Genomic analyses of wild argali, domestic sheep, and their hybrids provide insights into chromosome evolution, phenotypic variation, and germplasm innovation.

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O ammon polii, 2n = 56), a female Tibetan sheep (O aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Copper-Catalyzed Tandem Cyclization/Chalcogenation with Elemental S8/Se: Concise Synthesis of 3-(ß-Hydroxychalcogen)benzofurans.

A novel copper-catalyzed cyclization/chalcogenation of o-alkynylphenols with epoxides and elemental S8/Se was developed for the synthesis of a 3-chalcogen-benzofuran architecture in a domino process with no intermediate isolation or purification. Various sensitive functional groups were compatible at room temperature and furnished chalcogenation derivatives in moderate to good yields.

Berberine Modulates Macrophage Activation by Inducing Glycolysis.

Classical activation of macrophage and monocyte differentiation induced by ß-glucan is accompanied with metabolic change in glucose. However, the role of the metabolic rewiring in monocyte/macrophage activation remains elusive. In this study, we show that berberine induces aerobic glycolysis by blocking the tricarboxylic acid cycle and modulates cytokine responses in bone marrow-derived macrophages (BMDMs) from mice and human PBMC. 13-Methyberberine had activities on glucose metabolism and BMDM activation similar to those of berberine, whereas other tested derivatives lost both activities. Glucose transporter (GLUT)1 expression and total cellular hexokinase activity increased gradually in BMDMs in the presence of berberine. In the contrast, LPS upregulated GLUT1 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) levels in 6 h. Extracellular glucose levels and replacing glucose with galactose in culture medium affected the cytokine secretion of BMDMs. Berberine alleviated enteritis of Salmonella typhimurium infection and protected mice against endotoxic shock. In mice i.p. injected with LPS, the increase of serum TNF-α and the drop of blood glucose were attenuated by berberine treatment. These data together demonstrated that macrophage activation was closely related with glucose metabolism.

Boron difluoride modified zinc metal-organic framework-based "off-on" fluorescence sensor for tetracycline and Al3+ detection.

A novel fluorescence "off-on" probe was developed using a boron difluoride-modified zinc metal-organic framework (Zn-MOF3) for sensitive determination of tetracycline (TC) and Al3+. The Zn-MOF3 has excellent optical property and good applicability in aqueous phase. The fluorescence recorded at 436 nm was quenched at the excitation wavelength of 336 nm. Signal-off detection of tetracycline via fluorescence quenching of Zn-MOF3 is based on the inner filter effect. Fluorescence on-off-on detection of Al3+ occurs via the specific binding between tetracycline and Al3+. The limits of detection for TC and Al3+ were 28.4 nM and 106.7 nM, respectively. This probe exhibited high selectivity which was used for the determination of TC and Al3+ with satisfied recoveries (89.8 to 105.6% for TC, 90.0 to 110.4% for Al3+) and good precision (< 5%) in milk. The developed sensor represents the first "off-on" system for fluorescence detection of TC and Al3+ based on Zn-MOF3 with a better aspect of the innovation.

'On Water'-Promoted Three-Component Tandem Michael Addition/D-A Cycloaddition Reaction to Construct Polycyclic N-Heterocycles Derivatives.

'On Water'-promoted the three-component tandem Michael addition/D-A cycloaddition reaction in 80 °C at 3 h has been developed without employing any catalyst and organic solvent. The process allows facile access to polycyclic N-heterocycles derivatives contain indole and maleimide from easily accessible starting materials in moderate to high yields (up to 91 %). Compared with conventional reaction conditions, this reaction not only improves the reaction efficiency and rate but also minimizes the side reaction.

Incipient Fault Detection in a Hydraulic System Using Canonical Variable Analysis Combined with Adaptive Kernel Density Estimation.

Incipient fault detection in a hydraulic system is a challenge in the condition monitoring community. Existing research mainly monitors abnormal working conditions in hydraulic systems by separately detecting the key working parameter, which often causes a high miss warning rate for incipient faults due to the oversight of parameter dependence. A principal component analysis provides an effective method for incipient fault detection by taking the correlation of multiple parameters into consideration, but this technique assumes the systems are Gaussian-distributed, making it invalid for a dynamic non-Gaussian system. In this paper, we combine a canonical variable analysis (CVA) and adaptive kernel density estimation (AKDE) for the early fault detection of nonlinear dynamic hydraulic systems. The collected hydraulic system data set was used to construct the typical variable space, and the state space and residual space are divided to represent the characteristics of different correlations between the two variables, which are quantitatively described using Hotelling's T2 and Q. In order to investigate the proper upper control limits, AKDE was utilised to estimate the underlying probability density functions of T2 and Q by taking the nonlinearity of the hydraulic system variables into consideration. The advantages of the proposed approach for incipient fault detection are illustrated via a marine power plant lubrication system.

