3D-printed Model and guide plate for accurate resection of advanced cutaneous squamous cell carcinomas

PurposeAdvanced cutaneous squamous cell carcinomas (cSCC) can have unclear borders, and simple expanded resection may not only destroy surrounding normal tissues unnecessarily, but can also leave residual tumor cells behind. In this article, we describe a new method for resection and evaluate its accuracy.MethodsThe magnetic resonance imaging (MRI) data of 12 patients with advanced cSCC were reconstructed to obtain three-dimensional (3D) tumor models and guide plates for surgeries. Thirty-eight patients with the same cSCC stage, who underwent expanded resection, were included. The distances between the upper, lower, left and right horizontal margins and tumor pathological boundaries were classified as “positive”, “close” (0–6 mm), “adequate” (6–12 mm) or “excessive” (>12 mm). The positive margin rate and margin distance were compared between the groups.ResultsThe 3D tumor models of 12 patients were all successfully reconstructed. The positive rate of 48 surgical margins in the guide plate group was 2.1%, and the proportion of “adequate” margins was 70.8%. A total of 152 margins of 38 patients were included in the extended resection group, for which the positive rate was 13.8%; this was higher than that of the guide plate group (P = 0.045). The proportion of “adequate” margins was 27.6%, with group differences seen in the distance distribution (P < 0.01).ConclusionsIn surgical resection of advanced cSCC, compared with simple expanded resection, surgical planning using a 3D tumor model and guide plate can reduce the rate of horizontal surgical margins, and the probability of under- or over-resection.Clinical Trial Registration: http://www.chictr.org.cn, Identifier [No. ChiCTR2100050174]

Development of a Non-invasive Deep Brain Stimulator With Precise Positioning and Real-Time Monitoring of Bioimpedance

Methods by which to achieve non-invasive deep brain stimulation via temporally interfering with electric fields have been proposed, but the precision of the positioning of the stimulation and the reliability and stability of the outputs require improvement. In this study, a temporally interfering electrical stimulator was developed based on a neuromodulation technique using the interference modulation waveform produced by several high-frequency electrical stimuli to treat neurodegenerative diseases. The device and auxiliary software constitute a non-invasive neuromodulation system. The technical problems related to the multichannel high-precision output of the device were solved by an analog phase accumulator and a special driving circuit to reduce crosstalk. The function of measuring bioimpedance in real time was integrated into the stimulator to improve effectiveness. Finite element simulation and phantom measurements were performed to find the functional relations among the target coordinates, current ratio, and electrode position in the simplified model. Then, an appropriate approach was proposed to find electrode configurations for desired target locations in a detailed and realistic mouse model. A mouse validation experiment was carried out under the guidance of a simulation, and the reliability and positioning accuracy of temporally interfering electric stimulators were verified. Stimulator improvement and precision positioning solutions promise opportunities for further studies of temporally interfering electrical stimulation

Engineering the Ultrasensitive Transcription Factors by Fusing a Modular Oligomerization Domain

The dimerization and high-order oligomerization of transcription factors has endowed them with cooperative regulatory capabilities that play important roles in many cellular functions. However, such advanced regulatory capabilities have not been fully exploited in synthetic biology and genetic engineering. Here, we engineered a C-terminally fused oligomerization domain to improve the cooperativity of transcription factors. First, we found that two of three designed oligomerization domains significantly increased the cooperativity and ultrasensitivity of a transcription factor for the regulated promoter. Then, seven additional transcription factors were used to assess the modularity of the oligomerization domains, and their ultrasensitivity was generally improved, as assessed by their Hill coefficients. Moreover, we also demonstrated that the allosteric capability of the ligand-responsive domain remained intact when fusing with the designed oligomerization domain. As an example application, we showed that the engineered ultrasensitive transcription factor could be used to significantly improve the performance of a “stripe-forming” gene circuit. We envision that the oligomerization modules engineered in this study could act as a powerful tool to rapidly tune the underlying response profiles of synthetic gene circuits and metabolic pathway controllers

Apremilast Ameliorates Experimental Arthritis via Suppression of Th1 and Th17 Cells and Enhancement of CD4+Foxp3+ Regulatory T Cells Differentiation

Apremilast is a novel phosphodiesterase 4 (PDE4) inhibitor suppressing immune and inflammatory responses. We assessed the anti-inflammatory effects of Apremilast in type II collagen (CII)-induced arthritis (CIA) mouse model. To determine whether Apremilast can ameliorate arthritis onset in this model, Apremilast was given orally at day 14 after CII immunization. Bone erosion was measured by histological and micro-computed tomographic analysis. Anti-mouse CII antibody levels were measured by enzyme-linked immunosorbent assay, and Th17, Th1 cells, and CD4+Foxp3+ regulatory T (Treg) cells were assessed by flow cytometry in the lymph nodes. Human cartilage and rheumatoid arthritis (RA) synovial fibroblasts (RASFs) implantation in the severe combined immunodeficiency mouse model of RA were used to study the role of Apremilast in the suppression of RASF-mediated cartilage destruction in vivo. Compared with untreated and vehicle control groups, we found that Apremilast therapy delayed arthritis onset and reduced arthritis scores in the CIA model. Total serum IgG, IgG1, IgG2a, and IgG2b were all decreased in the Apremilast treatment groups. Moreover, Apremilast markedly prevented the development of bone erosions in CIA mice by CT analysis. Furthermore, in the Apremilast treated group, the frequency of Th17 cells and Th1 cells was significantly decreased while Treg cells’ frequency was significantly increased. The high dose of Apremilast (25 mg/kg) was superior to low dose (5 mg/kg) in treating CIA. Apremilast treatment reduced the migratory ability of RASFs and their destructive effect on cartilage. Compared with the model group, Apremilast treatment significantly reduced the RASFs invasion cartilage scores in both primary implant and contralateral implant models. Our data suggest that Apremilast is effective in treating autoimmune arthritis and preventing the bone erosion in the CIA model, implicating its therapeutic potential in patients with RA

