Comparative transcriptome revealed the molecular responses of Aconitum carmichaelii Debx. to downy mildew at different stages of disease development.

BACKGROUND: Aconitum carmichaelii Debx. has been widely used as a traditional medicinal herb for a long history in China. It is highly susceptible to various dangerous diseases during the cultivation process. Downy mildew is the most serious leaf disease of A. carmichaelii, affecting plant growth and ultimately leading to a reduction in yield. To better understand the response mechanism of A. carmichaelii leaves subjected to downy mildew, the contents of endogenous plant hormones as well as transcriptome sequencing were analyzed at five different infected stages. RESULTS: The content of 3-indoleacetic acid, abscisic acid, salicylic acid and jasmonic acid has changed significantly in A. carmichaelii leaves with the development of downy mildew, and related synthetic genes such as 9-cis-epoxycarotenoid dioxygenase and phenylalanine ammonia lyase were also significant for disease responses. The transcriptomic data indicated that the differentially expressed genes were primarily associated with plant hormone signal transduction, plant-pathogen interaction, the mitogen-activated protein kinase signaling pathway in plants, and phenylpropanoid biosynthesis. Many of these genes also showed potential functions for resisting downy mildew. Through weighted gene co-expression network analysis, the hub genes and genes that have high connectivity to them were identified, which could participate in plant immune responses. CONCLUSIONS: In this study, we elucidated the response and potential genes of A. carmichaelii to downy mildew, and observed the changes of endogenous hormones content at different infection stages, so as to contribute to the further screening and identification of genes involved in the defense of downy mildew.

Prospective Comparison of Standard and Deep Learning-reconstructed Turbo Spin-Echo MRI of the Shoulder.

Background Deep learning (DL)-based MRI reconstructions can reduce imaging times for turbo spin-echo (TSE) examinations. However, studies that prospectively use DL-based reconstructions of rapidly acquired, undersampled MRI in the shoulder are lacking. Purpose To compare the acquisition time, image quality, and diagnostic confidence of DL-reconstructed TSE (TSEDL) with standard TSE in patients indicated for shoulder MRI. Materials and Methods This prospective single-center study included consecutive adult patients with various shoulder abnormalities who were clinically referred for shoulder MRI between February and March 2023. Each participant underwent standard TSE MRI (proton density- and T1-weighted imaging; conventional TSE sequence was used as reference for comparison), followed by a prospectively undersampled accelerated TSEDL examination. Six musculoskeletal radiologists evaluated images using a four-point Likert scale (1, poor; 4, excellent) for overall image quality, perceived signal-to-noise ratio, sharpness, artifacts, and diagnostic confidence. The frequency of major pathologic features and acquisition times were also compared between the acquisition protocols. The intergroup comparisons were performed using the Wilcoxon signed rank test. Results Overall, 135 shoulders in 133 participants were evaluated (mean age, 47.9 years ± 17.1 [SD]; 73 female participants). The median acquisition time of the TSEDL protocol was lower than that of the standard TSE protocol (288 seconds [IQR, 288-288 seconds] vs 926 seconds [IQR, 926-950 seconds], respectively; P < .001), achieving a 69% lower acquisition time. TSEDL images were given higher scores for overall image quality, perceived signal-to-noise ratio, and artifacts (all P < .001). Similar frequency of pathologic features (P = .48 to > .99), sharpness (P = .06), or diagnostic confidence (P = .05) were noted between images from the two protocols. Conclusion In a clinical setting, TSEDL led to reduced examination time and higher image quality with similar diagnostic confidence compared with standard TSE MRI in the shoulder. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Chang and Chow in this issue.

Thermal Decomposition Mechanism of Ammonium Nitrate on the Main Crystal Surface of Ferric Oxide: Experimental and Theoretical Studies.

