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Abstract Background Polytrauma was defined as a severe traumatic injury and believed that it was a sudden and unpredictable incident. Is polytrauma really just a simple accident? In order to comprehensively answer this question, the study sought to determine the frequency and specific risk factors associated with polytrauma recidivism, while also comparing the initial and subsequent injury events among recidivists. Methods A multicenter, retrospective cohort study was conducted at four Advanced Trauma Centers’ emergency surgery or traumatic intensive care units (TICUs) between August 2020 and July 2023. A total of 2490 consecutive trauma patients who met the criteria consecutively were recruited and analyzed in the study. Risk factors for recurrent polytrauma were identified through the use of logistic regression analysis. A nomogram was created using the results from a multivariate logistic regression analysis and the rms package in R. Results In polytrauma, the rate of recidivism was 44.6% (672/1507), then recidivists were predominantly male (80.4%) and frequently within the 45 to 54 year-old age range (51.3%). Recidivists in polytrauma patients overall had a median time to reinjury of 27 months, as measured by the interquartile range (IQR). The polytrauma patients in the recent traumatic event were often more severe than that in the initial event, as patients had higher ISS scores and lower GCS scores (P

Abstract Background This study clarified the synergistic relationship among annual changes to specify the changes in agro-meteorological factors, soil characteristics and peanut growth in saline-alkali land near the estuary of the Yellow River Delta. We aimed to find the key factors affecting peanut production to optimize and regulate peanut planting mode in saline alkali soil. Results The daily average temperature from early May to late September in Lijin and Kenli was above 24 °C, with 470–600 mm of precipitation. The sunshine duration was 7.9 h/day and 7.3 h/day and the accumulated temperature was 3742 °C and 3809 °C, in Lijin and Kenli, respectively. Agro-meteorological conditions were suitable for peanut growth and development with the consistent main developmental period in the two experiment regions. The best sowing period was when the soil temperature stabilized above 18 °C in early May, and the best harvest was in mid-September. The soil volumetric water content in Lijin concentrated among 25–40%. Salt was mainly distributed in the 40–60 cm soil layers, and increased rapidly to 2.5 g kg− 1 in 0–20 cm cultivation layer in mid-May due to lack of precipitation. In Kenli experiment region, the soil volumetric water content ranged from 10 to 35%. Soil salinity was mainly distributed in the 20 cm soil layer, and the changes in salinity was little affected by precipitation. From mid-July to mid-August, the effective accumulated temperature of 5 cm soil layer was above 520 °C in both regions, which could ensure the normal pod development. The slow dynamic growth of kernel, high unfilled pod rate (26.99%) and low shelling rate (66.0%) might be the main reasons for low peanut yield in Lijin. Conclusion Soil salinity was the main factor affecting pod development and yield. It was also a key point in optimizing the peanut planting mode in the saline alkali land of the Yellow River Delta.

Arbuscular mycorrhizae (AM) fungi form symbiotic associations with plant roots, providing nutritional benefits and promoting plant growth and defenses against various stresses. Metabolic changes in the roots during AM fungal colonization are key to understanding the development and maintenance of these symbioses. Here, we investigated metabolic changes in the roots of peanut (Arachis hypogaea L.) plants during the colonization and development of AM symbiosis, and compared them to uncolonized roots. The primary changes during the initial stage of AM colonization were in the contents and compositions of phenylpropanoid and flavonoid compounds. These compounds function in signaling pathways that regulate recognition, interactions, and pre-colonization between roots and AM fungi. Flavonoid compounds decreased by 25% when the symbiosis was fully established compared to the initial colonization stage. After AM symbiosis was established, general metabolism strongly shifted toward the formation of lipids, amino acids, carboxylic acids, and carbohydrates. Lipid compounds increased by 8.5% from the pre-symbiotic stage to well-established symbiosis. Lyso-phosphatidylcholines, which are signaling compounds, were only present in AM roots, and decreased in content after the symbiosis was established. In the initial stage of AM establishment, the content of salicylic acid increased two-fold, whereas jasmonic acid and abscisic acid decreased compared to uncolonized roots. The jasmonic acid content decreased in roots after the symbiosis was well established. AM symbiosis was associated with high levels of calcium, magnesium, and D-(+)-mannose, which stimulated seedling growth. Overall, specific metabolites that favor the establishment of AM symbiosis were common in the roots, primarily during early colonization, whereas general metabolism was strongly altered when AM symbiosis was well-established. In conclusion, specialized metabolites function as signaling compounds to establish AM symbiosis. These compounds are no longer produced after the symbiosis between the roots and AM becomes fully established.

