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Abstract The study of target genes for the spontaneous regression phenomenon of neuroblastoma (NB) is still unclear. Common differentially expressed genes (DEGs) were identified by differential expression analysis in both public databases for the stage 4 death group and stage 4S survival group. The DEGs were ranked by constructing protein–protein interaction (PPI) network as well as calculating betweenness centrality (BC) values, and the relationship with NB prognosis was determined by performing univariate analysis, multifactor analysis, and lasso regression analysis on the top 10 genes and possibly correlated with spontaneous regression of NB. We identified a total of 173 DEGs, including 143 upregulated genes and 30 downregulated genes. PPI network showed a rich interaction between DEGs. We ranked the DEGs by calculating BC values and showed the top 10 genes, followed by univariate and multifactorial analyses, which showed that GRIA2, NTRK1, SCN9A, SLC18A2, CNR1, PIK3R1, and DGKB were associated with good prognosis, and CNR1 was the most closely associated with prognosis among them. By lasso regression analysis, we constructed a four‐gene risk score formula. We drew a nomogram to use in clinical work and two newly identified genes associated with good prognosis in NB: CNR1 and GIRA2.

Insertions–deletions (InDels) are the second most abundant molecular marker in the genome and have been widely used in molecular biology research along with simple sequence repeats (SSR) and single-nucleotide polymorphisms (SNP). However, InDel variant mining and marker development usually focuses on a single type of dimorphic InDel, which does not reflect the overall InDel diversity across the genome. Here, we developed Omni InDels for maize, soybean, and rice based on sequencing data and genome assembly that included InDel variants with base lengths from 1 bp to several Mb, and we conducted a detailed classification of Omni InDels. Moreover, we screened a set of InDels that are easily detected and typed (Perfect InDels) from the Omni InDels, verified the site authenticity using 3,587 germplasm resources from 11 groups, and analyzed the germplasm resources. Furthermore, we developed a Multi-InDel set based on the Omni InDels; each Multi-InDel contains multiple InDels, which greatly increases site polymorphism, they can be detected in multiple platforms such as fluorescent capillary electrophoresis and sequencing. Finally, we developed an online database website to make Omni InDels easy to use and share and developed a visual browsing function called “Variant viewer” for all Omni InDel sites to better display the variant distribution.

Abstract Contactin‐associated protein‐like 4 (Cntnap4) is critical for GABAergic transmission in the brain. Impaired Cntnap4 function is implicated in neurological disorders, such as autism; however, the role of Cntnap4 on memory processing is poorly understood. Here, we demonstrate that hippocampal Cntnap4 deficiency in female mice manifests as impaired cognitive function and synaptic plasticity. The underlying mechanisms may involve effects on the pro‐inflammatory response resulting in dysfunctional GABAergic transmission and activated tryptophan metabolism. To efficiently and accurately inhibit the pro‐inflammatory reaction, we established a biomimetic microglial nanoparticle strategy to deliver FDA‐approved PLX3397 (termed MNPs@PLX). We show MNPs@PLX successfully penetrates the blood brain barrier and facilitates microglial‐targeted delivery of PLX3397. Furthermore, MNPs@PLX attenuates cognitive decline, dysfunctional synaptic plasticity, and pro‐inflammatory response in female heterozygous Cntnap4 knockout mice. Together, our findings show loss of Cntnap4 causes pro‐inflammatory cognitive decline that is effectively prevented by supplementation with microglia‐specific inhibitors; thus validating the targeting of microglial function as a therapeutic intervention in neurocognitive disorders.

Sepsis-induced ALI is marked by physiological, pathological, and biochemical irregularities caused by infection. Growth differentiation factor 3 (GDF3) is closely associated with the inflammatory response. Accumulating evidence has demonstrated a close relationship between GDF3 expression and the severity and prognosis of sepsis. However, the precise mechanism by which GDF3 protects against ALI induced by sepsis is still unclear. Following the intravenous administration of GDF3 in this research, we noted a rise in the survival rate, a decrease in the severity of histopathological damage as evaluated through HE staining, a decline in the count of inflammatory cells in bronchoalveolar lavage fluid (BALF), a reduction in the ratio of lung wet/dry (W/D) weight, and a noteworthy decrease in the levels of pro-inflammatory cytokines in both serum and BALF when compared to septic mice who underwent cecal ligation and puncture (CLP). These collective findings unequivocally indicate the protective effects of GDF3 against sepsis-induced ALI. In addition, the GDF3 group showed a significant reduction in the mRNA expression of Caspase-1 and NLRP3 when compared to the CLP group. Following this, we performed in vitro tests to confirm these discoveries and obtained comparable outcomes, wherein the administration of GDF3 notably decreased the levels of Caspase-1 and NLRP3 mRNA and protein in macrophages in comparison to the LPS group. Furthermore, GDF3 exhibited the capacity to reduce the secretion of inflammatory molecules from macrophages. By illuminating the mechanism by which GDF 3 regulates macrophages, this offers a theoretical basis for preventing and treating sepsis-induced ALI.

Hastelloy X (HX) alloys with ideal strength and ductility match can be obtained by selective laser melting (SLM) and a proper follow-up heat treatment. This work studies the influence of scanning speed on grain size, grain boundary distribution, recrystallization and mechanical properties of as-built HX. These influences are reevaluated after a solution treatment at 1175 °C for 4h. The results reveal that the average grain size decreases, while the aspect ratio, texture intensity and the proportion of high-angle grain boundaries (HAGBs) increases with the increase of scanning speed. A small amount of recrystallization has occurred in the as-built alloys due to the cyclic thermal effect of SLM scanning. The finer grains and larger aspect ratio imply the higher energy storage during SLM, which will increase the recrystallizing nucleation rate. Solution treatment eliminates the fiber texture of 〈100〉//BD, significantly increases the HAGBs fraction and recrystallization fraction, reduces the grain aspect ratio, and coarsens the grains. With the increase of scanning speed, the strength of the Hastelloy X increases and the elongation decreases. The decrease of grain size is the main reason for the increase of yield strength.

In order to enhance traditional building materials, High-performance concrete (HPC) is being modified by adding carbon and basalt fibers with volume contents of 0.75–1.25% and 0.15–0.35%, respectively. The original mechanical properties are maintained while developing the material’s intelligent self-sensing and self-heating functions, which are tested for pressure sensitivity and bending sensitivity, and with electrothermal tests. The results demonstrate that carbon fiber can significantly reduce the matrix resistivity of high-performance concrete, reaching the percolation threshold at a content of 1%. The inclusion of basalt fibers in the material results in a decrease in resistivity. However, the addition of mixed fibers leads to improved mechanical–electrical sensitivity under compression and bending, with a positive hybrid effect. The optimal contents for carbon fiber and basalt are 0.75% and 0.3%, respectively. In electrothermal tests, the specimen can reach a temperature of 104.5 °C with a heating rate of 25.86 °C/h, indicating the potential for self-monitoring and the electric melting of ice and snow. These findings provide support for the intelligent improvement of building structures in the new era.

