Integrated photonics enables continuous-beam electron phase modulation.

Integrated photonics facilitates extensive control over fundamental light-matter interactions in manifold quantum systems including atoms1, trapped ions2,3, quantum dots4 and defect centres5. Ultrafast electron microscopy has recently made free-electron beams the subject of laser-based quantum manipulation and characterization6-11, enabling the observation of free-electron quantum walks12-14, attosecond electron pulses10,15-17 and holographic electromagnetic imaging18. Chip-based photonics19,20 promises unique applications in nanoscale quantum control and sensing but remains to be realized in electron microscopy. Here we merge integrated photonics with electron microscopy, demonstrating coherent phase modulation of a continuous electron beam using a silicon nitride microresonator. The high-finesse (Q0 ≈ 106) cavity enhancement and a waveguide designed for phase matching lead to efficient electron-light scattering at extremely low, continuous-wave optical powers. Specifically, we fully deplete the initial electron state at a cavity-coupled power of only 5.35 microwatts and generate >500 electron energy sidebands for several milliwatts. Moreover, we probe unidirectional intracavity fields with microelectronvolt resolution in electron-energy-gain spectroscopy21. The fibre-coupled photonic structures feature single-optical-mode electron-light interaction with full control over the input and output light. This approach establishes a versatile and highly efficient framework for enhanced electron beam control in the context of laser phase plates22, beam modulators and continuous-wave attosecond pulse trains23, resonantly enhanced spectroscopy24-26 and dielectric laser acceleration19,20,27. Our work introduces a universal platform for exploring free-electron quantum optics28-31, with potential future developments in strong coupling, local quantum probing and electron-photon entanglement.

The tricalbin family of membrane contact site tethers is involved in the transcriptional responses of Saccharomyces cerevisiae to glucose.

Cellular organelles maintain areas of close apposition with other organelles at which the cytosolic gap in between them is reduced to a minimum. These membrane contact sites (MCS) are vital for organelle communication and are formed by molecular tethers that physically connect opposing membranes. Although many regulatory pathways are known to converge at MCS, a link between MCS and transcriptional regulation-the primary mechanism through which cells adapt their metabolism to environmental cues-remains largely elusive. In this study, we performed RNA-sequencing on Saccharomyces cerevisiae cells lacking tricalbin proteins (Tcb1, Tcb2, and Tcb3), a family of tethering proteins that connect the endoplasmic reticulum with the plasma membrane and Golgi, to investigate if gene expression is altered when MCS are disrupted. Our results indicate that in the tcb1Δ2Δ3Δ strain, pathways responsive to a high-glucose environment, including glycolysis, fermentation, amino acid synthesis, and low-affinity glucose uptake, are upregulated. Conversely, pathways crucial during glucose depletion, such as the tricarboxylic acid cycle, respiration, high-affinity glucose uptake, and amino acid uptake are downregulated. In addition, we demonstrate that the altered gene expression of tcb1Δ2Δ3Δ in glucose metabolism correlates with increased growth, glucose consumption, CO2 production, and ethanol generation. In conclusion, our findings reveal that tricalbin protein deletion induces a shift in gene expression patterns mimicking cellular responses to a high-glucose environment. This suggests that MCS play a role in sensing and signaling pathways that modulate gene transcription in response to glucose availability.

Shear wave elastography-derived scoring system: application in the detection, subdivision and evaluation of systemic sclerosis.

