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This study examined how Eucommia ulmoides flavonoids (EUF) protect against intestinal oxidative stress induced by deoxynivalenol (DON) in weaned piglets. Forty weaned piglets were randomly assigned to four dietary groups for a period of 14 days. The piglets were fed a control diet (Control) or the Control diet supplemented with 100 mg EUF/kg (EUF group), 4 mg DON/kg diet (DON group) or both (EUF+DON group) in a 2×2 factorial design. DON-challenged piglets on the EUF-supplemented diet showed significant improvements in growth performance. They also had notably lower serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) compared to those not receiving supplementation (P<0.05). In the EUF group, the relative weights of the liver, spleen, and kidneys were significantly lower than those in the control group (P<0.05). However, there were no significant differences in the relative heart weights among the four groups (P>0.05). Piglets challenged with DON and fed a diet supplemented with EUF showed significantly lower levels of interleukin-8 (IL-8) and interferon-γ (IFN-γ) mRNA and protein expression in serum and intestinal tissues compared to those in the DON group (P < 0.05). The EUF+DON group significantly increased the serum levels of glutathione peroxidase (GSH-Px), reactive oxygen species (ROS), and total antioxidative capability enzymes compared to the DON group (P<0.05). The EUF and DON group had significantly higher villus height, crypt depth, and villus height to crypt depth ratio in the small intestine compared to the supplemented DON-challenged piglets (P<0.05). Moreover, compared to the DON group, EUF can significantly enhance the expression of nuclear factor erythroid 2-related factor 2(Nfr2)/Kelch-like ECH-associating protein 1(Keap1) and antioxidant genes (i.e., HO-1, GCLC, GCLM), as well as their proteins in the DON-induced small intestines of piglets (P<0.05). In conclusion, EUF helps protect piglets from intestinal oxidative stress caused by DON by influencing the Nrf2/Keap1 signaling pathway, thereby supporting their intestinal health., 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. Published by Elsevier Inc.)

Humans possess a remarkable ability to rapidly access diverse information from others' faces with just a brief glance, which is crucial for intricate social interactions. While previous studies using event-related potentials/fields have explored various face dimensions during this process, the interplay between these dimensions remains unclear. Here, by applying multivariate decoding analysis to neural signals recorded with optically pumped magnetometer magnetoencephalography, we systematically investigated the temporal interactions between invariant and variable aspects of face stimuli, including race, gender, age, and expression. First, our analysis revealed unique temporal structures for each face dimension with high test-retest reliability. Notably, expression and race exhibited a dominant and stably maintained temporal structure according to temporal generalization analysis. Further exploration into the mutual interactions among face dimensions uncovered age effects on gender and race, as well as expression effects on race, during the early stage (∼200-300 ms postface presentation). Additionally, we observed a relatively late effect of race on gender representation, peaking ∼350 ms after the stimulus onset. Taken together, our findings provide novel insights into the neural dynamics underlying the multidimensional aspects of face perception and illuminate the promising future of utilizing OPM-MEG for exploring higher-level human cognition., (Copyright © 2024 the authors.)

Background: Sleep disturbance is commonly reported by patients wearing an abduction brace after arthroscopic rotator cuff repair (ARCR). Although a sling has been proven noninferior to an abduction brace for function and repair integrity, there is no evidence-based medical support for the advantage of the sling in improving sleep quality compared with a brace., Purpose/hypothesis: This study aimed to compare the effects of a sling and an abduction brace on sleep quality and clinical outcomes after ARCR. It was hypothesized that immobilization in a sling would result in better sleep quality while not deteriorating clinical outcomes and bone-tendon healing compared with an abduction brace., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: A total of 142 consecutive patients with rotator cuff tears were randomly assigned to 2 groups: (1) the brace group, receiving abduction brace immobilization for 6 weeks, and (2) the sling group, receiving sling immobilization after ARCR for 6 weeks. The primary outcome was the Pittsburgh Sleep Quality Index at 6 weeks postoperatively. Secondary outcomes-American Shoulder and Elbow Surgeons score, Self-rating Anxiety Scale, pain, satisfaction, and tendon healing (using ultrasonography)-were evaluated until 1 year postoperatively., Results: Complete outcome measurements were obtained for 131 patients. The Pittsburgh Sleep Quality Index at 6 weeks was 11.1 ± 2.7 for the brace group and 9.2 ± 2.3 for the sling group ( P < .001), indicating a statistically significant advantage for the sling group. The sling group also reported significantly lower Self-rating Anxiety Scale, lower pain level, and higher satisfaction scores at 6 weeks. No significant difference was observed in outcome measures between groups at 1 year. The tendon healing rates (91% vs 88%, respectively) were comparable between the brace and sling groups within the first 1 year (risk ratio, 1.03 [95% CI, 0.92-1.16]; P = .59)., Conclusion: The use of a sling resulted in better sleep quality, less anxiety, and higher satisfaction compared with an abduction brace in the first 6 weeks after ARCR; nevertheless, functional outcomes and repair integrity were similar at 1 year postoperatively between the 2 groups. These findings indicate that a sling is appropriate for the postoperative care of ARCR. However, caution should be used when interpreting these results because the clinical relevance of sling-related benefits warrants further investigation., Registration: ChiCTR2200059967 (Chinese Clinical Trial Registry)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was financially supported by grants from the Chongqing Medical Scientific Research Project (No. 2023MSXM142), Chongqing Natural Science Foundation (No. cstc2019jcyjmsxmX0831), and the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJZD-K202300401) to H.C. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Stripe or yellow rust (YR) caused by Puccinia striiformis tritici ( Pst ) is an important foliar disease affecting wheat production globally. Resistant varieties are the most economically and environmentally effective way to manage this disease. The common winter wheat ( Triticum aestivum L.) cultivar Luomai 163 exhibited resistance to the Pst races CYR32 and CYR33 at the seedling stage and showed a high level of adult plant resistance in the field. To understand the genetic basis of YR resistance in this cultivar, 142 F 5 recombinant inbred lines (RILs) derived from cross Apav#1 × LM163 and both parents were genotyped with the 16K SNP array and bulked segregant analysis sequencing. The analysis detected a major gene, YrLM163 , at the seedling stage associated with the 1BL.1RS translocation. Additionally, three genes for resistance at the adult plant stage were detected on chromosome arms 1BL ( Lr46/Yr29/Pm39/Sr58 ), 6BS, and 6BL in Luomai 163, whereas Apav#1 contributed resistance at a quantitative trait locus (QTL) on 2BL. These QTL explained YR disease severity variations ranging from 6.9 to 54.8%. The kompetitive allele-specific PCR (KASP) markers KASP-2BL , KASP-6BS , and KASP-6BL for the three novel loci QYr.hzau-2BL , QYr.hzau-6BS , and QYr.hzau-6BL were developed and validated. QYr.hzau-1BL , QYr.hzau-2BL , and QYr.hzau-6BS showed varying degrees of resistance to YR when present individually or in combination based on genotype and phenotype analysis of a panel of 570 wheat accessions. Six RILs combining resistance alleles of all QTL, showing higher resistance to YR in the field than Luomai 163 with disease severities of 10.7 to 16.0%, are important germplasm resources for breeding programs to develop YR-resistant wheat varieties with good agronomic traits., Competing Interests: The author(s) declare no conflict of interest.

