An Automated Instance Segmentation Method for Crack Detection Integrated with CrackMover Data Augmentation.

Crack detection plays a critical role in ensuring road safety and maintenance. Traditional, manual, and semi-automatic detection methods have proven inefficient. Nowadays, the emergence of deep learning techniques has opened up new possibilities for automatic crack detection. However, there are few methods with both localization and segmentation abilities, and most perform poorly. The consistent nature of pavement over a small mileage range gives us the opportunity to make improvements. A novel data-augmentation strategy called CrackMover, specifically tailored for crack detection methods, is proposed. Experiments demonstrate the effectiveness of CrackMover for various methods. Moreover, this paper presents a new instance segmentation method for crack detection. It adopts a redesigned backbone network and incorporates a cascade structure for the region-based convolutional network (R-CNN) part. The experimental evaluation showcases significant performance improvements achieved by these approaches in crack detection. The proposed method achieves an average precision of 33.3%, surpassing Mask R-CNN with a Residual Network 50 backbone by 8.6%, proving its effectiveness in detecting crack distress.

[Advances on cyclopeptides of plants].

Cyclopeptides isolated from a variety of plants are a class of cyclic nitrogen-containing compounds, and they are primarily formed by peptide bonds between amino acids, generally containing 2 to 37 L-configuration encoded or non-encoded amino acid residues. Cyclopeptides have significant values in scientific research as natural small-molecule metabolites produced by plants. The available studies have revealed that such natural products are ubiquitous in plants, which mainly include cyclic dipeptides, cyclic tetrapeptides, cyclic pentapeptides, cyclic hexapeptides, cyclic heptapeptides, cyclic octapeptides, cyclic nonapeptides, and cyclic decapeptides. Among them, cyclic dipeptides, cyclic hexapeptides, and cyclic octapeptides are the major active compounds. It has been reported that plant cyclopeptides have novel and unique chemical structures. They possess diverse pharmacological activities, such as antineoplastic, antimicrobial, antimalarial, anti-inflammatory, and antiviral activities. This paper summarizes the research achievements of plant cyclopeptides since 2006, aiming to provide theoretical reference for the research and application of plant cyclopeptides in medicine, health, and agriculture fields.

Whole-genome resequencing reveals complex effects of geographical-palaeoclimatic interactions on diversification of moustache toads in East Asia.

Geographical features and palaeoclimatic fluctuations are two classical evolutionary forces that shape genetic diversification within species. Fine-grained analysis of the mechanisms involved through population demographic processes, however, remains limited. Taking advantage of two recently published reference genomes, we resequenced the genomes and examined the evolutionary history of the moustache toads, a group endemic to East Asia where complex topography and fluctuating palaeoclimate are known to have had profound impacts on organisms. Moustache toads probably originated in southeast Yunnan, China, and diversified towards the northwestern of Yunnan, as well as central and eastern China. Further exploration based on three widespread species (Leptobrachium ailaonicum, L. boringii and L. liui) using demographic modelling and species distribution models revealed that mountains and river valleys in East Asia not only functioned as geographical barriers, but also provided dispersal corridors and facilitated continuous migration or post-glacial secondary contact among moustache toad populations. Furthermore, periodic oscillation of effective population sizes accompanying fluctuations of historical temperature and population contraction at the Last Glacial Maximum support the widespread impact of climatic changes of the Pleistocene on species diversification in East Asia. This impact was moderate for populations of L. ailaonicum and L. boringii in the southwestern mountains but severe for populations of L. liui in the eastern lowland regions of continental East Asia, which is supported by different degrees of change of their effective population sizes. Our findings reveal mechanisms underlying genetic diversification among moustache toads, and highlight the power of genomic data and demographic modelling for examining complex historical population-level processes and for understanding how geographical and palaeoclimatic factors interactively shape current intraspecific diversity.

LncRNA nuclear-enriched abundant transcript 1 aggravates cerebral ischemia/reperfusion injury through activating early growth response-1/RNA binding motif protein 25 axis.

