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Social behavior is sexually dimorphic, which is regulated by gonadal hormones in the brain. Our recent study found that exposure to low doses of bisphenol-A (BPA) during adolescence, permanently alters social behavior in adult male mice, but the underlying mechanisms remain unclear. Using adolescent gonadectomy (GDX) male mice with testosterone propionate (TP, 0.5 mg/kg) supplement (TP-GDX), this study showed that BPA antagonized promoting effects of TP on social interaction, sexual behavior, and aggression in GDX mice. BPA eliminated the reversal effects of TP on GDX-induced decrease in the number of immunoreactive to arginine vasopressin (AVP-ir) neurons in the medial amygdala (MeA) and the levels of AVP receptor 1a (V1aR) in the MeA and the nucleus accumbens (NAc). In addition, BPA removed down-regulation in the levels of dopamine (DA) transporter (DAT) and DA receptor 1 (DR1) in the NAc of TP-GDX mice. BPA exposure reduced testosterone (T) levels in the brain and serum and the expression of androgen receptor (AR) protein in the amygdala and striatum of sham-operated and TP-GDX males. These results suggest that adolescent exposure to BPA inhibits regulation of androgen in AVP and DA systems of the brain regions associated with social behavior, and thus alters social behaviors of adult male mice.
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Grain size analysis is used to study grain size and distribution. It is a critical indicator in sedimentary simulation experiments (SSEs), which aids in understanding hydrodynamic conditions and identifying the features of sedimentary environments. Existing methods for grain size analysis based on images primarily focus on scenarios where grain edges are distinct or grain arrangements are regular. However, these methods are not suitable for images from SSEs. We proposed a deep learning model incorporating histogram layers for the analysis of SSE images with fuzzy grain edges and irregular arrangements. Firstly, ResNet18 was used to extract features from SSE images. These features were then input into the histogram layer to obtain local histogram features, which were concatenated to form comprehensive histogram features for the entire image. Finally, the histogram features were connected to a fully connected layer to estimate the grain size corresponding to the cumulative volume percentage. In addition, an applied workflow was developed. The results demonstrate that the proposed method achieved higher accuracy than the eight other models and was highly consistent with manual results in practice. The proposed method enhances the efficiency and accuracy of grain size analysis for images with irregular grain distribution and improves the quantification and automation of grain size analysis in SSEs. It can also be applied for grain size analysis in fields such as soil and geotechnical engineering.
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Whole-brain analysis of single-neuron morphology is crucial for unraveling the complex structure of the brain. However, large-scale neuron reconstruction from terabyte and even petabyte data of mammalian brains generated by state-of-the-art light microscopy is a daunting task. Here, we developed 'Gapr' (Gapr accelerates projectome reconstruction) that streamlines deep learning-based automatic reconstruction, 'automatic proofreading' that reduces human workloads at high-confidence sites, and high-throughput collaborative proofreading by crowd users through the Internet. Furthermore, Gapr offers a seamless user interface that ensures high proofreading speed per annotator, on-demand conversion for handling large datasets, flexible workflows tailored to diverse datasets and rigorous error tracking for quality control. Finally, we demonstrated Gapr's efficacy by reconstructing over 4,000 neurons in mouse brains, revealing the morphological diversity in cortical interneurons and hypothalamic neurons. Here, we present Gapr as a solution for large-scale single-neuron reconstruction projects.