The rapid development of modern electronic devices increasingly requires thermal management materials with controllable electrical properties, ranging from conductive and dielectric to insulating, to meet the needs of diverse applications. However, highly thermally conductive materials usually have a high electrical conductivity. Intrinsically highly thermally conductive, but electrically insulating materials are still limited to a few kinds of materials. To overcome the electrical-thermal conductance trade-off, here, we report a facile Pechini-based method to prepare multiple core (metal)/shell (metal oxide) engineered fillers, such as aluminum-oxide-coated and beryllium-oxide-coated Ag microspheres. In contrast to the previous in situ growth method which mainly focused on small-sized spheres with specific coating materials, our method combined with ultrafast joule heating treatment is more versatile and robust for varied-sized, especially large-sized core-shell fillers. Through size compounding, the as-synthesized core-shell-filled epoxy composites exhibit high isotropic thermal conductivity (∼3.8 W m -1 K -1 ) while maintaining high electrical resistivity (∼10 12 Ω cm) and good flowability, showing better heat dissipation properties than commercial thermally conductive packaging materials. The successful preparation of these core-shell fillers endows thermally conductive composites with controlled electrical properties for emerging electronic package applications, as demonstrated in circuit board and battery thermal management.

Immune checkpoint blockade (ICB) triggers tumor ferroptosis. However, most patients are unresponsive to ICB. Tumors might evade ferroptosis in the tumor microenvironment (TME). Here, we discover SLC13A3 is an itaconate transporter in tumor cells and endows tumor ferroptosis resistance, diminishing tumor immunity and ICB efficacy. Mechanistically, tumor cells uptake itaconate via SLC13A3 from tumor-associated macrophages (TAMs), thereby activating the NRF2-SLC7A11 pathway and escaping from immune-mediated ferroptosis. Structural modeling and molecular docking analysis identify a functional inhibitor for SLC13A3 (SLC13A3i). Deletion of ACOD1 (an essential enzyme for itaconate synthesis) in macrophages, genetic ablation of SLC13A3 in tumors, or treatment with SLC13A3i sensitize tumors to ferroptosis, curb tumor progression, and bolster ICB effectiveness. Thus, we identify the interplay between tumors and TAMs via the SLC13A3-itaconate-NRF2-SLC7A11 axis as a previously unknown immune ferroptosis resistant mechanism in the TME and SLC13A3 as a promising immunometabolic target for treating SLC13A3 + cancer., Competing Interests: Declaration of interests W.Z. serves as a scientific advisor or consultant for Cstone, Hanchor Bio, and NextCure. S. Wang is a consultant for Proteovant Therapeutics and owns stock in Roivant Sciences. S. Wang is a co-founder, paid consultant, and member of the board of directors of Ascentage Pharma Group International and owns stock in Ascentage. N.Z., Z.A., J.P.S., A.K.R., W.Z., H.L., S. Wang, and P.K. are listed inventors in a patent application (UTSH.P0407US.P1) related to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Myocardial infarction (MI) is a serious cardiovascular disease that often results in a significant decline in heart function and associated complications. α-SMA (α-smooth muscle cell actin) is an important biomarker in the process of cardiac remodeling and repair, and its expression level is closely related to myocardial remodeling and prognosis. Therefore, the purpose of this study was to investigate the potential of nanoparticles containing cardiomyocyte targeting peptides in predicting prognosis and α-SMA protein expression after myocardial infarction, with a view to providing new therapeutic strategies and clinical guidelines. In this study, a novel targeting nanoparticle was constructed, using cardiomyocyte specific peptides as targeting ligands, and characterized by loading different drugs. Subsequently, a mouse model of myocardial infarction was used to systematically evaluate the effect of nanoparticles on α-SMA protein expression and prognosis prediction ability after MI. The expression level of α-SMA was analyzed by Western blot and immunohistochemistry, and the prognosis was evaluated by cardiac function assessment. The study found that nanoparticles containing cardiomyocyte targeting peptides significantly increased α-SMA expression levels and improved heart function in animal models of myocardial infarction. Compared with the control group, the application of targeted nanoparticles was closely related to the level of myocardial cell repair and fibrosis, and could effectively predict the prognosis after myocardial infarction. Therefore, nanoparticles containing cardiomyocyte targeting peptides can not only effectively improve the expression of α-SMA, but also serve as an important prognostic tool after myocardial infarction., 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.)

Acquiring a highly efficient electrocatalyst capable of sustaining prolonged operation under high current density is of paramount importance for the process of electrocatalytic water splitting. Herein, Fe-doped phosphide (Fe-Ni 5 P 4 ) derived from the NiFc metal-organic framework (NiFc-MOF) (Fc: 1,1'-ferrocene dicarboxylate) shows high catalytic activity for overall water splitting (OWS). Fe-Ni 5 P 4 ||Fe-Ni 5 P 4 exhibits a low voltage of 1.72 V for OWS at 0.5 A cm -2 and permits stable operation for 2700 h in 1.0 m KOH. Remarkably, Fe-Ni 5 P 4 ||Fe-Ni 5 P 4 can sustain robust water splitting at an extra-large current density of 1 A cm -2 for 1170 h even in alkaline seawater. Theoretical calculations confirm that Fe doping simultaneously reduces the reaction barriers of coupling and desorption (O * →OOH * , OOH * →O 2 * ) in the oxygen evolution reaction (OER) and regulates the adsorption strength of the intermediates (H 2 O * , H * P 5 P 4 to possess excellent dual functional activity. This study offers a valuable reference for the advancement of highly durable electrocatalysts through the regulation derived from coordination frameworks, with significant implications for industrial applications and energy conversion technologies., (© 2024 Wiley‐VCH GmbH.)

Digital complete denture fabrication has advanced with the integration of computer-aided design and computer-aided manufacturing (CAD-CAM), intraoral scanning, and 3-dimensional printing. A method of fabricating a stackable CAD-CAM custom record tray for complete dentures is introduced. The method combines a custom tray, record base, and occlusion rim in a single piece., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Abdominal visceral pain is a predominant symptom in patients with chronic pancreatitis (CP); however, the underlying mechanism of pain in CP remains elusive. We hypothesized that astrocytes in the hypothalamic paraventricular nucleus (PVH) contribute to CP pain pathogenesis. A mouse model of CP was established by repeated intraperitoneal administration of caerulein to induce abdominal visceral pain. Abdominal mechanical stimulation, open field and elevated plus maze tests were performed to assess visceral pain and anxiety-like behavior. Fiber photometry, brain slice Ca 2+ imaging, electrophysiology, and immunohistochemistry were used to investigate the underlying mechanisms. Mice with CP displayed long-term abdominal mechanical allodynia and comorbid anxiety, which was accompanied by astrocyte glial fibrillary acidic protein reactivity, elevated Ca 2+ signaling, and astroglial glutamate transporter-1 (GLT-1) deficits in the PVH. Specifically, reducing astrocyte Ca 2+ signaling in the PVH via chemogenetics significantly rescued GLT-1 deficits and alleviated mechanical allodynia and anxiety in mice with CP. Furthermore, we found that GLT-1 deficits directly contributed to the hyperexcitability of VGLUT2 PVH neurons in mice with CP, and that pharmacological activation of GLT-1 alleviated the hyperexcitability of VGLUT2 PVH neurons, abdominal visceral pain, and anxiety in these mice. Taken together, our data suggest that dysfunctional astrocyte glutamate uptake in the PVH contributes to visceral pain and anxiety in mice with CP, highlighting GLT-1 as a potential therapeutic target for chronic pain in patients experiencing CP., (© 2024 Wiley Periodicals LLC.)