Introduction Applying and leveraging artificial intelligence within the healthcare domain has emerged as a fundamental pursuit to advance health. Data-driven models rooted in deep learning have become powerful tools for use in healthcare informatics. Nevertheless, healthcare data are highly sensitive and must be safeguarded, particularly information related to sexually transmissible infections (STIs) and human immunodeficiency virus (HIV). Methods We employed federated learning (FL) in combination with homomorphic encryption (HE) for STI/HIV prediction to train deep learning models on decentralized data while upholding rigorous privacy. The dataset included 168,459 data entries collected from eight countries between 2013 and 2018. The data for each country was split into two groups, with 70% allocated for training and 30% for testing. Our strategy was based on two-step aggregation to enhance model performance and leverage the area under the curve (AUC) and accuracy metrics and involved a secondary aggregation at the local level before utilizing the global model for each client. We introduced a dropout approach as an effective client-side solution to mitigate computational costs. Results Model performance was progressively enhanced from an AUC of 0.78 and an accuracy of 74.4% using the local model to an AUC of 0.94 and an accuracy of 90.7% using the more advanced model. Conclusion Our proposed model for STI/HIV risk prediction surpasses those achieved by local models and those constructed from centralized data sources, highlighting the potential of our approach to improve healthcare outcomes while safeguarding sensitive patient information.

Abstract Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type‐specific TMEM16F‐deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell‐expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.

Immune checkpoint blockade (ICB) therapy, particularly PD1/PDL1 inhibition, has demonstrated success in bolstering durable responses in patients. However, the response rate remains below 30 %. In this study, we developed a polymeric bispecific antibody (BsAb) targeting PD1/PDL1 to enhance ICB therapy. Specifically, poly(L-glutamic acid) (PGLU) was conjugated with a double cyclic Fc binding peptide, Fc-III-4C, through condensation reactions between the -COOH group of PGLU and the -NH2 group of Fc-III-4C. This conjugate was then mixed with αPD1 and αPDL1 monoclonal antibodies (mAbs) in an aqueous solution. Mechanistically, the PD1/PDL1 BsAb (BsAbαPD1+αPDL1) acts as a bridge between tumor cells and CD8+ T cells, continuously activating CD8+ T cells to a greater extent. This leads to significantly suppressed tumor growth and prolonged survival in a mouse model of colon cancer compared to treatment with either a single mAb or a mixture of free mAbs. The tumor suppression rate achieved by the BsAbαPD1+αPDL1 was 90.1 %, with a corresponding survival rate of 83.3 % after 48 days. Thus, this study underscores the effectiveness of the BsAbαPD1+αPDL1 as a synchronizing T cell engager and dual ICBs, offering theoretical guidance for clinical ICB therapy.

Summary: Gallbladder cancer (GBC) is characterized by a high degree of malignancy and a poor prognosis. This study revealed that circEZH2 was frequently upregulated in GBC tissues and correlated with advanced tumor-node-metastasis (TNM) stage in GBC patients. In vitro and in vivo experiments confirmed that circEZH2 promoted the proliferation and inhibited the ferroptosis of GBC. Besides, this study discovered that circEZH2 regulated lipid metabolism reprogramming in GBC cells. Mechanistically, circEZH2 promotes SCD1 expression by sponging miR-556-5p in GBC cells. In addition, IGF2BP2 enhances the stability of circEZH2 in an m6A-dependent manner, while circEZH2 suppresses the ubiquitination and degradation of IGF2BP2 by binding to IGF2BP2. Taken together, our findings indicated that circEZH2, upregulated via a positive feedback loop between circEZH2 and IGF2BP2, promotes GBC progression and lipid metabolism reprogramming through the miR-556-5p/SCD1 axis in GBC. circEZH2 may serve as a potential therapeutic target for GBC.