Abstract Neuroinflammation, for which microglia are the predominant contributors, is a significant risk factor for cognitive dysfunction. Riboflavin (also known as vitamin B2) ameliorates cognitive impairment via anti‐oxidative stress and anti‐inflammation properties; however, the underlying mechanisms linking riboflavin metabolism and microglial function in cognitive impairment remain unclear. Here, it is demonstrated that riboflavin kinase (RFK), a critical enzyme in riboflavin metabolism, is specifically expressed in microglia. An intermediate product of riboflavin, flavin mononucleotide (FMN), inhibited RFK expression via regulation of lysine‐specific methyltransferase 2B (KMT2B). FMN supplementation attenuated the pro‐inflammatory TNFR1/NF‐κB signaling pathway, and this effect is abolished by KMT2B overexpression. To improve the limited anti‐inflammatory efficiency of free FMN, a biomimetic microglial nanoparticle strategy (designated as MNPs@FMN) is established, which penetrated the blood brain barrier with enhanced microglial‐targeted delivery efficiency. Notably, MNPs@FMN ameliorated cognitive impairment and dysfunctional synaptic plasticity in a lipopolysaccharide‐induced inflammatory mouse model and in a 5xFAD mouse model of Alzheimer's disease. Taken together, biomimetic microglial delivery of FMN may serve as a potential therapeutic approach for inflammation‐dependent cognitive decline.

To maintain the ecosystem services of wetlands, this study developed an estimation method for suitable normalized difference vegetation index (NDVI) values by the integration of ecological water savings and phytoremediation requirements based on experiments and literature surveys in Baiyangdian Lake, North China. In terms of ecological water savings (namely, reducing wetland water consumption by reducing vegetation evapotranspiration), the upper limit of the reed community area was determined by the water replenishment plan of the lake to achieve water balance. In terms of phytoremediation, Grade III of the Chinese water quality grade scale, the target water quality of the lake, was considered to calculate the lower limit of the reed community area for the purpose of good water quality. Considering the two aspects of the requirements of ecological water savings and phytoremediation comprehensively, the suitable reed planning area and NDVI threshold were determined. The results indicated that the suitable reed planting area was 138.05 ∼ 146.43 km2, and the NDVI threshold was 0.155 ∼ 0.316 in the high-water-lever situation (6.8 ∼ 7.0 m). Concurrently, the appropriate reed planting area was 122.39 ∼ 128.24 km2, and the NDVI threshold was 0.137 ∼ 0.277 in the low-water-lever situation (6.5 ∼ 6.8 m). These findings expanded the use of NDVI in the relationship research between wetland vegetation patterns and water resource utilisations, providing support for making vegetation pattern adjustment decisions for wetland protection and restoration in water-scarce regions.

The increased activity of the mTOR pathway in bladder cancer has been extensively studied, but no satisfactory mTOR inhibitor has been found in bladder cancer. The role of AZD8055, a second-generation mTOR inhibitor, has not been reported in bladder cancer. Herein, we investigated the effects of AZD8055 on bladder cells and their interaction with macrophages in vivo and in vitro. In four bladder cancer cell lines, the phosphorylation of mTOR, AKT and S6K1 was suppressed by AZD8055. AZD8055 inhibited proliferation and induced G1 cell-cycle arrest and apoptosis of bladder cancer cells in a concentration-dependent manner. AZD8055 also inhibits the migration and invasion of bladder cancer cells by blocking EMT and MMP9. In addition, AZD8055 inhibited chemotaxis and M2 phenotype of macrophage after co-culture with bladder cancer cells. These anti-tumor effects of AZD8055 were verified in vivo. Our findings collectively demonstrated that low-dose AZD8055 induces cytotoxicity and apoptosis, and inhibits the Akt/mTOR activation, invasion and migration of bladder cancer. These findings also demonstrate that AZD8055 partially blocked the interactions of bladder cancer cells and macrophages. In conclusion, AZD8055 is a promising mTOR inhibitor for bladder cancer.

Summary: Background: Tongue images (the colour, size and shape of the tongue and the colour, thickness and moisture content of the tongue coating), reflecting the health state of the whole body according to the theory of traditional Chinese medicine (TCM), have been widely used in China for thousands of years. Herein, we investigated the value of tongue images and the tongue coating microbiome in the diagnosis of gastric cancer (GC). Methods: From May 2020 to January 2021, we simultaneously collected tongue images and tongue coating samples from 328 patients with GC (all newly diagnosed with GC) and 304 non-gastric cancer (NGC) participants in China, and 16 S rDNA was used to characterize the microbiome of the tongue coating samples. Then, artificial intelligence (AI) deep learning models were established to evaluate the value of tongue images and the tongue coating microbiome in the diagnosis of GC. Considering that tongue imaging is more convenient and economical as a diagnostic tool, we further conducted a prospective multicentre clinical study from May 2020 to March 2022 in China and recruited 937 patients with GC and 1911 participants with NGC from 10 centres across China to further evaluate the role of tongue images in the diagnosis of GC. Moreover, we verified this approach in another independent external validation cohort that included 294 patients with GC and 521 participants with NGC from 7 centres. This study is registered at ClinicalTrials.gov, NCT01090362. Findings: For the first time, we found that both tongue images and the tongue coating microbiome can be used as tools for the diagnosis of GC, and the area under the curve (AUC) value of the tongue image-based diagnostic model was 0.89. The AUC values of the tongue coating microbiome-based model reached 0.94 using genus data and 0.95 using species data. The results of the prospective multicentre clinical study showed that the AUC values of the three tongue image-based models for GCs reached 0.88–0.92 in the internal verification and 0.83–0.88 in the independent external verification, which were significantly superior to the combination of eight blood biomarkers. Interpretation: Our results suggest that tongue images can be used as a stable method for GC diagnosis and are significantly superior to conventional blood biomarkers. The three kinds of tongue image-based AI deep learning diagnostic models that we developed can be used to adequately distinguish patients with GC from participants with NGC, even early GC and precancerous lesions, such as atrophic gastritis (AG). Funding: The National Key R&D Program of China (2021YFA0910100), Program of Zhejiang Provincial TCM Sci-tech Plan (2018ZY006), Medical Science and Technology Project of Zhejiang Province (2022KY114, WKJ-ZJ-2104), Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer (JBZX-202006), Natural Science Foundation of Zhejiang Province (HDMY22H160008), Science and Technology Projects of Zhejiang Province (2019C03049), National Natural Science Foundation of China (82074245, 81973634, 82204828), and Chinese Postdoctoral Science Foundation (2022M713203).