Ischemic stroke is a major global health issue. Ischemia and subsequent reperfusion results in stroke-related brain injury. Previous studies have demonstrated that nuclear-enriched abundant transcript 1 (NEATa and early growth response 1 (EGR1) are involved in ischemia reperfusion (IR) injury). In this study, we aimed to explore the roles of NEAT1/EGR1 axis as well as its downstream effector RNA binding motif protein 25 (RBM25) in cerebral IR injury. Oxygen-glucose deprivation/reperfusion (OGD/R) and middle cerebral artery occlusion (MCAO) were used to establish in vitro and in vivo models of cerebral IR injury, respectively. According to our data, NEAT1, EGR1, and RBM25 levels were elevated in OGD/R-exposed SK-N-SH and SH-SY5Y cells and cerebral cortex of MCAO mice. NEAT1, EGR1, or RBM25 knockdown effectively reduced infarct volumes and apoptosis, and improved neurological function. Mechanistically, NEAT1 directly interacted with EGR1, which restrained WW domain containing E3 ubiquitin protein ligase 1 (WWP1)-mediated ubiquitination of EGR1 and subsequently caused EGR1 accumulation. EGR1 bound to RBM25 promoter and transcriptionally activated RBM25. Rescue experiments indicated that RBM25 overexpression abolished the therapeutic effects of NEAT1 knockdown. In conclusion, this work identified a novel NEAT1/EGR1/RBM25 axis in potentiating brain injury after IR insults, suggesting a potential therapeutic target for ischemic stroke.

Improving the Accuracy of an R-CNN-Based Crack Identification System Using Different Preprocessing Algorithms.

The accurate intelligent identification and detection of road cracks is a key issue in road maintenance, and it has become popular to perform this task through the field of computer vision. In this paper, we proposed a deep learning-based crack detection method that initially uses the idea of image sparse representation and compressed sensing to preprocess the datasets. Only the pixels that represent the crack features remain, while most pixels of non-crack features are relatively sparse, which can significantly improve the accuracy and efficiency of crack identification. The proposed method achieved good results based on the limited datasets of crack images. Various algorithms were tested, namely, linear smooth, median filtering, Gaussian smooth, and grayscale threshold, where the optimal parameters of the various algorithms were analyzed and trained with faster regions with convolutional neural network features (faster R-CNN). The results of the experiments showed that the proposed method has good robustness, with higher detection efficiency in the presence of, for example, road markings, shallow cracks, multiple cracks, and blurring. The result shows that the improvement of mean average precision (mAP) can reach 5% compared with the original method.

Crack Detection and Comparison Study Based on Faster R-CNN and Mask R-CNN.

The intelligent crack detection method is an important guarantee for the realization of intelligent operation and maintenance, and it is of great significance to traffic safety. In recent years, the recognition of road pavement cracks based on computer vision has attracted increasing attention. With the technological breakthroughs of general deep learning algorithms in recent years, detection algorithms based on deep learning and convolutional neural networks have achieved better results in the field of crack recognition. In this paper, deep learning is investigated to intelligently detect road cracks, and Faster R-CNN and Mask R-CNN are compared and analyzed. The results show that the joint training strategy is very effective, and we are able to ensure that both Faster R-CNN and Mask R-CNN complete the crack detection task when trained with only 130+ images and can outperform YOLOv3. However, the joint training strategy causes a degradation in the effectiveness of the bounding box detected by Mask R-CNN.

Geologic events coupled with Pleistocene climatic oscillations drove genetic variation of Omei treefrog (Rhacophorus omeimontis) in southern China.

