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While certain members of ubiquitin-coupled enzymes (E2s) have garnered attention as potential therapeutic targets across diverse diseases, research progress on Ubiquitin-Conjugating Enzyme 5 (UBC5)—a pivotal member of the E2s family involved in crucial cellular processes such as apoptosis, DNA repair, and signal transduction—has been relatively sluggish. Previous findings suggest that UBC5 plays a vital role in the ubiquitination of various target proteins implicated in diseases and homeostasis, particularly in various cancer types. This review comprehensively introduces the structure and biological functions of UBC5, with a specific focus on its contributions to the onset and advancement of diverse diseases. It suggests that targeting UBC5 holds promise as a therapeutic approach for disease therapy. Recent discoveries highlighting the high homology between UBC5, UBC1, and UBC4 have provided insight into the mechanism of UBC5 in protein degradation and the regulation of cellular functions. As our comprehension of the structural distinctions among UBC5 and its homologues, namely UBC1 and UBC4, advances, our understanding of UBC5's functional significance also expands. • UBC5, a ubiquitin-conjugating enzymes (E2s), affects disease progression, homeostasis, and various cancers. • This review outlines UBC5's structure, functions, and its role in disease onset and progression. • UBC5 is an appealing target for multiple disease therapeutic intervention. [ABSTRACT FROM AUTHOR]

[Display omitted] Although certain members of the Ubiquitin-specific peptidases (USPs) have been recognized as promising therapeutic targets for various diseases, research progress regarding USP21 has been relatively sluggish in its early stages. USP21 is a crucial member of the USPs subfamily, involved in diverse cellular processes such as apoptosis, DNA repair, and signal transduction. Research findings from the past decade demonstrate that USP21 mediates the deubiquitination of multiple well-known target proteins associated with critical cellular processes relevant to both disease and homeostasis, particularly in various cancers. This review comprehensively summarizes the structure and biological functions of USP21 with an emphasis on its role in tumorigenesis, and elucidates the advances on the discovery of tens of small-molecule inhibitors targeting USP21, which suggests that targeting USP21 may represent a potential strategy for cancer therapy. [ABSTRACT FROM AUTHOR]

• We characterized two CXCR4 genes from Japanese sea bass, Lateolabrax japonica. • CXCR4 transcripts were altered in Japanese sea bass upon Vibrio harveyi infection. • Knockdown of CXCR4a inhibited the expression of IgM in LPS stimulated B cells. • Knockdown of CXCR4a decreased the level of reactive oxygen species in B cells. CXC chemokine receptor 4 (CXCR4), a member of the G-protein-coupled receptor family, plays an important role in host immune responses. Within the teleost lineage, there are two paralogs of CXCR4; however, the role of CXCR4 in teleost B cells is poorly understood. In this study, we determined the cDNA sequences of the two CXCR4 paralogs from the Japanese sea bass (Lateolabrax japonica ; LjCXCR4a and LjCXCR4b). Sequence and phylogenetic tree analyses revealed that LjCXCR4a and LjCXCR4b are most closely related to CXCR4a and CXCR4b, respectively, in the large yellow croaker (Larimichthys crocea). CXCR4 transcripts were mainly expressed in the gills, and their expression in different tissues was altered upon infection with Vibrio harveyi. LjCXCR4a and LjCXCR4b protein levels were upregulated in infected B cells. Knockdown of LjCXCR4a and LjCXCR4b in B cells by RNA interference, the phagocytic activity of B cells was not affected. Furthermore, knockdown of LjCXCR4a, not of LjCXCR4b, was observed to inhibit LjIgM expression in lipopolysaccharide-stimulated B cells. In addition, knockdown of LjCXCR4a, not of LjCXCR4b, was found to reduce reactive oxygen species levels in B cells. Our results indicate that LjCXCR4a and LjCXCR4b modulate the immune response of Japanese sea bass B cells against bacterial infection, albeit via different pathways. [ABSTRACT FROM AUTHOR]

