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Knowledge of locations and activities of cis -regulatory elements (CREs) is needed to decipher basic mechanisms of gene regulation and to understand the impact of genetic variants on complex traits. Previous studies identified candidate CREs (cCREs) using epigenetic features in one species, making comparisons difficult between species. In contrast, we conducted an interspecies study defining epigenetic states and identifying cCREs in blood cell types to generate regulatory maps that are comparable between species, using integrative modeling of eight epigenetic features jointly in human and mouse in our Validated Systematic Integration (VISION) Project. The resulting catalogs of cCREs are useful resources for further studies of gene regulation in blood cells, indicated by high overlap with known functional elements and strong enrichment for human genetic variants associated with blood cell phenotypes. The contribution of each epigenetic state in cCREs to gene regulation, inferred from a multivariate regression, was used to estimate epigenetic state regulatory potential (esRP) scores for each cCRE in each cell type, which were used to categorize dynamic changes in cCREs. Groups of cCREs displaying similar patterns of regulatory activity in human and mouse cell types, obtained by joint clustering on esRP scores, harbor distinctive transcription factor binding motifs that are similar between species. An interspecies comparison of cCREs revealed both conserved and species-specific patterns of epigenetic evolution. Finally, we show that comparisons of the epigenetic landscape between species can reveal elements with similar roles in regulation, even in the absence of genomic sequence alignment., (© 2024 Xiang et al.; Published by Cold Spring Harbor Laboratory Press.)

Ferroptosis is an iron-dependent and lipid peroxides (LPO)-overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near-infrared photo-responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near-infrared (NIR-808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2-weighted magnetic resonance imaging (MRI) property. In summary, the FeP-based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics., (© 2024 Wiley‐VCH GmbH.)

Cytotoxic T lymphocytes (CTLs), also known as CD8 + T cells, participate in immune function by secreting various cytokines after recognizing specific antigens and class I major histocompatibility complex molecules associated with tumor cells, and thus have a key role in antitumor immunity. However, certain CD8 + T cells show low reactivity and thus cannot effectively remove tumor cells or viral antigens. Due to this heterogeneity, effective biomarkers representing these differences in CD8+ cells are needed. The identification of suitable biomarkers will also enhance the management of cancer treatment. Recent research has improved the understanding of CD8 + T lymphocytes in the tumor microenvironment and circulatory system. Treatment efficacy is impacted directly by the pathogenic response of CTLs, and thus, the use of adjuvant therapies to address these pathological changes, e.g., stimulating the increase in the proportion of reactive T cells or suppressing the proportion of terminally exhausted T cells, would be advantageous.

Tubulointerstitial fibrosis (TIF) is one of the key indicators in evaluating the renal function of patients. Mild TIF can cause a vicious cycle of renal tubular glomerular injury and aggravate renal disease. Therefore, studying the mechanisms underlying TIF is essential to identify therapeutic targets, thereby protecting the renal function of patients with timely intervention. Astragaloside IV (AS-IV) is a Chinese medicine component that has been shown to inhibit the occurrence and progression of TIF via multiple pathways. Previous studies have reported that AS-IV protected against TIF by inhibiting inflammation, autophagy, endoplasmic reticulum stress, macrophages, and transforming growth factor-β1, which laid the foundation for the development of a new preventive and therapeutic option for TIF., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Metagenomic next-generation sequencing (mNGS) is valuable for pathogen identification; however, distinguishing between infectious diseases and conditions with potentially similar clinical manifestations, including malignant tumors, is challenging. Therefore, we developed a method for simultaneous detection of infectious pathogens and cancer in blood samples., Methods: Plasma samples (n = 244) were collected from 150 and 94 patients with infections and hematological malignancies, respectively, and analyzed by mNGS for pathogen detection, alongside human tumor chromosomal copy number variation (CNV) analysis (≥5Mbp or 10Mbp CNV region). Further, an evaluation set, comprising 87 plasma samples, was analyzed by mNGS and human CNV analysis, to validate the feasibility of the method., Results: Among 94 patients with hematological malignancy, sensitivity values of CNV detection for tumor diagnosis were 69.15 % and 32.98 % for CNV region 5Mbp and 10Mbp, respectively, with corresponding specificities of 92.62 % and 100 % in the infection group. Area under the ROC curve (AUC) values for 5Mbp and 10Mbp region were 0.825 and 0.665, respectively, which was a significant difference of 0.160 (95 % CI: 0.110-0.210; p < 0.001), highlighting the superiority of 5Mbp output region data. Six patients with high-risk CNV results were identified in the validation study: three with history of tumor treatment, two eventually newly-diagnosed with hematological malignancies, and one with indeterminate final diagnosis., Conclusions: Concurrent CNV analysis alongside mNGS for infection diagnosis is promising for detecting malignant tumors. We recommend adopting a CNV region of 10Mbp over 5Mbp for our model, because of the lower false-positive rate (FPR)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

