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Using surfactants to improve the particle size of Arctium lappa L. polysaccharides, and the optimal process conditions were obtained by single factor and response surface method. The structure of Arctium lappa L. polysaccharides before and after improvement was characterized by UV, Fourier transform infrared spectroscopy (FT-IR), particle size, and scanning electron microscopy. The results showed that the optimal process conditions for improving the particle size of Arctium lappa L. polysaccharides were as follows: The surfactant was Tween-80, the concentration was 0.5%, the vortex time was 16 s, and the pH was 5.67, under these conditions, the particle size of Arctium lappa L. polysaccharides was 6.19±0.14 nm. FT-IR analysis showed that the modification with surfactants did not change the structure of Arctium lappa L. polysaccharides. The UV spectrum showed a slight fluctuation at 280 nm, which might be attributed to the UV absorption of surfactants in this wave band. The particle size analysis showed that the grain size of improved Arctium lappa L. polysaccharides decreased significantly compared with unimprovement. The scanning electron microscopy results showed that the improved Arctium lappa L. polysaccharides exhibited a more ordered spherical structure and more uniform sizes. This study can provide a theoretical basis for the preparation of a polysaccharide system with controlled particle size.

Poplar is one of the fastest-growing temperate trees in the world and is widely used in ornamental horticulture for shade. The root is essential for tree growth and development and its utilization potential is huge. Calcium (Ca), as a signaling molecule, is involved in the regulation of plant root development. However, the detailed underlying regulatory mechanism is elusive. In this study, we analyzed the morphological and transcriptomic variations of 84K poplar (Populus alba × P. glandulosa) in response to different calcium concentrations and found that low Ca2+ (1 mmol · L−1) promoted lateral root development, while deficiency (0.1 mmol · L−1 Ca2+) inhibited lateral root development. Co-expression analysis showed that Ca2+ channel glutamate receptors (GLRs) were present in various modules with significance for root development. Two GLR paralogous genes, PagGLR3.3a and PagGLR3.3b, were mainly expressed in roots and up-regulated under Ca2+ deficiency. The CRISPR/Cas9-mediated signal gene (crispr-PagGLR3.3a, PagGLR3.3b) and double gene (crispr-PagGLR3.3ab) mutants presented more and longer lateral roots. Anatomical analysis showed that crispr-PagGLR3.3ab plants had more xylem cells and promoted the development of secondary vascular tissues. Further transcriptomic analysis suggested that knockout of PagGLR3.3a and PagGLR3.3b led to the up-regulation of several genes related to protein phosphorylation, auxin efflux, lignin and hemicellulose biosynthesis as well as transcriptional regulation, which might contribute to lateral root growth. This study not only provides novel insight into how the Ca2+ channels mediated root growth and development in trees, but also provides a directive breeding of new poplar species for biofuel and bioenergy production.

Abstract Low-dose computed tomography (LDCT) has emerged as the preferred technology for diagnostic medical imaging due to the potential health risks associated with X-ray radiation and conventional computed tomography (CT) techniques. While LDCT utilizes a lower radiation dose compared to standard CT, it results in increased image noise, which can impair the accuracy of diagnoses. To mitigate this issue, advanced deep learning-based LDCT denoising algorithms have been developed. These primarily utilize Convolutional Neural Networks (CNNs) or Transformer Networks and often employ the Unet architecture, which enhances image detail by integrating feature maps from the encoder and decoder via skip connections. However, existing methods focus excessively on the optimization of the encoder and decoder structures while overlooking potential enhancements to the Unet architecture itself. This oversight can be problematic due to significant differences in feature map characteristics between the encoder and decoder, where simple fusion strategies may hinder effective image reconstruction. In this paper, we introduce WiTUnet, a novel LDCT image denoising method that utilizes nested, dense skip pathway in place of traditional skip connections to improve feature integration. Additionally, to address the high computational demands of conventional Transformers on large images, WiTUnet incorporates a windowed Transformer structure that processes images in smaller, non-overlapping segments, significantly reducing computational load. Moreover, our approach includes a Local Image Perception Enhancement (LiPe) module within both the encoder and decoder to replace the standard multi-layer perceptron (MLP) in Transformers, thereby improving the capture and representation of local image features. Through extensive experimental comparisons, WiTUnet has demonstrated superior performance over existing methods in critical metrics such as Peak Signal-to-Noise Ratio (PSNR), Structural Similarity (SSIM), and Root Mean Square Error (RMSE), significantly enhancing noise removal and image quality. The code is available on github https://github.com/woldier/WiTUNet .

Abstract With the advent of the digital economy era, digital management has become a hot topic of concern in both the industry and academia. Focusing on digital management in enterprises, this article consists of 750 CSSCI source journals indexed in the CNKI database from 2000 to 2022, 1303 articles in the literature and Web of Science core database were used as research objects, using CiteSpace and VOSviewer Perform bibliometric analysis using visual tools. Firstly, conduct data statistics on the overall collection and apply the author literature coupling method. Analyze representative literature. Secondly, by means of thematic temporal evolution and keyword emergence, we will sort out the development of domestic and foreign research. Expand the context. Next, we use keyword clustering method to explore recent hot topics in domestic and international research. Based on citation analysis and word cluster analysis, with the comprehensive results of "basic elements—management process—management effectiveness", a digital management theory for enterprises has been constructed on the IPO Panoramic Research Framework Model. Finally, future research directions are proposed. Firstly, the issue of digital technology abuse must be addressed through standardized management protocols. Secondly, the mechanisms by which digital technology impacts organizational performance warrant thorough investigation. Thirdly, the paradigm of collaboratively applying multiple digital technologies should be explored. Lastly, the design of an innovative digital ecosystem strategy based on a platform approach needs to be developed.

Abstract Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7–78.9%) and the DCR was 76% (95% CI: 54.9–90.6%). The mPFS was 6.0 months (95% CI: 5.4–9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.

Abstract Background Nipah virus (NiV) is a zoonotic pathogen that poses a significant threat because of its wide host range, multiple transmission modes, high transmissibility, and high mortality rates, affecting both human health and animal husbandry. In this study, we developed a one-step reverse transcription droplet digital PCR (RT-ddPCR) assay that targets the N gene of NiV. Results Our RT-ddPCR assay exhibited remarkable sensitivity, with a lower limit of detection of 6.91 copies/reaction. Importantly, it displayed no cross-reactivity with the other 13 common viruses and consistently delivered reliable results with a coefficient of variation below 10% across different concentrations. To validate the effectiveness of our RT-ddPCR assay, we detected 75 NiV armored RNA virus samples, mimicking real-world conditions, and negative control samples, and the RT-ddPCR results perfectly matched the simulated results. Furthermore, compared with a standard quantitative real-time PCR (qPCR) assay, our RT-ddPCR assay demonstrated greater stability when handling complex matrices with low viral loads. Conclusions These findings show that our NiV RT-ddPCR assay is exceptionally sensitive and provides a robust tool for quantitatively detecting NiV, particularly in stimulated field samples with low viral loads or complex matrices. This advancement has significant implications for early NiV monitoring, safeguarding human health and safety, and advancing animal husbandry practices.