Objective: To study the relationship between aging related genes (ARGs) and Major Depressive Disorder (MDD)., Methods: The datasets GSE98793, GSE52790 and GSE39653 for MDD were obtained from the GEO database, and ARGs were obtained from the Human Aging Genome Resources database. Differential expression genes (DEGs) screening and GO, KEGG enrichment analysis were performed to uncover the underlying mechanisms. To identify key ARGs associated with MDD (key ARG-DEGs), we employed machine learning methods such as LASSO, SVM, and Random Forest, as well as the plug-ins CytoHubba-MCC and MCODE methods. SsGSEA was used to analyze the immune infiltration of MDD and healthy controls. Furthermore, we created risk prediction nomograms model and ROC curves to assess not only the ability of key ARG-DEGs to diagnose MDD, but also predicted miRNAs and transcription factors (TFs) that might interact. Finally, a two-sample Mendelian randomization (MR) study was performed to confirm the association of identified key ARG-DEGs with depression., Results: DEGs of ARGs between MDD and healthy controls led to the identification of eight ARG-DEGs. GO and KEGG analysis revealed that the pathways associated with these eight ARG-DEGs were primarily concentrated in Foxo pathway, JAK-STAT pathway, Pl3K-AKT pathway, and metabolic diseases. A comprehensive analysis further narrowed down the 8 ARG-DEGs to 4 key ARG-DEGs: MMP9, IL7R, S100B, and EGF. Immune infiltration analysis indicated significant differences in CD8(+) T cells, macrophages, neutrophils, Th2 cells, and TIL cells between MDD and control groups, correlating with these four key ARG-DEGs. Based on these four key ARG-DEGs, a risk prediction model for MDD was developed. The miRNA-TF-mRNA interaction network of the key ARG-DEGs highlights the complexity of the regulatory process, providing valuable insights for future related research. The MR study suggested a potential causal relationship between MMP9 and the risk of depression., Conclusion: The process of aging, immune dysregulation, and MDD are closely interconnected. MMP9, IL7R, S100B, and EGF may be used as novel diagnostic biomarkers and potential therapeutic targets for MDD, especially MMP9., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The dysregulation of fucosyltransferases (FUTs) contributes to alterations in fucosylated epitope expression, which serve as distinctive features of cancer cells. Nonetheless, a comprehensive elucidation of the prognostic biological marker and therapeutic target of the FUTs family in pan-cancer remains elusive., Methods: Over 10,000 individuals' profiling information was examined, including information on 750 small molecule drugs, 33 types of cancer, and 24 types of immune cells. We focused on POFUT2's function and applied GSVA (Gene Set Variation Analysis) to calculate the FUT score. Survival and cancer pathways were found to be correlated with this score. After deriving a signature via univariate Cox and LASSO regression, we generated and analyzed the ROC curve and developed a nomogram., Results: Our comprehensive analysis revealed epigenetic, genomic, and immunogenomic changes in FUTs, particularly POFUT2, resulting in aberrant expression. Elevated frequencies of CNV (Copy number variation), SNV (Single Nucleotide Variant), and hypermethylation were observed in FUTs. Additionally, the survival of patients with various types of cancers may be predicted by FUT expression. Immune response and prognosis in numerous types of cancer were found to be strongly linked to aberrant POFUT2 expression. Pathway analysis unveiled the role of FUTs in apoptosis, epithelial-to-mesenchymal transition (EMT), cell cycle, DNA damage response, RAS/MAPK, TSC/mTOR, PI3K/AKT, AR, ER, and RTK. A prognostic index for patients diagnosed with adrenocortical carcinoma (ACC) was established by applying a risk model incorporating nine FUTs and based on the findings of the GSVA., Conclusions: FUTs, particularly POFUT2, emerge as candidate targets for improving the outcomes of immune therapy. The significance of aberrant MUC12 expression, cancer immune therapy, and patient survival in the context of diverse malignancies is enhanced by the strong correlation observed among these factors. Our five-gene risk signature provides patients with ACC with an independent prognostic indicator, emphasizing the critical function of these genes in inhibiting the immune system's response in ACC., (© 2024. The Author(s).)

Atractylodes lancea is an important Chinese herbal medicine, which is mainly produced in Jiangsu province, China. In June 2022, leaf spots symptom were observed on some A. lancea seedlings growing in a Chinese herbal medicine resource garden of Nanjing Botanical Garden, Jiangsu. Approximately 75% of 100 A. lancea seedlings suffered from the disease. Initially, gray to black spots appeared at the tip of the blade, then spread deep into the petiole, finally causing the blade to wither and fall. To isolate the pathogen, five diseased leaves were collected from five different seedlings. Leaf sections (3 to 4 mm) were excised from the margins between healthy and diseased tissues, surface sterilized in 75% alcohol for 30 s, then in 1.5% NaClO for 90 s, rinsed three times in sterilized distilled water, plated on potato dextrose agar (PDA) and incubated at 25℃in darkness. Pure cultures were obtained by monosporic isolation. Eighteen isolates were obtained, and 77.8% of isolates was identified as Alternaria spp. A representative isolate, CS4-1 was used for further investigation. The colony of CS4-1, growing on PDA was cotton-like and black to brown with gray-white aerial hyphae on their surfaces, and dark gray on the back. The conidia were solitary on conidiophores and were oval to pear-shaped, brown in color, with 1 to 4 transverse septa and 0 to 1 oblique septa, parietal cells extending into the beak, and measured 8.9 to 39.5×6.0 to 13.5 µm (n=35). These characteristics were consistent with the description of Alternaria spp. (Simmons 2007). Six DNA regions, i.e.,internal transcribed spacer (ITS), large subunit ribosomal RNA (LSU), small subunit ribosomal RNA (SSU), anonymous region OPA10-2, Alt a 1 major allergen (Alta1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and translation elongation factor 1-alpha (TEF1) with the respective GenBank Accession No. OP836052, OP836054, OP836051, OP851487, OP851488, OP851489, and OP851490, were amplified and sequenced with the primer pairs described by White et al. (1990) and Woudenberg et al. (2015). A neighbor-joining phylogenetic tree was generated by combining all sequenced loci in MEGA7, and CS4-1 clustered in the A. alternata clade. To test pathogenicity, 12 leaves, on three one-month-old A. lancea seedlings (four leaves from each seedling) were wounded with a sterile needle and inoculated with 20 μL of conidial suspension (1×106 spores/mL) on the left sides of leaves. The right sides of the leaves were inoculated with 20 µL sterile water and used as the control. All inoculated detached leaves and seedlings were covered with clear polyethylene bags to keep moisture and were incubated in a greenhouse at 25℃, 80% relative humidity, and a 12-h light/dark cycle. The experiment was repeated three times. After 4 days, typical gray to black spots were visible on the left sides of all inoculated leaves and the inoculated seedlings, and the right sides remained asymptomatic. Subsequently, the same fungus was reisolated and identified based on morphological and molecular traits. A. alternata has a very wide host range but has never been reported on A. lancea worldwide (nt.ars-grin.gov). Because of the medicinal value of A. lancea, further studies should be directed toward control of this disease.

The current magnetoencephalography (MEG) systems, which rely on cables for control and signal transmission, do not fully realize the potential of wearable optically pumped magnetometers (OPM). This study presents a significant advancement in wireless OPM-MEG by reducing magnetization in the electronics and developing a tailored wireless communication protocol. Our protocol effectively eliminates electromagnetic interference, particularly in the critical frequency bands of MEG signals, and accurately synchronizes the acquisition and stimulation channels with the host computer's clock. We have successfully achieved single-channel wireless OPM-MEG measurement and demonstrated its reliability by replicating three well-established experiments: The alpha rhythm, auditory evoked field, and steady-state visual evoked field in the human brain. Our prototype wireless OPM-MEG system not only streamlines the measurement process but also represents a major step forward in the development of wearable OPM-MEG applications in both neuroscience and clinical research., Competing Interests: Declaration of competing interest All 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. Published by Elsevier Inc.)