OBJECTIVES: To locate the most valuable sites for shear wave elastography (SWE) evaluation and to develop a clinically applicable scoring system based on SWE for systemic sclerosis (SSc) and to verify the accuracy for detection and subdivision and the correlation by modified Rodnan total skin score (mRTSS). METHODS: SSc patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) and symptomatic other rheumatic diseases (ORD) patients were included in this cross-sectional study. We assessed the skin stiffness at forehead, chest, abdomen, and bilateral fingers, hands, forearm, arms, thighs, legs, and feet, by palpation and SWE. Logistic regression was used to screen the most valuable sites for detection of SSc and subdivision of lcSSc and dcSSc, on which a scoring system was developed and verified. RESULTS: A total of 49 lcSSc, 51 dcSSc, and 36 ORD patients were included. The SWE-derived scoring system, including finger, hand, foot, arm, chest, and abdomen, reached a sensitivity and specificity of 80.0% and 94.4%, respectively, for diagnosing SSc at the cut-off value >24. The scoring system, including arm, chest, and abdomen, reached a sensitivity of 72.5% and specificity of 98.0% for subdividing dcSSc at the cut-off value >11. The kappa coefficient between the SWE-derived diagnosis and clinical diagnosis was 0.636 (P<0.001). The SWE-derived total scores of six sites had a strong correlation with mRTSS (r=0.757, p<0.001). CONCLUSIONS: The SWE-derived scoring system can be valuable in detection and evaluation of SSc in clinical application.

Recurrent stroke in a reproductive age women with patent foramen ovale.

BACKGROUND: Patent foramen ovale (PFO) is a known cause of ischemic stroke in young adults and combined oral contraceptives (COCs) are widely used by women of reproductive age. If young women with PFO are taking COCs, they may be subjected to a synergistic increase in the occurrence of stroke, though reports of ischemic stroke in this population are rare. We report a woman of reproductive age who was taking COC suffered repetitive ischemic strokes before a patent foramen ovale (PFO) was detected and closed, which may raise concerns in this field. CASE PRESENTATION: A 31-year-old woman presented to the emergency department with sudden-onset right upper- and lower-limb weakness and dysarthria for 1 hour, whose only risk factor of stroke was oral contraceptive use. On admission, she was alert with left gaze deviation, dysarthria, and right-sided hemiplegia. Her symptoms improved after receiving the revascularization therapy. About 24 hours later, her left eye experienced sudden painless vision loss. Then the PFO with a substantial right-to-left shunt was detected and then she received a trans-catheter closure of the defect. Over 3 months of follow-up, there were no signs of stroke, but visual loss persisted. CONCLUSION: This case of disabling stroke raises concerns regarding optimal management in primary and secondary prevention of stroke in young women on COCs with additional risk factors of stroke.

The dynamic features and microbial mechanism of nitrogen transformation for hydrothermal aqueous phase as fertilizer in dryland soil.

Hydrothermal aqueous phase (HAP) contains abundant organics and nutrients, which have potential to partially replace chemical fertilizers for enhancing plant growth and soil quality. However, the underlying reasons for low available nitrogen (N) and high N loss in dryland soil remain unclear. A cultivation experiment was conducted using HAP or urea to supply 160 mg N kg-1 in dryland soil. The dynamic changes of soil organic matters (SOMs), pH, N forms, and N cycling genes were investigated. Results showed that SOMs from HAP stimulated urease activity and ureC, which enhanced ammonification in turn. The high-molecular-weight SOMs relatively increased during 5-30 d and then biodegraded during 30-90 d, which SUV254 changed from 0.51 to 1.47 to 0.29 L-1 m-1. This affected ureC that changed from 5.58 to 5.34 to 5.75 lg copies g-1. Relative to urea, addition HAP enhanced ON mineralization by 8.40 times during 30-90 d due to higher ureC. It decreased NO3-N by 65.35%-77.32% but increased AOB and AOA by 0.25 and 0.90 lg copies g-1 at 5 d and 90 d, respectively. It little affected nirK and increased nosZ by 0.41 lg copies g-1 at 90 d. It increased N loss by 4.59 times. The soil pH for HAP was higher than that for urea after 11 d. The comprehensive effects of high SOMs and pH, including ammonification enhancement and nitrification activity inhibition, were the primary causes of high N loss. The core idea for developing high-efficiency HAP fertilizer is to moderately inhibit ammonification and promote nitrification.

Association between cognitive function and depressive symptoms in Chinese older adults: The mediating role of activities of daily living.

