Copper Deposition in Polydopamine Nanostructure to Promote Cuproptosis by Catalytically Inhibiting Copper Exporters of Tumor Cells for Cancer Immunotherapy.

Cuproptosis is an emerging programmed cell death, displaying great potential in cancer treatment. However, intracellular copper content to induce cuproptosis is unmet, which mainly ascribes to the intracellular pumping out equilibrium mechanism by copper exporter ATP7A and ATP7B. Therefore, it is necessary to break such export balance mechanisms for desired cuproptosis. Mediated by diethyldithiocarbamate (DTC) coordination, herein a strategy to efficiently assemble copper ions into polydopamine nanostructure (PDA-DTC/Cu) for reprogramming copper metabolism of tumor is developed. The deposited Cu2+ can effectively trigger the aggregation of lipoylated proteins to induce cuproptosis of tumor cells. Beyond elevating intracellular copper accumulation, PDA-DTC/Cu enables to break the balance of copper metabolism by disrupting mitochondrial function and restricting the adenosine triphosphate (ATP) energy supply, thus catalytically inhibiting the expressions of ATP7A and ATP7B of tumor cells to enhance cuproptosis. Meanwhile, the killed tumor cells can induce immunogenic cell death (ICD) to stimulate the immune response. Besides, PDA-DTC/Cu NPs can promote the repolarization of tumor-associated macrophages (TAMs ) to relieve the tumor immunosuppressive microenvironment (TIME). Collectively, PDA-DTC/Cu presented a promising "one stone two birds" strategy to realize copper accumulation and inhibit copper export simultaneously to enhance cuproptosis for 4T1 murine breast cancer immunotherapy.

miR-20a: a key regulator of orthodontic tooth movement via BMP2 signaling pathway modulation.

AIM: In this study, we aimed to establish a rat tooth movement model to assess miR-20's ability in enhancing the BMP2 signaling pathway and facilitate alveolar bone remodeling. METHOD: 60 male SD rats had nickel titanium spring devices placed between their left upper first molars and incisors, with the right side serving as the control. Forces were applied at varying durations (18h, 24h, 30h, 36h, 42h, 1d, 3d, 5d, 7d, 14d), and their bilateral maxillary molars and surrounding alveolar bones were retrieved for analysis. Fluorescent quantitative PCR was conducted to assess miR-20a, BMP2, Runx2, Bambi and Smad6 gene expression in alveolar bone, and western blot was performed to determine the protein levels of BMP2, Runx2, Bambi, and Smad6 after mechanical loading. RESULT: We successfully established an orthodontic tooth movement model in SD rats and revealed upregulated miR-20a expression and significantly increased BMP2 and Runx2 gene expression and protein synthesis in alveolar bone during molar tooth movement. Although Bambi and Smad6 gene expression did not significantly increase, their protein synthesis was found to decrease significantly. CONCLUSION: MiR-20a was found to be involved in rat tooth movement model alveolar bone remodeling, wherein it promoted remodeling by reducing Bambi and Smad6 protein synthesis through the BMP2 signaling pathway.

Molecular weaving.

Historically, the interlacing of strands at the molecular level has mainly been limited to coordination polymers and DNA. Despite being proposed on a number of occasions, the direct, bottom-up assembly of molecular building blocks into woven organic polymers remained an aspirational, but elusive, target for several decades. However, recent successes in two-dimensional and three-dimensional molecular-level weaving now offer new opportunities and research directions at the interface of polymer science and molecular nanotopology. This Perspective provides an overview of the features and potential of the periodic nanoscale weaving of polymer chains, distinguishing it from randomly entangled polymer networks and rigid crystalline frameworks. We review the background and experimental progress so far, and conclude by considering the potential of molecular weaving and outline some of the current and future challenges in this emerging field.

Synthesis of Self-healing and Light-, Thermal-, and Humidity-induced Deformative Polyurethane Actuator.

