Knoevenagel C═C Metathesis Enabled Glassy Vitrimers with High Rigidity, Toughness, and Malleability.

Thermosets, characterized by their permanent cross-linked networks, present significant challenges in recyclability and brittleness. In this work, we explore a polarized Knoevenagel C═C metathesis reaction for the development of rigid yet tough and malleable thermosets. Initial investigation on small molecule model reactions reveals the feasibility of conducting the base-catalyzed C═C metathesis reaction in a solvent-free environment. Subsequently, thermosetting poly(α-cyanocinnamate)s (PCCs) were synthesized via Knoevenagel condensation between a triarm cyanoacetate star and a dialdehyde. The thermal and mechanical properties of the developed PCCs can be easily modulated by altering the structure of the dialdehyde. Remarkably, the introduction of ether groups into the PCC leads to a combination of high rigidity and toughness with Young's modulus of ∼1590 MPa, an elongation at break of ∼79%, and a toughness reaching ∼30 MJ m3. These values are competitive to traditional thermosets, in Young's modulus but far exceed them in ductility and toughness. Moreover, the C═C metathesis facilitates stress relaxation within the bulk polymer networks, thus rendering PCCs excellent malleability and reprocessability. This work overcomes the traditional limitations of thermosets, introducing groundbreaking insights for the design of rigid yet tough and malleable thermosets, and contributing significantly to the sustainability of materials.

Recyclable, Malleable, and Strong Thermosets Enabled by Knoevenagel Adducts.

Plastic recycling is critical for waste management and achieving a circular economy, but it entails difficult trade-offs between performance and recyclability. Here, we report a thermoset, poly(α-cyanocinnamate) (PCC), synthesized using Knoevenagel condensation between terephthalaldehyde (TPA) and a triarm cyanoacetate star, that tackles this difficulty by harnessing its intrinsically conjugated and dynamic chemical characteristics. PCCs exhibit extraordinary thermal and mechanical properties with a typical Tg of ∼178 °C, Young's modulus of 3.8 GPa, and tensile strength of 102 MPa, along with remarkable flexibility and dimensional and chemical stabilities. Furthermore, end-of-life PCCs can be selectively degraded and partially recycled back into one starting monomer TPA for a new production cycle or reprocessed through dynamic exchange aided by cyanoacetate chain-ends. This study lays the scientific groundwork for the design of robust and recyclable thermosets, with transformative potential in plastic engineering.

Halogen Bonding Tripodal Metallo-Receptors for Phosphate Recognition and Sensing in Aqueous-Containing Organic Media.

The anion recognition and electrochemical anion-sensing properties of halogen-bonding (XB) tripodal zinc(II) receptors strategically designed and constructed for tetrahedral anion guest binding are described. The XB tris(iodotriazole)-containing hosts exhibit high affinities and selectivities for inorganic phosphate over other more basic, mono-charged oxoanions such as acetate and the halides in a competitive CD3 CN/D2 O (9 : 1 v/v) aqueous solvent mixture. 1 H NMR anion binding and electrochemical voltammetric anion sensing studies with redox-active ferrocene functionalised metallo-tripodal receptor analogues, reveal each of the XB tripods as superior anion complexants when compared to their tris(prototriazole)-containing, hydrogen bonding (HB) counterparts, not only exemplifying the halogen bond as a strong alternative interaction to the traditional hydrogen bond for molecular recognition but also providing rare evidence of the ability of XB receptors to preferentially bind the "harder" phosphate oxoanion over the "softer" and less hydrated halides in aqueous containing media.

Gap patterns and radiographic follow-up of newer-generation cementless total knee arthroplasty designs.