IntroductionInherited retinal diseases (IRDs) affect ∼4.5 million people worldwide. Elusive pathogenic variants in over 280 genes are associated with one or more clinical forms of IRDs. It is necessary to understand the complex interaction among retinal cell types and pathogenic genes by constructing a regulatory network. In this study, we attempt to establish a panoramic expression view of the cooperative work in retinal cells to understand the clinical manifestations and pathogenic bases underlying IRDs.MethodsSingle-cell RNA sequencing (scRNA-seq) data on the retinas from 35 retina samples of 3 species (human, mouse, and zebrafish) including 259,087 cells were adopted to perform a comparative analysis across species. Bioinformatic tools were used to conduct weighted gene co-expression network analysis (WGCNA), single-cell regulatory network analysis, cell–cell communication analysis, and trajectory inference analysis.ResultsThe cross-species comparison revealed shared or species-specific gene expression patterns at single-cell resolution, such as the stathmin family genes, which were highly expressed specifically in zebrafish Müller glias (MGs). Thirteen gene modules were identified, of which nine were associated with retinal cell types, and Gene Ontology (GO) enrichment of module genes was consistent with cell-specific highly expressed genes. Many IRD genes were identified as hub genes and cell-specific regulons. Most IRDs, especially the retinitis pigmentosa (RP) genes, were enriched in rod-specific regulons. Integrated expression and transcription regulatory network genes, such as congenital stationary night blindness (CSNB) genes GRK1, PDE6B, and TRPM1, showed cell-specific expression and transcription characteristics in either rods or bipolar cells (BCs). IRD genes showed evolutionary conservation (GNAT2, PDE6G, and SAG) and divergence (GNAT2, MT-ND4, and PDE6A) along the trajectory of photoreceptors (PRs) among species. In particular, the Leber congenital amaurosis (LCA) gene OTX2 showed high expression at the beginning of the trajectory of both PRs and BCs.ConclusionWe identified molecular pathways and cell types closely connected with IRDs, bridging the gap between gene expression, genetics, and pathogenesis. The IRD genes enriched in cell-specific modules and regulons suggest that these diseases share common etiological bases. Overall, mining of interspecies transcriptome data reveals conserved transcriptomic features of retinas across species and promising applications in both normal retina anatomy and retina pathology.

In the European Guideline on Management of Major Bleeding and Coagulopathy Following Trauma updated recently, there are 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points, including initial resuscitation and prevention of further bleeding, diagnosis and monitoring of bleeding, rapid control of bleeding, initial management of bleeding and coagulopathy, further goal-directed coagulation management, management of antithrombotic agents, thromboprophylaxis, guideline implementation and quality control, as welll as the management of tissue oxygenation, volume, fluids and temperature. In this paper, we introduce the recommendations and rationale of the guideline and add some newly published clinical study evidence. These information would be very helpful to the development and training of the guidelines or protocols for the management of the trauma patient with major haemorrhage and coagulopathy in China.

Abstract This paper presents a solution that prioritises high privacy protection and improves communication throughput for predicting the risk of sexually transmissible infections/human immunodeficiency virus (STIs/HIV). The approach utilised Federated Learning (FL) to construct a model from multiple clinics and key stakeholders. FL ensured that only models were shared between clinics, minimising the risk of personal information leakage. Additionally, an algorithm was explored on the FL manager side to construct a global model that aligns with the communication status of the system. Our proposed method introduced Random Forest Federated Learning for assessing the risk of STIs/HIV, incorporating a flexible aggregation process that can be adjusted to accommodate the capacious communication system. Experimental results demonstrated the significant potential of a solution for estimating STIs/HIV risk. In comparison with recent studies, our approach yielded superior results in terms of AUC (0.97) and accuracy ( $$93\%$$ 93 % ). Despite these promising findings, a limitation of the study lies in the experiment for man’s data, due to the self-reported nature of the data and sensitive content. which may be subject to participant bias. Future research could check the performance of the proposed framework in partnership with high-risk populations (e.g., men who have sex with men) to provide a more comprehensive understanding of the proposed framework’s impact and ultimately aim to improve health outcomes/health service optimisation.

