Primed 3D injectable microniches enabling low-dosage cell therapy for critical limb ischemia

The promise of cell therapy for repair and restoration of damaged tissues or organs relies on administration of large dose of cells whose healing benefits are still limited and sometimes irreproducible due to uncontrollable cell loss and death at lesion sites. Using a large amount of therapeutic cells increases the costs for cell processing and the risks of side effects. Optimal cell delivery strategies are therefore in urgent need to enhance the specificity, efficacy, and reproducibility of cell therapy leading to minimized cell dosage and side effects. Here, we addressed this unmet need by developing injectable 3D microscale cellular niches (microniches) based on biodegradable gelatin microcryogels (GMs). The microniches are constituted by in vitro priming human adipose-derived mesenchymal stem cells (hMSCs) seeded within GMs resulting in tissue-like ensembles with enriched extracellular matrices and enhanced cell–cell interactions. The primed 3D microniches facilitated cell protection from mechanical insults during injection and in vivo cell retention, survival, and ultimate therapeutic functions in treatment of critical limb ischemia (CLI) in mouse models compared with free cell-based therapy. In particular, 3D microniche-based therapy with 10[superscript 5] hMSCs realized better ischemic limb salvage than treatment with 10[superscript 6] free-injected hMSCs, the minimum dosage with therapeutic effects for treating CLI in literature. To the best of our knowledge, this is the first convincing demonstration of injectable and primed cell delivery strategy realizing superior therapeutic efficacy for treating CLI with the lowest cell dosage in mouse models. This study offers a widely applicable cell delivery platform technology to boost the healing power of cell regenerative therapy.National Natural Science Foundation (China) (Grant 81171474)National Natural Science Foundation (China) (Grant 51273106)National Natural Science Foundation (China) (Grant 81227901)Beijing Municipal Natural Science Foundation (Grant 157142090)National Basic Research Program of China (973 Program) (Grant 2011CB707701

ATM Transaction Status Feature Analysis and Anomaly Detection

In this paper, based on ATM transaction status analysis and anomaly detection problem, by analyzing the transaction statistics of a bank ATM application system, the characteristic parameters of ATM transaction status are extracted and analyzed, then a set of targets are designed. An abnormal monitoring scheme that can promptly and accurately alarm the four abnormal situations in which the trading volume is steep, the transaction failure rate is increased, the transaction processing is slow, and the transaction response time is too long. Firstly, the transaction data is divided to distinguish between working days, non-working days, trading volume troughs, and normal trading periods, to avoid data interference between different time periods and to take into account the data discontinuity. The characteristics of the anomaly data were identified by K-Means Clustering Analysis. Then the data is analyzed by B-P Neural Network method, the change rule of ATM transaction status with time is obtained. According to this rule, the ATM transaction status is judged, and the abnormal situation is alarmed in time. Finally, this paper increases the amount and type of data collected, then increases the influencing factors such as ATM popularity, holidays, transaction types into the model, uses the existing transaction data before and after the Spring Festival to verify, in order to obtain a more realistic monitoring and early warning program. The transaction status anomaly monitoring scheme designed in this paper not only can correctly judge but also timely alarm the financial aid equipment failure scenarios, so that the security of the financial self-service equipment trading system is guaranteed

Myeloid cell-derived LL-37 promotes lung cancer growth by activating Wnt/β-catenin signaling

Rationale: Antimicrobial peptides, such as cathelicidin LL-37/hCAP-18, are important effectors of the innate immune system with direct antibacterial activity. In addition, LL-37 is involved in the regulation of tumor cell growth. However, the molecular mechanisms underlying the functions of LL-37 in promoting lung cancer are not fully understood. Methods: The expression of LL-37 in the tissues and sera of patients with non-small cell lung cancer was determined through immunohistological, immunofluorescence analysis, and enzyme-linked immunosorbent assay. The animal model of wild-type and Cramp knockout mice was employed to evaluate the tumorigenic effect of LL-37 in non-small cell lung cancer. The mechanism of LL-37 involving in the promotion of lung tumor growth was evaluated via microarray analyses, recombinant protein treatment approaches in vitro, tumor immunohistochemical assays, and intervention studies in vivo. Results: LL-37 produced by myeloid cells was frequently upregulated in primary human lung cancer tissues. Moreover, its expression level correlated with poor clinical outcome. LL-37 activated Wnt/β-catenin signaling by inducing the phosphorylation of protein kinase B and subsequent phosphorylation of glycogen synthase kinase 3β mediated by the toll-like receptor-4 expressed in lung tumor cells. LL-37 treatment of tumor cells also decreased the levels of Axin2. In contrast, it elevated those of an RNA-binding protein (tristetraprolin), which may be involved in the mechanism through which LL-37 induces activation of Wnt/β-catenin. Conclusion: LL-37 may be a critical molecular link between tumor-supportive immune cells and tumors, facilitating the progression of lung cancer