In the process of rectangular box jacking, the friction resistance around the pipe is an important factor that causes the disturbance of the surrounding soil. To predict the influence of rectangular pipe jacking construction on stratum displacement more accurately, the calculation formula of horizontal displacement of soil is established based on the Mindlin solution of elastic mechanics, assuming the state of 'U' shaped mud sleeve combined with the stress analysis of pipe joint and the law of mud movement, and the vertical-horizontal displacement of stratum caused by additional stress on the front and friction resistance around the pipe is calculated. Finally, it is compared with the measured values of a rectangular box jacking project in Suzhou. The results show that before the pipe jacking head passes through a certain fracture, the effect of the additional stress on the surrounding soil is greater than the differential friction resistance around the pipe.However, after crossing the section, the cumulative effect of the latter is gradually greater than the former due to the increase inthe number of pipe segments and the "pull" effect of the friction resistance around the pipe jacking that haspassed through. The calculated value in the case of differential friction resistance is closer to the measured value than that in the case of uniform friction resistance, and the prediction effect is better.

Abstract The emergence of shotcrete provides a new idea for construction methods, but with the development of society, the traditional shotcrete has been unable to meet the needs of structure. Therefore, concrete with better material properties is needed to replace traditional shotcrete. Reactive powder concrete (RPC) is a well-known ultrahigh strength concrete and widely used. Its material properties are better than shotcrete. However, the sprayable performance of RPC and the properties of this sprayed materials have not been reported. Therefore, to make up for the deficiency of ordinary shotcrete, the material properties of sprayed RPC were studied in depth. Response surface method was used to study the effects of different silica fume content, fly ash content and steel fiber volume content on workability, mechanical properties and crack sensitivity. The sprayed reactive powder concrete (sprayed RPC) was proposed for the first time. All models were reliable through variance analysis. The performance of sprayed RPC was better when the workability was between 140 and 160 mm. When the silica fume/binder ratio was 15%, the fly ash/binder ratio was 13.203%, and the volume content of steel fibers was 2%, the mechanical properties and crack sensitivity of sprayed RPC can reach a satisfactory degree. By studying the workability, mechanical properties and crack sensitivity of sprayed RPC, the optimum mix ratio of sprayed RPC was obtained. Steel fiber sprayed RPC can detect structural damage. Results lay the foundation for popularization and application to practical engineering.

The Hailijin (HLJ) sandstone-type uranium deposit was newly discovered in the southwestern Songliao Basin in recent years. Different from the roll-front orebody of the sandstone-type uranium deposits with (phreatic oxidation) interlayer redox origin (or phreatic oxidation), the orebody of the HLJ uranium deposit is tabular-shaped and multi-stratiform. The kaolinite content in ore-controlling gray sandstones is significantly higher than that in oxidized sandstones, which have the highest kaolinite content in the less oxidized zone of sandstone-type uranium deposits in the basins of western China (such as Yili Basin and Turpan-Hami Basin). In order to identify the properties of ore-forming fluids and the genesis of the tabular-shaped orebody of the HLJ uranium deposit, trace element, scanning electron microscopy (SEM), X-ray diffraction (XRD), and uranium mineral electron probe (EPMA) analyses of different geochemical zone sandstones in ore-bearing strata were carried out. As a result, kaolinite, illite, and illite/smectite formation (I/S) appear to alternate with one another in ore-controlling gray sandstones, and the content of kaolinite is the highest in ores. SEM analysis also suggests that uranium minerals are commonly adsorbed on the surface of foliated and vermicular kaolinite or trapped within micropores of kaolinite. In this case, it is inferred that kaolinite in ore-controlling gray sandstones is of epigenetic origin, and the ore-bearing sandstones have undergone at least one transformation of acidic fluids. Combined with the regional paleoclimate, regional tectonics, and regional burial history, it is concluded that the acidic fluid originated from the uranium-rich source rocks of the Lower Cretaceous Jiufotang Formation, and the tabular-shaped orebody of the HLJ uranium deposit was formed by exudative metallogeny. When the uranium-rich acidic organic fluids exuded upward from deep levels along the faults to the target strata, the solubility of uranium and other polymetallic elements decreased because of the decrease in temperature and pressure, and uranium eventually precipitated and accumulated in sandstones with suitable permeability and porosity. However, it cannot be ruled out that the superimposition and transformation of uranium mineralization was caused by phreatic oxidation or local interlayer redox during the interval of exudative metallogeny.

In view of the time-consuming and laborious manual picking and sorting of strawberries, the direct impact of image recognition accuracy on automatic picking and the rapid development of deep learning(DL), a Faster Regions with Convolutional Neural Network features (R-CNN) strawberry recognition method that combines Mixup data augmentation, a ResNet(Residual Network)50 backbone feature extraction network and a Soft-NMS (Non-Maximum Suppression) algorithm, named the MRS Faster R-CNN, is proposed. In this paper, the transfer learning backbone feature extraction network VGG (Visual Geometry Group) 16 and ResNet50 are compared, and the superior ResNet50 is selected as the backbone network of MRS Faster R-CNN. The data augmentation method of Mixup image fusion is used to improve the learning and generalization ability of the model. The redundant bboxes (bounding boxes) are removed through Soft-NMS to obtain the best region proposal. The freezing phase is added to the training process, effectively reducing the occupation of video memory and shortening the training time. After experimental verification, the optimized model improved the AP (Average Precision) values of mature and immature strawberries by 0.26% and 5.34%, respectively, and the P(Precision) values by 0.81% and 6.34%, respectively, compared to the original model (R Faster R-CNN). Therefore, the MRS Faster R-CNN model proposed in this paper has great potential in the field of strawberry recognition and maturity classification and improves the recognition rate of small fruit and overlapping occluded fruit, thus providing an excellent solution for mechanized picking and sorting.

Spastin, a microtubule-severing enzyme, is known to be important for neurite outgrowth. However, the role of spastin post-translational modification, particularly its phosphorylation regulation in neuronal outgrowth, remains unclear. This study aimed to investigate the effects of eliminating spastin phosphorylation on the neurite outgrowth of rat hippocampal neurons. To accomplish this, we constructed a spastin mutant with eleven potential phosphorylation sites mutated to alanine. The phosphorylation levels of the wildtype spastin (WT) and the mutant (11A) were then detected using Phos-tag SDS-PAGE. The spastin constructs were transfected into COS7 cells for the observation of microtubule severing, and into rat hippocampal neurons for the detection of neuronal outgrowth. The results showed that compared to the spastin WT, the phosphorylation levels were significantly reduced in the spastin 11A mutant. The spastin mutant 11A impaired its ability to promote neurite length, branching, and complexity in hippocampal neurons, but did not affect its ability to sever microtubules in COS7 cells. In conclusion, the data suggest that mutations at multiple phosphorylation sites of spastin do not impair its microtubule cleavage ability in COS7 cells, but reduce its ability to promote neurite outgrowth in rat hippocampal neurons.

