Synergistic peptide combinations designed to suppress SARS-CoV-2.

The SARS-CoV-2, responsible for the COVID-19 pandemic, poses a significant threat to global healthcare. Peptide and peptide-based inhibitors, known for their safety, efficacy, and selectivity, have recently emerged as promising candidates for treating late-developing viral infections. In this study, three peptides were selected to target different stages of viral invasion, specifically ACE2 and S protein binding, as well as membrane fusion. The objective was to assess their ability to impede the entry of the SARS-CoV-2 Spike pseudotyped virus. Our findings revealed that a combination of these three peptides demonstrated enhanced antiviral effects. This outcome substantiates the feasibility of developing effective peptide combinations to combat diseases related to SARS-CoV-2. Moreover, the three-peptide combinations, designed to target multiple aspects of SARS-CoV-2 viral entry, exhibited heightened viral inhibition and broad-spectrum antiviral properties.

Brain Network Characterization of Preterm Infants With Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) affects the microstructure of white matter in preterm infants, but its influence on the changes of the brain structural network has not been elaborated. This study aims to investigate the connectivity characteristics of the brain structural network of BPD by using diffusion tensor imaging. METHODS: Thirty-three infants with BPD and 26 infants without BPD were enrolled in this study. Brain structural networks were constructed utilizing automated anatomic labeling mapping by tracing the fibers between each pair of regions in individual space. We calculated network metrics such as global efficiency, local efficiency, clustering coefficients, characteristic path length, and small-worldness. Then we compared the network metrics of these infants with those of 57 healthy term infants of comparable postmenstrual age at magnetic resonance imaging scan. Finally, network-based statistics was used to analyze the differences in brain network connectivity between the groups with and without BPD. RESULTS: Preterm infants with BPD had higher local efficiency and clustering coefficient, lower global efficiency, and longer characteristic path length. Also, preterm infants with BPD had decreased strength of limbic connections mainly in four brain regions: the left lingual gyrus, the left calcarine fissure and surrounding cortex, the right parahippocampal gyrus, and the left precuneus. CONCLUSIONS: Our findings suggest that preterm infants with BPD have lower network integration and higher segregation at term-equivalent age, which may reflect a compensatory mechanism. In addition, BPD affects brain regions involved in visual as well as cognitive functions; these findings provide a new approach to diagnose potential brain damage in preterm infants with BPD.

AppleQSM: Geometry-Based 3D Characterization of Apple Tree Architecture in Orchards.

The architecture of apple trees plays a pivotal role in shaping their growth and fruit-bearing potential, forming the foundation for precision apple management. Traditionally, 2D imaging technologies were employed to delineate the architectural traits of apple trees, but their accuracy was hampered by occlusion and perspective ambiguities. This study aimed to surmount these constraints by devising a 3D geometry-based processing pipeline for apple tree structure segmentation and architectural trait characterization, utilizing point clouds collected by a terrestrial laser scanner (TLS). The pipeline consisted of four modules: (a) data preprocessing module, (b) tree instance segmentation module, (c) tree structure segmentation module, and (d) architectural trait extraction module. The developed pipeline was used to analyze 84 trees of two representative apple cultivars, characterizing architectural traits such as tree height, trunk diameter, branch count, branch diameter, and branch angle. Experimental results indicated that the established pipeline attained an R2 of 0.92 and 0.83, and a mean absolute error (MAE) of 6.1 cm and 4.71 mm for tree height and trunk diameter at the tree level, respectively. Additionally, at the branch level, it achieved an R2 of 0.77 and 0.69, and a MAE of 6.86 mm and 7.48° for branch diameter and angle, respectively. The accurate measurement of these architectural traits can enable precision management in high-density apple orchards and bolster phenotyping endeavors in breeding programs. Moreover, bottlenecks of 3D tree characterization in general were comprehensively analyzed to reveal future development.

Quantitative reconstruction of a single super rainstorm using daily resolved δ18O of land snail shells.

