A water transfer printing method for contact lenses surface 2D MXene modification to resist bacterial infection and inflammation.

Contact lenses (CLs) are prone to adhesion and invasion by pollutants and pathogenic bacteria, leading to infection and inflammatory diseases. However, the functionalization of CL (biological functions such as anti-fouling, antibacterial, and anti-inflammatory) and maintaining its transparency still face great challenges. In this work, as a member of the MXenes family, vanadium carbide (V2C) is modified onto CL via a water transfer printing method after the formation of a tightly arranged uniform film at the water surface under the action of the Marangoni effect. The coating interface is stable owing to the electrostatic forces. The V2C-modified CL (V2C@CL) maintains optical clarity while providing good biocompatibility, strong antioxidant properties, and anti-inflammatory activities. In vitro antibacterial experiments indicate that V2C@CL shows excellent performance in bacterial anti-adhesion, sterilization, and anti-biofilm formation. Last, V2C@CL displays notable advantages of bacteria elimination and inflammation removal in infectious keratitis treatment.

An Antibiotic Nanobomb Constructed from pH-Responsive Chemical Bonds in Metal-Phenolic Network Nanoparticles for Biofilm Eradication and Corneal Ulcer Healing.

In the treatment of refractory corneal ulcers caused by Pseudomonas aeruginosa, antibacterial drugs delivery faces the drawbacks of low permeability and short ocular surface retention time. Hence, novel positively-charged modular nanoparticles (NPs) are developed to load tobramycin (TOB) through a one-step self-assembly method based on metal-phenolic network and Schiff base reaction using 3,4,5-trihydroxybenzaldehyde (THBA), ε-poly-ʟ-lysine (EPL), and Cu2+ as matrix components. In vitro antibacterial test demonstrates that THBA-Cu-TOB NPs exhibit efficient instantaneous sterilization owing to the rapid pH responsiveness to bacterial infections. Notably, only 2.6 µg mL-1 TOP is needed to eradicate P. aeruginosa biofilm in the nano-formed THBA-Cu-TOB owing to the greatly enhanced penetration, which is only 1.6% the concentration of free TOB (160 µg mL-1). In animal experiments, THBA-Cu-TOB NPs show significant advantages in ocular surface retention, corneal permeability, rapid sterilization, and inflammation elimination. Based on molecular biology analysis, the toll-like receptor 4 and nuclear factor kappa B signaling pathways are greatly downregulated as well as the reduction of inflammatory cytokines secretions. Such a simple and modular strategy in constructing nano-drug delivery platform offers a new idea for toxicity reduction, physiological barrier penetration, and intelligent drug delivery.

Dihydroartemisinin alleviates erosive bone destruction by modifying local Treg cells in inflamed joints: A novel role in the treatment of rheumatoid arthritis.

Treg cell-based therapy has exhibited promising efficacy in combatting rheumatoid arthritis (RA). Dihydroartemisinin (DHA) exerts broad immunomodulatory effects across various diseases, with its recent spotlight on T-cell regulation in autoimmune conditions. The modulation of DHA on Treg cells and its therapeutic role in RA has yet to be fully elucidated. This study seeks to unveil the influence of DHA on Treg cells in RA and furnish innovative substantiation for the potential of DHA to ameliorate RA. To this end, we initially scrutinized the impact of DHA-modulated Treg cells on osteoclast (OC) formation in vitro using Treg cell-bone marrow-derived monocyte (BMM) coculture systems. Subsequently, employing the collagen-induced arthritis (CIA) rat model, we validated the efficacy of DHA and probed its influence on Treg cells in the spleen and popliteal lymph nodes (PLN). Finally, leveraging deep proteomic analysis with data-independent acquisition (DIA) and parallel accumulation-serial fragmentation (PASEF) technology, we found the alterations in the Treg cell proteome in PLN by proteomic analysis. Our findings indicate that DHA augmented suppressive Treg cells, thereby impeding OC formation in vitro. Consistently, DHA mitigated erosive joint destruction and osteoclastogenesis by replenishing splenic and joint-draining lymph node Treg cells in CIA rats. Notably, DHA induced alterations in the Treg cell proteome in PLN, manifesting distinct upregulation of alloantigen Col2a1 (Type II collagen alfa 1 chain) and CD8a (T-cell surface glycoprotein CD8 alpha chain) in Treg cells, signifying DHA's targeted modulation of Treg cells, rendering them more adept at sustaining immune tolerance and impeding bone erosion. These results unveil a novel facet of DHA in the treatment of RA.