With the increasingly extensive application of road engineering, it is inevitable to consider the durability of pavement in harsh environment. In the southeast coastal areas, northwest salt lakes and saline soil areas of China, harsh natural climate conditions and enhanced salt have a significant negative impact on the service life of asphalt pavements. In addition, the durability of asphalt pavement has suffered irreparable harm of the man-made salt environment. In this paper, five typical salt environment characteristics of asphalt pavement has been analyzed. The experimental conditions affecting the durability of asphalt concrete are determined. Then the durability deterioration mechanism of asphalt concrete is discussed under the coupling action of salt and multiple factors. Subsequently, the evaluation methods of asphalt concrete are categorized and summarized using scales for road performance and structure. Finally, according to the degree of salt erosion damage of asphalt concrete, a series of measures to alleviate salt erosion are proposed. The results show that the performance of asphalt concrete suffers significantly in salt environment, and the cohesion of asphalt and the adhesion of asphalt-aggregate interface are key factors in the durability of asphalt concrete. It has beneficial theoretical and practical significance for improving the durability of asphalt concrete under harsh natural environment.

Summary: Background: Autism spectrum disorder (ASD) is a common neurodevelopmental disease, characterized by deficits in social communication, restricted and repetitive behaviours, and impaired fear memory processing. Severe gastrointestinal dysfunction and altered gut microbiome have been reported in ASD patients and animal models. Contactin associated protein-like 4 (CNTNAP4) has been suggested to be a novel risk gene, though its role in ASD remains unelucidated. Methods: Cntnap4−/− mice were generated to explore its role in ASD-related behavioural abnormalities. Electrophysiological recording was employed to examine GABAergic transmission in the basolateral amygdala (BLA) and prefrontal cortex. RNA-sequencing was performed to assess underlying mechanisms. 16S rDNA analysis was performed to explore changes in faecal microbial composition. Male Cntnap4−/− mice were fed with Lactobacillus reuteri (L. reuteri) or faecal microbiota to evaluate the effects of microbiota supplementation on the impaired fear conditioning mediated by Cntnap4 deficiency. Findings: Male Cntnap4−/− mice manifested deficiency in social behaviours and tone-cue fear conditioning. Notably, reduced GABAergic transmission and GABA receptor expression were found in the BLA but not the prefrontal cortex. In addition, gut Lactobacillus were less abundant in male Cntnap4−/− mice, and L. reuteri treatment or faecal microbiota transplantation rescued abnormal tone-cued fear memory and improved local GABAergic transmission in the BLA of male Cntnap4−/− mice. Interpretation: Cntnap4 shapes GABAergic transmission of amygdala and fear conditioning, and microbial intervention represents a promising therapy in ASD intervention. Funding: National Natural Science Foundation of China, Science and Technology Planning Project of Guangzhou, Guangzhou Medical University, and China Postdoctoral Science Foundation.

Abstract Background The underlying circular RNAs (circRNAs)-related competitive endogenous RNA (ceRNA) mechanisms of pathogenesis and prognosis in non-small cell lung cancer (NSCLC) remain unclear. Methods Differentially expressed circRNAs (DECs) in two Gene Expression Omnibus datasets (GSE101684 and GSE112214) were identified by utilizing R package (Limma). Circinteractome and StarBase databases were used to predict circRNA associated-miRNAs and mRNAs, respectively. Then, protein–protein interaction (PPI) network of hub genes and ceRNA network were constructed by STRING and Cytoscape. Also, analyses of functional enrichment, genomic mutation and diagnostic ROC were performed. TIMER database was used to analyze the association between immune infiltration and target genes. Kaplan–Meier analysis, cox regression and the nomogram prediction model were used to evaluate the prognostic value of target genes. Finally, the expression of potential circRNAs and target genes was validated in cell lines and tissues by quantitative real-time PCR (qRT-PCR) and Human Protein Atlas (HPA) database. Results In this study, 15 DECs were identified between NSCLC tissues and adjacent-normal tissues in two GEO datasets. Following the qRT-PCR corroboration, 7 DECs (hsa_circ_0002017, hsa_circ_0069244, hsa_circ_026337, hsa_circ_0002346, hsa_circ_0007386, hsa_circ_0008234, hsa_circ_0006857) were dramatically downregulated in A549 and SK-MES-1 compared with HFL-1 cells. Then, 12 circRNA-sponged miRNAs were screened by Circinteractome and StarBase, especially, hsa-miR-767-3p and hsa-miR-767-5p were significantly up-regulated and relevant to the prognosis. Utilizing the miRDB and Cytoscape, 12 miRNA-target genes were found. Functional enrichment, genomic mutation and diagnostic analyses were also performed. Among them, FNBP1, AKT3, HERC1, COL4A1, TOLLIP, ARRB1, FZD4 and PIK3R1 were related to the immune infiltration via TIMER database. The expression of ARRB1, FNBP1, FZD4, and HERC1 was correlated with poor overall survival (OS) in NSCLC patients by cox regression and nomogram. Furthermore, the hub-mRNAs were validated in cell lines and tissues. Conclusion We constructed the circRNA-miRNA-mRNA network that might provide novel insights into the pathogenesis of NSCLC and reveal promising immune infiltration and prognostic biomarkers.

Abstract Background With the broad application of high-throughput sequencing and its reduced cost, simple sequence repeat (SSR) genotyping by sequencing (SSR-GBS) has been widely used for interpreting genetic data across different fields, including population genetic diversity and structure analysis, the construction of genetic maps, and the investigation of intraspecies relationships. The development of accurate and efficient typing strategies for SSR-GBS is urgently needed and several tools have been published. However, to date, no suitable accurate genotyping method can tolerate single nucleotide variations (SNVs) in SSRs and flanking regions. These SNVs may be caused by PCR and sequencing errors or SNPs among varieties, and they directly affect sequence alignment and genotyping accuracy. Results Here, we report a new integrated strategy named the accurate microsatellite genotyping tool based on targeted sequencing (AMGT-TS) and provide a user-friendly web-based platform and command-line version of AMGT-TS. To handle SNVs in the SSRs or flanking regions, we developed a broad matching algorithm (BMA) that can quickly and accurately achieve SSR typing for ultradeep coverage and high-throughput analysis of loci with SNVs compatibility and grouping of typed reads for further in-depth information mining. To evaluate this tool, we tested 21 randomly sampled loci in eight maize varieties, accompanied by experimental validation on actual and simulated sequencing data. Our evaluation showed that, compared to other tools, AMGT-TS presented extremely accurate typing results with single base resolution for both homozygous and heterozygous samples. Conclusion This integrated strategy can achieve accurate SSR genotyping based on targeted sequencing, and it can tolerate single nucleotide variations in the SSRs and flanking regions. This method can be readily applied to divergent sequencing platforms and species and has excellent application prospects in genetic and population biology research. The web-based platform and command-line version of AMGT-TS are available at https://amgt-ts.plantdna.site:8445 and https://github.com/plantdna/amgt-ts , respectively.

