Adhesive and mechanical properties of the glue produced by 25 Drosophila species.

Drosophila glue, a bioadhesive produced by fly larvae to attach themselves to a substrate for several days, has recently gained attention for its peculiar adhesive and mechanical properties. Although Drosophila glue production was described more than 50 years ago, a general survey of the adhesive and mechanical properties of this proteinaceous gel across Drosophila species is lacking. To measure adhesion, we present here a protocol that is robust to variations in protocol parameters, pupal age and calculation methods. We find that the glue, which covers the entire pupal surface, increases the animal rigidity and plasticity when bound to a glass slide. Our survey of pupal adhesion in 25 Drosophilidae species reveals a wide range of phenotypes, from species that produce no or little glue and adhere little, to species that produce high amounts of glue and adhere strongly. One species, D. hydei, stands out from the rest and emerges as a promising model for the development of future bioadhesives, as it has the highest detachment force per glue area and produces relatively large amounts of glue relative to its size. We also observe that species that invest more in glue tend to live in more windy and less rainy climates, suggesting that differences in pupal adhesion properties across species are shaped by ecological factors. Our present survey provides a basis for future biomimetic studies based on Drosophila glue.

Trap colour strongly affects the ability of deep learning models to recognize insect species in images of sticky traps.

BACKGROUND: The use of computer vision and deep learning models to automatically classify insect species on sticky traps has proven to be a cost- and time-efficient approach to pest monitoring. As different species are attracted to different colours, the variety of sticky trap colours poses a challenge to the performance of the models. However, the effectiveness of deep learning in classifying pests on different coloured sticky traps has not yet been sufficiently explored. In this study, we aim to investigate the influence of sticky trap colour and imaging devices on the performance of deep learning models in classifying pests on sticky traps. RESULTS: Our results show that using the MobileNetV2 architecture with transparent sticky traps as training data, the model predicted the pest species on transparent sticky traps with an accuracy of at least 0.95 and on other sticky trap colours with at least 0.85 of the F1 score. Using a generalised linear model (GLM) and a Boruta feature selection algorithm, we also showed that the colour and architecture of the sticky traps significantly influenced the performance of the model. CONCLUSION: Our results support the development of an automatic classification of pests on a sticky trap, which should focus on colour and deep learning architecture to achieve good results. Future studies could aim to incorporate the trap system into pest monitoring, providing more accurate and cost-effective results in a pest management programme. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Novel temperature responsive polymer based sealant for embolization.

A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost-effective formulation. During the development process, particular attention was given to materials that were tunable, safe, and effective sealant agents. The thermo-responsive properties of poly(N-isopropylacrylamide) (PNIPAM) provides an ideal foundation to develop an optimized solution. Through a combination of model-based and material testing, a hydrogel was developed that balances conformational factors to achieve a customized transition temperature, radiopacity suitable for visualization, mechanical properties suitable for delivery via 3Fr catheter, sufficient cohesion once applied to resist migration under physiological pressures and an improved safety profile. Two applications, embolization of lymphatic leakage and exclusions of the left atrial appendage (LAA), to eliminate LAA dead space to reduce the risk of thromboembolic events, were considered. The material and benchtop results for this product demonstrate the suitability of this new material not only for these applications but also for other potential healthcare applications.

A sealant has been developed that improves upon current catheter-based treatments in the following ways: 1) Efficient delivery system, 2) No in situ polymerization, 3) No harmful byproducts, and 4) Cost-effective formulation.

Design and Improvement of Bone Adhesive in response to Clinical Needs.