Correction: Ocular biocompatibility evaluation of POSS nanomaterials for biomedical material applications.

[This corrects the article DOI: 10.1039/C5RA08668J.].

Bacterial elimination via cell membrane penetration by violet phosphorene peripheral sub-nanoneedles combined with oxidative stress.

The effectiveness of an antibacterial agent is strongly influenced by its antibacterial mechanism, which, in turn, depends on the agent's topological structure. In the natural world, the nanoprotrusions on the surface of insect wings give them excellent antimicrobial properties through physical penetration while being compatible with host cells. Inspired by the novel nanostructure of insect wings, violet phosphorus (VP), a new member of the phosphorus family, has antibacterial potential due to the sub-nanoneedle on its edge. Here, we demonstrate that VP and its exfoliated product, violet phosphorene nanosheets (VPNSs), have superior antibacterial capability against pathogens via cell membrane penetration induced by peripheral sub-nanoneedles combined with oxidative stress. The results show that VPNSs can inactivate more than 99.9% of two common pathogens (Escherichia coli and Staphylococcus aureus) and more than 99.9% of two antibiotic-resistant bacteria (Escherichia coli pUC19 and methicillin-resistant Staphylococcus aureus), while showing almost no toxicity toward normal cells at a high concentration of 2.0 mg mL-1. Moreover, VPNSs can achieve effective treatment of induced skin wound infections and bacterial keratitis (BK) by Staphylococcus aureus and methicillin-resistant Staphylococcus aureus, respectively, showing promising potential for ocular and skin wound infection theragnostics.

Hypoxia-induced ALKBH5 aggravates synovial aggression and inflammation in rheumatoid arthritis by regulating the m6A modification of CH25H.

Previous studies have shown that epigenetic factors are involved in the occurrence and development of rheumatoid arthritis (RA). However, the role of N6-methyladenosine (m6A) methylation in RA has not been determined. The aim of this study was to investigate the role and regulatory mechanisms of hypoxia-induced expression of the m6A demethylase alkB homolog 5 (ALKBH5) in RA fibroblast-like synoviocytes (FLSs). Synovial tissues were collected from RA and osteoarthritis (OA) patients, and RA FLSs were obtained. ALKBH5 expression in RA FLSs and collagen-induced arthritis (CIA) model rats was determined using quantitative reverse transcription-PCR (qRT-PCR), western blotting and immunohistochemistry (IHC). Using ALKBH5 overexpression and knockdown, we determined the role of ALKBH5 in RA FLS aggression and inflammation. The role of ALKBH5 in RA FLS regulation was explored using m6A-methylated RNA sequencing and methylated RNA immunoprecipitation coupled with quantitative real-time PCR. The expression of ALKBH5 was increased in RA synovial tissues, CIA model rats and RA FLSs, and a hypoxic environment increased the expression of ALKBH5 in FLSs. Increased expression of ALKBH5 promoted the proliferation and migration of RA-FLSs and inflammation. Conversely, decreased ALKBH5 expression inhibited the migration of RA-FLSs and inflammation. Mechanistically, hypoxia-induced ALKBH5 expression promoted FLS aggression and inflammation by regulating CH25H mRNA stability. Our study elucidated the functional roles of ALKBH5 and mRNA m6A methylation in RA and revealed that the HIF1α/2α-ALKBH5-CH25H pathway may be key for FLS aggression and inflammation. This study provides a novel approach for the treatment of RA by targeting the HIF1α/2α-ALKBH5-CH25H pathway.

Co-clinical Trial of Novel Bispecific Anti-HER2 Antibody Zanidatamab in Patient-Derived Xenografts.

