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Abstract Background Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. Methods In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. Results Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. Conclusion Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

The rockburst risk prediction based on microseismic (MS) data is an important research task in deep mine safety prevention. However, the lack of systematic research on explicit prediction indexes and the waste of a large amount of unlabeled data are still two main problems that hinder the development of rockburst prediction. In this paper, the acoustic emission (AE) event distribution at each coal rock deformation and failure stage is studied based on the laboratory experiment. The spatial-temporal evolution of rockburst in MS data of coal mine fields is explored. Based on systematic research of the AE and MS distribution features considering the physical logic of coal rock mass failure, nine different rockburst prediction indexes are employed to describe the MS data features before rockburst. Then, according to the rockburst prediction indexes, a new self-supervision rockburst risk prediction algorithm is constructed, consisting of the pre-trained model and fine-tuning model with the same encoder and decoder structure. The pre-trained model is trained with unlabeled MS data to automatically learn rockburst prediction index features by reconstructing the masked indexes. Based on the pre-trained encoder and decoder parameters, the fine-tuning model is trained with the labeled MS data to predict rockburst risk. A large number of experiments show that the proposed rockburst prediction self-supervision algorithm is far superior to previous algorithms, by effectively utilizing unlabeled data. The ablation experiment also proves the validity of the studied rockburst prediction indexes.

Mounting evidence has identified the rapid and sustained antidepressive and anxiolytic-like effects of esketamine. However, the underlying mechanism of this no-monoamine target rapid-onset antidepressant is still underexplored. Immune-inflammatory pathways and cell-mediated immune activation, mainly including inflammatory cytokines in plasma, play a pivotal role in the pathogenesis of major depressive disorder and are also a potential therapeutic target for MDD. The current study was designed to clarify the role of esketamine on the expression of plasma cytokines in a depressive-like model introduced by chronic variable stress (CVS). In this study, a 21-day consecutive CVS protocol was applied to produce depressive- and anxiety-like behaviors. After the single dose or 7-day repeated administration of esketamine or fluoxetine, the depressive- and anxiety-like behaviors and the expression of inflammatory cytokines in plasma were examined. Both a single dose of esketamine and 7-days repeated fluoxetine administration elicited anti-depressive and anxiolytic effects in mice exposed to CVS. Additionally, CVS produced significant changes in the plasma inflammatory factors, notably increasing the expression of IL-1β, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-β, and CXCL12, while reducing IL-10 and IL-33. With the administration of esketamine and fluoxetine, CVS-produced inflammatory disturbances were partially normalized. Together, our findings provide a novel insight that acute esketamine treatment could rescue CVS-produced depressive-like and anxiety-like behaviors in mice by normalizing the expression of inflammatory cytokines; this effect was similar to the repeated administration of fluoxetine. These results contributed to the understating of rapid anti-depressant effects elicited by esketamine.

Bandstop filters (BSFs) have many applications in suppressing interference signals and shielding specific bands. Among them, reconfigurable BSFs that cover more frequency bands by switching modes have great research value. In this paper, a novel synthesis approach for compact reconfigurable BSFs with controllable equal-ripple performance is proposed. By switching the ON/OFF state of the positive intrinsic negative (PIN) diode, the proposed reconfigurable BSF can be switched between single-BSF (S-BSF) and dual-BSF (D-BSF). Based on the synthesis approach, the equal-ripple levels of stopband and passband for S-BSF and D-BSF can be independently controlled. To verify, the equal-ripple levels of stopband and passband for S-BSF state and D-BSF state are independently controlled in four groups of examples. Finally, a reconfigurable BSF with a miniaturized size is designed and fabricated. The fabricated reconfigurable BSF behaves with 15 dB and 10 dB return loss (RL) in two different passbands of the D-BSF state, and 25 dB bandpass RL and controllable stopband rejection (SR) for the S-BSF state. The measured results are in good agreement with the electromagnetic (EM) simulation results.

