Twisted Structure Induced Solid-State Fluorescence and Room-Temperature Phosphorescence from Furan-Based Carbon Dots.

Boron doping can effectively induce solid-state fluorescence (SSF) in carbon dots (CDs); however, research on the intrinsic mechanism underlying this phenomenon is lacking. Herein, a design strategy for boron-doped furan-based CDs is proposed, CDs with aggregation-induced emission (AIE) properties are synthesized, and the mechanism by which boron atom dopants induces SSF and room-temperature phosphorescence (RTP) is elucidated. The morphology and structural characterization of the CDs indicate that boron doping leads to structural twisting of the CDs. The AIE phenomenon of CDs arises from the inhibition of the twisted structure motions and a reduction in the nonradiative relaxation rate during the aggregation process. In addition, CDs with twisted structures exhibit a smaller overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), effectively reducing the singlet-triplet splitting energy (ΔEST). CDs embedded in microcrystalline cellulose (MCC) exhibit green RTP because the nonradiative transitions are suppressed, and the excited triplet species remain stable. For the first time, this study reveals the structure-activity relationship between the twisted structure and optical properties of CDs, providing a new approach for the preparation of solid-state light-emitting CDs.

Solid-State Fluorescent Carbon Dots with Hydrophobic Modification Induced Red Emission for White Light-Emitting Diodes.

Herein, we developed red solid-state fluorescent carbon dots (SSF-CDs) through a one-step solvothermal method, utilizing acetone as the carbonization solvent. Optical and structural characterization revealed that the sp2 domains in the core of the R-CDs were consistently interrupted and that the oxygen-containing groups on the surface were replaced by alkyl groups. This substitution mitigates excessive π-π interactions, thereby preventing quenching of fluorescence in the solid state. Adjusting the molar ratio of citric acid (CA) and urea yielded solid fluorescent carbon dots (CDs) with panchromatic luminescence, indicating enhanced π-π interactions and more pronounced red shifts in the emission peaks. Furthermore, we found that this strategy is applicable to other carbon sources, including phenylenediamine, salicylic acid, and lignin. This research presents an innovative strategy for the fabrication of solid-state luminescent CDs.

Tannic Acid Film Based on One-Dimensional Supramolecular Self-Assembly for Electrical Conductivity and Oil-Water Separation.

Tannic acid is widely regarded as one of the most promising natural polyphenolic compounds. However, current research predominantly focuses on the utilization of its phenolic hydroxyl groups, with limited exploration of the functional potential of its aromatic structure. Herein, one-dimensional nanofibers based on supramolecular self-assembly were successfully prepared through the simple alkylation reaction of tannic acid and the π-π stacking of aromatic structures. These fibers, with lengths reaching tens of micrometers and an average height of 10 nm, were clearly observed using SEM and AFM. A film with excellent electrical conductivity (σ = 37.9 µS/cm) was fabricated by vacuum filtering the organic suspension of these fibers, which was 100-fold higher than that of the TA film. Additionally, the hydrophobic and lipophilic properties of Bn-TA were further investigated through oil-water separation experiments, where the Bn-TA membrane displayed excellent separation efficiency and durability, maintaining stable performance over multiple cycles. This strategy presents opportunities for the high-value utilization of tannic acid.

Enteropancreatic hormone changes in caloric-restricted diet interventions associate with post-intervention weight maintenance.

BACKGROUND & AIMS: To explore enteropancreatic hormone changes during isocaloric-restricted dietary interventions and their impact on post-intervention weight maintenance. METHODS: 253 individuals with overweight/obesity and prediabetes were randomly assigned to 25% isocaloric-restricted diets: Control diet, Traditional Jiangnan diet or Mediterranean diet. Serum hormones and clinical indices were evaluated at 0, 3 and 6 months. Body weight values were collected again 6 months after completing interventions. RESULTS: We observed decreased fasting and post-glucose load levels of glucagon, amylin, peptide YY, and glucagon-like peptide-1 (GLP-1) while increased ghrelin at three months after 25% calorie restriction (CR) of three dietary interventions, and most of these changes were sustained through the six month-treatment period. Interestingly, changes in appetite-inhibitory hormones glucagon, amylin and GLP-1 showed positive associations with body weight change while appetite-promoting hormone ghrelin showed an inverse association during intervention. Furthermore, subjects with more reduction in amylin and GLP-1, or more increase in ghrelin during intervention showed a greater increase in body weight after completing intervention. CONCLUSIONS: CR intervention results in consistent hormone signatures regardless of dietary patterns. More changes in amylin, GLP-1 or ghrelin levels during CR are associated with poor weight maintenance after intervention, supporting that CR-induced hormone changes as biomarkers for predicting weight maintenance after intervention. TRIAL REGISTRATION: Clinicaltrials.gov NCT03856762.