Zanidatamab is a bispecific human epidermal growth factor receptor 2 (HER2)-targeted antibody that has demonstrated antitumor activity in a broad range of HER2-amplified/expressing solid tumors. We determined the antitumor activity of zanidatamab in patient-derived xenograft (PDX) models developed from pretreatment or postprogression biopsies on the first-in-human zanidatamab phase I study (NCT02892123). Of 36 tumors implanted, 19 PDX models were established (52.7% take rate) from 17 patients. Established PDXs represented a broad range of HER2-expressing cancers, and in vivo testing demonstrated an association between antitumor activity in PDXs and matched patients in 7 of 8 co-clinical models tested. We also identified amplification of MET as a potential mechanism of acquired resistance to zanidatamab and demonstrated that MET inhibitors have single-agent activity and can enhance zanidatamab activity in vitro and in vivo. These findings provide evidence that PDXs can be developed from pretreatment biopsies in clinical trials and may provide insight into mechanisms of resistance. SIGNIFICANCE: We demonstrate that PDXs can be developed from pretreatment and postprogression biopsies in clinical trials and may represent a powerful preclinical tool. We identified amplification of MET as a potential mechanism of acquired resistance to the HER2 inhibitor zanidatamab and MET inhibitors alone and in combination as a therapeutic strategy. This article is featured in Selected Articles from This Issue, p. 695.

Retraction: Construction of a temperature-responsive terpolymer coating with recyclable bactericidal and self-cleaning antimicrobial properties.

Retraction of 'Construction of a temperature-responsive terpolymer coating with recyclable bactericidal and self-cleaning antimicrobial properties' by Bailiang Wang et al., Biomater. Sci., 2016, 4, 1731-1741, https://doi.org/10.1039/C6BM00587J.

Expression of concern: Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties.

Expression of concern for 'Bacterial self-defense antibiotics release from organic-inorganic hybrid multilayer films for long-term anti-adhesion and biofilm inhibition properties' by Qingwen Xu, Nanoscale, 2017, 9, 19245-19254, https://doi.org/10.1039/C7NR07106J.

Expression of concern: In vitro and in vivo evaluation of xanthan gum-succinic anhydride hydrogels for the ionic strength-sensitive release of antibacterial agents.

Expression of concern for 'In vitro and in vivo evaluation of xanthan gum-succinic anhydride hydrogels for the ionic strength-sensitive release of antibacterial agents' by Bailiang Wang et al., J. Mater. Chem. B, 2016, 4, 1853-1861, https://doi.org/10.1039/C5TB02046H.

Expression of concern: Bacterial infection microenvironment-responsive enzymatically degradable multilayer films for multifunctional antibacterial properties.

Expression of concern for 'Bacterial infection microenvironment-responsive enzymatically degradable multilayer films for multifunctional antibacterial properties' by Qingqing Yao et al., J. Mater. Chem. B, 2017, 5, 8532-8541, https://doi.org/10.1039/C7TB02114C.

Expression of concern: Synthesis of MA POSS-PMMA as an intraocular lens material with high light transmittance and good cytocompatibility.

Expression of concern for 'Synthesis of MA POSS-PMMA as an intraocular lens material with high light transmittance and good cytocompatibility' by Bailiang Wang et al., RSC Adv., 2014, 4, 52959-52966, https://doi.org/10.1039/C4RA08060B.

Retraction: A self-defensive antibacterial coating acting through the bacteria-triggered release of a hydrophobic antibiotic from layer-by-layer films.

Retraction of 'A self-defensive antibacterial coating acting through the bacteria-triggered release of a hydrophobic antibiotic from layer-by-layer films' by Bailiang Wang et al., J. Mater. Chem. B, 2017, 5, 1498-1506, https://doi.org/10.1039/C6TB02614A.

Intraoperative sensor technology quantifies inter-prosthesis pressure for predicting lower limb alignment after Oxford unicompartmental knee arthroplasty.

