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This original work investigated the optical properties and Monte-Carlo (MC) based simulation of light propagation in the flavedo of Nanfeng tangerine (NF) and Gannan navel orange (GN) infected by Penicillium italicum. The increase of absorption coefficient (μ a ) at around 482 nm and the decrease at around 675 nm were both observed in infected NF and GN during storage, indicating the accumulation of carotenoids and loss of chlorophyll. Particularly, the μ a in NF varied more intensively than GN, but the limited differences of reduced scattering coefficient (μ s ') were detected while postharvest infection. Besides, MC simulation of light propagation indicated that the photon packets weight and penetration depth at 482 nm in NF were reduced more than in GN flavedo, while there were almost no changes at the relatively low absorption wavelength of 926 nm. The simulated absorption energy at 482 nm in NF and GN presented more changes than those at 675 nm during infection, thus could provide better detection of citrus diseases. Furthermore, PLS-DA models can discriminate healthy and infected citrus, with the accuracy of 95.24 % for NF and 98.67 % for GN, respectively. Consequently, these results can provide theoretical fundamentals to improve modelling prediction robustness and accuracy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The utilization of rice heterosis is essential for ensuring global food security; however, its molecular mechanism remains unclear. In this study, comprehensive analyses of accessible chromatin regions (ACRs), DNA methylation, and gene expression in inter-subspecific hybrid and its parents were performed to determine the potential role of chromatin accessibility in rice heterosis. The hybrid exhibited abundant ACRs, in which the gene ACRs and proximal ACRs were directly related to transcriptional activation rather than the distal ACRs. Regarding the dynamic accessibility contribution of the parents, paternal ZHF1015 transmitted a greater number of ACRs to the hybrid. Accessible genotype-specific target genes were enriched with overrepresented transcription factors, indicating a unique regulatory network of genes in the hybrid. Compared with its parents, the differentially accessible chromatin regions with upregulated chromatin accessibility were much greater than those with downregulated chromatin accessibility, reflecting a stronger regulation in the hybrid. Furthermore, DNA methylation levels were negatively correlated with ACR intensity, and genes were strongly affected by CHH methylation in the hybrid. Chromatin accessibility positively regulated the overall expression level of each genotype. ACR-related genes with maternal Z04A-bias allele-specific expression tended to be enriched during carotenoid biosynthesis, whereas paternal ZHF1015-bias genes were more active in carbohydrate metabolism. Our findings provide a new perspective on the mechanism of heterosis based on chromatin accessibility in inter-subspecific hybrid rice., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Backgroud: Thymic atrophy marks the onset of immune aging, precipitating developmental anomalies in T cells. Numerous clinical and preclinical investigations have underscored the regulatory role of Ganoderma lucidum spores (GLS) in T cell development. However, the precise mechanisms underlying this regulation remain elusive. Methods: In this study, a mice model of estradiol benzoate (EB)-induced thymic atrophy was constructed, and the improvement effect of GLS on thymic atrophy was evaluated. Then, we employs multi-omics techniques to elucidate how GLS modulates T cell development amidst EB-induced thymic atrophy in mice. Results: GLS effectively mitigates EB-induced thymic damage by attenuating apoptotic thymic epithelial cells (TECs) and enhancing the output of CD4 + T cells into peripheral blood. During thymic T cell development, sporoderm-removed GLS (RGLS) promotes T cell receptor (TCR) α rearrangement by augmenting V-J fragment rearrangement frequency and efficiency. Notably, biased Vα14-Jα18 rearrangement fosters double-positive (DP) to invariant natural killer T (iNKT) cell differentiation, partially contingent on RGLS-mediated restriction of peptide-major histocompatibility complex I (pMHCⅠ)-CD8 interaction and augmented CD1d expression in DP thymocytes, thereby promoting DP to CD4 + iNKT cell development. Furthermore, RGLS amplifies interaction between a DP subpopulation, termed DPsel-7, and plasmacytoid dendritic cells (pDCs), likely facilitating the subsequent development of double-negative iNKT1 cells. Lastly, RGLS suppresses EB-induced upregulation of Abpob and Apoa4, curbing the clearance of CD4 + Abpob + and CD4 + Apoa4 + T cells by mTECs, resulting in enhanced CD4 + T cell output. Discussion: These findings indicate that the RGLS effectively mitigates EB-induced TEC apoptosis and compromised double-positive thymocyte development. These insights into RGLS's immunoregulatory role pave the way for its potential as a T-cell regeneration inducer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Yang, Pan, Wang, Li, Zhang, Fan and Li.)

Background: Inter-subspecific hybrid rice represents a significant breakthrough in agricultural genetics, offering higher yields and better resilience to various environmental stresses. While the utilization of these hybrids has shed light on the genetic processes underlying hybridization, understanding the molecular mechanisms driving heterosis remains a complex and ongoing challenge. Here, chromatin immunoprecipitation-sequencing (ChIP-seq) was used to analyze genome-wide profiles of H3K4me3 and H3K27me3 modifications in the inter-subspecific hybrid rice ZY19 and its parents, Z04A and ZHF1015, then combined them with the transcriptome and DNA methylation data to uncover the effects of histone modifications on gene expression and the contribution of epigenetic modifications to heterosis., Results: In the hybrid, there were 8,126 and 1,610 different peaks for H3K4me3 and H3K27me3 modifications when compared to its parents, respectively, with the majority of them originating from the parental lines. The different modifications between the hybrid and its parents were more frequently observed as higher levels in the hybrid than in the parents. In ZY19, there were 476 and 84 allele-specific genes with H3K4me3 and H3K27me3 modifications identified, representing 7.9% and 12% of the total analyzed genes, respectively. Only a small portion of genes that showed differences in parental H3K4me3 and H3K27me3 modifications which demonstrated allele-specific histone modifications (ASHM) in the hybrid. The H3K4me3 modification level in the hybrid was significantly lower compared to the parents. In the hybrid, DNA methylation occurs more frequently among histone modification target genes. Additionally, over 62.58% of differentially expressed genes (DEGs) were affected by epigenetic variations. Notably, there was a strong correlation observed between variations in H3K4me3 modifications and gene expression levels in the hybrid and its parents., Conclusion: These findings highlight the substantial impact of histone modifications and DNA methylation on gene expression during hybridization. Epigenetic variations play a crucial role in controlling the differential expression of genes, with potential implications for heterosis., (© 2024. The Author(s).)

Glucagon-like peptide 1 (GLP1), which is mainly processed and cleaved from proglucagon in enteroendocrine cells (EECs) of the intestinal tract, acts on the GLP1 receptor in pancreatic cells to stimulate insulin secretion and to inhibit glucagon secretion. However, GLP1 processing is not fully understood. Here, we show that reticulon 4B (Nogo-B), an endoplasmic reticulum (ER)-resident protein, interacts with the major proglucagon fragment of proglucagon to retain proglucagon on the ER, thereby inhibiting PCSK1-mediated cleavage of proglucagon in the Golgi. Intestinal Nogo-B knockout in male type 2 diabetes mellitus (T2DM) mice increases GLP1 and insulin levels and decreases glucagon levels, thereby alleviating pancreatic injury and insulin resistance. Finally, we identify aberrantly elevated Nogo-B expression and inhibited proglucagon cleavage in EECs from diabetic patients. Our study reveals the subcellular regulatory processes involving Nogo-B during GLP1 production and suggests intestinal Nogo-B as a potential therapeutic target for T2DM., (© 2024. The Author(s).)

