Dense Amorphous Passivation Layer Formed on Aluminum Alloy Surfaces by Femtosecond Laser-Assisted Oxygen-Rich Doping.

Aluminum (Al) alloy surfaces are prone to serious corrosion in humid and salt-laden environments, which promotes the development of numerous protective approaches. Although the amorphous state is more conducive to improve corrosion resistance compared with the crystalline state, it still faces coating design problems like insufficient adhesive strength and flaking-off tendency. Here, we propose a strategy of femtosecond laser-assisted oxygen-rich doping to in situ create a dense high-quality passivation layer on Al alloy surfaces. With respect to the femtosecond laser processing in traditional air ambience, the material surface modifications within the oxygen-rich environment demonstrate some distinctiveness. For the ridge area of the laser ablation grooves, the oxidation surface is separated into two layers: the outer region presents a loose and porous appearance similar to the observations in the air ambience, while the inner region exhibits complete and homogeneous oxidation, especially associated with the continuous distribution of the amorphous substance, in sharp contrast to the nanoscale discrete amorphous formation in the air case. Simultaneously, the high degree of material oxidization with the amorphous phase is also developed on the wallside area of the groove valleys, which is much different from the incomplete oxidation in the air ambience. As a result, the measured corrosion current decreases by 49 times to a value of Icorr = 1.19 × 10-10 A/cm2 relative to the laser treatment in the air environment. Such a method offers the prospect for elevating the anticorrosion performance of metal surfaces.

Cyclic anthraquinone derivatives, unique G-quadruplex binders, selectively induce cancer cell apoptosis and inhibit tumor growth.

Cyclic anthraquinone derivatives (cAQs), which link two side chains of 1,5-disubstituted anthraquinone as a threading DNA intercalator, have been developed as G-quartet (G4) DNA-specific ligands. Among the cAQs, cAQ-mBen linked through the 1,3-position of benzene had the strongest affinity for G4 recognition and stabilization in vitro and was confirmed to bind to the G4 structure in vivo, selectively inhibiting cancer cell proliferation in correlation with telomerase expression levels and triggering cell apoptosis. RNA-sequencing analysis further indicated that differentially expressed genes regulated by cAQ-mBen were profiled with more potential quadruplex-forming sequences. In the treatment of the tumor-bearing mouse model, cAQ-mBen could effectively reduce tumor tissue and had less adverse effects on healthy tissue. These results suggest that cAQ-mBen can be a potential cancer therapeutic agent as a G4 binder.

A Se-enriched Grifola frondosa polysaccharide induces macrophage activation by TLR4-mediated MAPK signaling pathway.

Se-polysaccharide (Se-GFP-22) from Se-enriched Grifola frondosa has double and cooperative activities of polysaccharide and Se. To delineate the underlying mechanism and signaling cascade involved in immune-stimulatory property of Se-GFP-22, the production of cellular mediators and key proteins in signaling pathway was examined. Results showed that Se-GFP-22 exhibited no cytotoxic and had a high capacity to promote macrophage phagocytosis, up-regulate interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and nitric oxide (NO) productions, as well as the relative messenger RNA (mRNA) expressions. In Se-GFP-22-induced macrophages, intracellular superoxide dismutase (SOD) activity was significantly increased to protect cells from oxidative injury. However, Se-GFP-22 induced macrophage activation was suppressed when the toll-like receptor 4 (TLR4) signaling pathway was blocked by a specific TLR4 inhibitor. According to the western blot analysis and the use of specific inhibitors against the mitogen-activated protein kinases (MAPK) signaling pathway, we speculated that Se-GFP-22 activated RAW264.7 macrophages through the TLR4-mediated MAPK signaling pathway. This study provides a molecular basis for the potential of Se-GFP-22 as a novel immune-stimulatory agent.

Study on the Effect of Hope Theory Combined with Psychological Intervention on the Improvement of Prognosis.

