Nitrogen-doped carbon dots derived from ellagic acid and L-tyrosine for photothermal anticancer and anti-inflammation.

Photothermal therapy (PTT) of tumor would ineluctably cause oxidative stress and related inflammation in adjacent normal tissues, leading to a discounted therapeutic outcome. To address this issue, herein an innovative therapeutic strategy that integrates photothermal anticancer and normal cell protection is developed. A new type of nitrogen-doped carbon dot (ET-CD) has been synthesized in one step by hydrothermal method using ellagic acid and L-tyrosine as reaction precursors. The as-prepared ET-CD exhibits high photothermal conversion efficiency and good photothermal stability. After intravenous injection, ET-CD can accumulate at the tumor site and the hyperthermia generated under near infrared laser irradiation effectively ablates tumor tissues, thereby significantly inhibiting tumor growth. Importantly, owing to the inherited antioxidant activity from ellagic acid, ET-CD can remove reactive oxygen and nitrogen species produced in the body and reduce the levels of inflammatory factors induced by oxidative stress, so as to alleviate the damage caused by heat-induced inflammation to normal cells and tissues while photothermal anticancer. These attractive features of ET-CD may open the exploration of innovative therapeutic strategies to promote the clinical application of PTT.

An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

Sialic acids as attachment factors in mosquitoes mediating Japanese encephalitis virus infection.

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.

Glutathione-triggered release of SO2 gas to augment oxidative stress for enhanced chemodynamic and sonodynamic therapy.

Recently, gas therapy has emerged as a promising alternative treatment for deep-seated tumors. However, some challenges regarding insufficient or uncontrolled gas generation as well as unclear therapeutic mechanisms restrict its further clinical application. Herein, a well-designed nanoreactor based on intracellular glutathione (GSH)-triggered generation of sulfur dioxide (SO2) gas to augment oxidative stress has been developed for synergistic chemodynamic therapy (CDT)/sonodynamic therapy (SDT)/SO2 gas therapy. The nanoreactor (designed as CCM@FH-DNs) is constructed by employing iron-doped hollow mesoporous silica nanoparticles as carriers, the surface of which was modified with the SO2 prodrug 2,4-dinitrobenzenesulfonyl (DNs) and further coated with cancer cell membranes for homologous targeting. The CCM@FH-DNs can not only serve as a Fenton-like agent for CDT, but also as a sonosensitizer for SDT. Importantly, CCM@FH-DNs can release SO2 for SO2-mediated gas therapy. Both in vitro and in vivo evaluations demonstrate that the CCM@FH-DNs nanoreactor performs well in augmenting oxidative stress for SO2 gas therapy-enhanced CDT/SDT via GSH depletion and glutathione peroxidase-4 enzyme deactivation as well as superoxide dismutase inhibition. Moreover, the doped iron ions ensure that the CCM@FH-DNs nanoreactors enable magnetic resonance imaging-guided therapy. Such a GSH-triggered SO2 gas therapy-enhanced CDT/SDT strategy provides an intelligent paradigm for developing efficient tumor microenvironment-responsive treatments.

Manganese(III) Phthalocyanine Complex Nanoparticle-Loaded Glucose Oxidase to Enhance Tumor Inhibition through Energy Metabolism and Macrophage Polarization.

Elevated levels of reactive oxygen species (ROS) have demonstrated efficacy in eliminating tumor cells by modifying the tumor microenvironment and inducing the polarization of tumor-associated macrophages (TAMs). Nevertheless, the transient nature and limited diffusion distance inherent in ROS present significant challenges in cancer treatment. In response to these limitations, we have developed a nanoparticle (MnClPc-HSA@GOx) that not only inhibits tumor energy metabolism but also facilitates the transition of TAMs from the M2 type (anti-inflammatory type) to the M1 type (proinflammatory type). MnClPc-HSA@GOx comprises a manganese phthalocyanine complex (MnClPc) enveloped in human serum albumin (HSA), with glucose oxidase (GOx) loaded onto MnClPc@HSA nanoparticles. GOx was employed to catalyze the decomposition of glucose to produce H2O2 and gluconic acid. Additionally, in the presence of MnClPc, it catalyzes the conversion of H2O2 into •O2- and 1O2. Results indicate that the nanoparticle effectively impedes the glucose supply to tumor cells and suppresses their energy metabolism. Simultaneously, the ROS-mediated polarization of TAMs induces a shift from M2 to M1 macrophages, resulting in a potent inhibitory effect on tumors. This dual-action strategy holds promising clinical inhibition applications in the treatment of cancer.

