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Abstract Background Periodontitis is a chronic inflammatory disease characterized by the destruction of the components of the periodontium. It significantly impacts oral health and has been linked to systemic conditions like cardiovascular disease and diabetes. The critical role of neutrophils in the occurrence and development of chronic periodontitis has been paid increasing attention. The study aimed to explore the protective effects of D-mannose on chronic periodontitis and determine whether its underlying mechanisms is related to neutrophils. Methods To explore the protective effects of D-mannose on chronic periodontitis, the eight-week-old Sprague Dawley rat model of lipopolysaccharide (LPS)-induced periodontitis was established, followed by D-mannose treatment by oral gavage. To evaluate the protective effects of D-mannose against periodontal bone loss, methylene blue staining, hematoxylin and eosin (H&E) staining, and micro-CT scanning were utilized. Then, immunofluorescence (IF), Western Blot, and RT-PCR were applied to assess the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and IL-17), anti-inflammatory cytokine (IL-10), tumor necrosis factor-alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), ten-eleven translocation 2 (TET2), and key glycolytic enzymes (HK1, HK2, PFKFB3), and to examine D-mannose’s impact on the recruitment and activation of neutrophils in the gingiva. Additionally, neutrophils isolated from the peripheral blood of healthy rats were treated with LPS and D-mannose, and changes in the expression levels of myeloperoxidase (MPO), IL-1β, IL-6, IL-17, IL-10, and TET2 were observed via IF. Results In vivo, D-mannose inhibited LPS-induced alveolar bone resorption in rats. After D-mannose treatment, the expression levels of IL-17 (p

Abstract Background This study focused on the aging mechanism and degradation of mechanical and structural features of elastodontic appliances (EA) under artificial and intraoral aging to achieve oral myofunctional therapy with particular removable silicone elastomer devices. Materials and methods EAs artificially aged in saliva with different pH values were investigated through cyclic compression testing along with characterization techniques (Scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy), and characterization analysis was also performed on clinically retrieved EAs. Results Artificial aging was found to have minimal effect on the structural properties of EAs, and intraorally aged samples showed perceptible micro-morphology. The Mullins index and peak stress decreased (P

Creep, as a long-term deformation characteristic of shotcrete, significantly influences the load-bearing performance and durability of tunnel support structures. This study conducted creep tests on shotcrete under varying stress levels. The results reveal that shotcrete exhibits linear creep response within the stress range of 30%–40%, while the critical stress range for nonlinear creep response occurs between 40% and 50%. Employing SEM-EDS and XRD analysis methods, the impact of accelerator on the microstructure evolution and creep mechanism of shotcrete is explored. The accelerator accelerates the hydration of C3S, promoting the generation of AFt and C–S–H gel, leading to rapid solidification of the matrix and enhanced early strength. With the consumption of SO42− ions, AFt gradually transforms into AFm, resulting in increased matrix porosity. This phenomenon contributes to the reduced later-stage strength and substantial creep deformation of shotcrete. Based on experimental outcomes, this study evaluates the applicability of existing creep calculation models to shotcrete.

Magnesium alloys, noted for their substantial mechanical strength and exceptional biocompatibility, are increasingly being considered for use in biodegradable implants. However, their rapid degradation and significant hydrogen release have limited their applications in orthopaedics. In this study, a novel Mg-RE-Sr alloy was created by friction stir processing to modify its microstructure and enhance its degradation performance. Through microstructural characterization, the friction stir processing effectively refined the grains, accelerated the re-dissolution of precipitates, and ensured a uniform distribution of these phases. The processed alloy demonstrated improved comprehensive properties, with an in vitro corrosion rate of approximately 0.4 mm/y and increases in ultimate tensile strength and elongation by 37 % and 166 %, respectively. Notably, in vivo experiments involving a rat subcutaneous implantation model revealed a slower degradation rate of 0.09 mm/y and a uniform degradation process, basically achieving the requirements for ideal performance in orthopaedic applications. The superior degradation characteristics were attributed to the synergistic effect of attenuated galvanic corrosion and the formation of a dense Y(OH)3/Y2O3 film induced by an exceptional microstructure with a highly solid-soluted matrix and uniformly refined precipitates. Meanwhile, the alloys exhibited excellent biocompatibility and did not cause undesirable inflammation or produce toxic degradation products. These improvements in biocompatibility and degradation characteristics indicate great promise for the use of this friction stir processed alloy in osteosynthesis systems in the clinical setting.

As a kind of complex system with strong nonlinearity, strong coupling, time variance, redundancy, and high dimension, the modeling, motion control, and stability analysis of an underwater vehicle-manipulator system(UVMS) are very challenging. In dynamics modeling, the traditional Lagrange equation is often used to model the complex UVMS with high degrees of freedom, which requires the operation of derivation and partial derivation of the generalized coordinates and their derivatives and will face the problems of a large amount of calculation and low modeling efficiency. Therefore, this paper proposed a simplified dynamics modeling method for UVMS with 6+n degree-of-freedom based on the quasi-Lagrange equation, which could reduce the amount of calculation in the symbolic formula derivation and improve the modeling efficiency and the accuracy of the results. Finally, the numerical simulation of a UVMS model was carried out with the physical parameters of the underwater vehicle BlueROV and the underwater manipulator Reach Alpha, and the simulation results verified the complex coupling of the UVMS. The dynamics model based on the proposed method had a clear equation form, which not only provided strong support for the study of control algorithms and the optimization of coupling forces but also a basis for the design of dynamics parameters and the study of trajectory planning.

Abstract Background Cardiovascular function and metabolic homeostasis are closely linked, but the underlying mechanisms are not fully understood. Corin is a protease that activates atrial natriuretic peptide (ANP), an essential hormone for normal blood pressure and cardiac function. The goal of this study is to investigate a potential corin and ANP function in regulating liver glycogen metabolism and glucose homeostasis. Methods Liver glycogen and blood glucose levels were analyzed in Corin or Nppa (encoding ANP) knockout (KO) mice. ANP signaling was examined in livers from Corin and Nppa KO mice and in cultured human and mouse hepatocytes by western blotting. Results We found that Corin and Nppa KO mice had reduced liver glycogen contents and increased blood glucose levels. By analyzing conditional KO mice lacking either cardiac or renal Corin, we showed that cardiac corin and ANP act in an endocrine manner to enhance cGMP-protein kinase G (PKG)-AKT-GSK3 signaling in hepatocytes. In cultured hepatocytes, ANP treatment stimulated PKG signaling, glucose uptake, and glycogen production, which could be blocked by small molecule PKG and AKT inhibitors. Conclusions Our results indicate that corin and ANP are important regulators in liver glycogen metabolism and glucose homeostasis, suggesting that defects in the corin and ANP pathway may contribute to both cardiovascular and metabolic diseases.

Abstract Objectives To develop and validate a quantitative model for predicting serosal invasion based on multi-parameters in preoperative dual-energy CT (DECT). Materials and methods A total of 342 LAGC patients who underwent gastrectomy and DECT from six centers were divided into one training cohort (TC), and two validation cohorts (VCs). Dual-phase enhanced DECT-derived iodine concentration (IC), water concentration, and monochromatic attenuation of lesions, along with clinical information, were measured and collected. The independent predictors among these characteristics for serosal invasion were screened with Spearman correlation analysis and logistic regression (LR) analysis. A quantitative model was developed based on LR classifier with fivefold cross-validation for predicting the serosal invasion in LAGC. We comprehensively tested the model and investigated its value in survival analysis. Results A quantitative model was established using IC, 70 keV, 100 keV monochromatic attenuations in the venous phase, and CT-reported T4a, which were independent predictors of serosal invasion. The proposed model had the area-under-the-curve (AUC) values of 0.889 for TC and 0.860 and 0.837 for VCs. Subgroup analysis showed that the model could well discriminate T3 from T4a groups, and T2 from T4a groups in all cohorts (all p

Highlights The large-scale, high-strength, super-tough, and multifunctional nacre-like heterocyclic aramid (HA)/MXene@polypyrrole (PPy) (HMP) nanocomposite papers were fabricated using the in-situ assembly of PPy onto the HA/MXene hydrogel template. The "brick-and-mortar" layered structure and abundant hydrogen-bonding interactions among MXene, PPy, and HA respond cooperatively to external stress and effectively increase the mechanical properties of HMP nanocomposite papers. The templating effect from HA/MXene was utilized to guide the assembly of conducting polymers, leading to high electrical conductivity and outstanding electromagnetic interference shielding performance.

