An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome.

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.

Transcription factor ZmDof22 enhances drought tolerance by regulating stomatal movement and antioxidant enzymes activities in maize (Zea mays L.).

KEY MESSAGE: The Dof22 gene encoding a deoxyribonucleic acid binding with one finger in maize, which is associated with its drought tolerance. The identification of drought stress regulatory genes is essential for the genetic improvement of maize yield. Deoxyribonucleic acid binding with one finger (Dof), a plant-specific transcription factor family, is involved in signal transduction, morphogenesis, and environmental stress responses. In present study, by weighted correlation network analysis (WGCNA) and gene co-expression network analysis, 15 putative Dof genes were identified from maize that respond to drought and rewatering. A real-time fluorescence quantitative PCR showed that these 15 genes were strongly induced by drought and ABA treatment, and among them ZmDof22 was highly induced by drought and ABA treatment. Its expression level increased by nearly 200 times after drought stress and more than 50 times after ABA treatment. After the normal conditions were restored, the expression levels were nearly 100 times and 40 times of those before treatment, respectively. The Gal4-LexA/UAS system and transcriptional activation analysis indicate that ZmDof22 is a transcriptional activator regulating drought tolerance and recovery ability in maize. Further, overexpressed transgenic and mutant plants of ZmDof22 by CRISPR/Cas9, indicates that the ZmDof22, improves maize drought tolerance by promoting stomatal closure, reduces water loss, and enhances antioxidant enzyme activity by participating in the ABA pathways. Taken together, our findings laid a foundation for further functional studies of the ZmDof gene family and provided insights into the role of the ZmDof22 regulatory network in controlling drought tolerance and recovery ability of maize.

Emergence of colistin-resistant Stenotrophomonas maltophilia with high virulence in natural aquatic environments.

The presence of Stenotrophomonas maltophilia in aquatic environments poses great health risks to immunocompromised individuals because of its multidrug resistance and resultant high mortality. However, a significant gap exists in the isolation and understanding of colistin-resistant S. maltophilia in aquatic environments. In this study, nine colistin-resistant S. maltophilia strains isolated from natural lakes were explored, and their phylogenetic relationship, biofilm formation, virulence, and antibiotic resistance profiles and underlying genetic determinants were assessed. After genome analysis, besides known multi-locus sequence typing (MLST) of ST532, new assigned ST965 and ST966 which phylogenetically clustered into soil isolates were found firstly. All the isolates exhibited resistance to multiple antibiotics, including aminoglycosides, beta-lactams, tetracyclines, and even colistin, with the highest minimum inhibitory concentration (MIC) against colistin reaching 640 mg/L. Comparative genomic analysis revealed aph(3')-Iic, blaL1, tetT, phoP, mcr-3, arnA, pmrE, and efflux pump genes as the genetic determinants underlying this multidrug resistance. Notably, the biofilm-forming capacities of the newly discovered ST965 and ST966 isolates were significant stronger than those of the known ST532 isolates (p < 0.01), resulting in the death of over 50 % of the Galleria mellonella population within 1 day of injection. The ST965 isolates demonstrated the highest virulence against G. mellonella, followed by the ST966 isolates and ST532 isolates which was phylogenetically clustered with clinical isolates, indicating that the novel S. maltophilia strains of ST965 and ST966 may pose considerable health risks to humans. Our findings provide insights into colistin-resistant S. maltophilia in aquatic environments and raise concerns about the health risks posed by the newly assigned sequence types of colistin-resistant S. maltophilia with potential high virulence in natural aquatic environments.

Identification of the Maize PP2C Gene Family and Functional Studies on the Role of ZmPP2C15 in Drought Tolerance.