BACKGROUND: Interest in cementless total knee arthroplasty (TKA) has increased with advancement of biomaterials and implant design and associated improved longevity. We sought to evaluate the gap patterns and radiolucent zones radiographically for 2 newer-generation cementless TKA designs. METHODS: We retrospectively reviewed our single-institution database between January 2017 and December 2019. We identified patients with a porous keeled tibia base-plate with 4-bullet cruciform spikes and peri-apatite coated femoral component (study group 1) and patients who received a cementless porous coated femoral component and rotating platform tibia baseplate with 4 peripheral porous coated pegs around a central cone (study group 2). We identified gap patterns at 6 weeks and at 1 year or more postoperatively on radiographs, noting indications for reoperation. RESULTS: We identified 228 patients in study group 1 and 41 patients in study group 2. At 1-year follow-up, we found evidence of resolved femoral gaps in 52 (72.2%) of 72 patients in study group 1 and 10 (58.8%) of 17 patients in study group 2 (p = 0.124). We identified 27 (84.3%) of 32 patients in study group 1 and 7 (70.0%) of 10 patients in study group 2 with resolved tibia gaps (p = 0.313). After 1 year, there were significantly more Zone 3a femoral zonal radiolucent gaps (p = 0.001) and Zone 8 tibia zonal radiolucent gaps (p = 0.002) in study group 2 than in study group 1. There were 4 reoperations for study group 1 and 0 reoperations for study group 2. CONCLUSION: The modern cementless TKA systems have varied gap patterns in postoperative radiographs, which may be attributed to the implant design. Most radiolucent gaps resolve radiographically on follow-up.

Catalyst-Free α-Acetyl Cinnamate/Acetoacetate Exchange to Enable High Creep-Resistant Vitrimers.

Vitrimers represent an emerging class of polymeric materials that combine the desirable characteristics of both thermoplastics and thermosets achieved through the design of dynamic covalent bonds within the polymer networks. However, these materials are prone to creep due to the inherent instability of dynamic covalent bonds. Consequently, there are pressing demands for the development of robust and stable dynamic covalent chemistries. Here, we report a catalyst-free α-acetyl cinnamate/acetoacetate (α-AC/A) exchange reaction to develop vitrimers with remarkable creep resistance. Small-molecule model studies revealed that the α-AC/A exchange occurred at temperatures above 140 °C in bulk, whereas at 120 °C, this reaction was absent. For demonstration in the case of polymers, copolymers derived from common vinyl monomers were crosslinked with terephthalaldehyde to produce α-AC/A vitrimers with tunable thermal and mechanical performance. All resulting α-AC/A vitrimers exhibited high stability, especially in terms of creep resistance at 120 °C, while retaining commendable reprocessability when subjected to high temperatures. This work showcases the α-AC/A exchange reaction as a novel and robust dynamic covalent chemistry capable of imparting both reprocessability and high stability to cross-linked networks.

Rapid synthesis of auxin via a new tryptophan-dependent pathway is required for shade avoidance in plants.

Plants grown at high densities perceive a decrease in the red to far-red (R:FR) ratio of incoming light, resulting from absorption of red light by canopy leaves and reflection of far-red light from neighboring plants. These changes in light quality trigger a series of responses known collectively as the shade avoidance syndrome. During shade avoidance, stems elongate at the expense of leaf and storage organ expansion, branching is inhibited, and flowering is accelerated. We identified several loci in Arabidopsis, mutations in which lead to plants defective in multiple shade avoidance responses. Here we describe TAA1, an aminotransferase, and show that TAA1 catalyzes the formation of indole-3-pyruvic acid (IPA) from L-tryptophan (L-Trp), the first step in a previously proposed, but uncharacterized, auxin biosynthetic pathway. This pathway is rapidly deployed to synthesize auxin at the high levels required to initiate the multiple changes in body plan associated with shade avoidance.

No Difference in Subsidence Between Modern Monoblock and Modular Titanium Fluted Tapered Femoral Stems.