Tumor invasion and metastasis are the underlying causes of the high mortality rate of oral squamous cell carcinoma (OSCC). Energy metabolism reprogramming has been identified as a crucial process mediating tumor metastasis, thus indicating an urgent need for in-depth investigation of the specific mechanisms of tumor energy metabolism. Here, we identified an RNA-binding protein, DAZ associated protein 1 (DAZAP1), as a tumor-promoting factor with an important role in OSCC progression. DAZAP1 was significantly upregulated in OSCC, which enhanced the migration and invasion of OSCC cells and induced the epithelial-mesenchymal transition (EMT). RNA-seq analysis and experimental validation demonstrated that DAZAP1 regulates mitochondrial energy metabolism in OSCC. Mechanistically, DAZAP1 underwent liquid-liquid phase separation (LLPS) to accumulate in the nucleus where it enhanced cytochrome-c oxidase 16 (COX16) expression by regulating pre-mRNA alternative splicing, thereby promoting OSCC invasion and mitochondrial respiration. In mouse OSCC models, loss of DAZAP1 suppressed EMT, downregulated COX16, and reduced tumor growth and metastasis. In OSCC patient samples, expression of DAZAP1 positively correlated with COX16, and high expression of both proteins was associated with poor patient prognosis. Together, these findings revealed a mechanism by which DAZAP1 supports mitochondrial metabolism and tumor development of OSCC, suggesting the potential of therapeutic strategies targeting DAZAP1 to block OSCC invasion and metastasis.

Recently, research on polyoxometalates (POMs) has gained significant momentum. Owing to their properties as electronic sponges, POMs catalyst harbor substantial potential in lithium-sulfur battery research. However, POMs undergo a transformation into reduced heteropoly blue (HPB) during electrochemical reactions, which then dissolve into the electrolyte, resulting in catalyst loss. In this research, we amalgamated 18-crown-6 (CR6) with K3PW12O40, (KPW), synthesized a novel POM-based supramolecular compound, and integrated it with graphene oxide (GO) to fabricate a multi-functional composite polypropylene (PP) separator KPW-CR6/GO/PP. The crown ether array was employed to immobilize POM and construct ion transport channels, thereby enhancing the Li+ migration rate and capturing polysulfides. Subsequently, leveraging the stable structure and redox properties of POM, the polysulfide is catalyzed to transform and inhibit the shuttle effect, thereby protecting the Li anode. The lithium-sulfur batteries with the Crown ether-POM supramolecular compound separators, exhibit enhanced capacity and stability (1073.3 mAh g-1 at 1.0 C, and 81.5% retention rate after 250 cycles). The battery (S loading: 3.2 mg cm-2) presents an initial specific discharge capacity of 543.4 mAh g-1 at 0.5 C, with 89.8% of the capacity retained after 160 cycles. This underlines the practical application potential of Crown ether-POM supramolecular materials in Li-S batteries., (© 2024 Wiley‐VCH GmbH.)

In this work, visible and near-infrared 'point' (Vis-NIR) spectroscopy and hyperspectral imaging (Vis-NIR-HSI) techniques were applied on three different apple cultivars to compare their firmness prediction performances based on a large intra-variability of individual fruit, and develop rapid and simple models to visualize the variability of apple firmness on three apple cultivars. Apples with high degree of intra-variability can strongly affect the prediction model performances. The apple firmness prediction accuracy can be improved based on the large intra-variability samples with the coefficient variation (CV) values over 10%. The least squares-support vector machine (LS-SVM) models based on Vis-NIR-HSI spectra had better performances for firmness prediction than that of Vis-NIR spectroscopy, with the with the R c 2 over 0.84. Finally, The Vis-NIR-HSI technique combined with least squares-support vector machine (LS-SVM) models were successfully applied to visualize the spatial the variability of apple firmness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The aim of this study to explore the use of new-media health information and its influence on their health and health management., Methods: A total of 208 elderly people in Qiqihar City were selected as the survey objects, and a questionnaire was used to investigate their access to health information through new-media platforms. We analyze the factors ( e.g., education、pre-retirement occupation, etc.) in the use of health information on new-media platforms., Results: Monthly income, educational level, pre-retirement occupation and attention of the new-media of the elderly had significant effects on health information acquisition (p < 0.05)., Conclusion: The use of new-media health information among the elderly was diversified and had an impact on their health management. We should standardize the management of new-media health information dissemination platforms and publicize the use of new-media health information in a targeted way, to improve the self-health management of the elderly and reduce their burden on the national medical system., (© 2024. The Author(s).)

Research Question: What are the metabolic characteristics of follicular fluid in patients with ovarian endometriosis undergoing IVF?, Design: This was an exploratory cohort study on endometriosis. In total, 19 infertile patients with ovarian endometriosis diagnosed by laparoscopy, and 23 controls matched in terms of age and body mass index (women with infertility due to male or tubal factors) were enrolled in this study. All patients underwent IVF treatment with a gonadotrophin-releasing hormone antagonist protocol, and follicular fluid was collected at oocyte retrieval. The metabolomics of follicular fluid samples was analysed using an ultra-high-performance liquid chromatography Orbitrap Exploris mass spectrometer (UHPLC-OE-MS). The best combination of biomarkers was selected by performing stepwise logistic regression analysis with backward elimination., Results: Fifteen metabolites were identified as biomarkers associated with endometriosis. A final model containing 8-hydroxy-2-deoxyguanosine, biotin, n-acetyl-L-methionine and n-methylnicotinamide was constructed. Receiver operating characteristic analysis confirmed the value of these parameters in diagnosing endometriosis, with sensitivity of 94.7% and specificity of 95.7%. Enrichment analysis via the Kyoto Encyclopedia of Genes and Genome showed that 15 metabolites were enriched in eight metabolic pathways., Conclusion: Metabolomics based on UHPLC-OE-MS effectively characterized the metabolomics analysis of follicular fluid in patients with ovarian endometriosis. These findings may provide a new basis for better understanding of how diseases progress, and for the discovery of new biomarkers., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The conversion of DNA 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes represents a significant epigenetic modification, yet its role in early human embryos remains largely unknown. Here we showed that the early human embryo inherited a significant amount of 5hmCs from an oocyte, which unexpectedly underwent de novo hydroxymethylation during its growth. Furthermore, the generation of 5hmC in the paternal genome after fertilization roughly followed the maternal pattern, which was linked to DNA methylation dynamics and regions of sustained methylation. The 5hmCs persisted until the eight-cell stage and exhibited high enrichment at OTX2 binding sites, whereas knockdown of OTX2 in human embryos compromised the expression of early lineage genes. Specifically, the depletion of 5hmC affected the activation of embryonic genes, which was further evaluated by ectopically expressing mouse Tet3 in human early embryos. These findings revealed distinct dynamics of 5hmC and unravelled its multifaceted functions in early human embryonic development., (© 2024. The Author(s).)

This study aimed to elucidate responses of the bacterial structure and diversity of the rhizosphere in flowering broomcorn millet after rehydration following drought stress. In this study, the broomcorn millet varieties 'Hequ red millet' (A1) and 'Yanshu No.10' (A2), known for their different drought tolerance levels, were selected as experimental materials. The plants were subjected to rehydration after drought stress at the flowering stage, while normal watering (A1CK and A2CK) served as the control. Soil samples were collected at 10 days (A11, A21, A1CK1, and A2CK1) and 20 days (A12, A22, A1CK2, and A2CK2) after rehydration. High-throughput sequencing technology was employed to investigate the variations in bacterial community structure, diversity, and metabolic functions in the rhizosphere of the broomcorn millet at different time points following rehydration. The findings indicated that the operational taxonomic units (OTUs) of bacteria in the rhizosphere of broomcorn millet were notably influenced by the duration of treatment, with a significant decrease in OTUs observed after 20 days of rehydration. However, bacterial Alpha diversity was not significantly impacted by rehydration following drought stress. The bacterial community in the rhizosphere of broomcorn millet was mainly composed of Actinobacteria and Proteobacteria . After rewatering for 10 to 20 days after drought stress, the abundance of Sphingomonas and Aeromicrobium in the rhizosphere soil of the two varieties of broomcorn millet decreased gradually. Compared with Yanshu No.10, the abundance of Pseudarthrobacter in the rhizosphere of Hequ red millet gradually increased. A Beta diversity analysis revealed variations in the dissimilarities of the bacterial community which corresponded to different rehydration durations. The relative abundance of bacterial metabolic functions in the rhizosphere of broomcorn millet was lower after 20 days of rehydration, compared to measurements after 10 days of rehydration. This observation might be attributed to the exchange of materials between broomcorn millet and microorganisms during the initial rehydration stage to repair the effects of drought, as well as to the enrichment of numerous microorganisms to sustain the stability of the community structure. This study helps to comprehend the alterations to the bacterial structure and diversity in the rhizosphere of broomcorn millet following drought stress and rehydration. It sheds light on the growth status of broomcorn millet and its rhizosphere microorganisms under real environmental influences, thereby enhancing research on the drought tolerance mechanisms of broomcorn millet.

