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5G networks have an efficient effect in providing quality of experience and massive Internet of things (IoT) communication. Applications of 5G-IoT networks have been expanded rapidly, including in smart medical healthcare. Emergency medical services (EMS) hold an assignable proportion in our lives, which has become a complex network of all types of professionals, including care in an ambulance. A 5G network with EMS can simplify the medical treatment process and improve the efficiency of patient treatment. The importance of healthcare-related privacy preservation is rising. If the work of privacy preservation fails, not only will medical institutes have economic and credibility losses but also property losses and even the lives of patients will be harmed. This paper proposes a privacy-preserved ID-based secure communication scheme in 5G-IoT telemedicine systems that can achieve the features below. (i) The proposed scheme is the first scheme that integrates the process of telemedicine systems and EMS; (ii) the proposed scheme allows emergency signals to be transmitted immediately with decreasing risk of secret key leakage; (iii) the information of the patient and their prehospital treatments can be transmitted securely while transferring the patient to the destination medical institute; (iv) the quality of healthcare services can be assured while preserving the privacy of the patient; (v) the proposed scheme supports not only normal situations but also emergencies. (vi) the proposed scheme can resist potential attacks.

Hydrogels are widely used in tissue engineering owing to their high water retention and soft characteristics. It remains a challenge to develop hydrogels with tunable degradation rates, proper environmental responsiveness, and injectability. In this study, biodegradable difunctional polyurethane (DFPU) nanoparticle dispersions are synthesized from an eco‐friendly waterborne process involving the use of glyoxal. Such DFPU is used to crosslink chitosan (CS). Schiff base linkages between DFPU and CS successfully produce self‐healing hydrogels at room temperature. Moreover, cryogels are generated after being frozen at −20 °C. These gels are found to be sensitive to low pH and amine‐containing molecules owing to the property of Schiff bases. Furthermore, the degradation rates can be adjusted by the type of the component oligodiols in DFPU. Rheological evaluation verifies the excellent self‐healing properties (≈100% recovery after damage). Both the self‐healing gels and cryogels are injectable (through 26‐gauge and 18‐gauge needles, respectively) and biocompatible. Rat implantation at 14 d shows the low immune responses of cryogels. The functionalized biodegradable polyurethane nanoparticles represent a new platform of crosslinkers for biomacromolecules such as chitosan through the dynamic Schiff reaction that may give rise to a wide variety of self‐healing gels and cryogels for biomedical applications. A new biodegradable waterborne difunctional polyurethane (DFPU) crosslinker is obtained by modifying waterborne polyurethane (PU) with glyoxal. Adding the crosslinker to glycol chitosan (CS) produces CS‐PU self‐healing hydrogel at room temperature and generates CS‐PU cryogel after being temporally frozen at −20 °C. Both gels are featured with injectability (26‐gauge and 18‐gauge needles, respectively), multiresponsiveness, tunable degradation rates, good cell proliferation, and biocompatibility.

Lung cancer is the leading cause of cancer-related mortality worldwide, and its tumorigenesis involves the accumulation of genetic and epigenetic events in the respiratory epithelium. Epigenetic modifications, such as DNA methylation, RNA modification, and histone modifications, have been widely reported to play an important role in lung cancer development and in other pulmonary diseases. Whereas the functionality of DNA and chromatin modifications referred to as epigenetics is widely characterized, various modifications of RNA nucleotides have recently come into prominence as functionally important. N6-methyladosine (m6A) is the most prevalent internal modification in mRNAs, and its machinery of writers, erasers, and readers is well-characterized. However, several other nucleotide modifications of mRNAs and various noncoding RNAs have also been shown to play an important role in the regulation of biological processes and pathology. Such epitranscriptomic modifications play an important role in regulating various aspects of RNA metabolism, including transcription, translation, splicing, and stability. The dysregulation of epitranscriptomic machinery has been implicated in the pathological processes associated with carcinogenesis including uncontrolled cell proliferation, migration, invasion, and epithelial-mesenchymal transition. In recent years, with the advancement of RNA sequencing technology, high-resolution maps of different modifications in various tissues, organs, or disease models are being constantly reported at a dramatic speed. This facilitates further understanding of the relationship between disease development and epitranscriptomics, shedding light on new therapeutic possibilities. In this review, we summarize the basic information on RNA modifications, including m6A, m1A, m5C, m7G, pseudouridine, and A-to-I editing. We then demonstrate their relation to different kinds of lung diseases, especially lung cancer. By comparing the different roles RNA modifications play in the development processes of different diseases, this review may provide some new insights and offer a better understanding of RNA epigenetics and its involvement in pulmonary diseases.

