Explore the vast range of titles available.

Despite exceptional experimental efforts to map out the human interactome, the continued data incompleteness limits our ability to understand the molecular roots of human disease. Computational tools offer a promising alternative, helping identify biologically significant, yet unmapped protein-protein interactions (PPIs). While link prediction methods connect proteins on the basis of biological or network-based similarity, interacting proteins are not necessarily similar and similar proteins do not necessarily interact. Here, we offer structural and evolutionary evidence that proteins interact not if they are similar to each other, but if one of them is similar to the other’s partners. This approach, that mathematically relies on network paths of length three (L3), significantly outperforms all existing link prediction methods. Given its high accuracy, we show that L3 can offer mechanistic insights into disease mechanisms and can complement future experimental efforts to complete the human interactome. Computational protein-protein interaction (PPI) prediction has the potential to complement experimental efforts to map interactomes. Here, the authors show that proteins tend to interact if one is similar to the other’s partners and that PPI prediction based on this principle is highly accurate.

Chipscale micro- and nano-optomechanical systems, hinging on the intangible radiation-pressure force, have shown their unique strength in sensing, signal transduction, and exploration of quantum physics with mechanical resonators. Optomechanical crystals, as one of the leading device platforms, enable simultaneous molding of the band structure of optical photons and microwave phonons with strong optomechanical coupling. Here, we demonstrate a new breed of optomechanical crystals in two-dimensional slab-on-substrate structures empowered by mechanical bound states in the continuum (BICs) at 8 GHz. We show symmetry-induced BIC emergence with optomechanical couplings up to g /2 π ≈ 2.5 MHz per unit cell, on par with low-dimensional optomechanical crystals. Our work paves the way towards exploration of photon-phonon interaction beyond suspended microcavities, which might lead to new applications of optomechanics from phonon sensing to quantum transduction. Unsuspended optomechanical systems might enable unique applications for quantum sensing and transduction. Here, the authors demonstrate a two-dimensional slab-on-substrate optomechanical crystal empowered by mechanical bound states in the continuum.

Phonon trapping has an immense impact in many areas of science and technology, from the antennas of interferometric gravitational wave detectors to chip-scale quantum micro- and nano-mechanical oscillators. It usually relies on the mechanical suspension—an approach, while isolating selected vibrational modes, leads to serious drawbacks for interrogation of the trapped phonons, including limited heat capacity and excess noises via measurements. To circumvent these constraints, we realize a paradigm of phonon trapping using mechanical bound states in the continuum (BICs) with topological features and conducted an in-depth characterization of the mechanical losses both at room and cryogenic temperatures. Our findings of mechanical BICs combining the microwave frequency and macroscopic size unveil a unique platform for realizing mechanical oscillators in both classical and quantum regimes. The paradigm of mechanical BICs might lead to unprecedented sensing modalities for applications such as rare-event searches and the exploration of the foundations of quantum mechanics in unreached parameter spaces. Typically, phonon trapping is performed using mechanically suspended structures which have many limitations. Here the authors study a phononic structure that supports mechanical bound states in the continuum (BICs) at microwave frequencies with topological features.

Exosomes are small membrane particles which are widely found in various cell lines and physiological fluids in mammalian. MicroRNAs (miRNAs) enclosed in exosomes have been identified as proper signatures for many diseases and response to therapies. However, the composition of exosomes and enclosed miRNAs in fishes has not been investigated. Cynoglossus semilaevis is an important commercial flatfish with ambiguous distinction between males and females before sex maturation, which leads to screening difficulty in reproduction and cultivation. An effective detection method was required for sex differentiation of C. semilaevis . In this work, we successfully identified exosomes in C. semilaevis serum. The analysis of nucleotide composition showed that miRNA dominated in exosomes. Thereafter the miRNA profiles in exosomes from males and females were sequenced and compared to identify the signature miRNAs corresponding to sex differentiation. The functions of signature miRNAs were analyzed by target matching and annotation. Furthermore, 7 miRNAs with high expression in males were selected from signature miRNAs as the markers for sex identification with their expression profiles verified by real time quantitative PCR. Exosomes were first found in fish serum in this work. Investigation of marker miRNAs supplies an effective index for the filtration of male and female C. semilaevis in cultivation.

