Nomogram Predicts Prognostic Factors for Head and Neck Cutaneous Melanoma: A Population-Based Analysis.

BACKGROUND: The head and neck cutaneous melanoma (HNCM) accounts for 20% of newly diagnosed melanoma. Research on prognostic models for their survival yet remains largely unexplored. This study employed a nomogram approach to develop and validate a predictive model for both overall survival (OS) and disease-specific survival (DSS) in patients with HNCM. METHODS: This study analyzed the HNCM patients diagnosed between 2004 and 2014 from Surveillance, Epidemiology, and End Results database. To identify independent prognostic factors for HNCM, we integrated results from univariate Cox regression analysis, random survival forests, and LASSO regression with cross-validation. A nomogram was designed and validated based on the identified characteristics to predict the 3-, 5-, and 8-year OS and DSS of patients with HNCM. RESULTS: Age, Stage, Ulceration, Thickness, Chemotherapy, lymph node metastasis, and Radiation were identified as independent prognostic factors. The nomogram achieved a satisfactory performance with C-indices of 0.824(DSS) and 0.757(OS) in the training cohort and 0.827(DSS) and 0.749(OS) in the validation cohort, respectively. The area under the curves for the OS at 3, 5, and 8 years were 0.789, 0.788, and 0.794 for the training cohort, and 0.778, 0.776, and 0.795 for the validation cohort, respectively. For DSS, the area under the curves at 3, 5, and 8 years were 0.859, 0.842, and 0.828 in the training cohort, and 0.864, 0.844, and 0.834 in the validation cohort, respectively. The calibration curve showed that there was a strong correlation between the observed outcomes and the predicted survival probability. CONCLUSIONS: This study established and validated predictive nomograms for HNCM patients with robust predictive performance.

VirGrapher: a graph-based viral identifier for long sequences from metagenomes.

Viruses are the most abundant biological entities on earth and are important components of microbial communities. A metagenome contains all microorganisms from an environmental sample. Correctly identifying viruses from these mixed sequences is critical in viral analyses. It is common to identify long viral sequences, which has already been passed thought pipelines of assembly and binning. Existing deep learning-based methods divide these long sequences into short subsequences and identify them separately. This makes the relationships between them be omitted, leading to poor performance on identifying long viral sequences. In this paper, VirGrapher is proposed to improve the identification performance of long viral sequences by constructing relationships among short subsequences from long ones. VirGrapher see a long sequence as a graph and uses a Graph Convolutional Network (GCN) model to learn multilayer connections between nodes from sequences after a GCN-based node embedding model. VirGrapher achieves a better AUC value and accuracy on validation set, which is better than three benchmark methods.

Effects of hTERT transfection on the telomere and telomerase of Periplaneta americana cells in vitro.

Telomere and telomerase are crucial factors in cell division and chromosome stability. Telomerase activity in most cells depends on the transcription control by the telomerase reverse transcriptase (TERT). The introduction of an exogenous human TERT (hTERT) in cultured cells could enhance telomerase activity and elongate the lifespan of various cells. Telomere elongation mechanisms vary between insects and are complex and unusual. Whether the use of exogenous hTERT can immortalize primary insect cells remains to be investigated. In this study, we used a recombinant virus expressing hTERT to infect primary cultured cells of Periplaneta americana and evaluated its effects on insect cell immortalization. We found that hTERT was successfully expressed and promoted the growth of P. americana cells, shortening their doubling time. This was due to the ability of hTERT to increase the activity of telomerase in P. americana cells, thus prolonging the telomeres. Our study lays the foundation for understanding the mechanisms of telomere elongation in P. americana, and suggests that the introduction of hTERT into insect cells could be an efficient way to establish certain insect cell lines.

Integrated multifunctional nanoplatform for fluorescence detection and inactivation of Staphylococcus aureus.

Foodborne illness caused by Staphylococcus aureus (S. aureus) has posed a significant threat to human health. Herein, an integrated multifunctional nanoplatform was developed for fluorescence detection and inactivation of S. aureus based on cascade signal amplification coupled with single strand DNA-template copper nanoparticles (ssDNA-Cu NPs). Benefiting from reasonable design, one-step cascade signal amplification was achieved through strand displacement amplification combined with rolling circle amplification, followed by in-situ generation of copper nanoparticles. S. aureus detection could be performed through naked eye observation and microplate reader measurement of the red fluorescence signal. The multifunctional nanoplatform had satisfactory specificity and sensitivity, achieving 5.2 CFU mL-1 detection limit and successful detection of 7.3 CFU of S. aureus in spiked egg after < 5 h of enrichment. Moreover, ssDNA-Cu NPs could eliminate S. aureus to avoid secondary bacterial contamination without further treatment. Therefore, this multifunctional nanoplatform has potential application in food safety dtection.