Causal relationship between IgA nephropathy and common neuropsychiatric disorders: A two-sample mendelian randomization analysis.

OBJECTIVE: Utilizing two-sample Mendelian randomization (TSMR), this study seeks to determine the causal relationship between IgA nephropathy and five prevalent neuropsychiatric disorders. By exploring the genetic associations between IgA nephropathy and neuropsychiatric disorders, this research aims to contribute to the prevention of neuropsychiatric disorders in patients with IgA nephropathy. METHODS: Public genome-wide association study databases were searched, with IgA nephropathy as the exposure factor, including 15,587 patients with IgA nephropathy and 462,197 healthy controls. The outcome factors were five common neuropsychiatric disorders (bipolar disorder, depressive disorder, schizophrenia, anorexia nervosa, and Alzheimer's disease), with outcome data drawn from five datasets in the PGC and GWAScatalog databases. Inverse-variance weighting served as the primary method for causal effect estimation, supplemented by MR-Egger, weighted median, weighted mode, and simple mode methods. Heterogeneity was tested using Cochran's Q test, and sensitivity analysis was conducted using MR-Egger and MR-presso. RESULTS: MR analysis indicated a positive causal relationship between IgA nephropathy and depressive disorder (OR = 1.010, 95%CI: 1.003-1.017, P = 3.27 × 10-3), and a potential positive causal relationship between IgA nephropathy and anorexia nervosa (OR = 1.165, 95%CI: 1.030-1.319, P = 0.015). CONCLUSION: There is a positive causal relationship between IgA nephropathy and depressive disorder, and a potential positive causal relationship with anorexia nervosa. No causal relationship was found with schizophrenia, bipolar disorder, or Alzheimer's disease.

Cohort Profile: the prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde, China (Speed-Shunde Cohort).

AIMS: The objective of the prospective cohort study on the incidence of metabolic diseases and risk factors in Shunde (Speed-Shunde cohort) was to evaluate the incidence of cardiovascular-kidney-metabolic (CKM) syndrome and metabolic-associated multimorbidity, such as diabetes, hypertension, dyslipidemia, and metabolic dysfunction-associated steatotic liver disease (MASLD) in Shunde, Foshan, Guangdong, China. Additionally, the study sought to identify the potential determinants that may impact the development of these conditions and the potential consequences that may result. METHODS AND RESULT: In the Speed-Shunde cohort, data were gathered via questionnaires, physical measurements, and laboratory analyses encompassing demographic data, behavioral tendencies, anthropometric assessments, controlled attenuation parameters and liver stiffness measurement utilizing vibration-controlled transient elastography (VCTE), as well as serum and urine detection (such as oral 75g glucose tolerance tests, hemoglobin A1c levels, lipid profiles, liver and renal function tests, urinary microalbumin and creatinine levels, etc.). The baseline data were gathered from October 2021 to September 2022 from over 10,000 Chinese community-based adults and the follow-up surveys would be conducted every two or three years. Blood and urine samples were obtained and stored for future omics data acquisition. Initial analyses revealed the prevalence and risk factors associated with metabolic-associated multimorbidity. CONCLUSIONS: The Speed-Shunde Cohort study is a longitudinal community-based cohort with comprehensive CKM health and metabolic-associated multimorbidity assessment. It will provide valuable insights into these conditions' development, progression, and interrelationships, potentially informing future prevention and treatment strategies.

CD2 glycoprotein and CD44 structure and prevention of diabetes nephropathy: Central characteristics of related genes based on WGCNA and PPI.