A "once-in-a-millennium" super rainstorm battered Zhengzhou, central China, from 07/17/2021 to 07/22/2021 (named "7.20" Zhengzhou rainstorm). It killed 398 people and caused billions of dollars in damage. A pressing question is whether rainstorms of this intensity can be effectively documented by geological archives to understand better their historical variabilities beyond the range of meteorological data. Here, four land snail shells were collected from Zhengzhou, and weekly to daily resolved snail shell δ18O records from June to September of 2021 were obtained by gas-source mass spectrometry and secondary ion mass spectrometry. The daily resolved records show a dramatic negative shift between 06/18/2021 and 09/18/2021, which has been attributed to the "7.20" Zhengzhou rainstorm. Moreover, the measured amplitude of this shift is consistent with the theoretical value estimated from the flux balance model and instrumental data for the "7.20" Zhengzhou rainstorm. Our results suggest that the ultra-high resolution δ18O of land snail shells have the potential to reconstruct local synoptic scale rainstorms quantitatively, and thus fossil snail shells in sedimentary strata can be valuable material for investigating the historical variability of local rainstorms under different climate backgrounds.

Role of maternal-fetal immune tolerance in the establishment and maintenance of pregnancy.

ABSTRACT: Normal pregnancy is a contradictory and complicated physiological process. Although the fetus carries the human leukocyte antigen (HLA) inherited from the paternal line, it does not cause maternal immune rejection. As the only exception to immunological principles, maternal-fetal immune tolerance has been a reproductive immunology focus. In early pregnancy, fetal extravillous trophoblast cells (EVTs) invade decidual tissues and come into direct contact with maternal decidual immune cells (DICs) and decidual stromal cells (DSCs) to establish a sophisticated maternal-fetal crosstalk. This study reviews previous research results and focuses on the establishment and maintenance mechanism of maternal-fetal tolerance based on maternal-fetal crosstalk. Insights into maternal-fetal tolerance will not only improve understanding of normal pregnancy but will also contribute to novel therapeutic strategies for recurrent spontaneous abortion, pre-eclampsia, and premature birth.

Long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array modes.

We propose to realize a long range topography by dispersion unmatched spectral-domain interferometry based on virtually imaged phased array (VIPA) modes. By filtering the continuous spectrum of a supercontinuum source through a side-entrance Fabry-Perot etalon configured at two input angles, two groups of VIPA modes are generated. A method based on unmatched dispersion is proposed for non-aliasing reconstruction of the true depth from the interference spectrum under-sampled at two groups of VIPA modes. With the high spectral resolution provided by the VIPA modes instead of the grating-based spectrometer, only a 10 dB falloff in sensitivity over a range of 10 mm was demonstrated. The feasibility of the proposed method was confirmed by topography of a sample of gauge blocks and a model of three-dimensional (3D) printed tooth. The occlusal surface of the tooth model was further quantitatively evaluated, demonstrating its potential application in long range 3D topography.

T1 Pre- and Post-contrast Delta Histogram Parameters in Predicting the Grade of Meningioma and Their Relationship to Ki-67 Proliferation Index.

RATIONALE AND OBJECTIVES: To explore the feasibility of delta histogram parameters (including absolute delta histogram parameters (AdHP) and relative delta histogram parameters (RdHP)) in predicting the grade of meningioma and to further investigate whether delta histogram parameters correlate with the Ki-67 proliferation index. METHODS: 92 patients with meningioma who underwent MRI examination (including T1-weighted (T1) and contrast-enhanced T1-weighted images (T1C)) were enrolled in this retrospective study. A total of 46 low-grade cases formed the low-grade group (grade 1, LGM), and a total of 46 high-grade cases formed the high-grade group (38 grade 2, 8 grade 3, HGM). Histogram parameters (HP) of T1 and T1C were extracted. Subsequently, morphological MRI features, AdHP (AdHP=T1CHP-T1HP), and RdHP (RdHP=(T1CHP-T1HP)/T1HP) were recorded and compared, respectively. Binary logistic regression analysis was used to obtain combined performance of the significant parameters. Diagnostic performance was identified by ROC. Spearman's correlation coefficients were taken to assess the relationship between delta histogram parameters and the Ki-67 proliferation index. RESULTS: In morphological MRI features, HGM is more prone to lobulation and necrosis/cystic changes (all p < 0.05). In delta histogram parameters, HGM exhibits higher mean, Perc.01, Perc.25, Perc.50, Perc.75, Perc.99, SD, and variance of AdHP, maximum, mean, Perc.25, Perc.50, Perc.75, and Perc.99 of RdHP, compared to LGM (all p < 0.00357). The optimal predictive performance was obtained by combining morphological MRI features and delta histogram parameters with an AUC of 0.945. Significant correlations were observed between significant delta histogram parameters and the Ki-67 proliferation index (all p < 0.05). CONCLUSION: Delta histogram parameter is a promising potential biomarker, which may be helpful in noninvasive predicting the grade and proliferative activity of meningioma.