In order to alleviate the shortage of underground aggregate sources and time cost of vibration and compaction during backfilling, a new type of high-porous low-cementitious waste backfilling material (HPLCM), which was composed of self-compacting slurry and loose packing waste with high porosity, was developed to achieve the purpose of low cementitious backfilling. Uniaxial compression tests were carried out on HPLCM in the laboratory, using orthogonal strength variables of cement slurry and waste aggregate, to study their failure strength characteristics and statistical laws. Considering the combined impact of solid waste and slurry strength, a generalized strength model of shear fracture was established based on the fracture statistical results. The coupled strength utilization ratio of solid waste aggregate and self-compacted slurry was defined, and the optimal ratio and cost of mix proportion of HPLCM were analyzed. The results indicate that the uniaxial compressive strength and failure mode of HPLCM are jointly controlled by the component strength of self-compacting cementitious slurry and solid waste aggregate. The strength of both components has a positive correlation with the strength of HPLCM, which is limited by the weaker component, and when one component grows stronger, the failure mode will be dominated by the other component. The uniaxial compressive test of HPLCM presents shear failure modes, including shear planes in single oblique and cross oblique patterns with an average angle of 55.4°. The density of loose packing aggregates can be reduced from 85% to 58% by using the proposed backfilling material, and the strength of cementitious slurry can be optimized within the optimal mixing range to maximize the utilization of filling material strength when the strength of in-situ solid waste aggregates is obtained. Thus, the compaction time of solid filling and the amount of single gangue can be reduced.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a general term for a class of diseases that are mostly caused by intrauterine genetic development limitation. Without timely intervention, certain children with CAKUT may experience progressive decompensation and a rapid decline in renal function, which will ultimately result in end-stage renal disease. At present, a comprehensive understanding of the pathogenic signaling events of CAKUT is lacking. The role of long noncoding RNAs (lncRNAs) in renal development and disease have recently received much interest. In previous research, we discovered that mice overexpressing the lncRNA 4933425B07Rik (Rik) showed a range of CAKUT phenotypes, primarily renal hypoplasia. The current study investigated the molecular basis of renal hypoplasia caused by Rik overexpression. We first used Rapid Amplification of cDNA ends (RACE) to obtain the full-length sequence of Rik in Rik+/+;Hoxb7 mice. Mouse proximal renal tubule epithelial cells (MPTCs) line with Rik overexpression was constructed using lentiviral methods, and mouse metanephric mesenchyme cell line (MK3) with Rik knockout was then constructed by the CRISPR‒Cas9 method. We performed RNA-seq on the Rik-overexpressing cell line to explore possible differentially expressed molecules and pathways. mRNA expression was confirmed by qRT‒PCR. Reduced levels of Wnt10b, Fzd8, and β-catenin were observed when Rik was expressed robustly. On the other hand, these genes were more highly expressed when Rik was knocked out. These results imply that overabundance of Rik might inhibit the Wnt/β-catenin signaling pathway, which may result in renal hypoplasia. In general, such research might help shed light on CAKUT causes and processes and offer guidance for creating new prophylactic and therapeutic strategies.

The fluorophore source of red emissive oPD&CAT system CDs is the 5,14-dihydroquinoxalino[2,3-b] phenazine (DHQP), formed in the initial reaction stage. Subsequently, the DHQP was connected with carbon core. The excited electrons of the molecular state can transfer into the energy level of CDs, which leads to UV excitation red emissive intensity decreased.

Rock and soil masses in geotechnical engineering projects, such as tunnels, mines and slopes, undergo relative motion, exhibiting mechanical characteristics of solid–fluid transition under critical conditions. This work analyzes the characteristics of the solid–fluid transition interface and the mode of load transfer through biaxial compression particle flow photoelastic experiments on granular materials. The study documents that this interface forms an arch shape, marked by a force chain arch. The granular material exhibits two distinct states depending on its position: below the arch, the granular material is in a solid–fluid transitional state, with bearing capacity reduced, while above the arch, it is in a stable solid state, capable of bearing the overlying rock layer’s load. The presence of the force chain arch alters the direction of the originally downward-transferring load, redirecting it along the trajectory of the arch. Analysis of the force and stability of the force chain arch revealed that the arch shape parameters and boundary loads control the instability of the arch. Changes in the overlying and lateral loads lead to different types of instability of the force chain arch. The findings of the study are crucial for underground engineering construction and for the prevention of geological disasters related to granular material.

