Layered subsurface in Utopia Basin of Mars revealed by Zhurong rover radar.

Exploring the subsurface structure and stratification of Mars advances our understanding of Martian geology, hydrological evolution and palaeoclimatic changes, and has been a main task for past and continuing Mars exploration missions1-10. Utopia Planitia, the smooth plains of volcanic and sedimentary strata that infilled the Utopia impact crater, has been a prime target for such exploration as it is inferred to have hosted an ancient ocean on Mars11-13. However, 45 years have passed since Viking-2 provided ground-based detection results. Here we report an in situ ground-penetrating radar survey of Martian subsurface structure in a southern marginal area of Utopia Planitia conducted by the Zhurong rover of the Tianwen-1 mission. A detailed subsurface image profile is constructed along the roughly 1,171 m traverse of the rover, showing an approximately 70-m-thick, multi-layered structure below a less than 10-m-thick regolith. Although alternative models deserve further scrutiny, the new radar image suggests the occurrence of episodic hydraulic flooding sedimentation that is interpreted to represent the basin infilling of Utopia Planitia during the Late Hesperian to Amazonian. While no direct evidence for the existence of liquid water was found within the radar detection depth range, we cannot rule out the presence of saline ice in the subsurface of the landing area.

The AGAMOUS-LIKE 16-GENERAL REGULATORY FACTOR 1 module regulates axillary bud outgrowth via catabolism of abscisic acid in cucumber.

Lateral branches are important components of shoot architecture and directly affect crop yield and production cost. Although sporadic studies have implicated abscisic acid (ABA) biosynthesis in axillary bud outgrowth, the function of ABA catabolism and its upstream regulators in shoot branching remain elusive. Here, we showed that the MADS-box transcription factor AGAMOUS-LIKE 16 (CsAGL16) is a positive regulator of axillary bud outgrowth in cucumber (Cucumis sativus). Functional disruption of CsAGL16 led to reduced bud outgrowth, whereas overexpression of CsAGL16 resulted in enhanced branching. CsAGL16 directly binds to the promoter of the ABA 8'-hydroxylase gene CsCYP707A4 and promotes its expression. Loss of CsCYP707A4 function inhibited axillary bud outgrowth and increased ABA levels. Elevated expression of CsCYP707A4 or treatment with an ABA biosynthesis inhibitor largely rescued the Csagl16 mutant phenotype. Moreover, cucumber General Regulatory Factor 1 (CsGRF1) interacts with CsAGL16 and antagonizes CsAGL16-mediated CsCYP707A4 activation. Disruption of CsGRF1 resulted in elongated branches and decreased ABA levels in the axillary buds. The Csagl16 Csgrf1 double mutant exhibited a branching phenotype resembling that of the Csagl16 single mutant. Therefore, our data suggest that the CsAGL16-CsGRF1 module regulates axillary bud outgrowth via CsCYP707A4-mediated ABA catabolism in cucumber. Our findings provide a strategy to manipulate ABA levels in axillary buds during crop breeding to produce desirable branching phenotypes.

Natural variation in CRABS CLAW contributes to fruit length divergence in cucumber.

Fruit length is a key domestication trait that affects crop yield and appearance. Cucumber (Cucumis sativus) fruits vary from 5 to 60 cm in length. Despite the identification of several regulators and multiple quantitative trait loci (QTLs) underlying fruit length, the natural variation, and molecular mechanisms underlying differences in fruit length are poorly understood. Through map-based cloning, we identified a nonsynonymous polymorphism (G to A) in CRABS CLAW (CsCRC) as underlying the major-effect fruit size/shape QTL FS5.2 in cucumber. The short-fruit allele CsCRCA is a rare allele that has only been found in round-fruited semi-wild Xishuangbanna cucumbers. A near-isogenic line (NIL) homozygous for CsCRCA exhibited a 34∼39% reduction in fruit length. Introducing CsCRCG into this NIL rescued the short-fruit phenotype, and knockdown of CsCRCG resulted in shorter fruit and smaller cells. In natural cucumber populations, CsCRCG expression was positively correlated with fruit length. Further, CsCRCG, but not CsCRCA, targets the downstream auxin-responsive protein gene CsARP1 to regulate its expression. Knockout of CsARP1 produced shorter fruit with smaller cells. Hence, our work suggests that CsCRCG positively regulates fruit elongation through transcriptional activation of CsARP1 and thus enhances cell expansion. Using different CsCRC alleles provides a strategy to manipulate fruit length in cucumber breeding.