Enhanced YOLO v3 for precise detection of apparent damage on bridges amidst complex backgrounds.

A bridge disease identification approach based on an enhanced YOLO v3 algorithm is suggested to increase the accuracy of apparent disease detection of concrete bridges under complex backgrounds. First, the YOLO v3 network structure is enhanced to better accommodate the dense distribution and large variation of disease scale characteristics, and the detection layer incorporates the squeeze and excitation (SE) networks attention mechanism module and spatial pyramid pooling module to strengthen the semantic feature extraction ability. Secondly, CIoU with better localization ability is selected as the loss function for training. Finally, the K-means algorithm is used for anchor frame clustering on the bridge surface disease defects dataset. 1363 datasets containing exposed reinforcement, spalling, and water erosion damage of bridges are produced, and network training is done after manual labelling and data improvement in order to test the efficacy of the algorithm described in this paper. According to the trial results, the YOLO v3 model has enhanced more than the original model in terms of precision rate, recall rate, Average Precision (AP), and other indicators. Its overall mean Average Precision (mAP) value has also grown by 5.5%. With the RTX2080Ti graphics card, the detection frame rate increases to 84 Frames Per Second, enabling more precise and real-time bridge illness detection.

A multicenter study of the mid-term outcomes of patients with uncomplicated type B aortic dissection after distal porous Talos stent-graft implantation.

OBJECTIVES: The Talos stent-graft has extended length to improve aortic remodeling, and distal porous design to decrease the rate of spinal cord ischemia. This study retrospectively analyzed its mid-term outcomes for uncomplicated type B aortic dissection in a multicenter study. METHODS: The primary safety endpoint was 30-day major adverse events, including all-cause mortality, dissection-related mortality, conversion to open surgery, and device-related adverse events. The primary efficacy endpoint was treatment success at 12 months post-operation, defined as no technical failure or secondary dissection-related reintervention. The survival status of the patients was visualized using the Kaplan-Meier curve. Aortic growth was assessed at four levels, and spinal cord ischemia was evaluated at 12 months. RESULTS: 113 patients participated with a mean age of 54.4 (11.1) years and 71.7% (81/113) were male. The 30-day mortality was 0.9% (1/113), no conversions to open surgery or device-related adverse events were recorded. The 12-month treatment success rate was 99.1% (112/113), with no dissection-related reinterventions. There was no spinal cord or visceral ischemia at 12 months. At a median of 34 months follow-up, 9 further deaths were recorded and the 3-year survival rate was 91.7%. The percentage of aortic growth was 1.8% (2/111) at the tracheal bifurcation, 3.6% (4/111) below the left atrium, 6.0% (5/83) above the celiac artery, and 12.1% (9/74) below the lower renal artery. The total thrombosis rate of the false lumen at the stented segment was 80.5% (91/113). CONCLUSIONS: The results showed satisfactory results of Talos stent-graft in terms of safety and efficacy. More data are needed to confirm the long-term performance.

Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis.

Disulfidptosis was recently reported to be caused by abnormal disulfide accumulation in cells with high SLC7A11 levels subjected to glucose starvation, suggesting that targeting disulfidptosis was a potential strategy for cancer treatment. We analyzed the relationships between gene expression and mutations and prognoses of patients. In addition, the correlation between gene expression and immune cell infiltration was explored. The potential regulatory mechanisms of these genes were assessed by investigating their related signaling pathways involved in cancer, their expression patterns, and their cellular localization. Most cancer types showed a negative correlation between the gene-set variation analysis (GSVA) scores and infiltration of B cells and neutrophils, and a positive correlation between GSVA scores and infiltration of natural killer T and induced regulatory T cells. Single-cell analysis revealed that ACTB, DSTN, and MYL6 were highly expressed in different bladder urothelial carcinoma subtypes, but MYH10 showed a low expression. Immunofluorescence staining showed that actin cytoskeleton proteins were mainly localized in the actin filaments and plasma membrane. Notably, IQGAP1 was localized in the cell junctions. In conclusion, this study provided an overview of disulfidptosis-related actin cytoskeleton genes in pan-cancer. These genes were associated with the survival of patients and might be involved in cancer-related pathways.