The study examined the functional properties of lactic yeast-fermented Tartary buckwheat sprout with passion and pineapple juice (Tatary buckwheat sprout juice). Pineapple and passion fruit were included during fermentation to improve the sensory and nutritional quality of the juice. We initially created a juice with Tartary buckwheat sprouts, and then fermented it with Lactobacillus plantarum and yeast (Saccharomyces cerevisiae) to produce a novel fermented sprout juice. Our results indicated that the best organoleptic quality was achieved when the inoculum of Lactobacillus plantarum was 2%, the inoculum of yeast was 1%, and the fermentation time was 30 hours. The results showed that fermentation resulted in a 1.55-fold increase in the total amino acid content, with fresh sweet amino acids increasing by 1.75-fold and sour-bitter amino acids increasing by 1.33-fold. Additionally, the levels of acetic acid, lactic acid, citric acid, and tartaric acid in the buckwheat sprout juice increased by 12.31%, 11.45%, 4.22%, and 3.88%, respectively. GC-MS analysis revealed a significant increase of volatile flavoring substances, such as alcohols and esters, by more than 24.7% in the fermentation products. From the results, yeast-Lactobacillus fermentation process may effectively improve the nutritional values of Tartary buckwheat sprout juice.

Background: Streptococcus agalactiae is a recognized pathogen that primarily affects infants and pregnant women. However, its increasingly important role in causing invasive infections among non-pregnant adults has become a significant health concern due to the severity and variety of its clinical impacts. Methods: Nonduplicate S. agalactiae clinical strains associated with clinical infections (n = 139) were isolated from non-pregnant adults in Shandong, China. Antibiotic susceptibility testing, whole-genome sequencing and genomic analyses were conducted to characterize the genome and identify resistance features of these strains. Results: The strains exhibited universal susceptibility to penicillin, ampicillin, cefotaxime, meropenem, linezolid and vancomycin. Notably, high resistance rates were observed for erythromycin (91.4%), clindamycin (89.2%), levofloxacin (84.2%), tetracycline (54.0%) and, to a lesser extent, chloramphenicol (12.9%). Serotyping revealed seven serotypes and one non-typeable strain. Serotypes Ia, Ib, III and V predominated, representing 95.7% of the strains. Nineteen sequence types were categorized into seven clonal complexes, with CC10 being the most prevalent at 48.9%. The resistance genes mreA (100%), ermB (70.5%) and tetM (46.0%) were commonly detected. All the isolates carried at least one pilus backbone determinant and one alpha-like protein gene, with the PI-1+PI-2a and the bca gene being the most frequent at 84.2% and 54.7%, respectively. Conclusions: While S. agalactiae strains in non-pregnant adults retain sensitivity to β-lactam antibiotics, the elevated resistance to erythromycin, clindamycin, levofloxacin and tetracycline is concerning. Given the growing elderly population worldwide, the burden of S. agalactiae infections is significant. Continuous surveillance of serotype distribution and antibiotic resistance patterns is imperative for targeted prevention and therapeutic strategies.

Artificial intelligence (AI) holds significant promise in transforming medical imaging, enhancing diagnostics, and refining treatment strategies. However, the reliance on extensive multicenter datasets for training AI models poses challenges due to privacy concerns. Federated learning provides a solution by facilitating collaborative model training across multiple centers without sharing raw data. This study introduces a federated attention-consistent learning (FACL) framework to address challenges associated with large-scale pathological images and data heterogeneity. FACL enhances model generalization by maximizing attention consistency between local clients and the server model. To ensure privacy and validate robustness, we incorporated differential privacy by introducing noise during parameter transfer. We assessed the effectiveness of FACL in cancer diagnosis and Gleason grading tasks using 19,461 whole-slide images of prostate cancer from multiple centers. In the diagnosis task, FACL achieved an area under the curve (AUC) of 0.9718, outperforming seven centers with an average AUC of 0.9499 when categories are relatively balanced. For the Gleason grading task, FACL attained a Kappa score of 0.8463, surpassing the average Kappa score of 0.7379 from six centers. In conclusion, FACL offers a robust, accurate, and cost-effective AI training model for prostate cancer pathology while maintaining effective data safeguards.

Abstract Background The development of acquired EGFR-TKI treatment resistance is still a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). This study aimed to investigate the role of HDAC1/FOXK1/miR-33a signaling in EGFR-TKI resistance. Methods The expression levels of miR‐33a, HDAC1, and FOXK1 were examined using quantitative polymerase chain reaction (PCR) and bioinformatics analysis. Cell proliferation, migration, and apoptosis were explored by cell number assay, Transwell, and flow cytometry assays, respectively. After overexpression or knockdown of HDAC1, miR-33a expression in the cells, cell functions were tested. Immunoprecipitation and correlation analyses were used to evaluate the interaction between HDAC1 and FOXK1 protein. The tumor-suppressive role of miR-33a was investigated by animal experiments. Results The suppression of miR-33a increased TKI resistance by affecting cell proliferation, migration, and apoptosis in gefitinib-resistant cells. HDAC1 is the key upstream molecule that inhibits miR-33 expression. HDAC1 upregulation increased gefitinib resistance by its binding to FOXK1 in cells to silence miR-33a expression. MiR-33a overexpression exerts tumor-suppressive effects by negatively regulating ABCB7 and p70S6K1 expression. Moreover, overexpression of miR-33a inhibited tumor growth in a xenograft nude mouse model. Conclusions HDAC1/FOXK1 upregulation and miR-33a silencing are new mechanisms of EGFR-TKI resistance in NSCLC.

Abstract Intermetallic compounds (IMCs) with ordered atomic structure have gained great attention as nanocatalysts for its enhanced activity and stability. Although the reliance of IMC preparation on high-temperature annealing is well known, a comprehensive understanding of the formation mechanisms of IMCs in this process is currently lacking. Here, we employ aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (AC-HAADF-STEM) to track the formation process of IMCs on carbon supports during in-situ annealing, by taking PtFe as a case study within an industry-relevant impregnation synthesis framework. We directly discern five different stages at the atomic level: initial atomic precursors; Pt cluster formation; Pt-Fe disordered alloying; structurally ordered Pt3Fe formation, and final Pt3Fe-PtFe IMC conversion. In particular, we find that the crucial role of high-temperature annealing resides in facilitating the diffusion of Fe towards Pt, enabling the creation of alloys with the targeted stoichiometric ratio, which in turn provides the thermodynamic driving force for the disorder-to-order transition.

Abstract Super-enhancers are a class of DNA cis-regulatory elements that can regulate cell identity, cell fate, stem cell pluripotency, and even tumorigenesis. Increasing evidence shows that epigenetic modifications play an important role in the pathogenesis of various types of cancer. However, the current research is far from enough to reveal the complex mechanism behind it. This study found a super-enhancer enriched with abnormally active histone modifications in pancreatic ductal adenocarcinoma (PDAC), called DKK1-super-enhancer (DKK1-SE). The major active component of DKK1-SE is component enhancer e1. Mechanistically, AP1 induces chromatin remodeling in component enhancer e1 and activates the transcriptional activity of DKK1. Moreover, DKK1 was closely related to the malignant clinical features of PDAC. Deletion or knockdown of DKK1-SE significantly inhibited the proliferation, colony formation, motility, migration, and invasion of PDAC cells in vitro, and these phenomena were partly mitigated upon rescuing DKK1 expression. In vivo, DKK1-SE deficiency not only inhibited tumor proliferation but also reduced the complexity of the tumor microenvironment. This study identifies that DKK1-SE drives DKK1 expression by recruiting AP1 transcription factors, exerting oncogenic effects in PDAC, and enhancing the complexity of the tumor microenvironment.