Controlled breaking of a chemical bond by mechanical forces can provide key insight into reaction mechanisms. Here the authors, using atomic force microscopy and computations, measure the forces involved in breaking a single dative bond between a CO molecule and a ferrous phthalocyanine complex.

ObjectiveTo compare the efficacy of liver resection (LR), radiofrequency ablation (RFA), and radiofrequency ablation combined with transcatheter arterial chemoembolization (RFA+TACE) in the treatment of very-early- and early-stage hepatocellular carcinoma (HCC).MethodsWe systemically searched the PubMed, Embase, and Cochrane Library databases. Randomized controlled trials (RCTs) and observational analyses with propensity score-matched cohort analyses (PSMs) comparing any two of the three treatments were included in this study. The primary result was overall survival (OS) and the secondary result was recurrence-free survival (RFS), which were analyzed by calculating the hazard ratio (HR) and 95% confidence intervals (CI).ResultsA total of 25 studies (4249 patients), including 10 RCTs and 15 PSM observational studies, met the inclusion criteria. Although there was no significant difference between LR and RFA in terms of one-year OS, though LR showed superior performance for three- and five-year OS (at three years, HR: 0.74, 95% CI: 0.56-0.96; at five years, HR: 0.73, 95% CI: 0.55-0.94). In addition, significantly higher rates of RFS at one-, three- and five-year follow-up were found for LR than for RFA alone (at one year, HR: 0.68, 95% CI: 0.51-0.92; at three years, HR: 0.67, 95% CI: 0.55-0.81; at five years, HR: 0.61, 95% CI: 0.48-0.78). The combination of RFA+TACE was superior to RFA alone based on one-year RFS (HR: 0.57, 95% CI: 0.34-0.96), while there were no significant differences in OS at one, three, and five years, and in RFS at three and five years.ConclusionsFor very-early- and early-stage HCC, this systematic review and network meta-analysis showed that the efficacy of LR is superior to that of RFA alone, regardless of whether the evaluation is based on either OS or RFS. The advantages of RFA+TACE compared to RFA alone are limited, and further studies are needed to determine whether combination therapy is necessary, i.e., results in significantly improved outcomes. Systematic Review RegistrationThe study was registered with http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42022299269

Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium–microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known—each is a free base tetrapyrrole macrocycle with a dioxobacteriochlorin (14), oxochlorin (3), or porphyrin (1) chromophore. Each compound displays two, three, or four open β-pyrrole positions and two, one, or zero appended C-glycoside (or –OH or –OAc) groups, respectively; the appended groups form part of a geminal disubstitution motif flanking the oxo moiety in the pyrroline ring. The distinct structures and repertoire of tolyporphins stand alone in the large pigments-of-life family. Efforts to understand the cyanobacterial origin, biosynthetic pathways, structural diversity, physiological roles, and potential pharmacological properties of tolyporphins have attracted a broad spectrum of researchers from diverse scientific areas. The identification of putative biosynthetic gene clusters in the HT-58-2 cyanobacterial genome and accompanying studies suggest a new biosynthetic paradigm in the tetrapyrrole arena. The present review provides a comprehensive treatment of the rich science concerning tolyporphins.

The BDS multipath delay error is highly related to the surrounding monitoring environment, which cannot be eliminated or mitigated by applying the double difference observation model. In the actual monitoring environment, due to the complexity of the BDS constellation, it is difficult for existing algorithms to consider GEO, IGSO, MEO and other different orbital types of satellites for real-time and efficient multipath error reduction. Therefore, we propose a novel BDS dual-frequency multipath error reduction method for real deformation monitoring for BDS considering various satellite orbit types. This method extracts the single error residual of each satellite based on the assumption of “zero mean” and divides the appropriate grid density of GEO and IGSO/MEO, respectively, to construct a dual-frequency multipath hemispherical map model suitable for BDS satellites with different orbital types. This method can realize the multipath error elimination of the observed values of different orbits and different frequencies. The results of simulation experiments and real deformation monitoring data demonstrate that this method can effectively eliminate low-frequency multipath delay errors in the observation domain and coordinate domain. After multipath correction, the precision of the horizontal coordinates and height coordinates are 1.7 mm and 4.6 mm. The precision of the horizontal coordinate and height coordinate is increased by 50% and 60%, respectively. The fixed rate of ambiguity increased by 5–7%.

BackgroundIntracerebral hemorrhage (ICH) is a stroke syndrome with an unfavorable prognosis. Currently, there is no comprehensive clinical indicator for mortality prediction of ICH patients. The purpose of our study was to construct and evaluate a nomogram for predicting the 30-day mortality risk of ICH patients.MethodsICH patients were extracted from the MIMIC-III database according to the ICD-9 code and randomly divided into training and verification cohorts. The least absolute shrinkage and selection operator (LASSO) method and multivariate logistic regression were applied to determine independent risk factors. These risk factors were used to construct a nomogram model for predicting the 30-day mortality risk of ICH patients. The nomogram was verified by the area under the receiver operating characteristic curve (AUC), integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA).ResultsA total of 890 ICH patients were included in the study. Logistic regression analysis revealed that age (OR = 1.05, P < 0.001), Glasgow Coma Scale score (OR = 0.91, P < 0.001), creatinine (OR = 1.30, P < 0.001), white blood cell count (OR = 1.10, P < 0.001), temperature (OR = 1.73, P < 0.001), glucose (OR = 1.01, P < 0.001), urine output (OR = 1.00, P = 0.020), and bleeding volume (OR = 1.02, P < 0.001) were independent risk factors for 30-day mortality of ICH patients. The calibration curve indicated that the nomogram was well calibrated. When predicting the 30-day mortality risk, the nomogram exhibited good discrimination in the training and validation cohorts (C-index: 0.782 and 0.778, respectively). The AUCs were 0.778, 0.733, and 0.728 for the nomogram, Simplified Acute Physiology Score II (SAPSII), and Oxford Acute Severity of Illness Score (OASIS), respectively, in the validation cohort. The IDI and NRI calculations and DCA analysis revealed that the nomogram model had a greater net benefit than the SAPSII and OASIS scoring systems.ConclusionThis study identified independent risk factors for 30-day mortality of ICH patients and constructed a predictive nomogram model, which may help to improve the prognosis of ICH patients.