Abstract Corin is a protease that activates atrial natriuretic peptide (ANP), a hormone in cardiovascular homeostasis. Structurally, ANP is similar to C-type natriuretic peptide (CNP) crucial in bone development. Here, we examine the role of corin and ANP in chondrocyte differentiation and bone formation. We show that in Corin and Nppa (encoding ANP) knockout (KO) mice, chondrocyte differentiation is impaired, resulting in shortened limb long bones. In adult mice, Corin and Nppa deficiency impairs bone density and microarchitecture. Molecular studies in cartilages from newborn Corin and Nppa KO mice and in cultured chondrocytes indicate that corin and ANP act in chondrocytes via cGMP-dependent protein kinase G signaling to inhibit mitogen-activated protein kinase phosphorylation and stimulate glycogen synthase kinase-3β phosphorylation and β-catenin upregulation. These results indicate that corin and ANP signaling regulates chondrocyte differentiation in bone development and homeostasis, suggesting that enhancing ANP signaling may improve bone quality in patients with osteoporosis.

Abstract Background Subarachnoid hemorrhage (SAH) is a life -threatening cerebrovascular disease, where early brain injury (EBI) stands as a primary contributor to mortality and unfavorable patient outcomes. Neuronal ferroptosis emerges as a key pathological mechanism underlying EBI in SAH. Targeting ferroptosis for therapeutic intervention in SAH holds significant promise as a treatment strategy. Methods SAH model was induced via intravascular puncture and quantitatively assessed the presence of neuronal ferroptosis in the early phase of SAH using FJC staining, Prussian blue staining, as well as malondialdehyde (MDA) and glutathione (GSH) measurements. Hyaluronic acid-coated ursolic acid nanoparticles (HA-PEG-UA NPs) were prepared using the solvent evaporation method. We investigated the in vivo distribution of HA-PEG-UA NPs in SAH model through IVIS and fluorescence observation, and examined their impact on short-term neurological function and cortical neurological injury. Finally, we assessed the effect of UA on the Nrf-2/SLC7A11/GPX4 axis via Western Blot analysis. Results We successfully developed self-assembled UA NPs with hyaluronic acid to target the increased CD44 expression in the SAH-afflicted brain. The resulting HA-PEG-UA NPs facilitated delivery and enrichment of UA within the SAH-affected region. The targeted delivery of UA to the SAH region can effectively inhibit neuronal ferroptosis, improve neurological deficits, and prognosis in mice. Its mechanism of action is associated with the activation of the Nrf-2/SLC7A11/GPX4 signaling pathway. Conclusions Brain-targeted HA-PEG-UA NPs was successfully developed and hold the potential to enhance SAH prognosis by limiting neuronal ferroptosis via modulation of the Nrf-2/SLC7A11/GPX4 signal. Graphical Abstract

Taking advantage of green energy is becoming increasingly popular. However, when it comes to the storage I/O, where storage devices usually schedule nodes based on the intensity of the storage workload, the irregular fluctuations of green energy lead to the mismatch of peaks and valleys between green energy and storage workloads, which increases the difficulty of scheduling storage resources. To address this issue, a tiering-cooperative energy-efficient scheme for hybrid NVM-SSD storage system, called MixSave, is proposed. MixSave customizes the energy-saving strategies for each layer and tunes them cooperatively between layers, reducing overall energy usage. It efficiently tiers NVM and SSD and replicates data among them based on their performance and energy characteristics, achieving both high performance and large capacity. The workload-driven strategy is used by the NVM layer, which is used for caching, to ensure the best performance, and the number of active NVM devices depends on the storage workload. Meanwhile, the SSD layer employs a green energy-oriented strategy to conserve traditional energy, and the number of active SSD devices will be proportionally to the amount of green energy supplied. Evaluation results show that, when compared with energy-save-unaware approaches, MixSave degrades performance by less than 4% and saves traditional energy by 73% to 80% and 55% to 61% under light and heavy workloads, respectively.

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related mortality among men, characterized by significant heterogeneity that complicates diagnosis and treatment. Methods and results To enhance our understanding of PCa, we utilized single-cell RNA sequencing (scRNA-seq) data to identify distinct malignant epithelial cell subpopulations and their molecular characteristics. By integrating scRNA-seq data with bulk RNA-seq data, we constructed a prognostic risk score model. The influence of key genes identified in the risk score on PCa was validated through both in vitro and in vivo experiments. Our study revealed eight unique malignant epithelial cell clusters, each exhibiting distinct molecular characteristics and biological functions. KEGG and GO enrichment analyses highlighted their involvement in various pathways. The prognostic risk score model demonstrated strong predictive power for patient outcomes, particularly in predicting progression-free survival (PFS). Notably, KLHL17, identified as a high-risk gene, was found to significantly impact PCa cell proliferation, migration, invasion, and apoptosis upon knockdown. This finding was further validated in vivo using a subcutaneous xenograft tumor model, where reduced KLHL17 expression led to decreased tumor growth. Conclusion Our research provides a comprehensive analysis of PCa heterogeneity and highlights KLHL17 as a potential therapeutic target.

Chuanhong congou black tea was made from seven tea plant species that were grown in Yibin, including 'Sichuan Medium and Small Leaf Group Species' 'Fuding Dabai' 'Fuyun 6' 'Mingshan 131' 'Qingxin Oolong' 'Tianfu 5' and 'Tianfu 6'. The main differentiating ingredients in Chuanhong congou black tea, which was produced from the fresh leaves of several tea plant species, were examined using sensory evaluation, electronic nose (E-nose), headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), odor activity value (OAV), and partial least squares discriminant analysis (PLS-DA). The findings indicated that the black tea derived from the fresh leaves of the seven different tea kinds was sweet, with the 'Sichuan Medium and Small Leaf Group Species' scoring the highest and having a little fruity flavor. A total of 84 volatile aroma compounds, including 29 alcohols, 12 aldehydes, 15 esters, 12 alkenes, 7 acids, 5 ketones and 4 other hydrocarbons were found. There were 14 kinds of common aroma compounds in the 7 samples, and the contents of aroma compounds were significantly different among different samples (P1). Eight key differential aroma compounds were identified in the black tea samples of different tea plant varieties, including geraniol, linalool, methyl salicylate, phenylethanol, styrene, 2-hexenal, (E)-linalool oxide (furan-type) and citral. In summary, the types and contents of aroma substances of Chuanhong cougou black tea made from fresh leaves of different tea plant varieties differ greatly. The study results can provide reference for selecting suitable tea plant varieties for Chuanhong cougou black tea.

Abstract The contact finger electrical connection structure is a crucial component of high voltage bushings, and its safety and reliability directly impact the operational stability of the bushing. To investigate electrical contact performance of the contact finger under eccentric conditions, a three‐dimensional electrical, thermal, and force multi‐physics coupling calculation model was established. Additionally, a test platform was constructed to measure electrical contact characteristics of the contact finger. The contact characteristics of the contact finger when the male head was axially deflected and radially offset compared to the female head were obtained. The research findings indicate when the male head deflects axially, the contact force changes of the contact finger blades on both sides are opposite. Moreover, as the axial deflection angle of the male head increases, the resistance of the electrical connection structure shows a rising‐slow decreasing‐fluctuating trend. The resistance is highest at 3°, with a resistance increase rate of 7.35%. Furthermore, the resistance of the electrical connection structure varies with the radial offset of the male head, following a power function. Contact failure occurs when the radial offset is 1.31 mm, and the resistance increase rate reaches 24.9% at a radial offset of 1.58 mm.