Abstract Background Forkhead-box protein P1 (FOXP1) has been proposed to have both oncogenic and tumor-suppressive properties, depending on tumor heterogeneity. However, the role of FOXP1 in intrahepatic cholangiocarcinoma (ICC) has not been previously reported. Methods Immunohistochemistry was performed to detect FOXP1 expression in ICC and normal liver tissues. The relationship between FOXP1 levels and the clinicopathological characteristics of patients with ICC was evaluated. Finally, in vitro and in vivo experiments were conducted to examine the regulatory role of FOXP1 in ICC cells. Results FOXP1 was significantly downregulated in the ICC compared to their peritumoral tissues (p

Abstract Ultrasound‐generated antigens combined with TLR7/8 agonists as adjuvants have demonstrated significant anti‐tumor efficacy as an in‐situ vaccine. However, the use of TLR7/8 agonists can cause severe inflammatory responses. In this study, we present a novel tumor‐targeting nano‐adjuvant termed aPDL1‐PLG/R848 NPs, which are composed of aPDL1 antibody, Fc‐III‐4C peptide linker (Fc‐linker) and poly(L‐glutamic acid)‐grafted‐R848. Under ultrasound irradiation, antigen‐presenting cells activate immune mechanisms in vivo under dual stimulation of in situ antigens and immune adjuvants. The strategy inhibits primary tumor growth and induces a strong antigen‐specific immune memory effect to prevent tumor recurrence in vivo. This work offers a safe and potent platform for an in situ cancer vaccine based on ultrasound therapy.

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is poorly treated due to the presence of an inhibitory immune microenvironment. Tumor-associated macrophages (TAM) are an important component of TME. ALOX5 is an important lipid metabolism enzyme in cancer progression, but the mechanism by which it regulates TAM to promote ICC progression is unknown. The aim of this study was to investigate the potential mechanism of TAM regulation by ALOX5 and the translational effect of targeting ALOX5. Methods In this study, we investigated the association between the spatial localization of epithelial cells and TAMs by combining scRNA-seq analysis with multiplex immunofluorescence analysis. Through bulk sequencing analysis and spatial analysis, lipid metabolism genes closely related to TAM infiltration were screened. In vitro co-culture model was constructed to verify that ALOX5 and its downstream metabolite LTB4 promote M2 macrophage migration. Bulk sequencing after co-culture combined with single-cell analysis was performed to identify key pathways for up-regulation of M2 macrophage migration. Finally, the effect of CSF1R inhibitor (PLX3397) combined with ALOX5 inhibitor (Zileuton) in vivo was investigated by by xenograft tumor formation experiment in nude mice. Results ALOX5 in ICC cells was a key lipid metabolism gene affecting the infiltration of M2 macrophages in TME. Mechanically, LTB4, a metabolite downstream of ALOX5, recruited M2 macrophages to migrate around tumor cells by binding to BLT1/BLT2 and activating the PI3K pathway, which ultimately lead to the promotion of ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor effectively reduced tumor volume and M2 macrophage infiltration abundance. Conclusion In ICC, LTB4, a metabolite secreted by ALOX5 of epithelial cells, binded to BLT1/BLT2 on TAM surface to activate PI3K pathway and promote TAM migration, thus promoting ICC progression. Targeting CSF1R in combination with ALOX5 inhibitor for ICC is a promising combination therapy modality.