Non-Invasive Diagnosis of Prostate Cancer and High-Grade Prostate Cancer Using Multiparametric Ultrasonography and Serological Examination.

OBJECTIVES: This study aimed to assess the efficacy of multiparametric ultrasonography (mpUS) combined with serological examination, as a non-invasive method, in detecting prostate cancer (PCa) or high-grade prostate cancer (HGPCa) respectively. METHODS: A cohort of 245 individuals with clinically suspected PCa were enrolled. All subjects underwent a comprehensive evaluation, including basic data collection, serological testing, mpUS and prostate biopsy. Random Forest (RF) models were developed, and the mean area under the curve (AUC) in 100 cross-validations was used to assess the performance in distinguishing PCa from HGPCa. RESULTS: mpUS features showed significant differences (p < 0.001) between the PCa and non-PCa groups, as well as between the HGPCa and low-grade prostate cancer (LGPCa) groups including prostate-specific antigen density (PSAD), transrectal real-time elastography (TRTE) and intensity difference (ID). The RF model, based on these features, demonstrated an excellent discriminative ability for PCa with a mean area under the curve (AUC) of 0.896. Additionally, another model incorporating free prostate-specific antigen (FPSA) and color Doppler flow imaging (CDFI) achieved a high accuracy in predicting HGPCa with a mean AUC of 0.830. The nomogram derived from these models exhibited excellent individualized prediction of PCa and HGPCa. CONCLUSION: The RF models incorporating mpUS and serological variables achieved satisfactory accuracies in predicting PCa and HGPCa.

Characterization and function analysis of cathepsin C in Marsupenaeusjaponicus.

Cathepsin C is a cysteine protease widely found in invertebrates and vertebrates, and has the important physiological role participating in proteolysis in vivo and activating various functional proteases in immune/inflammatory cells in the animals. In order to study the role of cathepsin C in the disease resistance of shrimp, we cloned cathepsin C gene (MjcathC) from Marsupenaeus japonicus, analyzed its expression patterns in various tissues, performed MjcathC-knockdown, and finally challenged experimental shrimps with Vibrio alginolyticus and WSSV. The results have shown the full length of MjcathC is 1782 bp, containing an open reading frame of 1350 bp encoding 449 amino acids. Homology analysis revealed that the predicted amino acid sequence of MjcathC shared respectively 88.42 %, 87.36 % and 87.58 % similarity with Penaeus monodon, Fenneropenaeus penicillatus and Litopenaeus vannamei. The expression levels of MjcathC in various tissues of healthy M. japonicus are the highest in the liver, followed by the gills and heart, and the lowest in the stomach. The expression levels of MjcathC were significantly up-regulated in all examined tissues of shrimp challenged with WSSV or V. alginolyticus. After knockdown-MjcathC using RNAi technology in M. japonicus, the expression levels of lectin and heat shock protein 70 in MjcathC-knockdown shrimp were significantly down-regulated, and the mortality of MjcathC-knockdown shrimp challenged by WSSV and V. alginolyticus significantly increased. Knockdown of the MjcathC reduced the resistance of M. japonicus to WSSV and V. alginolyticus. The above results have indicated that cathepsin C may play an important role in the antibacterial and antiviral innate immunity of M. japonicus.

Utilization and outcomes of the 21-gene recurrence score in de novo metastatic breast cancer.

BACKGROUND: Limited data exist regarding the utility and validity of the 21-gene recurrence score (RS) in patients with de novo metastatic breast cancer (dnMBC). This study aimed to investigate the practice patterns as well as associated survival outcomes based on 21-gene RS in dnMBC. RESEARCH DESIGN AND METHODS: The Surveillance, Epidemiology, and End Results Oncotype database was queried for women with hormone receptor-positive and Her2-negative dnMBC. RESULTS: A total of 153 patients were identified, including 62.7% and 37.3% of patients who had RS < 26 and ≥ 26, respectively. Patients with RS ≥ 26 were more likely to receive chemotherapy compared to those with RS < 26 (61.4% vs. 28.1%, p < 0.001). Patients with RS ≥ 26 had an inferior breast cancer-specific survival (BCSS) (2-year BCSS: 84.3% vs. 89.5, p = 0.067) and overall survival (OS) compared to those with RS < 26 (2-year OS: 76.9% vs. 87.4%, p = 0.018). The multivariate Cox proportional hazard models showed that those with RS ≥ 26 had a significantly inferior BCSS (hazard ratio [HR] 2.251, 95% confidence interval [CI] 1.056-4.799, p = 0.036) and OS (HR 2.151, 95%CI 1.123-4.120, p = 0.021) compared to those with RS < 26. CONCLUSIONS: The 21-gene RS assay is an important prognostic factor in patients with dnMBC.