Abstract Accurate calculation of equivalent circuit parameters is a prerequisite for accurately calculating the large‐capacity synchronous condenser parameter model. Due to its special transient operating conditions, the high transient magnetic saturation effect during operation causes the non‐linearity and time‐varying of the equivalent circuit parameters. The field mutual leakage reactance is the critical factor affecting the field current, and the time‐varying of the equivalent circuit parameters is closely related to the field current. However, the existing equivalent circuit parameter calculation methods considering field leakage reactance cannot achieve time‐varying parameters. A calculation method of time‐varying equivalent circuit parameters based on a back propagation neural network algorithm is proposed, which solves the calculation problem of time‐varying equivalent circuit parameters considering field mutual leakage reactance. Then, a 300MVar condenser is taken as the research object, and the proposed method is used to simulate the different operating conditions of the condenser and verified by the finite element method and experiment. The results show that the method improves the calculation accuracy of the equivalent circuit parameter model, reduces the calculation time, and applies to different operating conditions.

Introduction Tobacco smoking is a major risk factor for various diseases worldwide, including pancreatic exocrine diseases such as pancreatitis and pancreatic cancer (PC). Currently, few studies have examined the impact of smoking cessation on the likelihood of common pancreatic exocrine diseases. This study sought to determine whether smoking cessation would reduce pancreatitis and PC morbidity. Methods This cohort study used data from the UK Biobank (UKB) to examine the association between smoking status and the likelihood of pancreatitis and PC among 492855 participants. The subjects were divided into never smokers, ex-smokers, and current smokers. Using a multivariate-adjusted binary logistic regression model, we analyzed the relationship between different smoking conditions and the likelihood of pancreatitis and PC. Further, we studied the impact of smoking cessation on pancreatitis and PC compared with current smoking. Results After adjusting for potential confounders, current smokers had higher odds for acute pancreatitis (AP) (AOR=1.38; 95% CI: 1.18–1.61), chronic pancreatitis (CP) (AOR=3.29; 95% CI: 2.35–4.62) and PC (AOR=1.72; 95% CI: 1.42–2.09). People who quit smoking had comparable odds for the diseases as those who never smoked. Compared with current smokers, ex-smokers had reduced odds for AP (AOR=0.76; 95% CI: 0.64–0.89), CP (AOR=0.31; 95% CI: 0.21–0.46), and PC (AOR=0.62; 95% CI: 0.50–0.76). Subgroup analysis revealed reduced odds for these pancreatic diseases in males and females. Conclusions Smokers have an increased odds for pancreatitis and pancreatic cancer. Moreover, smoking cessation can significantly reduce the odds for acute pancreatitis, chronic pancreatitis and pancreatic cancer.

Abstract Mucosa-associated lymphoid tissue lymphoma-translocation protein 1 (MALT1) is an attractive target for the development of modulatory compounds in the treatment of lymphoma and other cancers. While the three-dimensional structure of MALT1 has been previously determined through X-ray analysis, its dynamic behaviour in solution has remained unexplored. We present here dynamic analyses of the apo MALT1 form along with the E549A mutation. This investigation used NMR 15N relaxation and NOE measurements between side-chain methyl groups. Our findings confirm that MALT1 exists as a monomer in solution, and demonstrate that the domains display semi-independent movements in relation to each other. Our dynamic study, covering multiple time scales, along with the assessment of conformational populations by Molecular Dynamic simulations, Alpha Fold modelling and PCA analysis, put the side chain of residue W580 in an inward position, shedding light at potential mechanisms underlying the allosteric regulation of this enzyme.

Abstract To unveil the nature of amorphous states, single‐element amorphous metals have been the perfect research subject due to the simplest composition. However, the extreme crystal nucleation and growth rate in single‐element metal make the synthesis of single‐element amorphous metals seemingly impossible in the past. Fortunately, benefited by several delicate synthetic strategies developed recently, the single‐element amorphous metals have been successfully demonstrated. This review aims to provide a systematic overview of the synthesis of single‐element amorphous metals covering the challenges in physics and recent achievements. In addition, current understanding of the atomic and electronic structures of single‐element amorphous metal has also been included. Finally, the challenges that worth further investigation are discussed. By identifying the potential avenues for further exploration, this review aims to contribute valuable insights that will propel the cognition of single‐element amorphous metals.

Abstract In recent years, the precisely controlled synthesis of chiral twisted molecular carbons has emerged as a forefront topic in the research of carbon materials. Molecular carbons refer to carbon nanomaterials synthesized with precision at the atomic level. Through rational design, rigid and stable chiral twisted structures can be synthesized. The exploration in the field of chiral twisted molecular carbons is key to fully understanding the various twisted configurations of carbon materials and delving into the relationship between structure design and functionality. This review explores chiral twisted configurations of carbon nanomaterials such as nanographene, carbon nanobelts, carbon nanosheets, graphdiyne, etc. It emphasizes the role of photocyclization, Scholl reaction, and Diels–Alder reactions in achieving precise chiral control and discusses a range of innovative design strategies. These strategies have led to the development of various twisted structures, such as helical, propeller, and Möbius strip configurations. The introduction of chirality, combined with the inherent exceptional optical properties of nanocarbon materials, has facilitated the creation of materials with superior chiroptical performances. This advancement is driving applications in fields such as optoelectronics and chiral optics.

Abstract Catalyst systems populated by high-density single atoms are crucial for improving catalytic activity and selectivity, which can potentially maximize the industrial prospects of heterogeneous single-atom catalysts (SACs). However, achieving high-loading SACs with metal contents above 10 wt% remains challenging. Here we describe a general negative pressure annealing strategy to fabricate ultrahigh-loading SACs with metal contents up to 27.3–44.8 wt% for 13 different metals on a typical carbon nitride matrix. Furthermore, our approach enables the synthesis of high-entropy single-atom catalysts (HESACs) that exhibit the coexistence of multiple metal single atoms with high metal contents. In-situ aberration-corrected HAADF-STEM (AC-STEM) combined with ex-situ X-ray absorption fine structure (XAFS) demonstrate that the negative pressure annealing treatment accelerates the removal of anionic ligand in metal precursors and boosts the bonding of metal species with N defective sites, enabling the formation of dense N-coordinated metal sites. Increasing metal loading on a platinum (Pt) SAC to 41.8 wt% significantly enhances the activity of propane oxidation towards liquid products, including acetone, methanol, and acetic acid et al. This work presents a straightforward and universal approach for achieving many low-cost and high-density SACs for efficient catalytic transformations.

