Exploring Employment Intentions of College Students in Small and Medium-sized Cities against the Backdrop of High-Quality Economic Development: Taking Huai’an City as an Example

Against the backdrop of high-quality development of the national economy, the development of each city is also facing transformation and upgrading. Cities need high-quality development, and high-quality talents are the key. The problem of attracting high-quality talents in domestic small and medium-sized cities in high-quality development needs to be solved urgently. This paper takes Huai’an, a third-tier city in China, as an example, to understand the intentions and confusions of college students when they seek employment. The qualitative approach of semi-structured interviews is employed. The study finds that in small and medium-sized cities, factors hindering college students from staying in local cities for employment include that the intensity of the government in publicizing high-quality development has not reached to most college students, the guide courses in colleges and universities meet difficulties in the process of delivery, and college students' own career planning are not guided well. In response to the above problems, this paper puts forward suggestions such as strengthening the positive interaction between schools and college students, enhancing the publicity of high-quality urban development among college students, and closely integrating college students’ career guidance courses with local development. Quality development attracts more high-quality talents

MyoPS-Net: Myocardial Pathology Segmentation with Flexible Combination of Multi-Sequence CMR Images

Myocardial pathology segmentation (MyoPS) can be a prerequisite for the accurate diagnosis and treatment planning of myocardial infarction. However, achieving this segmentation is challenging, mainly due to the inadequate and indistinct information from an image. In this work, we develop an end-to-end deep neural network, referred to as MyoPS-Net, to flexibly combine five-sequence cardiac magnetic resonance (CMR) images for MyoPS. To extract precise and adequate information, we design an effective yet flexible architecture to extract and fuse cross-modal features. This architecture can tackle different numbers of CMR images and complex combinations of modalities, with output branches targeting specific pathologies. To impose anatomical knowledge on the segmentation results, we first propose a module to regularize myocardium consistency and localize the pathologies, and then introduce an inclusiveness loss to utilize relations between myocardial scars and edema. We evaluated the proposed MyoPS-Net on two datasets, i.e., a private one consisting of 50 paired multi-sequence CMR images and a public one from MICCAI2020 MyoPS Challenge. Experimental results showed that MyoPS-Net could achieve state-of-the-art performance in various scenarios. Note that in practical clinics, the subjects may not have full sequences, such as missing LGE CMR or mapping CMR scans. We therefore conducted extensive experiments to investigate the performance of the proposed method in dealing with such complex combinations of different CMR sequences. Results proved the superiority and generalizability of MyoPS-Net, and more importantly, indicated a practical clinical application

Dissolving microneedles for drug delivery

Microneedles are individual needles or arrays of needles in micro-scale widely used in transdermal drug delivery. They achieve painless administration with delivery of low but sufficient dose of therapeutic agents. Dissolving microneedles, made from biodegradable materials, are able to control drug release by altering their compositions and fabrication processes. In this study, we designed a double-layered biodegradable microneedles model, which functioned as a two-speed drug delivery system with consistent release of two kinds of drugs in 2 hours and 2 days respectively in vitro. This model also possessed strong mechanical strength with elasticity in penetration of flat skin model and irregular surface model following delivery of inclusions capsulated in the microneedles, which provided skin diseases and ocular diseases with a beneficial drug delivery method in further study.​Master of Science (Biomedical Engineering

Expansion microscopy: A chemical approach for super-resolution microscopy.

Super-resolution microscopy is a series of imaging techniques that bypass the diffraction limit of resolution. Since the 1990s, optical approaches, such as single-molecular localization microscopy, have allowed us to visualize biological samples from the sub-organelle to the molecular level. Recently, a chemical approach called expansion microscopy emerged as a new trend in super-resolution microscopy. It physically enlarges cells and tissues, which leads to an increase in the effective resolution of any microscope by the length expansion factor. Compared with optical approaches, expansion microscopy has a lower cost and higher imaging depth but requires a more complex procedure. The integration of expansion microscopy and advanced microscopes significantly pushed forward the boundary of super-resolution microscopy. This review covers the current state of the art in expansion microscopy, including the latest methods and their applications, as well as challenges and opportunities for future research

