NDF is a transcription factor that stimulates elongation by RNA polymerase II.

RNA polymerase II (Pol II) elongation is a critical step in gene expression. Here we found that NDF, which was identified as a bilaterian nucleosome-destabilizing factor, is also a Pol II transcription factor that stimulates elongation with plain DNA templates in the absence of nucleosomes. NDF binds directly to Pol II and enhances elongation by a different mechanism than that used by transcription factor TFIIS. Moreover, yeast Pdp3, which is related to NDF, binds to Pol II and stimulates elongation. Thus, NDF is a Pol II binding transcription elongation factor that is localized over gene bodies and is conserved from yeast to humans.

Rapid detection of neurons in widefield calcium imaging datasets after training with synthetic data.

Widefield microscopy can provide optical access to multi-millimeter fields of view and thousands of neurons in mammalian brains at video rate. However, tissue scattering and background contamination results in signal deterioration, making the extraction of neuronal activity challenging, laborious and time consuming. Here we present our deep-learning-based widefield neuron finder (DeepWonder), which is trained by simulated functional recordings and effectively works on experimental data to achieve high-fidelity neuronal extraction. Equipped with systematic background contribution priors, DeepWonder conducts neuronal inference with an order-of-magnitude-faster speed and improved accuracy compared with alternative approaches. DeepWonder removes background contaminations and is computationally efficient. Specifically, DeepWonder accomplishes 50-fold signal-to-background ratio enhancement when processing terabytes-scale cortex-wide functional recordings, with over 14,000 neurons extracted in 17 h.

Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis.

Chicken lung is an important target organ of avian influenza virus (AIV) infection, and different pathogenic virus strains lead to opposite prognosis. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of 16 cell types (19 clusters) in the lung tissue of chickens infected with H5N1 highly pathogenic avian influenza virus (HPAIV) and H9N2 low pathogenic avian influenza virus (LPAIV), respectively. Notably, we developed a valuable catalog of marker genes for these cell types. Compared to H9N2 AIV infection, H5N1 AIV infection induced extensive virus replication and the immune reaction across most cell types simultaneously. More importantly, we propose that infiltrating inflammatory macrophages (clusters 0, 1, and 14) with massive viral replication, pro-inflammatory cytokines (IFN-ß, IL1ß, IL6 and IL8), and emerging interaction of various cell populations through CCL4, CCL19 and CXCL13, potentially contributed to the H5N1 AIV driven inflammatory lung injury. Our data revealed complex but distinct immune response landscapes in the lung tissue of chickens after H5N1 and H9N2 AIV infection, and deciphered the potential mechanisms underlying AIV-driven inflammatory reactions in chicken. Furthermore, this article provides a rich database for the molecular basis of different cell-type responses to AIV infection.

DT-13 inhibits the proliferation of pancreatic cancer by inducing apoptosis via AMPK-mTOR signaling.

BACKGROUND/OBJECTIVE: DT-13, the principal active component of Mysidium shortscapes from the Liliaceae family, has garnered substantial interest in cancer therapy owing to its potential anticancer properties. This study investigated the effects of DT-13 on the proliferation and apoptosis of human pancreatic cancer cell lines and aimed to elucidate the underlying mechanisms. METHODS: PANC1 and CFPAC1 cells were exposed to DT-13 and their proliferation was assessed using RTCA and clone formation assays. Apoptotic protein expression was analyzed by western blotting, and apoptotic cells were identified by flow cytometry. RNA was extracted from DT-13 treated and untreated PANC1 cells for RNA sequencing. Differentially expressed genes were identified and subjected to GO bioprocess, KEGG pathway analysis, and western blotting. Finally, to evaluate tumor growth, CFPAC1 cells were subcutaneously injected into BALB/c nude mice. RESULTS: DT-13 inhibited proliferation and induced apoptosis of PANC1 and CFPAC1 cells by activating the AMPK/mTOR pathway and suppressing p70 S6K. Moreover, DT-13 hindered the growth of CFPAC1 xenograft tumors in nude mice. CONCLUSIONS: DT-13 effectively inhibited the growth of human pancreatic cancer cells.

Pemigatinib, a selective FGFR inhibitor overcomes ABCB1-mediated multidrug resistance in cancer cells.

