Full-length circRNA sequencing method using low-input RNAs and profiling of circRNAs in MPTP-PD mice on a nanopore platform.

Considering the importance of accurate information of full-length (FL) transcripts in functional analysis, researchers prefer to develop new sequencing methods based on third-generation sequencing (TGS) rather than short-read sequencing. Several FL circRNA sequencing strategies have been developed. However, the current methods are inapplicable to low-biomass samples, since a large amount of total RNAs are acquired for circRNA enrichment before library preparation. In this work, we developed an effective method to detect FL circRNAs from a nanogram level (1-100 ng) of total RNAs based on a nanopore platform. Additionally, prior to the library preparation process, we added a series of 24 nt barcodes for each sample to reduce the cost and operating time. Using this method, we profiled circRNA expression in the striatum, hippocampus and cerebral cortex of a Parkinson's disease (PD) mouse model. Over 6% of reads were effective for FL circRNA identification in most datasets. Notably, a reduction in the RNA initial input resulted in a lower correlation between replicates and the detection efficiency for longer circRNA, but the lowest input (1 ng) was able to detect numerous FL circRNAs. Next, we systematically identified over 263 934 circRNAs in PD and healthy mice using the lower-input FL sequencing method, some of which came from 50.52% of PD-associated genes. Moreover, significant changes were observed in the circRNA expression pattern at an isoform level, and high-confidence protein translation evidence was predicted. Overall, we developed an effective method to characterize FL circRNAs from low-input samples and provide a comprehensive insight into the biological function of circRNAs in PD at an isoform level.

Sol-gel synthesis of magnesium oxide nanoparticles and their evaluation as a therapeutic agent for the treatment of osteoarthritis.

Aim: We synthesized MgO NPs via sol-gel reaction and investigated them as carriers to deliver Mg2+ to the affected joint for osteoarthritis (OA).Materials & methods: The physicochemical properties of samples were characterized by transmission electron microscope (TEM), dynamic light scattering (DLS) and x-ray diffraction (XRD). The release of Mg2+ was monitored by ICP-MS. The potential cytotoxicity was evaluated using MTT assay. The efficacy and biosafety were evaluated in a rabbit OA model.Results: MgO NPs can prolong the Mg2+ release time from 0.5 h to 12 h. No significant cytotoxicity was observed when concentrations below 250 µg/ml. Intra-articular samples could effectively alleviate the degeneration and destruction of the cartilage.Conclusion: this study demonstrates the potential of MgO NPs as a safe and effective treatment of OA. Simultaneously, the size of the particles may play a significant role in influencing the therapeutic outcome.

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The impact of reading metacognitive strategies on mathematics learning efficiency and performance: An analysis using PISA 2018 data in China.

The current study employed latent profile analysis to examine the application patterns of students' reading metacognitive strategies using PISA 2018 data in China. Subsequently, it explored the differences in students' mathematics learning efficiency and performance. The results revealed that: (1) Six types of reading metacognitive strategies application patterns were identified: "Novice - indifferent," "Veteran - average," "Novice - low evaluating," "Veteran - skilled," "Novice - mixed," and "Novice - arbitrary." (2) The primary factors that affect the classification of reading metacognitive strategies application patterns were gender, and family economic, social, and cultural statuses (ESCS). (3) Mathematics learning time could positively predict performance overall, but the mathematics learning time of "Veteran - skilled" and "Novice - mixed" students had no significant correlation with their mathematics performance. The findings suggests that educators should not blindly increase students' mathematics learning time but instead provide appropriate guidance based on their mastery patterns of reading metacognitive strategies to enhance mathematics learning efficiency and performance.

Unraveling genomic diversity and positive selection signatures of Qaidam cattle through whole-genome re-sequencing.