Abstract Background Chondroitin polymerizing factor (CHPF) has been found to be involved in the development of numerous cancers and correlated with poor prognosis. However, its role in the tumorigenesis and development of colorectal cancer (CRC) remains unknown. Methods In our research, we explored CHPF expression and clinicopathological characteristics using The Cancer Genome Atlas Program (TCGA), UALCAN, GSE9348, TIMER2.0 and The Human Protein Atlas (HPA) database, in addition, we validated CHPF expression in CRC cell lines by Real-Time Quantitative PCR (qRT-PCR) and Western blot (WB). KM-Plotter, PrognoScan and TCGA were also utilized to verify its prognosis value in CRC. Small-interfer RNA (Si-RNA) was used to perform Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2′-deoxyuridine (EDU), transwell and wound healing assays to testify its function on the tumor progression. Based on TCGA database, we probed potential biological mechanism by which CHPF play its role via clusterProfiler package and GEPIA database and we validated their correlation by WB assay. Moreover, we explored its potential association with the tumor microenvironment (TME), immune infiltrated cells, immune checkpoints, tumor mutation burden (TMB) as well as microsatellite instability (MSI), and investigated immunotherapy sensitivity via Tumor Immune Dysfunction and Exclusion (TIDE) algorithm as well as potentially effective therapeutic drugs via pRRophetic algorithm. Results CHPF was identified upregulated in CRC tissues and cells, correlated with poor prognosis, and nodal metastasis status, stage and histological subtype. Down-regulation of CHPF inhibited CRC cell proliferation, migration and its expression correlated with wnt pathway key molecules. In addition, high expression of CHPF was positively correlated with TME scores, Regulatory T cells (Tregs) cell infiltration degree, Programmed death-1 (PD-1), MSI-high (MSI-H), and TIDE scores, however, not with TMB. Targeted drug analysis showed that patients with high CHPF expression were more sensitive to telatinib, recaparib, serdemetan, and trametinib. Conclusion CHPF could promote the proliferation and migration of CRC cells and lead to poor prognosis, possibly through wnt pathways as well as changes in TME. Patients with high expression of CHPF had poor efficacy in immunotherapy, which might be related to Tregs cell infiltration. Above all, it might offer more reliable guidance for future immunotherapy.

The Jingyang–Weinan Fault that Xi’an Metro Line 10 crosses is a Holocene active fault, and its future stick-slip earthquakes and coseismic dislocations pose a potential threat to the metro line. To reveal the deformation and stratum stress characteristics of the site caused by the stick-slip seismic and coseismic dislocations of the Jingyang–Weinan Fault zone, based on the Jingyang–Weinan fault zone crossed by Xi’an Metro Line 10, the geomechanical model of the fault zone site coseismic dislocations and stick-slip seismic was established, and the numerical simulation analysis of the stratum deformation and stress field characteristics of fault zone site was carried out considering different dislocation amounts and seismic intensity. The results show that under the coseismic dislocation, the stress reduction and strengthening zones appear in the hanging wall and footwall near the fault zone, and the site presents an inverse “S” shaped differential settlement failure. The differential displacement peaks at the fault zone, and the plastic zone is concentrated here. The deformation range and plastic zone of the hanging wall are 1.67 times and 2.50 times more than that of the footwall, respectively. The displacement and differential deformation of the site near the fault zone reach the peak value under the stick-slip earthquake. The influence range of the site displacement during the large earthquake is approximately 6.50 times more than that during the medium earthquake. It has a typical magnification effect on the hanging wall, and the displacement decreases linearly far away from the fault zone. The amplification factor of peak surface acceleration (PGA) in the large earthquake is 1.14 times more than that in the medium earthquake. The site shows “V” shear failure; the plastic zones of hanging wall and footwall in the large earthquake is about 1.40 times and 1.00 times larger than that in the medium earthquake, respectively. This study can provide a scientific basis for the seismic fortification of Xi’an Metro Line lines crossing the Jingyang–Weinan fault zone.

Abstract Background Our facial skin hosts millions of microorganisms, primarily bacteria, crucial for skin health by maintaining the physical barrier, modulating immune response, and metabolizing bioactive materials. Aging significantly influences the composition and function of the facial microbiome, impacting skin immunity, hydration, and inflammation, highlighting potential avenues for interventions targeting aging-related facial microbes amidst changes in skin physiological properties. Results We conducted a multi-center and deep sequencing survey to investigate the intricate interplay of aging, skin physio-optical conditions, and facial microbiome. Leveraging a newly-generated dataset of 2737 species-level metagenome-assembled genomes (MAGs), our integrative analysis highlighted aging as the primary driver, influencing both facial microbiome composition and key skin characteristics, including moisture, sebum production, gloss, pH, elasticity, and sensitivity. Further mediation analysis revealed that skin characteristics significantly impacted the microbiome, mostly as a mediator of aging. Utilizing this dataset, we uncovered two consistent cutotypes across sampling cities and identified aging-related microbial MAGs. Additionally, a Facial Aging Index (FAI) was formulated based on the microbiome, uncovering the cutotype-dependent effects of unhealthy lifestyles on skin aging. Finally, we distinguished aging related microbial pathways influenced by lifestyles with cutotype-dependent effect. Conclusions Together, our findings emphasize aging’s central role in facial microbiome dynamics, and support personalized skin microbiome interventions by targeting lifestyle, skin properties, and aging-related microbial factors. Video Abstract

Abstract Phototherapy is a promising antitumor modality, which consists of photothermal therapy (PTT) and photodynamic therapy (PDT). However, the efficacy of phototherapy is dramatically hampered by local hypoxia in tumors, overexpression of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand-1 (PD-L1) on tumor cells. To address these issues, self-assembled multifunctional polymeric micelles (RIMNA) were developed to co-deliver photosensitizer indocyanine green (ICG), oxygenator MnO2, IDO inhibitor NLG919, and toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). It is worth noting that RIMNA polymeric micelles had good stability, uniform morphology, superior biocompatibility, and intensified PTT/PDT effect. What’s more, RIMNA-mediated IDO inhibition combined with programmed death receptor-1 (PD-1)/PD-L1 blockade considerably improved immunosuppression and promoted immune activation. RIMNA-based photoimmunotherapy synergized with PD-1 antibody could remarkably inhibit primary tumor proliferation, as well as stimulate the immunity to greatly suppress lung metastasis and distant tumor growth. This study offers an efficient method to reinforce the efficacy of phototherapy and alleviate immunosuppression, thereby bringing clinical benefits to cancer treatment. Graphical Abstract

For landslide prevention and control, it is essential to establish a landslide susceptibility prediction framework that can explain the model’s decision-making process. Wushan County, Chongqing was selected as the study area, and seventeen landslide conditioning factors were initially chosen for this investigation. GeoDetector was used to remove noise factors and reduce the latitude of the data. The research investigates the use of three machine learning methods for assessing landslide susceptibility: SVM, RF, and XGBoost, and finally explains the decision mechanism of the model by SHAP-PDP. The results indicate that XGBoost has better evaluation results than RF and SVM. And XGBoost uncertainty is lower. The integrated interpretation framework based on SHAP-PDP can evaluate and interpret landslide susceptibility models both globally and locally, which is of great practical significance for the application of machine learning in landslide prediction.

A novel sub-class of S-adenosyl-l-methionine (SAM)-dependent methyltransferases catalyze atypical chemical transformations in the biosynthesis of anthracyclines. Exemplified by RdmB from Streptomyces purpurascens, it was found with 10-decarboxylative hydroxylation activity on anthracyclines. We herein investigated the catalytic activities of RdmB and discovered a previously unknown 4-O-methylation activity. The site-directed mutagenesis studies proved that the residue at position R307 and N260 are vital for the decarboxylative hydroxylation and 4-O-methylation, respectively, which define two distinct catalytic centers in RdmB. Furthermore, the multifunctionality of RdmB activity was found as cofactor-dependent and stepwise. Our findings expand the versatility and importance of methyltransferases and should aid studies to enrich the structural diversity and bioactivities of anthracyclines.

