Programming hydrogel adhesion with engineered polymer network topology.

Hydrogel adhesion that can be easily modulated in magnitude, space, and time is desirable in many emerging applications ranging from tissue engineering and soft robotics to wearable devices. In synthetic materials, these complex adhesion behaviors are often achieved individually with mechanisms and apparatus that are difficult to integrate. Here, we report a universal strategy to embody multifaceted adhesion programmability in synthetic hydrogels. By designing the surface network topology of a hydrogel, supramolecular linkages that result in contrasting adhesion behaviors are formed on the hydrogel interface. The incorporation of different topological linkages leads to dynamically tunable adhesion with high-resolution spatial programmability without alteration of bulk mechanics and chemistry. Further, the association of linkages enables stable and tunable adhesion kinetics that can be tailored to suit different applications. We rationalize the physics of polymer chain slippage, rupture, and diffusion at play in the emergence of the programmable behaviors. With the understanding, we design and fabricate various soft devices such as smart wound patches, fluidic channels, drug-eluting devices, and reconfigurable soft robotics. Our study presents a simple and robust platform in which adhesion controllability in multiple aspects can be easily integrated into a single design of a hydrogel network.

Strigolactones alleviate AlCl3 stress by vacuolar compartmentalization and cell wall blocking in apple.

Poor management and excess fertilization of apple (Malus domestica Borkh.) orchards are causing increasingly serious soil acidification, resulting in Al toxicity and direct poisoning of roots. Strigolactones (SLs) are reported to be involved in plant responses to abiotic stress, but their role and mechanism under AlCl3 stress remain unknown. Here, we found that applying 1 µm GR24 (an SL analoge) significantly alleviated AlCl3 stress of M26 apple rootstock, mainly by blocking the movement of Al through cell wall and by vacuolar compartmentalization of Al. RNA-seq analysis identified the core transcription factor gene MdWRKY53, and overexpressing MdWRKY53 enhanced AlCl3 tolerance in transgenic apple plants through the same mechanism as GR24. Subsequently, we identified MdPMEI45 (encoding pectin methylesterase inhibitor) and MdALS3 (encoding an Al transporter) as downstream target genes of MdWRKY53 using chromatin immunoprecipitation followed by sequencing (ChIP-seq). GR24 enhanced the interaction between MdWRKY53 and the transcription factor MdTCP15, further increasing the binding of MdWRKY53 to the MdPMEI45 promoter and inducing MdPMEI45 expression to prevent Al from crossing cell wall. MdWRKY53 also bound to the promoter of MdALS3 and enhanced its transcription to compartmentalize Al in vacuoles under AlCl3 stress. We therefore identified two modules involved in alleviating AlCl3 stress in woody plant apple: the SL-WRKY+TCP-PMEI module required for excluding external Al by blocking the entry of Al3+ into cells and the SL-WRKY-ALS module allowing internal detoxification of Al through vacuolar compartmentalization. These findings lay a foundation for the practical application of SLs in agriculture.

Mimicking the retinal neuron functions by a photoresponsive single transistor with a double gate.

To realize a low-cost neuromorphic visual system, employing an artificial neuron capable of mimicking the retinal neuron functions is essential. A photoresponsive single transistor neuron composed of a vertical silicon nanowire is proposed. Similar to retinal neurons, various photoresponsive characteristics of the single transistor neuron can be modulated by light intensity as well as wavelength and have a high responsivity to green light like the human eye. The device is designed with a cylindrical surrounding double-gate structure, enclosed by an independently controlled outer gate and inner gate. The outer gate has the function of selectively inhibiting neuron activity, which can mimic lateral inhibition of amacrine cells to ganglion cells, and the inner gate can be utilized for the adjustment of the firing threshold voltage, which can be used to mimic the regulation of photoresponsivity by horizontal cells for adaptive visual perception. Furthermore, a myelination function that controls the speed of information transmission is obtained according to the inherent asymmetric source/drain structure of a vertical silicon nanowire. This work can enable photoresponsive neuronal function using only a single transistor, providing a promising hardware implementation for building miniaturized neuromorphic vision systems at low cost.

