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Human papillomavirus (HPV) is a class of envelope-free double-stranded DNA virus. HPV infection has been strongly associated with the development of many malignancies, such as cervical, anal and oral cancers. The viral oncoproteins E6 and E7 perform central roles on HPV-induced carcinogenic processes. During tumor development, it usually goes along with the activation of abnormal signaling pathways. E6 and E7 induces changes in cell cycle, proliferation, invasion, metastasis and other biological behaviors by affecting downstream tumor-related signaling pathways, thus promoting malignant transformation of cells and ultimately leading to tumorigenesis and progression. Here, we summarized that E6 and E7 proteins promote HPV-associated tumorigenesis and development by regulating the activation of various tumor-related signaling pathways, for example, the Wnt/β-catenin, PI3K/Akt, and NF-kB signaling pathway. We also discussed the importance of HPV-encoded E6 and E7 and their regulated tumor-related signaling pathways for the diagnosis and effective treatment of HPV-associated tumors.

The survival rates of patients with nasopharyngeal carcinoma (NPC) have improved significantly, but there is no consensus on whether they can be considered cured. We aimed to determine whether a statistical cure could be achieved for patients with NPC in the contemporary therapeutic landscape.

Cancer metabolic reprogramming enhances its malignant behaviors and drug resistance, which is regulated by POU domain transcription factors. This study explored the effect of POU domain class 2 transcription factor 1 (POU2F1) on metabolic reprogramming in colon cancer. The POU2F1 expression was analyzed in GEO dataset, TCGA cohorts and human colon cancer tissues by bioinformatics and immunohistochemistry. The effects of altered POU2F1 expression on proliferation, glucose metabolism and oxaliplatin sensitivity of colon cancer cells were tested. The impacts of POU2F1 on aldolase A (ALDOA) expression and malignant behaviors of colon cancer cells were examined. We found that up-regulated POU2F1 expression was associated with worse prognosis and oxaliplatin resistance in colon cancer. POU2F1 enhanced the proliferation, aerobic glycolysis and the pentose phosphate pathway (PPP) activity, but reduced oxidative stress and apoptosis in colon cancer cells, dependent on up-regulating ALDOA expression. Mechanistically, POU2F1 directly bound to the ALDOA promoter to enhance the ALDOA promoter activity in colon cancer cells. Moreover, activation of the POU2F1-ALDOA axis decreased the sensitivity to oxaliplatin in colon cancer cells. These data indicate that the POU2F1-ALDOA axis promotes the progression and oxaliplatin resistance by enhancing metabolic reprogramming in colon cancer. Our findings suggest that the POU2F1-ALDOA axis may be new therapeutic targets to overcome oxaliplatin resistance in colon cancer.

Seeking catalysts with high electrocatalytic activity for ambient-condition N2reduction reaction (NRR) remains an ongoing challenge due to the chemical inertness of N2. Herein, defect-rich WS2nanosheets (WS2−x) were designed as an efficient electrocatalyst for NRR, which were prepared viavulcanizing the oxygen-vacancy-rich tungsten oxide in a vacuum tube. The sulfur defects were conducive to the adsorption and activation of N2. In neutral electrolyte of 0.1 mol L−1Na2SO4at −0.60 V vs.reversible hydrogen electrode, such WS2−xoffered a high Faradaic efficiency of 12.1% with a NH3generation rate of 16.38 µg h−1mgcat−1.

MXene-based materials were suggested to be promising candidates for electrocatalytic nitrogen reduction due to their exceptional properties