Background Maize is an important model organism for genetics and genomics research. Though reference genomes of maize are available, some genomes of important genetic germplasms for maize breeding are still lacking, for instance, the cultivar Dan340, which is a backbone inbred line of the LvDa Red Cob Group with several desirable characteristics. In this study, we constructed a high-quality chromosome-level reference genome for Dan340 by using long HiFi reads, short reads, and Hi-C. The final assembly of the Dan340 genome was 2348.72 Mb, which was anchored to 10 chromosomes. Repeat sequences accounted for 73.40% of the genome and 39,733 protein-coding genes were annotated. Comparative genomic analysis between Dan340 and other maize lines identified that 1806 genes from 359 gene families were specific to Dan340. Conclusions Our genome assembly and annotation provide a valuable resource for improving maize breeding and further understanding the intraspecific genome diversity in maize.

This article presents a Lyapunov precise integral-based analysis method for seismic structures with added viscous fluid dampers. This study uses the full stress algorithm as the optimization method, considering the mean square of interstory drifts as the optimization objective, the position of the damper as the optimization object, and the random vibration analysis method as the calculation method to optimize seismic frame structures with viscous dampers. A precise integral solution is derived for the Lyapunov equation based on the general expression of the Lyapunov differential equation for the damping system under the excitation of a nonstationary stochastic process using two types of modulation functions: g(t)=1 and g(t)=t. Finally, the optimal damping arrangement is achieved using this method with a six-layer non-eccentric planar frame. In addition, the optimization results of this study are verified with those in the literature using time-history analysis, which verifies the feasibility and effectiveness of the proposed method. This study provides a method for the optimal configuration of dampers for seismic response of structures, which is beneficial for engineering applications and the protection of seismic structures.

This study aims to develop spay reactive powder concrete (SRPC) with excellent mechanical and self-sensing properties by using carbon fiber (CF) as reinforcement material in combination with RPC base mix ratio. A Box–Behnken model was designed using the response surface method to study the influence of silica fume (SF), fly ash (FA), and CF on the compressive strength and strain sensitivity coefficient (SSC) of SRPC with different dosages. Variance regression was used to analyze the interaction of each factor on the index, and multi-index optimization technology was utilized to optimize the response scheme. Results show that the compressive strength is 107.272 MPa and SSC is 34.429 under optimized conditions of 18% SF, 17.097% FA, and 0.5% CF. The strain sensitivity coefficient of SRPC is 5–17 times higher than that of the conventional strain gauge used for monitoring concrete. SRPC was prepared by adjusting the dosage of the water reducer and stirring time at a 0.2 water–binder ratio.

Given the importance of tripartite motif (TRIM) proteins in diverse cellular biological processes and that their dysregulation contributes to cancer progression, we constructed a robust TRIM family signature to stratify patients with kidney renal clear cell carcinoma (KIRC). Transcriptomic profiles and corresponding clinical information of KIRC patients were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. Prognosis-related TRIM family genes were screened and used to construct a novel TRIM family-based signature for the training cohort. The accuracy and generalizability of the prognostic signature were assessed in testing, entire, and external ICGC cohorts. We analyzed correlations among prognostic signatures, tumor immune microenvironment, and immune cell infiltration. The results of univariate Cox regression and Kaplan-Meier survival analyses revealed 27 TRIMs that were robustly associated with the prognosis of patients with KIRC. We applied Lasso regression and multivariate Cox regression analyses to develop a prognostic signature containing the TRIM1, 13, 35, 26, 55, 2, 47, and 27 genes to predict the survival of patients with KIRC. The accuracy and generalizability of this signature were confirmed in internal and external validation cohorts. We also constructed a predictive nomogram based on the signature and the clinicopathological characteristics of sex, age, and T and M status to aid clinical decision-making. We analyzed immune cell infiltration analysis and found that CD8 T cells, memory resting CD4 T cells, and M2 macrophages were the most enriched components in the KIRC tumor immune microenvironment. A higher level of immune infiltration by plasma cells, follicular helper T cells, and activated NK cells, and a lower level of immune infiltration by memory resting CD4 T cells, M1 and M2 macrophages, and resting dendritic cells were associated with higher risk scores. Overall, our eight-gene TRIM family signature has sufficient accuracy and generalizability for predicting the overall survival of patients with KIRC. Furthermore, this prognostic signature is associated with tumor immune status and distinct immune cell infiltrates in the tumor microenvironment.

Dasatinib treatment is approved as first-line therapy for chronic myeloid leukemia. However, pulmonary hypertension (PH) is a highly morbid and often fatal side-effect of dasatinib, characterized by progressive pulmonary vascular remodeling. Melatonin exerts strong antioxidant capacity against the progression of cardiovascular system diseases. The present work aimed to investigate the effect of melatonin on dasatinib-aggravated hypoxic PH and explore its possible mechanisms. Dasatinib-aggravated rat experimental model of hypoxic PH was established by utilizing dasatinib under hypoxia. The results indicated that melatonin could attenuate dasatinib-aggravated pulmonary pressure and vascular remodeling in rats under hypoxia. Additionally, melatonin attenuated the activity of XO, the content of MDA, the expression of NOX4, and elevated the activity of CAT, GPx, and SOD, the expression of SOD2, which were caused by dasatinib under hypoxia. In vitro, dasatinib led to decreased LDH activity and production of NO in human pulmonary microvascular endothelial cells (HPMECs), moreover increased generation of ROS, and expression of NOX4 both in HPMECs and primary rat pulmonary arterial smooth muscle cells (PASMCs) under hypoxia. Dasatinib up-regulated the expression of cleaved caspase-3 and the ratio of apoptotic cells in HPMECs, and also elevated the percentage of S phase and the expression of Cyclin D1 in primary PASMCs under hypoxia. Melatonin ameliorated dasatinib-aggravated oxidative damage and apoptosis in HPMECs, meanwhile reduced oxidative stress level, proliferation, and repressed the stability of HIF1-α protein in PASMCs under hypoxia. In conclusion, melatonin significantly attenuates dasatinib-aggravated hypoxic PH by inhibiting pulmonary vascular remodeling in rats. The possible mechanisms involved protecting endothelial cells and inhibiting abnormal proliferation of smooth muscle cells. Our findings may suggest that melatonin has potential clinical value as a therapeutic approach to alleviate dasatinib-aggravated hypoxic PH.

Aiming at the safety problem of high gas emission in 2303 fully mechanized caving face of Cuijiagou Coal Mine, the evolution law of “three zons” in goaf is studied by using physical similarity simulation and UDEC numerical simulation experiment on the basis of analyzing the failure characteristics of overlying rock in fully mechanized caving mining of extra thick coal seam. The mathematical model of mining fracture elliptical paraboloid zone is established, the favorable area of overburden fracture gas extraction is determined, and the gas extraction scheme of low-medium-high drilling phase combination is proposed, and the engineering application is carried out. The results show that the height of the 2303 fully mechanized caving face is 33 m, the fracture zone height is 110 m, the range below 55 m of the coal seam floor and the outer elliptical set is the favorable area of gas extraction, and the gas concentration in the upper corner is less than 0.6% through the implementation of the low-medium-high drilling extraction scheme. The gas concentration in the return lane is less than 0.5%, which effectively guarantees the safe and efficient recovery of the working face.

