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Abstract Background Urothelial carcinoma (UC) is the second most common urological malignancy. Despite numerous molecular markers have been evaluated during the past decades, no urothelial markers for diagnosis and recurrence monitoring have shown consistent clinical utility. Methods The methylation level of tissue samples from public database and clinical collected were analyzed. Patients with UC and benign diseases of the urinary system (BUD) were enrolled to establish TAGMe (TAG of Methylation) assessment in a training cohort (n = 567) using restriction enzyme-based bisulfite-free qPCR. The performance of TAGMe assessment was further verified in the validation cohort (n = 198). Urine samples from 57 UC patients undergoing postoperative surveillance were collected monthly for six months after surgery to assess the TAGMe methylation. Results We identified TAGMe as a potentially novel Universal-Cancer-Only Methylation (UCOM) marker was hypermethylated in multi-type cancers and investigated its application in UC. Restriction enzyme-based bisulfite-free qPCR was used for detection, and the results of which were consistent with gold standard pyrosequencing. Importantly, hypermethylated TAGMe showed excellent sensitivity of 88.9% (95% CI: 81.4–94.1%) and specificity of 90.0% (95% CI: 81.9–95.3%) in efficiently distinguishing UC from BUD patients in urine and also performed well in different clinical scenarios of UC. Moreover, the abnormality of TAGMe as an indicator of recurrence might precede clinical recurrence by three months to one year, which provided an invaluable time window for timely and effective intervention to prevent UC upstaging. Conclusion TAGMe assessment based on a novel single target in urine is effective and easy to perform in UC diagnosis and recurrence monitoring, which may reduce the burden of cystoscopy. Trial registration ChiCTR2100052507. Registered on 30 October 2021

High-molecular-weight glutenin subunits (HMW-GS) are an important component of total cereal proteins in wheat. It is closely related to the processing quality of flour. Here, we analyzed allelic variations at the Glu-1 locus in 163 wheat accessions from Hubei Province, China with SDS-PAGE. Among the 15 alleles detected, alleles 1, 7+8, and 2+12 were the major alleles, and 7, 6+8, and 2+10 were rare alleles. The breeding lines had higher genetic diversity than the commercial varieties. Alleles 7 and 6+8 significantly reduced the grain protein content and wet gluten content of wheat. The “1, 7+9, 5+10” and “1, 14+15, and 2+12” allelic combinations significantly increased the grain protein content, hardness index, test weight, and wet gluten content of wheat. Alleles 7+9, 14+15, and 5+10 were identified as alleles related to high wheat quality. The “1, 7, 5+10”, “1, 6+8, 5+10”, “null, 7+9, 2+12”, “1, 14+15, 2+12”, and “1, 7+9, 5+10” allelic combinations had greater effects on wheat grain quality traits. These results demonstrate the effects of HMW-GS on wheat grain quality traits and provide a reference for the genetic improvement of wheat quality.

Summary: Neuropathic pain is a debilitating condition resulting from damage to the nervous system. Imbalance of spinal excitation and inhibition has been proposed to contribute to neuropathic pain. However, the structural basis of this imbalance remains unknown. Using a preclinical model of neuropathic pain, we show that microglia selectively engulf spinal synapses that are formed by central neurons and spare those of peripheral sensory neurons. Furthermore, we reveal that removal of inhibitory and excitatory synapses exhibits distinct temporal patterns, in which microglia-mediated inhibitory synapse removal precedes excitatory synapse removal. We also find selective and gradual increase in complement depositions on dorsal horn synapses that corresponds to the temporal pattern of microglial synapse pruning activity and type-specific synapse loss. Together, these results define a specific role for microglia in the progression of neuropathic pain pathogenesis and implicate these immune cells in structural remodeling of dorsal horn circuitry.

Mice with experimental nerve damage can display long‑lasting neuropathic pain behavior. We show here that 4 months and later after nerve injury, male but not female mice displayed telomere length (TL) reduction and p53‑mediated cellular senescence in the spinal cord, resulting in maintenance of pain and associated with decreased lifespan. Nerve injury increased the number of p53‑positive spinal cord neurons, astrocytes, and microglia, but only in microglia was the increase male‑specific, matching a robust sex specificity of TL reduction in this cell type, which has been previously implicated in male‑specific pain processing. Pain hypersensitivity was reversed by repeated intrathecal administration of a p53‑specific senolytic peptide, only in male mice and only many months after injury. Analysis of UK Biobank data revealed sex-specific relevance of this pathway in humans, featuring male‑specific genetic association of the human p53 locus (TP53) with chronic pain and a male-specific effect of chronic pain on mortality. Our findings demonstrate the existence of a biological mechanism maintaining pain behavior, at least in males, occurring much later than the time span of virtually all extant preclinical studies.