Fracture represents one of the most common diagnoses in contemporary medical practice, with the majority of cases traditionally addressed through metallic device fixation. However, this approach is marred by several drawbacks, including prolonged operative durations, considerable expenses, suboptimal applicability to comminuted fractures, increased infection risks, and the inevitable requirement for secondary surgery. The inherent advantages of bone adhesives in these fields have garnered the attention of orthopedic surgeons, who have commenced utilizing biocompatible and biodegradable bone adhesives to bond and stabilize bone fragments. Regrettably, the current bone adhesives generally exhibit insufficient adhesive strength in vivo environments, and it is desirable for them to possess effective osteogenesis to facilitate fracture healing. Consequently, aligning bone adhesives with practical clinical demands remains a significant hurdle, which has catalyzed a surge in research endeavors. Within this review, the conceptual framework, characteristics, and design ideas of bone adhesives based on clinical needs are delineated. Recent advancements in this domain, specifically focusing on the enhancement of two pivotal characteristics-adhesive strength and osteogenic potential are also reviewed. Finally, a prospective analysis of the future advancements in bone adhesives, offering new insights into solutions for diverse clinical problems is presented.

Effectiveness of surgical approach in the management of non-traumatic corneal perforations.

CLINICAL RELEVANCE: Non-traumatic aetiologies are one of the leading causes of corneal perforations. The management of corneal perforation is quite challenging and complex for anterior segment surgeons. The appropriate surgical approach for each case is usually determined on the basis of a combination of many different parameters. BACKGROUND: The study aimed to evaluate surgical approach options and outcomes in the treatment of non-traumatic corneal perforations. METHODS: Patient data who underwent surgery for non-traumatic corneal perforation between 2016 and 2023 were retrospectively evaluated. Medical records were assessed in terms of age, gender, perforation aetiology, the first and last examination notes, surgical approach, follow-up time, and additional surgeries and outcomes according to anatomical, therapeutic and functional success. Anterior segment photographs were investigated for thorough explanation of the examinations. RESULTS: Forty-five eyes of 45 patients were included (mean age 61.2 ± 22.4 (90-2), female/male ratio 20/25). Surgical approaches applied according to the size and location of the perforation site included fibrin glue application (6), amniotic membrane transplantation (AMT) (9), corneal patch graft application(15), and tectonic keratoplasty (15). The ratio of inflammatory and infectious causes as the two main indications was 29/16. Globe integrity was ensured with the first surgery in 27 eyes. However, 17 eyes required secondary surgical attempts due to failure of the first approach and 1 eye underwent evisceration. AMT was the least successful method among other methods in anatomical, therapeutic, and functional assessment. CONCLUSION: There are various surgical approaches for repairing non-traumatic corneal perforations, each with its own advantages and disadvantages. These include high tissue resistance, the ability to remove necrotic tissue, ease of access, and anti-inflammatory activity. It is possible to successfully repair corneal perforations with single and combined methods, considering the above-mentioned features, especially depending on the size and location of the defect. While AMT is a viable and time-saving choice - especially in the lack of donor tissues - further interventions are necessary in most circumstances.

Three-dimensional (3-D) fluoride molecular glue to improve the SnO2/perovskite interface for efficient perovskite solar cells.

Aiming at numerous defects at SnO2/perovskite interface and lattice mismatch in perovskite solar cells (PSCs), we design a kind of three-dimensional (3D) molecular glue (KBF4-TFMSA), which is derived from strong intramolecular hydrogen bonding interaction between potassium tetrafluoroborate (KBF4) and trifluoromethanesulfonamide (TFMSA). A remarkable efficiency of 25.8% with negligible hysteresis and a stabilized power output of 25.0% have been achieved, in addition, 24.57% certified efficiency of 1 cm2 device is also obtained. Further investigation reveals that this KBF4-TFMSA can interact with oxygen vacancies and under-coordinated Sn(IV) from the SnO2, in the meantime, FA+ (NH2-C=NH) and K+ cations can be well fixed by hydrogen bonding interaction between FA+  and BF4-, and electrostatic attraction between sulfonyl oxygen and K+ ions, respectively. Thereby, FAPbI3 crystal grain sizes are increased, interfacial defects are significantly reduced and carrier extraction/transport is facilitated, leading to better cell performance and excellent stabilities. Non-encapsulated devices can maintain 91% of their initial efficiency under maximum-power-point (MPP) tracking while continuous illumination (~100 mW cm-2) for 1000 h, and retain 91% of the initial efficiency after 1000 h "double 60" damp-heat stability testing (60°C and 60%RH (RH, relatively humidity)).