The Thomsen-Friedenreich (TF) antigen has proven to be a promising target for developing novel therapeutic cancer vaccines. Here, a new strategy that TF antigen covalently coupled with KRN7000 and vizantin was developed. The resulting three-component vaccine KRN7000-TF-vizantin simultaneously triggers invariant natural killer T (iNKT) cells and macrophage-inducible C-type lectin (Mincle) signaling pathways, eliciting much stronger TF-specific immune responses than glycoprotein vaccine TF-KLH/alum and the corresponding two-component conjugate vaccines TF-KRN7000 and TF-vizantin. The analysis of IgG isotypes and the secretion of cytokines revealed that KRN7000-TF-vizantin induced Th1/Th2 mixed immune responses, where Th1 was dominant. In vivo experiments demonstrated that KRN7000-TF-vizantin increased the survival rate and survival time of tumor-challenged mice, and surviving mice rejected further tumor attacks without any additional treatment. This work demonstrates that covalently coupled KRN7000 and vizantin could serve as a promising TF-based vaccine carrier for antitumor immune therapy, and KRN7000-TF-vizantin features great potential to be a vaccine candidate.

Computed tomography (CT) stands as a ubiquitous medical diagnostic tool. Nonetheless, the radiation-related concerns associated with CT scans have raised public apprehensions. Mitigating radiation dosage in CT imaging poses an inherent challenge as it inevitably compromises the fidelity of CT reconstructions, impacting diagnostic accuracy. While previous deep learning techniques have exhibited promise in enhancing CT reconstruction quality, they remain hindered by the reliance on paired data, which is arduous to procure. In this study, we present a novel approach named Variational Score Solver (VSS) for solving sparse-view reconstruction without paired data. Our approach entails the acquisition of a probability distribution from densely sampled CT reconstructions, employing a latent diffusion model. High-quality reconstruction outcomes are achieved through an iterative process, wherein the diffusion model serves as the prior term, subsequently integrated with the data consistency term. Notably, rather than directly employing the prior diffusion model, we distill prior knowledge by finding the fixed point of the diffusion model. This framework empowers us to exercise precise control over the process. Moreover, we depart from modeling the reconstruction outcomes as deterministic values, opting instead for a distribution-based approach. This enables us to achieve more accurate reconstructions utilizing a trainable model. Our approach introduces a fresh perspective to the realm of zero-shot CT reconstruction, circumventing the constraints of supervised learning. Our extensive qualitative and quantitative experiments unequivocally demonstrate that VSS surpasses other contemporary unsupervised and achieves comparable results compared with the most advance supervised methods in sparse-view reconstruction tasks. Codes are available in https://github.com/fpsandnoob/vss.

The study used the Delphi method to conduct two rounds of expert consultations involving 23 experts nationwide, aiming to establish the comprehensive index system for field epidemiological investigations of viral respiratory infectious diseases and determine the weights assigned to each index through the hierarchical analysis. Both rounds of consultation witnessed a 100% participation rate among all experts, with a coefficient of authority (Cr) reaching 0.89. The Kendall's W coefficients for assessing the importance and feasibility in both rounds were 0.108, 0.234, 0.439 and 0.427, respectively. Finally, an index system consisting of seven first-level indicators, 18 second-level indicators, and 36 third-level indicators was constructed for the technical guidelines governing field epidemiological investigations into viral respiratory infectious diseases, and the weight of each indicator was established. The index system constructed in this study has a high degree of scientificity, reliability and operability, but it still needs to be further adjusted and improved in combination with the epidemiological characteristics of viral respiratory infectious diseases.

With the advent of an aging population, the study of aging and related research has been increasingly prominent, focusing on how to fully understand and delay aging-a key concern for contemporary medical professionals. Stroke is an acute focal neurological deficit. Globally, ischemic stroke accounts for only 60-70% of all strokes, meanwhile, it is the second leading cause of death. With the introduction of the concept of biomarkers of ageing, the research of ischemic stroke or acute brain injury in relation to these biomarkers has remained fragmented. In this review, we aim to consolidate the current evidence, highlighting the intricate relationship between ischemic stroke and aging-related hallmarks during its occurrence. By providing a comprehensive overview, we hope to offer researchers a broader perspective on how acute injury mechanisms intertwine with aging. We hope to present a new viewpoint and a more complete evaluation framework for future research and exploration in the field of aging.

Calcium influx via the L-type voltage-gated Ca v 1.2 calcium channel in smooth muscle cells regulates vascular contraction. Calcium channel blockers (CCBs) are widely used to treat hypertension by inhibiting Ca v 1.2 channels. Using the vascular smooth muscle cell line, A7r5 and primary culture of cerebral vascular smooth muscle cells, we found that the expression and function of Ca v 1.2 channels are downregulated during hypoxia. Furthermore, hypoxia induces structural changes in Ca v 1.2 channels via alternative splicing. The expression of exon 9* is upregulated, whereas exon 33 is downregulated. Such structural alterations of Ca v 1.2 channels are caused by the decreased expression of RNA-binding proteins RNA-binding protein fox-1 homolog 1 and 2 (RbFox1 and RbFox2). Overexpression of RbFox1 and RbFox2 prevents hypoxia-induced exon 9* inclusion and exon 33 exclusion. Importantly, such structural alterations of the Ca v 1.2 channel partly contribute to the enhanced sensitivity of Ca v 1.2 to isradipine (a CCB) under hypoxia. Overexpression of RbFox1 and RbFox2 successfully reduces isradipine sensitivity in hypoxic smooth muscle cells. Our results suggest a new strategy to manage ischemic diseases such as stroke and myocardial infarction., (© 2024 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Angiogenesis is crucial for successful bone defect repair. Co-transplanting Bone Marrow Stromal Cells (BMSCs) and Endothelial Cells (ECs) has shown promise for vascular augmentation, but it face challenges in hostile tissue microenvironments, including poor cell survival and limited efficacy. In this study, the mitochondria of human BMSCs are isolated and transplanted to BMSCs from the same batch and passage number (BMSCs mito ). The transplanted mitochondria significantly boosted the ability of BMSCs mito -ECs to promote angiogenesis, as assessed by in vitro tube formation and spheroid sprouting assays, as well as in vivo transplantation experiments in balb/c mouse and SD rat models. The Dll4-Notch1 signaling pathway is found to play a key role in BMSCs mito -induced endothelial tube formation. Co-transplanting BMSCs mito with ECs in a rat cranial bone defect significantly improves functional vascular network formation, and improve bone repair outcomes. These findings thus highlight that mitochondrial transplantation, by acting through the DLL4-Notch1 signaling pathway, represents a promising therapeutic strategy for enhancing angiogenesis and improving bone repair. Hence, mitochondrial transplantation to BMSCS as a therapeutic approach for promoting angiogenesis offers valuable insights and holds much promise for innovative regenerative medicine therapies., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Peroxymonosulfate (PMS), which is dominated by free radical (SO 4 •- ) pathway, has a good removal effect on organic pollutants in complex water matrices. In this article, a new catalyst (CFM@NC) was synthesized by hydrothermal carbonization method with chitosan (CS) as N and C precursors, and used to activate PMS to degrade dye wastewater. CFM@NC/PMS system can degrade 50 mg·L -1 rhodamine B by 99.59 % within 30 min, and the degradation rate remains as high as 97.32 % after 5 cycles. It has good complex background matrices, acid-base anti-interference ability (pH 2.6-10.1), universality and reusability. It can degrade methyl orange and methylene blue by >98 % within 30 min. The high efficiency of the composite is due to the fact that CS-modified MoS 2 as a carrier exposes a large number of active sites, which not only disperses CuFe 2 O 4 nanoparticles and improves the stability of the catalyst, but also provides abundant electron rich groups, which promotes the activation of PMS and the production of reactive oxygen species (ROS). PMS is effectively activated by catalytic sites (Cu + /Cu 2+ , Fe 2+ /Fe 3+ , Mo 4+ /Mo 6+ , pyridine N, pyrrole N, edge sulfur and hydroxyl group) to produce a large number of radicals to attack RhB molecules, causing chromophore cleavage, ring opening, and mineralization. Among them, free radical SO 4 •- is the main ROS for RhB degradation. This work is expected to provide a new idea for the design and synthesis of environmentally friendly and efficient heterogeneous catalysts., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled, “Chitosan-derived N-doped carbon supported Cu/Fe co-doped MoS(2)nanoparticles as peroxymonosulfate activator for efficient dyes degradation”., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acquired pulmonary artery branch stenosis without main pulmonary artery involvement due to external compression by neoplasia has been described in human and veterinary medicine. Over time, this can result in right ventricular hypertension and right-sided heart failure. Endovascular stenting offers quick relief from signs, while the underlying cause is addressed. Here, we present a dog with severe right pulmonary artery compression caused by a chemodectoma, which was treated with two, overlapping, self-expanding vascular stents and chemotherapy. The patient experienced immediate symptomatic relief, progressive stent expansion over time, and has been free of clinical symptoms for 5 months post implantation., 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 Ferrel, Winter, Maneval, Matz, Bergman, Starbird, Koehler and Liao.)

