In-Situ Surface Repair of FAPbBr3 Quantum Dots toward High-Performance Pure-Green Perovskite Light-Emitting Diodes.

Metal halide perovskite light-emitting diodes (PeLEDs) are ideal for high-resolution displays due to their tunable emission, narrow spectra, and low-cost processing. Colloidal FAPbBr3 perovskite quantum dots (PeQDs) enhance radiative recombination, making them efficient for pure-green PeLEDs. However, their low stability and surface defects limit their practical application. Here, we address these challenges by proposing an in situ surface repair strategy using benzhydroxamic acid (BHA) as a modifier. We demonstrated that BHA can coordinate with Pb2+ ions and form hydrogen bonds with FA+ and halide ions, effectively reducing nonradiative recombination and maintaining the integrity of the PeQDs. High-quality FAPbBr3 PeQDs with a photoluminescence quantum yield (PLQY) of up to 92.5% were achieved, leading to pure-green PeLEDs with an external quantum efficiency (EQE) of 24.8% and a maximum luminance of 40,231 cd m-2, providing a feasible and promising perspective for advanced solid-state lighting and displays.

Survey of Microstructures and Dimensional Accuracy of Various Microlattice Designs Using Additively Manufactured 718 Superalloy.

Microlattices hold significant potential for developing lightweight structures for the aeronautics and astronautics industries. Laser Powder Bed Fusion (LPBF) is an attractive method for producing these structures due to its capacity for achieving high-resolution, intricately designed architectures. However, defects, such as cracks, in the as-printed alloys degrade mechanical properties, particularly tensile strength, and thereby limit their applications. This study examines the effects of microlattice architecture and relative density on crack formation in the as-printed 718 superalloy. Complex microlattice design and higher relative density are more prone to large-scale crack formation. The mechanisms behind these phenomena are discussed. This study reveals that microlattice type and relative density are crucial factors in defect formation in LPBF metallic alloys. The transmission electron microscopy observations show roughly round γ″ precipitates with an average size of 10 nm in the as-printed 718 without heat treatment. This work demonstrates the feasibility of the additive manufacturing of complex microlattices using 718 superalloys towards architectured lightweight structures.

Stearoyl coenzyme A desaturase 1 (SCD1) regulates foot-and-mouth disease virus replication by modulating host cell lipid metabolism and viral protein 2C-mediated replication complex formation.

The life cycle of foot-and-mouth disease virus (FMDV) is tightly regulated by host cell lipid metabolism. In previous studies, we reported downregulated expression of stearoyl coenzyme A desaturase-1 (SCD1), a key enzyme of fatty acid metabolism, in BHK-VEC cells (a virus-negative cell line derived from BKH-21 cells with persistent FMDV infection) on comparing transcriptomic data for BHK-VEC and BHK-21 cells (Y. Yuan et al., Front Cell Infect Microbiol 12:940906, 2022, https://doi.org/10.3389/fcimb.2022.940906; L. Han et al., Vet Microbiol 263:109247, 2021, https://doi.org/10.1016/j.vetmic.2021.109247). In the present study, we identify that SCD1 regulates FMDV replication. SCD1 overexpression or exogenous addition of oleic acid (OA), a product of the enzymatic activity of SCD1, increased FMDV replication in both BHK-21 cells and SCD1-knockdown cells. Overexpression of SCD1 or exogenous addition of OA restored FMDV infection and replication in BHK-VEC cells, and OA also promoted FMDV replication in BHK-21 cells with persistent FMDV infection. SCD1 recruited the nonstructural FMDV protein 2C to a detergent-resistant membrane located in the perinuclear region of cells to form replication complexes. Inhibiting SCD1 enzyme activity resulted in a significantly decreased number of FMDV replication complexes with abnormal morphology. Inhibition of SCD1 activity also effectively decreased the replication of other RNA viruses such as respiratory enteric orphan virus-3-176, poliovirus-1, enterovirus 71, and vesicular stomatitis virus. Our results demonstrate that SCD1, as a key host regulator of RNA virus replication, is a potential target for developing novel drugs against infections by RNA viruses. IMPORTANCE: Many positive-stranded RNA viruses, including foot-and-mouth disease virus (FMDV), alter host membranes and lipid metabolism to create a suitable microenvironment for their survival and replication within host cells. In FMDV-infected cells, the endoplasmic reticulum membrane is remodeled, forming vesicular structures that rely heavily on increased free fatty acids, thereby linking lipid metabolism to the FMDV replication complex. Nonstructural FMDV protein 2C is crucial for this complex, while host cell enzyme stearoyl coenzyme A desaturase 1 (SCD1) is vital for lipid metabolism. We found that FMDV infection alters SCD1 expression in host cells. Inhibiting SCD1 expression or its enzymatic activity markedly decreases FMDV replication, while supplementing oleic acid, a catalytic product of SCD1, regulates FMDV replication. Additionally, SCD1 forms part of the FMDV replication complex and helps recruit 2C to a detergent-resistant membrane. Our study provides insights into the pathogenesis of FMDV and a potential novel drug target against the virus.