Abstract Background Insulin controls hyperglycemia caused by diabetes, and virtually all treatments require exogenous insulin. However, the product’s extensive post-translational modifications have hindered the manufacture of recombinant insulin. Result Here we report a novel production method for a monomeric B22Asp desB30 insulin analog (B22D desB30 insulin). Its precursor, DPIP, is fused to an N-terminal chitin-binding domain and intein self-cleavage tag. The fusion protein is expressed and purified from E. coli and immobilized on chitin resins. DPIP is then released using an optimized pH shift and converted to mature insulin via trypsin digest. The resulting product appears monomeric, > 90% pure and devoid of any exogenous enzyme. Conclusion Thus, biologically active insulin analog can be efficiently produced in bacteria and potentially applicable in the treatment of human diabetes.

Polypropylene fibers are added to concrete to improve the toughness of the material. Manufactured sand and fly ash with high content are used to reduce the impact on the environment and cost. The response surface method (RSM) was used to design the test and study the mechanical and bending properties of polypropylene-fiber-reinforced high-performance concrete (PPFHPC). Three process variables, including the content of polypropylene fiber (1%, 1.5%, and 2%), content of fly ash (45%, 60%, and 75%), and water-binder (W/B) ratio (0.27, 0.3, and 0.33), were considered as factors. The compressive strength, flexural strength, flexural-compressive ratio, splitting tensile strength, and first-crack strength and bending strength of thin plate were evaluated. The prediction model established by the RSM showed the correlation and predictability between the response and the factors, and the corresponding relationship equation between the factors and the response was obtained. Results of multiobjective optimization indicated that the optimal three factors (content of PPF, FA, and W/B) were 2%, 62%, and 0.27. The established model can be used to predict the basic mechanical properties and bending properties of materials. This test laid a theoretical foundation for the development of PPFHPC materials.

In order to study the mechanical performance of Engineered Cementitious Composites (ECCs) mixed with carbon black (CB), manufactured sand (MS), and polypropylene fiber (PPF), response surface methodology (RSM) was used to design the experiment, and three process variables including PPF content, fly ash content (FA), and CB content were selected as factors. The flexural strength, compressive strength, flexural-compressive ratio, and splitting tensile strength were used as four responses to study the mechanical performance. The prediction model indicates that there is a good correlation between the factors and the responses. Multiobjective optimization results show that the optimal content of the three factors is 2.4%, 58.48%, and 1.09%, respectively, for the carbon black, and manufactured sand of polypropylene fiber reinforced ECC development laid a foundation.

Based on traditional titanium-based composites and the design concept of biomimetic laminated structures, the continuous SiC ceramic fiber, ductile metal Ti foil, and intermetallic Ti2AlNb foil were selected as structural components, which were alternately stacked in the sequence of Ti2AlNb-Ti-SiCf-Ti-Ti2AlNb to prepare the continuous SiC ceramic fiber-reinforced titanium-based laminated composite. The methods adopted were vacuum hot-pressing and ceramic fiber braiding. In the prepared state, the composite’s structural components were metallurgically bonded ideally, and the continuous SiC ceramic fiber was equidistantly distributed in the ductile metal Ti matrix. This composite’s phase is mainly composed of α-Ti, β-Ti, SiC, TiC, O, and B2 phases. In addition, along the ceramic SiC fiber lengthwise, the tensile test was performed on this composite at room temperature and a high temperature of 600°C, with the ultimate tensile strength being 948.76 MPa and 526.62 MPa, respectively, and, in this process, the fiber was debonded and pulled out. Meanwhile, the composite’s bending strength was measured to be 1506.21 MPa in a three-point bending test, and, under this bending load, the mode of crack propagation and failure mechanism were analyzed.

Laser powder bed fusion (LPBF) technic is suitable for manufacturing metal parts with complex shapes and internal channels. The energy input and post heat treatment have great influence on the formability, microstructure and properties of the metallic materials. In this work, Hastelloy X superalloy is fabricated by LPBF with a variation of laser power, and then post-treated by hot isostatic pressing and solution treatment. Influences of laser power and heat treatment on microstructure features of as-built sample are evaluated. The correlation among laser power, microstructure features and tensile properties of heat-treated samples are revealed. The results reveal that average grain size, aspect ratio, texture intensity increases while the proportion of high-angle grain boundaries decreases with the increase of laser power. Precipitates of Cr-rich carbides along grain boundary are observed after post heat treatment. Post-treatment promotes the twinned recrystallization, grain coarsening and texture degradation. Yield strength increases while tensile strength decreases with the increase in laser power. The higher vertical yield strength of sample with laser power of 320 W could be attributed to its larger aspect ratio and more twin boundaries. 280 W is the preferred laser power to obtain the best overall tensile properties. This study is helpful for the exploration of optimal LPBF process and post heat treatment, by which Ni-based superalloys with a good balance between strength and ductility can be produced.

The multifunctionality and sustainability of ecosystems are strongly dependent on their ability to withstand and recover from disturbances—that is, ecosystem resilience (ER). However, the dynamics and attributes of ER remain largely unknown, especially in China, where climatic and anthropogenic pressures are high. In this study, we evaluated spatiotemporal patterns of ER in China from 2001 to 2020 using solar-induced chlorophyll fluorescence. We estimated the relative independent importance of climate change, CO _2 , and anthropogenic factors on changes in ER signals. The results showed that more than half of the ecosystems in the study area have experienced ER gain followed by ER loss during the past two decades. Before breakpoints (BPs), climate change explained 58.29% of the ER change associated with increasing precipitation. After BPs, 65.10% of the ER change was most affected by CO _2 , and drought from rising temperature further deteriorated ER loss. We highlight that relationships between changes in ER and climate are spatially heterogeneous and suggest increased negative radiative effects of CO _2 , associated with global warming, on ecosystem stability due to the saturated canopy photosynthesis. These findings have crucial implications for future climate change mitigation, carbon peak, and carbon neutrality targets.

