Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus.

Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic.

Crosstalk suppression of extrinsic Fabry-Perot interferometric sensor array based on five-step phase shift demodulation scheme using multiwavelength averaging.

A five-step phase shift demodulation scheme based on a multiwavelength averaging method is proposed to suppress crosstalk within an extrinsic Fabry-Perot interferometric (EFPI) sensor array. The paper focuses on a two-element sensing system based on the EFPI sensors to investigate the crosstalk in the EFPI sensor array. A detailed theoretical analysis of crosstalk suppression using the proposed demodulation method is presented. Numerical simulations and experiments are put forward to demonstrate the effectiveness of the proposed demodulation scheme in suppressing crosstalk under varying parameters. The results of the multiwavelength demodulation scheme indicate superior crosstalk suppression capability in contrast to the conventional five-step phase shift demodulation scheme based on a single-wavelength demodulation method. Furthermore, the paper reveals the enhanced crosstalk suppression capability of the proposed demodulation scheme when the cavity length difference between elements is not equal to zero. It alleviates the requirement for consistent cavity length among different elements in the sensing array. The proposed demodulation scheme exhibits excellent crosstalk suppression capabilities in optical multiplexing arrays by decreasing the dependency on extinction ratio and could be potentially used in the large-scale optical hydrophone array system.

RP11-296E3.2 acts as an important molecular chaperone for YBX1 and promotes colorectal cancer proliferation and metastasis by activating STAT3.

BACKGROUND: RP11-296E3.2 is a novel long noncoding RNA (lncRNA) associated with colorectal cancer (CRC) metastasis, that was reported in our previous clinical studies. However, the mechanisms of RP11-296E3.2 in colorectal tumorigenesis remain elusive. METHODS: RNA sequencing (RNA-seq), Fluorescence in situ hybridization (FISH), Transwell assays and others, were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vitro. In situ and metastatic tumor models were performed to evaluate the function of RP11-296E3.2 for proliferation and metastasis in vivo. RNA-pulldown, RNA-interacting protein immunoprecipitation (RIP), tissue microarray (TMA) assay, a luciferase reporter assay, chromatin immunoprecipitation (ChIP) and others were performed to explore the mechanisms by which RP11-296E3.2 regulates CRC tumorigenesis. RESULTS: RP11-296E3.2 was confirmed to be associated with CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, RP11-296E3.2 directly bound to recombinant Y-Box Binding Protein 1 (YBX1) and enhanced signal transducer and activator of transcription 3 (STAT3) transcription and phosphorylation. YBX1 promoted the CRC cell proliferation and migration, while knockdown of RP11-296E3.2 attenuated the effects of YBX1 on CRC cell proliferation, and metastasis and the expression of several related downstream genes. We are the first to discover and confirm the existence of the YBX1/STAT3 pathway, a pathway dependent on RP11-296E3.2. CONCLUSION: Together, these novel findings show that the RP11-296E3.2/YBX1 pathway promotes colorectal tumorigenesis and progression by activating STAT3 transcription and phosphorylation, and suggest that RP11-296E3.2 is a potential diagnostic biomarker and therapeutic target in CRC.

Reservoir computing decoupling memory-nonlinearity trade-off.

Reservoir computing (RC), a variant recurrent neural network, has very compact architecture and ability to efficiently reconstruct nonlinear dynamics by combining both memory capacity and nonlinear transformations. However, in the standard RC framework, there is a trade-off between memory capacity and nonlinear mapping, which limits its ability to handle complex tasks with long-term dependencies. To overcome this limitation, this paper proposes a new RC framework called neural delayed reservoir computing (ND-RC) with a chain structure reservoir that can decouple the memory capacity and nonlinearity, allowing for independent tuning of them, respectively. The proposed ND-RC model offers a promising solution to the memory-nonlinearity trade-off problem in RC and provides a more flexible and effective approach for modeling complex nonlinear systems with long-term dependencies. The proposed ND-RC framework is validated with typical benchmark nonlinear systems and is particularly successful in reconstructing and predicting the Mackey-Glass system with high time delays. The memory-nonlinearity decoupling ability is further confirmed by several standard tests.

Sex effects on carcass characteristics, meat quality traits and meat amino acid and fatty acid compositions in a novel Duroc line pig.