Large underground caverns are characterized by high geostress, high sidewalls and complex geological conditions, which make the rock masses suffer a series of failures in the process of excavation. The excavation of the large underground powerhouse of the Baihetan Hydropower Station in China is based on the drilling and blasting method with small steps and weak-vibration blasting. To thoroughly understand the mechanism of blasting excavation on the surrounding rock, in situ microseismic (MS) monitoring system was established to analyze the blast-induced microseismicity of the large underground powerhouse of the Baihetan Hydropower Station. The waveform characteristics of blasting events and rock fracturing events are distinguished first. Then, the spatial distribution of density contours of MS events and rock mass seismic deformation induced by blasting excavation are obtained. The results show that the blast-induced risk areas are mainly concentrated in the downstream sidewall of the underground powerhouse. MS monitoring in real time during the excavation process can provide data reference for the dynamic optimization of on-site construction schemes. [ABSTRACT FROM AUTHOR]

Urocortin (UCN) is a hormone in the hypothalamic–pituitary–adrenal axis that is expressed in various immune cells. However, the function of teleost UCN in the immune system remains unclear. In this study, we cloned the cDNA sequence of UCN from ayu Plecoglossus altivelis (PaUCN). Sequence and phylogenetic tree analyses showed that PaUCN clustered within the fish UCN 1 group and was most related to the rainbow trout (Oncorhynchus mykiss) UCN. PaUCN was expressed in all tested tissues and its expression increased in the liver, spleen, head kidney, and gill upon Vibrio anguillarum infection. Mature PaUCN protein (mPaUCN) treatment affected the phagocytosis and bacterial killing of monocytes/macrophages (MO/MФ). mPaUCN reduced pro-inflammatory cytokine expression in MO/MФ, which was partially mediated via interaction with ayu interleukin-6. mPaUCN reduced bacterial load and increased the survival of V. anguillarum -infected ayu. Overall, UCN as an endocrine factor regulates the immune response of ayu after infection by activating MO/MФ, thus contributing to enhance fish survival. • We characterized a UCN gene from ayu, Plecoglossus altivelis. • UCN improved the phagocytosis and of bacterial killing of monocytes/macrophages. • UCN interacted with IL-6 to inhibit inflammation in monocytes/macrophages. [ABSTRACT FROM AUTHOR]

• We characterized two PU.1 genes from ayu, Plecoglossus altivelis. • The PU.1 transcripts were altered in ayu upon Vibrio anguillarum infection. • PaPU.1a knockdown decreased inflammatory cytokine expression. • PaPU.1b knockdown attenuated MO/MФ bacterial killing capability. Transcription factor PU.1 is a regulator of macrophage function, however, the specific function of PU.1 in teleost monocytes/macrophages (MO/MФ) remains unknown. We determined the cDNA sequence of two PU.1 genes from ayu (Plecoglossus altivelis ; PaPU.1a and PaPU.1b). Sequence comparisons showed that PaPU.1 were most closely related to the PU.1 of rainbow smelt (Osmerus mordax). The PU.1 transcripts were mainly expressed in the spleen, and their expression was altered in various tissues upon infection with Vibrio anguillarum. PaPU.1a and PaPU.1b proteins were upregulated in MO/MФ, after infection. RNA interference was employed to knockdown PaPU.1a and PaPU.1b to investigate their function in MO/MФ. The expression of inflammatory cytokines was regulated by PaPU.1a, but not PaPU.1b, in ayu MO/MФ upon V. anguillarum infection. Both PaPU.1a and PaPU.1b knockdown lowered the phagocytic activity of MO/MФ. Furthermore, PaPU.1b knockdown attenuated MO/MФ bacterial killing capability. Our results indicate that two PaPU.1 genes differentially modulate the immune response in ayu MO/MФ against bacterial infection. [ABSTRACT FROM AUTHOR]

Histone methylation is a key posttranslational modification of chromatin, and its dysregulation affects a wide array of nuclear activities including the maintenance of genome integrity, transcriptional regulation, and epigenetic inheritance. Variations in the pattern of histone methylation influence both physiological and pathological events. Lysine-specific demethylase 5A (KDM5A, also known as JARID1A or RBP2) is a KDM5 Jumonji histone demethylase subfamily member that erases di- and tri-methyl groups from lysine 4 of histone H3. Emerging studies indicate that KDM5A is responsible for driving multiple human diseases, particularly cancers. In this review, we summarize the roles of KDM5A in human cancers, survey the field of KDM5A inhibitors including their anticancer activity and modes of action, and the current challenges and potential opportunities of this field. [ABSTRACT FROM AUTHOR]