Thrombocytopenia is a condition where the platelet count is under 100 × 10 9 /L, which is caused by various disorders. However, the mechanism of thrombocytopenia is still unclear. Hence, we tried to investigate the correlation between immune thrombocytopenia (ITP) and single nucleotide polymorphisms (SNPs) of genes related to T cell activation. There were 32 ITP patients and 30 healthy controls enrolled in this study. PCR and sequencing were used to find out the significant SNPs, which we focused on the promoter region of CTLA4 and CD28. In this study, the ITP cases were divided into primary ITP group, secondary ITP group, and the combination of the two to the follow-up analysis. Moreover, dual-luciferase reporter assay was used to evaluate the transcription activity of the significant SNP. We found the − 1765_rs11571315 of CTLA4 gene was associated with primary ITP (p = 0.006), secondary ITP (p = 0.008), and the combination of the two (p = 0.003). Moreover, the −318_rs5742909 also had statistical significance in secondary ITP group that was only caused by autoimmune disease (p = 0.019). In functional study, the rs5742909 would decrease 19% of the transcription activity when it carried a T-allele at this position (p = 0.040). It was noted that CTLA4 gene polymorphism was related to ITP but not CD28. According to our results, we surmised that CTLA4 is involved in the pathogenesis of ITP, and the secondary ITP result from the lower CTLA4 expression that leads to T cell over-activation.

The fifth generation (5G) mobile network delivers high peak data rates with ultra-low latency and massive network capacity. Wireless sensor network (WSN) in Internet of Thing (IoT) architecture is of prominent use in 5G-enabled applications. The electronic healthcare (e-health) system has gained a lot of research attention since it allows e-health users to store and share data in a convenient way. By the support of 5G technology, healthcare data produced by sensor nodes are transited in the e-health system with high efficiency and reliability. It helps in reducing the treatment cost, providing efficient services, better analysis reports, and faster access to treatment. However, security and privacy issues become big concerns when the number of sensors and mobile devices is increasing. Moreover, existing single-server architecture requires to store a massive number of identities and passwords, which causes a significant database cost. In this paper, we propose a three-factor fast authentication scheme with time bound and user anonymity for multi-server e-health systems in 5G-based wireless sensor networks. In our work, the three-factor authentication scheme integrating biometrics, password, and smart card ensures a high-security sensor-enabled environment for communicating parties. User anonymity is preserved during communication process. Besides, time bound authentication can be applied to various healthcare scenarios to enhance security. The proposed protocol includes fast authentication, which can provide a fast communication for participating parties. Our protocol is also designed with multi-server architecture to simplify network load and significantly save database cost. Furthermore, security proof and performance analysis results show that our proposed protocol can resist various attacks and bear a rational communication cost.

Inherited Retinal Diseases (IRDs) are considered one of the leading causes of blindness worldwide. However, the majority of them still lack a safe and effective treatment due to their complexity and genetic heterogeneity. Recently, gene therapy is gaining importance as an efficient strategy to address IRDs which were previously considered incurable. The development of the clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system has strongly empowered the field of gene therapy. However, successful gene modifications rely on the efficient delivery of CRISPR-Cas9 components into the complex three-dimensional (3D) architecture of the human retinal tissue. Intriguing findings in the field of nanoparticles (NPs) meet all the criteria required for CRISPR-Cas9 delivery and have made a great contribution toward its therapeutic applications. In addition, exploiting induced pluripotent stem cell (iPSC) technology and in vitro 3D retinal organoids paved the way for prospective clinical trials of the CRISPR-Cas9 system in treating IRDs. This review highlights important advances in NP-based gene therapy, the CRISPR-Cas9 system, and iPSC-derived retinal organoids with a focus on IRDs. Collectively, these studies establish a multidisciplinary approach by integrating nanomedicine and stem cell technologies and demonstrate the utility of retina organoids in developing effective therapies for IRDs.

Lung cancer is the leading cause of death from cancer in Taiwan and throughout the world. Immunotherapy has revealed promising and significant efficacy in NSCLC, through immune checkpoint inhibition by blocking programmed cell death protein (PD)-1/PD-1 ligand (PD-L1) signaling pathway to restore patients’ T-cell immunity. One novel type of long, non-coding RNAs, circular RNAs (circRNAs), are endogenous, stable, and widely expressed in tissues, saliva, blood, urine, and exosomes. Our previous results revealed that the plasma level of hsa_circ_0000190 can be monitored by liquid-biopsy-based droplet digital PCR and may serve as a valuable blood-based biomarker to monitor the disease progression and the efficacy of immunotherapy. In this study, hsa_circ_0000190 was shown to increase the PD-L1 mRNA-mediated soluble PD-L1 (sPD-L1) expression, consequently interfering with the efficacy of anti-PD-L1 antibody and T-cell activation, which may result in immunotherapy resistance and poor outcome. Our results unraveled that hsa_circ_0000190 facilitated the tumorigenesis and immune evasion of NSCLC by upregulating sPD-L1 expression, potentially developing a different aspect in elucidating the molecular immunopathogenesis of NSCLC. Hsa_circ_0000190 upregulation can be an effective indicator for the progression of NSCLC, and hsa_circ_0000190 downregulation may possess a potential therapeutic value for the treatment of NSCLC in combination with immunotherapy.

