Stachyose ameliorates myocardial ischemia-reperfusion injury by inhibiting cardiomyocyte ferroptosis and macrophage pyroptosis.

Myocardial ischemia-reperfusion injury (MIRI) is a complex pathological process that results from the restoration of blood flow to ischemic myocardium, leading to a series of detrimental effects including oxidative stress and inflammation. Stachyose, a naturally occurring oligosaccharide found in traditional Chinese medicinal herbs, has been suggested to possess therapeutic properties against various pathological conditions. However, its impact on MIRI and the underlying mechanisms have not been fully elucidated. In this study, we aimed to investigate the therapeutic effects of stachyose on MIRI and to uncover the molecular mechanisms involved. Using both in vivo and in vitro models of MIRI, we evaluated the effects of stachyose on cardiac function and cell death pathways. Our results indicate that stachyose significantly improves cardiac function and reduces infarct size in MIRI mice. Mechanistically, stachyose modulates the ferroptotic pathway in cardiomyocytes by upregulating the expression of glutathione peroxidase 4 (GPX4) and reducing lipid peroxides and iron levels. Additionally, stachyose inhibits the pyroptotic pathway in macrophages by downregulating the expression of NLRP3, gasdermin D (GSMD-N), and cleaved-caspase-1, leading to decreased levels of proinflammatory cytokines interleukin (IL)-1ß and IL-18. This study demonstrates that stachyose exerts a protective effect against MIRI by targeting both ferroptosis and pyroptosis pathways, suggesting its potential as a novel therapeutic agent for the treatment of MIRI. Further research is warranted to explore the detailed mechanisms and therapeutic potential of stachyose in clinical settings.

Evaluating Surgical Accuracy in Bimaxillary Surgery: A Systematic Review and Meta-Analysis of Mandible-First versus Maxilla-First Approaches.

BACKGROUND: Mandible-first surgery (MdFS) has gained attention as an alternative to the traditional maxilla-first surgery (MxFS) in bimaxillary procedures. Given the distinct sequence of operations between these approaches, evaluating the clinical advantages of MdFS compared to MxFS is crucial for optimizing surgical decision-making. This systematic review and meta-analysis examine intraoperative achievability and postoperative stability between these two surgical approaches. METHODS: A thorough literature search was performed using PubMed, Embase, Web of Science, and MEDLINE, covering articles published from 2013 to 2023. Studies included were retrospective, prospective, and randomized trials that compared the accuracy and/or stability of MdFS with MxFS. The primary endpoint for the meta-analysis was the standardized mean difference in surgical accuracy for translational movements, with a secondary focus on rotational accuracy. RESULTS: A total of 11 studies encompassing 712 patients met the inclusion criteria. The analysis suggested that MdFS might reduce accuracy in the sagittal dimension (CI, 0.05 to 0.74) but offered greater achievability in the vertical direction (CI, - 0.47 to - 0.07). Additionally, MdFS was associated with a relatively posterior (CI, - 1.18 to - 0.60) and inferior (CI, - 0.64 to - 0.07) positioning of the maxillomandibular complex. CONCLUSION: Despite certain limitations, our findings indicate that MdFS can achieve clinical outcomes similar to MxFS in terms of both accuracy and stability. However, further researches with larger sample sizes and more rigorous study designs are necessary to validate these conclusions. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of contents or the online Instructions to Authors www.springer.com/00266 .

Urine is better for rare earth elements bimonitoring in long-term exposed population: An exposure-response relationship study.

With the soaring use of rare earth elements (REEs) worldwidely in high-technology and clean energy industries, there were growing concerns for adverse health effect from the REEs exposure. However, there is a lack of biomonitoring research concerning both urine and blood in population with definite exposure. We performed a biomonitoring study that involved 103 REEs exposed males and 110 males as non-REEs exposed controls. We measured the levels of REEs in environment and urine and blood samples from participants, and explored the exposure-response relationship between REEs in environment and body fluids. The effects of exposure duration and smoking status on the internal exposure level of REEs were also investigated. The results showed environmental REEs level of exposure group was significantly higher than that of control group (range of geometric mean of exposure vs. control: 1.08-4.07 × 104 ng/m3 vs.

Ion Leakage Current Control for Polycrystalline Metal Halide Perovskite Direct X-ray Detectors.