The protein phosphatase PP2C plays an important role in plant responses to stress. Therefore, the identification of maize PP2C genes that respond to drought stress is particularly important for the improvement and creation of new drought-resistant assortments of maize. In this study, we identified 102 ZmPP2C genes in maize at the genome-wide level. We analyzed the physicochemical properties of 102 ZmPP2Cs and constructed a phylogenetic tree with Arabidopsis. By analyzing the gene structure, conserved protein motifs, and synteny, the ZmPP2Cs were found to be strongly conserved during evolution. Sixteen core genes involved in drought stress and rewatering were screened using gene co-expression network mapping and expression profiling. The qRT-PCR results showed 16 genes were induced by abscisic acid (ABA), drought, and NaCl treatments. Notably, ZmPP2C15 exhibited a substantial expression difference. Through genetic transformation, we overexpressed ZmPP2C15 and generated the CRISPR/Cas9 knockout maize mutant zmpp2c15. Overexpressing ZmPP2C15 in Arabidopsis under drought stress enhanced growth and survival compared with WT plants. The leaves exhibited heightened superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT) activities, elevated proline (Pro) content, and reduced malondialdehyde (MDA) content. Conversely, zmpp2c15 mutant plants displayed severe leaf dryness, curling, and wilting under drought stress. Their leaf activities of SOD, POD, APX, and CAT were lower than those in B104, while MDA was higher. This suggests that ZmPP2C15 positively regulates drought tolerance in maize by affecting the antioxidant enzyme activity and osmoregulatory substance content. Subcellular localization revealed that ZmPP2C15 was localized in the nucleus and cytoplasm. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments demonstrated ZmPP2C15's interaction with ZmWIN1, ZmADT2, ZmsodC, Zmcab, and ZmLHC2. These findings establish a foundation for understanding maize PP2C gene functions, offering genetic resources and insights for molecular design breeding for drought tolerance.

Performance evaluation of quantitative material decomposition in slow kVp switching dual-energy CT.

BACKGROUND: Slow kVp switching technique is an important approach to realize dual-energy CT (DECT) imaging, but its performance has not been thoroughly investigated yet. OBJECTIVE: This study aims at comparing and evaluating the DECT imaging performance of different slow kVp switching protocols, and thus helps determining the optimal system settings. METHODS: To investigate the impact of energy separation, two different beam filtration schemes are compared: the stationary beam filtration and dynamic beam filtration. Moreover, uniform tube voltage modulation and weighted tube voltage modulation are compared along with various modulation frequencies. A model-based direct decomposition algorithm is employed to generate the water and iodine material bases. Both numerical and physical experiments are conducted to verify the slow kVp switching DECT imaging performance. RESULTS: Numerical and experimental results demonstrate that the material decomposition is less sensitive to beam filtration, voltage modulation type and modulation frequency. As a result, robust material-specific quantitative decomposition can be achieved in slow kVp switching DECT imaging. CONCLUSIONS: Quantitative DECT imaging can be implemented with slow kVp switching under a variety of system settings.

Developments of Fms-like Tyrosine Kinase 3 Inhibitors as Anticancer Agents for AML Treatment.

BACKGROUND: FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated gene in acute myeloid leukemia. As a receptor tyrosine kinase (RTK), FLT3 plays a role in the proliferation and differentiation of hematopoietic stem cells. As the most frequent molecular alteration in AML, FLT3 has drawn the attention of many researchers, and a lot of small molecule inhibitors targeting FLT3 have been intensively investigated as potential drugs for AML therapy. METHODS: In this paper, PubMed and SciFinder® were used as a tool; the publications about "FLT3 inhibitor" and "Acute myeloid leukemia" were surveyed from 2014 to the present with an exclusion of those published as patents. RESULTS: In this study, the structural characterization and biological activities of representative FLT3 inhibitors were summarized. The major challenges and future directions for further research are discussed. CONCLUSION: Recently, numerous FLT3 inhibitors have been discovered and employed in FLT3-mutated AML treatment. In order to overcome the drug resistance caused by FLT3 mutations, screening multitargets FLT3 inhibitors has become the main research direction. In addition, the emergence of irreversible FLT3 inhibitors also provides new ideas for discovering new FLT3 inhibitors.

Electrical Properties of Human Lung Nodules In Vitro From 100 Hz to 100 MHz.