Optimization of immunosuppression strategies for the establishment of chronic hepatitis E virus infection in rabbits.

Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like perforin and FasL) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants.

Integrated MicroRNA and Secretome Analysis of Human Endometrial Organoids Reveal the miR-3194-5p/Aquaporin/S100A9 Module in Regulating Trophoblast Functions.

Successful placentation requires delicate communication between the endometrium and trophoblasts. The invasion and integration of trophoblasts into the endometrium during early pregnancy are crucial to placentation. Dysregulation of these functions is associated with various pregnancy complications, such as miscarriage and preeclampsia. The endometrial microenvironment has an important influence on trophoblast cell functions. The precise effect of the endometrial gland secretome on trophoblast functions remains uncertain. We hypothesized that the hormonal environment regulates the miRNA profile and secretome of the human endometrial gland, which subsequently modulates trophoblast functions during early pregnancy. Human endometrial tissues were obtained from endometrial biopsies with written consent. Endometrial organoids were established in matrix gel under defined culture conditions. They were treated with hormones mimicking the environment of the proliferative phase (Estrogen, E2), secretory phase (E2+Progesterone, P4), and early pregnancy (E2+P4+Human Chorionic Gonadotropin, hCG). miRNA-seq was performed on the treated organoids. Organoid secretions were also collected for mass spectrometric analysis. The viability and invasion/migration of the trophoblasts after treatment with the organoid secretome were determined by cytotoxicity assay and transwell assay, respectively. Endometrial organoids with the ability to respond to sex steroid hormones were successfully developed from human endometrial glands. By establishing the first secretome profiles and miRNA atlas of these endometrial organoids to the hormonal changes followed by trophoblast functional assays, we demonstrated that sex steroid hormones modulate aquaporin (AQP)1/9 and S100A9 secretions through miR-3194 activation in endometrial epithelial cells, which in turn enhanced trophoblast migration and invasion during early pregnancy. By using a human endometrial organoid model, we demonstrated for the first time that the hormonal regulation of the endometrial gland secretome is crucial to regulating the functions of human trophoblasts during early pregnancy. The study provides the basis for understanding the regulation of early placental development in humans.

The CsHEC1-CsOVATE module contributes to fruit neck length variation via modulating auxin biosynthesis in cucumber.

Fruit neck is the proximal portion of the fruit with undesirable taste that has detrimental effects on fruit shape and commercial value in cucumber. Despite the dramatic variations in fruit neck length of cucumber germplasms, the genes and regulatory mechanisms underlying fruit neck elongation remain mysterious. In this study, we found that Cucumis sativus HECATE1 (CsHEC1) was highly expressed in fruit neck. Knockout of CsHEC1 resulted in shortened fruit neck and decreased auxin accumulation, whereas overexpression of CsHEC1 displayed the opposite effects, suggesting that CsHEC1 positively regulated fruit neck length by modulating local auxin level. Further analysis showed that CsHEC1 directly bound to the promoter of the auxin biosynthesis gene YUCCA4 (CsYUC4) and activated its expression. Enhanced expression of CsYUC4 resulted in elongated fruit neck and elevated auxin content. Moreover, knockout of CsOVATE resulted in longer fruit neck and higher auxin. Genetic and biochemical data showed that CsOVATE physically interacted with CsHEC1 to antagonize its function by attenuating the CsHEC1-mediated CsYUC4 transcriptional activation. In cucumber germplasms, the expression of CsHEC1 and CsYUC4 positively correlated with fruit neck length, while that of CsOVATE showed a negative correlation. Together, our results revealed a CsHEC1-CsOVATE regulatory module that confers fruit neck length variation via CsYUC4-mediated auxin biosynthesis in cucumber.

Enhanced Direct Exchange Interaction and Hybridization by Single-Atom Linkers for High Curie Temperature and Superior Visible-Light Harvesting in Cr3(CN3)2.