Decomposition-assisted analysis of transmission in periodic resonator arrays using mode-matching method.

This paper focuses on analysing acoustic structures containing locally reacting resonators, aiming to establish a framework for discussing sound properties related to scattering and transmission in a periodic resonator array. The paper introduces an analytical model for the input surface impedance of non-uniform resonator arrays, which is a challenging task when addressing sound propagation to the opposite side of the array. To address this challenge, a mode-matching method is employed within a one-dimensional periodic structure combined with the decomposition of the initial mirror-symmetric system into symmetric and antisymmetric sub-systems. This procedure leads to simplified analytical solutions of transmission problems about non-uniform resonator arrays, and its accuracy is verified through numerical simulations. The proposed method provides insights into mode shapes and amplitudes, thereby complementing numerical simulations and enabling a comprehensive understanding of sound fields beyond conventional results such as pressure fields and sound absorption coefficients alone. The model of a periodic varying-height resonator array presented herein involves developing mathematical equations or simulations to capture the physical characteristics and interactions of the resonators. This approach empowers researchers to predict and comprehend the non-uniform array's transmission behaviour and performance characteristics, with diverse applications spanning various systems, including electromagnetic devices.

Understanding hepatitis E vaccination intention among women of childbearing-age: A theory-based cross-sectional study.

OBJECTIVES: The purpose of this study was to investigate the HEV vaccination intention, its determinants, and overall influence mechanisms among childbearing-age women. METHOD: The current study was cross-sectional and conducted online from June 25, 2023 to September 25, 2023 in Nanjing, China. Logistic regression models were constructed to identify the intention-associated background factors. Technology Acceptance Model (TAM) and Theory of Planned Behavior (TPB) were integrated and expanded as TAM-TPB model to further investigate the determinants and overall influence mechanism of HEV vaccination intention among this population using structural equation modeling. RESULTS: A total of 423 eligible participants were included in this study. High general HEV knowledge was independently associated with an increased intention to get HEV vaccination (OR = 1.97, 95 % CI: 1.11-3.58, P = 0.023). All the hypotheses proposed in the theoretical TAM-TPB model were supported, with perceived ease of use, perceived usefulness, attitude, subjective norm, and perceived behavioral control positively affecting the intention of HEV vaccination (all P values <0.05), while perceived risk (P = 0.003) exhibited an inverse association with HEV vaccination intention. The model achieved an acceptable fit, and the total explained variance of HEV vaccination intention was as high as 86.20 %. Moreover, no significant common method bias was observed. CONCLUSION: This is the first theory-based study that explored the HEV vaccination intention, its determinants, and overall influence mechanism among childbearing-age women. The results of the current study are of great importance for improving the understanding of the HEV vaccination intention among females of childbearing age.