In general object detection, scale variation is always a big challenge. At present, feature pyramid networks are employed in numerous methods to alleviate the problems caused by large scale range of objects in object detection, which makes use of multi-level features extracted from the backbone for top-down upsampling and fusion to acquire a set of multi-scale depth image features. However, the feature pyramid network proposed by Ghiasi et al. adopts a simple fusion method, which fails to consider the fusion feature context, and therefore, it is difficult to acquire good features. In addition, the fusion of multi-scale features directly by traditional upsampling is prone to feature misalignment and loss of details. In this paper, an adaptive feature pyramid network is proposed based on the feature pyramid network to alleviate the foregoing potential problems, which includes two major designs, i.e., adaptive feature upsampling and adaptive feature fusion. The adaptive feature upsampling aims to predict a group of sampling points of each pixel through some models, and constitute feature representation of the pixel by feature combination of sampling points, while adaptive feature fusion is to construct pixel-level fusion weights between fusion features through attention mechanism. The experimental results verified the effectiveness of the method proposed in this paper. On the public object detection dataset MS-COCO test-dev, Faster R-CNN model achieved performance improvement of 1.2 AP by virtue of the adaptive feature pyramid network, and FCOS model could achieve performance improvement of 1.0 AP. What’s more, the experiments also validated that the adaptive feature pyramid network proposed herein was more accurate for object localization.

In this study, cement mortars with different strengths are poured into the large void matrix asphalt macadam material as a semiflexible pavement (SFP) material and the experimental research is carried out. The current research on SFP is mainly focused on the performance of grouting materials and the influence of grouting matrix materials on the overall mechanical properties of SFP and road performance. However, there are some flaws in the study of the influence of grouting material strength on the performance of SFP materials: the difference between the strengths of the selected grouting materials is relatively small, and in some studies, the chosen grouting material strength is low, which leads to insignificant improvements of SFP material performance; besides, the research indicators are also not very comprehensive. In this study, cement grouting asphalt macadam materials are selected as the research object to examine the effect of grouting material strength on the mechanical properties and road performance of SFP materials. Grouting materials with strengths of 19.8 MPa, 30.7 MPa, and 40.2 MPa were poured into the matrix asphalt macadam with a target void ratio of 24% and asphalt content of 2.9% to prepare the corresponding SFP test specimens. The SFP specimens were then subjected to the compressive test, flexural and tensile test, high-temperature stability test, and low-temperature crack resistance test, and the compressive resilient modulus was measured, thereby analyzing the effect of the cement slurry strength on the cement grouting asphalt macadam materials. The results show that when the strength of the cement mortar is 19.8 MPa, 30.7 MPa, and 40.2 MPa, the corresponding SFP material has better mechanical properties. When the strength of the grouting material is 40.2 MPa, the compressive strength of the SFP material is about the same as that of the grouting material. The strength is more than double that of 19.8 MPa and 30.7 MPa, and the flexural tensile strength and elastic modulus also have the above growth laws. The low-temperature crack resistance and high-temperature stability of the SFP material are enhanced with the increase in the strength of the grouting material. When the strength of the grouting material is 40.2 MPa, the mechanical properties and road performance of the SFP material are relatively better. This study provides a reference for strengthening the mechanical properties of SFP materials and boosting the crack resistance of SFP.

