Epstein-Barr virus positive gastric cancer: the pathological basis of CT findings and radiomics models prediction.

PURPOSE: To analyze the clinicopathologic information and CT imaging features of Epstein-Barr virus (EBV)-positive gastric cancer (GC) and establish CT-based radiomics models to predict the EBV status of GC. METHODS: This retrospective study included 144 GC cases, including 48 EBV-positive cases. Pathological and immunohistochemical information was collected. CT enlarged LN and morphological characteristics were also assessed. Radiomics models were constructed to predict the EBV status, including decision tree (DT), logistic regression (LR), random forest (RF), and support vector machine (SVM). RESULTS: T stage, Lauren classification, histological differentiation, nerve invasion, VEGFR2, E-cadherin, PD-L1, and Ki67 differed significantly between the EBV-positive and -negative groups (p = 0.015, 0.030, 0.006, 0.022, 0.028, 0.030, < 0.001, and < 0.001, respectively). CT enlarged LN and large ulceration differed significantly between the two groups (p = 0.019 and 0.043, respectively). The number of patients in the training and validation cohorts was 100 (with 33 EBV-positive cases) and 44 (with 15 EBV-positive cases). In the training cohort, the radiomics models using DT, LR, RF, and SVM yielded areas under the curve (AUCs) of 0.905, 0.771, 0.836, and 0.886, respectively. In the validation cohort, the diagnostic efficacy of radiomics models using the four classifiers were 0.737, 0.722, 0.751, and 0.713, respectively. CONCLUSION: A significantly higher proportion of CT enlarged LN and a significantly lower proportion of large ulceration were found in EBV-positive GC. The prediction efficiency of radiomics models with different classifiers to predict EBV status in GC was good.

The oncogenic role and regulatory mechanism of ACAA2 in human ovarian cancer.

Acetyl-CoAacyltransferase2 (ACAA2) is a key enzyme in the fatty acid oxidation pathway that catalyzes the final step of mitochondrial ß oxidation, which plays an important role in fatty acid metabolism. The expression of ACAA2 is closely related to the occurrence and malignant progression of tumors. However, the function of ACAA2 in ovarian cancer is unclear. The expression level and prognostic value of ACAA2 were analyzed by databases. Gain and loss of function were carried out to explore the function of ACAA2 in ovarian cancer. RNA-seq and bioinformatics methods were applied to illustrate the regulatory mechanism of ACAA2. ACAA2 overexpression promoted the growth, proliferation, migration, and invasion of ovarian cancer, and ACAA2 knockdown inhibited the malignant progression of ovarian cancer as well as the ability of subcutaneous tumor formation in nude mice. At the same time, we found that OGT can induce glycosylation modification of ACAA2 and regulate the karyoplasmic distribution of ACAA2. OGT plays a vital role in ovarian cancer as a function of oncogenes. In addition, through RNA-seq sequencing, we found that ACAA2 regulates the expression of DIXDC1. ACAA2 regulated the malignant progression of ovarian cancer through the WNT/ß-Catenin signaling pathway probably. ACAA2 is an oncogene in ovarian cancer and has the potential to be a target for ovarian cancer therapy.

Application of covalent modality in proximity-induced drug pharmacology: Early development, current strategy, and feature directions.

With a growing number of covalent drugs securing FDA approval as successful therapies across various indications, particularly in the realm of cancer treatment, the covalent modulating strategy is undergoing a resurgence. The renewed interest in covalent bioactive compounds has captured significant attention from both the academic and biopharmaceutical industry sectors. Covalent chemistry presents several advantages over traditional noncovalent proximity-induced drugs, including heightened potency, reduced molecular size, and the ability to target "undruggable" entities. Within this perspective, we have compiled a comprehensive overview of current covalent modalities applied to proximity-induced molecules, delving into their advantages and drawbacks. Our aim is to stimulate more profound insights and ideas within the scientific community, guiding future research endeavors in this dynamic field.

Thermal-Rectified Gradient Porous Polymeric Film for Solar-Thermal Regulatory Cooling.