OBJECTIVES: Exploring the relationship between cognitive functioning and depressive symptoms in Chinese older adults and the mediating role of the ability to perform activities of daily living. METHODS: This study included 5775 older adults, and correlation analysis and linear regression were used to analyze the relationship between the variables and mediated effects. RESULTS: Cognitive functioning and the ability to perform daily living significantly influenced the depressive state (ß = -0.163, p < 0.01; ß = 0.288, p < 0.01), and the ability to perform daily living partially mediated the effect between the two, with an effect size of 27.95%. CONCLUSION: Cognitive function can influence depressive status through the ability to perform activities of daily living, and individualized intervention strategies should be developed for older adults to maintain or delay cognitive decline, preserve the ability to perform activities of daily living, and reduce the risk of depression.

Prognostic value of the pretreatment systemic immune-inflammation index in patients with prostate cancer: a systematic review and meta-analysis.

BACKGROUND: The systemic immune-inflammation index (SII) is a novel biomarker to predict the prognosis of some malignant tumors based on neutrophil, platelet, and lymphocyte counts. Evidence is scarce about the prognostic value of SII for prostate cancer patients. This systematic review and meta-analysis was conducted to explore the prognostic value of the SII in prostate cancer. METHODS: The PubMed, Embase, Web of Science, and Cochrane Library (CENTRAL) databases were searched to determine eligible studies from inception to August 15, 2022. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to pool the results. Statistical analyses were conducted by using Stata 17.0 software. RESULTS: A total of 12 studies with 8083 patients were included. The quantitative synthesis showed that a high SII was related to poor overall survival (OS) (HR = 1.44, 95% CI 1.23-1.69, p < 0.001). Furthermore, a subgroup analysis showed that a high SII was associated with poor OS in the groups of any ethnicity, tumor type, and cutoff value. An increased SII was also associated with inferior progression-free survival (PFS) (HR = 1.80, 95% CI 1.27-2.56, p = 0.001). In the subgroup analysis, a high SII value was related to poor PFS in Asian patients (HR = 4.03, 95% CI 1.07-15.17, p = 0.04) and a cutoff value > 580 (HR = 1.19, 95% CI 1.04-1.36, p = 0.01). CONCLUSION: Based on the current evidence, a high pretreatment SII may be associated with poor OS and PFS. The SII may serve as an important prognostic indicator in patients with prostate cancer. More rigorously designed studies are needed to explore the SII and the prognosis of prostate cancer.

Effect of CeO2-Reinforcement on Pb Absorption by Coconut Coir-Derived Magnetic Biochar.

Magnetic separable biochar holds great promise for the treatment of Pb2+-contaminated wastewater. However, the absorption effect of unmodified magnetic biochar is poor. Considering this gap in knowledge, CeO2-doped magnetic coconut coir biochar (Ce-MCB) and magnetic coconut coir biochar (MCB) for Pb2+ absorption were prepared by the impregnation method, and the efficiency of Ce-MCB for Pb2+ absorption was evaluated in comparison with MCB. Conducting the absorption experiments, the study provided theoretical support for the exploration of the absorption mechanism. The quantitative analysis exposed that the enhanced absorption capacity of Ce-MCB was attributed to the increase in oxygen-containing functional groups and mineral precipitation. The Langmuir and Freundlich isotherm model showed that Ce-MCB is a suitable adsorbent for Pb2+. The absorption characteristics of Ce-MCB was fit well with the pseudo-second-order (PSO) and Langmuir models, which revealed that the absorption of Pb2+ in water was monolayer chemisorption with a maximum theoretical adsorption capacity of 140.83 mg·g-1. The adsorption capacity of Ce-MCB for Pb(II) was sustained above 70% after four cycles. In addition, the saturation magnetization intensity of Ce-MCB was 7.15 emu·g-1, which was sufficient to separate out from the solution. Overall, Ce-MCB has wide application prospects in terms of biomass resources recycling and environmental conservation.

Identification of sex determination locus in sea cucumber Apostichopus japonicus using genome-wide association study.

