Search

Abstract The growth factor Neuregulin-1 (NRG1) has pleiotropic roles in proliferation and differentiation of the stem cell niche in different tissues. It has been implicated in gut, brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote that these NRG1 isoforms arise from a myeloid-specific transcriptional start site (TSS) previously uncharacterized. Long-read sequencing was used to identify eight high-confidence NRG1-VII transcripts. These transcripts presented major structural differences from one another, through the use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in primary human monocytes and tissue resident macrophages and induced pluripotent stem cell-derived macrophages (iPSC-derived macrophages). Isoform switching via cassette exon usage and alternate polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII is the major class expressed by the myeloid lineage, including tissue-resident macrophages. Analysis of public gene expression data indicates that monocytes and macrophages are a primary source of NRG1. The size and structure of class VII isoforms suggests that they may be more diffusible through tissues than other NRG1 classes. However, the specific roles of class VII variants in tissue homeostasis and repair have not yet been determined.

Developing novel nanoparticle-based bioprobes utilized in clinical settings with imaging resolutions ranging from cell to tissue levels is a major challenge for tumor diagnosis and treatment. Herein, an optimized strategy for designing a Fe3O4-based bioprobe for dual-modal cancer imaging based on surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI) is introduced. Excellent SERS activity of ultrasmall Fe3O4 nanoparticles (NPs) was discovered, and a 5 × 10−9 M limit of detection for crystal violet molecules was successfully obtained. The high-efficiency interfacial photon-induced charge transfer in Fe3O4 NPs was promoted by multiple electronic energy levels ascribed to the multiple valence states of Fe, which was observed using ultraviolet–visible diffuse reflectance spectroscopy. Density functional theory calculations were utilized to reveal that the narrow band gap and high electron density of states of ultrasmall Fe3O4 NPs significantly boosted the vibronic coupling resonances in the SERS system upon illumination. The subtypes of cancer cells were accurately recognized via high-resolution SERS imaging in vitro using the prepared Fe3O4-based bioprobe with high sensitivity and good specificity. Notably, Fe3O4-based bioprobes simultaneously exhibited T1-weighted MRI contrast enhancement with an active targeting capability for tumors in vivo. To the best of our knowledge, this is the first report on the use of pure semiconductor-based SERS-MRI dual-modal nanoprobes in tumor imaging in vivo and in vitro, which has been previously realized only using semiconductor–metal complex materials. The non-metallic materials with SERS–MRI dual-modal imaging established in this report are a promising cancer diagnostic platform, which not only showed excellent performance in early tumor diagnosis but also possesses great potential for image-guided tumor treatment.

Abstract Deep learning methods have emerged as powerful tools for analyzing histopathological images, but current methods are often specialized for specific domains and software environments, and few open-source options exist for deploying models in an interactive interface. Experimenting with different deep learning approaches typically requires switching software libraries and reprocessing data, reducing the feasibility and practicality of experimenting with new architectures. We developed a flexible deep learning library for histopathology called Slideflow, a package which supports a broad array of deep learning methods for digital pathology and includes a fast whole-slide interface for deploying trained models. Slideflow includes unique tools for whole-slide image data processing, efficient stain normalization and augmentation, weakly-supervised whole-slide classification, uncertainty quantification, feature generation, feature space analysis, and explainability. Whole-slide image processing is highly optimized, enabling whole-slide tile extraction at 40x magnification in 2.5 s per slide. The framework-agnostic data processing pipeline enables rapid experimentation with new methods built with either Tensorflow or PyTorch, and the graphical user interface supports real-time visualization of slides, predictions, heatmaps, and feature space characteristics on a variety of hardware devices, including ARM-based devices such as the Raspberry Pi.