IL-6 signaling plays a crucial role in the survival and metastasis of skin cancer. NEDD4L acts as a suppressor of IL-6 signaling by targeting GP130 degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma. Skin tumors were induced in wild-type and Nedd4l-knockout mice, and activation of the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cutaneous squamous cell carcinoma tissues from patients. Nedd4l deficiency significantly promoted 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The APPswe/PS1ΔE9 mouse is a double transgenic murine model that harbors two transgenes for Alzheimer's Disease (AD)-related mutant proteins. We previously discovered that this double transgenic animal had a premature immunosenescence phenotype. However, it is unclear how this phenotype progresses to a later stage. This study aimed to elucidate the changes in systemic characteristics aside from those associated with AD between elderly APPswe/PS1ΔE9 mice and littermate control wild-type mice. Tumors in all organs were considerably more frequent in AD mice aged 24 months than in the control wild-type mice. In addition, the survival rate of aged AD mice was considerably lower than that of wild-type control mice. Further, we discovered that the phenotypic difference was mainly caused by severe immunological aging, as evidenced by a high proportion of exhausted T lymphocytes in AD mice compared to wild-type mice of the same age. Based on our findings, the harm produced by normal aging is not as severe as immunological senescence. Addressing immunological aging, as opposed to anti-aging alone, may be a more crucial target for a long life free of cancer., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Acute myeloid leukemia (AML) is a challenging disease with high rates of recurrence. The role of the cancer-related gene GRHL2 in AML has not been widely studied. Methods: Peripheral blood samples were collected from 73 AML patients and 68 healthy controls. Droplet digital PCR was used to detect GRHL2 methylation levels to explore the value of GRHL2 methylation in the diagnosis, treatment response and prognosis of AML. Result: GRHL2 methylation was significantly increased in AML patients (p < 0.01), with high diagnostic accuracy (area under the curve: 0.848; p < 0.001). GRHL2 methylation was correlated with chemotherapy response (p < 0.05) and is an independent prognostic factor for AML (p < 0.05). Conclusion: GRHL2 methylation is expected to serve as a biomarker for diagnosing AML patients and predicting prognosis.

Purpose: To evaluate the safety and effectiveness of intra-sac thrombin injection to remedy type II endoleaks (T2ELs) during endovascular aneurysm repair (EVAR)., Materials and Methods: 224 cases abdominal aortic aneurysm (AAA) were treated with EVAR. For the 52 cases of intra-operative type II endoleaks and 8 cases of ruptured AAAs, after the grafts were deployed, thrombin was injected into the aneurysm sac through a preset catheter. The occurrence of endoleaks post-EVAR were followed up with by Computed Tomography (CT) angiogram. The diameter and the volume of the aneurysm sac were also measured. Endpoints included incidence of T2ELs, AAA sac shrinkage and re-intervention rate and all-cause mortality., Results: The overall technical success rate was 100%. Fifty-two patients were followed up with for 9-56 (median 24) months. No serious complications were observed during follow-up. The incidence of endoleak was 5.8% (3/52) during follow-up. The maximum diameter of the aneurysm decreased from 61.1 ± 14.2 mm to 53.7 ± 10.6 mm, 47.9 ± 8.3 mm and 43.7 ± 7.2 mm (87.9%, 78.4% and 71.5% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively ( P < .05). The volume of the aneurysm sac shrank from 236.2 ± 136.2 cm 3 to 202.6 ± 114.1 cm 3 , 155.6 ± 68.4 cm 3 and 129.7 ± 52.4 cm 3 (85.8%, 65.9%, and 54.9% of pre-EVAR) at the 6-month, 1-year and 2-year follow-up, respectively ( P < .05). The rate of various endoleaks was 5.8% (3/52) and the re-intervention rate was 1.9% (1/52) in this research., Conclusions: Clinical outcomes show that intra-sac injection of thrombin during EVAR is safe and may be effective in remedying small amount and low-velocity endoleaks and promoting shrinkage of the aneurysm sac., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The mevalonate-diphosphate decarboxylase (MVD) gene, a member of the mevalonate pathway, plays a critical role in regulating the biosynthesis of cholesterol, steroid hormones, and non-steroid isoprenoids. Previous studies have suggested that the MVD c.746 T > C mutation is a major pathogenic gene of porokeratosis (PK), an autoinflammatory keratinization disease (AIKD) with unclear pathogenesis, few effective treatments, and no suitable animal model. To investigate the function of Mvd F250S/+ mutation, we developed a novel Mvd F250S/+ mouse model carrying an equivalent point mutation to the most common genetic variation among Chinese PK patients (MVD F249S/+ ) using CRISPR/Cas9 technology, which exhibited reduced cutaneous expression of Mvd protein. In the absence of external stimulation, Mvd F250S/+ mice did not display specific phenotypes. However, upon induction with imiquimod (IMQ), Mvd F250S/+ mice exhibited decreased susceptibility to skin acute inflammation compared to wild-type (WT) mice, as evidenced by reduced cutaneous proliferation and lower protein levels of IL-17a and IL-1β. Additionally, after IMQ induction, the Mvd F250S/+ mice exhibited downregulated collagen generation and upregulated expression of Fabp3 compared to WT mice, whereas no significant changes in the key genes related to cholesterol regulation were found. Furthermore, the Mvd F250S/+ mutation activated autophagy. Our findings provided insights into the biological function of MVD in the skin., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Online health communities (OHCs) provide knowledge for users, enabling conversations across a broad range of health topics. The development of OHCs depends on users' motivations to share health knowledge. Yet little literature has explored how perceived benefits and costs affect users' motivations for sharing both general and specific knowledge. Based on social exchange theory, we propose a research model that comprises intrinsic benefits (sense of self-worth, satisfaction), extrinsic benefits (social support, reputation, and online attention), cognitive cost, and executional cost to investigate the effects of these factors on users' motivations for general and specific knowledge sharing. We compare the different effects of these factors on users' motivations for knowledge sharing. Results demonstrate positive effects of intrinsic and extrinsic benefits on users' motivations for general and specific knowledge sharing. Differences exist in the negative effects of cognitive and executional costs on users' motivations for general and specific knowledge sharing. This study contributes to promoting the enrichment of online health knowledge and provides implications for the development of OHCs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To explore rational measures to improve medical undergraduates' scientific research quality by investigating and analyzing their scientific research situation. A questionnaire survey was conducted in March 2022 among medical college/university undergraduates across four grades and five majors. Five hundred and ninety-four questionnaires were distributed, and 553 valid copies were returned, with a 93.1% return rate. The results showed that 61.5% of the students had an intense interest in research experiments, and 46.8% thought it was important for undergraduates to participate in research experiments, but only 17.5% often participated in them. Among the students, 85.0% thought that the main factors preventing them from participating in research experiments were academic stress and insufficient time, and 82.6% hoped that mentors would focus on practical skills training; only 13.0% read literature at least once per week, and 93.5% were not proficient at organizing and using literature. Among the participating undergraduates, more than half were strongly interested in scientific research, but academic stress, unclear participation modes, and insufficient literature retrieval skills limited undergraduate scientific research practice and improvement of scientific quality. Therefore, it is essential to cultivate undergraduates' interest in scientific research, ensure that they have spare time to engage in scientific research, improve the undergraduate scientific research mentorship system, and enhance relevant scientific research abilities to cultivate more innovative talent in scientific research., (© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)