Abstract Biosynthesis drives the cell volume increase during T cell activation. However, the contribution of cell volume regulation in TCR signaling during T lymphoblast formation and its underlying mechanisms remain unclear. Here we show that cell volume regulation is required for optimal T cell activation. Inhibition of VRACs (volume-regulated anion channels) and deletion of leucine-rich repeat-containing protein 8A (LRRC8A) channel components impair T cell activation and function, particularly under weak TCR stimulation. Additionally, LRRC8A has distinct influences on mRNA transcriptional profiles, indicating the prominent effects of cell volume regulation for T cell functions. Moreover, cell volume regulation via LRRC8A controls T cell-mediated antiviral immunity and shapes the TCR repertoire in the thymus. Mechanistically, LRRC8A governs stringent cell volume increase via regulated volume decrease (RVD) during T cell blast formation to keep the TCR signaling molecules at an adequate density. Together, our results show a further layer of T cell activation regulation that LRRC8A functions as a cell volume controlling “valve” to facilitate T cell activation.

Introduction: The prognosis of advanced renal carcinoma is not ideal, necessitating the exploration of novel treatment strategies. Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) possess the dual capability of CA4 (targeting blood vessels to induce tumor necrosis) and BLZ945 (inducing M2 macrophage apoptosis), thereby inhibiting tumor growth.Methods: Here, the therapeutic effects and underlying mechanism was explored by CCK-8 cytotoxicity experiment, transwell cell invasion and migration experiment, H&E, western blot analysis, immunohistochemistry, flow cytometry, and other techniques.Results: These results demonstrated that CB-NPs could inhibit the growth of Renca cells and subcutaneous tumors in mice, with an impressive tumor inhibition rate of 88.0%. Results suggested that CB-NPs can induce necrosis in renal carcinoma cells and tissues, downregulate VEGFA expression, promote renal carcinoma cell apoptosis, and reduce the polarization of M2 macrophages.Discussion: These findings offer innovative perspectives for the treatment of advanced renal carcinoma.

PurposeCurrent research has not extensively explored the correlation between Systemic Inflammatory Index (SII) and prostate-specific antibody (PSA) levels. This study aimed to investigate the relationship between the SII and PSA levels in American males aged > 40 years without prostate cancer.MethodsData were obtained from the 2003-2010 National Health and Nutrition Examination Survey (NHANES). Patients without complete SII or PSA data were excluded. Multiple linear regression models were used to investigate the possibility of a linear association between the SII and PSA levels. Fitted smoothed curves and threshold effect analyses were used to characterize the nonlinear relationships.ResultsThe study included 5982 male participants over the age of 40 years from the United States. The average SII (mean ± standard deviation) was 562.78 ± 355.60. The mean value of PSA was 1.85 ± 3.24. The results showed that SII exhibited a positive correlation with PSA (β = 0.0005, 95% CI: (0.0002, 0.0007)), and an interaction test indicated that the effects of age, body mass index, hypertension, and diabetes were not significant for this positive correlation between SII and PSA (all P > 0.05). We discovered an inverted U-shaped connection between the SII and PSA with a turning point (K) of 1168.18 by using a two-segment linear regression model. To the left of the turning point, there was a positive connection between SII and PSA (β = 0.0009,95% CI: (0.0006, 0.0012); P < 0.0001).ConclusionIn the population of men over 40 years old without prostate cancer, SII and PSA exhibited a non-linear relationship. Specifically, there was a positive correlation between SII and PSA levels when the SII value was < 1168.18.

ObjectiveThis study was designed to systematically review the efficacy and safety of repeated transcranial magnetic stimulation (rTMS) combined with escitalopram in treating major depressive disorder (MDD).MethodsDatabases including PubMed, Embase, Cochrane, Web of Science, CNKI, Wanfang, VIP Journal, and China Biomedical Literature databases were electronically searched for randomized controlled trials of rTMS combined with escitalopram intervention for MDD treatment from the inception of these databases to 27 May 2023. Two reviewers independently screened the studies, extracted the data, and assessed the quality of the included studies. R 4.2.2 was then used for a meta-analysis.ResultsIn total, 19 articles involving 1,032 patients were included. The results of the meta-analysis showed that Hamilton Depression Rating Scale (HAMD) scores were significantly lower in the group receiving rTMS combined with escitalopram (experimental group) than that in the control group [weighted mean difference (WMD) = −5.30, 95% confidence interval (95% CI): −6.44 to −4.17, p