Neuropeptide Y receptor activation preserves inner retinal integrity through PI3K/Akt signaling in a glaucoma mouse model.

Neuropeptide Y (NPY), an endogenous peptide composed of 36 amino acids, has been investigated as a potential therapeutic agent for neurodegenerative diseases due to its neuroprotective attributes. This study investigated the neuroprotective effects of NPY in a mouse model of glaucoma characterized by elevated intraocular pressure (IOP) and progressive retinal ganglion cell degeneration. Elevated IOP in mice was induced through intracameral microbead injections, accompanied by intravitreal administration of NPY peptide. The results demonstrated that NPY treatment preserved both the structural and functional integrity of the inner retina and mitigated axonal damage and degenerative changes in the optic nerve under high IOP conditions. Further, NPY treatment effectively reduced inflammatory glial cell activation, as evidenced by decreased expression of glial fibrillary acidic protein and Iba-1. Notably, endogenous NPY expression and its receptors (NPY-Y1R and NPY-Y4R) levels were negatively affected in the retina under elevated IOP conditions. NPY treatment restored these changes to a significant extent. Molecular analysis revealed that NPY mediates its protective effects through the mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways. These findings highlight the therapeutic potential of NPY in glaucoma treatment, underscoring its capacity to preserve retinal health, modulate receptor expression under stress, reduce neuroinflammation, and impart protection against axonal impairment.

Low Contact Resistance on Monolayer MoS2 Field-Effect Transistors Achieved by CMOS-Compatible Metal Contacts.

Contact engineering on monolayer layer (ML) semiconducting transition metal dichalcogenides (TMDs) is considered the most challenging problem toward using these materials as a transistor channel in future advanced technology nodes. The typically observed strong Fermi-level pinning induced in part by the reaction of the source/drain contact metal and the ML TMD frequently results in a large Schottky barrier height, which limits the electrical performance of ML TMD field-effect transistors (FETs). However, at a microscopic level, little is known about how interface defects or reaction sites impact the electrical performance of ML TMD FETs. In this work, we have performed statistically meaningful electrical measurements on at least 120 FETs combined with careful surface analysis to unveil contact resistance dependence on interface chemistry. In particular, we achieved a low contact resistance for ML MoS2 FETs with ultrahigh-vacuum (UHV, 3 × 10-11 mbar) deposited Ni contacts, ∼500 Ω·µm, which is 5 times lower than the contact resistance achieved when deposited under high-vacuum (HV, 3 × 10-6 mbar) conditions. These electrical results strongly correlate with our surface analysis observations. X-ray photoelectron spectroscopy (XPS) revealed significant bonding species between Ni and MoS2 under UHV conditions compared to that under HV. We also studied the Bi/MoS2 interface under UHV and HV deposition conditions. Different from the case of Ni, we do not observe a difference in contact resistance or interface chemistry between contacts deposited under UHV and HV. Finally, this article also explores the thermal stability and reliability of the two contact metals employed here.

A bibliometric analysis of transcranial alternating current stimulation.

Background: Transcranial alternating current stimulation (tACS) can apply currents of varying intensity to the scalp, modulating cortical excitability and brain activity. tACS is a relatively new neuromodulation intervention that is now widely used in clinical practice. Many papers related to tACS have been published in various journals. However, there are no articles that objectively and directly introduce the development trend and research hotspots of tACS. Therefore, the aim of this study is to use CiteSpace to visually analyze the recent tACS-related publications, systematically and in detail summarize the current research hotspots and trends in this field, and provide valuable information for future tACS-related research. Material and methods: The database Web of Science Core Collection Science Citation Index Expanded was used and searched from build to 4 August 2023. Using the CiteSpace to analyze the authors, institutions, countries, keywords, co-cited authors, journals, and references. Results: A total of 677 papers were obtained. From 2008 to 2023, the number of publications shows an increasing trend, albeit with some fluctuations. The most productive country in this field was Germany. The institution with the highest number of publications is Carl von Ossietzky University of Oldenburg (n = 50). According to Bradford's law, 7 journals are considered core journals in the field. Herrmann, CS was the author with the most publications (n = 40), while Antal, A was the author with the highest number of co-citations (n = 391) and betweenness centrality (n = 0.16). Disease, neural mechanisms of the brain and electric stimulation are the major research areas in the field. The effect of tACS in different diseases, multi-site stimulation, combined treatment and evaluation are the future research hotspots and trends. Conclusion: tACS has research value and research potential, and more and more researchers are paying attention to it. The findings of this bibliometric study provide the current status and trends in the clinical research of tACS and may help researchers to identify hotspots s and explore new research directions in this field.