Qaidam cattle are a typical Chinese native breed inhabiting northwest China. They bear the characteristics of high cold and roughage tolerance, low-oxygen adaptability and good meat quality. To analyze the genetic diversity of Qaidam cattle, 60 samples were sequenced using whole-genome resequencing technology, along with 192 published sets of whole-genome sequencing data of Indian indicine cattle, Chinese indicine cattle, North Chinese cattle breeds, East Asian taurine cattle, Eurasian taurine cattle and European taurine cattle as controls. It was found that Qaidam cattle have rich genetic diversity in Bos taurus, but the degree of inbreeding is also high, which needs further protection. The phylogenetic analysis, principal component analysis and ancestral component analysis showed that Qaidam cattle mainly originated from East Asian taurine cattle. Qaidam cattle had a closer genetic relationship with the North Chinese cattle breeds and the least differentiation from Mongolian cattle. Annotating the selection signals obtained by composite likelihood ratio, nucleotide diversity analysis, integrated haplotype score, genetic differentiation index, genetic diversity ratio and cross-population extended haplotype homozygosity methods, several genes associated with immunity, reproduction, meat, milk, growth and adaptation showed strong selection signals. In general, this study provides genetic evidence for understanding the germplasm characteristics of Qaidam cattle. At the same time, it lays a foundation for the scientific and reasonable protection and utilization of genetic resources of Chinese local cattle breeds, which has great theoretical and practical significance.

Curcumin Improves Functional Recovery of Ruptured Tendon by Promoting Tenogenesis via PI3K/Akt Signaling.

OBJECTIVE: In our previous study, we found that local release of curcumin from nanomicelles prevents peritendinous adhesion during Achilles tendon healing. The aim of this study is to further investigate the signaling integrated by curcumin to direct the tenogenetic program of tendon stem cells contributing to tendon healing. METHODS: A surgical model of tendon rupture and repair (TRR) was established in rats. Peritendinous adhesion and inflammation, biomechanical function, and expression of ß-catenin and epithelial cellular adhesion molecule (EpCAM) were determined. A dataset was analyzed to investigate differentially expressed genes and enriched genes related to the signaling pathways. Tendon stem cells were treated with curcumin to investigate the cellular and molecular events as well as the signaling pathway. RESULTS: In rat TRR model, curcumin treatment resulted in not only significantly decreased peritendinous inflammatory but also improved tendon functional recovery along with significantly increased expressions of EpCAM and ß-catenin. Analysis of the dataset indicated that the enriched genes were positively related to differentiation pathways but negatively related to proliferation pathways. In rat tendon stem cells, curcumin treatment inhibited proliferation but promoted differentiation. Curcumin's antioxidative activity was associated with tenogenesis. The upregulated expression of tendon lineage-specific markers was dependent on phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway which could be a potential mechanism of tenogenesis of curcumin treatment. CONCLUSION: Curcumin could improve tendon functional recovery via promoting tenogenesis in addition to its antioxidant and anti-inflammatory activities. Curcumin induced differentiation of tendon stem/progenitor cell into tenocytes via PI3K/Akt signaling pathway. This finding provided evidence for the application of curcumin to prevent adhesion during tendon repair.

Inhibition of CD44 suppresses the formation of fibrotic scar after spinal cord injury via the JAK2/STAT3 signaling pathway.

Fibrotic scar is one of the main impediments to axon regeneration following spinal cord injury (SCI). In this study, we found that CD44 was upregulated during the formation of fibrotic scar, and blocking CD44 by IM7 caused downregulation of fibrosis-related extracellular matrix proteins at both 2 and 12 weeks post-spinal cord injury. More Biotinylated dextran amine (BDA)-traced corticospinal tract axons crossed the scar area and extended into the distal region after IM7 administration. A recovery of motor and sensory function was observed based on Basso Mouse Scale (BMS) scores and tail-flick test. In vitro experiments revealed that inhibiting CD44 and JAK2/STAT3 signaling pathway decreased the proliferation, differentiation, and migration of fibroblasts induced by the inflammatory supernatant. Collectively, these findings highlight the critical role of CD44 and its downstream JAK2/STAT3 signaling pathway in fibrotic scar formation, suggesting a potential therapeutic target for SCI.

Predicting glucocorticoid effectiveness in thyroid eye disease: combined value from serological lipid metabolism and an orbital MRI parameter.