Designing two-dimensional (2D) ferromagnetic (FM) semiconductors with elevated Curie temperature, high carrier mobility, and strong light harvesting is challenging but crucial to the development of spintronics with multifunctionalities. Herein, we show first-principles computation evidence of the 2D metal-organic framework Kagome ferromagnet Cr3(CN3)2. Monolayer Cr3(CN3)2 is predicted to be an FM semiconductor with a record-high Curie temperature of 943 K owing to the use of a single-atom linker (N), which results in strong direct d-p exchange interaction and hybridization between dyz/xz and pz of Cr and N, as well as excellent matching characteristics in energy and symmetry. The single-atom linker structural feature also leads to notable band dispersion and a relatively high carrier mobility of 420 cm2 V-1 s-1. Moreover, under the in-plane strain, 2D Cr3(CN3)2 can be tuned to possess a strong visible-light-harvesting functionality. These novel properties render monolayer Cr3(CN3)2 a distinct 2D ferromagnet with high potential for the development of multifunctional spintronics.

Solvated Electrons Generated on the Surface of Na-SPHI for Boosting Visible Light Photocatalytic Hydrogen Evolution with Ultra-High AQE.

Enhancing the utilization of visible-light-active semiconductors with an excellent apparent quantum efficiency (AQE) remains a significant and challenging goal in the realm of photocatalytic water splitting. In this study, a fully condensed sulfur-doped poly(heptazine imide) metalized with Na (Na-SPHI) is synthesized by an ionothermal method by using eutectic NaCl/LiCl mixture as the ionic solvent. Comprehensive characterizations of the obtained Na-SPHI reveal several advantageous features, including heightened light absorption, facilitated exciton dissociation, and expedited charge transfer. More importantly, solvated electron, powerful reducing agents, can be generated on the surface of Na-SPHI upon irradiation with visible light. Benefiting from above advantage, the Na-SPHI exhibits an excellent H2 evolution rate of 571.8 µmol·h-1 under visible light illumination and a super-high AQE of 61.7% at 420 nm. This research emphasizes the significance of the solvated electron on the surface of photocatalyst in overcoming the challenges associated with visible light-driven photocatalysis, showcasing its potential application in photocatalytic water splitting.

Polaronic Nonlinear Optical Response and All-Optical Switching Based on an Ionic Metal Oxide.

It has been well-established that light-matter interactions, as manifested by diverse linear and nonlinear optical (NLO) processes, are mediated by real and virtual particles, such as electrons, phonons, and excitons. Polarons, often regarded as electrons dressed by phonons, are known to contribute to exotic behaviors of solids, from superconductivity to photocatalysis, while their role in materials' NLO response remains largely unexplored. Here, the NLO response mediated by polarons supported by a model ionic metal oxide, TiO2, is examined. It is observed that the formation of polaronic states within the bandgap results in a dramatic enhancement of NLO absorption coefficient by over 130 times for photon energies in the sub-bandgap regions, characterized by a 100 fs scale ultrafast response that is typical for thermalized electrons in metals. The ultrafast polaronic NLO response is then exploited for the development of all-optical switches for ultrafast pulse generation in near-infrared (NIR) fiber lasers and modulation of optical signal in the telecommunication band based on evanescent interaction on a planar waveguide chip. These results suggest that the polarons supported by dielectric ionic oxides can fill the gaps left by dielectric and metallic materials and serve as a novel platform for nonlinear photonic applications.

Tailoring Broadband Nonlinear Optical Characteristics and Ultrafast Photocarrier Dynamics of Bi2O2S Nanosheets by Defect Engineering.

