Targeting anoikis resistance as a strategy for cancer therapy.

Anoikis, known as matrix detachment-induced apoptosis or detachment-induced cell death, is crucial for tissue development and homeostasis. Cancer cells develop means to evade anoikis, e.g. anoikis resistance, thereby allowing for cells to survive under anchorage-independent conditions. Uncovering the mechanisms of anoikis resistance will provide details about cancer metastasis, and potential strategies against cancer cell dissemination and metastasis. Here, we summarize the principal elements and core molecular mechanisms of anoikis and anoikis resistance. We discuss the latest progress of how anoikis and anoikis resistance are regulated in cancers. Furthermore, we summarize emerging data on selective compounds and nanomedicines, explaining how inhibiting anoikis resistance can serve as a meaningful treatment modality against cancers. Finally, we discuss the key limitations of this therapeutic paradigm and possible strategies to overcome them. In this review, we suggest that pharmacological modulation of anoikis and anoikis resistance by bioactive compounds could surmount anoikis resistance, highlighting a promising therapeutic regimen that could be used to overcome anoikis resistance in cancers.

Cuproptosis: A novel therapeutic target for overcoming cancer drug resistance.

Cuproptosis is a newly identified form of cell death driven by copper. Recently, the role of copper and copper triggered cell death in the pathogenesis of cancers have attracted attentions. Cuproptosis has garnered enormous interest in cancer research communities because of its great potential for cancer therapy. Copper-based treatment exerts an inhibiting role in tumor growth and may open the door for the treatment of chemotherapy-insensitive tumors. In this review, we provide a critical analysis on copper homeostasis and the role of copper dysregulation in the development and progression of cancers. Then the core molecular mechanisms of cuproptosis and its role in cancer is discussed, followed by summarizing the current understanding of copper-based agents (copper chelators, copper ionophores, and copper complexes-based dynamic therapy) for cancer treatment. Additionally, we summarize the emerging data on copper complexes-based agents and copper ionophores to subdue tumor chemotherapy resistance in different types of cancers. We also review the small-molecule compounds and nanoparticles (NPs) that may kill cancer cells by inducing cuproptosis, which will shed new light on the development of anticancer drugs through inducing cuproptosis in the future. Finally, the important concepts and pressing questions of cuproptosis in future research that should be focused on were discussed. This review article suggests that targeting cuproptosis could be a novel antitumor therapy and treatment strategy to overcome cancer drug resistance.

FMRP promotes transcription-coupled homologous recombination via facilitating TET1-mediated m5C RNA modification demethylation.

RNA modifications regulate a variety of cellular processes including DNA repair.The RNA methyltransferase TRDMT1 generates methyl-5-cytosine (m5C) on messen-ger RNA (mRNA) at DNA double-strand breaks (DSBs) in transcribed regions, pro-moting transcription-coupled homologous recombination (HR). Here, we identifiedthat Fragile X mental retardation protein (FMRP) promotes transcription-coupled HRvia its interaction with both the m5C writer TRDMT1 and the m5C eraser ten-eleventranslocation protein 1 (TET1). TRDMT1, FMRP, and TET1 function in a temporalorder at the transcriptionally active sites of DSBs. FMRP displays a higher affinity forDNA:RNA hybrids containing m5C-modified RNA than for hybrids without modifica-tion and facilitates demethylation of m5C by TET1 in vitro. Loss of either the chroma-tin- or RNA-binding domain of FMRP compromises demethylation of damage-inducedm5C in cells. Importantly, FMRP is required for R-loop resolving in cells. Due to unre-solved R-loop and m5C preventing completion of DSB repair, FMRP depletion or lowexpression leads to delayed repair of DSBs at transcriptionally active sites and sensitizescancer cells to radiation in a BRCA-independent manner. Together, ourfindings presentan m5C reader, FMRP, which acts as a coordinator between the m5C writer and eraserto promote mRNA-dependent repair and cell survival in cancer.

Targeting lysosomal quality control as a therapeutic strategy against aging and diseases.