Emerging Trends in the Application of Extracellular Vesicles as Novel Oral Delivery Vehicles for Therapeutics in Inflammatory Diseases.

Inflammation involves complex immune responses where cytokines such as TNF-α, IL-1, and IL-6 promote vasodilation and increased vascular permeability to facilitate immune cell migration to inflammation sites. Persistent inflammation is linked to diseases like cancer, arthritis, and neurodegenerative disorders. Although oral anti-inflammatory drugs are favored for their non-invasiveness and cost-effectiveness, their efficacy is often compromised due to gastrointestinal degradation and limited bioavailability. Recent advancements highlight the potential of extracellular vesicles (EVs) as nanocarriers that enhance drug delivery by encapsulating therapeutic agents, ensuring targeted release and reduced toxicity. These EVs, derived from dietary sources and cell cultures, exhibit excellent biocompatibility and stability, presenting a novel approach in anti-inflammatory therapies. This review discusses the classification and advantages of orally administered EVs (O-EVs), their mechanism of action, and their emerging role in treating inflammatory conditions, positioning them as promising vectors in the development of innovative anti-inflammatory drug delivery systems.

Direct Growth of Vertical Graphene on Fiber Electrodes and Its Application in Alternating Current Line-Filtering Capacitors.

Fiber-shaped electrochemical capacitors (FSECs) have garnered substantial attention to emerging portable, flexible, and wearable electronic devices. However, achieving high electronic and ionic conductivity in fiber electrodes while maintaining a large specific surface area is still a challenge for enhancing the capacitance and rapid response of FSECs. Here, we present an electric-field-assisted cold-wall plasma-enhanced chemical vapor (EFCW-PECVD) method for direct growth of vertical graphene (VG) on fiber electrodes, which is incorporated in the FSECs. The customized reactor mainly consists of two radio frequency coils: one for plasma generation and the other for substrate heating. Precise temperature control can be achieved by adjusting the conductive plates and the applied power. With induction heating, only the substrate is heated to above 500 °C within just 5 min, maintaining a low temperature in the gas phase for the growth of VG with a high quality. Using this method, VG was easily grown on metallic fibers. The VG-coated titanium fibers for FSECs exhibit an ultrahigh rate performance and quick ion transport, enabling the conversion of an alternating current signal to a direct current signal and demonstrating outstanding filtering capabilities.

Unlocking comprehensive molecular design across all scenarios with large language model and unordered chemical language.

Molecular generation stands at the forefront of AI-driven technologies, playing a crucial role in accelerating the development of small molecule drugs. The intricate nature of practical drug discovery necessitates the development of a versatile molecular generation framework that can tackle diverse drug design challenges. However, existing methodologies often struggle to encompass all aspects of small molecule drug design, particularly those rooted in language models, especially in tasks like linker design, due to the autoregressive nature of large language model-based approaches. To empower a language model for a wider range of molecular design tasks, we introduce an unordered simplified molecular-input line-entry system based on fragments (FU-SMILES). Building upon this foundation, we propose FragGPT, a universal fragment-based molecular generation model. Initially pretrained on extensive molecular datasets, FragGPT utilizes FU-SMILES to facilitate efficient generation across various practical applications, such as de novo molecule design, linker design, R-group exploration, scaffold hopping, and side chain optimization. Furthermore, we integrate conditional generation and reinforcement learning (RL) methodologies to ensure that the generated molecules possess multiple desired biological and physicochemical properties. Experimental results across diverse scenarios validate FragGPT's superiority in generating molecules with enhanced properties and novel structures, outperforming existing state-of-the-art models. Moreover, its robust drug design capability is further corroborated through real-world drug design cases.

