MiRNAs are important posttranscriptional regulators of plant development. Many miRNAs, such as the conserved miR164 species, are encoded by families of MIRNA genes, but the specific roles of individual MIRNA genes are largely undefined. Here, we characterize the functions and regulatory mechanisms of SlMIR164A, one of the primary genes of Sly‐miR164, in tomato. We show that SlMIR164A is preferentially expressed at late stages of fruit development and plays a vital role in controlling fruit ripening and quality. Loss of function of SlMIR164A by CRISPR/Cas9‐mediated mutagenesis results in accelerated fruit ripening and enhanced chloroplast development, which leads to altered sugar and organic acid contents and affects the nutritional quality of fruits. We also show that SlMIR164A modulates fruit ripening and quality through specific target genes, SlNAM2 and SlNAM3, which control key regulators of chloroplast function and fruit ripening processes. MIR164 genes have been shown to play conserved roles in regulating organ ageing, such as leaf senescence and fruit ripening, in a variety of plants, but whether and how their family members in tomato exert the same function remain to be elucidated. Our results reveal a previously undiscovered role of SlMIR164A in ripening control, which will further our understanding of the actions of MIR164 family, as well as the mechanisms of fruit ripening and quality control in tomato. Moreover, as loss of SlMIR164A exhibits minor impacts on organ morphology, our results can be leveraged in tomato breeding for specific manipulation of fruit ripening and quality to facilitate tomato improvement in agriculture. In this report, we show that Sly‐miR164 produced from SlMIR164A acts through its target genes NAM2/NAM3 to regulate fruit chloroplast function and fruit ripening, which together impact fruit quality in tomato.