Ischemic stroke (IS) is a debilitating neurological disorder with limited treatment options. Extracellular vesicles (EVs) have emerged as crucial lipid bilayer particles derived from various cell types that facilitate intercellular communication and enable the exchange of proteins, lipids, and genetic material. Microglia are resident brain cells that play a crucial role in brain development, maintenance of neuronal networks, and injury repair. They secrete numerous extracellular vesicles in different states. Recent evidence indicates that microglia-derived extracellular vesicles (M-EVs) actively participate in mediating various biological processes, such as neuroprotection and neurorepair, in stroke, making them an excellent therapeutic approach for treating this condition. This review comprehensively summarizes the latest research on M-EVs in stroke and explores their potential as novel therapeutic targets for this disorder. Additionally, it provides an overview of the effects and functions of M-EVs on stroke recovery to facilitate the development of clinically relevant therapies for IS., 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.)

Glycine as one of the most abundant amino acids in human proteins, with extensive applications in both life and industry, is conventionally synthesized through complex procedures or toxic feedstocks. In this study, we present a facile and benign electrochemical pathway for synthesis of glycine through reductive coupling of glyoxylic acid and nitrate over a copper-bismuth bimetal catalyst derived from a metal-organic framework (MOF) array on copper foam (Cu/Bi-C@CF). Remarkably, Cu/Bi-C@CF achieves a fantastic selectivity of 89 %, corresponding a high Faraday efficiency of 65.9 %. From control experiments, the introduction of Bi caused the binding energy of Cu shift to a lower state, which leads to a high selectivity towards the formation of key intermediate hydroxylamine rather than ammonia product, facilitating the formation of oxime and providing additional sites for subsequent hydrogenation reaction on the way to glycine. Moreover, the derivation of MOF arrays ensures the effective dispersion of Bi and enhances the stability of Cu/Bi-C@CF. This innovative approach not only presents sustainable pathways for the production of value-added organonitrogen compounds utilizing readily available carbon and nitrogen sources, but also provides novel insights into the design of multistage structural catalysts for sequential reactions., (© 2024 Wiley-VCH GmbH.)

Herein, we report the first example of a highly enantioselective alkylative aziridine ring opening. Under the catalysis of a chiral nickel/pyridine-imidazoline complex, asymmetric C(sp 3 )-C(sp 3 ) cross-electrophile coupling between racemic N -sulfonyl styrenyl aziridines and readily available primary alkyl bromides furnishes a variety of highly enantioenriched phenethylamine derivatives with complete regiocontrol and good functional group tolerance. Preliminary mechanistic studies support a reaction pathway consisting of regioselective iodolysis of aziridines in situ and subsequent enantioconvergent coupling of the generated β-amino benzyl iodides with alkyl bromides.

Hydrogen energy, due to its clean and efficient nature, has shown great potential during the current transition period in the shipbuilding industry. However, the application of hydrogen energy in ship energy systems is influenced by variations in operational load and the integration of new energy sources during actual navigation. To address these issues, this paper focuses on optimizing and scheduling the operation of ships under various navigation conditions, considering the distributed nature of hydrogen energy. System simulations were conducted to model the photovoltaic (PV), proton exchange membrane fuel cells (PEMFCs), lithium batteries (LIBs), electrolytic cells (ECs), and energy storage modules of yacht energy systems. Component boundaries and objective functions were set, and two cases (excess photovoltaic state and constant power state) were designed to optimize and regulate the energy balance of hydrogen-powered yachts, enhancing their comprehensive utilization of renewable energy. By comparing the changes in ship energy under the two cases, it was concluded that case 1 ensures the maximum utilization of renewable energy. When photovoltaic power generation is insufficient, the PEMFC and LIB in the system provide the required power to achieve a supply-demand balance. Moreover, when PV power generation is sufficient, hydrogen energy is used to store renewable energy. The optimization method designed in this study can, to some extent, maximize the application of renewable energy in new energy yachts, ensuring the efficiency of the comprehensive energy system of new energy yachts, reducing emissions, and improving the sustainability and economic efficiency of the ships., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Soluble sugars contribute to the taste and flavor of citrus fruit. Potassium (K), known as a quality element, plays key roles in improving sugar accumulation and fruit quality, but the mechanism is largely unknown. This study aims to elucidate how K improves sugar accumulation by regulating carbon flow from source leaves to fruit in Newhall navel orange. We found that optimal fruit K concentrations around 1.5% improved sugar accumulation and fruit quality in citrus. K application increased the strength of both sink and source, as indicated by the increased fruit growth rate, enzyme activities and expression levels of key genes involved in sucrose (Suc) metabolism in fruit and leaf. K application also facilitated Suc transport from source leaves to fruit, as confirmed by the enhanced 13 C-Suc level in fruit. Furthermore, we found that navel orange used the symplastic pathway for transporting Suc from source leaves to fruit, and K application enhanced symplastic loading, as demonstrated by the intensified carboxyfluorescein signal and increased plasmodesmata density in leaves. The findings reveal that K stimulates fruit sugar accumulation by increasing carbon flow from source leaves to fruit in Newhall navel orange., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Abstract: Backgrounds: This study aimed to investigate the relationship between Cx43 expression and autophagy mediated by the AMPK-mTOR-Ulk1 signaling pathway in jaundice heart. Methods: In this study, a jaundice model was established in common bile duct ligation (CBDL) rats. Cardiac injury was assessed using various methods including myocardial injury indicators, echocardiography, transmission electron microscopy, hematoxylin and eosin staining, Masson staining, immunohistochemical analyses, and immunofluorescence staining. We investigated the regulatory relationship between Cx43, autophagy, and the AMPK-mTOR-ULK pathway in vivo by administering autophagy agonists (Rapa), autophagy inhibitors (3-MA), and Cx43 inhibitors (Gap 26). In vitro , we observed the relationship between autophagy and the AMPK-mTOR-ULK1 pathway in cells by exposing them to the AMPK inhibitor Compound C and the AMPK activator AICAR. Results: We found that CBDL induced autophagy through the AMPK-mTOR-ULK pathway, leading to the inhibition of myocardial dysfunction. Rapamycin pretreatment with CBDL3d exhibited a protective effect against myocardial injury and promoted autophagy. In contrast, 3-MA had no impact. Pretreatment with rapamycin at CBDL2w enhanced autophagy and aggravated cardiac injury; however, inhibition of autophagy using 3-MA attenuated cardiac injury. Cell viability was enhanced by AMPK inhibitors and inhibited by AMPK agonists. In addition, we observed that increased autophagy led to decreased Cx43 expression, which negatively affected cardiac function. Conclusions: CBDL induces myocardial injury in rats and activates autophagy through the AMPK-mTOR-ULK pathway, resulting in decreased Cx43 protein levels. A moderate increase in early autophagy in CBDL can improve cardiac injury, while late inhibition of autophagy can reduce myocardial injury., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by the Shock Society.)