In order to evaluate the effect of the hope theory combined with psychological intervention on patients with intracranial aneurysms after surgical treatment, a total of 98 patients with intracranial aneurysm surgery admitted to our hospital from March 2019 to January 2021 were analyzed. According to the random number table method, all patients are divided into two groups: the traditional group and the experimental group. After intracranial aneurysm surgery, the patients of the traditional group and of the joint group are treated with conventional nursing and hope theory combined with psychological intervention nursing mode, respectively. The results demonstrate that the hope theory combined with psychological intervention can improve the level of postoperative patients with intracranial aneurysm life hope, self-efficacy, and postoperative quality of life.

Identification of novel saltiness-enhancing peptides from yeast extract and their mechanism of action for transmembrane channel-like 4 (TMC4) protein through experimental and integrated computational modeling.

Excessive consumption of sodium salt is one of the important inducers of cardiovascular and cerebrovascular diseases. The reduction of physical labor and attention to health make research on low-sodium salt imminent. Ultrafiltration, gel filtration, preparative high-performance liquid chromatography, and liquid chromatography with tandem mass spectrometry were employed for further purification and identification of the salty enhancing peptides in yeast extracts. Moreover, human transmembrane channel-like 4 (TMC4) was constructed and evaluated by computer-based methods, and salt-enhancing peptides were identified based on its allosteric sites. PN, NSE, NE and SPE were further determined to be salty enhancing peptides through sensory evaluation, and their taste mechanism was investigated. The results presented here suggest that silicon screening focused on TMC4 allosteric sites and sensory evaluation experiments can greatly increase the discoverability and identifiability of salty enhancer peptides, and this strategy is the first to be applied to the development of salty enhancer peptides.

Fish oil-containing lipid emulsions prevention on parenteral nutrition-associated cholestasis in very low birth weight infants: a meta-analysis.

BACKGROUND: The effect of fish oil-containing lipid emulsions on preventing parenteral nutrition-associated cholestasis (PNAC) in very low birth weight (VLBW) infants is not known. Thus, we conducted a meta-analysis to identify any prevention effect. METHODS: PubMed, EMBASE, and CENTRAL were searched up to 26 January 2021 for studies related to the preventive effect of fish oil-containing lipid emulsions and fish oil-free lipid emulsions on cholestasis in VLBW infants. Revman 5.3 was used to synthesize the results. A fixed-effect model was used to summarize the data when the heterogeneity was non-significant (I2 < 50%), and a random-effects model was used when the heterogeneity was significant (I2 > 50%). RESULTS: Of 728 articles, 11 randomized controlled trials met the inclusion criteria. The meta-analysis indicated that fish oil-containing lipid emulsion reduced the occurrence of PNAC significantly with risk ratio (RR) = 0.53, 95% confidence interval (CI) 0.36-0.80, P = 0.002. The heterogeneity was non-significant with I2 = 23%. Subgroup analysis based on parenteral nutrition duration and median birth weight was performed. The synthesis results for patients with parenteral nutrition duration exceeding 14 days revealed I2 = 35% (P = 0.15) and pooled RR = 0.47, 95% CI 0.30-0.73, P = 0.0008; and for patients with duration less than 14 days revealed I2 = 0% (P = 0.72) and pooled RR = 1.14, 95% CI 0.39-3.35, P = 0.81. The synthesis for patients with birth weight more than 1000 g revealed I2 = 0% (P = 0.41) and pooled RR = 0.55, 95% CI 0.26-1.18, P = 0.12; and for patients with birth weight below 1000 g revealed I2 = 44% (P = 0.11) and pooled RR = 0.53, 95% CI 0.33-0.85, P = 0.009. CONCLUSIONS: The fish oil-containing lipid emulsion can reduce the occurrence of PNAC in VLBW infants based on the available original randomized controlled trial studies, especially for patients with parenteral nutrition duration exceeding 14 days and extremely low birth weight infants. Future studies should be performed before a definitive conclusion can be established.

Characterization of odor-active compounds in moso bamboo (Phyllostachys pubescens Mazel) leaf via gas chromatography-ion mobility spectrometry, one- and two-dimensional gas chromatography-olfactory-mass spectrometry, and electronic nose.

