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]

Polymer Nanoparticle-Based Chemotherapy for Spinal Malignancies

Malignant spinal tumors, categorized into primary and metastatic ones, are one of the most serious diseases due to their high morbidity and mortality rates. Common primary spinal tumors include chordoma, chondrosarcoma, osteosarcoma, Ewing’s sarcoma, and multiple myeloma. Spinal malignancies are not only locally invasive and destructive to adjacent structures, such as bone, neural, and vascular structures, but also disruptive to distant organs (e.g., lung). Current treatments for spinal malignancies, including wide resection, radiotherapy, and chemotherapy, have made significant progress like improving patients’ quality of life. Among them, chemotherapy plays an important role, but its potential for clinical application is limited by severe side effects and drug resistance. To ameliorate the current situation, various polymer nanoparticles have been developed as promising excipients to facilitate the effective treatment of spinal malignancies by utilizing their potent advantages, for example, targeting, stimuli response, and synergetic effect. This review overviews the development of polymer nanoparticles for antineoplastic delivery in the treatment of spinal malignancies and discusses future prospects of polymer nanoparticle-based treatment methods

Identification of <em>CHIP</em> as a novel causative gene for autosomal recessive cerebellar ataxia

Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia

PLSCR1 is a cell-autonomous defence factor against SARS-CoV-2 infection

Understanding protective immunity to COVID-19 facilitates preparedness for future pandemics and combats new SARS-CoV-2 variants emerging in the human population. Neutralizing antibodies have been widely studied; however, on the basis of large-scale exome sequencing of protected versus severely ill patients with COVID-19, local cell-autonomous defence is also crucial1,2,3,4. Here we identify phospholipid scramblase 1 (PLSCR1) as a potent cell-autonomous restriction factor against live SARS-CoV-2 infection in parallel genome-wide CRISPR–Cas9 screens of human lung epithelia and hepatocytes before and after stimulation with interferon-γ (IFNγ). IFNγ-induced PLSCR1 not only restricted SARS-CoV-2 USA-WA1/2020, but was also effective against the Delta B.1.617.2 and Omicron BA.1 lineages. Its robust activity extended to other highly pathogenic coronaviruses, was functionally conserved in bats and mice, and interfered with the uptake of SARS-CoV-2 in both the endocytic and the TMPRSS2-dependent fusion routes. Whole-cell 4Pi single-molecule switching nanoscopy together with bipartite nano-reporter assays found that PLSCR1 directly targeted SARS-CoV-2-containing vesicles to prevent spike-mediated fusion and viral escape. A PLSCR1 C-terminal β-barrel domain—but not lipid scramblase activity—was essential for this fusogenic blockade. Our mechanistic studies, together with reports that COVID-associated PLSCR1 mutations are found in some susceptible people3,4, identify an anti-coronavirus protein that interferes at a late entry step before viral RNA is released into the host-cell cytosol

Short-Term Influence of Recent Trial History on Perceptual Choice Changes with Stimulus Strength

Perceptual decisions, especially for difficult stimuli, can be influenced by choices and outcomes in previous trials. However, it is not well understood how stimulus strength modulates the temporal characteristics as well as the magnitude of trial history influence. We addressed this question using a contrast detection task in freely moving mice. We found that, at lower as compared to higher stimulus contrast, the current choice of the mice was more influenced by choices and outcomes in the past trials and the influence emerged from a longer history. To examine the neural basis of stimulus strength-dependent history influence, we recorded from the secondary motor cortex (M2), a prefrontal region that plays an important role in cue-guided actions and memory-guided behaviors. We found that more M2 neurons conveyed information about choices on the past two trials at lower than at higher contrast. Furthermore, history-trial activity in M2 was important for decoding upcoming choice at low contrast. Thus, trial history influence of perceptual choice is adaptive to the strength of sensory evidence, which may be important for action selection in a dynamic environment