BACKGROUND: Sex determination mechanisms are complicated and diverse across taxonomic categories. Sea cucumber Apostichopus japonicus is a benthic echinoderm, which is the closest group of invertebrates to chordate, and important economic and ecologically aquaculture species in China. A. japonicus is dioecious, and no phenotypic differences between males and females can be detected before sexual maturation. Identification of sex determination locus will broaden knowledge about sex-determination mechanism in echinoderms, which allows for the identification of sex-linked markers and increases the efficiency of sea cucumber breeding industry. RESULTS: Here, we integrated assembly of a novel chromosome-level genome and resequencing of female and male populations to investigate the sex determination mechanisms of A. japonicus. We built a chromosome-level genome assembly AJH1.0 using Hi-C technology. The assembly AJH1.0 consists of 23 chromosomes ranging from 22.4 to 60.4 Mb. To identify the sex-determination locus of A. japonicus, we conducted genome-wide association study (GWAS) and analyses of distribution characteristics of sex-specific SNPs and fixation index FST. The GWAS analysis showed that multiple sex-associated loci were located on several chromosomes, including chromosome 4 (24.8%), followed by chromosome 9 (10.7%), chromosome 17 (10.4%), and chromosome 18 (14.1%). Furthermore, analyzing the homozygous and heterozygous genotypes of plenty of sex-specific SNPs in females and males confirmed that A. japonicus might have a XX/XY sex determination system. As a physical region of 10 Mb on chromosome 4 included the highest number of sex-specific SNPs and higher FST values, this region was considered as the candidate sex determination region (SDR) in A. japonicus. CONCLUSIONS: In the present study, we integrated genome-wide association study and analyses of sex-specific variations to investigate sex determination mechanisms. This will bring novel insights into gene regulation during primitive gonadogenesis and differentiation and identification of master sex determination gene in sea cucumber. In the sea cucumber industry, investigation of molecular mechanisms of sex determination will be helpful for artificial fertilization and precise breeding.

The Application of Texture Feature Analysis of Rectus Femoris Based on Local Binary Pattern (LBP) Combined With Gray-Level Co-Occurrence Matrix (GLCM) in Sarcopenia.

OBJECTIVES: In order to detect the changes in muscle texture of sarcopenia and to explore a new method of ultrasound assessment of muscle changes in sarcopenia. METHODS: we used the local binary pattern (LBP) combined with gray-level co-occurrence matrix (GLCM) method to extract and quantitatively analyze the texture information of the rectus femoris of different people, and initially verified the robustness of this method to image gain changes. We recruited young volunteers, elderly volunteers without sarcopenia, and elderly volunteers with sarcopenia in this cross-sectional study. We scanned the rectus femoris and extracted their muscle texture features. RESULTS: We found that when ultrasonographic gain varied from 40% to 70%, the intraclass correlation coefficient (ICC) of contrast, entropy, and homogeneity were 0.989, 0.973, and 0.989, respectively. Body mass index was significantly related to contrast (r = 0.285, P < .05), and age had a significant correlation with contrast and homogeneity (r = -0.259 and r = 0.269, P < .05). The elderly volunteers with sarcopenia had the highest entropy (0.363 [0.342-0.403]) and homogeneity (2.203 [2.162-2.277]) in the texture of the rectus femoris among the three groups, and at the same time had the lowest contrast (44.583 [43.492-47.399]), and all P < .05. CONCLUSION: LBP combined with GLCM can be a stable method for extracting muscle texture features. At the same time, the contrast, entropy, and homogeneity of the rectus femoris of the elderly with sarcopenia were significantly different from those of the young volunteers and the elderly without sarcopenia, suggesting the texture features of rectus femoris are potential parameters for evaluating muscle function and pathological changes.

Study on Efficient Adsorption Mechanism of Pb2+ by Magnetic Coconut Biochar.