P: -glycoprotein (P-gp/ABCB1) overexpression is one of the primary causes of multidrug resistance (MDR). Therefore, it is crucial to discover effective pharmaceuticals to combat multidrug resistance mediated by ABCB1. Pemigatinib is a selective the fibroblast growth factor receptor (FGFR) inhibitor that is used to treat a variety of solid tumors, Clinical Trials for Urothelial Carcinoma (NCT02872714) completed its research on Pemigatinib. This study aimed to determine whether Pemigatinib can reverse ABCB1-mediated multidrug resistance, as well as its mechanism of action. Pemigatinib substantially reversed ABCB1-mediated multidrug resistance, as determined by a CCK8 assay, and immunofluorescence experiments revealed that Pemigatinib had no effect on the intracellular localization of ABCB1. Pemigatinib was discovered to increase intracellular drug accumulation, thereby reversing multidrug resistance. In addition, Docking analysis revealed that Pemigatinib and ABCB1 have a high affinity for one another. This study concludes that Pemigatinib is capable of reversing the multidrug resistance mediated by ABCB1, offering ideas and references for the clinical application of Pemigatinib.

De novo assembly of the complete mitochondrial genome of pepino (Solanum muricatum) using PacBio HiFi sequencing: insights into structure, phylogenetic implications, and RNA editing.

BACKGROUND: Solanum muricatum is an emerging horticultural fruit crop with rich nutritional and antioxidant properties. Although the chromosome-scale genome of this species has been sequenced, its mitochondrial genome sequence has not been reported to date. RESULTS: PacBio HiFi sequencing was used to assemble the circular mitogenome of S. muricatum, which was 433,466 bp in length. In total, 38 protein-coding, 19 tRNA, and 3 rRNA genes were annotated. The reticulate mitochondrial conformations with multiple junctions were verified by polymerase chain reaction, and codon usage, sequence repeats, and gene migration from chloroplast to mitochondrial genome were determined. A collinearity analysis of eight Solanum mitogenomes revealed high structural variability. Overall, 585 RNA editing sites in protein coding genes were identified based on RNA-seq data. Among them, mttB was the most frequently edited (52 times), followed by ccmB (46 times). A phylogenetic analysis based on the S. muricatum mitogenome and those of 39 other taxa (including 25 Solanaceae species) revealed the evolutionary and taxonomic status of S. muricatum. CONCLUSIONS: We provide the first report of the assembled and annotated S. muricatum mitogenome. This information will help to lay the groundwork for future research on the evolutionary biology of Solanaceae species. Furthermore, the results will assist the development of molecular breeding strategies for S. muricatum based on the most beneficial agronomic traits of this species.

Microstructure-Assisted Wafer-Scale Fabrication of Perovskite Microlaser Arrays.

All inorganic lead halide perovskites exhibit fascinating optical and optoelectronic characteristics for on-chip lasing, but the lack of precise control of wafer-scale fabrication for perovskite microstructure arrays restricts their potential applications in on-chip-integrated devices. In this work, a microstructure-template assisted crystallization method is demonstrated via a designed chemical vapor deposition process, achieving the controllable fabrication of homogeneous perovskite micro-hemispheroid (PeMH) arrays spanning the entire surface area of a 4-inch wafer. Benefiting from the low-loss whispering gallery resonance and plasmon-enhanced light-matter interactions in well-confined hybrid cavities, this CsPbX3/Ag (X = Cl, Br) plasmonic microlasers exhibit quite low thresholds below 10 µJ cm-2. Interestingly, these thresholds can be efficiently modulated through the manipulation of plasmonic resonance and electromagnetic field mode in PeMHs owning various diameters. This strategy not only provides a valuable methodology for the large-scale fabrication of perovskite microstructures but also endorses the potential of all-inorganic perovskite nanostructures as promising candidates for on-chip-integrated light sources.

High-Performance Multifunctional Carbon Fibrous Sponges Derived from Pitch.

3D carbon-based porous sponges are recognized for significant potential in oil absorption and electromagnetic interference (EMI). However, their widespread application is hindered by a common compromise between high performance and affordability of mass production. Herein, a novel approach is introduced that involves laser-assisted micro-zone heating melt-blown spinning (LMHMS) to address this challenge by creating pitch-based submicron carbon fibers (PSCFs) sponge with 3D interconnected structures. These structures bestow the resulting sponge exceptional characteristics including low density (≈20 mg cm-3), high porosity (≈99%), remarkable compressibility (80% maximum strain), and superior conductivity (≈628 S m-1). The resultant PSCF sponges realize an oil/organic solvent sorption capacity over 56 g/g and possess remarkable regenerated ability. In addition to their effectiveness in cleaning up oil/organic solvent spills, they also demonstrated strong electromagnetic shielding capabilities, with a total shielding effectiveness (SE) exceeding 60 dB across the X-band GHz range. In virtue of extreme lightweight of ≈20 mg cm-3, the specific SE of the PSCF sponge reaches as high as ≈1466 dB cm3 g-1, surpassing the performance of numerous carbon-based porous structures. Thus, the unique blend of properties renders these sponges promising for transforming strategies in addressing oil/organic solvent contaminations and providing effective protection against EMI.

