Search

Iron isotope compositions, along with the partial extraction of iron in its various forms, can be utilized to investigate the complex interplay of iron migration and transformation with respect to iron isotope patterns. This study investigated the iron composition of a typical loess-paleosol sequence in Northeast China and aimed to understand the influence of iron migration and transformation of the typical loess-paleosol sequence on iron isotopes and environmental and climatic changes that occurred in the region over time by analyzing the distribution and characteristics of iron compositions in sedimentary layers. Samples were collected from Chaoyang in Northeast China, and the iron isotopic composition was analyzed using the multi-receiver inductively coupled plasma mass spectrometer (MC-ICP-MS). The findings revealed depth-dependent variations in the content of different iron forms, reflecting paleoclimatic shifts primarily through pedogenic transformation processes. Notably, iron migration within the section was observed to be limited. The variations in the reddening index and magnetic susceptibility of the loess-paleosol were primarily influenced by the presence of free iron (Fed), exhibiting a range of colors from yellow to red-yellow and red. The δ56Fe values for loess and paleosols ranged from 0.097 ± 0.035‰ to 0.167 ± 0.010‰, with an average of 0.133 ± 0.024‰ and a coefficient of variation (CV) of 15.66% at the stratum scale. These values indicated a systematic enrichment of heavy iron isotopes and a significant negative correlation with the slightly fluctuating total iron content. Specifically, our analysis highlighted distinct differences in δ56Fe values between paleosol (0.126 ± 0.024‰) and loess (0.146 ± 0.021‰). The δ56Fe in Fed was negative, averaging −0.101 ± 0.022‰, while the δ56Fe in silicate-bound iron was positive, averaging 0.156 ± 0.032‰. Intense pedogenesis, driven by warm and wet climates, facilitated iron transformations and migrations, resulting in the accumulation of light iron isotopes in the paleosols. These transformations and migrations were predominantly observed in microdomains characterized by iron depletions and concentrations, as reflected in the profile morphologies. However, the limited iron transformations and migrations did not result in significant Fe redistribution within the soil section, as evidenced by the limited variations in δ56Fe with soil depth at the stratum scale. Sampling from the stratum or pedogenic horizon could potentially create the illusion of the minimal fractionation of iron isotopes within the sequence. Therefore, a detailed examination of the iron isotope composition in the micro-domains of the loess-paleosol sequence is crucial to elucidate the fractionation processes and mechanisms of iron isotopes during the formation of these sequences. [ABSTRACT FROM AUTHOR]

Recently, π–π stacked antiaromatic π‐systems have received considerable attention because they can exhibit stacked‐ring aromaticity due to substantial intermolecular orbital interactions. Here, we report three antiaromatic norcorrole dimers that self‐assemble to form supramolecular architectures through chiral self‐sorting. A 2,2’‐linked norcorrole dimer with 3,5‐di‐tert‐butylphenyl groups forms a π‐stacked dimer both in solid and solution states via homochiral self‐sorting. Its association constant in solution is (3.6±1.7)×105 M−1 at 20 °C. In the solid state, 3,3’‐linked norcorrole dimers with 3,5‐di‐tert‐butylphenyl and phenyl groups afford macrocyclic and helical supramolecular assemblies via heterochiral and homochiral self‐sorting, respectively. Notably, the subtle modification in the substituent resulted in a complete change in the structure of the aggregates and the chiral self‐sorting mode. The present findings demonstrate that structural manipulation in antiaromatic monomer units leads to the formation of various supramolecular assemblies on the basis of the attractive interactions between antiaromatic π‐systems. [ABSTRACT FROM AUTHOR]

As immunotherapy makes its way into the perioperative setting, a growing number of clinical trials are expanding the evidence base for resectable non-small cell lung cancer (NSCLC) management. Identifying the optimal treatment pattern—whether it's neoadjuvant, adjuvant, or a combination of both—is a crucial next step, particularly in pinpointing which patients benefit the most. This decision-making process requires a multi-disciplinary treatment team capable of utilizing tissue and plasma genomic testing to inform therapeutic choices. Leveraging the perioperative treatment platform, it remains pivotal to integrate circulating tumor DNA (ctDNA) monitoring into clinical trial design efficiently and provide clear guidance on treatment. [ABSTRACT FROM AUTHOR]

Introduction: Well-calibrated models for personalized prognostication of patients with gastrointestinal neuroendocrine neoplasms (GINENs) are limited. This study aimed to develop and validate a machine-learning model to predict the survival of patients with GINENs. Methods: Oblique random survival forest (ORSF) model, Cox proportional hazard risk model, Cox model with least absolute shrinkage and selection operator penalization, CoxBoost, Survival Gradient Boosting Machine, Extreme Gradient Boosting survival regression, DeepHit, DeepSurv, DNNSurv, logistic-hazard model, and PC-hazard model were compared. We further tuned hyperparameters and selected variables for the best-performing ORSF. Then, the final ORSF model was validated. Results: A total of 43,444 patients with GINENs were included. The median (interquartile range) survival time was 53 (19–102) months. The ORSF model performed best, in which age, histology, M stage, tumor size, primary tumor site, sex, tumor number, surgery, lymph nodes removed, N stage, race, and grade were ranked as important variables. However, chemotherapy and radiotherapy were not necessary for the ORSF model. The ORSF model had an overall C index of 0.86 (95% confidence interval, 0.85–0.87). The area under the receiver operation curves at 1, 3, 5, and 10 years were 0.91, 0.89, 0.87, and 0.80, respectively. The decision curve analysis showed superior clinical usefulness of the ORSF model than the American Joint Committee on Cancer Stage. A nomogram and an online tool were given. Conclusion: The machine learning ORSF model could precisely predict the survival of patients with GINENs, with the ability to identify patients at high risk for death and probably guide clinical practice. [ABSTRACT FROM AUTHOR]

The authors review the literature on last mile delivery logistics within commercial and humanitarian supply chains from 2010 to the end of 2021. The scope of the last mile, including last mile logistics, last mile distribution, and last-mile mile delivery, is covered. A unifying terminology of the major concepts in this field and a bibliometric analysis are provided. Based on the analysis, the authors further classify and discuss the literature into three clusters: humanitarian relief, commercial logistics, and emerging technologies. Within each generated cluster, research gaps and current trends are identified. Future research directions are suggested based on this literature review. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by motor neuron degeneration. The development of ALS involves metabolite alterations leading to tissue lesions in the nervous system. Recent advances in neuroimaging have significantly improved our understanding of the underlying pathophysiology of ALS, with findings supporting the corticoefferent axonal disease progression theory. Current studies on neuroimaging in ALS have demonstrated inconsistencies, which may be due to small sample sizes, insufficient statistical power, overinterpretation of findings, and the inherent heterogeneity of ALS. Deriving meaningful conclusions solely from individual imaging metrics in ALS studies remains challenging, and integrating multimodal imaging techniques shows promise for detecting valuable ALS biomarkers. In addition to giving an overview of the principles and techniques of different neuroimaging modalities, this review describes the potential of neuroimaging biomarkers in the diagnosis and prognostication of ALS. We provide an insight into the underlying pathology, highlighting the need for standardized protocols and multicenter collaborations to advance ALS research. [ABSTRACT FROM AUTHOR]

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead. [ABSTRACT FROM AUTHOR]