Covalent conjugates of pumpkin seed protein isolate (PSPI) and different polyphenols (epigallocatechin gallate (EGCG), chlorogenic acid (CA) and gallic acid (GA)) were prepared at pH 9.0 to develop covalent microparticles to protect the stability of polyphenols under storage and digestive conditions. The results for polyphenol-bound equivalents, free amino group contents, sulfhydryl contents and Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis (SDS-PAGE) indicated that polyphenols were covalently bonded with PSPI, while the secondary structure of conjugates became more regular and stable compared with PSPI alone due to the covalent interactions. EGCG-PSPI conjugates displayed the highest polyphenol-bound equivalents (204.75 nmol/mg) and most stable structure compared with CA-PSPI and GA-PSPI because of the eight active phenolic hydroxyl groups within EGCG, which provided more sites for covalent and non-covalent interactions. Accordingly, EGCG-PSPI microparticles (5–8 μm) were fabricated by cluster aggregation of nano- and micro-sized particles through pH shifting treatment. Compared with the EGCG control, EGCG-PSPI microparticles efficiently increased the retention rate of free radical scavenging activity to 47.47%, 22.04% and 39.94% under light, freeze-thaw cycle storage conditions and simulated intestinal fluids, respectively. Therefore, polyphenol-PSPI covalent conjugate microparticles had great potential to be used as efficient carriers for stabilizing the DPPH radical scavenging ability of polyphenols under illumination storage, freeze-thaw and digestive conditions.

Long-palate, lung and nasal epithelium clone 1 (LPLUNC1) is a tumour suppressor gene in nasopharyngeal carcinoma (NPC), and low expression of LPLUNC1 is associated with poor prognosis. Our previous study showed that LPLUNC1 upregulates Prohibitin 1 (PHB1), a pleiotropic protein that functions as a tumour suppressor gene in various cancers. Low expression of PHB1 was also found to be associated with the poor prognosis of NPC patients. However, the mechanisms by which LPLUNC1 upregulates PHB1 and the potential role of PHB1 in NPC are unclear. Here, we found that LPLUNC1 stabilised PHB1 by inhibiting PHB1 ubiquitination, which is mediated by E3 ligase TRIM21. LPLUNC1 competitively impaired the binding of PHB1 to TRIM21 due to its stronger binding affinity to PHB1, suppressing the ubiquitination of PHB1. Therefore, our study indicates that PHB1 acted as a tumour suppressor gene by inhibiting NF-κB activity. Depletion of PHB1 significantly attenuated the anti-tumour effects of LPLUNC1 in NPC cells, and the inhibitory effect of LPLUNC1 on NF-κB activity was thus reversed. Together, our findings revealed a novel mechanism underlying the anticancer effect of LPLUNC1 and clarified that PHB1 may represent a novel, promising candidate tumour suppressor gene in NPC, with potential therapeutic target value.

As a typical tumor microenvironment‐responsive therapy, chemodynamic therapy (CDT), producing hydroxyl radicals (•OH) to eliminate tumor cells, has demonstrated great promise. Nevertheless, there are still major challenges: •OH generated from endogenous H2O2is usually insufficient; the CDT effect is strongly dependent on the pre‐reaction with glutathione. Addressing the challenges, Au@MnSe2core–shell nanoagent for synergetic chemodynamic‐photothermo‐photocatalytic therapy combined with tetramodal imaging, including magnetic resonance imaging, computed tomography, photoacoustic, and infrared thermal imaging is reported. Distinct from the reported glutathione‐depleting agents, Mn2+in MnSe2allows immediate generation of •OH, independent of pre‐reaction. Meanwhile, Mn3+consumes glutathione by its conversion to Mn2+. The Au‐MnSe2combination promotes photothermal conversion and photocatalytic reaction, resulting in largely enhanced •OH generation from endogenous H2O2and significant hyperthermia. Meanwhile, immune response is effectively activated: the intratumoral expression of programmed cell death‐1 and proinflammatory cytokines increase to 4–7 folds; the cytotoxic and helper T lymphocytes cells in the tumor area increase to more than 2.5‐folds; an evident, temporary systemic immunostimulatory effect is demonstrated. High tumor inhibition rate (≈97.3%) and greatly prolonged survival are obtained. This highly‐integrated design coordinating three different therapies with four different imaging modals provide new possibilities for high‐performance theranostic nanoagents. Employing the Au@MnSe2core–shell nanoagent, synergetic chemodynamic‐photothermo‐photocatalytic therapy with tetramodal imaging is realized. Distinct from the reported glutathione‐depleting agents, Mn2+in MnSe2allows immediate generation of •OH, independent of pre‐reaction. Besides the high •OH generation efficiency from endogenous H2O2and hyperthermia, significant immune response is activated. High tumor inhibition rate and greatly prolonged survival are obtained.