Carbon nanofibers (CNFs) are usually prepared by the carbonization of cellulose aerogels obtained from freeze-drying. However, cellulose with low concentration (below 1 wt%) is required to maintain the good porosity of the aerogels due to the strong hydrogen bonding between the cellulose molecules. In order to address this problem, here, ultralight cellulose-derived CNFs have been fabricated by freeze-drying cyclohexane (CHE)/cellulose nanofiber emulsions and carbonization. Field emission scanning electron microscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy are used to characterize the resulting CNFs. It is found that the CNFs consist of three-dimensional carbon networks, whose microstructure is easily adjusted by changing the CHE ratio (from 0 to 25 vol%) in the emulsions. The CNFs with high porosity are attributed to the fact that CHE as the oil phase can effectively weaken the hydrogen bonding and reduce the aggregation of the cellulose nanofibers. Carbon lattice defects and residual oxygen-containing functional groups are regarded as polarization centers, leading to the enhancement of dielectric loss. The conductive carbon networks also improve the conductive loss. All these factors improve the microwave absorption performance of the CNFs. So, the produced CNFs exhibit a superior electromagnetic wave performance with a minimum reflection loss of −42.18 dB and effective absorption bandwidth up to 4.9 GHz at 2 mm with a filling ratio of 2 wt%. This work provides a simple, low-cost, and sustainable synthesis route for CNFs used for ultralight high-performance microwave absorption materials.

BackgroundThe use of large language models (LLM) has recently gained popularity in diverse areas, including answering questions posted by patients as well as medical professionals.ObjectiveTo evaluate the performance and limitations of LLMs in providing the correct diagnosis for a complex clinical case.DesignSeventy-five consecutive clinical cases were selected from the Massachusetts General Hospital Case Records, and differential diagnoses were generated by OpenAI’s GPT3.5 and 4 models.ResultsThe mean number of diagnoses provided by the Massachusetts General Hospital case discussants was 16.77, by GPT3.5 30 and by GPT4 15.45 (p

In this paper, we study the following quasilinear Schrödinger–Poisson system in $\mathbb{R}^3$ \begin{equation*} \begin{cases} -\Delta u+V(x)u+\lambda \phi u=f(x,u),&x\in{\mathbb{R}^3},\\ -\Delta \phi-\varepsilon^4\Delta_4\phi=\lambda u^2,&x\in{\mathbb{R}^3}, \end{cases} \end{equation*} where $\lambda$ and $\varepsilon$ are positive parameters, $\Delta_4u=\hbox{div}(|\nabla u|^2\nabla u)$, $V$ is a continuous and periodic potential function with positive infimum, $f(x,t)\in C( \mathbb{R}^3\times \mathbb{R},\mathbb{R})$ is periodic with respect to $x$ and only needs to satisfy some superquadratic growth conditions with respect to $t$. One nontrivial solution is obtained for $\lambda$ small enough and $\varepsilon$ fixed by a combination of variational methods and truncation technique.

Abstract Spin systems are an attractive candidate for quantum-enhanced metrology. Here we develop a variational method to generate metrological states in small dipolar-interacting spin ensembles with limited qubit control. For both regular and disordered spatial spin configurations the generated states enable sensing beyond the standard quantum limit (SQL) and, for small spin numbers, approach the Heisenberg limit (HL). Depending on the circuit depth and the level of readout noise, the resulting states resemble Greenberger-Horne-Zeilinger (GHZ) states or Spin Squeezed States (SSS). Sensing beyond the SQL holds in the presence of finite spin polarization and a non-Markovian noise environment. The developed black-box optimization techniques for small spin numbers (N ≤ 10) are directly applicable to diamond-based nanoscale field sensing, where the sensor size limits N and conventional squeezing approaches fail.

Guilin is situated in the southern part of China with abundant rainfall. There are 137 reservoirs, which are widely used for irrigation, flood control, water supply and power generation. However, there has been a lack of systematic and full-coverage remote sensing monitoring of reservoir dams for a long time. According to the latest public literature, high-resolution unmanned aerial vehicle (UAV) remote sensing has not been used to detect changes on the reservoir dams of Guilin. In this paper, an intelligent segmentation change detection method is proposed to complete the detection of dam change based on multitemporal high-resolution UAV remote sensing data. Firstly, an enhanced GrabCut that fuses the linear spectral clustering (LSC) superpixel mapping matrix and the Sobel edge operator is proposed to extract the features of reservoir dams. The edge operator is introduced into GrabCut to redefine the new energy function’s smooth item, which makes the segmentation results of enhanced GrabCut more robust and accurate. Then, through image registration, the multitemporal dam extraction results are unified to the same coordinate system to complete the difference operation, and finally the dam change results are obtained. The experimental results of two representative reservoir dams in Guilin show that the proposed method can achieve a very high accuracy of change detection, which is an important reference for related research.