BACKGROUND: Pleistocene climatic oscillations and historical geological events may both influence current patterns of genetic variation, and the species in southern China that faced unique climatic and topographical events have complex evolutionary histories. However, the relative contributions of climatic oscillations and geographical events to the genetic variation of these species remain undetermined. To investigate patterns of genetic variation and to test the hypotheses about the factors that shaped the distribution of this genetic variation in species of southern China, mitochondrial genes (cytochrome b and NADH dehydrogenase subunit 2) and nine microsatellite loci of the Omei tree frog (Rhacophorus omeimontis) were amplified in this study. RESULTS: The genetic diversity in the populations of R. omeimontis was high. The phylogenetic trees reconstructed from the mitochondrial DNA (mtDNA) haplotypes and the Bayesian genetic clustering analysis based on microsatellite data both revealed that all populations were divided into three lineages (SC, HG and YN). The two most recent splitting events among the lineages coincided with recent geological events (including the intense uplift of the Qinghai-Tibet Plateau, QTP and the subsequent movements of the Yun-Gui Plateau, YGP) and the Pleistocene glaciations. Significant expansion signals were not detected in mismatch analyses or neutrality tests. And the effective population size of each lineage was stable during the Pleistocene. CONCLUSIONS: Based on the results of this study, complex geological events (the recent dramatic uplift of the QTP and the subsequent movements of the YGP) and the Pleistocene glaciations were apparent drivers of the rapid divergence of the R. omeimontis lineages. Each diverged lineages survived in situ with limited gene exchanges, and the stable demographics of lineages indicate that the Pleistocene climatic oscillations were inconsequential for this species. The analysis of genetic variation in populations of R. omeimontis contributes to the understanding of the effects of changes in climate and of geographical events on the dynamic development of contemporary patterns of genetic variation in the species of southern China.

Impacts of climate change on the distribution of Sichuan snub-nosed monkeys (Rhinopithecus roxellana) in Shennongjia area, China.

Understanding the effects of climate change on primate ranging patterns is crucial for conservation planning. Rhinopithecus roxellana is an endangered primate species distributed in mountainous forests at the elevation of 1500-3500 m a.s.l. in China. Our study site, the Shennongjia National Nature Reserve, represents the eastern-most distribution of this species. This area has experienced significant habitat loss and fragmentation because of human population growth, increased farming and logging, and climate change. To estimate how changes in temperature and rainfall will affect the presumed future distribution of this species, we examined eco-geographic factors including bioclimate, habitat (vegetation type, landcover, etc.), topography, and human impact (human population, gross domestic product, etc.), and provide suggestions for management and conservation. We used a maximum entropy approach to predict the location and distribution of habitats suitable for R. roxellana in the present, 2020, 2050, and 2080 based on 33 environmental parameters, three general circulation models, three emissions scenarios, and two dispersal hypotheses. According to the ensemble modeling, we found range reductions of almost 30% by 2020, 70% by 2050, and over 80% by 2080. Although no obvious differences were found in distribution change based on full and zero dispersal assumptions, our results revealed range reductions in response to elevational, latitudinal, and longitudinal gradients, with the monkeys forced to migrate to higher elevations over time. Bioclimte factors, such as temperature, precipitation, evapo-transpiration, and aridity condition, were dominant contributors to range shifting. As habitat loss due to human influence and climate change is likely to be even more severe in the future, we considered three conservation hot-spots in the Shennongjia area and recommended: (i) securing existing reserves and establishing new reserves, (ii) re-designing management systems to include the Shenongjia reserve and the surrounding reserves and highlighting ecosystem protection at higher elevations, and (iii) using finer-scale research to guide the conservation planning and education in order to enhance protection and awareness in the local community. National and provincial conservation policies should integrate projections of climate change in making effective conservation strategies.

Evolution by selection, recombination, and gene duplication in MHC class I genes of two Rhacophoridae species.

BACKGROUND: Comparison of major histocompatibility complex (MHC) genes across vertebrate species can reveal molecular mechanisms underlying the evolution of adaptive immunity-related proteins. As the first terrestrial tetrapods, amphibians deserve special attention because of their exposure to probably increased spectrum of microorganisms compared with ancestral aquatic fishes. Knowledge regarding the evolutionary patterns and mechanisms associated with amphibian MHC genes remains limited. The goal of the present study was to isolate MHC class I genes from two Rhacophoridae species (Rhacophorus omeimontis and Polypedates megacephalus) and examine their evolution. RESULTS: We identified 27 MHC class I alleles spanning the region from exon 2 to 4 in 38 tree frogs. The available evidence suggests that these 27 sequences all belong to classical MHC class I (MHC Ia) genes. Although several anuran species only display one MHC class Ia locus, at least two or three loci were observed in P. megacephalus and R. omeimontis, indicating that the number of MHC class Ia loci varies among anuran species. Recombination events, which mainly involve the entire exons, played an important role in shaping the genetic diversity of the 27 MHC class Ia alleles. In addition, signals of positive selection were found in Rhacophoridae MHC class Ia genes. Amino acid sites strongly suggested by program to be under positive selection basically accorded with the putative antigen binding sites deduced from crystal structure of human HLA. Phylogenetic relationships among MHC class I alleles revealed the presence of trans-species polymorphisms. CONCLUSIONS: In the two Rhacophoridae species (1) there are two or three MHC class Ia loci; (2) recombination mainly occurs between the entire exons of MHC class Ia genes; (3) balancing selection, gene duplication and recombination all contribute to the diversity of MHC class Ia genes. These findings broaden our knowledge on the evolution of amphibian MHC systems.