Poly(ionic liquid) (PIL)‐based porous membranes are extensively investigated as soft polymer actuators. While PILs have shown significant advancements in membrane fabrication and stabilization of metal nanoparticles (MNPs), research on integrating MNPs into porous membranes to achieve actuation behavior under multiple stimuli is limited. Herein, this work presents a new paradigm for designing a porous PIL‐polyacrylic acid (PAA) membrane with a distinct MNP gradient via a top‐bottom diffusion approach involving a metal salt precursor solution and NaBH4 as a reducing agent. The strong binding sites provided by PILs, combined with the gradient distribution of ‐COO− groups across the membrane cross‐section, play a significant role in controlling the MNPs' gradient distribution. Interestingly, the MNPs within the membrane display excellent catalytic activity in exothermic reactions such as H2O2 decomposition, dissipating uneven heat that quickly permeates the membrane network. This induces asymmetrical swelling of polymer chains, resulting in rapid membrane bending. Furthermore, such MNP‐loaded membrane could serve as a portable test paper for visually monitoring H2O2. This advancement paves the way for the development of intricate smart actuation materials and expands their practical applications in various real‐life scenarios. [ABSTRACT FROM AUTHOR]

Entanglement purification is an important and useful tool in quantum communications that allows parties to enhance the entanglement of a set of less-entangled particles using local operations and classical communication. Utilizing photon polarization parity checks implemented through the coupling system between a single-sided cavity and a charged quantum dot, an entanglement purification scheme is proposed in this paper. The fidelity and the success probability of the scheme are calculated under bit-flip error channel and depolarizing channel, respectively. Furthermore, the impact of imperfect quantum-dot-cavity coupling system is investigated, and the feasibility is discussed. In the strong coupling and weak cavity side leakage regime, our scheme can approach the maximal fidelities and success probabilities in theory. So the scheme has potential applications in long-distance quantum communication with the development of relevant technologies. [ABSTRACT FROM AUTHOR]

[Display omitted] No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab. [ABSTRACT FROM AUTHOR]

This paper presents a unified experimental and numerical investigation on the transition from brittle to ductile behavior in a low-porosity sandstone under drained conditions. The experimental results demonstrate a transition in the mechanical behavior from brittle faulting to dilatant ductile flow at room temperature with an increase in effective confining pressure, suggesting that microcracking-controlled local friction is the underlying plastic deformation mechanism. For constitutive modeling, the sandstone is considered as a heterogeneous medium composed of a pores-weakened elastic solid matrix and distributed microcracks. By following a two-step homogenization procedure and irreversible thermodynamics framework, a micromechanics-based elastoplastic damage model incorporating a non-associated local plastic flow rule is formulated, in which the coupling between plasticity, damage and pore pressure is taken into account. In this context, a non-associated macroscopic effective strength criterion as an inherent part of the corresponding model is derived. Originally, a theoretical linear relation between critical state of damage at peak strength and effective confining pressure is established, which is efficient in describing post-peak softening behavior. Comparisons of numerical simulations with experimental data demonstrate that the proposed model effectively reproduces the main features of the sandstone with a brittle-ductile transition. • A transition from brittle to ductile behavior in a saturated low-porosity sandstone is observed. • A non-associated micromechanics-based constitutive model is developed. • A non-associated macroscopic effective strength criterion is derived. • A linear relation between critical damage and effective confining pressure is established. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer (OC) is one of the most common gynecological tumors with high morbidity and mortality. Altered serum N-glycome has been observed in many diseases, while the association between serum protein N-glycosylation and OC progression remains unclear, particularly for the onset of carcinogenesis from benign neoplasms to cancer. Methods: Herein, a mass spectrometry based high-throughput technique was applied to characterize serum N-glycome profile in individuals with healthy controls, benign neoplasms and different stages of OC. To elucidate the alterations of glycan features in OC progression, an orthogonal strategy with lectin-based ELISA was performed. Results: It was observed that the initiation and development of OC was associated with increased high-mannosylationand agalactosylation, concurrently with decreased total sialylation of serum, each of which gained at least moderately accurate merits. The most important individual N-glycans in each glycan group was H7N2, H3N5 and H5N4S2F1, respectively. Notably, serum N-glycome could be used to accurately discriminate OC patients from benign cohorts, with a comparable or even higher diagnostic score compared to CA125 and HE4. Furthermore, bioinformatics analysis based discriminative model verified the diagnostic performance of serum N-glycome for OC in two independent sets. Conclusions: These findings demonstrated the great potential of serum N-glycome for OC diagnosis and precancerous lesion prediction, paving a new way for OC screening and monitoring. [ABSTRACT FROM AUTHOR]

Synthetic Aperture Radar (SAR) imagery is significant in remote sensing, but the limited spatial resolution results in restricted detail and clarity. Current super-resolution methods confront challenges such as complex network structure, insufficient sensing capability, and difficulty extracting features with local and global dependencies. To address these challenges, DMSC-GAN, a SAR image super-resolution technique based on the c-GAN framework, is introduced in this study. The design objective of DMSC-GAN is to enhance the flexibility and controllability of the model by utilizing conditional inputs to modulate the generated image features. The method uses an encoder–decoder structure to construct a generator and introduces a feature extraction module that combines convolutional operations with Deformable Multi-Head Self-Attention (DMSA). This module can efficiently capture the features of objects of various shapes and extract important background information needed to recover complex image textures. In addition, a multi-scale feature extraction pyramid layer helps to capture image details at different scales. DMSC-GAN combines perceptual loss and feature matching loss and, with the enhanced dual-scale discriminator, successfully extracts features from SAR images for high-quality super-resolution reconstruction. Extensive experiments confirm the excellent performance of DMSC-GAN, which significantly improves the spatial resolution and visual quality of SAR images. This framework demonstrates strong capabilities and potential in advancing super-resolution techniques for SAR images. [ABSTRACT FROM AUTHOR]

Dermal papilla cells (DPCs) undergo premature ageing in androgenetic alopecia and senescent alopecia. As critical components of hair follicle reconstruction, DPCs are also prone to senescence in vitro, resulting in a diminished hair follicle inductivity capacity. Dermal sheath cup cells (DSCCs), a specific subset of hair follicle mesenchymal stem cells, intimately linked to the function of DPCs. The primary objective of this research is to investigate the anti‐ageing effect of exosomes derived from DSCCs (ExoDSCCs) on DPCs. Exosomes were utilized to treat H2O2‐induced DPCs or long‐generation DPCs(P10). Our findings demonstrate that ExoDSCCs(P3) promote the proliferation, viability and migration of senescent DPCs while inhibiting cell apoptosis. The expression of senescence marker SA‐β‐Gal were significantly downregulated in senescent DPCs. When treated with ExoDSCCs(P3), expression of inducibility related markers alkaline phosphatase and Versican were significantly upregulated. Additionally, ExoDSCCs(P3) activated the Wnt/β‐catenin signalling in vitro. In patch assay, ExoDSCCs(P3) significantly promoted hair follicle reconstruction in senescent DPCs. In summary, our work highlights that ExoDSCCs(P3) may restore the biological functions and improve the hair follicle induction ability of senescent DPCs. Therefore, ExoDSCCs(P3) may represent a new strategy for intervening in the ageing process of DPCs, contributing to the prevention of senile alopecia. [ABSTRACT FROM AUTHOR]