Image matching between the optical and synthetic aperture radar (SAR) is one of the most fundamental problems for earth observation. In recent years, many researchers have used hand-made descriptors with their expertise to find matches between optical and SAR images. However, due to the large nonlinear radiation difference between optical images and SAR images, the image matching becomes very difficult. To deal with the problems, the article proposes an efficient feature matching and position matching algorithm (MatchosNet) based on local deep feature descriptor. First, A new dataset is presented by collecting a large number of corresponding SAR images and optical images. Then a deep convolutional network with dense blocks and cross stage partial networks is designed to generate deep feature descriptors. Next, the hard L2 loss function and ARCpatch loss function are designed to improve matching effect. In addition, on the basis of feature matching, the two-dimensional (2-D) Gaussian function voting algorithm is designed to further match the position of optical images and SAR images of different sizes. Finally, a large number of quantitative experiments show that MatchosNet has a excellent matching effect in feature matching and position matching. The code will be released at: https://github.com/LiaoYun0x0/Feature-Matching-and-Position-Matching-between-Optical-and-SAR.

In this paper, we study the existence of ground state solutions for the following nonlinearly coupled systems of Choquard type with lower critical exponent by variational methods \begin{equation*} \begin{cases} \displaystyle-\Delta u+V(x)u=(I_\alpha\ast|u|^{\frac{\alpha}{N}+1})|u|^{\frac{\alpha}{N}-1}u+p|u|^{p-2}u|\upsilon|^q,&\mbox{in }\mathbb{R}^N,\\ \displaystyle-\Delta\upsilon+V(x)\upsilon=(I_\alpha\ast|\upsilon|^{\frac{\alpha}{N}+1})|\upsilon|^{\frac{\alpha}{N}-1}\upsilon+q|\upsilon|^{q-2}\upsilon|u|^p,&\mbox{in } \mathbb{R}^N. \end{cases} \end{equation*} Where $N\geq3$, $\alpha\in(0,N)$, $I_\alpha$ is the Riesz potential, $p,q\in\big(1,\sqrt{\frac{N}{N-2}}\big)$ and $Np+(N+2)q

Abstract Background Off‐label drug prescribing is common in pediatric clinical medicine, though the extent and impact of this practice in pediatric oncology has not yet been characterized. Methods We completed a retrospective single‐institution cohort study evaluating prevalence, characteristics, and clinical outcomes of off‐label prescribing of 108 FDA‐approved targeted anticancer drugs in patients

Wind shear induced by the velocity difference has an important effect on the stably stratified turbulent flow in the atmospheric convective boundary layer (CBL). Cases with different velocity difference are conducted by Large-eddy simulation (LES) to reveal the contribution of shear effect to entrainment. The result shows that the shear-generated turbulent kinetic energy (TKE) in the entrainment layer is partially consumed by the negative buoyancy, which increases the entrainment flux minimum and enhances the entrainment flux ratio in the range of 0.188 - 0.352. Based on the hypothesis of the independence of the shear-generated TKE and buoyancygenerated TKE, an approach for the fraction of the shear-generated TKE available for entrainment is proposed, and the averaged fraction reaches 38.5%, but the evolution tends to increase with the enlargement of velocity difference.