POOE: predicting oomycete effectors based on a pre-trained large protein language model.

Oomycetes are fungus-like eukaryotic microorganisms which can cause catastrophic diseases in many plants. Successful infection of oomycetes depends highly on their effector proteins that are secreted into plant cells to subvert plant immunity. Thus, systematic identification of effectors from the oomycete proteomes remains an initial but crucial step in understanding plant-pathogen relationships. However, the number of experimentally identified oomycete effectors is still limited. Currently, only a few bioinformatics predictors exist to detect potential effectors, and their prediction performance needs to be improved. Here, we used the sequence embeddings from a pre-trained large protein language model (ProtTrans) as input and developed a support vector machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance with an area under the precision-recall curve of 0.804 (area under the receiver operating characteristic curve = 0.893, accuracy = 0.874, precision = 0.777, recall = 0.684, and specificity = 0.936) in the fivefold cross-validation, considerably outperforming various combinations of popular machine learning algorithms and other commonly used sequence encoding schemes. A similar prediction performance was also observed in the independent test. Compared with the existing oomycete effector prediction methods, POOE provided very competitive and promising performance, suggesting that ProtTrans effectively captures rich protein semantic information and dramatically improves the prediction task. We anticipate that POOE can accelerate the identification of oomycete effectors and provide new hints to systematically understand the functional roles of effectors in plant-pathogen interactions. The web server of POOE is freely accessible at http://zzdlab.com/pooe/index.php. The corresponding source codes and data sets are also available at https://github.com/zzdlabzm/POOE.IMPORTANCEIn this work, we use the sequence representations from a pre-trained large protein language model (ProtTrans) as input and develop a Support Vector Machine-based method called POOE for predicting oomycete effectors. POOE could achieve a highly accurate performance in the independent test set, considerably outperforming existing oomycete effector prediction methods. We expect that this new bioinformatics tool will accelerate the identification of oomycete effectors and further guide the experimental efforts to interrogate the functional roles of effectors in plant-pathogen interaction.

AraPathogen2.0: An Improved Prediction of Plant-Pathogen Protein-Protein Interactions Empowered by the Natural Language Processing Technique.

Plant-pathogen protein-protein interactions (PPIs) play crucial roles in the arm race between plants and pathogens. Therefore, the identification of these interspecies PPIs is very important for the mechanistic understanding of pathogen infection and plant immunity. Computational prediction methods can complement experimental efforts, but their predictive performance still needs to be improved. Motivated by the rapid development of natural language processing and its successful applications in the field of protein bioinformatics, here we present an improved XGBoost-based plant-pathogen PPI predictor (i.e., AraPathogen2.0), in which sequence encodings from the pretrained protein language model ESM2 and Arabidopsis PPI network-related node representations from the graph embedding technique struc2vec are used as input. Stringent benchmark experiments showed that AraPathogen2.0 could achieve a better performance than its precedent version, especially for processing the test data set with novel proteins unseen in the training data.

Economic values of reproductive and growth traits in Chinese Yiling sheep.