Emodin, a natural anthraquinone derivative, possesses anti-proliferative and anti-inflammatory properties in skin diseases. However, little information is available on the efficacy of emodin in treating acne vulgaris (acne). This study aims to investigate the protective effects and potential mechanisms of emodin as an anti-acne agent. In vitro, SZ95 sebocytes was chose to establish an acneigenic cellular model. We found that emodin effectively inhibited proliferation, induced cell cycle arrest and apoptosis of SZ95 sebocytes in a dose-dependent manner. To evaluate the lipid-lowering potential of emodin, we examined the levels of lipid contents and lipogenic transcription factors, and found that both lipid production and protein expression of PPARγ, LXR α/β, and SREBP-1 were decreased after treatment with emodin. Furthermore, our results revealed that emodin inhibited sebaceous lipogenesis induced by insulin-like growth factor 1 (IGF-1), which was accompanied by a potent inhibition of the phosphoinositide-3-kinase (PI3K)/Akt/forkhead box protein O1 (FoxO1) pathway. In detail, emodin augmented the inhibitory effect of isotretinoin and PI3K inhibitor LY294002, while attenuating the activation of IGF-1 on PI3K/Akt/FoxO1 pathway. In addition, emodin could decrease the secretion of pro-inflammatory cytokines IL-6 and IL-8, and suppress the expression of NLRP3, capase-1, IL-1β, and IL-18 in SZ95 sebocytes exposed to Cutibacterium acnes. Overall, our study provides preliminary evidence supporting the anti-growth, anti-lipogenic and anti-inflammatory properties of emodin, indicating the potential therapeutic application of emodin for acne treatment. [ABSTRACT FROM AUTHOR]

To investigate the prospective association of frailty status with the long-term risk of elderly-onset IBD in a large prospective cohort. Participants free of IBD and cancer at enrollment from the UK Biobank cohort were included. Baseline pre-frail and frail status was measured by Fried phenotype including weight loss, exhaustion, low grip strength, low physical activity and slow walking pace, defined as meeting one or two criteria and meeting three or more criteria. Primary outcome was elderly-onset IBD, including elderly-onset ulcerative colitis (UC) and Crohn's disease (CD). Multivariable Cox regression was conducted to examine the related associations. Overall, 417,253 participants (aged 56.18 ± 8.09 years) were included. Of whom, 19,243 (4.6 %) and 188,219 (45.1 %) were considered frail and pre-frail, respectively. During a median of 12.4 years follow-up, 1503 elderly-onset IBD cases (1001 UC, 413 CD, and 89 IBD-Unclassified) were identified. Compared with non-frail, individuals with frail (HR=1.40, 95 %CI: 1.13–1.73) and pre-frail (HR=1.15, 1.03–1.28) showed significantly higher risk of elderly-onset IBD after multivariable adjustment (P trend <0.001). The positive association was more evident regarding risk of elderly-onset CD (HR=2.16, 1.49–3.13 for frail; HR=1.49,1.20–1.85 for pre-frail; P trend <0.001). Sensitivity analyses and subgroup analyses according to age, gender and body mass index (BMI) demonstrated similar results. Frailty and pre-frailty are associated with increased risk of elderly-onset IBD, particularly elderly-onset CD. [ABSTRACT FROM AUTHOR]

Electron cyclotron harmonic (ECH) waves can scatter electrons into the atmosphere causing diffuse aurora with diffusion coefficients depending on the wave frequency. Here we report the Van Allen Probe observations of chirping ECH elements, which are fine structures with a frequency‐chirping rate of ∼kHz/s. 1,834 samples are identified in the 51‐month database and over 93 percent of them exhibit a falling tone pattern. ECH elements cover a broad region from 18 Magnetic Local Time (MLT) through dawn to 14 MLT with L = 4 − 7, and mainly occur in the region of 00–07 MLT with L = 5 − 6. More ECH elements are observed with the occurrence region extending to lower L‐shells during the geomagnetic activity period. Chirping ECH elements can propagate to |MLAT| ∼ 20°, but be confined by the contour of magnetic field strength. The statistical results can be applied on the global simulation of ECH‐induced electron penetration. Plain Language Summary: Electron cyclotron harmonic (ECH) wave plays a critical role in the magnetospheric dynamics by diffusing energetic electrons into the atmosphere. Previous studies show that the diffusion coefficients are very sensitive to the wave frequency. Here based on the Van Allen Probes data, we report the presence of ECH frequency chirping structures (so‐called chirping ECH elements) in the magnetosphere. The duration of ECH elements is comparable with the well‐known chorus elements. Adopting a 51‐month database, we study the statistical properties of such ECH elements. All of the ECH elements occur in the first harmonic band and more than 93 percent of them are falling tones. ECH elements cover a broad range of L = 4 − 7 from 18 MLT through dawn to 14 MLT, and mainly appear in the region L = 5 − 6 at the midnight to dawn sector. It is widely accepted that ECH waves generally occur in the equatorial region. Here the ECH elements can propagate to |MLAT| ∼ 20°. Moreover, when the geomagnetic activities get more intense, more ECH elements can be observed and they can extend to lower L‐shells. The current results could be important for investigating their generation mechanism and quantifying the ECH‐electron resonance process. Key Points: All chirping electron cyclotron harmonic (ECH) elements (1,834 samples) occur in the first harmonic band, showing a distinct preference to falling tone structures (>93%)The chirping ECH elements cover a broad region of radiation belts, with a higher occurrence in the region of 00–07 Magnetic Local Time (MLT) with L = 5 − 6As the AE index increases, the occurrence region of chirping ECH elements extends to lower L‐shells [ABSTRACT FROM AUTHOR]

Asymmetric arylation of secondary phosphine oxides (SPOs) has been rapidly developed, while there are few theoretical studies reported. DFT computations were carried out to study the whole catalytic cycle of Pd/Xiao‐Phos‐catalyzed asymmetric arylation of SPOs, and a modified mechanism including tautomerization and arylation was presented. Some new tautomerization mechanisms have been traversed, including base‐assisted and Pd/Xiao‐Phos‐catalyzed tautomerization. These are different from the existing report, where base‐assisted tautomerization is the most favored. The resulting intermediate enters the downstream arylation directly. Furthermore, oxidative addition is identified as the enantioselectivity‐determining step. IGMH analysis results indicate that the different non‐bonding interactions between Xiao‐Phos and SPO parts determine the enantioselectivity. This work not only provides deeper insights into the self‐adaptive property of SadPhos ligands but also offers valuable guidance for ligand design. Newly proposed tautomerization mechanisms will also bring some inspiration to subsequent related research. [ABSTRACT FROM AUTHOR]