CDC45 promotes the stemness and metastasis in lung adenocarcinoma by affecting the cell cycle.

OBJECTIVE: This study aimed to assess the functions of cell division cycle protein 45 (CDC45) in Non-small cell lung cancer (NSCLC) cancer and its effects on stemness and metastasis. METHODS: Firstly, differentially expressed genes related to lung cancer metastasis and stemness were screened by differential analysis and lasso regression. Then, in vitro, experiments such as colony formation assay, scratch assay, and transwell assay were conducted to evaluate the impact of CDC45 knockdown on the proliferation and migration abilities of lung cancer cells. Western blotting was used to measure the expression levels of related proteins and investigate the regulation of CDC45 on the cell cycle. Finally, in vivo model with subcutaneous injection of lung cancer cells was performed to verify the effect of CDC45 on tumor growth. RESULTS: This study identified CDC45 as a key gene potentially influencing tumor stemness and lymph node metastasis. Knockdown of CDC45 not only suppressed the proliferation and migration abilities of lung cancer cells but also caused cell cycle arrest at the G2/M phase. Further analysis revealed a negative correlation between CDC45 and cell cycle-related proteins, stemness-related markers, and tumor mutations. Mouse experiments confirmed that CDC45 knockdown inhibited tumor growth. CONCLUSION: As a novel regulator of stemness, CDC45 plays a role in regulating lung cancer cell proliferation, migration, and cell cycle. Therefore, CDC45 may serve as a potential target for lung cancer treatment and provide a reference for further mechanistic research and therapeutic development.

S100P facilitates LUAD progression via PKA/c-Jun-mediated tumor-associated macrophage recruitment and polarization.

S100P, a member of the S100 calcium-binding protein family, is closely associated with abnormal proliferation, invasion, and metastasis of various cancers. However, its role in the lung adenocarcinoma (LUAD) tumor microenvironment (TME) remains unclear. In this study, we observed specific expression of S100P on tumor cells in LUAD patients through tissue immunofluorescence analysis. Furthermore, this expression was strongly correlated with the recruitment and polarization of tumor-associated macrophages (TAMs). Bioinformatics analysis revealed that high S100P expression is associated with poorer overall survival in LUAD patients. Subsequently, a subcutaneous mouse model demonstrated that S100P promotes recruitment and polarization of TAMs towards the M2 type. Finally, in vitro studies on LUAD cells revealed that S100P enhances the secretion of chemokines and polarizing factors by activating the PKA/c-Jun pathway, which is implicated in TAM recruitment and polarization towards the M2 phenotype. Moreover, inhibition of c-Jun expression impedes the ability of TAMs to infiltrate and polarize towards the M2 phenotype. In conclusion, our study demonstrates that S100P facilitates LUAD cells growth by recruiting M2 TAMs through PKA/c-Jun signaling, resulting in the production of various cytokines. Considering these findings, S100P holds promise as an important diagnostic marker and potential therapeutic target for LUAD.

Exploring new frontiers: cell surface vimentin as an emerging marker for circulating tumor cells and a promising therapeutic target in advanced gastric Cancer.