Intelligent actuating materials have drawn enormous attention because of their potential applications in soft robots, smart sensors, bionics, etc. Aiming to integrate light, thermal, and humidity stimuli deformations and self-healing function into a single polymer, a smart actuating polyurethane material CPPU-50 is designed and successfully synthesized through co-polymerization of azobenzene-containing Azo-C12 , polyethylene glycol 200 (PEG200), and 4,4'-diphenylmethane diisocyanate (MDI) at a ratio of 1:1:2. The obtained polyurethane CPPU-50 exhibits good photoinduced bending, thermal responsive shape memory effect, humidity triggered deflections and self-healing properties. Furthermore, an actuator combining light and thermal stimuli is created and the self-healing CPPU-50 film can withstand the object of 1800 times without tearing. This work can pave a way for further development of long-lived multi-stimuli-responsive actuating devices and intelligent materials.

Psychological impact and perceptions of orthodontic treatment of adult patients with different motivations.

INTRODUCTION: Motivations, perceptions, and psychosocial states of adult patients with orthodontic disorders in China have not been widely studied. The study assessed the psychosocial states and perceptions of adult patients undergoing orthodontic treatments with different motivations. METHODS: Two hundred forty-three adult patients (mean age, 30.2 ± 7.4 years; women, 79.0%) undergoing orthodontic treatment were recruited from a tertiary stomatology hospital. The patients answered a patient-centered questionnaire regarding motivations and perceptions of orthodontic treatment and the Psychosocial Impact of Dental Aesthetics Questionnaire. Data were analyzed using the chi-square test on the basis of multiple responses. Multiple linear regression analyses were performed to determine the association between motivation factors and the Psychosocial Impact of Dental Aesthetics Questionnaire subscale scores (P <0.05). RESULTS: Patients with various motivations were as follows: occlusal function reason (70.4%), dental esthetic reason (54.7%), facial esthetic reason (24.3%), and following others' suggestions (18.5%). Patients with esthetic or occlusal motivations exhibited significantly greater need and interest for orthodontic treatment (P <0.001). Multiple linear regression analyses revealed that the scores of social impact, psychological impact, and esthetic concern subscales were significantly associated with both dental and facial esthetic motivations (P <0.001). CONCLUSIONS: The primary motivations of Chinese patients were observed to be improved esthetics and occlusal function. Patients with esthetic or occlusal motivations exhibited significantly greater need and interest in treatment. Patients with facial or dental esthetic motivations experienced greater impacts of psychosocial states. Therefore, the patient motivations and impacts of esthetic-related psychosocial states on them should be considered during treatment.

Biomechanical behaviour of implant prostheses and adjacent teeth according to bone quality: A finite element analysis.

The contribution of biomechanical factors in the formation of proximal contact loss has been observed, but there is little research on the mechanisms by which they contribute. Using finite element analysis, this study aimed to analyse the impact of bone quality on the biomechanical behaviour of a dentition consisting of implant prostheses and adjacent teeth. The occlusal load was applied on the implant/tooth crown. In the mesiodistal direction, the adjacent natural tooth mesially to the implant denture had the tendency for mesial movement, while the distal adjacent natural tooth had the tendency for distal movement. For the supporting bone around the mesial adjacent tooth, the maximum/minimum principal stress and strain values on the mesial side of the bone were higher than those on the distal side of the bone. Stress and strain values on the mesial side of the supporting bone around the distal adjacent tooth were lower than those on the distal side. With decreasing bone density, displacements of teeth and the implant denture, principal stresses and equivalent strains on tooth supporting bone increased. Studies on biomechanical behaviours of a tooth-implant dentition may provide a deeper understanding of implant-induced dental adaptive processes such as proximal contact loss.

A Multi-Scale Study on Deformation and Failure Process of Metallic Structures in Extreme Environment.