Brain-derived neurotrophic factor (BDNF) is vital for synaptic plasticity, cell persistence, and neuronal development in peripheral and central nervous systems (CNS). Numerous intracellular signalling pathways involving BDNF are well recognized to affect neurogenesis, synaptic function, cell viability, and cognitive function, which in turn affects pathological and physiological aspects of neurons. Stroke has a significant psycho-socioeconomic impact globally. Central post-stroke pain (CPSP), also known as a type of chronic neuropathic pain, is caused by injury to the CNS following a stroke, specifically damage to the somatosensory system. BDNF regulates a broad range of functions directly or via its biologically active isoforms, regulating multiple signalling pathways through interactions with different types of receptors. BDNF has been shown to play a major role in facilitating neuroplasticity during post-stroke recovery and a pro-nociceptive role in pain development in the nervous system. BDNF-tyrosine kinase receptors B (TrkB) pathway promotes neurite outgrowth, neurogenesis, and the prevention of apoptosis, which helps in stroke recovery. Meanwhile, BDNF overexpression plays a role in CPSP via the activation of purinergic receptors P2X4R and P2X7R. The neuronal hyperexcitability that causes CPSP is linked with BDNF-TrkB interactions, changes in ion channels and inflammatory reactions. This review provides an overview of BDNF synthesis, interactions with certain receptors, and potential functions in regulating signalling pathways associated with stroke and CPSP. The pathophysiological mechanisms underlying CPSP, the role of BDNF in CPSP, and the challenges and current treatment strategies targeting BDNF are also discussed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

JOURNAL/nrgr/04.03/01300535-202502000-00029/figure1/v/2024-05-28T214302Z/r/image-tiff Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell-derived neural stem cell exosomes (hiPSC-NSC-Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits, enhanced blood-brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC-NSC-Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, and tumor necrosis factor-α post-intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood-brain barrier integrity. Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

The purpose of this study was to analyze the role of transcription factor in Desmodium styracifolium , proving that the DsWRKY6 transcription factor was related to the plant phenotypes of Desmodium styracifolium - cv. 'GuangYaoDa1' and it could be used in molecular-assisted breeding. 'GuangYaoDa1' was used as the material and its DNA was the template to clone DsWRKY6, the transgenic Arabidopsis thaliana line was constructed by agrobacterium tumefaciens‑mediated transformation. Transgenic Arabidopsis thaliana was cultivated to study phenotype and physiological and biochemical indexes. Phenotypic observation showed that DsWRKY6 transgenic Arabidopsis thaliana had a faster growth rate while compared with the control group, they had longer lengths of main stem, lateral branches of cauline leaves, and root, but a lower number of cauline leaves and lateral branches of cauline leaves. And it also showed that their flowering and fruiting periods were advanced. The results of physiological and biochemical indexes showed that the relative expressions of DsWRKY6 increased and the abscisic acid content significantly increased in DsWRKY6 transgenic Arabidopsis thaliana compared with the control group. According to the above results, DsWRKY6 could regulate the advancing of flowering and fruiting periods caused by the improvement of abscisic acid content, and expression of the DsWRKY6 transcription factor might be the cause of the upright growth of 'GuangYaoDa1'.

Eutrophication has become one of the greatest threats to aquatic ecosystems. The release of phosphorus (P) from sediments exerts a critical role on eutrophication level. Both manganese (Mn) and iron (Fe), sensitive to redox conditions, own strong affinity for P. Numerous works have demonstrated that Fe was a key factor to drive P cycle in sediments. However, the role of Mn on P mobilization remains largely unexplored. Herein, the mechanism of P mobilization driven by Mn were investigated in a seasonal anoxic reservoir. Diffusive gradients in thin films (DGT) results, from both field investigations and laboratory incubations, showed P was synchronously distributed and significantly positive correlated (r 2  ≥ 0.40, p < 0.01) with Mn, suggested that P cycle was associated with Mn. X-ray photoelectron spectroscopy (XPS) results showed that in the outer layers at the top 1 cm sediment pellet the contents of Mn and P occurred significantly synchronize changed, while that of Fe remains virtually unchanged when oxygen conditions changed. This demonstrated that Mn is likely to be the key factor affect P cycle. Most importantly, the relative content of Mn(III) changed the most (≈20 %) interpreted that Mn(III) is the key Mn species dominants the P mobilization. Furthermore, Dual-Beam scanning electron microscope (DB-SEM) maps clearly showed the co-enrichment of P and Mn in oxic sediments, confirmed P was mainly hosted by Mn minerals. In contrast, the random distributions and weak or negative correlations between P and Fe implied that P cycle was decouple with Fe, this resulted from that Fe was almost deposited as inert Fe fractions (>99.2 %) in reducing sediments. This study significantly expanded our knowledge on the geochemical behavior of P influenced by Mn in aquatic sediments., 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.)

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder that caused by NF1 mutations. NF1 gene encodes neurofibromin (a GTPase-activating protein) and plays a regulatory role in many signalling pathway such as the Ras/MAPK pathway, which is important for regulating cell growth, proliferation and neural development. Therefore, NF1 gene mutations causes the excessive activation of signalling pathways and uncontrolled cell growth. NF1 exhibits complete genetic penetrance and clinical heterogeneity. Glomerular disease has rarely been reported in patients with NF1, especially in children. Currently, the relationship between NF1 and nephrotic syndrome is unclear. Here, we present a case of NF1 with nephrotic syndrome and further explore the association between NF1 and glomerular diseases. It also reminds clinicians that NF1 has complex and highly variable clinical manifestations and that a comprehensive workup is essential for patients., (© 2024 Asian Pacific Society of Nephrology.)