Diabetic nephropathy (DN) is a prevalent complication of diabetes mellitus, characterized by complex pathogenesis that involves numerous molecules and signaling pathways. Among these, CD2 glycoprotein and CD44 play pivotal roles in cell adhesion, signal transduction, and inflammatory responses, potentially contributing significantly to the onset and progression of DN. This study aimed to investigate the central features of CD2 glycoprotein and CD44 in preventing diabetic nephropathy. To achieve this, kidney tissue sample data from DN patients were sourced from a public gene expression database. The roles of CD2 glycoprotein and CD44 within the PPI network were then analyzed, focusing on their interactions with other related genes. WGCNA analysis identified several significant gene modules associated with DN, including CD2 glycoprotein and CD44. PPI network analysis showed that these two proteins had a high degree of connectivity in the network, suggesting that they may be central regulatory molecules of DN. Further functional enrichment analysis revealed the potentially important role of CD2 glycoprotein and CD44 in diabetic nephropathy.

Recent progress of ferroptosis in cancers and drug discovery.

Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation. In addition, a series of small-molecule compounds have been developed, including erastin, RSL3, and FIN56, which can be used as ferroptosis inducers. The combination of ferroptosis inducers with anticancer drugs can produce a significant synergistic effect in cancer treatment, and patients treated with these combinations exhibit a better prognosis than patients receiving traditional therapy. Therefore, a thorough understanding of the roles of ferroptosis in cancer is of great significance for the treatment of cancer. This review mainly elaborates the molecular biological characteristics and mechanism of ferroptosis, summarizes the function of ferroptosis in cancer development and treatment,illustrates the application of ferroptosis in patient's prognosis prediction and drug discovery, and discusses the prospects of targeting ferroptosis.

The effects of repetitive transcranial magnetic and transcranial direct current stimulation on memory functions in older adults with mild cognitive impairment: a systematic review and meta-analysis.

Mild cognitive impairment (MCI) is a condition that impairs activities of daily living, and often transforms to dementia. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) show promise in improving cognitive functions in MCI patients. In this meta-analysis, we aimed to compare the effects of rTMS and tDCS on memory functions in MCI patients. We explored eight databases from their inception to March 16, 2024. We obtained 11 studies with 406 patients with MCI. We used the standardized mean difference (SMD) with a 95% confidence interval (CI) to synthesize the effect size. rTMS and tDCS significantly improved memory functions in MCI patients (SMD = 0.61; 95% CI: 0.41-0.82; p < 0.00001; I2 = 22%). In subgroup analysis of number of stimulation sessions, both rTMS and tDCS over 10 sessions (SMD = 0.84; 95% CI: 0.50-1.17, p < 0.00001, I2 = 0%) significantly improved the memory function in MCI patients. The subgroup analyses on different stimulation types (SMD = 0.78; 95% CI: 0.51-1.06; p < 0.00001; I2 = 0%) and treatment persistent effects (SMD = 0.93; 95% CI: 0.51-1.35, p < 0.0001, I2 = 0%) showed that rTMS was more effective than tDCS. rTMS with a stimulation frequency of 10 Hz (SMD = 0.86; 95% CI: 0.51-1.21; p < 0.00001; I2 = 0%) and over 10 sessions (SMD = 0.98; 95% CI: 0.58-1.38; p < 0.00001; I2 = 0%) at multiple sites (SMD = 0.97; 95% CI: 0.44-1.49; p = 0.0003; I2 = 0%) showed a great improvement in the memory performance of patients with MCI. rTMS was more likely to appear temporary side effects (risk ratio (RR) = 3.18, 95% CI: 1.29-7.83, p = 0.01). This meta-analysis suggests that rTMS and tDCS are safe and efficient tools to improve memory functions in patients with MCI, while rTMS had a larger effect than tDCS. rTMS with a stimulation frequency of 10 Hz targeted on multiple sites over 10 sessions showed the greatest effect. We could not conclude parameters of tDCS because of insufficient data. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024558991.

TIMP1 promotes thyroid cancer cell progression through macrophage phenotypic polarization via the PI3K/AKT signaling pathway.

