Are comparable studies really comparable? Suggestions from a problem-solving experiment on urban and rural great tits.

Performance in tests of various cognitive abilities has often been compared, both within and between species. In intraspecific comparisons, habitat effects on cognition has been a popular topic, frequently with an underlying assumption that urban animals should perform better than their rural conspecifics. In this study, we tested problem-solving ability in great tits Parus major, in a string-pulling and a plug-opening test. Our aim was to compare performance between urban and rural great tits, and to compare their performance with previously published problem solving studies. Our great tits perfomed better in string-pulling than their conspecifics in previous studies (solving success: 54%), and better than their close relative, the mountain chickadee Poecile gambeli, in the plug-opening test (solving success: 70%). Solving latency became shorter over four repeated sessions, indicating learning abilities, and showed among-individual correlation between the two tests. However, the solving ability did not differ between habitat types in either test. Somewhat unexpectedly, we found marked differences between study years even though we tried to keep conditions identical. These were probably due to small changes to the experimental protocol between years, for example the unavoidable changes of observers and changes in the size and material of test devices. This has an important implication: if small changes in an otherwise identical set-up can have strong effects, meaningful comparisons of cognitive performance between different labs must be extremely hard. In a wider perspective this highlights the replicability problem often present in animal behaviour studies.

A Facile Approach to Construct Novel Polyesters as Soft Midblock for Thermoplastic Elastomers.

The development of innovative synthetic strategies to create functional polycaprolactones is highly demanded for advanced material applications. In this contribution, we reported a facile synthetic strategy to prepare a class of CL-based monomers (R-TO) derived from epoxides. They readily polymerize via well-controlled ring-opening polymerization (ROP) to afford a series of polyesters P(R-TO) with high molecular weight (Mn up to 350 kDa). Sequential addition copolymerization of MTO and L-lactide (L-LA) allowed to access of a series of ABA triblock copolymers with composition-dependent mechanical properties. Notably, P(L-LA)100-b-P(MTO)500-b-P(L-LA)100 containing the amorphous P(MTO) segment as a soft midblock and crystalline P(L-LA) domain as hard end block behaved as an excellent thermoplastic elastomer (TPE) with high elongation at break (1438 ± 204%), tensile strength (23.5 ± 1.7 MPa), and outstanding elastic recovery (>88%).

Is there evidence for the(sole) use of third ventriculostomy in the treatment of Idiopathic. Intracranial Hypertension: A Literature Review.

BACKGROUND: Idiopathic intracranial hypertension (IIH) remains a poorly understood condition with no standardised treatment. Treatment is therefore generally individualised. Recent isolated reports have begun to describe the use of third ventriculostomy (open or closed) for the treatment of IIH. This review aims to communicate the current evidence for the use of third ventriculostomy in IIH. METHODS: A systemic review, using PubMed, was performed of studies describing the use of third ventriculostomy, either open or closed, for the treatment of idiopathic intracranial hypertension. RESULTS: Only 3 studies for a total of 3 patients were found in which a third ventriculostomy was performed for the treatment of IIH. CONCLUSION: Despite very plausible proposed mechanisms of action, there is currently a paucity of both studies and, therefore, evidence for the use of either endoscopic or open third ventriculostomy for the treatment of IIH. The studies done to date do strongly suggest that further consideration is warranted.

Nynrin preserves hematopoietic stem cell function by inhibiting the mitochondrial permeability transition pore opening.

Mitochondria are key regulators of hematopoietic stem cell (HSC) homeostasis. Our research identifies the transcription factor Nynrin as a crucial regulator of HSC maintenance by modulating mitochondrial function. Nynrin is highly expressed in HSCs under both steady-state and stress conditions. The knockout Nynrin diminishes HSC frequency, dormancy, and self-renewal, with increased mitochondrial dysfunction indicated by abnormal mPTP opening, mitochondrial swelling, and elevated ROS levels. These changes reduce HSC radiation tolerance and promote necrosis-like phenotypes. By contrast, Nynrin overexpression in HSCs diminishes irradiation (IR)-induced lethality. The deletion of Nynrin activates Ppif, leading to overexpression of cyclophilin D (CypD) and further mitochondrial dysfunction. Strategies such as Ppif haploinsufficiency or pharmacological inhibition of CypD significantly mitigate these effects, restoring HSC function in Nynrin-deficient mice. This study identifies Nynrin as a critical regulator of mitochondrial function in HSCs, highlighting potential therapeutic targets for preserving stem cell viability during cancer treatment.