Abstract In order to optimise resource allocation within the province, a two‐stage scheduling model for provincial‐level power grids, encompassing day‐ahead and intra‐day stages is proposed. Firstly, a Conditional Generative Adversarial Network is employed to generate scenarios for load and new energy output. Based on the generated scenario set, the model takes into account the uncertainty and permissible error intervals of new energy and load, utilising conditional value at risk to measure the system scheduling risk. In the day‐ahead stage, an optimisation model is proposed, considering intra‐provincial power purchase demands, with the goal of minimising system operating costs, including risk costs. It optimises day‐ahead scheduling and contingency plans to ensure economic efficiency and robustness of the system based on extreme scenarios. During the training phase, the dataset is enhanced using Conditional Generative Adversarial Network and updated daily, improving the training effectiveness of the multi‐agent proximal policy optimisation intra‐day scheduling model. In the intra‐day stage, the intra‐day scheduling model utilises ultra‐short‐term forecasting data as input to generate contingency plans for dispatching reserve units. Experiments conducted on the IEEE 39‐node system validate the feasibility and effectiveness of the proposed approach.

Abstract Background The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN). Methods In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN. Results The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90–14.25), 6.92 (2.51–19.08), and 7.33 (2.69–20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09–4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%. Conclusions The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

Abstract Background Schizochytrium sp. is commercially used for production of docosahexaenoic acid (DHA). Schizochytrium sp. utilizes the polyketide synthase complex (PKS) and a single type I fatty acid synthase (FAS) to synthesize polyunsaturated fatty acids and saturated fatty acids, respectively. The acyl carrier protein (ACP) domains of FAS or PKS are used to load acyl groups during fatty acids biosynthesis. Phosphopantetheinyl transferase (PPTase) transfers the pantetheine moiety from Coenzyme A to the conserved serine residue of an inactive ACP domain to produce its active form. Results In this study, in order to improve production and content of DHA, we decreased the expression of fas, strengthened the expression of the PKS pathway, and enhanced the supply of active ACP in Schizochytrium sp. ATCC20888. Weakening the expression of fas or disruption of orfA both led to growth defect and reduction of lipid yields in the resulting strains WFAS and DPKSA, indicating that both FAS and PKS were indispensable for growth and lipid accumulation. Although WFAS had a higher DHA content in total fatty acids than the wild-type strain (WT), its growth defect and low DHA yield hinders its use for DHA production. Overexpression of the orfAB, orfC, orfC-DH (truncated orfC), or ppt promoted DHA and lipid production, respectively. The yields and contents of DHA were further increased by combined overexpression of these genes. Highest values of DHA yield (7.2 g/L) and DHA content (40.6%) were achieved in a recombinant OPKSABC-PPT, ⁓56.5% and 15.3% higher than the WT values, respectively. Conclusions This study demonstrates that genetic engineering of the fatty acid biosynthetic pathways provides a new strategy to enhance DHA production in Schizochytrium.

Limited evidence was available on ambient air pollution and pediatric atopic dermatitis (AD). The study aimed to evaluate the associations between short-term exposure to air pollutants and outpatient visits for pediatric AD. From 2016–2018, we collected data on six criteria air pollutants (PM2.5, PM10, NO2, SO2, CO and O3) and daily outpatient visits for pediatric AD in 66 hospitals, covering all districts in Shanghai, China. The over-dispersed Poisson generalized additive model (GAM) was applied to fit the associations of criteria air pollutants with hospital visits. Two-pollutant models were fitted and stratified analyses by sex, age and season were conducted. We identified 477,833 outpatient visits for pediatric AD. Each interquartile range (IQR) increase in PM2.5 (IQR: 30.9 μg/m3), PM10 (8.9 μg/m3), NO2 (25.5 μg/m3), SO2 (5.8 μg/m3) and CO (0.283 mg/m3) on the concurrent day was significantly associated with increments of 2.08 % (95 % CI: 0.53 %, 3.65 %), 2.53 % (95 % CI: 0.87 %, 4.22 %), 8.14 % (95 % CI: 6.24 %, 10.08 %), 5.67 % (95 % CI: 3.58 %, 7.80 %), and 2.27 % (95 % CI: 0.70 %, 3.87 %) in pediatric AD outpatient visits, respectively. The effects of NO2 remained robust after adjustment for other air pollutants. The exposure-response curves for PM2.5 and PM10 were steeper for moderate-lower concentrations, with a flatten curves at high concentration; nearly linear relationships were found for NO2. Higher associations of NO2 exposure on AD were detected in children under 6 years old (p=0.01); and we observed larger effect of air pollutants in cool seasons (p

Abstract In integrated circuits (ICs), the parasitic capacitance is one of the crucial factors that degrade the circuit dynamic performance; for instance, it reduces the operating frequency of the circuit. Eliminating the parasitic capacitance in organic transistors is notoriously challenging due to the inherent tradeoff between manufacturing costs and interlayer alignment accuracy. Here, we overcome such a limitation using a cost‐effective method for fabricating organic thin‐film transistors and rectifying diodes without redundant electrode overlaps. This is achieved by placing all electrodes horizontally and introducing sub‐100 nm gaps for separation. A representative small‐scale IC consisting of five‐stage ring oscillators based on the obtained nonparasitic transistors and diodes is fabricated on flexible substrates, which performs reliably at a low driving voltage of 1 V. Notably, the oscillator exhibits signal propagation delays of 5.8 μs per stage at a supply voltage of 20 V when utilizing pentacene as the active layer. Since parasitic capacitance has been a common challenge for all types of thin‐film transistors, our approach may pave the way toward the realization of flexible and large‐area ICs based on other emerging and highly performing semiconductors.

Abstract High‐grade serous tubo‐ovarian cancer (HGSTOC) is an aggressive gynecological malignancy including homologous recombination deficient (HRD) and homologous recombination proficient (HRP) groups. Despite the therapeutic potential of poly (ADP‐ribose) polymerase inhibitors (PARPis) and anti‐PDCD1 antibodies, acquired resistance in HRD and suboptimal response in HRP patients necessitate more precise treatment. Herein, single‐cell RNA and single‐cell T‐cell receptor sequencing on 5 HRD and 3 HRP tumors are performed to decipher the heterogeneous tumor immune microenvironment (TIME), along with multiplex immunohistochemistry staining and animal experiments for validation. HRD tumors are enriched with immunogenic epithelial cells, FGFR1+PDGFRβ+ myCAFs, M1 macrophages, tumor reactive CD8+/CD4+ Tregs, whereas HRP tumors are enriched with HDAC1‐expressing epithelial cells, indolent CAFs, M2 macrophages, and bystander CD4+/CD8+ T cells. Significantly, customized therapies are proposed. For HRD patients, targeting FGFR1+PDGFRβ+ myCAFs via tyrosine kinase inhibitors, targeting Tregs via anti‐CCR8 antibodies/TNFRSF4 stimulation, and targeting CXCL13+ exhausted T cells by blocking PDCD1/CTLA‐4/LAG‐3/TIGIT are proposed. For HRP patients, targeting indolent CAFs, targeting M2 macrophages via CSF‐1/CSF‐1R inhibitors, targeting bystander T cells via tumor vaccines, and targeting epithelial cells via HDAC inhibitors. The study provides comprehensive insights into HRD and HRP TIME and tailored therapeutic approaches, addressing the challenges of PARPi‐resistant HRD and refractory HRP tumors.