Patterning of oncogenic Ras clustering in live cells using vertically aligned nanostructure arrays

As a dominant oncogenic protein, Ras is well-known to segregate into clusters on the plasma membrane for activating downstream signaling. However, current technologies for direct measurements of Ras clustering are limited to sophisticated high-resolution techniques like electron microscopy and fluorescence lifetime imaging. To further promote fundamental investigations and the related drug development, we hereby introduce a nanobar-based platform which effectively guides Ras clusters into quantifiable patterns in live cells that is resolvable under conventional microscopy. Major Ras isoforms, K-Ras, H-Ras, and N-Ras were differentiated, as well as their highly prevalent oncogenic mutants G12V and G13D. Moreover, the isoform specificity and the sensitivity of a Ras inhibitor were successfully characterized on nanobars. We envision that this nanobar-based platform will serve as an effective tool to read Ras clustering on the plasma membrane, enabling a novel avenue both to decipher Ras regulations and to facilitate anti-Ras drug development.Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)Accepted versionThis work is funded by Singapore Ministry of Education (MOE) (W. Zhao, RG145/18 and RG112/20), the Singapore National Research Foundation (W. Zhao, NRF2019-NRF-ISF003-3292), the NTU Start-up Grant (W. Zhao), the NTU-NNI Neurotechnology Fellowship (W. Zhao), DFG (K. Rajalingam), and Ageing Research Institute for Society and Education (ARISE) NTU for the research scholarship (H. Mu)

Aligning multi-sequence CMR towards fully automated myocardial pathology segmentation

Myocardial pathology segmentation (MyoPS) is critical for the risk stratification and treatment planning of myocardial infarction (MI). Multi-sequence cardiac magnetic resonance (MS-CMR) images can provide valuable information. For instance, balanced steady-state free precession cine sequences present clear anatomical boundaries, while late gadolinium enhancement and T2-weighted CMR sequences visualize myocardial scar and edema of MI, respectively. Existing methods usually fuse anatomical and pathological information from different CMR sequences for MyoPS, but assume that these images have been spatially aligned. However, MS-CMR images are usually unaligned due to the respiratory motions in clinical practices, which poses additional challenges for MyoPS. This work presents an automatic MyoPS framework for unaligned MS-CMR images. Specifically, we design a combined computing model for simultaneous image registration and information fusion, which aggregates multi-sequence features into a common space to extract anatomical structures (i.e., myocardium). Consequently, we can highlight the informative regions in the common space via the extracted myocardium to improve MyoPS performance, considering the spatial relationship between myocardial pathologies and myocardium. Experiments on a private MS-CMR dataset and a public dataset from the MYOPS2020 challenge show that our framework could achieve promising performance for fully automatic MyoPS.</p

Guiding irregular nuclear morphology on nanopillar arrays for malignancy differentiation in tumor cells

For more than a century, abnormal nuclei in tumor cells, presenting subnuclear invaginations and folds on the nuclear envelope, have been known to be associated with high malignancy and poor prognosis. However, current nuclear morphology analysis focuses on the features of the entire nucleus, overlooking the malignancy-related subnuclear features in nanometer scale. The main technical challenge is to probe such tiny and randomly distributed features inside cells. We here employ nanopillar arrays to guide subnuclear features into ordered patterns, enabling their quantification as a strong indicator of cell malignancy. Both breast and liver cancer cells were validated as well as the quantification of nuclear abnormality heterogeneity. The alterations of subnuclear patterns were also explored as effective readouts for drug treatment. We envision that this nanopillar-enabled quantification of subnuclear abnormal features in tumor cells opens a new angle in characterizing malignant cells and studying the unique nuclear biology in cancer.Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)This work is supported by the Singapore Ministry of Education (MOE) (W.Z., RG145/18 and RG112/20), the Singapore National Research Foundation (W.Z., NRF2019-NRF-ISF003- 3292), the Institute for Digital Molecular Analytics and Science (IDMxS) supported by MOE funding under the Research Centres of Excellence scheme (W.Z.), the NTU Start-up Grant (W.Z.), the NTU-NNI Neurotechnology Fellowship (W.Z.), and AIRC IG-24614 and Sapienza AR1181642EE61111 (I.S.)