Fibrinogen: connecting the blood circulatory system with CNS scar formation.

Wound healing of the central nervous system (CNS) is characterized by the classical phases of 'hemostasis', 'inflammation', 'proliferation', and 'remodeling'. Uncontrolled wound healing results in pathological scar formation hindering tissue remodeling and functional recovery in the CNS. Initial blood protein extravasation and activation of the coagulation cascade secure hemostasis in CNS diseases featuring openings in the blood-brain barrier. However, the relevance of blood-derived coagulation factors was overlooked for some time in CNS wound healing and scarring. Recent advancements in animal models and human tissue analysis implicate the blood-derived coagulation factor fibrinogen as a molecular link between vascular permeability and scar formation. In this perspective, we summarize the current understanding of how fibrinogen orchestrates scar formation and highlight fibrinogen-induced signaling pathways in diverse neural and non-neural cells that may contribute to scarring in CNS disease. We particularly highlight a role of fibrinogen in the formation of the lesion border between the healthy neural tissue and the fibrotic scar. Finally, we suggest novel therapeutic strategies via manipulating the fibrinogen-scar-forming cell interaction to improve functional outcomes.

Volumetric Additive Manufacturing of Dicyclopentadiene by Solid-State Photopolymerization.

Polymerization in the solid state is generally infeasible due to restrictions on mobility. However, in this work, the solid-state photopolymerization of crystalline dicyclopentadiene is demonstrated via photoinitiated ring-opening metathesis polymerization. The source of mobility in the solid state is attributed to the plastic crystal nature of dicyclopentadiene, which yields local short-range mobility due to orientational degrees of freedom. Polymerization in the solid state enables photopatterning, volumetric additive manufacturing of free-standing structures, and fabrication with embedded components. Solid-state photopolymerization of dicyclopentadiene offers a new paradigm for advanced and freeform fabrication of high-performance thermosets.

Light-responsive transcription factors VvHYH and VvGATA24 mediate wax terpenoid biosynthesis in Vitis vinifera.

The cuticular wax that covers the surfaces of plants is the first barrier against environmental stresses and increasingly accumulates with light exposure. However, the molecular basis of light-responsive wax biosynthesis remains elusive. In grape (Vitis vinifera), light exposure resulted in higher wax terpenoid content and lower decay and abscission rates than controls kept in darkness. Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA-seq data were integrated to draw the chromatin accessibility and cis-elements regulatory map to identify the potential action sites. Terpenoid synthase 12 (VvTPS12) and 3-Hydroxy-3-methylglutaryl-CoA reductase 2 (VvHMGR2) were identified as grape wax biosynthesis targets, while VvHYH and VvGATA24 were identified as terpenoid biosynthesis activators, as more abundant wax crystals and higher wax terpenoid content were observed in transiently overexpressed grape berries and Nicotiana benthamiana leaves. The interaction between VvHYH and the open chromatin of VvTPS12 was confirmed qualitatively using a dual luciferase assay and quantitatively using surface plasma resonance, with an equilibrium dissociation constant of 2.81 nM identified via the latter approach. Molecular docking simulation implied the structural nature of this interaction, indicating that 24 amino acid residues of VvHYH, including Arg106A, could bind to the VvTPS12 G-box cis-element. VvGATA24 directly bound to the open chromatin of VvHMGR2, with an equilibrium dissociation constant of 8.59 nM. 12 amino acid residues of VvGATA24, including Pro218B, interacted with the VvHMGR2 GATA-box cis-element. Our work characterizes the mechanism underlying light-mediated wax terpenoid biosynthesis and provides gene targets for future molecular breeding.

