Molecular characterization, expression and immune functional analysis of cystatin 10 in turbot.

BACKGROUND: Cystatin is a protease inhibitor that also regulates genes expression linked to inflammation and plays a role in defense and regulation. METHODS AND RESULTS: Cystatin 10 (Smcys10) was cloned from Scophthalmus maximus and encodes a 145 amino acid polypeptide. The results of qRT-PCR showed that Smcys10 exhibited tissue-specific expression patterns, and its expression was significantly higher in the skin than in other tissues. The expression level of Smcys10 was significantly different in the skin, gill, head kidney, spleen and macrophages after Vibrio anguillarum infection, indicating that Smcys10 may play an important role in resistance to V. anguillarum infection. The recombinant Smcys10 protein showed binding and agglutinating activity in a Ca2+-dependent manner against bacteria. rSmcys10 treatment upregulated the expression of IL-10, TNF-α and TGF-ß in macrophages of turbot and hindered the release of lactate dehydrogenase (LDH) from macrophages after V. anguillarum infection, which confirmed that rSmcys10 reduced the damage to macrophages by V. anguillarum. The NF-κB pathway was suppressed by Smcys10, as demonstrated by dual-luciferase analysis. CONCLUSIONS: These results indicated that Smcys10 is involved in the host antibacterial immune response.

Genome-wide identification, characterization, molecular evolution and expression profiling analysis of scavenger receptors in black rockfish (Sebastes schlegelii).

The scavenger receptors (SRs) gene family is considered as the membrane-associated pattern recognition receptors that plays important roles in the immune responses of organisms. However, there is currently limited research on the systematic identification of the SRs gene family in teleost and their role in the innate immunity of S. schegelii. In this study, we identified and annotated 15 SRs genes in S. schegelii. Through phylogenetic analysis, analysis of conserved domains, gene structure, and motif composition, we found that SRs gene family within different classes were relatively conserved. Additionally, we used qRT-PCR to analyze the expression patterns of SRs genes in immune-related tissues from healthy and Acinetobacter johnsonii-infected S. schegelii. The results showed that SRs genes exhibited different tissue expression patterns and the expression of SRs genes significantly changed after A. johnsonii infection. These results provided a valuable basis for further understanding of the functions of SRs in the innate immune response of S. schegelii.

C-type lectin 12B/4E of black rockfish (Sebastes schlegelii) macrophages as pattern recognition receptors in the antibacterial mechanism of exploration.

As lower vertebrates, fish have both innate and adaptive immune systems, but the role of the adaptive immune system is limited, and the innate immune system plays an important role in the resistance to pathogen infection. C-type lectins (CLRs) are one of the major pattern recognition receptors (PRRs) of the innate immune system. CLRs can combine with pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) to trigger NF-κB signaling pathway and exert immune efficacy. In this study, Ssclec12b and Ssclec4e of the C-type lectins, were found to be significantly up-regulated in the transcripts of Sebastes schlegelii macrophages stimulated by bacteria. The identification, expression and function of these lectins were studied. In addition, the recombinant proteins of the above two CLRs were obtained by prokaryotic expression. We found that rSsCLEC12B and rSsCLEC4E could bind to a variety of bacteria in a Ca2+-dependent manner, and promoted the agglutination of bacteria and blood cells. rSsCLEC12B and rSsCLEC4E assisted macrophages to recognize PAMPs and activate the NF-κB signaling pathway, thereby promoting the expression of inflammatory factors (TNF-α, IL-1ß, IL-6, IL-8) and regulating the early immune inflammation of macrophages. These results suggested that SsCLEC12B and SsCLEC4E could serve as PRRs in S. schlegelii macrophages to recognize pathogens and participate in the host antimicrobial immune process, and provided a valuable reference for the study of CLRs involved in fish innate immunity.

Initial Experience with Hybrid Partial Nephrectomy with Ultrasound-guided Balloon Catheter Occlusion of the Renal Artery for Recurrent Renal Tumors.