It is a macro-micro model study for defect initiation, growth and crack propagation of metallic truss structure under high engine temperature and pressure conditions during the reentry atmosphere. Till now, the multi-scale simulation methods for these processes are still unclear. We explore the deformation and failure processes from macroscale to nanoscale using the Gas-Kinetic Unified Algorithm (GKUA) and all-atomic, molecular dynamic (MD) simulation method. The behaviors of the dislocations, defect evolution and crack propagation until failure for Aluminum-Magnesium (Al-Mg) alloy are considered with the different temperature background and strain fields. The results of distributions of temperature and strain field in the aerodynamic environment obtained by molecular dynamics simulations are in good agreement with those obtained from the macroscopic Boltzmann method. Compared to the tensile loading, the alloy structure is more sensitive to compression loading. The polycrystalline Al-Mg alloy has higher yield strength with a larger grain size. It is due to the translation of plastic deformation mode from grain boundary (GB) sliding to dislocation slip and the accumulation of dislocation line. Our findings have paved a new way to analyze and predict the metallic structural failure by micro-scale analysis under the aerodynamic thermal extreme environment of the reentry spacecraft on service expiration.

Three-dimensional positional accuracy of intraoral and laboratory implant scan bodies.

STATEMENT OF PROBLEM: In the implant digital workflow, scan bodies provide the 3D position of digital implants in the virtual dental arch. However, limited evidence is available on scan body accuracy, selection, and usage. PURPOSE: The purpose of this in vitro study was to evaluate the 3D positional accuracy of 4 intraoral and 6 laboratory scan body systems to the implants and laboratory replicas of an implant system under various torque magnitudes. MATERIAL AND METHODS: Ten test groups comprising 4 intraoral (I): Medentika L-Series (MS), Straumann CARES Mono (SM), Core 3D (CO), Straumann RC (SS); and 6 laboratory (L): Nobel Procera Pos Locator (NP), Sirona InPost (SR), Amann Girrbach (AG), Straumann CARES Mono (SM), Core 3D (CO), Straumann RC (SS) scan bodies were derived from 7 scan body systems. Of these, 3 systems (SM, CO, SS) are used for both intraoral and laboratory applications. The scan bodies were tested on Straumann Bone Level Regular CrossFit implants or laboratory replicas. Eight test groups allowed for the variation of torque application (5, 10, and 15 Ncm), while 2 test groups (NP, SR) were hand positioned only. Prefabricated metal abutments (ME) for both implants and laboratory replicas served as controls. A coordinate measuring machine measured four 3D positional accuracy variables: vertical linear distortion (dz), 2D tolerance displacement (dr), global linear distortion (dR), and scan body height discrepancy (ΔH) (n=10). The data were analyzed with 2-way analysis of variance tests and post hoc analysis with Tukey tests (α=.05). RESULTS: For both intraoral and laboratory test groups, 2-way ANOVA found that the system had a significant effect on all distortion variables (P<.001), while torque magnitude had a significant effect only on dz and ΔH (P<.001). Overall, mean dz ranged from 5 ±12 µm for L-AG at 15 Ncm to 23 ±14 µm for L-AG at 5 Ncm. Mean dr ranged from 5 ±4 µm for I-SM at 15 Ncm to 73 ±41 µm for L-SS at 10 Ncm, and mean dR ranged from 11 ±6 µm for I-SM at 10 Ncm to 74 ±41 µm for L-SS at 10 Ncm. Mean ΔH ranged from -5 ±10 µm for I-SM at 15 Ncm to 23 ±14 µm for L-AG at 5 Ncm. Among intraoral test groups, for dz and ΔH, all the test groups except for I-SM at 15 Ncm and I-MS at 10 and 15 Ncm were significantly more positive than the control (P<.001). For dr, I-SS at 5, 10, and 15 Ncm was significantly different from the control (P<.001). For dR, only I-SS at 5 Ncm was significantly different from the control (P<.001). Among laboratory test groups, for dz and ΔH, L-AG at 5 Ncm and L-CO at 15 Ncm were significantly more positive than the control (P<.001). For dr, L-SS at 10 and 15 Ncm were significantly different from the control (P<.001). For dR, only L-SS at 10 Ncm was significantly different from the control (P<.001). Intraoral and laboratory systems show comparable 3D positional accuracy. CONCLUSIONS: Overall, I-SS and L-SS were the least accurate. The system tested had a significant effect on 3D positional accuracy, while torque magnitude had no consistent effect across all systems.

