Tissue factor pathway inhibitors disrupt structures of rhabdovirus/ranairidovirus and inhibit viral infection in Chinese perch, Siniperca chuatsi.

Viral diseases have caused great economic losses to the aquaculture industry. However, there are currently no specific drugs to treat these diseases. Herein, we utilized Siniperca chuatsi as an experimental model, and successfully extracted two tissue factor pathway inhibitors (TFPIs) that were highly distributed in different tissues. We then designed four novel peptides based on the TFPIs, named TS20, TS25, TS16, and TS30. Among them, TS25 and TS30 showed good biosafety and high antiviral activity. Further studies showed that TS25 and TS30 exerted their antiviral functions by preventing viruses from invading Chinese perch brain (CPB) cells and disrupting Siniperca chuatsi rhabdovirus (SCRV)/Siniperca chuatsi ranairidovirus (SCRIV) viral structures. Additionally, compared with the control group, TS25 and TS30 could significantly reduce the mortality of Siniperca chuatsi, the relative protection rates of TS25 against SCRV and SCRIV were 71.25 % and 53.85 % respectively, and the relative protection rate of TS30 against SCRIV was 69.23 %, indicating that they also had significant antiviral activity in vivo. This study provided an approach for designing peptides with biosafety and antiviral activity based on host proteins, which had potential applications in the prevention and treatment of viral diseases.

Quercetin ameliorates ulcerative colitis by activating aryl hydrocarbon receptor to improve intestinal barrier integrity.

Ulcerative colitis (UC) pathogenesis is largely associated with intestinal epithelial barrier dysfunction. A therapeutic approach to UC involves the repair of damaged intestinal barrier. Our study aimed to investigate whether aryl hydrocarbon receptor (AhR) mediated the intestinal barrier repair effects of quercetin to ameliorate UC. 3% dextran sulfate sodium was used to induce colitic mice, and quercetin (25, 50, and 100 mg/kg) was administered orally for 10 days to assess the therapeutic effects. In vitro, Caco-2 cells were used to explore the effect of quercetin on tight junction protein expression and AhR activation. The results showed that quercetin alleviated colitic mice by restoring tight junctions (TJs) integrity via an AhR-dependent manner (p < 0.05). In vitro, quercetin dose-dependently elevated the expressions of TJs protein ZO-1 and Claudin1, and activated AhR by enhancing the expression of CYP1A1 and facilitating AhR nuclear translocation in Caco-2 cells (p < 0.05). While AhR antagonist CH223191 reversed the therapeutic effects of quercetin (p < 0.05) and blocked quercetin-induced AhR activation and enhancement of TJs protein (p < 0.05). In conclusion, quercetin repaired intestinal barrier dysfunction by activating AhR-mediated enhancement of TJs to alleviate UC. Our research offered new perspectives on how quercetin enhanced intestinal barrier function.

Transport and transformations of cadmium in water-biofilm-sediment phases as affected by hydrodynamic conditions.

Hydrodynamic conditions play a crucial role in governing the fate, transport, and risks of metal elements. However, the contribution of hydrodynamic conditions to the fate and transport of heavy metals among water, sediment, and biofilm phases is poorly understood. In our study, we conducted experiments in controlled hydrodynamic conditions using a total of 6 two-phase and 9 three-phase mesocosms consisting of water, biofilm, and sediment. We also measured Cd (cadmium) specification in different phases to assess how hydrodynamic forces control Cd bioavailability. We found that turbulent flow destroyed the surface morphology of the biofilm and significantly decreased the content of extracellular polymeric substances (p < 0.05). This led to a decrease in the biofilm's adsorption capacity for Cd, with the maximum adsorption capacity (0.124 mg/g) being one-tenth of that under static conditions (1.256 mg/g). The Cd chemical forms in the biofilm and sediment were significantly different, with the highest amount of Cd in the biofilm being acid-exchangeable, accounting for up to 95.1% of the total Cd content. Cd was more easily released in the biofilm due to its weak binding state, while Cd in the sediment existed in more stable chemical forms. Hydrodynamic conditions altered the migration behavior and distribution characteristics of Cd in the system by changing the adsorption capacity of the biofilm and sediment for Cd. Cd mobility increased in laminar flow but decreased in turbulent flow. These results enhance our understanding of the underlying mechanisms that control the mobility and bioavailability of metals in aquatic environments with varying hydrodynamic conditions.