Soft tissue inflammation around upper third molar cause limited mouth opening: common but overlooked.

OBJECTIVES: The aim of this study was to explore inflammation of soft tissue around the upper third molar as a prevalent cause of limited mouth opening, identify the clinical and radiographic features, and summarize the therapeutic effectiveness of tooth extraction. MATERIALS AND METHODS: A retrospective analysis of data from 264 patients with limited mouth opening over the last five years was performed. RESULTS: Among the 264 patients, 24 (9.1%) had inflammation of the soft tissue around the upper third molar, which was the second most common cause of limited mouth opening. Twenty-one of the twenty-four affected patients, with an average mouth opening of 19.1 ± 7.6 mm, underwent upper third molar extraction. Gingival tenderness around the upper third molar or maxillary tuberosity mucosa was a characteristic clinical manifestation (p < 0.05). The characteristic features on maxillofacial CT included soft tissue swelling around the upper third molar and gap narrowing between the maxillary nodules and the mandibular ascending branch. Post extraction, the average mouth opening increased to 31.4 ± 4.9 mm (p < 0.05), and follow-up CT demonstrated regression of the inflammatory soft tissue around the upper third molar. CONCLUSIONS: Inflammation of soft tissue around the upper third molar is a common cause of limited mouth opening. Symptoms of pain associated with the upper third molar and distinctive findings on enhanced maxillofacial CT scans are crucial for diagnosis. Upper third molar extraction yields favorable therapeutic outcomes. CLINICAL RELEVANCE: Inflammation of the soft tissue around the maxillary third molar commonly causes limited mouth opening, but this phenomenon has long been overlooked. Clarifying this etiology can reduce the number of misdiagnosed patients with restricted mouth opening and enable more efficient treatment for patients.

The OsMYC2-JA feedback loop regulates diurnal flower-opening time via cell wall loosening in rice.

Diurnal flower-opening time (DFOT), the time of spikelet opening during the day, is an important trait for hybrid rice (Oryza sativa L.) seed production. Hybrids between indica and japonica rice varieties have strong heterosis, but the parental lines usually have different, nonoverlapping DFOTs. This reduces the success of hybrid seed production in crosses between indica and japonica subspecies, thus hindering the utilization of indica and japonica inter-subspecies heterosis. However, little is known about the molecular mechanisms regulating DFOT in rice. Here, we obtained japonica rice lines with a DFOT 1.5 h earlier than the wild type by overexpressing OsMYC2, a gene encoding a key transcription factor in the jasmonate (JA) signaling pathway. OsMYC2 is activated by JA signaling and directly regulates the transcription of genes related to JA biosynthesis and cell wall metabolism. Overexpressing OsMYC2 led to significantly increased JA contents and decreased cellulose and hemicellulose contents in lodicule cells, as well as the softening of lodicule cell walls. This may facilitate the swelling of lodicules, resulting in early diurnal flower-opening. These results suggest that the OsMYC2-JA feedback loop regulates DFOT in rice via cell wall remodeling. These findings shed light on the understanding of regulatory mechanism of the DFOT of plants, which should promote the development of indica and japonica varieties suitable for hybrid rice breeding.

Evaluation of the Best Method for Orthodontic Correction of Skeletal Deep Bites in Growing Patients: A Systematic Review.

This review aimed to evaluate the currently available evidence regarding the best method of correcting deep bites in growing patients. In September 2023, a search was conducted electronically across the following databases: PubMed®, Web of Science™, Scopus®, Embase®, Google™ Scholar, and Cochrane Library. In this systematic review, randomized control trials (RCTs), controlled clinical trials (CCTs), and cohort studies of growing patients with deep bite malocclusion who received treatment with the primary objective of treating the deep bite were included. Risk of bias of the included studies was assessed using two different tools; one tool was applied for RCTs and the other one for the CCTs and cohort studies. One RCT, one CCT, and one cohort study were included (85 patients). The flat fixed acrylic bite plane was superior in terms of duration of treatment when compared to the inclined fixed acrylic bite plane and the utility arch with posterior intermaxillary elastics. Limited evidence indicates that the inclined fixed acrylic bite plane causes a significant increase in the lower incisor inclination and a significant increase in the angle between the mandible and the anterior cranial base (SNB). However, limited evidence indicates that the utility arch with posterior intermaxillary elastics causes a significant decrease in the angle between the maxilla and the anterior cranial base (SNA). Regarding the vertical skeletal changes, it was found that the three methods were comparable; in each case, the vertical dimension of the face increased because of a significant increase in the lower first molar height. There is a need for further studies to strengthen the evidence of the treatment efficacy of the employed methods, with more RCTs to be conducted in this regard.