BACKGROUND: Circulating tumor cells (CTCs) hold immense promise in guiding treatment strategies for advanced gastric cancer (GC). However, their clinical impact has been limited due to challenges in identifying epithelial-mesenchymal transition (EMT)-CTCs using conventional methods. METHODS: To bridge this knowledge gap, we established a detection platform for CTCs based on the distinctive biomarker cell surface vimentin (CSV). A prospective study involving 127 GC patients was conducted, comparing CTCs enumeration using both EpCAM and CSV. This approach enabled the detection of both regular and EMT-CTCs, providing a comprehensive analysis. Spiking assays and WES were employed to verify the reliability of this marker and technique. To explore the potential inducer of CSV+CTCs formation, a combination of Tandem Mass Tag (TMT) quantitative proteomics, m6A RNA immunoprecipitation-qPCR (MeRIP-qPCR), single-base elongation- and ligation-based qPCR amplification method (SELECT) and RNA sequencing (RNA-seq) were utilized to screen and confirm the potential target gene. Both in vitro and in vivo experiments were performed to explore the molecular mechanism of CSV expression regulation and its role in GC metastasis. RESULTS: Our findings revealed the potential of CSV in predicting therapeutic responses and long-term prognosis for advanced GC patients. Additionally, compared to the conventional EpCAM-based CTCs detection method, the CSV-specific positive selection CTCs assay was significantly better for evaluating the therapeutic response and prognosis in advanced GC patients and successfully predicted disease progression 14.25 months earlier than radiology evaluation. Apart from its excellent role as a detection marker, CSV emerges as a promising therapeutic target for attenuating GC metastasis. It was found that fat mass and obesity associated protein (FTO) could act as a potential catalyst for CSV+CTCs formation, and its impact on the insulin-like growth factor-I receptor (IGF-IR) mRNA decay through m6A modification. The activation of IGF-I/IGF-IR signaling enhanced the translocation of vimentin from the cytoplasm to the cell surface through phosphorylation of vimentin at serine 39 (S39). In a GC mouse model, the simultaneous inhibition of CSV and blockade of the IGF-IR pathway yielded promising outcomes. CONCLUSION: In summary, leveraging CSV as a universal CTCs marker represents a significant breakthrough in advancing personalized medicine for patients with advanced GC. This research not only paves the way for tailored therapeutic strategies but also underscores the pivotal role of CSV in enhancing GC management, opening new frontiers for precision medicine.

Intranasal oxytocin as a treatment for anxiety and autism: From subclinical to clinical applications.

Animal and human studies have demonstrated that intranasal oxytocin (OT) can penetrate the brain and induce cognitive, emotional, and behavioral changes, particularly in social functioning. Consequently, numerous investigations have explored the potential of OT as a treatment for anxiety and autism, conditions characterized by social deficits. Although both subclinical and clinical studies provide converging evidence of the therapeutic effects of OT in reducing anxiety levels and improving social symptoms in autism, results are not always consistent. Additionally, the pharmacological mechanism of OT requires further elucidation for its effective clinical application. Therefore, this review aims to examine the contentious findings concerning the effects of OT on anxiety and autism, offer interpretations of the inconsistent results from the perspectives of individual differences and varying approaches to OT administration, and shed light on the underlying mechanisms of OT. Ultimately, standardization of dosage, frequency of administration, formulation characteristics, and nasal spray devices is proposed as essential for future human studies and clinical applications of OT treatment.

In vivo study on osteogenic efficiency of nHA/ gel porous scaffold with nacre water-soluble matrix.

BACKGROUND/PURPOSE: Nano-hydroxyapatite (nHA)/ gel porous scaffolds loaded with WSM carriers are promising bone replacement materials that can improve osseointegration ability. This investigation aimed to evaluate the osteoinductive activity by implanting the composition of nano-hydroxyapatite (nHA)/ Gel porous scaffolds as a carrier of WSM via an animal model. MATERIALS AND METHODS: WSM was extracted and nHA was added to the matrix to construct porous composite scaffolds. The dose-effect curve of WSM concentration and alkaline phosphatase (ALP) activity was made by culturing rat osteoblasts and examining the absorbance. Three different materials were implanted into critical size defects (CSD) in the skulls of rats, which were further divided into four groups: WSM nHA /Gel group, n-WSM nHA /Gel group, HA powder group, and control group. RESULTS: WSM (150 µg/mL-250µg/mL) effectively improved the activity of ALP in rat osteoblasts. All rats in each group had normal healing. WSM-loaded nHA /Gel group showed better performance on newly-formed bone tissue of rat skull and back at 4th week and 8th week, respectively. At the 4th week, the network of woven bone formed in the WSM-loaded nHA/Gel scaffold material. At 8th week, the reticular trabecular bone in the WSM-loaded scaffold material became dense lamellar bone, and the defect was mature lamellar bone. In the subcutaneous implantation experiment, WSM-loaded nHA/Gel scaffold material showed a better performance of heterotopic ossification than the pure nHA/Gel scaffold material. CONCLUSION: WSM promotes osteoblast differentiation and bone mineralization. The results confirm that the nHA/ Gel Porous Scaffold with Nacre Water-Soluble Matrix has a significant bone promoting effect and can be used as a choice for tissue engineering to repair bone defects.