OBJECTIVE: The incidence of pulmonary nodules has been increasing over the past 30 years. Different types of nodules are associated with varying degrees of malignancy, and they engender inconsistent treatment approaches. Therefore, correct distinction is essential for the optimal treatment and recovery of the patients. The commonly-used medical imaging methods have limitations in distinguishing lung nodules to date. A new approach to this problem may be provided by electrical properties of lung nodules. Nevertheless, difference identification is the basis of correct distinction. So, this paper aims to investigate the differences in electrical properties between various lung nodules. METHODS: At variance with existing studies, benign samples were included for analysis. A total of 252 specimens were collected, including 126 normal tissues, 15 benign nodules, 76 adenocarcinomas, and 35 squamous cell carcinomas. The dispersion properties of each tissue were measured over a frequency range of 100 Hz to 100 MHz. And the relaxation mechanism was analyzed by fitting the Cole-Cole plot. The corresponding equivalent circuit was estimated accordingly. RESULTS: Results validated the significant differences between malignant and normal tissue. Significant differences between benign and malignant lesions were observed in conductivity and relative permittivity. Adenocarcinomas and squamous cell carcinomas are significantly different in conductivity, first-order, second-order differences of conductivity, α-band Cole-Cole plot parameters and capacitance of equivalent circuit. The combination of the different features increased the tissue groups' differences measured by Euclidean distance up to 94.7%. CONCLUSION AND SIGNIFICANCE: In conclusion, the four tissue groups reveal dissimilarity in electrical properties. This characteristic potentially lends itself to future diagnosis of non-invasive lung cancer.

A key genetic factor governing arabinan utilization in the gut microbiome alleviates constipation.

Impaired gastrointestinal motility is associated with gut dysbiosis. Probiotics, such as Bifidobacteria, can improve this bowel disorder; however, efficacy is strain-dependent. We determine that a genetic factor, the abfA cluster governing arabinan utilization, in Bifidobacterium longum impacts treatment efficacy against functional constipation (FC). In mice with FC, B. longum, but not an abfA mutant, improved gastrointestinal transit time, an affect that was dependent upon dietary arabinan. abfA genes were identified in other commensal bacteria, whose effects in ameliorating murine FC were similarly abfA-dependent. In a double-blind, randomized, placebo-controlled clinical trial, supplementation with abfA-cluster-carrying B. longum, but not an abfA-deficient strain, enriched arabinan-utilization residents, increased beneficial metabolites, and improved FC symptoms. Across human cohorts, abfA-cluster abundance can predict FC, and transplantation of abfA cluster-enriched human microbiota to FC-induced germ-free mice improved gut motility. Collectively, these findings demonstrate a role for microbial abfA cluster in ameliorating FC, establishing principles for genomics-directed probiotic therapies.

A Note on Improving Variational Estimation for Multidimensional Item Response Theory.

Survey instruments and assessments are frequently used in many domains of social science. When the constructs that these assessments try to measure become multifaceted, multidimensional item response theory (MIRT) provides a unified framework and convenient statistical tool for item analysis, calibration, and scoring. However, the computational challenge of estimating MIRT models prohibits its wide use because many of the extant methods can hardly provide results in a realistic time frame when the number of dimensions, sample size, and test length are large. Instead, variational estimation methods, such as Gaussian variational expectation-maximization (GVEM) algorithm, have been recently proposed to solve the estimation challenge by providing a fast and accurate solution. However, results have shown that variational estimation methods may produce some bias on discrimination parameters during confirmatory model estimation, and this note proposes an importance-weighted version of GVEM (i.e., IW-GVEM) to correct for such bias under MIRT models. We also use the adaptive moment estimation method to update the learning rate for gradient descent automatically. Our simulations show that IW-GVEM can effectively correct bias with modest increase of computation time, compared with GVEM. The proposed method may also shed light on improving the variational estimation for other psychometrics models.

Cross-cohort single-nucleotide-variant profiling of gut microbiota suggests a novel gut-health assessment approach.

IMPORTANCE: Most studies focused much on the change in abundance and often failed to explain the microbiome variation related to disease conditions, Herein, we argue that microbial genetic changes can precede the ecological changes associated with the host physiological changes and, thus, would offer a new information layer from metagenomic data for predictive modeling of diseases. Interestingly, we preliminarily found a few genetic biomarkers on SCFA production can cover most chronic diseases involved in the meta-analysis. In the future, it is of both scientific and clinical significance to further explore the dynamic interactions between adaptive evolution and ecology of gut microbiota associated with host health status.

