ATM, BLM, and CDH1 gene co-mutations in a high-grade endometrial stromal sarcoma patient with multiple abdominal cavity metastases: a case report and literature review.

BACKGROUND: High-grade endometrial stromal sarcoma (HG-ESS) is a rare malignant tumor with poor prognosis. To overcome the limitations of current treatment for advanced patients, the intervention of targeted drug therapy is urgently needed. CASE PRESENTATION: A 74-year-old married woman who presented with abdominal distension and lower abdominal pain was admitted to Hebei General Hospital. After surgery, immunohistochemical staining revealed a malignant tumor which was consistent with HG-ESS. Tumor recurrence occurred 2 months after surgery. Then the patient underwent chemotherapy with two courses but responded poorly. Subsequently we observed ATM, BLM, and CDH1 co-mutations by Next Generation Sequencing (NGS). Then the patient received pamiparib, which resulted in a 10-month progression-free survival (PFS) and is now stable with the administration of sintilimab in combination with pamiparib and anlotinib. CONCLUSIONS: Due to the successful use of poly ADP-ribose polymerase inhibitor (PARPi) on HG-ESS, we suggest that the selection of effective targeted drugs combined with anti- programmed death-1 (PD-1) drug therapy based on genetic testing may become a new option for the treatment of homologous repair deficient (HR-deficient) HG-ESS.

Enhancing the detonation performance of azobistriazole energetic derivatives via inducing N-oxide groups.

The N-oxide strategy plays a crucial role in regulating the performance and safety of energetic materials. This study mainly addresses the question of how the N-oxide group affects the properties of azobistriazole and its derivatives. Our findings indicate that the N-oxide group can increase the density of the system, and its effect on the enthalpy of formation depends on the specific situation. The N-oxide groups can effectively improve the density and energetic properties. Some of the energetic derivatives containing N-oxide groups have a density as high as 2.097 g cm-3 (D3-NO(2)) and a detonation velocity as high as 10 275 m s-1 (C6-NO(2)). The effect of N-oxide groups on the enthalpy of formation depends on the specific circumstances. The effect of N-oxide groups on the stability of azobistriazole energetic derivatives is relatively complex. Among them, the N-oxide group on the triazole ring has an opposite effect on the bond dissociation enthalpy of functional groups. When the N-oxide group is on the 1,2,3-triazole ring, it can improve C-R (R is equal to C(NO2)3, NF2, NHNO2, NO2, and ONO2 respectively) bond dissociation enthalpy, and when it is on the 1,2,4-triazole ring, it will reduce the C-R bond dissociation enthalpy. When the N-oxide group is located on the azo bond, the bond dissociation enthalpy of the azo bond will be significantly reduced. This article systematically explores the effect of N-oxide groups on the properties of azobistriazole energetic derivatives, which will help people better utilize N-oxide groups to design and synthesize new energetic materials.

Fault Diagnosis and Prediction System for Metal Wire Feeding Additive Manufacturing.

In the process of metal wire and additive manufacturing, due to changes in temperature, humidity, current, voltage, and other parameters, as well as the failure of machinery and equipment, a failure may occur in the manufacturing process that seriously affects the current situation of production efficiency and product quality. Based on the demand for monitoring of the key impact parameters of additive manufacturing, this paper develops a parameter monitoring and prediction system for the additive manufacturing feeding process to provide a basis for future fault diagnosis. The fault diagnosis and prediction system for metal wire supply and additive manufacturing utilizes STM 32 as its core, enabling the capture and transmission of temperature, humidity, current, and voltage data. The upper computer system, designed on the LabVIEW 2019 virtual instrument platform, incorporates an LSTM neural network model and facilitates a connection between LabVIEW and MATLAB 2019 to achieve the prediction function. The monitoring and prediction system established in this study is intended to provide basic research assistance in the field of fault diagnosis.

Impact of polystyrene nanoplastics on apoptosis and inflammation in zebrafish larvae: Insights from reactive oxygen species perspective.

