Novel Scorpion Toxin ω-Buthitoxin-Hf1a Selectively Inhibits Calcium Influx via CaV3.3 and CaV3.2 and Alleviates Allodynia in a Mouse Model of Acute Postsurgical Pain.

Venom peptides have evolved to target a wide range of membrane proteins through diverse mechanisms of action and structures, providing promising therapeutic leads for diseases, including pain, epilepsy, and cancer, as well as unique probes of ion channel structure-function. In this work, a high-throughput FLIPR window current screening assay on T-type CaV3.2 guided the isolation of a novel peptide named ω-Buthitoxin-Hf1a from scorpion Hottentotta franzwerneri crude venom. At only 10 amino acid residues with one disulfide bond, it is not only the smallest venom peptide known to target T-type CaVs but also the smallest structured scorpion venom peptide yet discovered. Synthetic Hf1a peptides were prepared with C-terminal amidation (Hf1a-NH2) or a free C-terminus (Hf1a-OH). Electrophysiological characterization revealed Hf1a-NH2 to be a concentration-dependent partial inhibitor of CaV3.2 (IC50 = 1.18 µM) and CaV3.3 (IC50 = 0.49 µM) depolarized currents but was ineffective at CaV3.1. Hf1a-OH did not show activity against any of the three T-type subtypes. Additionally, neither form showed activity against N-type CaV2.2 or L-type calcium channels. The three-dimensional structure of Hf1a-NH2 was determined using NMR spectroscopy and used in docking studies to predict its binding site at CaV3.2 and CaV3.3. As both CaV3.2 and CaV3.3 have been implicated in peripheral pain signaling, the analgesic potential of Hf1a-NH2 was explored in vivo in a mouse model of incision-induced acute post-surgical pain. Consistent with this role, Hf1a-NH2 produced antiallodynia in both mechanical and thermal pain.

[Association between hypertension and oral cancer prognosis in non-smoking and non-drinking women].

OBJECTIVE: To explore the association between hypertension and prognosis of oral cancer patients in non-smoking and non-drinking women. METHODS: From September 2010 to February 2019, 362 non-smoking and non-drinking female patients with pathologically confirmed oral cancer were recruited and followed up in the First Affiliated Hospital of Fujian Medical University. The patients were divided into hypertension group and non-hypertensive group, and the Kaplan-Meier method was performed to calculate the cumulative survival rate. The survival curve was tested by the log-rank method for differences between the two groups. Cox proportional regression model was utilized to explore the prognostic factors. 1∶1 propensity score matching was applied in order to verify the above findings. Stratified analysis was used to explore the prognosis of oral cancer treated by different method and fish intake between two groups respectively. RESULTS: The Cox proportional hazards model showed that the risk of death of hypertension patients was 1.976 times than nonhypertensive patients(95%CI 1.003-3.890), the risk of death for patients with lymph node metastasis was 2.938 times than patients without metastasis(95%CI 1.318-6.551), the risk of death for patients underwent surgery combined with adjuvant therapy was 0.454 times than surgery alone(95%CI 0.236-0.875). After propensity score matching, the Cox proportional hazard model showed that the risk of death for patients with hypertension was 2.987 times than non-hypertensive patients(95%CI 1.050-8.497). The result of stratified analysis showed that the risk of death for non-hypertensive patients with surgery combined with adjuvant therapy was 0.233 times than patients with surgery alone(95%CI 0.085-0.643) and the risk of death in patients with hypertension who consumed fish ≥3 times/week was 0.020 times higher than that in women with oral cancer who consumed fish<3 times/week(95%CI 0.001-0.392). CONCLUSION: Hypertension is an independent prognostic factor for oral cancer in non-smoking and non-drinking women. Non-hypertensive patients underwent surgery combined with adjuvant therapy can reduce the risk of death and the increase of fish intake can improve the prognosis of hypertensive female oral cancer patients.

Formation Mechanism of Aluminide Diffusion Coatings on Ti and Ti-6Al-4V Alloy at the Early Stages of Deposition by Pack Cementation.

The diffusion coatings were deposited on commercially pure Ti and Ti-6Al-4V alloy at up to 1000 °C for up to 10 h using the pack cementation method. The pack powders consisted of 4 wt% Al (Al reservoir) and 4 wt% NH4Cl (activator) which were balanced with Al2O3 (inert filler). The growth kinetics of coatings were gravimetrically measured by a high precision balance. The aluminised specimens were characterised by means of scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and X-ray diffraction (XRD). At the early stages of deposition, a TiO2 (rutile) scale, other than aluminide coating, was developed on both materials at <900 °C. As the experimental temperature arose above 900 °C, the rutile layer became unstable and reduced to the low oxidation state of Ti oxides. When the temperature increased to 1000 °C, the TiO2 scale dissociated almost completely and the aluminide coating began to develop. After a triple-layered coating was generated, the coating growth was governed by the outward migration of Ti species from the substrates and obeyed the parabolic law. The coating formed consisted of an outer layer of Al3Ti, a mid-layer of Al2Ti and an inner layer of AlTi. The outer layer of Al3Ti dominated the thickness of the aluminide coating.