Adrenergic receptors (ARs) are members of the G-protein-coupled receptor superfamily that can be categorized into αARs and βARs. The specific function of ARs in teleost monocytes/macrophages (MO/MФ) remains unknown. We determined the cDNA sequence of ARs from ayu (Plecoglossus altivelis ; PaαAR and PaβAR). Sequence comparisons showed that PaαAR was most closely related to the αAR of the Japanese flounder and Nile tilapia, while PaβAR was most closely related to the βAR of Atlantic salmon. The AR transcripts were mainly expressed in the spleen, and their expression was altered in various tissues upon infection with Vibrio anguillarum. PaαAR and PaβAR proteins were upregulated in MO/MФ after infection, and PaβAR knockdown resulted in a pro-inflammatory status in ayu MO/MФ upon V. anguillarum infection and lowered the phagocytic activity of MO/MФ. Our results indicate that PaβAR plays the role of an anti-inflammatory mediator in the immune response of ayu against bacterial infection. • We characterized ARs gene from ayu, Plecoglossus altivelis. • ARs transcripts were altered in ayu upon Vibrio anguillarum infection. • PaβAR activation promoted the phagocytosis of ayu moncytes/macrophages. • PaβAR acts as an anti-inflammatory mediator in Vibrio anguillarum infected ayu MO/MФ. [ABSTRACT FROM AUTHOR]

Micropterus salmoides rhabdovirus (MSRV) is one of the main pathogens of largemouth bass, leading to serious economic losses. The G protein, as the only envelope protein present on the surface of MSRV virion, contains immune-related antigenic determinants, thereby becoming the primary target for the design of MSRV vaccines. Here, we displayed the G protein on the surface of yeast cells (named EBY100/pYD1-G) and conducted a preliminary assessment of the protective efficacy of the recombinant yeast vaccine. Upon oral vaccination, a robust immune response was observed in systemic and mucosal tissue. Remarkably, following the MSRV challenge, the relative percent survival of EBY100/pYD1-G treated largemouth bass significantly increased to 66.7 %. In addition, oral administration inhibited viral replication and alleviated the pathological symptoms of MSRV-infected largemouth bass. These results suggest that EBY100/pYD1-G could be used as a potential oral vaccine against MSRV infection. • An oral vaccine was conducted by displaying MSRV G protein in the surface of Saccharomyces cerevisiae. • The oral vaccine induced high level of G protein specific antibody in largemouth bass. • Oral vaccination provided 66.7 % relative percent survival in MSRV-infected largemouth bass. • Oral administration suppressed the viral load and alleviated histological damage in largemouth bass tissues. [ABSTRACT FROM AUTHOR]

[Display omitted] Histone demethylation is a kind of epigenetic modification mediated by a variety of enzymes and participates in regulating multiple physiological and pathological events. Lysine-specific demethylase 7A is a kind of α-ketoglutarate- and Fe(II)-dependent demethylase belonging to the PHF2/8 subfamily of the JmjC demethylases. KDM7A is mainly localized in the nucleus and contributes to transcriptional activation via removing mono- and di-methyl groups from the lysine residues 9 and 27 of Histone H3. Mounting studies support that KDM7A is not only necessary for normal embryonic, neural, and skeletal development, but also associated with cancer, inflammation, osteoporosis, and other diseases. Herein, the structure of KDM7A is described by comparing the similarities and differences of its amino acid sequences of KDM7A and other Histone demethylases; the functions of KDM7A in homeostasis and dyshomeostasis are summarized via documenting its content and related signaling; the currently known KDM7A-specific inhibitors and their structural relationship are listed based on their structure optimization and pharmacological activities; and the challenges and opportunities in exploring functions and developing targeted agents of KDM7A are also prospected via presenting encountered problems and potential solutions, which will provide an insight in functional exploration and drug discovery for KDM7A-related diseases. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are highly expressed in leukocytes and macrophages, which play a role in the innate immune response. Here, the cDNA sequence of MMP25 from Japanese sea bass (Lateolabrax japonicus) (LjMMP25) was identified. Phylogenetic analysis revealed that LjMMP25 was most closely related to large yellow croaker MMP25. Multiple sequence alignment of LjMMP25 with MMP25 sequences from other teleosts revealed that regions of known functional importance were highly conserved. Expression analysis revealed that LjMMP25 was highly expressed in the head kidney and widely expressed in other tissues including gill, spleen, and liver. LjMMP25 was found to regulate inflammatory cytokine production and promote phagocytosis and bacterial killing in monocytes/macrophages (MO/MФ). Furthermore, LjMMP25 regulated the inflammatory response by modulating NF-κB signaling. These findings reveal new information about the role of LjMMP25 in regulating pro-inflammatory responses in this species. • We characterized MMP25 gene from Japanese sea bass, Lateolabrax japonicus. • LjMMP25 improved the phagocytosis and bacterial killing of MO/MФ. • LjMMP25 regulated the pro-inflammatory response by NF-κB signaling in MO/MФ. [ABSTRACT FROM AUTHOR]