Lewis Acid Catalyzed Cyclopropane Ring-Opening-Cyclization Cascade Using Thioureas as a N,N-bisnucleophile: Synthesis of Bicyclic Furo-, Pyrano-, and Pyrrololactams via a Formal [4+1]-Addition.

Fused bicyclic cyclopropanes were converted by Lewis acid-catalysis with thioureas to furo-, pyrano, and pyrrolo-lactams with yields of up to 99% and high diastere-oselectivity. The formation of the title compounds, repre-senting a formal [4+1]-cycloaddition to a donor-acceptor substituted cyclopropane, follows a cascade reaction involving SN1-type ring-opening addition and cyclization. Thiourea, being a cost-effective and odorless reagent, acts as an N,N-bis-nucleophile to generate bicyclic compounds containing an N­substituted γ-lactam moiety.

Reliability of mandibular range of motion measurements in healthy children.

BACKGROUND: Mandibular range of motion (MROM) variables are widely used to evaluate oral function. OBJECTIVE: The aim of this study was to establish the reliability of MROM variables in healthy children. METHODS: In this cross-sectional study, healthy children were examined 2 weeks apart. The following MROM variables were established: active maximum interincisal opening (AMIO), passive maximum interincisal opening (PMIO), protrusion and left and right laterotrusion. The reliability of the MROM measurements was determined by analysing the intra-class correlation coefficient (ICC), standard error of measurement (SEM), smallest detectable change (SDC) and limits of agreement (LoA). RESULTS: A total of 167 healthy children were examined. The ICC indicated good reliability for AMIO (0.885); excellent reliability for PMIO (0.925); and moderate reliability for protrusion (0.578), laterotrusion left (0.601) and laterotrusion right (0.634). The SDC was 0.9 mm for AMIO, 0.4 mm for PMIO, 2.2 mm for protrusion, 1.6 mm for laterotrusion left and 1.4 mm for laterotrusion right. The LoA was -5.67 to 5.82 for AMIO, -3.90 to 3.57 for PMIO, -3.89 to 3.55 for protrusion, -2.99 to 2.77 for laterotrusion left, and - 2.71 to 2.77 for laterotrusion right. CONCLUSIONS: AMIO and PMIO measurements are both highly reliable in healthy children. The low SDC indicate that AMIO and PMIO are promising longitudinal measurements. Protrusion and laterotrusion measurements had moderate reliability. These results support our clinical recommendation to measure AMIO rather than PMIO, as PMIO is more difficult and more time-consuming to perform than AMIO.

Monitoring and assessment of CO2 and NO2 in schools within the Sentinel Schools Network of Catalonia during the COVID-19 era.