Ehrlichia chaffeensis infects and proliferates inside monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. After internalization, E. chaffeensis resides in specialized membrane-bound inclusions, E. chaffeensis -containing vesicles (ECVs), to evade from host cell innate immune responses and obtain nutrients. However, mechanisms exploited by host cells to inhibit E. chaffeensis growth in ECVs are still largely unknown. Here we demonstrate that host cells recognize E. chaffeensis Ech&#95;1067, a penicillin-binding protein, and then upregulate the expression of PIT1, which is a phosphate transporter and transports phosphate from ECVs to the cytosol to inhibit bacterial growth. We found that host cells upregulate the PIT1 expression upon E. chaffeensis infection using transcriptome sequencing, qRT-PCR and Western blotting, and PIT1 is localized on the ECV membrane in infected THP-1 cells using confocal microscopy. Silence of PIT1 using shRNA enhances E. chaffeensis intracellular growth. Finally, we found that E. chaffeensis Ech&#95;1067 induces the upregulation of PIT1 expression through the MyD88-NF-κB pathway using recombinant protein for stimulation and siRNA for silence. Our findings deepen the understanding of the innate immune responses of host cells to inhibit bacterial intracellular growth and facilitate the development of new therapeutics for HME.

Unlike other cancers with widespread screening (breast, colorectal, cervical, prostate, and skin), lung nodule biopsies for positive screenings have higher morbidity with clinical complications. Development of non-invasive diagnostic biomarkers could thereby significantly enhance lung cancer management for at-risk patients. Here, we leverage Mendelian Randomization (MR) to investigate the plasma proteome and metabolome for potential biomarkers relevant to lung cancer. Utilizing bidirectional MR and co-localization analyses, we identify novel associations, highlighting inverse relationships between plasma proteins SFTPB and KDELC2 in lung adenocarcinoma (LUAD) and positive associations of TCL1A with lung squamous cell carcinoma (LUSC) and CNTN1 with small cell lung cancer (SCLC). Additionally, our work reveals significant negative correlations between metabolites such as theobromine and paraxanthine, along with paraxanthine-related ratios, in both LUAD and LUSC. Conversely, positive correlations are found in caffeine/paraxanthine and arachidonate (20:4n6)/paraxanthine ratios with these cancer types. Through single-cell sequencing data of normal lung tissue, we further explore the role of lung tissue-specific protein SFTPB in carcinogenesis. These findings offer new insights into lung cancer etiology, potentially guiding the development of diagnostic biomarkers and therapeutic approaches., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Therapeutic cancer vaccines are among the first FDA-approved cancer immunotherapies. Among them, it remains a major challenge to achieve robust lymph-node (LN) accumulation. However, delivering cargo into LN is difficult owing to the unique structure of the lymphatics, and clinical responses have been largely disappointing. Herein, inspired by the Migrated-DCs homing from the periphery to the LNs, an injectable hydrogel-based polypeptide vaccine system is described for enhancing immunostimulatory efficacy, which could form a local niche of vaccine "hitchhiking" on DCs. The OVA peptide modified by lipophilic DSPE domains in the hydrogel is spontaneously inserted into the cell membrane to achieve "antigen anchoring" on DCs in vivo. Overall, OVA peptide achieves active access LNs through recruiting and "hitchhiking" subcutaneous Migrated-DCs. Remarkably, it is demonstrated that the composite hydrogel enhances LNs targeting efficacy by approximately six-fold compared to free OVA peptide. Then, OVA peptide can be removed from the cell surface under a typical acidic microenvironment within the LNs, further share them with LN-resident APCs via the "One-to-Many" strategy (One Migrated-DC corresponding to Many LN-resident APCs), thereby activating powerful immune stimulation. Moreover, the hydrogel vaccine exhibits significant tumor growth inhibition in melanoma and inhibits pulmonary metastatic nodule formation., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

In order to clarify the effect of different fertilizers on foxtail millet quality under low nitrogen conditions, we used JGNo.21 and LZGNo.2 as experimental materials and set up five treatments, including non-fertilization, nitrogen, phosphorus, compound, and organic fertilizers, to study the regulation of different fertilizer types on agronomic traits, nutrient fractions, and pasting characteristics of foxtail millet under low nitrogen conditions. Compared with the control, all of the fertilizers improved the agronomic traits of JGNo.21 to a certain extent. Nitrogen and compound fertilizer treatments reduced the starch content of JGNo.21; the starch content was reduced by 0.55% and 0.07% under nitrogen and compound fertilizers treatments. Phosphorus and organic fertilizers increased starch content, and starch content increased by 0.50% and 0.56% under phosphorus and organic fertilizer treatments. The effect of each fertilizer treatment on protein content was completely opposite to that of starch; different fertilizer treatments reduced the fat content of JGNo.21 and increased the fiber content. Among them, nitrogen and phosphorus fertilizers increased the yellow pigment content; the yellow pigment content increased by 1.21% and 2.64% under nitrogen and phosphorus fertilizer treatments. Organic and compound fertilizers reduced the content of yellow pigment; the yellow pigment content was reduced by 3.36% and 2.79% under organic and compound fertilizer treatments. Nitrogen and organic fertilizers increased the fat content of LZGNo.2; the fat content increased by 2.62% and 1.98% under nitrogen, organic fertilizer treatment. Compound and phosphorus fertilizer decreased the fat content; the fat content decreased by 2.16% and 2.90% under compound and phosphorus fertilizer treatment. Different fertilizer treatments reduced the cellulose and yellow pigment content of LZGNo.2. The content of essential, non-essential, and total amino acids of JGNo.21 was increased under compound and nitrogen fertilizer treatments and decreased under organic and phosphorus fertilizer treatments. The content of essential, non-essential, and total amino acids of LZGNo.2 was significantly higher under compound, nitrogen, and organic fertilizer treatments compared with control and significantly decreased under phosphorus fertilizer treatments. Nitrogen and compound fertilizer treatments significantly reduced the values of peak viscosity, trough viscosity, breakdown viscosity, final viscosity, setback viscosity, and pasting time of each index of JGNo.21; phosphorus and organic fertilizer treatments improved the values of each index. In contrast, the pasting viscosity of LZGNo.2 increased under phosphorus fertilizer treatment and decreased under nitrogen fertilizer treatment. Reasonable fertilization can improve the quality of foxtail millet, which provides a scientific theoretical basis for improving the quality of foxtail millet.