In-depth studies of carcass characters and meat quality could provide insight both for breeding improvement and food development in pigs. Breed and gender are two main factors affected the carcass and meat altitude, which plays important roles in pork industry. The aim of this study was to evaluate the sex effects on carcass characteristics and meat quality traits in a novel Duroc strain pig crossbred from French line, American line and Canadian line pigs. A total of 30 pigs (15 surgical-castrated males and 15 females) with similar birthweight (1.8 ± 0.13 kg) was used in experiment. During the experiment period, all pigs were fed same commercial diets. Overall, female pigs observed higher (p < 0.05) carcass weight, slaughter backfat, loin muscle area, loin muscle depth, carcass yield, pH on 45 min, meat histidine and essential amino acid (AA) compositions, and eicosenoic, unsaturation and free fatty acids (FA) compositions compared with meat from castrated males. Whereas, castrated males' meat showed better altitude (p < 0.05) on meat lightness, meat moisture content percentage, total umami AA and stearic acid and saturated FA compositions than those from female ones. In conclusion, the results of this study provide evidence on the sex effects on meat quality and carcass parameters in Duroc strain pigs. Furthermore, this study also give a reference on the relationship between sex and carcass and meat characteristics in Durco strain pigs.

Interleukin 35: protective role and mechanism in type 1 diabetes.

Interleukin 35 (IL-35), a cytokine secreted by regulatory T (Treg) cells from the differentiation of conventional CD4+ T cells, is a member of the IL-12 family. The IL-12 family of cytokines exhibits an anti-inflammatory property. IL-35 has recently been shown to influence the immune modulation in various diseases, including inflammatory bowel disease, Graves' disease, rheumatoid arthritis, colitis, psoriasis, and type 1 diabetes (T1D). T1D is an immune-related disease caused by destruction of pancreatic ß cells, characterized by an absolute lack of insulin. Recently, studies have suggested that protective effects of IL-35 work by improving blood glucose levels and preventing an attack of inflammatory factors on the islets. The protective mechanism may be closely related to the anti-inflammatory properties of IL-35, which include regulating macrophage phenotype, suppressing T cell proliferation, decreasing the differentiation of Th17 cells, increasing the Treg cell population, and inducing IL-35-producing regulatory T cells (iTr35). Here, we review the protective effects and mechanisms of action of IL-35 in T1D.

Selective Reductive Coupling of Vinyl Azaarenes and Alkynes via Photoredox Cobalt Dual Catalysis.

A visible light-induced Co-catalyzed highly regio- and stereoselective reductive coupling of vinyl azaarenes and alkynes has been developed. Notably, Hünig's base together with simple ethanol has been successfully applied as the hydrogen sources instead of commonly used Hantzsch esters in this catalytic photoredox reaction. This approach has considerable advantages for the straightforward synthesis of stereodefined multiple substituted alkenes bearing an azaarene motif, such as excellent regioselectivity (>20 : 1 for >30 examples) and stereoselectivity (>20 : 1 E/Z), broad substrate scope and good functional group compatibility under mild reaction conditions, which has been utilized in the concise synthesis of natural product monomorine I. A reasonable catalytic reaction pathway involving protolysis of the cobaltacyclopentene intermediate has been proposed based on the mechanistic studies.

Regio- and Stereoselective Reductive Coupling of Alkynes and Crotononitrile.

A new regio- and stereoselective reductive coupling of alkynes and crotononitrile has been developed via visible light organophotoredox cobalt dual catalysis. A variety of enantioenriched homoallylic nitriles bearing a stereodefined trisubstituted alkene have been easily synthesized with good to excellent regio- (up to >20:1 rr), stereo- (>20:1 E/Z), and enantioselectivity (up to 98% ee) control under mild conditions. The corresponding nitrile products were smoothly converted into various chiral building blocks. Remarkably, a simple organic base together with water have been utilized as hydrogen sources in this photoinduced reductive reaction.

Boryl Radical Activation of Benzylic C-OH Bond: Cross-Electrophile Coupling of Free Alcohols and CO2 via Photoredox Catalysis.

A new strategy for the direct cleavage of the C(sp3)-OH bond has been developed via activation of free alcohols with neutral diphenyl boryl radical generated from sodium tetraphenylborate under mild visible light photoredox conditions. This strategy has been verified by cross-electrophile coupling of free alcohols and carbon dioxide for the synthesis of carboxylic acids. Direct transformation of a range of primary, secondary, and tertiary benzyl alcohols to acids has been achieved. Control experiments and computational studies indicate that activation of alcohols with neutral boryl radical undergoes homolysis of the C(sp3)-OH bond, generating alkyl radicals. After reducing the alkyl radical into carbon anion under photoredox conditions, the following carboxylation with CO2 affords the coupling product.

Mid-infrared silicon photonic phase shifter based on microelectromechanical system.