Fluorescence determination of chloramphenicol in milk powder using carbon dot decorated silver metal-organic frameworks.

Carbon dot decorated silver metal-organic frameworks (CD-MOFs) were successfully synthesized at room temperature by adding CDs during the formation of Ag-MOFs. The CD-MOFs have excellent optical property, stability, and good fluorescence intensity in water compared with other solvents. The fluorescence intensity of CD-MOFs was relatively stable in the range of pH 5-9. It was used to construct a sensitive and reliable fluorescent sensor for the determination of chloramphenicol (CAP). When the CAP was introduced into the CD-MOFs, the fluorescence at 427 nm was quenched at the excitation wavelength of 332 nm. Wide linear relationships were established for CAP with a limit of detection of 44 nM. The fluorescent sensor has been applied to determine CAP in milk powder sample with satisfied recoveries (104 to 109%) and good precision (< 4%). The photoinduced electron-transfer is the most important mechanism contributing to the fluorescence quenching. The synthesized CD-MOFs provide a new orientation for fluorescence determination of chloramphenicol in real samples.

HRANet: Hierarchical region-aware network for crowd counting.

Aiming to tackle the most intractable problems of scale variation and complex backgrounds in crowd counting, we present an innovative framework called Hierarchical Region-Aware Network (HRANet) for crowd counting in this paper, which can better focus on crowd regions to accurately predict crowd density. In our implementation, first, we design a Region-Aware Module (RAM) to capture the internal differences within different regions of the feature map, thus adaptively extracting contextual features within different regions. Furthermore, we propose a Region Recalibration Module (RRM) which adopts a novel region-aware attention mechanism (RAAM) to further recalibrate the feature weights of different regions. By the integration of the above two modules, the influence of background regions can be effectively suppressed. Besides, considering the local correlations within different regions of the crowd density map, a Region Awareness Loss (RAL) is designed to reduce false identification while producing the locally consistent density map. Extensive experiments on five challenging datasets demonstrate that the proposed method significantly outperforms existing methods in terms of counting accuracy and quality of the generated density map. In addition, a series of specific experiments in crowd gathering scenes indicate that our method can be practically applied to crowd localization.

Assembly of polycyclic N-heterocycles via copper-catalyzed cycloamination of indolylquinones and aromatic amines.

The copper-catalyzed cycloamination of indolylquinones and various (hetero)aromatic amines under ligand-free conditions for the synthesis of polycyclic N-heterocycles has been developed. This method allows facile access to polycyclic N-heterocycles with the tolerance of chloride, bromide, amino, thio, etc. groups in moderate to high yields (60-89%).

Electrochemically C-H/S-H Oxidative Cross-Coupling between Quinoxalin-2(1H)-ones and Thiols for the Synthesis of 3-Thioquinoxalinones.

An electrochemical method for the C(sp2)-H thioetherification of quinoxalin-2(1H)-ones with primary, secondary, and tertiary thiols has been reported. Various quinoxalin-2(1H)-ones underwent this thioetherification smoothly under metal- and chemical oxidant-free conditions, affording 3-alkylthiol-substituted quinoxalin-2(1H)-ones in moderate to good yields.

