Sex differences in aberrant functional connectivity of three core networks and subcortical networks in medication-free adolescent-onset major depressive disorder.

Major depressive disorder demonstrated sex differences in prevalence and symptoms, which were more pronounced during adolescence. Yet, research on sex-specific brain network characteristics in adolescent-onset major depressive disorder remains limited. This study investigated sex-specific and nonspecific alterations in resting-state functional connectivity of three core networks (frontoparietal network, salience network, and default mode network) and subcortical networks in adolescent-onset major depressive disorder, using seed-based resting-state functional connectivity in 50 medication-free patients with adolescent-onset major depressive disorder and 56 healthy controls. Irrespective of sex, compared with healthy controls, adolescent-onset major depressive disorder patients showed hypoconnectivity between bilateral hippocampus and right superior temporal gyrus (default mode network). More importantly, we further found that females with adolescent-onset major depressive disorder exhibited hypoconnectivity within the default mode network (medial prefrontal cortex), and between the subcortical regions (i.e. amygdala, striatum, and thalamus) with the default mode network (angular gyrus and posterior cingulate cortex) and the frontoparietal network (dorsal prefrontal cortex), while the opposite patterns of resting-state functional connectivity alterations were observed in males with adolescent-onset major depressive disorder, relative to their sex-matched healthy controls. Moreover, several sex-specific resting-state functional connectivity changes were correlated with age of onset, sleep disturbance, and anxiety in adolescent-onset major depressive disorder with different sex. These findings suggested that these sex-specific resting-state functional connectivity alterations may reflect the differences in brain development or processes related to early illness onset, underscoring the necessity for sex-tailored diagnostic and therapeutic approaches in adolescent-onset major depressive disorder.

Study on the mechanism of miR-7562 regulating ATG5 and ATG12 genes in Penaeus monodon under Vibrio harveyi infection.

MicroRNAs (miRNAs) play a fundamental role in the post-transcriptional regulation of genes and are pivotal in modulating immune responses in marine species, particularly during pathogen assaults. This study focused on the function of miR-7562 and its regulatory effects on autophagy against Vibrio harveyi infection in the black tiger shrimp (Penaeus monodon), an economically important aquatic species. We successfully cloned and characterized two essential autophagy-related genes (ATGs) from P. monodon, PmATG5 and PmATG12, and then identified the miRNAs potentially involved in co-regulating these genes, which were notably miR-7562, miR-8485, and miR-278. Subsequent bacterial challenge experiments and dual-luciferase reporter assays identified miR-7562 as the principal regulator of both genes, particularly by targeting the 3'UTR of each gene. By manipulating the in vivo levels of miR-7562 using mimics and antagomirs, we found significant differences in the expression of PmATG5 and PmATG12, which corresponded to alterations in autophagic activity. Notably, miR-7562 overexpression resulted in the downregulation of PmATG5 and PmATG12, leading to a subdued autophagic response. Conversely, miR-7562 knockdown elevated the expression levels of these genes, thereby enhancing autophagic activity. Our findings further revealed that during V. harveyi infection, miR-7562 continued to influence the autophagic pathway by specifically targeting the ATG5-ATG12 complex. This research not only sheds light on the miRNA-dependent mechanisms governing autophagic immunity in shrimp but also proposes miR-7562 as a promising target for therapeutic strategies intended to strengthen disease resistance within the crustacean aquaculture industry.

Effect of contrast agent on T2-weighted fat-suppressed imaging and diffusion-weighted imaging in the diagnosis of breast tumors.