BACKGROUND: Subsidence remains a concern when utilizing tapered fluted titanium (TFT) femoral stems and may lead to leg length discrepancy, impingement, instability, and failure to obtain osseointegration. This study aims to compare stem subsidence across 3 modern TFT stems. Our secondary aim was to investigate the influence of bicortical contact or "scratch fit" on subsidence, as well as the role of intraoperative imaging in maximizing bicortical contact and preventing stem subsidence. METHODS: A retrospective review of 271 hip arthroplasties utilizing modern TFT stems at a single institution was performed. Three stem designs were included in the analysis: 1 monoblock TFT stem (n = 91) and 2 modular TFT stems (n = 90; n = 90). Patient demographics, Paprosky femoral bone loss classification, bicortical contact, utilization of intraoperative imaging, and stem subsidence (comparison of initial postoperative radiograph to the latest follow-up radiograph-minimum 3 months) were recorded. RESULTS: There was no statistically significant difference in overall subsidence (P = .191) or the incidence of subsidence >5 millimeters between stems (P = .126). Subgroup analysis based on femoral bone loss grading showed no difference in subsidence between stems. Increased bicortical contact was associated with reduced subsidence (P = .004). Intraoperative imaging was used in 46.5% (126 of 271) of cases; this was not correlated with bicortical contact (P = .673) or subsidence (P = .521). CONCLUSION: All 3 modern TFT stems were highly successful and associated with low rates of subsidence, regardless of modular or monoblock design. Surgeons should select the stem that they feel is most clinically appropriate.

Minimum 5-Year Clinical Outcomes and Survivorship for a Single Revision Total Knee Arthroplasty System Using Hybrid Fixation and Press-Fit Stems.

BACKGROUND: Hybrid fixation, utilizing diaphyseal press-fit stems and cement fixation in the tibial and femoral metaphyseal areas, has long been a strategy for revision total knee arthroplasty (rTKA). The purpose of this study was to evaluate the clinical outcomes and survivorships of hybrid fixation using a single rTKA revision system with a minimum of 5 years follow-up. METHODS: We reviewed our prospectively collected database to identify 281 patients who underwent rTKA using a single revision system with hybrid fixation and press-fit stems between July 2006 and August 2016. We reviewed the clinical outcome scores, including the Knee Society Score, Western Ontario and McMaster Universities Osteoarthritis index, and Veterans RAND 12 Item Health Survey. We also evaluated the 5 and 10-year survivorships and the indications for reoperations. The cohort had a mean age of 70 years (range, 45.2 to 92.0) and a mean body mass index of 33.4 (range, 17.3 to 55.8). The mean time from rTKA surgery was 11.1 years (range, 5.3 to 15.5). RESULTS: Paired t-test analyses showed significant improvements from preoperative versus postoperative clinical outcome scores (P < .001) for Knee Society Score, Western Ontario and McMaster Universities Osteoarthritis, and Veterans RAND 12 Item Health Survey Physical component. Prosthetic joint infections after index rTKA were the most common failure mode with 29 patients requiring reoperations. Rerevision due to aseptic loosening was uncommon (6 patients) with a cumulative survival rate of 95.2% at 5 years and 94.2% at 10 years. CONCLUSION: The use of this single rTKA system utilizing press fit stems combined with hybrid fixation provided significant improvements in the clinical outcomes and excellent survivorships at 5 and 10 years.

Injectable Hybrid-Crosslinked Hydrogels as Fatigue-Resistant and Shape-Stable Skin Depots.

Injectable hydrogels have gained considerable attention, but they are typically mechanically weak and subject to repeated physiological stresses in the body. Herein, we prepared polyurethane diacrylate (EPC-DA) hydrogels, which are injectable and can be photocrosslinked into fatigue-resistant implants. The mechanical properties can be tuned by changing photocrosslinking conditions, and the hybrid-crosslinked EPC-DA hydrogels exhibited high stability and sustained release properties. In contrast to common injectable hydrogels, EPC-DA hydrogels exhibited excellent antifatigue properties with >90% recovery during cyclic compression tests and showed shape stability after application of force and immersion in an aqueous buffer for 35 days. The EPC-DA hydrogel formed a shape-stable hydrogel depot in an ex vivo porcine skin model, with establishment of a temporary soft gel before in situ fixing by UV crosslinking. Hybrid crosslinking using injectable polymeric micelles or nanoparticles may be a general strategy for producing hydrogel implants resistant to physiological stresses.