Metal halide perovskites have emerged as promising materials for X-ray detection due to their high X-ray attenuation coefficients, defect tolerance, and suitability for large-area, low-temperature fabrication. However, the intrinsic high ion conductivity of these materials presents challenges, such as high dark current density and current drift, which impair the stability and sensitivity of perovskite X-ray detectors. This study introduces an approach to mitigating these issues by incorporating 2,2,3,3,3-pentafluoropropylamine hydrochloride (PFH) into polycrystalline MAPbI3-xClx films using a one-step blade-coating method. PFH aggregates at grain boundaries, raising local vacuum energy levels and passivating surface defects, thereby reducing ion conductivity without affecting electron conductivity. As a result, this approach significantly reduces the dark current and enhances sensitivity, achieving a low detection limit of 14.7 nGyair/s. Additionally, it improves signal stability, consistency, and response speed of the detector. These findings suggest that PFH is a promising additive for advancing the performance and practical application of polycrystalline metal halide perovskite-based X-ray detectors.

Identification and functional analysis of C-type lectin from mosquito Aedes albopictus in response to dengue virus infection.

BACKGROUND: C-type lectins (CTLs) are a large family of proteins with sugar-binding activity. CTLs contain an evolutionarily conserved C-type lectin domain (CTLD) that binds microbial carbohydrates in a calcium-dependent manner, thereby playing a key role in both microbial pathogenesis and innate immune responses. Aedes albopictus is an important vector for transmitting dengue virus (DENV) worldwide. Currently, the molecular characteristics and functions of CTLs in Ae. albopictus are largely unknown. METHODS: Transcripts encoding CTL proteins in the Ae. albopictus genome assembly were analyzed via sequence blast. Phylogenetic analysis and molecular characterization were performed to identify the functional domains of the CTLs. Quantitative analysis was performed to determine the gene expression features of CTLs during mosquito development and in different tissues of female adults after blood feeding. In addition, the functional role of CTLs in response to DENV infection was investigated in Ae. albopictus mosquito cells. RESULTS: We identified 39 transcripts encoding CTL proteins in the Ae. albopictus transcriptome. Aedes albopictus CTLs are classified into three groups based on the number of CTLDs and the domain architecture. These included 29 CTL-Ss (single-CTLDs), 1 immulectins (dual-CTLD) and 9 CTL-Xs (CTLDs with other domains). Phylogenetic analysis and structural modeling indicated that CTLs in Ae. albopictus are highly conserved with the homologous CTLs in Aedes aegypti. The expression profile assay revealed differential expression patterns of CTLs in both developmental stages and in adult female tissues. Knockdown and overexpression of three CTLs (CTL-S12, S17 and S19) confirmed that they can promote dengue virus infection in Ae. albopictus cells. CONCLUSIONS: The CTL genes in Ae. albopictus mosquito and other mosquito species are evolutionarily conserved and exhibit different developmental and tissue expression features. The functional assay indicated that three CTLs in Ae. albopictus mosquitoes are involved in promoting dengue virus infection. Our study revealed that CTLs play important roles in both the physiological processes and viral infection in mosquito vectors.

Cellulose-based yellow-green emitting carbon dots with large Stokes shift as effective "turn off-on" fluorescence platforms for Cr (VI) and AA dual efficacy detection.

BACKGROUND: Hexavalent chromium (Cr (VI)) is highly carcinogenic to humans. Ascorbic acid (AA) deficiency can be hazardous to health. And the dual-effect fluorescence detection of them is an important research topic. Carbon dots (CDs) based on cellulose are excellent candidates for the fluorescence probes due to their low cost and environmental friendliness. But most of them exhibit shortwave emission, small Stokes shift and poor fluorescence performance, all of which limit their use. Therefore, there is an urgent need for cellulose CDs with longer emission wavelengths and larger Stokes shifts in dual-effect fluorescence detection of Cr (VI) and AA. RESULTS: Under optimal conditions (180 °C, 12 h), we prepared cellulose-based nitrogen-doped carbon dots (N-CDs) by a simple one-step hydrothermal process, which display longer emission wavelengths (ex: 370 nm, em: 510 nm), larger Stokes shifts (140 nm) and high fluorescence quantum yield (QY: 19.27 %). The continuous "turn-off" and "turn-off-on" fluorescence detection platforms were constructed based on the internal filtering effect (IFE) between Cr6+ and N-CDs, and Cr6+ reduced to Cr3+ by AA at pH = 6. The platform has been successfully simultaneous detect Cr (VI) and AA with a wide range of 0.01-40 µM and 0.1-100 µM. And the lowest limits of detection (LOD) are 0.0303 µM and 0.072 µM, respectively. In the presence of some other metals, non-metal ions and water-soluble acids in the fruits, this fluorescent platform can demonstrate a high level of interference immunity. SIGNIFICANCE AND NOVELTY: This represents the first yellow-green cellulose-based N-CDs with large Stokes shift for dual-effect detection of Cr (VI) and AA in real water samples and fresh fruits. The fluorescence detection platform has the advantage of low volume detection. Less than 2 mL of sample is required for testing and results are available in <5 min. This method is rare and supply a novel idea for the quantitative monitoring of Cr (VI) and AA.