Polymeric Nanofiber-Carbon Nanotube Composite Mats as Fast-Equilibrium Passive Samplers for Polar Organic Contaminants.

To improve the performance of polymeric electrospun nanofiber mats (ENMs) for equilibrium passive sampling applications in water, we integrated two types of multiwalled carbon nanotubes (CNTs; with and without surface carboxyl groups) into polyacrylonitrile (PAN) and polystyrene (PS) ENMs. For 11 polar and moderately hydrophobic compounds (-0.07 ≤ logKOW ≤ 3.13), 90% of equilibrium uptake was achieved in under 0.8 days (t90% values) in nonmixed ENM-CNT systems. Sorption capacity of ENM-CNTs was between 2- and 50-fold greater than pure polymer ENMs, with equilibrium partition coefficients (KENM-W values) ranging from 1.4 to 3.1 log units (L/kg) depending on polymer type (hydrophilic PAN or hydrophobic PS), CNT loading (i.e., values increased with weight percent (wt %) of CNTs), and CNT type (i.e., greater uptake with carboxylated CNTs composites). During field deployment at Muddy Creek in North Liberty, Iowa, optimal ENM-CNTs (PAN with 20 wt % carboxylated CNTs) yielded atrazine concentrations in surface water with a 40% difference relative to analysis of a same-day grab sample. We also observed a mean percent difference of 30 (±20)% when comparing ENM-CNT sampler results to grab sample data collected within 1 week of deployment. With their rapid, high capacity uptake and small material footprint, ENM-CNT equilibrium passive samplers represent a promising alternative to complement traditional integrative passive samplers while offering convenience over large volume grab sampling.

The effect of cyclic tensile force on the actin cytoskeleton organization and morphology of human periodontal ligament cells.

To explore Girdin/Akt pathway protein expression and morphology change by cyclic tension in the periodontal ligament cells. Human periodontal ligament cells were exposed to cyclic tension force at 4000 µstrain and 0.5 Hz for 6 h though a four-point bending system. Cyclic tension force upregulated F-actin, Girdin and Akt expression in hPDL. In transmission electron microscope assay showed that there are more and bigger mitochondria, more and longer cynapses, more cellular organisms after tension force stimulation than control. The actin filament was changed to be regular lines and pointed to poles of cells. However, we found that the Girdin-depleted cells are small and there are more micro-organisms including more lysosomes and matrix vesicles than control. These finding suggest that the STAT3/Girdin/Akt pathway in PDL to response to mechanical stimulation as well, and Girdin may play a significant role in triggering cell proliferation and migration during orthodontic treatment. It provided an insight into the molecular basis for development of a vitro cell model in studying orthodontic treatment.

MA104 Cell line presents characteristics suitable for enterovirus A71 isolation and proliferation.

Enterovirus A71 (EV-A71), one of the most important causative agents of hand, foot and mouth disease (HFMD) in children, can lead to severe clinical outcomes, even death. However, the infection spectrum of EV-A71 in different cell lines remains unknown. Therefore, in this study, the biological characteristics of EV-A71 Subgroup C4 in different cell lines were investigated. To this end, the infectivity of EV-A71Jinan1002 isolated from children with severe HFMD was assessed in 18 different host cell lines. It was found that the MA104 cell line displayed biological characteristics suitable for EV-A71 Subgroup C4 strain isolation and proliferation; indeed, it was found that a broad spectrum of cell lines can be infected by EV-A71Jinan1002. Among the screened cells, four cell lines (HEK293, RD, MA104 and Marc145) produced high 50% tissue culture infective dose (TCID50 ) values calculated in viral proliferations (ranged from 10(7.6) to 10(7.8) ); the TCID50 being negatively associated with the time to appearance of CPE. Proliferation curves demonstrated that EV-A71Jinan1002 amplifies more efficiently in MA104, Hep-2 and RD cells. Remarkably, the virus isolation rate was much higher in MA104 cells than in RD cells. Thus this study, to our knowledge, is for the first to explore the infection spectrum of EV-A71 subgroup C4 in such a large number of different cell lines. Our data provide useful reference data for facilitating further study of EV-A71.

