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Abstract The utilization of visible-near infrared (Vis–NIR) spectroscopy presents a nondestructive, fast, reliable and cost-effective approach to predicting total nitrogen (TN) and organic carbon (OC) levels. This study employed a combination of Vis–NIR spectroscopy, partial least-squares regression (PLSR), and support vector machine (SVM) models to investigate the effects of mining on TN and OC stocks in both the topsoil (0–10 cm) and subsoil (10–40 cm). 105 soil samples were collected from agricultural areas near an iron mine, polluted, moderately-polluted, and non-polluted sites. Results indicated that soils at the non-polluted site had the highest of soil OC stocks (7.5 kg m–2) and total nitrogen (2.5 kg m–2), followed by the moderately-polluted site. Furthermore, it was observed that soils from the polluted site displayed the highest spectral reflectance. The spectral bands in the range of 500–700 nm showed the strongest correlation with soil organic carbon content. Notably, the SVM method utilizing Vis–NIR spectroscopy provided superior predictions for both subsoil and topsoil organic carbon and total nitrogen compared to the PLSR methods. Additionally, SVM demonstrated better performance in predicting topsoil soil organic carbon (R2 = 0.87, RMSE = 0.13%, and RPD = 2.8) and total nitrogen (R2 = 0.91, RMSE = 0.13%, and RPD = 2.4) compared to the subsoil, owing to the larger OM content in the topsoils.

Connected automated vehicles (CAVs) rely heavily on intelligent algorithms and remote sensors. If the control center or on-board sensors are under cyber-attack due to the security vulnerability of wireless communication, it can cause significant damage to CAVs or passengers. The primary objective of this study is to model cyber-attacked traffic flow and evaluate the impacts of cyber-attack on the traffic system filled with CAVs in a connected environment. Based on the analysis on environmental perception system and possible cyber-attacks on sensors, a novel lane-changing model for CAVs is proposed and multiple traffic scenarios for cyber-attacks are designed. The impact of the proportion of cyber-attacked vehicles and the severity of the cyber-attack on the lane-changing process is then quantitatively analyzed. The evaluation indexes include spatio-temporal evolution of average speed, spatial distribution of selected lane-changing gaps, lane-changing rate distribution, lane-changing preparation search time, efficiency and safety. Finally, the numerical simulation results show that the freeway traffic near an off-ramp is more sensitive to the proportion of cyber-attacked vehicles than to the severity of the cyber-attack. Also, when the traffic system is under cyber-attack, more unsafe back gaps are chosen for lane-changing, especially in the center lane. Therefore, more lane-changing maneuvers are concentrated on approaching the off-ramp, causing severe congestions and potential rear-end collisions. In addition, as the number of cyber-attacked vehicles and the severity of cyber-attacks increase, the road capacity and safety level will rapidly decrease. The results of this study can provide a theoretical basis for accident avoidance and efficiency improvement for the design of CAVs and management of automated highway systems.

Abstract Introduction Artificial cervical disc replacement (ACDR) is a widely accepted surgical procedure in the treatment of cervical radiculopathy and myelopathy. However, some research suggests that ACDR may redistribute more load onto the facet joints, potentially leading to postoperative axial pain in certain patients. Earlier studies have indicated that facet tropism is prevalent in the lower cervical spine and can significantly increase facet joint pressure. The present study aims to investigate the changes in the biomechanical environment of the cervical spine after ACDR using different prosthese when facet tropism is present. Methods A C2-C7 cervical spine finite element model was created. Symmetrical, moderate asymmetrical (7 degrees tropism), and severe asymmetrical (14 degrees tropism) models were created at the C5/C6 level by adjusting the left-side facet. C5/C6 ACDR with Prestige LP, Prodisc-C vivo, and Mobi-C were simulated in all models. A 75 N follower load and 1 N⋅m moment was applied to initiate flexion, extension, lateral bending, and axial rotation, and the range of motions (ROMs), facet contact forces(FCFs), and facet capsule stress were recorded. Results In the presence of facet tropism, all ACDR models exhibited significantly higher FCFs and facet capsule stress compared to the intact model. In the asymmetric model, FCFs on the right side were significantly increased in neutral position, extension, left bending and right rotation, and on both sides in right bending and left rotation compared to the symmetric model. All ACDR model in the presence of facet tropism, exhibited significantly higher facet capsule stresses at all positions compared to the symmetric model. The stress distribution on the facet surface and the capsule ligament in the asymmetrical models was different from that in the symmetrical model. Conclusions The existence of facet tropism could considerably increase FCFs and facet capsule stress after ACDR with Prestige-LP, Prodisc-C Vivo, and Mobi-C. None of the three different designs of implants were able to effectively protect the facet joints in the presence of facet tropism. Research into designing new implants may be needed to improve this situation. Clinical trials are needed to validate the impact of facet tropism.