In recent years, there has been a growing focus on the toxicity and mortality induced by nanoplastics (NPs) in aquatic organisms. However, studies investigating mechanisms underlying oxidative stress (OS), apoptosis, and inflammation induced by NPs in fish remain limited. This study observed that polystyrene NPs (PS-NPs) were accumulated into zebrafish larvae and zebrafish embryonic fibroblast (ZF4 cells), accompanied by the occurrence of pathological damage both at the cellular and tissue-organ level. Additionally, the transcriptional up-regulation of NADPH oxidases (NOXs) and subsequent excessive generation of reactive oxygen species (ROS) resulted in notable changes in the relative mRNA and protein expression levels associated with antioxidant oxidase systems in larvae. Furthermore, the study identified the impact of NPs on mitochondrial ultrastructural, resulting in mitochondrial depolarization and downregulation of mRNA expression related to the electron transport chain due to excessive ROS generation. Short-term exposure to NPs also triggered apoptosis and inflammation in zebrafish larvae, evident from significant up-regulation in mRNA expressions of proapoptotic factors and NF-κB proinflammatory signaling pathway, as well as increased transcription and protein levels of pro-inflammatory factors in larvae. Inhibition of intracellular excessive ROS effectively reduced the induction of apoptosis, NF-κB P65 nuclear migration levels, and cytokine secretion, underscoring OS as a pivotal factor throughout the process of apoptosis and inflammatory responses induced by NPs. This research significantly advances our comprehension of biological effects and underlying mechanisms of NPs in freshwater fish.

Drug-target interaction prediction using knowledge graph embedding.

The prediction of drug-target interactions (DTIs) is a critical phase in the sustainable drug development process, especially when the research focus is to capitalize on the repositioning of existing drugs. Computational approaches to predicting DTIs can provide important insights into drug mechanisms of action. However, current methods for predicting DTIs based on the structural information of the knowledge graph may suffer from the sparseness and incompleteness of the knowledge graph and neglect the latent type information of the knowledge graph. In this paper, we propose TTModel, a knowledge graph embedding model for DTI prediction. By exploiting biomedical text and type information, TTModel can learn latent text semantics and type information to improve the performance of representation learning. Comprehensive experiments on two public datasets demonstrate that our model outperforms the state-of-the-art methods significantly on the task of DTI prediction.

Deciphering the molecular landscape of rheumatoid arthritis offers new insights into the stratified treatment for the condition.

Background: For Rheumatoid Arthritis (RA), a long-term chronic illness, it is essential to identify and describe patient subtypes with comparable goal status and molecular biomarkers. This study aims to develop and validate a new subtyping scheme that integrates genome-scale transcriptomic profiles of RA peripheral blood genes, providing a fresh perspective for stratified treatments. Methods: We utilized independent microarray datasets of RA peripheral blood mononuclear cells (PBMCs). Up-regulated differentially expressed genes (DEGs) were subjected to functional enrichment analysis. Unsupervised cluster analysis was then employed to identify RA peripheral blood gene expression-driven subtypes. We defined three distinct clustering subtypes based on the identified 404 up-regulated DEGs. Results: Subtype A, named NE-driving, was enriched in pathways related to neutrophil activation and responses to bacteria. Subtype B, termed interferon-driving (IFN-driving), exhibited abundant B cells and showed increased expression of transcripts involved in IFN signaling and defense responses to viruses. In Subtype C, an enrichment of CD8+ T-cells was found, ultimately defining it as CD8+ T-cells-driving. The RA subtyping scheme was validated using the XGBoost machine learning algorithm. We also evaluated the therapeutic outcomes of biological disease-modifying anti-rheumatic drugs. Conclusions: The findings provide valuable insights for deep stratification, enabling the design of molecular diagnosis and serving as a reference for stratified therapy in RA patients in the future.

Species pool and soil properties in mangrove habitats influence the species-immigration process of diazotrophic communities across southern China.