The Cosmology Large Angular Scale Surveyor Receiver Design

The Cosmology Large Angular Scale Surveyor consists of four instruments performing a CMB polarization survey. Currently, the 40 GHz and first 90 GHz instruments are deployed and observing, with the second 90 GHz and a multichroic 150/220 GHz instrument to follow. The receiver is a central component of each instrument's design and functionality. This paper describes the CLASS receiver design, using the first 90 GHz receiver as a primary reference. Cryogenic cooling and filters maintain a cold, low-noise environment for the detectors. We have achieved receiver detector temperatures below 50 mK in the 40 GHz instrument for 85% of the initial 1.5 years of operation, and observed in-band efficiency that is consistent with pre-deployment estimates. At 90 GHz, less than 26% of in-band power is lost to the filters and lenses in the receiver, allowing for high optical efficiency. We discuss the mounting scheme for the filters and lenses, the alignment of the cold optics and detectors, stray light control, and magnetic shielding.Comment: Fixed formatting of abstract; 20 Pages, 11 Figures, SPIE Conference Proceeding

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

Travel despite the COVID-19 pandemic: Implications for tourism recovery

The COVID-19 pandemic has devastated the global tourism industry. This study explores why some Chinese residents travel during the pandemic. A mixed-methods research design was adopted, guided by the health belief model and relevant literature. Through 21 interviews with Chinese tourists who took an overnight leisure trip in May 2020, and a national survey among Chinese residents, this study explored factors influencing Chinese residents' travel-related decisions and behaviors during the pandemic. Results outline the influences of health beliefs, government trust, past travel experience, and psychological capital on tourists' risk-reduction behaviors. Theoretical and practical implications are provided regarding tourism recovery during pandemics

The global prevalence of oral leukoplakia: a systematic review and meta-analysis from 1996 to 2022

Abstract Background Oral leukoplakia(OLK) is a common oral potentially malignant disorder. The global prevalence of solely OLK was published in 2003, while the prevalence varied among different studies. In recent years, large-scale summary and definition-related analyses obtain insufficient attention. This study aimed to perform a systematic review of prevalence studies of oral leukoplakia and assess predisposing factors of its occurrence. Methods The search terms ("Oral leukoplakia" OR OLK OR leukoplakia) AND (prevalence OR incidence OR epidemiology) were searched in databases (Pubmed, Embase, Scopus, and Web of Science) for OLK studies published from January 1996 until December 2022. The estimated prevalence calculation and risk of bias analysis used STATA 16.0. Results We obtained 69 studies, including 1,263,028 participants, from 28 countries, and 6 continents. The prevalence was 1.39%, varying from 0.12 to 33.33%. The overall pooled estimated prevalence of OLK was 2.23% for population-based studies, 1.36% for clinic-based population studies, and 9.10% for specific populations. The pooled prevalence in different continents ranged from 0.33 to 11.74% with a statistical difference in the population-based calculation. The estimated prevalence of OLK was higher in males than in females. Those who smoked and consumed alcohol had a higher prevalence than those who did not. Conclusion Combining data from 69 published studies, the prevalence of OLK was determined as 1.39% and the pooling estimated global prevalence was 3.41%. The prevalence was relatively consistent and stable across different continents and different definitions. A higher pooled estimated prevalence was found among males, those aged over 60 years old, smokers, and alcohol consumers. The results from the included studies in this systematic review revealed that the prevalence was relatively consistent and stable across various definitions and continents, which may help in developing global treatment and prevention strategies for oral leukoplakia

To Achieve a Bullseye: Factors Related to Corneal Refractive Therapy Orthokeratology Lens Toricity

This retrospective study investigated the toricity of dual-axis corneal refractive therapy (CRT) orthokeratology lenses and corneal parameters, including flat keratometry (FK), flat eccentricity (e), steep e, corneal astigmatism, and the difference in elevation at 8 mm chord length. We analyzed the right eyes of 143 adolescent patients who underwent ocular examinations, subjective refraction, and corneal topography before CRT lens fitting by trial lens evaluation. After orthokeratology treatment, all patients underwent a topography map with an intact plus power ring and decentration of &lt;1 mm. The mean patient age was 10.7 &plusmn; 2.2 years old; 33% were male. The lens toricity range was 25&ndash;100 &micro;m. Multiple linear regression analysis showed significant associations between CRT lens toricity and corneal astigmatism (&beta; = 10.913, t = 3.012, p = 0.003) and the difference in elevation at 8 mm chord length (&beta; = 0.681, t = 4.049, p &lt; 0.001); no association was found between CRT lens toricity and FK, flat e, or steep e (all p &gt; 0.05). Corneal astigmatism was positively associated with difference in elevation at 8 mm chord length (r = 0.743, p &lt; 0.001, Pearson&rsquo;s correlation), and corneal astigmatism and the difference in elevation at 8 mm chord length were positively associated with CRT lens toricity (r = 0.657 and r = 0.643, respectively; both p &lt; 0.01, Spearman&rsquo;s correlation). These results suggest that difference in elevation at 8 mm chord length can be used to conveniently estimate CRT lens toricity in clinical practice, using the equation Y (CRT lens toricity) = 1.02X (difference in elevation at 8 mm chord length) + 20.3