The leaf of moso bamboo (Phyllostachys pubescens Mazel) is rich in odorant compounds, which is important natural materials for the production of flavor. It also contains phenolic acids, amino acids and peptides, which is a potential source of natural bioactive compounds. The study of odor-active compounds in bamboo leaves can provide a basis for the discovery of natural flavor. The leaf, stem, and powder of moso bamboo were analyzed by gas chromatography-ion mobility spectrometry (GC-IMS). Main odor-active compounds in moso bamboo leaf were analyzed and characterized by (1) a gas chromatography olfactory mass spectrometry (GC-O-MS), (2) two-dimensional gas chromatography olfactory mass spectrometry (GC × GC-O-MS) and (3) electronic nose (E-nose). Based on aroma extract dilution analysis (AEDA), 13 key odor-active compounds with high flavor dilution (FD) factor (≥27), including 3-methyl-1-butanol, (E)-2-hexenal, ethyl hexanoate, (Z)-4-heptenenal, 6-methyl-5-hepten-2-one, octanal, ethyl (Z)-3-hexenoate, 1-hexanol, (Z)-3-hexen-1-ol, (E, E)-2,4-heptadienal, (Z)-2-hexen-1-ol, 1-octen-3-ol and benzaldehyde, were further analyzed. The compounds detected by the above four methods were (E)-2-hexenal, 6-methyl-5-hepten-2-one, octanal, (E, E)-2,4-heptadienal, 1-octen-3-ol and benzaldehyde, and all of which were the main and potential odorants of moso bamboo leaf.

Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression.

The histone methyltransferase SETD3 plays critical roles in various biological events, and its dysregulation is often associated with human diseases including cancer. However, the underlying regulatory mechanism remains elusive. Here, we reported that ubiquitin-specific peptidase 27 (USP27) promotes tumor cell growth by specifically interacting with SETD3, negatively regulating its ubiquitination, and enhancing its stability. Inhibition of USP27 expression led to the downregulation of SETD3 protein level, the blockade of the cell proliferation and tumorigenesis of hepatocellular carcinoma (HCC) cells. In addition, we found that USP27 and SETD3 expression is positively correlated in HCC tissues. Notably, higher expression of USP27 and SETD3 predicts a worse survival in HCC patients. Collectively, these data elucidated that a USP27-dependent mechanism controls SETD3 protein levels and facilitates its oncogenic role in liver tumorigenesis.

Synergetic PtNP@Co3O4 hollow nanopolyhedrals as peroxidase-like nanozymes for the dual-channel homogeneous biosensing of prostate-specific antigen.

In this paper, novel synergetic PtNP@Co3O4 hollow nanopolyhedrals with peroxidase-like activities are designed and prepared, which can be used as electrochemical and colorimetric signal labels for the enzyme-free dual-channel homogeneous sensing of prostate-specific antigen. When prostate-specific antigens are present, the aptamer-modified PtNP@Co3O4 hollow nanopolyhedrals and magnetic beads form sandwich structures, which have excellent peroxidase-like activities, because of the synergetic effect of PtNP@Co3O4 hollow nanopolyhedrals. The sandwich structures can be separated from the mixture by the magnetic effect of the magnetic beads and catalyze the redox reactions between H2O2 and TMB, generating quantitative electrochemical and colorimetric responses in homogeneous solution simultaneously. Under the optimized conditions, the linear range of both electrochemical (0.01 to 10 ng/ml) and colorimetric (0.01-15 ng/ml) channels can satisfy the demand of prostate-specific antigen detection in clinic (4 ng/ml), and the electrochemical and colorimetric channels have a low detection limit of 0.0079 ng/ml and 0.01 ng/ml respectively without using natural enzymes. The strategy by using synergetic PtNP@Co3O4 hollow nanopolyhedrals as signal probes provides a promising scheme for developing simple, rapid, reliable, and ultrasensitive dual-channel homogeneous biosensors, which has a great potential as a powerful tool in prostate cancer diagnosis.

pQLyCar: Peptide-based dynamic query-driven sample rescaling strategy for identifying carboxylation sites combined with KNN and SVM.