A cofactor-induced repressive type of transcription factor condensation can be induced by synthetic peptides to suppress tumorigenesis.

Transcriptional factors (TFs) act as key determinants of cell death and survival by differentially modulating gene expression. Here, we identified many TFs, including TEAD4, that form condensates in stressed cells. In contrast to YAP-induced transcription-activating condensates of TEAD4, we found that co-factors such as VGLL4 and RFXANK alternatively induced repressive TEAD4 condensates to trigger cell death upon glucose starvation. Focusing on VGLL4, we demonstrated that heterotypic interactions between TEAD4 and VGLL4 favor the oligomerization and assembly of large TEAD4 condensates with a nonclassical inhibitory function, i.e., causing DNA/chromatin to be aggregated and entangled, which eventually impede gene expression. Based on these findings, we engineered a peptide derived from the TEAD4-binding motif of VGLL4 to selectively induce TEAD4 repressive condensation. This "glue" peptide displayed a strong antitumor effect in genetic and xenograft mouse models of gastric cancer via inhibition of TEAD4-related gene transcription. This new type of repressive TF phase separation exemplifies how cofactors can orchestrate opposite functions of a given TF, and offers potential new antitumor strategies via artificial induction of repressive condensation.

Sticky Science: Using Complex Coacervate Adhesives for Biomedical Applications.

Tissue adhesives are used for various medical applications, including wound closure, bleeding control, and bone healing. Currently available options often show weak adhesion or cause adverse effects. Recently, there has been an increasing interest in complex coacervates as medical adhesives. Complex coacervates are formed by mixing oppositely charged macromolecules that associate and undergo liquid-liquid phase separation, in which the dense bottom phase is the complex coacervate. Complex coacervates are strong and often biocompatible, and show strong underwater adhesion. The properties of the resulting materials are tunable by intrinsic factors such as polymer chemistry, molecular weight, charge density, and topology of the macromolecules, as well as extrinsic factors such as temperature, pH, and salt concentration. Therefore, complex coacervates are interesting new candidates for medical adhesives. In this review, it is described how complex coacervates form and how different factors influence their behavior. Next, an overview of recent studies on complex coacervates in the context of medical adhesives is presented. The application of complex coacervates as hemostatic or embolic agents, skin or bone repair adhesives, and soft tissue sealants is discussed. Lastly, additional possibilities for utilizing these materials in the future are discussed.

Molecular glue triggers degradation of PHGDH by enhancing the interaction between DDB1 and PHGDH.

Cancer stem cells (CSCs) play a pivotal role in tumor initiation, proliferation, metastasis, drug resistance, and recurrence. Consequently, targeting CSCs has emerged as a promising avenue for cancer therapy. Recently, 3-phosphoglycerate dehydrogenase (PHGDH) has been identified as being intricately associated with the regulation of numerous cancer stem cells. Yet, reports detailing the functional regulators of PHGDH that can mitigate the stemness across cancer types are limited. In this study, the novel "molecular glue" LXH-3-71 was identified, and it robustly induced degradation of PHGDH, thereby modulating the stemness of colorectal cancer cells (CRCs) both in vitro and in vivo. Remarkably, LXH-3-71 was observed to form a dynamic chimera, between PHGDH and the DDB1-CRL E3 ligase. These insights not only elucidate the anti-CSCs mechanism of the lead compound but also suggest that degradation of PHGDH may be a more viable therapeutic strategy than the development of PHGDH inhibitors. Additionally, compound LXH-3-71 was leveraged as a novel ligand for the DDB1-CRL E3 ligase, facilitating the development of new PROTAC molecules targeting EGFR and CDK4 degradation.