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Background: Salvianolic acid B (SAB) is a major component of Salvia miltiorrhiza root (Danshen), widely used in East/Southeast Asia for centuries to treat cardiovascular diseases. Danshen depside salt, 85% of which is made up of SAB, is approved in China to treat chronic angina. Although clinical observations suggest that Danshen extracts inhibited arterial and venous thrombosis, the exact mechanism has not been adequately elucidated. Objective: To delineate the antithrombotic mechanisms of SAB. Methods: We applied platelet aggregation and coagulation assays, perfusion chambers, and intravital microscopy models. The inhibition kinetics and binding affinity of SAB to thrombin are measured by thrombin enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. We used molecular in silico docking models to predict the interactions of SAB with thrombin. Results: SAB dose-dependently inhibited platelet activation and aggregation induced by thrombin. SAB also reduced platelet aggregation induced by adenosine diphosphate and collagen. SAB attenuated blood coagulation by modifying fibrin network structures and significantly decreased thrombus formation in mouse cremaster arterioles and perfusion chambers. The direct SAB-thrombin interaction was confirmed by enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. Interestingly, SAB shares key structural similarities with the trisubstituted benzimidazole class of thrombin inhibitors, such as dabigatran. Molecular docking models predicted the binding of SAB to the thrombin active site. Conclusion: Our data established SAB as the first herb-derived direct thrombin catalytic site inhibitor, suppressing thrombosis through both thrombin-dependent and thrombin-independent pathways. Purified SAB may be a cost-effective agent for treating arterial and deep vein thrombosis.
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2D single-phase multiferroic materials with the coexistence of electric and spin polarization offer a tantalizing potential for high-density multilevel data storage. One of the current limitations for application is the scarcity of the materials, especially those combine ferromagnetism and ferroelectricity at high temperatures. Here, robust ferrimagnetism and ferroelectricity in 2D É-Fe2O3 samples with both single-crystalline and polycrystalline form are demonstrated. Interestingly, the polycrystalline nanosheets also exhibit easily switchable ferroelectric polarizations comparable to that of single crystals. The existence of grain boundary does not hinder the switching and retention of ferroelectric polarization. Furthermore, the É-Fe2O3 nanosheets show ferrimagnetic and ferroelectric Curie temperatures up to 800 K, which reaches record highs in 2D single-phase multiferroic materials. This work provides important progress in the exploration of 2D high-temperature single-phase multiferroics for potentially compact high-temperature information nanodevices.
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BACKGROUND & AIMS: Obesity has been linked to various detrimental health consequences. While there is established evidence of a negative correlation between seafood consumption and obesity in adults, the current research on the association between seafood intake in childhood/adolescence and the risk of obesity is lacking. Our aim was to evaluate the association between seafood intake in childhood/adolescence and the risk of obesity in a Chinese nationwide cohort. METHODS: We utilized data from the China Health and Nutrition Survey (CHNS) from the year of 1997 to 2015. Seafood consumption was evaluated through 3-day 24-hour recalls. In our study, overweight/obesity status was determined based on the Chinese Criteria of Overweight and Obesity in School-age Children and Adolescents (WS/T 586-2018), while abdominal obesity status was determined according to the Chinese Criteria of Waist Circumference Screening Threshold among Children and Adolescents (WS/T 611-2018). RESULTS: During an average follow-up of 7.9 years, 404 cases developed overweight/obesity among 2206 participants in the seafood-overweight/obesity analysis, while 381 cases developed abdominal obesity among 2256 participants in the seafood-abdominal-obesity analysis. The high-consumer group was associated with 35% lower risk of overweight/obesity risk and 26% lower risk of abdominal obesity after fully adjusting for sociodemographic and lifestyle factors, compared with the non-consumer group. Considering different cooking methods, boiled seafood consumption was associated with 43% lower risk of overweight/obesity and 23% lower risk of abdominal obesity in the fully adjusted model, while stir-fried seafood did not demonstrate a statistical significance. CONCLUSION: Higher intake of seafood in childhood/adolescents, particularly in a boiled way, was associated with lower obesity risk.