Regulation of warming on the mixed decomposition of Artemisia ordosica and Leymus secalinus litter in Mu Us Desert, China is time-dependent.

Warming drives material cycling in terrestrial ecosystems by affecting litter decomposition, as it can alter litter yield, quality and decomposer composition and activity. The effect of warming on the decomposition of mixed litter in arid and semi-arid zones remains unknown. We investigated the mass loss and nutrient release dynamics during 450 days of decomposition of Artemisia ordosica, Leymus secalinus, and their mixture in Mu Us Desert by open-top chambers and litter bags. The results showed interspecific differences in the responses to warming, in that warming promoted mass loss and N and P release from L. secalinus and inhibited mass loss and P but promoting N release from A. ordosica. Mixing of A. ordosica and L. secalinus litter inhibited decomposition. Warming enhanced the antagonistic effects of mixed decomposition. The total mass loss of mixed litter was decreased by 9%, and the release of N and P was decreased by 4.9% and 12.6%, respectively. The antagonistic effects of mixed litter mass loss and P release under the warming treatment gradually strengthened with time, with N release changing from a synergistic to an antagonistic effect at 150 d. The non-additive effects produced by the mixed decomposition of A. ordosica and L. secalinus litter were jointly regulated by temperature and time. Future research on mixed litter decomposition should consider the interaction between temperature and time.

Microglia in retinal diseases: From pathogenesis towards therapeutic strategies.

Microglia, a widely dispersed cohort of immune cells in the retina, are intricately involved in a diverse range of pivotal biological processes, including inflammation, vascular development, complement activation, antigen presentation, and phagocytosis. Within the retinal milieu, microglia are crucial for the clearance of dead cells and cellular debris, release of anti-inflammatory agents, and orchestration of vascular network remodeling to maintain homeostasis. In addition, microglia are key mediators of neuroinflammation. Triggered by oxidative stress, elevated intraocular pressure, genetic anomalies, and immune dysregulation, microglia release numerous inflammatory cytokines, contributing to the pathogenesis of various retinal disorders. Recent studies on the ontogeny and broad functions of microglia in the retina have elucidated their characteristics during retinal development, homeostasis, and disease. Furthermore, therapeutic strategies that target microglia and their effector cytokines have been developed and shown positive results for some retinal diseases. Therefore, we systematically review the microglial ontogeny in the retina, elucidate their dual roles in retinal homeostasis and disease pathogenesis, and demonstrate microglia-based targeted therapeutic strategies for retinal diseases.

Transcriptome analysis unveils PLSCR1 associated with microglial polarization in neuropathic pain.

Neuropathic pain (NP) continues to be a significant problem that lacks effective treatment. Our study sought to explore a new promising gene target for the treatment of NP. Differential and enrichment analyses were performed on 24,197 genes and 12,088 genes from the NP microglial microarray and sequencing dataset. Candidate differentially expressed genes (DEGs), functions, and signaling pathways that are closely related to NP were identified by analyzing the bioinformatic results. For in vivo experiments, mice were divided into the sham and NP groups. The expressions of DEGs were validated to screen out the NP hub genes. For in vitro experiments, the hub genes in resting M0-BV2 and polarized M1-BV2 microglia were examined by immunofluorescence, flow cytometry, and qRT-PCR. DEGs in the NP microarray and sequencing data shared five candidate genes, CD244, MEGF9, PCGF2, PLSCR1, and NECAB2. The results of the in vivo experiment showed that the NP model group exhibited higher expression of PLSCR1 and MEGF9 compared to the sham group. The enrichment results of the DEGs revealed the biological processes of "response to lipopolysaccharide". PLSCR1 was highly expressed in the lipopolysaccharide-induced M1-BV2 microglia. PLSCR1 is a potential gene associated with microglial polarization in NP. These findings provide a new view on understanding the pathogenesis mechanism of NP.