Mid-infrared (MIR) photonic integrated circuits have generated considerable interest, owing to their potential applications, such as thermal imaging and biochemical sensing. A challenging area in the field is the development of reconfigurable approaches for the enhancement of on-chip functions, where a phase shifter plays an important role. Here, we demonstrate a MIR microelectromechanical system (MEMS) phase shifter by utilizing an asymmetric slot waveguide with subwavelength grating (SWG) claddings. The MEMS-enabled device can be easily integrated into a fully suspended waveguide with SWG cladding, built on a silicon-on-insulator (SOI) platform. Through engineering of the SWG design, the device achieves a maximum phase shift of 6π, with an insertion loss of 4 dB and a half-wave-voltage-length product (VπLπ) of 2.6 V·cm. Moreover, the time response of the device is measured as 13 µs (rise time) and 5 µs (fall time).

Exact Quasiparticle Properties of a Heavy Polaron in BCS Fermi Superfluids.

We present the Ramsey response and radio-frequency spectroscopy of a heavy impurity immersed in an interacting Fermi superfluid, using the exact functional determinant approach. We describe the Fermi superfluid through the conventional Bardeen-Cooper-Schrieffer theory and investigate the role of the pairing gap on quasiparticle properties revealed by the two spectroscopies. The energy cost for pair breaking prevents Anderson's orthogonality catastrophe that occurs in a noninteracting Fermi gas and allows the existence of polaron quasiparticles in the exactly solvable heavy impurity limit. Hence, we rigorously confirm the remarkable features such as dark continuum, molecule-hole continuum, and repulsive polaron. For a magnetic impurity scattering at finite temperature, we predict additional resonances related to the subgap Yu-Shiba-Rusinov bound state, whose positions can be used to measure the superfluid pairing gap. For a nonmagnetic scattering at zero temperature, we surprisingly find undamped repulsive polarons. These exact results might be readily observed in quantum gas experiments with Bose-Fermi mixtures that have a large-mass ratio.

Ni-MOF Functionalized Carbon Dots with Fluorescence and Adsorption Performance for Rapid Detection of Fe (III) and Ascorbic Acid.

In this work, an "on-off-on" fluorescent probe based on Ni-MOF functionalized Nitrogen-doped carbon quantum dots (Ni-MOF-NCDs) was developed. Ni-MOF-NCDs was characterized by FT-IR, TEM, SEM, and XPS. The presence of Fe (III) will reduce the fluorescence intensity of Ni-MOF-NCDs and "turn off" the fluorescence signal at emission peak of 390 nm, while the signal can be "turn on" after the addition of ascorbic acid (AA). The Ni-MOF-NCDs was established as an "on-off-on" fluorescent probe for the detection of Fe (III) and AA with the linear ranges of 0.029-8.0 µg/mL and 0.263-18.0 µg/mL, respectively. The method has been successfully applied to the detection of water samples and foods with satisfactory recovery. The experimental results showed that Ni-MOF-NCDs not only had the fluorescence properties of NCDs, but also had the adsorption performance of Ni-MOF.

An All-Fiber Optical Sensor Combined with FBG and CFBG-FP for Attitude Estimation.

In order to meet the needs of attitude correction of the optical fiber sensor array, an all-fiber optical sensor combined with FBG and CFBG-FP is proposed to monitor its attitude angle. The FBG sensor for pitch and roll angles detection employs a geometric model solution to shift the center wavelength of the three fiber Bragg gratings connected to it through the mass sphere, allowing for pitch and roll angle detection. Based on the magnetostrictive effect, the CFBG-FP sensor for heading angle detection employs changes of the cavity length of the chirped grating Fabry-Pérot cavity connected to its surface. The method of interpolation data processing and derivation of the attitude angle matrix is used to realize heading angle detection. The experimental results indicate that the FBG sensor for the pitch and roll angles detection has an effective detection range of 180 degrees and an angle measurement error of less than 1.5 degrees. Meanwhile, in the region beyond 10 degrees in the geomagnetic north-south direction, the angle measurement error of the CFBG-FP sensor for the heading angle detection is less than 1.3 degrees. Moreover, the impact of temperature in the system is minimized, demonstrating the validity of this combined fiber optical approach in the attitude angle measurements.

Highly Regio- and Enantioselective Reductive Coupling of Alkynes and Aldehydes via Photoredox Cobalt Dual Catalysis.