Many species of animals exhibit caregiving or aggression toward conspecific offspring. The neural mechanisms underlying the infanticide and pup care remain poorly understood. Here, using monogamous mandarin voles (Microtus mandarinus), we found that more oxytocin (OT) neurons in the paraventricular nucleus (PVN) were activated during pup caring than infanticide. Optogenetic activation of OT neurons in the PVN facilitated pup caring in male and female mandarin voles. In infanticide voles, optogenetic activation of PVN OT cells or PVN-medial prefrontal cortex (mPFC) OT projection fibers prolonged latency to approach and attack pups, whereas inhibition of these OT neurons or projections facilitated approach and infanticide. Optogenetic activation of PVN OT neuron projections to the mPFC in males shortened the latency to approach and retrieve pups and facilitated the initiation of pup care, but produced no effects on pup-care females. In addition, OT release in the mPFC increased upon approaching and retrieving pups, and decreased upon attacking pups. Intraperitoneal injection of OT promoted pup care and inhibited infanticide behavior. It is suggested that the OT system, especially PVN OT neurons projecting to mPFC, modulates pup-directed behaviors and OT can be used to treat abnormal behavioral responses associated with some psychological diseases such as depression and psychosis.

Traffic data imputation is crucial for the reliability and efficiency of intelligent transportation systems (ITSs), forming the foundation for downstream tasks like traffic prediction and management. However, existing deep learning-based imputation methods struggle with two significant challenges: poor performance under high missing data rates and the limited incorporation of external traffic-related factors. To address these challenges, we propose a novel knowledge graph-enhanced generative adversarial network (KG-GAN) for traffic data imputation. Our approach uniquely integrates external knowledge with traffic spatiotemporal dependencies to improve data imputation quality. Specifically, we construct a fine-grained knowledge graph (KG) that differentiates attributes and relationships of external factors such as points of interest (POI) and weather conditions, facilitating more robust knowledge representation learning. We then introduce a knowledge-aware embedding cell (EM-cell) that merges traffic data with these learned external representations, providing richer inputs for the spatiotemporal GAN. Extensive experiments on a large-scale real-world traffic dataset demonstrate that KG-GAN significantly outperforms state-of-the-art methods under various missing data scenarios. Additionally, ablation studies confirm the superior performance gained from incorporating external knowledge, underscoring the importance of this approach in addressing complex missing data patterns.

Breast cancer is the most diagnosed malignancy and major cause of cancer death among women population in the worldwide. Ferroptosis is a recently discovered iron-dependent regulated cell death involved in tumor progression and therapeutic response. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells like developing iron nanoparticles as a therapeutic agent. However, resistance to ferroptosis is a vital distinctive hallmark of cancer. Therefore, further investigation of the mechanism of ferroptosis resistance to enhance its tumor sensitivity is essential for ferroptosis-target breast cancer therapy. Our results revealed that the activation of C5a/C5aR pathway can drive resistance to ferroptosis and reshaping breast cancer immune microenvironment. Accordingly, loading PEG-Fe3O4 with C5aRA significantly improved the anti-tumor effect of PEG- Fe3O4 by inhibiting ferroptosis resistance and increasing macrophage polarization toward M1 phenotype. Our findings presented a novel cancer therapy strategy that combined cancer cell metal metabolism regulation and immunotherapy. The study also provided support for further evaluation of PEG- Fe3O4@C5aRA as a novel therapeutic strategy for breast cancer in clinical trials.

Nanoplastics are ubiquitous in our daily lives, raising concerns about their potential impact on the human brain. Many studies reported that nanoplastics permeate the blood-brain barrier and influence cellular processes in mouse models. However, the neurotoxic effects of ingesting nanoplastics on human brain remain poorly understood. Here, we treated cerebral organoids with polystyrene nanoplastics to model the effects of nanoplastic exposure on human brain. Importantly, we found that mitochondria might be the significant organelles affected by polystyrene nanoplastics using immunostaing and RNA-seq analysis. Subsequently, we observed the increased cell death and decreased cell differentiation in our cerebral organoids. In conclusion, our findings shed insights on the mechanisms underlying the toxicity of nanoplastics on human brain organoids, providing an evaluation system in detection potential environmental toxicity on human brain.

The ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-β family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-β signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/NO

Abstract Understanding the regulation of normal erythroid development will help to develop new potential therapeutic strategies for disorders of the erythroid lineage. Cellular repressor of E1A‐stimulated genes 1 (CREG1) is a glycoprotein that has been implicated in the regulation of tissue homeostasis. However, its role in erythropoiesis remains largely undefined. In this study, it is found that CREG1 expression increases progressively during erythroid differentiation. In zebrafish, creg1 mRNA is preferentially expressed within the intermediate cell mass (ICM)/peripheral blood island (PBI) region where primitive erythropoiesis occurs. Loss of creg1 leads to anemia caused by defective erythroid differentiation and excessive apoptosis of erythroid progenitors. Mechanistically, creg1 deficiency results in reduced activation of TGF‐β/Smad2 signaling pathway. Treatment with an agonist of the Smad2 pathway (IDE2) could significantly restore the defective erythroid development in creg1−/− mutants. Further, Klf1, identified as a key target gene downstream of the TGF‐β/Smad2 signaling pathway, is involved in creg1 deficiency‐induced aberrant erythropoiesis. Thus, this study reveals a previously unrecognized role for Creg1 as a critical regulator of erythropoiesis, mediated at least in part by the TGF‐β/Smad2‐Klf1 axis. This finding may contribute to the understanding of normal erythropoiesis and the pathogenesis of erythroid disorders.

Abstract For decades, many marine animals have been considered to exhibit cosmopolitan or transoceanic distribution. This situation is prevalent in Asia, where many species were collected and named by American or European experts in the 1700s to early 1900s. Using the windowpane oysters Placuna—a small genus of bivalves with five recognized species—we show that careful analysis is required to reassess the validity of these species. Currently, only two species of Placuna (P. placenta and P. ephippium) widely reported in the Indo‐Pacific region have been recorded from Chinese coastal waters. Here, we described two new species of Placuna from China. Placuna vitream sp. nov. can be distinguished from P. placenta by its larger ridge angle. Phylogenetic analysis using five gene fragments fully supported that P. vitream sp. nov. is a sister to the specimen from Singapore identified as P. placenta and more distant from other Placuna species with available molecular data. Besides, based on subfossil shells, we describe Placuna aestuaria sp. nov. that differs from its congeneric species by its broad hinge, medium ridge angle, and nearly straight ridges. Finally, we suggest a combination of hinge structure and ridge angle that can be used for identifying Placuna species and preparing a key to this genus. Our findings of two new species expand the diversity of Placuna and prompt reassessment of the many presumably widely distributed marine species in Asia.

Contemporary research on the walking environment focuses closely on the construction logic and internal correlation. Walkability is one of the vital characteristics of the old town street space. To understand how to improve the old town street space effectively, the investigation of the correlation mechanism of street walkability is essential. This study utilizes structural equation model (SEM) to construct a street walkability measurement model composed of four unobserved factors. Then, take Old Southern Area in Nanjing as an example, integrate Depthmap, ArcGIS and Python to obtain multi-source data, and establish a database of observed factors on street space. Finally, the matrix of the observed factors is set by SEM to calculate the correlation of the unobserved factors. This paper provides a novel technical approach for the correlation study of spatial construction logic as well as a reference for strengthening the spatial quality of the contemporary built environment.