Plasma exosomes from patients with active thyroid-associated orbitopathy induce inflammation and fibrosis in orbital fibroblasts.

BACKGROUND: The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. METHODS: OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. RESULTS: Pla-Exos derived from active TAO patients (Pla-ExosTAO-A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO-A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO-A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. CONCLUSION: Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.

ZmWAK02 encoding an RD-WAK protein confers maize resistance against gray leaf spot.

Gray leaf spot (GLS) caused by Cercospora zeina or C. zeae-maydis is a major maize disease throughout the world. Although more than 100 QTLs resistant against GLS have been identified, very few of them have been cloned. Here, we identified a major resistance QTL against GLS, qRglsSB, explaining 58.42% phenotypic variation in SB12×SA101 BC1 F1 population. By fine-mapping, it was narrowed down into a 928 kb region. By using transgenic lines, mutants and complementation lines, it was confirmed that the ZmWAK02 gene, encoding an RD wall-associated kinase, is the responsible gene in qRglsSB resistant against GLS. The introgression of the ZmWAK02 gene into hybrid lines significantly improves their grain yield in the presence of GLS pressure and does not reduce their grain yield in the absence of GLS. In summary, we cloned a gene, ZmWAK02, conferring large effect of GLS resistance and confirmed its great value in maize breeding.

Feature decoupled knowledge distillation enabled lightweight image transmission through multimode fibers.

Multimode fibers (MMF) show tremendous potential in transmitting high-capacity spatial information. However, the quality of multimode transmission is quite sensitive to inherent scattering characteristics of MMF and almost inevitable external perturbations. Previous research has shown that deep learning may break through this limitation, while deep neural networks are intricately designed with huge computational complexity. In this study, we propose a novel feature decoupled knowledge distillation (KD) framework for lightweight image transmission through MMF. In this framework, the frequency-principle-inspired feature decoupled module significantly improves image transmission quality and the lightweight student model can reach the performance of the sophisticated teacher model through KD. This work represents the first effort, to the best of our knowledge, that successfully applies a KD-based framework for image transmission through scattering media. Experimental results demonstrate that even with up to 93.4% reduction in model computational complexity, we can still achieve averaged Structure Similarity Index Measure (SSIM) of 0.76, 0.85, and 0.90 in Fashion-MNIST, EMNIST, and MNIST images respectively, which are very close to the performance of cumbersome teacher models. This work dramatically reduces the complexity of high-fidelity image transmission through MMF and holds broad prospects for applications in resource-constrained environments and hardware implementations.

113Gbps rainbow visible light laser communication system based on 10λ laser WDM emitting module in fiber-free space-fiber link.

With the advent of the sixth-generation mobile communication standard (6 G), the visible light communication (VLC) technology based on wavelength division multiplexing (WDM) technology can effectively solve the problem of shortage of spectrum resources and insufficient channel capacity. This paper introduces one of our technical achievements, namely the construction of a near-real-time visible light laser communication (VLLC) system based on WDM, which includes a self-designed 10-λ fully-packaged visible light laser emission module, 1 m multimode fiber - 0.175 m free space - 1 m multimode fiber optical transmission link, and receiver array. In the transmitter system, we adopt adaptive discrete multitone (DMT) modulation technique combined with Quadrature Amplitude Modulation (QAM) modulation scheme to obtain maximum spectral efficiency (SE). In the receiving system, we utilize the sparse-structured reservoir computing post-equalization algorithm to achieve superior equalization performance on the basis of the traditional post-equalization algorithm. The experimental results indicate that this quasi-real-time communication system has achieved a signal transmission rate of 113.175Gbps. To the best of our knowledge, this work has set a record in the field of high-speed visible light laser communication. Therefore, the laser communication system constructed by this work, with its flexibility in deployment and high-speed performance, demonstrates the significant potential application of visible light laser communication in data center interconnection and high-speed indoor access networks.