Abstract Dental diseases such as caries and periodontitis have been common public health problems. Dental disease treatment can be achieved through stem cell-based dental regeneration. Biophysical cues determine the fate of stem cells and govern the success of dental regeneration. Some studies have manifested exosomes derived from stem cells could not only inherit biophysical signals in microenvironment but also evade some issues in the treatment with stem cells. Nowadays, biophysical cue-regulated exosomes become another promising therapy in dental regenerative medicine. However, methods to improve the efficacy of exosome therapy and the underlying mechanisms are still unresolved. In this review, the association between biophysical cues and dental diseases was summarized. We retrospected the role of exosomes regulated by biophysical cues in curing dental diseases and promoting dental regeneration. Our research also delved into the mechanisms by which biophysical cues control the biogenesis, release, and uptake of exosomes, as well as potential methods to enhance the effectiveness of exosomes. The aim of this review was to underscore the important place biophysical cue-regulated exosomes occupy in the realm of dentistry, and to explore novel targets for dental diseases.

Abstract Tryptophol (IET) is a metabolite derived from L-tryptophan that can be isolated from plants, bacteria, and fungi and has a wide range of biological activities in living systems. Despite the fact that IET biosynthesis pathways exist naturally in living organisms, industrial-scale production of IET and its derivatives is solely based on environmentally unfriendly chemical conversion. With diminishing petroleum reserves and a significant increase in global demand in all major commercial segments, it becomes essential to develop new technologies to produce chemicals from renewable resources and under mild conditions, such as microbial fermentation. Here we characterized and engineered the less-studied L-tryptophan pathway and IET biosynthesis in the baker’s yeast Saccharomyces cerevisiae, with the goal of investigating microbial fermentation as an alternative/green strategy to produce IET. In detail, we divided the aromatic amino acids (AAAs) metabolism related to IET synthesis into the shikimate pathway, the L-tryptophan pathway, the competing L-tyrosine/L-phenylalanine pathways, and the Ehrlich pathway based on a modular engineering concept. Through stepwise engineering of these modules, we obtained a yeast mutant capable of producing IET up to 1.04 g/L through fed-batch fermentation, a ~ 650-fold improvement over the wild-type strain. Besides, our engineering process also revealed many insights about the regulation of AAAs metabolism in S. cerevisiae. Finally, during our engineering process, we also discovered yeast mutants that accumulate anthranilate and L-tryptophan, both of which are precursors of various valuable secondary metabolites from fungi and plants. These strains could be developed to the chassis for natural product biosynthesis upon introducing heterologous pathways.

Objective The unclear clinical outcomes of two different zero‐profile implants with different number of screws in hybrid surgery restricts the choice of patient‐specific implants. This study aims to compare two different implants on its postoperative subsidence, motion stabilization and clinical outcomes. It also provides references to the most reasonable implant choice in fusion surgery. Methods This was a retrospective study. From February 2014 to March 2022, 173 patients who underwent hybrid surgery were included. Among them, 122 received surgery with a four screw implant, while 51 received a two screw implant. We analyzed the significance of patient‐specific factors, radiographic factors and clinical outcomes. The Wilcoxon rank sum test, t tests/analysis of variance (ANOVA) test and stepwise multivariate logistic regression were adopted for statistical analysis. Results No statistically significant difference was observed between the two screw and four screw groups in terms of immediate, middle, and long‐term stability and fusion rate (p > 0.05). However, the two screws group had higher FSU height subsidence at 3, 6, and 12 months postoperatively and higher rates of significant subsidence at three and 6 months postoperatively (p

Abstract This study delves into the correlation between the triglyceride glucose-body mass index (TyG-BMI) index upon hospital admission and clinical outcomes among this patient population. We investigated the association between TyG-BMI at hospital admission and clinical outcomes in this patient group, and analyzed data from the Medical Information Mart for Intensive Care IV database, identifying acute pancreatitis (AP) patients admitted to ICUs and stratifying them by TyG-BMI quartiles. We assessed the relationship between TyG-BMI and mortality (both in-hospital and ICU) using Cox proportional hazards regression and restricted cubic splines. The cohort included 419 patients, average age 56.34 ± 16.62 years, with a majority being male (61.58%). Hospital and ICU mortality rates were 11.93% and 7.16%, respectively. Higher TyG-BMI was positively correlated with increased all-cause mortality. Patients in the highest TyG-BMI quartile had significantly greater risks of in-hospital and ICU mortality. An S-shaped curve in the spline analysis indicated a threshold effect at a TyG-BMI of 243 for increased in-hospital mortality risk. TyG-BMI is a reliable predictor of both in-hospital and ICU mortality in severely ill AP patients, suggesting its utility in enhancing risk assessment and guiding clinical interventions for this vulnerable population.