Objective: The aim of this study is to compare the efficacy and safety of complete multi-level vs. iliac-only revascularization for the treatment of concomitant iliac and superficial femoral artery (SFA) occlusive disease., Methods: A total of 139 consecutive adult patients with severe stenosis and occlusive iliac and SFA disease with Rutherford categories 2-5 underwent multi-level ( n  = 71) and iliac-only ( n  = 68) revascularization at the Department of Intervention Vascular Surgery, Peking University Third Hospital, and Aerospace Center Hospital, between March 2015 and June 2017. Improvement in Rutherford class, perioperative major adverse events, the length of stay, survival rate, and limb salvage rate were assessed. The neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were compared between the two groups., Results: At 48 months, improvement in the Rutherford category was observed in the two groups with no significant difference ( P  = 0.809). Additionally, the two groups were similar concerning the primary patency (84.0% vs. 79.1%, P  = 0.717) and limb salvage rate (93.1% vs. 91.3%, P  = 0.781). A higher proportion of the perioperative major adverse events (33.8% vs. 27.9%, P  = 0.455), the all-cause mortality (11.3% vs. 8.8%, P  = 0.632), and the average length of hospital stay [7.0 (6.0, 11.0) vs. 7.0 (5.0, 8.0), P  = 0.037] were seen in the multi-level group compared with the iliac-only group., Conclusion: For concomitant iliac and superficial femoral artery occlusive disease, iliac-only revascularization has favorable efficacy and safety outcomes compared with complete multi-level revascularization in selected patients with patent profunda femoris artery and at least one healthy outflow tract of the infrapopliteal artery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Ren, Li, Zhuang, Li, Luan, Wang and Ding.)

Transcriptional enhancers have been extensively characterized, but cis-regulatory elements involved in acute gene repression have received less attention. Transcription factor GATA1 promotes erythroid differentiation by activating and repressing distinct gene sets. Here, we study the mechanism by which GATA1 silences the proliferative gene Kit during murine erythroid cell maturation and define stages from initial loss of activation to heterochromatinization. We find that GATA1 inactivates a potent upstream enhancer but concomitantly creates a discrete intronic regulatory region marked by H3K27ac, short noncoding RNAs, and de novo chromatin looping. This enhancer-like element forms transiently and serves to delay Kit silencing. The element is ultimately erased via the FOG1/NuRD deacetylase complex, as revealed by the study of a disease-associated GATA1 variant. Hence, regulatory sites can be self-limiting by dynamic co-factor usage. Genome-wide analyses across cell types and species uncover transiently active elements at numerous genes during repression, suggesting that modulation of silencing kinetics is widespread., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14 + cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.

Transcription at most promoters is divergent, initiating at closely spaced oppositely oriented core promoters to produce sense transcripts along with often unstable upstream antisense transcripts (uasTrx). How antisense transcription is regulated and to what extent it is coordinated with sense transcription is not well understood. Here, by combining acute degradation of the multi-functional transcription factor CTCF and nascent transcription measurements, we find that CTCF specifically suppresses antisense but not sense transcription at hundreds of divergent promoters. Primary transcript RNA-FISH shows that CTCF lowers burst fraction but not burst intensity of uasTrx and that co-bursting of sense and antisense transcripts is disfavored. Genome editing, chromatin conformation studies and high-resolution transcript mapping revealed that precisely positioned CTCF directly suppresses the initiation of uasTrx, in a manner independent of its architectural function. In sum, CTCF shapes the transcriptional landscape in part by suppressing upstream antisense transcription., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Purpose: It has been shown that activation of autophagy promotes the development of pulmonary arterial hypertension (PAH). Meanwhile, forkhead box M1 (FOXM1) has been found to induce autophagy in several types of cancer. However, it is still unclear whether FOXM1 mediates autophagy activation in PAH, and detailed mechanisms responsible for these processes are indefinite., Method: PAH was induced by a single intraperitoneal injection of monocrotaline (MCT) to rats. The right ventricle systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), percentage of medial wall thickness (%MT), α-smooth muscle actin (α-SMA) staining, and Ki67 staining were performed to evaluate the development of PAH. The protein levels of FOXM1, phospho-focal adhesion kinase (p-FAK), FAK, and LC3B were determined by immunoblotting or immunohistochemistry., Results: FOXM1 protein level and FAK activity were significantly increased in MCT-induced PAH rats, this was accompanied with the activation of autophagy. Pharmacological inhibition of FOXM1 or FAK suppressed MCT-induced autophagy activation, decreased RVSP, RVHI and %MT in MCT-induced PAH rats, and inhibited the proliferation of pulmonary arterial smooth muscle cells and pulmonary vessel muscularization in MCT-induced PAH rats., Conclusion: FOXM1 promotes the development of PAH by inducing FAK phosphorylation and subsequent activation of autophagy in MCT-treated rats., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There are many Fusarium graminearum contaminations in barley that are often associated with malt and beer quality issues. Thus, it is important to find a biological antifungal agent to prevent the growth of F. graminearum during malting. Minimum inhibition concentration (MIC) of chitosan for mycelial growth and spore germination of F. graminearum was 2.6 g/L and 1.6 g/L, respectively, indicating that the F. graminearum strain was highly sensitive toward chitosan. Chitosan with a molecular weight of 102.7 kDa was added at 0.5 g/kg during the first steeping stage, resulting in the maximum inhibition rate of F. graminearm in barley. The biomass of F. graminearm and deoxynivalenol content in the infected barley at the end of germination with 0.5 g/kg chitosan treatment were decreased by 50.7% and 70.5%, respectively, when compared with the infected barley without chitosan. Chitosan could remove the negative effects of F. graminearm infection on barley germination and malt quality, which makes the application of chitosan during the steeping process as a potential antifungal agent in the malting process to protect from F. graminearum infection.