Glycogen synthase kinase-3 (GSK3), consisting of GSK3α and GSK3β subtypes, is a complex protein kinase that regulates numerous substrates. Research has observed increased GSK3 expression in the brains of Alzheimer's disease (AD) patients and models. AD is a neurodegenerative disorder with diverse pathogenesis and notable cognitive impairments, characterized by Aβ aggregation and excessive tau phosphorylation. This article provides an overview of GSK3's structure and regulation, extensively analyzing its relationship with AD factors. GSK3 overactivation disrupts neural growth, development, and function. It directly promotes tau phosphorylation, regulates amyloid precursor protein (APP) cleavage, leading to Aβ formation, and directly or indirectly triggers neuroinflammation and oxidative damage. We also summarize preclinical research highlighting the inhibition of GSK3 activity as a primary therapeutic approach for AD. Finally, pending issues like the lack of highly specific and affinity-driven GSK3 inhibitors, are raised and expected to be addressed in future research. In conclusion, GSK3 represents a target in AD treatment, filled with hope, challenges, opportunities, and obstacles., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background and Objective: Computer-based biomedical image segmentation plays a crucial role in planning of assisted diagnostics and therapy. However, due to the variable size and irregular shape of the segmentation target, it is still a challenge to construct an effective medical image segmentation structure. Recently, hybrid architectures based on convolutional neural networks (CNNs) and transformers were proposed. However, most current backbones directly replace one or all convolutional layers with transformer blocks, regardless of the semantic gap between features. Thus, how to sufficiently and effectively eliminate the semantic gap as well as combine the global and local information is a critical challenge., Methods: To address the challenge, we propose a novel structure, called BiU-Net, which integrates CNNs and transformers with a two-stage fusion strategy. In the first fusion stage, called Single-Scale Fusion (SSF) stage, the encoding layers of the CNNs and transformers are coupled, with both having the same feature map size. The SSF stage aims to reconstruct local features based on CNNs and long-range information based on transformers in each encoding block. In the second stage, Multi-Scale Fusion (MSF), BiU-Net interacts with multi-scale features from various encoding layers to eliminate the semantic gap between deep and shallow layers. Furthermore, a Context-Aware Block (CAB) is embedded in the bottleneck to reinforce multi-scale features in the decoder., Results: Experiments on four public datasets were conducted. On the BUSI dataset, our BiU-Net achieved 85.50 % on Dice coefficient (Dice), 76.73 % on intersection over union (IoU), and 97.23 % on accuracy (ACC). Compared to the state-of-the-art method, BiU-Net improves Dice by 1.17 %. For the Monuseg dataset, the proposed method attained the highest scores, reaching 80.27 % and 67.22 % for Dice and IoU. The BiU-Net achieves 95.33 % and 81.22 % Dice on the PH2 and DRIVE datasets., Conclusions: The results of our experiments showed that BiU-Net transcends existing state-of-the-art methods on four publicly available biomedical datasets. Due to the powerful multi-scale feature extraction ability, our proposed BiU-Net is a versatile medical image segmentation framework for various types of medical images. The source code is released on (https://github.com/ZYLandy/BiU-Net)., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest with respect to the research, authorship, and publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In the study, a sweet wine koji (YQ-5) was successfully selected to make frozen Chinese sweet rice wine dough (F-CD) for flavor enrichment. Subsequently, the effects of single improver (SI: xanthan gum, potassium carbonate, antifreeze protein, diacetyl tartaric esters of monoglycerides and composite improver (XPADG: Four improvers mixed in proportion) on the texture, rheological properties, microstructure, water status, protein secondary structure, volatile flavor substances and sensory properties of F-CD during frozen storage were investigated. The results indicated that XPADG slowed the increase in freezable water and water mobility in the dough, giving dough the most stable rheological properties and minimizing the damage of freezing to the secondary structure and microstructure of proteins. Besides, GC-QTOF/MS analysis showed that XPADG may facilitate the retention of flavoring substances in F-CD after storage for 6 days. Finally, the sensory evaluation showed that XPADG imparted good sensory properties to the product after freezing for 6 days., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Tigecycline and the newly Food and Drug Administration-approved tetracyclines, including eravacycline and omadacycline, are regarded as last-resort treatments for multidrug-resistant Enterobacterales. However, tigecycline resistance in Klebsiella pneumoniae has increased, especially the underlying mechanism of heteroresistance is unclear. This study aimed to elucidate the mechanisms underlying tigecycline resistance and heteroresistance in clinical K. pneumoniae isolates. A total of 153 clinical K. pneumoniae isolates were collected, and identified 15 tigecycline-resistant and three tigecycline-heteroresistant isolates using broth microdilution and population analysis profile methods, respectively. Total RNAs from K. pneumoniae ATCC13883 and the laboratory-induced tigecycline-resistant strain were extracted and sequenced on an Illumina platform. Differentially expressed genes and regulatory small RNAs (sRNAs) were analyzed and validated in clinical isolates of K. pneumoniae using quantitative real-time PCR. RNA sequencing results showed that mdtABC efflux pump genes were significantly upregulated in the tigecycline-resistant strains. Overexpression of mdtABC was observed in a clinical K. pneumoniae isolate, which increased tigecycline minimum inhibitory concentrations (MICs) and was involved in tigecycline heteroresistance. Sequencing analysis of sRNA demonstrated that candidate sRNA-120 directly interacted with the mdtABC operon and was downregulated in tigecycline-resistant strains. We generated an sRNA-120 deletion mutation strain and a complemented strain of K. pneumoniae. The sRNA-120 deletion strain displayed increased mRNA levels of mdtA, mdtB, and mdtC and an increase in MICs of tigecycline. The complemented strain of sRNA-120 restored the mRNA levels of these genes and the susceptibility to tigecycline. RNA antisense purification and parallel reaction monitoring mass spectrometry were performed to verify the interactions between sRNA-120 and mdtABC. Collectively, our study highlights that the post-transcriptional repression of mdtABC through sRNA-120 may provide an additional layer of efflux pump gene expression control, which is important for resistance and heteroresistance in clinical K. pneumoniae isolates., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Machine learning methods have been used in identifying omics markers for a variety of phenotypes. We aimed to examine whether a supervised machine learning algorithm can improve identification of alcohol-associated transcriptomic markers. In this study, we analysed array-based, whole-blood derived expression data for 17 873 gene transcripts in 5508 Framingham Heart Study participants. By using the Boruta algorithm, a supervised random forest (RF)-based feature selection method, we selected twenty-five alcohol-associated transcripts. In a testing set (30 % of entire study participants), AUC (area under the receiver operating characteristics curve) of these twenty-five transcripts were 0·73, 0·69 and 0·66 for non-drinkers v . moderate drinkers, non-drinkers v . heavy drinkers and moderate drinkers v . heavy drinkers, respectively. The AUC of the selected transcripts by the Boruta method were comparable to those identified using conventional linear regression models, for example, AUC of 1958 transcripts identified by conventional linear regression models (false discovery rate < 0·2) were 0·74, 0·66 and 0·65, respectively. With Bonferroni correction for the twenty-five Boruta method-selected transcripts and three CVD risk factors (i.e. at P < 6·7e-4), we observed thirteen transcripts were associated with obesity, three transcripts with type 2 diabetes and one transcript with hypertension. For example, we observed that alcohol consumption was inversely associated with the expression of DOCK4 , IL4R , and SORT1 , and DOCK4 and SORT1 were positively associated with obesity, and IL4R was inversely associated with hypertension. In conclusion, using a supervised machine learning method, the RF-based Boruta algorithm, we identified novel alcohol-associated gene transcripts.

Engineered protein fibers are promising biomaterials with diverse applications due to their tunable protein structure and outstanding mechanical properties. However, it remains challenging at the molecular level to achieve satisfied mechanical properties and environmental tolerance simultaneously, especially under extreme acid conditions. Herein, the construction of artificial fibers comprising chimeric proteins made of rigid amyloid peptide and flexible cationic elastin-like protein (ELP) module is reported. The amyloid peptide readily assembles into highly organized β-sheet structures that can be further strengthened by the coordination of Cu 2+ , while the flexible ELP module allows the formation of imine-based crosslinking networks. These double networks synergistically enhance the mechanical properties of the fibers, leading to a high tensile strength and toughness, overwhelming many reported recombinant spidroin fibers. Notably, the coordination of Cu 2+ with serine residues could stabilize β-sheet structures in the fibers under acidic conditions, which makes the fibers robust against acid, thus enabling their successful utilization in gastric perforation suturing. This work highlights the customization of double networks at the molecular level to create tailored high-performance protein fibers for various application scenarios., (© 2024 Wiley‐VCH GmbH.)