Lysine carboxylation is one of the most crucial type of post-translation modification, which plays a significant role in catalytic mechanisms. Therefore, it is essential to study lysine carboxylation and explore its biological mechanism. Compared with traditional experimental methods that are labor-intensive and time-consuming, computational methods are much more convenience and faster. Therefore, it is urgent to establish an accurate carboxylation identification model. Herein we proposed a method, named pQLyCar for identification of lysine carboxylation using SVM as classifier. In pQLyCar, a peptide-based dynamic query-driven sample rescaling strategy (pDQD-SR) is proposed to address the class imbalance of training data, which builds a specific prediction model for each query sample. KNN algorithm calculates distance between samples according to original sequences instead of feature vectors. Information entropy is applied to select optimal size of sliding window and various types of sequence- and position-based features are incorporated for construction of feature space, including residues composition (RC), K-space and position-special amino acid propensity (PSAAP). Finally, the performance of pQLyCar is measured with a specificity of 96.49% and a sensibility of 99.59% using jackknife test method, which indicated that pQLyCar method can be a useful tool for prediction of lysine carboxylation sites.

Rutaecarpine Increases Anticancer Drug Sensitivity in Drug-Resistant Cells through MARCH8-Dependent ABCB1 Degradation.

The overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) subfamily B member 1 (ABCB1; P-glycoprotein; MDR1) in some types of cancer cells is one of the mechanisms responsible for the development of multidrug resistance (MDR), which leads to the failure of chemotherapy. Therefore, it is important to inhibit the activity or reduce the expression level of ABCB1 to maintain an effective intracellular level of chemotherapeutic drugs. In this study, we found that rutaecarpine, a bioactive alkaloid isolated from Evodia Rutaecarpa, has the capacity to reverse ABCB1-mediated MDR. Our data indicated that the reversal effect of rutaecarpine was related to the attenuation of the protein level of ABCB1. Mechanistically, we demonstrated that ABCB1 is a newly discovered substrate of E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8). MARCH8 can interact with ABCB1 and promote its ubiquitination and degradation. In short, rutaecarpine increased the degradation of ABCB1 protein by upregulating the protein level of MARCH8, thereby antagonizing ABCB1-mediated MDR. Notably, the treatment of rutaecarpine combined with other anticancer drugs exhibits a therapeutic effect on transplanted tumors. Therefore, our study provides a potential chemotherapeutic strategy of co-administrating rutaecarpine with other conventional chemotherapeutic agents to overcome MDR and improve therapeutic effect.

AimR Adopts Preexisting Dimer Conformations for Specific Target Recognition in Lysis-Lysogeny Decisions of Bacillus Phage phi3T.

A bacteriophage switches between lytic and lysogenic life cycles. The AimR-AimP-AimX communication system is responsible for phage lysis-lysogeny decisions during the infection of Bacillus subtilis. AimX is a regulator biasing phage lysis, AimR is a transcription factor activating AimX expression, and AimP is an arbitrium peptide that determines phage lysogeny by deactivating AimR. A strain-specific mechanism for the lysis-lysogeny decisions is proposed in SPbeta and phi3T phages. That is, the arbitrium peptide of the SPbeta phage stabilizes the SPbeta AimR (spAimR) dimer, whereas the phi3T-derived peptide disassembles the phi3T AimR (phAimR) dimer into a monomer. Here, we find that phAimR does not undergo dimer-to-monomer conversion upon arbitrium peptide binding. Gel-filtration, static light scattering (SLS) and analytical ultracentrifugation (AUC) results show that phAimR is dimeric regardless of the presence of arbitrium peptide. Small-angle X-ray scattering (SAXS) reveals that the arbitrium peptide binding makes an extended dimeric conformation. Single-molecule fluorescence resonance energy transfer (smFRET) analysis reveals that the phAimR dimer fluctuates among two distinct conformational states, and each preexisting state is selectively recognized by the arbitrium peptide or the target DNA, respectively. Collectively, our biophysical characterization of the phAimR dynamics underlying specific target recognition provides new mechanistic insights into understanding lysis-lysogeny decisions in Bacillus phage phi3T.