Investigating the ERG a-wave and Retinal Diseases with Rod Equivalent Circuit Model Based on the APD.

Most empirically supported mathematical models of rod cells lack theoretical support from actual physical devices. Therefore, this paper proposes an equivalent circuit model for the rod is proposed based on the photoconductive properties of the avalanche photodetector (APD) and combined with the electrical properties of the rod. The model employs the photodetector to simulate the source of the photocurrent in outer segments of rod cells and takes into account the electrical properties of the inner and outer segments, the nucleus, and the synaptic terminals. It successfully simulates the trans-retinal voltage generated by the intracellular and extracellular flow of photocurrent in the outer segment of dark-adapted rods. Moreover, the typical waveform characteristics of two retinal diseases, the enhanced short wavelength sensitivity (SWS) cone syndrome and retinitis pigmentosa (RP), are investigated on the basis of electroretinogram (ERG) a-wave. This will further elucidate the function of the visual system and the ERG a-wave characteristics of the related diseases. Comparison with published experimental results validates the reliability of the model presented. Our study provides new ideas and strategies for the diagnosis of retinal diseases and provides some theoretical support for the application of photodetectors in the fabrication of artificial retinal devices.

Melatonin promotes Al3+ compartmentalization via H+ transport and ion gradients in Malus hupehensis.

Soil acidification in apple (Malus domestica) orchards results in the release of rhizotoxic aluminum ions (Al3+) into soil. Melatonin (MT) participates in plant responses to abiotic stress; however, its role in AlCl3 stress in apple remains unknown. In this study, root application of MT (1 µM) substantially alleviated AlCl3 stress (300 µM) in Pingyi Tiancha (Malus hupehensis), which was reflected by higher fresh and dry weight, increased photosynthetic capacity, and longer and more roots compared with plants that did not receive MT treatment. MT functioned mainly by regulating vacuolar H+/Al3+ exchange and maintaining H+ homeostasis in the cytoplasm under AlCl3 stress. Transcriptome deep sequencing analysis identified the transcription factor gene SENSITIVE TO PROTON RHIZOTOXICITY 1 (MdSTOP1) was induced by both AlCl3 and MT treatments. Overexpressing MdSTOP1 in apple increased AlCl3 tolerance by enhancing vacuolar H+/Al3+ exchange and H+ efflux to the apoplast. We identified 2 transporter genes, ALUMINUM SENSITIVE 3 (MdALS3) and SODIUM HYDROGEN EXCHANGER 2 (MdNHX2), as downstream targets of MdSTOP1. MdSTOP1 interacted with the transcription factor NAM ATAF and CUC 2 (MdNAC2) to induce MdALS3 expression, which reduced Al toxicity by transferring Al3+ from the cytoplasm to the vacuole. Furthermore, MdSTOP1 and MdNAC2 coregulated MdNHX2 expression to increase H+ efflux from the vacuole to the cytoplasm to promote Al3+ compartmentalization and maintain cation balance in the vacuole. Taken together, our findings reveal an MT-STOP1 + NAC2-NHX2/ALS3-vacuolar H+/Al3+ exchange model for the alleviation of AlCl3 stress in apple, laying a foundation for practical applications of MT in agriculture.

Solibacillus ferritrahens sp. nov., a novel siderophore-producing bacterium isolated from Wumeng Mountain National Nature Reserve in Yunnan Province.