Long noncoding RNA HAND2-AS1 reduced the viability of hepatocellular carcinoma via targeting microRNA-300/SOCS5 axis.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most prevalent human cancers with high mortality. Long non-coding RNA heart and neural crest derivatives expressed 2 anti-sense 1 (HAND2-AS1) is down-regulated in several cancers including HCC, yet the precise mechanisms how HAND2-AS1 regulates cell survival in HCC remains poorly understood. METHODS: The expression levels of HAND2-AS1 and miR-300 were measured using quantitative real-time PCR. The protein levels of suppressor of cytokine signaling 5 (SOCS5), Bcl-2, Bax and cleaved caspase-3 were determined by Western blot. Cell viability and cell proliferation were assessed using cell counting kit-8 and clone formation assay, respectively. Cell apoptosis was detected using flow cytometry. The interactions between HAND2-AS1 and miR-300, miR-300 and SOCS5 were validated using luciferase reporter assay. RESULTS: HAND2-AS1 was down-regulated in HCC tissues and cell lines, and the expression level of HAND2-AS1 was positively correlated to patient survival. HAND2-AS1 over-expression reduced viability and proliferation in HCC cells. Elevated HAND2-AS1 level induced apoptosis in HCC cells, accompanied with increased Bax and cleaved caspase-3 levels and decreased Bcl-2 level. We also validated that HAND2-AS1 acted as a sponge of miR-300, and there was a negative correlation between expression levels of HAND2-AS1 and miR-300 in HCC tissues. Furthermore, we found that SOCS5 was a downstream target of miR-300. In addition, miR-300 mimics abolished HAND2-AS1-mediated inhibition of cell viability and proliferation. miR-300 mimics also reversed the HAND2-AS1-induced apoptosis in HCC cells. CONCLUSION: lncRNA HAND2-AS1 inhibits proliferation in HCC through regulating miR-300/SOCS5 axis.

Dynamic DNA methylation of ovaries during pubertal transition in gilts.

BACKGROUND: In female mammals, the initiation of puberty, coupling with the dramatically morphological changes in ovaries, indicates the sexual and follicular maturation. Previous studies have suggested that the disrupted DNA methylation results in the delayed puberty. However, to date, the changes in ovarian methylomes during pubertal transition have not been investigated. In this study, using gilts as a pubertal model, the genome-wide DNA methylation were profiled to explore their dynamics during pubertal transition across Pre-, In- and Post-puberty. RESULTS: During pubertal transition, the follicles underwent maturation and luteinization, coupled with the significant changes in the mRNA expression of DNMT1 and DNMT3a. DNA methylation levels of In-puberty were higher than that of Pre- and Post-puberty at the locations of genes and CpG islands (CGIs). Analysis of the DNA methylation changes identified 12,313, 20,960 and 17,694 differentially methylated CpGs (DMCs) for the comparisons of Pre- vs. In-, In vs. Post-, and Pre- vs. Post-puberty, respectively. Moreover, the CGIs, upstream and exonic regions showed a significant underrepresentation of DMCs, but the CGI shores, CGI shelves, intronic, downstream and intergenic regions showed a significant overrepresentation of DMCs. Furthermore, biological functions of these methylation changes enriched in PI3K-Akt signaling pathway, GnRH signaling pathway, and Insulin secretion, and the mRNA expressions of several genes of these signaling pathway, including MMP2, ESR1, GSK3B, FGF21, IGF1R, and TAC3, were significantly changed across Pre-, In- and Post-puberty in ovaries. CONCLUSIONS: During pubertal transition in gilts, the DNA methylation changes of ovaries were likely to affect the transcription of genes related to PI3K-Akt signaling pathway, GnRH signaling pathway, and Insulin secretion. These observations can provide new insight into the epigenetic mechanism of follicular and sexual maturation during pubertal transition in mammals.

[Clinical and genetic analysis of two cases with Rubinstein-Taybi syndrome].

OBJECTIVE: To summarize the clinical characteristics and identify gene mutations of 2 probands with Rubinstein-Taybi syndrome (RSTS). METHODS: Clinical characteristics of 2 probands with Rubinstein-Taybi syndrome were summarized. Genomic DNA was extracted from peripheral blood samples from the patients and their parents. Genomic DNA was subjected to whole exome next generation sequencing. Suspected variants were confirmed by Sanger sequencing. RESULTS: The two patients were characterized by typical facial features, broad thumbs and big toes, intellectual disability, and postnatal growth retardation. Two variants of the CREBBP gene, namely c.3779+1G>A and c.5052_c.5053insT, were respectively identified in the 2 patients. Among these, c.3779+1G>A was a previously known pathological mutation, while c.5052_c.5053insT was unreported previously. Both variants were predicted to be pathological. CONCLUSION: Two cases of Rubinstein-Taybi syndrome were diagnosed, which facilitated the diagnosis and genetic counselling.

Synchronization of Fractional-Order Complex Chaotic Systems Based on Observers.