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Inquéritos Nutricionais , Alimentos Marinhos , Humanos , Criança , Feminino , Adolescente , Masculino , Alimentos Marinhos/estatística & dados numéricos , China/epidemiologia , Estudos de Coortes , Inquéritos Nutricionais/estatística & dados numéricos , Inquéritos Nutricionais/métodos , Fatores de Risco , Obesidade Infantil/epidemiologia , Dieta/estatística & dados numéricos , Dieta/métodos , Dieta/efeitos adversos , Obesidade Abdominal/epidemiologia , Sobrepeso/epidemiologiaRESUMO
Male animals often display higher levels of aggression than females. However, the neural circuitry mechanisms underlying this sexually dimorphic aggression remain elusive. Here, we identify a hypothalamic-amygdala circuit that mediates male-biased aggression in mice. Specifically, the ventrolateral part of the ventromedial hypothalamus (VMHvl), a sexually dimorphic region associated with eliciting male-biased aggression, projects densely to the posterior substantia innominata (pSI), an area that promotes similar levels of attack in both sexes of mice. Although the VMHvl innervates the pSI unidirectionally through both excitatory and inhibitory connections, it is the excitatory VMHvl-pSI projections that are strengthened in males to promote aggression, whereas the inhibitory connections that reduce aggressive behavior are strengthened in females. Consequently, the convergent hypothalamic input onto the pSI leads to heightened pSI activity in males, resulting in male-biased aggression. Our findings reveal a sexually distinct excitation-inhibition balance of a hypothalamic-amygdala circuit that underlies sexually dimorphic aggression.
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Sleep deprivation (SD) triggers mitochondrial dysfunction and neural inflammation, leading to cognitive impairment and mental issues. However, the mechanism involving mitochondrial dysfunction and neural inflammation still remains unclear. Here, we report that SD rats exhibited multiple behavioral disorders, brain oxidative stress, and robust brain mitochondrial DNA (mtDNA) oxidation. In particular, SD activated microglia and microglial mtDNA efflux to the cytosol and provoked brain pro-inflammatory cytokines. We observed that the mtDNA efflux and pro-inflammatory cytokines significantly reduced with the suppression of the mtDNA oxidation. With the treatment of a novel mitochondrial nutrient, hydroxytyrosol butyrate (HTHB), the SD-induced behavioral disorders were significantly ameliorated while mtDNA oxidation, mtDNA release, and NF-κB activation were remarkably alleviated in both the rat brain and the N9 microglial cell line. Together, these results indicate that microglial mtDNA oxidation and the resultant release induced by SD mediate neural inflammation and HTHB prevents mtDNA oxidation and efflux, providing a potential treatment for SD-induced mental issues.
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BACKGROUND: As research on diabetes continues to advance, more complex classifications of this disease have emerged, revealing the existence of special types of diabetes, and many of these patients are prone to misdiagnosis and underdiagnosis, leading to treatment delays and increased health care costs. The purpose of this study was to identify four causes of secondary diabetes. CASE SUMMARY: Secondary diabetes can be caused by various factors, some of which are often overlooked. These factors include genetic defects, autoimmune disorders, and diabetes induced by tumours. This paper describes four types of secondary diabetes caused by Williams-Beuren syndrome, Prader-Willi syndrome, pituitary adenoma, and IgG4-related diseases. These cases deviate significantly from the typical progression of the disease due to their low incidence and rarity, often leading to their neglect in clinical practice. In comparison to regular diabetes patients, the four individuals described here exhibited distinct characteristics. Standard hypoglycaemic treatments failed to effectively control the disease. Subsequently, a series of examinations and follow-up history confirmed the diagnosis and underlying cause of diabetes. Upon addressing the primary condition, such as excising a pituitary adenoma, providing glucocorticoid supplementation, and implementing symptomatic treatments, all patients experienced a considerable decrease in blood glucose levels, which were subsequently maintained within a stable range. Furthermore, other accompanying symptoms improved. CONCLUSION: Rare diseases causing secondary diabetes are often not considered in the diagnosis of diabetes. Therefore, it is crucial to conduct genetic tests, antibody detection and other appropriate diagnostic measures when necessary to facilitate early diagnosis and intervention through proactive and efficient management of the underlying condition, ultimately improving patient outcomes.