Background: Although previous studies have shown that the injection of contrast agents can improve image quality, the specific impact of this on T2-weighted fat-suppressed (T2 FS) and diffusion-weighted imaging (DWI) sequences in the diagnosis of breast cancer remains incompletely understood. In particular, there is insufficient research on how contrast agents affect the signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and apparent diffusion coefficient (ADC) values within these sequences, and how these changes influence the diagnosis of benign and malignant breast tumors. Methods: Breast magnetic resonance images (MRI) were obtained from 178 consecutive patients on a 3T scanner. The SNR and CNR of lesions on T2 FS sequence were calculated before and after contrast agent injection and compared. Differences between pre- and post-contrast ADC in identifying different tumor types were compared using the Kruskal-Wallis H-test and the paired comparison test. The accuracy of ADC values between pre- and post-contrast in distinguishing benign and malignant breast masses was assessed using receiver operating characteristic (ROC) curves. Results: The SNR and CNR of T2 FS sequence increased after contrast injection, and especially for invasive cancer and benign tumor, the increase was significant. For DWI, there was a slight increase or decrease of ADC values after contrast injection, but the ADC values before and after contrast had a similar effect in identifying different types of tumors. In the ROC curve analysis for assessing benign and malignant breast tumors, the area under the curve (AUC) before and after contrast showed similar results. Conclusions: Contrast agent injection can improve the SNR and CNR of T2 FS sequence, thus providing higher quality images for the diagnosis of breast lesions. Furthermore, injection of contrast agent had little effect on the ability of ADC values to identify different types of lesions and both ADC values before and after the contrast agent were able to distinguish between benign and malignant tumors with almost the same accuracy.

Changes of GH-IGFs and its relationship with growth retardation in children with bronchial asthma.

OBJECTIVE: To explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. METHODS: 112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. RESULTS: GH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 µg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. CONCLUSION: GH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

Metabolic pathway-based subtyping reveals distinct microenvironmental states associated with diffuse large B-cell lymphoma outcomes.

Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. Assigning patients to different risk categories and cytogenetic abnormality and genetic mutation groups has been widely applied for prognostic stratification of DLBCL. Increasing evidence has demonstrated that dysregulated metabolic processes contribute to the initiation and progression of DLBCL. Metabolic competition within the tumor microenvironment is also known to influence immune cell metabolism. However, metabolism- and immune-related stratification has not been established. Here, 1660 genes involved in 84 metabolic pathways were selected and tested to establish metabolic clusters (MECs) of DLBCL. MECs established based on independent lymphoma datasets distinguished different survival outcomes. The CIBERSORT algorithm and EcoTyper were applied to quantify the relative abundance of immune cell types and identify variation in cell states for 13 lineages comprising the tumor micro environment among different MECs, respectively. Functional characterization showed that MECs were an indicator of the immune microenvironment and correlated with distinctive mutational characteristics and oncogenic signaling pathways. The novel immune-related MECs exhibited promising clinical prognostic value and potential for informing DLBCL treatment decisions.

Bilateral Simultaneous Basal Ganglia Hemorrhage: A Case Report.

BACKGROUND Simultaneous bilateral basal ganglia hemorrhage is an infrequent occurrence in medical literature. The etiology of bilateral basal ganglia intracerebral hemorrhage remains elusive, in contrast to that of unilateral basal ganglia hypertensive intracerebral hemorrhage, resulting in lack of consensus among scholars. Importantly, patients with uremia and cerebral hemorrhage, especially patients with large hematoma volumes, exhibit a markedly elevated mortality rate. Patients can benefit from implementation of positive and efficacious therapeutic approaches. CASE REPORT We present a clinical case involving a 42-year-old male patient who was admitted to the hospital in a comatose state. The initial head computed tomography scan revealed the presence of simultaneous basal ganglia hemorrhage; this phenomenon could potentially be attributed to the occurrence of cerebral hemorrhage induced by severe renal hypertension in individuals with uremia. The patient underwent emergency surgical intervention to evacuate the hematoma, followed by continuous blood purification treatment. Ultimately, these interventions have the potential to improve patient outcomes. CONCLUSIONS Incidence of bilateral basal ganglia hemorrhage is exceptionally rare and associated with an unfavorable prognosis, often resulting in mortality among individuals with severe underlying conditions or complications. The hematoma was successfully eliminated through the use of skull resection and neuroendoscopy techniques, resulting in favorable outcomes. The implementation of bedside continuous hemodialysis in patients with uremic cerebral hemorrhage can enhance therapeutic efficacy, thus warranting its recommendation for similar cases. Based on our observations, it is plausible that severe hypertension plays a contributory role in the development of simultaneous bilateral basal ganglia bleeding.