Sleep health is a novel concept, a multidimensional sleep-wakefulness pattern that adapts to individual, social, and environmental demands to promote physical and mental well-being. Current research has found that sleep health is not only associated with physiological health issues such as diabetes, overweight/obesity, and cardiovascular risks but also has significant impacts on mental health issues such as anxiety and depression. Previous sleep-related studies have primarily focused on identifying and treating sleep disorders and problems, with less attention to the positive attributes of sleep health. This review summarizes studies on sleep health, including its definition, measurement tools, and correlations with health outcomes, aiming to foster a more comprehensive understanding of sleep health and provide a reference for research on sleep health among Chinese residents.

AbstractContext Sepsis-induced acute lung injury (ALI) is associated with high morbidity and mortality. Rhodiola rosea L. (Crassulaceae) (RR) and its extracts have shown anti-inflammatory, antioxidant, immunomodulatory, and lung-protective effects.Objective This study elucidates the molecular mechanisms of RR against sepsis-induced ALI.Materials and methods The pivotal targets of RR against sepsis-induced ALI and underlying mechanisms were revealed by network pharmacology and molecular docking. Human umbilical vein endothelial cells (HUVECs) were stimulated by 1 μg/mL lipopolysaccharide for 0.5 h and treated with 6.3, 12.5, 25, 50, 100, and 200 μg/mL RR for 24 h. Then, the lipopolysaccharide-stimulated HUVECs were subjected to cell counting kit-8 (CCK-8), enzyme-linked immunosorbent, apoptosis, and Western blot analyses. C57BL/6 mice were divided into sham, model, low-dose (40 mg/kg), mid-dose (80 mg/kg), and high-dose (160 mg/kg) RR groups. The mouse model was constructed through caecal ligation and puncture, and histological, apoptosis, and Western blot analyses were performed for further validation.Results We identified six hub targets (MPO, HRAS, PPARG, FGF2, JUN, and IL6), and the PI3K-AKT pathway was the core pathway. CCK-8 assays showed that RR promoted the viability of the lipopolysaccharide-stimulated HUVECs [median effective dose (ED50) = 18.98 μg/mL]. Furthermore, RR inhibited inflammation, oxidative stress, cell apoptosis, and PI3K-AKT activation in lipopolysaccharide-stimulated HUVECs and ALI mice, which was consistent with the network pharmacology results.Discussion and conclusion This study provides foundational knowledge of the effective components, potential targets, and molecular mechanisms of RR against ALI, which could be critical for developing targeted therapeutic strategies for sepsis-induced ALI.

ObjectiveTo evaluate the current status of hypertension prevention and control management operation mechanisms in Chinese mainland, explore the impact of their improvement on hypertension prevention and control effects, and provide a reference for enhancing hypertension prevention and control management. MethodsPolicy documents related to hypertension prevention and control from January 1 2000 to December 31, 2018 in 31 provinces (municipalities and autonomous regions) in Chinese mainland were collected. The current status of hypertension prevention and control management operation mechanisms in Chinese mainland was systematically evaluated according to the appropriate public health system evaluation model and standard. A logistic regression model was used to analyze the impact of the improvement of management operation mechanisms on hypertension prevention and control effects. ResultsIn 2018, the appropriateness of hypertension prevention and control management operation mechanisms in Chinese mainland was 43.68%, with an increase of 21.64% compared to 2000, but there was still a gap of 48.61% from the appropriate standard. Among them, the appropriateness of coordination and incentive mechanisms was the lowest (14.03%), and the appropriateness of planning and evaluation mechanisms was the highest (63.04%). In terms of specific positioning, the coverage of medium and long-term plans (100.00%) and the completeness of content and form (94.45%) were relatively high, while the feasibility of management mechanisms was only 9.76%. The results of logistic regression analysis showed that the improvement of management operation mechanisms helped control blood pressure in hypertensive patients (OR = 1.012, P = 0.007) and maintain the stability of patients’ blood pressure (OR = 1.010, P = 0.029). Conclusion From 2000 to 2018, the construction of hypertension prevention and control management mechanisms in Chinese mainland tended to be improved, effectively promoting the improvement of hypertension prevention and control management levels. However, it is still necessary to further establish and improve coordination and incentive mechanisms and clarify the division of departmental responsibilities.

Abstract The aims of this study were to investigate the heavy metal pollution status and distribution and to analyze the relationships among metal concentrations of different links in the dairy production chain. Chromium (Cr), arsenic (As), cadmium (Cd), lead (Pb), copper (Cu), and zinc (Zn) levels in water, fodder, milk, blood, hair, and feces samples collected from cows from five dairy farms in China were measured. The concentrations of Cr, As, Cd, Pb, Cu, and Zn were 4.61–11.11, 0.06–0.46, 0.17–0.29, 2.84–4.23, 4.11–7.72, and 7.23–19.91 mg/kg in silage; 12.72–40.85, 0.76–2.40, 0.05–0.16, 4.73–9.16, 44.14–78.46, and 4148.51–4845.20 μg/L in milk; 33.59–60.73, 0.09–3.57, 0.29–1.78, 20.14–39.20, 821.34–1007.45, and 2665.10–4929.95 μg/L in blood; 0.59–1.06, 0.02–0.09, 0.08–0.11, 1.70–2.09, 6.45–8.64, and 9.73–1.56 mg/kg in hair; 31.75–296.35, 0.33–5.96, 0.18–0.53, 3.35–9.06, 12.27–41.39, and 56.54–196.34 mg/kg in feces, respectively. The concentrations of heavy metals in hair were higher than those in the other samples and when combined with the results from the silage and tissue samples, we can assume that cow's hair can be used as a biological indicator for heavy metal contamination in the dairy production chain.

Abstract In the last ten years, stem cell (SC) therapy has been extensively used to treat a range of conditions such as degenerative illnesses, ischemia-related organ dysfunction, diabetes, and neurological disorders. However, the clinical application of these therapies is limited due to the poor survival and differentiation potential of stem cells (SCs). Extracorporeal shock wave therapy (ESWT), as a non-invasive therapy, has shown great application potential in enhancing the proliferation, differentiation, migration, and recruitment of stem cells, offering new possibilities for utilizing ESWT in conjunction with stem cells for the treatment of different systemic conditions. The review provides a detailed overview of the advances in using ESWT with SCs to treat musculoskeletal, cardiovascular, genitourinary, and nervous system conditions, suggesting that ESWT is a promising strategy for enhancing the efficacy of SC therapy for various diseases.

Abstract Hydrogen sulfide is essential in numerous physiological and pathological processes and has emerged as a promising cancer imaging and signaling molecule and a potentially versatile therapeutic agent. However, the endogenous levels of hydrogen sulfide remain insufficient to perform its biological functions, and thus, developing novel strategies that amplify hydrogen sulfide signals at lesion sites is of increasing interest. In this work, a nanoplatform (SNP) based on hydrogen sulfide-responsive self-immolative poly(thiocarbamate) with localized hydrogen sulfide signal amplification capability is developed to encapsulate a hydrogen sulfide-responsive fluorescent probe (e.g., hemicyanine dye; p-Cy) or an anticancer prodrug (e.g., doxorubicin; p-DOX) to form a nanoprobe (SNPp-Cy) or nanomedicine (SNPp-DOX) for cancer imaging and therapy, respectively. SNPp-Cy exhibits a low detection limit for hydrogen sulfide, enabling ultrasensitive detection of small (

Abstract Eosinophils, traditionally associated with allergic phenomena, play a pivotal role in inflammatory responses. Despite accumulating evidence suggesting their pro-inflammatory function upon activation, the underlying mechanisms governing eosinophil activation remain incompletely characterized. In this study, we investigate the local activation of pulmonary and colon eosinophils within the inflammatory microenvironment. Leveraging transcriptional sequencing, we identify TGF-β as a putative regulator of eosinophil activation, leading to the secretion of granule proteins, including peroxidase. Genetic deletion of TGF-β receptors on eosinophils resulted in the inhibition of peroxidase synthesis, affirming the significance of TGF-β signaling in eosinophil activation. Using models of HDM-induced asthma and DSS-induced colitis, we demonstrate the indispensability of TGF-β-driven eosinophil activation in both disease contexts. Notably, while TGF-β signaling did not significantly influence asthmatic inflammation, its knockout conferred protection against experimental colitis. This study delineates a distinct pattern of eosinophil activation within inflammatory responses, highlighting the pivotal role of TGF-β signaling in regulating eosinophil behavior. These findings deepen our comprehension of eosinophil-related pathophysiology and may pave the way for targeted therapeutic approaches in allergic and inflammatory diseases.