In this paper, the potential of a broadband metasurface for ground penetrating radar (GPR) signal enhancement is investigated by simulation and experiments. Simulation results show that the reflection at the air-MUT interface can be reduced from 35% to 5% over a broad frequency range (relative bandwidth up to 44%) when the broadband metasurface is in place. Measured reflectance is consistent with the simulation results. Meanwhile, the electric field strength measurement results demonstrate that the transmitted electromagnetic signals can be amplified when the reflection is reduced over the same frequency range. GPR experiments verified that clear hyperbolic signals emerged for commonly undetectable pipes when the high-frequency signals are enhanced. The proposed broadband metasurface can be an effective solution for the detection of nonmetallic inclusions in high-lossy media.

Liver chips have been developed to recapitulate in vivo physiological conditions to enhance hepatocyte functions for assessing acute responses to drugs. To develop liver chips that can assess repeated dosing chronic hepatotoxicity, we need to ensure that hepatocyte functions be maintained at constant values over two weeks in stable culture conditions of sterility, temperature, pH, fluidic-flow of culture media and drugs. We have designed a perfusion-incubator-liver-chip (PIC) for 3D cell culture, that assures a tangential flow of the media over the spheroids culture. Rat hepatocyte spheroids constrained between a cover glass and a porous-ultrathin Parylene C membrane experienced optimal mass transfer and limited shear stress from the flowing culture media; maintained cell viability over 24 days. Hepatocyte functions were significantly improved and maintained at constant values (urea, albumin synthesis, and CYP450 enzyme activities) for 14 days. The chip act as an incubator, having 5% CO 2 pressure-driven culture-media flow, on-chip heater and active debubbler. It operates in a biosafety cabinet, thus minimizing risk of contamination. The chronic drug response to repeated dosing of Diclofenac and Acetaminophen evaluated in PIC were more sensitive than the static culture control.

Three-dimensional (3D) bioprinting is a family of enabling technologies that can be used to manufacture human organs with predefined hierarchical structures, material constituents and physiological functions. The main objective of these technologies is to produce high-throughput and/or customized organ substitutes (or bioartificial organs) with heterogeneous cell types or stem cells along with other biomaterials that are able to repair, replace or restore the defect/failure counterparts. Gelatin-based hydrogels, such as gelatin/fibrinogen, gelatin/hyaluronan and gelatin/alginate/fibrinogen, have unique features in organ 3D bioprinting technologies. This article is an overview of the intrinsic/extrinsic properties of the gelatin-based hydrogels in organ 3D bioprinting areas with advanced technologies, theories and principles. The state of the art of the physical/chemical crosslinking methods of the gelatin-based hydrogels being used to overcome the weak mechanical properties is highlighted. A multicellular model made from adipose-derived stem cell proliferation and differentiation in the predefined 3D constructs is emphasized. Multi-nozzle extrusion-based organ 3D bioprinting technologies have the distinguished potential to eventually manufacture implantable bioartificial organs for purposes such as customized organ restoration, high-throughput drug screening and metabolic syndrome model establishment.

To ensure the successful implementation of the old community renewal project (OCRP), it is essential for the participants to allocate the project risks reasonably. Firstly, this study comprehensively identifies the 20 key risk factors of the OCRP. Secondly, an index system is established from three dimensions to evaluate the risk allocation ability of participants, including a total of nine evaluation indexes. Furthermore, a risk-sharing model based on TOPSIS method and bargaining game model is proposed to determine the optimal risk bearer and risk-taking ratio between the government and the private sector in OCRP. Finally, an OCRP in Chongqing is taken as a case study to verify the applicability of the developed model. The results indicate that in OCRP under PPP mode, the government need to independently bear 7 risks related to politics, law, policy, while the private sector needs to independently bear 8 risks mainly from project financing, design, construction, operation, and maintenance stages. In addition, the risk-taking ratios of 5 risks that require both parties to share are divided. The research findings provide references for ensuring the smooth implementation of urban renewal and sustainable development.