Large-scale mtDNA screening reveals a surprising matrilineal complexity in east Asia and its implications to the peopling of the region.

In order to achieve a thorough coverage of the basal lineages in the Chinese matrilineal pool, we have sequenced the mitochondrial DNA (mtDNA) control region and partial coding region segments of 6,093 mtDNAs sampled from 84 populations across China. By comparing with the available complete mtDNA sequences, 194 of those mtDNAs could not be firmly assigned into the available haplogroups. Completely sequencing 51 representatives selected from these unclassified mtDNAs identified a number of novel lineages, including five novel basal haplogroups that directly emanate from the Eurasian founder nodes (M and N). No matrilineal contribution from the archaic hominid was observed. Subsequent analyses suggested that these newly identified basal lineages likely represent the genetic relics of modern humans initially peopling East Asia instead of being the results of gene flow from the neighboring regions. The observation that most of the newly recognized mtDNA lineages have already differentiated and show the highest genetic diversity in southern China provided additional evidence in support of the Southern Route peopling hypothesis of East Asians. Specifically, the enrichment of most of the basal lineages in southern China and their rather ancient ages in Late Pleistocene further suggested that this region was likely the genetic reservoir of modern humans after they entered East Asia.

Revisiting the role of the Himalayas in peopling Nepal: insights from mitochondrial genomes.

Himalayas was believed to be a formidably geographical barrier between South and East Asia. The observed high frequency of the East Eurasian paternal lineages in Nepal led some researchers to suggest that these lineages were introduced into Nepal from Tibet directly; however, it is also possible that the East Eurasian genetic components might trace their origins to northeast India where abundant East Eurasian maternal lineages have been detected. To trace the origin of the Nepalese maternal genetic components, especially those of East Eurasian ancestry, and then to better understand the role of the Himalayas in peopling Nepal, we have studied the matenal genetic composition extensively, especially the East Eurasian lineages, in Nepalese and its surrounding populations. Our results revealed the closer affinity between the Nepalese and the Tibetans, specifically, the Nepalese lineages of the East Eurasian ancestry generally are phylogenetically closer with the ones from Tibet, albeit a few mitochondrial DNA haplotypes, likely resulted from recent gene flow, were shared between the Nepalese and northeast Indians. It seems that Tibet was most likely to be the homeland for most of the East Eurasian in the Nepalese. Taking into account the previous observation on Y chromosome, now it is convincing that bearer of the East Eurasian genetic components had entered Nepal across the Himalayas around 6 kilo years ago (kya), a scenario in good agreement with the previous results from linguistics and archeology.

Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau.

Due to its numerous environmental extremes, the Tibetan Plateau--the world's highest plateau--is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.

Inland post-glacial dispersal in East Asia revealed by mitochondrial haplogroup M9a'b.