The discovery of water-soluble indazole derivatives as potent microtubule polymerization inhibitors.

Taking a previously discovered indazole derivative 1 as a lead, systematic structural modifications were performed with an indazole core at the 1- and 6-positions to improve its aqueous solubility. Among the designed indazole derivatives, 6-methylpyridin-3-yl indazole derivative 8l and 1H-indol-4-yl indazole derivative 8m exhibited high potency in the low nanomolar range against A549, Huh-7, and T24 cancer cells, including Taxol-resistant variant cells (A549/Tax). As a hydrochloride salt, 8l exhibited much improved aqueous solubility, and its log P value fell into a favorable range. In mechanistic studies, 8l impeded tubulin polymerization through interacting with the colchicine site, resulting in cell cycle arrest and cellular apoptosis. In addition, compared to lead compound 1, 8l reduced cell migration and led to more potent inhibition of tumor growth in vivo without apparent toxicity. In summary, indazole derivative 8l could work as a potential anticancer agent and deserves further investigation for cancer therapy.

Understanding the "individual drug reaction" from the perspective of the interaction between probiotics and lovastatin in vitro and in vivo.

BACKGROUND: The existence of the gut microbiota produces an "individual drug reaction." As members of the intestinal microbiota, probiotics, although they have prebiotic functions, may accelerate the degradation of drugs, thereby affecting drug efficacy. Lovastatin is one of the well-recognized lipid-lowering drugs. Its main action site is the liver. Therefore, if it is degraded in advance by gastrointestinal probiotics, its efficacy may be reduced. RESULTS: Here, we designed a two-stage experiment in vitro and in vivo to explore the degradation of lovastatin by probiotics. In vitro, the degradation of lovastatin by 83 strains of Lactiplantibacillus plantarum and the "star strain" Lacticaseibacillus paracasei strain Shirota was investigated by high-performance liquid chromatography (HPLC). The results showed that probiotics could degrade lovastatin to varying degrees. Subsequently, we selected Lactiplantibacillus plantarum A5 (16.87%) with the strongest ability to degrade lovastatin, Lactiplantibacillus plantarum C3 (4.61%) with the weakest ability to degrade lovastatin and Lacticaseibacillus paracasei strain Shirota (17.6%) as representative probiotics for in vivo experiments. In vivo, the therapeutic effect of lovastatin combined with probiotics on golden hamsters with mixed hyperlipidemia was evaluated by measuring blood indicators, intestinal microbiota metagenomic sequencing, and the liver transcriptome. The results showed that the intake of probiotics did not affect the efficacy of lovastatin and could slow the inflammatory reaction of the liver. CONCLUSIONS: The supplementation of probiotics produced beneficial metabolites in the intestine by promoting beneficial microbes. Intestinal metabolites affected the expression of the liver genes through the gut-liver axis, increased the relative content of the essential amino acids, and finally improved the liver inflammatory response of the host. This study aims to reveal the impact of probiotics on the human body from a unique perspective, suggesting the impact of taking probiotics while taking drugs. Video Abstract.

Genome-wide identification of NF-Y gene family in maize (Zea mays L.) and the positive role of ZmNF-YC12 in drought resistance and recovery ability.