Understanding the decomposition process of ammonium nitrate (AN) on catalyst surfaces is crucial for the development of practical and efficient catalysts in AN-based propellants. In this study, two types of nano-Fe2O3 catalysts were synthesized: spherical particles with high-exposure (104) facets and flaky particles with high-exposure (110) facets. Through thermal analysis and particle size analysis, it was found that the nanosheet-Fe2O3 catalyst achieved more complete AN decomposition despite having a larger average particle size compared to nanosphere-Fe2O3. Subsequently, the effects of AN pyrolysis on the (110) and (104) facets were investigated by theoretical simulations. Through studying the interaction between AN and crystal facets, it was determined that the electron transfer efficiency on the (110) facet is stronger compared to that on the (104) facet. Additionally, the free-energy step diagrams for the reaction of the AN molecule on the two facets were calculated with the DFT + U method. Comparative analysis led us to conclude that the (110) facet of α-Fe2O3 is more favorable for AN pyrolysis compared to the (104) facet. Our study seeks to deepen the understanding of the mechanism underlying AN pyrolysis and present new ideas for the development of effective catalysts in AN pyrolysis.

Ring Finger Protein 215 Negatively Regulates Type I IFN Production via Blocking NF-κB p65 Activation.

Germline-encoded pattern recognition receptors (PRRs) recognize molecules frequently found in pathogens (pathogen-associated molecular patterns [PAMPs]) during viral infection. This process induces production of IFNs, leading to expression of IFN-stimulated genes to establish a cellular antiviral state against viral infection. However, aberrant activation of the IFN system may cause immunopathological damage and systemic autoimmune diseases such as systemic lupus erythematosus. Stringent control of IFN signaling activation is critical for maintaining homoeostasis of the immune system; yet, the mechanisms responsible for its precise regulation remain to be elucidated. In this study, we identified that ring finger protein 215 (RNF215), a zinc finger protein, was upregulated by viral infection in human macrophages. In addition, we demonstrated that RNF215 inhibited the production of type I IFNs at least in part via interacting with p65, a subunit of NF-κB, and repressed the accumulation of NF-κB in the promoter region of IFNB1. Moreover, we found that the expression of RNF215 negatively correlated with type I IFNs in patients with systemic lupus erythematosus, indicating that RNF215 plays an important role in the pathogenesis of autoimmune diseases. Collectively, our data identified RNF215 as a key negative regulator of type I IFNs and suggested RNF215 as a potential target for intervention in diseases with aberrant IFN production.

Exploring suicide resilience experiences in Chinese youth after self-poisoning: A qualitative study.

OBJECTIVE: This inquiry probes the suicide resilience experiences in suicide attempts by self-poisoning among Chinese youth. The study's goal is to provide healthcare professionals with critical insights to develop effective interventions that enhance suicide prevention measures and diminish the likelihood of subsequent attempts. METHODS: Utilizing a qualitative phenomenological approach, we conducted semi-structured interviews with 12 youths (Mean age = 21.1 ± 2.8 years; n = 7 females) who survived suicide attempts by self-poisoning. Data analysis was performed using Colaizzi's seven-step method, a rigorous method entailing iterative reading for the extraction of key statements and the distillation of thematic essence. RESULTS: Four primary themes with ten sub-themes were extracted: (1) New understanding of life (cherish life, and meaning of life), (2) Self-Reconciliation (self-acceptance, self-understanding, and self-openness), (3) Personal empowerment (increased self-reliance, increased responsibility, and increased emotional regulation), and (4) Life redesigning (faith in the future, and plan for the future). CONCLUSIONS: The findings reveal a potential for psychological growth and beneficial transformation in youth following suicide attempts by self-poisoning. These insights advocate for the integration of positive psychology principles in therapeutic interventions for this demographic.

Targeting FoxO transcription factors with HDAC inhibitors for the treatment of osteoarthritis.

OBJECTIVES: Osteoarthritis (OA) features ageing-related defects in cellular homeostasis mechanisms in articular cartilage. These defects are associated with suppression of forkhead box O (FoxO) transcription factors. FoxO1 or FoxO3 deficient mice show early onset OA while FoxO1 protects against oxidative stress in chondrocytes and promotes expression of autophagy genes and the essential joint lubricant proteoglycan 4 (PRG4). The objective of this study was to identify small molecules that can increase FoxO1 expression. METHODS: We constructed a reporter cell line with FoxO1 promoter sequences and performed high-throughput screening (HTS) of the Repurposing, Focused Rescue and Accelerated Medchem (ReFRAME) library . Hits from the HTS were validated and function was assessed in human chondrocytes, meniscus cells and synoviocytes and following administration to mice. The most promising hit, the histone deacetylase inhibitor (HDACI) panobinostat was tested in a murine OA model. RESULTS: Among the top hits were HDACI and testing in human chondrocytes, meniscus cells and synoviocytes showed that panobinostat was the most promising compound as it increased the expression of autophagy genes and PRG4 while suppressing the basal and IL-1ß induced expression of inflammatory mediators and extracellular matrix degrading enzymes. Intraperitoneal administration of panobinostat also suppressed the expression of mediators of OA pathogenesis induced by intra-articular injection of IL-1ß. In a murine OA model, panobinostat reduced the severity of histological changes in cartilage, synovium and subchondral bone and improved pain behaviours. CONCLUSION: Panobinostat has a clinically relevant activity profile and is a candidate for OA symptom and structure modification.