Microbial immigration is an ecological process in natural environments; however, the ecological trade-off mechanisms that govern the balance between species extinction and migration are still lacking. In this study, we investigated the mechanisms underlying the migration of diazotrophic communities from soil to leaves across six natural mangrove habitats in southern China. The results showed that the diazotrophic alpha and beta diversity exhibited significant regional and locational variations. The diazotrophic species pool gradually increased from the leaves to nonrhizosphere soil at each site, exhibiting a vertical distribution pattern. Mantel test analyses suggested that climate factors, particularly mean annual temperature, significantly influenced the structure of the diazotrophic community. The diazotrophic community assembly was mainly governed by dispersal limitation in soil and root samples, whereas dispersal limitation and ecological drift were dominant in leaves. Partial least squares path modeling revealed that the species pool and soil properties, particularly the oxidation-reduction potential and pH, were closely linked to the species-immigration ratio of diazotrophic communities. Our study provides novel insights for understanding the ecological trait diversity patterns and spread pathways of functional microbial communities between below- and aboveground habitats in natural ecosystems.IMPORTANCEEnvironmental selection plays key roles in microbial transmission. In this study, we have provided a comprehensive framework to elucidate the driving patterns of the ecological trade-offs in diazotrophic communities across large-scale mangrove habitats. Our research revealed that Bradyrhizobium japonicum, Marinobacterium lutimaris, and Agrobacterium tumefaciens were more abundant in root-associated soil than in leaves by internal and external pathways. The nonrhizospheric and rhizospheric soil samples harbored the most core amplicon sequence variants, indicating that these dominant diazotrophs could adapt to broader ecological niches. Correlation analysis indicated that the diversities of the diazotrophic community were regulated by biotic and abiotic factors. Furthermore, this study found a lower species immigration ratio in the soil than in the leaves. Both species pool and soil properties regulate the species-immigration mechanisms of the diazotrophic community. These results suggest that substantial species immigration is a widespread ecological process, leading to alterations in local community diversity across diverse host environments.

Effect of esketamine combined with dexmedetomidine on delirium in sedation for mechanically ventilated ICU patients: protocol for a nested substudy within a randomized controlled trial.

BACKGROUND: Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients. METHODS: This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days. DISCUSSION: There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450). TRIAL REGISTRATION: ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Exceptional Nexus in Bose-Einstein Condensates with Collective Dissipation.

In multistate non-Hermitian systems, higher-order exceptional points and exotic phenomena with no analogues in two-level systems arise. A paradigm is the exceptional nexus (EX), a third-order EP as the cusp singularity of exceptional arcs (EAs), that has a hybrid topological nature. Using atomic Bose-Einstein condensates to implement a dissipative three-state system, we experimentally realize an EX within a two-parameter space, despite the absence of symmetry. The engineered dissipation exhibits density dependence due to the collective atomic response to resonant light. Based on extensive analysis of the system's decay dynamics, we demonstrate the formation of an EX from the coalescence of two EAs with distinct geometries. These structures arise from the different roles played by dissipation in the strong coupling limit and quantum Zeno regime. Our Letter paves the way for exploring higher-order exceptional physics in the many-body setting of ultracold atoms.

Common Needs of Patients with Diabetic Kidney Disease: Qualitative Analysis Based on Disease-Specific Social Media Platforms.

Background: Diabetic kidney disease (DKD) patients require comprehensive disease education and mutual support to cope with various challenges. Social media platforms provide opportunities for DKD patients to access information and interact with peers. However, qualitative analysis of DKD patients' real-world concerns and needs on social media is lacking. Methods: A qualitative study was conducted to analyze DKD patients' posts on Facebook and Baidu DKD-specific forums from June 2013 to June 2023. Posts were retrieved, and the forum with the most DKD-related posts from each platform was selected using stratified random sampling. Thematic analysis was performed to identify common themes, which were categorized and quantified. Results: In total, 746 DKD-related posts were analyzed, generating 203 keyword categories with 954 tags. Three main themes emerged: Diagnosis and Comorbidities (50.2%), Treatment and Prevention (29.7%), and Lifestyle and Psychology (20.1%). Patients were most concerned about DKD diagnosis, staging, comorbidities, and interpreting diagnostic indicators. They also sought information on treatment advancements, medications, renal replacement therapies, and traditional Chinese medicine. Diet, exercise, work-life balance, family planning, and mental well-being were key lifestyle and psychological concerns. Conclusion: This study reveals DKD patients' primary needs and concerns on social media, which can guide healthcare professionals in providing targeted education and support. Meeting patients' needs through comprehensive education and counseling can improve treatment adherence and prognosis, though challenges remain in addressing all issues in real-world practice.