Taste is an important quality attribute of tea. In order to find out the taste quality of green teas made from the major varieties in Wanzhou district, Chongqing, the taste profile of the tea infusions was determined by sensory evaluation and 5 taste components including catechins, free amino acids, alkaloids, flavanols and their glycosides, and organic acids were analyzed by targeted detection methods. The results showed that there were obvious differences in the taste quality of green teas prepared from the 4 varieties of tea trees. Sichuan middle- and small-leafed tea group variety had a strong taste, and ‘Anji Baicha’ had an obvious fresh and brisk taste with mellow sweet aftertaste. ‘Fuding Dabaicha’ tasted strong with fresh and brisk taste and mellow sweet aftertaste. ‘Zhonghuang 1’ tasted fresh and brisk but less strong. The results of taste component analysis showed that the Sichuan middle- and small-leafed tea group variety contained high contents of catechins but low contents of free amino acids. ‘Anji Baicha’ had the highest content of free amino acids. The content of each flavor component was high in ‘Fuding Dabaicha’, and the contents of total flavor components and water extract of ‘Zhonghuang 1’ were low. The results of principal component analysis (PCA) showed that the 4 varieties could be well distinguished. Thirteen major taste contributors such as rutin and caffeine were identified. The differential analysis indicated that aspartic acid, glutamic acid and theanine were the major contributors to the fresh and brisk taste characteristics of ‘Anji Baicha’ and ‘Fuding Dabaicha’. Yangmeiin-3-O-galactoside and chrysin were the major taste contributors for ‘Zhonghuang 1’ that distinguished it from the other 3 varieties. There were also large differences in taste components within the Sichuan middle- and small-leafed tea group variety, with samples C4 and C5 being closer to each other. They both contained high contents of flavonoid glycosides, having a strong astringent taste. This study provides a reference for research to improve the flavor quality of green tea in Wanzhou district.

Abstract Background Understanding the mechanism of male sterility is crucial for producing hybrid seeds and developing sterile germplasm resources. However, only a few cytoplasmic male sterility (CMS) lines of cotton have been produced due to several challenges, like inadequate variation of agronomic traits, incomplete sterility, weak resilience of restorer lines, and difficulty in combining strong dominance. Therefore, the morphological and cytological identification of CMS in cotton will facilitate hybrid breeding. Results Two F2 segregating populations of cotton were constructed from cytoplasmic male sterile lines (HaA and 01A, maternal) and restorer lines (HaR and 26R, paternal). Genetic analysis of these populations revealed a segregation ratio of 3:1 for fertile to sterile plants. Phenotypic analysis indicated no significant differences in traits of flower bud development between sterile and fertile plants. However, sterile plants exhibited smaller floral organs, shortened filament lengths, and anther atrophy on the flowering day in comparison with the fertile plants. When performed scanning electron microscopy (SEM), the two F2 populations revealed morphological variations in the anther epidermis. Cellular analysis showed no significant differences in pollen development before pollen maturation. Interestingly, between the pollen maturation and flowering stages, the tapetum layer of sterile plants degenerated prematurely, resulting in abnormal pollen grains and gradual pollen degradation. Conclusion The results of this study suggest that fertility-restoring genes are controlled by a single dominant gene. Sterile plants exhibit distinctive floral morphology, which is characterized by stamen atrophy and abnormal anthers. Pollen abortion occurs between pollen maturity and flowering, indicating that premature tapetum degradation may be the primary cause of pollen abortion. Overall, our study provides a theoretical basis for utilizing CMS in hybrid breeding and in-depth investigation of the dominant configuration of cotton hybrid combinations, mechanisms of sterility, and the role of sterile and restorer genes.

Abstract SLAMF9, a member of the conserved lymphocyte activation molecules family (SLAMF), has been less investigated compared to other SLAMs, especially concerning its implications across various cancer types. In our systematic pan-cancer investigation, we observed elevated SLAMF9 expression in various tumor tissues, which was correlated with reduced patient survival across most malignancies. Correlation analyses further revealed significant associations between SLAMF9 expression and immune cell infiltrates, immune checkpoint inhibitors, tumor mutation load, microsatellite instability, and epithelial–mesenchymal transition (EMT) scores. Cell-based assays demonstrated that SLAMF9 knockdown attenuated the proliferative, motile, and invasive capacities of colorectal cancer (CRC) cells. In a nude mouse xenograft model, suppression of SLAMF9 expression substantially inhibited tumor growth. These findings highlight the potential of SLAMF9 as a prognostic and therapeutic biomarker across tumors, with notable implications for CRC cell proliferation and migration.

Background Acute myocardial infarction (AMI) is one of the common cardiovascular diseases, and despite the widespread use of biomarkers for myocardial necrosis, morbidity and mortality of AMI remain high. Objective To investigate the expression levels and clinical significance of miR-126, mitochondrial components and adhesion molecules in endothelial microparticles (EMPs) . Methods A total of 50 patients with AMI (AMI group), 50 patients with stable coronary artery disease (SCAD) (SCAD group) and 50 healthy subjects (control group) were enrolled in the People's Hospital of Xinjiang Uygur Autonomous Region from September 2021 to September 2022. AMI patients and SCAD patients were hospitalized in our hospital and received percutaneous coronary intervention (PCI), and all healthy subjects were evaluated by the physical examination center of our hospital. Peripheral blood samples and general data of three groups were collected. The morphology of the microparticles (MPs) was observed by transmission electron microscopy (TEM), the level of EMPs was identified by flow cytometry, and the expression of miR-126 in EMPs was detected by fluorescence quantitative PCR. ELISA was used to detect the levels of mitochondrial reactive oxygen species (ROS) and intracellular adhesion molecules [vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin] in EMPs. Results As observed by TEM, the membrane structure of the isolated MPs was intact and its diameter ranged from 100 to 400 nm. Compared with the control group, the expression of miR-126 in plasma EMPs in the AMI group was significantly decreased (P

Accurate estimation of turbulence field is of great importance in aerospace, and existing means of obtaining turbulence field is inadequate in terms of resolution or accuracy. Experimental measurements are accurate but often have a limited number of observation points, and numerical computations can obtain full-field data but the accuracy is difficult to guarantee. The data assimilation method integrates experimental observation and numerical simulation, which is an effective tool for flow field reconstruction. This paper explored the effectiveness of data assimilation method based on ensemble transform Kalman filter(ETKF) in spatial flow field reconstruction, and also discussed the reconstruction accuracy and computational efficiency of different iterative updates, namely ETKF-M and ETKF-D, which update state variables based on turbulence model and flow field data respectively. Using the ONERA M6 airfoil as a numerical example, the algorithm was experimented by combining the pressure measurement data from 271 pressure holes on the airfoil surface from the wind tunnel test. The results show that different iterative updates of ETKF method can effectively modify the prediction of the turbulence model, and the ETKF-D improves the computational efficiency by 83% compared with the ETKF-M. In addition, two groups of 1/4 experimental observation points at different locations were selected for assimilation experiments, and results with different accuracies were obtained. It indicates that the accuracy of reconstruction is closely related to the location and number of assimilated observation points.