The Guangdong historical trail comprises two ancient trails, known as Yile (宜乐) and Xijing (西京); can be found within the borders of Lechang (乐昌); and is an integral part of the northern section of the Guangdong historical trail, connecting Hunan and Guangdong. Along these routes, there are various types of ancestral halls. The objectives of this study include analyzing various levels of information about ancestral hall architecture, determining their respective importance through AHP hierarchical analysis, classifying architectural features via cluster analysis using SPSS, and exploring the geographical distribution trajectories of ancestral halls along the ancient paths using GIS technology. Ultimately, this study seeks to shed light on the influence of different cultures brought by the ancient road on the distribution of architectural types and identify three distinct types of ancestral halls.

Summary: DEAH-Box Helicase 38 (DHX38) is a pre-mRNA splicing factor and also a disease-causing gene of autosomal recessive retinitis pigmentosa (arRP). The role of DHX38 in the development and maintenance of the retina remains largely unknown. In this study, by using the dhx38 knockout zebrafish model, we demonstrated that Dhx38 deficiency causes severe differentiation defects and apoptosis of retinal progenitor cells (RPCs) through disrupted mitosis and increased DNA damage. Furthermore, we found a significant accumulation of R-loops in the dhx38-deficient RPCs and human cell lines. Finally, we found that DNA replication stress is the prerequisite for R-loop-induced DNA damage in the DHX38 knockdown cells. Taken together, our study demonstrates a necessary role of DHX38 in the development of retina and reveals a DHX38/R-loop/replication stress/DNA damage regulatory axis that is relatively independent of the known functions of DHX38 in mitosis control.

The Ca2+/CaM signal transduction pathway helps plants adapt to environmental stress. However, our knowledge on the functional proteins of Ca2+/CaM pathway in peanut (Arachis hypogeae L.) remains limited. In the present study, a novel calmodulin 4 (CaM4)-binding protein S-adenosyl-methionine synthetase 1 (SAMS1) in peanut was identified using a yeast two-hybrid assay. Expression of AhSAMS1 was induced by Ca2+, ABA, and salt stress. To elucidate the function of AhSAMS1, physiological and phenotypic analyses were performed with wild-type and transgenic materials. Overexpression of AhSAMS1 increased spermidine and spermidine synthesis while decreased the contents of ethylene, thereby eliminating excessive reactive oxygen species (ROS) in transgenic lines under salt stress. AhSAMS1 reduced uptake of Na+ and leakage of K+ from mesophyll cells, and was less sensitive to salt stress during early seedling growth, in agreement with the induction of SOS and NHX genes Transcriptomics combined with epigenetic regulation uncovered relationships between differentially expressed genes and differentially methylated regions, which raised the salt tolerance and plants growth. Our findings support a model in which the role of AhSAMS1 in the ROS-dependent regulation of ion homeostasis was enhanced by Ca2+/CaM while AhSAMS1-induced methylation was regulated by CaM, thus providing a new strategy for increasing the tolerance of plants to salt stress.

Abstract Background Arbuscular Mycorrhizal Fungi (AMF) are beneficial microorganisms in soil-plant interactions; however, the underlying mechanisms regarding their roles in legumes environmental stress remain elusive. Present trials were undertaken to study the effect of AMF on the ameliorating of salt, drought, and cold stress in peanut (Arachis hypogaea L.) plants. A new product of AMF combined with Rhizophagus irregularis SA, Rhizophagus clarus BEG142, Glomus lamellosum ON393, and Funneliformis mosseae BEG95 (1: 1: 1: 1, w/w/w/w) was inoculated with peanut and the physiological and metabolomic responses of the AMF-inoculated and non-inoculated peanut plants to salt, drought, and cold stress were comprehensively characterized, respectively. Results AMF-inoculated plants exhibited higher plant growth, leaf relative water content (RWC), net photosynthetic rate, maximal photochemical efficiency of photosystem II (PSII) (Fv/Fm), activities of antioxidant enzymes, and K+: Na+ ratio while lower leaf relative electrolyte conductivity (REC), concentration of malondialdehyde (MDA), and the accumulation of reactive oxygen species (ROS) under stressful conditions. Moreover, the structures of chloroplast thylakoids and mitochondria in AMF-inoculated plants were less damaged by these stresses. Non-targeted metabolomics indicated that AMF altered numerous pathways associated with organic acids and amino acid metabolisms in peanut roots under both normal-growth and stressful conditions, which were further improved by the osmolytes accumulation data. Conclusion This study provides a promising AMF product and demonstrates that this AMF combination could enhance peanut salt, drought, and cold stress tolerance through improving plant growth, protecting photosystem, enhancing antioxidant system, and regulating osmotic adjustment.