T cells rely on their T cell receptors (TCRs) to discern foreign antigens presented by human leukocyte antigen (HLA) proteins. The TCRs of an individual contain a record of this individual's past immune activities, such as immune response to infections or vaccines. Mining the TCR data may recover useful information or biomarkers for immune related diseases or conditions. Some TCRs are observed only in the individuals with certain HLA alleles, and thus characterizing TCRs requires a thorough understanding of TCR-HLA associations. The extensive diversity of HLA alleles and the rareness of some HLA alleles present a formidable challenge for this task. Existing methods either treat HLA as a categorical variable or represent an HLA by its alphanumeric name, and have limited ability to generalize to the HLAs that are not seen in the training process. To address this challenge, we propose a neural network-based method named Deep learning Prediction of TCR-HLA association (DePTH) to predict TCR-HLA associations based on their amino acid sequences. We demonstrate that DePTH is capable of making reasonable predictions for TCR-HLA associations, even when neither the HLA nor the TCR have been included in the training dataset. Furthermore, we establish that DePTH can be used to quantify the functional similarities among HLA alleles, and that these HLA similarities are associated with the survival outcomes of cancer patients who received immune checkpoint blockade treatments. Author summary: T cells are critical components of the human immune system. A T cell receptor (TCR) is a protein complex found on the surface of T cells, and it determines the antigens that a T cell recognizes. The TCR repertoire, which is the collection of all the TCRs within an individual, provides rich information about the history and current activities of the immune system. A TCR-antigen interaction is mediated by a protein called human leukocyte antigen (HLA). HLA genes are highly polymorphic in the human population, contributing to the variation of human immune response to different types of antigens. Studying the associations between TCRs and HLAs can help us identify functional TCRs given the HLAs of an individual. To this end, we develop a deep learning method to predict TCR-HLA associations based on their amino acid sequences. This method allows us to borrow information across different HLA genes. We demonstrate that the predictions of our model can be used to quantify the functional similarities of HLA alleles and such similarities are associated with cancer patients' survival outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: The developmental process, divided into four different stages (egg, larva, pupa and adult), is the main reason for their remarkable diversification and expansion of the insect group Holometabola. Advanced morphological techniques have been used to demonstrate the 3D thoracic anatomical structures of the holometalous model organism fruit fly, Drosophila melanogaster, before and after emergence, in order to uncover the transformation process of the muscles, nerves, and gut during development. Skeletal changes affect the original positions of the muscles. The muscles vary in size, not only becoming longer and broader, but also shorter and narrower. Different muscle shapes may appear during development. The number of bundles may also vary. The soft tissues in the body may fix the free ends of the growing muscles, and a strong adult skeleton likely causes the absence of some muscles and tendons. The flight muscles appear very early, probably to achieve full functionality of these very large adult-specific muscles in time. There are some differences during the same developmental period between the two sexes. Most muscles of the larvae and adults with similar attachment positions change their functions from supporting crawling to supporting flying and walking under the control of a more complex ventral nerve cord. The midguts of the larva and the adult are nearly the same. The model organism Drosophila melanogaster, as a species of Holometabola, undergoes a series of transformations during metamorphosis. To deeply understand its development, it is crucial to study its anatomy during the key developmental stages. We describe the anatomical systems of the thorax, including the endoskeleton, musculature, nervous ganglion, and digestive system, from the late pupal stage to the adult stage, based on micro-CT and 3D visualizations. The development of the endoskeleton causes original and insertional changes in muscles. Several muscles change their shape during development in a non-uniform manner with respect to both absolute and relative size; some become longer and broader, while others shorten and become narrower. Muscular shape may vary during development. The number of muscular bundles also increases or decreases. Growing muscles are probably anchored by the tissues in the stroma. Some muscles and tendons are absent in the adult stage, possibly due to the hardened sclerites. Nearly all flight muscles are present by the third day of the pupal stage, which may be due to the presence of more myofibers with enough mitochondria to support flight power. There are sexual differences in the same developmental period. In contrast to the endodermal digestive system, the functions of most thoracic muscles change in the development from the larva to the adult in order to support more complex locomotion under the control of a more structured ventral nerve cord based on the serial homology proposed herein. [ABSTRACT FROM AUTHOR]

Background: Camrelizumab has shown encouraging efficacy in advanced non-small cell lung cancer (NSCLC), either as monotherapy or combined with chemotherapy. However, evidence of neoadjuvant camrelizumab for NSCLC remains lacking. Methods: Patients with NSCLC treated with neoadjuvant camrelizumab-based therapy followed by surgery between December 2020 and September 2021 were retrospectively reviewed. Demographic and clinical data, details of neoadjuvant therapy and surgical information were retrieved. Results: In this multicenter retrospective real-world study, 96 patients were included. Ninety-five patients (99.0%) received neoadjuvant camrelizumab combined with platinum-based chemotherapy, with a median of 2 cycles (range 1–6). The median interval from the last dose to surgery was 33 days (range 13–102 days). Seventy patients (72.9%) underwent minimally invasive surgery. Lobectomy was the most frequent surgical procedure (94 [97.9%]). The median estimated intraoperative blood loss was 100 mL (range 5–1200 mL), and the median operative time was 3.0 h (range 1.5–6.5 h). The R0 resection rate was 93.8%. Twenty-one patients (21.9%) experienced postoperative complications, with the most common being cough and pain (both 6 [6.3%]). The overall response rate was 77.1% (95% CI 67.4–85.0%), and the disease control rate was 93.8% (95% CI 86.9–97.7%). Twenty-six patients (27.1%, 95% CI 18.5–37.1%) had pathological complete response. Neoadjuvant treatment-related adverse events of grade ≥ 3 were reported in seven patients (7.3%), with the most frequent being abnormal liver enzymes (two [2.1%]). No treatment-related deaths were reported. Conclusion: The real-world data indicated that camrelizumab-based therapy had promising efficacy for NSCLC in the neoadjuvant setting, with manageable toxicities. Prospective studies investigating neoadjuvant camrelizumab are warranted. [ABSTRACT FROM AUTHOR]

To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P < 0.01), as well as age, LVEF, heart rate at anaerobic domain, peak oxygen uptake in kilograms of body weight, percentage of peak oxygen uptake to the predicted value, the oxygen uptake efficiency slope and carbon dioxide ventilation equivalent slope (P < 0.05). Multivariate analysis showed gender, age, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave, ST-T change, and peak oxygen pulse were independent risk factors of CHD. The pre-test probability model of CHD combined with CPET indexes has good distinguish and calibrate ability, its prediction accuracy is slightly better than DCS and UDFM, which still needs to be verified externally in more samples. [ABSTRACT FROM AUTHOR]

For an integrable hierarchy which possesses a bihamiltonian structure with semisimple hydrodynamic limit, we prove that the linear reciprocal transformation with respect to any of its symmetry transforms it to another bihamiltonian integrable hierarchy. Moreover, we show that the central invariants of the bihamiltonian structure are preserved under such a linear reciprocal transformation. [ABSTRACT FROM AUTHOR]

Use of hydrogen‐bonded organic frameworks (HOFs) for enzyme immobilization faces challenges in the improvement of enzyme activity recovery and the assembly of cofactor‐dependent multienzyme systems. Herein, we report a polyelectrolyte‐assisted encapsulation approach (PAEA) that enables two cascades with four oxidoreductases and two nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) cofactors co‐encapsulated in BioHOF‐1 with excellent cargo loading and over 100 % cascade activity. The key role of the polyelectrolyte is to coat enzymes and tether NAD(P)H, thus interacting with HOF monomers in place of enzymes, avoiding the destruction of enzymes by HOF monomers. The versatility and efficiency of PAEA are further illustrated by an HOF‐101‐based bio‐nanoreactor. Moreover, the immobilization by PAEA makes enzymes and NAD(P)H display excellent stability and recyclability. This study has demonstrated a facile and versatile PAEA for fabricating cofactor‐dependent multienzyme cascade nanoreactors with HOFs. [ABSTRACT FROM AUTHOR]

Use of hydrogen‐bonded organic frameworks (HOFs) for enzyme immobilization faces challenges in the improvement of enzyme activity recovery and the assembly of cofactor‐dependent multienzyme systems. Herein, we report a polyelectrolyte‐assisted encapsulation approach (PAEA) that enables two cascades with four oxidoreductases and two nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) cofactors co‐encapsulated in BioHOF‐1 with excellent cargo loading and over 100 % cascade activity. The key role of the polyelectrolyte is to coat enzymes and tether NAD(P)H, thus interacting with HOF monomers in place of enzymes, avoiding the destruction of enzymes by HOF monomers. The versatility and efficiency of PAEA are further illustrated by an HOF‐101‐based bio‐nanoreactor. Moreover, the immobilization by PAEA makes enzymes and NAD(P)H display excellent stability and recyclability. This study has demonstrated a facile and versatile PAEA for fabricating cofactor‐dependent multienzyme cascade nanoreactors with HOFs. [ABSTRACT FROM AUTHOR]