Membrane fouling is one of the biggest challenges in the widespread application of membrane bioreactors. In this study, a combined system of anaerobic-anoxic-oxic membrane bioreactor (A2O-MBR) and worm reactor (WR) was established for fouling control. In A2O-MBR-WR, the membrane filtration cycle was prolonged by 66.7% due to the confluence of microaerobic treatment and worm predation in WR with the interaction between WR and A2O-MBR. Compared with conventional A2O-MBR, membrane rejection of soluble and colloidal foulants (SCF) in the combined system was decreased by 26.0%, which could be attributed to the higher biodegradability of SCF and the higher bacterial activity in A2O-MBR. Although floc size in A2O-MBR was reduced due to sludge disintegration and worm predation in WR, changes of floc surface properties could counteract this negative effect on fouling. Complex effects of sludge flocs on membrane fouling were further analyzed by the interaction energy between sludge flocs and the clean/fouled membrane based on extended Derjaguin-Landau-Verwey-Overbeek (XDLVO) theory. The energy barriers indicated that flocs in A2O-MBR-WR were difficult to adhere to the membrane and were more likely to detach. Moreover, high-throughput sequencing analysis revealed that the microbial community of the cake layer in the combined system was more even and had a higher proportion of foulants degradation related bacteria, which was beneficial for fouling mitigation. The combination of A2O-MBR and WR has shown significant advantages in membrane fouling mitigation. Keywords: Worm reactor, Membrane fouling, Sludge floc, Interaction energy, Microbial community

Summary: Aggregation-induced emission (AIE) system has long been regarded as a promising substitute to overcome the aggregation-caused quenching in traditional luminescent liquid crystals, which could further enhance its efficiency and application. However, due to the intrinsic weak interaction between hybrid components, heterogeneous inorganic materials-induced AIE process was rarely reported. In this study, trace amounts of amorphous Ag2S microrods and an AIE-active liquid crystalline compound tetraphenylethylene-propylbenzene (TPE-PPE) were proposed to construct additional intense interaction to trigger AIE effect. The enhanced concentration of unsaturated Ag ions and excess positive charge on Ag2S surface promote a cation-π interaction with TPE-PPE, leading to a 36-fold increase in fluorescence, which is predominately high in luminescent liquid crystal system. To the best of our knowledge, this is the first report of the AIE process activated by cation-π interaction. This novel approach would provide guidance to fabricate high-luminescence meso phases for future luminescent display device. : Microstructure; Nanoparticles; Optoelectronics Subject Areas: Microstructure, Nanoparticles, Optoelectronics

Abstract In this paper, we study the following nonlinear Klein–Gordon–Maxwell system: {−Δu+V(x)u−(2ω+ϕ)ϕu=f(x,u)+λh(x)|u|q−2u,x∈R3,Δϕ=(ω+ϕ)u2,x∈R3,(Pλ) $$ \textstyle\begin{cases} -\Delta u+ V(x)u-(2\omega +\phi )\phi u = f(x,u)+\lambda h(x) \vert u \vert ^{q-2}u, & x\in \mathbb{R}^{3},\\ \Delta \phi = (\omega +\phi )u^{2}, & x\in \mathbb{R}^{3}, \end{cases}\displaystyle \quad (\mathrm{P_{\lambda }}) $$ where ω and λ are positive constants, V is a continuous function with negative infimum, q∈(1,2) $q\in (1,2)$, h∈L22−q(R3) $h\in L^{\frac{2}{2-q}}(\mathbb{R}^{3})$ is a positive potential function. Under the classic Ambrosetti–Rabinowitz condition, nontrivial solutions are obtained via the symmetric mountain pass theorem and the mountain pass theorem. In our paper, the nonlinearity F can also change sign and does not need to satisfy any 4-superlinear condition. We extend and improve some existing results to some extent.

Abstract In this paper, we study the following nonlinear Klein–Gordon–Maxwell system: {−Δu+u−(2ω+ϕ)ϕu=λa(x)|u|r−2u−b(x)|u|q−2u,x∈R3,Δϕ=(ω+ϕ)u2,x∈R3,(P) $$\begin{aligned} \textstyle\begin{cases} -\Delta u+ u-(2\omega +\phi )\phi u =\lambda a(x) \vert u \vert ^{r-2}u-b(x) \vert u \vert ^{q-2}u, & x\in \mathbb{R}^{3},\\ \Delta \phi = (\omega +\phi )u^{2}, & x\in \mathbb{R}^{3}, \end{cases}\displaystyle \hspace{75pt}(\mathrm{P}) \end{aligned}$$ where ω is a positive constant, q>2 $q>2$, r∈(2,min{6,q}) $r\in (2,\min \{6,q\})$, a∈L66−r(R3) $a\in L^{\frac{6}{6-r}}(\mathbb{R}^{3})$ is a positive potential, b∈Lloc1(R3) $b\in L^{1}_{\mathrm{loc}}(\mathbb{R}^{3})$ is also a positive potential. Under some integrability assumption on aq−2br−2 $\frac{a^{q-2}}{b^{r-2}}$, nonexistence and existence results are obtained depending on λ via variational methods.