A gram-stain-positive, aerobic, rod-shaped bacterial strain capable of producing siderophores, named YIM B08730T, was isolated from a soil sample collected from Wumeng Mountain National Nature Reserve, Zhaotong City, Yunnan Province. Growth occurred at 10-45 °C (optimum, 35-40 â„ƒ), pH 7.0-9.0 (optimum, 7.0) and in the presence of 0-5 % (w/v) NaCl (optimum, 0-1 %, w/v). A comparative analysis of the 16S rRNA gene sequence (1558 bp) of strain YIM B08730T showed the highest similarity to Solibacillus isronensis JCM 13838T (96.2 %), followed by Solibacillus silvestris DSM 12223T (96.0 %) and Solibacillus kalamii ISSFR-015T (95.4 %). The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and one unidentified lipid. The main respiratory quinone of strain YIM B08730T was menaquinone 7 (MK-7). The major fatty acids were iso-C15:0 and C16:1ω7c alcohol. The digital DNA-DNA hybridization and average nucleotide identity values between strain YIM B08730T and the reference strain S. isronensis JCM 13838T were 24.8 % and 81.2 %, respectively. The G + C content of the genomic DNA was 37.1 mol%. The genome of the novel strain contained genes associated with the production of siderophores, and it also revealed other functional gene clusters involved in plant growth promotion and soil bioremediation. Based on these phenotypic, chemotaxonomic and phylogenetic analyses, strain YIM B08730T is considered to be a novel species of the genus Solibacillus, for which the name Solibacillus ferritrahens sp. nov. is proposed. The type strain is YIM B08730T (= NBRC 116268T = CGMCC 1.60169T).

Long-term follow-up of pallidal deep brain stimulation for craniocervical dystonia: is the globus pallidus internus the best target?

OBJECTIVE: Craniocervical dystonia (CCD) is a common type of segmental dystonia, which is a disabling disease that has been frequently misdiagnosed. Blepharospasm or cervical dystonia is the most usual symptom initially. Although deep brain stimulation (DBS) of the globus pallidus internus (GPi) has been widely used for treating CCD, its clinical outcome has been primarily evaluated in small-scale studies. This research examines the sustained clinical effectiveness of DBS of the GPi in individuals diagnosed with CCD. METHODS: The authors report 24 patients (14 women, 10 men) with refractory CCD who underwent DBS of the GPi between 2016 and 2023. The severity and disability of the dystonia were evaluated using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The BFMDRS scores were collected preoperatively, 6 months postoperatively, and at the most recent follow-up visit. RESULTS: The mean age at onset was 52.0 ± 11.0 years (range 33-71 years) and the mean disease duration was 63.3 ± 73.3 months (range 7-360 months) (values for continuous variables are expressed as the mean ± SD). The mean follow-up period was 37.5 ± 23.5 months (range 6-84 months). The mean total BFMDRS motor scores at the 3 different time points were 13.3 ± 9.4 preoperatively, 5.0 ± 4.7 (55.3% improvement, p < 0.001) at 6 months, and 4.5 ± 3.6 (56.6% improvement, p < 0.001) at last follow-up. The outcomes were deemed poor in 6 individuals. CONCLUSIONS: Inferences drawn from the findings suggest that DBS of the GPi has long-lasting effectiveness and certain limitations in managing refractory CCD. The expected stability of the clinical outcome is not achieved. Patients with specific types of dystonia might consider targets other than GPi for a more precise therapy.

Regulatory Mechanism through Which Old Soybean Leaves Respond to Mn Toxicity Stress.