Previously, lysosomes were primarily referred to as the digestive organelles and recycling centers within cells. Recent discoveries have expanded the lysosomal functional scope and revealed their critical roles in nutrient sensing, epigenetic regulation, plasma membrane repair, lipid transport, ion homeostasis, and cellular stress response. Lysosomal dysfunction is also found to be associated with aging and several diseases. Therefore, function of macroautophagy, a lysosome-dependent intracellular degradation system, has been identified as one of the updated twelve hallmarks of aging. In this review, we begin by introducing the concept of lysosomal quality control (LQC), which is a cellular machinery that maintains the number, morphology, and function of lysosomes through different processes such as lysosomal biogenesis, reformation, fission, fusion, turnover, lysophagy, exocytosis, and membrane permeabilization and repair. Next, we summarize the results from studies reporting the association between LQC dysregulation and aging/various disorders. Subsequently, we explore the emerging therapeutic strategies that target distinct aspects of LQC for treating diseases and combatting aging. Lastly, we underscore the existing knowledge gap and propose potential avenues for future research.

Proximity-Induced Bipedal DNA Walker for Accurately Visualizing microRNA in Living Cancer Cell.

DNA walker, a type of dynamic DNA device that is capable of moving progressively along prescribed walking tracks, has emerged as an ideal and powerful tool for biosensing and bioimaging. However, most of the reported three-dimensional (3D) DNA walker were merely designed for the detection of a single target, and they were not capable of achieving universal applicability. Herein, we reported for the first time the development of a proximity-induced 3D bipedal DNA walker for imaging of low abundance biomolecules. As a proof of concept, miRNA-34a, a biomarker of breast cancer, is chosen as the model system to demonstrate this approach. In our design, the 3D bipedal DNA walker can be generated only by the specific recognition of two proximity probes for miRNA-34a. Meanwhile, it stochastically and autonomously traveled on 3D tracks (gold nanoparticles) via catalytic hairpin assembly (CHA), resulting in the amplified fluorescence signal. In comparison with some conventional DNA walkers that were utilized for living cell imaging, the 3D DNA walkers induced by proximity ligation assay can greatly improve and ensure the high selectivity of bioanalysis. By taking advantage of these unique features, the proximity-induced 3D bipedal DNA walker successfully realizes accurate and effective monitoring of target miRNA-34a expression levels in living cells, affording a universal, valuable, and promising platform for low-abundance cancer biomarker detection and accurate identification of cancer.

Mechanical Robust GO/PVA Hydrogel for Strong and Recyclable Adhesion in Air, Underwater, and Underoil Environments.

Adhesive hydrogels are considered to be promising interfacial adhesive materials for various applications; however, their adhesive strength is significantly reduced when immersed in liquid environments (water and oil) due to obstruction of the liquid layer or swelling in liquid, and they could not always be reused when the failure of the adhesive performance occurred. Herein, a graphite oxide/poly(vinyl alcohol) (GO/PVA) hydrogel with strong adhesion in air and under liquid environments was developed by rationally regulating the interactions of water and dimethyl sulfoxide (DMSO) in the binary liquid system. The strong interaction between water and DMSO allowed the water layer of the GO/PVA hydrogel on the hydrogel surface to act as a shield to repel oil in air, under water, and even when immersed in oil, and it also endowed the obtained hydrogel with antiswelling property when immersed in water and oil. Importantly, the GO/PVA hydrogel could serve as an advanced adhesive to firmly bond different substrates in air, under water, and under oil, and interestingly, its dry and wet adhesive performance was repeatable and recyclable. This work is expected to be an important addition to the field of adhesive soft materials.

Design, synthesis and biological evaluation of quinazoline and pyrrolo[3,2-d]pyrimidine derivatives as TLR7 agonists for antiviral agents.

Pattern recognition receptors (PRRs) play a critical role in the innate immune response, and toll-like receptor 7 (TLR7) is an important member of PRRs. Although several TLR7 agonists are available, most of them are being tested clinically, with only one available on the market. Thus, it is imperative to develop new TLR7 agonists. In this study, we designed and synthesized three kinds of quinazoline derivatives and five kinds of pyrrolo[3,2-d]pyrimidine derivatives targeting TLR7. The antiviral efficacy of these compounds was evaluated in vitro and in vivo. Our findings indicated that four kinds of compounds showed exceptional antiviral activity. Furthermore, molecular docking studies confirmed that compound 11 successfully positioned itself in the pocket of the TLR7 guanosine loading site with a binding energy of -4.45 kcal mol-1. These results suggested that these compounds might be potential antiviral agents.

Molecular and functional characterization of porcine poly C binding protein 1 (PCBP1).