Substituent effects of cyclic naphthalene diimide on G-quadruplex binding and the inhibition of cancer cell growth.

Interaction of cyclic naphthalene diimide derivatives (cNDIs), 1-4, with TA-core and c-myc as G-quartet (G4) DNA was studied under dilute or molecular crowding condition. Binding study for TA-core based on an isothermal titration calorimetry showed that 1-4 has 106 M-1 order of binding affinity with the following order: 1 > 4 > 2 > 3 under both conditions. Meting temperature (Tm) of TA-core obtained from the temperature dependence of circular dichroism spectra shows that TA-core was most stabilized by 4, which is in agreement with the result of PCR stop assay and the stabilization effect for 1-3 was correlated with their binding affinity under dilute condition. 3 showed specific growth inhibition of cancer cell line Ca9-22 at <0.03 µM of IC50, with no inhibitory effect against normal bone marrow cells. 3, which has highest value of ΔH/ΔG, shows the highest inhibition ability for Ca9-22, carrying a highest expression level of telomerase mRNA.

Autophagy Induction by Trichodermic Acid Attenuates Endoplasmic Reticulum Stress-Mediated Apoptosis in Colon Cancer Cells.

Colorectal cancer (CRC) is the third leading malignant tumor in the world, which has high morbidity and mortality. In this study we found that trichodermic acid (TDA), a secondary metabolite isolated from the plant endophytic fungus Penicillium ochrochloronthe with a variety of biological and pharmacological activities, exhibited the antitumor effects on colorectal cancer cells in vitro and in vivo. Our results showed that TDA inhibited the proliferation of colon cancer cells in a dose-dependent manner. TDA induces sustained endoplasmic reticulum stress, which triggers apoptosis through IRE1α/XBP1 and PERK/ATF4/CHOP pathways. In addition, we found that TDA mediated endoplasmic reticulum stress also induces autophagy as a protective mechanism. Moreover, combined treatment of TDA with autophagy inhibitors significantly enhanced its anticancer effect. In conclusion, our results indicated that TDA can induce ER stress and autophagy mediated apoptosis, suggesting that targeting ER stress and autophagy may be an effective strategy for the treatment of CRC.

The Involvement of Ubiquitination Machinery in Cell Cycle Regulation and Cancer Progression.

The cell cycle is a collection of events by which cellular components such as genetic materials and cytoplasmic components are accurately divided into two daughter cells. The cell-cycle transition is primarily driven by the activation of cyclin-dependent kinases (CDKs), the activities of which are regulated by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors (CKIs). Thus, the ubiquitin-proteasome system (UPS) plays a pivotal role in the regulation of the cell-cycle process via recognition, interaction, and ubiquitination or deubiquitination of key proteins. The illegitimate degradation of tumor suppressor proteins and oncoproteins or, inversely, abnormally high accumulation results in cell proliferation deregulation, genomic instability, and cancer occurrence. In this review, we demonstrate the diversity and complexity of the UPS machinery regulation of the cell cycle. A profound understanding of the ubiquitination machinery will provide new insights into the regulation of the cell-cycle transition, cancer treatment, and the development of anti-cancer drugs.

Cyclovirobuxine D Induced-Mitophagy through the p65/BNIP3/LC3 Axis Potentiates Its Apoptosis-Inducing Effects in Lung Cancer Cells.