Neural network-based predefined-time bipartite formation tracking control of uncertain heterogeneous Euler-Lagrange systems in task space.

The main problem addressed in this paper is the task-space bipartite formation tracking problem of uncertain heterogeneous Euler-Lagrange systems in predefined time. To solve this problem, an effective hierarchical predefined-time control algorithm is designed. This algorithm utilizes a non-singular sliding surface, allowing for the adjustment of the upper bound of the settling time as a flexible parameter. Key components of the proposed approach include an estimator for the leader's states and a controller tailored to the formation problem. To mitigate the effects of dynamic uncertainties in the system, the radial basis function neural network is integrated into the methodology. Finally, the effectiveness and validity of the proposed algorithm are demonstrated through numerical simulations, showcasing their practical applicability and efficacy.

GPX8+ cancer-associated fibroblast, as a cancer-promoting factor in lung adenocarcinoma, is related to the immunosuppressive microenvironment.

BACKGROUND: Cancer-associated fibroblasts (CAFs) play a crucial role in the tumor microenvironment of lung adenocarcinoma (LUAD) and are often associated with poorer clinical outcomes. This study aimed to screen for CAF-specific genes that could serve as promising therapeutic targets for LUAD. METHODS: We established a single-cell transcriptional profile of LUAD, focusing on genetic changes in fibroblasts. Next, we identified key genes associated with fibroblasts through weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis. Then, we evaluated the relationship between glutathione peroxidase 8 (GPX8) and clinical features in multiple independent LUAD cohorts. Furthermore, we analyzed immune infiltration to shed light on the relationship between GPX8 immune microenvironment remodeling. For clinical treatment, we used the tumor immune dysfunction and exclusion (TIDE) algorithm to assess the immunotherapy prediction efficiency of GPX8. After that, we screened potential therapeutic drugs for LUAD by the connectivity map (cMAP). Finally, we conducted a cell trajectory analysis of GPX8+ CAFs to show their unique function. RESULTS: Fibroblasts were found to be enriched in tumor tissues. Then we identified GPX8 as a key gene associated with CAFs through comprehensive bioinformatics analysis. Further analysis across multiple LUAD cohorts demonstrated the relationship between GPX8 and poor prognosis. Additionally, we found that GPX8 played a role in inducing the formation of an immunosuppressive microenvironment. The TIDE method indicated that patients with low GPX8 expression were more likely to be responsive to immunotherapy. Using the cMAP, we identified beta-CCP as a potential drug-related to GPX8. Finally, cell trajectory analysis provided insights into the dynamic process of GPX8+ CAFs formation. CONCLUSIONS: This study elucidates the association between GPX8+ CAFs and poor prognosis, as well as the induction of immunosuppressive formation in LUAD. These findings suggest that targeting GPX8+ CAFs could potentially serve as a therapeutic strategy for the treatment of LUAD.

Spin-degree manipulation for one-dimensional room-temperature ferromagnetism in a haldane system.

The intricate correlation between lattice geometry, topological behavior and charge degrees of freedom plays a key role in determining the physical and chemical properties of a quantum-magnetic system. Herein, we investigate the introduction of the unusual oxidation state as an alternative pathway to modulate the magnetic ground state in the well-known S = 1 Haldane system nickelate Y2BaNiO5 (YBNO). YBNO is topologically reduced to incorporate d9-Ni+ (S = 1/2) in the one-dimensional Haldane chain system. The random distribution of Ni+ for the first time results in the emergence of a one-dimensional ferromagnetic phase with a transition temperature far above room temperature. Theoretical calculations reveal that the antiferromagnetic interplay can evolve into ferromagnetic interactions with the presence of oxygen vacancies, which promotes the formation of ferromagnetic order within one-dimensional nickel chains. The unusual electronic instabilities in the nickel-based Haldane system may offer new possibilities towards unconventional physical and chemical properties from quantum interactions.