Purpose: The aim was to determine the combined value of serological lipid metabolism and an orbital MRI quantitative parameter in predicting the effectiveness of glucocorticoid (GC) therapy in patients with thyroid eye disease (TED). Methods: This study retrospectively enrolled 46 patients with active and moderate-to-severe TED (GC-effective group, n = 29; GC-ineffective group, n = 17). Serological lipid metabolism, the orbital MRI-based minimum signal intensity ratio of extraocular muscles (EOM-SIRmin), as well as other clinical parameters before GC therapy were collected and compared between the two groups. Multivariate logistic regression and receiver operating characteristic curve analysis were adopted to identify independent predictable variables and assess their predictive performances. Results: Compared to the GC-ineffective group, the GC-effective group showed lower serum total cholesterol levels (P = 0.006), lower serum low-density lipoprotein cholesterol levels (P = 0.019), higher EOM-SIRmin values (P = 0.005), and shorter disease durations (P = 0.017). Serum total cholesterol and EOM-SIRmin were found to be independent predictors of GC-effective TED through multivariate analysis (odds ratios = 0.253 and 2.036 per 0.1 units, respectively) (both P < 0.05). The integration of serum total cholesterol ≤4.8 mmol/L and EOM-SIRmin ≥ 1.12 had a better predictive efficacy (area under the curve, 0.834) than EOM-SIRmin alone, with a sensitivity of 75.9% and a specificity of 82.4% (P = 0.031). Conclusion: Serological lipid metabolism, combined with an orbital MRI-derived parameter, was a useful marker for predicting the effectiveness of GCs in patients with active and moderate-to-severe TED.

The levels of immunosuppressive checkpoint protein PD-L1 and tumor-infiltrating lymphocytes were integrated to reveal the glioma tumor microenvironment.

In spite of significant strides in the realm of cancer biology and therapeutic interventions, the clinical prognosis for patients afflicted with glioblastoma (GBM) remains distressingly dismal. The tumor immune microenvironment (TIME), a crucial player in the progression, treatment response, and prognostic trajectory of glioma, warrants thorough exploration. Within this intricate microcosm, the immunosuppressive checkpoint protein PD-L1 and tumor-infiltrating lymphocytes (TILs) emerge as pivotal constituents, underscoring their potential role in deciphering glioma biology and informing treatment strategies. However, prognostic models based on the association between PD-L1 expression and TIL infiltration in the tumor immune microenvironment have not been established. The aim of this study was to explore TIME genes associated with PD-L1 expression and TIL invasion and to construct a risk score for predicting the overall survival (OS) of GBM patients based on these genes. The samples were separately classified according to the PD-L1 expression level and TIL score and TIME-related genes were identified using differential expression and weighted gene co-expression network analysis. The DEGs were subjected to least absolute contraction and selection operator (LASSO) -Cox regression to construct TIME associated risk score (TIMErisk). A TIMErisk was developed based on STEAP3 and CXCL13 genes. The STLEAP3 was demonstrated to be involved in glioma progression. The results showed that the patients in the high TIMErisk group had poor OS compared with subjects in the low TIMErisk group. The biological phenotypes associated with TIMErisk were analyzed in terms of functional enrichment, tumor immune profile, and tumor mutation profile. The results on tumor immune dysfunction and exclusion dysfunction (TIDE) score and immune surface score (IPS) showed that GBM patients with different TIME risks had different responses to immunotherapy. Tumor purity analysis indicated that PD-L1 and TIL scores were positively correlated with TIMErisk score and negatively correlated with tumor purity. These results show that the TIMErisk-based prognostic model had high predictive value for the prognosis and immune characteristics of GBM patients. Immunohistochemical staining images of patients in the high and low TIMErisk groups were analyzed, showing that the degree of immune cell infiltration was higher in the high TIMErisk group relative to the low TIMErisk group. The present study provides a basis for understanding glioma tumor microenvironment and a foundation for conducting comprehensive immunogenomic analysis.

A comprehensive analysis of library preparation methods shows high heterogeneity of extrachromosomal circular DNA but distinct chromosomal amount levels reflecting different cell states.

Extrachromosomal circular DNA (eccDNA) was discovered several decades ago, but little is known about its function. With the development of sequencing technology, several library preparation methods have been developed to elucidate the biogenesis and function of eccDNA. However, different treatment methods have certain biases that can lead to their erroneous interpretation. To address these issues, we compared the performance of different library preparation methods. Our investigation revealed that the utilization of rolling-circle amplification (RCA) and restriction enzyme linearization of mitochondrial DNA (mtDNA) significantly enhanced the efficiency of enriching extrachromosomal circular DNA (eccDNA). However, it also introduced certain biases, such as an unclear peak in ∼160-200 bp periodicity and the absence of a typical motif pattern. Furthermore, given that RCA can lead to a disproportionate change in copy numbers, eccDNA quantification using split and discordant reads should be avoided. Analysis of the genomic and elements distribution of the overall population of eccDNA molecules revealed a high correlation between the replicates, and provided a possible stability signature for eccDNA, which could potentially reflect different cell lines or cell states. However, we found only a few eccDNA with identical junction sites in each replicate, showing a high degree of heterogeneity of eccDNA. The emergence of different motif patterns flanking junctional sites in eccDNAs of varying sizes suggests the involvement of multiple potential mechanisms in eccDNA generation. This study comprehensively compares and discusses various essential approaches for eccDNA library preparation, offering valuable insights and practical advice to researchers involved in characterizing eccDNA.