Citrus yellow vein-clearing virus (CYVCV) is an increasing threat to citrus cultivation. Notably, the role of zinc finger proteins (ZFPs) in mediating viral resistance in citrus plants is unclear. In this study, we demonstrate that ZFPs ClSUP and ClDOF3.4 enhance citrus defense responses against CYVCV in Eureka lemon. ClSUP interacted with the coat protein (CP) of CYVCV to reduce CP accumulation and inhibit its silencing suppressor function. Overexpression of CISUP triggered reactive oxygen species (ROS) and salicylic acid (SA) pathways, and enhanced resistance to CYVCV infection. In contrast, ClSUP-silencing resulted in increased CP accumulation and down-regulated ROS and SA-related genes. ClDOF3.4 interacts with ClSUP to facilitate its interactions with CP. Furthermore, ClDOF3.4 synergistically regulated the accumulation of ROS and SA with ClSUP and accelerated the down-regulation of CP accumulation. Transgenic plants co-expressing ClSUP and ClDOF3.4 remarkedly decrease the CYVCV. These findings provide a new reference for understanding the interaction mechanism between the host and CYVCV., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8 + T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4 + breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4 + cancer., Competing Interests: Declaration of interests W.Z. has served as a scientific advisor or consultant for Cstone, NextCure, and Hanchorbio. S. Wang is a co-founder and paid consultant of Ascentage Pharma Group International and owns stock in Ascentage. L.C. has been a scientific founder, consultant, and/or board observer for NextCure, Normunity, Tayu, Zai Lab, Tpioneer, Vcanbio, OncoC4, and GenomiCare and has sponsored research funds from NextCure, Normunity, and DynamiCure. This research is conducted independently and has not received resources from and is unrelated to the scientific and commercial pursuits of these industrial entities, including NextCure., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cell-to-cell mitochondrial transfer has recently been shown to play a role in maintaining physiological functions of cell. We previously illustrated that mitochondrial transfer within osteocyte dendritic network regulates bone tissue homeostasis. However, the mechanism of triggering this process has not been explored. Here, we showed that stressed osteocytes in mice release adenosine diphosphate (ADP), resulting in triggering mitochondrial transfer from healthy osteocytes to restore the oxygen consumption rate (OCR) and to alleviate reactive oxygen species accumulation. Furthermore, we identified that P2Y2 and P2Y6 transduced the ADP signal to regulate osteocyte mitochondrial transfer. We showed that mitochondrial metabolism is impaired in aged osteocytes, and there were more extracellular nucleotides release into the matrix in aged cortical bone due to compromised membrane integrity. Conditioned medium from aged osteocytes triggered mitochondrial transfer between osteocytes to enhance the energy metabolism. Together, using osteocyte as an example, this study showed new insights into how extracellular ADP triggers healthy cells to rescue energy metabolism crisis in stressed cells via mitochondrial transfer in tissue homeostasis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Backgroup: The pathogenesis of shoulder impingement syndrome (SIS) is still unclear, and its questionable causal relationship with rotator cuff (RC) injury has led to confusion in treatment. The purpose of this study was to explore the bidirectional causal relationship between SIS and RC injury., Methods: SIS and RC injury datasets downloaded from the IEU Open GWAS project and GWAS catalog databases. Inverse variance weighted (IVW), MR Egger, Weighted median, and Weighted mode were used in this Mendelian randomization (MR) analysis. Cochran's Q test, leave-one-out, and funnel plot method were used to evaluate heterogeneity between single nucleotide polymorphisms (SNPs). MR-Egger regression was used to test the horizontal pleiotropy of this study., Results: The IVW method (OR = 1.189, P = 0.0059) suggest the putative causal effect of RC injury on SIS. The results of MR Egger method (OR = 1.236, P = 0.2013), weighted median method (OR = 1.097, P = 0.2428) and weighted mode method (OR = 1.013, P = 0.930) showed no statistically significant (OR = 1.069071, P = 0.6173). Heterogeneity test and horizontal pleiotropy analysis suggested that there was no significant heterogeneity and horizontal pleiotropy in the results of this MR analysis. The reverse MR analysis showed heterogeneity, and the conclusion needs to be further explored., Conclusions: The results of MR analysis support that RC injury may be causally associated with SIS., (© 2024. The Author(s).)

In recent years, score-based diffusion models have emerged as effective tools for estimating score functions from empirical data distributions, particularly in integrating implicit priors with inverse problems like CT reconstruction. However, score-based diffusion models are rarely explored in challenging tasks such as metal artifact reduction (MAR). In this paper, we introduce the BiConstraints Diffusion Model for Metal Artifact Reduction (BCDMAR), an innovative approach that enhances iterative reconstruction with a conditional diffusion model for MAR. This method employs a metal artifact degradation operator in place of the traditional metal-excluded projection operator in the data-fidelity term, thereby preserving structure details around metal regions. However, scorebased diffusion models tend to be susceptible to grayscale shifts and unreliable structures, making it challenging to reach an optimal solution. To address this, we utilize a precorrected image as a prior constraint, guiding the generation of the score-based diffusion model. By iteratively applying the score-based diffusion model and the data-fidelity step in each sampling iteration, BCDMAR effectively maintains reliable tissue representation around metal regions and produces highly consistent structures in non-metal regions. Through extensive experiments focused on metal artifact reduction tasks, BCDMAR demonstrates superior performance over other state-of-the-art unsupervised and supervised methods, both quantitatively and in terms of visual results.

Background: Recent studies have shown that the triglyceride glucose index (TyG) and cystatin C (CysC) are closely related to cardiovascular disease, but there is limited research on the prognosis of patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). The aim of this study was to explore the predictive value of the combination of the TyG index and CysC in predicting major adverse cardiovascular events (MACEs) in ACS patients who underwent PCI., Methods: This retrospective study included 319 ACS patients who underwent PCI. The clinical endpoint was the occurrence of MACEs, including all-cause mortality, heart failure, non-fatal myocardial infarction, target vessel revascularization, and angina requiring hospitalization. Patients were classified into MACEs (65 cases) and non-MACEs (254 cases) groups. Univariate factor and multivariate analysis were used to identify predictors of MACEs. The receiver operating curve (ROC) of the prediction model of MACEs was determined. Additionally, the net reclassification improvement and integrated discrimination improvement indexes were calculated to further assess the additional predictive value of the risk factors for MACEs. Subgroup and interaction analysis between the TyG index combined with CysC and MACEs were conducted in various subgroups. Patients were stratified according to the optimal cutoff point value of the TyG index and the CysC determined by ROC curve analysis. The Kaplan-Meier analysis method was used to construct a survival curve 1 year after PCI., Results: During a median follow-up period of 14 months, 65 (20.38%) patients had experienced at least one primary endpoint event. Multivariate logistic regression analysis indicated that the TyG index and CysC were independently associated with an increased risk of MACEs after PCI (OR, 2.513, 95% CI 1.451-4.351, P= 0.001; and OR, 4.741, 95% CI 1.344-16.731, P=0.016, respectively). The addition of the TyG index and CysC to the baseline risk model had the strongest incremental effect for predicting MACEs in terms of the C-statistic from 0.789 (95% CI 0.723-0.855, P<0.001) to 0.799 (95% CI 0.733-0.865, P<0.001). Furthermore, Kaplan-Meier analysis demonstrated that a TyG index greater than 9.325 and a CysC value greater than 1.065 mg/ml were significantly associated with an increased risk of MACEs (log-rank, all P < 0.01)., Conclusion: The TyG index predicts MACEs after PCI in patients with ASC independent of known cardiovascular risk factors. Adjustment of the CysC by the TyG index further improves the predictive ability for MACEs in patients with ACS undergoing PCI. Thus, both of them are expected to become new prognostic indicators for MACEs in patients with ACS after PCI., 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 Wang, Liao, Tang, Chen and Zhang.)

In this opinion piece, we consider the meaning of the term 'wild type' in the context of microbiology. This is especially pertinent in the post-genomic era, where we have a greater awareness of species diversity than ever before. Genomic heterogeneity, in vitro evolution/selection pressures, definition of 'the wild', the size and importance of the pan-genome, gene-gene interactions (epistasis), and the nature of the 'wild-type gene' are all discussed. We conclude that wild type is an outdated and even misleading phrase that should be gradually phased out.