Structural and functional insights into the 2'-O-methyltransferase of SARS-CoV-2.

A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16 (nsp16), 2'-O-methyltransferase (2'-O-MTase), to cap their RNAs through ribose 2'-O-methylation modification. This process is crucial for maintaining viral genome stability, facilitating efficient translation, and enabling immune escape. Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10, insights into its molecular mechanism have so far been limited. In this study, we systematically characterized the 2'-O-MTase activity of nsp16 in SARS-CoV-2, focusing on its dependence on nsp10 stimulation. We observed cross-reactivity between nsp16 and nsp10 in various coronaviruses due to a conserved interaction interface. However, a single residue substitution (K58T) in SARS-CoV-2 nsp10 restricted the functional activation of MERS-CoV nsp16. Furthermore, the cofactor nsp10 effectively enhanced the binding of nsp16 to the substrate RNA and the methyl donor S-adenosyl-l-methionine (SAM). Mechanistically, His-80, Lys-93, and Gly-94 of nsp10 interacted with Asp-102, Ser-105, and Asp-106 of nsp16, respectively, thereby effectively stabilizing the SAM binding pocket. Lys-43 of nsp10 interacted with Lys-38 and Gly-39 of nsp16 to dynamically regulate the RNA binding pocket and facilitate precise binding of RNA to the nsp16/nsp10 complex. By assessing the conformational epitopes of nsp16/nsp10 complex, we further determined the critical residues involved in 2'-O-MTase activity. Additionally, we utilized an in vitro biochemical platform to screen potential inhibitors targeting 2'-O-MTase activity. Overall, our results significantly enhance the understanding of viral 2'-O methylation process and mechanism, providing valuable targets for antiviral drug development.

A human commensal-pathogenic fungus suppresses host immunity via targeting TBK1.

Candida albicans stably colonizes humans but is the leading cause of hospital-acquired fungemia. Traditionally, masking immunogenic moieties has been viewed as a tactic for immune evasion. Here, we demonstrate that C. albicans blocks type I interferon (IFN-I) signaling via translocating an effector protein Cmi1 into host cells. Mechanistically, Cmi1 binds and inhibits TANK-binding kinase 1 (TBK1) to abrogate IFN-regulatory factor 3 (IRF3) phosphorylation, thereby suppressing the IFN-I cascade. Murine infection with a cmi1 mutant displays an exaggerated IFN-I response in both kidneys and bone-marrow-derived macrophages, leading to rapid fungal clearance and host survival. Remarkably, the lack of CMI1 compromises gut commensalism and increases IFN-I response in mouse colonic cells. These phenotypes of cmi1 are rescued by the depletion of IFN-I receptor. This work establishes the importance of TBK1 inhibition in fungal pathogenesis and reveals that a human commensal-pathogenic fungus significantly impacts host immunity during gut colonization and infection via delivering effector proteins into host cells.

Metformin synergizes with gilteritinib in treating FLT3-mutated leukemia via targeting PLK1 signaling.

Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g., gilteritinib) are effective, they face challenges such as drug resistance, relapse, and high costs. Here, we report that metformin, a cheap, safe, and widely used anti-diabetic agent, exhibits a striking synergistic effect with gilteritinib in treating FLT3-ITD AML. Metformin significantly sensitizes FLT3-ITD AML cells (including TKI-resistant ones) to gilteritinib. Metformin plus gilteritinib (low dose) dramatically suppresses leukemia progression and prolongs survival in FLT3-ITD AML mouse models. Mechanistically, the combinational treatment cooperatively suppresses polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.