Microstructure Evolution of Vacuum Diffusion-Bonded 304 Stainless Steel/20 Carbon Steel Bimetallic Interface after Solution Treatment.

In this study, a 304 stainless steel (304 SS)/20 carbon steel (20 CS) bimetal was prepared by vacuum diffusion bonding, with 20 CS as the substrate and 304 SS as the cladding layer, and the interfacial microstructure and bonding strength before and after solution treatment were studied. The 304 SS and The 20 CS formed a strong metallurgical bond after being held at 1380 °C for 60 min without defects such as unbonded regions. Diffusion of Cr and Ni atoms from the 304 SS to the 20 CS occurred, and the C atoms diffused from the 20 CS to the 304 SS, forming a carburized region. A pearlitic region with an average width of approximately 20 µm was formed on the 20 CS side. After solution treatment, austenitization was formed in the carburized region, which was accompanied by the formation of twin crystals. The interfacial bonding strength of the bimetal was measured to be 485 MPa, which increased to 547 MPa after the solution treatment.

Studies of phantom-solution systems for boron neutron capture therapy.

This study aims to establish phantom-solution systems suitable for estimating doses in boron neutron capture therapy (BNCT). The phantom containing three typical solutions, H3BO3, LiOH, and Gd(NO3)3·6H2O with different concentrations and nuclide abundances have been studied since the nuclides 10B, 6Li, and 157Gd are capable of absorbing thermal neutrons. The results indicate that all three phantom-solution systems, with suitable concentrations and nuclide abundances, effectively distinguish between the nitrogen dose and the hydrogen dose for dose measurement in BNCT.

Identification of potential diagnostic biomarkers for hypertension via integrated analysis of gene expression and DNA methylation.

OBJECTIVE: Hypertension refers to the elevated blood pressure (BP) in arteries, with a BP reading of 140/90 mm Hg or higher in adults. Over 40% of >25-year-old population have suffered from hypertension. Thus, this study aimed to find novel diagnostic biomarkers for hypertension. METHODS: All hypertension-related mRNA and methylation datasets were downloaded from the GEO database. Liner model method was used to identify differentially expressed genes (DEGs) between hypertension and control groups. Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes enrichment analysis was employed to obtain functional information. CpG sites and the corresponding genes associated with hypertension were screened using epigenome-wide association study (EWAS) analysis. RESULTS: There were 37 DEGs between the hypertension group and control group, which were significantly enriched in 84 Biological Process terms, 31 Cellular Component terms, 18 Molecular Function terms and 9 signalling pathways. EWAS results indicated that 1072 CpG sites were associated with hypertension occurrence, corresponding to 1029 genes. After cross-analysis, complement factor D (CFD) and OTU deubiquitinase, ubiquitin aldehyde binding 2 (OTUB2) with methylation modification were identified as diagnostic markers for hypertension. CONCLUSION: In conclusion, CFD and OTUB2 were potential biomarkers of hypertension occurrence. Our results will provide more information for hypertension diagnosis and would be more reliable combined with multiple biomarkers.

In the GSE24752 dataset, there were 37 differentially expressed genes between the hypertension group and the normal group.In the GSE42774 dataset, there were 1072 CpG sites, corresponding to 1029 genes, associated with hypertension occurrence.CFD and OTUB2 were potential biomarkers that were associated with hypertension occurrence.

An algorithm for forensic toolmark comparisons.

Forensic toolmark analysis traditionally relies on subjective human judgment, leading to inconsistencies and lack of transparency. The multitude of variables, including angles and directions of mark generation, further complicates comparisons. To address this, we first generate a dataset of 3D toolmarks from various angles and directions using consecutively manufactured slotted screwdrivers. By using PAM clustering, we find that there is clustering by tool rather than angle or direction. Using Known Match and Known Non-Match densities, we establish thresholds for classification. Fitting Beta distributions to the densities, we allow for the derivation of likelihood ratios for new toolmark pairs. With a cross-validated sensitivity of 98 % and specificity of 96 %, our approach enhances the reliability of toolmark analysis. This approach is applicable to slotted screwdrivers, and for screwdrivers that are made with a similar production method. With data collection of other tools and factors, it could be applied to compare toolmarks of other types. This empirically trained, open-source solution offers forensic examiners a standardized means to objectively compare toolmarks, potentially decreasing the number of miscarriages of justice in the legal system.