Endometrial cancer (EC) is one of the most common gynecologic cancers in developed countries. Presently, it is imperative to develop a reliable, noninvasive, or minimally invasive detection method for EC. We explored the possibility of using DNA methylation marker from endometrial brush samples (with a “Tao brush”) and cervical scrapes (with a “Pap brush”) for early detection of EC. We analyzed the methylation data of EC and normal endometrial tissues from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data sets. An optimized methylation-sensitive restriction enzyme combined with real-time fluorescent quantitative PCR (MSRE-qPCR) was used for methylation detection. Included in the training set were 143 endometrial tissues, 103 Tao, and 109 Pap brush samples. The validation set included 110 Tao and 112 Pap brush samples. PCDHGB7 was significantly hypermethylated in EC compared with normal endometrial tissues in the TCGA and GEO data sets (AUC >0.95), which was verified in clinical samples. In the Pap brush samples, the AUC was 0.86 with 80.65% sensitivity and 82.81% specificity, whereas the Tao brush samples exhibited higher specificity (95.31%). The combination of Tao and Pap brush samples significantly increased the sensitivity to 90.32%. In the validation set, the final model yielded a sensitivity of 98.61%, specificity of 60.53%, positive predictive value of 82.56%, and negative predictive value of 95.83%. These results demonstrate the potential application of the novel methylation marker, hypermethylated PCDHGB7, in cervical scrapings and endometrial brush, which provides a viable, noninvasive, or minimally invasive method for early endometrial cancer detection across different clinical features and histologies to supplement current hysteroscopy diagnosis.

Background:Lung cancer has a very high incidence rate and is one of the commonly diagnosed tumors in developed countries.Aims:To investigate the effect of wogonin on A549 and A427 lung cancer cells and explore the mechanism involved.Study Design:Cell study.Methods:The cytotoxicity effect of wogonin on A549 and A427 lung cancer and BEAS-2B cells was assessed by MTT assay. The onset of apoptosis was assessed by flow cytometry using Annexin V FITC/PI staining. Western blotting was used for the determination of changes in apoptotic protein expression.Results:Wogonin treatment exhibited cytotoxicity effect selectively on A549 and A427 cells without affecting BEAS-2B normal lung cells. The viability of A549 and A427 cells was reduced to 31% and 34%, respectively, on treatment with 50 μM of wogonin; however, there was no significant reduction in BEAS-2B cell viability on treatment with the same concentration of it. Moreover, the percentage of apoptotic A427 cells showed a significant (p

The Sayashk tin (Sn) deposit is located within the southern part of the Eastern Junggar orogenic belt in Xinjiang Province and forms part of the Kalamaili alkaline granite belt. There are many Sn polymetallic deposits in the area. To constrain the age, genesis, and tectonic setting of the Sayashk tin deposit in the East Junggar region, we conducted a bulk-rock geochemical analysis of the granite porphyry (SR1) and medium- to fine-grained granite (SR2) hosts of the deposit, LA-ICP-MS zircon U–Pb dating and Lu–Hf isotopic analysis, as well as molybdenite Re–OS dating and combined our results with the metallogenic conditions and other geological characteristics of the deposit. The results show that the Sayashk Sn deposit is indeed spatially, temporally, and genetically closely related to the granite porphyry and medium-fine-grained granite. Both zircon U–Pb ages are 308.2 ± 1.5 Ma and 310.9 ± 1.5 Ma, respectively. The isochron age of molybdenite is 301.4 ± 6.7 Ma, which represents the crystallization age of the granite porphyry and medium-fine-grained granite. Therefore, all of them formed in the late Carboniferous epoch. The medium-fine-grained granites and granite porphyry are characteristically rich in Si and alkali, poor in Ca and Mg, rich in high field-strength elements (HFSE, e.g., Zr, Hf) and Ce, and deficient in Ba, Sr, Eu, P, and Ti. They are typical A-type granites, showing the characteristics of a mixed crustal mantle source. The εHf(t) values of the zircon from the granite porphyry (SR1) range from 10.27 to 16.17 (average 13.71), εHf(t) values of the zircon from the medium-fine-grained granites (SR2) are between 5.72 and 9.21 (average 7.08), and the single model ages (TDM1) and two-stage model ages (TDM2) of the granite porphyry (SR1) fall within the ranges of 319~535 Ma and 339~644 Ma. The single model ages (TDM1) and two-stage model ages (TDM2) of the medium-fine-grained granites (SR2) fall within the ranges of 346~479 Ma and 309~557 Ma. There is little difference between their two-stage model ages and zircon U–Pb ages, indicating that the Sayashk granite may be the product of partial melting of juvenile crustal. Combined with previous research results, the Sayashk Sn deposit formed in a post-collision extensional tectonic setting after the late Carboniferous in the Kalamaili area.