Manganese (Mn) is a heavy metal that can cause excessive Mn poisoning in plants, disrupting microstructural homeostasis and impairing growth and development. However, the specific response mechanisms of leaves to Mn poisoning have not been fully elucidated. This study revealed that Mn poisoning of soybean plants resulted in yellowing of old leaves. Physiological assessments of these old leaves revealed significant increases in the antioxidant enzymes activities (peroxidase (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX), and catalase (CAT)) and elevated levels of malondialdehyde (MDA), proline, indoleacetic acid (IAA), and salicylic acid (SA), under 100 µM Mn toxicity. Conversely, the levels of abscisic acid (ABA), gibberellin 3 (GA3), and jasmonic acid (JA) significantly decreased. The Mn content in the affected leaves significantly increased, while the levels of Ca, Na, K, and Cu decreased. Transcriptome analysis revealed 2258 differentially expressed genes in the Mn-stressed leaves, 744 of which were upregulated and 1514 were downregulated; these genes included genes associated with ion transporters, hormone synthesis, and various enzymes. Quantitative RT-PCR (qRT-PCR) verification of fifteen genes confirmed altered gene expression in the Mn-stressed leaves. These findings suggest a complex gene regulatory mechanism under Mn toxicity and stress, providing a foundation for further exploration of Mn tolerance-related gene regulatory mechanisms in soybean leaves. Using the methods described above, this study will investigate the molecular mechanism of old soybean leaves' response to Mn poisoning, identify key genes that play regulatory roles in Mn toxicity stress, and lay the groundwork for cultivating high-quality soybean varieties with Mn toxicity tolerance traits.

Melatonin enhances KCl salinity tolerance by maintaining K+ homeostasis in Malus hupehensis.

Large amounts of potash fertilizer are often applied to apple (Malus domestica) orchards to enhance fruit quality and yields, but this treatment aggravates KCl-based salinity stress. Melatonin (MT) is involved in a variety of abiotic stress responses in plants. However, its role in KCl stress tolerance is still unknown. In the present study, we determined that an appropriate concentration (100 µm) of MT significantly alleviated KCl stress in Malus hupehensis by enhancing K+ efflux out of cells and compartmentalizing K+ in vacuoles. Transcriptome deep-sequencing analysis identified the core transcription factor gene MdWRKY53, whose expression responded to both KCl and MT treatment. Overexpressing MdWRKY53 enhanced KCl tolerance in transgenic apple plants by increasing K+ efflux and K+ compartmentalization. Subsequently, we characterized the transporter genes MdGORK1 and MdNHX2 as downstream targets of MdWRKY53 by ChIP-seq. MdGORK1 localized to the plasma membrane and enhanced K+ efflux to increase KCl tolerance in transgenic apple plants. Moreover, overexpressing MdNHX2 enhanced the KCl tolerance of transgenic apple plants/callus by compartmentalizing K+ into the vacuole. RT-qPCR and LUC activity analyses indicated that MdWRKY53 binds to the promoters of MdGORK1 and MdNHX2 and induces their transcription. Taken together, our findings reveal that the MT-WRKY53-GORK1/NHX2-K+ module regulates K+ homeostasis to enhance KCl stress tolerance in apple. These findings shed light on the molecular mechanism of apple response to KCl-based salinity stress and lay the foundation for the practical application of MT in salt stress.

Efficient and systematic parameter extraction based on rate equations by DFB equivalent circuit model.

The conventional direct parameter extraction method generally suffers from cumbersome due to redundant experiments. An efficient and systematical parameter extracting solution is proposed based on an equivalent circuit model of distributed feedback (DFB) lasers. The successfully built circuit model includes the necessary intrinsic parameters in the rate equations and the extrinsic parameters to provide a better approximation of the actual laser. This method is experimentally verified through a DFB laser chip measurement of electronic and optical performance under the same conditions. Finally, the nine intrinsic parameters in the rate equations and five extrinsic parameters in the model are efficiently extracted using this technique from a set of experimental characteristics of a DFB laser chip. Modeled and measured results for the laser output characteristics exhibit good agreement when the extracted parameters are used. The method is versatile for other semiconductor lasers that can be modeled using rate equations. Comparison with simulation results of published laser models further validates the reliability of the presented model and extraction method.

Topical application of TOPK inhibitor OTS514 suppresses psoriatic progression by inducing keratinocytes cell cycle arrest and apoptosis.