Abstract The carcinogenic role of FASN by regulating lipid metabolism reprogramming has been well-established in multiple tumors. However, whether mechanisms during intrahepatic cholangiocarcinoma (ICC) progression, such as circRNAs, regulate FASN expression remains unknown. Here we demonstrate a lipid metabolism-related circRNA, circMBOAT2 (hsa_circ_0007334 in circBase), frequently upregulated in ICC tissues, and positively correlated with ICC malignant features. CircMBOAT2 knockdown inhibits the growth and metastasis of ICC cells. Mechanistically, circMBOAT2 combines with PTBP1 and protects PTBP1 from ubiquitin/proteasome-dependent degradation, impairing the function of PTBP1 to transfer FASN mRNA from the nucleus to the cytoplasm. Moreover, circMBOAT2 and FASN have the same effect on fatty acid profile, unsaturated fatty acids instead of saturated fatty acids are primarily regulated and associated with malignant behaviors of ICC cells. The levels of lipid peroxidation and ROS were significantly higher when FASN was knocked down and recovered when circMBOAT2 was overexpressed. Our results identified that circMBOAT2 was upregulated in ICC and promoted progression by stabilizing PTBP1 to facilitate FASN mRNA cytoplasmic export, which altered lipid metabolic profile and regulated redox homeostasis in ICC, suggesting that circMBOAT2 may serve as an available therapeutic target for ICC with active lipid metabolism.

Abstract Mutations in TUB-like protein 1 (TULP1) are associated with severe early-onset retinal degeneration in humans. However, the pathogenesis remains largely unknown. There are two homologous genes of TULP1 in zebrafish, namely tulp1a and tulp1b. Here, we generated the single knockout (tulp1a −/− and tulp1b −/− ) and double knockout (tulp1-dKO) models in zebrafish. Knockout of tulp1a resulted in the mislocalization of UV cone opsins and the degeneration of UV cones specifically, while knockout of tulp1b resulted in mislocalization of rod opsins and rod-cone degeneration. In the tulp1-dKO zebrafish, mislocalization of opsins was present in all types of photoreceptors, and severe degeneration was observed at a very early age, mimicking the clinical manifestations of TULP1 patients. Photoreceptor cilium length was significantly reduced in the tulp1-dKO retinas. RNA-seq analysis showed that the expression of tektin2 (tekt2), a ciliary and flagellar microtubule structural component, was downregulated in the tulp1-dKO zebrafish. Dual-luciferase reporter assay suggested that Tulp1a and Tulp1b transcriptionally activate the promoter of tekt2. In addition, ferroptosis might be activated in the tulp1-dKO zebrafish, as suggested by the up-regulation of genes related to the ferroptosis pathway, the shrinkage of mitochondria, reduction or disappearance of mitochondria cristae, and the iron and lipid droplet deposition in the retina of tulp1-dKO zebrafish. In conclusion, our study establishes an appropriate zebrafish model for TULP1-associated retinal degeneration and proposes that loss of TULP1 causes defects in cilia structure and opsin trafficking through the downregulation of tekt2, which further increases the death of photoreceptors via ferroptosis. These findings offer insight into the pathogenesis and clinical treatment of early-onset retinal degeneration.

Abstract As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich‐structured dual‐drug depot is developed to trigger a self‐intensified starvation therapy and hypoxia‐induced chemotherapy sequentially. The two outer layers are 3D‐printed using a calcium‐crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic‐co‐glycolic acid)‐based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia‐inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual‐drug‐loaded sandwich‐like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation.