Background: Gorlin-Goltz syndrome (GS) is an inherited disease characterized by predisposition to basal cell carcinomas (BCCs) and various developmental defects, whose numerous disease-causing PTCH1 mutations have been identified in the hedgehog (Hh) signaling pathway., Methods: In this study, whole exome sequencing was used to screen for both somatic and germline deleterious mutations in three sisters with a lethal GS. The mutations we found were confirmed by subcloning and Sanger sequencing of the genomic DNA. RNA-seq was performed to profile gene expression in paired BCCs samples and the expression levels for selected genes were validated by quantitative PCR., Results: The clinical and histopathologic features were analyzed for the proband in the three-generation GS family. We identified the insertion mutation PTCH1 c.1341dupA (p. L448Tfs*49), which segregated with BCC phenotype and contributed to the death of two in four patients from a Chinese family with GS. Compared with adjacent non-cancerous tissues (ANCT), four second-hit mutations were found in four of the six pairs of BCC from three patients. Of note, somatic genomic alterations in all six BCC samples were mainly clustered into non-clock-like Signature 7 (ultraviolet mutagenesis) and 11 (related to certain alkylating agents). Both RNA-seq and quantitative RT-PCR confirmed that the mRNA levels of PTCH1 and its effector GLI1 were markedly upregulated in six pairs of BCC samples versus ANCT., Conclusions: The distinct non-clock-like signatures of BCCs indicated that GS was not a life-threatening illness. The main reasons for untimely death of GS patients were PTCH1 mutation, exposure to intense ultraviolet radiationand the poor economic conditions., (© 2022. The Author(s).)

The human induced pluripotent stem cell (iPSC) line SMBCi017-A was derived from urine cells of a 20 year old male healthy control donor. The generated iPSCs had normal karyotype, expressed chromosomal stability pluripotency hallmarks and differentiated into the three primary germ layers., (Copyright © 2022. Published by Elsevier B.V.)

Surface emitting lasers are attractive light sources for silicon integrated photonic circuits. High speed direct operation is of great importance for these lasers in high capacity and low cost on-chip communication system. Here, we demonstrate a 1.3 µm surface emitting ridge-waveguide distributed feedback (DFB) laser with second order grating and λ/4 phase shift grating, which can achieve a 24 Gb/s operation over a wide temperature. The fabricated lasers can achieve low threshold current as 6.8 mA, and 12.5 mA at 20, and 70°C, respectively. Stable single mode operation has been observed with high side mode suppression ratio (SMSR) > 40 dB at all temperatures (20-70 °C). Meanwhile, the surface emitting optical power can reach 1.7 mW at high temperature as 70 °C. 3 dB bandwidth of small signal response is 21 GHz and 12 GHz at 20 °C and 70 °C respectively. The far-field divergence angle of surface emitting beam is 13.4°×20.2° of 10 µm length second order grating coupler. The proposed laser may have great advantages of single mode, high speed modulation and good temperature tolerance. In addition, compared with conventional DFB lasers, the surface emitting DFB laser has no additional manufacturing process, which is simple to fabricate and easy to integrate with silicon platform.