T-LAK cell-oriented protein kinase (TOPK) potently promotes malignant proliferation of tumour cells and is considered as a maker of tumour progression. Psoriasis is a common inflammatory skin disease characterized by abnormal proliferation of keratinocytes. However, the role of TOPK in psoriasis has not been well elucidated. This study aims to investigate the expression and role of TOPK in psoriasis, and the role of TOPK inhibitor in psoriasis attenuation. Gene Expression Omnibus datasets derived from psoriasis patients and psoriatic model mice were screened for analysis. Skin specimens from psoriasis patients were collected for TOPK immunohistochemical staining to investigate the expression and localization of TOPK. Next, psoriatic mice model was established to further confirm TOPK expression pattern. Then, TOPK inhibitor was applied to investigate the role of TOPK in psoriasis progression. Finally, cell proliferation assay, apoptosis assay and cell cycle analysis were performed to investigate the potential mechanism involved. Our study showed that TOPK was upregulated in the lesions of both psoriasis patients and psoriatic model mice, and TOPK levels were positively associated with psoriasis progression. TOPK was upregulated in psoriatic lesions and expressed predominantly by epidermal keratinocytes. In addition, TOPK levels in epidermal keratinocytes were positively correlated with epidermal hyperplasia. Furthermore, topical application of TOPK inhibitor OTS514 obviously alleviated disease severity and epidermal hyperplasia. Mechanismly, inhibiting TOPK induces G2/M phase arrest and apoptosis of keratinocytes, thereby attenuating epidermal hyperplasia and disease progression. Collectively, this study identifies that upregulation of TOPK in keratinocytes promotes psoriatic progression, and inhibiting TOPK attenuates epidermal hyperplasia and psoriatic progression.

Association of cortical gyrification, white matter microstructure, and phenotypic profile in medication-naïve obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is thought to arise from dysconnectivity among interlinked brain regions resulting in a wide spectrum of clinical manifestations. Cortical gyrification, a key morphological feature of human cerebral cortex, has been considered associated with developmental connectivity in early life. Monitoring cortical gyrification alterations may provide new insights into the developmental pathogenesis of OCD. METHODS: Sixty-two medication-naive patients with OCD and 59 healthy controls (HCs) were included in this study. Local gyrification index (LGI) was extracted from T1-weighted MRI data to identify the gyrification changes in OCD. Total distortion (splay, bend, or twist of fibers) was calculated using diffusion-weighted MRI data to examine the changes in white matter microstructure in patients with OCD. RESULTS: Compared with HCs, patients with OCD showed significantly increased LGI in bilateral medial frontal gyrus and the right precuneus, where the mean LGI was positively correlated with anxiety score. Patients with OCD also showed significantly decreased total distortion in the body, genu, and splenium of the corpus callosum (CC), where the average distortion was negatively correlated with anxiety scores. Intriguingly, the mean LGI of the affected cortical regions was significantly correlated with the mean distortion of the affected white matter tracts in patients with OCD. CONCLUSIONS: We demonstrated associations among increased LGI, aberrant white matter geometry, and higher anxiety in patients with OCD. Our findings indicate that developmental dysconnectivity-driven alterations in cortical folding are one of the neural substrates underlying the clinical manifestations of OCD.

The significance of EphA2-regulated Wnt/ß-catenin signal pathway in promoting the metastasis of HBV-related hepatocellular carcinoma.