To establish a pre-test probability model of coronary heart disease (CHD) combined with cardiopulmonary exercise test (CPET) indexes and to compare the clinical effectiveness with Duke clinical score (DCS) and updated Diamond-Forrester model (UDFM), thus further explore the predictive value. 342 cases were used to establish the prediction model equation and another 80 cases were used to verify the effectiveness. The patients were divided into CHD group (n = 157) and non-CHD group (n = 185) according to coronary artery stenosis degree >50% or not. Combining DCS and UDFM as reference models with CPET indexes, a multivariate logistic regression model was established. The area under the ROC curve of the three models were calculated to compare the predictive effectiveness. There were significant differences in gender, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave and ST-T change between two groups (P < 0.01), as well as age, LVEF, heart rate at anaerobic domain, peak oxygen uptake in kilograms of body weight, percentage of peak oxygen uptake to the predicted value, the oxygen uptake efficiency slope and carbon dioxide ventilation equivalent slope (P < 0.05). Multivariate analysis showed gender, age, chest pain type, myocardial infarction history, hypertension history, smoking, pathological Q wave, ST-T change, and peak oxygen pulse were independent risk factors of CHD. The pre-test probability model of CHD combined with CPET indexes has good distinguish and calibrate ability, its prediction accuracy is slightly better than DCS and UDFM, which still needs to be verified externally in more samples. [ABSTRACT FROM AUTHOR]

A laser scanning strategy for fabricating deep surface grooves using a continuous-wave fiber laser was investigated in this study. Because the low productivity of short-pulsed-wave lasers limits their application to a small scale, a continuous-wave (CW) fiber laser that can provide a high power density was used for the rapid fabrication of deep grooves. An innovative tailored laser scanning strategy of fabricating patterned deep grooves was analytically designed based on the power density and interaction time. Considering the thermophysical properties of the material, controlled laser processing parameters were determined for fabricating surface grooves with rectangular and chevron cross-sectional patterns. To confirm the usefulness of the research results, the scanning strategy obtained in this study was applied for achieving high-quality joining between injection-molded metal–plastic hybrids (MPHs). A deep-surface-grooved A5052 aluminum alloy sheet was bonded to two plastics, polyamide and polypropylene, via injection molding. Lap shear tensile tests of the MPHs revealed their significantly enhanced joining strength owing to a better mechanical interlocking of the groove. The developed laser scanning strategy using a CW fiber laser can be widely applied in the fabrication of deep grooves of various cross-sections with high reliability. [ABSTRACT FROM AUTHOR]

In the research on water splitting at neutral pH, phosphorus-containing transition metal oxyhydroxides are often employed for catalyzing the oxygen evolution reaction (OER). We investigated a cobalt–phosphate catalyst (CoCat) representing this material class. We found that CoCat films prepared with potassium phosphate release phosphorus in phosphate-free electrolytes within hours, contrasting orders of magnitude's faster K+ release. For P speciation and binding mode characterization, we performed technically challenging X-ray absorption spectroscopy experiments at the P K-edge and analyzed the resulting XANES and EXAFS spectra. The CoCat-internal phosphorus is present in the form of phosphate ions. Most phosphate species are likely linked to cobalt ions in Co–O–PO3 motifs, where the connecting oxygen could be a terminal or bridging ligand in Co-oxide fragments (P–Co distance, ~3.1 Å), with additional ionic bonds to K+ ions (P–K distance, ~3.3 Å). The phosphate coordination bond is stronger than the ionic K+-binding, explaining the strongly diverging ion release rates of phosphate and K+. Our results support a structural role of phosphate in the CoCat, with these ions binding at the margins of Co-oxide fragments, thereby limiting the long-range material ordering. The relations of catalyst-internal phosphate ions to cobalt's redox-state changes, proton transfer, and catalytic activity are discussed. [ABSTRACT FROM AUTHOR]

Research on biomarker-driven therapy and immune check-point blockade in non-small cell lung cancer (NSCLC) is rapidly evolving. The width and depth of clinical trials have also dramatically improved in an unprecedented speed. The personalized treatment paradigm evolved every year. In this review, we summarize the promising agents that have shifted the treatment paradigm for NSCLC patients across all stages, including targeted therapy and immunotherapy using checkpoint inhibitors. Based on recent evidence, we propose treatment algorithms for NSCLC and propose several unsolved clinical issues, which are being explored in ongoing clinical trials. The results of these trials are likely to impact future clinical practice. [ABSTRACT FROM AUTHOR]

Background: The tumor-adipose microenvironment (TAME) is characterized by the enrichment of adipocytes, and is considered a special ecosystem that supports cancer progression. However, the heterogeneity and diversity of adipocytes in TAME remains poorly understood. Methods: We conducted a single-cell RNA sequencing analysis of adipocytes in mouse and human white adipose tissue (WAT). We analyzed several adipocyte subtypes to evaluate their relationship and potential as prognostic factors for overall survival (OS). The potential drugs are screened by using bioinformatics methods. The tumor-promoting effects of a typical adipocyte subtype in breast cancer are validated by performing in vitro functional assays and immunohistochemistry (IHC) in clinical samples. Results: We profiled a comprehensive single-cell atlas of adipocyte in mouse and human WAT and described their characteristics, origins, development, functions and interactions with immune cells. Several cancer-associated adipocyte subtypes, namely DPP4+ adipocytes in visceral adipose and ADIPOQ+ adipocytes in subcutaneous adipose, are identified. We found that high levels of these subtypes are associated with unfavorable outcomes in four typical adipose-associated cancers. Some potential drugs including Trametinib, Selumetinib and Ulixertinib are discovered. Emphatically, knockdown of adiponectin receptor 1 (AdipoR1) and AdipoR2 impaired the proliferation and invasion of breast cancer cells. Patients with AdipoR2-high breast cancer display significantly shorter relapse-free survival (RFS) than those with AdipoR2-low breast cancer. Conclusion: Our results provide a novel understanding of TAME at the single-cell level. Based on our findings, several adipocyte subtypes have negative impact on prognosis. These cancer-associated adipocytes may serve as key prognostic predictor and potential targets for treatment in the future. [ABSTRACT FROM AUTHOR]

In organic purity assessment, chromatography separation with a suitable detector is required. Diode array detection (DAD) has been a widely used technique for high-performance liquid chromatography (HPLC) analyses, but its application is limited to compounds with sufficient UV chromophores. Charged aerosol detector (CAD), as a mass-dependent detector, is advantageous for providing a nearly uniform response for analytes, regardless of their structures. In this study, 11 non-volatile compounds with/without UV chromophores were analyzed by CAD using continuous direct injection mode. The RSDs of CAD responses were within 17%. For saccharides and bisphenols, especially, the RSDs were lower (2.12% and 8.14%, respectively). Since bisphenols exist in UV chromophores, their HPLC–DAD responses were studied and compared with CAD responses, with CAD showing a more uniform response. Besides, the key parameters of HPLC-CAD were optimized and the developed method was verified using a Certified Reference Material (CRM, dulcitol, GBW06144). The area normalization result of dulcitol measured by HPLC-CAD was 99.89% ± 0.02% (n = 6), consistent with the certified value of 99.8% ± 0.2% (k = 2). The result of this work indicated that the HPLC-CAD method could be a good complementary tool to traditional techniques for the purity assessment of organic compounds, especially for compounds lacking UV chromophores. [ABSTRACT FROM AUTHOR]