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The co-infection of Newcastle disease virus (NDV) and Mycoplasma gallisepticum (MG) has a detrimental effect on chicken production performance, exerts a deleterious impact on poultry production performance, resulting in substantial economic losses. However, the exact impact and underlying mechanisms remain ambiguous. In this study, co-infection models were established both in vivo and in vitro. Through these models, it was found that the co-infection facilitated the replication of MG and NDV, as well as MG induced pathogenesis. The administration of lentogenic NDV resulted in the suppression of the innate immune response in vivo. At cellular level, co-infection promoted MG induced apoptosis through caspase-dependent mitochondrial endogenous pathway and suppressed the inflammatory secretion. This research contributes novel insights in co-infection.
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Galinhas , Coinfecção , Infecções por Mycoplasma , Mycoplasma gallisepticum , Doença de Newcastle , Vírus da Doença de Newcastle , Doenças das Aves Domésticas , Mycoplasma gallisepticum/patogenicidade , Animais , Vírus da Doença de Newcastle/patogenicidade , Vírus da Doença de Newcastle/fisiologia , Coinfecção/microbiologia , Coinfecção/veterinária , Coinfecção/virologia , Infecções por Mycoplasma/veterinária , Infecções por Mycoplasma/microbiologia , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/virologia , Doença de Newcastle/virologia , Apoptose , Imunidade Inata , Replicação ViralRESUMO
In traditional von Neumann computing architecture, the efficiency of the system is often hindered by the data transmission bottleneck between the processor and memory. A prevalent approach to mitigate this limitation is the use of non-volatile memory for in-memory computing, with spin-orbit torque (SOT) magnetic random-access memory (MRAM) being a leading area of research. In this study, we numerically demonstrate that a precise combination of damping-like and field-like spin-orbit torques can facilitate precessional magnetization switching. This mechanism enables the binary memristivity of magnetic tunnel junctions (MTJs) through the modulation of the amplitude and width of input current pulses. Building on this foundation, we have developed a scheme for a reconfigurable spintronic logic gate capable of directly implementing Boolean functions such as AND, OR, and XOR. This work is anticipated to leverage the sub-nanosecond dynamics of SOT-MRAM cells, potentially catalyzing further experimental developments in spintronic devices for in-memory computing.
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Graphene-based warm uterus acupoint paste (GWUAP) is an emerging non-drug alternative therapy for the treatment of primary dysmenorrhea (PD), but the underlying mechanism is still unclear. SD female rats were randomly divided into control group, model group and treatment group to explore the mechanism of GWUAP in the treatment of PD. Combined with 16S rDNA and fecal metabolomics, the diversity of microbiota and metabolites in each group was comprehensively evaluated. In this study, GWUAP reduced the torsion score of PD model rats, improved the pathological morphology of uterine tissue, reduced the pathological damage score of uterine tissue, and reversed the expression levels of inflammatory factors, pain factors and sex hormones. The 16 S rDNA sequencing of fecal samples showed that the abundance of Lactobacillus in the intestinal flora of the model group decreased and the abundance of Romboutsia increased, while the abundance of Lactobacillus in the intestinal flora of the treatment group increased and the abundance of Romboutsia decreased, which improved the imbalance of flora diversity in PD rats. In addition, 32 metabolites related to therapeutic effects were identified by metabolomics of fecal samples. Moreover, there is a close correlation between fecal microbiota and metabolites. Therefore, the mechanism of GWUAP in the treatment of PD remains to be further studied.