A Co-catalyzed highly regio- and enantioselective reductive coupling of alkynes and aldehydes has been developed under visible light photoredox dual catalysis. A variety of enantioenriched allylic alcohols have been obtained by using unsymmetrical internal alkynes and commercially available catalyst, chiral ligand, and reagents. It is noteworthy that this approach has considerable advantages, such as excellent regio- (>95:5 for >40 examples), stereo- (up to >95:5 E/Z), and enantioselectivity (92-99% ee, >35 examples) control, mild reaction conditions, broad substrate scope, and good functional group compatibility, making it a great improvement to enantioselective alkyne-aldehyde reductive coupling reactions.

Use of artificial intelligence for detection of gastric lesions by magnetically controlled capsule endoscopy.

BACKGROUND AND AIMS: Magnetically controlled capsule endoscopy (MCE) has become an efficient diagnostic modality for gastric diseases. We developed a novel automatic gastric lesion detection system to assist in diagnosis and reduce inter-physician variations. This study aimed to evaluate the diagnostic capability of the computer-aided detection system for MCE images. METHODS: We developed a novel automatic gastric lesion detection system based on a convolutional neural network (CNN) and faster region-based convolutional neural network (RCNN). A total of 1,023,955 MCE images from 797 patients were used to train and test the system. These images were divided into 7 categories (erosion, polyp, ulcer, submucosal tumor, xanthoma, normal mucosa, and invalid images). The primary endpoint was the sensitivity of the system. RESULTS: The system detected gastric focal lesions with 96.2% sensitivity (95% confidence interval [CI], 95.7%-96.5%), 76.2% specificity (95% CI, 75.97%-76.3%), 16.0% positive predictive value (95% CI, 15.7%-16.3%), 99.7% negative predictive value (95% CI, 99.74%-99.79%), and 77.1% accuracy (95% CI, 76.9%-77.3%) (sensitivity was 99.3% for erosions; 96.5% for polyps; 89.3% for ulcers; 87.2% for submucosal tumors; 90.6% for xanthomas; 67.8% for normal; and 96.1% for invalid images). Analysis of the receiver operating characteristic curve showed that the area under the curve for all positive images was 0.84. Image processing time was 44 milliseconds per image for the system and 0.38 ± 0.29 seconds per image for clinicians (P < .001). The kappa value of 2 times repeated reads was 1. CONCLUSIONS: The CNN faster-RCNN-based diagnostic program system showed good performance in diagnosing gastric focal lesions in MCE images.

Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis of mRNA splicing relevant proteins in aging HSPCs.

BACKGROUND: HSPC (hematopoietic stem/progenitor cell) aging was closely associated with the organism aging, senile diseases and hematopoietic related diseases. Therefore, study on HSPC aging is of great significance to further elucidate the mechanisms of aging and to treat hematopoietic disease resulting from HSPC aging. Little attention had been paid to mRNA splicing as a mechanism underlying HSPC senescence. RESULTS: We used our lab's patented in vitro aging model of HSPCs to analyze mRNA splicing relevant protein alterations with iTRAQ-based proteomic analysis. We found that not only the notable mRNA splicing genes such as SR, hnRNP, WBP11, Sf3b1, Ptbp1 and U2AF1 but also the scarcely reported mRNA splicing relevant genes such as Rbmxl1, Dhx16, Pcbp2, Pabpc1 were significantly down-regulated. We further verified their gene expressions by qRT-PCR. In addition, we reported the effect of Spliceostatin A (SSA), which inhibits mRNA splicing in vivo and in vitro, on HSPC aging. CONCLUSIONS: It was concluded that mRNA splicing emerged as an important factor for the vulnerability of HSPC aging. This study improved our understanding of the role of mRNA splicing in the HSPC aging process.

Single-Cell Membrane Potential Fluctuations Evince Network Scale-Freeness and Quasicriticality.