BACKGROUND: Poly C Binding Protein 1 (PCBP1) belongs to the heterogeneous nuclear ribonucleoprotein family. It is a multifunctional protein that participates in several functional circuits and plays a variety of roles in cellular processes. Although PCBP1 has been identified in several mammals, its function in porcine was unclear. RESULTS: In this study, we cloned the gene of porcine PCBP1 and analyzed its evolutionary relationships among different species. We found porcine PCBP1 protein sequence was similar to that of other animals. The subcellular localization of PCBP1 in porcine kidney cells 15 (PK-15) cells was analyzed by immunofluorescence assay (IFA) and revealed that PCBP1 was mainly localized to the nucleus. Reverse transcription-quantitative PCR (RT-qPCR) was used to compare PCBP1 mRNA levels in different tissues of 30-day-old pigs. Results indicated that PCBP1 was expressed in various tissues and was most abundant in the liver. Finally, the effects of PCBP1 on cell cycle and apoptosis were investigated following its overexpression or knockdown in PK-15 cells. The findings demonstrated that PCBP1 knockdown arrested cell cycle in G0/G1 phase, and enhanced cell apoptosis. CONCLUSIONS: Porcine PCBP1 is a highly conserved protein, plays an important role in determining cell fate, and its functions need further study.

Overcoming cancer chemotherapy resistance by the induction of ferroptosis.

Development of resistance to chemotherapy in cancer continues to be a major challenge in cancer management. Ferroptosis, a unique type of cell death, is mechanistically and morphologically different from other forms of cell death. Ferroptosis plays a pivotal role in inhibiting tumour growth and has presented new opportunities for treatment of chemotherapy-insensitive tumours in recent years. Emerging studies have suggested that ferroptosis can regulate the therapeutic responses of tumours. Accumulating evidence supports ferroptosis as a potential target for chemotherapy resistance. Pharmacological induction of ferroptosis could reverse drug resistance in tumours. In this review article, we first discuss the key principles of chemotherapeutic resistance in cancer. We then provide a brief overview of the core mechanisms of ferroptosis in cancer chemotherapeutic drug resistance. Finally, we summarise the emerging data that supports the fact that chemotherapy resistance in different types of cancers could be subdued by pharmacologically inducing ferroptosis. This review article suggests that pharmacological induction of ferroptosis by bioactive compounds (ferroptosis inducers) could overcome chemotherapeutic drug resistance. This article also highlights some promising therapeutic avenues that could be used to overcome chemotherapeutic drug resistance in cancer.

T3 + 3: 3 + 3 Design With Delayed Outcomes.

Delayed outcome is common in phase I oncology clinical trials. It causes logistic difficulty, wastes resources, and prolongs the trial duration. This article investigates this issue and proposes the time-to-event 3 + 3 (T3 + 3) design, which utilizes the actual follow-up time for at-risk patients with pending toxicity outcomes. The T3 + 3 design allows continuous accrual without unnecessary trial suspension and is costless and implementable with pretabulated dose decision rules. Besides, the T3 + 3 design uses the isotonic regression to estimate the toxicity rates across dose levels and therefore can accommodate for any targeted toxicity rate for maximum tolerated dose (MTD). It dramatically facilitates the trial preparation and conduct without intensive computation and statistical consultation. The extension to other algorithm-based phase I dose-finding designs (e.g., i3 + 3 design) is also studied. Comprehensive computer simulation studies are conducted to investigate the performance of the T3 + 3 design under various dose-toxicity scenarios. The results confirm that the T3 + 3 design substantially shortens the trial duration compared with the conventional 3 + 3 design and yields much higher accuracy in MTD identification than the rolling six design. In summary, the T3 + 3 design addresses the delayed outcome issue while keeping the desirable features of the 3 + 3 design, such as simplicity, transparency, and costless implementation. It has great potential to accelerate early-phase drug development.

Epigenetic modification of m6A regulator proteins in cancer.

Divergent N6-methyladenosine (m6A) modifications are dynamic and reversible posttranscriptional RNA modifications that are mediated by m6A regulators or m6A RNA methylation regulators, i.e., methyltransferases ("writers"), demethylases ("erasers"), and m6A-binding proteins ("readers"). Aberrant m6A modifications are associated with cancer occurrence, development, progression, and prognosis. Numerous studies have established that aberrant m6A regulators function as either tumor suppressors or oncogenes in multiple tumor types. However, the functions and mechanisms of m6A regulators in cancer remain largely elusive and should be explored. Emerging studies suggest that m6A regulators can be modulated by epigenetic modifications, namely, ubiquitination, SUMOylation, acetylation, methylation, phosphorylation, O-GlcNAcylation, ISGylation, and lactylation or via noncoding RNA action, in cancer. This review summarizes the current roles of m6A regulators in cancer. The roles and mechanisms for epigenetic modification of m6A regulators in cancer genesis are segregated. The review will improve the understanding of the epigenetic regulatory mechanisms of m6A regulators.