In response to the global impact of the COVID-19 pandemic, international and national authorities, including those in Catalonia (Spain), recognized the crucial need to ensure proper ventilation in classrooms, emphasizing the importance of safe and healthy indoor environments for face-to-face learning. The present work, conducted within the COVID-19 Sentinel Schools Network of Catalonia (CSSNC) framework, aimed to monitor carbon dioxide (CO2) and nitrogen dioxide (NO2) concentrations in 23 schools, ensuring a comprehensive sample regarding educational levels, daily scholar schedules, and classroom typologies distributed across the four provinces of Catalonia. The research spanned three study periods: March and April 2021, October 2021 to January 2022, and March to June 2022. Briefly, 28%, 25%, and 37% of classrooms surpassed the 700 parts per million (ppm) CO2 limit in each study period, respectively. Generally, CO2 averages were lower in preschool classrooms (mean ± SD = 486 ± 106 ppm), while high school classrooms displayed the highest CO2 concentrations (mean ± SD = 710 ± 253 ppm). Moreover, classrooms in towns (<30000 inhabitants) exhibited higher CO2 levels as compared to classrooms from schools located in cities. As for NO2, the highest averages were obtained in urban areas, particularly in the Barcelona metropolitan area (e.g. mean indoor levels of 24.56 µg m-3 as compared to 11.05 µg m-3 in towns). In addition, the Indoor/Outdoor ratio (I/O ratio) in towns was the lowest (0.60). These results, together with the higher concentration of CO2 indoors, could indicate poorer ventilation in town schools. The results of this study are anticipated to contribute to implementing evidence-based measures to improve indoor air quality (IAQ) in educational settings.

The impact of temperature, humidity and closing school on the mumps epidemic: a case study in the mainland of China.

BACKGROUND: To control resurging infectious diseases like mumps, it is necessary to resort to effective control and preventive measures. These measures include increasing vaccine coverage, providing the community with advice on how to reduce exposure, and closing schools. To justify such intervention, it is important to understand how well each of these measures helps to limit transmission. METHODS: In this paper, we propose a simple SEILR (susceptible-exposed-symptomatically infectious-asymptomatically infectious-recovered) model by using a novel transmission rate function to incorporate temperature, humidity, and closing school factors. This new transmission rate function allows us to verify the impact of each factor either separately or combined. Using reported mumps cases from 2004 to 2018 in the mainland of China, we perform data fitting and parameter estimation to evaluate the basic reproduction number  R 0 . As a wide range of one-dose measles, mumps, and rubella (MMR) vaccine programs in China started only in 2008, we use different vaccination proportions for the first Stage I period (from 2004 to 2008) and the second Stage II period (from 2009 to 2018). This allows us to verify the importance of higher vaccine coverage with a possible second dose of MMR vaccine. RESULTS: We find that the basic reproduction number  R 0  is generally between 1 and 3. We then use the Akaike Information Criteria to assess the extent to which each of the three factors contributed to the spread of mumps. The findings suggest that the impact of all three factors is substantial, with temperature having the most significant impact, followed by school opening and closing, and finally humidity. CONCLUSION: We conclude that the strategy of increasing vaccine coverage, changing micro-climate (temperature and humidity), and closing schools can greatly reduce mumps transmission.

Mechanisms of impact of alcohol availability interventions from the perspective of 63 diverse alcohol licensing stakeholders: a qualitative interview study.

Aims: Interventions restricting temporal and spatial availability of alcohol are associated with reduced harm, but the pathways by which specific interventions have impact are poorly understood. We examined mechanisms of impact from the perspective of diverse licensing stakeholders. Methods: Fifty-three in-depth interviews were conducted with licensing stakeholders (from public health teams [PHTs], police, local authority licensing teams and lawyers, and alcohol premises licensing committees) from 20 local government areas. Interviewees were recruited as part of the Exploring the impact of alcohol licensing in England and Scotland (ExILEnS) study. Data were analyzed thematically and preliminary themes/subthemes were discussed during online groups with a different sample of public health and licensing professionals (n = 10). Findings: Most interviewees struggled to articulate how availability interventions might lead to changes in alcohol consumption or harms. Five overarching mechanisms were identified: access, visibility, premises and area-level norms, affordability, and management of the night-time economy, with specific pathways identified for certain subgroups/premises types. The mechanisms by which alcohol availability interventions may impact on alcohol consumption and harms are diverse, but were poorly understood. Conclusions: These findings will inform licensing and availability policy and advocacy, highlighting the need for further scrutiny of the evidence underpinning identified mechanisms, and primary research to address knowledge gaps.

Improvement of absorbability, osteoconductivity, and strength of a ß-tricalcium phosphate spacer for opening wedge high tibial osteotomy: clinical evaluations with 106 patients.