Subthreshold Micropulse Laser Versus Oral Spironolactone in Chronic Central Serous Chorioretinopathy: A Quasi-Randomized Controlled Trial.

Purpose: To compare the efficacy and safety of subthreshold micropulse laser (SML) and spironolactone therapy for treating chronic central serous chorioretinopathy (CSC). Methods: This was a quasi-randomized controlled trial. Eligible patients were quasi-randomized at a 1:1 ratio to receive SML or oral spironolactone and were assessed at 3 months after treatment. Results: A total of 84 patients (90 eyes) were randomly assigned to receive SML (n = 45) or spironolactone (n = 39) initially. At last follow-up, 59.5% of patients in the SML group had complete resolution of subretinal fluid (SRF) compared to 43.6% in spironolactone group (P = 0.362). The mean visual acuity did not significantly improve between the two groups (0.38 ± 0.44 vs. 0.43 ± 0.43 logMAR). The central retinal thickness was decreased from 335.06 ± 120.25 µm to 222.15 ± 94.90 µm in the SML group and from 308.02 ± 90.69 µm to 257.27 ± 102.28 µm in the spironolactone group. After treatment, subfoveal choroidal thickness, total choroidal area, and stromal and luminal choroidal area were significantly lower in the spironolactone group as compared to the SML group. During the entire visit, the recurrence rate of SRF was 9.1% in the SML group compared to 35.3% in the spironolactone group. Slight adverse events occurred more frequently in the spironolactone group (0% vs. 16%). Conclusions: Both SML and oral spironolactone were effective and safe treatments to ameliorate retinal anatomical structures for chronic CSC. A lower recurrence rate and fewer adverse effects were observed in the SML group, and better choroidal structure recovery was seen in the spironolactone group. Translational Relevance: The investigation of SML and oral spironolactone may inform evidence-based clinical decisions for chronic CSC patients.

Identification and validation of basement membrane-associated gene AGRN as prognostic and immune-associated biomarkers in colorectal cancer patients.

Colorectal cancer (COCA) has a poor prognosis, with growing evidence implicating basement membranes (BMs) in cancer progression. Our goal was to investigate the role and predictive significance of BMs in COCA patients. We obtained BMs-related genes from cutting-edge research and used TCGA and GTEx databases for mRNA expression and patient information. Cox regression and LASSO regression were used for prognostic gene selection and risk model construction. We compared prognosis using Kaplan-Meier analysis and examined drug sensitivity differences. The CMAP dataset identified potential small molecule drugs. In vitro tests involved suppressing a crucial gene to observe its impact on tumour metastasis. We developed a 12 BMs-based approach, finding it to be an independent prognostic factor. Functional analysis showed BMs concentrated in cancer-associated pathways, correlating with immune cell infiltration and immune checkpoint activation. High-risk individuals exhibited increased drug sensitivity. AGRN levels were linked to decreased progression-free survival (p < 0.001). AGRN knockdown suppressed tumour growth and metastasis. Our study offers new perspectives on BMs in COCA, concluding that AGRN is a dependable biomarker for patient survival and prognosis.

Super-resolution diffractive neural network for all-optical direction of arrival estimation beyond diffraction limits.

Wireless sensing of the wave propagation direction from radio sources lays the foundation for communication, radar, navigation, etc. However, the existing signal processing paradigm for the direction of arrival estimation requires the radio frequency electronic circuit to demodulate and sample the multichannel baseband signals followed by a complicated computing process, which places the fundamental limit on its sensing speed and energy efficiency. Here, we propose the super-resolution diffractive neural networks (S-DNN) to process electromagnetic (EM) waves directly for the DOA estimation at the speed of light. The multilayer meta-structures of S-DNN generate super-oscillatory angular responses in local angular regions that can perform the all-optical DOA estimation with angular resolutions beyond the diffraction limit. The spatial-temporal multiplexing of passive and reconfigurable S-DNNs is utilized to achieve high-resolution DOA estimation over a wide field of view. The S-DNN is validated for the DOA estimation of multiple radio sources over 5 GHz frequency bandwidth with estimation latency over two to four orders of magnitude lower than the state-of-the-art commercial devices in principle. The results achieve the angular resolution over an order of magnitude, experimentally demonstrated with four times, higher than diffraction-limited resolution. We also apply S-DNN's edge computing capability, assisted by reconfigurable intelligent surfaces, for extremely low-latency integrated sensing and communication with low power consumption. Our work is a significant step towards utilizing photonic computing processors to facilitate various wireless sensing and communication tasks with advantages in both computing paradigms and performance over electronic computing.