Low-dimensional bismuth oxychalcogenides have shown promising potential in optoelectronics due to their high stability, photoresponse, and carrier mobility. However, the relevant studies on deep understanding for Bi2O2S is quite limited. Here, comprehensive experimental and computational investigations are conducted in the regulated band structure, nonlinear optical (NLO) characteristics, and carrier dynamics of Bi2O2S nanosheets via defect engineering, taking O vacancy (OV) and substitutional Se doping as examples. As the OV continuously increased to ≈35%, the optical bandgaps progressively narrow from ≈1.21 to ≈0.81 eV and NLO wavelengths are extended to near-infrared regions with enhanced saturable absorption. Simultaneously, the relaxation processes are effectively accelerated from tens of picoseconds to several picoseconds, as the generated defect energy levels can serve as both additional absorption cross-sections and fast relaxation channels supported by theoretical calculations. Furthermore, substitutional Se doping in Bi2O2S nanosheets also modulate their optical properties with the similar trends. As a proof-of-concept, passively mode-locked pulsed lasers in the ≈1.0 µm based on the defect-rich samples (≈35% OV and ≈50% Se-doping) exhibit excellent performance. This work deepens the insight of defect functions on optical properties of Bi2O2S nanosheets and provides new avenues for designing advanced photonic devices based on low-dimensional bismuth oxychalcogenides.

SlERF.G3-Like mediates a hierarchical transcriptional cascade to regulate ripening and metabolic changes in tomato fruit.

The tomato ripening process contains complex changes, including ethylene signalling, cell wall softening and numerous metabolic changes. So far, much is still unknown about how tomato plants precisely coordinate fruit maturation and metabolic regulation. In this paper, the ERF family transcription factor SlERF.G3-Like in tomato was found to be involved in the regulation of ethylene synthesis, cell wall degradation and the flavonoid pathway. We show that the master ripening regulator SlRIN was found to directly bind to the promoter region of SlERF.G3-Like to activate its expression. In addition, we managed to increase the production of resveratrol derivatives from ~1.44 mg/g DW in E8:VvStSy line to ~2.43 mg/g DW by crossing p35S: SlERF.G3-Like with the E8:VvStSy line. Our data provide direct evidence that SlERF.G3-Like, a hierarchical transcriptional factor, can directly manipulate pathways in which tomatoes can coordinate fruit maturation and metabolic changes. We also attest that SlERF.G3-Like can be used as an effective tool for phenylpropanoid metabolic engineering.

The exocyst subunit CsExo70B promotes both fruit length and disease resistance via regulating receptor kinase abundance at plasma membrane in cucumber.

Plant defence against pathogens generally occurs at the expense of growth and yield. Uncoupling the inverse relationship between growth and defence is of great importance for crop breeding, while the underlying genes and regulatory mechanisms remain largely elusive. The exocytosis complex was shown to play an important role in the trafficking of receptor kinases (RKs) to the plasma membrane (PM). Here, we found a Cucumis sativus exocytosis subunit Exo70B (CsExo70B) regulates the abundance of both development and defence RKs at the PM to promote fruit elongation and disease resistance in cucumber. Knockout of CsExo70B resulted in shorter fruit and susceptibility to pathogens. Mechanistically, CsExo70B associates with the developmental RK CsERECTA, which promotes fruit longitudinal growth in cucumber, and contributes to its accumulation at the PM. On the other side, CsExo70B confers to the spectrum resistance to pathogens in cucumber via a similar regulatory module of defence RKs. Moreover, CsExo70B overexpression lines showed an increased fruit yield as well as disease resistance. Collectively, our work reveals a regulatory mechanism that CsExo70B promotes both fruit elongation and disease resistance by maintaining appropriate RK levels at the PM and thus provides a possible strategy for superior cucumber breeding with high yield and robust pathogen resistance.

Pillar[5]arene-Based Ion-Pair Recognition for Encapsulation of a Stilbazolium-Type Dye with Enhanced Photophysical Properties and Nonlinear Optical Activity.

Constructing organic composite materials through molecular recognition has emerged as an important theme in materials science. Here we report an ion-pair recognition system involving the use of a propoxylated pillar[5]arene (PrP5) to modulate the solid-state photophysical properties of dye trans-4'-(dimethylamino)-N-methyl-4-stilbazolium hexafluorophosphate (DMASP). Single crystal X-ray diffraction analysis reveals that the dye guest DMASP is encapsulated by PrP5 to form a 2:1 host-guest complex 2PrP5⸧DMASP in the crystalline state. The macrocyclic skeleton of PrP5 imposes restrictions on the intramolecular motions of the dye guest, leading to a significant enhancement of its fluorescence emission. Additionally, within the 2PrP5⸧DMASP complex crystal structure, DMASP molecules are found to display two possible opposite orientations in the one-dimensional channels formed by PrP5 molecules. This arrangement is believed to alter the overall solid-state packing structure of DMASP, thereby activating its nonlinear optical activity. This work not only reports a novel ion-pair molecular recognition system based on pillararenes but also provides valuable insights into the modulation of the crystalline state photophysical properties of organic dyes via cocrystal engineering.