Congenital talipes equinovarus (CTEV) is a congenital malformation affecting approximately 1/700-1/1000 of live borns. To date extensive epidemiological and biological studies have been operated to solve this issue, the most meaningful findings in clubfoot genetics involve PITX1 variants, which were associated with clubfoot phenotype in mice and humans. According to recent studies, the PITX1-TBX4 transcriptional pathway regulatory for early limb development has identified a key developmental pathway in clubfoot etiology by the common disease-rare hypothesis. However, the precise mechanisms causing this disease remain elusive. The pluripotent stem cell line SMBCi018-A will enable proper in vitro disease modeling of CTEV., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Methylmalonic acidemia(MMA) is an autosomal recessive hereditary disease caused by methylmalonyl-CoA mutase defect or its coenzyme cobalamin metabolism defect. The mutation of the MMACHC gene leads to metabolic disorder of coenzyme cobalamin, resulting in abnormal accumulation of methylmalonic acid, and finally leads to impairment of multiple organs' functions. Here we generated an induced pluripotent stem cells (iPSCs) line named SMBCi019-A, using urine cells (UCs) derived from a 10-year-old male MMA patient who carried two heterozygous gene mutations in MMACHC c.438G > A (p.w146x) and c.609G > A (p.w203x). The generated iPSCs retained the mutations can function as a cellular model of MMA., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Osteogenesis imperfecta (OI) is a group of genetic disorders characterized mainly by fractures and bone deformities. It has been established that gene mutations, particularly those in COL1A1 and COL1A2, account for most phenotypes. Here, we generated an induced pluripotent stem cells (iPSCs) line named SMBCi014-A using urine cells (UCs) derived from a 15-year-old female OI type I patient who carried the frame-shift mutation of the COL1A1 gene (exon35:c.2450delC:p.P817fs). The patient had a family history of mild fractures and a blue sclera. Therefore, our study established a patient-derived site-specific cellular model of OI to better understand the osteogenic mechanism., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Uncooled direct modulation DFB laser offers high speed transmission rate over a wide temperature range with high reliability and low cost, making it a cost-effective light source choice for 5G fronthaul and data center applications. However, a significant 3dB bandwidth decrease can be observed in high temperature for conventional DFB lasers. We present an uncooled DFB laser operating up to 85°C with extended direct modulation bandwidth and high reliability based on a novel groove-in-trench ridge waveguide structure, where two narrow grooves penetrating the active layer are etched symmetrically in the two conventional trenches by deep wet etching, respectively. By optimizing the distance between the groove and the mesa stripe, we obtain a 3dB bandwidth of 15.3 GHz at 85°C, which is a 3.7 GHz improvement compared with the conventional ridge waveguide DFB laser. Transmissions of 25 Gb/s NRZ signal at 25°C and 85°C with clear eye openings have been demonstrated. It also achieves 25 Gb/s transmission over 10 km optical fiber with a low power penalty of 0.5 dB for a bit error rate of 10 -12 at 85°C. In addition, the result of 2000-hour aging test shows that the proposed groove-in-trench structure DFB lasers have the same excellent reliability as the conventional ones.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by deficiency of paternal gene expression in the 15q11.2-q13 chromosome imprinted region. Hyperphagia and dysgnosia are typical clinical features in the early-childhood of patient. We generated an induced pluripotent stem cell (iPSC) line SMBCi011-A from a 6 years old male PWS patient, the line expressed pluripotent signs and had ability to differentiate into three germ layers in vivo., (Copyright © 2022. Published by Elsevier B.V.)

Familial hypercholesterolemia (FH; OMIM: # 143890) is a common inherited autosomal dominant disease, characterized by high-level low-density lipoprotein cholesterol (LDL-C) in plasma. Elevated LDL-C levels is closely related with atherosclerotic plaques and premature cardiovascular disease if not treated in time. Here we generated an induced pluripotent stem cell (iPSC) line using urine cells (UCs) derived from an 8-year-old male FH patient who carrying two coding and pathogenic mutations of low-density lipoprotein receptor (LDLR) gene (exon12:c.C1747T and exon13: c. 1948 del G). This induced pluripotent stem cell line named SMBCi009-A can be used to understand more cellular details about FH., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

The human induced pluripotent stem cell (iPSC) line SMBCi013-A was derived from urine cells of a 29 year old male affected by Wilson's disease. Two heterozygous mutations in the ATP7B gene were detected by whole exon sequencing (c.2303C > A and c.3334C > T). The reprogramming factors (OCT-4, SOX-2, KLF4, miR-302-367) were delivered using non-integrating episomal plasmids. The resulting iPSCs were pluripotent, have chromosomal stability, and the ability to differentiate into the three germ layers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Mobile health applications (mHealth apps) have created innovative service channels for patients with chronic diseases. These innovative service channels require physicians to actively use mHealth apps. However, few studies investigate physicians' participation in mHealth apps., Objective: This study aims to empirically explore factors affecting physicians' usage behaviors of mHealth apps. Based on the extended Unified Theory of Acceptance and Use of Technology (UTAUT2) and mHealth apps features, we propose a research model including altruism, cognitive trust, and online ratings., Methods: We collected data from physicians who have used mHealth apps and conducted a factor analysis to verify the convergence and discriminative effects. We used a hierarchical regression method to test the path coefficients and statistical significance of our research model. In addition, we adopted bootstrapping approach and further analyzed the mediating effects of behavioral intention between all antecedent variables and physicians' usage behavior. Finally, we conducted three robustness analyses to test the validity of results and tested the constructs to verify the common method bias., Results: Our results support the effects of performance expectancy, effort expectancy, social influence, and altruism on the behavioral intentions of physicians using mHealth apps. Moreover, facilitating conditions and habits positively affect physicians using mHealth apps through the mediating effort of behavioral intention. Physicians' cognitive trust and online rating have significant effects on their usage behaviors through the mediating efforts of behavioral intention., Conclusions: This study contributes to the existing literature on UTAUT2 extension of physicians' acceptance of mHealth apps by adding altruism, cognitive trust, and online ratings. The results of this study provide a novel perspective in understanding the factors affecting physicians' usage behaviors on mHealth apps in China and provide such apps' managers with an insight into the promotion of physicians' active acceptance and usage behaviors., (© 2021. The Author(s).)