Mesoporous black TiO2 hollow shells with controlled cavity size for enhanced visible light photocatalysis.

Black TiO2 formed by introducing lattice disorder into pristine TiO2 has a narrowed band gap and suppresses the recombination of charge carriers. This provides a potential strategy for visible light photocatalysis. However, the microstructural design of black TiO2 for a higher optimization of visible light is still in high demand. In this work, we proposed the preparation of black TiO2 hollow shells with controllable cavity diameters using silica spheres as templates for the cavities and the NaBH4 reduction method. The decreased cavity size resulted in a hollow shell with an enhanced visible-light absorption and improved photocatalytic performance. Moreover, we demonstrated that this cavity can be combined with gold nanoparticles (AuNPs) to form AuNPs@black TiO2 yolk-shells. The AuNPs provided additional visible light absorption and promoted the separation of photogenerated carriers in the yolk-shell structures. This further improved the photocatalysis, the degradation rate of Cr(VI) can reach 0.066 min-1. Our work evaluated the effect of the cavity size on the photocatalytic performance of hollow and yolk-shell structures and provided concepts for the further enhancement of visible-light photocatalysis.

Isolation and identification of two pathogens causing leaf spot of Fritillaria taipaiensis P. Y. Li. in China.

Fritillaria taipaiensis P. Y. Li is one of the biological sources for Fritillariae Cirrhosae Bulbus. Its bulbs are widely used for treating respiratory diseases such as pneumonia, bronchitis and influenza. Cultivated F. taipaiensis suffers from many diseases during its growing season. Leaf spot is a destructive disease that is increasingly affecting F. taipaiensis and can cause an incidence of up to 30% in severe cases. Leaf spot inhibits the growth of F. taipaiensis by causing disease spots on the surface of leaves. In severe cases, these spots can result in leaf desiccation and blackspot formation at the lesion site, leading to a decrease in photosynthesis. Leaf spot has shown little benefit, and it can even result in a reduced yield of bulbs and the death of plants. According to previous studies, Alternaria alternata has been identified as the pathogen of leaf spot in many medicinal plants, but the main pathogens of the leaf spot of F. taipeiensis remains uncertain. In this paper, five isolates from diseased leaves of F. taipaiensis were isolated and purified and the pathogenicity test showed that isolates B-5 and B-7 induced leaf spot symptoms on healthy F. taipaiensis leaves. Integrating multiple phylogenetic analyses of rDNA using Internal transcribed spacer region (ITS), Beta-tubulin (TUB2), RNA polymerase II second largest subunit (RPB2) and Translation elongation factor 1-alpha (TEF1-a) primers, strain B-5 and strain B-7 were eventually identified as Didymella segeticola and A. alternata. This is also the first report on the pathogens that cause leaf spot in F. taipaiensis in China.

Whole-tumor histogram analysis of diffusion-weighted imaging and dynamic contrast-enhanced MRI for soft tissue sarcoma: correlation with HIF-1alpha expression.