What information single neurons receive about general neural circuit activity is a fundamental question for neuroscience. Somatic membrane potential (Vm) fluctuations are driven by the convergence of synaptic inputs from a diverse cross-section of upstream neurons. Furthermore, neural activity is often scale-free, implying that some measurements should be the same, whether taken at large or small scales. Together, convergence and scale-freeness support the hypothesis that single Vm recordings carry useful information about high-dimensional cortical activity. Conveniently, the theory of "critical branching networks" (one purported explanation for scale-freeness) provides testable predictions about scale-free measurements that are readily applied to Vm fluctuations. To investigate, we obtained whole-cell current-clamp recordings of pyramidal neurons in visual cortex of turtles with unknown genders. We isolated fluctuations in Vm below the firing threshold and analyzed them by adapting the definition of "neuronal avalanches" (i.e., spurts of population spiking). The Vm fluctuations which we analyzed were scale-free and consistent with critical branching. These findings recapitulated results from large-scale cortical population data obtained separately in complementary experiments using microelectrode arrays described previously (Shew et al., 2015). Simultaneously recorded single-unit local field potential did not provide a good match, demonstrating the specific utility of Vm Modeling shows that estimation of dynamical network properties from neuronal inputs is most accurate when networks are structured as critical branching networks. In conclusion, these findings extend evidence of critical phenomena while also establishing subthreshold pyramidal neuron Vm fluctuations as an informative gauge of high-dimensional cortical population activity.SIGNIFICANCE STATEMENT The relationship between membrane potential (Vm) dynamics of single neurons and population dynamics is indispensable to understanding cortical circuits. Just as important to the biophysics of computation are emergent properties such as scale-freeness, where critical branching networks offer insight. This report makes progress on both fronts by comparing statistics from single-neuron whole-cell recordings with population statistics obtained with microelectrode arrays. Not only are fluctuations of somatic Vm scale-free, they match fluctuations of population activity. Thus, our results demonstrate appropriation of the brain's own subsampling method (convergence of synaptic inputs) while extending the range of fundamental evidence for critical phenomena in neural systems from the previously observed mesoscale (fMRI, LFP, population spiking) to the microscale, namely, Vm fluctuations.

Diverse coactive neurons encode stimulus-driven and stimulus-independent variables.

Both experimenter-controlled stimuli and stimulus-independent variables impact cortical neural activity. A major hurdle to understanding neural representation is distinguishing between qualitatively different causes of the fluctuating population activity. We applied an unsupervised low-rank tensor decomposition analysis to the recorded population activity in the visual cortex of awake mice in response to repeated presentations of naturalistic visual stimuli. We found that neurons covaried largely independently of individual neuron stimulus response reliability and thus encoded both stimulus-driven and stimulus-independent variables. Importantly, a neuron's response reliability and the neuronal coactivation patterns substantially reorganized for different external visual inputs. Analysis of recurrent balanced neural network models revealed that both the stimulus specificity and the mixed encoding of qualitatively different variables can arise from clustered external inputs. These results establish that coactive neurons with diverse response reliability mediate a mixed representation of stimulus-driven and stimulus-independent variables in the visual cortex.NEW & NOTEWORTHY V1 neurons covary largely independently of individual neuron's response reliability. A single neuron's response reliability imposes only a weak constraint on its encoding capabilities. Visual stimulus instructs a neuron's reliability and coactivation pattern. Network models revealed using clustered external inputs.

Consistent Theory of Self-Bound Quantum Droplets with Bosonic Pairing.

We revisit the Bogoliubov theory of quantum droplets proposed by Petrov [Phys. Rev. Lett. 115, 155302 (2015)PRLTAO0031-900710.1103/PhysRevLett.115.155302] for an ultracold Bose-Bose mixture, where the mean-field collapse is stabilized by the Lee-Huang-Yang quantum fluctuations. We show that a loophole in Petrov's theory, i.e., the ignorance of the softening complex Bogoliubov spectrum, can be naturally removed by the introduction of bosonic pairing. The pairing leads to weaker mean-field attractions, and also a stronger Lee-Huang-Yang term in the case of unequal intraspecies interactions. As a result, the equilibrium density for the formation of self-bound droplets significantly decreases in the deep droplet regime, in agreement with a recent observation from diffusion Monte Carlo simulations. Our construction of a consistent Bogoliubov theory paves the way to understand the puzzling low critical number of small quantum droplets observed in the experiment [C. Cabrera et al., Science 359, 301 (2018)SCIEAS0036-807510.1126/science.aao5686].

Few-Body Perspective of a Quantum Anomaly in Two-Dimensional Fermi Gases.

A quantum anomaly manifests itself in the deviation of the breathing mode frequency from the scale invariant value of 2ω in two-dimensional harmonically trapped Fermi gases, where ω is the trapping frequency. Its recent experimental observation with cold atoms reveals an unexpected role played by the effective range of interactions, which requires a quantitative theoretical understanding. Here we provide accurate, benchmark results on a quantum anomaly from a few-body perspective. We consider the breathing mode of a few trapped interacting fermions in two dimensions up to six particles and present the mode frequency as a function of scattering length for a wide range of effective range. We show that the maximum quantum anomaly gradually reduces as the effective range increases while the maximum position shifts towards the weak-coupling limit. We extrapolate our few-body results to the many-body limit and find a good agreement with the experimental measurements. Our results may also be directly applicable to a few-fermion system prepared in microtraps and optical tweezers.