Abstract Background At present, fat transplantation is widely used in the plastic surgery industry, but the long-term preservation rate of transplanted fat decreases because of complications such as oil cysts due to the inability in macrophages to metabolize absorption. In cell-assisted lipotransfer technology, adipose-derived stem cells (ASCs) can influence the inflammatory response of grafts through the immunoregulation in macrophages, and the lipid metabolism in macrophages plays an important role in this process. Therefore, we hypothesized ASCs could improve the retention rate of fat grafts by regulating the progress of lipid metabolism in macrophages. Methods We established fat transplantation and ASC-assisted fat transplantation model in C57BL/6 mice in vivo, and bone marrow-derived macrophages cocultured with apoptotic adipocytes were treated with or without ASCs in vitro. Graft retention, tissue structure, fibrosis, macrophage phenotype transformation, lipid deposition, mitochondrial morphology, oxygen consumption rate (OCR), fatty acid β-oxidation (FAO) level, and ATP production were assessed. Additionally, fat transplantation and ASC-assisted fat transplantation model was treated with etomoxir which inhibits mitochondrial FAO. Macrophages pretreated with etomoxir were co-cultured with apoptotic adipocytes and treated with or without ASCs. The method aboved was used for detection and verification. Results In vivo, ASC-assisted fat transplantation improved macrophage mitochondrial expression and FAO level, promoted the early transformation of M2 macrophages, reduced the long-term lipid deposition of macrophages, and improved the retention rate of fat grafts. In vitro, ASCs up-regulated the level of mitochondrial FAO, OCR and ATP production in macrophages, reduced lipid deposition of macrophages and promoted M2 macrophages polarization by paracine function. The ability of ASCs in group pretreated with etomoxir to reduce the foaming of macrophages, promote the transformation to M2 macrophages, and improve the retention rate of fat transplantation was weakened. Conclusions ASCs increased the retention rate of transplanted fat by upregulating mitochondrial FAO to promote M2 polaration in macrophages. In addition, ASCs up-regulate mitochondrial FAO by paracrine effect to reduce foam cells formation and promote M2 transformation in macrophages in vitro.

Due to matching biomechanical properties and significant biological activity, Mg-based implants present great potential in orthopedic applications. In recent years, the biocompatibility and therapeutic effect of magnesium-based implants have been widely investigated in trauma repair. In contrast, the R&D work of Mg-based implants in spinal fusion is still limited. This review firstly introduced the general background for Mg-based implants. Secondly, the mechanical properties and degradation behaviors of Mg and its traditional and novel alloys were reviewed. Then, different surface modification techniques of Mg-based implants were described. Thirdly, this review comprehensively summarized the biological pathways of Mg degradation to promote bone formation in neuro-musculoskeletal circuit, angiogenesis with H-type vessel formation, osteogenesis with osteoblasts activation and chondrocyte ossification as an integrated system. Fourthly, this review followed the translation process of Mg-based implants via updating the preclinical studies in fracture fixation, sports trauma repair and reconstruction, and bone distraction for large bone defect. Furthermore, the pilot clinical studies were involved to demonstrate the reliable clinical safety and satisfactory bioactive effects of Mg-based implants in bone formation. Finally, this review introduced the background of spine fusion surgeryand the challenges of biological matching cage development. At last, this review prospected the translation potential of a hybrid Mg-PEEK spine fusion cage design.

Plastic pollution is widely present in terrestrial and aquatic ecosystems, and microplastics (MPs) can be detected in organisms. In situ detection methods for MPs in organisms have attracted widespread attention. Traditional imaging characterization methods of MPs, including stereo microscopes and fluorescence microscopy, are typically used to image artificially added microsphere standards under laboratory conditions. However, they cannot specifically identify MPs in biological samples. Thus, there is a need for a detection technique that can provide spatial distribution information of MPs in biological samples as well as measure their quality and quantity. In this perspective, to obtain high-resolution images with chemical composition analysis, we compared ion sources for ionizing plastic macromolecules and mass analyzers for analyzing macromolecules. Matrix-assisted laser desorption/ionization (MALDI) is suitable for imaging characterization, while time-of-flight (TOF) and Orbitrap mass spectrometry are suitable for polymer mass spectrometry analysis. Furthermore, we propose a technique that combines MALDI with TOF or Orbitrap, which holds promise for the in situ imaging of MPs in biological samples.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