Solar-thermal regulation concerning thermal insulation and solar modulation is pivotal for cooling textiles and smart buildings. Nevertheless, a contradiction arises in balancing the demand to prevent external heat infiltration with the efficient dissipation of excess heat from enclosed spaces. Here, a concentration-gradient polymerization strategy is presented for fabricating a gradient porous polymeric film comprising interconnected polymeric microspheres. This method involves establishing an electric field-driven gradient distribution of charged crosslinkers in the precursor solution, followed by subsequent polymerization and freeze-drying processes. The resulting porous film exhibits a significant porosity gradient along its thickness, leading to exceptional unidirectional thermal insulation capabilities with a thermal rectification factor of 21%. The gradient porous film, with its thermal rectification properties, effectively reconciles the conflicting demands of diverse thermal conductivity for cooling unheated and spontaneously heated enclosed spaces. Consequently, the gradient porous film demonstrates remarkable enhancements in solar-thermal management, achieving temperature reductions of 3.0 and 4.1 °C for unheated and spontaneously heated enclosed spaces, respectively, compared to uniform porous films. The developed gradient-structured porous film thus holds promise for the development of thermal-rectified materials tailored to regulate solar-thermal conditions within enclosed environments.

International Normalized Ratio Predicts Recurrence and Bleeding in Patients With Acute Venous Thromboembolism Who Undergo Direct Oral Anticoagulants.

Prothrombin time/international normalized ratio (PT/INR) is related to both antithrombotic effect and risk of bleeding. Its role in the prediction of venous thromboembolism (VTE) recurrence and bleeding for patients with acute VTE who undergo direct oral anticoagulants (DOACs) treatment is unclear, despite previous studies revealed some association between them. The predictive efficiency of INR for VTE recurrence and bleeding were analyzed in a retrospective cohort with VTE patients who underwent DOACs treatment. Then its predictive efficiency for VTE recurrence and bleeding were validated in a prospective cohort with the acquired cutoffs range, and compared with anti-Xa level, DASH and VTE-BLEED scores. In the retrospective cohort (n = 1083), the sensitivity and specificity of INR for the prediction of VTE recurrence were 79.4% and 92.8%, respectively. The area under the curve (AUC) was 0.881 (0.803-0.960)(P = .025). The cutoff value of INR was 0.9. The sensitivity and specificity of INR for the prediction of bleeding were 85.7% and 77.9%, respectively. The AUC was 0.876 (0.786-0.967)(P < .001). The cutoff value of INR was 2.1. In the prospective cohort (n = 202), the calibration showed that there were 4 (50%) patients with VTE recurrence, 156 (97.5%) patients with non-recurrence and bleeding (non-R&B), and 20 (58.8%) patients with bleeding in the low (INR < 0.9)(n = 8), intermediate (0.9 ≤ INR ≤ 2.1)(n = 160), and high (INR > 2.1)(n = 34) groups, respectively. The baseline PT/INR value at the initiation of DOACs treatment is an independent predictor for VTE recurrence and bleeding in patients with acute VTE who undergo DOACs treatment.

Rice OseIF6.1 encodes a eukaryotic translation initiation factor and is essential for the development of grain and anther.

The eIF6 proteins are distributed extensively in eukaryotes and play diverse and essential roles. The bona fide eIF6 protein in Arabidopsis, At-eIF6;1, is essential for embryogenesis. However, the role of eIF6 proteins in rice growth and development remains elusive and requires further investigation. Here, we characterized the functions of OseIF6.1, which is homologous to At-eIF6;1. OseIF6.1 encodes an eukaryotic translation initiation factor with a conserved eIF6 domain. The knockdown of OseIF6.1 resulted in a decrease in grain length and pollen sterility, whereas the overexpression of OseIF6.1 displayed opposite phenotypes. Further studies revealed that OseIF6.1 regulates grain shape by influencing cell expansion and proliferation. In addition, OseIF6.1 interacts with OsNMD3, which is a nuclear export adaptor for the 60S ribosomal subunit. The knockdown of OsNMD3 in plants exhibited reduced fertility and seed setting. Therefore, our findings have significantly enriched the current understanding of the role of OseIF6.1 in rice growth and development.

Mulberry leaf polysaccharide improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora, enhancing immune regulation and antioxidant capacity.