Rac1 promotes the reprogramming of glucose metabolism and the growth of colon cancer cells through upregulating SOX9.

Metabolic reprogramming is the survival rule of tumor cells, and tumor cells can meet their high metabolic requirements by changing the energy metabolism mode. Metabolic reprogramming of tumor cells is an important biochemical basis of tumor malignant phenotypes. Ras-related C3 botulinum toxin substrate 1 (Rac1) is abnormally expressed in a variety of tumors and plays an important role in the proliferation, invasion, and migration of tumor cells. However, the role of Rac1 in tumor metabolic reprogramming is still unclear. Herein, we revealed that Rac1 was highly expressed in colon cancer tissues and cell lines. Rac1 promotes the proliferation, migration, and invasion of colon cancer cells by upregulating SOX9, which as a transcription factor can directly bind to the promoters of HK2 and G6PD genes and regulate their transcriptional activity. Rac1 upregulates the expression of SOX9 through the PI3K/AKT signaling pathway. Moreover, Rac1 can promote glycolysis and the activation of the pentose phosphate pathway in colon cancer cells by mediating the axis of SOX9/HK2/G6PD. These findings reveal novel regulatory axes involving Rac1/SOX9/HK2/G6PD in the development and progression of colon cancer, providing novel promising therapeutic targets.

LPLUNC1 reduces glycolysis in nasopharyngeal carcinoma cells through the PHB1-p53/c-Myc axis.

Cancer cells prefer glycolysis to support their proliferation. Our previous studies have shown that the long palate, lung, and nasal epithelial cell clone 1 (LPLUNC1) can upregulate prohibitin 1 (PHB1) expression to inhibit the proliferation of nasopharyngeal carcinoma (NPC) cells. Given that PHB1 is an important regulator of cell energy metabolism, we explored whether and how LPLUNC1 regulated glucose glycolysis in NPC cells. LPLUNC1 or PHB1 overexpression decreased glycolysis and increased oxidative phosphorylation (OXPHOS)-related protein expression in NPC cells, promoting phosphorylated PHB1 nuclear translocation through 14-3-3σ. LPLUNC1 overexpression also increased p53 but decreased c-Myc expression in NPC cells, which were crucial for the decrease in glycolysis and increase in OXPHOS-related protein expression induced by LPLUNC1 overexpression. Finally, we found that treatment with all-trans retinoic acid (ATRA) reduced the viability and clonogenicity of NPC cells, decreased glycolysis, and increased OXPHOS-related protein expression by enhancing LPLUNC1 expression in NPC cells. Therefore, the LPLUNC1-PHB1-p53/c-Myc axis decreased glycolysis in NPC cells, and ATRA upregulated LPLUNC1 expression, ATRA maybe a promising drug for the treatment of NPC.

Epidermal growth factor receptor promotes infectious spleen and kidney necrosis virus invasion via PI3K-Akt signaling pathway.