Objectives: This study aims to compare the clinical effectiveness of transforaminal endoscopic spine system (TESSYS) technique combined with selective nerve root block (SNRB) in treating patients with far lateral lumbar disc herniation (FLDH) and patients with central or paracentral herniation (C/PDH)., Patients and Methods: Between June 2015 and June 2019, a total of 204 patients (80 males, 124 females; mean age: 62.3±5.4 years; range, 51 to 66 years) with a herniated disc were included. Of these, 22 consecutive adult patients with FLDH formed the FLDH group, while 182 patients with C/PDH formed the C/PDH group. Considering that FLDH was a rare type of LDH and occurred outside the spinal canal, the patients with LDH in the spinal canal (C/PDH) were selected as the controls in our study. All cases received ultrasound-guided SNRB to identify the diseased disc and treated by the TESSYS technique. Data including demographics, duration of operation, duration of hospital stay, surgical cost, complications, Visual Analog Scale (VAS) scores for the back and leg, and Oswestry Disability Index (ODI) scores and the modified MacNab criteria were analyzed., Results: The FLDH group presented the similar clinical outcomes and costs with the C/PDH group. No significant differences in the VAS score, ODI score, and Macnab score were observed between the groups (p>0.05 for all). Both groups showed the significantly improved postoperative VAS scores on Day 3, at 1, 3, 6, and 12 months compared to baseline. The postoperative ODI scores at 6 and 12 months were also significantly improved (p<0.05). At the final follow-up at 12 months, the FLDH group showed the MacNab criteria rating excellent and good of 81.8% and C/PDH group showed 84.62%., Conclusion: The FLDH patients presented the comparable clinical effectiveness with C/PDH patients. Based on these findings, the TESSYS technique combined with ultrasound-guided SNRB for FLDH is safe and feasible with caution, although the risk of nerve root injury may be worried.

The aging of the immune system is not only an inevitable result but also an important cause of physical aging. The aging of the immune system is rooted in the aging of hematopoietic cells (HSCs), which manifests as decreasing functionality of the adaptive immune system and the innate immune system. C57BL/6 mice of different ages were collected in this study to better understand the changes in the structures of the innate and adaptive immune systems in individuals of different ages and the distribution and changes in immune cells with stem cell properties. The immune cells of the innate and adaptive immune systems, including DCs, monocytes, macrophages, CD4 + T lymphocytes, CD8 + T lymphocytes, and B lymphocytes, were assessed, and the proportions of cells with stem cell properties among these immune cell populations were also tested. Overall, immune cells in the peripheral blood, spleen, and bone marrow of mice exhibit certain regular properties with increasing age. The trend of changes in immune cells in different immune organs differs with age. The changes in lymphocytes in the peripheral blood are more sensitive. Their proportions increase slowly with age and then decrease rapidly to a very low level (less than 5%) after a certain point (9 or 13 months old). Nine to 13 months of age is the most critical time point for assessing changes in the immune system of mice and the most critical time point for detecting changes in the proportion of stem cells. After 13 months of age, the balance and stability of stem cells in mice are disrupted, and animals begin to age rapidly. The ratio of Ly6A to E + CD117 + cells in the peripheral blood, particularly lymphocytes involved in adaptive immunity, represents a specific marker for predicting immune senescence and body senescence., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Animal models of rheumatoid arthritis (RA) are essential for studying the pathogenesis of RA in vivo and determining the efficacy of anti-RA drugs. During the past decades, numerous rodent models of arthritis have been evaluated as potential models and the modeling methods are relatively well-developed. Among these models, the collagen-induced arthritis (CIA) mouse model is the first choice and the most widely used because it may be generated rapidly and inexpensively and is relatively similar in pathogenesis to human RA. To date, there have been numerous classic studies and reviews discussing related pathogeneses and modeling methods. Based on this knowledge, combined with the latest convenient and effective methods for CIA model construction, the present review aims to introduce the model to beginners and clarify important details regarding its use. Information on the origin and pathogenesis of the CIA model, the protocol for establishing it, the rate of successful arthritis induction and the methods used to evaluate the severity of arthritis are briefly summarized. With this information, it is expected that researchers who have recently entered the field or are not familiar with this information will be able to start quickly, avoid unnecessary errors and obtain reliable results., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Luan et al.)

Abnormal gene expression and secreted protein levels are accompanied by extensive pathological changes. Secreted frizzled related protein (SFRP) family members are antagonistic inhibitors of the Wnt signaling pathway, and they were recently found to be involved in the pathogenesis of a variety of metabolic diseases, which has led to extensive interest in SFRPs. Previous reports highlighted the importance of SFRPs in lipid metabolism, obesity, type 2 diabetes mellitus and cardiovascular diseases. In this review, we provide a detailed introduction of SFRPs, including their structural characteristics, receptors, inhibitors, signaling pathways and metabolic disease impacts. In addition to summarizing the pathologies and potential molecular mechanisms associated with SFRPs, this review further suggests the potential future use of SFRPs as disease biomarkers therapeutic targets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guan, Zhang, Luan, Xu, Huang, Yu, Gou and Xu.)

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare, low- to intermediate-grade sarcoma, which represents a diagnostic imaging challenge. This study aimed to analyze the clinical and ultrasound features of primary and recurrent DFSP to improve the diagnosis., Methods: Clinical, imaging, and pathological data from a total of 58 patients (23 patients with primary DFSP and 35 patients with recurrent DFSP) were retrospectively reviewed., Results: There was no statistically significant difference in age, sex, tumor size, or echogenicity between the two groups. Most of the primary DFSP lesions involved the overlying dermis and hypodermis, while most of the recurrent DFSP lesions were fixated to more deeply seated structures at the original surgical incision. Red nodules on the skin were found more frequently in the primary group. There were statistically significant differences in the type of lesion and ultrasound tumor morphology (p < 0.050). The lesions in the primary group showed more tentacle-like projections or a "claw" sign, while the lesions in the recurrent group were more commonly oval, lobulated, and irregularly shaped. Hypervascularity was common in both groups., Conclusions: For primary DFSP, a slow-growing, red nodule on the skin involving the overlying dermis and hypodermis, more frequently a hypoechoic mass with tentacle-like projections or a "claw" sign, was observed. For recurrent DFSP, palpable subcutaneous nodules or subcutaneous masses at the original surgical incision and oval, lobulated, and irregularly shaped lesions were more commonly observed. This may be useful for improving diagnostic accuracy., (© 2021. The Author(s).)