The adipogenic differentiation ability of human adipose-derived mesenchymal stem cells (hADSCs) is critical for the construction of tissue engineering adipose, which shows promising applications in plastic surgery and regenerative medicine. RAB37 is a member of the small RabGTPase family and plays a critical role in vesicle trafficking. However, the role of RAB37 in adipogenic differentiation of hADSCs remains unclear. Here, we report that both the mRNA and protein levels of RAB37 fluctuated during adipogenic differentiation. Upregulation of RAB37 was observed at the early stage of adipogenic differentiation, which was accompanied by increased expression of transcription factors PPARγ2 and C/EBPα, and lipoprotein lipase (LPL). Overexpression of RAB37 promoted adipogenesis of hADSCs, as revealed by Oil Red O staining and increased expression of PPARγ2, C/EBPα, and LPL. Several upregulated cytokines related to RAB37-mediated adipogenic differentiation were identified using a cytokine array, including tissue inhibitor of matrix metalloproteinase 1 (TIMP1). ELISA confirmed that upregulation of RAB37 increased the secretion of TIMP1 by hADSCs. Proximity ligation assay showed that RAB37 interacts with TIMP1 directly. Knockdown of TIMP1 compromised RAB37-mediated adipogenic differentiation. In addition, TIMP1 binds membrane receptor CD63 and integrin β1. RAB37 promotes Tyr397 phosphorylation of FAK, an important protein kinase of the integrin β1 signaling. Moreover, both knockdown of CD63 and inhibitor of FAK impeded RAB37-mediated adipogenic differentiation. In conclusion, RAB37 positively regulates adipogenic differentiation of hADSCs via the TIMP1/CD63/integrin β1 signaling pathway.

Indoor thermal comfort in primary classrooms is important to students' learning and health. The studies focusing on it, especially under the subtropical plateau monsoon climate, are scarce. In this study, the indoor thermal comfort surveys and parameter measurements were made over the period from October 2018 to December 2018 in Kunming, China. A series of indoor thermal comfort and outdoor parameters were measured each 1 h and subjective questionnaire surveys were performed on the selected 20 students every week except on holidays. A series of three-dimensional numerical simulations were carried out using ANSYS Fluent. Keywords: Indoor thermal comfort, PMV, PPD, Primary school classrooms, Field study

ABSTRACT Low doses of antibiotics can trigger secondary metabolite biosynthesis in bacteria, but the underlying mechanisms are generally unknown. We sought to better understand this phenomenon by studying how the antibiotic trimethoprim activates the synthesis of the virulence factor malleilactone in Burkholderia thailandensis. Using transcriptomics, quantitative multiplexed proteomics, and primary metabolomics, we systematically mapped the changes induced by trimethoprim. Surprisingly, even subinhibitory doses of the antibiotic resulted in broad transcriptional and translational alterations, with ∼8.5% of the transcriptome and ∼5% of the proteome up- or downregulated >4-fold. Follow-up studies with genetic-biochemical experiments showed that the induction of malleilactone synthesis can be sufficiently explained by the accumulation of methionine biosynthetic precursors, notably homoserine, as a result of inhibition of the folate pathway. Homoserine activated the malleilactone gene cluster via the transcriptional regulator MalR and gave rise to a secondary metabolome which was very similar to that generated by trimethoprim. Our work highlights the expansive changes that low-dose trimethoprim induces on bacterial physiology and provides insights into its stimulatory effect on secondary metabolism. IMPORTANCE The discovery of antibiotics ranks among the most significant accomplishments of the last century. Although the targets of nearly all clinical antibiotics are known, our understanding regarding their natural functions and the effects of subinhibitory concentrations is in its infancy. Stimulatory rather than inhibitory functions have been attributed to low-dose antibiotics. Among these, we previously found that antibiotics activate silent biosynthetic genes and thereby enhance the metabolic output of bacteria. The regulatory circuits underlying this phenomenon are unknown. We take a first step toward elucidating these circuits and show that low doses of trimethoprim (Tmp) have cell-wide effects on the saprophyte Burkholderia thailandensis. Most importantly, inhibition of one-carbon metabolic processes by Tmp leads to an accumulation of homoserine, which induces the production of an otherwise silent cytotoxin via a LuxR-type transcriptional regulator. These results provide a starting point for uncovering the molecular basis of the hormetic effects of antibiotics.