By designing a state observer, a new type of synchronization named complex modified projective synchronization is investigated in a class of nonlinear fractional-order complex chaotic systems. Combining stability results of the fractional-order systems and the pole placement method, this paper proves the stability of fractional-order error systems and realizes complex modified projective synchronization. This method is so effective that it can be applied in engineering. Additionally, the proposed synchronization strategy is suitable for all fractional-order chaotic systems, including fractional-order hyper-chaotic systems. Finally, two numerical examples are studied to show the correctness of this new synchronization strategy.

Structure-property analysis of julolidine-based nonlinear optical chromophores for the optimization of microscopic and macroscopic nonlinearity.

Four NLO chromophores with different acceptors and modified julolidine donors were facilely synthesized to tune their intramolecular charge-transfer energy gaps for the investigation of the structure-property relationships. The photophysical properties of the UV-Vis absorption spectra, fluorescence spectra and solvatochromism were measured and analyzed to understand the effect of electron-donating strength and electron-withdrawing strength on intramolecular charge-transfer. Density functional theory calculations were carried out to investigate the electron density of the frontier orbitals, energy gap, molecular microscopic dipole moment and hyperpolarizability. The change tendency of the microscopic hyperpolarizability in different dielectric environments in association with the solvatochromism in absorption was analyzed. Meanwhile, the macroscopic electro-optic performance in relation to molecular structure variation and microscopic properties was further analyzed, revealing that chromophores with a larger solvatochromism exhibited higher microscopic hyperpolarizability and macroscopic electro-optic coefficients. Our investigation of the structure-property relationship gave a reliable insight into molecular design for high performance nonlinear optical chromophores.

Simultaneous detection of α-Lactoalbumin, ß-Lactoglobulin and Lactoferrin in milk by Visualized Microarray.

BACKGROUND: α-Lactalbumin (a-LA), ß-lactoglobulin (ß-LG) and lactoferrin (LF) are of high nutritional value which have made ingredients of choice in the formulation of modern foods and beverages. There remains an urgent need to develop novel biosensing methods for quantification featuring reduced cost, improved sensitivity, selectivity and more rapid response, especially for simultaneous detection of multiple whey proteins. RESULTS: A novel visualized microarray method was developed for the determination of a-LA, ß-LG and LF in milk samples without the need for complex or time-consuming pre-treatment steps. The measurement principle was based on the competitive immunological reaction and silver enhancement technique. In this case, a visible array dots as the detectable signals were further amplified and developed by the silver enhancement reagents. The microarray could be assayed by the microarray scanner. The detection limits (S/N = 3) were estimated to be 40 ng/mL (α-LA), 50 ng/mL (ß-LG), 30 ng/mL (LF) (n = 6). CONCLUSIONS: The method could be used to simultaneously analyze the whey protein contents of various raw milk samples and ultra-high temperature treated (UHT) milk samples including skimmed milk and high calcium milk. The analytical results were in good agreement with that of the high performance liquid chromatography. The presented visualized microarray has showed its advantages such as high-throughput, specificity, sensitivity and cost-effective for analysis of various milk samples.

Causal relationship between insomnia and thyroid disease: A bidirectional Mendelian randomization study.

OBJECTIVE: Some correlations between thyroid disorders and insomnia have been found in previous studies; however, the causal relationship between them is unclear. The aim of this study was to investigate the causal relationship between insomnia and five thyroid disorders (hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer). METHODS: We assessed the causal relationship between insomnia and thyroid disorders using inverse variance weighted, weighted median, and Mendelian randomization (MR)-Egger analyses in MR analyses and then used inverse MR analyses to assess the causal relationship between thyroid disorders and insomnia. RESULTS: MR analysis showed that insomnia did not increase the risk of hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer. However, reverse MR analysis showed that thyroid cancer increased the risk of insomnia (OR = 1.01, 95%CI: 1.00-1.02, p = .01), and the other four thyroid disorders had no direct causal relationship with insomnia. Sensitivity analyses indicated that the results were robust and no pleiotropy or heterogeneity was detected. CONCLUSION: This study did not find evidence of a bidirectional causal relationship between genetically predicted insomnia and hyperthyroidism, hypothyroidism, thyroiditis, and thyroid nodules. However, we found that although insomnia does not increase the risk of thyroid cancer, thyroid cancer does increase the risk of insomnia.

Study on a Strong Polymer Gel by the Addition of Micron Graphite Oxide Powder and Its Plugging of Fracture.