Treatment of a mandibular functional shift in an adolescent boy with temporomandibular disorder and crossbites.

A mandibular functional shift usually poses a challenge for orthodontists, especially when it is accompanied by a temporomandibular disorder (TMD). Accurate diagnosis and complete elimination of the etiologic factors are the keys to an esthetic and stable outcome. This article describes the treatment of a teenager with a mandibular functional shift, TMD symptoms, and facial asymmetry resulting from an asymmetric maxillary arch form and multiple crossbites as occlusal interferences. The treatment alternatives and effective orthodontic techniques are described. To optimize the treatment results and prevent the recurrence of the TMD after treatment, the displaced mandible was repositioned by full-time wearing of a splint for 10 months. Adhesive bite-blocks were used to maintain the newly acquired mandibular position during fixed appliance treatment. A series of nickel-titanium and stainless steel rectangular archwires was placed in the maxillary arch to reshape it for 8 months after alignment. Finally, the displaced mandible was steadily seated into its physiologic position with fine occlusion. The TMD symptoms disappeared and never relapsed after treatment. At 2 years 3 months of retention, there was good stability. The combined splint and fixed appliance approach resolved an intractable clinical problem and avoided using additional appliances. An esthetic, functional, and stable outcome was achieved that satisfied both the patient and his parents.

[Recent advances and perspective in the study of the nano-reinforcing materials for molecular imprinting of proteins].

Molecular imprinting technique (MIT) involves the synthesis of polymer in the presence of a template to produce complementary binding sites in terms of its size, shape and functional group orientation. Such kind of polymer possesses specific recognition ability towards its template molecule. Despite the rapid development of MIT over the years, the majority of the template molecules that have been studied are small molecules, while molecular imprinting of proteins remains a significant yet challenging task due to their large size, structural flexibility and complex conformation. This review, we summarized the research findings over the past years, and discussed the nano-reinforcing materials used to prepare molecular imprinting of proteins and the perspective of these nano-reinforcing materials.

[Bond strengths of absorbable polylactic acid root canal post with three different adhesives].

OBJECTIVE: To find absorbable adhesives with suitable bonding properties for the absorbable polylactic acid root canal post. To test and compare the bond strengths of absorbable polylactic acid root canal post with three different adhesives. METHODS: The absorbable polylactic acid root canal posts were used to restore the extracted teeth, using 3 different adhesives: cyanoacrylates, fibrin sealant and glass ionomer cement. The teeth were prepared into slices for micro-push-out test. The bond strength was statistically analyzed using ANOVA. The specimens were examined using microscope and the failure mode was divided into four categories: cohesive failure between absorbable polylactic acid root canal posts and adhesives, cohesive failure between dentin and adhesives, failure within the adhesives and failure within the absorbable polylactic acid root canal posts. RESULTS: The bond strength of cyanoacrylates [(16.83 ± 6.97) MPa] and glass ionomer cement [(12.10 ± 5.09) MPa] were significantly higher than fibrin sealant [(1.17 ± 0.50) MPa], P<0.001. There was no significant difference between cyanoacrylates and glass ionomer cement (P=0.156). In the group of cyanoacrylates, the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives was 25.0%, the cohesive failure between the dentin and the adhesives was 16.7%, the failure within the adhesives was 33.3%, and the failure within the absorbable polylactic acid root canal posts was 25.0%. In the group of fibrin sealant, the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives was 66.7%, the cohesive failure between the dentin and the adhesives was 22.2%, the failure within the adhesives was 11.1%. In the group of glass ionomer cement, the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives was 87.5%, the failure within the adhesives was 12.5%. The major failure mode in fibrin sealant and glass ionomer cement was the cohesive failure between the absorbable polylactic acid root canal posts and the adhesives. No major failure modes were found in the group of cyanoacrylates. CONCLUSION: The bond strength of fibrin sealant is low, which cannot meet the requirement of clinical use. The bond strengths of cyanoacrylates and glass ionomer cement are suitable for clinical use. The cyanoacrylates are a kind of absorbable adhesive which has suitable bonding properties for the absorbable polylactic acid root canal post.