Research on reliability mapping of 5G low orbit constellation network slice based on deep reinforcement learning.

Reliability mapping of 5G low orbit constellation network slice is an important means to ensure link network communication. The problem of state space explosion is a typical problem. The deep reinforcement learning method is introduced. Under the 5G low orbit constellation integrated network architecture based on software definition network (SDN) and network function virtualization (NFV), the resource requirements and resource constraints of the virtual network function (VNF) are comprehensively considered to build the 5G low orbit constellation network slice reliability mapping model, and the reliability mapping model parameters are trained and learned by using deep reinforcement learning, solve the problem of state space explosion in the reliability mapping process of 5G low orbit constellation network slices. In addition, node backup and link backup strategies based on importance are adopted to solve the problem that VNF/link reliability is difficult to meet in the reliability mapping process of 5G low orbit constellation network slice. The experimental results show that this method improves the network throughput, packet loss rate and intra slice traffic of 5G low orbit constellation, and can completely repair network faults within 0.3 s; For different number of 5G low orbit constellation network slicing requests, the reliability of this method remains above 98%; For SFC with different lengths, the average network delay of this method is less than 0.15 s.

Dilute Electrolytes with Fluorine-free Ether Solvents for 4.5 V Lithium Metal Batteries.

The limited oxidation stability of ether solvents has posed significant challenges for their applications in high-voltage lithium metal batteries (LMBs). To tackle this issue, the prevailing strategy either adopts a high concentration of fluorinated salts or relies on highly fluorinated solvents, which will significantly increase the manufacturing cost and create severe environmental hazards. Herein, an alternative and sustainable salt engineering approach is proposed to enable the utilization of dilute electrolytes consisting of fluorine (F)-free ethers in high-voltage LMBs. The proposed 0.8 M electrolyte supports stable lithium plating-stripping with a high Coulombic efficiency of 99.47% and effectively mitigates the metal dissolution, phase transition, and gas release issues of the LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode upon charging to high voltages. Consequently, the 4.5 V high-loading Li||NCM 811 cell shows a capacity retention of 75.2% after 300 cycles. Multimodal experimental characterizations coupled with theoretical investigations demonstrate that the boron-containing salt plays a pivotal role in forming the passivation layers on both anode and cathode. The present simple and cost-effective electrolyte design strategy offers a promising and alternative avenue for using commercially mature, environmentally benign, and low-cost F-free ethers in high-voltage LMBs.

Ectopic Activation of Fgf8 in Dental Mesenchyme Causes Incisor Agenesis and Molar Microdontia.

Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.

Optimized Adsorption-Catalytic Conversion for Lithium Polysulfides by Constructing Bimetallic Compounds for Lithium-Sulfur Batteries.

Although lithium-sulfur batteries possess the advantage of high theoretical specific capacity, the inevitable shuttle effect of lithium polysulfides is still a difficult problem restricting its application. The design of highly active catalysts to promote the redox reaction during charge-discharge and thus reduce the existence time of lithium polysulfides in the electrolyte is the mainstream solution at present. In particular, bimetallic compounds can provide more active sites and exhibit better catalytic properties than single-component metal compounds by regulating the electronic structure of the catalysts. In this work, bimetallic compounds-nitrogen-doped carbon nanotubes (NiCo)Se2-NCNT and (CuCo)Se2-NCNT are designed by introducing Ni and Cu into CoSe2, respectively. The (CuCo)Se2-NCNT delivers an optimized adsorption-catalytic conversion for lithium polysulfide, benefitting from adjusted electron structure with downshifted d-band center and increased electron fill number of Co in (CuCo)Se2 compared with that of (NiCo)Se2. This endows (CuCo)Se2 moderate adsorption strength for lithium polysulfides and better catalytic properties for their conversion. As a result, the lithium-sulfur batteries with (CuCo)Se2-NCNT achieve a high specific capacity of 1051.06 mAh g-1 at 1C and an enhanced rate property with a specific capacity of 838.27 mAh g-1 at 4C. The work provides meaningful insights into the design of bimetallic compounds as catalysts for lithium-sulfur batteries.