Purpose: This retrospective study aims to assess the efficacy of the combined application of electromagnetic navigation (EMN) and porcine fibrin sealant (PFS) in the microwave ablation (MWA) treatment of lung tumors. Material and methods: In our department from January 2022 to August 2023, 73 patients underwent MWA under standard computed tomography (CT) guidance (CT group) or CT guidance with additional application of EMN and PFS (CT-EMN-PFS group), respectively. The basic data of patients were recorded and analyzed using the Student's t-test and Chi-square test between the two groups, and single factor and multi-factors binary logistic regression analyses were conducted to determine the risk factors of pneumothorax; meanwhile the incidence of complications, the number of CT scans and dose length product (DLP) were calculated and compared between the two guidance modes. Results: Forty-seven patients underwent standard CT-guided MWA, meanwhile the remaining 26 patients underwent CT-guided MWA with combined application of EMN and PFS. The patients with lesions close to the bronchi or interlobar fissures, and underlying emphysema had a higher risk of pneumothorax, the corresponding odds ratio (OR) was 23.290 (p = 0.004), 33.300 (p = 0.019), and 8.007 (p = 0.012), respectively; the combined use of EMN and PFS could reduce the incidence of pneumothorax, with an OR of 0.094 (95 % confidence interval [CI]: 0.015–0.602, p = 0.013). The incidence rates of pneumothorax, pneumorrhagia and pleural effusion were 59.57 %, 61.70 %, and 19.15 % respectively in the CT group, and 30.77 %, 50.00 % and 7.69 % respectively in the CT-EMN-PFS group. The incidence rate of pneumothorax in the CT-EMN-PFS group was significantly lower than that in the CT group (p = 0.017). The median number of CT scans was 9 in the CT group and 5 in the CT-EMN-PFS group, respectively, meanwhile the median DLP was 1060.69 mGy*cm in the CT group and 600.04 mGy*cm in the CT-EMN-PFS group, respectively, which indicated there was a statistical difference in the amount of radiation exposure between the two groups (p

Abstract Actin nucleotide-dependent actin remodeling is essential to orchestrate signal transduction and cell adaptation. Rapid energy starvation requires accurate and timely reorganization of the actin network. Despite distinct treadmilling mechanisms of ADP- and ATP-actin filaments, their filament structures are nearly identical. How other actin-binding proteins regulate ADP-actin filament assembly is unclear. Here, we show that Spa2 which is the polarisome scaffold protein specifically remodels ADP-actin upon energy starvation in budding yeast. Spa2 triggers ADP-actin monomer nucleation rapidly through a dimeric core of Spa2 (aa 281-535). Concurrently, the intrinsically disordered region (IDR, aa 1-281) guides Spa2 undergoing phase separation and wetting on the surface of ADP-G-actin-derived F-actin and bundles the filaments. Both ADP-actin-specific nucleation and bundling activities of Spa2 are actin D-loop dependent. The IDR and nucleation core of Spa2 are evolutionarily conserved by coexistence in the fungus kingdom, suggesting a universal adaptation mechanism in the fungal kingdom in response to glucose starvation, regulating ADP-G-actin and ADP-F-actin with high nucleotide homogeneity.

Abstract Bisphosphonate-related osteonecrosis of jaw (BRONJ) is characterized by impaired osteogenic differentiation of orofacial bone marrow stromal cells (BMSCs). Corin has recently been demonstrated to act as a key regulator in bone development and orthopedic disorders. However, the role of corin in BRONJ-related BMSCs dysfunction remains unclarified. A m6A epitranscriptomic microarray study from our group shows that the CORIN gene is significantly upregulated and m6A hypermethylated during orofacial BMSCs osteogenic differentiation. Corin knockdown inhibits BMSCs osteogenic differentiation, whereas corin overexpression or soluble corin (sCorin) exerts a promotion effect. Furthermore, corin expression is negatively regulated by bisphosphonates (BPs). Corin overexpression or sCorin reverses BPs-impaired BMSCs differentiation ability. Mechanistically, we find altered expression of phos-ERK in corin knockdown/overexpression BMSCs and BMSCs under sCorin stimulation. PD98059 (a selective ERK inhibitor) blocks the corin-mediated promotion effect. With regard to the high methylation level of corin during osteogenic differentiation, we apply a non-selective m6A methylase inhibitor, Cycloleucine, which also blocks the corin-mediated promotion effect. Furthermore, we demonstrate that METTL7A modulates corin m6A modification and reverses BPs-impaired BMSCs function, indicating that METTL7A regulates corin expression and thus contributes to orofacial BMSCs differentiation ability. To conclude, our study reveals that corin reverses BPs-induced BMSCs dysfunction, and METTL7A-mediated corin m6A modification underlies corin promotion of osteogenic differentiation via the ERK pathway. We hope this brings new insights into future clinical treatments for BRONJ.

Ni-based single-crystal superalloys are normally prepared by directional solidification. Due to different solidification sequences, Ni-based single-crystal superalloys exhibit a typical dendritic arm structure, and the element segregation in the dendritic arm can affect the high temperature mechanical properties of the alloy. Solid solution treatment has a certain extent to reduce the inter-dendritic and dendritic arm between the concentrations of the elements, thereby changing the alloy micro-nano view parameters to improve the high temperature mechanical properties of the alloy. In this study, nanoindentation experiments were carried out on the inter-dendritic and dendritic arm of the cast and solid solution samples. The micromechanical parameters were calculated. The amounts of changes in elemental concentration were discussed with the results of the energy dispersive spectroscopy and electron probe microanalysis, so as to analyse the relationship between the micromechanical parameters and the changes in elemental concentration. The results show that solid solution treatment has a significant impact on the elastic modulus, with an increase of 114.7% of the inter-dendritic region and an increase of 142.7% of the dendritic arm. However, solid solution treatment has little effect on the hardness, with no significant change in the hardness of the inter-dendritic region and an increase of 43.86% of the dendritic arm. Solid solution treatment has a more significant effect on improving the segregation behavior of Al and Co elements, with the segregation coefficients of Al and Co elements in the inter-dendritic region decreasing and increasing by 36% and 19%, and the segregation coefficients of Al and Co elements in the dendritic arm region decreasing and increasing by 29% and 34%.

In this paper, we were concerned with the multiplicity of the large periodic solutions to a super-linear wave equation with a general variable coefficient. In general, the variable coefficient $ \rho(\cdot) $ needs to be satisfied $ \text{ess inf}\, \eta_\rho(\cdot) > 0 $ with $ \eta_\rho(\cdot) = \frac{1}{2}\frac{\rho''}{\rho}-\frac{1}{4}\big(\frac{\rho'}{\rho}\big)^2 $. Especially, the case $ \eta_\rho(\cdot) = 0 $ is presented as an open problem in [Trans. Amer. Math. 349: 2015-2048, 1997]. Here, without any restrictions on $ \eta_{\rho}(\cdot) $, we established the multiplicity of large periodic solutions for the Dirichlet-Neumann boundary condition and Dirichlet-Robin boundary condition when the period $ T = 2\pi\frac{2a-1}{b} $ with $ a, b \in \mathbb{N}^+ $. The key ingredient of the proof is the combination of the variational method and an approximation argument. Since the sign of $ \eta_\rho(\cdot) $ can change, our results can be applied to the classical wave equation.