BACKGROUND: Hepatitis B virus (HBV) infection is closely associated with the malignant progression of hepatocellular carcinoma (HCC). However, the mechanism involved in the HBV-related HCC development remains poorly understood. Hence, the aim of this study is to investigate the regulatory mechanism of EphA2-induced epithelial-mesenchymal transition (EMT) in the metastasis of HBV-related HCC cells. METHODS AND RESULTS: The expression level of EphA2 was determined in HBV-related human HCC cells. Then, the effects of EphA2 silencing on the EMT-associated proteins, the Wnt/ß-catenin signal pathway and the metastatic potential of HBV-related HCC cells were evaluated. Finally, the inhibitory role of Entecavir (a potent antiviral drug for HBV) on EphA2-induced EMT was explored. The present study revealed that the EphA2 expression level was increased in HBV-related HCC cells compared with non-related HCC cells. Following EphA2 knockdown, the downregulation of Vimentin, ß-catenin and p-GSK-3ßSer9 expressions, the upregulation of E-cadherin expression, and the suppressed migration and invasion ability of HBV-related HCC cells were found. Additionally, Entecavir was proved to have a significant inhibitory effect on EphA2-induced EMT via attenuating the Wnt/ß-catenin signal pathway. CONCLUSIONS: In this study, we found that EphA2-induced EMT was involved in the enhanced metastatic potential of HBV-related HCC cells through the activation of the Wnt/ß-catenin signal pathway.

Pseudomonas subflava sp. nov., a new Gram-negative bacterium isolated from Guishan in Yunnan province, south-west China.

A new Gram-negative, rod-shaped, flagellated bacterium was isolated from soil in the Guishan, Xinping County, Yuxi City, Yunnan Province, China, and named YIM B01952T. Growth occurred at 10-40 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.5) and with up to ≤ 5.0% (w/v) NaCl on Tryptic Soy Broth Agar (TSA) plates. Phylogenetic analysis based on the 16S rRNA gene and draft-genome sequence showed that strain YIM B01952T belonged to the genus Pseudomonas, and was closely related to the type strain of Pseudomonas alcaligenes (sequence similarity was 98.8%). The digital DNA-DNA hybridization (dDDH) value between strain YIM B01952T and the parallel strain P. alcaligenes ATCC 14909T was 49.0% based on the draft genome sequence. The predominant menaquinone was Q-9. The major fatty acids were summed feature 8 (C18:1 ω6c and/or C18:1 ω7c), summed feature 3 (C16:1 ω6c and/or C16:1 ω7c) and C16:0. The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, and phosphatidylglycerol. The genome size of strain YIM B01952T was 4.341 Mb, comprising 4156 predicted genes with a DNA G + C content of 66.4 mol%. In addition, we detected that strain YIM B01952T had some traditional functional genes (plant growth promotion and multidrug resistance), unique genes through genome comparison and analysis with similar strains. Based on genetic analyses and biochemical characterization, the strain YIM B01952T was identified as a novel species in the genus Pseudomonas, for which the name Pseudomonas subflava sp. nov. is proposed. The type strain is YIM B01952T (=CCTCC AB 2021498T = KCTC 92073T).

Chitinolyticbacter albus sp. Nov., A Novel Chitin-Degrading Bacterium Isolated from Ancient Wood Rhizosphere Soil.

In this study, a novel aerobic mesophilic bacterial strain with capable of degrading chitin, designated YIM B06366T, was isolated and classified. The rod-shaped, Gram-stain-negative, on-spore-forming bacterium originated from rhizosphere soil sample collected in Kunming City, Yunnan Province, southwest PR China. Strain YIM B06366T exhibited growth at temperatures between 20 and 35 °C (optimum, 30 °C) and at pH 6.0-8.0 (optimum, pH 6.0). The analysis of 16S rRNA gene sequence similarity revealed that strain YIM B06366T was most closely related to type strain Chitinolyticbacter meiyuanensis SYBC-H1T (98.9%). Phylogenetic analysis based on genome data indicated that strain YIM B06366T should be assigned to the genus Chitinolyticbacter. The Average Nucleotide Identity (ANI) and digital DNA-DNA Hybridization (dDDH) values between strain YIM B06366T and the reference strain Chitinolyticbacter meiyuanensis SYBC-H1T were 84.4% and 27.7%, respectively. The major fatty acids included Summed Feature 3 (C16:1 ω6c/C16:1 ω7c), Summed Feature 8 (C18:1 ω6c/C18:1 ω7c), and C16:0. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, aminophospholipids, and two unidentified phospholipids. The predominant menaquinone was Q-8, and the genomic DNA G + C content was 64.1%. Considering the polyphasic taxonomic evidence, strain YIM B06366T is proposed as a novel species within the genus Chitinolyticbacter, named Chitinolyticbacter albus sp. nov. (type strain YIM B06366T = KCTC 92434T = CCTCC AB 2022163T).