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Pontos de Acupuntura , Dismenorreia , Metabolômica , Ratos Sprague-Dawley , Animais , Feminino , Dismenorreia/terapia , Dismenorreia/tratamento farmacológico , Ratos , Microbioma Gastrointestinal/efeitos dos fármacos , RNA Ribossômico 16S/genética , Fezes/microbiologia , DNA Ribossômico/genéticaRESUMO
Prostate cancer (PCa) is the second most prevalent malignancy among men worldwide. The aberrant activation of androgen receptor (AR) signaling has been recognized as a crucial oncogenic driver for PCa and AR antagonists are widely used in PCa therapy. To develop novel AR antagonist, a machine-learning MIEC-SVM model was established for the virtual screening and 51 candidates were selected and submitted for bioactivity evaluation. To our surprise, a new-scaffold AR antagonist C2 with comparable bioactivity with Enz was identified at the initial round of screening. C2 showed pronounced inhibition on the transcriptional function (IC50 = 0.63 µM) and nuclear translocation of AR and significant antiproliferative and antimetastatic activity on PCa cell line of LNCaP. In addition, C2 exhibited a stronger ability to block the cell cycle of LNCaP than Enz at lower dose and superior AR specificity. Our study highlights the success of MIEC-SVM in discovering AR antagonists, and compound C2 presents a promising new scaffold for the development of AR-targeted therapeutics.
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BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a premalignant biliary-type epithelial neoplasm with intraductal papillary or villous growth. Currently reported local palliative therapeutic modalities, including endoscopic nasobiliary drainage, stenting and biliary curettage, endoscopic biliary polypectomy, percutaneous biliary drainage, laser ablation, argon plasma coagulation, photodynamic therapy, and radiofrequency ablation to relieve mechanical obstruction are limited with weaknesses and disadvantages. We have applied percutaneous transhepatic cholangioscopy (PTCS)-assisted biliary polypectomy (PTCS-BP) technique for the management of IPNB including mucin-hypersecreting cast-like and polypoid type tumors since 2010. AIM: To assess the technical feasibility, efficacy, and safety of PTCS-BP for local palliative treatment of IPNB. METHODS: Patients with mucin-hypersecreting cast-like or polypoid type IPNB and receiving PTCS-BP between September 2010 and December 2019 were included. PTCS-BP was performed by using a half-moon type snare with a soft stainless-steel wire, and the tumor was snared and resected with electrocautery. The primary outcome was its feasibility, indicated by technical success. The secondary outcomes were efficacy, including therapeutic success, curative resection, and clinical success, and safety. RESULTS: Five patients (four with mucin-hypersecreting cast-like type and one with polypoid type IPNB) were included. Low- and high-grade intraepithelial neoplasia (HGIN) and recurrent IPNB with invasive carcinoma were observed in one, two, and two patients, respectively. Repeated cholangitis and/or obstructive jaundice were presented in all four patients with mucin-hypersecreting cast-like type IPNB. All five patients achieved technical success of PTCS-BP. Four patients (three with mucin-hypersecreting cast-like type and one with polypoid type IPNB) obtained therapeutic success; one with mucin-hypersecreting cast-like type tumors in the intrahepatic small bile duct and HGIN had residual tumors. All four patients with mucin-hypersecreting IPNB achieved clinical success. The patient with polypoid type IPNB achieved curative resection. There were no PTCS-BP-related serious adverse events. CONCLUSION: PTCS-BP appears to be feasible, efficacious, and safe for local palliative treatment of both mucin-hypersecreting cast-like and polypoid type IPNB.
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The mammary gland is a fundamental structure of the breast and plays an essential role in reproduction. Human mammary epithelial cells (HMECs), which are the origin cells of breast cancer and other breast-related inflammatory diseases, have garnered considerable attention. However, isolating and culturing primary HMECs in vitro for research purposes has been challenging due to their highly differentiated, keratinized nature and their short lifespan. Therefore, developing a simple and efficient method to isolate and culture HMECs is of great scientific value for the study of breast biology and breast-related diseases. In this study, we successfully isolated primary HMECs from small amounts of mammary tissue by digestion with a mixture of enzymes combined with an initial culture in 5% fetal bovine serum-DMEM containing the Rho-associated kinase (ROCK) inhibitor Y-27632, followed by culture expansion in serum-free keratinocyte medium. This approach selectively promotes the growth of epithelial cells, resulting in an optimized cell yield. The simplicity and convenience of this method make it suitable for both laboratory and clinical research, which should provide valuable insights into these important areas of study.