This study aimed to calculate the economic value (EV) of reproductive and growth traits for Yiling sheep. A bio-economic model was developed to assess the economic value of litter size (LS), litter size at weaning (LSW), age at first lambing (AFL), lambing interval (LI), birth weight (BW), weaning weight (WW), and 6-month body weight (6MW). The sensitivity of the economic value of traits to changes in market prices was also analyzed. In this study, the trait with the highest EV was LSW (427.97 ¥), followed by LS (419.96 ¥), BW (52.13 ¥), 6MW (14.46 ¥), WW (11.03 ¥), AFL (-0.51 ¥), and LI (-9.09 ¥). LS was the most important trait in the production system with a relative economic weight of 22.81%, followed by 6MW and LSW with relative economic weights of 18.98% and 19.01%, respectively. All traits assessed, except AFL and LI, had positive economic values, indicating that genetic improvement of these traits would have a positive impact on profitability. The results of the sensitivity analysis showed that the economic value of AFL was not sensitive to price changes. All growth traits were unaffected by price changes in labor and medical costs. In addition, the LS, LSW, LI, WW, and 6MW were sensitive to changes in liveweight and feed prices. Generally, as feed prices increased, the economic value of all traits except LI and BW decreased. Except for LI and BW, the economic value of all traits increased due to the rise in liveweight prices. This suggested that liveweight and feed prices significantly affect the profitability of the production system.

Imaging Changes in Liver After Chemotherapy for Colon Cancer: A Case Report.

BACKGROUND: Colon cancer with liver metastasis is a common occurrence in clinical practice. The presence of liver metastasis has a significant impact on the treatment strategy of patients, so the first step is to diagnose whether it is liver metastasis. Imaging is one of the auxiliary methods for diagnosing liver metastases, but due to the presence of different diseases with the same shadow, we need to be cautious when using imaging methods for the diagnosis of liver metastases. CASE PRESENTATION: We report a 53-year-old female patient with sigmoid colon cancer and perforation who underwent a surgical operation. Three years after the operation, reexamination of the liver through computed tomography and magnetic resonance imagery scanning revealed multiple progressive liver lesions. However, the liver biopsy did not show malignant changes. Repeated analysis of the patient's liver magnetic resonance imaging revealed that multiple liver nodules were significantly enhanced in the arterial phase and that the portal vein density/signal ratio was higher than that of the liver parenchyma. The coincidence of doughnut-shaped nodules and high signal in the hepatobiliary phase, combined with the results of pathological liver puncture examination, led to nodular regenerative hyperplasia being considered as a possible diagnosis. CONCLUSION: A review of the relevant literature showed that following oxaliplatin chemotherapy for colorectal cancer, it is not uncommon for doughnut-shaped nodules with obvious enhancement in the middle hepatic artery phase and high signal intensity in the hepatobiliary phase to develop. Such changes should be paid sufficient attention by radiologists.

Heme Oxygenase-1 Is Involved in the Repair of Oxidative Damage Induced by Oxidized Fish Oil in Litopenaeus vannamei by Sulforaphane.

Heme oxygenase-1 (HO-1), which could be highly induced under the stimulation of oxidative stress, functions in reducing the damage caused by oxidative stress, and sulforaphane (SFN) is an antioxidant. This study aims to investigate whether HO-1 is involved in the repair of oxidative damage induced by oxidized fish oil (OFO) in Litopenaeus vannamei by sulforaphane (SFN). The oxidative stress model of L. vannamei was established by feeding OFO feed (OFO accounts for 6%), and they were divided into the following four groups: control group (injected with dsRNA-EGFP and fed with common feed), dsRNA-HO-1 group (dsRNA-HO-1, common feed), dsRNA-HO-1 + SFN group (dsRNA-HO-1, supplement 50 mg kg-1 SFN feed), and SFN group (dsRNA-EGFP, supplement 50 mg kg-1 SFN feed). The results showed that the expression level of HO-1 in the dsRNA-HO-1 + SFN group was significantly increased compared with the dsRNA-HO-1 group (p < 0.05). The activities of SOD in muscle and GPX in hepatopancreas and serum of the dsRNA-HO-1 group were significantly lower than those of the control group, and MDA content in the dsRNA-HO-1 group was the highest among the four groups. However, SFN treatment increased the activities of GPX and SOD in hepatopancreas, muscle, and serum and significantly reduced the content of MDA (p < 0.05). SFN activated HO-1, upregulated the expression of antioxidant-related genes (CAT, SOD, GST, GPX, Trx, HIF-1α, Nrf2, prx 2, Hsp 70), and autophagy genes (ATG 3, ATG 5), and stabilized the expression of apoptosis genes (caspase 2, caspase 3) in the hepatopancreas (p < 0.05). In addition, knocking down HO-1 aggravated the vacuolation of hepatopancreas and increased the apoptosis of hepatopancreas, while the supplement of SFN could repair the vacuolation of hepatopancreas and reduce the apoptosis signal. In summary, HO-1 is involved in the repair of the oxidative damage induced by OFO in L. vannamei by SFN.