Detecting genes that affect specific traits (such as human diseases and crop yields) is important for treating complex diseases and improving crop quality. A genome-wide association study (GWAS) provides new insights and directions for understanding complex traits by identifying important single nucleotide polymorphisms. Many GWAS summary statistics data related to various complex traits have been gathered recently. Studies have shown that GWAS risk loci and expression quantitative trait loci (eQTLs) often have a lot of overlaps, which makes gene expression gradually become an important intermediary to reveal the regulatory role of GWAS. In this review, we review three types of gene-trait association detection methods of integrating GWAS summary statistics and eQTLs data, namely colocalization methods, transcriptome-wide association study-oriented approaches, and Mendelian randomization-related methods. At the theoretical level, we discussed the differences, relationships, advantages, and disadvantages of various algorithms in the three kinds of gene-trait association detection methods. To further discuss the performance of various methods, we summarize the significant gene sets that influence high-density lipoprotein, low-density lipoprotein, total cholesterol, and triglyceride reported in 16 studies. We discuss the performance of various algorithms using the datasets of the four lipid traits. The advantages and limitations of various algorithms are analyzed based on experimental results, and we suggest directions for follow-up studies on detecting gene-trait associations., (© 2024. Science China Press.)

Crops were the main source of human food, which have met the increasingly diversified demand of consumers. Sensors were used to monitor crop phenotypes and environmental information in real time, which will provide a theoretical reference for optimizing crop growth environment, resisting biotic and abiotic stresses, and improve crop yield. Compared with non-contact monitoring methods such as optical imaging and remote sensing, wearable sensing technology had higher time and spatial resolution. However, the existing crop sensors were mainly rigid mechanical structures, which were easy to cause damage to crop organs, and there were still challenges in terms of accuracy and biosafety. Emerging flexible sensors had attracted wide attention in the field of crop phenotype monitoring due to their excellent mechanical properties and biocompatibility. The article introduced the key technologies involved in the preparation of flexible wearable sensors from the aspects of flexible preparation materials and advanced preparation processes. The monitoring function of flexible sensors in crop growth was highlighted, including the monitoring of crop nutrient, physiological, ecological and growth environment information. The monitoring principle, performance together with pros and cons of each sensor were analyzed. Furthermore, the future opportunities and challenges of flexible wearable devices in crop monitoring were discussed in detail from the aspects of new sensing theory, sensing materials, sensing structures, wireless power supply technology and agricultural sensor network, which will provide reference for smart agricultural management system based on crop flexible sensors, and realize efficient management of agricultural production and resources., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yan, Zhang, Wang, Zhang and Fu.)

Authenticating whole wheat foods poses a significant challenge for both the grain industry and consumers. Alkylresorcinols (ARs), serving as biomarkers of whole wheat, play a crucial role in assessing the authenticity of whole wheat foods. Herein, we introduce a novel molecularly imprinted electrochemical sensor with modifications involving a molecularly imprinted polymer (MIP) and MXene nanosheets, enabling highly sensitive and selective detection of ARs. Notably, we specifically chose 5-heneicosylresorcinol (AR21), the predominant homologue in whole wheat, as the template molecule. α-Cyclodextrin and acrylamide served as dual functional monomers, establishing a robust multiple interaction between the MIP and AR21. As a result, the sensor exhibited a wide linear range of 0.005 to 100 μg·mL -1 and a low detection limit of 2.52 ng·mL -1 , demonstrating exceptional selectivity and stability. When applied to commercial whole wheat foods, the assay achieved satisfactory recoveries and accuracy, strongly validating the practicality and effectiveness of this analytical technique.

Purpose: Head and neck cancer is the sixth most common type of cancer worldwide, wherein the immune responses are closely associated with disease occurrence, development, and prognosis. Investigation of the role of immunogenic cell death-related genes (ICDGs) in adaptive immune response activation may provide cues into the mechanism underlying the outcome of HNSCC immunotherapy., Methods: ICDGs expression patterns in HNSCC were analyzed, after which consensus clustering in HNSCC cohort conducted. A 4-gene prognostic model was constructed through LASSO and Cox regression analyses to analyze the prognostic index using the TCGA dataset, followed by validation with two GEO datasets. The distribution of immune cells and the response to immunotherapy were compared between different risk subtypes through multiple algorithms. Moreover, immunohistochemical (IHC) analyses were conducted to validate the prognostic value of HSP90AA1 as a predictor of HNSCC patient prognosis. In vitro assays were performed to further detect the effect of HSP90AA1 in the development of HNSCC., Results: A novel prognostic index based on four ICDGs was constructed and proved to be useful as an independent factor of HNSCC prognosis. The risk score derived from this model grouped patients into high- and low-risk subtypes, wherein the high-risk subtype had worse survival outcomes and poorer immunotherapy response. IHC analysis validated the applicability of HSP90AA1 as a predictor of prognosis of HNSCC patients. HSP90AA1 expression in tumor cells promotes the progression of HNSCC., Conclusions: Together, these results highlight a novel four-gene prognostic signature as a valuable tool to assess survival status and prognosis of HNSCC patients., (© 2024. The Author(s).)

Neutrophil extracellular traps (NETs) are reticular structures composed of neutrophil elastase (NE), cathepsin G (CG) and DNA-histone enzyme complexes. Accumulating evidence has revealed that NETs play important roles in tumor progression, metastasis, and thrombosis. However, our understanding of its clinical value and mechanism of action in oral squamous cell carcinoma (OSCC) is limited and has not yet been systematically described. Here, we aimed to investigate the clinical significance of NETs in OSCC and the mechanisms by which they affect its invasive and metastatic capacity. Our results demonstrated that high enrichment of NETs is associated with poor prognosis in OSCC, and mechanistic studies have shown that NE in NETs promotes invasion and metastasis via NLRP3-mediated inhibition of pyroptosis in OSCC. These findings may provide a new therapeutic approach for OSCC., (© 2024. The Author(s).)

Objectives: To evaluate its effect of an evidence-based nursing program for nasal irrigation after endoscopic sinus surgery in patients with chronic rhinosinusitis (CRS)., Methods: A total of 66 patients with CRS were randomly divided into two groups, for which the experimental group received evidence-based nasal irrigation nursing, and the control group received conventional nursing. Differences in Sino-Nasal Outcome Test-20 (SNOT-20), visual analogue scale (VAS), Lund-Mackay CT, Endoscopic Lund Kennedy Score (LKES) and overall efficacy were assessed between the two groups., Results: 2, 4 and 12 weeks after the intervention, the scores of SNOT-20, VAS, Lund-Mackay CT and LKES in the two groups were significantly lower than those before the surgery (P < 0.05). Compared with the control group, the scores were significantly lower in the experimental group (P < 0.05). 12 weeks after the intervention, the overall effective rate of treatment in the experimental group was 90.62%, while the control group was 16.43%, but the difference was not statistically significant in treatment effect (P > 0.05)., Conclusions: The implementation of nasal irrigation evidence-based nursing program for patients with CRS after endoscopic sinus surgery can promote postoperative nasal mucosal recovery, improve treatment efficiency, and help improve patient comfort, quality of life and other subjective feelings., Trial Registration: The study was registered retrospectively with reference number ChiCTR2300075484 on 06/09/2023, available at: https://www.chictr.org.cn ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Drug-resistant bacterial infection and biofilm formation are the key inhibitors of wound healing, and new strategies are urgently needed to address these issues. In this study, we designed a pH-responsive co-assembled peptide hydrogel to inhibit Methicillin-resistant Staphylococcus aureus (MRSA) infection and promote wound healing. We synthesized a cationic short peptide (Nap-FFKKK) and a co-assembled hydrogel with curcumin at pH ∼ 7.8. The loaded curcumin was continuously released in a weak acid environment (pH ∼ 5.5). The lysine-rich cationic peptide inhibited biofilm formation in MRSA via electrostatic interaction with the negatively charged bacterial cell surface and, thus, provided a reinforcing antibacterial effect with curcumin. In vitro antibacterial experiments showed that the co-assembled system considerably reduced the minimum inhibitory concentration of curcumin against MRSA by 10-fold and promoted wound healing in a mouse model of MRSA-infected wounds. This study provides a simple and promising strategy to treat drug-resistant bacterial infections in wounds.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8 + T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8 + T cells, driven by specific stromal cells such as CTHCR1 + fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8 + T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers., (© 2024. The Author(s).)