RNA modifications in cancer.

Currently, more than 170 modifications have been identified on RNA. Among these RNA modifications, various methylations account for two-thirds of total cases and exist on almost all RNAs. Roles of RNA modifications in cancer are garnering increasing interest. The research on m6A RNA methylation in cancer is in full swing at present. However, there are still many other popular RNA modifications involved in the regulation of gene expression post-transcriptionally besides m6A RNA methylation. In this review, we focus on several important RNA modifications including m1A, m5C, m7G, 2'-O-Me, Ψ and A-to-I editing in cancer, which will provide a new perspective on tumourigenesis by peeking into the complex regulatory network of epigenetic RNA modifications, transcript processing, and protein translation.

Genome-wide association study on resistance of cultivated soybean to Fusarium oxysporum root rot in Northeast China.

BACKGROUND: Fusarium oxysporum is a prevalent fungal pathogen that diminishes soybean yield through seedling disease and root rot. Preventing Fusarium oxysporum root rot (FORR) damage entails on the identification of resistance genes and developing resistant cultivars. Therefore, conducting fine mapping and marker development for FORR resistance genes is of great significance for fostering the cultivation of resistant varieties. In this study, 350 soybean germplasm accessions, mainly from Northeast China, underwent genotyping using the SoySNP50K Illumina BeadChip, which includes 52,041 single nucleotide polymorphisms (SNPs). Their resistance to FORR was assessed in a greenhouse. Genome-wide association studies utilizing the general linear model, mixed linear model, compressed mixed linear model, and settlement of MLM under progressively exclusive relationship models were conducted to identify marker-trait associations while effectively controlling for population structure. RESULTS: The results demonstrated that these models effectively managed population structure. Eight SNP loci significantly associated with FORR resistance in soybean were detected, primarily located on Chromosome 6. Notably, there was a strong linkage disequilibrium between the large-effect SNPs ss715595462 and ss715595463, contributing substantially to phenotypic variation. Within the genetic interval encompassing these loci, 28 genes were present, with one gene Glyma.06G088400 encoding a protein kinase family protein containing a leucine-rich repeat domain identified as a potential candidate gene in the reference genome of Williams82. Additionally, quantitative real-time reverse transcription polymerase chain reaction analysis evaluated the gene expression levels between highly resistant and susceptible accessions, focusing on primary root tissues collected at different time points after F. oxysporum inoculation. Among the examined genes, only this gene emerged as the strongest candidate associated with FORR resistance. CONCLUSIONS: The identification of this candidate gene Glyma.06G088400 improves our understanding of soybean resistance to FORR and the markers strongly linked to resistance can be beneficial for molecular marker-assisted selection in breeding resistant soybean accessions against F. oxysporum.

Major genetic locus with pleiotropism determined seed-related traits in cultivated and wild soybeans.

KEY MESSAGE: Here, a novel pleiotropic QTL qSS14 simultaneously regulating four seed size traits and two consistently detected QTLs qSW17 and qSLW02 were identified across multiple years. Seed-related traits were the key agronomic traits that have been artificially selected during the domestication of wild soybean. Identifying the genetic loci and genes that regulate seed size could clarify the genetic variations in seed-related traits and provide novel insights into high-yield soybean breeding. In this study, we used a high-density genetic map constructed by F10 RIL populations from a cross between Glycine max and Glycine soja to detect additive QTLs for seven seed-related traits over the last three years. As a result, we identified one novel pleiotropic QTL, qSS14, that simultaneously controlled four seed size traits (100-seed weight, seed length, seed width, and seed thickness) and two consistently detected QTLs, qSW17, and qSLW02, in multiple years of phenotypic data. Furthermore, we predicted two, two and three candidate genes within these three critical loci based on the parental resequencing data and gene function annotations. And the relative expression of four candidate genes GLYMA_14G155100, GLYMA_17G061000, GLYMA_02G273100, and GLYMA_02G273300 showed significant differences among parents and the extreme materials through qRT-PCR analysis. These findings could facilitate the determination of beneficial genes in wild soybean and contribute to our understanding of the soybean domestication process.

miR-196b-5p-mediated downregulation of TSPAN12 and GATA6 promotes tumor progression in non-small cell lung cancer.