Repeat partial nephrectomy (PN) is an effective treatment in improving the prognosis for patients with recurrent renal cancer after initial PN. However, salvage PN (sPN) is inevitably associated with a higher rate of complications, largely because of intraperitoneal adhesions and fibrosis. Here we describe three initial cases for which recurrent renal tumors were treated with a novel minimally invasive approach, namely Ultrasound-guided Renal Artery Balloon catheter Occluded Hybrid Partial Nephrectomy (UBo-HPN).With laparoscopic ultrasound (LUS) guiding a Fogarty catheter to occlude the arterial blood supply, dissection of the renal hilum and most of the abdominal cavity can be avoided. UBo-HPN was successfully performed in three patients. One case of postoperative fever (Clavien-Dindo grade II) occurred, with no other complications. The mean operative time was 106 min, with a mean warm ischemia time of 21 min. UBo-HPN may be considered a safe and effective alternative for sPN, with a minimally invasive surgical footprint and better surgical outcomes.

Coulomb blockade and Coulomb staircases in CoBi nanoislands on SrTiO3(001).

We successfully fabricated two-dimensional metallic CoBi nanoislands on SrTiO3(001) substrate by molecular beam epitaxy, and systematically investigated their electronic structures by scanning tunneling microscopy and spectroscopyin situat 4.2 K. Coulomb blockade and Coulomb staircases with discrete and well-separated levels are observed for the individual nanoisland, which is attributed to single-electron tunneling via two tunnel junction barriers. They are in excellent agreement with the simulations based on orthodox theory. Furthermore, we demonstrated that the Coulomb blockade becomes weaker with increasing temperature and almost disappears at ∼22 K in our variable temperature experiment, and its full-width at half-maximum of dI/dVpeaks with temperature is ∼6 mV. Our results provide a new platform for designing single-electron transistors that have potential applications in future microelectronics.

Continuous dynamic measurement of frequency scanning interferometry based on motion phase synchronization compensation and calibration.

We present a continuous dynamic frequency scanning interferometry (DFSI) measurement method based on motion phase synchronization compensation and calibration. By introducing heterodyne interferometry (HI) synchronization measurement and frequency scanning interferometry (FSI) motion phase compensation, dynamic continuous measurement is achieved and effectively suppresses the distance error introduced by the Doppler effect (DE). Based on this, the influence of the initial optical frequency deviation (OFD) of the tunable laser and the OFD of the HI laser on the dynamic absolute distance measurement (DADM) is analyzed; the relationships between the error of DADM with the variation of the OFD and the target motion parameters are investigated; and the residual DE introduced by the OFD is shown as the fundamental cause of the degradation of the accuracy of DFSI. We propose an online optical frequency measurement method based on HI combined with H13C14N gas absorption cells to resolve this problem. High-precision motion phase compensation is achieved by calibrating the optical frequency (fixed frequency) of the measured HI laser and the initial frequency of the tunable laser online during measurement and then performing motion phase calibration. To verify the effectiveness of our method, an optical frequency calibration experiment, a continuous DADM experiment, and a precision evaluation experiment were conducted, and a highly accurate continuous DADM was achieved.

Real-time high-precision FMCW laser range extraction method based on a hardware multiplier array.

Frequency-modulated continuous wave (FMCW) laser interferometry is an ideal large-scale absolute distance measurement method. It has advantages of high precision and noncooperative target measurement capability, with no blind spot for ranging. To meet the requirements of high-precision, high-speed 3D topography measurement technologies, a faster measurement speed of FMCW LiDAR at each measurement point is required. To solve the shortcomings of the existing technology, a real-time high-precision hardware solution method (including but not limited to FPGA and GPU) for lidar beat frequency signals is provided here based on hardware multiplier arrays to reduce lidar beat frequency signal processing time and to save energy and resource consumption during processing. A high-speed FPGA architecture was also designed for the frequency-modulated continuous wave lidar range extraction algorithm. The whole algorithm was designed and implemented in real time based on the principle of full-pipelines and parallelism. The results show that the processing speed of the FPGA system is faster than that of current top-performing software implementations.

Adaptive control with unknown mass estimation for a quadrotor-slung-load system.

In aerial load transportation applications, knowing the mass of the load in advance is not always possible. The load dynamics depend on its mass and using a high-performance model-based controller with an inaccurate mass will introduce unmodeled disturbances to the system that will negatively affect the closed-loop performance. This paper addresses the design of a trajectory tracking controller for a quadrotor with a slung-load that has an unknown mass. The proposed solution is an adaptive controller with online estimation designed using the backstepping technique. Nonlinear control laws for thrust and angular velocity, and an adaption law for mass estimation are proposed, which guarantee the convergence of the trajectory tracking and the estimation errors to zero, and are robust to variations in load mass. Simulation and experimental results are presented to assess the validity and performance of the proposed controller.