Polysaccharides are generally considered to have immune enhancing functions, and mulberry leaf polysaccharide is the main active substance in mulberry leaves, while there are few studies on whether mulberry leaf polysaccharide (MLP) has an effect on immunosuppression and intestinal damage caused by cyclophosphamide (CTX), we investigated whether MLP has an ameliorative effect on intestinal damage caused by CTX. A total of 210 1-day-old Mahuang cocks were selected for this experiment. Were equally divided into six groups and used to evaluate the immune effect of MLP. Our results showed that MLP significantly enhanced the growth performance of chicks and significantly elevated the secretion of cytokines (IL-1ß, IL-10, IL-6, TNF-α, and IFN-γ), immunoglobulins and antioxidant enzymes in the serum of immunosuppressed chicks. It attenuated jejunal damage and elevated the expression of jejunal tight junction proteins Claudin1, Zo-1 and MUC2, which protected intestinal health. MLP activated TLR4-MyD88-NF-κB pathway and enhanced the expression of TLR4, MyD88 and NF-κB, which served to protect the intestine. 16S rDNA gene high-throughput sequencing showed that MLP increased species richness, restored CTX-induced gut microbiome imbalance, and enhanced the abundance of probiotic bacteria in the gut. MLP improves cyclophosphamide-induced growth inhibition and intestinal damage in chicks by modulating intestinal flora and enhancing immune regulation and antioxidant capacity. In conclusion, this study provides a scientific basis for MLP as an immune enhancer to regulate chick intestinal flora and protect chick intestinal mucosal damage.

Habitat Suitability and Determinants for Anatidae in Multi-Watershed Composite Wetlands in Anhui, China.

Habitat suitability analysis is essential in habitat and species conservation. Anatidae are known for their migratory behaviour, high population density, and wide distribution range. Understanding their habitat utilzation and influencing factors is crucial in targeted conservation and management. In this study, we collected Anatidae diversity data, including the number of species, through field surveys from October 2021 to March 2022 and thirty habitat variables through an online database in Anhui Province, China. By using MaxEnt, we simulated the habitat suitability of twenty-one Anatidae species, revealing potential distribution sites in Anhui Province. Generalized linear mixed models (GLMM) were employed to identify factors affecting the distribution of geese and ducks. The results showed that high-suitability habitats were predominantly located in the large lakes of the Yangtze River floodplain. The GLMM analysis showed significant correlations between Anatidae richness and altitude, distribution of farmland, and human footprint. In addition, ducks were more sensitive to the human interference factor than geese. In summary, the lakes in the Yangtze River floodplain emerged as the most important Anatidae habitats in Anhui Province due to their abundant wetland resources, flat terrain, and high distribution of farmlands. These findings provide a scientific basis for the development of relevant conservation strategies and measures, aiding in wildlife epidemic monitoring, prevention, and control.

Rational Design of a Novel Class of Human ClpP Agonists through a Ring-Opening Strategy with Enhanced Antileukemia Activity.

The activation of Homo sapiens Casein lysing protease P (HsClpP) by a chemical or genetic strategy has been proved to be a new potential therapy in acute myeloid leukemia (AML). However, limited efficacy has been achieved with classic agonist imipridone ONC201. Here, a novel class of HsClpP agonists is designed and synthesized using a ring-opening strategy based on the lead compound 1 reported in our previous study. Among these novel scaffold agonists, compound 7k exhibited remarkably enhanced proteolytic activity of HsClpP (EC50 = 0.79 ± 0.03 µM) and antitumor activity in vitro (IC50 = 0.038 ± 0.003 µM). Moreover, the intraperitoneal administration of compound 7k markedly suppressed tumor growth in Mv4-11 xenograft models, achieving a tumor growth inhibition rate of 88%. Concurrently, 7k displayed advantageous pharmacokinetic properties in vivo. This study underscores the promise of compound 7k as a significant HsClpP agonist and an antileukemia drug candidate, warranting further exploration for AML treatment.

Satellite NO2 Retrieval Complicated by Aerosol Composition over Global Urban Agglomerations: Seasonal Variations and Long-Term Trends (2001-2018).