Increasing evidence suggests that tissue inhibitor of metalloproteinase 1 (TIMP1) played a pivotal role in immune regulation. Our study focused on examining the expression and function of TIMP1 in humans, particularly in its regulation of tumor-associated macrophages (TAMs) in papillary thyroid carcinoma (PTC). We observed an upregulation of TIMP1 in 16 different types of malignancies, including thyroid cancer. TIMP1 shaped the inflammatory TME in PTC. Inhibiting the expression of TIMP1 has been demonstrated to reduce the malignant biological traits of PTC cells. Furthermore, reducing TIMP1 expression impeded M2 macrophage polarization as well as facilitated M1 macrophage polarization in PTC. ELISA results demonstrated that downregulated TIMP1 expression correlated with decreased levels of IL10 and TGF-ß in cell supernatants. Furthermore, the supernatant from polarized macrophages in the TIMP1-silenced group inhibited the motility of wild-type PTC cells. Therefore, TIMP1 may enhance the progression of PTC by stimulating the PI3K/AKT pathway via the secretion of IL10 and TGF-ß, consequently influencing M2-type polarization in TAMs.

m6A modification of VEGFA mRNA by RBM15/YTHDF2/IGF2BP3 contributes to angiogenesis of hepatocellular carcinoma.

Vascular endothelial growth factor A (VEGFA) plays a critical role as a potent angiogenesis factor and is highly expressed in hepatocellular carcinoma (HCC). Although the expression of VEGFA has been strongly linked to the aggressive nature of HCC, the specific posttranscriptional modifications that might contribute to VEGFA expression and HCC angiogenesis are not yet well understood. In this study, we aimed to investigate the epitranscriptome regulation of VEGFA in HCC. A comprehensive analysis integrating MeRIP-seq, RNA-seq, and crosslinking-immunprecipitation-seq data revealed that VEGFA was hypermethylated in HCC and identified the potential m6A regulators of VEGFA including a m6A methyltransferase complex component RBM15 and the two readers, YTHDF2 and IGF2BP3. Through rigorous cell and molecular biology experiments, RBM15 was validated as a key component of methyltransferase complex responsible for m6A methylation of VEGFA, which was subsequently recognized and stabilized by IGF2BP3 and YTHDF2, leading to enhanced VEGFA expression and VEGFA-related functions such as human umbilical vascular endothelial cells (HUVEC) migration and tube formation. In the HCC xenograft model, knockdown of RBM15, IGF2BP3, or YTHDF2 resulted in reduced expression of VEGFA, accompanied by significant inhibition of tumor growth closely associated with VEGFA expression and angiogenesis. Furthermore, our analysis of HCC clinical samples identified positive correlations between the expression levels of VEGFA and the regulators RBM15, IGF2BP3, and YTHDF2. Collectively, these findings offer novel insights into the posttranscriptional modulation of VEGFA and provide potential avenues for alternative approaches to antiangiogenesis therapy targeting VEGFA.

High-level ceftriaxone resistance due to transfer of penA allele 60.001 into endemic gonococcal lineages in Hangzhou, China.

OBJECTIVES: Neisseria gonorrhoeae strains associated with the high-level ceftriaxone-resistant FC428 clone or containing its main resistance determinant, penA allele 60.001, have shown global transmission. In Hangzhou, China, 10% of the isolates were associated with the FC428 clone in 2019. Here, we investigated ceftriaxone resistance and the prevalence of FC428-associated strains in Hangzhou in 2020-22. METHODS: A total of 209 gonococcal isolates were investigated for antimicrobial susceptibility to ceftriaxone and other antibiotics by agar dilution method. Sequence types and penA alleles were determined by PCR and sequence analysis. RESULTS: Resistance to ceftriaxone (MIC > 0.125 mg/L) was observed for 16% (33/209) of the isolates, whereas 6.7% (14/209) of the isolates displayed high-level ceftriaxone resistance (MIC = 1 mg/L). These 14 high-level ceftriaxone-resistant isolates and another isolate displaying an MIC = 0.25 mg/L contained penA allele 60.001, with eight of these isolates, all from 2020 to 2021 belonging to MLST ST1903, the sequence type commonly associated with the original FC428 clone. Importantly, the six penA allele 60.001-containing isolates from 2022 belonged to MLST ST8123, ST7365 and ST7367, which are among the most frequently encountered sequence types found in China. Therefore, these results indicate that endemic lineages in China have acquired penA allele 60.001. CONCLUSIONS: Here, we report continued transmission of gonococcal strains associated with the FC428 clone or containing penA allele 60.001 in Hangzhou. A major concern for public health is the acquisition of penA allele 60.001 by successful endemic lineages, which might enhance the transmission of this high-level ceftriaxone resistance trait.