Abstract Due to the COVID‐19 pandemic, many rapid antimicrobial agents have developed intensively. Carbon dots (CDs), a new type of carbon‐based nanomaterials, shows great potential against emerging infectious diseases and antimicrobial‐resistant infections due to their unique optical properties, excellent biocompatibility, and easy surface modification. With the definition of the CDs structure and properties, synthesis, and characteristic technology improvement, the research on the CDs as antimicrobial agents has made significant progress. However, the lack of high repeatable and exact preparation methods, and the regular antimicrobial activity make it far from practical application. In this review, we summarize the most recent progress and challenges of CDs antimicrobial. First, an overview of the characteristics and properties is given, and the advantage of CDs applied to antimicrobial is further discussed. Then, it focuses on research progress on antimicrobial mechanisms under different conditions, the critical factors affecting their antimicrobial activity, and the practical antimicrobial applications. Finally, the main challenges and future research perspectives of antimicrobial CDs are proposed.

Musashi 2 (MSI2) is an RNA-binding protein that regulates mRNA translation of numerous intracellular targets and plays an important role in the development of cancer. However, the prognostic value of MSI2 in various cancers remains controversial. Herein, we conducted this meta-analysis including 21 studies with 2640 patients searched from PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure databases, and WanFang databases to accurately assess the prognostic significance of MSI2 in various cancers. Our results indicated that high MSI2 expression was significantly related to poor overall survival (HR = 1.84, 95% CI: 1.66-2.05, P < 0.001) and disease-free survival (HR = 1.73, 95% CI: 1.35-2.22, P < 0.001). In addition, MSI2 positive expression was associated with certain phenotypes of tumor aggressiveness, such as clinical stage, depth of invasion, lymph node metastasis, liver metastasis and tumor size. In conclusion, elevated MSI2 expression is closely correlated with poor prognosis in various cancers, and may serve as a potential molecular target for cancer patients.

Adverse intrauterine and early postnatal environment cause reduced nephron endowment and subsequent hypertension, chronic kidney disease (CKD). Exploring modifiable approaches is particularly important to alleviate the global burden of CKD. Enhanced glomerular progenitor cell apoptosis is a major contributor to renal developmental programming. The differentially expressed protein perlecan, which we previously identified using proteomics, is an important extracellular matrix glycoprotein, and its domain V (endorepellin) can inhibit apoptosis through a paracrine form. In explanted mice embryonic metanephros, we found that endorepellin can rescue glomeruli-deficit phenotype resulting from malnutrition, and this protective effect was also verified in vivo using a renal developmental programming model which was given a low-protein diet during pregnancy. We further demonstrated that endorepellin significantly inhibited glomerular progenitor cell apoptosis which activates ERK1/2 phosphorylation. Our results show that endorepellin rescues the nephron number reduction in renal developmental programming, possibly through the inhibition of progenitor cell apoptosis via the ERK1/2 pathway.

Abstract Background Osteoporosis and cardiovascular diseases (CVDs) are 2 major public health problems. Osteoporosis and CVDs may be linked but the association between lipid profile and osteoporosis is still controversial. The purpose of this study was to examine the associations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) with osteoporosis. Methods Using inpatients’ and outpatients’ electronic medical records (EMR) and dual X-ray absorptiometry (DXA) database stored at The Second Hospital of Jilin University, we included 481 individuals with complete and valid lipid and bone mineral density (BMD) data in 2017. Serum samples were used to measure TC, LDL-C, HDL-C and TG. Femoral neck and total hip BMD were measured by DXA; osteoporosis was defined as femoral neck or total hip T-score ≤ -2.5. Multivariable logistic regression models were used to test the associations of TC, LDL-C, HDL-C and TG with osteoporosis. Results The mean age for included individuals was 62.7 years (SD = 8.6 years); 60.1 % of them were female. Each standard deviation (SD) increase in TC (Odds Ratio [OR]: 1.48; 95 % Confidence Interval [CI]: 1.06–2.07) and TG (OR: 1.67; 95 % CI: 1.16–2.39) were associated with increased risk of osteoporosis; LDL-C and HDL-C levels were not associated with osteoporosis. Age, sex and body mass index (BMI) did not interact with the relationships of TC and TG with osteoporosis (all P > 0.10). Conclusions Higher TC and TG levels were associated with greater risk of osteoporosis in this cross-sectional study.