Background: A decrease in the number and activity of thymic epithelial cells (TECs) is an important factor in thymic degeneration. Mesenchymal stem cells (MSCs) treating thymic ageing is a promising strategy, but the DNA methylation modification mechanism in TECs remains unclear. Methods: Aged rhesus monkeys were treated with MSCs to establish a thymic senescence model, and hematoxylin-eosin (HE) staining, immunofluorescence staining, and ELISA were performed to observe the structure and function of the thymus. TEC aging model and MSCs co-culture system were established to detect DNA methylation modification and transcriptomic changes, correlation analysis between transcription factor methylation and mRNA expression, and q-PCR, immunofluorescence staining, and Western blot were used to identified key genes. Results: MSCs improved the structure and function of thymus in elderly macaque monkeys; reduced the expression levels of β-Gal, P16, and P21; and increased the activity of aging TECs. There were 501 genes with increased methylation in the promoter region in the treated group compared with the untreated group, among which 23 genes were involved in the negative regulation of cell growth, proliferation and apoptosis, while 591 genes had decreased methylation, among which 37 genes were associated with promoting cell growth and proliferation and inhibiting apoptosis. Furthermore, 66 genes showed a negative correlation between promoter methylation levels and gene transcription; specifically, PDE5A, DUOX2, LAMP1 and SVIL were downregulated with increased methylation, inhibiting growth and development, while POLR3G, PGF, CHTF18, KRT17, FOXJ1, NGF, DYRK3, LRP8, CDT1, PRELID1, F2R, KNTC1 and TRIM3 were upregulated with decreased methylation, promoting cell growth. Conclusion: MSCs improve the structure and function of aged thymus, which involves the regulation of DNA methylation profiles and a decrease in the methylation level of the transcription factor NGF to specifically upregulate KRT17 and FOXJ1 to promote the proliferation of TECs.

Spatiotemporal axle temperature forecasting is crucial for real-time failure detection in locomotive control systems, significantly enhancing reliability and facilitating early maintenance. Motivated by the need for more accurate and reliable prediction models, this paper proposes a novel ensemble graph convolutional recurrent unit network. This innovative approach aims to develop a highly reliable and accurate spatiotemporal axle temperature forecasting model, thereby increasing locomotive safety and operational efficiency. The modeling structure involves three key steps: (1) the GCN module extracts and aggregates spatiotemporal temperature data and deep feature information from the raw data of different axles; (2) these features are fed into GRU and BiLSTM networks for modeling and forecasting; (3) the ICA algorithm optimizes the fusion weight coefficients to combine the forecasting results from GRU and BiLSTM, achieving superior outcomes. Comparative experiments demonstrate that the proposed model achieves RMSE values of 0.2517 °C, 0.2011 °C, and 0.2079 °C across three temperature series, respectively, indicating superior prediction accuracy and reduced errors compared to benchmark models in all experimental scenarios. The Wilcoxon signed-rank test further confirms the statistical significance of the result improvements with high confidence.

Objective: The objective of this study is to comprehensively understand the psychological experience of primiparous women during breastfeeding while dealing with lactating mastitis and to establish a reliable foundation for tailored support measures. Methods: Twenty primiparous mothers from a tertiary hospital in Beijing between January and March 2023 were chosen using purposive sampling for semi-structured interviews. After conducting 20 interviews, data saturation was achieved. The Colaizzi’s seven-step analytical approach was employed to analyze, summarize, and refine the identified themes. Results: Among primiparous women afflicted by lactating mastitis, the primary themes regarding breastfeeding attitudes included three key aspects: (1) uncertainty during the initial diagnosis phase, (2) intricate emotional journey during treatment, and (3) positive psychological outlook during the recovery stage. Conclusion: Primiparous women undergoing lactating mastitis experience substantial physical and psychological strain. It is crucial for medical personnel, family caregivers, and society at large to be attuned to the emotions of these patients. Tailored support measures should be offered to enhance patients’ physical and mental well-being and facilitate disease recovery.