Incorporation of tellurium into polycyclic compounds may endow them with unique chemical and optoelectronic properties which are not observed in their lighter chalcogen analogues. Herein, a telluropyran‐containing polycyclic compound (T1) synthesized through a ring‐expansion reaction from the corresponding tellurophene analogue can be reversibly oxidized into halogen adducts T1•X2 (X=Cl, Br, I) with the formation of two Te−X bonds. Their chemical structures have been verified by two‐dimensional 1H‐1H correlation spectroscopy and single crystal X‐ray diffraction analysis. The halogen oxidations of T1 and the reverse thermal eliminations as well as the halogen exchange in halogen adducts T1•X2 have been systematically investigated and compared by UV‐vis absorption titration, electrochemical measurements, thermogravimetric analysis, and density functional calculations (DFT). The oxidation of Te(II) in T1 to Te(IV) in T1•X2 results in the switch from aromaticity to nonaromaticity for the six‐membered telluropyran ring, as revealed by nucleus‐independent chemical shift calculations. It is also found that the halides in the halogen adducts can be exchanged by lighter ones, but not vice versa. The stabilities of the oxidized products are in the order of T1•Cl2>T1•Br2>T1•I2, which are consistent with the calculated rate constants and energy barriers of the elimination reactions. [ABSTRACT FROM AUTHOR]

This series of papers is devoted to the study of Virasoro symmetries of deformations of the Principal Hierarchy associated with a semisimple Frobenius manifold. The main tool we use is a generalization of the bihamiltonian cohomology called the variational bihamiltonian cohomology. In the present paper, we give its definition and compute the associated cohomology groups that will be used in our study of Virasoro symmetries. As an application of the variational bihamiltonian cohomology theory, we classify conformal bihamiltonian structures with semisimple hydrodynamic limits. [ABSTRACT FROM AUTHOR]

Background: The long-term prognosis of patients with hepatocellular carcinoma (HCC) after surgery remains far from satisfactory, especially in patients with microvascular invasion (MVI). This study aimed to evaluate the potential survival benefit from adjuvant lenvatinib for patients with HCC and MVI. Methods: Patients with HCC after curative hepatectomy were reviewed. All patients were divided into 2 groups according to adjuvant lenvatinib. Propensity score matching (PSM) analysis was used to reduce selection bias and make the results more robust. Survival curves are shown by the Kaplan-Meier (K-M) analysis and compared by the Log-rank test. Univariate and multivariate Cox regression analyses were performed to determine the independent risk factors. Results: Of 179 patients enrolled in this study, 43 (24%) patients received adjuvant lenvatinib. After PSM analysis, 31 pairs of patients were enrolled for further analysis. Survival analysis before and after PSM analysis showed a better prognosis in the adjuvant lenvatinib group (all P <.05). The adverse events associated with oral lenvatinib were acceptable. Multivariate Cox regression analysis showed that adjuvant lenvatinib was an independent protective factor for improving overall survival (OS) (hazard ratio [HR] = 0.455, 95% confidence interval [CI] = 0.249-0.831, P =.001) and recurrence-free survival (RFS) (HR = 0.523, 95% CI = 0.308-0.886, P =.016). Conclusions: Postoperative adjuvant targeted therapy can improve the long-term prognosis of patients with HCC and MVI. Therefore, in clinical practice, oral lenvatinib should be recommended for patients with HCC and MVI to decrease tumor recurrence and improve long-term survival. [ABSTRACT FROM AUTHOR]

Electron cyclotron harmonic (ECH) waves, which are responsible for the diffuse aurora, are usually observed with the strongest intensity in the first band. Here, we present observations of enhanced higher‐band ECH with wave intensities above 10−3 mV2m−2 Hz−1 by Van Allen Probes. Fully thermal simulation results indicate that these waves can be locally excited by the observed electron distributions, and higher plasma density and lower magnetic strength are favorable for generating the enhanced higher‐band ECH. The pitch angle diffusion coefficient Dαα $\left\langle {D}_{\alpha \alpha }\right\rangle $ of the higher‐band ECH can exceed 10−5 s−1 inside the loss cone for energetic electrons (300 eV–∼15 keV), greater than the momentum diffusion coefficient Dpp $\left\langle {D}_{pp}\right\rangle $ by ∼100 times. It is suggested that the enhanced higher‐band ECH can also efficiently scatter these electrons into the loss cone and contribute to the diffuse aurora. Plain Language Summary: Electron cyclotron harmonic (ECH) waves are electrostatic emissions usually observed with the strongest intensity in the first band. Numerous works have demonstrated that the first‐band ECH waves can be responsible for diffuse auroral electron precipitation. However, so far the role of higher‐band ECH waves has not been confirmed. Here, we report an enhanced higher‐band ECH event with wave intensities above 10−3 mV2m−2 Hz−1 from Van Allen Probes. Using the realistic parameters, we conduct fully thermal simulations to investigate the generation of such ECH. The results indicate that growth rates can well reproduce the observed wave spectral characteristics in all four harmonic bands, and the higher density and lower magnetic field strength are favorable for generating enhanced higher‐band ECH. We calculate the diffusion coefficients to estimate the effect of the higher‐band ECH on electrons. The pitch angle diffusion coefficients induced by higher‐band ECH are ∼2 orders of magnitude greater than the momentum diffusion coefficients over a broad pitch angle range and exceed 10−5 s−1 inside the loss cone for energetic electrons. This indicates that the enhanced higher‐band ECH can also efficiently scatter these energetic electrons into the loss cone and potentially contribute to the diffuse aurora, similar to the first‐band ECH. Key Points: Enhanced higher‐band Electron cyclotron harmonic (ECH) waves with electric spectral density above 10−3 mV2m−2 Hz−1 were observed by Van Allen ProbesFully thermal simulations show that higher density and lower magnetic strength are favorable for generating enhanced higher‐band ECHEnhanced higher‐band ECH can cause efficient scattering loss of energetic electrons and contribute to the diffuse aurora [ABSTRACT FROM AUTHOR]

Stimuli‐responsive porous materials have captured much attention due to the on‐demand tunable properties. Most reported stimuli‐responsive porous materials are based on molecule isomerism or host‐guest interaction, and it is highly desired to develop new types based on different responsive mechanism. Herein, inspired by natural cells which have the ability to fuse and divide induced by external stimulation, we report a new type of stimuli‐responsive porous material based on detachment mechanism. A detachable porous organic polymer, namely DT‐POP‐1, is fabricated from the polymerization of anthracene‐containing monomer (AnMon) when irradiated by 365 nm UV light. DT‐POP‐1 can detach into the monomer AnMon when irradiated with 275 nm UV light or heat. Such polymerization/detachment is reversible. The detachment results in a big difference in porosity and adsorption capacity, making the present detachable porous polymer highly promising in adsorptive separation and drug delivery. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive porous materials have captured much attention due to the on‐demand tunable properties. Most reported stimuli‐responsive porous materials are based on molecule isomerism or host‐guest interaction, and it is highly desired to develop new types based on different responsive mechanism. Herein, inspired by natural cells which have the ability to fuse and divide induced by external stimulation, we report a new type of stimuli‐responsive porous material based on detachment mechanism. A detachable porous organic polymer, namely DT‐POP‐1, is fabricated from the polymerization of anthracene‐containing monomer (AnMon) when irradiated by 365 nm UV light. DT‐POP‐1 can detach into the monomer AnMon when irradiated with 275 nm UV light or heat. Such polymerization/detachment is reversible. The detachment results in a big difference in porosity and adsorption capacity, making the present detachable porous polymer highly promising in adsorptive separation and drug delivery. [ABSTRACT FROM AUTHOR]