Infectious spleen and kidney necrosis virus disease (ISKNVD) caused significant economic losses to the fishery industry. Epidermal growth factor receptor (EGFR), phosphatidylinositide 3-kinase (PI3K) played an important role in ISKNV invasion. However, the molecular regulatory mechanisms among EGFR, PI3K-Akt, and ISKNV invasion are not clear. In this study, ISKNV infection rapidly induced EGFR activation. While, EGFR activation promoted virus entry, but EGFR inhibitors and specific RNA (siRNA) decreased virus invasion. The PI3K-Akt as downstream signalling of EGFR was activated upon ISKNV infection. Consistent with the trends of EGFR, Akt activation increased ISKNV entry into cells, Akt inhibition by specific inhibitor or siRNA decreased ISKNV invasion. Akt silencing combination with EGFR activation showed that EGFR activation regulation ISKNV invasion is required for activation of the Akt signalling pathway. Those data demonstrated that ISKNV-induced EGFR activation positively regulated virus invasion by PI3K-Akt pathway and provided a better understanding of the mechanism of EGFR-PI3K-Akt involved in ISKNV invasion.

Fine mapping of the grain chalkiness quantitative trait locus qCGP6 reveals the involvement of Wx in grain chalkiness formation.

Grain chalkiness is an important index of rice appearance quality and is negatively associated with rice processing and eating quality. However, the genetic mechanism underlying chalkiness formation is largely unknown. To identify the genetic basis of chalkiness, 410 recombinant inbred lines (RILs) derived from two representative indica rice varieties, Shuhui498 (R498) and Yihui3551 (R3551), were used to discover quantitative trait loci (QTLs). The two parental lines and RILs were grown in three locations in China under three controlled fertilizer application levels. Analyses indicated that chalkiness was significantly affected by genotype, the environment, and the interaction between the two, and that heritability was high. Several QTLs were isolated, including the two stable QTLs qCGP6 and qCGP8. Fine mapping and candidate gene verification of qCGP6 showed that Wx may play a key role in chalkiness formation. Chromosomal segment substitution lines (CSSLs) and near-isogenic lines (NILs) carrying the Wxa or Wxin allele produced more chalky grain than the R498 parent. A similar result was also observed in the 3611 background. Notably, the effect of the Wx genotype on rice chalkiness was shown to be dependent on environmental conditions, and Wx alleles exhibited different sensitivities to shading treatment. Using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9), the Wxa promoter region was successfully edited; down-regulating Wx alleviates chalkiness formation in NILR498-Wxa. This study developed a new strategy for synergistic improvement of eating and appearance qualities in rice, and created a novel Wx allele with great potential in breeding applications.

Isolation and pathogenicity evaluation of Escherichia coli O157:H7 from common carp, Cyprinus carpio.

Escherichia coli O157:H7 is the primary serotype of enterohaemorrhagic E. coli (EHEC), which can cause diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. It is considered as a major health concern due to it being a zoonotic disease that is transmitted through food. In this study, a pathogenic bacterium was isolated from infected carp, which identified as E. coli O157:H7 named X21 through genetic sequencing, phylogenetic analysis, physiological and biochemical tests. In the experiment, crucian carp was used as a model to study the pathogenicity of the isolate, the pathological histological observations and cytokines expression of fish tissues were determined after bacterial challenge. The results showed that severe pathological damage observed in the liver, spleen, headkidney of fish infected with isolate X21. Besides, we found that accumulation of IgT+ B cells in the lamina propria of intestine, and up-regulation of SUCH-r, IL-1ß, IL-10, IL-11, MyD88, and TNF-α gene in various tissues. After challenged, the survivability of crucian carp infected with isolate X21 stands at a mere 14.27%. To our knowledge, this is the first report that E. coli O157:H7 infected the freshwater fish C. carpio, which indicates that this bacterium is a potential threat to public health and freshwater fish aquaculture.

Whether the Golgi protein 73 could be a diagnostic serological marker in hepatocellular carcinoma: a meta analysis.