Tropospheric nitrogen dioxide (NO2) poses a serious threat to the environmental quality and public health. Satellite NO2 observations have been continuously used to monitor NO2 variations and improve model performances. However, the accuracy of satellite NO2 retrieval depends on the knowledge of aerosol optical properties, in particular for urban agglomerations accompanied by significant changes in aerosol characteristics. In this study, we investigate the impacts of aerosol composition on tropospheric NO2 retrieval for an 18 year global data set from Global Ozone Monitoring Experiment (GOME)-series satellite sensors. With a focus on cloud-free scenes dominated by the presence of aerosols, individual aerosol composition affects the uncertainties of tropospheric NO2 columns through impacts on the aerosol loading amount, relative vertical distribution of aerosol and NO2, aerosol absorption properties, and surface albedo determination. Among aerosol compositions, secondary inorganic aerosol mostly dominates the NO2 uncertainty by up to 43.5% in urban agglomerations, while organic aerosols contribute significantly to the NO2 uncertainty by -8.9 to 37.3% during biomass burning seasons. The possible contrary influences from different aerosol species highlight the importance and complexity of aerosol correction on tropospheric NO2 retrieval and indicate the need for a full picture of aerosol properties. This is of particular importance for interpreting seasonal variations or long-term trends of tropospheric NO2 columns as well as for mitigating ozone and fine particulate matter pollution.

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury: a randomized controlled study.

JOURNAL/nrgr/04.03/01300535-202412000-00032/figure1/v/2024-04-08T165401Z/r/image-tiff For patients with chronic spinal cord injury, the conventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection, pressure sores, osteoporosis, and deep vein thrombosis. Surgery is rarely performed on spinal cord injury in the chronic phase, and few treatments have been proven effective in chronic spinal cord injury patients. Development of effective therapies for chronic spinal cord injury patients is needed. We conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal cord injury to compare intensive rehabilitation (weight-bearing walking training) alone with surgical intervention plus intensive rehabilitation. This clinical trial was registered at ClinicalTrials.gov (NCT02663310). The goal of surgical intervention was spinal cord detethering, restoration of cerebrospinal fluid flow, and elimination of residual spinal cord compression. We found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement, reduced spasticity, and more rapid bowel and bladder functional recovery than weight-bearing walking training alone. Overall, the surgical procedures and intensive rehabilitation were safe. American Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 injuries. Surgery combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

Hybrid Moiré Excitons and Trions in Twisted MoTe2-MoSe2 Heterobilayers.

We report experimental and theoretical studies of MoTe2-MoSe2 heterobilayers with rigid moiré superlattices controlled by the twist angle. Using an effective continuum model that combines resonant interlayer electron tunneling with stacking-dependent moiré potentials, we identify the nature of moiré excitons and the dependence of their energies, oscillator strengths, and Landé g-factors on the twist angle. Within the same framework, we interpret distinct signatures of bound complexes among electrons and moiré excitons in nearly collinear heterostacks. Our work provides a fundamental understanding of hybrid moiré excitons and trions in MoTe2-MoSe2 heterobilayers and establishes the material system as a prime candidate for optical studies of correlated phenomena in moiré lattices.

Fast Li Replenishment Channels-Assisted Recycling of Degraded Layered Cathodes with Enhanced Cycling Performance and Thermal Stability.

The direct recycling of cathode materials in lithium-ion batteries is important for environmental protection and resource conservation. The key regeneration processes are composition replenishment and atom rearrangement, both of which depend on the migration and diffusion of atoms. However, for the direct recycling of degraded LiNi0.5 Co0.2 Mn0.3 O2 (D-NCM523) cathode, the irreversible phase transitions that accumulate during the long-term cycles block the Li diffusion channels with a high diffusion energy barrier, making it difficult to fully repair the layered structure and resulting in rapid capacity decay. To address the challenge, fast Li replenishment channels are rebuilt to regulate the surface phase and effectively assist the regeneration process with a reduced energy barrier. This method reduces the amount of Li supplement by >75% and shortens the sintering time (only 2 h) to fully regenerate D-NCM523, compared to general direct recycling methods. The regenerated NCM523 (LCMB-NCM523) exhibits a satisfactory repaired specific capacity of 160 mAh g-1 and excellent cycling stability, retaining 78% of its capacity after 300 cycles. In addition, LCMB-NCM523 is recycled with improved thermal decomposition peak temperature and enables 200 cycles even at 60 °C, greatly improving safety. This work proposes a promising way for the large-scale direct regeneration of layered cathodes.

Determinants of consumer intention to adopt a self-service technology strategy for last-mile delivery in Guangzhou, China.