Coronavirus infection induces a variety of cellular antiviral responses either dependent on or independent of type I interferons (IFNs). Our previous studies using Affymetrix microarray and transcriptomic analysis revealed the differential induction of three IFN-stimulated genes (ISGs), IRF1, ISG15 and ISG20, by gammacoronavirus infectious bronchitis virus (IBV) infection of IFN-deficient Vero cells and IFN-competent, p53-defcient H1299 cells, respectively. In this report, the induction kinetics and anti-IBV functions of these ISGs as well as mechanisms underlying their differential induction are characterized. The results confirmed that these three ISGs were indeed differentially induced in H1299 and Vero cells infected with IBV, significantly more upregulation of IRF1, ISG15 and ISG20 was elicited in IBV-infected Vero cells than that in H1299 cells. Induction of these ISGs was also detected in cells infected with human coronavirus-OC43 (HCoV-OC43) and porcine epidemic diarrhea virus (PEDV), respectively. Manipulation of their expression by overexpression, knockdown and/or knockout demonstrated that IRF1 played an active role in suppressing IBV replication, mainly through the activation of the IFN pathway. However, a minor, if any, role in inhibiting IBV replication was played by ISG15 and ISG20. Furthermore, p53, but not IRF1, was implicated in regulating the IBV infection-induced upregulation of ISG15 and ISG20. This study provides new information on the mechanisms underlying the induction of these ISGs and their contributions to the host cell antiviral response during IBV infection. • IBV infection of H1299 and IFN-β-deficient Vero cells differentially regulates the expression of IRF1, ISG15 and ISG20. • Overexpression of IRF1 suppresses IBV replication mainly through the induction of IFN pathways. • The endogenous IRF1 plays a minor role in the inhibition of IBV replication and in the induction of ISG15 and ISG20. • Overexpression of ISG15 and ISG20 does not significantly suppress IBV replication. • IBV-induced ISG15 and ISG20 expression is partially p53-dependent, but not by IRF1. [ABSTRACT FROM AUTHOR]

Reciprocal spin‐orbit coupling (SOC) via geometric phase with flat optics provides a promising platform for shaping and controlling paraxial structured light. Current devices, from the pioneering q‐plates to the recent J‐plates, provide only spin‐dependent wavefront modulation without amplitude control. However, achieving control over all the spatial dimensions of paraxial SOC states requires spin‐dependent control of corresponding complex amplitude, which remains challenging for flat optics. Here, to address this issue, a new type of flat‐optics elements termed structured geometric phase gratings is presented, that is capable of conjugated complex‐amplitude control for orthogonal input circular polarizations. By using a microstructured liquid crystal photoalignment technique, a series of flat‐optics elements is engineered and their excellent precision in arbitrary SOC control is shown. This principle unlocks the full‐field control of paraxial structured light via flat optics, providing a promising way to develop an information exchange and processing units for general photonic SOC states, as well as extra‐/intracavity mode convertors for high‐precision laser beam shaping. [ABSTRACT FROM AUTHOR]

Electrohydraulic shock wave (EHSW) is seemingly one of the simplest and most common products of microsecond pulsed discharge (μsPD) in water; however, its generation process remains far less clear. To study the influence of current waveforms on the generation of an EHSW, we conducted discharge current interception experiments using a bypass branch in the circuit. The current interception time Δt is properly controlled so that the discharge current through the water gap can be terminated at a chosen time. Results show that the peak pressure Pm is first linearly increasing with Δt, and then Pm reaches a stable value. The expansion of the spark channel with increasing velocities will enhance the peak pressure. This phase can be regarded as the accelerated expansion phase (AEP) of the piston theory. The transition area of the Pm–Δt relationship of this experimental setup shows that the AEP lasts for about tm = 5 μs. After the AEP, the deposited energy will help to maintain a higher pressure in the falling edge of the pressure waves. The full width at half maximum of the waveforms finally approaches 12.5 μs in our tests. The experimental results provide evidence of the piston theory in interpreting the generation of EHSW induced by μsPD. [ABSTRACT FROM AUTHOR]

Magnetosonic (MS) wave is one of the most common electromagnetic emissions in the magnetosphere, while quasi‐electrostatic magnetosonic (QEMS) waves are seldom observed. Here we present an interesting QEMS event detected by Van Allen Probe A on 9 January 2014, in which the presence of multi‐band QEMS emissions shows evident correlations with relatively low plasma densities (∼10 cm−3) and enhancements of suprathermal (∼10 − 100 eV) proton fluxes. Based on the observed proton distributions, simulations demonstrate very similar profiles to the observed QEMS in the wave spectral characteristics. Parametric studies indicate that the QEMS growth rate can increase by ∼20 times with the plasma density decreasing from 50 to 10 cm−3. Effective growth rates of higher‐band QEMS occur when the suprathermal proton population is sufficiently large. This study reveals that low densities and large suprathermal proton populations are favorable for generating distinct multi‐band QEMS in the magnetosphere. Plain Language Summary: Magnetosonic (MS) wave is one of the most common electromagnetic emissions in the magnetosphere, while quasi‐electrostatic magnetosonic (QEMS) wave is seldom observed. Here we report an interesting event detected by Van Allen Probe A on 9 January 2014, in which multi‐band QEMS emissions occurred exactly corresponding to the presence of low plasma densities (∼10 cm−3) and enhancements of suprathermal (∼10 − 100 eV) proton fluxes. Based on the observed data of three typical time intervals, we perform simulations to investigate how the plasma density and suprathermal protons affect the generation of QEMS. Our results are quite comparable with the observations in the patterns of wave intensity and frequency characteristics. We then adjust the parameters and find that QEMS growth rate increases by ∼20 times with the plasma density decreasing from 50 to 10 cm−3. Effective growth rates of higher‐band QEMS only occur when the suprathermal proton population is ≥0.75 cm−3. These results demonstrate that the low plasma density is propitious for generating distinct QEMS, and a sufficiently large suprathermal proton population is beneficial for forming the multi‐band structure of QEMS. Key Points: Multi‐band quasi‐electrostatic magnetosonic (QEMS) was observed exactly corresponding to low plasma densities and enhanced suprathermal proton fluxesSimulations indicate that QEMS growth rate can increase by about 20 times with the plasma density decreasing from 50 to 10 cm−3A large suprathermal (∼10–100 eV) proton population is favorable for extending the QEMS to higher bands [ABSTRACT FROM AUTHOR]

The occupation tendencies of Cr, Cu, Mo, Nb, Ni, Ti and V in Fcc-Fe stacking fault containing vacancy were studied by the first principles calculations. The effects of C, N and Nb, Ti co-segregation in the region of vacancy is discussed. The results are as follows: the substitutional elements Cr, Cu, Mo, Ni, Nb, Ti and interstitial elements C, N have no segregation tendency at the stacking fault of Fcc-Fe (111) plane. When the stacking fault contains vacancy, the above elements have the tendency to segregate around the vacancy, and C, N tend to occupy vacancy and their segregation tendency is the stronger than that of substitutional elements. C, N are easily co-segregated with Nb, Ti in the region of vacancy. It is difficult for Mo to aggregate around the carbonitride precipitates, which is conducive to the use of nano-scale carbide and nitride precipitation strengthening in high Mo austenitic steel, and simultaneously improves corrosion resistance. Nb and Ti tend to aggregate around the vacancy where occupied by C, N. [ABSTRACT FROM AUTHOR]

A cold collision between atoms and molecules (<1 K) is one of the hot research fields in atomic and molecular physics. At low temperatures, the number of partial waves participating in the collision process decreases dramatically, and quantum phenomena start to emerge. The reaction is often dominated by quantum tunneling, and pronounced resonances can exist on collision cross sections. Here, we report on an apparatus designed for studying cold collisions between metastable noble gas atoms and alkali atoms. Our apparatus features a combined Magneto-Optical-Trap (MOT) and velocity map imaging (VMI) system. The center of a Rb MOT is overlapped with the VMI system. Cold Kr* atoms are launched toward the Rb atoms to induce Kr* + Rb reactions. The collision energy between the two species can be varied from 100 mK to 20 K. With this setup, we are planning to explore the quantum phenomena in Kr* + Rb cold collisions, including the shape resonance and stereodynamics in the reaction. [ABSTRACT FROM AUTHOR]