Abstract. Background:. Cumulative evidence suggests that A-kinase interacting protein 1 (AKIP1) plays an important role in tumor progression. However, the prognostic value of AKIP1 expression in various cancers remains unclear. Here, we conducted a meta-analysis to evaluate the prognostic value of AKIP1 expression in patients with cancer. Methods:. The PubMed, Web of Science, EMBASE, CNKI, and Wanfang databases were systematically searched to identify studies in which the effect of AKIP1 expression on prognosis (overall survival or disease-free survival) was investigated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the effect of AKIP1 expression on patient survival. Odds ratios (ORs) with 95% CIs were pooled to estimate the association between AKIP1 expression and clinicopathological characteristics of patients with cancer. Results:. Nineteen eligible studies, encompassing 3979 patients, were included in the meta-analysis. AKIP1 expression was negatively associated with overall survival (HR = 1.86, 95% CI: 1.58–2.18, P

Congenital anomalies of the kidney and urinary tract (CAKUT) are some of the most common developmental defects and have a complicated etiology, indicating an interaction of (epi-) genetic and environmental factors. Single gene mutations and copy number variations (CNVs) do not explain most cases of CAKUT, and simultaneous contributions of more than one gene (di-, oligo-, or polygenic effects; i.e., complex genetics) may lead to the pathogenesis of CAKUT. Robo2 plays a key role in regulating ureteric bud (UB) formation in the embryo, with mutations leading to supernumerary kidneys. Gen1 is a candidate gene associated with CAKUT because of its important role in early metanephric development in mice. We established a mouse model with double disruption of Robo2 and Gen1 using a piggyBac transposon and found that double gene mutation led to significantly increased CAKUT phenotypes in Robo2PB/+Gen1PB/+ mouse offspring, especially a duplicated collecting system. Increased ectopic UB formation was observed in the Robo2PB/+Gen1PB/+ mice during the embryonic period. Robo2 and Gen1 exert synergistic effects on mouse kidney development, promoting cell proliferation by activating the GDNF/RET pathway and downstream MAPK/ERK signaling. Our findings provide a disease model for CAKUT as an oligogenic disorder.

Immunofluorescence staining is a very common method for the subcellular localization study of proteins. A tissue-chopping-based immunofluorescence staining method for chloroplast proteins overcomes the restriction of plant cell wall, makes the operation simpler, and uses less experimental materials. Here we provide some improvements for this method. We found that the stained tissues can be directly observed with a confocal microscope without tissue lysis. Samples maintained at a low temperature (0–4 °C) throughout the process can reduce the intensity of chlorophyll autofluorescence and the background signal. A low temperature is also good for the storage of the sample. Fluorescence signal of the stained samples can be kept for several weeks if they are stored at −20 °C. FtsZ is an essential component of the chloroplast division apparatus. We demonstrated this method with the immunofluorescence staining of FtsZ1 in wildtype Arabidopsis and some chloroplast division mutants. We also successfully tested this method by the immunofluorescence staining of FtsZ1 in many other plants, including woody plants. With these procedures, the performance of tissue-chopping-based immunofluorescence staining method are further improved.