Self-service technology (SST) is a logistic innovation in e-commerce that enhances last-mile delivery efficiency in supply chain management. By combining Innovation Diffusion Theory with Resource Matching Theory, we proposed a comprehensive framework to explain the relationships between beliefs, attitude, and intention in Guanzhou, China. The findings revealed that attitude played a crucial role in influencing consumer intention to adopt SST and that attitude has direct and indirect effects. Additionally, consumer perceptions of compatibility, relative advantage, reliability, and complexity indirectly affected their adoption intention through attitude. These factors had positive and negative effects. The results highlighted the importance of attitudes as immediate predictors of intention, as consumer attitudes (favorable and unfavorable) were shaped by their perceptions. We conclude by recommending strategies to promote positive attitudes toward SST and enhance safety, efficiency, and the overall user experience.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer.

BACKGROUND: A growing number of clinical examples suggest that coronavirus disease 2019 (COVID-19) appears to have an impact on the treatment of patients with liver cancer compared to the normal population, and the prevalence of COVID-19 is significantly higher in patients with liver cancer. However, this mechanism of action has not been clarified. AIM: To investigate the disease relevance of COVID-19 in liver cancer. METHODS: Gene sets for COVID-19 (GSE180226) and liver cancer (GSE87630) were obtained from the Gene Expression Omnibus database. After identifying the common differentially expressed genes (DEGs) of COVID-19 and liver cancer, functional enrichment analysis, protein-protein interaction network construction and screening and analysis of hub genes were performed. Subsequently, the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed. RESULTS: Of 518 common DEGs were obtained by screening for functional analysis. Fifteen hub genes including aurora kinase B, cyclin B2, cell division cycle 20, cell division cycle associated 8, nucleolar and spindle associated protein 1, etc., were further identified from DEGs using the "cytoHubba" plugin. Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation, cell cycle and other functions, and they may serve as potential molecular markers for COVID-19 and liver cancer. Finally, we selected 10 of the hub genes for in vitro expression validation in liver cancer cells. CONCLUSION: Our study reveals a common pathogenesis of liver cancer and COVID-19. These common pathways and key genes may provide new ideas for further mechanistic studies.

Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug-resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis-related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy-sensitive cases, Ferrous ion (Fe2+ ) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2 O2 ) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR-resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion-mediated ferroptosis by TFRC. Upregulation of TFRC in ADR-resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.

Exploring the Landscape of Hydrogel Therapy for Spinal Cord Injury: A Bibliometric and Visual Analysis (1991-2023).

BACKGROUND: This study aimed to conduct a bibliometric analysis of the literature on hydrogel therapy for spinal cord injury to visualize the research status, identify hotspots, and explore the development trends in this field. METHODS: Web of science Core Collection database was searched for relevant studies published between January 1991 and December 2023. Data such as journal title, author information, institutional affiliation, country, citation, and keywords were extracted. Bibliometrix, CiteSpace, and VOSviewer were used to perform bibliometric analysis of the retrieved data. RESULTS: A total of 1099 articles pertaining to hydrogel therapy for spinal cord injury were retrieved, revealing an upward trajectory in both annual publication volume and cumulative publication volume. Biomaterials emerged as the journal with the highest number of publications and the most rapid cumulative publication growth, contributing 84 articles. Among authors, Shoichet MS stood out with the highest number of publications and citations, totaling 66 articles. The University of Toronto led in institutional contributions with 65 publications, while China dominated in country-specific publications, accounting for 374 articles. However, to foster significant academic achievements, it is imperative for diverse authors, institutions, and countries to enhance collaboration. Current research in this field concentrates on scaffold architecture, nerve growth factor, the fibrotic microenvironment, and guidance channels. Simultaneously, upcoming research directions prioritize 3D bioprinting, injectable hydrogel, inflammation, and nanoparticles within the realm of hydrogel therapy for spinal cord injuries. CONCLUSIONS: In summary, this study provided a comprehensive analysis of the current research status and frontiers of hydrogel therapy for spinal cord injury. The findings provide a foundation for future research and clinical translation efforts of hydrogel therapy in this field.

Room Temperature NH3 Selective Gas Sensors Based on Double-Shell Hierarchical SnO2@polyaniline Composites.