Comparison of postpartum incontinence outcomes after vacuum-assisted and forceps-assisted deliveries in a tertiary maternity unit.

INTRODUCTION AND HYPOTHESIS: Forceps-assisted deliveries are an established risk factor for pelvic organ prolapse and pelvic floor injury. However, specific comparison of incontinence outcomes between vacuum-assisted and forceps-assisted deliveries are scarce in the literature. We aimed to compare the initial impact of vacuum and forceps deliveries on new-onset urinary and faecal incontinence as well as pelvic floor muscle strength, with the hypothesis that incontinence outcomes were poorer after forceps- than after vacuum-assisted delivery. METHODS: This is a retrospective cohort study of incontinence outcomes in patients who had primary vacuum- or forceps-assisted delivery. The study population included 108 postpartum patients who had undergone operative vaginal delivery (63 vacuum-assisted, 45 forceps-assisted), met the inclusion criteria and attended the postpartum assessment service. Outcomes studied were the presence and severity of symptoms manifesting beyond 1 month postpartum - faecal incontinence and stress, urgency and mixed urinary incontinence - as well as pelvic floor muscle strength scores based on the modified Oxford scale. RESULTS: Prevalence of new-onset urinary and faecal incontinence was 35.6% in the forceps group and 30.2% in the vacuum group. The data suggest that there is no significant difference in the prevalence of new-onset incontinence symptoms (p = 0.70, difference in prevalence [forceps - vacuum]: 5.4%, 95% CI -0.25, +0.15), frequency (p = 0.40) and amount (p = 0.48) of urine leakage or mean muscle strength scores (p = 0.89). CONCLUSION: In our maternity unit, we observed that type of operative vaginal delivery was not associated with significant differences in urinary incontinence and pelvic floor muscle strength outcomes.

Halogen Bonding Ionophore for Potentiometric Iodide Sensing.

Iodide (I-) is an essential micronutrient for thyroid function. Hence, rapid and portable sensing is important for I- quantification in food and biological samples. Herein, we report the first example of a halogen bonding (XB) tripodal ionophore (XB1) which is selective for the I- anion. NMR binding studies of XB1 and its H-triazole analog HB2 with I- demonstrated the dominant influence of XB interactions between the ionophore and the I- analyte. The phase boundary model was applied to formulate iodide-selective electrodes with the ionophore XB1. The optimal electrode exhibited a near-Nernstian response of -51.9 mV per decade within a large dynamic range (10-1 to 10-6 M) and notably anti-Hofmeister selectivity for I- over thiocyanate (SCN-), enabling the in situ determination of I- in complex samples. This work establishes XB as a viable supramolecular interaction in the potentiometric sensing of anions.

Increased constraint of rotating hinge knee prosthesis is associated with poorer clinical outcomes as compared to constrained condylar knee prosthesis in total knee arthroplasty.

The aim of this study was to evaluate whether there are any differences in patient-reported outcome measures between semi-constrained condylar constrained knee (CCK) and fully constrained rotating hinge knee (RHK) prostheses in midterm follow-up. We reviewed prospectively collected data of our hospital arthroplasty registry between 2007 and 2014. Thirty-nine patients were identified to have RHK prosthesis TKA and matched for a number of primary/revision TKA, gender, age, body mass index and pre-operative clinical scores to a control group of 78 patients with CCK TKA. Patient demographics, range of movement, varus/valgus deformity, Short Form 36 (SF-36) scores, Oxford Knee Score (OKS), Knee Society Score (KSS) and patient satisfaction were evaluated. Pre-operatively, the RHK and the control group of CCK had similar demographics, proportion of primary/revision TKA and baseline clinical scores (p > 0.05). At 2-year follow-up, patients with CCK prostheses had significantly better clinical outcomes as compared to patients with RHK prosthesis in terms of KSS functional scores, OKS, SF-36 sub-domains of physical functioning, physical role functioning and physical component score. We conclude that at midterm follow-up of 2 years, the CCK patients as compared to RHK patients reported better clinical and functional outcomes in terms of OKS, KSS functional score and SF-36 with a greater proportion of patients who were satisfied and had their expectations met by surgery. Further biomechanical studies are needed to investigate the association between component constraint and clinical outcomes for these prostheses.