Management of refractory rectal variceal bleed using computed tomography.

The management of refractory rectal variceal bleed using a minimally invasive percutaneous approach is described. Rectal varices are portosystemic collaterals that arise as a complication of portal hypertension. Bleeding is less common from rectal varices than from esophageal varices, but it is potentially life-threatening. Hence, it is of interest to describe a novel minimally invasive percutaneous technique to control refractory bleeding from rectal varices in a complex scenario where other proven treatments have failed. In the present study, a 28-year-old male presented to the Emergency department with one episode of hematemesis, hematochezia and severe abdominal pain. Sigmoidoscopy revealed actively bleeding rectal varices. CT abdominal angiogram revealed variceal formation in the rectum. we successfully performed CT guided percutaneous N- butyl cyanoacrylate (NBCA) glue injection of rectal varices with immediate and complete cessation of rectal bleed after failed endoscopic sclerotherapy.

Recent advances in mesoporous silica nanoparticles formulations and drug delivery for wound healing.

Wound healing is a natural process that can be disrupted by disease. Nanotechnology is a promising platform for the development of new therapeutic agents to accelerate acute and chronic wound healing. Drug delivery by means of nanoparticles as well as wound dressings have emerged as suitable options to improving the healing process. The characteristics of mesoporous silica nanoparticles (MSNs) make them efficient carriers of pharmaceutical agents alone or in combination with dressings. In order to maximize the effect of a drug and minimize its adverse consequences, it may be possible to include targeted and intelligent release of the drug into the design of MSNs. Its use to facilitate closure of adjacent sides of a cut as a tissue adhesive, local wound healing, controlled drug release and induction of blood coagulation are possible applications of MSNs. This review summarizes research on MSN applications for wound healing. It includes a general overview, wound healing phases, MSN formulation, therapeutic possibilities of MSNs and MSN-based drug delivery systems for wound healing.

Effect of Silica Nanoparticle Treatment on Adhesion between Tissue-like Substrates and In Vivo Skin Wound Sealing.

Silica nanoparticles are innovative solutions of surgical glue that can readily adhere to various tissue-like substrates without the need for time-consuming chemical reactions or ultraviolet irradiation. Herein, 10 nm-sized silica nanoparticle (SiNP10) treatment exhibited maximum adhesion strength in the porcine heart tissue model, which was approximately 7.15 times higher than that of the control group of non-treatment. We assessed the effects of silica nanoparticle treatment on in vivo skin wounds by scoring tissue adhesion and inflammation using histological images. Compared to the commercial cyanoacrylate skin adhesive (Dermabond), suppression of inflammatory cytokine levels in the incision wound skin was observed. We further quantified the expression of angiogenic growth factors and connective tissue formation-related proteins. On day 5 after wound closing treatment, the expression levels of PDGF-BB growth factor were significantly higher in SiNP10 treatment (0.64 ± 0.03) compared to Dermabond (0.07 ± 0.05). This stimulated angiogenesis and connective tissue formation in the skin of the incision wound may be associated with the promoting effects of SiNP10 treatment on wound closure and tissue adhesion.

An updated patent review of BRD4 degraders.

INTRODUCTION: Bromodomain-containing protein 4 (BRD4), an important epigenetic reader, is closely associated with the pathogenesis and development of many diseases, including various cancers, inflammation, and infectious diseases. Targeting BRD4 inhibition or protein elimination with small molecules represents a promising therapeutic strategy, particularly for cancer therapy. AREAS COVERED: The recent advances of patented BRD4 degraders were summarized. The challenges, opportunities, and future directions for developing novel potent and selective BRD4 degraders are also discussed. The patents of BRD4 degraders were searched using the SciFinder and Cortellis Drug Discovery Intelligence database. EXPERT OPINION: BRD4 degraders exhibit superior efficacy and selectivity to BRD4 inhibitors, given their unique mechanism of protein degradation instead of protein inhibition. Excitingly, RNK05047 is now in phase I/II clinical trials, indicating that selective BRD4 protein degradation may offer a viable therapeutic strategy, particularly for cancer. Targeting BRD4 with small-molecule degraders provides a promising approach with the potential to overcome therapeutic resistance for treating various BRD4-associated diseases.