The white spot syndrome virus (WSSV) is an efficiently destructive pathogen in shrimp farming, which has contributed to enormous economic losses in the global shrimp sector. After antiviral activity screening in our small molecule drug library, we found a medicine, 2-amino-4-(4-hydroxy-3-methoxyphenyl)-5-oxo-4 H ,5 H -pyrano [3,2-c] chromene-3‑carbonitrile (serial number: Coumarin 3004), significantly inhibited WSSV replication in Litopenaeus vannamei and reduced the mortality of WSSV-infected L. vannamei. The data indicated that the replication inhibition of WSSV exceeded 60% after WSSV particles pre-incubation with 10 mg/L Coumarin 3004 for 4 h. Moreover, Coumarin 3004 showed a stable efficacy for two days in aquacultural water, which provided a potential for its aquaculture application. The approach of consecutive Coumarin 3004 changes further decreased the mortality of WSSV-infected L. vannamei , which allows novel possibilities for treating WSSV infection. Meanwhile, up-regulation of four antimicrobial peptides (AMPs) related gene expressions revealed that Coumarin 3004 may promote AMPs-related expressions and inhibit WSSV replication. Although Coumarin 3004 blocked the horizontal transmission of WSSV in a cohabitation model, it did not entirely block the transmission. Taken together, Coumarin 3004 is a potentially excellent therapeutic agent against WSSV propagation in shrimp farming. • A nitrile phenylpropanoid derivative (Coumarin 3004) significantly inhibited WSSV proliferation in Litopenaeus vannamei. • Maintenance treatment is an interesting avenue for treating WSSV. • Coumarin 3004 promoted the expression of AMPs and thus enhanced the antiviral effect. [ABSTRACT FROM AUTHOR]

Lysine-specific demethylase 5A (KDM5A, also named RBP2 or JARID1A) is a demethylase that can remove methyl groups from histones H3K4me1/2/3. It is aberrantly expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. Pharmacological inhibition of KDM5A has been reported to significantly attenuate tumor progression in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. This review will present the structural aspects of KDM5A, its role in carcinogenesis, a comparison of currently available approaches for screening KDM5A inhibitors, a classification of KDM5A inhibitors, and its potential as a drug target in cancer therapy. [Display omitted] • KDM5A is a Fe(II)- and α-ketoglutaric acid (2-OG)-dependent histone specific demethylase, which can remove methyl groups from histones H3K4me1/2/3. • KDM5A contributes to cancer cell proliferation, cell metastasis and invasiveness, drug resistance, and is associated with poor prognosis. • KDM5A inhibitors exhibited significantly anti-cancer activity in vitro and in vivo in a range of solid tumors and acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with high mortality and drug resistance and no targeted drug available at present. Compound 4 , a staurosporine alkaloid derived from Streptomyces sp. NBU3142 in a marine sponge, exhibits potent anti-TNBC activity. This research investigated its impact on MDA-MB-231 cells and their drug-resistant variants. The findings highlighted that compound 4 inhibits breast cancer cell migration, induces apoptosis, arrests the cell cycle, and promotes cellular senescence in both regular and paclitaxel-resistant MDA-MB-231 cells. Additionally, this study identified mitogen-activated protein kinase kinase kinase 11 (MAP3K11) as a target of compound 4 , implicating its role in breast tumorigenesis by affecting cell proliferation, migration, and cell cycle progression.