BACKGROUND: An ideal synthetic spacer for medial opening wedge high tibial osteotomy (MOWHTO) has not yet been developed. The authors have developed a new ß-tricalcium phosphate (ß-TCP) spacer with 60% porosity (N-CP60) by modifying the micro- and macro-pore structures of a conventional ß-TCP spacer (CP60) that is widely used in clinical practice. The purpose of this study was to compare the absorbability, osteoconductivity, and in vivo strength of the N-CP60 spacer with those of the CP60 spacer, when used in MOWHTO. METHODS: First, the porosity, diameter distribution of macro- and micropores, and compressive strength of each ß-TCP block were examined using methodology of biomaterial science. Secondly, a clinical study was performed using a total of 106 patients (106 knees) with MOWHTO, who were followed up for 18 months after surgery. In these knees, the N-CP60 and CP-60 spacers were implanted into 49 tibias and 57 tibias, respectively. The absorbability and osteoconductivity were radiologically evaluated by measuring the area of the implanted spacer remaining unabsorbed and assessing with the Hemert's score, respectively. The incidence of cracking in the implanted spacers was determined using computed radiography. Statistical comparisons were made with non-parametric tests. The significance level was set at p = 0.05. RESULTS: The N-CP60 and CP60 blocks had almost the same porosity (mean, 61.0% and 58.7%, respectively). The diameter of macropores was significantly larger (p < 0.0001) in the N-CP60 block than in the CP60 block, while the diameter of micropores was significantly smaller (p = 0.019) in the N-CP60 block. The ultimate strength of the N-CP60 block (median, 36.8 MPa) was significantly greater (p < 0.01) than that of the CP60 block (31.6 MPa). As for the clinical evaluations, the absorption rate of the N-CP60 spacer at 18 months after implantation (mean, 48.0%) was significantly greater (p < 0.001) than that of the CP60 spacer (29.0%). The osteoconductivity of the N-CP60 spacer was slightly but significantly higher (p = 0.0408) than that of the CP60 spacer only in zone 1. The incidence of in vivo cracking of the posteriorly located N-CP60 spacer at one month (mean, 75.5%) was significantly lower (p = 0.0035) than that of the CP60 spacer (91.2%). CONCLUSIONS: The absorbability, osteoconductivity, and compressive strength of the new N-CP60 spacer were significantly improved by modifying the macro- and micro-pore structures, compared with the conventional CP60 spacer. The N-CP60 spacer is more clinically useful than the CP60 spacer. TRIAL REGISTRATION NUMBER: H29-0002.

MSO-GP: 3-D segmentation of large and complex conjoined tree structures.

Robust segmentation of large and complex conjoined tree structures in 3-D is a major challenge in computer vision. This is particularly true in computational biology, where we often encounter large data structures in size, but few in number, which poses a hard problem for learning algorithms. We show that merging multiscale opening with geodesic path propagation, can shed new light on this classic machine vision challenge, while circumventing the learning issue by developing an unsupervised visual geometry approach (digital topology/morphometry). The novelty of the proposed MSO-GP method comes from the geodesic path propagation being guided by a skeletonization of the conjoined structure that helps to achieve robust segmentation results in a particularly challenging task in this area, that of artery-vein separation from non-contrast pulmonary computed tomography angiograms. This is an important first step in measuring vascular geometry to then diagnose pulmonary diseases and to develop image-based phenotypes. We first present proof-of-concept results on synthetic data, and then verify the performance on pig lung and human lung data with less segmentation time and user intervention needs than those of the competing methods.

Efficacy and safety of transanal opening of intersphincteric space in the treatment of high complex anal fistula: A meta­analysis.