The sudden outbreak of coronavirus disease 2019 (COVID-19) in early 2020 has dramatically changed people's lives. Some countries have taken mass home quarantine to control the virus. However, the side effects of quarantine have rarely been interrogated by current COVID-19 research. This study thus investigates the effects of online social support on the public's beliefs in overcoming COVID-19 by embracing their cognition and emotion during the epidemic. First, by crawling and content analysis of the messages posted on "Baidu COVID-19 bar", this study identified 5 types of online social support given or received by the public during COVID-19. On this basis, a model explaining the public's beliefs was developed from the perspectives of online social support, cognition and emotion. 334 valid online questionnaires were collected to examine the proposed model and hypotheses. The results show that cognition has a direct effect on the belief, while emotion affects the belief via a full mediating effect of cognition. Tangible support and esteem support can directly affect the public's beliefs, and educational level significantly moderates these effects. In addition, the public's cognition is influenced by informational support, however, emotion is not influenced by social support but by other factors (e.g., information disclosure, material supplies and frustration caused by the epidemic). These research results provide a deep insight into how to reduce the negative effects of quarantine, consolidate the theoretical basis of the public's beliefs, and have important practical implications for individuals and the government in dealing with such emergencies., (© 2021 Elsevier Ltd. All rights reserved.)

LilrB2 is an Aβ receptor with high affinity, which not only contributes to memory deficits but also mediates the loss of synaptic plasticity. Thus, Aβ-LilrB2 interaction inhibitors (ALIs) might be a potential therapeutic strategy for Alzheimer's disease. In this study, an ELISA-based interaction assay was established as a novel approach to identify ALIs and was used to screen 110 compounds from a compound library. Among the 110 compounds, four compounds presented IC 50 values lower than the positive control flusipirilene. The two phenyl-1,3,5-triazine derivatives (compound 103 and 104) displayed inhibitory activities with the IC 50 of 0.23 μM and 0.05 μM respectively. The neuroprotection activities of the hit compounds were evaluated in SH-SY5Y cell line. Compound 104 presented good safety and neuroprotective effects against Aβ. Further study of its effect on the downstream pathway of Aβ indicated that compound 104 was able to reverse the Aβ induced cofilin dephosphorylation, tau hyperphosphorylation and neurite outgrowth inhibition. The docking study showed that fluspirilene and compound 104 were favorably positioned into the Ben 3 and 4 binding pockets via their aromatic ring, which was similar to that reported for Aβ. Based on these facts, compound 104 can be identified as a potential ALI which might be of therapeutic importance for AD treatment., (Copyright © 2021. Published by Elsevier Inc.)

Background: The MVD gene mutations are identified in porokeratosis, which is considered a skin-specific autoinflammatory keratinization disease. However, the biological function of MVD gene remains largely unknown. Therefore, we analyzed the function of mvda gene, orthologous to the human MVD gene, in developing zebrafish., Methods: Morpholino antisense oligonucleotide technique was used to generate mvda loss-of-function phenotypes. Knockdown of mvda was confirmed by RT-PCR and Sanger sequencing. Scanning and transmission electron microscopy were performed to analyze the morphology of the epidermis. Angiogenesis study was presented using the Tg(fli1a:EGFP) y1 transgenic strain. In addition, acridine orange staining was used to examine the apoptotic cells in vivo., Results: As expected, the mvda morphants showed abnormal morphology of the epidermis. Moreover, we observed ectopic sprouts in trunk angiogenesis and impaired formation of the caudal vein plexus in the mvda-deficient zebrafish. Besides, increased apoptosis was found throughout the tail, heart, and eyes in mvda zebrafish morphants., Conclusions: These findings indicated the essential role of mvda in the early development of zebrafish. This was the first in vivo knockdown study of the zebrafish mvda gene, which might offer insight into the biological function of the human MVD gene.

Muscle-bone interaction might regulate bone remodeling in an endocrine manner, but the exact mediators have not been identified. Previous in vitro studies suggest that exosomal miRNAs are a candidate for this interaction. Here we present an in vivo study to show that targeted knockout of a muscle-specific miR-23a cluster including miR-23a, miR-27, and miR-24-2 in skeletal muscle tissues can suppress bone remodeling in mice. The effect of miR-23a cluster seem to not be related to aging, but can worsen the pathological extent of osteoporosis in mice. Our findings suggest that muscle-derived miRNAs may contribute to bone metabolism regulation through exosomes in muscle-bone interaction., Competing Interests: The authors have no conflicts of interest to disclose., (2021, International Research and Cooperation Association for Bio & Socio - Sciences Advancement.)

Purpose: Bone destruction and pain caused by cancer is one of the most devastating complications of cancer patients with bone metastases, and it seriously affects the quality of patients' life. Extracellular matrix metalloproteinase inducer (EMMPRIN) is a cell adhesion molecule with increased expression in a variety of tumors. This study focused to clarify the specific function of EMMPRIN in bone metastasis of breast cancer., Materials and Methods: Adenovirus with shRNA-EMMPRIN was transfected into MRMT-1 rat breast carcinoma cells, and the MRMT-1 cells with different expression levels of EMMPRIN were implanted into the bone marrow cavity of rat tibia. Next, the effect of down-regulation of EMMPRIN was evaluated as follows: bone damage was detected by X-ray radiological and tartrate-resistant acid phosphatase staining; the tumor burden was evaluated by hematoxylin and eosin staining; the test of pain-related behaviors was assessed used the bilateral paw withdrawal mechanical threshold; and the levels of secretory factors in tumor conditioned medium were determined by using enzyme-linked immunosorbent assay., Results: We found that down-regulation of EMMPRIN in tumor cells can simultaneously reduce tumor burden, relieve cancer-induced bone destruction and pain., Conclusion: EMMPRIN is expected to be a therapeutic target for relieving bone metastasis of breast cancer and alleviating cancer-induced bone destruction and pain. The method of targeting EMMPRIN may be a promising strategy for the treatment of cancer in the future.