Investigating the role of killer cell immunoglobulin-like receptors and human leukocyte antigen genetic variants in hepatitis C virus infection.

The genetic diversity of killer cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) genes influences the host's immune response to viral pathogens. This study aims to explore the impact of five single nucleotide polymorphisms (SNPs) in KIR3DL2 and HLA-A genes on hepatitis C virus (HCV) infection. A total of 2251 individuals were included in the case-control study. SNPs including KIR3DL2 rs11672983, rs3745902, rs1654644, and HLA-A rs3869062, rs12202296 were genotyped. By controlling various confounding factors using a modified logistic regression model, as well as incorporating stratified analysis, joint effects analysis, and multidimensional bioinformatics analysis, we analyzed the relationship between SNPs and HCV infection. The logistic regression analysis showed a correlation between KIR3DL2 rs11672983 AA, KIR3DL2 rs3745902 TT, and increased HCV susceptibility (p < 0.01). Stratified analysis indicated that KIR3DL2 rs1654644 and HLA-A rs3869062 also heightened HCV susceptibility in certain subgroups. A linear trend of rising HCV infection rates was observed when combining KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT (ptrend = 0.007). Bioinformatics analysis suggested these SNPs' regulatory potential and their role in altering messenger RNA secondary structure, implying their functional relevance in HCV susceptibility. Our findings indicate that KIR3DL2 rs11672983 AA and KIR3DL2 rs3745902 TT are significantly associated with increased susceptibility to HCV infection.

A Synopsis of Dicranum Hedw. (Dicranaceae, Bryophyta) in China, with Special References to Four Species Newly Reported and Re-Evaluation of Dicranum psathyrum Klazenga.

Dicranum Hedw. is a highly diverse and widely distributed genus within Dicranaceae. The species diversity and distribution of this genus in China, however, remain not well known. A new revision of Dicranum in China using morphological and molecular phylogenetic methods confirms that China has 39 species, including four newly reported species, D. bardunovii Tubanova & Ignatova, D. dispersum Engelmark, D. schljakovii Ignatova & Tubanova, and D. spadiceum J.E.Zetterst. Dicranum psathyrum Klazenga is transferred to Dicranoloma (Renauld) Renauld as a new synonym of Dicranoloma fragile Broth. Two species, Dicranum brevifolium (Lindb.) Lindb. and D. viride (Sull. & Lesq.) Lindb. are excluded from the bryoflora of China. A key to the Chinese Dicranum species is also provided. These results indicate an underestimation of the distribution range of numerous Dicranum species, underscoring the need for further in-depth investigations into the worldwide Dicranum diversity.

Highly Accurate and Efficient Deep Learning Paradigm for Full-Atom Protein Loop Modeling with KarmaLoop.

Protein loop modeling is a challenging yet highly nontrivial task in protein structure prediction. Despite recent progress, existing methods including knowledge-based, ab initio, hybrid, and deep learning (DL) methods fall substantially short of either atomic accuracy or computational efficiency. To overcome these limitations, we present KarmaLoop, a novel paradigm that distinguishes itself as the first DL method centered on full-atom (encompassing both backbone and side-chain heavy atoms) protein loop modeling. Our results demonstrate that KarmaLoop considerably outperforms conventional and DL-based methods of loop modeling in terms of both accuracy and efficiency, with the average RMSDs of 1.77 and 1.95 Å for the CASP13+14 and CASP15 benchmark datasets, respectively, and manifests at least 2 orders of magnitude speedup in general compared with other methods. Consequently, our comprehensive evaluations indicate that KarmaLoop provides a state-of-the-art DL solution for protein loop modeling, with the potential to hasten the advancement of protein engineering, antibody-antigen recognition, and drug design.