Clinical significance of modified unilateral puncture percutaneous vertebroplasty guided by 3D- printed guides in the treatment of osteoporotic vertebral compression fractures: a retrospective study.

OBJECTIVE: To investigate the clinical significance of using 3D printing guides in modified unilateral puncture percutaneous vertebroplasty (PVP) for the treatment of osteoporotic vertebral compression fractures (OVCF), and to explore a new method for preventing paravertebral vein leakage during PVP in conjunction with a previous study of the optimal puncture-side bone cement/vertebral volume ratio(PSBCV/VV%). METHODS: This retrospective study analyzed 99 patients who underwent unilateral puncture PVP between January 2023 and December 2023. Patients were divided into a guide plate group (46 patients) and a conventional group (53 patients). The guide plate group underwent modified unilateral puncture PVP with the guidance of 3D printing guides, while the conventional group underwent unilateral puncture PVP using the conventional pedicle approach. The distribution of bone cement, surgical outcomes, and the occurrence of cement leakage into paravertebral veins were observed in both groups. RESULTS: The guide plate group had significantly shorter operating time and required fewer fluoroscopies compared to the conventional group. The amount of bone cement volume (BCV) used in the guide plate group was higher, but the amount of bone cement volume on the puncture side(PSBCV), the PSBCV/VV%, and the rate of paravertebral vein leakage were lower in the guide plate group compared to the conventional group (P < 0.05). Within each group, significant improvements in anterior vertebral margin height, Cobb angle, visual analog scale (VAS) score, and Oswestry Disability Index (ODI) were observed at 1 day and 1 month postoperatively compared to preoperative values (P < 0.05). CONCLUSION: Using 3D printing guides in modified unilateral puncture PVP is a safe and effective method for treating OVCF. And it has the advantages of short operation time, less fluoroscopy, even distribution of bone cement, and a low rate of paravertebral vein leakage.

Optimization of Fuzzy Control Parameters for Wind Farms and Battery Energy Storage Systems Based on an Enhanced Artificial Bee Colony Algorithm under Multi-Source Sensor Data.

With the rapid development of sensors and other devices, precise control for the generation of new energy, especially in the context of highly stochastic wind power generation, has been strongly supported. However, large-scale wind farm grid connection can cause the power system to enter a low inertia state, leading to frequency instability. Battery energy storage systems (BESSs) have the advantages of a fast response speed and high flexibility, and can be applied to wind farm systems to improve the frequency fluctuation problem in the process of grid connection. To address the frequency fluctuation problem caused by the parameter error of the fuzzy membership function in the fuzzy control of a doubly fed induction generator (DFIG) and a BESS, this paper proposes an improved Artificial Bee Colony (ABC) algorithm based on multi-source sensor data for optimizing the fuzzy controller to improve the frequency control ability of BESSs and DFIGs. A Gaussian wandering mechanism was introduced to improve the ABC algorithm and enhance the convergence speed of the algorithm, and the improved ABC algorithm was optimized for the selection of fuzzy control affiliation function parameters to improve the frequency response performance. The effectiveness of the proposed control strategy was verified on the MATLAB/Simulink simulation platform. After optimization using the proposed control strategy, the oscillation amplitude was reduced by 0.15 Hz, the precision was increased by 40%, and the steady-state frequency deviation was reduced by 26%. The results show that the method proposed in this paper provides a great improvement in the frequency stability of coordinated systems of wind farms and BESSs.

Accuracy and influencing factors of Type B2 vessels in predicting the invasion depth of superficial esophageal squamous cell carcinoma under narrow-band imaging magnifying endoscopy.

