Generation of Human Epidermis-Derived Mesenchymal Stem Cell-like Pluripotent Cells and their reprogramming in mouse chimeras

Stem cells can be derived from the embryo (embryonic stem cells, ESCs), from adult tissues (adult stem cells, ASCs), and by induction of fibroblasts (induced pluripotent stem cells, iPSs). Ethical problems, immunological rejection, and difficulties in obtaining human tissues limit the use of ESCs in clinical medicine. Induced pluripotent stem cells are difficult to maintain in vitro and carry a greater risk of tumor formation. Furthermore, the complexity of maintenance and propagation is especially difficult in the clinic. Adult stem cells can be isolated from several adult tissues and present the possibility of self-transplantation for the clinical treatment of a variety of human diseases. Recently, several ASCs have been successfully isolated and cultured in vitro, including hematopoietic stem cells (HSCs) , mesenchymal stem cells (MSCs), epidermis stem cells, neural stem cells (NSCs), adipose-derived stem cells (ADSCs), islet stem cells, and germ line stem cells. Human mesenchymal stem cells originate mainly from bone marrow, cord blood, and placenta, but epidermis-derived MSCs have not yet been isolated. We isolated small spindle-shaped cells with strong proliferative potential during the culture of human epidermis cells and designed a medium to isolate and propagate these cells. They resembled MSCs morphologically and demonstrated pluripotency in vivo; thus, we defined these cells as human epidermis-derived mesenchymal stem cell-like pluripotent cells (hEMSCPCs). These hEMSCPCs present a possible new cell resource for tissue engineering and regenerative medicine

Boosting Oxygen and Peroxide Reduction Reactions on PdCu Intermetallic Cubes

Palladium‐based nanocatalysts have the potential to replace platinum‐based catalysts for fuel‐cell reactions in alkaline electrolytes, especially PdCu intermetallic nanoparticles with high electrochemical activity and stability. However, unlike the synthetic methods for obtaining the nanoparticles, the effect of PdCu shape on the performance is relatively less well studied. Here, we demonstrate the facet dependence of PdCu intermetallics on the oxygen reduction reaction (ORR) and peroxide reduction, and reveal that the {100} dominant PdCu cubes have a much higher ORR mass activity and specific activity than spheres at 0.9 V vs. RHE, which is four and five times that of commercial Pd/C and Pt/C catalysts, respectively, and show only a 31.7 % decay after 30 000 cycles in the stability test. Moreover, cubic PdCu nanoparticles show higher peroxide electroreduction activity than Pd cubes and PdCu spheres. Density functional theory (DFT) calculation reveals that the huge difference originates from the reduction in oxygen adsorption energy and energy barrier of peroxide decomposition on the ordered {100} PdCu surface. Given the relationship between the shape and electrochemical performance, this study will contribute to further research on electrocatalytic improvements of catalysts in alkaline environments.Shape the future: PdCu intermetallic cubes and spheres are synthesized to investigate the facet dependence on the oxygen reduction reaction and peroxide reduction. The cubes show large improvements in mass activity towards both reactions, compared with the spheres. DFT calculation uncovers that the dominant {100} faces of the cubes offer more appropriate oxygen adsorption and are thermodynamically favorable for peroxide reduction compared to the surface of spheres.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155903/1/celc202000381.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155903/2/celc202000381_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155903/3/celc202000381-sup-0001-misc_information.pd

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation

Cable Force Calculation of Cable Hoisting of CFST Arch Bridge Research

To effectively control the stress state and spatial alignment of arch ribs in the cable hoisting construction of a long-span, concrete-filled, steel tube arch bridge and ensure the safety of the structure, it is necessary to calculate and determine the appropriate cable force. Based on the actual project of a double-span, concrete-filled, steel tubular arch bridge, the construction stage of the left span of the bridge from the beginning of construction to the closure is taken as an example. The linear control method of “quiet do not move” is adopted. Based on the principle that the vertical displacement of the front end of the installed segment caused by the self-weight of the new hoisting segment is equal to the vertical displacement of the front end of the previous segment caused by the tension of the new hoisting segment, the tension cable force is calculated by forward iteration. Finally, based on the theory of the stress-free state method, the ideal linear design of the structure was achieved. The results show that after the closure of the bridge, the error range of the cable tension force is −13.33–15.40% on the left bank and −8.37–11.00% on the right bank. The elevation error of the arch rib is −0.003–0.043 m on the left bank and −0.007–0.032 m on the right bank. The overall stress error of the bridge arch is ±7.0 MPa. The error between the theoretical value and the actual value is within the scope of the specification requirements, which meets the specification requirements. After the closure, the arch shape of the bridge meets the smooth requirements