TMS-evoked potential in the dorsolateral prefrontal cortex to assess the severity of depression disease: a TMS-EEG study

Objective: The combined use of transcranial magnetic stimulation and electroencephalography (TMS-EEG), as a powerful technique that can non-invasively probe the state of the brain, can be used as a method to study neurophysiological markers in the field of psychiatric disorders and discover potential diagnostic predictors. This study used TMS-evoked potentials (TEPs) to study the cortical activity of patients with major depressive disorder depression (MDD) and the correlation with clinical symptoms to provide an electrophysiological basis for the clinical diagnosis.Methods: A total of 41 patients and 42 healthy controls were recruited to study. Using TMS-EEG techniques to measure the left dorsolateral prefrontal cortex (DLPFC) ‘s TEP index and evaluate the clinical symptoms of MDD patients using the Hamilton Depression Scale-24 (HAMD-24).Results: MDD subjects performing TMS-EEG on the DLPFC showed lower cortical excitability P60 index levels than healthy controls. Further analysis revealed that the degree of P60 excitability within the DLPFC of MDD patients was significantly negatively correlated with the severity of depression.Conclusion: The low levels of P60 exhibited in DLPFC reflect low excitability in MDD; the P60 component can be used as a biomarker for MDD in clinical assessment tools

Photocatalytic Activity Enhancement of Anatase TiO 2

We employed high-energy ball-milling technique to fabricate TiO/TiO2 heterogeneous nanostructures. XRD proved the existence of TiO/TiO2 heterogeneous structures. SEM and HRTEM investigation evidenced that the mean particle size and mean grain size of the as-prepared samples are 23 nm and 13 nm, respectively. UV-Vis spectra exhibited that TiO has enhanced the visible light absorption of TiO2 and has changed the Eg of TiO2. UPS examination indicated that the electron work function (EWF) of TiO is higher than that of TiO2. Photocatalytic degradation experiments revealed that an appropriate TiO content can enhance the photocatalytic activity of pure anatase TiO2. The best photocatalytic activity of TiO/TiO2 heterogeneous nanostructures is even better than that of Au-deposited TiO2 by keeping high degradation efficiency of 93%. The internal electrical field producing in TiO/TiO2 heterogeneous nanostructures was considered to be dominantly responsible for the enhanced photocatalytic activity. Therefore, the substitution of TiO with noble metal in TiO2 will be widely used in the future due to its low cost. This study also provides a clear direction of enhancing photocatalytic activity of TiO2: incorporating a guest compound into TiO2 with an appropriate content if the compound has much higher electron work function than that of TiO2

Chemical Composition, Antimicrobial and Insecticidal Activities of Essential Oils of Discarded Perfume Lemon and Leaves (Citrus Limon (L.) Burm. F.) as Possible Sources of Functional Botanical Agents

Two essential oils were isolated from discarded perfume lemon and leaves (Citrus limon (L.) Burm. F.) by hydro-distillation with good yield (0.044% for perfume lemon and 0.338% for leaves). Their biological activities were evaluated against five selected bacterial strains and Aedes albopictus (Ae. albopictus, Diptera: Culicidae). Chemical composition indicated that both essential oils were rich in essential phytochemicals including hydrocarbons, monoterpenes and sesquiterpene. These constituents revealed some variability among the oils displaying interesting chemotypes (R)-(+)-limonene (12.29–49.63%), citronellal (5.37–78.70%) and citronellol (2.98–7.18%). The biological assessments proved that the two essential oils had similar effect against bacterial (inhibition zones diameter ranging from 7.27 ± 0.06 to 10.37 ± 0.15 mm; MICs and MBCs ranging from 1.6 to 6.4 mg/mL); against Ae. albopictus larvae (LC(50) ranging from 384.81 to 395.09 ppm) and adult mosquito (LD(50) ranging from 133.059 to 218.962 μg/cm(2)); the activity of the two chemotypes ((R)-(+)-limonene and citronellal): larvae (LC(50) ranging from 267.08 to 295.28 ppm), which were all presented in dose-dependent manners. Through this work, we have showcased that recycling and reusing of agriculture by-products, such as discarded perfume lemon and leaves can produce eco-friendly alternatives in bacterial disinfectants and mosquito control product

Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents

A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus strains. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative showed good potency against all four strains of Staphylococcus (MIC = 1.25 - 5 μmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase structure to rationalize the observed antibacterial activity. Therefore, this series of GA derivatives have strong potential for the development of a new type of triterpenoid antibacterial agent