Dynamic nonlinearity errors in laser Doppler vibrometer measurements induced by environmental vibration and error correction.

Laser Doppler vibrometers (LDVs) are widely used for vibration testing in various fields. Nonlinearity errors are the key factor affecting the measurement accuracy of LDVs. The conventional Heydemann method cannot correct nonlinearity errors produced by noisy environments. Thus, we establish a novel model to describe dynamic nonlinearity errors produced in noisy environments and propose a compensation method to mitigate signal distortion. The performance of the proposed method is assessed by performing both simulations and experiments. The results of experiments carried out in a noisy environment indicate that the proposed method suppresses the nonlinearity to 30 nm compared to 737 nm using the conventional Heydemann correction. The proposed method can improve the accuracy of LDV measurements in industrial environments.

Research on the Mechanism of Liuwei Dihuang Decoction for Osteoporosis Based on Systematic Biological Strategies.

Background: Osteoporosis is an important health problem worldwide. Liuwei Dihuang Decoction (LDD) and its main ingredients may have a good clinical effect on osteoporosis. Meanwhile, its mechanism for treating osteoporosis needs to be further revealed in order to provide a basis for future drug development. Methods: A systematic biological methodology was utilized to construct and analyze the LDD-osteoporosis network. After that, the human transcription data of LDD intervention in patients with osteoporosis and protein arrays data of LDD intervention in osteoporosis rats were collected. The human transcription data analysis, protein arrays data analysis, and molecular docking were performed to validate the findings of the prediction network (LDD-osteoporosis PPI network). Finally, animal experiments were conducted to verify the prediction results of systematic pharmacology. Results: (1) LDD-osteoporosis PPI network shows the potential compounds, potential targets (such as ALB, IGF1, SRC, and ESR1), clusters, biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and signaling and Reactome pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) of LDD intervention in osteoporosis. (2) Human transcriptomics data and protein arrays data validated the findings of the LDD-osteoporosis PPI network. (3) The animal experiments showed that LDD can improve bone mineral density (BMD), increase serum estradiol (E2) and alkaline phosphatase (ALP) levels, and upregulate Wnt3a and ß-catenin mRNA expression (P < 0.05). (4) Molecular docking results showed that alisol A, dioscin, loganin, oleanolic acid, pachymic acid, and ursolic acid may stably bind to JAK2, ESR1, and CTNNB1. Conclusion: LDD may have a therapeutic effect on osteoporosis through regulating the targets (such as ALB, IGF1, SRC, and ESR1), biological processes (such as positive regulation of calmodulin 1-monooxygenase activity, estrogen metabolism, and endothelial cell proliferation), and pathways (such as JAK-STAT signaling pathway, osteoclast differentiation, and degradation of the extracellular matrix) found in this research.

Associations between ATG16L1 gene polymorphism and antineutrophil cytoplasmic antibody-associated vasculitis in the Chinese Guangxi population: A case-control study.

BACKGROUND: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy-related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population. METHODS: One hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case-control study. Multiplex polymerase chain reaction combined with high-throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis. RESULTS: rs4663402 and rs4663396 were in Hardy-Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D' = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p > 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03). CONCLUSIONS: Our results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.

[Corrigendum] MicroRNA­10b promotes migration and invasion through KLF4 and HOXD10 in human bladder cancer.

Following the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 2 on p. 1835, which was designed to show how miR­10b promotes the migration and invasion of human bladder cancer cell lines in vitro, there appeared to be several overlapping panels such that certain of the data may have been derived from the same original sources, even though they were intended to show the results obtained under different experimental conditions. The authors have re­examined their original data, and have realized that the errors arose as a consequence of inadvertently misfiling and mishandling the data. The corrected version of Fig. 2 is shown below. Note that these errors did not affect the overall conclusions reported in the study. All the authors agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish it; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 31: 1832­1838, 2014; DOI: 10.3892/or.2014.3048].

Erratum: Inhibition of SMYD2 suppresses tumor progression by down-regulating microRNA-125b and attenuates multi-drug resistance in renal cell carcinoma: Erratum.

[This corrects the article DOI: 10.7150/thno.37628.].

Research Progress of Transparent Electrode Materials with Sandwich Structure.