Lead ion (Pb2+) in wastewater cannot be biodegraded and destroyed. It can easily be enriched in living organisms, which causes serious harm to the environment and human health. Among the existing treatment technologies, adsorption is a green and efficient way to treat heavy metal contamination. Novel KMnO4-treated magnetic biochar (KFBC) was successfully synthesized by the addition of Fe(NO3)3 and KMnO4 treatment during carbonization following Pb2+ adsorption. SEM-EDS, XPS, and ICP-OES were used to evaluate the KFBC and magnetic biochar (FBC) on the surface morphology, surface chemistry characteristics, surface functional groups, and Pb2+ adsorption behavior. The effects of pH on the Pb2+ solution, initial concentration of Pb2+, adsorption time, and influencing ions on the adsorption amount of Pb2+ were examined, and the adsorption mechanisms of FBC and KFBC on Pb2+ were investigated. The results showed that pH had a strong influence on the adsorption of KFBC and the optimum adsorption pH was 5. The saturation adsorption capacity fitted by the model was 170.668 mg/g. The successful loading of manganese oxides and the enhanced oxygen functional groups, as evidenced by XPS and FTIR data, improved KFBC for heavy metal adsorption. Mineral precipitation, functional group complexation, and π-electron interactions were the primary adsorption processes.

Identification of an Epigenetically Marked Locus within the Sex Determination Region of Channel Catfish.

Channel catfish has an XY sex determination system. However, the X and Y chromosomes harbor an identical gene content of 950 genes each. In this study, we conducted comparative analyses of methylome and transcriptome of genetic males and genetic females before gonadal differentiation to provide insights into the mechanisms of sex determination. Differentially methylated CpG sites (DMCs) were predominantly identified on the sex chromosome, most notably within the sex determination region (SDR), although the overall methylation profiles across the entire genome were similar between genetic males and females. The drastic differences in methylation were located within the SDR at nucleotide position 14.0-20.3 Mb of the sex chromosome, making this region an epigenetically marked locus within the sex determination region. Most of the differentially methylated CpG sites were hypermethylated in females and hypomethylated in males, suggesting potential involvement of methylation modification in sex determination in channel catfish. Along with the differential methylation in the SDR, a number of differentially expressed genes within the SDR were also identified between genetic males and females, making them potential candidate genes for sex determination and differentiation in channel catfish.

Direct and pleiotropic effects of the Masou Salmon Delta-5 Desaturase transgene in F1 channel catfish (Ictalurus punctatus).

Channel catfish (Ictalurus punctatus) is the primary culture species in the US along with its hybrid made with male blue catfish, I. furcatus. In an effort to improve the nutritional value of channel catfish, the masou salmon Δ5-desaturase like gene (D5D) driven by the common carp beta-actin promoter (ßactin) was inserted into channel catfish. The objectives of this study were to determine the effectiveness of ßactin-D5D for improving n-3 fatty acid production in F1 transgenic channel catfish, as well as examine pleiotropic effects on growth, proximate analysis, disease resistance, and other performance traits. Transgenic F1 channel catfish showed a 33% increase in the relative proportion of n-3 fatty acids coupled with a 15% decrease in n-6 fatty acids and a 17% decrease in n-9 fatty acids when compared to non-transgenic full-siblings (P < 0.01, P < 0.01, P < 0.01). However, while the relative proportion of n-3 fatty acids was achieved, the total amount of fatty acids in the transgenic fish decreased resulting in a reduction of all fatty acids. Insertion of the ßactin-D5D transgene into channel catfish also had large effects on the body composition, and growth of channel catfish. Transgenic channel catfish grew faster, were more disease resistant, had higher protein and moisture percentage, but lower fat percentage than full-sib controls. There were sex effects as performance changes were more dramatic and significant in males. The ßactin-D5D transgenic channel catfish were also more uniform in their fatty acid composition, growth and other traits.

[Thickness of A1 Pulley Measured by High-frequency Ultrasound and Its Influence Factors in Healthy Volunteers].