Mitophagy plays a pro-survival or pro-death role that is cellular-context- and stress-condition-dependent. In this study, we revealed that cyclovirobuxine D (CVB-D), a natural compound derived from Buxus microphylla, was able to provoke mitophagy in lung cancer cells. CVB-D-induced mitophagy potentiates apoptosis by promoting mitochondrial dysfunction. Mechanistically, CVB-D initiates mitophagy by enhancing the expression of the mitophagy receptor BNIP3 and strengthening its interaction with LC3 to provoke mitophagy. Our results further showed that p65, a transcriptional suppressor of BNIP3, is downregulated upon CVB-D treatment. The ectopic expression of p65 inhibits BNIP3 expression, while its knockdown significantly abolishes its transcriptional repression on BNIP3 upon CVB-D treatment. Importantly, nude mice bearing subcutaneous xenograft tumors presented retarded growth upon CVB-D treatment. Overall, we demonstrated that CVB-D treatment can provoke mitophagy and further revealed that the p65/BNIP3/LC3 axis is one potential mechanism involved in CVB-D-induced mitophagy in lung cancer cells, thus providing an effective antitumor therapeutic strategy for the treatment of lung cancer patients.

Clinical features of sodium-taurocholate cotransporting polypeptide deficiency in pediatric patients: case series and literature review.

Sodium-taurocholate cotransporting polypeptide (NTCP) deficiency is a newly reported hereditary bile acid metabolic disease. Here we describe the clinical characteristics of 12 cases of pediatric NTCP deficiency, as well as review 60 previously reported cases in the literature in order to provide better guidance for pediatricians. The clinical records, laboratory and imaging data were collected of 12 cases who were treated at the pediatric infectious disease department of the West China Second University Hospital of Sichuan University, China, from December 2018 to July 2020. PubMed and Wanfang databases were searched and 11 studies including 60 pediatric NTCP deficiency patients from January 2015 to November 2020 were retrieved. In our center, there were 4 girls and 8 boys, with a median age at admission of 9.9 months (range, 2.2 to 70 months). Six patients (50%) had prolonged neonatal jaundice. All of the patients (12/12; 100%) had normal growth and development. The reason for the first visit was prolonged neonatal jaundice (4/12, 33.3%), non-liver related diseases (6/12, 50%) and routine checkup (2/12, 16.7%). Hypercholanemia was documented in 12/12 (100%), elevated aspartate aminotransferase (AST) in 6/12 (50%), and elevated alanine aminotransferase (ALT) in 1/12 (8.3%). All of the patients (12/12; 100%) had homozygous mutations of c.800C>T in SLC10A1. Sixty patients (22 girls and 38 boys) were included in the literature review; 36 (60%) had hyperbilirubinemia after 1 month. The reasons for testing for hypercholanemia were identified in 47/60 cases, and included prolonged neonatal jaundice and neonatal transient cholestasis in 26 (26/47, 55.3%); non-liver related diseases in 14 (14/47, 29.8%); routine medical examination in 3 (3/14, 6.4%); volunteer recruitment in 1 (1/14, 7.1%); dark urine in 1 (1/47, 2.1%). Hypercholanemia was confirmed in 60/60 (100%); 31 (51.7%) had elevated AST, and 10 (16.7%) had elevated ALT. Among 59 Chinese patients, 52 (88.1%) had homozygous mutations of c.800C>T in SLC10A1. The most common symptom of pediatric NTCP deficiency is jaundice. NTCP deficiency can also be detected during routine check-ups. The common biochemical features are hypercholanemia and elevated AST. Screening for c.800C>T mutation in SLC10A1 is useful for primary genetic screening in Chinese infants with persistent hypercholanemia after infectious, structural, and immunological factors are excluded.

Neoadjuvant chemotherapy efficacy and prognostic factors in 187 cervical cancer patients with IB2 and IIA2 stage. / 187例IB2和IIA2æœŸå®«é¢ˆç™Œæ–°è¾ åŠ©åŒ–ç–—ç–—æ•ˆåŠé¢„åŽçš„å½±å“å› ç´ .