BACKGROUND: The Value of Golgi protein 73 (GP73) in the diagnosis of Hepatocellular carcinoma (HCC) remains controversial, especially in its differentiation between HCC and cirrhosis. Besides, some papers showed that GP73 levels are correlated with liver fibrosis. This study conducts a meta-analysis to evaluate the value of GP73 in diagnosing HCC and differential diagnosing HCC from liver cirrhosis. METHODS: 36 studies with a sample size of 8314 cases concerning the accuracy of GP73 in the diagnosis of HCC were selected through a systematic review. Seven of these studies included a total of 438 HCC samples and 426 cirrhosis samples and calculated the sensitivity and specificity of GP73 for differential diagnosing HCC from cirrhosis. QUADAS (quality assessment of diagnostic accuracy studies) was used to evaluate the quality of literature. Statistical analyses were performed using StataSE16 software. RESULTS: The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and the area under the curve were 0.79(95%CI 0.74-0.83),0.85(95%CI 0.80-0.89),5.4(95%CI 3.8-7.5), 0.25(95%CI 0.20-0.31), 22(95%CI 13-35), and 0.88 for GP73 diagnosing HCC;0.74(95%CI 0.64-0.81),0.70(95%CI 0.49-0.85),2.40(95%CI 1.3-4.7),0.38(95%CI 0.23-0.61),6(95%CI 2-19), and 0.78 for GP73 differential diagnosing HCC from liver cirrhosis. CONCLUSION: The results suggest that GP73 has a high diagnostic value for HCC and a moderate value for differential diagnosis of HCC from liver cirrhosis.

Impacts and mechanisms of alternative mRNA splicing in cancer metabolism, immune response, and therapeutics.

Alternative pre-mRNA splicing (AS) provides the potential to produce diversity at RNA and protein levels. Disruptions in the regulation of pre-mRNA splicing can lead to diseases. With the development of transcriptome and genome sequencing technology, increasing diseases have been identified to be associated with abnormal splicing of mRNAs. In tumors, abnormal alternative splicing frequently plays critical roles in cancer pathogenesis and may be considered as new biomarkers and therapeutic targets for cancer intervention. Metabolic abnormalities and immune disorders are important hallmarks of cancer. AS produces multiple different isoforms and diversifies protein expression, which is utilized by the immune and metabolic reprogramming systems to expand gene functions. The abnormal splicing events contributed to tumor progression, partially due to effects on immune response and metabolic reprogramming. Herein, we reviewed the vital role of alternative splicing in regulating cancer metabolism and immune response. We discussed how alternative splicing regulates metabolic reprogramming of cancer cells and antitumor immune response, and the possible strategies to targeting alternative splicing pathways or splicing-regulated metabolic pathway in the context of anticancer immunotherapy. Further, we highlighted the challenges and discuss the perspectives for RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms.

Preeclampsia complicated with hypofibrinogenemia: 2 case reports and review of the literature.

BACKGROUND: Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by postpartum haemorrhage (PPH). CASE: Two women diagnosed as preeclampsia and hypofibrinogenemia developed severe PPH after undergoing Cesarean sections. Besides supplement with fibrinogen concentrate and supportive treatment, the second patient got administration of heparin after delivery and bleeding was stopped. The haemorrhage in case 1 didn't disappear until an hysterectomy. The two patients both recovered and were discharged soon. CONCLUSIONS: Severe preeclampsia patients with hypofibrinogenemia could suffer PPH. It's necessary to detect and master coagulation function. Heparin could be considered to balance hypercoagulation and hypocoagulation to avoid catastrophic haemorrhage and hysterectomy.

Wogonin regulates colonocyte metabolism via PPARγ to inhibit Enterobacteriaceae against dextran sulfate sodium-induced colitis in mice.