OBJECTIVE: To investigate the correlation of histogram metrics from diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters with HIF-1alpha expression in soft tissue sarcoma (STS). METHODS: We enrolled 71 patients with STS who underwent 3.0-T MRI, including conventional MRI, DWI, and DCE-MRI sequences. Location, maximum tumor diameter, envelope, T2-weighted tumor heterogeneity, peritumoral edema, peritumoral enhancement, necrosis, tail-like pattern, bone invasion, and vessel/nerve invasion and/or encasement were determined using conventional MRI images. The whole-tumor histogram metrics were calculated on the apparent diffusion coefficient (ADC), Ktrans, Kep, and Ve maps. Independent-samples t test and one-way ANOVA were used for testing the differences between normally distributed categorical data with HIF-1alpha expression. Pearson and Spearman correlations and multiple linear regression analyses were performed to determine the correlations between histogram metrics and HIF-1alpha expression. Survival curves were plotted using the Kaplan-Meier method. RESULTS: Regarding conventional MRI features, only highly heterogeneous on T2-weighted images (55.6 ± 19.9% vs. 45.4 ± 20.5%, p = 0.041) and more than 50% necrotic area (57.3 ± 20.4% vs. 43.9 ± 19.7%, p = 0.002) were prone to indicate STS with higher HIF-1alpha expression. Histogram metrics obtained from ADC (mean, median, 10th, and 25th percentile values), Ktrans (mean, median, 75th, and 90th percentile values), and Kep (90th percentile values) were significantly correlated with HIF-1alpha expression. Multiple linear regression analysis demonstrated that more than 50% necrosis, ADCskewness, Ktrans90th, and grade III were independently associated with HIF-1alpha expression. CONCLUSION: DWI and DCE-MRI histogram parameters were significantly correlated with HIF-1alpha expression in STS. KEY POINTS: • DWI and DCE-MRI histogram parameters are correlated with HIF-1alpha expression in STS. • More than 50% necrosis, ADCskewness, Ktrans90th, and grade III were independently associated with HIF-1alpha expression in STS.

Accuracy of new-generation intraocular lens calculation formulas in eyes with variations in predicted refraction.

PURPOSE: To investigate the characteristics of eyes with large variations in predicted refraction using four traditional intraocular lens (IOL) formulas and evaluate the accuracy of new-generation intraocular lens power calculation formulas. METHODS: Eyes that had variation in predicted refraction (≥ 0.75 D) using four traditional formulas (SRK/T, Holladay 1, Hoffer Q, and Haigis formulas) were included. Axial length (AL), anterior chamber depth (ACD), average keratometry (AK), and the ratio of axial length to corneal radius (AL/CR) were measured. New-generation formulas (Barrett Universal II, Emmetropia Verifying Optical 2.0, Kane, and Pearl-DGS formulas) and traditional formulas were compared. The median absolute error (MedAE) was the main parameter to evaluate the accuracy of formulas. RESULTS: A total of 79 participants (79 eyes) who had variation in predicted refraction of (≥ 0.75 D) using four traditional formulas out of 510 eyes (510 patients) underwent uncomplicated cataract surgeries. The Barrett Universal II (0.29 D), EVO 2.0 (0.31 D), Kane (0.30 D), and Pearl-DGS (0.33 D) formulas produced significantly lower median absolute errors (MedAEs) than the Hoffer Q (0.61 D) and Holladay 1 (0.59 D) formulas (P < 0.01). The Wang-Koch (WK) adjustment significantly improved the accuracy of the Holladay 1 formula in long eyes (P < 0.001). CONCLUSIONS: Abnormal AL, ACD, and AK are more likely to lead to prediction errors using traditional formulas. New-generation formulas and traditional formulas with WK adjustment showed satisfactory prediction accuracy.

Cartilage Matrix Changes in Hindfoot Joints in Chronic Ankle Instability Patients After Anatomic Repair Using T2-Mapping: Initial Experience With 3-Year Follow-Up.