Synthetic spidroin fibers have not yet attained the same level of toughness and stability as natural spider silks due to the complexity of composition and hierarchical structure. Particularly, understanding the intricate interactions between spidroin components in spider fiber is still elusive. Herein, we report modular design and preparation of spidroin-mimetic fibers composed of a conservative C-terminus spidroin module, two different natural β-sheets modules, and a non-spidroin random-coil module. The resulting fibers exhibit a toughness of ~200 MJ/m 3 , reaching the highest value among the reported artificial spider silks. The interactions between two components of recombinant spidroins facilitate the intermolecular co-assembly of β-sheets, thereby enhancing the mechanical strength and reducing batch-to-batch variability in the dual-component spidroin fibers. Additionally, the dual-component spidroin fibers offer potential applications in implantable or even edible devices. Therefore, our work presents a generic strategy to develop high-performance protein fibers for diverse translations in different scenarios., (© 2024 Wiley‐VCH GmbH.)

Floral meristem termination is a key step leading to carpel initiation and fruit development. The frequent occurrence of heat stress due to global warming often disrupts floral determinacy, resulting in defective fruit formation. However, the detailed mechanism behind this phenomenon is largely unknown. Here, we identify CRABS CLAW a (SlCRCa) as a key regulator of floral meristem termination in tomato. SlCRCa functions as an indispensable floral meristem terminator by suppressing SlWUS activity through the TOMATO AGAMOUS 1 (TAG1)-KNUCKLES (SlKNU)-INHIBITOR OF MERISTEM ACTIVITY (SlIMA) network. A direct binding assay revealed that SlCRCa specifically binds to the promoter and second intron of WUSCHEL (SlWUS). We also demonstrate that SlCRCa expression depends on brassinosteroid homeostasis in the floral meristem, which is repressed by heat stress via the circadian factor EARLY FLOWERING 3 (SlELF3). These results provide new insights into floral meristem termination and the heat stress response in flowers and fruits of tomato and suggest that SlCRCa provides a platform for multiple protein interactions that may epigenetically abrogate stem cell activity at the transition from floral meristem to carpel initiation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The demand for identification of maize varieties has increased dramatically due to the phenomenon of mixed seeds and inferior varieties pretending to be high-quality varieties continuing to occur. It is urgent to solve the problem of efficient and accurate identification of maize varieties. A hyperspectral image acquisition system was used to acquire images of maize seeds. Regions of interest (ROI) with an embryo size of 10 × 10 pixel were extracted, and the average spectral information in the range of 949.43-1709.49 nm was intercepted for the subsequent study in order to eliminate random noise at both ends. Savitzky-Golay (SG) smoothing algorithm and multiple scattering correction (MSC) were used to pretreat the full-band spectrum. The feature wavelengths were screened by successive projection algorithms (SPA), competitive adaptive reweighted sampling (CARS) single screening, and two combinations of CARS-SPA and CARS + SPA, respectively. Support vector machines (SVMs) and models optimized based on genetic algorithm (GA), particle swarm optimization (PSO) were established by using full bands (FB) and feature bands as the model input. The results showed that the MSC-(CARS-SPA)-GA-SVM model had the best performance with 93.00% of the test set accuracy, 8 feature variables, and a running time of 24.45 s. MSC pretreatment can effectively eliminate the scattering effect of spectral data, and the feature wavelengths extracted by CARS-SPA can represent all wavelength information. The study proved that hyperspectral imaging combined with GA-SVM can realize the identification of maize varieties, which provided a theoretical basis for maize variety classification and authenticity identification., (© 2024 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Tuning fork, consisting of two fork arms and a fork handle, has a stable and rigid structure. Inspired by this structure, a tuning fork-shaped DNA (TF-DNA) fluorescence aptasensor was constructed to detect ochratoxin A (OTA) and aflatoxin B1 (AFB1). A TF-DNA double-stranded structure capable of attaching both OTA aptamer labeled with the FAM fluorescent group (FAM-Apt) and AFB1 aptamer labeled with the ROX fluorescent group (ROX-Apt) was designed and linked to magnetic beads. This TF-DNA double-stranded structure can provide a stable platform for dual-target detection. In the presence of OTA and AFB1, FAM-Apt and ROX-Apt preferentially bound to them and detached from the TF-DNA double-stranded structure. Dual-signal fluorescent probes were collected from the supernatant by magnetic separation, and achieved fluorescence enhancement at 520 nm and 607 nm, respectively. The linear ranges are 0.05 ng/mL to 100 ng/mL for OTA and 0.1 ng/mL to 100 ng/mL for AFB1, and the detection limits are 0.015 ng/mL and 0.045 ng/mL, respectively. The developed sensor has the advantages of simple and fast preparation, good specificity and reproducibility, which is promising for the simultaneous determination of multiple hazardous substances in food., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: In light of the public health burden of the COVID-19 pandemic, boosting the safety and immunogenicity of COVID-19 vaccines is of great concern. Numerous Traditional Chinese medicine (TCM) preparations have shown to beneficially modulate immunity. Based on pilot experiments in mice that showed that supplementation with Huoxiang Suling Shuanghua Decoction (HSSD) significantly enhances serum anti-RBD IgG titers after inoculation with recombinant SARS-CoV-2 S-RBD protein, we conducted this randomized, double-blind, placebo-controlled clinical trial aimed to evaluate the potential immunogenicity boosting effect of oral HSSD after a third homologous immunization with Sinovac's CoronaVac SARS-CoV-2 (CVS) inactivated vaccine., Methods: A total of 70 participants were randomly assigned (1:1 ratio) to receive a third dose of CVS vaccination and either oral placebo or oral HSSD for 7 days. Safety aspects were assessed by recording local and systemic adverse events, and by blood and urine biochemistry and liver and kidney function tests. Main outcomes evaluated included serum anti-RBD IgG titer, T lymphocyte subsets, serum IgG and IgM levels, complement components (C3 and C4), and serum cytokines (IL-6 and IFN-γ). In addition, metabolomics technology was used to analyze differential metabolite expression after supplementation with HSSD., Results: Following a third CVS vaccination, significantly increased serum anti-RBD IgG titer, reduced serum IL-6 levels, increased serum IgG, IgM, and C3 and C4 levels, and improved cellular immunity, evidenced by reduce balance deviations in the distribution of lymphocyte subsets, was observed in the HSSD group compared with the placebo group. No serious adverse events were recorded in either group. Serum metabolomics results suggested that the mechanisms by which HSSD boosted the immunogenicity of the CVS vaccine are related to differential regulation of purine metabolism, vitamin B6 metabolism, folate biosynthesis, arginine and proline metabolism, and steroid hormone biosynthesis., Conclusion: Oral HSSD boosts the immunogenicity of the CVS vaccine in young and adult individuals. This trial provides clinical reference for evaluation of TCM immunomodulators to improve the immune response to COVID-19 vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tang, Wang, Zhang, Fei, Zhang, Liu, Lv, Wang, Lv, Nan, Tao, Chen, Chen, Jiang and Zhang.)

Acute promyelocytic leukemia (APL) is generally driven by PML::RARA, but approximately 2% of variant APL patients do not contain this fusion gene and pose challenges in diagnosis and treatment. Here, we reported an aggressive APL patient with variant TNRC18::RARA fusion gene, who was resistant to standard differentiation induction therapy consisting of all-trans retinoic acid (ATRA) and arsenic trioxide but achieved complete remission with venetoclax plus ATRA. Mechanistically, venetoclax possesses synergistic effects in ATRA-induced TNRC18::RARA-positive cell differentiation., (© 2023 The Authors. Molecular Carcinogenesis published by Wiley Periodicals LLC.)