Fast Adversarial Training With Adaptive Step Size.

While adversarial training and its variants have shown to be the most effective algorithms to defend against adversarial attacks, their extremely slow training process makes it hard to scale to large datasets like ImageNet. The key idea of recent works to accelerate adversarial training is to substitute multi-step attacks (e.g., PGD) with single-step attacks (e.g., FGSM). However, these single-step methods suffer from catastrophic overfitting, where the accuracy against PGD attack suddenly drops to nearly 0% during training, and the network totally loses its robustness. In this work, we study the phenomenon from the perspective of training instances. We show that catastrophic overfitting is instance-dependent, and fitting instances with larger input gradient norm is more likely to cause catastrophic overfitting. Based on our findings, we propose a simple but effective method, Adversarial Training with Adaptive Step size (ATAS). ATAS learns an instance-wise adaptive step size that is inversely proportional to its gradient norm. Our theoretical analysis shows that ATAS converges faster than the commonly adopted non-adaptive counterparts. Empirically, ATAS consistently mitigates catastrophic overfitting and achieves higher robust accuracy on CIFAR10, CIFAR100, and ImageNet when evaluated on various adversarial budgets. Our code is released at https://github.com/HuangZhiChao95/ATAS.

Applicability of the cognitive model of generalized anxiety disorder to adolescents' sleep quality: A cross-sectional and longitudinal analysis.

Background: Poor sleep quality is a prevalent health issue among adolescents, and few studies have examined the variables affecting adolescents' sleep quality from the perspective of the co-occurrence of sleep issues and anxiety disorders. Therefore, the current study investigated whether the cognitive model of generalized anxiety disorder applies to adolescents' sleep quality. Method: In Study 1, a total of 2042 adolescents were recruited and they completed questionnaires relating to worry, intolerance of uncertainty (IU), negative problem orientation (NPO), cognitive avoidance (CA), and sleep quality. In Study 2, a total of 379 adolescents participated in a six-month longitudinal survey to verify the model that was obtained in Study 1. Results: Study 1 showed the modified cognitive model of generalized anxiety disorder can be applied to adolescents' sleep quality. Specifically, IU was a higher-order vulnerability factor that directly affected worry, and indirectly fostered worry via NPO and CA, where worry only mediated the relationships between IU, NPO, and sleep quality. However, CA exerted no independent effect on worry or sleep quality beyond the influences of IU and NPO, therefore, it dropped out of the final model. Study 2 partially confirmed the above model again from the longitudinal perspective. Conclusion: The present study constructs a new model to explain adolescents' sleep quality, providing a foundation for future interventions.

TGF-ß score based on silico analysis can robustly predict prognosis and immunological characteristics in lower-grade glioma: the evidence from multicenter studies.

INTRODUCTION: Nowadays, mounting evidence shows that variations in TGF-ß signaling pathway-related components influence tumor development. Current research has patents describing the use of anti-TGF-ß antibodies and checkpoint inhibitors for the treatment of proliferative diseases. Importantly, TGF-ß signaling pathway is significant for lower-grade glioma (LGG) to evade host immunity. Loss of particular tumor antigens and shutdown of professional antigen-presenting cell activity may render the anti-tumor response ineffective in LGG patients. However, the prognostic significance of TGF-ß related genes in LGG is still unknown. METHODS: We collected RNA-seq data from the GTEx database (normal cortical tissues), the Cancer Genome Atlas database (TCGA-LGG), and the Chinese Glioma Genome Atlas database (CGGA-693 and CGGA-325) for conducting our investigation. RESULTS: In addition, previous publications were explored for the 223 regulators of the TGF-ß signaling pathway, and 30 regulators with abnormal expression in TCGA and GTEx database were identified. In order to identify hub prognostic regulators, least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression analysis were used to screen from differentially expressed genes (DEGs). On the basis of 11 genes from LASSO-Cox regression analysis (NEDD8, CHRD, TGFBR1, TP53, BMP2, LRRC32, THBS2, ID1, NOG, TNF, and SERPINE1), TGF-ß score was calculated. Multiple statistical approaches verified the predictive value of the TGF-ß score for the training cohort and two external validation cohorts. Considering the importance of the TGF-ß signaling pathway in immune regulation, we evaluated the prediction of the TGF-ß score for immunological characteristics and the possible application of the immunotherapeutic response using six algorithms (TIMER, CIBERSORT, QUANTISEQ, MCP-counter, XCELL and EPIC) and three immunotherapy cohorts (GSE78820, Imvigor-210 and PRJEB23709). Notably, we compared our risk signature with the signature in ten publications in the meta-cohort (TCGA-LGG, CGGA-693 and CGGA-325), and the TGF-ß score had the best predictive efficiency (C-index =0.812). CONCLUSION: In conclusion, our findings suggest that TGF-ß signaling pathway-related signatures are prognostic biomarkers in LGG and provide a novel tool for tumor microenvironment (TME) assessment.