Upregulation of CDC25B by transcription factor TEAD4 drives invasion and inhibits cisplatin sensitivity through cell adhesion in stomach adenocarcinoma.

Cisplatin is crucial in management of advanced stomach adenocarcinoma, whereas development of chemotherapy resistance hinders overall efficacy of cisplatin. This work aims to explore role of CDC25B in cisplatin sensitivity in stomach adenocarcinoma and offer a possible mechanism for explaining its function. By using bioinformatics approaches, CDC25B and TEAD4 expression levels in stomach adenocarcinoma tissues and enriched pathways of CDC25B were analyzed. qRT-PCR of CDC25B and TEAD4 expression in stomach adenocarcinoma cells, CCK-8 detection of cell viability and IC50 values, and colony formation assay on cell proliferation were performed. Cell adhesion experiment detected cell adhesion ability. Western blot detected expression of proteins related to cell adhesion, specifically Muc-1, ICAM-1, VCAM-1. Dual luciferase assay and ChIP experiment verified binding relationship between TEAD4 and CDC25B. CDC25B was upregulated in stomach adenocarcinoma tissues and cells, enriched in focal adhesion pathway. Treatment with cell adhesion inhibitors revealed that CDC25B overexpression inhibits the sensitivity of stomach adenocarcinoma to cisplatin through the cell adhesion pathway. CDC25B has an upstream transcription factor TEAD4, which targeted and bound to CDC25B and was highly expressed in stomach adenocarcinoma. Rescue experiment revealed that knocking down TEAD4 weakened suppressive impact of CDC25B overexpression on sensitivity of stomach adenocarcinoma cells to cisplatin. Transcription factor TEAD4 could activate the transcription of CDC25B through cell adhesion to drive cell invasion and reduce sensitivity of stomach adenocarcinoma to cisplatin. TEAD4 and CDC25B may become new targets for management of stomach adenocarcinoma.

Mechanistic Insights into Tanshinone IIA in the Amelioration of Post-Thyroidectomy Hypoparathyroidism.

BACKGROUND: Thyroidectomy causes impaired blood supply to the parathyroid glands, which leads to hypoparathyroidism. Tanshinone IIA (Tan IIA) is helpful in blood activation and cardiovascular protection. Therefore, the efficacy of Tan IIA in improving hypoparathyroidism was explored in this study. METHODS: New Zealand white rabbits were utilized to establish a unilateral parathyroid gland ischemia injury model. The model was created by selectively ligating the main blood supply vessel of one parathyroid gland, and the rabbits were then divided into three groups receiving 1, 5, and 10 mg/kg of Tan IIA. Serum calcium and parathyroid hormone (PTH) levels were measured using specialized assay kits. Immunohistochemistry was used to assess the microvessel density (MVD) in parathyroid glands. Western blotting (WB) was used to analyze protein expression related to the PI3K/AKT signaling pathway and the pathway-associated HIF-1α and VEGF. Moreover, MMP-2 and MMP-9 involved in angiogenesis were detected by WB. RESULTS: Tan IIA treatment effectively restored serum calcium and PTH levels in a dose-dependent manner. Notably, MVD in the parathyroid glands increased significantly, especially at higher doses. The Tan IIA treatment also elevated the p-PI3K/PI3K and p-AKT/AKT ratios, indicating that the PI3K/AKT pathway was reactivated. Moreover, Tan IIA significantly restored the decreased expression levels of VEGF and HIF-1α caused by parathyroid surgery. Additionally, Tan IIA increased MMP-2 and MMP-9 levels. CONCLUSION: Tan IIA activates the PI3K/AKT pathway, promotes angiogenesis by modulating VEGF, HIF-1α, MMP-2, and MMP-9, thereby further enhancing MVD within the parathyroid glands. This study demonstrates that Tan IIA improved post-thyroidectomy hypoparathyroidism.