To investigate the potential effects and mechanism of wogonin on dextran sulfate sodium (DSS)-induced colitis, 70 male mice were administered wogonin (12.5, 25, 50 mg·kg-1 ·d-1 , i.g.) for 10 days, meanwhile, in order to induce colitis, the mice were free to drink 3% DSS for 6 days. We found that wogonin could obviously ameliorate DSS-induced colitis, including preventing colon shortening and inhibiting pathological damage. In addition, wogonin could increase the expression of PPARγ, which not only restores intestinal epithelial hypoxia but also inhibits iNOS protein to reduce intestinal nitrite levels. All these effects facilitated a reduction in the abundance of Enterobacteriaceae in DSS-induced colitis mice. Therefore, compared with the DSS group, the number of Enterobacteriaceae in the intestinal flora was significantly reduced after administration of wogonin or rosiglitazone by 16s rDNA technology. We also verified that wogonin could promote the expression of PPARγ mRNA and protein in Caco-2 cells, and this effect disappeared when PPARγ signal was inhibited. In conclusion, our study suggested that wogonin can activate the PPARγ signal of the Intestinal epithelium to ameliorate the Intestinal inflammation caused by Enterobacteriaceae bacteria expansion.

A novel nomogram and risk classification system for predicting overall survival in head and neck squamous cell cancer with distant metastasis at initial diagnosis.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is one of the most invasive cancer types globally, and distant metastasis (DM) is associated with a poor prognosis. The objective of this study was designed to construct a novel nomogram and risk classification system to predict overall survival (OS) in HNSCC patients presenting with DM at initial diagnosis. METHODS: HNSCC patients with initially diagnosed DM between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Firstly, all patients were randomly assigned to a training cohort and validation cohort (8:2), respectively. The Cox proportional hazards regression model was used to analyze the prognostic factors associated with OS. Then, the nomogram based on the prognostic factors and the predictive ability of the nomogram were assessed by the calibration curves, receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Finally, a risk classification system was established according to the nomogram scores. RESULTS: A total of 1240 patients initially diagnosed with HNSCC with DM were included, and the 6-, 12- and 18-month OS of HNSCC with DM were 62.7%, 40.8% and 30%, respectively. The independent prognostic factors for HNSCC patients with DM included age, marital status, primary site, T stage, N stage, bone metastasis, brain metastasis, liver metastasis, lung metastasis, surgery, radiotherapy and chemotherapy. Based on the independent prognostic factors, a nomogram was constructed to predict OS in HNSCC patients with DM. The C-index values of the nomogram were 0.713 in the training cohort and 0.674 in the validation cohort, respectively. The calibration curves and DCA also indicated the good predictability of the nomogram. Finally, a risk classification system was built and it revealed a statistically significant difference among the three groups of patients according to the nomogram scores. CONCLUSIONS: Factors associated with the overall survival of HNSCC patients with DM were found. According to the identified factors, we generated a nomogram and risk classification system to predict the OS of patients with initially diagnosed HNSCC with DM. The prognostic nomogram and risk classification system can help to assess survival time and provide guidance when making treatment decisions for HNSCC patients with DM.

Effects of couple-based dyadic interventions on breast cancer patients and their intimate partners: A systematic review and meta-analysis.

AIMS: To evaluate the effects of couple-based dyadic interventions on breast cancer patients and their intimate partners and compare the effects between interventions with different durations (<3 months; =3 months; >3 months). DESIGN: A systematic review and meta-analysis. DATA SOURCES: Six English databases, PubMed, Embase, Web of Science Core Collection, the Cochrane Library, Medline, PsycINFO, and three Chinese databases, China National Knowledge Infrastructure (CNKI), WanFang, and Weipu (VIP), from database inception to 19 February 2022. REVIEW METHODS: The quality of the included RCTs was evaluated using the Cochrane risk-of-bias tool and the data analysis was performed by using RevMan 5.4 and Stata 15. The outcomes were categorized into five aspects: dyadic relationship, overall quality of life (QOL), physical health, psychological health and social adjustment. RESULTS: Nineteen RCTs were included. For patients' overall effects, couple-based dyadic interventions can improve sexual frequency, psychological health (anxiety; depression; well-being; body image) and social adjustment (family function-cohesion; social function-total). In the subgroup analysis, it can adjust patients' relationship satisfaction (>3 months), sexual frequency (>3 months), depression (<3 months and >3 months), well-being (>3 months), and body image (3 months). For intimate partners, no statistically significant overall effects were found, and all results in the subgroup analyses showed no statistical significance. CONCLUSIONS: The results revealed the different effects of couple-based dyadic interventions on dyads. It also suggested that tailored intervention duration should be a focus in future studies to obtain the potential actor-partner benefits. IMPACT: This study revealed that the overall effects of the couple-based dyadic interventions include enhancing patients' sexual frequency, psychological health and social adjustment. Clinical practitioners should consider the intimate partners' outcomes and conduct couple-based dyadic interventions that contain more tailored elements to achieve better effects. NO PATIENT OR PUBLIC CONTRIBUTION: Registration: The systematic review and meta-analysis of RCTs has been registered in PROSPERO (Number: CRD 42021286679).