The discharge of industrial solid waste in China is large, which is easy to cause damage to the ecological environment and threaten human health, so the resource reuse of industrial solid waste has aroused widespread concern in society. According to the potential fire prevention and extinguishing characteristics of the solid waste, the solid waste can be used as a raw material for preparing the mine fire prevention and extinguishing composite gel, so that the recycling of the waste resource can be realized, and the purpose of preventing and controlling the spontaneous combustion fire of the coal mine can also be achieved. In order to further promote the resource utilization of industrial solid waste in mine fire prevention and extinguishing composite gel materials, and improve and develop its application in mine fire prevention and control, the fire prevention and extinguishing mechanism of mine fire prevention and extinguishing composite gel was summarized, the fire prevention and extinguishing characteristics of solid waste were summarized, and the gelling mechanism and influencing factors of mine fire prevention and extinguishing composite gel prepared by solid waste were discussed. This paper expounds the glue-injecting technology and the present application situation of the compound gel for mine fire prevention and extinguishing. In view of the current research, it is found that the gelling mechanism of solid waste composite gel is not clear, the gelling activity of solid waste is not effectively stimulated, the sedimentation tube is blocked in the transportation process of solid waste composite gel, and the safety of solid waste application, and the solution direction and future research focus are put forward. Uch as micro-scale simulation, composite activation, novel activation materials, intelligent glue injection, ionic curing and the like. On the basis of the above solutions, the future research focus of the preparation of mine fire prevention and extinguishing composite gel from solid waste is prospected, and the future research will focus on the efficient utilization of solid waste in the preparation of fire prevention and extinguishing composite gel, the long-term fire prevention and extinguishment of solid waste composite gel, and the integrated monitoring system of intelligent gel fire prevention. These research directions are conducive to the high value-added utilization of industrial solid waste in mine fire prevention and extinguishing composite gel materials, and large-scale use in the prevention and control of coal mine spontaneous combustion fires, to ensure the safety of national property and worker’lives.

Abstract Background The diagnosis of tuberculous pleurisy (TP) presents a significant challenge due to the low bacterial load in pleural effusion (PE) samples. Cell-free Mycobacterium tuberculosis DNA (cf-TB) in PE samples is considered an optimal biomarker for diagnosing TP. This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size. Methods Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022. Following centrifugation, sediments obtained from PE were used for Xpert MTB/RIF (Xpert) and mycobacterial culture, while the supernatants were subjected to cf-TB testing. This study employed a composite reference standard to definite TP, which was characterized by any positive result for Mycobacterium tuberculosis (MTB) through either PE culture, PE Xpert, or pleural biopsy. Results A total of 1412 participants underwent screening, and 1344 (95.2%) were subsequently enrolled in this study. Data from 1241 (92.3%) participants were included, comprising 284 with definite TP, 677 with clinically diagnosed TP, and 280 without TP. The sensitivity of cf-TB testing in definite TP was 73.6% (95% CI 68.2–78.4), significantly higher than both Xpert (40.8%, 95% CI 35.3–46.7, P

Abstract Background In the repair of massive tissue defects using expanded large skin flaps, the incidence of complications increases with the size of the expanded area. Currently, stem cell therapy has limitations to solve this problem. We hypothesized that conditioned medium of adipose-derived stem cells (ADSC-CM) collected following mechanical pretreatment can assist skin expansion. Methods Rat aortic endothelial cells and fibroblasts were cultured with ADSC-CM collected under 0%, 10%, 12%, and 15% stretching force. Ten-milliliter cylindrical soft tissue expanders were subcutaneously implanted into the backs of 36 Sprague-Dawley rats. The 0% and 10% stretch groups were injected with ADSC-CM collected under 0% and 10% stretching force, respectively, while the control group was not injected. After 3, 7, 14, and 30 days of expansion, expanded skin tissue was harvested for staining and qPCR analyses. Results Endothelial cells had the best lumen formation and highest migration rate, and fibroblasts secreted the most collagen upon culture with ADSC-CM collected under 10% stretching force. The skin expansion rate was significantly increased in the 10% stretch group. After 7 days of expansion, the number of blood vessels in the expanded area, expression of the angiogenesis-associated proteins vascular endothelial growth factor, basic fibroblast growth factor, and hepatocyte growth factor, and collagen deposition were significantly increased in the 10% stretch group. Conclusions The optimal mechanical force upregulates specific paracrine proteins in ADSCs to increase angiogenesis and collagen secretion, and thereby promote skin regeneration and expansion. This study provides a new auxiliary method to expand large skin flaps.

Abstract Introduction Current physical activity guidelines recommend 150 min of moderate-to-vigorous physical activity (MVPA) for health benefits, regardless of the pattern of MVPA. However, MVPA that occurs in sessions (MVPA-S) may have different health implications compared to MVPA that is not accumulated in sessions (MVPA-nonS). This study aimed to investigate the associations of MVPA-S and MVPA-nonS with mortality. Methods We conducted a cohort study of the National Health and Nutrition Examination Survey 2003–2006 (n = 5,658) with accelerometer-measured physical activity at baseline and mortality followed through December 31, 2019. A session was defined as a time window of 30 min or longer where the average intensity was at or above 2020 counts/minute. MVPA accumulated within such sessions was quantified as MVPA-S, while MVPA accumulated outside the sessions was quantified as MVPA-nonS. We examined the joint association of MVPA-S and MVPA-nonS by classifying the participants into four groups (both

Abstract Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π–π stacking interaction and a water–magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.