Congenital anomalies of the kidney and urinary tract (CAKUT) is a common birth defect and is the leading cause of end-stage renal disease in children. The etiology of CAKUT is complex and includes mainly genetic and environmental factors. However, these factors cannot fully explain the etiological mechanism of CAKUT. Recently, participation of long non-coding RNAs (lncRNAs) in the development of the circulatory and nervous systems was demonstrated; however, the role of lncRNAs in the development of the kidney and urinary tract system is unclear. In this study, we used the piggyBac (PB) transposon-based mutagenesis to construct a mouse with lncRNA 4933425B07Rik (Rik) PB insertion (RikPB/PB) and detected overexpression of Rik and a variety of developmental abnormalities in the urinary system after PB insertion, mainly including renal hypo/dysplasia. The number of ureteric bud (UB) branches in the RikPB/PB embryonic kidney was significantly decreased in embryonic kidney culture. Only bone morphogenetic protein 4 (Bmp4), a key molecule regulating UB branching, is significantly downregulated in RikPB/PB embryonic kidney, while the expression levels of other molecules involved in the regulation of UB branching were not significantly different according to the RNA-sequencing (RNA-seq) data, and the results were verified by quantitative real-time polymerase chain reaction (RT-PCR) and immunofluorescence assays. Besides, the expression of pSmad1/5/8, a downstream molecule of BMP4 signaling, decreased by immunofluorescence. These findings suggest that abnormal expression of Rik may cause a reduction in the UB branches by reducing the expression levels of the UB branching-related molecule Bmp4, thus leading to the development of CAKUT.

Based on a large-scale X-section pile-net composite foundation model, we experimentally studied the dynamic characteristics of the pile-net composite foundation under a high-speed railway train load; analyzed the distribution characteristics of the dynamic stress, dynamic displacement, speed, and acceleration of the foundation soil under different train speeds; and investigated the vibration response of the track subgrade foundation system, as well as the distribution characteristics and attenuation pattern of the dynamic stress inside the subgrade foundation under cyclic train loading. The following results are obtained. The peak vertical vibration speed and the peak acceleration attenuate by 90% and 62.5%, respectively, after passing through the embankment. The vibration velocity increases linearly with the train speed; the ratio of the peak dynamic soil stresses at the top of the piles and between the piles is approximately 3.4. The change in train speed does not have a large influence on the peak dynamic displacement or peak dynamic soil stress. The peak spectral vibration acceleration caused by the train loading is located within the range of medium-to-low-frequency vibrations, and the characteristic frequency corresponds to the passing frequency of the bogies and carriages; as the train speed increases, the peak spectral vibration acceleration increases, and the high-frequency components increase significantly.

The composite cementitious materials were prepared with lead-zinc tailings, lead-zinc smelting slag, and cement clinker. The effect of material ratio on the mechanical properties, the phase analysis, and microstructures were investigated. The effect of the pH and stripping time on the leaching amount of lead ion was discussed. The results show that the additive amount of the tailings should be minimized for the cementitious materials meeting the strength requirements, controlled within 10%. The leaching amount of cementitious materials remains low in a larger range of pH, which can effectively reduce the leaching of heavy metal lead. The leaching kinetics of lead ions in the three kinds of samples could be better described by the pseudo-second-model.

Context: Bone mineral density (BMD) T-score references may be updated when the peak BMD of the population is unclear and warrants reevaluation.Objective: To update BMD T-score references using the peak BMD from the most recent National Health and Nutrition Examination Survey (NHANES) data.Methods: This cross-sectional study used NHANES data from 2005 to 2014. Non-Hispanic White females between the ages of 10 and 40 years (N = 1549) were our target population to estimate peak BMD (SD). Individuals aged ≥ 50 years (N = 5523) were used to compare the percentages of osteoporosis and low bone mass based on existing and updated BMD T-score references. BMD data within the age at attainment of peak BMD ± 5 years were used to calculate updated BMD T-score references.Results: The updated average of BMD (SD) for diagnosing osteoporosis at the femoral neck and lumbar spine were 0.888 g/cm2 (0.121 g/cm2) and 1.065 g/cm2 (0.122 g/cm2), respectively. The percentages of individuals with osteoporosis at the femoral neck and low bone mass at the femoral neck and lumbar spine based on the updated BMD T-score references were higher than the percentages of people designated with these outcomes under the existing guidelines (P < 0.001). However, we observed the opposite pattern for lumbar spine osteoporosis (P < 0.001).Conclusions: We calculated new BMD T-score references at the femoral neck and lumbar spine. We found significant differences in the percentages of individuals classified as having osteoporosis and low bone mass between the updated and existing BMD T-score references. [ABSTRACT FROM AUTHOR]