Depolymerization and decolorization of kraft lignin by bacterium Comamonas sp. B-9.

There is no commercial or industrial-scale process for the remediation of black liquor using microorganisms to date. One of the most important causes is that most microorganisms are not able to use lignin as their principal metabolic carbon or energy source. The bacterial strain Comamonas sp. B-9 has shown remarkable ability to degrade kraft lignin and decolorize black liquor using lignin as its principal metabolic carbon and energy source. This report looks at the depolymerization and decolorization of kraft lignin by Comamonas sp. B-9. The degradation, decolorization, and total carbon removal reached 45, 54, and 47.3%, respectively, after 7 days treatment. Comamonas sp. B-9 was capable of depolymerizing kraft lignin effectively as analyzed by gel permeation chromatography and decolorization via degrading benzene ring structures as shown using Fourier transform infrared spectroscopy analysis.

Effect of glycine powder air-polishing as an adjunct in the treatment of peri-implant mucositis: a pilot clinical trial.

BACKGROUND: Glycine powder air-polishing (GPAP) has the potential to effectively erase biofilms and may improve the treatment efficacy of peri-implant mucositis. This pilot clinical trial evaluated the effect of GPAP as an adjunct in treating peri-implant mucositis. MATERIALS AND METHODS: Twenty-four subjects having at least one implant with peri-implant mucositis were randomly assigned to test (12 subjects with 17 implants) and control (12 subjects with 16 implants) groups. Following baseline assessment, all subjects received oral hygiene instruction and non-surgical debridement. In the test group, the sites with probing depth (PD) ≥4 mm were additionally treated by GPAP for 5 sec. Clinical parameters were measured at 1-week, 1-month, and 3-month recall visits. RESULTS: At the 3-month visit, the mean reductions in PD at site level were 0.93 ± 0.93 mm and 0.91 ± 0.98 mm in the test and control groups, respectively (P < 0.05), and no significant difference existed between two groups. Mean bleeding score was also significantly reduced in both groups after the intervention. No complications or discomfort were reported during the study. CONCLUSIONS: This pilot clinical trial suggests that non-surgical mechanical debridement may effectively control peri-implant mucositis, and adjunctive GPAP treatment seems to have a limited beneficial effect as compared with mechanical debridement alone. However, further clinical trials with a large sample size are needed to confirm this preliminary observation.

A controlled release of antibiotics from calcium phosphate-coated poly(lactic-co-glycolic acid) particles and their in vitro efficacy against Staphylococcus aureus biofilm.

Ceramic-polymer hybrid particles, intended for osteomyelitis treatment, were fabricated by preparing poly(lactic-co-glycolic acid) particles through an emulsion solvent evaporation technique, followed by calcium phosphate (CaP) coating via a surface adsorption-nucleation method. The presence of CaP coating on the surface of the particles was confirmed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Subsequently, two antibiotics for treating bone infection, nafcillin (hydrophilic) and levofloxacin (amphiphilic), were loaded into these hybrid particles and their in vitro drug release studies were investigated. The CaP coating was shown to reduce burst release, while providing sustained release of the antibiotics for up to 4 weeks. In vitro bacterial study against Staphylococcus aureus demonstrated the capability of these antibiotic-loaded hybrid particles to inhibit biofilm formation as well as deteriorate established biofilm, making this hybrid system a potential candidate for further investigation for osteomyelitis treatment.

Green, pH-Sensitive, Highly Stretchable, and Hydrogen Bond-Dominated Ionogel for Wound Healing Activity.