BACKGROUND: Anatomic repair is widely accepted as the primary surgical treatment for chronic lateral ankle instability (CLAI). T2-mapping is a powerful tool for quantitative assessment of biochemical changes in cartilage matrix. PURPOSE: To longitudinally evaluate cartilage matrix changes in the hindfoot joints of CLAI patients before and after anatomic repair by using T2-mapping with magnetic resonance imaging (MRI). STUDY TYPE: Prospective. SUBJECTS: Thirty-two CLAI patients (males/females = 20/12) and 21 healthy controls (males/females = 13/7). FIELD STRENGTH/SEQUENCE: 3 T; sagittal multi-echo spin-echo technique (T2-mapping), coronal, sagittal, and axial spin-echo PD-FS, and sagittal T1WI sequences. ASSESSMENT: MRI examinations were performed in CLAI patients at baseline (prior to surgery) and 3 years after anatomic repair and in healthy controls. On T2-maps, the hindfoot joints were segmented into 16 cartilage subregions. The T2 value of each subregion was measured. All patients were evaluated with the American Orthopedic Foot and Ankle Society (AOFAS) scale at baseline and after surgery. STATISTICAL TESTS: Analysis of variance (ANOVA) and Student's t-test were used. The differences corresponding to P < 0.05 were considered statistically significant. RESULTS: At baseline, the T2 values in most cartilage subregions of talar dome and medial posterior subtalar joint (pSTJ) were higher in CLAI patients than in healthy controls. After surgery, only the T2 value of anteriomedial talar dome decreased from that at baseline (31.11 ± 3.88 msec vs. 34.27 ± 5.30 msec). The T2 values of other subregions with elevated T2 values remained higher than healthy controls. There were no significant differences in T2 values in the midtarsal joints between CLAI patients and healthy controls (P = 0.262, 0.104, 0.169, 0.103). Postoperatively, the patients' AOFAS scores improved significantly from 67.81 to 89.13. DATA CONCLUSION: CLAI patients exhibited elevated T2 values in most subregions of talar dome and medial pSTJ. After anatomic repair, although the patients exhibited good clinical outcomes, the elevated T2 values could not be fully recovered. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 4.

Nanomechanical analysis of SARS-CoV-2 variants and predictions of infectiousness and lethality.

As variants of the pathogen that causes COVID-19 spread around the world, estimates of infectiousness and lethality of newly emerging strains are important. Here we report a predictive model that associates molecular motions and vibrational patterns of the virus spike protein with infectiousness and lethality. The key finding is that most SARS-CoV-2 variants are predicted to be more infectious and less lethal compared to the original spike protein. However, lineage B.1.351 (Beta variant) is predicted to be less infectious and more lethal, and lineage B.1.1.7 (Alpha variant) is predicted to have both higher infectivity and lethality, showing the potential of the virus to mutate towards different performance regimes. The relatively more recent lineage B.1.617.2 (Delta variant), although contains a few key spike mutations other than D614G, behaves quite similar to the single D614G mutation in both vibrational and predicted epidemiological aspects, which might explain its rapid circulation given the prevalence of D614G. This work may provide a tool to estimate the epidemiological effects of new variants, and offer a pathway to screen mutations against high threat levels. Moreover, the nanomechanical approach, as a novel tool to predict virus-cell interactions, may further open up the door towards better understanding other viruses.

Diverse phylogenomic datasets uncover a concordant scenario of laurasiatherian interordinal relationships.

Resolving the interordinal relationships in the mammalian superorder Laurasiatheria has been among the most intractable problems in higher-level mammalian systematics, with many conflicting hypotheses having been proposed. The present study collected three different sources of genome-scale data with comprehensive taxon sampling of laurasiatherian species, including two protein-coding datasets (4,186 protein-coding genes for an amino acid dataset comprising 2,761,247 amino acid residues and a nucleotide dataset comprising 5,516,340 nucleotides from 1st and 2nd codon positions), an intronic dataset (1,210 introns comprising 1,162,723 nucleotides) and an ultraconserved elements (UCEs) dataset (1,246 UCEs comprising 1,946,472 nucleotides) from 40 species representing all six laurasiatherian orders and 7 non-laurasiatherian outgroups. Remarkably, phylogenetic trees reconstructed with the four datasets using different tree-building methods (RAxML, FastTree, ASTRAL and MP-EST) all supported the relationship (Eulipotyphla, (Chiroptera, ((Carnivora, Pholidota), (Cetartiodactyla, Perissodactyla)))). We find a resolution of interordinal relationships of Laurasiatheria among all types of markers used in the present study, and the likelihood ratio tests for tree comparisons confirmed that the present tree topology is the optimal hypothesis compared to other examined hypotheses. Jackknifing subsampling analyses demonstrate that the results of laurasiatherian tree reconstruction varied with the number of loci and ordinal representatives used, which are likely the two main contributors to phylogenetic disagreements of Laurasiatheria seen in previous studies. Our study provides significant insight into laurasiatherian evolution, and moreover, an important methodological strategy and reference for resolving phylogenies of adaptive radiation, which have been a long-standing challenge in the field of phylogenetics.