The nonrenewable nature of fossil energy has led to a gradual decrease in reserves. Meanwhile, as society becomes increasingly aware of the severe pollution caused by fossil energy, the demand for clean energy, such as solar energy, is rising. Moreover, in recent years, electronic devices with screens, such as mobile phones and computers, have had increasingly higher requirements for light transmittance. Whether in solar cells or in the display elements of electronic devices, transparent conductive films directly affect the performance of these devices as a cover layer. In this context, the development of transparent electrodes with low sheet resistance and high light transmittance has become one of the most urgent issues in related fields. At the same time, conventional electrodes can no longer meet the needs of some of the current flexible devices. Because of the high sheet resistance, poor light transmittance, and poor bending stability of the conventional tin-doped indium tin oxide conductive film and fluorine-doped tin oxide transparent conductive glass, there is a need to find alternatives with better performance. In this article, the progress of research on transparent electrode materials with sandwich structures and their advantages is reviewed according to the classification of conductive materials to provide reference for research in related fields.

CD46 splice variant enhances translation of specific mRNAs linked to an aggressive tumor cell phenotype in bladder cancer.

CD46 is well known to be involved in diverse biological processes. Although several splice variants of CD46 have been identified, little is known about the contribution of alternative splicing to its tumorigenic functions. In this study, we found that exclusion of CD46 exon 13 is significantly increased in bladder cancer (BCa) samples. In BCa cell lines, enforced expression of CD46-CYT2 (exon 13-skipping isoform) promoted, and CD46-CYT1 (exon 13-containing isoform) attenuated, cell growth, migration, and tumorigenicity in a xenograft model. We also applied interaction proteomics to identify exhaustively the complexes containing the CYT1 or CYT2 domain in EJ-1 cells. 320 proteins were identified that interact with the CYT1 and/or CYT2 domain, and most of them are new interactors. Using an internal ribosome entry site (IRES)-dependent reporter system, we established that CD46 could regulate mRNA translation through an interaction with the translation machinery. We also identified heterogeneous nuclear ribonucleoprotein (hnRNP)A1 as a novel CYT2 binding partner, and this interaction facilitates the interaction of hnRNPA1 with IRES RNA to promote IRES-dependent translation of HIF1a and c-Myc. Strikingly, the splicing factor SRSF1 is highly correlated with CD46 exon 13 exclusion in clinical BCa samples. Taken together, our findings contribute to understanding the role of CD46 in BCa development.

Optimize the management of urological tube-related emergencies during the coronavirus disease 2019 (COVID-19) pandemic.

BACKGROUND: To introduce and determine the value of optimized strategies for the management of urological tube-related emergencies with increased incidence, complexity and operational risk during the global spread of coronavirus disease 2019 (COVID-19). METHODS: All emergent urological patients at Tongji Hospital, Wuhan, during the period of January 23 (the beginning of lockdown in Wuhan) to March 23, 2020, and the corresponding period in 2019 were recruited to form this study's COVID-19 group and control group, respectively. Tongji Hospital has the most concentrated and strongest Chinese medical teams to treat the largest number of severe COVID-19 patients. Patients in the control group were routinely treated, while patients in the COVID-19 group were managed following the optimized principles and strategies. The case incidence for each type of tube-related emergency was recorded. Baseline characteristics and management outcomes (surgery time, secondary complex operation rate, readmission rate, COVID-19 infection rate) were analyzed and compared across the control and COVID-19 periods. RESULTS: The total emergent urological patients during the COVID-19 period was 42, whereas during the control period, it was 124. The incidence of tube-related emergencies increased from 53% to 88% (P<0.001) during the COVID-19 period. In particular, the incidence of nephrostomy tube-related (31% vs. 15%, P=0.027) and single-J stent-related problems (19% vs. 6%, P=0.009) increased significantly. The mean surgery times across the two periods were comparable. The number of secondary complex operations increased from 12 (18%) to 14 (38%) (P=0.028) during the COVID 19-period. The number of 2-week postoperative readmission decreased from 10 (15%) to 1 (3%) (P=0.049). No participants contracted during the COVID-19 period. CONCLUSIONS: Urological tube-related emergencies have been found to have a higher incidence and require more complicated and dangerous operations during the COVID-19 pandemic. However, the optimized management strategies introduced in this study are efficient, and safe for both urologists and patients.