BACKGROUND: Archaeological studies have revealed a series of cultural changes around the Last Glacial Maximum in East Asia; whether these changes left any signatures in the gene pool of East Asians remains poorly indicated. To achieve deeper insights into the demographic history of modern humans in East Asia around the Last Glacial Maximum, we extensively analyzed mitochondrial DNA haplogroup M9a'b, a specific haplogroup that was suggested to have some potential for tracing the migration around the Last Glacial Maximum in East Eurasia. RESULTS: A total of 837 M9a'b mitochondrial DNAs (583 from the literature, while the remaining 254 were newly collected in this study) pinpointed from over 28,000 subjects residing across East Eurasia were studied here. Fifty-nine representative samples were further selected for total mitochondrial DNA sequencing so we could better understand the phylogeny within M9a'b. Based on the updated phylogeny, an extensive phylogeographic analysis was carried out to reveal the differentiation of haplogroup M9a'b and to reconstruct the dispersal histories. CONCLUSIONS: Our results indicated that southern China and/or Southeast Asia likely served as the source of some post-Last Glacial Maximum dispersal(s). The detailed dissection of haplogroup M9a'b revealed the existence of an inland dispersal in mainland East Asia during the post-glacial period. It was this dispersal that expanded not only to western China but also to northeast India and the south Himalaya region. A similar phylogeographic distribution pattern was also observed for haplogroup F1c, thus substantiating our proposition. This inland post-glacial dispersal was in agreement with the spread of the Mesolithic culture originating in South China and northern Vietnam.

Development of novel microsatellite markers in the Omei treefrog (Rhacophorus omeimontis).

Eleven novel microsatellite markers were developed and characterized for the Omei treefrog (Rhacophorus omeimontis) using the fast isolation by AFLP of sequences containing repeats method. Polymorphism of each locus was tested in 24 individuals from two wild populations. The number of alleles per locus ranged from 4 to 15, the average observed and expected heterozygosity per locus ranged from 0.250 to 0.839 and from 0.562 to 0.914, respectively. Two of the 11 microsatellite loci showed significant deviations from Hardy-Weinberg equilibrium. Two locus pairs showed significant linkage disequilibrium. Neither evidence of scoring error due to stuttering nor evidence of large allele dropout was found at all of the 11 loci, but evidence of null alleles was indicated at two loci because of general excess of homozygotes for most allele size classes. These polymorphic loci will be useful markers in studying mate choice of the Omei treefrog.

[Expression of osteopontin in labial glands of patients with primary Sjögren's syndrome].

OBJECTIVE: To investigate the mRNA transcription and protein expression of osteopontin (OPN) and to analyze the possible role of OPN in primary Sjögren's syndrome (pSS). METHODS: In this study, 24 patients with pSS were selected and diagnosed according to the American-European Consensus Group criteria. The control group was composed of 14 subjects. Total RNA from labial glands was extracted. The target gene and ß-actin acted as templates to perform reverse transcript polymerase chain reaction (RT-PCR). Then mRNA expression of the target gene were semi-quantitated by the OD ratio of the target gene to ß-actin bands on gel under densitometry. Immunohistocheical analysis was used to determine the expression of proteins of the target genes in labial glands from patients and healthy control. RESULTS: In contrast to the control group, the mRNA transcription and protein level of the target genes in labial glands in pSS patients were significantly increased statistically (P<0.05). Spearman and Pearson rank correlation coefficients were used for analyzing the correlation of lymphocytes foci-score (LFS) with OPN expressions, the level of the mRNA transcription (0.407, P=0.049) and protein expression of OPN (0.476, P=0.039) was positively correlated with the LFS. Immunohistochemistry detected that OPN protein was not only mainly expressed in intracytoplasm of the gland duct, but also in infiltrated lymphocytes. CONCLUSION: OPN is higher expressed in the basal and surface of labial glands of pSS patients, which may contribute to the destruction of labial glands.

[Characteristics of vascular morphology and vascular endothelial growth factor in patients with osteoarthritis and rheumatoid arthritis].