Identification and validation of two major QTL for grain number per spike on chromosomes 2B and 2D in bread wheat (Triticum aestivum L.).

KEY MESSAGE: Major QTL for grain number per spike were identified on chromosomes 2B and 2D. Haplotypes and candidate genes of QGns.cib-2B.1 were analyzed. Grain number per spike (GNS) is one of the main components of wheat yield. Genetic dissection of their regulatory factors is essential to improve the yield potential. In present study, a recombinant inbred line population comprising 180 lines developed from the cross between a high GNS line W7268 and a cultivar Chuanyu12 was employed to identify quantitative trait loci (QTL) associated with GNS across six environments. Two major QTL, QGns.cib-2B.1 and QGns.cib-2D.1, were detected in at least four environments with the phenotypic variations of 12.99-27.07% and 8.50-13.79%, respectively. And significant interactions were observed between the two major QTL. In addition, QGns.cib-2B.1 is a QTL cluster for GNS, grain number per spikelet and fertile tiller number, and they were validated in different genetic backgrounds using Kompetitive Allele Specific PCR (KASP) markers. QGns.cib-2B.1 showed pleotropic effects on other yield-related traits including plant height, spike length, and spikelet number per spike, but did not significantly affect thousand grain weight which suggested that it might be potentially applicable in breeding program. Comparison analysis suggested that QGns.cib-2B.1 might be a novel QTL. Furthermore, haplotype analysis of QGns.cib-2B.1 indicated that it is a hot spot of artificial selection during wheat improvement. Based on the expression patterns, gene annotation, orthologs analysis and sequence variations, the candidate genes of QGns.cib-2B.1 were predicted. Collectively, the major QTL and KASP markers reported here provided a wealth of information for the genetic basis of GNS and grain yield improvement.

Design, synthesis, and biological evaluation of new bis-benzylisoquinoline-based analogues as potential neuromuscular blocking agents.

Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a's binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.

Multiflower-like ReS2/NiAl-LDH Heterojunction for Visible-Light-Driven Photocatalytic CO2 Reduction.

The development of high-efficiency heterojunction photocatalysts has been recognized as an effective approach to facilitate photocatalytic CO2 reduction. In this research, we successfully synthesized a novel multiflower-like ReS2/NiAl-LDH heterojunction through a hydrothermal method. Remarkably, when exposed to visible-light irradiation, 2-ReS2/NiAl-LDH demonstrated an exceptional CO production rate of 272.26 µmol·g-1·h-1, which was 4.0 and 10.8 times higher than that of pristine NiAl-LDH and ReS2. The intertwined structure of ReS2 and NiAl-LDH promoted the efficient transfer and separation of photogenerated carriers, thereby significantly enhancing the photocatalytic CO2 reduction capabilities of the ReS2/NiAl-LDH. Furthermore, the carrier transfer pathway for the 2-ReS2/NiAl-LDH heterojunction was elucidated, suggesting a type II scheme mechanism, as evidenced by photochemical deposition experiments. The findings of this study offer valuable insights and pave the way for future research in the design and construction of LDH-based and ReS2-based heterojunctions for efficient photocatalytic CO2 reduction.

Design and synthesis of matrine derivatives for anti myocardial ischemia-reperfusion injury by promoting angiogenesis.

Myocardial ischemia/reperfusion (MI/R) is a common cardiovascular disease that seriously affects the quality of life and prognosis of patients. In recent years, matrine has attracted widespread attention in the treatment of cardiovascular diseases. This study designed, synthesized, and characterized 20 new matrine derivatives and studied their protective effects on ischemia-reperfusion injury through in vivo and in vitro experiments. Based on cellular assays, most newly synthesized derivatives have a certain protective effect on Hypoxia/Reoxygenation (H/R) induced H9C2 cell damage, with compound 22 having the best activity and effectively reducing cell apoptosis and necrosis. In vitro experimental data shows that compound 22 can significantly reduce the infarct size of rat myocardium and improve cardiac function after MI/R injury. In summary, compound 22 is a new potential cardioprotective agent that can promote angiogenesis and enhance antioxidant activity by activating ADCY5, CREB3l4, and VEGFA, thereby protecting myocardial cell apoptosis and necrosis induced by MI/R.