Jumonji domain-containing protein D3 (JMJD3) is a 2-oxoglutarate-dependent dioxygenase that specifically removes transcriptional repression marks di- and tri-methylated groups from lysine 27 on histone 3 (H3K27me2/3). The erasure of these marks leads to the activation of some associated genes, thereby influencing various biological processes, such as development, differentiation, and immune response. However, comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking. Here, we provide a comprehensive overview of JMJD3, including its structure, functions, and involvement in inflammatory pathways. In addition, we summarize the evidence supporting JMJD3's role in several inflammatory diseases, as well as the potential therapeutic applications of JMJD3 inhibitors. Additionally, we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s).)

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke 1,2 , but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms 3-7 . Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke 4 . Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels 4-7 . We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists., (© 2024. The Author(s).)

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management., (© 2024. The Author(s).)

RNA-binding proteins (RBPs) are kinds of proteins with either singular or multiple RNA-binding domains (RBDs), and they can assembly into ribonucleic acid-protein complexes, which mediate transportation, editing, splicing, stabilization, translational efficiency, or epigenetic modifications of their binding RNA partners, and thereby modulate various physiological and pathological processes. CUG-BP, Elav-like family 1 (CELF1) is a member of the CELF family of RBPs with high affinity to the GU-rich elements in mRNA, and thus exerting control over critical processes including mRNA splicing, translation, and decay. Mounting studies support that CELF1 is correlated with occurrence, genesis and development and represents a potential therapeutical target for these malignant diseases. Herein, we present the structure and function of CELF1, outline its role and regulatory mechanisms in varieties of homeostasis and diseases, summarize the identified CELF1 regulators and their structure-activity relationships, and prospect the current challenges and their solutions during studies on CELF1 functions and corresponding drug discovery, which will facilitate the establishment of a targeted regulatory network for CELF1 in diseases and advance CELF1 as a potential drug target for disease therapy., (© 2024. The Author(s).)

Importance: Although Micropterus salmoides rhabdovirus (MSRV) causes serious fish epidemics worldwide, the detailed mechanism of MSRV entry into host cells remains unknown. Here, we comprehensively investigated the mechanism of MSRV entry into epithelioma papulosum cyprinid (EPC) cells. This study demonstrated that MSRV enters EPC cells via a low pH, dynamin-dependent, microtubule-dependent, and clathrin-mediated endocytosis. Subsequently, MSRV transports from early endosomes to late endosomes and further into lysosomes in a microtubule-dependent manner. The characterization of MSRV entry will further advance the understanding of rhabdovirus cellular entry pathways and provide novel targets for antiviral drug against MSRV infection., Competing Interests: The authors declare no conflict of interest.

Threat and extinction memories are crucial for organisms' survival in changing environments. These memories are believed to be encoded by separate ensembles of neurons in the brain, but their whereabouts remain elusive. Using an auditory fear-conditioning and extinction paradigm in male mice, here we discovered that two distinct projection neuron subpopulations in physical proximity within the insular cortex (IC), targeting the central amygdala (CeA) and nucleus accumbens (NAc), respectively, to encode fear and extinction memories. Reciprocal intracortical inhibition of these two IC subpopulations gates the emergence of either fear or extinction memory. Using rabies-virus-assisted tracing, we found IC-NAc projection neurons to be preferentially innervated by intercortical inputs from the orbitofrontal cortex (OFC), specifically enhancing extinction to override fear memory. These results demonstrate that IC serves as an operation node harboring distinct projection neurons that decipher fear or extinction memory under the top-down executive control from OFC., (© 2022. The Author(s).)