Junction plakoglobin regulates and destabilizes HIF2α to inhibit tumorigenesis of renal cell carcinoma.

BACKGROUND: Increased hypoxia-inducible factor 2α (HIF2α) activation is a common event in clear cell renal cell carcinoma (ccRCC) progression. However, the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated. We conducted this study to access the potential link between junction plakoglobin (JUP) and HIF2α in ccRCC. METHODS: Affinity purification and mass spectrometry (AP-MS) screening, glutathione-s-transferase (GST) pull-down and co-immunoprecipitation (Co-IP) assays were performed to detect the interacting proteins of HIF2α. Quantitative PCR (qPCR) and Western blotting were used to detect the expression of JUP in human ccRCC samples. Luciferase reporter assays, chromatin immunoprecipitation (ChIP), cycloheximide chase assays, and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α. Cell Counting Kit-8 (CCK-8) assays, colony formation assays, transwell assays, and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells. RESULTS: We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau (VHL) and histone deacetylases 1/2 (HDAC1/2) to HIF2α to regulate its stability and transactivation. JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo. Importantly, the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes. CONCLUSION: Taken together, these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.

No detection of SARS-CoV-2 from urine, expressed prostatic secretions, and semen in 74 recovered COVID-19 male patients: A perspective and urogenital evaluation.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been spreading all over the world since December 2019. However, medical information regarding the urogenital involvement in recovered COVID-19 patients is limited or unknown. OBJECTIVES: To comprehensively evaluate urogenital involvement in recovered COVID-19 patients. MATERIALS AND METHODS: Men aged between 20 years and 50 years who were diagnosed with SARS-CoV-2 infection and recovered when the study was conducted were enrolled in our study. Demographic and clinical characteristics, and history of hospitalization were collected and analyzed. Urine, expressed prostatic secretions (EPSs), and semen samples were collected for SARS-CoV-2 RNA detection. Semen quality and hormonal profiles were analyzed. RESULTS: Among 74 male recovered COVID-19 patients, 11 (14.9%) were asymptomatic, classified into mild type, and 31 (41.9%) were classified into moderate type. The remaining patients (32/74, 43.2%) had severe pneumonia. No critically ill recovered COVID-19 patient was recruited in our cohort. The median interval between last positive pharyngeal swab RT-PCR test and semen samples collection was 80 days (IQR, 64-93). The median age was 31 years (IQR, 27-36; range, 21-49), and the median body mass index (BMI) was 24.40 (IQR, 22.55-27.30). Forty-five (61.6%) men were married, and 28 (38.4%) were unmarried. Fifty-three (72.6%) patients denied cigarette smoking, 18 (24.7%) were active smokers, and 2 of them were past smokers. The majority of our participants (53/74, 72.6%) did not consume alcohol. Fever occurred in most of the patients (75.3%), and 63 of them had abnormal chest CT images. Only one patient complained of scrotal discomfort during the course of COVID-19, which was ruled out orchitis by MRI (data not shown). A total of 205 samples were collected for SARS-CoV-2 detection (74 urine samples, 70 semen samples, and 61 EPS samples). However, viral nucleic acid was not detected in body fluids from the urogenital system. In terms of hormonal profiles, the levels of FSH, LH, testosterone, and estradiol were 5.20 [4.23] mIU/mL, 3.95 [1.63] mIU/mL, 3.65 [1.19] ng/mL, and 39.48 [12.51] pg/mL, respectively. And these values were within the normal limits. The overall semen quality of recovered COVID-19 patients was above the lower reference limit released by the WHO. While compared with healthy control, sperm concentration, total sperm count, and total motility were significantly declined. In addition, different clinical types of COVID-19 have no significant difference in semen parameters, but total sperm count showed a descending trend. Interestingly, subjects with a longer recovery time showed worse data for sperm quality. Small sample size and lacking semen parameters before the infection are the major limitations of our study. DISCUSSION AND CONCLUSIONS: To the best of our knowledge, it is the largest cohort study with longest follow-up for urogenital evaluation comprehensively so far. Direct urogenital involvement was not found in the recovered COVID-19 male patients. SARS-CoV-2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly, while hormonal profiles remained normal. Moreover, patients with a long time (≥90 days) since recovery had lower total sperm count. Great attention and further study should be conducted and follow-up on the reproductive function in the following months.