Epidemiological features and prognosis for primary gastrointestinal follicular lymphoma.

Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.

Asymmetric evolution of ISG15 homologs and the immune adaptation to LBUSV infection in spotted seabass (Lateolabrax maculatus).

The battle between host and viral is ubiquitous across all ecosystems. Despite this, research is scarce on the antiviral characteristics of fish, particularly in those that primarily rely on innate immune responses. This study, comprehensively explored the genetic and antiviral features of ISG15 in spotted seabass, focusing on its response to largemouth bass ulcerative syndrome virus (LBUSV). Through whole-genome BLAST and PCR cloning, two ISG15 homologs, namely LmISG15a and LmISG15b, were identified in spotted seabass, both encoding highly conserved proteins. However, a distinctive contrast emerged in their expression patterns, with LmISG15a exhibiting high expression in immune organs while LmISG15b remained largely silent across various organs. Regulatory elements analysis indicated an asymmetric evolution of the two ISG15s, with the minimal expression of LmISG15b may attribute to the loss of a necessary ISRE and an additional instability "ATTTA" motif. Association analysis demonstrated a significant correlation between LmISG15a expression and LBUSV infection. Subsequent antiviral activity detection revealed that LmISG15a interacted with LBUSV, inhibiting its replication by activating ISGylation and downstream pro-inflammatory mediators. In summary, this study unveils a distinct evolutionary strategy of fish antiviral gene ISG15 and delineates its kinetic characteristics in response to LBUSV infection.

Structural and functional abnormalities in first-episode drug-naïve pediatric idiopathic generalized epilepsy.

The aim of this study was to investigate brain structure and corresponding static and dynamic functional connectivity (sFC & dFC) abnormalities in untreated, first-episode pediatric idiopathic generalized epilepsy (IGE), with the goal of better understanding the underlying pathological mechanisms of IGE. Thirty-one children with IGE and 31 age-matched healthy controls (HC) were recruited. Structural magnetic resonance imaging (sMRI) data were acquired, and voxel-based morphometry (VBM) analysis were performed to reveal abnormal gray matter volume (GMV). Moreover, sFC and dFC analyses were conducted using the brain areas exhibiting abnormal GMV as seed regions to explore abnormal functional couplings. Compared to HC, the IGE group exhibited increased GMV in left middle cingulate cortex (MCC) and right parahippocampus (ParaHipp). In addition, the analyses of dFC and sFC with MCC and ParaHipp as seeds revealed more extensive functional connectivity (FC) changes in dFC. Notably, the structurally and functionally abnormal brain areas were primarily localized in the default mode network (DMN). However, our study did not find any significant associations between these altered neuroimaging measurements and clinical outcomes. This study uncovered microstructural changes as well as corresponding sFC and dFC changes in patients with new-onset, untreated pediatric IGE. The affected brain regions were primarily located within the DMN, highlighting the DMN's crucial role in the development of pediatric IGE.

Efficacy and influencing factors of CO2 laser, topical photodynamic therapy versus therapy combined with CO2 laser pretreatment for vaginal low-grade squamous intraepithelial lesions with high-risk HPV infection.