Neural-network-based carrier-less amplitude phase modulated signal generation and end-to-end optimization for fiber-terahertz integrated communication system.

In fiber-terahertz integrated communication systems, nonlinear distortion and inter-symbol interference (ISI) will degrade transmission performance. Pre-compensation is an efficient method to handle the channel distortion as it can avoid noise boosting during channel compensation and reduce receiver side signal processing algorithmic complexity at user-end (UE) considering the asymmetric access scenario. In this paper, we propose and experimentally demonstrate a neural-network (NN)-based carrier-less amplitude phase (CAP) modulated signal generation and end-to-end optimization method for a fiber-terahertz integrated communication system. The CAP signal is generated directly from quadrature amplitude modulation symbols and pre-compensated through a transmitter NN, which allows the receiver to demodulate the signal with simple linear digital signal process (DSP). In generating the CAP signal, the NN based transmitter learns a group of filters, which can generate, up-convert, and pre-compensate the signals. Based on the proposed method, a fiber-terahertz integration access system at 220 GHz is demonstrated and a sensitivity gain of 1.2 dB is achieved at a transmission speed of 50 Gbps and the forward error correction (FEC) bit error rate (BER) threshold of 1 × 10-2 compared with the baseline after 10-km fiber transmission and 1-m wireless delivering.

Modulation format recognition in a UVLC system based on an ultra-lightweight model with communication-informed knowledge distillation.

Modulation format recognition (MFR) is a key technology for adaptive optical systems, but it faces significant challenges in underwater visible light communication (UVLC) due to the complex channel environment. Recent advances in deep learning have enabled remarkable achievements in image recognition, owing to the powerful feature extraction of neural networks (NN). However, the high computational complexity of NN limits their practicality in UVLC systems. This paper proposes a communication-informed knowledge distillation (CIKD) method that achieves high-precision and low-latency MFR with an ultra-lightweight student model. The student model consists of only one linear dense layer under a communication-informed auxiliary system and is trained under the guidance of a high-complexity and high-precision teacher model. The MFR task involves eight modulation formats: PAM4, QPSK, 8QAM-CIR, 8QAM-DIA, 16QAM, 16APSK, 32QAM, and 32APSK. Experimental results show that the student model based on CIKD can achieve comparable accuracy to the teacher model. After knowledge transfer, the prediction accuracy of the student model can be increased by up to 87%. Besides, it is worth noting that CIKD's inference accuracy can reach up to 100%. Moreover, the parameters constituting the student model in CIKD correspond to merely 18% of the parameters found in the teacher model, which facilitates the hardware deployment and online data processing of MFR algorithms in UVLC systems.

Wide field-of-view laser-based white light transmitter for visible light communications.

The advancement demands of high-speed wireless data link ask for higher requirements on visible light communication (VLC), where wide coverage stands as a critical criterion. Here, we present the design and implementation of a transmitter structure capable of emitting a high-power wide-coverage white light laser. This laser source exhibits excellent stability, with an irradiation range extending to a half-angle of 20°. Its high brightness satisfies the needs of indoor illumination while maintaining excellent communication performance. Utilizing bit-loading discrete multi-tone modulation, a peak data transmission rate of 3.24 Gbps has been achieved, spanning 1 to 5 m. Remarkably, the data rates exceed 2.5 Gbps within a 40° range at a distance of 5 m, enabling a long-distance, wide coverage, high-speed VLC link for future mobile network applications.

Net-432-Gb/s/λ PS-PAM transmission based on advanced DSP and single DAC for 400†G/λ IM/DD links.

The escalating surge in datacenter traffic creates a pressing demand for augmenting the capacity of cost-effective intensity modulation and direct detection (IM/DD) systems. In this Letter, we report the demonstration of the single-lane 128-GBaud probabilistically shaped (PS)-PAM-20 IM/DD transmission using only a single digital-to-analog converter (DAC) for a net 400 G/λ system. Based on the advanced digital signal processing (DSP), we achieve net bitrates of up to 437 Gb/s for optical back-to-back and 432 Gb/s after the 0.5-km SSMF transmission in the C-band with 128-Gbaud PS-PAM-20 signals. This work is the latest demonstration on ultra-high-order PS-PAM signals achieving net bitrates exceeding 400 Gb/s despite symbol rate limitations. Notably, to the best of our knowledge, the realized net information rate ([net bitrate]/[symbol rate]) of 3.37 marks a new achievement within the domain of 400 G/λ IM/DD systems, with promising implications for enhancing bandwidth efficiency in the upcoming 1.6-Tb Ethernet scenario.