Nuclear factor Y (NF-Y) genes play important roles in many biological processes, such as leaf growth, nitrogen nutrition, and drought resistance. However, the biological functions of these transcription factor family members have not been systematically analyzed in maize. In the present study, a total of 52 ZmNF-Y genes were identified and classified into three groups in the maize genome. An analysis of the evolutionary relationship, gene structure, and conserved motifs of these genes supports the evolutionary conservation of NF-Y family genes in maize. The tissue expression profiles based on RNA-seq data showed that all genes apart from ZmNF-Y16, ZmNF-YC15, and ZmNF-YC17 were expressed in different maize tissues. A weighted correlation network analysis was conducted and a gene co expression network method was used to analyze the transcriptome sequencing results; six core genes responding to drought and rewatering were identified. A real time fluorescence quantitative analysis showed that these six genes responded to high temperature, drought, high salt, and abscisic acid (ABA) treatments, and subsequent restoration to normal levels. ZmNF-YC12 was highly induced by drought and rewatering treatments. The ZmNF-YC12 protein was localized in the nucleus, and the Gal4-LexA/UAS system and a transactivation analysis demonstrated that ZmNF-YC12 in maize (Zea mays L.) is a transcriptional activator that regulates drought resistance and recovery ability. Silencing ZmNF-YC12 reduced net photosynthesis, chlorophyll content, antioxidant (superoxide dismutase, catalase, peroxidase and ascorbate peroxidase) system activation, and soluble protein and proline contents; it increased the malondialdehyde content, the relative water content, and the water loss rate, which weakened drought resistance and the recoverability of maize. These results provide insights into understanding the evolution of ZmNF-Y family genes in maize and their potential roles in genetic improvement. Our work provides a foundation for subsequent functional studies of the NF-Y gene family and provides deep insights into the role of the ZmNF-YC12 regulatory network in controlling drought resistance and the recoverability of maize.

Once-Weekly Basal Insulin Fc Demonstrated Similar Glycemic Control to Once-Daily Insulin Degludec in Insulin-Naive Patients With Type 2 Diabetes: A Phase 2 Randomized Control Trial.

OBJECTIVE: Basal insulin Fc (BIF) (insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed the safety and efficacy of BIF versus degludec in insulin-naive patients with type 2 diabetes (T2D) previously treated with oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS: During this randomized, parallel, open-label study, 278 insulin-naive patients with T2D were randomly assigned (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period. Both groups were titrated to fasting glucose of 80-100 mg/dL (4.4 to <5.6 mmol/L). The primary end point was HbA1c change from baseline to week 26 (noninferiority margin 0.4%). Secondary end points included fasting blood glucose (FBG), six-point glucose profiles, and rate of hypoglycemia. RESULTS: After 26 weeks of treatment, BIF demonstrated a noninferior HbA1c change from baseline versus degludec, with a treatment difference of 0.06% (90% CI -0.11, 0.24; P = 0.56). Both BIF and degludec treatment led to significant reductions in FBG from baseline. At week 26, the between-treatment difference for BIF versus degludec was 4.7 mg/dL (90% CI 0.1, 9.3; P = 0.09). The rate of level 2 hypoglycemia was low and not significantly different between treatment groups (BIF 0.22 events/patient/year, degludec 0.15 events/patient/year; P = 0.64); there was no severe hypoglycemia. The occurrence of treatment-emergent adverse events was also similar between BIF and degludec. CONCLUSIONS: Once-weekly BIF achieved excellent glycemic control similar to degludec, with no concerning hypoglycemia or other safety findings.

Modulation of Visual Responses and Ocular Dominance by Contralateral Inhibitory Activation in the Mouse Visual Cortex.

Both hemispheres connect with each other by excitatory callosal projections, and whether inhibitory interneurons, usually believed to have local innervation, engage in transcallosal activity modulation is unknown. Here, we used optogenetics in combination with cell-type-specific channelrhodopsin-2 expression to activate different inhibitory neuron subpopulations in the visual cortex and recorded the response of the entire visual cortex using intrinsic signal optical imaging. We found that optogenetic stimulation of inhibitory neurons reduced spontaneous activity (increase in the reflection of illumination) in the binocular area of the contralateral hemisphere, although these stimulations had different local effects ipsilaterally. The activation of contralateral interneurons differentially affected both eye responses to visual stimuli and, thus, changed ocular dominance. Optogenetic silencing of excitatory neurons affects the ipsilateral eye response and ocular dominance in the contralateral cortex to a lesser extent. Our results revealed a transcallosal effect of interneuron activation in the mouse visual cortex.

Learning Latent and Hierarchical Structures in Cognitive Diagnosis Models.