Potential Therapeutic Effects of Policosanol from Insect Wax on Caenorhabditis elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The standard treatments for PD focus on symptom relief rather than attempting to address the underlying degenerative processes completely. This study aimed to evaluate the potential therapeutic effects of policosanol derived from insect wax (PIW) by investigating improvements in disease symptoms represented in Caenorhabditis elegans models of PD. For our assessments, we used the following three models: NL5901, which is a transgenic model for α-synuclein aggregation; wild-type N2 induced with 6-hydroxydopamine (6-OHDA); and 6-OHDA-induced BZ555 as a model for loss of dopaminergic neurons (DNs). Specifically, we examined the effects of PIW treatment on α-synuclein aggregation, the loss of DNs, lipid abundance, and the lifespan of treated organisms. Further, we examined treatment-related changes in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), adenosine triphosphate (ATP), glutathione S-transferase (GST), and superoxide dismutase (SOD), as well as the mRNA production profiles of relevant genes. A 10 µg/mL dose of PIW reduced the aggregation of α-synuclein in NL5901 and suppressed the loss of DNs in 6-OHDA-induced BZ555. Overall, PIW treatment decreased ROS and MDA levels, restored lipid abundance, and prolonged the lifespans of worms in all the three models, which may be associated with changes in the expression profiles of genes related to cell survival and oxidative stress response pathways. Our findings show that PIW alleviated the symptoms of PD in these models, possibly by regulating the stress responses initiated by injuries such as α-synuclein aggregation or 6-OHDA treatment.

Improving Effect of the Policosanol from Ericerus pela Wax on Learning and Memory Impairment Caused by Scopolamine in Mice.

Policosanol (PC) is a mixture of long-chain fatty alcohols that exhibits multiple biological activities, such as reducing blood lipid and cholesterol levels, lowering blood pressure, and extenuating liver inflammation. To assess PC's impact on cognitive behavior and function, PC was prepared from Ericerus pela wax using a reduction method and analyzed using gas chromatography (GC). A total of 60 mice were randomly divided into six groups of 10 animals each: control (0.5% CMC-Na solution, i.g.), model (0.5% CMC-Na solution, i.g.), donepezil (3 mg/kg, i.g.), PC low- (2 g/kg, i.g.), medium (4 g/kg, i.g.), and high- (6 g/kg, i.g.) dose groups. All the groups were administered daily for 28 consecutive days. There were four parameters­escape latency, crossings of platform, swimming distance, and time spent in the target quadrant­that were recorded to evaluate the cognitive performance of mice in the Morris Water Maze (MWM). After MWM testing, the levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) that were present in brain tissue were determined using assay kits. The GC data showed that PC consisted of four major components: tetracosanol (14.40%), hexacosanol (48.97%), octacosanol (25.40%), and triacontanol (4.80%). In the MWM test, PC significantly decreased the escape latency (p < 0.05) and increased the crossings of the platform (p < 0.05) and swimming distance (p < 0.05) and time in the target quadrant (p < 0.05) in rodents compared to that in the model group. Moreover, PC increased the levels of ACh, SOD, and GSH; inhibited AChE; and reduced MDA in the brain tissue of the tested animals. This is the first report to evaluate the efficacy of PC for cognitive behavior and function in animals. Our findings demonstrate that PC from E. pela wax is likely to exert an enhancing effect on learning and memory by promoting the cholinergic system and attenuating oxidative stress, which will provide a new insight into the efficacy of PC and expand its application in the food, nutraceutical, and beverage industries.

An embryonic cell line from the American cockroach Periplaneta americana L. (Blattaria: Blattidae) exhibits susceptibility to AcMNPV.

Although the baculovirus expression vector system (BEVS) is widely used in the production of recombinant proteins, only a few lepidopteran insect cell lines have been successfully used so far. This study aimed at evaluating the characteristics of an embryonic cell line from the American cockroach Periplaneta americana L., RIRI-PA1, and determining whether it could be used in recombinant protein expression. Wild type Autographa californica multiple nucleopolyhedrovirus (AcMNPV-wt) and green fluorescent protein (GFP)-replicating recombinant baculoviruses (AcMNPV-GFP) were used to infect RIRI-PA1 respectively, demonstrating that RIRI-PA1 cells could be infected by AcMNPV and express recombinant proteins. Within 24 h of infection with AcMNPV-GFP, the GFP expression was higher than that in Sf21 cells. Furthermore, the infection of RIRI-PA1 cells increased gradually (multiplicity of infection, 10) within 24 h, while in Sf21 cells, the infection only began to increase within 48 h. However, after exposure for 96-168 h, the virus progeny and recombinant protein production of RIRI-PA1 cells was lower than those of Sf21 cells. Western blotting revealed that RIRI-PA1 cells could express recombinant GFP, and the protein expression level positively correlated with the multiplicity of infection. In conclusion, this is the first report that a cell line from P. americana has shown susceptibility to infection from a baculovirus and likewise express recombinant protein. Although the yield of recombinant GFP was not as high as that of Sf21 cells, the results nonetheless showed that RIRI-PA1 had an infection rate advantage in the short term (within 24 h of infection), which is of great value for further development and utilization.