It is difficult to plug the fracture water channeling of a fractured low-permeability reservoir during water flooding by using the conventional acrylamide polymer gel due to its weak mechanical properties. For this problem, micron graphite powder is added to enhance the comprehensive properties of the acrylamide polymer gel, which can improve the plugging effect of fracture water channeling. The chemical principle of this process is that the hydroxyl and carboxyl groups of the layered micron graphite powder can undergo physicochemical interactions with the amide groups of the polyacrylamide molecule chain. As a rigid structure, the graphite powder can support the flexible skeleton of the original polyacrylamide molecule chain. Through the synergy of the rigid and flexible structures, the viscoelasticity, thermal stability, tensile performance, and plugging ability of the new-type gel can be significantly enhanced. Compared with a single acrylamide gel, after adding 3000 mg/L of micrometer-sized graphite powder, the elastic modulus, the viscous modulus, the phase transition temperature, the breakthrough pressure gradient, the elongation at break, and the tensile stress of the acrylamide gel are all greatly improved. After adding the graphite powder to the polyacrylamide gel, the fracture water channeling can be effectively plugged. The characteristics of the networked water flow channel are obvious during the injected water break through the gel in the fracture. The breakthrough pressure of water flooding is high. The experimental results are an attempt to develop a new gel material for the water plugging of a fractured low-permeability reservoir.

Modified guanidine gel fracturing fluid system and performance optimization for ultra-deep and ultra-high temperature oil and gas reservoirs.

The development of deep high-temperature oil and gas reservoirs gives rise to a rise in reservoir temperature along with the depth of the oil reservoir, thereby imposing higher requirements on the heat resistance of fracturing fluid. Guar gum fracturing fluid has difficulty tolerating temperatures exceeding 160 °C, thereby demanding the development of corresponding cross-linking agents, temperature stabilizers, and other additives to enhance the thermal stability of the fracturing system. Considering the distinctive characteristics of deep and ultra-deep reservoirs, such as extreme burial depth (exceeding 6000 m), ultra-high temperature (higher than 160 °C), and high fracturing pressure, an experimental modification of a guar gum fracturing fluid system was carried out, specifically tailored for ultra-high temperatures. The experiment identified and selected individual agents for ultra-high temperature fracturing fluids, including crosslinking agents, thermal stabilizers, flowback aids, and clay inhibitors. Through rigorous experimentation, these key agents for an ultra-high temperature fracturing fluid system have been successfully developed, including the optimal thickener GBA1-2, crosslinking agent BA1-1, anti-swelling agent FB-1, and gel breaker TS-1. The evaluation of diverse additive dosages has facilitated the development of an optimal guar fracturing fluid system, which exhibits outstanding high-temperature resistance while minimizing damage and friction. The outcomes of our experiments indicate that even after subjecting our ultra-high temperature fracturing fluid to 2 h of shearing at 170 s-1 at 180 °C, its viscosity remained above 200 mPa s-a distinct proof of its superior performance in withstanding high temperatures. This achievement represents a substantial progress in providing a suitable fracturing fluid system for the transformation and stimulation of ultra-deep and ultra-high temperature reservoirs, and also lays a solid foundation for further exploration and application in related fields in the future.

Multifunctional carbon aerogels loaded with pea-pod-like carbon nanotubes for outstanding electromagnetic wave absorption performance.

Although ordered porous carbon materials (PCMs) have shown promising potential in the field of electromagnetic wave absorption (EWA), creating multifunctional PCMs with outstanding microwave absorption performance remains a significant challenge. Herein, ordered porous carbon aerogels loaded with pea-pod-like nitrogen-doped carbon nanotubes (CNTs) were fabricated via orientation freeze-drying followed by high-temperature pyrolysis. The optimized aerogel exhibits extraordinary EWA performance with a broad effective absorption bandwidth of 7.68 GHz and exceptionally strong absorption of -91.58 dB at a low filling ratio of only 3 wt%, which is the largest absorption strength among all known aerogels to date. The exceptional EWA performance is attributed to the synergistic effect of abundant loss mechanisms resulting from a unique pod-like structure in ordered porous carbon aerogel, where nitrogen-doped CNTs encapsulate magnetic alloy nanoparticles. Optimized aerogel exhibits superior compressive elasticity, thermal insulation, and light weight, laying the groundwork for designing practical next-generation EWA materials.