Anion Recognition in Water by Charge-Neutral Halogen and Chalcogen Bonding Foldamer Receptors.

A novel strategy for the recognition of anions in water using charge-neutral σ-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, weakly hydrated anions such as I- and ReO4-. This is achieved through the formation of 2:1 host-guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent σ-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple σ-hole-anion interactions and hydrophobic collapse results in I- affinities in water that exceed all known σ-hole receptors, including cationic systems (ß2 up to 1.68 × 1011 M-2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.

Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation.

The transient receptor potential cation channel mucolipin 1 (TRPML1) channel is a conduit for lysosomal calcium efflux, and channel activity may be affected by lysosomal contents. The lysosomes of retinal pigmented epithelial (RPE) cells are particularly susceptible to build-up of lysosomal waste products because they must degrade the outer segments phagocytosed daily from adjacent photoreceptors; incomplete degradation leads to accumulation of lipid waste in lysosomes. This study asks whether stimulation of TRPML1 can release lysosomal calcium in RPE cells and whether such release is affected by lysosomal accumulations. The TRPML agonist ML-SA1 raised cytoplasmic calcium levels in mouse RPE cells, hesRPE cells, and ARPE-19 cells; this increase was rapid, robust, reversible, and reproducible. The increase was not altered by extracellular calcium removal or by thapsigargin but was eliminated by lysosomal rupture with glycyl-l-phenylalanine-ß-naphthylamide. Treatment with desipramine to inhibit acid sphingomyelinase or YM201636 to inhibit PIKfyve also reduced the cytoplasmic calcium increase triggered by ML-SA1, whereas RPE cells from TRPML1-/- mice showed no response to ML-SA1. Cotreatment with chloroquine and U18666A induced formation of neutral, autofluorescent lipid in RPE lysosomes and decreased lysosomal Ca2+ release. Lysosomal Ca2+ release was also impaired in RPE cells from the ATP-binding cassette, subfamily A, member 4-/- mouse model of Stargardt's retinal dystrophy. Neither TRPML1 mRNA nor total lysosomal calcium levels were altered in these models, suggesting a more direct effect on the channel. In summary, stimulation of TRPML1 elevates cytoplasmic calcium levels in RPE cells, but this response is reduced by lysosomal accumulation.-Gómez, N. M., Lu, W. Lim, J. C., Kiselyov, K., Campagno, K. E., Grishchuk, Y., Slaugenhaupt, S. A., Pfeffer, B., Fliesler, S. J., Mitchell, C. H. Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation.

Isoselective Lactide Ring Opening Polymerisation using [2]Rotaxane Catalysts.

Polylactide (PLA) is a fully biodegradable and recyclable plastic, produced from a bio-derived monomer: it is a circular economy plastic. Its properties depend upon its stereochemistry and isotactic PLA shows superior thermal-mechanical performances. Here, a new means to control tacticity by exploiting rotaxane conformational dynamism is described. Dynamic achiral [2]rotaxanes can show high isoselectivity (Pi =0.8, 298 K) without requiring any chiral additives and enchain by a chain end control mechanism. The organocatalytic dynamic stereoselectivity is likely applicable to other small-molecule and polymerization catalyses.

Sacral chordoma: clinical experience of a series of 11 patients over 18 years.

Sacral chordoma are rare low-to-intermediate grade malignant tumours that occur most commonly within the sacrum. Sacrectomy with wide resection margins seems to offer the best long-term prognosis.  This study aims to review the management of sacral chordomas including the duration of symptoms, features, treatment, complications and local recurrence rate following surgery at a tertiary centre. We retrospectively reviewed 11 patients treated at our institution between years 1999 and 2015. Patient data included age, sex, history, radiographs, surgical details, onset of recurrence, subsequent treatment, disease-free survival and overall survival were analyzed. Nine patients underwent surgical management with 1 through a sacral approach and eight patients through a combined abdominosacral approach. Despite wide resection in our series, sacral chordoma poses a major problem with approximately 60% of patients having local recurrence in their follow-up.