Purification of polyphenols from Phyllanthus emblica L. pomace using macroporous resins: Antioxidant activity and potential anti-Alzheimer's effects.

Phyllanthus emblica L. pomace is a waste residue obtained following juicing that contains many polyphenols. In this study, NKA-II resin was selected as the optimal macroporous resin for separation and employed to separate the crude polyphenol extract of P. emblica pomace. The separation conditions were optimized, and the polyphenol content, polyphenol components, antioxidant activity, and potential anti-Alzheimer's effects of the extract were measured before and after purification. Results showed that the polyphenol content of the purified extract was 656.85 mg/g, which was 2.1 times higher than that of the nonpurified form. Further, the polyphenol components of the pomace, which was like that of the fruit, did not vary after purification. The antioxidant activity of the purified extract was also significantly improved. Moreover, purified extract significantly reduced the paralysis rate of the transgenic Caenorhabditis elegans model of Alzheimer's disease, and the mechanism was related to maintenance of redox homeostasis. PRACTICAL APPLICATION: The polyphenol content and antioxidant activity of purified polyphenol from Phyllanthus emblica L. pomace extracts were significantly improved using optimal separation methods with NKA-II macroporous resin and 70% aqueous ethanol as the eluent in this study. Moreover, purified polyphenols showed potential effects in alleviating Alzheimer's disease. These results suggest that polyphenols separated from P. emblica pomace are valuable for further research and development, and the utilization rate of P. emblica fruit is improved due to the further development of P. emblica pomace.

Angiogenesis effects of 4-methoxy benzyl alcohol on cerebral ischemia-reperfusion injury via regulation of VEGF-Ang/Tie2 balance.

Angiogenesis facilitates the formation of microvascular networks and promotes neurological deficit recovery after cerebral ischemia-reperfusion injury (CIRI). This study investigated the angiogenesis effects of 4-methoxy benzyl alcohol (4-MA) on CIRI. The angiogenesis effects of 4-MA and the potential underlying mechanisms were assessed based on a middle cerebral artery occlusion/reperfusion (MCAO/R) rat model and a hind limb ischemic (HLI) mouse model. Immunofluorescence was conducted to detect microvessel density, and Western blotting and polymerase chain reaction were performed to determine the expression of angiogenesis-promoting factors. In addition, we investigated whether the angiogenesis effects of 4-MA caused damage to the blood-brain barrier (BBB). After treatment with 4-MA (20 mg/kg) for 7 days, the neurological deficits recovered and microvessel density in the cerebral cortex increased in the MCAO/R rats. Additionally, 4-MA also regulated the expression of angiogenesis factors, with an increase in vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression and a decrease in angiopoietin 1 (Ang-1), Ang-2, and Tie-2 expression in both MCAO/R rats and HLI mice. Moreover, 4-MA increased the expression of angiogenesis-promoting factors without exacerbating BBB cascade damage in MCAO/R rats. Our results indicated that 4-MA may contribute to the formation of microvascular networks, thus promoting neurological deficit recovery after CIRI.

Effect of policosanol from insect wax on amyloid ß-peptide-induced toxicity in a transgenic Caenorhabditis elegans model of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD), an age-related neurodegenerative disorder and a serious public health concern, is mainly caused by ß-amyloid (Aß)-induced toxicity. Currently, a limited number of drugs are effective against AD, and only a few are used for its treatment. According to traditional Chinese medicine, white wax is mainly composed of policosanol, hexacosanol, and octacosanol. Policosanol has been shown to reduce lipid levels in blood and alleviate the symptoms associated with diabetic complications and neurodegenerative disorders, such as Parkinson's disease and AD. However, the efficacy of policosanol depends on the purity and composition of the preparation, and the therapeutic efficacy of policosanol derived from insect wax (PIW) in AD is unknown. METHODS: Here, we identified the main components of PIW and investigated the effects of PIW on Aß-induced toxicity and life-span in a transgenic Caenorhabditis elegans model of AD, CL4176. Furthermore, we estimated the expression of amyloid precursor-like protein (apl-1) and the genes involved in various pathways associated with longevity and alleviation of AD-related symptoms in PIW-fed CL4176. RESULTS: PIW mainly consists of tetracosanol, hexacosanol, octacosanol, and triacontanol; it could decrease the Aß-induced paralysis rate from 86.87 to 66.97% (P < 0.01) and extend the life-span from 6.2 d to 7.8 d (P < 0.001) in CL4176 worms. Furthermore, PIW downregulated apl-1, a gene known to be associated with the levels of Aß deposits in C. elegans. Additionally, our results showed that PIW modulated the expression of genes associated with longevity-related pathways such as heat shock response, anti-oxidative stress, and glutamine cysteine synthetase. CONCLUSION: Our findings suggest that PIW may be a potential therapeutic agent for the prevention and treatment of AD. However, its effects on murine models and patients with AD need to be explored further.