Gait Analysis with Wearables Is a Potential Progression Marker in Parkinson&rsquo;s Disease

Gait disturbance is a prototypical feature of Parkinson&rsquo;s disease (PD), and the quantification of gait using wearable sensors is promising. This study aimed to identify gait impairment in the early and progressive stages of PD according to the Hoehn and Yahr (H&ndash;Y) scale. A total of 138 PD patients and 56 healthy controls (HCs) were included in our research. We collected gait parameters using the JiBuEn gait-analysis system. For spatiotemporal gait parameters and kinematic gait parameters, we observed significant differences in stride length (SL), gait velocity, the variability of SL, heel strike angle, and the range of motion (ROM) of the ankle, knee, and hip joints between HCs and PD patients in H&ndash;Y &#8544;-&#8545;. The changes worsened with the progression of PD. The differences in the asymmetry index of the SL and ROM of the hip were found between HCs and patients in H&ndash;Y &#8547;. Additionally, these gait parameters were significantly associated with Unified Parkinson&rsquo;s Disease Rating Scale and Parkinson&rsquo;s Disease Questionnaire-39. This study demonstrated that gait impairment occurs in the early stage of PD and deteriorates with the progression of the disease. The gait parameters mentioned above may help to detect PD earlier and assess the progression of PD

A subset of flavaglines inhibits KRAS nanoclustering and activation.

The RAS oncogenes are frequently mutated in human cancers and among the three isoforms (KRAS, HRAS and NRAS), KRAS is the most frequently mutated oncogene. Here, we demonstrate that a subset of flavaglines, a class of natural anti-tumour drugs and chemical ligands of prohibitins, inhibit RAS GTP loading and oncogene activation in cells at nanomolar concentrations. Treatment with rocaglamide, the first discovered flavagline, inhibited the nanoclustering of KRAS, but not HRAS and NRAS, at specific phospholipid-enriched plasma membrane domains. We further demonstrate that plasma membrane-associated prohibitins directly interact with KRAS, phosphatidylserine and phosphatidic acid, and these interactions are disrupted by rocaglamide but not by the structurally related flavagline FL1. Depletion of prohibitin-1 phenocopied the rocaglamide-mediated effects on KRAS activation and stability. We also demonstrate that flavaglines inhibit the oncogenic growth of KRAS-mutated cells and that treatment with rocaglamide reduces non-small-cell lung carcinoma (NSCLC) tumour nodules in autochthonous KRAS-driven mouse models without severe side effects. Our data suggest that it will be promising to further develop flavagline derivatives as specific KRAS inhibitors for clinical applications

Membrane curvature sensing of the lipid-anchored K-Ras small GTPase

Plasma membrane (PM) curvature defines cell shape and intracellular organelle morphologies and is a fundamental cell property. Growth/proliferation is more stimulated in flatter cells than the same cells in elongated shapes. PM-anchored K-Ras small GTPase regulates cell growth/proliferation and plays key roles in cancer. The lipid-anchored K-Ras form nanoclusters selectively enriched with specific phospholipids, such as phosphatidylserine (PS), for efficient effector recruitment and activation. K-Ras function may, thus, be sensitive to changing lipid distribution at membranes with different curvatures. Here, we used complementary methods to manipulate membrane curvature of intact/live cells, native PM blebs, and synthetic liposomes. We show that the spatiotemporal organization and signaling of an oncogenic mutant K-RasG12V favor flatter membranes with low curvature. Our findings are consistent with the more stimulated growth/proliferation in flatter cells. Depletion of endogenous PS abolishes K-RasG12V PM curvature sensing. In cells and synthetic bilayers, only mixed-chain PS species, but not other PS species tested, mediate K-RasG12V membrane curvature sensing. Thus, K-Ras nanoclusters act as relay stations to convert mechanical perturbations to mitogenic signaling.Published versio