The warping effects may predominate in geometrically nonlinear analysis of open cross-section members. The formulation of conventional beam-column elements incorporating the warping effects is cumbersome due to the method considering the inconsistency between the shear center and centroid. To develop a concise warping element formulation, this paper presents a transformation matrix to integrate the inconsistent effects into the element stiffness matrix. The co-rotational (CR) method used to establish the element equilibrium conditions in the geometrically nonlinear analysis is adopted to simplify the element formulation and improve the efficiency of nonlinear analysis. A new beam-column element explicitly considering the warping deformation and the Wagner effects is derived based on the CR method and the Euler–Bernoulli beam theory. A detailed kinematic description is provided for considering large deflections and rigid body motions. Based on the mechanical characteristic, the coordinate and the rigid body motion transformation matrices are given. The secant relationship is developed to evaluate the element internal forces accurately and effectively in each iteration. Several verification examples are provided to validate the proposed method's reliability and robustness. The verifications demonstrate that the proposed element leads to considerable computational advantages. The results of this paper are useful for future upgrading of frame analysis software with warping degrees-of-freedom (DOFs). [ABSTRACT FROM AUTHOR]

Pseudomonas putida KT2440 is a well-known model organism for the medium-chain-length (mcl) polyhydroxyalkanoate (PHA) accumulation. (R)-Specific enoyl-coenzyme A hydratase (PhaJ) was considered to be the main supplier of monomers for PHA synthesis by converting the β-oxidation intermediate, trans-2-enoyl-CoA to (R)-3-hydroxyacyl-CoA when fatty acids (FA) are used. Three PhaJ homologues, PhaJ1, PhaJ4 and MaoC, are annotated in P. putida KT2440. To investigate the relationship of fatty acids–PHA metabolism and the role of each PhaJ in PHA biosynthesis in P. putida KT2440, a series of P. putida KT2440 knockouts was obtained. PHA content and monomer composition in wild type (WT) and mutants under different growth conditions were analysed. PhaJ4 was the main monomer supplier for PHA synthesis with FA as sole carbon and energy source, with preference towards C8 and C10 substrate, whereas PhaJ1 showed preference for the C6 substrate. However, when all three PhaJ homologues were deleted, the mutant still accumulated PHA up to 10.7% of the cell dry weight (CDW). The deletion of (R)-3-hydroxydecanoyl-ACP:CoA transacylase (PhaG), which connects de novo FA and PHA synthesis pathways, while causing a further 1.8-fold decrease in PHA content, did not abolish PHA accumulation. Further proteome analysis revealed quinoprotein alcohol dehydrogenases PedE and PedH as potential monomer suppliers, but when these were deleted, the PHA level remained at 2.2–14.8% CDW depending on the fatty acid used and whether nitrogen limitation was applied. Therefore, it is likely that some other non-specific dehydrogenases supply monomers for PHA synthesis, demonstrating the redundancy of PHA metabolism. Key points: • β-oxidation intermediates are converted to PHA monomers by hydratases PhaJ1, PhaJ4 and MaoC in Pseudomonas putida KT2440. • When these are deleted, the PHA level decreases, but it is not abolished. • PHA non-specific enzyme(s) also contributes to PHA metabolism in KT2440. [ABSTRACT FROM AUTHOR]

In this study, for the first time, a silver-based metal–organic framework (Ag-MOF) was synthesized and used as the electrochemiluminescence (ECL) emitter for building an ECL sensor. After modification with chitosan (CS) and gold nanoparticles (Au NPs), the ECL stability of Ag-MOF was improved. To detect mercury ions, a biosensor was constructed using the mercury ion aptamer and steric effect of streptavidin. First, the capture strand (cDNA) with terminal-modified sulfhydryl group was attached to the electrode surface by the Au–S bond. Then, the mercury-ion aptamer (Apt-Hg) modified with biotin was anchored to the electrode by complementary pairing with cDNA. Streptavidin (SA) could be fixed on the electrode by linking with biotin, thereby reducing the ECL signal. However, in the presence of mercury ions, the aptamer was removed and streptavidin could not be immobilized on the electrode. Hence, the ECL signal of the sensor increased with the concentration of mercury ions, which was linear in the range from 1 μM to 300 fM. The detection limit could reach 66 fM (S/N = 3). The sensor provided a new method for the detection of mercury ions. [ABSTRACT FROM AUTHOR]

Three S‐fused polycyclic aromatic hydrocarbons (PAHs) bearing cyclopenta[b]thiopyran moieties have been designed and successfully synthesized. With the conjugation extension, the absorption onset of the longest PAH reaches 1110 nm. All the three S‐fused PAHs exhibit significant halochromic properties in both solution and solid states. Upon protonation, the proton is incorporated on the cyclopentadiene ring while the positive charge is localized on the thiopyrylium ring. Moreover, no significant difference can be found for the two shorter PAHs upon the protonation by different organic acids, such as trifluoroacetic acid (TFA) and trifluoromethanesulfonic acid (TfOH), while the longest PAH can be only mono‐protonated by TFA but di‐protonated by stronger TfOH. Furthermore, after protonation, the non‐emissive S‐fused PAHs exhibit strong fluorescence and can be regenerated by simply neutralization with triethylamine. The enhanced emission of mono‐protonated products stem from S2→S0 transitions, which disobey the Kasha's rule. [ABSTRACT FROM AUTHOR]

Simple Summary: A newly identified non-AUG-initiated ORF, ORF3a, encoded by members of the genus Polerovirus, is required for long-distance movement in plants. However, its functions in host protein interactions still remain unclear. Here, we systemically investigated Brassica yellows virus (BrYV)-P3a interacting proteins in plants. In total, 138 genes with annotations were obtained. Furthermore, Arabidopsis thaliana purine permease 14, glucosinolate transporter 1, and nitrate transporter 1.7 were verified to interact with P3a in vivo and were downregulated in response to BrYV during the late stages of viral infection. We used pup14, gtr1, and nrt1.7, the T-DNA insertion mutants, to preliminarily characterize their roles in the BrYV infection process. Viruses are obligate parasites that only undergo genomic replication in their host organisms. ORF3a, a newly identified non-AUG-initiated ORF encoded by members of the genus Polerovirus, is required for long-distance movement in plants. However, its interactions with host proteins still remain unclear. Here, we used Brassica yellows virus (BrYV)-P3a as bait to screen a plant split-ubiquitin-based membrane yeast two-hybrid (MYTH) cDNA library to explain the functional role of P3a in viral infections. In total, 138 genes with annotations were obtained. Bioinformatics analyses revealed that the genes from carbon fixation in photosynthetic, photosynthesis pathways, and MAPK signaling were affected. Furthermore, Arabidopsis thaliana purine permease 14 (AtPUP14), glucosinolate transporter 1 (AtGTR1), and nitrate transporter 1.7 (AtNRT1.7) were verified to interact with P3a in vivo. P3a and these three interacting proteins mainly co-localized in the cytoplasm. Expression levels of AtPUP14, AtGTR1, and AtNRT1.7 were significantly reduced in response to BrYV during the late stages of viral infection. In addition, we characterized the roles of AtPUP14, AtGTR1, and AtNRT1.7 in BrYV infection in A. thaliana using T-DNA insertion mutants, and the pup14, gtr1, and nrt1.7 mutants influenced BrYV infection to different degrees. [ABSTRACT FROM AUTHOR]

Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and HEK293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism. • DNlg3 C-terminal fragment could translocate into the nuclear and regulate the transcription. • Dnlg3 null flies showed an increased expression of the innate immune response genes. • A single knockout of a synaptic molecule in Drosophila would lead to the stronger activation of the entire innate immune responses. [ABSTRACT FROM AUTHOR]