Integrating Anion-π+ Interaction and Crowded Conformation to Develop Multifunctional NIR AIEgen for Effective Tumor Theranostics via Hippo-YAP Pathway.

The technology of aggregation-induced emission (AIE) presents a promising avenue for fluorescence imaging-guided photodynamic cancer therapy. However, existing near-infrared AIE photosensitizers (PSs) frequently encounter limitations, including tedious synthesis, poor tumor retention, and a limited understanding of the underlying molecular biology mechanism. Herein, an effective molecular design paradigm of anion-π+ interaction combined with the inherently crowded conformation that could enhance fluorescence efficacy and reactive oxygen species generation was proposed through a concise synthetic method. Mechanistically, upon photosensitization, the Hippo signaling pathway contributes to the death of melanoma cells and promotes the nuclear location of its downstream factor, yes-associated protein, which regulates the transcription and expression of apoptosis-related genes. The finding in this study would trigger the development of high-performance and versatile AIE PSs for precision cancer therapy based on a definite regulatory mechanism.

More Is Better: Dual-Acceptor Engineering for Constructing Second Near-Infrared Aggregation-Induced Emission Luminogens to Boost Multimodal Phototheranostics.

The manipulation of electron donor/acceptor (D/A) shows an endless impetus for innovating optical materials. Currently, there is booming development in electron donor design, while research on electron acceptor engineering has received limited attention. Inspired by the philosophical idea of "more is different", two systems with D'-D-A-D-D' (1A system) and D'-D-A-A-D-D' (2A system) structures based on acceptor engineering were designed and studied. It was demonstrated that the 1A system presented a weak aggregation-induced emission (AIE) to aggregation-caused quenching (ACQ) phenomenon, along with the increased acceptor electrophilicity and planarity. In sharp contrast, the 2A system with one more acceptor exhibited an opposite ACQ-to-AIE transformation. Interestingly, the fluorophore with a more electron-deficient A-A moiety in the 2A system displayed superior AIE activity. More importantly, all compounds in the 2A system showed significantly higher molar absorptivity (ε) in comparison to their counterparts in the 1A system. Thanks to the highest ε, near-infrared-II (NIR-II, 1000-1700 nm) emission, desirable AIE property, favorable reactive oxygen species (ROS) generation, and high photothermal conversion efficiency, a representative member of the 2A system handily performed in fluorescence-photoacoustic-photothermal multimodal imaging-guided photodynamic-photothermal collaborative therapy for efficient tumor elimination. Meanwhile, the NIR-II fluorescence imaging of blood vessels and lymph nodes in living mice was also accomplished. This study provides the first evidence that the dual-connected acceptor tactic could be a new molecular design direction for the AIE effect, resulting in high ε, aggregation-intensified NIR-II fluorescence emission, and improved ROS and heat generation capacities of phototheranostic agents.

A mitochondria-targeted multifunctional nanoplatform combining carbon monoxide delivery with O2-independent free radical burst under 1064 nm light irradiation for efficient hypoxic tumor therapy.

In situ mitochondrial oxidative stress amplification is an effective strategy to improve efficacy of cancer treatment. In this work, a tumor and mitochondria dual-targeted multifunctional nanoplatform CMS@AIPH@PDA@COTPP@FA (CAPCTF) was prepared, in which a thermally decomposable radical initiator AIPH was loaded inside the mesoporores of CuxMoySz (CMS) nanoparticles with polydopamine (PDA) covered films that were further covalently functionalized by a mitochondria-targeted CO donor (COTPP) and a directing group of folic acid (FA). The prepared CAPCTF nanoplatform selectively accumulated in cancer cells and further targeted the mitochondrial organelle where carbon monoxide (CO) and O2-independent free radicals (•OH/•R) were in situ generated upon 1064 nm laser irradiation. Furthermore, the CMS nanocarrier was capable of depleting the GSH overexpressed in the tumor microenvironment (TME), thus preventing free radical scavenging. As a result, the CAPCTF nanoplatform exhibited outstanding in vitro and in vivo antitumor efficacy under hypoxic conditions. This provides an innovative strategy that combines O2-independent free radicals (•OH/•R) generation, CO delivery and GSH consumption to amplify intracellular oxidative stresses and induce mitochondrial dysfunction, thus leading to cancer cells eradication, which may have significant implications for personalized hypoxic tumor treatment.