Cell shape reflects the spatial configuration resulting from the equilibrium of cellular and environmental signals and is considered a highly relevant indicator of its function and biological properties. For cancer cells, various physiological and environmental challenges, including chemotherapy, cause a cell state transition, which is accompanied by a continuous morphological alteration that is often extremely difficult to recognize even by direct microscopic inspection. To determine whether deep learning-based image analysis enables the detection of cell shape reflecting a crucial cell state alteration, we used the oral cancer cell line resistant to chemotherapy but having cell morphology nearly indiscernible from its non-resistant parental cells. We then implemented the automatic approach via deep learning methods based on EfficienNet-B3 models, along with over- and down-sampling techniques to determine whether image analysis of the Convolutional Neural Network (CNN) can accomplish three-class classification of non-cancer cells vs. cancer cells with and without chemoresistance. We also examine the capability of CNN-based image analysis to approximate the composition of chemoresistant cancer cells within a population. We show that the classification model achieves at least 98.33% accuracy by the CNN model trained with over- and down-sampling techniques. For heterogeneous populations, the best model can approximate the true proportions of non-chemoresistant and chemoresistant cancer cells with Root Mean Square Error (RMSE) reduced to 0.16 by Ensemble Learning (EL). In conclusion, our study demonstrates the potential of CNN models to identify altered cell shapes that are visually challenging to recognize, thus supporting future applications with this automatic approach to image analysis.

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by symmetrical joint inflammation and destruction. Methotrexate (MTX) is a first-line treatment, but about 40% of patients need to switch to other disease-modifying antirheumatic drugs (DMARDs) due to inadequate efficacy or adverse effects. Pharmacogenomic studies have shown that genotypes may affect drug metabolism, efficacy, and toxicity. Methods This study analyzed the correlation between MTX metabolism-related genes, including SLC19A1, ABCB1, SLCO1B1, and MTHFR, and efficacy in 84 RA patients treated with MTX, using the chi-square test or Fisher’s exact test combined with three gene models. Results The results showed that the 129 bp insertion allele of the SLC19A1 gene was associated with drug efficacy. Compared with the X/X genotype, patients carrying at least one INS-allele (INS/INS + X/ins) would have higher odds of showing improvement ( p  = 0.047, OR = 2.564, 95% CI = 0.999–6.580). The CTTGTACTTGTA of rs4149096 and the C-allele of rs2291075 were associated with improvement ( p  = 0.036, OR = 4.145, 95% CI = 1.028–16.715), but the same allele was negatively associated with good response ( p  = 0.036, OR = 0.188, 95% CI = 0.042–0.827). Conclusions The rs4149096 and rs2291075 showed significant differences between moderate response and no response, as well as between good and moderate responders; however, no significant association was observed between improvement and no response, reflecting a typical nonlinear dose-response effect. The 129 bp insertion of the SLC19A1 gene was positively correlated with better treatment response, suggesting it may be more directly involved in MTX carriage or metabolism, exerting a stable additive effect on drug efficacy. In conclusion, these results highlight the importance of MTX-related genotypes in treatment improvement and intensity, and support their potential as predictive markers of treatment response.

Healthcare is now an important part of daily life because of rising consciousness of health management. Medical professionals can know users’ health condition if they are able to access information immediately. Telemedicine systems, which provides long distance medical communication and services, is a multi-functional remote medical service that can help patients in bed in long-distance communication environments. As telemedicine systems work in public networks, privacy preservation issue of sensitive and private transmitted information is important. One of the means of proving a user’s identity are user-controlled single sign-on (UCSSO) authentication scheme, which can establish a secure communication channel using authenticated session keys between the users and servers of telemedicine systems, without threats of eavesdropping, impersonation, etc., and allow patients access to multiple telemedicine services with a pair of identity and password. In this paper, we proposed a smartcard-based user-controlled single sign-on (SC-UCSSO) for telemedicine systems that not only remains above merits but achieves privacy preservation and enhances security and performance compared to previous schemes that were proved with BAN logic and automated validation of internet security protocols and applications (AVISPA).