BACKGROUND: Vaginal intraepithelial neoplasia (VaIN) is a group of diseases of squamous epithelial dysplasia and carcinoma in situ occurring in the vagina, which is associated with high-risk human papillomavirus (HR-HPV) infection. OBJECTIVES: To evaluate the efficacy and safety of Carbon dioxide (CO2) laser, 5-aminolevulinic acid photodynamic therapy (PDT) and PDT combined with CO2 laser pretreatment for VaIN1 with HR-HPV infection, and analyze the factors affecting the clearance of HR-HPV. METHODS: Patients with HR-HPV infection and pathological diagnosis of VaIN1 and received laser or PDT or PDT combined with laser pretreatment were recruited. A total of 45 patients received one to three times CO2 laser (laser Group), 15 patients received three times PDT (PDT Group) and 15 patients received CO2 laser once and PDT three times (laser + PDT Group). HPV testing, cytology and colposcopy examinations at 3-6 months and 9-12 months after treatment were analyzed to assess the outcomes of the treatment. RESULTS: There was no significant difference in regression rate of VaIN1 among the laser Group, the PDT Group and the laser + PDT Group (3-6 month follow-up: 57.78% vs 73.3% vs 80 %, 9-12 month follow-up: 68.89% vs 80% vs 86.67 %, P>0.05). HR-HPV remission rates were also similar in the three groups (3-6 month follow-up: 26.67% vs 46.67% vs 46.67 %, 9-12 month follow-up: 40 % in all groups, P>0.05). Compared to HR-HPV negative group, patients in the HR-HPV positive group were older and had more pregnancies. Menopause and multiple vaginal lesions were more common in the HR-HPV positive group. Adverse reactions were mild in the PDT Group. The laser Group and the laser + PDT Group had more adverse effects, such as increased vaginal secretion, vaginal bleeding, scarring and local pain. CONCLUSION: For patients with VaIN1 at risk of progression, ALA-PDT presents itself as a viable choice for those who are well-informed and can consent to its costs and benefits. The addition of CO2 laser pretreatment may not increase the benefit of ALA-PDT treatment of VaIN1. Older age, menopause, more times of pregnancies, and multiple vaginal lesions might affect HR-HPV regression.

Intracranial solitary fibrous tumor in a 15-year-old girl: illustrative case.

BACKGROUND: Solitary fibrous tumor (SFT) is an infrequent spindle cell tumor derived from mesenchymal tissue, which can manifest in diverse anatomical locations, primarily in the pleural cavity and infrequently in the central nervous system. SFT is predominantly observed in individuals aged between 40 and 50 years old, with a slightly higher occurrence in males than in females. OBSERVATIONS: This case report describes a female, age 15, who had migraines for 2 months prior to the diagnosis of an intracranial tumor. Computed tomography and magnetic resonance imaging showed a mass located in the right parietooccipital region with surrounding edema and a compressed right lateral ventricle. Neurosurgery was utilized to successfully remove the mass, and single intracranial fibrous tumor (grade I) was identified by postoperative pathological analysis. During an 8-month follow-up period, the patient did not experience any recurrences. LESSONS: SFT is often misdiagnosed as meningioma because of their similar imaging characteristics. However, identifying the distinctive features of SFT on magnetic resonance imaging can distinguish it from meningioma and help to select appropriate treatment. The complete preoperative imaging data for this case indicated a highly vascularized tumor. Preoperative vascular embolization treatment reduced any difficulties during the subsequent tumor resection and minimized intraoperative bleeding.

Optimising cervical cancer screening during pregnancy: a study of liquid-based cytology and HPV DNA co-test.

This study assessed the efficacy of ThinPrep cytologic test and human papillomavirus (HPV) co-test in cervical cancer screening during pregnancy. A cohort of 8,712 pregnant women from Ren Ji Hospital participated in the study. Among them, 601 (6.90%) tested positive for high-risk HPV (HR-HPV) and 38 (0.44%) exhibited abnormal cytology results (ASCUS+). Following positive HR-HPV findings, 423 patients underwent colposcopy, and 114 individuals suspected of having high-grade squamous intraepithelial lesion and cervical cancer (HSIL+) underwent cervical biopsy. Histological examination revealed 60 cases of normal pathology (52.63%), 35 cases of low-grade squamous intraepithelial lesion (30.70%), 17 cases of HSIL (14.91%), and 2 cases of cervical cancer (1.75%). The incidence of HSIL+ in HPV 16/18 group was significantly higher than that in non-HPV16/18 group (10.53% vs. 6.14%, P < 0.05). Subsequent evaluation of the clinical performance of cytology alone, primary HPV screening, and co-testing for HSIL+ detection revealed that the HSIL+ detection rate was lowest with cytology alone. These findings suggest that HPV testing, either alone or combined with cytology, presents an efficient screening strategy for pregnant women, underscoring the potential for improved sensitivity in cervical cancer screening during pregnancy. The significantly higher incidence of HSIL+ in the HPV16/18 group emphasizes the importance of genotype-specific considerations.