Abstract Tissue-resident memory T cells (TRMs) play a critical role in cancer immunity by offering quick and effective immune responses. However, the cellular heterogeneity of TRMs and their significance in cervical cancer (CC) remain unknown. In this study, we generated and analyzed single-cell RNA sequencing data from 12,945 TRMs (ITGAE + CD3D + ) and 25,627 non-TRMs (ITGAE − CD3D + ), derived from 11 CC tissues and 5 normal cervical tissues. We found that TRMs were more immunoreactive than non-TRMs, and TRMs in CC tissues were more activated than those in normal cervical tissues. Six CD8+ TRM subclusters and one CD4+ TRM subcluster were identified. Among them, CXCL13 + CD8+ TRMs were more abundant in CC tissues than in normal cervical tissues, had both cytotoxic and inhibitory features, and were enriched in pathways related to defense responses to the virus. Meanwhile, PLAC8 + CD8+ TRMs were less abundant in CC tissues than in normal cervical tissues but had highly cytotoxic features. The signature gene set scores of both cell subclusters were positively correlated with the overall survival and progression-free survival of patients with CC following radiotherapy. Of note, the association between HLA-E and NKG2A, either alone or in a complex with CD94, was enriched in CXCL13 + CD8+ TRMs interacting with epithelial cells at CC tissues. The in-depth characterization of TRMs heterogeneity in the microenvironment of CC could have important implications for advancing treatment and improving the prognosis of patients with CC.

Abstract Nitrogen-containing compounds, such as amines, hydrazines, and heterocycles, play an indispensable role in medicine, agriculture, and materials. Alkylated derivatives of these compounds, especially in sterically congested environments, remain a challenge to prepare. Here we report a versatile method for the regioselective hydroamination of readily available unactivated olefins with diazirines. Over fifty examples are reported, including the protecting group-free amination of fourteen different natural products. A broad functional group tolerance includes alcohols, ketones, aldehydes, and epoxides. The proximate products of these reactions are diaziridines, which, under mild conditions, are converted to primary amines, hydrazines, and heterocycles. Five target- and diversity-oriented syntheses of pharmaceutical compounds are shown, along with the preparation of a bis-15N diazirine validated in the late-stage isotopic labeling of an RNA splicing modulator candidate. In this work, we report using diazirine (1) as an electrophilic nitrogen source in a regioselective hydroamination reaction, and the diversification of the resulting diaziridines.

Abstract With the gradual liberalization of the three-child policy and the development of assisted reproductive technology in China, the number of women with high-risk pregnancies is gradually increasing. In this study, 4211 fetuses who underwent chromosomal microarray analysis (CMA) with high-risk prenatal indications were analysed. The results showed that the overall prenatal detection rate of CMA was 11.4% (480/4211), with detection rates of 5.82% (245/4211) for abnormal chromosome numbers and 5.58% (235/4211) for copy number variants. Additionally, the detection rates of clinically significant copy number variants were 3.78% (159/4211) and 1.8% (76/4211) for variants of uncertain significance. The detection rates of fetal chromosomal abnormalities were 6.42% (30/467) for pregnant women with advanced maternal age (AMA), 6.01% (50/832) for high-risk maternal serum screening (MSS) results, 39.09% (224/573) with abnormal non-invasive prenatal testing (NIPT) results, 9.21% (127/1379) with abnormal ultrasound results, and 5.1% (49/960) for other indications. Follow-up results were available for 4211 patients, including 3677 (3677/4211, 87.32%) whose infants were normal after birth, 462 (462/4211, 10.97%) who terminated their pregnancy, 51 (51/4211, 1.21%) whose infants were abnormal after birth, and 21 (21/4211, 0.50%) who refused follow-up. The results of this study demonstrate significant variation in the diagnostic rate of chromosomal microarray analysis across different indications, providing valuable guidance for clinicians to assess the applicability of CMA technology in prenatal diagnosis.

Abstract Background Pure red cell aplasia (PRCA) in neuromyelitis optica spectrum disorder (NMOSD) has not been reported before. This study presents a patient with NMOSD who developed PRCA. Case presentation A 54-year-old female was admitted in January 2023 for dysuria and progressive numbness and weakness of lower limbs. She had difficulty standing and walking in a straight line. Both lower limbs were positive for the Babinski and Chaddock signs. MRI showed abnormal signals in the spinal cord. Aquaporin-4-IgG (AQP-4-IgG) was positive (1:320), and NMOSD was confirmed. Intravenous immunoglobulin and methylprednisolone were given, and the symptoms improved. She received maintenance treatment with methylprednisolone tablets, and the dosage was gradually reduced. She was readmitted for fatigue, palpitations, and shortness of breath in May 2023. Bone marrow aspiration and biopsy showed elevated erythroid precursors and erythroid hypoplasia, with normal megakaryocytes and myeloid precursors. Chest CT showed no mediastinal lymph node enlargement or thymoma. PRCA secondary to NMOSD was diagnosed. Recombinant human erythropoietin was given. Her condition improved after 1.5 months, as indicated by blood cell count and imaging. Conclusions This case suggests that PRCA can be secondary to NMOSD. A comprehensive immune function and bone marrow evaluation might be necessary if abnormal blood cells are found while managing NMOSD.

Abstract Background Trastuzumab and pertuzumab combination has been approved for the treatment of patients with HER2-positive metastatic breast cancer. However, trastuzumab and pertuzumab combination did not show improvement in overall survival in patients with HER2-positive metastatic gastric cancer. Methods We developed a new HER2-targeted monoclonal antibody, HLX22, targeting HER2 subdomain IV as trastuzumab but with non-overlapping epitopes. We examined the antitumor effects of this novel HER2-antibody in gastric cell lines and cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Results HLX22 in combination with HLX02 (trastuzumab biosimilar) induced enhancement of HER2/HER2 homodimers and HER2/EGFR heterodimers internalization, which ultimately led to the reduction in signal transductions involving STAT3, P70 S6, and AKT; gene expressions of FGF-FGFR-PI3K-MTOR, EGF-EGFR-RAS, TGF-β-SMAD, PLCG and cell cycle progression related pathways that favor tumor development, proliferation, progression, migration and survival in gastric cancer cell line NCI-N87 were also reduced. These differing but complementary actions contributed to the synergistic antitumor efficacy of the HLX22 and HLX02 combination in gastric cancer cell lines, CDX and PDX. In addition, HLX22 in combination with HLX02 demonstrated stronger antitumor efficacy than HLX02 and HLX11 (a potential pertuzumab biosimilar) combination treatment both in vitro and in vivo. Conclusions These results suggested that the application of non-competing antibodies HLX22 and HLX02 targeting HER2 subdomain IV together may be of substantial benefit to gastric cancer patients who currently respond suboptimal to trastuzumab therapy.

Honey is rich in nutrients and has a wide range of biological activities. However, due to the different botanical origins, geographical origins, entomological origins, and maturity, honey shows significant differences in their endogenous compositions and nutritional values. Volatile organic compounds (VOCs) are closely related to the characteristic properties of honey, and can be used to characterize the differences between honey. Gas chromatography-ion mobility spectroscopy (GC-IMS) is a new technology which combines gas chromatography with ion mobility spectroscopy for the determination of VOCs. In recent years, GC-IMS has been gradually applied to entomological origins identification, geographical origin tracing, botanical origin differentiation, adulteration identification and maturity evaluation of honey, and has achieved good results, showing great application potential in honey quality evaluation. In this paper, the application research progress of GC-IMS for honey quality evaluation is summarized. It is suggested that future research should be carried out from the aspects of establishing honey GC-IMS database, developing GC-IMS equipment with fusion quantitative function, developing the technical standard of quality evaluation based on GC-IMS, and using GC-IMS in combination with other detection technologies，in order to provide reference for the application of GC-IMS for honey quality control, flavor research and product development.