Microplastics (MPs) migrate by adsorbing heavy metals in aquatic environments and act as their carriers. However, the aging mechanisms of MPs in the environment and the interactions between MPs and heavy metals in aquatic environments require further study. In this study, two kinds of materials, polyamide (PA) and polylactic acid (PLA) were used as target MPs, and the effects of UV irradiation on the physical and chemical properties of the MPs and the adsorption behavior of Cu(II) were investigated. The results showed that after UV irradiation, pits, folds and pores appeared on the surface of aged MPs, the specific surface area (SSA) increased, the content of oxygen-containing functional groups increased, and the crystallinity decreased. These changes enhanced the adsorption capacity of aged MPs for Cu(II) pollutants. The adsorption behavior of the PA and PLA MPs for Cu(II) conformed to the pseudo-second-order model and Langmuir isotherm model, indicating that the monolayer chemical adsorption was dominant. The maximum amounts of aged PA and PLA reached 1.415 and 1.398 mg/g, respectively, which were 1.59 and 1.76 times of virgin MPs, respectively. The effects of pH and salinity on the adsorption of Cu(II) by the MPs were significant. Moreover, factors such as pH, salinity and dosage had significant effects on the adsorption of Cu(II) by MPs. Oxidative complexation between the oxygen-containing groups of the MPs and Cu(II) is an important adsorption mechanism. These findings reveal that the UV irradiation aging of MPs can enhance the adsorption of Cu(II) and increase their role as pollutant carriers, which is crucial for assessing the ecological risk of MPs and heavy metals coexisting in aquatic environments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Significance: Early diagnosis of depression is crucial for effective treatment. Our study utilizes functional near-infrared spectroscopy (fNIRS) and machine learning to accurately classify mild and severe depression, providing an objective auxiliary diagnostic tool for mental health workers., Aim: Develop prediction models to distinguish between severe and mild depression using fNIRS data., Approach: We collected the fNIRS data from 140 subjects and applied a complete ensemble empirical mode decomposition with an adaptive noise-wavelet threshold combined denoising method (CEEMDAN-WPT) to remove noise during the verbal fluency task. The temporal features (TF) and correlation features (CF) from 18 prefrontal lobe channels of subjects were extracted as predictors. Using recursive feature elimination with cross-validation, we identified optimal TF or CF and examined their role in distinguishing between severe and mild depression. Machine learning algorithms were used for classification., Results: The combination of TF and CF as inputs for the prediction model yielded higher classification accuracy than using either TF or CF alone. Among the prediction models, the SVM-based model demonstrates excellent performance in nested cross-validation, achieving an accuracy rate of 92.8%., Conclusions: The proposed model can effectively distinguish mild depression from severe depression., (© 2024 The Authors.)

Multiple myeloma (MM) is a hematologic malignancy notorious for its high relapse rate and development of drug resistance, in which cell adhesion-mediated drug resistance plays a critical role. This study integrated four RNA sequencing datasets (CoMMpass, GSE136337, GSE9782, and GSE2658) and focused on analyzing 1706 adhesion-related genes. Rigorous univariate Cox regression analysis identified 18 key prognosis-related genes, including KIF14, TROAP, FLNA, MSN, LGALS1, PECAM1, and ALCAM, which demonstrated the strongest associations with poor overall survival (OS) in MM patients. To comprehensively evaluate the impact of cell adhesion on MM prognosis, an adhesion-related risk score (ARRS) model was constructed using Lasso Cox regression analysis. The ARRS model emerged as an independent prognostic factor for predicting OS. Furthermore, our findings revealed that a heightened cell adhesion effect correlated with tumor resistance to DNA-damaging drugs, protein kinase inhibitors, and drugs targeting the PI3K/Akt/mTOR signaling pathway. Nevertheless, we identified promising drug candidates, such as tirofiban, pirenzepine, erlotinib, and bosutinib, which exhibit potential in reversing this resistance. In vitro , experiments employing NCIH929, RPMI8226, and AMO1 cell lines confirmed that MM cell lines with high ARRS exhibited poor sensitivity to the aforementioned candidate drugs. By employing siRNA-mediated knockdown of the key ARRS model gene KIF14, we observed suppressed proliferation of NCIH929 cells, along with decreased adhesion to BMSCs and fibronectin. This study presents compelling evidence establishing cell adhesion as a significant prognostic factor in MM. Additionally, potential molecular mechanisms underlying adhesion-related resistance are proposed, along with viable strategies to overcome such resistance. These findings provide a solid scientific foundation for facilitating clinically stratified treatment of MM., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2024 Hu et al.)

It is generally believed that at-Γ bound states in the continuum (BICs) are enclosed by a linearly polarized vortex in momentum space when the structures have mirror (σ z ) symmetry, in-plane inversion ( I ) symmetry, and time reversal symmetry ( T ). Here, we reveal an anomalous situation in which at-Γ BICs can be enclosed by linearly and elliptically polarized far-field even when the σ z , I , and T symmetries are all maintained in non-Bravais lattices, which is radically different from previous cognition. Asymmetric, diatomic structures are designed to elaborate this intriguing phenomenon. By controlling the geometric parameters or refractive indexes of the two meta-atoms, the far-field polarization around the at-Γ BICs gradually deviates from linear polarization and approaches circular polarization. Our findings reveal that non-Bravais lattices can provide a novel platform to manipulate the far-field polarization, showing important applications in quantum entanglement, structured light, and radiation modulation.

Background: Both genetics and vitamin D deficiency are associated with childhood obesity. However, the role of vitamin D status between polygenic and childhood obesity has been unknown. The current study aimed to determine the relation between genetic factors, vitamin D status, and BMI-for-age z score (zBMI) in Chinese preschool children., Methods: A total of 1046 participants aged 3.7 to 6.6 years old from the Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack (LHEAPITNP) were included in this study. The polygenic risk score (PRS) was established based on 55 BMI-related single nucleotide polymorphisms (SNPs) derived from a published genome-wide association study (GWAS) for BMI. Serum 25(OH)D was used as an index of vitamin D status and measured with liquid chromatography-tandem mass spectrometry (LC/MS-MS) assay. The Wilcoxon test or Kruskal-Wallis test was used to compare the differences of variables between different groups and Spearman correlation analysis was used for analyzing the correlations between the PRS, 25(OH)D levels, and zBMI., Results: The PRS showed a positive relation to zBMI ( r s = 0.0953, p = 0.0022) and 25(OH)D showed a negative relation to zBMI ( r s = -0.1082, p = 0.0005) in the full-adjustment model. In addition, the differences in zBMI at different vitamin D statuses in the low-risk PRS group and the intermediate-risk PRS group were both statistically significant ( p low = 0.0308, p intermediate = 0.0121), the median zBMI was both higher at vitamin D insufficiency status. And the difference in zBMI between different genetic risk groups was also statistically significant at vitamin D sufficiency status ( p = 0.0077). Furthermore, genetic risk showed a positive relation to zBMI at vitamin D sufficiency status, and the p for trend was 0.0028., Conclusions: Our findings suggested that vitamin D was related to zBMI negatively in Chinese preschoolers and maintaining adequate vitamin D levels may only contribute to lower the zBMI in preschoolers with low and intermediate genetic susceptibility.