Non-invasive diagnosis of primary Sjögren's syndrome using ultrasonography and transcriptome biomarkers.

Diagnosing primary Sjögren's syndrome (pSS) is difficult due to clinical heterogeneity and the absence of non-invasive specific biomarkers. To develop non-invasive pSS diagnosis methods that integrate classic clinical indexes, major salivary gland ultrasonography (SGUS), and gene expression profiles shared by labial gland and peripheral blood, we conducted a study on a cohort of 358 subjects. We identified differentially expressed genes (DEGs) in glands and blood that were enriched in defense response to virus and type I interferon production pathways. Four upregulated DEGs common in glands and blood were identified as hub genes based on the protein-protein interaction networks. A random forest model was trained using features, including SGUS, anti-SSA/Ro60, keratoconjunctivitis sicca tests, and gene expression levels of MX1 and RSAD2. The model achieved comparable pSS diagnosis accuracy to the golden standard method based on labial gland biopsy. Our findings implicate this novel model as a promising diagnosis technique of pSS.

A novel perlucin-like protein (PLP) protects Litopenaeus vannamei against Vibrio harveyi infection.

C-type lectins (CTLs), as pattern recognition receptors (PRRs), play an important role in the innate immunity of Litopenaeus vannamei. In this study, a novel CTL, named perlucin-like protein (PLP), was identified from L. vannamei, which shared homology sequences of PLP from Penaeus monodon. PLP from L. vannamei was expressed in the hepatopancreas, eyestalk, muscle and brain and could be activated in the tissues (hepatopancreas, muscle, gill and intestine) after infection with the pathogen Vibrio harveyi. Bacteria (Vibrio alginolyticus, V. parahaemolyticus, V. harveyi, Streptococcus agalactiae and Bacillus subtilis) could be bound and agglutinated by the PLP recombinant protein in a Ca2+-dependent manner. Moreover, PLP could stabilise the expression of the immune-related genes (ALF, SOD, HSP70, Toll4 and IMD) and apoptosis gene (Caspase2). The RNAi of PLP could remarkably affect the expression of antioxidant gene, antimicrobial peptide genes, other CTLs, apoptosis genes, Toll signaling pathways, and IMD signaling pathways. Moreover, PLP reduced the bacterial load in the hepatopancreas. These results suggested that PLP was involved in the innate immune response against V. harveyi infection by recognising bacterial pathogens and activating the expression of immune-related and apoptosis genes.

CircNCOR1 regulates breast cancer radiotherapy efficacy by regulating CDK2 via hsa-miR-638 binding.

BACKGROUND: Despite aggressive local and regional therapy, triple-negative breast cancer (TNBC) is characterized by an increased risk of locoregional recurrence. RNA-sequencing data has identified a large number of circRNAs in primary breast cancers, but the role of specific circRNAs in regulating the radiosensitivity of TNBC is not fully understood. This research aimed to investigate the function of circNCOR1 in the radiosensitivity of TNBC. METHODS: CircRNA high-throughput sequencing was conducted on two breast cancer MDA-MB-231 and BT549 cell lines after 6 Gy radiation. The relationship between circNCOR1, hsa-miR-638, and CDK2 was determined by RNA immunoprecipitation (RIP), FISH and luciferase assays. The proliferation and apoptosis of breast cancer cells were measured by CCK8, flow cytometry, colony formation assays, and western blot. RESULTS: Differential expression of circRNAs was closely related to the proliferation of breast cancer cells after irradiation. Overexpression of circNCOR1 facilitated the proliferation of MDA-MB-231 and BT549 cells and impaired the radiosensitivity of breast cancer cells. Additionally, circNCOR1 acted as a sponge for hsa-miR-638 to regulate the downstream target protein CDK2. Overexpression of hsa-miR-638 promoted apoptosis of breast cancer cells, while overexpression of CDK2 alleviated apoptosis and increased proliferation and clonogenicity. In vivo, overexpression of circNCOR1 partially reversed radiation-induced loosening of tumor structures and enhanced tumor cell proliferation. CONCLUSION: Our results demonstrated that circNCOR1 bounds to hsa-miR-638 and targets CDK2, thereby regulating the radiosensitivity of TNBC.