Abstract We explore superoscillations within the context of classical and quantum field theories, presenting novel solutions to Klein–Gordon’s, Dirac’s, Maxwell’s and Einstein’s equations. In particular, we illustrate a procedure of second quantization of fields and how to construct a Fock space which encompasses Superoscillating states. Furthermore, we extend the application of superoscillations to quantum tunnelings, scatterings and mixings of particles, squeezed states and potential advancements in laser interferometry, which could open new avenues for experimental tests of quantum gravity effects. By delving into the relationship among superoscillations and phenomena such as Hawking radiation, the black hole (BH) information and the Firewall paradox, we propose an alternative mechanism for information transfer across the BH event horizon.

Abstract Outlet short circuit on the low‐voltage (LV) side and winding inter‐turn short circuit faults are hazardous to transformer operation. To investigate the formation mechanism of winding insulation faults of distribution transformer, ANSYS Maxwell was used to build a coupled magnetic field‐circuit model with the same structural dimension as the actual distribution transformer. An outlet short circuit and winding inter‐turn insulation faults were set by using the voltage‐controlled switch in the external circuit of the model. Subsequently, the differences in the electromagnetic characteristics and the electrodynamic force distributions of the windings under three operating conditions, namely, nominal load, three‐phase outlet short circuit on the LV side and inter‐turn insulation failure were studied, respectively. The results show that compared with the rated load, in the cases of outlet short circuit and inter‐turn insulation faults, the amplitude of winding current increases by 20 and 50 times, the magnetic field strength grows by 20 and 17 times, and the electrodynamic force rises by 400 and 230 times, respectively. Outlet short circuit fault is more likely to cause the winding instability and deformation, and inter‐turn short circuit fault can easily burn out winding insulation. Therefore, corresponding preventive measures were proposed.

Abstract Objective This study aims to conduct an in-depth genomic analysis of a carbapenem-resistant Proteus mirabilis strain to uncover the distribution and mechanisms of its resistance genes. Methods The research primarily utilized whole-genome sequencing to analyze the genome of the Proteus mirabilis strain. Additionally, antibiotic susceptibility tests were conducted to evaluate the strain’s sensitivity to various antibiotics, and related case information was collected to analyze the clinical distribution characteristics of the resistant strain. Results Study on bacterial strain WF3430 from a tetanus and pneumonia patient reveals resistance to multiple antibiotics due to extensive use. Whole-genome sequencing exposes a 4,045,480 bp chromosome carrying 29 antibiotic resistance genes. Two multidrug-resistant (MDR) gene regions, resembling Tn6577 and Tn6589, were identified (MDR Region 1: 64.83 Kb, MDR Region 2: 85.64 Kbp). These regions, consist of integrative and conjugative elements (ICE) structures, highlight the intricate multidrug resistance in clinical settings. Conclusion This study found that a CR-PMI strain exhibits a unique mechanism for acquiring antimicrobial resistance genes, such as bla NDM−1, located on the chromosome instead of plasmids. According to the results, there is increasing complexity in the mechanisms of horizontal transmission of resistance, necessitating a comprehensive understanding and implementation of targeted control measures in both hospital and community settings.

Aim: The main objective of this study was to investigate the antitumor effect of a mouse anti-human glypican-1 (GPC1) monoclonal antibody (mAb) on non-small cell lung carcinoma (NSCLC) and associated molecular mechanisms. Methods: The anti-proliferative and anti-migratory activities of anti-GPC1 mAb were examined in A549 and H460 NSCLC cells and LL97A lung fibroblasts. The inhibitory effect of anti-GPC1 mAb on tumor growth was evaluated in an orthotopic lung tumor model. Results: The in vitro study showed that anti-GPC1 mAb profoundly inhibited the anchorage-independent growth of A549 and H460 NSCLC cells and exhibited relatively high cytotoxic activities towards LL97A lung fibroblasts, A549/LL97A and H460/LL97A coculture spheroids. Moreover, anti-GPC1 mAb significantly decreased the expression of phospho-Src (p-Src; Tyr416), p-Akt (Ser473) and β-catenin in the co-cultured LL97A lung fibroblasts, and the expression of phospho-mitogen-activated protein kinase kinase (p-MEK; Ser217/221) and phospho-90 kDa ribosomal s6 kinase (p-p90RSK; Ser380) in co-cultured A549 cells. When anti-GPC1 mAb was administered to tumor-bearing mice, the inhibitory effect of anti-GPC1 mAb on the orthotopic lung tumor growth was not statistically significant. Nonetheless, results of Western blot analysis showed significant decrease in the phosphorylation of fibroblast growth factor receptor 1 (FGFR1) at Tyr766, Src at Tyr416, extracellular signal-regulated kinase (ERK) at Thr202/Tyr204, 90 kDa ribosomal S6 kinase (RSK) at Ser380, glycogen synthase kinases 3α (GSK3α) at Ser21 and GSK3β at Ser9 in tumor tissues. These data implicate that anti-GPC1 mAb treatment impairs the interaction between tumor cells and tumor associated fibroblasts by attenuating the paracrine FGFR signal transduction. Conclusions: The relatively potent cytotoxicity of anti-GPC1 mAb in lung fibroblasts and its potential inhibitory effect on the paracrine FGFR signal transduction warrant further studies on the combined use of this mAb with targeted therapeutics to improve therapeutic outcomes in lung cancer.

Abstract The ability of indoor plants to purify benzene pollution is the basic basis for the selection of plants for ecological remediation of indoor benzene pollution. In this study, the purification rate and the purification amount per unit leaf area of 13 test plants at three benzene concentrations were determined by indoor fumigation experiments, and the benzene absorption and purification abilityability of indoor plants were comprehensively evaluated. The results showed that (1) there was a significant correlation between benzene concentration and purification rate and purification amount per unit leaf area. (2) At the three concentrations, Spathiphyllum floribundum showed the highest purification rate and Sansevieria trifasciata var. laurentii showed the highest purification per unit leaf area. (3) The combined results showed that Sansevieria trifasciata var. laurentii, Spathiphyllum floribundum and Aloe arborescens were the strongest absorbers and purifiers, while Podocarpus nagi and Anthurium andraeanum ‘Pink champin’ had the weakest absorption and purification capacity. The results of this study provide a theoretical basis and reference for the selection of plants with strong capacities to adsorb and purify benzene pollution in indoor air.

As the aging population increases, the prevalence of cardiovascular disease rises annually. In this context, the evaluation of cardiac function using medical imaging techniques plays a pivotal role in the diagnosis and treatment of cardiovascular disease. Cardiac segmentation is a prerequisite for assessing cardiac function and has been closely studied by clinicians and scientific researchers. This paper provides a comprehensive review of the literature from the past decade on cardiac segmentation, categorizing the studies into traditional segmentation approaches and deep learning methodologies. Emphasis is placed on the detailed discussion of segmentation methods based on active contours and atlas models; deep learning algorithms based on U-Net and full convolution neural network (FCN) are also extensively discussed. In particular, this paper elaborates various approaches to enhance deep learning networks and achieve accurate segmentation of specific cardiac regions. These approaches include incorporating local modules, optimizing loss functions, and enhancing network architectures. A comprehensive summary of the aforementioned methods is presented, considering three imaging modalities: cardiac magnetic resonance imaging, computed tomography, and ultrasonic cardiogram. Lastly, the article concludes by summarizing the current research status and discussing research directions for further exploration.