Summary: Exploring highly surface-enhanced Raman scattering (SERS)-active semiconductors is urgently required for practical applications. Here, with the guidance of theoretical calculations, amorphous rhodium sulfide microbowls with high enhancement factor (1 × 105) and low limit of detection (10−7 M) for rhodamine 6G are successfully developed. This remarkable sensitivity is attributed to quasi-resonance Raman effect and multiple light scattering. The first-principles calculations show that the energy gap of 4-nitrobenzenethiol adsorbed on Rh3S6 is greatly decreased by shifting its lowest unoccupied molecular orbital (LUMO) energy level close to the LUMO of Rh3S6, enabling quasi-resonance Raman effect by visible light. The finite-difference time-domain simulations demonstrate the efficient photon trapping ability enabled by multiple light scattering. The optimum wavelength of ∼633 nm for SERS is predicted in simulations and confirmed in experiments. Our results provide both a deep insight of the photo-driven charge transfer process and an important guidance for designing SERS-active semiconductors. : Chemistry; Analytical Chemistry; Materials Science; Amorphous Material Subject Areas: Chemistry, Analytical Chemistry, Materials Science, Amorphous Material

We investigate a class of fractional Schrödinger-Poisson system via variational methods. By using symmetric mountain pass theorem, we prove the existence of multiple solutions. Moreover, by using dual fountain theorem, we prove the above system has a sequence of negative energy solutions, and the corresponding energy values tend to 0. These results extend some known results in previous papers.

Studying the thickness of the convective boundary layer (CBL) is helpful for understanding atmospheric structure and the diffusion of air pollutants. When there is velocity shear in CBL, the flow field structure is very different from that of shear-free CBL, which makes the thickness model of the entrainment zone deviate. A large-eddy simulation (LES) approach is carried out for a horizontally homogeneous, atmospheric CBL, with a shear effect promoted by velocity difference to explore the bulk scaling model of the entrainment zone thickness. The post-processed data indicate that the existing bulk scaling models cannot synthetically represent the effects of shear and buoyancy on entrainment, resulting in reduced accuracy or limited applicability. Based on the fraction of turbulent kinetic energy (TKE) used for entrainment, a different form of the characteristic velocity scale, which includes the shear effect, is proposed, and a modified bulk scaling model that uses a potential temperature gradient to replace the potential temperature jump across the entrainment zone is constructed with the numerical results. The new model is found to provide an improved prediction of the entrainment zone thickness in a sheared CBL.

In this paper, we are concerned with the multiplicity of nontrivial radial solutions for the following elliptic equation \begin{equation*} \begin{cases} - \Delta u +V(x)u = -\lambda Q(x)|u|^{q-2}u+ Q(x)f(u),\quad x\in\mathbb{R}^N,\\ u(x)\rightarrow 0,\quad \hbox{as}\ |x|\rightarrow +\infty,\end{cases} \tag*{(P)$_\lambda$} \end{equation*} where $1

In this paper, we are concerned with the multiplicity of nontrivial radial solutions for the following elliptic equations (P)λ: -Δu+Vxu=λQxuq-2u+Qxfu,x∈RN; u(x)→0, as x→+∞, where 1

Solutions and weakly compact uniform attractor for the nonautonomous long-short wave equations with translation compact forces were studied in a bounded domain. We first established the existence and the uniqueness of the solution to the system by using Galerkin method and then obtained the uniform absorbing set and the weakly compact uniform attractor of the problem by applying techniques of constructing skew product flow in the extended phase space.