Research on path planning for clear aligner flexible manufacturing.

In recent years, clear aligner can enhance individual appearance with dental defects, so it used more and more widely. However, in manufacturing process, there are still some problems, such as low degree of automation and high equipment cost. The problem of coordinate system mismatch between gingival curve point cloud and dental CAD model is faced to. The PCA-ICP registration algorithm is proposed, which includes coarse match algorithm and improve-ICP registration algorithm. The principal component analysis (PCA) based method can roughly find the posture relationship between the two point clouds. Using z-level dynamic hierarchical, the ICP registration can accurately find the posture between these two clouds. The final registration maximum distance error is 0.03 mm, which is smaller than robot machining error. Secondly, the clear aligner machining process is conducted to verify the registration effectiveness. Before machining, the path is generated based on the well registered gingival curve. After full registration, the tool path is calculated by establishing a local coordinate system between the workpiece and the tool to avoid interference. This path is calculated and generated as an executable program for ABB industrial robots. Finally, the robot was used for flexible cutting of clear aligners and was able to extract products, ensuring the effectiveness of the proposed research. This method can effectively solve the limitations of traditional milling path planning under such complex conditions.

A dual-function mixed-culture biofilm for sulfadiazine removal and electricity production using bio-electrochemical system.

Sulfadiazine (SDZ) is frequently detected in environmental samples, arousing much concern due to its toxicity and hard degradation. This study investigated the electricity generation capabilities, SDZ removal and microbial communities of a highly efficient mixed-culture system using repeated transfer enrichments in a bio-electrochemical system. The mixed-culture biofilm (S160-T2) produced a remarkable current density of 954.12 ± 15.08 µA cm-2 with 160 mg/L SDZ, which was 32.9 and 1.8 times higher than that of Geobacter sulfurreducens PCA with 40 mg/L SDZ and without additional SDZ, respectively. Especially, the impressive SDZ removal rate of 98.76 ± 0.79% was achieved within 96 h using the further acclimatized mixed-culture. The removal efficiency of this mixed-culture for SDZ through the bio-electrochemical system was 1.1 times higher than that using simple anaerobic biodegradation. Furthermore, the current density and removal efficiency in this system gradually decreased with increasing SDZ concentrations from 0 to 800 mg/L. In addition, community diversity data demonstrated that the dominant genera, Geobacter and Escherichia-Shigella, were enriched in mixed-culture biofilm, which might be responsible for the current production and SDZ removal. This work confirmed the important roles of acclimatized microbial consortia and co-substrates in the simultaneous removal of SDZ and electricity generation in an electrochemical system.

Mitigation of Parasitic and Drift Capacitance-Induced Nonlinear Current Responses for Stable and Sensitive Perovskite X-ray Detectors.

The development of perovskite direct X-ray detectors shows potential for advancing medical imaging and industrial inspection precision. To ensure the optimal energy conversion efficiency of X-rays for reducing radiation doses, it is necessary for perovskites with thicknesses reaching hundreds of micrometers or even several millimeters to be utilized. However, the nonlinear current response becomes uncertain with such high thicknesses. For instance, the prevailing theory regarding the rapid trapping and release of charges by shallow-level defects falls short in explaining the nonlinear current response observed in high-quality single-crystal samples. Moreover, a significant nonlinear current response can degrade the detection performance. Here, we elucidate peculiar parasitic and drift capacitance-induced nonlinear current responses in perovskites, which arise from bulk structural deficiencies and interface junction width variation in addition to shallow-level defects. Both theoretical analysis and experimental findings demonstrate the effective suppression of nonlinear current responses by establishing bulk heterojunctions and refining interface junctions. Consequently, we have successfully developed highly linear current-responsive detectors based on polycrystalline MAPbI3 thick films. Notably, these detectors achieve a record sensitivity of 2.3 × 104 µC·Gyair-1·cm-2 under 100 kVp X-ray irradiation with a low bias of 0.1 V/µm, enabling enduring and high-resolution X-ray imaging for high-density objects. Successful fabrication and testing of a 64 × 64-pixel flat-panel prototype detector affirm the widespread applicability of these strategies in rectifying nonlinear current responses in perovskite-based X-ray detectors.