Abstract Background Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. Methods In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. Results Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFβR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFβR1 induced similar effects to H19 deficiency. Conclusions In summary, our findings demonstrate that the H19/let-7 g/TGFβR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.

Abstract Mycotoxins, which are secondary metabolites produced by toxicogenic fungi, are natural food toxins that cause acute and chronic adverse reactions in humans and animals. The genus Fusarium is one of three major genera of mycotoxin‐producing fungi. Trichothecenes, fumonisins, and zearalenone are the major Fusarium mycotoxins that occur worldwide. Fusarium mycotoxins have the potential to infiltrate the human food chain via contamination during crop production and food processing, eventually threatening human health. The occurrence and development of Fusarium mycotoxin contamination will change with climate change, especially with variations in temperature, precipitation, and carbon dioxide concentration. To address these challenges, researchers have built a series of effective models to forecast the occurrence of Fusarium mycotoxins and provide guidance for crop production. Fusarium mycotoxins frequently exist in food products at extremely low levels, thus necessitating the development of highly sensitive and reliable detection techniques. Numerous successful detection methods have been developed to meet the requirements of various situations, and an increasing number of methods are moving toward high‐throughput features. Although Fusarium mycotoxins cannot be completely eliminated, numerous agronomic, chemical, physical, and biological methods can lower Fusarium mycotoxin contamination to safe levels during the preharvest and postharvest stages. These theoretical innovations and technological advances have the potential to facilitate the development of comprehensive strategies for effectively managing Fusarium mycotoxin contamination in the future.

Precise prediction of the remaining useful life (RUL) of rolling bearings is crucial for ensuring the smooth functioning of machinery and minimizing maintenance costs. The time-domain features can reflect the degenerative state of the bearings and reduce the impact of random noise present in the original signal, which is often used for life prediction. However, obtaining ideal training data for RUL prediction is challenging. Thus, this paper presents a bearing RUL prediction method based on unsupervised learning sample augmentation, establishes a VAE-GAN model, and expands the time-domain features that are calculated based on the original vibration signals. By combining the advantages of VAE and GAN in data generation, the generated data can better represent the degradation state of the bearings. The original data and generated data are mixed to realize data augmentation. At the same time, the dynamic time warping (DTW) algorithm is introduced to measure the similarity of the dataset, establishing the mapping relationship between the training set and target sequence, thereby enhancing the prediction accuracy of supervised learning. Experiments employing the XJTU-SY rolling element bearing accelerated life test dataset, IMS dataset, and pantograph data indicate that the proposed method yields high accuracy in bearing RUL prediction.

During checking continuous waveform record, it was found that some stations of Tianjin such as EWZ were significantly affected by one unknown noise, and EWZ station was the most seriously affected. Long term observations had also found that this noise cannot be observed for uncertainly several days each year. This noise was all year round and did not change with day and night time, and it had been existed for many years. This noise was different from typical environmental background noise and had some fixed characteristics. This article studied the noise from several aspects such as its own characteristic, its coverage of influence, spectral characteristics, and impact on earthquake records. The research has shown that the noise was not affected by natural factors such as weather and season, and had a characteristic of amplitude decreasing as the distance increasing from EWZ station. The main frequency of this noise ranged 1～2 Hz. The impact of noise was relatively wide and it can be recorded by 12 surrounding stations, with YGZ station being the farthest and approximately 58 km away from EWZ station. Through polarization analysis, it was found that the propagation of noise had a specific directionality, so it is preliminary judged that this noise had the characteristic of fixed source noise. This noise will have an impact on seismic records, reducing the seismic phase pickup rate, and even completely submerging it in the noise. Frequency filtering can improve it.

Abstract. Aging is accompanied by significant inhibition of hematopoietic and immune system function and disruption of bone marrow structure. Aging-related alterations in the inflammatory response, immunity, and stem cell niches are at the root of hematopoietic aging. Understanding the molecular mechanisms underlying hematopoietic and bone marrow aging can aid the clinical treatment of aging-related diseases. In particular, it is unknown how the niche reprograms hematopoietic stem cells (HSCs) in an age-dependent manner to maintain normal hematopoiesis in elderly individuals. Recently, specific inhibitors and blood exchange methods have been shown to reshape the hematopoietic niche and reverse hematopoietic aging. Here, we present the latest scientific discoveries related to hematopoietic aging and hematopoietic system rejuvenation, discuss the relationships between hematopoietic niche aging and HSC aging, and describe related studies on stem cell-mediated regulation of hematopoietic aging, aiming to provide new ideas for further study.