Abstract The etiopathogenesis of severe acute pancreatitis (SAP) remains poorly understood. We aim to investigate the role of immune cells Infiltration Characteristics during SAP progression. Gene expression profiles of the GSE194331 dataset were retrieved from the GEO. Lasso regression and random forest algorithms were employed to select feature genes from genes related to SAP progression and immune responses. CIBERSORT was utilized to estimate differences in immune cell types and proportions and the relationship between immune cells and gene expression. We performed pathway enrichment analysis using GSEA to examine disparities in KEGG signaling pathways when comparing the two groups. Additionally, CMap analysis was executed to identify prospective small molecular compounds. The three hub genes (CBLB, JADE2, RNF144A) were identified that can predict SAP progression. Analysis of CIBERSORT and TISIDB databases has shown that there are significant differences in immune cell expression levels between the normal and SAP groups, and three hub genes (CBLB, JADE2, RNF144A) were highly correlated with multiple immune cells, regulating the characteristics of immune cell infiltration in the microenvironment. Finally, drug prediction through the Connectivity Map database suggested that compounds such as Entecavir, KU-0063794, Y-27632, and Antipyrine have certain effects as potential targeted drugs for the treatment of SAP. CBLB, JADE2, and RNF144A are hub genes in SAP, potentially playing important roles in SAP progression. This finding further broadens the understanding of the etiopathogenesis of SAP and provides a feasible basis for future research on diagnostic and immunotherapeutic targets for SAP.

Abstract Background Weed control is essential for agricultural floor management in vineyards and the inter-row mulching is an eco-friendly practice to inhibit weed growth via filtering out photosynthetically active radiation. Besides weed suppression, inter-row mulching can influence grapevine growth and the accumulation of metabolites in grape berries. However, the complex interaction of multiple factors in the field challenges the understanding of molecular mechanisms on the regulated metabolites. In the current study, black geotextile inter-row mulch (M) was applied for two vintages (2016–2017) from anthesis to harvest. Metabolomics and transcriptomics analysis were conducted in two vintages, aiming to provide insights into metabolic and molecular responses of Cabernet Sauvignon grapes to M in a semi-arid climate. Results Upregulation of genes related to photosynthesis and heat shock proteins confirmed that M weakened the total light exposure and grapes suffered heat stress, resulting in lower sugar-acid ratio at harvest. Key genes responsible for enhancements in phenylalanine, glutamine, ornithine, arginine, and C6 alcohol concentrations, and the downward trend in ε-viniferin, anthocyanins, flavonols, terpenes, and norisoprenoids in M grapes were identified. In addition, several modules significantly correlated with the metabolic biomarkers through weighted correlation network analysis, and the potential key transcription factors regulating the above metabolites including VviGATA11, VviHSFA6B, and VviWRKY03 were also identified. Conclusion This study provides a valuable overview of metabolic and transcriptomic responses of M grapes in semi-arid climates, which could facilitate understanding the complex regulatory network of metabolites in response to microclimate changes.

Salinity is a major abiotic stress that seriously affects crop growth worldwide. In this work, we aimed to isolate potential halotolerant plant growth-promoting rhizobacteria (PGPR) to mitigate the adverse impacts of salt stress in rice. An isolate, D2, with multiple plant growth-promoting (PGP) characteristics was identified as Enterobacter asburiae D2. Strain D2 could produce indole-3-acetic acid and siderophore. It also exhibited phosphate solubilization and 1-aminocyclopropane-1-carboxylic deaminase activity. Genome analysis further provided insights into the molecular mechanism of its PGP abilities. Strain D2 inoculation efficiently stimulated rice growth under both normal and saline conditions. Compared with the non-inoculated plants, a significant increase in plant height (18.1–34.7%), root length (25.9–57.1%), root dry weight (57.1–150%), and shoot dry weight (17.3–50.4%) was recorded in inoculated rice seedlings. Meanwhile, rice seedlings inoculated with strain D2 showed improvement in chlorophyll and proline content, while the oxidant damage was reduced in these plants in comparison with the control group. Moreover, the K+/Na+ ratio of the inoculated rice seedlings exposed to NaCl and Na2CO3 was higher than that of the uninoculated groups. These results imply that Enterobacter asburiae D2 is a potential PGPR that can be used for alleviation of salt stress in rice.

Abstract While Phorbol-12-myristate-13-acetate-induced protein 1 (Noxa/PMAIP1) assumes a pivotal role in numerous tumors, its clinical implications and underlying mechanisms of gastric cancer (GC) are yet enigmatic. In this investigation, our primary objective was to scrutinize the clinical relevance and potential mechanisms of Noxa in gastric cancer. Immunohistochemical analysis was conducted on tissue microarrays comprising samples from a meticulously characterized cohort of 84 gastric cancer patients, accompanied by follow-up data, to assess the expression of Noxa. Additionally, Noxa expression levels in gastric cancer clinical samples and cell lines were measured through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. The effect of Noxa expression on the prognosis of patients with gastric cancer was evaluated using Kaplan–Meier survival. Further insight into the role of Noxa in driving gastric cancer progression was gained through an array of experimental techniques, including cell viability assays (CCK8), plate cloning assays, transwell assays, scratch assays, and real-time cell analysis (RTCA). Potential upstream microRNAs (miRNAs) that might modulate Noxa were identified through rigorous bioinformatics analysis, substantiated by luciferase reporter assays and Western blot experiments. Additionally, we utilized RNA sequencing, qRT-PCR, and Western blot to identify proteins binding to Noxa and potential downstream target. Finally, we utilized BALB/c nude mice to explore the role of Noxa in vivo. Our investigation unveiled a marked downregulation of Noxa expression in gastric cancer and underscored its significance as a pivotal prognostic factor influencing overall survival (OS). Noxa overexpression exerted a substantial inhibitory effect on the proliferation, migration and invasion of GC cells. Bioinformatic analysis and dual luciferase reporter assays unveiled the capacity of hsa-miR-200b-3p to interact with the 3′-UTR of Noxa mRNA, thereby orchestrating a downregulation of Noxa expression in vitro, consequently promoting tumor progression in GC. Our transcriptome analysis, coupled with mechanistic validation, elucidated a role for Noxa in modulating the expression of ZNF519 in the Mitophagy-animal pathway. The depletion of ZNF519 effectively reversed the oncogenic attributes induced by Noxa. Upregulation of Noxa expression suppressed the tumorigenesis of GC in vivo. The current investigation sheds light on the pivotal role of the hsa-miR-200b-3p/Noxa/ZNF519 axis in elucidating the pathogenesis of gastric cancer, offering a promising avenue for targeted therapeutic interventions in the management of this challenging malignancy.