Effect of Drying-Rewetting cycles on the metal adsorption and tolerance of natural biofilms.

Drying-rewetting (D-RW) cycles can induce changes in biofilms by forcing the microbial community to tolerate and adapt to environmental pressure. Existing studies have mostly focused on the impact of D-RW cycles on the microbial community structure, and little attention has been paid to how D-RW cycles may change the biofilm tolerance and adsorption of heavy metals. We experimentally evaluated the effect of repeated D-RW cycles on the Cd2+ and Pb2+ adsorption and tolerance of biofilms. The equilibrium adsorption capacity of the biofilm decreased as the number of D-RW cycles was increased, which was attributed to a change in affinity between the biofilm and metal ions. For a binary metal system, the D-RW cycles affected the competitive adsorption of Cd2+ and Pb2+ by the biofilm. A synergistic effect was observed with one and three D-RW cycles, while an antagonistic effect was observed for the control film and five D-RW cycles. The tolerance of the biofilm to Cd2+ and Pb2+ increased with the number of D-RW cycles. The stress from the D-RW cycles may have increased the relative abundance of drought-tolerant bacteria, which altered the biofilm functions and thus indirectly affected the heavy metal adsorption capacity.

Effect of illness perception on predicting breast cancer-related lymphedema risk management behaviours among breast cancer patients: A comparison between dimensions and profiles.

AIM: This study aimed to explore the utility of latent profile analysis of illness perception, in comparison to treating illness perception as several dimensions, to predict breast cancer-related lymphedema risk management behaviours among Chinese breast cancer patients. METHODS: This is a 3-month longitudinal study. From August 2019 to January 2021, patients who recently underwent breast cancer surgery including axillary lymphadenectomy were recruited. Illness perception and risk management behaviours were measured by breast cancer-related lymphedema specific questionnaires before discharge following surgery (n = 268) and at 3 months postsurgery (n = 213), respectively. RESULTS: Treating illness perception as several dimensions, 'illness coherence' and 'timeline (cyclical)' dimensions were found to be significantly associated with breast cancer-related lymphedema risk management behaviours. Using the latent profile analysis, two illness perception profiles were identified and significant differences were revealed in breast cancer-related lymphedema risk management behaviours between them. Overall, illness perception profiles explained smaller amounts of variability in breast cancer-related lymphedema risk management behaviours than illness perception dimensions. CONCLUSION: Future studies could combine these two different perspectives of illness perception regarding breast cancer-related lymphedema into the design of interventions to improve breast cancer-related lymphedema risk management behaviours.

Self-management and illness perception among cervical cancer patients: A cross-sectional study.

AIM: This study aimed to describe self-management among cervical cancer patients and to elucidate the relationship between illness perception and self-management in patients with cervical cancer. METHODS: This was a cross-sectional study. A convenience sample of 220 cervical cancer patients was recruited from the gynaecology outpatient department of a cancer hospital. Data were collected from September 2018 to February 2019. Self-management and illness perception were assessed using the Cancer Self-Management Assessment Scale and the Revised Illness Perception Questionnaire for cervical cancer, respectively. Data were analysed using Pearson correlation analysis, univariate analysis and hierarchical linear regression analysis. RESULTS: The mean score of self-management was 3.87 ± 0.53, and daily life management showed the highest score (4.18 ± 0.58), while symptom management was the lowest (3.11 ± 082). Hierarchical linear regression analysis showed that family monthly income per person, types of surgery and personal control were factors that significantly influenced self-management. CONCLUSIONS: The results demonstrate that self-management among patients with cervical cancer needs to be improved. The significant influence of illness perception offers an opportunity for nurses to improve self-management behaviours of patients with cervical cancer.