Abstract The stalk of Allium fistulosum contains dietary fibers with complicated monosaccharide composition and glycosidic bond linkages, which renders it a better dietary fiber supplement. However, the unfavorable odor, majorly contributed by allicin, limits its applications. Although many physical and chemical methods have been developed to remove allicin, there is currently no comparison between their efficiencies. Here, we comprehensively compare all these methods of eliminating allicin in the Allium stalk by starting with optimization of the allicin extraction method. Results indicate that incubation of the chopped Allium stalk with water for 20 min and extraction with 75% ethanol reached a maximal extraction yield. Different methods of allicin elimination are examined, and physical removal of allicin by blanching at 100 °C reaches a maximal clearance rate of 73.3%, rendering it the most efficient and effective method eliminating allicin from the stalk of Allium fistulosum for the preparation of a totally green dietary fiber.

Asthma is a complex heterogeneous and inflammatory disease with an increasing incidence worldwide. Here, UHPLC-Q-Exactive-MSE analysis revealed that 21 alkaloids and 1 coumarin compound (Scopoletin) were identified in SDLTAs. In mouse model, SDLTAs treatment reduced the airway pathological damage, the levels of IL-4, IL-5, IgE, MUC5AC, and splenic index. In cell model, SDLTAs treatment significantly decreased IL-6, IL-8, MUC5AC, and mucus secretion induced by LPS. Network pharmacology studies revealed that the main active ingredients of SDLTAs, including oxysophoridine, oxymatrine, scopoletin and sophoridine, target TLR4, DPP4, IL6 and TNF, as well as regulate IL-17 signaling pathway, TNF signaling pathway, and toll-like receptor signaling pathway, leading to relief of asthma on an inflammatory basis. Docking results showed that the binding energy of the main active ingredients of SDLTAs to TLR4 and MyD88 varied from −5.38 kcal/mol to −4.01 kcal/mol. Further, SDLTAs down-regulated the expression of TLR4, MyD88 and p-c-Jun.

Edaravone Dexborneol (EDB), comprised of edaravone and (+)- bornel, has been demonstrated to have synergistic effects of antioxidant and anti-inflammatory, which makes it to be applied for stroke as a protectant. However, the underlying mechanism of neuroprotection of EDB has not been fully elucidated. Increasing evidence has shown that neurotoxic A1 astrocytes were closely related to neuronal death after cerebral ischemia. However, whether EDB could provide neuroprotection by modulating the activation of astrocytes has not yet been elucidated. The present study aimed to explore whether EDB afforded neuroprotection by modulating A1 polarization of astrocytes and the down-stream signaling after cerebral ischemia. We first validated the neuroprotective effects of EDB in mice suffering focal cerebral ischemia via evaluating behavioral test, infarct volumes and neuronal survival. As for the down-stream signaling, our data further showed that EDB alleviated neuronal death by suppressing activation of neurotoxic A1 astrocytes via inhibition of NF-κB signaling pathway in vitro. Additionally, administration of EDB reduced the number of A1 reactive astrocytes in mice of focal cerebral ischemia. The above findings demonstrated that EDB provided neuroprotective effect by inhibiting neurotoxic activation of A1 astrocytes in animal model of cerebral ischemia, which indicated that EDB-mediated phenotypic regulation of astrocytes is a potential research direction to promote neurological recovery in central nervous system (CNS) diseases.

Wetland ecosystems play a pivotal role in terrestrial carbon and water cycles, thereby possessing great potential to regulate terrestrial water use efficiency (WUE), which is calculated as the ratio of gross primary productivity (GPP) to evapotranspiration (ET). However, it remains unclear the possible changes in wetland WUE under present and future climate conditions. In this research, WUE variations in a Phragmites australis-dominated freshwater wetland were determined by the eddy covariance method during 2020–2023. Further, we projected future GPP, ET, and WUE under four Representative Concentration Pathway (RCP) scenarios based on five Earth System Models. The 3-year average field observation suggested that the P. australis marsh exhibited high GPP (1149 g C m−2), but consumed large amounts of water through ET (611 mm H2O), resulting in relatively low WUE (1.89 g C mm−1 H2O). During wet years, the studied marsh consumed much more water through evaporation than through transpiration, thus exhibiting lower WUE. Contrarily, large amounts of water were utilized to maintain high primary productivity through transpiration in 2021–2022 dry year, leading to higher WUE. In future scenarios, GPP in the P. australis marsh shows consistently faster uptrends compared to ET from 2020 to 2100, consequently yielding persistent growths of WUE. Future growths of WUE indicate that P. australis marsh tends consume more water for maintaining productivity levels rather than loss via evaporation under future climate conditions, thereby intensifying the carbon–water interaction. Driven by the most rapid growth of environmental drivers, the RCP8.5 scenario shows the fastest increasing trends in GPP, ET, and WUE among four RCP scenarios, whereas the reverse ocurres under RCP2.6 scenario. Overall, our study advocates for more comprehensive research encompassing field observation and model simulation to address the current knowledge gap regarding the response of wetland WUE to contemporary and future climate change.