Dynamic Response of Ti-6Al-2Zr-1Mo-1V Alloy Manufactured by Laser Powder-Bed Fusion.

Titanium parts fabricated by additive manufacturing, i.e., laser or electron beam-powder bed fusion (L- or EB-PBF), usually exhibit columnar grain structures along the build direction, resulting in both microstructural and mechanical anisotropy. Post-heat treatments are usually used to reduce or eliminate such anisotropy. In this work, Ti-6Al-2Zr-1Mo-1V (TA15) alloy samples were fabricated by L-PBF to investigate the effect of post-heat treatment and load direction on the dynamic response of the samples. Post-heat treatments included single-step annealing at 800 °C (HT) and a hot isotropic press (HIP). The as-built and heat-treated samples were dynamically compressed using a split Hopkinson pressure bar at a strain rate of 3000 s-1 along the horizontal and vertical directions paralleled to the load direction. The microstructural observation revealed that the as-built TA15 sample exhibited columnar grains with fine martensite inside. The HT sample exhibited a fine lamellar structure, whereas the HIP sample exhibited a coarse lamellar structure. The dynamic compression results showed that post-heat treatment at 800 °C led to reduced flow stress but enhanced uniform plastic strain and damage absorption work. However, the HIP samples exhibited both higher stress, uniform plastic strain, and damage absorption work owing to the microstructure coarsening. Additionally, the load direction had a subtle influence on the flow stress, indicating the negligible anisotropy of flow stress in the samples. However, there was more significant anisotropy of the uniform plastic strain and damage absorption. The samples had a higher load-bearing capacity when dynamically compressed perpendicular to the build direction.

Lysophosphatidic Acid (LPA) and Its Receptors in Mood Regulation: A Systematic Review of the Molecular Mechanisms and Therapeutic Potential.

Mood disorders affect over 300 million individuals worldwide, often characterized by their chronic and refractory nature, posing significant threats to patient life. There has been a notable increase in mood disorders among American adolescents and young adults, with a rising number of suicide attempts and fatalities, highlighting a growing association between mood disorders and suicidal outcomes. Dysregulation within the neuroimmune-endocrine system is now recognized as one of the fundamental biological mechanisms underlying mood and mood disorders. Lysophosphatidic acid (LPA), a novel mediator of mood behavior, induces anxiety-like and depression-like phenotypes through its receptors LPA1 and LPA5, regulating synaptic neurotransmission and plasticity. Consequently, LPA has garnered substantial interest in the study of mood regulation. This study aimed to elucidate the molecular mechanisms of lysophosphatidic acid and its receptors, along with LPA receptor ligands, in mood regulation and to explore their potential therapeutic efficacy in treating mood disorders. A comprehensive literature search was conducted using the PubMed and Web of Science databases, identifying 208 articles through keyword searches up to June 2024. After excluding duplicates, irrelevant publications, and those restricted by open access limitations, 21 scientific papers were included in this review. The findings indicate that LPA/LPA receptor modulation could be beneficial in treating mood disorders, suggesting that pharmacological agents or gintonin, an extract from ginseng, may serve as effective therapeutic strategies. This study opens new avenues for future research into how lysophosphatidic acid and its receptors, as well as lysophosphatidic acid receptor ligands, influence emotional behavior in animals and humans.

Selenoprotein W modulates tau homeostasis in an Alzheimer's disease mouse model.