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Técnicas de Cultura de Células , Células Epiteliais , Glândulas Mamárias Humanas , Humanos , Células Epiteliais/citologia , Feminino , Glândulas Mamárias Humanas/citologia , Técnicas de Cultura de Células/métodos , Amidas/farmacologia , Piridinas/farmacologia , Técnicas Citológicas/métodos , Quinases Associadas a rho/antagonistas & inibidoresRESUMO
Brain-inspired neuromorphic computing has attracted widespread attention owing to its ability to perform parallel and energy-efficient computation. However, the synaptic weight of amorphous/polycrystalline oxide based memristor usually exhibits large nonlinear behavior with high asymmetry, which aggravates the complexity of peripheral circuit system. Controllable growth of conductive filaments is highly demanded for achieving the highly linear conductance modulation. However, the stochastic behavior of the filament growth in commonly used amorphous/polycrystalline oxide memristor makes it very challenging. Here, the epitaxially grown Hf0.5Zr0.5O2-based memristor with the linearity and symmetry approaching ideal case is reported. A layer of Cu nanoparticles is inserted into epitaxially grown Hf0.5Zr0.5O2 film to form the grain boundaries due to the breaking of the epitaxial growth. By combining with the local electric field enhancement, the growth of filament is confined in the grain boundaries due to the fact that the diffusion of oxygen vacancy in crystalline lattice is more difficult than that in the grain boundaries. Furthermore, the decimal operation and high-accuracy neural network are demonstrated by utilizing the highly linear and multi-level conductance modulation capacity. This method opens an avenue to control the filament growth for the application of resistance random access memory (RRAM) and neuromorphic computing.
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BACKGROUND: A wide range of connexins are situated between normal-normal cells, cancer-cancer cells, and cancer-normal cells. Abnormalities in connexin expression are typically accompanied by cancer development; however, no systematic studies have examined the role of Gap Junction Protein Beta 3 (GJB3) in the context of tumor progression and immunity, especially when considering a broad range of cancer types. METHODS: In this study, data on GJB3 expression were gathered from Genotype-Tissue Expression, Cancer Cell Line Encyclopedia, and The Cancer Genome Atlas databases. Then, we analyzed the relationship between GJB3 expression and tumor characteristics. In vitro experiments using colony formation, EdU, CCK8, transwell migration assays, immunohistochemistry and western blot were performed to investigate the function of GJB3 in tumor progression of various cell lines. A drug sensitivity analysis of GJB3 was performed using the Genomics of Drug Sensitivity in Cancer database. RESULT: Our findings demonstrate that GJB3 is widely expressed in various cancers and correlates significantly with disease stages, patient survival, immunotherapy response, and pharmaceutical guidance. Additionally, GJB3 plays a role in different cancer pathways, as well as in different immune and molecular subtypes of cancer. Co-expression of GJB3 with immune checkpoint genes was observed. Further experiments showed that knockdown of GJB3 inhibited the PI3K/AKT pathway and resulted in reduced proliferation, migration, and viability of different cancer cells. CONCLUSION: Overall, GJB3 shows potential as a molecular biomarker and therapeutic target for various cancers, particularly lung adenocarcinomas, mesothelioma, pancreatic adenocarcinoma. Thus, GJB3 may represent a new therapeutic target for a wide range of cancers.
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Biomarcadores Tumorais , Conexinas , Imunoterapia , Neoplasias , Humanos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Prognóstico , Conexinas/genética , Conexinas/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/genética , Movimento Celular/genéticaRESUMO
Primary Breast Angiosarcoma (PBA) is an exceptionally rare form of breast cancer, accounting for less than 0.05% of all breast cancers. It is characterized by a high level of malignancy, invasiveness, and has a prognosis that is typically poor. The lack of distinctive clinical features makes it prone to underdiagnosis and misdiagnosis. This study retrospectively examines a case utilizing multimodal ultrasound imaging techniques (including 2D ultrasound, contrast-enhanced ultrasound, and ultrasound elastography) for diagnosing PBA. Furthermore, the study reviews relevant literature to summarize the ultrasound characteristics of PBA, with the aim of improving understanding of this elusive condition.