Uterine Artery Pseudoaneurysm after Total Abdominal Hysterectomy Managed by Ultrasound-guided Percutaneous Glue Injection.

Uterine artery pseudoaneurysm (UAP) following abdominal hysterectomy is an uncommon complication. However, it can cause life-threatening bleeding, necessitating early diagnosis and intervention. Imaging is vital in its prompt diagnosis and aids in planning interventions. Here, we describe a case of recurrent massive per-vaginal bleeding from a left UAP developed following total abdominal hysterectomy and bilateral salpingo-oophorectomy. Bleeding was successfully managed with percutaneous ultrasound-guided glue (N-butyl cyanoacrylate) injection into the aneurysmal sac. The patient is doing well without any recurrent bleeding.

Reversal of Fetal Compromise Following In Utero Treatment of Vein of Galen Malformation Using Glue.

OBJECTIVE: To treat the fetus presenting with in utero compromise due to a large vein of Galen malformation (VOGM) using glue embolization. METHODS: The fetus that was referred for termination of pregnancy at 30 weeks of gestation due to severe cardiomegaly, mild pericardial effusion and large VOGM was evaluated using ultrasound. There was reversed end diastolic flow in the umbilical artery Doppler indicating imminent fetal demise in the premature fetus weighing <1200 g. Considering the request of parents, a treatment similar to recently reported cases of VOGM embolization in utero was attempted as an emergency procedure to salvage the baby. Due to unavailability of coils, financial constraints and urgent need for intervention, n-butyl cyanoacrylate glue with lipiodol was used to embolize the venous outflow of VOGM outflow under ultrasonographic guidance. RESULTS: There was immediate correction of the umbilical artery Doppler waveform with the establishment of a normal flow pattern. The cardiomegaly resolved over 3 weeks and fetal MRI done 2 weeks later showed normal brain architecture with no evidence of hemorrhage or infarction. Pregnancy was continued for 4 weeks after the procedure and terminated at 36 weeks. A female baby weighing 1900 g was delivered by Cesarean section with an Apgar of 8/10. Though initially the baby did well, with mild ventriculomegaly reported on postnatal day 5, she eventually presented at 3 months of age with cardiac failure. As the MRI showed encephalomalacia, due to uncertainty of neurological outcome, further treatment was not pursued by the parents and the baby died a few days later. CONCLUSION: To our knowledge, this is the first report on the use of glue to treat VOGM prenatally. Though technically successful in correcting the in utero compromise, the baby eventually expired. Cases of in utero embolization using coils and glue have shown success in reversing prenatal pathology and improving survival. However, long-term outcomes including neurological status are yet to be reported.

Splenic Artery Pseudoaneurysm Management With Cyanoacrylate Glue: A Case Report.

We present the case of a 40-year-old female who presented with abdominal pain, hematochezia, and melena for the past week and was diagnosed with a pseudoaneurysm emanating from the mid-splenic artery. The patient was managed with endovascular cyanoacrylate glue embolization, resulting in the complete resolution of an impending catastrophic hemorrhagic shock.

Novel potent molecular glue degraders against broad range of hematological cancer cell lines via multiple neosubstrates degradation.