Pulsars are good clocks in the universe. One fundamental question is that why they are good clocks？ This is related to the braking mechanism of pulsars. Nowadays pulsar timing is done with unprecedented accuracy. More pulsars have braking indices measured. The period derivative of intermittent pulsars and magnetars can vary by a factor of several. However, during pulsar studies, the magnetic dipole braking in vacuum is still often assumed. It is shown that the fundamental assumption of magnetic dipole braking （vacuum condition） does not exist and it is not consistent with the observations. The physical torque must consider the presence of the pulsar magnetosphere. Among various efforts, the wind braking model can explain many observations of pulsars and magnetars in a unified way. It is also consistent with the up-to-date observations. It is time for a paradigm shift in pulsar studies： from magnetic dipole braking to wind braking. As one alternative to the magnetospheric model, the fallback disk model is also discussed.

The gut microbiota is implicated in the pathogenesis of hyperuricemia (HUA) and gout. However, it remains unclear whether probiotics residing in the host gut, such as Lactobacillus , can prevent HUA development. Herein, we isolated Lactobacillus plantarum SQ001 from the cecum of HUA geese and conducted in vitro assays on uric acid (UA) and nucleoside co-culture. Metabolomics and genome-wide analyses, revealed that this strain may promote nucleoside uptake and hydrolysis through its nucleoside hydrolase gene. The functional role of iunH gene was confirmed via heterologous expression and gene knockout studies. Oral administration of L. plantarum SQ001 resulted in increased abundance of Lactobacillus species and reduced serum UA levels. Furthermore, it downregulated hepatic xanthine oxidase, a key enzyme involved in UA synthesis, as well as renal reabsorption protein GLUT9, while enhancing the expression of renal excretion protein ABCG2. Our findings suggest that L. plantarum has potential to ameliorate gut microbial dysbiosis with HUA, thereby offering insights into its potential application as a probiotic therapy for individuals with HUA or gout. Our blood contains many components, including waste products that need to be transported to the kidneys, where they can exit the body through urine. One such molecule, known as uric acid, forms when cells break down old DNA and other similar molecules. This process has several steps, with DNA being broken down into intermediate molecules called nucleosides before being converted into uric acid. If the amount of uric acid in the bloodstream becomes too high (a condition known as hyperuricemia), humans and other animals can develop high blood pressure, chronic kidney disease and other illnesses. Recent studies suggest that some types of ‘friendly’ bacteria living in the human gut may influence how uric acid levels are regulated. But the precise role these bacteria play remains unclear. Here, Fu, Luo et al. isolated one of these friendly bacterial species, known as Lactobacillus plantarum, from the gut of geese with hyperuricemia. The team grew the bacteria in the laboratory in two environments: one containing uric acid and the other containing nucleosides. The experiments revealed that while Lactobacillus plantarum does not directly act on uric acid, it does have enzymes that can convert nucleosides into other molecules. Further investigations, using whole-genome and metabolomic analyses, showed that Lactobacillus plantarum contains three genes encoding enzymes that act on a type of nucleoside known as a purine. Knocking out one of these genes prevented the bacteria from being able to convert purines into other molecules. Subsequently, Fu, Luo et al. demonstrated that Lactobacillus plantarum helps to mitigate the effects of hyperuricemia in geese and mice. These findings provide valuable insights into how microbes living in the gut regulate uric acid levels in their hosts. They may also inform future strategies for preventing and treating hyperuricemia in humans.