Lower selenium levels are observed in Alzheimer's disease (AD) brains, while supplementation shows multiple benefits. Selenoprotein W (SELENOW) is sensitive to selenium changes and binds to tau, reducing tau accumulation. However, whether restoration of SELENOW has any protective effect in AD models and its underlying mechanism remain unknown. Here, we confirm the association between SELENOW downregulation and tau pathology, revealing SELENOW's role in promoting tau degradation through the ubiquitin‒proteasome system. SELENOW competes with Hsp70 to interact with tau, promoting its ubiquitination and inhibiting tau acetylation at K281. SELENOW deficiency leads to synaptic defects, tau dysregulation and impaired long-term potentiation, resulting in memory deficits in mice. Conversely, SELENOW overexpression in the triple transgenic AD mice ameliorates memory impairment and tau-related pathologies, featuring decreased 4-repeat tau isoform, phosphorylation at Ser396 and Ser404, neurofibrillary tangles and neuroinflammation. Thus, SELENOW contributes to the regulation of tau homeostasis and synaptic maintenance, implicating its potential role in AD.

Interface-regulated S-type core-shell PCN-224@TiO2 heterojunction for visible-light-driven generation of singlet oxygen for selective photooxidation of 2-chloroethyl ethyl sulfide.

Selective oxidation of sulfur mustard gas (HD) to non-toxic sulfoxide by the visible-light-catalyzed generation of singlet oxygen (1O2) is a promising degradation strategy. Although PCN-224 can absorb visible light, it suffers from rapid electron-hole recombination and low redox capacity, which limits the performance of HD degradation. Titanium dioxide (TiO2) is an excellent photocatalyst but it lacks visible-light-activity in degrading HD. In this study, PCN-224@TiO2 heterojunction with S-type core-shell structure was synthesized by in-situ growth method to prolong the visible light absorption capacity of TiO2 and inhibit the rapid recombination of PCN-224. The interface formation and internal electric field were optimized by adjusting the Zr/Ti ratio to enhance the charge transfer, redox capacity, electron-hole separation, and visible light absorption. In this study, the formation of heterojunction composites based on Zr-O-Ti linkages is demonstrated by a series of characterization methods. It is demonstrated by experiments and theoretical calculations that PCN-224@TiO2 can generate nearly 100 % 1O2 under visible light conditions without a sacrificial agent, resulting in efficient and selective oxidation of 2-chloroethyl ethyl sulfide (CEES), a simulant of HD, to non-toxic sulfoxide form.

Insight into the regulatory mechanism of ß-arrestin2 and its emerging role in diseases.

ß-arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein-coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. Previous studies have demonstrated that ß-arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post-transcriptional modifications can affect the expression of ß-arrestin2. Furthermore, post-translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S-nitrosylation affect the cellular localization of ß-arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of ß-arrestin2. This review summarizes the structure and function of ß-arrestin2 and reveals the mechanisms involved in the regulation of ß-arrestin2 at multiple levels. Additionally, recent studies on the role of ß-arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting ß-arrestin2.

Dense Perovskite Thick Film Enabled by Saturated Solution Filling for Sensitive X-ray Detection and Imaging.

Thick polycrystalline perovskite films synthesized by using solution processes show great potential in X-ray detection applications. However, due to the evaporation of the solvent, many pinholes and defects appear in the thick films, which deteriorate their optoelectronic properties and diminish their X-ray detection performance. Therefore, the preparation of large area and dense perovskite thick films is desired. Herein, we propose an effective strategy of filling the pores with a saturated precursor solution. By adding the saturated perovskite solution to the polycrystalline perovskite thick film, the original perovskite film will not be destroyed because of the solution-solute equilibrium relationship. Instead, it promotes in situ crystal growth within the thick film during the annealing process. The loosely packed grains in the original thick perovskite film are connected, and the pores and defects are partially filled and fixed. Finally, a much denser perovskite thick film with improved optoelectronic properties has been obtained. The optimized thick film exhibits an X-ray sensitivity of 1616.01 µC Gyair-1 cm-2 under an electric field of 44.44 V mm-1 and a low detection limit of 28.64 nGyair s-1 under an electric field of 22.22 V mm-1. These values exceed the 323.86 µC Gyair-1 cm-2 and 40.52 nGyair s-1 of the pristine perovskite thick film measured under the same conditions. The optimized thick film also shows promising working stability and X-ray imaging capability.