General Construction of Asymmetric Amine Ethers via Efficient Transesterification.

A novel method to prepare asymmetric amine ethers is reported. Tertiary amine alcohol hydrogen sulfate intermediates are prepared through a reactive distillation process, followed by the transesterification process to afford eventually asymmetric amine ethers. Experiments and DFT calculations revealed the essential roles the sulfate group plays in the highly selective monoesterification process. This clean method is tolerant towards various functional groups with good yields under mild condition, which is obviously superior compared to the conventional processes.

Discovery of Unusual Ajmaline-Macroline Type Bisindole Alkaloids from Alstonia macrophylla by Building Blocks-Based Molecular Networking.

Three unusual ajmaline-macroline type bisindole alkaloids, alsmaphylines A-C, together with their postulated biogenetic precursors, were isolated from the stem barks and leaves of Alstonia macrophylla via the building blocks-based molecular network (BBMN) strategy. Alsmaphyline A represents a rare ajmaline-macroline type bisindole alkaloid with an S-shape polycyclic ring system. Alsmaphylines B and C are two novel ajmaline-macroline type bisindole alkaloids with N-1-C-21' linkages, and the former possesses an unconventional stacked conformation due to the presence of intramolecular noncovalent interactions. The chemical structures including absolute configurations of alsmaphylines A-C were established by comprehensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray crystallography. In addition, a plausible biosynthetic pathway of these bisindole alkaloids as well as their ability to promote the protein synthesis on HT22 cells were discussed.

Identification of a novel marker and its associated laccase gene for regulating ear length in tropical and subtropical maize lines.

KEY MESSAGE: This study revealed the identification of a novel gene, Zm00001d042906, that regulates maize ear length by modulating lignin synthesis and reported a molecular marker for selecting maize lines with elongated ears. Maize ear length has garnered considerable attention due to its high correlation with yield. In this study, six maize inbred lines of significant importance in maize breeding were used as parents. The temperate maize inbred line Ye107, characterized by a short ear, was crossed with five tropical or subtropical inbred lines featuring longer ears, creating a multi-parent population displaying significant variations in ear length. Through genome-wide association studies and mutation analysis, the A/G variation at SNP_183573532 on chromosome 3 was identified as an effective site for discriminating long-ear maize. Furthermore, the associated gene Zm00001d042906 was found to correlate with maize ear length. Zm00001d042906 was functionally annotated as a laccase (Lac4), which showed activity and influenced lignin synthesis in the midsection cells of the cob, thereby regulating maize ear length. This study further reports a novel molecular marker and a new gene that can assist maize breeding programs in selecting varieties with elongated ears.

Synthesis of Aminomethylpyridine-Decorated Polyamidoamine Dendrimer/Apple Residue for the Efficient Capture of Cd(II).

Water contamination irritated by Cd(II) brings about severe damage to the ecosystem and to human health. The decontamination of Cd(II) by the adsorption method is a promising technology. Here, we construct aminomethylpyridine-functionalized polyamidoamine (PAMAM) dendrimer/apple residue biosorbents (AP-G1.0-AMP and AP-G2.0-AMP) for adsorbing Cd(II) from aqueous solution. The adsorption behaviors of the biosorbents for Cd(II) were comprehensively evaluated. The maximum adsorption capacities of AP-G1.0-AMP and AP-G2.0-AMP for Cd(II) are 1.40 and 1.44 mmol·g-1 at pH 6. The adsorption process for Cd(II) is swift and can reach equilibrium after 120 min. The film diffusion process dominates the adsorption kinetics, and a pseudo-second-order model is appropriate to depict this process. The uptake of Cd(II) can be promoted by increasing concentration and temperature. The adsorption isotherm follows the Langmuir model with a chemisorption mechanism. The biosorbents also display satisfied adsorption for Cd(II) in real aqueous media. The adsorption mechanism indicates that C-N, N═C, C-O, CONH, N-H, and O-H groups participate in the adsorption for Cd(II). The biosorbents display a good regeneration property and can be reused with practical value. The as-prepared biosorbents show great potential for removing Cd(II) from water solutions with remarkable significance.