Objectives: To evaluate and compare the effectiveness of Endoflas and Zinc Oxide Eugenol (ZOE) as root canal filling materials (RCFMs) for the pulpectomy of deciduous teeth by analyzing multiple clinical and radiographic success and failure follow-ups in previously published studies. Data: All clinical studies that investigated the pulpectomy of the deciduous teeth of children aged 3–9 years. Sources: The databases used for source identification included MEDLINE (via PubMed), Scopus, Web of Science, and the Cochrane Library. No limitations were imposed on the publication year or language. The selection of studies and extraction of relevant study characteristics were conducted from December 26, 2021, to September 7, 2023. Additionally, the risk of bias (RoB) in the included studies was evaluated by using a RoB instrument (RoB 2). Eligible studies were then combined, and a random-effects model was applied by using the maximum likelihood estimations of log risk ratios and their corresponding 95% confidence intervals. Study selection: Of the 3913 records found in the abovementioned databases, nine were eligible for systematic review and eight were eligible for meta-analysis. The studies included 628 pulpectomies of deciduous molar teeth in children. The overall results showed that compared with Endoflas, ZOE was associated with a higher risk ratio for clinical evaluation (LOG[RR] = 0.06, CI 0.03–0.09, p-value 0.001) and radiographic evaluation (LOG[RR] = 0.68, CI 0.35–1.00, p-value 0.001). This association was highly significant at 6- and 9-month follow-ups. Conclusion: Compared with ZOE, Endoflas was associated with a lower risk of the clinical and radiographic failure of deciduous teeth pulpectomy and a 6%–6.8% higher risk ratio, especially at 6- and 9-month follow-ups. Clinical significance: This study suggests the superiority of Endoflas over ZOE as an RCFM for deciduous teeth.

Objective: To rigorously evaluate the short-term and long-term effectiveness of Tuina (TN), alone and in combination with physiotherapy (PT), for Chronic nonspecific low back pain (CNLBP) through a comprehensive, high-quality clinical trial. Methods: This randomized, single-blind trial was conducted from September 2020 to July 2023, involving 204 CNLBP patients from the First Affiliated Hospital of Jinan University. Participants underwent a baseline assessment, 6 treatment sessions over 8 weeks, a post-treatment evaluation in the 9th week, and a 20-week follow-up. Participants were randomly assigned to TN, PT, or a combination of TN and PT (TP) groups. Each treatment involved 6 sessions with a minimum 7-day interval, each lasting 30 minutes. Primary outcome was the change in Visual Analog Scale (VAS) for pain. Secondary outcomes included the Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), Range of Motion (ROM) of the spine, Traditional Chinese Medicine Syndrome Scale (TCMSS), and adverse events (AE). Results: Among the 204 participants, 67.16 % were female, and 88.73 % completed the 20-week follow-up. All groups showed significant reductions in VAS scores post-treatment and at follow-up. Secondary outcomes improved significantly, with notable decreases in ODI and TCMSS scores. Pairwise comparisons within groups indicated statistical significance, particularly in ODI scores, with clinical relevance. No significant differences were found between the groups. ROM and SF-36 showed statistical but not clinical significance. Only one AE (0.49 %) was reported, with no severe incidents. Conclusion: All treatment groups, including TN, TP, and PT, demonstrated significant reductions in VAS scores for CNLBP patients, with effects lasting up to 20 weeks. While TN and TP showed substantial improvements in secondary outcomes, particularly in ODI scores, no significant differences were found between the groups. These findings suggest that all treatments can be effective for managing CNLBP, supporting clinical practitioners in selecting appropriate interventions for patients, especially for those unable to engage in active exercises, utilizing passive movements like TN to enhance health outcomes.

The off-axis three-mirror anastigmatic (TMA) optical system has the advantages of eliminating all primary aberrations, having no aperture obscuration, no chromatic aberration, and good environmental adaptability, making it essential in high-performance optical instruments. Freeform surfaces, with their rich degrees of freedom (DOFs) in mathematical representation, positively affect the image quality and sensitivity of optical systems. When applied correctly to off-axis TMA optical systems, they can achieve fast F-numbers, large fields of view (FOVs), and long focal lengths. There are dozens of configurations for off-axis TMA optical systems, and freeform surfaces can be combined in numerous ways within these systems. This paper first analyzes the sensitivity of off-axis TMA optical systems with different configurations, selects the configuration with the lowest sensitivity, and combines it with a low sensitivity freeform surface combination to achieve high-performance freeform off-axis TMA optical systems with low sensitivity.

IntroductionHepatoid adenocarcinoma of the lung (HAL) is a special type of adenocarcinoma originating from the lung with adenoid- and hepatocyte-like differentiation. HAL is rare in clinical practice. Here, we present the case of a patient with HAL.Case presentationA 59-year-old man was admitted to the hospital 4 days because of lung mas observed. Chest computed tomography (CT) revealed a lobulated mass shadow in the right lower lobe, approximately 3.5 × 3.3 cm in size. CT-guided percutaneous biopsy of the right lower lung was performed. The pathological results indicated a moderately to poorly differentiated adenocarcinoma. The patient underwent thoracoscopic right middle and lower lobectomy and systematic lymph node dissection. The postoperative pathology was primary HAL, with the staging of T2bN2M0 (stage III A). Recurrence-free survival and overall survival were 6 and 19 months, respectively Preoperatively, the level of alpha-fetoprotein was negative; however, after recurrence, it increased to 87.8.ConclusionPulmonary hepatoid adenocarcinoma is a rare subtype of malignant lung tumor, combined silicosis is more rare. Early surgical intervention can benefit patients in the early stages of the disease, whereas chemotherapy remains the main systemic treatment modality for postoperative and advanced stages. With the increasing popularity of genetic testing, it is important to focus on improving genetic examination.

ABSTRACT Background Despite significant advances in lung cancer treatment, cisplatin (DDP)‐based chemotherapy remains a cornerstone for managing the disease. However, the prevalence of chemoresistance presents a major challenge, limiting its effectiveness and contributing to poor outcomes. This underscores the urgent need for novel therapeutic strategies to overcome chemoresistance and improve chemotherapy efficacy in lung cancer patients. Exploring approaches to sensitize tumors to cisplatin could enhance treatment responses and overall survival rates. Methods and Results Our study utilized a variety of lung cancer models, including cell lines, mouse models, and patient‐derived organoids, to validate the synergistic cytotoxic effects of dihydroartemisinin (DHA) and cisplatin (DDP). When combined with DDP, we demonstrate that DHA is a promising therapeutic agent that effectively triggers ferroptosis in lung cancer cells, offering a potential strategy for overcoming chemoresistance. Mechanistically, the combination of DHA and DDP synergistically enhances ZIP14 expression, modulating iron homeostasis and upregulating oxidative stress, leading to both in vitro and in vivo ferroptosis. Notably, our findings revealed that the sequential administration of DDP followed by DHA significantly increases ZIP14 expression and induces superior therapeutic outcomes compared to the simultaneous administration or DHA followed by DDP. This observation underscores the importance of the drug administration order in optimizing treatment efficacy, providing new insights into enhancing chemotherapy response in lung cancer. Conclusion Our findings suggest that combining dihydroartemisinin (DHA) with cisplatin (DDP) presents a promising strategy to overcome chemoresistance in lung cancer patients. Importantly, administering DHA during chemotherapy intervals could further optimize treatment outcomes, enhancing the overall efficacy of lung cancer chemotherapy.

IntroductionLittle was known about the relationship between sleep disturbances and depressive and anxiety disorders, as well as the efficacy of treatment regimens.MethodsDuring 2021 to 2023, a total of 417 participants were screened by Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA-14) for psychological status, and Pittsburgh sleep quality index (PSQI) assessment. 409 participants were finally enrolled, of which 188 (45.97%) were suffered from sleep disorders. All participants were received polysomnography (PSG) followed by six-week pharmacological treatment of escitalopram and zopiclone, and finally assessed by HAMD-17 and HAMA-14 for treatment efficacy.ResultPSG monitoring indicated that participants with depression experienced prolonged rapid eye movement sleep latency (REMSL) and increased wakefulness after sleep onset (WASO) (P=0.030 and P=0.002, respectively). Those with anxiety disorders demonstrated a significantly higher percentage of non-rapid eye movement sleep (NREM%) and reduced WASO (P=0.013 and P=0.001, respectively). After six-weeks pharmacological treatment, participants with or without sleep disorders exhibited with similar efficacy outcomes of depression and anxiety disorders (P>0.05). However, every point of PSQI increment at baseline would decrease 0.78 and 0.85 times of probability of effective pharmacological treatment of depression and anxiety disorders. Moreover, participants with both effective outcomes of depression and anxiety disorders were found significant shorter sleep onset latency (SOL) (P