Mg2TiO4 spinel modified by nitrogen doping as a Visible-Light-Active photocatalyst for antibacterial activity.

Nitrogen doped Mg2TiO4 spinel, i.e. Mg2TiO4-xNy, has been synthesized and investigated as a photocatalyst for antibacterial activity. Mg2TiO4-xNy demonstrates superior photocatalytic activity for E. coli disinfection under visible light illumination (λ ≥ 400 nm). Complete disinfection of E. coli at a bacterial cell density of 1.0 × 107 CFU mL-1 can be achieved within merely 60 min. Mg2TiO4-xNy is capable of generating superoxide radicals (•O2 -) under visible light illumination which are the reactive oxygen species (ROSs) for bacteria disinfection. DFT calculations have verified the importance of nitrogen dopants in improving the visible light sensitivity of Mg2TiO4-xNy. The facile synthesis, low cost, good biocompatibility and high disinfection activity of Mg2TiO4-xNy warrant promising applications in the field of water purification and antibacterial products.

Quantitative T2 mapping-based tendon healing is related to the clinical outcomes during the first year after arthroscopic rotator cuff repair.

PURPOSE: The objective of this study was to determine the correlation between quantitative T2 mapping-based tendon healing and clinical outcomes during the first year after arthroscopic rotator cuff repair. METHODS: Twenty-two patients with rotator cuff tear were prospectively recruited. Serial clinical and MRI follow-up assessments were carried out at 1 month, 6 months and 12 months after surgery. Twenty healthy volunteers were involved and were examined with clinical and MRI assessments. Clinical assessments included Constant Score (CS), the American Shoulder and Elbow Surgeons (ASES), the modified University of California, Los Angles (UCLA) scores and Visual Analog Scale (VAS). The region of interest of tendon healing was defined directly over the medial suture anchor on T2 mapping. Spearman correlation coefficient was used to analyze the correlations between MRI measurements and clinical outcomes. RESULTS: All clinical scores indicated significant improvements over the postoperative observation period compared with the initial preoperative values (all P < 0.001). At 12 months, all of the patients returned to their daily life activities. The T2 values of the healing site significantly decreased over time (P < 0.001) and were comparable to those of healthy tendons at 12 months (n.s.). Additionally, the T2 values were negatively correlated with CS (r = - 0.5, P < 0.001), ASES (r = - 0.5, P < 0.001), and UCLA (r = - 0.5, P < 0.001); and positively correlated with VAS score (r = 0.4, P < 0.001). No significant correlations were found between Sugaya classification and clinical scores (all n.s.). CONCLUSIONS: With regard to tendon healing during the first follow-up year, the T2 values of the healing site decreased with the improvement of clinical outcomes over time. LEVEL OF EVIDENCE: II.

Tumour-associated macrophages as a novel target of VEGI-251 in cancer therapy.

Tumour-associated macrophages (TAMs), which possess M2-like characters and are derived from immature monocytes in the circulatory system, represent a predominant population of inflammatory cells in solid tumours. TAM infiltration in tumour microenvironment can be used as an important prognostic marker in many cancer types and is a potential target for cancer prevention or treatment. VEGI-251 not only is involved in the inhibition of tumour angiogenesis, but also participates in the regulation of host immunity. This work aimed to investigate the involvement of VEGI-251 in the regulation of specific antitumour immunity. We found that recombinant human VEGI-251(rhVEGI-251) efficiently mediated the elimination of TAMs in tumour tissue in mice, and induced apoptosis of purified TAMs in vitro. During this process, caspase-8 and caspase-3 were activated, leading to PARP cleavage and apoptosis. Most importantly, we further elucidated the mechanism underlying VEGI-251-triggered TAM apoptosis, which suggests that ASK1, an intermediate component of the VEGI-251, activates the JNK pathway via TRAF2 in a potentially DR3-dependent manner in the process of TAM apoptosis. Collectively, our findings provide new insights into the basic mechanisms underlying the actions of VEGI-251 that might lead to future development of antitumour therapeutic strategies using VEGI-251 to target TAMs.

Bioinformatics analysis of long non-coding RNAs involved in nerve regeneration following sciatic nerve injury.