Rhodiola rosea L. improved intestinal digestive enzyme activities, inflammatory response, barrier and microbiota dysbiosis in Lateolabrax maculatus juveniles fed with high-carbohydrate diets.

A 56-d feeding trial was conducted to evaluate the influences of Rhodiola rosea L. on digestive enzyme activities, intestinal barrier, inflammatory response, and microbiota dysbiosis in Lateolabrax maculatus juveniles (9.37 ± 0.03 g) fed with high-carbohydrate diets. Six diets were designed: a control diet (20% corn starch, Control), high-carbohydrate diet (30% corn starch, HC1), and four high-carbohydrate diets supplemented with Rhodiola rosea L. at 30, 60, 90 and 120 mg/kg (HC2, HC3, HC4 and HC5, respectively). Compared with the control group, the HC1 diet remarkably increased α-amylase, lipase, and chymotrypsin activities in the intestine (p < 0.05), as well as the mRNA levels of Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 (p < 0.05) and the relative abundance of Proteobacteria and Photobacterium in the intestine, which belong to the phylum and genus level, respectively. But the opposite trend was found in muscular thickness and villus lengths (p < 0.05), the mRNA levels of Occludin, ZO-1, and TGF-ß (p < 0.05), at the level of phylum and genus level in the HC1 group, and the relative abundance of Firmicutes, Bacteroidetes, and Bacillus in the intestine compared with the control group. Intestinal chymotrypsin activity was significantly higher in the HC3 group and intestinal muscular thickness and villus lengths were also significantly higher in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). In addition, Occludin mRNA expression in the intestine was significantly increased in the HC2, HC4, and HC5 groups compared to the HC1 group. ZO-1 and TGF-ß mRNA expression in the intestine were significantly increased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). At the phylum level, the relative abundance of Firmicutes and Bacteroidetes was higher in the intestine in the HC2, HC3, HC4, and HC5 groups than that in the HC1 group. On the contrary, intestinal lipase and chymotrypsin activities were significantly decreased in the HC2 group compared to the HC1 group, respectively (p < 0.05). The Claudin-15, NF-κB, TNF-α, IL-1ß, and IL-8 mRNA expression in the intestine were significantly decreased in the HC2, HC3, HC4, and HC5 groups compared to the HC1 group (p < 0.05). Besides, at the genus level, compared to the HC1 group, the relative abundance of Photobacterium in the intestine and the diversity of the intestinal microbiota in the HC2, HC3, HC4, and HC5 groups were all decreased. In conclusion, these results demonstrated that the addition of Rhodiola rosea L. in high-carbohydrate diets can improve intestinal digestive enzyme activities, inflammatory response and intestinal barrier-related gene expression, and microbiota dysbiosis in L. maculatus. The suitable supplemental level of Rhodiola rosea L. in high-carbohydrate diets of L. maculatus is 60 mg/kg.

Long-term outcomes with HLX01 (HanliKang®), a rituximab biosimilar, in previously untreated patients with diffuse large B-cell lymphoma: 5-year follow-up results of the phase 3 HLX01-NHL03 study.

HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2-76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9-87.5%) and 75.4% (95% CI: 68.9-82.6%)( HR: 0.75, 95% CI 0.47-1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4-84.6%) and 73.0% (95% CI: 66.3-80.3%) (HR: 0.84, 95% CI 0.54-1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

Upregulation of tumor suppressor PIAS3 by Honokiol promotes tumor cell apoptosis via selective inhibition of STAT3 tyrosine 705 phosphorylation.