OBJECTIVE: To investigate A1 pulley thickness of flexor tendon in healthy volunteers and to analyze its influence factors. METHODS: The study included 90 healthy volunteers and the A1 pulley thickness at bilateral fingers was measured using high frequency ultrasound. The following parameters were recorded for each participant: age, gender, weight, height, body mass index (BMI). RESULTS: High-frequency ultrasound can clearly show A1 pulley. There was no significant difference in A1 pulley thickness between the bilateral fingers ( P>0.05). A1 pulley thickness was significantly different in different fingers ( P<0.05). Further comparison showed that A1 pulley thickness could be divided into two subsets: thumb and little finger ((0.196±0.051) mm), index, middle and ring fingers ((0.230±0.055) mm). A1 pulley thickness was positively correlated with age ( r=0.468, P<0.001). The normal reference ranges for thumb and little finger were 0.09-0.23 mm, 0.12-0.30 mm and 0.12-0.32 mm, respectively. The normal reference ranges for index, middle and ring fingers were 0.11-0.27 mm, 0.15-0.35 mm and 0.17-0.35 mm in volunteers aged 3-19 yr., 20-49 yr., and ≥50 yr., respectively. Gender and BMI had negligible impact on A1 pulley thickness ( P>0.05). CONCLUSION: High-frequency ultrasound can clearly show and measure A1 pulley. Site and age should be taken into account when determining the reference range of normal A1 pulley thickness. High-frequency ultrasound can be a quantitative evaluation method for A1 pulley lesions.

Electron energy loss of ultraviolet plasmonic modes in aluminum nanodisks.

We theoretically investigated electron energy loss spectroscopy (EELS) of ultraviolet surface plasmon modes in aluminum nanodisks. Using full-wave Maxell electromagnetic simulations, we studied the impact of the diameter on the resonant modes of the nanodisks. We found that the mode behavior can be separately classified for two distinct cases: (1) flat nanodisks where the diameter is much larger than the thickness and (2) thick nanodisks where the diameter is comparable to the thickness. While the multipolar edge modes and breathing modes of flat nanostructures have previously been interpreted using intuitive, analytical models based on surface plasmon polariton (SPP) modes of a thin-film stack, it has been found that the true dispersion relation of the multipolar edge modes deviates significantly from the SPP dispersion relation. Here, we developed a modified intuitive model that uses effective wavelength theory to accurately model this dispersion relation with significantly less computational overhead compared to full-wave Maxwell electromagnetic simulations. However, for the case of thick nanodisks, this effective wavelength theory breaks down, and such intuitive models are no longer viable. We found that this is because some modes of the thick nanodisks carry a polar (i.e., out of the substrate plane or along the electron beam direction) dependence and cannot be simply categorized as radial breathing modes or angular (azimuthal) multipolar edge modes. This polar dependence leads to radiative losses, motivating the use of simultaneous EELS and cathodoluminescence measurements when experimentally investigating the complex mode behavior of thick nanostructures.

Preoperative fibrinogen-to-albumin ratio, a potential prognostic factor for patients with stage IB-IIA cervical cancer.

BACKGROUND: Previous studies have shown that fibrinogen-to-albumin ratio (FAR) is a novel prognostic immune biomarker in various diseases. In this study, we investigated the role of FAR in the prognosis of patients with stage IB-IIA cervical cancer (CC). METHODS: A total of 278 eligible participants with newly diagnosed CC (stage IB-IIA) who had undergone radical hysterectomy followed by adjuvant chemotherapy were enrolled in this study. Demographics, clinicopathological variables, and laboratory tests were obtained from the medical records. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were evaluated by univariate and multivariate Cox proportional regression analyses. The association between OS, RFS, and FAR was assessed by the Kaplan-Meier method using log-rank test. RESULTS: FAR was associated with age, International Federation of Gynecology and Obstetrics (FIGO) stage, depth of the invasion, and C-reactive protein (CRP) level (P < 0.05). Preoperative FAR was an effective predictor for OS in CC patients with a cut-off value of 7.75 and an area under the curve (AUC) of 0.707 (P < 0.001). The univariate and multivariate Cox analyses indicated that FIGO stage and FAR were two independent risk factors for both OS and RFS (P < 0.05). Kaplan-Meier analysis confirmed that patients with high FAR levels showed significantly lower RFS (P = 0.004) and OS (P = 0.003) than those with low FAR levels. CONCLUSIONS: This study indicated that elevated preoperative FAR might be a novel prognostic factor for CC patients with stage IB-IIA.

The Y chromosome sequence of the channel catfish suggests novel sex determination mechanisms in teleost fish.