Abstract Physical factors in the cellular microenvironment have critical effects on stem cell differentiation. The utilization of physical factors to promote the osteogenic differentiation of stem cells has been established as a new strategy for developing bone tissue engineering scaffolds. In this context, scaffolds with multiscale anisotropy are considered to possess biomimetic properties, which are advantageous for their biological performance. In the present study, a novel magnetic anisotropic hydrogel (MAH) with magnetic and topographic anisotropy was designed by combining static magnetic field-induced magnetic nanomaterials and a hydrogel. In in vitro studies, the MAH exhibited excellent biocompatibility and osteogenic bioactivity. The alkaline phosphatase activity and the expression of osteogenic-related genes and proteins induced by the MAH were greater than those induced by the pure PEGDA–GelMA hydrogel (PGH) and the magnetic isotropic hydrogel (MIH). In addition, the present study revealed that the dual anisotropic properties of the MAH activated the NOTCH1/2 pathway by upregulating SNHG5 and downstream SIRT6, which modulates the level of NOTCH1/2 by antagonizing DNMT1 protein stability, ultimately inducing the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Furthermore, the MAH, MIH, and PGH were tested for in vivo bone regeneration in rabbits with femur defects, and the results demonstrated that the MAH effectively stimulated bone regeneration. Taken together, these findings suggest that this magnetically and topographically anisotropic biomimetic hydrogel might be a promising candidate for application in the field of bone tissue regeneration.

The host restricts Salmonella enterica serovar Typhimurium infection of the gut via inflammasome-dependent sloughing of infected epithelial cells. Here we determined that concurrent caspase 1/11-dependent release of the goblet cell-derived mucin, Muc2, into the intestinal lumen also controls Salmonella burdens in infected mice. The increased release of mucins from goblet cells in the cecum and nearby proximal colon, and the subsequent thickening of the protective mucus barrier layer in the distal colon, were all dependent on the cytokines interleukin (IL)-18 and IL-22, as deficiencies in either cytokine resulted in reduced mucin secretion. Supplementation of IL-18 into IL-22 deficient mice restored mucin secretion, indicating that IL-22 acted upstream of IL-18 secretion during infection. In contrast, IL-18 and IL-22 independent signaling through Nlrp6 underlies only a modest, infection-induced increase in mucin secretion from goblet cells in the distal colon. These findings reveal that inflammasome signaling orchestrates multiple levels of protection centered on the intestinal epithelium, including pyroptosis and expulsion of infected enterocytes, as well as the release of mucins by goblet cells in the cecum and along the length of the colon. Our studies underscore the pivotal, multi-faceted role of inflammasome signaling in promoting host defense at the intestinal mucosal surface.

The grooved-filled asphalt pavement has certain advantages in terms of pavement ice-breaking and anti-skid. However, the performances of the filling material limit its development. In this study, a polyurethane urea (PUU) - waste rubber particles (WRP) composite filling material was prepared by using a polyurethane (PU) and adding polyurea (PUa) with a similar microstructure as the cementing material, and adding WRP as the elastic reinforcing phase. The proportions of nine PUU-WRP composite materials were designed by changing the particle size and content of WRP, and then the filled composite materials were evaluated in terms of physical and mechanical properties, ice adhesion properties, interface bonding properties and aging resistance. The test results showed that the shore hardness, tensile strength, compression permanent deformation, and contact angle of PUU-WRP composite decreased as content of the WRP increased. Except the ice adhesion force results were the opposite. On the other hand, increased the WRP size resulted in increase in PUU-WRP composite’s shore hardness, compression permanent deformation, and ice adhesion force, while the tensile strength and contact angle were the opposite. The surface of the PUU-WRP composite material was hydrophobic, and the maximum contact angle was 102.3°. The reduction of WRP particle size and dosage was beneficial for reducing the ice adhesion force on the surface of PUU-WRP composite materials. The maximum interfacial shear and tensile strength of PUU-WRP composite material were 1.082 MPa and 0.244 MPa, respectively. After 42 days of UV aging, the maximum attenuation rate did not exceed 30 %. After the immersion test, the tensile strength attenuation of PUU-WRP composite material was basically controlled within 10 %. Finally, based on the fuzzy comprehensive evaluation (FCE) method, it was recommended to use WRP with a particle size of 0.6 mm and a dosage of 30 wt%-40 wt%.

Abstract Precise control of quantum structures in hybrid nanocrystals requires advancements in scientific methodologies. Here, on the design of tunable CsPbBr3/Cs4PbBr6 quantum dots are reported by developing a unique discrete phase transformation approach in Cs4PbBr6 nanocrystals. Unlike conventional hybrid systems that emit solely in the green region, this current strategy produces adjustable luminescence in the blue (450 nm), cyan (480 nm), and green (510 nm) regions with high photoluminescence quantum yields up to 45%, 60%, and 85%, respectively. Concentration‐dependent studies reveal that phase transformation mechanisms and the factors that drive CsBr removal occur at lower dilutions while the dissolution–recrystallization process dominates at higher dilutions. When the polymer‐CsPbBr3/Cs4PbBr6 integrated into a field‐effected transistor the resulting phototransistors featured enhanced photosensitivity exceeding 105, being the highest reported for an n‐type phototransistor, while maintaining good transistor performances as compared to devices consisting of polymer‐CsPbBr3 NCs.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

Summary: Bombinin-BO1 (BO1), a bombinin peptide derived from the skin secretion of Bombina orientalis, exhibits broad-spectrum antimicrobial activity. To date, the anticancer effect of BO1 remains unclear. This study confirmed cytotoxicity of BO1 on hepatocellular carcinoma cells by inducing S-phase cycle block and apoptosis. In addition, BO1 was found to be localized in cytoplasm through endocytosis. The combined results of pull down, mass spectrometry, and co-immunoprecipitation suggested that BO1 induced misfolding of CDK1 and degradation by competitively binding HSP90A with Cdc37. It was verified that overexpression of HSP90A in BO1-treated cells significantly inhibited degradation of CDK1. In vivo, BO1 inhibited tumor without being toxic to individuals. This study reveals the anti-tumor mechanism of BO1 in inducing cell-cycle arrest and apoptosis by interfering with HSP90A-Cdc37-CDK1 system. This is the first study to analyze the mechanism of BO1 regulation of tumor cells, providing theoretical basis for BO1 treatment of hepatocellular carcinoma.

Abstract Human stem cells and derivatives transplantation are widely used to treat nervous system diseases, while the fate determination of transplanted cells is not well elucidated. To explore cell fate changes of human brain organoids before and after transplantation, human brain organoids are transplanted into prefrontal cortex (PFC) and hippocampus (HIP), respectively. Single‐cell sequencing is then performed. According to time‐series sample comparison, transplanted cells mainly undergo neural development at 2 months post‐transplantation (MPT) and then glial development at 4MPT, respectively. A different brain region sample comparison shows that organoids grafted to PFC have obtained cell fate close to those of host cells in PFC, other than HIP, which may be regulated by the abundant expression of dopamine (DA) and acetylcholine (Ach) in PFC. Meanwhile, morphological complexity of human astrocyte grafts is greater in PFC than in HIP. DA and Ach both activate the calcium activity and increase morphological complexity of astrocytes in vitro. This study demonstrates that human brain organoids receive host niche factor regulation after transplantation, resulting in the alignment of grafted cell fate with implanted brain regions, which may contribute to a better understanding of cell transplantation and regenerative medicine.