The Zhangxuan district in North China, also known as Northwestern Hebei “Golden Triangle,” develops many intrusion-hosted lode-gold deposits. The Dongping gold deposit in the Zhangxuan district is well known for its unique hosting of rocks and ore mineral assemblages. Magnetite and pyrite are common minerals that widely exist in ores of the Dongping deposit. To get a better understanding of the evolution of the ore-forming fluids responsible for mineralization, we report on an integrated study on the electron microprobe analysis (EMPA) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis of magnetite and pyrite from the deposit. The major results are as follows: The magnetite grains from the Dongping deposit show a variable content of major and trace elements such as Ti, Al, Si, Fe, Mn, Cr, Na, V, and Co, and the majority of the magnetite contain low Ti contents, revealing potential properties of hydrothermal magnetite. The flat time-resolved signals of LA-ICP-MS imply that the majority of trace elements in magnetite exist in the form of isomorphism, except for some incompatible trace elements. Magnetites from the Dongping deposit have compositional characteristics of hydrothermal origins, and the genetic discriminant diagrams of Ti–V, Ti–Ni/Cr or (Ca + Al + Mn)–(Ti + V) show that they may be originated from magma differentiated hydrothermal solutions. Co, Ni in pyrite from Dongping mainly enter the lattice via isomorphism, and Cu, Zn, Ag, W, Sn, Au, Pb, and Bi are partitioned into pyrite as micro/nano- mineral inclusions. The Co, Ni content, and the Ni/Co ratios, indicated that the temperature of the ore-forming fluids has decreased from Py-1 to Py-2, and the enrichment of Au in Py-2 may be related to the cooling and boiling of the fluids.

Low temperature storage is widely used to maintain the postharvest quality of table grape. However, grape clusters easily undergo deterioration without treatment during the storage time. The main goal of this study was to evaluate the effect of postharvest 1-methylcyclopropene (1-MCP), calcium chloride (1%) and ethanol (16%), and the combination of 1-MCP with calcium chloride and ethanol treatments on maintenance of quality of table grapes ‘Kyoho’ (Vitis vinifera × Vitis labrusca) under 5 °C and 0 °C storage. Changes in decay incidence, weight loss, rachis browning and quality indexes of grape clusters were investigated. The results were as follows: all treatments significantly reduced the decay incidence, weight loss, rachis browning at both low temperatures storage; 1-MCP had positive effect for reducing the decay incidence in early stage, but no effect in late stage; there are no significant variations of taste and color quality indexes under two low temperatures storage, regardless of the treatments. Overall findings suggested that the combination of 1-MCP with calcium chloride and ethanol treatment is suitable for short-term 0 °C storage, while for long-term 0 °C storage, calcium chloride (1%) and ethanol (16%) treatment should be selected.

Background/Aims: To evaluate the effect of Liuweibuqi capsules on chronic obstructive pulmonary disease (COPD) through the JAK/STAT pathway. Methods: Lung function was measured with a spirometer. Changes in lung histology were observed using H&E staining. Cigarette smoke extract combined with lipopolysaccharide (CSE+LPS) was used to establish the cellular COPD model. Cytokine levels were determined using ELISA, and changes in the JAK/STAT pathway were evaluated using western blotting. The CCK8 method and flow cytometry were used to measure cell viability and apoptosis, respectively. Results: Liuweibuqi capsules reduced the damage in the lung tissues and the loss of lung function in the COPD rats. Additionally, the levels of interleukin (IL)-1β, interferon γ (IFNγ), IL-6, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 were higher, whereas IL-10 was lower in the model control (MC) and CSE+LPS groups than in the normal group. The phosphorylation levels of JAK1, JAK2, STAT1, STAT3 and STAT5 were higher and the levels of SOCS1 and SOCS3 were lower in the MC group and CSE+LPS group compared with the normal group. After Liuweibuqi capsule treatment, the expression of inflammatory cytokines and elements of the JAK/STAT pathway were lower. In addition, over-expression of STAT3 blocked the effects of the Liuweibuqi capsules on the release of inflammatory cytokines, cell viability and apoptosis. Conclusion: Our findings suggested that Liuweibuqi capsule might effectively ameliorate the progression of COPD via the JAK/STAT pathway.