Hematopoietic stem/progenitor cells (HSPCs) are supported and regulated by niche cells in the bone marrow with an important characterization of physiological hypoxia. However, how hypoxia regulates HSPCs is still unclear. Here, we find that meteorin (Metrn) from hypoxic macrophages restrains HSPC mobilization. Hypoxia-induced factor 1α and Yin Yang 1 induce the high expression of Metrn in macrophages, and macrophage-specific Metrn knockout increases HSPC mobilization through modulating HSPC proliferation and migration. Mechanistically, Metrn interacts with its receptor 5-hydroxytryptamine receptor 2b (Htr2b) to regulate the reactive oxygen species levels in HSPCs through targeting phospholipase C signaling. The reactive oxygen species levels are reduced in HSPCs of macrophage-specific Metrn knockout mice with activated phospholipase C signaling. Targeting the Metrn/Htr2b axis could therefore be a potential strategy to improve HSPC mobilization for stem cell-based therapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Chronic pollution in aquatic ecosystems can lead to many adverse effects, including a greater susceptibility to pathogens among resident biota. Trifloxystrobin (TFS) is a strobilurin fungicide widely used in Asia to control soybean rust. However, it has the potential to enter aquatic ecosystems, where it may impair fish resistance to viral infections. To explore the potential environmental risks of TFS, we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus (SVCV). Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge, SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini (EPC) cells and zebrafish exposed to 25 μg/L TFS. Results showed that the highest viral load was more than 100-fold that of the controls. Intracellular biochemical assays indicated that autophagy was induced by TFS, and associated changes included an increase in autophagosomes, conversion of LC3-II, accumulation of Beclin-1, and degradation of P62 in EPC cells and zebrafish. In addition, TFS markedly decreased the expression and phosphorylation of mTOR, indicating that activation of TFS may be associated with the mTOR-mediated autophagy pathway. This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.

Acute brain injury caused by subarachnoid hemorrhage is the major cause of poor prognosis. The pathology of subarachnoid hemorrhage likely involves major morphological changes in the microcirculation. However, previous studies primarily used fixed tissue or delayed injury models. Therefore, in the present study, we used in vivo imaging to observe the dynamic changes in cerebral microcirculation after subarachnoid hemorrhage. Subarachnoid hemorrhage was induced by perforation of the bifurcation of the middle cerebral and anterior cerebral arteries in male C57/BL6 mice. The diameter of pial arterioles and venules was measured by in vivo fluorescence microscopy at different time points within 180 minutes after subarachnoid hemorrhage. Cerebral blood flow was examined and leukocyte adhesion/albumin extravasation was determined at different time points before and after subarachnoid hemorrhage. Cerebral pial microcirculation was abnormal and cerebral blood flow was reduced after subarachnoid hemorrhage. Acute vasoconstriction occurred predominantly in the arterioles instead of the venules. A progressive increase in the number of adherent leukocytes in venules and substantial albumin extravasation were observed between 10 and 180 minutes after subarachnoid hemorrhage. These results show that major changes in microcirculation occur in the early stage of subarachnoid hemorrhage. Our findings may promote the development of novel therapeutic strategies for the early treatment of subarachnoid hemorrhage., Competing Interests: None declared

Taking Yangmai 18, widely cultivated in south of Huaihe River, as experimental material, this study investigated the effects of application of 0, 30, 60, 90 and 120 m3 x hm(-2) pig farm slurry (PS) at the wintering stage combined with the application of 0, 30, 60, 90 kg x hm(-2) urea at the heading stage on medium- and micro-element contents and quality of wheat. The results showed that the Ca, Mg and Fe contents of plant firstly decreased then increased with the extension of the growth period, but the Cu, Zn and Mn contents decreased continuously through the growth period. Ca, Mg, Cu and Zn reached the highest value at every growth stage except the jointing stage when applying 120 m3 x hm(-2) PS with 90 kg x hm(-2) urea. Fe and Mn reached the highest value at every growth stage when applying 120 m3 x hm(-2) PS with 90 kg x hm(-2) urea. The contents of Ca, Mg, Cu, Zn, Fe and Mn all increased with increasing PS application across the growth period. Regarding the quality of wheat, applying 90 m3 x hm(-2) PS with 60 kg x hm(-2) urea was the best fertilization pattern. Combined applications of anaerobically treated PS with N fertilizer could increase medium- and micro-element contents and quality of wheat. Generally, it was recommended to apply 60-120 m3 x hm(-2) PS at the wintering stage and 90 kg x hm(-2) urea at the heading stage under field conditions.