OBJECTIVE: To study the differences in vascular morphology and vascular endothelial growth factor (VEGF) of early knee osteoarthritis and rheumatoid arthritis and to evaluate whether VEGF mRNA and VEGF protein expression correlate with disease activity and vascular morphology. METHODS: VEGF mRNA and VEGF protein in OA and RA synovium were detected by means of in situ hybridization and immunohistochemistry. Vascular morphology was assessed by arthroscopy. The level of VEGF protein expression of synovium was evaluated to make sure whether it was correlated with disease activity and macroscopic observation by arthroscopy. RESULTS: Significant differences of VEGF mRNA and protein expression were found in synovium lining layer region, perivascular region and sub-lining region between OA and RA. The correlations were found between VEGF expression in sub-lining region and erythrocyte sedimentation rate (ESR) in OA, in synovium lining layer and the counts of platelet in RA, in sub-lining region and C-reaction protein (CRP) in RA. The correlation was found between VEGF expression and synovium lining layer, between VEGF expression and synovial hypertrophy in sub-lining region in OA; The expression of VEGF in synovium lining layer in RA demonstrated its correlation with vascular morphology, tortuous vessels, and vascular density. CONCLUSION: There is differential VEGF mRNA/VEGF protein expression between OA and RA in each layer of synovial membrane. This phenomenon may be responsible for the pathogenic mechanisms of osteoarthritis and rheumatoid arthritis.

[Relationship between oxidative stress and depression in patients with rheumatoid arthritis].

OBJECTIVE: To investigate the relationship between oxidative stress and depression in patients with rheumatoid arthritis (RA). METHODS: In the study, 129 patients with RA were assessed using the Hamilton depression rating scale (HAMD), Zung self-rating depression scale (SDS), Zung self-rating anxiety scale (SAS), symptom checklist 90 (SCL-90), and other multiple item questionnaires. Oxidative-stress-related parameters in sera and indexes of oxidative damage were monitored during a pretreatment period. The patients were divided into depression (group A, HAMD≥20) and nondepression groups (group B,HAMD<20) based on an HAMD score cutoff of 20. In addition, 20 healthy donors were classified as group C. RESULTS: A statistically significant increase in SDS score was observed in group A (59.12±10.18) when compared with group B (39.24±5.02) (t=0.42,P < 0.01). A statistically significant increase was observed in SAS score in group A (59.12±10.18) in comparison with group B (39.24±5.02) (t=1.48,P<0.01). Antisuperoxide anion capacity was significantly decreased in group A (393.76±43.35) in comparison with group B (456.98±93.86) and group C (483.51±30.64) (F=3.95, P=0.03), whereas serum malondialdehyde (MDA) levels of group A (13.84±3.35) were higher than those of group B (9.42±3.52) and group C (7.86±3.21)(F=12.01, P=0.01). Pearson correlation analysis revealed that depression was positively correlated with MDA (r=0.58,P<0.05), but negatively with A-ASC (r =-0.30, P<0.05). CONCLUSION: The oxidative damage occurs in patients with rheumatoid arthritis, and lower antioxidant defences exist in depressive patients. The oxidative stress may promote the development of depression.

LncRNA RMRP accelerates autophagy-mediated neurons apoptosis through miR-3142/TRIB3 signaling axis in alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a major neurodegenerative disorder. The functions of lncRNA RMRP have been characterized mainly in various human cancers. However, the functional network of RMRP in AD progression remains unknown. METHODS: Human serum samples, AD transgenic (Tg) mice as well as SH-SY5Y cells were used in this study. The RNA expression patterns of RMRP, miR-3142 and TRIB3 were assessed by quantitative real-time PCR (qRT-PCR). Levels of apoptosis- or autophagy-associated biomarkers and TRIB3 level were evaluated using immunohistochemistry (IHC), western blotting or immunofluorescence assays, respectively. Bioinformatics methods and luciferase assays were used to predict and validate the interactions among RMRP, miR-3142, and TRIB3. Flow cytometry, TUNEL staining and EdU assays were used to examine the apoptosis and proliferation of neurons, respectively. RESULTS: The elevated RMRP and TRIB3 expressions and activation of autophagy were observed in AD. Knockdown of RMRP restrained neuronal apoptosis and autophagy activation in vitro and in vivo. Interestingly, TRIB3 overexpression reversed the biological effects of RMRP silencing on Aß1-42-induced cell apoptosis and autophagy. Further mechanistic analysis showed RMRP acted as a sponge of miR-3142 to elevate TRIB3 level. CONCLUSION: These data illustrated that knockdown of RMRP inhibited autophagy and apoptosis via regulating miR-3142/TRIB3 axis in AD, suggesting that inhibition of RMRP maybe a therapeutic strategy for AD.