Cloud applications provides users with services that can be accessed on demand through the Internet. Fertile service frameworks are considered one of the most critical ingredients for the envisaged benefits so as to further interactions among cloud computing resources and application components. Such foundations should lead to the proliferation of new innovative services and applications. The research community has been exploring the Open Service Gateway initiative's (OSGi) potential as a top candidate for cloud application platforms. Although the current OSGi specification provides some level of support for dynamic service discovery, tracking, and composition, more should be done to be able to adequately address the need for diverse interaction patterns for cloud applications. This paper introduces a novel service framework built upon OSGi platforms that supports a directed-acyclic-graph style composition of constituent services. Given a declarative blueprint of service interconnections and interactions, the framework can find and assemble corresponding component services to form a real application. Our proposal can enable a realistic topology of service component interlinkings beyond linear chaining interactions as supported by the status quo. The design, implementation details, and validation results of our workflow-based service composition framework architecture are discussed in the paper.

Clinical RNA-seq datasets can predict clinical outcomes. Here, Shen et al. report a statistical method for survival analysis of mRNA isoform variation using clinical RNA-seq datasets, and the identified isoform based survival predictors outperform gene expression based survival predictors using TCGA data on six cancer types.

Monodisperse resorcinol formaldehyde resin (RF) microspheres are an important polymeric material because of their rich surface functional group and uniform structural characteristics and have been increasingly applied as an electrode material, catalyst support, absorbent, and carbon microsphere precursor. The polymerization conditions, such as the gelation/solidification temperature and the residence time, can largely influence the physical properties and the formation of the 3D polymeric network of the RF microspheres as well as the carbon microspheres. However, few studies have reported on the complexity of the gelation and solidification processes of resol. In this work, we developed a new RF microsphere preparation device that contains three units: a droplet generation unit, a curing unit, and a collection unit. In this system, we controlled the gelation and solidification processes of the resol and observed its curing behavior, which helped us to uncover the curing mechanism of resol. Finally, we obtained the optimized polymerization parameters, obtaining uniform RF microspheres with a variation coefficient of 4.94%. The prepared porous RF microspheres presented a high absorption ability, reaching ~90% at 10 min. Thus, our method demonstrated the practicality of on-chip monodisperse microspheres synthesis. The product was useful in drug delivery and adsorbing large poisonous molecules.

Droplet microfluidics technology is recently a highly interesting platform in material fabrication. Droplets can precisely monitor and control entire material fabrication processes and are superior to conventional bulk techniques. Droplet production is controlled by regulating the channel geometry and flow rates of each fluid. The micro-scale size of droplets results in rapid heat and mass-transfer rates. When used as templates, droplets can be used to develop reproducible and scalable microparticles with tailored sizes, shapes and morphologies, which are difficult to obtain using traditional bulk methods. This technology can revolutionize material processing and application platforms. Generally, microparticle preparation methods involve three steps: (1) the formation of micro-droplets using a microfluidics generator; (2) shaping the droplets in micro-channels; and (3) solidifying the droplets to form microparticles. This review discusses the production of microparticles produced by droplet microfluidics according to their morphological categories, which generally determine their physicochemical properties and applications.

Multiple myeloma (MM) is a cancer of antibody-making plasma cells. It frequently harbors alterations in DNA and chromosome copy numbers, and can be divided into two major subtypes, hyperdiploid (HMM) and non-hyperdiploid multiple myeloma (NHMM). The two subtypes have different survival prognosis, possibly due to different but converging paths to oncogenesis. Existing methods for identifying the two subtypes are fluorescence in situ hybridization (FISH) and copy number microarrays, with increased cost and sample requirements. We hypothesize that chromosome alterations have their imprint in gene expression through dosage effect. Using five MM expression datasets that have HMM status measured by FISH and copy number microarrays, we have developed and validated a K-nearest-neighbor method to classify MM into HMM and NHMM based on gene expression profiles. Classification accuracy for test datasets ranges from 0.83 to 0.88. This classification will enable researchers to study differences and commonalities of the two MM subtypes in disease biology and prognosis using expression datasets without need for additional subtype measurements. Our study also supports the advantages of using cancer specific characteristics in feature design and pooling multiple rounds of classification results to improve accuracy. We provide R source code and processed datasets at www.ChengLiLab.org/software.