Physical and Mechanical Properties of Novel Multilayer Bamboo Laminated Composites Derived from Bamboo Veneer.

Compared with wood, bamboo has a special fiber gradient structure. Bamboo fibers have attracted attention as reinforced polymer composites. This study investigated the effects of lamination and fiber volume on the physical and mechanical properties of bamboo laminated composites (BLCs). Six types of BLC were derived by parallel and cross laminating bamboo veneers with high, middle, and low fiber volumes. The results indicated that the laminated structure and fiber volume significantly influenced the BLC properties. Microstructural analysis showed that parallel lamination and low fiber volume were more conducive to resin penetration and enhanced the bonding strength. Both the bending and tensile strengths of the cross lamination were lower than those of the parallel lamination. BLCs made of veneers with high and middle fiber volumes and parallel lamination had the maximum bending and tensile strengths (145.1 and 101.53 MPa, respectively). When tested for water resistance, parallel and cross lamination inhibited expansion in the thickness (TSR, 0.56-2.14%) and width (WSR, 0.07-1.61%) directions, respectively. Laminated structures and veneers with varying fiber volume contents should be chosen according to the specific application scenarios. This study provides a reference for selecting an appropriate BLC structure and fiber volume based on application.

Higher maternal thyroid resistance indices were associated with increased neonatal thyroid-stimulating hormone- analyses based on the Huizhou mother-infant cohort.

Objectives: This study aimed to explore the relationship of maternal thyroid function and thyroid resistance parameters with neonatal thyroid-stimulating hormone (TSH). Methods: This work was a longitudinal study. Singleton pregnant women without a history of thyroid disorders were recruited in their first prenatal visit from October 2018 to June 2020. Maternal thyroid markers including TSH, free triiodothyronine (FT3), free thyroxine (FT4), and neonatal TSH were tested in the clinical laboratory of the hospital by electrochemiluminescence immunoassay. Thyroid resistance indices including Thyroid Feedback Quantile-based Index (TFQI), TSH index (TSHI), and thyrotroph T4 resistance index (TT4RI) were estimated in accordance with maternal FT4 and TSH levels. Multivariable linear and logistic regression was applied to explore the associations of maternal thyroid indices with infantile TSH level. Results: A total of 3,210 mothers and 2,991 newborns with valid TSH data were included for analysis. Multivariable linear regression indicated that maternal thyroid variables were significantly and positively associated with neonatal TSH levels with standardized coefficients of 0.085 for TSH, 0.102 for FT3, 0.100 for FT4, 0.076 for TSHI, 0.087 for TFQI, and 0.089 for TT4RI (all P < 0.001). Compared with the lowest quartile, the highest quartile of TSHI [odds ratio (OR) = 1.590, 95% CI: 0.928-2.724; Ptrend = 0.025], TFQI (OR = 1.746, 95% CI: 1.005-3.034; Ptrend = 0.016), and TT4RI (OR = 1.730, 95% CI: 1.021-2.934; Ptrend = 0.030) were significantly associated with an increased risk of elevated neonatal TSH (>5 mIU/L) in a dose-response manner. Conclusion: The longitudinal data demonstrated that maternal thyroid resistance indices and thyroid hormones in the first half of gestation were positively associated with neonatal TSH levels. The findings offered an additionally practical recommendation to improve the current screening algorithms for congenital hypothyroidism.