The natural product Honokiol exhibits robust antitumor activity against a range of cancers, and it has also received approval to undergo phase I clinical trial testing. We confrmed that honokiol can promote the apoptotic death of tumor cells through cell experiments. Then siRNA constructs specific for PIAS3, PIAS3 overexpression plasmid and the mutation of the STAT3 Tyr705 residue were used to confirm the mechanism of Honokiol-induced apoptosis. Finally, we confrmed that honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation through the in vivo and in vitro experiments. Honokiol was ultimately found to reduce tumor cell viability by promoting apoptosis through a mechanism dependent on the ability of Honokiol to promote PIAS3 upregulation and the selective inhibition of p-STAT3 (Tyr705) without affecting p-STAT3 (Ser727) or p-STAT1 (Tyr701) levels. PIAS3 knockdown and overexpression in tumor cells altered STAT3 activation and associated DNA binding activity through the control of Tyr705 phosphorylation via PIAS3-STAT3 complex formation, ultimately shaping Honokiol-induced tumor cell apoptosis. Honokiol was also confirmed to significantly prolong the survival of mice bearing xenograft tumors in a PIAS3-dependent fashion. Together, these findings highlight a novel pathway through which Honokiol can promote PIAS3 upregulation, in turn suppressing STAT3 Tyr705 phosphorylation and promoting the apoptotic death of tumor cells.

Effect of polypropylene microplastics on virus resistance in spotted sea bass (Lateolabrax maculatus).

Microplastics (MPs) pollution is a hot issue of global concern. Polypropylene microplastics (PP-MPs) age quickly in the marine environment and break down into smaller particles because of their relatively low temperature resistance, poor ultraviolet resistance, and poor antioxidant capacity, making them one of the major pollutants in the ocean. We assessed whether long-term exposure to micron-sized PP-MPs influences fish susceptibility to viral diseases. We found that exposure to PP-MPs (1-6 µm and 10-30 µm) at concentrations of 500 and 5000 µg/L resulted in uptake into spleen and kidney tissues of Lateolabrax maculatus. Increased activation of melanomacrophage centers was visible in histopathological sections of spleen from fish exposed to PP-MPs, and greater deterioration was observed in the spleen of fish infected by largemouth bass ulcerative syndrome virus after PP-MPs exposure. Additionally, exposure to PP-MPs led to significant cytotoxicity and a negative impact on the antiviral ability of cells. PP-MPs exposure had inhibitory or toxic effects on the immune system in spotted sea bass, which accelerated virus replication in vivo and decreased the expression of the innate immune- and acquired immune related genes in spleen and kidney tissues, thus increasing fish susceptibility to viral diseases. These results indicate that the long-term presence of micron-sized PP-MPs might impact fish resistance to disease, thereby posing a far-reaching problem for marine organisms.

Type II interferons (IFN-γ and IFN-γrel) activate downstream genes through various potential receptor combinations to exert antiviral functions in spotted sea bass (Lateolabrax maculatus).

Type II interferons (IFNs) exert antiviral functions by binding to receptors and activating downstream signaling pathways. However, our understanding of the antiviral functions and the receptor complex model of type II IFNs in teleost fish remains limited. In this study, we determined the functions of type II IFNs (LmIFN-γ and LmIFN-γrel) in Lateolabrax maculatus and assessed their antiviral ability mediated by their combination with different cytokine receptor family B members (LmCRFB6, LmCRFB13, and LmCRFB17). After infection with largemouth bass ulcer syndrome virus (LBUSV), the expression levels of LmIFNs and LmCRFBs increased significantly in vitro and in vivo. Incubation or injection with LmIFNs-His activated the expressions of LmISG15, LmMx, and LmIRF1. LmIFN-γ and LmIFN-γrel both bound to the extracellular domains of the three CRFBs via Pull-down. Furthermore, LmIFN-γ combined with LmCRFB6, LmCRFB6+LmCRFB13, and LmCRFB6+LmCRFB13+LmCRFB17 and LmIFN-γrel combined with all combinations containing LmCRFB17 induced the transcription of downstream genes and reduced the number of LBUSV copies. Therefore, type II IFNs (LmIFN-γ and LmIFN-γrel) contribute to enhanced antiviral immunity in L. maculatus and that ligand-receptor combinations effectively suppress virus replication. These findings provide a reference for future studies of the signal transduction mechanism of type II IFNs in teleost fish.