The Brucella Effector BspI Suppresses Inflammation via Inhibition of IRE1 Kinase Activity during Brucella Infection.

Mammalian GTPase-activating proteins (GAPs) can inhibit innate immunity signaling in a spatiotemporal fashion; however, the role of bacterial GAPs in mediating innate immunity remains unknown. In this study, we show that BspI, a Brucella type IV secretion system (T4SS) effector protein, containing a GAP domain at the C terminus, negatively regulates proinflammatory responses and host protection to Brucella abotus infection in a mouse model. In macrophages, BspI inhibits the activation of inositol-requiring enzyme 1 (IRE1) kinase, but it does not inhibit activation of ATF6 and PERK. BspI suppresses induction of proinflammatory cytokines via inhibiting the activity of IRE1 kinase caused by VceC, a type IV secretion system effector protein that localizes to the endoplasmic reticulum. Ectopically expressed BspI interacts with IRE1 in HeLa cells. The inhibitory function of BspI depends on its GAP domain but not on interaction with small GTPase Ras-associated binding protein 1B (RAB1B). Collectively, these data support a model where BspI, in a GAP domain-dependent manner, inhibits activation of IRE1 to prevent proinflammatory cytokine responses.

Prediction of drug-induced hepatotoxicity based on histopathological whole slide images.

Liver is an important metabolic organ in human body and is sensitive to toxic chemicals or drugs. Adverse reactions caused by drug hepatotoxicity will damage the liver and hepatotoxicity is the leading cause of removal of approved drugs from the market. Therefore, it is of great significance to identify liver toxicity as early as possible in the drug development process. In this study, we developed a predictive model for drug hepatotoxicity based on histopathological whole slide images (WSI) which are the by-product of drug experiments and have received little attention. To better represent the WSIs, we constructed a graph representation for each WSI by dividing it into small patches, taking sampled patches as nodes and calculating the correlation coefficients between node features as the edges of the graph structure. Then a WSI-level graph convolutional network (GCN) was built to effectively extract the node information of the graph and predict the toxicity. In addition, we introduced a gated attention global context vector (gaGCV) to combine the global context to make node features to contain more comprehensive information. The results validated on rat liver in vivo data from the Open TG-GATES show that the use of WSI for the prediction of toxicity is feasible and effective.

A Dual-mode platform for the rapid detection of Escherichia coli O157:H7 based on CRISPR/Cas12a and RPA.

Escherichia coli O157:H7 (E. coli O157:H7) is a foodborne pathogenic microorganism that is commonly found in the environment and poses a significant threat to human health, public safety, and economic stability worldwide. Thus, early detection is essential for E. coli O157:H7 control. In recent years, a series of E. coli O157:H7 detection methods have been developed, but the sensitivity and portability of the methods still need improvement. Therefore, in this study, a rapid and efficient testing platform based on the CRISPR/Cas12a cleavage reaction was constructed. Through the integration of recombinant polymerase amplification and lateral flow chromatography, we established a dual-interpretation-mode detection platform based on CRISPR/Cas12a-derived fluorescence and lateral flow chromatography for the detection of E. coli O157:H7. For the fluorescence detection method, the limits of detection (LODs) of genomic DNA and E. coli O157:H7 were 1.8 fg/µL and 2.4 CFU/mL, respectively, within 40 min. Conversely, for the lateral flow detection method, LODs of 1.8 fg/µL and 2.4 × 102 CFU/mL were achieved for genomic DNA and E. coli O157:H7, respectively, within 45 min. This detection strategy offered higher sensitivity and lower equipment requirements than industry standards. In conclusion, the established platform showed excellent specificity and strong universality. Modifying the target gene and its primers can broaden the platform's applicability to detect various other foodborne pathogens.