OBJECTIVE: To evaluate the accuracy of Type B2 based on narrow-band imaging-magnifying endoscopy (NBI-ME) in judging invasion depth of superficial esophageal squamous cell carcinoma (SESCC) and analyze potential influencing factors. METHOD: Data from 113 patients where Type B2 was observed by magnifying endoscopy and confirmed by postoperative pathology as SESCC at the First Affiliated Hospital of Fujian Medical University and Fujian Provincial Hospital from January 2015 to April 2024 were retrospectively analyzed. Patients were divided into correct prediction and incorrect prediction groups according to the postoperative pathological results, and the prediction accuracy was calculated. The incorrect prediction group was further divided into overestimation and underestimation groups to identify the influential factors for overprediction and underprediction, respectively. The independent influential factors for the prediction were assessed using multivariate Cox logistic regression analysis. RESULTS: B2-narrow (Type B2 area ≤ 5 mm) (p < 0.001) and Type B2 around erosion (p = 0.040) were independent risk factors of overpredicting the invasion depth of SESCC based on Type B2. The presence of significant endoscopic features was an independent protective factor for overpredicting the invasion depth of SESCC (p = 0.014), whereas the presence of significant features under endoscopy was an independent risk factor for the underprediction (p = 0.005). CONCLUSION: B2-narrow (Type B2 area ≤ 5 mm), Type B2 vessels around erosion, and non- significant endoscopic features are closely related to overpredicting the invasion depth of SESCC based on Type B2, and the presence of significant endoscopic features is closely associated with underprediction.

Patient-Reported Outcomes in Chinese Patients with Locally Advanced or Recurrent Colorectal Cancer After Pelvic Exenteration.

BACKGROUND: Pelvic exenteration (PE) is often the only curative treatment option for selected locally advanced and locally recurrent colorectal cancer associated with significant morbidity. Open and laparoscopic approaches were accepted for this procedure. OBJECTIVE: This study aimed to examine the Chinese patient-reported outcomes (PROs) and health-related quality of life (HRQoL) after PE. METHODS: A total of 122 enrolled participants were asked to complete PROs at baseline and 1, 3, 6, 9 and 12 months after PE. PROs included seven symptoms from the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The HRQoL was assessed using the Functional Assessment of Cancer Therapy-Colorectal (FACT-C). RESULTS: The overall postoperative complication rate was 41.0%. Patients experienced lower physical and functional well-being and FACT-C 1 month after surgery, then gradually recovered. The FACT-C score returned to baseline 9 months after surgery. Social and emotional well-being did not show signs of recovery until 6 months after the surgical procedure, and did not fully return to baseline until 12 months post-surgery. Symptom rates of insomnia, anxiety, discouragement, and sadness (composite score >0) did not improve significantly from baseline until 12 months after surgery. CONCLUSIONS: PE is a feasible treatment choice for locally advanced primary and recurrent colorectal cancer. Social, psychological, and emotional recovery in the Chinese population after PE tends to be slower compared with the physical condition.

The AKT inhibitor AZD5363 elicits synthetic lethality in ARID1A-deficient gastric cancer cells via induction of pyroptosis.

BACKGROUND: Gastric cancer (GC) is a deadly disease with poor overall survival and limited therapeutic options. Genetic alterations such as mutations and/or deletions in chromatin remodeling gene AT-rich interactive domain 1 A (ARID1A) occur frequently in GC. Although ARID1A mutations/deletions are not a druggable target for conventional treatments, novel therapeutic strategies based on a synthetic lethal approach may be effective for the treatment of ARID1A-deficient cancers. METHODS: A kinase inhibitor library containing 551 compounds was screened in ARID1A isogenic GC cells for the ability to induce synthetic lethality effect. Selected hits' activity was validated, and the mechanism of the most potent candidate drug, AKT inhibitor AD5363 (capivasertib), on induction of the synthetic lethality with ARID1A deficiency was investigated. RESULTS: After robust vulnerability screening of 551 diverse protein kinase inhibitors, we identified the AKT inhibitor AZD5363 as being the most potent lead compound in inhibiting viability of ARID1A-/- cells. A synthetic lethality between loss of ARID1A expression and AKT inhibition by AZD5363 was validated in both GC cell model system and xenograft model. Mechanistically, AZD5363 treatment induced pyroptotic cell death in ARID1A-deficient GC cells through activation of the Caspase-3/GSDME pathway. Furthermore, ARID1A occupied the AKT gene promoter and regulated its transcription negatively, thus the GC cells deficient in ARID1A showed increased expression and phosphorylation of AKT. CONCLUSIONS: Our study demonstrates a novel synthetic lethality interaction and unique mechanism between ARID1A loss and AKT inhibition, which may provide a therapeutic and mechanistic rationale for targeted therapy on patients with ARID1A-defective GC who are most likely to be beneficial to AZD5363 treatment.