Purpose: The aim of this study is to quantify inter-prosthetic pressures at different knee angles in Oxford unicompartmental knee arthroplasty (OUKA) and its correlation with postoperative lower limb alignment. Methods: This study included 101 patients (122 knees) who underwent OUKA from March 2022 to July 2022. The previously designed matrix flexible force sensor was used to measure the inter-prosthesis pressure of different knee joint angles during the UKA operation, and the force variation trend and gap balance difference were obtained. The correlation between inter-prosthesis pressure and postoperative lower limb alignment index including hip-knee-ankle angle (HKAA) and posterior tibial slope (PTS) was analyzed. The effect of PTS change (ΔPTS) on the inter-prosthesis pressure and the range of motion (ROM) of the knee joint was analyzed. Radiographic and short-term clinical outcomes of included patients were assessed. Results: The inter-prosthesis pressure of the different knee joint angles during the operation was not consistent. The mean inter-prosthesis pressure and gap balance difference were 73.68.28 ± 41.65N and 36.48 ± 20.58N. The inter-prosthesis pressure at 0° and 20° was positively correlated with postoperative HKAA (p < 0.001). ΔPTS was positively correlated with the pressure at the end of knee extension and negatively correlated with the pressure at the end of knee flexion (p < 0.001). The HKAA, ROM, degree of fixed knee flexion deformity, and knee society score of the included patients were significantly improved compared with those before the operation (p < 0.001). Conclusion: The inter-prosthesis pressure measured at the knee extension position can predict postoperative HKAA to some degree. Changes in PTS will affect the inter-prosthesis pressure at the end of flexion and end of knee extension, but this change is not related to the range of motion of the knee joint.

Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers.

PURPOSE: Cyclin E (CCNE1) has been proposed as a biomarker of sensitivity to adavosertib, a Wee1 kinase inhibitor, and a mechanism of resistance to HER2-targeted therapy. EXPERIMENTAL DESIGN: Copy number and genomic sequencing data from The Cancer Genome Atlas and MD Anderson Cancer Center databases were analyzed to assess ERBB2 and CCNE1 expression. Molecular characteristics of tumors and patient-derived xenografts (PDX) were assessed by next-generation sequencing, whole-exome sequencing, fluorescent in situ hybridization, and IHC. In vitro, CCNE1 was overexpressed or knocked down in HER2+ cell lines to evaluate drug combination efficacy. In vivo, NSG mice bearing PDXs were subjected to combinatorial therapy with various treatment regimens, followed by tumor growth assessment. Pharmacodynamic markers in PDXs were characterized by IHC and reverse-phase protein array. RESULTS: Among several ERBB2-amplified cancers, CCNE1 co-amplification was identified (gastric 37%, endometroid 43%, and ovarian serous adenocarcinoma 41%). We hypothesized that adavosertib may enhance activity of HER2 antibody-drug conjugate trastuzumab deruxtecan (T-DXd). In vitro, sensitivity to T-DXd was decreased by cyclin E overexpression and increased by knockdown, and adavosertib was synergistic with topoisomerase I inhibitor DXd. In vivo, the T-DXd + adavosertib combination significantly increased γH2AX and antitumor activity in HER2 low, cyclin E amplified gastroesophageal cancer PDX models and prolonged event-free survival (EFS) in a HER2-overexpressing gastroesophageal cancer model. T-DXd + adavosertib treatment also increased EFS in other HER2-expressing tumor types, including a T-DXd-treated colon cancer model. CONCLUSIONS: We provide rationale for combining T-DXd with adavosertib in HER2-expressing cancers, especially with co-occuring CCNE1 amplifications. See related commentary by Rolfo et al., p. 4317.

Clinical Outcomes of Unicompartmental Knee Arthroplasty in Patients with Full-versus Partial-Thickness Cartilage Loss: A Systematic Review and Meta-Analysis.