Comprehensive analysis of key genes and pathways for biological and clinical implications in thyroid-associated ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) is a common and organ-specific autoimmune disease. Early diagnosis and novel treatments are essential to improve the prognosis of TAO patients. Therefore, the current work was performed to identify the key genes and pathways for the biological and clinical implications of TAO through comprehensive bioinformatics analysis and a series of clinical validations. METHODS: GSE105149 and GSE185952 were obtained from the Gene Expression Omnibus (GEO) database for analysis. The data were normalized to identify the common differentially expressed genes (DEGs) between the two datasets, and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to assess key pathways in TAO. Protein-protein interaction (PPI) networks and hub genes among the common DEGs were identified. Furthermore, we collected the general information and blood samples from 50 TAO patients and 20 healthy controls (HCs), and the expression levels of the proteins encoded by hub genes in serum were detected by enzyme-linked immunosorbent assay (ELISA). Then we further assessed the relationship between the ELISA data and the TAO development. RESULTS: Several common pathways, including neuroactive ligand-receptor interaction, the IL-17 signaling pathway, and the TNF signaling pathway, were identified in both datasets. In parallel, 52 common DEGs were identified. The KEGG analysis showed that these common DEGs are mainly enriched in long-term depression, the VEGF signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway, and cytokine-cytokine receptor interactions. The key hub genes PRKCG, OSM, DPP4, LRRTM1, CXCL6, and CSF3R were screened out through the PPI network. As confirmation, the ELISA results indicated that protein expression levels of PRKCG, OSM, CSF3R, and DPP4 were significantly upregulated in TAO patients compared with HCs. In addition, PRKCG and DPP4 were verified to show value in diagnosing TAO, and CSF3R was found to be a valuable diagnostic marker in distinguishing active TAO from inactive TAO. CONCLUSIONS: Inflammation- and neuromodulation-related pathways might be closely associated with TAO. Based on the clinical verification, OSM, CSF3R, CXCL6, DPP4, and PRKCG may serve as inflammation- or neuromodulation-related biomarkers for TAO, providing novel insights for the diagnosis and treatment of TAO.

Optically Transparent Bamboo: Preparation, Properties, and Applications.

The enormous pressures of energy consumption and the severe pollution produced by non-renewable resources have prompted researchers to develop various environmentally friendly energy-saving materials. Transparent bamboo represents an emerging result of biomass material research that has been identified and studied for its many advantages, including light weight, excellent light transmittance, environmental sustainability, superior mechanical properties, and low thermal conductivity. The present review summarizes methods for preparing transparent bamboo, including delignification and resin impregnation. Next, transparent bamboo performance is quantified in terms of optical, mechanical, and thermal conductivity characteristics and compared with other conventional and emerging synthetic materials. Potential applications of transparent bamboo are then discussed using various functionalizations achieved through doping nanomaterials or modified resins to realize advanced energy-efficient building materials, decorative elements, and optoelectronic devices. Finally, challenges associated with the preparation, performance improvement, and production scaling of transparent bamboo are summarized, suggesting opportunities for the future development of this novel, bio-based, and advanced material.

Novel Method of Full-Length RNA-seq That Expands the Identification of Non-Polyadenylated RNAs Using Nanopore Sequencing.

The occurrence of diseases displayed transcriptome alteration, including both coding and non-coding transcripts. The third-generation sequencing (TGS) technologies allow for intensive and comprehensive research of the transcriptome. However, the present standard TGS RNA sequencing method is unable to detect many of the non-polyadenylated [non-poly(A)] RNAs. To obtain more complete transcriptome information, we presented a new comprehensive sequencing approach by performing conventional poly(A) RNA-sequencing combined with the sequencing of non-poly(A) RNA fraction which was tailed by poly(U) on HepG2 and HL-7702 cell lines, enabling the detection of multiple categories of non-poly(A) RNAs excluded by the existing standard approach. Moreover, the length distribution of the full-splice match transcripts was longer than that assembled by short-reads, which contributed to characterizing alternative splicing events and provided a comprehensive portrait of transcriptional complexity. Besides the detection of genes with differential expression patterns in the poly(A) library between HepG2 and HL-7702, we also found a cancer-related non-coding gene in the poly(U) data, that is, growth arrest special 5 (GAS5). Collectively, our results suggested that the novel method effectively captured both poly(A) and non-poly(A) transcripts in the tested cell lines and allowed a deeper exploration of the transcriptome.

Radiodynamic therapy with CsI(na)@MgO nanoparticles and 5-aminolevulinic acid.