StreptomeDB 3.0: an updated compendium of streptomycetes natural products.

Antimicrobial resistance is an emerging global health threat necessitating the rapid development of novel antimicrobials. Remarkably, the vast majority of currently available antibiotics are natural products (NPs) isolated from streptomycetes, soil-dwelling bacteria of the genus Streptomyces. However, there is still a huge reservoir of streptomycetes NPs which remains pharmaceutically untapped and a compendium thereof could serve as a source of inspiration for the rational design of novel antibiotics. Initially released in 2012, StreptomeDB (http://www.pharmbioinf.uni-freiburg.de/streptomedb) is the first and only public online database that enables the interactive phylogenetic exploration of streptomycetes and their isolated or mutasynthesized NPs. In this third release, there are substantial improvements over its forerunners, especially in terms of data content. For instance, about 2500 unique NPs were newly annotated through manual curation of about 1300 PubMed-indexed articles, published in the last five years since the second release. To increase interoperability, StreptomeDB entries were hyperlinked to several spectral, (bio)chemical and chemical vendor databases, and also to a genome-based NP prediction server. Moreover, predicted pharmacokinetic and toxicity profiles were added. Lastly, some recent real-world use cases of StreptomeDB are highlighted, to illustrate its applicability in life sciences.

Prediction of osteoporosis using radiomics analysis derived from single source dual energy CT.

BACKGROUND: With the aging population of society, the incidence rate of osteoporosis is increasing year by year. Early diagnosis of osteoporosis plays a significant role in the progress of disease prevention. As newly developed technology, computed tomography (CT) radiomics could discover radiomic features difficult to recognize visually, providing convenient, comprehensive and accurate osteoporosis diagnosis. This study aimed to develop and validate a clinical-radiomics model based on the monochromatic imaging of single source dual-energy CT for osteoporosis prediction. METHODS: One hundred sixty-four participants who underwent both single source dual-energy CT and quantitative computed tomography (QCT) lumbar-spine examination were enrolled in a study cohort including training datasets (n = 114 [30 osteoporosis and 84 non-osteoporosis]) and validation datasets (n = 50 [12 osteoporosis and 38 non-osteoporosis]). One hundred seven radiomics features were extracted from 70-keV monochromatic CT images. With QCT as the reference standard, a radiomics signature was built by using least absolute shrinkage and selection operator (LASSO) regression on the basis of reproducible features. A clinical-radiomics model was constructed by incorporating the radiomics signature and a significant clinical predictor (age) using multivariate logistic regression analysis. Model performance was assessed by its calibration, discrimination and clinical usefulness. RESULTS: The radiomics signature comprised 14 selected features and showed good calibration and discrimination in both training and validation cohorts. The clinical-radiomics model, which incorporated the radiomics signature and a significant clinical predictor (age), also showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.938 (95% confidence interval, 0.903-0.952) in the training cohort and an AUC of 0.988 (95% confidence interval, 0.967-0.998) in the validation cohort, and good calibration. The clinical-radiomics model stratified participants into groups with osteoporosis and non-osteoporosis with an accuracy of 94.0% in the validation cohort. Decision curve analysis (DCA) demonstrated that the radiomics signature and the clinical-radiomics model were clinically useful. CONCLUSIONS: The clinical-radiomics model incorporating the radiomics signature and a clinical parameter had a good ability to predict osteoporosis based on dual-energy CT monoenergetic imaging.

MiR-19 3b regulated the formation of coat colors by targeting WNT10A and GNAI2 in Cashmere goats.