Clinical Efficacy of Cortex Daphnes (Zushima) Patch in Patients With Symptomatic Knee Osteoarthritis: A Multicenter Non-Inferiority Randomized Controlled Clinical Trial.

Background: Osteoarthritis (OA) is imposing substantial burdens on individuals and society with the aging population. Cortex Daphnes patch is widely used for symptomatic knee OA in China with a satisfying clinical efficacy; however, there is scant clinical evidence supporting its use. To evaluate its efficacy, we conducted a multicenter, non-inferiority, randomized, parallel-group study comparing Cortex Daphnes patch with topical nonsteroidal anti-inflammatory drugs in patients with knee OA (NCT02770950). Methods: A total of 264 symptomatic knee OA patients were treated with Cortex Daphnes or indomethacin cataplasms applied to affected sites once daily for 2 weeks. The primary outcome was improvement in knee pain on walking as assessed using a visual analog scale (VAS). The non-inferiority margin based on the full analysis population was set as -5 mm on the pain VAS. The secondary outcomes were changes of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score, WOMAC scores for pain, function and stiffness, the 36-item Short Form Health Survey (SF-36), and global assessment of knees by the patients. Responder rates for pain VAS, WOMAC total score, and WOMAC pain were also included in the secondary outcomes. Results: The Cortex Daphnes patch was non-inferior to indomethacin cataplasms for the primary outcome with a group difference (Cortex Daphnes patch-indomethacin cataplasm) of 2.1 mm (95% confidence interval: 2.1-6.4); similar results were found in the per-protocol population. For all other outcomes, no significant differences were found in the full analysis set or in the per-protocol analysis set, except the responder rates for WOMAC pain was higher in the Cortex Daphnes patch group than in the indomethacin cataplasm group (78.4 vs. 64.7%, p = 0.022) in the per-protocol analysis set. Overall, 28.8% patients in the Cortex Daphnes patch group and 9.8% in the indomethacin cataplasm group reported treatment-related adverse events, the vast majority of which were mild-to-moderate skin irritation, resulting in only 3.8 and 0.8% of patients dropping out, respectively. Conclusion: The Cortex Daphnes patch, which provides satisfactory analgesic efficacy and enhances the physical function of the knee, as well as improving quality of life, may be a promising alternative to knee OA.

SNHG12 Promotes Angiogenesis Following Ischemic Stroke via Regulating miR-150/VEGF Pathway.

The promotion of angiogenesis is a promising therapeutic strategy for ischemic stroke. Many long noncoding RNAs (lncRNAs) are related to angiogenesis following ischemic stroke. LncRNA small nucleolar RNA host gene 12 (SNHG12) was upregulated in oxygen-glucose deprivation (OGD)-exposed primary brain microvascular endothelial cells and in microvessel from middle cerebral artery occlusion (MCAO) animal brains. However, the role and underlying mechanism of SNHG12 in ischemic stroke especially associated with angiogenesis process remain unknown. The expression of SNHG12 and miR-150 was determined in OGD-stimulated mouse brain microvascular endothelial (bEnd.3) cells. The role and mechanism of SNHG12 in the angiogenesis after ischemic stroke were investigated using gain- and loss-of function approaches both in OGD-exposed bEnd.3 cells and in MCAO mouse models. We found SNHG12 expression was elevated, whereas miR-150 reduced in OGD-exposed bEnd.3 cells. Upregulation of SNHG12 elevated, and SNHG12 knockdown suppressed the capillary-like tube formation, viability, migration, and VEGF expression in OGD-injured bEnd.3 cells. miR-150 mimic reversed, whereas anti-miR-150 further strengthened the effect of SNHG12 upregulation on the angiogenesis in bEnd.3 cells. Furthermore, we found that SNHG12 functioned as a competing endogenous RNA for miR-150 to regulate VEGF expression. Additionally, overexpression of SNHG12 improved the recovery of neurological function, reduced infarct volume and miR-150 expression, increased vascular density and VEGF expression in the infarct border zone of MCAO mice. In conclusion, SNHG12 promotes the angiogenesis following ischemic stroke via miR-150/VEGF pathway, which further clarified the mechanism of angiogenesis after ischemic stroke and provides a target for the treatment of this disease.