BACKGROUND: Radiodynamic therapy (RDT) holds the potential to overcome the shallow tissue penetration issue associated with conventional photodynamic therapy (PDT). To this end, complex and sometimes toxic scintillator-photosensitizer nanoconjugates are often used, posing barriers for large-scale manufacturing and regulatory approval. METHODS: Herein, we report a streamlined RDT strategy based on CsI(Na)@MgO nanoparticles and 5-aminolevulinic acid (5-ALA). 5-ALA is a clinically approved photosensitizer, converted to protoporphyrin IX (PpIX) in cancer cells' mitochondria. CsI(Na)@MgO nanoparticles produce strong ~ 410 nm X-ray luminescence, which matches the Soret band of PpIX. We hypothesize that the CsI(Na)@MgO-and-5-ALA combination can mediate RDT wherein mitochondria-targeted PDT synergizes with DNA-targeted irradiation for efficient cancer cell killing. Because scintillator nanoparticles and photosensitizer are administered separately, the approach forgoes issues such as self-quenching or uncontrolled release of photosensitizers. RESULTS: When tested in vitro with 4T1 cells, the CsI(Na)@MgO and 5-ALA combination elevated radiation-induced reactive oxygen species (ROS), enhancing damages to mitochondria, DNA, and lipids, eventually reducing cell proliferation and clonogenicity. When tested in vivo in 4T1 models, RDT with the CsI(Na)@MgO and 5-ALA combination significantly improved tumor suppression and animal survival relative to radiation therapy (RT) alone. After treatment, the scintillator nanoparticles, made of low-toxic alkali and halide elements, were efficiently excreted, causing no detectable harm to the hosts. CONCLUSIONS: Our studies show that separately administering CsI(Na)@MgO nanoparticles and 5-ALA represents a safe and streamlined RDT approach with potential in clinical translation.

Rapid Spontaneous Total Fusion of Neuropathic Arthropathy of the Wrist After Limited Intercarpal Arthrodesis: A Case Report and Brief Literature Review.

Background: Previous reports on the treatment of neuropathic arthropathy of the wrist were generally conservative, with few case reports of treatment with osteoarticular surgery. Case Presentation: A 25-year-old right-handed male complained of unpainful swelling of the dorsal aspect of his right wrist for 3 years. He was at that time diagnosed with synovitis and radiocarpal arthritis. The patient underwent a partial Four-Corner Arthrodesis and Synoviectomy to preserve motor function. Over the next 2 months, his right wrist also developed painful redness, with progressive swelling and stiffness. Rheumatoid arthritis, tuberculosis arthritis, and infectious diseases were ruled out in this case. Magnetic resonance imaging (MRI) indicated that he had Chiari II syringomyelia so the patient was eventually diagnosed with destructive neuropathic arthropathy (syringomyelia). After 2 months of conservative treatment, the patient's right wrist spontaneously and completely fused and the pain disappeared. Conclusion: Neuropathic arthropathy of the wrist is a rare but clinically significant disease due to its effect on the function of the active limb. Surgeons should rule out a diagnosis of it when treating patients with wrist swelling and osteoarticular abnormalities, otherwise, limited intercarpal arthrodesis should not be taken as a treatment option. Inappropriate partial surgery is likely to lead to rapid total fusion of neuropathic arthropathy of the wrist.

7-Dehydrocholesterol Encapsulated Polymeric Nanoparticles As a Radiation-Responsive Sensitizer for Enhancing Radiation Therapy.

Therapeutics that can be activated by radiation in situ to enhance the efficacy of radiotherapy are highly desirable. Herein, 7-Dehydrocholesterol (7-DHC), a biosynthetic precursor of cholesterol, as a radiosensitizer, exploiting its ability to propagate the free radical chain reaction is explored. The studies show that 7-DHC can react with radiation-induced reactive oxygen species and in turn promote lipid peroxidation, double-strand breaks, and mitochondrial damage in cancer cells. For efficient delivery, 7-DHC is encapsulated into poly(lactic-co-glycolic acid) nanoparticles, forming 7-DHC@PLGA NPs. When tested in CT26 tumor bearing mice, 7-DHC@PLGA NPs significantly enhanced the efficacy of radiotherapy, causing complete tumor eradication in 30% of the treated animals. After treatment, 7-DHC is converted to cholesterol, causing no detectable side effects or hypercalcemia. 7-DHC@PLGA NPs represent a radiation-responsive sensitizer with great potential in clinical translation.