CCCTC-binding factor (CTCF) is a conserved zinc finger transcription factor implicated in a wide range of functions, including genome organization, transcription activation, and elongation. To explore the basis for CTCF functional diversity, we coupled an auxin-induced degron system with precision nuclear run-on. Unexpectedly, oriented CTCF motifs in gene bodies are associated with transcriptional stalling in a manner independent of bound CTCF. Moreover, CTCF at different binding sites (CBSs) displays highly variable resistance to degradation. Motif sequence does not significantly predict degradation behavior, but location at chromatin boundaries and chromatin loop anchors, as well as co-occupancy with cohesin, are associated with delayed degradation. Single-molecule tracking experiments link chromatin residence time to CTCF degradation kinetics, which has ramifications regarding architectural CTCF functions. Our study highlights the heterogeneity of CBSs, uncovers properties specific to architecturally important CBSs, and provides insights into the basic processes of genome organization and transcription regulation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is a chronic neurodegenerative disease that has been recognized as one of the most intractable medical problems with heavy social and economic costs. Amyloid-β (Aβ) has been identified as a major factor that participates in AD progression through its neurotoxic effects. The major mechanism of Aβ-induced neurotoxicity is by interacting with membrane receptors and subsequent triggering of aberrant cellular signaling. Besides, Aβ transporters also plays an important role by affecting Aβ homeostasis. Thus, these Aβ receptors and transporters are potential targets for the development of AD therapies. Here, we summarize the reported therapeutic strategies targeting Aβ receptors and transporters to provide a molecular basis for future rational design of anti-AD agents.

Multiple Osteochondroma is an abnormal skeleton development autosomal dominant genetic disease which caused by the mutation of EXT1 gene. In this study, we generated induced pluripotent stem cells (iPSCs) from the mesenchymal stem cells (MSCs) of a 12-year-old male patient by reprogramming MSCs with non-integrative vectors. The iPSCs line expresses pluripotent markers, has a normal male karyotype and can differentiate into the three germ layers., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

A non-integrated induced pluripotent stem cell (iPSC) line was established using urine cells (UCs) derived from a healthy 32-year-old male. The patient-derived iPSC line SMBCi006-A exhibited a normal karyotype, expressed pluripotency markers and possessed trilineage differentiation potential. This cell line may serve as a basis for disease modeling, and help explore the molecular pathogenesis further., (Copyright © 2020. Published by Elsevier B.V.)

Objectives: Pancreatic acinar necrosis is a typical feature in the early phase of severe acute pancreatitis (SAP). Muscarinic acetylcholine receptor M3 (CHRM3) has been reported to play important roles in promoting insulin secretion and tumor cell proliferation, but its effect on necrosis remains unknown. This study revealed the important role of CHRM3 in regulating L-arginine-induced SAP and the molecular mechanisms., Methods: To verify the function of CHRM3, pancreatic tissues and primary acinar cells of CRISPR/Cas9-mediated Chrm3 knockout mice were used in CHRM3 knockdown experiments, and to ascertain the CHRM3 overexpression, PLV-EGFP-Chrm3 plasmids were transfected in acinar cells in vitro., Results: In L-arginine-induced SAP, CHRM3 is activated and regulates SAP through the mitogen-activated protein kinase/p38 pathway. Moreover, the expression of miR-31-5p decreased in the SAP model both in vitro and in vivo. Mir-31-5p effects the necrosis of acinar cells in SAP by upregulating the target gene RIP3, and miR-31-5p is a downstream miRNA of CHRM3., Conclusions: Necrosis in L-arginine-induced SAP is promoted by CHRM3 through the mitogen-activated protein kinase-p38/miR-31-5p/RIP3 axis.

A human induced pluripotent stem cell (iPSC) line was generated from the urine cells of a 8-year-old female with Gaucher disease with the homozygous changes c.1448 T>C in the GBA gene. Reprogramming factors OCT4, SOX2, KLF4, and miR-302-367 were delivered using a non-integrative plasmid. Our iPSCs showed complete pluripotency, normal genetic stability, and the ability to differentiate into three germ layers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

The levels of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1), a type I transmembrane glycoprotein broadly expressed on the majority of hematopoietic cells, such as T/B cells and natural killer cells, vary significantly during cell differentiation and activation. Previous studies focused mainly on the role of LAIR-1 in physiology and some pathological conditions, including autoimmune diseases. It has been shown that LAIR-1 mediates immune suppression, further resulting in uncontrolled inflammation. Furthermore, recent studies showed that LAIR-1 participates in the development of hematopoietic and non-hematopoietic tumors as well as malaria. This review summarizes the current findings on LAIR-1 in various diseases, its potential roles in pathogenesis, and provides new insight into the treatment of patients through suppression of the function of LAIR-1., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Mutations in the neurofibromin (NF1) gene cause neurofibromatosis type 1 (NF1), a complex tumour predisposition syndrome. Here, we generated two induced pluripotent stem cell (iPSC) lines using urine cells (UCs) derived from a 21-year-old female NF1 patient carrying c.496&#95;497delGT mutation in the NF1 gene (p.Val166LeufsTer7). The newly derived SMBCi003-A and SMBCi003-B iPSC lines used as a cellular model to unravel pathogenesis of NF1., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)