Cognitive Diagnosis Models (CDMs) are a special family of discrete latent variable models that are widely used in educational and psychological measurement. A key component of CDMs is the Q-matrix characterizing the dependence structure between the items and the latent attributes. Additionally, researchers also assume in many applications certain hierarchical structures among the latent attributes to characterize their dependence. In most CDM applications, the attribute-attribute hierarchical structures, the item-attribute Q-matrix, the item-level diagnostic models, as well as the number of latent attributes, need to be fully or partially pre-specified, which however may be subjective and misspecified as noted by many recent studies. This paper considers the problem of jointly learning these latent and hierarchical structures in CDMs from observed data with minimal model assumptions. Specifically, a penalized likelihood approach is proposed to select the number of attributes and estimate the latent and hierarchical structures simultaneously. An expectation-maximization (EM) algorithm is developed for efficient computation, and statistical consistency theory is also established under mild conditions. The good performance of the proposed method is illustrated by simulation studies and real data applications in educational assessment.

Tactile cues are important to environmental novelty during repeated open field tests.

The open field test (OFT) is a commonly used protocol to measure anxiety-like behaviors in rodents. Exploration in the central area of the open field and rearing frequency are often readouts of anxiety measurement. However, concerns about carry-over effects associated with repeated assessments limit its application, with the underlying mechanisms of this phenomenon still to be fully described. Here, we showed that repeated OFTs in the same mice led to reductions in the percentage of time spent in the central area and frequency of rearing. This effect reduced with an increase in the intervals between test. The decay caused by repeated OFTs was due to habituation, rather than frequent handling of the experimenter, since novel environments could prevent decay from repeated OFTs. Our results also indicated that tactile cues of the environment played important roles in the habituation of repeated OFTs. Furthermore, the decay of central area activity and rearing behavior during repeated OFTs would be blocked if the hippocampal CA1 was lesioned, suggesting that CA1 is a crucial region for habituation of the OFT in mice. Taken together, our study uncovers the important roles of tactile cues and hippocampal CA1 during repeated OFTs in mice.

Bridging Parametric and Nonparametric Methods in Cognitive Diagnosis.

A number of parametric and nonparametric methods for estimating cognitive diagnosis models (CDMs) have been developed and applied in a wide range of contexts. However, in the literature, a wide chasm exists between these two families of methods, and their relationship to each other is not well understood. In this paper, we propose a unified estimation framework to bridge the divide between parametric and nonparametric methods in cognitive diagnosis to better understand their relationship. We also develop iterative joint estimation algorithms and establish consistency properties within the proposed framework. Lastly, we present comprehensive simulation results to compare different methods and provide practical recommendations on the appropriate use of the proposed framework in various CDM contexts.

Corticotropin releasing factor neurons in the visual cortex mediate long-term changes in visual function induced by early adversity.

Early adversity can cause malfunction of the visual system in adulthood. Adult female but not male mice undergoing early chronic mild stress (ECMS) maintain ocular dominance (OD) plasticity after the critical period. How early stressful experiences have a long-term impact on it is largely unknown. Here, we observed a wide distribution of corticotropin-releasing factor (CRF)-positive neurons, which mainly colocalized with a subpopulation of GABAergic interneurons in the mouse primary visual cortex (V1). Optogenetic activation of CRF-positive neurons transfected with AAV-ChR2 evoked inhibitory currents in nearby pyramidal cells. ECMS induced a reduction in the expression of CRF mRNA in adult mouse V1. Chemogenetic activation of V1 CRF neurons impaired OD plasticity in adult ECMS females. We further showed that local administration of the corticotropin releasing factor receptor 1 (CRFR1) antagonist via an osmotic minipump into the visual cortex mimicked OD plasticity in adult ECMS females. Whole-cell recording in layer 2/3 pyramidal neurons revealed that the CRFR1 antagonist reduced the short-term depression (STD) of evoked inhibitory postsynaptic current (IPSC) in females but not in males. Likewise, CRF agonists have the opposite effect. In summary, our findings indicate that the local CRF-CRFR1 system within V1 may mediate the long-term and sex-dependent effect of early stress experiences on visual plasticity and provide a target for the prevention of visual deficits in adults with a history of early-life adversity.