OBJECTIVE: The objective of the study was to compare postoperative patient-reported outcomes and reoperation rates following unicompartmental knee arthroplasty (UKA) between patients with full-thickness cartilage loss (FTCL) and partial-thickness cartilage loss (PTCL). DESIGN: Multiple databases, including PubMed, Embase, Cochrane Library, and CNKI, were searched until October 2019 for studies comparing the Oxford Knee Score (OKS), American Knee Society (AKS) score, and reoperation rates between patients with FTCL and PTCL following UKA. Data analysis was performed using Review Manager software. RESULTS: A total of 613 UKA cases from 5 retrospective cohort studies were included. The mean difference in postoperative OKSs was significantly higher by 2.92 in FTCL group than in PTCL group (95% confidence interval [CI] = -5.29 to -0.55; P = 0.02). Improvement in OKS was significantly higher by 2.69 in FTCL group than in PTCL group (95% CI = -4.79 to -0.60; P = 0.01). However, the differences in OKSs were not clinically significant. The mean difference in AKS knee scores was similar between the 2 groups (95% CI = -9.14 to -3.34; P = 0.36), whereas the pooled mean difference in AKS function scores was higher by 5.63 in FTCL group than in PTCL group (95% CI = -9.27 to -1.98; P = 0.002), which was clinically relevant. The reoperation rates were statistically higher in PTCL group than in FTCL group (odds ratio = 2.24; 95% CI = 1.15 to 4.38; P = 0.02). CONCLUSIONS: Patients with FTCL achieved superior postoperative patient-reported outcomes and lower reoperation rates following UKA compared with those with PTCL. Thus, we believe this procedure should only be applied to end-stage medial osteoarthritis of the knee joint.

Subchondral Bone Plate Classification: A New and More Sensitive Approach for Predicting the Prognosis of Osteonecrosis of the Femoral Head.

BACKGROUND: This study explores the impact of subchondral bone plate necrosis on the development of the osteonecrosis of femoral head (ONFH) and its joint collapse. METHODS: This retrospective study included 76 ONFH patients (89 consecutive hips) with Association for Research on Osseous Circulation stage II who received conservative treatment without surgical intervention. The mean follow-up time was 15.60 ± 12.29 months. ONFH was divided into 2 types (I and II): Type I with a necrotic lesion involving subchondral bone plate and Type II with a necrotic lesion not involving subchondral bone plate. The radiological evaluations were based on plain x-rays. The data were analyzed using SPSS 26.0 statistical software. RESULTS: The collapse rate in Type I ONFH was significantly higher than that in Type II ONFH (P < 0.001). The survival time of hips with Type I ONFH was significantly shorter than those with Type II ONFH and with the endpoint of the femoral head collapse (P < 0.001). The collapse rate of Type I in the new classification (80.95%) was higher compared with that of the China-Japan Friendship Hospital (CJFH) classification (63.64%), and the difference was statistically significant (χ2 = 1.776, P = 0.024). CONCLUSION: Subchondral bone plate necrosis is an important factor that affects ONFH collapse and prognosis. Current classification using subchondral bone plate necrosis is more sensitive for predicting collapse compared with the CJFH classification. Effective treatments should be taken to prevent collapse if ONFH necrotic lesions involve the subchondral bone plate.

A Novel "Inside-Out" Intraocular Nanomedicine Delivery Mode for Nanomaterials' Biological Effect Enhanced Choroidal Neovascularization Occlusion and Microenvironment Regulation.

Photodynamic therapy (PDT) is commonly used in choroidal neovascularization (CNV) treatment due to the superior light transmittance of the eye. However, PDT often leads to surrounding tissue damage and further microenvironmental deterioration, including exacerbated hypoxia, inflammation, and secondary neovascularization. In this work, Pt nanoparticles (NPs) and Au NPs decorated zeolitic imidazolate framework-8 nanoplatform is developed to load indocyanine green for precise PDT and microenvironment amelioration, which can penetrate the internal limiting membrane through Müller cells endocytosis and target to CNV by surface-grafted cyclo(Arg-Gly-Asp-d-Phe-Lys) after intravitreal injection. The excessive H2 O2 in the CNV microenvironment is catalyzed by catalase-like Pt NPs for hypoxia relief and enhanced PDT occlusion of neovascular. Meanwhile, Au NPs show significant anti-inflammatory and anti-angiogenesis properties in regulating macrophages and blocking vascular endothelial growth factor (VEGF). Compared with verteporfin treatment, the mRNA expressions of hypoxia-inducible factor-1α and VEGF in the nanoplatform group are downregulated by 90.2% and 81.7%, respectively. Therefore, the nanoplatform realizes a comprehensive CNV treatment effect based on the high drug loading capacity and biosafety. The CNV treatment mode developed in this work provides a valuable reference for treating other diseases with similar physiological barriers that limit drug delivery and similar microenvironment.