Little is known about the role of epigenetic modification in axon regeneration following peripheral nerve injury. The purpose of the present study was to investigate the role of long non-coding RNAs (lncRNAs) in the regulation of axon regeneration. We used bioinformatics to perform microarray analysis and screened total 476 lncRNAs and 129 microRNAs (miRNAs) of differentially expressed genes after sciatic nerve injury in mice. lncRNA-GM4208 and lncRNA-GM30085 were examined, and the changes in lncRNA expression in the L4-L6 dorsal root ganglia (DRG) following sciatic nerve crush injury were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of lncRNAs in the DRG changed, indicating that they might be related to nerve regeneration in the DRG following peripheral nerve injury.

LncRNA HOTTIP enhances human osteogenic BMSCs differentiation via interaction with WDR5 and activation of Wnt/ß-catenin signalling pathway.

To uncover the underlying molecular mechanism of long non-coding RNA in the osteogenic differentiation process of bone marrow mesenchymal stem cells (BMSCs), HOXA transcript at the distal tip (HOTTIP) was selected by using a lncRNA microarray assay. Results showed that HOTTIP was significantly upregulated during osteogenic differentiation of human BMSCs. Downregulation of HOTTIP by shRNA inhibited the osteogenic differentiation of BMSCs. Overexpression of HOTTIP by lentiviral vector promoted human BMSCs osteogenic differentiation by increasing the transcription of ß-catenin. RIP assay and RNA pulldown assay confirmed the interaction between HOTTIP and WDR5, a transcription factor binding to the promoter of ß-catenin. The interaction promoted the translocation of WDR5 into the nucleus and increased the transcription of ß-catenin. Implanted HOTTIP-overexpressing BMSCs increased ectopic bone formation in nude mice. HOTTIP is a conservative long noncoding RNA that is essential for osteogenic differentiation of BMSC. HOTTIP enhances osteogenic differentiation via interaction with WDR5 and up-regulation of ß-catenin gene expression, therefore activating Wnt/ß-catenin signalling pathway.

A Randomized Controlled Trial on the Effects of Low-Dose Extracorporeal Shockwave Therapy in Patients With Knee Osteoarthritis.

OBJECTIVE: To test the efficacy of low-dose extracorporeal shockwave therapy (ESWT) on osteoarthritis knee pain, lower limb function, and cartilage alteration for patients with knee osteoarthritis. DESIGN: Randomized controlled trial with placebo control. SETTING: Outpatient physical therapy clinics within a hospital network. PARTICIPANTS: Eligible volunteers (N=63) with knee osteoarthritis (Kellgren-Lawrence grade II or III) were randomly assigned to 2 groups. INTERVENTIONS: Patients in the experimental group received low-dose ESWT for 4 weeks while those in the placebo group got sham shockwave therapy. Both groups maintained a usual level of home exercise. MAIN OUTCOME MEASURES: Knee pain and physical function were measured using a visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lequesne index at baseline, 5 weeks, and 12 weeks. Cartilage alteration was measured analyzing the transverse relaxation time (T2) mapping. RESULTS: The VAS score, WOMAC, and Lequesne index of the ESWT group were significantly better than those of the placebo group at 5 and 12 weeks (P<.05). Both groups showed improvement in pain and disability scores over the 12-week follow-up period (P<.05). In terms of imaging results, there was no significant difference in T2 values between groups during the trial, although T2 values of the ESWT group at 12 weeks significantly increased compared to those at baseline (P=.004). The number and prevalence of adverse effects were similar between the 2 groups, and no serious side effects were found. CONCLUSIONS: A 4-week treatment of low-dose ESWT was superior to placebo for pain easement and functional improvement in patients with mild to moderate knee osteoarthritis but had some negative effects on articular cartilage.

Add-drop filter with complex waveguide Bragg grating and multimode interferometer operating on arbitrarily spaced channels.

We present a silicon nitride/silicon dioxide add-drop filter operating on arbitrarily spaced channels using multimode interferometers (MMIs) and complex waveguide Bragg gratings (CWBGs). The add-drop filter shows a rejection ratio of >40 dB on all five channels, with a line width of 1.2 nm and an on-chip loss of <1 dB. By designing the CWBG with the Layer Peeling/Layer Adding algorithm, this MMI-CWBG add-drop filter platform has the capability for ultrabroadband add-drop operation on arbitrarily spaced channels.