Background: Low-dose computed tomography (LDCT) is a diagnostic imaging technique designed to minimize radiation exposure to the patient. However, this reduction in radiation may compromise computed tomography (CT) image quality, adversely impacting clinical diagnoses. Various advanced LDCT methods have emerged to mitigate this challenge, relying on well-matched LDCT and normal-dose CT (NDCT) image pairs for training. Nevertheless, these methods often face difficulties in distinguishing image details from nonuniformly distributed noise, limiting their denoising efficacy. Additionally, acquiring suitably paired datasets in the medical domain poses challenges, further constraining their applicability. Hence, the objective of this study was to develop an innovative denoising framework for LDCT images employing unpaired data., Methods: In this paper, we propose a LDCT denoising network (DNCNN) that alleviates the need for aligning LDCT and NDCT images. Our approach employs generative adversarial networks (GANs) to learn and model the noise present in LDCT images, establishing a mapping from the pseudo-LDCT to the actual NDCT domain without the need for paired CT images., Results: Within the domain of weakly supervised methods, our proposed model exhibited superior objective metrics on the simulated dataset when compared to CycleGAN and selective kernel-based cycle-consistent GAN (SKFCycleGAN): the peak signal-to-noise ratio (PSNR) was 43.9441, the structural similarity index measure (SSIM) was 0.9660, and the visual information fidelity (VIF) was 0.7707. In the clinical dataset, we conducted a visual effect analysis by observing various tissues through different observation windows. Our proposed method achieved a no-reference structural sharpness (NRSS) value of 0.6171, which was closest to that of the NDCT images (NRSS =0.6049), demonstrating its superiority over other denoising techniques in preserving details, maintaining structural integrity, and enhancing edge contrast., Conclusions: Through extensive experiments on both simulated and clinical datasets, we demonstrated the superior efficacy of our proposed method in terms of denoising quality and quantity. Our method exhibits superiority over both supervised techniques, including block-matching and 3D filtering (BM3D), residual encoder-decoder convolutional neural network (RED-CNN), and Wasserstein generative adversarial network-VGG (WGAN-VGG), and over weakly supervised approaches, including CycleGAN and SKFCycleGAN., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-68/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Purpose: The coronavirus disease 2019 (COVID-19), one of the most significant recent emerging infectious diseases, has evolved into a global pandemic, resulting in an unprecedented public health crisis with substantial morbidity. The aim of this study was to investigate the care experiences of nursing staff during the COVID-19 pandemic., Methods: A qualitative, exploratory interview study. This study was conducted from August 2022 to January 2023. Participants were recruited from a medical center in northern Taiwan. A purposive sampling approach was employed to select the participants, and in-depth interviews were conducted with a total of 30 individuals. The collected data were analyzed using content analysis., Results: The findings of this study revealed five themes that summarized the care experiences of participants during the COVID-19 pandemic, enhanced nursing competence in pandemic mitigation, adherence to clear safety measures, effective adaptation to the stress of the "unknown," and recognition of the meaning of the pandemic mitigation experience., Conclusion: This study informs pandemic readiness for nurses and policy enhancement. Medical institutions and governments must prioritize policies ensuring staffing, PPE access, and mental health support. Educators and administrators should elevate on-the-job crisis management training. Future planning should cater to Taiwanese nurses' needs during unforeseen crises such as COVID-19., (Copyright © 2024. Published by Elsevier B.V.)

Background: Vascular dementia (VaD), the second most prevalent type of dementia, lacks a well-defined cause and effective treatment. Our objective was to utilize bioinformatics analysis to discover the fundamental disease-causing genes and pathological mechanisms in individuals diagnosed with VaD., Methods: To identify potential pathogenic genes associated with VaD, we conducted weighted gene co-expression network analysis (WGCNA), differential expression analysis, and protein-protein interaction (PPI) analysis. The exploration of potential biological mechanisms involved the utilization of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Moreover, a bilateral common carotid artery stenosis (BCAS) mouse model of VaD was established, and the expression of the hub gene, its relationship with cognitive function and its potential pathogenic mechanism were verified by cognitive behavior tests, cerebral blood flow measurement, Western blotting, and immunofluorescence experiments., Results: This study identified 293 DEGs from the brain cortex of VaD patients and healthy controls, among these genes, the Toll-like receptor 2 (TLR2) gene was identified as hub gene, and it was associated with the apoptosis-related pathway PI3K/AKT.The BCAS model demonstrated that the use of TLR2 inhibitors greatly enhanced the cognitive function of the mice (p < 0.05). Additionally, there was a notable decrease in the number of apoptotic cells in the brain cortex of the mice (p < 0.01). Moreover, significant alterations in the levels of proteins related to the PI3K/AKT pathway and cleaved-caspase3 proteins were detected (p < 0.05)., Conclusions: TLR2 plays a role in the pathophysiology of VaD by enhancing the neuronal apoptotic pathway, suggesting it could be a promising therapeutic target., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

N6-methyladenosine (m6A) RNA modification has recently emerged as an essential regulator of normal and malignant hematopoiesis. As a reversible epigenetic modification found in messenger RNAs and non-coding RNAs, m6A affects the fate of the modified RNA molecules. It is essential in most vital bioprocesses, contributing to cancer development. Here, we review the up-to-date knowledge of the pathological functions and underlying molecular mechanism of m6A modifications in normal hematopoiesis, leukemia pathogenesis, and drug response/resistance. At last, we discuss the critical role of m6A in immune response, the therapeutic potential of targeting m6A regulators, and the possible combination therapy for AML., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Catheter-related thrombosis is a common complication of the peripherally inserted central catheter (PICC) in neonates, leading to unintended tube removal and significantly affecting neonatal health and safety. Despite widespread reporting on the estimated occurrence and factors contributing to neonatal PICC-related thrombosis, these findings have not been synthesized., Objectives: The purpose of this study was to determine the incidence and risk factors of neonatal PICC-related thrombosis., Design: Systematic literature review and meta-analysis., Methods: Two independent researchers systematically explored multiple databases-such as PubMed, Medline, Embase and the Cochrane Library-from their inception until October 2023. Our study aggregates and scrutinizes studies specifically addressing the incidence and risk factors of neonatal PICC-related thrombosis. Employing the RevMan 5.3 software, a meta-analysis was executed to determine the incidence of both thrombosis and odds ratios (OR), accompanied by their respective 95% confidence intervals (CI) for the risk factors., Results: A total of 327 articles were screened, and data from 24 studies were used in synthesis. Neonatal PICC-related thrombosis incidence varied from 0.23% to 17.91%. The pooled incidence was 2% (95% CI: 1%-2%; I 2  = 94%; p < .0001). The study identified 12 risk factors, including insertion sites in the lower extremities (OR = 0.22; 95% CI: 0.09-0.56; p = .001), gestational age <28 weeks, abdominal pathology, fresh frozen plasma by day 5 > 50 mL/kg, PICC tip location (proximal placement), two lumens, three lumens, prolonged hospital stay, infection, mothers' use of anticoagulants, patients with cardiac insufficiency and being twin-to-twin transfusion syndrome donor., Conclusions: The analysis indicates an overall pooled incidence of neonatal PICC-related thrombosis of 2%. Twelve factors were identified as risks associated with neonatal PICC-related thrombosis. Understanding the risk factors can provide evidence-based recommendations for improving awareness, control and treatment and better nursing management., Relevance to Clinical Practice: This systematic review and meta-analysis illuminates the incidence and risk factors linked to neonatal PICC-related thrombosis, delivering essential insights pivotal for clinical decision-making and enhancing patient care within neonatal health care settings., (© 2024 British Association of Critical Care Nurses.)

Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990-2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology.

Objective: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms., Methods: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly., Results: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884)., Conclusion: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions., (© 2024. The Author(s).)