gQuant, an Automated Tool for Quantitative Glycomic Data Analysis

MALDI-MS-based glycan isotope labeling methods have been effectively and widely used for quantitative glycomics. However, interpretation of the data produced by MALDI-MS is inaccurate and tedious because the bioinformatic tools are inadequate. In this work, we present gQuant, an automated tool for MALDI-MS-based glycan isotope labeling data processing. gQuant was designed with a set of dedicated algorithms to improve the efficiency, accuracy and convenience of quantitation data processing. When tested on the reference data set, gQuant showed a fast processing speed, as it was able to search the glycan data of model glycoproteins in a few minutes and reported more results than the manual analysis did. The reported quantitation ratios matched well with the experimental glycan mixture ratios ranging from 1:10 to 10:1. In addition, gQuant is fully open-source and is coded in Python, which is supported by most operating systems, and it has a user-friendly interface. gQuant can be easily adapted by users for specific experimental designs, such as specific glycan databases, different derivatization types and relative quantitation designs and can thus facilitate fast glycomic quantitation for clinical sample analysis using MALDI-MS-based stable isotope labeling

超薄四面体非晶碳膜光学常数的精确测定

Objective To explore accurate measurement of optical constants of the ultrathin tetrahedral amorphous carbon (ta-C) films by combined usage of spectral ellipsometry (SE) and spectrophotometry. Methods As the amount of unknown parameters determined by ellipsometry method was larger than the number of equations and the ellipsometric equations had no unique solution, the accurate determination of the optical constants of the ultrathin ta-C film accurately was difficult when independently using ellipsometric parameters for fitting due to the strong statistical influence of the film thickness on refractive index and extinction coefficient. Therefore, in this paper, ellipsometric parameters and transmittance (hereinafter referred to as SE+T) were simultaneously fitted to obtain optical constants more easily and rapidly. Results The results showed that the film had typical characteristics of amorphous carbon films. There were obvious differences in optical constants obtained by SE and SE+T. The maximum difference value of extinction coefficient k was up to 0.020 in the visible and infrared area and was 0.005 in the ultraviolet area. The maximum difference value of the refractive index n was 0.04 at wavelengths above 500 nm. The n value tended to be consistent by the two methods in the ultraviolet and visible area. The fitting results had better uniqueness by SE+T and the fitted optical constants were smooth. Conclusion This method of SE+T is suitable for accurate measurement of optical constants of ultrathin ta-C films within measurement range

Effects of Simultaneous Application of Double Chelating Agents to Pb-Contaminated Soil on the Phytoremediation Efficiency of Indocalamus decorus Q. H. Dai and the Soil Environment

Recent studies have shown that the combined application of ethylenediaminetetraacetic acid (EDTA) and degradable chelating agents can enhance EDTA&rsquo;s affinity for heavy metals and reduce its toxicity, but the effect of this combination on the phytoremediation remains largely unknown. This study evaluated and compared the effects of EDTA, nitrilotriacetic acid (NTA), and glutamic acid-N,N-diacetic acid (GLDA) alone (E, N, G treatment), and in combination (EN and EG treatment), on the growth of dwarf bamboo (Indocalamus decorus Q. H. Dai), their phytoremediation efficiency, and the soil environment in Pb-contaminated soil. The results showed that treatment E significantly reduced the biomass, while treatments N and EN were more conducive to the distribution of aerial plant biomass. Except for treatment E, the total Pb accumulation in all treatments increased significantly, with the highest increase in treatment EN. For double chelating agents, the acid-soluble Pb concentrations in rhizosphere and non-rhizosphere soils of treatments EN and EG were lower than those of treatment E, and the soil water-soluble Pb content after 20 days of treatment EN was significantly lower than that of treatment EG. Furthermore, chelating agents generally increased soil-enzyme activity in rhizosphere soil, indicating that chelating agents may promote plant heavy-metal uptake by changing the rhizosphere environment. In conclusion, treatment EN had the highest phytoremediation efficiency and significantly lower environmental risk than treatments E and EG, highlighting its massive potential for application in phytoremediation of Pb-contaminated soil when combined with I. decorus