MiRNAs as a series of small noncoding RNAs that play a crucial part in regulating coat color and hair follicle development. In the previous Solexa sequencing experiments, there were many miRNAs expressed differentially in alpacas with different coat color, including miR-193b.But the mechanism of miR-193b in mammalian pigmentation is still unknown. In this study, bioinformatics analysis showed that WNT10A and GNAI2 might be the target genes of miR-193b. qRT-PCR showed the expression of miR-193b in white Cashmere goats' skins was obviously lower than that in browns, and the expression of WNT10A and GNAI2 were similar with miR-193b. The protein levels of WNT10A and GNAI2 indicated the same findings. Furthermore, the expression of WNT10A and GNAI2 in keratinocytes were analyzed from mRNA and protein levels, the results manifested that the group of overexpression of miR-193b in HaCaT cells increased the expressions of target genes, and miR-193b inhibition group reduced expressions. Luciferase report assays confirmed that the targeting relationship between miR-193b and target genes (WNT10A and GNAI2), the results showed that miR-193b was positively correlated with target genes. These experimental data showed that miR-193b might participate in adjustment of coat color in skin tissue of Cashmere goat by targeting WNT10A and GNAI2.

MiR-125b regulates the differentiation of hair follicles in Fine-wool Sheep and Cashmere goats by targeting MXD4 and FGFR2.

With the development of miRNAs identification technology, more and more miRNAs have been discovered, and the role of miRNAs in the development of animal hair follicles has become a focus of research on hair-producing animals. In the previous experiment, compare the microRNA (miRNA) trancriptomes of goats and sheep skin using Solexa sequencing and differentially expressed miR-125b was screened. However, the mechanism of miR-125b regulating hair follicle development is not clear. Therefore, in the present study, the expression of miR-125b, MXD4 and FGFR2 in skin tissue of Fine-wool Sheep and Cashmere goats and HEK-293T cells was examined by qPCR and Western blot. Furthermore, the correlation between miR-125b and the predicted target gene (MXD4, FGFR2) was verified using the Dual-luciferase Reporter assay. We demonstrated that the expression of MXD4 and FGFR2 in Cashmere goats was significantly higher than that of Fine-wool Sheep, and the expression was opposite to that of miR-125b. miR-125b can down-regulate the levels of MXD4 and FGFR2. Dual-luciferase reporter gene assay showed that miR-125b could bind to the 3'-UTR region of target genes FGFR2 and MXD4, suggesting that MXD4 and FGFR2 were target genes of miR-125b. This study has shown that the growth and development of hair follicles in skin tissue of Fine-wool Sheep and Cashmere goats from the new regulatory levels of miRNAs, and clarified the mechanism of miR-125b and its target genes in the development of hair follicles in the skin.

MiR-21 regulated hair follicle cycle development in Cashmere goats by targeting FGF18 and SMAD7.

Increasing Cashmere production can add value because it is the primary product of Cashmere goats. Recent years, peoples find miRNAs are crucial in regulating the development of hair follicle. Following Solexa sequencing, many miRNAs were distinguishingly expressed in telogen skin samples of goats and sheep in earlier study. But the method through which miR-21 controls the growth of hair follicles is still ambiguous. Bioinformatics analysis was used to predict the target genes of miR-21. The mRNA level of miR-21 in telogen Cashmere goat skins was higher than in anagen, according to the results of qRT-PCR, and the target genes expressed similarly with miR-21. Western blot showed similar trend, the protein expression of FGF18 and SMAD7 were lower in anagen samples. The Dual-Luciferase reporter assay confirmed miRNA-21's relationship with its target gene, and the consequences indicated found FGF18 and SMAD7 have positive correlations with miR-21. Western blot and qRT-PCR distinguished the expression of protein and mRNA in miR-21 and its target genes. According to the consequence, we found that target genes expression was increased by miR-21 in HaCaT cells. This study identified that miR-21 might take part in the development of Cashmere goat's hair follicles by targeting FGF18 and SMAD7.