Objectives: To investigate the role of oral microbiome in promoting oral squamous cell carcinoma (OSCC) development., Materials and Methods: We investigated the salivary microbiome of 108 controls and 70 OSCC cases by16S rRNA gene sequencing and detected the fluorescence signal of OSCC-related pathological bacteria by fluorescence in situ hybridization assay (FISH). The invasion and migration assays were used to show the differences of invasive and migrative abilities between control and experimental groups. Quantitative real-time PCR and Western blotting were used to verify the epithelial-to-mesenchymal transition (EMT)., Results: In our study, the overall microbiome abundance and composition were richer in the 108 controls than in the 70 OSCC cases. We demonstrated that Streptococcus, Capnocytophaga, Peptostreptococcus, and Lactobacillus were highly abundant in the saliva of OSCC patients by 16S rDNA sequencing and FISH. Moreover, we found that Capnocytophaga gingivalis (C. gingivalis) was highly presented in OSCC tissues by FISH. We focused on C. gingivalis and found that its supernatant induced OSCC cells to undergo EMT, causing the cells to acquire a mesenchymal phenotype associated with highly invasive and metastatic properties., Conclusion: Taken together, these results indicated that C. gingivalis might invade OSCC tissues and played an important role in OSCC by promoting OSCC invasion and metastasis by inducing EMT. Hence, the role of C. gingivalis in cancer progression revealed a new direction for the research of OSCC., (© 2022 Wiley Periodicals LLC.)

Objective: To investigate the association of polymorphisms in SEC16B rs633715, DNAJC27 rs713586, FTO rs11642015 and MC4R rs6567160 with overweight and obesity in Han Chinese preschool children., Methods: A total of 749 Han Chinese preschool children from Henan and Guizhou Province of Long-term Health Effects Assessment Project of Infants and Toddlers Nutritional Pack were selected for the study and divided into an overweight and obese group and a normal control group in 2022. rs633715, rs713586, rs11642015 and rs6567160 were genotyped using Kompetitive allele-specific PCR(KASP) technology. The distribution of genotypic polymorphisms was compared using the χ~2 test. The association between the four loci and overweight and obesity in preschool children was analyzed using a multifactorial logistic regression model., Results: The statistical analysis revealed a significant disparity(P&lt;0.05) in the distribution of genotypic polymorphisms of rs633715 and rs6567160 among preschoolers in Henan and Guizhou Province. CC heterozygous mutant and recessive models at rs633715 locus were associated with susceptibility to overweight and obesity in preschool children [OR and 95% CI 2.915(1.163-7.305), and 2.997(1.226-7.323), respectively, both P&lt;0.05]. TC heterozygous mutant and dominant models at rs713586 locus were also associated susceptibility to overweight and obesity in preschool children(OR and 95% CI were 2.362(1.054-5.289)and 2.362(1.054-5.289), respectively, both P&lt;0.05). rs11642015 and rs6567160 loci were not associated with susceptibility to overweight and obesity in preschool children(P&gt;0.05). The result of the analysis of the cumulative effect of rs633715 and rs713586 showed that the number of genotypes carrying the risk genotype was positively associated with the risk of overweight and obesity in preschool children(P&#95;(trend)&lt;0.01)., Conclusion: Among Han Chinese preschool children, SEC16B rs633715 and DNAJC27 rs713586 were associated with susceptibility to overweight and obesity in preschool children. Moreover, rs633715 and rs713586 had a cumulative effect on susceptibility to overweight and obesity in preschool children, the number of risk genotypes carried was positively associated with childhood overweight and obesity risk.

Background: Grip strength has prognostic value for aging-related health outcomes. Whether the associations of grip strength with the risk of dementia and Alzheimer's disease (AD) vary by the genetic risk of AD and related dementias (ADD) is unknown., Methods: This study included 148 659 older adults of white British ancestry (aged ≥60 years) participating in UK Biobank with no dementia, and self-reported poor health status at baseline. Polygenic risk scores (PRS) for ADD were calculated based on 64 genetic variants. Grip strength was measured by hand dynamometers., Results: The hazard ratios (HR) of dementia (n = 4 963) and AD (n = 2 373) for high genetic risk of ADD were 2.36 (95% confidence interval [CI]: 2.15-2.59) and 3.00 (95% CI: 2.61-3.44), respectively, compared with low genetic risk. Compared with the bottom tertile of grip strength, the top tertile of grip strength had a hazard ratio (HR) of 0.69 (95% CI: 0.64-0.74) for incident dementia, and 0.74 (95% CI: 0.66-0.82) for incident AD, after adjustment for confounders and PRS for ADD. The risk of dementia and AD was lower with the top grip strength tertile within each level of genetic susceptibility to ADD. There was no evidence of multiplicative interaction between grip strength and genetic susceptibility to ADD for both dementia (p value: .241) and AD (p value: .314)., Conclusions: Older adults with higher PRS for ADD are at higher risk of developing dementia and AD. The risk of dementia and AD was lower in individuals with higher grip strength, regardless of their level of genetic susceptibility to ADD., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

The echo state network (ESN) is a recurrent neural network that has yielded state-of-the-art results in many areas owing to its rapid learning ability and the fact that the weights of input neurons and hidden neurons are fixed throughout the learning process. However, the setting procedure for initializing the ESN's recurrent structure may lead to difficulties in designing a sound reservoir that matches a specific task. This paper proposes an improved pre-training method to adjust the model's parameters and topology to obtain an adaptive reservoir for a given application. Two strategies, namely global random selection and ensemble training, are introduced to pre-train the randomly initialized ESN model. Specifically, particle swarm optimization is applied to optimize chosen fixed and global weight values within the network, and the reliability and stability of the pre-trained model are enhanced by employing the ensemble training strategy. In addition, we test the feasibility of the model for time series prediction on six benchmarks and two real-life datasets. The experimental results show a clear enhancement in the ESN learning results. Furthermore, the proposed global random selection and ensemble training strategies are also applied to pre-train the extreme learning machine (ELM), which has a similar training process to the ESN model. Numerical experiments are subsequently carried out on the above-mentioned eight datasets. The experimental findings consistently show that the performance of the proposed pre-trained ELM model is also improved significantly. The suggested two strategies can thus enhance the ESN and ELM models' prediction accuracy and adaptability.

Ehrlichia chaffeensis infects human monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening zoonosis. After internalization, E. chaffeensis resides in membrane-bound inclusions, E. chaffeensis -containing vesicles (ECVs), which have early endosome-like characteristics and fuse with early autophagosomes but not lysosomes, to evade host innate immune microbicidal mechanisms and obtain nutrients for bacterial intracellular growth. The mechanisms exploited by E. chaffeensis to modulate intracellular vesicle trafficking in host cells have not been comprehensively studied. Here, we demonstrate that E. chaffeensis type IV secretion system (T4SS) effector Etf-3 induces RAB15 upregulation in host cells and that RAB15, which is localized on ECVs, inhibits ECV fusion with lysosomes and induces autophagy. We found that E. chaffeensis infection upregulated RAB15 expression using qRT-PCR, and RAB15 was colocalized with E. chaffeensis using confocal microscopy. Silence of RAB15 using siRNA enhanced ECV maturation to late endosomes and fusion with lysosomes, as well as inhibited host cell autophagy. Overexpression of Etf-3 in host cells specifically induced RAB15 upregulation and autophagy. Our findings deepen the understanding of E. chaffeensis pathogenesis and adaptation in hosts as well as the function of RAB15 and facilitate the development of new therapeutics for HME.

Serine metabolism is involved in various biological processes. Here we investigate primary functions of the phosphorylated pathway of serine biosynthesis in a non-vascular plant Marchantia polymorpha by analyzing knockout mutants of MpPGDH encoding 3-phosphoglycerate dehydrogenase in this pathway. Growth phenotypes indicate that serine from the phosphorylated pathway in the dark is crucial for thallus growth. Sperm development requires serine from the phosphorylated pathway, while egg formation does not. Functional MpPGDH in the maternal genome is necessary for embryo and sporophyte development. Under high CO 2 where the glycolate pathway of serine biosynthesis is inhibited, suppressed thallus growth of the mutants is not fully recovered by exogenously-supplemented serine, suggesting the importance of serine homeostasis involving the phosphorylated and glycolate pathways. Metabolomic phenotypes indicate that the phosphorylated pathway mainly influences the tricarboxylic acid cycle, the amino acid and nucleotide metabolism, and lipid metabolism. These results indicate the importance of the phosphorylated pathway of serine biosynthesis in the dark, in the development of sperm, embryo, and sporophyte, and metabolism in M. polymorpha., (© 2024. The Author(s).)