Lung cancer is the leading cause of cancer-related deaths worldwide and non-small cell lung cancer (NSCLC) accounts for over 80% of lung cancer cases. The RNA binding protein, QKI, belongs to the STAR family and plays tumor-suppressive functions in NSCLC. QKI-5 is a major isoform of QKIs and is predominantly expressed in NSCLC. However, the underlying mechanisms of QKI-5 in NSCLC progression remain unclear. We found that QKI-5 regulated microRNA (miRNA), miR-196b-5p, and its expression was significantly up-regulated in NSCLC tissues. Up-regulated miR-196b-5p promotes lung cancer cell migration, proliferation, and cell cycle through directly targeting the tumor suppressors, GATA6 and TSPAN12. Both GATA6 and TSPAN12 expressions were down-regulated in NSCLC patient tissue samples and were negatively correlated with miR-196b-5p expression. Mouse xenograft models demonstrated that miR-196b-5p functions as a potent onco-miRNA, whereas TSPAN12 functions as a tumor suppressor in NSCLC in vivo. QKI-5 bound to miR-196b-5p and influenced its stability, resulting in up-regulated miR-196b-5p expression in NSCLC. Further analysis showed that hypomethylation in the promoter region enhanced miR-196b-5p expression in NSCLC. Our findings indicate that QKI-5 may exhibit novel anticancer mechanisms by regulating miRNA in NSCLC, and targeting the QKI5∼miR-196b-5p∼GATA6/TSPAN12 pathway may enable effectively treating some NSCLCs.

An electrochemical determination strategy for miRNA based on bimetallic nanozyme and toehold-mediated DNA replacement procedure.

An electrochemical strategy based on bimetallic nanozyme in collaboration with toehold-mediated DNA replacement effect is proposed for the sensitive determination of miRNA-21. The AuPt nanoparticles (AuPt NPs) are prepared as a catalytic beacon; it shows favorable peroxidase properties with a Michaelis contant (Km) of 0.072 mM for H2O2, which is capable of catalyzing H2O2 to induce an intense redox reaction, and causing a measurable electrochemical signal. To further enhance the strength of the signal response, a novel toehold-mediated DNA replacement strategy is employed. DNA strands with specific sequences are modified on electrodes and AuPt NPs, respectively. In the presence of miRNA-21, a cyclic substitution effect is subsequently activated via a specific toehold sequence and leads to a large accumulation of AuPt NPs on the electrodes. Subsequently, a strong signal depending on the amount of miRNA-21 is obtained after adding a small amount of H2O2. The analytical range of this determination method is from 0.1 pM to 1.0 nM, and the LOD is 84.1 fM. The spike recoveries for serum samples are 95.0 to 102.4% and the RSD values are 3.7 to 5.8%. The results suggests a promising application of the established method in clinical testing and disease diagnosis.

The protective role of curcumin in human dental pulp stem cells stimulated by lipopolysaccharide via inhibiting NF-κB p65 phosphorylation to suppress NLRP3 inflammasome activation.

OBJECTIVES: This study aims to investigate the anti-inflammatory effect of curcumin and underlying mechanisms regarding the modulation of the nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome in human dental pulp stem cells (hDPSCs). MATERIALS AND METHODS: The impact of curcumin on the viability of hDPSCs was evaluated. The effect of curcumin on the expression of IL-1ß and NLRP3 in hDPSCs stimulated by lipopolysaccharide (LPS) was assessed. Then, LPS-primed hDPSCs were pre-treated with curcumin before ATP triggering NLRP3 inflammasome activation, and NLRP3 inflammasome-related mediators were assessed. The mechanism of curcumin inactivation of LPS plus ATP-induced inflammasome associated with NF-κB pathway was explored. The NF-κB pathway related pro-inflammatory mediators at mRNA and protein levels were evaluated. The expression of NF-κB p65 and phosphorylation p65 was visualized after curcumin or NF-κB inhibitor administrating respectively in hDPSCs with an activated NLRP3 inflammasome. Statistical analysis was performed. RESULTS: While curcumin at the concentration of 0.5-5 µM showed no obvious impact on the viability of hDPSCs, it significantly decreased IL-1ß and NLRP3 mRNA expression in LPS-induced hDPSCs in a dose-dependent manner. Curcumin significantly inhibited the LPS plus ATP-primed NLRP3 inflammasome activation in hDPSCs (NLRP3, ASC, caspase-1, and IL-1ß). Curcumin evidently attenuated the LPS plus ATP-induced expression of NF-κB pathway-related pro-inflammatory mediators (IL-6, IL-8, TNF-α, and COX-2). Furthermore, curcumin effectively reduced p65 phosphorylation, which acts as an NF-κB inhibitor in hDPSCs with an activated NLRP3 inflammasome. CONCLUSIONS: Curcumin pre-treatment may exert an anti-inflammatory role via inactivation of the NLRP3 inflammasome by inhibiting NF-κB p65 phosphorylation in cultured hDPSCs. CLINICAL RELEVANCE: Curcumin may have therapeutic potential in pulp inflammation.

Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression and Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis.

Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis, including lung adenocarcinoma (LUAD). However, the functional and regulatory mechanisms of lncRNAs in LUAD remain poorly understood. In this study, we investigated the role of lncRNA ZBED5-AS1 in LUAD. We found that ZBED5-AS1 was upregulated in LUAD specimens and overexpressed in LUAD cell lines. ZBED5-AS1 promoted LUAD cell proliferation, migration, and invasion in vitro and promoted LUAD cell growth in vivo. ZBED5-AS1 promoted ZNF146 expression, activating the ATR/Chk1 pathway and leading to LUAD progression. We observed that exosomes from LUAD cells have a higher expression of ZBED5-AS1 compared with exosomes from the normal cell line BEAS-2B. Coculture experiments with exosomes showed that ZBED5-AS1 expression was downregulated after coculture with Si-ZBED5-AS1 exosomes, and coculture with exosomes with low ZBED5-AS1 expression inhibited proliferation and invasion of LUAD cells. Our results indicate that ZBED5-AS1 functions as an oncogenic factor in LUAD cells by targeting the ZNF146/ATR/Chk1 axis.

Perovskite Scintillators for Improved X-ray Detection and Imaging.

Halide perovskites (HPs) recently have emerged as one class of competitive scintillators for X-ray detection and imaging owing to its high quantum efficiency, short decay time, superior X-ray absorption capacity, low cost, and ease of crystal growth. The tunable structure and versatile chemical compositions of halide perovskites provide distinguishable advantages over traditional inorganic scintillators for optimizing scintillation performance. Since the first observation of the scintillation phenomenon in HPs, substantial efforts have been devoted to expanding the inventory of HP scintillators and regulating material properties. Understanding the relationship between the structure and scintillation properties of HP scintillators is essential for developing materials with improved X-ray detection and imaging capacities. This review summarizes strategies for improving the light yield of HP scintillators and provides a roadmap for improving the X-ray imaging performance. Additionally, methods for controlling the light propagation direction in HP scintillators are highlighted for improving X-ray imaging resolution. Finally, we highlight the current challenge in HP scintillators and provide a perspective on the future development of this emerging scintillator.

Emergence of a Lanthanide Chalcogenide as an Ideal Scintillator for a Flexible X-ray Detector.

The development of high-performance X-ray detectors requires scintillators with fast decay time, high light yield, stability, and X-ray absorption capacity, which are difficult to achieve in a single material. Here, we present the first example of a lanthanide chalcogenide of LaCsSiS4 : 1 % Ce3+ that simultaneously integrates multiple desirable properties for an ideal scintillator. LaCsSiS4 : 1 % Ce3+ demonstrates a remarkably low detection limit of 43.13 nGyair s-1 and a high photoluminescence quantum yield of 98.24 %, resulting in a high light yield of 50480±1441 photons/MeV. Notably, LaCsSiS4 : 1 % Ce3+ exhibits a fast decay time of only 29.35±0.16 ns, making it one of the fastest scintillators among all lanthanide-based inorganic scintillators. Furthermore, this material shows robust radiation and moisture resistance, endowing it with suitability for chemical processing under solution conditions. To demonstrate the X-ray imaging capacity of LaCsSiS4 : 1 % Ce3+ , we fabricated a flexible X-ray detector that achieved a high spatial resolution of 8.2 lp mm-1 . This work highlights the potential of lanthanide chalcogenide as a promising candidate for high-performance scintillators.