Morphology and structure play a crucial role in influencing the performance of gas sensors. Hollow structures, in particular, not only increase the specific surface area of the material but also enhance the collision frequency of gases within the shell, and have been studied in depth in the field of gas sensing. Taking SnO2 as an illustrative example, a dual-shell structure SnO2 (D-SnO2) was prepared. D-SnO2@Polyaniline (PANI) (DSPx, x represents D-SnO2 molar content) composites were synthesized via the in situ oxidative polymerization method, and simultaneously deposited onto a polyethylene terephthalate (PET) substrate to fabricate an electrode-free, flexible sensor. The impact of the SnO2 content on the sensing performance of the DSPx-based sensor for NH3 detection at room temperature was discussed. The results showed that the response of a 20 mol% D-SnO2@PANI (DSP20) sensor to 100 ppm NH3 at room temperature is 37.92, which is 5.1 times higher than that of a pristine PANI sensor. Moreover, the DSP20 sensor demonstrated a rapid response and recovery rate at the concentration of 10 ppm NH3, with response and recovery times of 182 s and 86 s.

Triphenyltin induced darker body coloration by disrupting melanocortin system and pteridine metabolic pathway in a reef fish, Amphiprion ocellaris.

Triphenyltin (TPT) is a typical persistent organic pollutant whose occurrence in coral reef ecosystems may threaten the survival of reef fishes. In this study, a brightly colored representative reef fish, Amphiprion ocellaris was used to explore the effects of TPT at environmental levels (1, 10, and 100 ng/L) on skin pigment synthesis. After the fish were exposed to TPT for 60 days, the skin became darker, owing to an increase in the relative area of black stripes, a decrease in orange color values while an increase in brown color values, and an increase in the number of melanocytes in the orange part of the skin tissues. To explore the mechanisms by which TPT induces darker body coloration, the enzymatic activity and gene expression levels of the members of melanocortin system that affect melanin synthesis were evaluated. Leptin levels and lepr expression were found to be increased after TPT exposure, which likely contributed to the increase found in pomc expression and α-melanocyte-stimulating hormone (α-MSH) levels. Then Tyr activity and mc1r, tyr, tyrp1, mitf, and dct were upregulated, ultimately increasing melanin levels. Importantly, RT-qPCR results were consistent with the transcriptome analysis of trends in lepr and pomc expression. Because the orange color values decreased, pterin levels and the pteridine metabolic pathway were also evaluated. The results showed that TPT induced BH4 levels and spr, xdh, and gch1 expression associated with pteridine synthesis decreased, ultimately decreasing the colored pterin content (sepiapterin). We conclude that TPT exposure interferes with the melanocortin system and pteridine metabolic pathway to increase melanin and decrease colored pterin levels, leading to darker body coloration in A. ocellaris. Given the importance of body coloration for the survival and reproduction of reef fishes, studies on the effects of pollutants (others alongside TPT) on body coloration are of high priority.

Oxidized DJ-1 activates the p-IKK/NF-κB/Beclin1 pathway by binding PTEN to induce autophagy and exacerbate myocardial ischemia-reperfusion injury.

Patients with myocardial infarction have a much worse prognosis when they have myocardial ischemia-reperfusion (I/R) injury. Further research into the molecular basis of myocardial I/R injury is therefore urgently needed, as well as the identification of novel therapeutic targets and linkages to interventions. Three cysteine residues are present in DJ-1 at amino acids 46, 53, and 106 sites, with the cysteine at position 106 being the most oxidation-prone. This study sought to understand how oxidized DJ-1(C106) contributes to myocardial I/R damage. Rats' left anterior descending branches were tied off to establish a myocardial I/R model in vivo. A myocardial I/R model in vitro was established via anoxia/reoxygenation (A/R) of H9c2 cells. The results showed that autophagy increased after I/R, accompanied by the increased expression of oxidized DJ-1 (ox-DJ-1). In contrast, after pretreatment with NAC (N-acetylcysteine, a ROS scavenger) or Comp-23 (Compound-23, a specific antioxidant binding to the C106 site of DJ-1), the levels of ox-DJ-1, autophagy and LDH release decreased, and cell survival rate increased. Furthermore, the inhibition of interaction between ox-DJ-1 and PTEN could increase PTEN phosphatase activity, inhibit the p-IKK/NF-κB/Beclin1 pathway, reduce injurious autophagy, and alleviate A/R injury. However, BA (Betulinic acid, a NF-κB agonist) was able to reverse the protective effects produced by Comp-23 pretreatment. In conclusion, ox-DJ-1 could activate detrimental autophagy through the PTEN/p-IKK/NF-κB/Beclin1 pathway and exacerbate myocardial I/R injury.