BACKGROUND: Sex determination mechanisms in teleost fish broadly differ from mammals and birds, with sex chromosomes that are far less differentiated and recombination often occurring along the length of the X and Y chromosomes, posing major challenges for the identification of specific sex determination genes. Here, we take an innovative approach of comparative genome analysis of the genomic sequences of the X chromosome and newly sequenced Y chromosome in the channel catfish. RESULTS: Using a YY channel catfish as the sequencing template, we generated, assembled, and annotated the Y genome sequence of channel catfish. The genome sequence assembly had a contig N50 size of 2.7 Mb and a scaffold N50 size of 26.7 Mb. Genetic linkage and GWAS analyses placed the sex determination locus within a genetic distance less than 0.5 cM and physical distance of 8.9 Mb. However, comparison of the channel catfish X and Y chromosome sequences showed no sex-specific genes. Instead, comparative RNA-Seq analysis between females and males revealed exclusive sex-specific expression of an isoform of the breast cancer anti-resistance 1 (BCAR1) gene in the male during early sex differentiation. Experimental knockout of BCAR1 gene converted genetic males (XY) to phenotypic females, suggesting BCAR1 as a putative sex determination gene. CONCLUSIONS: We present the first Y chromosome sequence among teleost fish, and one of the few whole Y chromosome sequences among vertebrate species. Comparative analyses suggest that sex-specific isoform expression through alternative splicing may underlie sex determination processes in the channel catfish, and we identify BCAR1 as a potential sex determination gene.

Post-transcriptional regulation through alternative splicing after infection with Flavobacterium columnare in channel catfish (Ictalurus punctatus).

Columnaris disease has long been recognized as a serious problem worldwide which affects both wild and cultured freshwater fish including the commercially important channel catfish (Ictalurus punctatus). The fundamental molecular mechanisms of the host immune response to the causative agent Flavobacterium columnare remain unclear, though gene expression analysis after the bacterial infection has been conducted. Alternative splicing, a post-transcriptional regulation process to modulate gene expression and increase the proteomic diversity, has not yet been studied in channel catfish following infection with F. columnare. In this study, genomic information and RNA-Seq datasets of channel catfish were used to characterize the changes of alternative splicing after the infection. Alternative splicing was shown to be induced by F. columnare infection, with 8.0% increase in alternative splicing event at early infection stage. Intriguingly, genes involved in RNA binding and RNA splicing themselves were significantly enriched in differentially alternatively spliced (DAS) gene sets after infection. This finding was consistent with our previous study in channel catfish following infection with Edwardsiella ictaluri. It was suggested to be a universal mechanism that genes involved in RNA binding and splicing were regulated to undergo differential alternative splicing after stresses in channel catfish. Moreover, many immune genes were observed to be differentially alternatively spliced after infection. Further studies need to be performed to get a deeper view of molecular regulation on alternative splicing after stresses, setting a foundation for developing catfish broodstocks with enhanced disease resistance.

Targeting c-met receptor tyrosine kinase by the DNA aptamer SL1 as a potential novel therapeutic option for myeloma.

Hepatocyte growth factor (HGF)/c-met pathway activation has been implicated in the pathogenesis of multiple myeloma (MM), and blocking this pathway has been considered a rational therapeutic strategy for treating MM. Aptamers are single-stranded nucleic acid molecules that fold into complex 3D structures and bind to a variety of targets. Recently, it was reported that DNA aptamer SL1 exhibited high specificity and affinity for c-met and inhibited HGF/c-met signaling in SNU-5 cells. However, as the first c-met-targeted DNA aptamer to be identified, application of SL1 to myeloma treatment requires further investigation. Here, we explore the potential application of SL1 in MM. Our results indicated that c-met expression is gradually increased in MM patients and contributes to poor outcomes. SL1 selectively bound to c-met-positive MM cells but not to normal B cells and suppressed the growth, migration and adhesion of MM cells in vitro in a co-culture model performed with HS5 cells, wherein SL1 inhibited HGF-induced activation of c-met signaling. In vivo and ex vivo fluorescence imaging showed that SL1 accumulated in the c-met positive tumour areas. In addition, SL1 was active against CD138+ primary MM cells and displayed a synergistic inhibition effect with bortezomib. Collectively, our data suggested that SL1 could be beneficial as a c-met targeted antagonist in MM.