Grain Refinement of Ti-15Mo-3Al-2.7Nb-0.2Si Alloy with the Rotation of TiB Whiskers by Powder Metallurgy and Canned Hot Extrusion

In situ synthesized TiB whiskers (TiBw) reinforced Ti-15Mo-3Al-2.7Nb-0.2Si alloys were successfully manufactured by pre-sintering and canned hot extrusion via adding TiB2 powders. During pre-sintering, most TiB2 were reacted with Ti atoms to produce TiB. During extrusion, the continuous dynamic recrystallization (CDRX) of β grains was promoted with the rotation of TiBw, and CDRXed grains were strongly inhibited by TiBw with hindering dislocation motion. Eventually, the grain sizes of composites decreased obviously. Furthermore, the stress transmitted from the matrix to TiBw for strengthening in a tensile test, besides grain refinement. Meanwhile, the fractured TiBw and microcracks around them contributed to fracturing

Modeling of the Effect of Secondary Orientation on the Micro Deformation Behavior of Ni-Based Single Crystal Superalloys

In this paper, a supercell modeling of secondary orientation was established using 90 cubic mosaic units made up of γ’ phase embedded in γ matrix, in accordance with an actual structure of Ni-based single crystal superalloys (NSCS). The effects of secondary orientation on the deformation behavior and microstructure evolution of NSCS under uniaxial tensile were studied by a three-dimensional molecular dynamics (MD) simulation. Simulation results showed that secondary orientation had a significant effect on mechanical properties of NSCS, that is, a big fluctuation was found in tensile strength which dropped down almost 50% from a peak (corresponding to the secondary orientations of 18° and 45°) to a trough (those of 34° and 63°). Mechanisms of secondary orientation affecting the deformation behavior were further discussed systematically. The deformation of NSCS under uniaxial tensile was a process tending towards amorphization of microstructure, together with the dislocation formation, merging and break-up. On a micro viewpoint, this work for us will be useful to apprehend the tensile deformation conduct of NSCS

Systematic Characterization of DNA Methyltransferases Family in Tumor Progression and Antitumor Immunity

Objective: DNA methylation is an essential epigenetic marker governed by DNA methyltransferases (DNMTs), which can influence cancer onset and progression. However, few studies have provided an integrated analysis of the relevance of DNMT family genes to cell stemness, the tumor microenvironment (TME), and immunotherapy biomarkers across diverse cancers. Methods: This study investigated the impact of five DNMTs on transcriptional profiles, prognosis, and their association with Ki67 expression, epithelial–mesenchymal transition signatures, stemness scores, the TME, and immunological markers across 31 cancer types from recognized public databases. Results: The results indicated that DNMT1/DNMT3B/DNMT3A expression increased, whereas TRDMT1/DNMT3L expression decreased in most cancer types. DNMT family genes were identified as prognostic risk factors for numerous cancers, as well as being prominently associated with immune, stromal, and ESTIMATE scores, as well as with immune-infiltrating cell levels. Expression of the well-known immune checkpoints, PDCD1 and CILA4, was noticeably related to DNMT1/DNMT3A/DNMT3B expression. Finally, we validated the role of DNMT1 in MCF-7 and HepG2-C3A cell lines through its knockdown, whereafter a decrease in cell proliferation and migration ability in vitro was observed. Conclusion: Our study comprehensively expounded that DNMT family genes not only behave as promising prognostic factors but also have the potential to serve as therapeutic targets in cancer immunotherapy for various types of cancer

Protocol to establish a lung adenocarcinoma immunotherapy allograft mouse model with FACS and immunofluorescence-based analysis of tumor response

Summary: Anti-PD-1/PD-L1 therapy shows long-term effects in many cancer types, but resistance and relapse remain the main limitations of this therapy. Here, we describe a protocol to evaluate the tumor response to immunotherapy in a mouse lung cancer model. The protocol includes the establishment of the lung cancer mouse model, anti-PD-1 treatment, tumor-infiltrating lymphocyte isolation, immunofluorescence, and flow cytometry analysis. This protocol can also be applied to other cancer types and immunotherapies.For complete details on the use and execution of this protocol, please refer to Yu et al. (2021