Acid-Regulated Switching of Metal Cation and Anion Guest Binding in Halogen-Bonding Rotaxanes.

The ability of natural enzymes to regulate their guest binding affinities and preferences through the use of co-ligands which alter the features of the binding site is fundamental to biological homeostatic control. Herein, the rarely exploited orthosteric control of guest binding is demonstrated using neutral halogen bonding [2]rotaxanes, in which a chemical stimulus (acid) interacting with the interlocked host binding site switches the host's native guest preference from metal cations to anions. When neutral, the rotaxanes exhibit pronounced transition metal cation affinity and comparatively weak anion binding properties. However, the addition of acid attenuates the rotaxanes' ability to coordinate cations, while concurrently enabling strong binding of halides through charge assisted halogen bonding and hydrogen bonding interactions in competitive aqueous solvent media. The appendage of a fluorescent anthracene reporter group to the rotaxane framework also enables diagnostic sensory responses to cation/anion binding.

Thermodynamics of Anion Binding by Chalcogen Bonding Receptors.

The application of chalcogen bonding (ChB) to anion recognition is an underdeveloped area of host-guest supramolecular chemistry. The chemical instability of heavier chalcogen derivatives may in part be responsible for the lack of progress. Herein, the synthesis of a new structurally simple, tellurium-based ChB binding motif is reported, the robust stability of which has enabled the thermodynamic properties for ChB halide anion binding in polar aprotic and wet protic organic solvent media to be elucidated. The thermodynamic data reveals how the subtle interplay between ChB host, anion guest and solvent dictates halide binding selectivity and affinity trends. These findings help to provide a deeper insight into the nature of the ChB-anion interaction.

A Chiral Halogen-Bonding [3]Rotaxane for the Recognition and Sensing of Biologically Relevant Dicarboxylate Anions.

The unprecedented application of a chiral halogen-bonding [3]rotaxane host system for the discrimination of stereo- and E/Z geometric isomers of a dicarboxylate anion guest is described. Synthesised by a chloride anion templation strategy, the [3]rotaxane host recognises dicarboxylates through the formation of 1:1 stoichiometric sandwich complexes. This process was analysed by molecular dynamics simulations, which revealed the critical synergy of halogen and hydrogen bonding interactions in anion discrimination. In addition, the centrally located chiral (S)-BINOL motif of the [3]rotaxane axle component facilitates the complexed dicarboxylate species to be sensed via a fluorescence response.

Enantioselective Anion Recognition by Chiral Halogen-Bonding [2]Rotaxanes.

The application of chiral interlocked host molecules for discrimination of guest enantiomers has been largely overlooked, which is surprising given their unique three-dimensional binding cavities capable of guest encapsulation. Herein, we combined the stringent linear geometric interaction constraints of halogen bonding (XB), the noncovalent interaction between an electrophilic halogen atom and a Lewis base, with highly preorganized and conformationally restricted chiral cavities of [2]rotaxanes to achieve enantioselective anion recognition. Representing the first detailed investigation of the use of chiral XB rotaxanes for this purpose, extensive 1H NMR binding studies and molecular dynamics (MD) simulation experiments revealed that the chiral rotaxane cavity significantly enhances enantiodiscrimination compared to the non-interlocked free axle and macrocycle components. Furthermore, by examining the enantioselectivities of a family of structurally similar XB [2]rotaxanes containing different combinations of chiral and achiral macrocycle and axle components, the dominant influence of the chiral macrocycle in our rotaxane design for determining the effectiveness of chiral discrimination is demonstrated. MD simulations reveal the crucial geometric roles played by the XB interactions in orientating the bound enantiomeric anion guests for chiral selectivity, as well as the critical importance of the anions' hydration shells in governing binding affinity and enantiodiscrimination.