To improve the compatibility between flame retardant and epoxy resin (EP) matrix, amino phenyl copper phosphate-9, 10-dihydro-9-oxygen-10-phospha-phenanthrene-10-oxide (CuPPA-DOPO) is synthesized through surface grafting, which is blended with EP matrix to prepare EP/CuPPA-DOPO composites. The amorphous structure of CuPPA-DOPO is characterized by X-ray diffraction and Fourier-transform infrared spectroscopy. Scanning electron microscope (SEM) images indicate that the agglomeration of hybrids is improved, resisting the intense intermolecular attractions on account of the acting force between CuPPA and DOPO. The results of thermal analysis show that CuPPA-DOPO can promote the premature decomposition of EP and increase the residual amount of EP composites. It is worth mentioning that EP/6 wt% CuPPA-DOPO composites reach UL-94 V-1 level and limiting oxygen index (LOI) of 32.6%. Meanwhile, their peak heat release rate (PHRR), peak smoke production release (PSPR) and CO2 production (CO2P) are decreased by 52.5%, 26.1% and 41.4%, respectively, compared with those of EP. The inhibition effect of CuPPA-DOPO on the combustion of EP may be due to the release of phosphorus and ammonia free radicals, as well as the catalytic charring ability of metal oxides and phosphorus phases.

Catechol and hydroquinone are widely applied in industrial synthesis while they are typical toxic organic pollutants. Efficient adsorptive removal of catechol and hydroquinone is highly needed. In this research, activated carbon fibre (ACF) was used for the kinetic removal of the two pollutants. As catechol and hydroquinone have different pKa values, it was found that the highest uptake of catechol and hydroquinone was observed at pH 11.0 and 5.0, respectively. The adsorption kinetics for catechol and hydroquinone were compared. The removal of hydroquinone is higher than that of catechol at almost all the pH conditions. At pH 7.0, the uptake of catechol and hydroquinone on ACF were 125.8 and 200.4 mg/g, respectively. As both Elovich and pseudo-second-order kinetic models could better describe the adsorption process, the adsorption of catechol and hydroquinone onto ACF might be chemisorption. The rate determining step might be diffusive in nature for the uptake of catechol and hydroquinone. Linear pseudo-second-order kinetic model fitted the experimental data better than pseudo-first-order kinetic model. The presence of natural organic matter, humic acid, could inhibit the uptake of catechol and hydroquinone on ACF profoundly.

In order to optimize the interface performance of copper/steel bimetallic composite and avoid the degradation of the composite performance owing to the difference of thermal-physical properties, HS211/ER50-6 composite structure was fabricated by arc additive technology, and Fe–Ni and Cu–Al flux-cored wires were designed as transition materials to realize the gradient connection of the interface area. Microstructure observation and mechanical properties testing were used to characterize the properties of the samples. The results showed that gradient connection can be achieved by adding the transition layer of Fe–Ni and Cu–Al flux-cored wires. Fe-rich phases with different morphologies were found in the interface region, which strengthened the matrix as the second phase. The corrosion resistance of the Fe–Ni transition layer region was better than Cu–Al, and the impact absorption energy reached 925 kJ/m2. The tensile strength of Fe–Ni samples reached 326.5 MPa, and the fracture location of the two groups of samples were both the copper side deposition.

Spastin is one of the proteins which lead to hereditary spastic paraplegia (HSP), whose dysfunction towards microtubule severing and membrane transporting is critically important. The present study is to elucidate the mechanisms of the protein stability regulation of spastin. The ubiquitin encoding plasmids are transfected into COS-7 cells with different fusion tags including Green Fluorescent Protein (GFP), mCherry and Flag. The expression level of spastin was detected, microtubule severing activity and neurite outgrowth were quantified. The data showed that ubiquitin overexpression significantly induced the decreased expression of spastin, suppressed the activity of microtubule severing in COS-7 cells and inhibited the promoting effect on neurite outgrowth in cultured hippocampal neurons. Furthermore, when modulating the overexpression experiments of ubiquitin, it was found that relatively small tag like Flag, but not large tags such as GFP or mCherry fused with ubiquitin, retained the activity on spastin stability. The present study investigated the effects of small/large tags addition to ubiquitin and the novel mechanisms of post-transcriptional modifications of spastin on regulating neurite outgrowth, in the attempt to experimentally elucidate the mechanisms that control the level or stability of spastin in hereditary spastic paraplegia.

Bladder cancer (BC) is the most common malignant tumor of the urinary system and is associated with high morbidity and mortality; however, the molecular mechanism underlying its occurrence is not clear. In this study, the gene expression profile and related clinical information of GSE13507 were downloaded from the Gene Expression Omnibus (GEO) database. RNA sequencing (RNA-seq) expression data and related clinical information were retrieved from The Cancer Genome Atlas (TCGA) database. Overlapping genes were identified by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). Then, we carried out functional enrichment analysis to understand the potential biological functions of these co-expressed genes. Finally, we performed a protein–protein interaction (PPI) analysis combined with survival analysis. Using the CytoHubba plug-in of Cytoscape, TROAP, CENPF, PRC1, AURKB, CCNB2, CDC20, TTK, CEP55, ASPM, and CDCA8 were identified as candidate central genes. According to the survival analysis, the high expression of TTK was related to the poor overall survival (OS) of patients with BC. TTK may also affect the bladder tumor microenvironment (TME) by affecting the number of immune cells. The expression level of TTK was verified by immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR), and the tumor-promoting effect of TTK in BC cells was confirmed in vitro. Our results also identified the MSC-AS1/hsa-miR-664b-3p/TTK regulatory axis, which may also play an important role in the progression of BC, but further research is needed to verify this result. In summary, our results provide a new idea for accurate early diagnosis, clinical treatment, and prognosis of BC

A targeted strategy for treating cancer is antibody-directed enzyme prodrug therapy, where the enzyme attached to the antibody causes conversion of an inactive small-molecule prodrug into an active drug. A limitation may be the diffusion of the active drug away from the antibody target site. A related strategy with radiotherapeutics entails enzymatically promoted conversion of a soluble to insoluble radiotherapeutic agent, thereby immobilizing the latter at the target site. Such a molecular brachytherapy has been scarcely investigated. In distinct research, the advent of molecular designs for aggregation-induced emission (AIE) suggests translational use in molecular brachytherapy. Here, several 2-(2-hydroxyphenyl)benzothiazole substrates that readily aggregate in aqueous solution (and afford AIE) were elaborated in this regard. In particular, (1) the 2-(2-hydroxyphenyl) unit was derivatized to bear a pegylated phosphodiester that imparts water solubility yet undergoes enzymatic cleavage, and (2) a p-phenol unit was attached to the benzo moiety to provide a reactive site for final-step iodination (here examined with natural abundance iodide). The pegylated phosphodiester-iodinated benzothiazole undergoes conversion from aqueous-soluble to aqueous-insoluble upon treatment with a phosphatase or phosphodiesterase. The aggregation is essential to molecular brachytherapy, whereas the induced emission of AIE is not essential but provides a convenient basis for research development. Altogether, 21 compounds were synthesized (18 new, 3 known via new routes). Taken together, blending biomedical strategies of enzyme prodrug therapy with materials chemistry concerning substances that undergo AIE may comprise a step forward on the long road toward molecular brachytherapy.