The function of prohibitins in mitochondria and the clinical potentials.

Prohibitins (PHBs) are a class of highly evolutionarily conserved proteins that widely distribute in prokaryotes and eukaryotes. PHBs function in cell growth and proliferation or differentiation, regulating metabolism and signaling pathways. PHBs have different subcellular localization in eukaryotes, but they are mainly located in mitochondria. In the mitochondria, PHBs stabilize the structure of the mitochondrial membrane and regulate mitochondrial autophagy, mitochondrial dynamics, mitochondrial biogenesis and quality control, and mitochondrial unfolded protein response. PHBs has shown to be associated with many diseases, such as mitochondria diseases, cancers, infectious diseases, and so on. Some molecule targets of PHBs can interfere with the occurrence and development of diseases. Therefore, this review clarifies the functions of PHBs in mitochondria, and provides a summary of the potential values in clinics.

Subcellular-Targeted Near-Infrared-Responsive Nanomedicine with Synergistic Chemo-photothermal Therapy against Multidrug Resistant Cancer.

Multidrug resistance (MDR) is a major obstacle to effective cancer treatment. Therefore, developing effective approaches for overcoming the limitation of MDR in cancer therapy is very essential. Chemotherapy combined with photothermal therapy (PTT) is a potential therapeutic option against MDR. Herein, we developed a subcellular-targeted near-infrared (NIR)-responsive nanomedicine (Fe3O4@PDA-TPP/S2-PEG-hyd-DOX, abbreviated as Fe3O4-ATSPD) as a new photothermal agent with improved photothermal stability and efficiency. This system demonstrates high stability in blood circulation and can be accumulated at the tumor site by magnetic targeting enhanced permeability and retention effect (EPR). Near-infrared (NIR) irradiation at the tumor site generates a photothermal effect from the photosensitizer Fe3O4@PDA, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the conjugated drugs released under low pH condition in endosomes or lysosomes cause nucleus DNA damage and cell apoptosis. This subcellular-targeted NIR-responsive nanomedicine with efficient integration of diagnosis and therapy could significantly enhance MDR cancer treatment by combination of chemotherapy and PTT.

Characterization and function of mandarin fish c-Myc during viral infection process.

c-Myc is a transcription factor and master regulator of cellular metabolism, and plays a critical role in virus replication by regulating glutamine metabolism. In this study, the open-reading frame (ORF) of c-Myc, designated as Sc-c-Myc, was cloned and sequenced. Multiple alignment of the amino acid sequence showed that the conserved domain of Sc-c-Myc, including the helix-loop-helix-zipper (bHLHzip) domain and Myc N-terminal region, shared high identities with other homologues from different species. Sc-c-Myc mRNA was widely expressed in the examined tissues of mandarin fish, and the higher mRNA levels was expressed in hind kidney. Moreover, mRNA and protein level of Sc-c-Myc was significantly increased in the Chinese perch brain (CPB) cells and spleen of mandarin fish post infection with infectious spleen and kidney necrosis virus (ISKNV) and Siniperca chuatsi rhabdovirus (SCRV). Sc-c-Myc overexpression promoted ISKNV and SCRV replication, on the contrary, knocking down Sc-c-Myc restrained ISKNV and SCRV replication. These results indicated that Sc-c-Myc involved in ISKNV and SCRV replication and proliferation, providing a potential target for the development of new therapic strategy against ISKNV and SCRV.