Soluble dietary fiber has anti-tumor effect and is closely related to human health. At present the structure of soluble dietary fiber from foxtail millet (FMB-SDF) and its anti-tumor effect remain unclear. In this study, the structure of FMB-SDF was characterized, and its effects on the colon cancer were investigated. The results showed that under optimal extraction conditions the yield of FMB-SDF was 14.25 %. Based on the monosaccharide composition, methylation results and NMR analysis, the preliminary structure of FMB-SDF was inferred to be a glucan. Interestingly, FMB-SDF markedly inhibited the colony formation ability of HCT116 and HT-29 cells and could significantly induce the increase of reactive oxygen species (ROS) and apoptosis of HCT116 and HT-29 cells. The results of animal experiments showed that FMB-SDF could significantly alleviate clinical symptoms of colon cancer in mice. These results provide a theoretical basis for the exploitation and utilization of FMB-SDF against colon cancer.

Traceability is a fundamental issue for ensuring accuracy of nanometrology. A shortened traceability chain is advantageous for reducing calibration steps, thus reducing errors and raising application efficiency. A novel kind of two-dimensional grating is manufactured by atom lithography, whose pitch and (orthogonal) angle values are directly determined by natural constants, offering a feasible approach for effectively shortening the traceability chain. The PTB’s calibration results show that the two-dimensional grating has excellent orthogonality with a deviation of only 0.001°. The application of two-dimensional grating is demonstrated for the characterization of the angular distortion of a SEM, showing its great application potential.

Abstract The accurate segmentation of blood vessels plays a crucial role in screening, diagnosis and treatment of multiple diseases. However, current automated segmentation approaches do not pay enough attention to the vascular topology errors (such as mistaking vessel‐breakpoints), resulting in considerable scattered vessel‐fragments in segmentation results. This article proposes a retinal vessel segmentation model using multi‐scale context gating and breakpoint attention mechanism, called MCG&BA‐Net. Specifically, it obtains a feature map containing contextual information of vessels through an introduced multi‐scale context module, and then filters the redundant features and noises by a gated structure to highlight target features. Furthermore, a kind of breakpoint attention module is proposed, which can locate and focus on potential breakpoint areas, thereby facilitating accurate segmentation results of tree‐like fine vessels. Extensive confirmatory and comparative experiments have been conducted on five public datasets, including three benchmark datasets, that is, DRIVE, CHASDB1 and SATRE, and two clinical datasets, that is, fundusimage1000 and RFMID. The AUC scores on the benchmark datasets are 0.9878, 0.9923 and 0.9942, respectively. Among them, the AUC score on CHADEDB1 and STARE outperforms the state‐of‐the‐art results. In addition, experimental results on the two clinical datasets demonstrate strong generalization capability of the propose method, indicating high clinical application values.

The slag dumps formed by mining activities are irregular granular media. Their particle size gradations are complex and granule structures are unstable.The stress between particles is transferred through the dependently unstable force chain. Taking the typical copper slag as the study object, its granule structure was investigated using CT scanning technology. According to plane compression and corresponding numerical simulation tests on coarse particles of different mass fraction contents, stress-straincurves, force chain evolutions and granule structure changes were obtained.Further, the synergistic effect between granule structure and force chain evolutionon macro-mechanics was discussed. Meanwhile, the compression law of granular material was revealed. The results show that the direction of force chain evolution direction inslag granular materialis consistent with the direction of pressure. The macro-compressive strength of slag increases first and then decreases with increasing coarse particle (>5 mm) mass fraction content and reaches the maximum compressive strength at the optimal coarse particle ratio of 50%. The granule structure and the soft-hard structure inforce chains have a significant synergistic effect. The granule structure change in slag granular material will experience three stages during compression process: the rapid compaction stage, particle crushing stage and stable compression stage. In the process of slag landfill, it is important to keep uniform filling and reasonable compaction to make it enter the stable compression stage, as well as controlling the optimal grading of coarse particles.