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Neoplasias da Mama , Mama , Hemangiossarcoma , Imagem Multimodal , Ultrassonografia Mamária , Humanos , Hemangiossarcoma/diagnóstico por imagem , Feminino , Neoplasias da Mama/diagnóstico por imagem , Ultrassonografia Mamária/métodos , Imagem Multimodal/métodos , Mama/diagnóstico por imagem , Meios de Contraste , Pessoa de Meia-Idade , Técnicas de Imagem por Elasticidade/métodos , Diagnóstico DiferencialRESUMO
BACKGROUND: Currently, there is a scarcity of reliable biomarkers that can accurately forecast the outcome and prognosis of transarterial chemoembolization (TACE). In this study, we assessed the diagnostic efficacy of serum glutathione reductase (GR) as a biomarker for hepatocellular carcinoma (HCC) and its practicality in predicting TACE treatment response. METHODS: The baseline positive rate and level of serum GR were analyzed and compared between HCC group and control group. Serum GR levels were assessed at three specific time points in 181 patients with unresectable HCC who underwent TACE (HCC-TACE). The correlation between serum GR levels and clinical pathological factors, tumor reactivity, and prognosis was investigated. The modified Response Evaluation Criteria in Solid Tumors (mRECIST) was utilized for assessing the treatment response to TACE. A nomogram for predicting the response to TACE treatment efficacy was developed. RESULTS: Serum GR demonstrated superior diagnostic performance in HCC patients. The baseline levels of serum GR were associated with the patient's age, tumor size, BCLC staging, and tumor thrombi of the portal vein (TTPV) (p < 0.05). Elevated baseline levels of serum GR were also identified as independent prognostic factors for predicting lower overall survival (OS) and shorter time to radiological progression (TTP) (p < 0.001). Moreover, it is worth noting that non-responders group exhibited a substantial increase in median GR level in the fourth week following TACE treatment (p < 0.0001), whereas the median GR level of responders group did not display a significant augmentation (p > 0.05). Lastly, the changes in serum GRt1-t3 were negatively correlated with TTP (p < 0.001). The nomogram developed to predict the risk of mRECIST responsiveness in patients with HCC-TACE demonstrated excellent discriminatory ability. CONCLUSION: Serum GR can serve as a valuable biomarker for the diagnosis of HCC and for predicting the therapeutic efficacy and prognosis of TACE treatment.
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Biomarcadores Tumorais , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Glutationa Redutase , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Biomarcadores Tumorais/sangue , Idoso , Glutationa Redutase/sangue , Resultado do Tratamento , Adulto , NomogramasRESUMO
The orbitofrontal cortex (ORB), a region crucial for stimulus-reward association, decision-making, and flexible behaviors, extensively connects with other brain areas. However, brain-wide inputs to projection-defined ORB neurons and the distribution of inhibitory neurons postsynaptic to neurons in specific ORB subregions remain poorly characterized. Here we mapped the inputs of five types of projection-specific ORB neurons and ORB outputs to two types of inhibitory neurons. We found that different projection-defined ORB neurons received inputs from similar cortical and thalamic regions, albeit with quantitative variations, particularly in somatomotor areas and medial groups of the dorsal thalamus. By counting parvalbumin (PV) or somatostatin (SST) interneurons innervated by neurons in specific ORB subregions, we found a higher fraction of PV neurons in sensory cortices and a higher fraction of SST neurons in subcortical regions targeted by medial ORB neurons. These results provide insights into understanding and investigating the function of specific ORB neurons.