BACKGROUND: Targeted protein degradation of neosubstrates plays a crucial role in hematological cancer treatment involving immunomodulatory imide drugs (IMiDs) therapy. Nevertheless, the persistence of inevitable drug resistance and hematological toxicities represents a significant obstacle to their clinical effectiveness. METHODS: Phenotypic profiling of a small molecule compounds library in multiple hematological cancer cell lines was conducted to screen for hit degraders. Molecular dynamic-based rational design and cell-based functional assays were conducted to develop more potent degraders. Multiple myeloma (MM) tumor xenograft models were employed to investigate the antitumor efficacy of the degraders as single or combined agents with standard of care agents. Unbiased proteomics was employed to identify multiple therapeutically relevant neosubstrates targeted by the degraders. MM patient-derived cell lines (PDCs) and a panel of solid cancer cell lines were utilized to investigate the effects of candidate degrader on different stage of MM cells and solid malignancies. Unbiased proteomics of IMiDs-resistant MM cells, cell-based functional assays and RT-PCR analysis of clinical MM specimens were utilized to explore the role of BRD9 associated with IMiDs resistance and MM progression. RESULTS: We identified a novel cereblon (CRBN)-dependent lead degrader with phthalazinone scaffold, MGD-4, which induced the degradation of Ikaros proteins. We further developed a novel potent candidate, MGD-28, significantly inhibited the growth of hematological cancer cells and induced the degradation of IKZF1/2/3 and CK1α with nanomolar potency via a Cullin-CRBN dependent pathway. Oral administration of MGD-4 and MGD-28 effectively inhibited MM tumor growth and exhibited significant synergistic effects with standard of care agents. MGD-28 exhibited preferentially profound cytotoxicity towards MM PDCs at different disease stages and broad antiproliferative activity in multiple solid malignancies. BRD9 modulated IMiDs resistance, and the expression of BRD9 was significant positively correlated with IKZF1/2/3 and CK1α in MM specimens at different stages. We also observed pronounced synergetic efficacy between the BRD9 inhibitor and MGD-28 for MM treatment. CONCLUSIONS: Our findings present a strategy for the multi-targeted degradation of Ikaros proteins and CK1α against hematological cancers, which may be expanded to additional targets and indications. This strategy may enhance efficacy treatment against multiple hematological cancers and solid tumors.

Treatment of Corneal Dermoid with Fibrin Glue Boned Multi-Layer Lenticules from Small Incision Lenticules Extraction Surgery: A Preliminary Study of Five Patients.

PURPOSE: Dermoid excision combined with lamellar keratoplasty was one of the most common surgical techniques for corneal dermoid. Due to the huge shortage of corneal donors, small incision lenticule extraction (SMILE) derived lenticules might be the novel and feasible corneal grafts instead of traditional corneal donors. Therefore, we tried to use FG boned multi-layer lenticules as grafts in the treatment of corneal dermoid. METHODS: Five patients (the oldest patient was 54 years old and the youngest case was 5 years old) were diagnosed with corneal dermoid and complaining of blurred vision or unsatisfied cosmetic appearance. All patients underwent corneal dermoid excision combined with FG boned multi-layer corneal lenticules transplantation. Slit-lamp microscopy and anterior-segmental optical coherence tomography(AS-OCT)were used to observe ocular appearance, corneal grafts survival, epithelialization, transparency, interlamellar fluid accumulation and the degradation of FG. The preoperative and postoperative change of best-corrected visual acuity (BCVA) and astigmatism were respectively recorded. RESULTS: All patients were satisfied with the postoperative cosmetic results. BCVA had been increased and astigmatism had been decreased in all cases. We observed that the FG boned multi-layer corneal lenticules were covered with smooth corneal epithelium in one week after transplantation and successfully adhered to the corneal beds, without any dislocation or interlayer separation. FG was gradually degraded and absorbed within 1 month after surgery. The lenticule grafts grew well without rejection and kept transparency during the follow-up period. CONCLUSIONS: FG boned multi-layer lenticules would be the novel and feasible substitute for lamellar keratoplasty in the treatment of corneal dermoid. FG could not be only used as binder adhering multi-layer lenticules, closing the interlayer space of multi-layer lenticules, preventing the formation of interlayer fluid, but also increasing the thickness and toughness of lenticules, and therefore which is more facilitate to intraoperative suture.