Traditional hydrogel dressings generally have poor mechanical properties and stability when subjected to external stress due to the undesirable chain entanglement structure of their single valence bond compositions. Therefore, it is particularly important to develop a type of gel dressing with good mechanical strength, stability, and environment-friendly monitoring. In this work, a transparent, pH-sensitive, highly stretchable, and biocompatible anthocyanidin ionogel dressing was prepared, realizing green and accurate detection. Attributed to the antibacterial activity of the ionic liquid, the biocompatibility of the pectin, and the ability to scavenge free radicals of the anthocyanidin, the ionogel dressing exhibited excellent re-epithelialization in the 14 day wound healing process. Besides, changes in pH values monitoring of the ionogel over 3 days coincided with normal wound exudate. The obtained ionogel also showed good water retention, swelling properties, mechanical stretchability, and 5 week stability, illustrating great potential in wound dressings.

Arthropod Phylotranscriptomics With a Special Focus on the Basal Phylogeny of the Myriapoda.

Arthropoda represents the most diverse animal phylum, but clarifying the phylogenetic relationships among arthropod taxa remains challenging given the numerous arthropod lineages that diverged over a short period of time. In order to resolve the most controversial aspects of deep arthropod phylogeny, focusing on the Myriapoda, we conducted phylogenetic analyses based on ten super-matrices comprised of 751 to 1,233 orthologous genes across 64 representative arthropod species, including 28 transcriptomes that were newly generated in this study. Our findings provide unambiguous support for the monophyly of the higher arthropod taxa, Chelicerata, Mandibulata, Myriapoda, Pancrustacea, and Hexapoda, while the Crustacea are paraphyletic, with the class Remipedia supported as the lineage most closely related to hexapods. Within the Hexapoda, our results largely affirm previously proposed phylogenetic relationships among deep hexapod lineages, except that the Paraneoptera (Hemiptera, Thysanoptera, and Psocodea) was recovered as a monophyletic lineage in some analyses. The results corroborated the recently proposed phylogenetic framework of the four myriapod classes, wherein Symphyla and Pauropoda, as well as Chilopoda and Diplopoda, are each proposed to be sister taxa. The findings provide important insights into understanding the phylogeny and evolution of arthropods.

An observational study on the safety of teprotumumab based on FAERS database.

OBJECTIVE: Teprotumumab plays an important role in thyroid eye disease pathogenesis and progression. We intend to mine the adverse event (AE) signals from a relevant database, thereby contributing to the safe use of teprotumumab. METHODS: The data obtained from the ASCII data packages in the FAERS database from January 2020 to the second quarter of 2023 were imported into the SAS software (version 9.4) for data cleaning and analysis. Disproportionality analysis was performed using the reporting odds ratio (ROR) in conjunction with the United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) omnibus standard method to detect positive signals. PARTICIPANTS: This retrospective observational study relied on adverse drug reactions reported to the FDA through FAERS, which is a standard public system for spontaneous reporting. RESULTS: Collectively, 2171 AE reports for teprotumumab were collected, among which 108 significant signals were identified involving 17 system organ classes. The SOC of ear and labyrinth disorders included the most AE signals and reports. Muscle spasms, fatigue, headache, nausea, diarrhea, alopecia, blood glucose increased, hypoacusis, tinnitus, and diabetes mellitus were the top ten PTs ranked by the frequency of reporting, meanwhile, the two high-strength signals of thyroid-stimulating immunoglobulin increase (ROR 662.89, 95% CI 182.40-2409.19) and gingival recession (ROR 125.13, 95% CI 79.70-196.45) were not documented in the drug instruction. Meanwhile, we found a higher risk of increased blood glucose, deafness, and decreased appetite for male patients, and headache for female patients. CONCLUSIONS: Clinical application of teprotumumab should be closely monitored for ototoxicity, nail abnormalities, and menstrual changes, as well as for AEs not mentioned in the drug instruction, including gingival recession, thyroid-stimulating immunoglobulin increase, and so on.