OBJECTIVES: To investigate the efficacy and prognostic factors for patients receiving neoadjuvant chemotherapy (NACT) before operation in stage IB2 and IIA2 cervical cancer. METHODS: A total of 187 patients with IB2 and IIA2 cervical cancer who received NACT combined surgery from January 2005 to January 2016 were enrolled. All patients were divided into an effective group (n=142) and an ineffective group (n=45) according to the chemotherapy efficacy. Clinical characteristics (containing tumor diameter, hematological inflammatory indexes, etc.) before chemotherapy and postoperative pathology between the two groups were compared. Patient survival analysis was performed by Kaplan-Meier method. The methods of univariate and multifactor analysis were used to analyze the relationship between NACT curative effect, postoperative pathological factors, and survival of patients. RESULTS: The number of patients with tumor diameter less than 5 cm was more in the chemotherapy effective group than that in the ineffective group (P=0.015). Three hematological inflammatory indexes (systemic inflammatory response index, neutrophil-lymphocyte ratio, and monocyte-lymphocyte ratio) in the effective group were lower than those in the ineffective group, respectively (P<0.05). The rates of pelvic lymph node metastasis and cervical deep myometrial invasion in the effective group were lower than those in the ineffective group (P<0.05). The 3-year and 5-year overall survival of NACT patients were 92.6% and 82.9%, respectively. Univariate analysis showed that chemotherapy efficacy, hematological inflammatory indexes, pelvic lymph node metastasis, and cervical deep myometrial invasion were related to the survival of patients (P<0.05). Further multivariate analysis demonstrated that pelvic lymph node metastasis was an independent risk factor for survival of patients (P<0.001), whereas effective NACT treatment was a protective factor for survival of patients (P<0.001). CONCLUSIONS: Tumor diameter and hematologic inflammation indexes before treatment are the relevant factors for NACT efficacy in patients with IB2 and IIA2 cervical cancer. Chemotherapy efficacy and pelvic lymph node metastasis are prognostic factors for NACT patients.

The Interaction of Cyclic Naphthalene Diimide with G-Quadruplex under Molecular Crowding Condition.

G-quadruplex specific targeting molecules, also termed as G4 ligands, are attracting increasing attention for their ability to recognize and stabilize G-quadruplex and high potentiality for biological regulation. However, G4 ligands recognizing G-quadruplex were generally investigated within a dilute condition, which might be interfered with under a cellular crowding environment. Here, we designed and synthesized several new cyclic naphthalene diimide (cNDI) derivatives, and investigated their interaction with G-quadruplex under molecular crowding condition (40% v/v polyethylene glycol (PEG)200) to mimic the cellular condition. The results indicated that, under molecular crowding conditions, cNDI derivatives were still able to recognize and stabilize G-quadruplex structures based on circular dichroism measurement. The binding affinities were slightly decreased but still comparatively high upon determination by isothermal titration calorimetry and UV-vis absorbance spectroscopy. More interestingly, cNDI derivatives were observed with preference to induce a telomere sequence to form a hybrid G-quadruplex under cation-deficient molecular crowding conditions.

Cyclic Naphthalene Diimide with a Ferrocene Moiety as a Redox-Active Tetraplex-DNA Ligand.

Cyclic naphthalene diimides (cNDIs), with a ferrocene moiety (cFNDs) and different linker lengths between the ferrocene and cNDI moieties, were designed and synthesized as redox-active, tetraplex-DNA ligands. Intramolecular stacking was observed between ferrocene and the NDI planes, which could affect the binding properties for G-quadruplexes. Interestingly, the circular dichroism spectrum of one of these compounds clearly shows new Cotton effects around 320-380 and 240 nm, which can be considered a direct evidence of intramolecular stacking of ferrocene and the NDI. Regarding recognition of hybrid G-quadruplexes, the less rigid structures (longer linkers) show higher binding affinity (106 m-1 order of magnitude). All new compounds show higher selectivity for G4 during electrochemical detection than noncyclic FND derivatives, which further identifies the redox-active potentiality of the cFNDs. Two of the three compounds tested even show preferential inhibition of cell growth in cancer cells over normal cells in a low concentration range, highlighting the potential for bioapplications of these cFNDs.