The best treatment of high complex anal fistula (HCAF) is to avoid anal incontinence while improving the cure rate. On this basis, several surgical procedures for preserving the anal sphincter have been proposed. The purpose of the present study was to evaluate the efficacy and safety of transanal opening of intersphincteric space for treating HCAF. PubMed, Cochrane Library, China National Knowledge Infrastructure and the Wanfang databases were searched to collate all the articles on transanal opening of intersphincteric space for treating HCAF. A total of two researchers independently completed the whole process, from screening and inclusion to data extraction and the data was included in the RevMan 5.3 software for analysis. The main outcomes included the patients' essential characteristics, primary healing rate, management after recurrence, final healing rate, anal incontinence score before and after surgery, postoperative complication rate and types of complications. A total of six articles were included in this meta-analysis. The results showed that the weighted final healing rate of patients following transanal opening of intersphincteric space was 89% [risk differences (RD)=0.89; 95% confidence interval (CI)=0.86-0.92; I2=0%; P<0.00001]. The results of the anal incontinence score showed that there was no significant difference between the results before and after transanal opening of intersphincteric space surgery mean differences [(MD)=-0.04, Cl=-0.10-0.02, I2=0%; P=0.21]. Only 11 patients were reported to have complications, including urinary retention and bleeding following transanal opening of intersphincteric space with a complication rate of 8% (11/138) and the weighted average complication rate was 6% (RD=0.06,95% CI=0.02-0.10; I2=9%; P=0.003). Transanal opening of intersphincteric space has a high cure rate, a favorable anal incontinence score, fewer types of postoperative complications and a low complication rate; it can be used as a minimally invasive and sphincter-preserving surgical method for treating HCAF and is worthy of further promotion and research in clinical practice.

Unforeseen cascading effects of an inlet opening.

The opening of the Cacela Inlet (southern Portugal) in 2010 led to unforeseen effects observed after 2017, including an extreme acceleration of the retreat of the inland lagoon margin from about 0.2 to 2 m/year. This was a consequence of the development of a large flood delta in an area of limited accommodation space, forcing the main tidal channel to move inland. The coastal retreat currently affects a flat sandy area that separates the old and inactive Cacela cliff from the lagoon. Between 2025 and 2030, the currently inactive Cacela cliff is likely to become active again, posing a potential risk of damage to a medieval fortress and the existing settlement of Cacela Velha, an unforeseen cascading effect of the opening of the inlet. In order to prevent instability and damage to this legally protected area of national and public interest, several coastal management measures will be required.

A glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy.

Diabetic nephropathy is a severe complication of diabetes. Treatment of diabetic nephropathy is an important challenge due to persistent hyperglycemia and elevated levels of reactive oxygen species (ROS) in the kidney. Herein, we designed a glycopolymersome that can treat type 2 diabetic nephropathy by effectively inhibiting hyperglycemia and ROS-associated diabetic nephropathy pathogenesis. The glycopolymersome is self-assembled from phenylboronic acid derivative-containing copolymer, poly(ethylene oxide)45-block-poly[(aspartic acid)13-stat-glucosamine24-stat-(phenylboronic acid)18-stat-(phenylboronic acid pinacol ester)3] [PEO45-b-P(Asp13-stat-GA24-stat-PBA18-stat-PAPE3)]. PBA segment can reversibly bind blood glucose or GA segment for long-term regulation of blood glucose levels; PAPE segment can scavenge excessive ROS for renoprotection. In vitro studies confirmed that the glycopolymersomes exhibit efficient blood glucose responsiveness within 2 h and satisfactory ROS-scavenging ability with 500 µM H2O2. Moreover, the glycopolymersomes display long-acting regulation of blood glucose levels in type 2 diabetic nephropathy mice within 32 h. Dihydroethidium staining revealed that these glycopolymersomes reduced ROS to normal levels in the kidney, which led to 61.7% and 76.6% reduction in creatinine and urea levels, respectively, along with suppressing renal apoptosis, collagen accumulation, and glycogen deposition in type 2 diabetic nephropathy mice. Notably, the polypeptide-based glycopolymersome was synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCAs), thereby exhibiting favorable biodegradability. Overall, we proposed a new glycopolymersome strategy for 'drug-free' treatment of diabetic nephropathy, which could be extended to encompass the design of various multifunctional nanoparticles targeting diabetes and its associated complications.