BackgroundWe developed a new predictive staging system to explore the heterogeneity of survival in newly diagnosed multiple myeloma (NDMM) patients in the real world.MethodsIn this retrospective study, we evaluated the predictive value of cytogenetic abnormal and clinical data in 375 patients with NDMM at our center. Established a weighted MM prognostic scoring system risk model and validated its predicted PFS and OS by external cohort.ResultsElevated lactate dehydrogenase levels (1 point), international staging system stage II/III (1 point), 1q21+ ≥ 52.75% (0.5 point), del (17p) ≥ 3.5% (0.5 point), and t (14;16) ≥ 35.25% (1 point) had independent prognostic significance. Patients were further divided into three risk groups: low (I) (score 0–0.5, 16.5%), intermediate (II) (score 1, 46.7%), and high (III) (score 1.5–3, 36.8%). In the training cohort, the 3-year PFS was 79.5% vs. 65.3% vs. 40.3% (p < 0.001), and the 3-year OS was 87.7% vs.70.1% vs. 55% (p < 0.001) for the three risk groups. In the external validation cohort, the 3-year PFS was 85.5% vs.61.2% vs. 43.1% (p < 0.001) and the 3-year OS was 91.4% vs.83.5% vs. 56.9% (p < 0.001) for the three risk groups.ConclusionThe risk stratification of this model shows good discrimination and calibration, and its application in clinical practice can improve the risk assessment of patients with NDMM and guide personalized treatment strategies.

To identify what are the dominant lactic acid bacteria (LAB) involved in the fermentation of salt-free sauerkraut, and optimize its industrial culture conditions, we isolated and identified a strain of LAB, which is referred to as Lactobacillus sp. DF_001, with the preservation number CCTCC NO: M20232593, from five different regions in Guizhou Province. Industrial culture conditions were optimized using Plackett-Burman and Central Composite design experiments, and the potential role of this LAB in salt-free sauerkraut fermentation was validated. Bioproduction was optimal with a culture time of 66 h, starch/water ratio of 1.7% and inoculum of 0.02%, which gave approximately three-fold higher yield than the basal culture medium DeMan-Rogosa-Sharpe medium (MRS). The LAB was used in small-scale industrial experiments. The Dafang LAB significantly enhanced the sensory score of the salt-free sauerkraut products by about 32% compared to the control group. The total acid content increased by about 32% and the sugar and nitrite contents were reduced by 67.27 and 69.58%, respectively. The total number of bacterial colonies decreased by 37.5%. All other indicators complied with the national standard, providing overall the basis to improve salt-free sauerkraut fermentation.

PurposeCurrently, a range of electromagnetic therapies, including magnetic field therapy, micro-currents therapy, and tumor treating fields, are under investigation for their potential in central nervous system tumor research. Each of these electromagnetic therapies possesses distinct effects and limitations. Our focus is on overcoming these limitations by developing a novel electric field generator. This generator operates by producing alternating induced currents within the tumor area through electromagnetic induction.MethodsFinite element analysis was employed to calculate the distribution of electric fields. Cell viability was assessed using the CCK-8 assay. Tumor volumes and weights served as indicators to evaluate the effectiveness of TTIF. The in-vivo imaging system was utilized to confirm tumor growth in the brains of mice.ResultsTTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo.ConclusionTTIF significantly inhibited the proliferation of U87 cells both in vitro and in vivo. Consequently, TTIF emerges as a potential treatment option for patients with progressive or metastatic GBM.

Objective To investigate the change in choroidal components of patients with Graves’ ophthalmopathy (GO) with different degrees of disease activity and severity by using the image binarisation method of optical coherence tomography (OCT).Methods This cross-sectional study included 151 eyes of 90 patients with GO. Patients were grouped according to the clinical activity score (CAS) and disease severity. Total choroidal area (TCA), luminal area, stromal area (SA) and choroidal vascularity index (CVI) were acquired by image binarisation of the OCT. Ocular parameters between groups were compared using generalised estimating equations, accounting for intereye correlation and adjusting for relevant factors.Results As for the included eyes, 104 eyes were inactive GO and 47 eyes were active GO. Local choroidal thicknesses were thicker in active GO than in inactive GO. TCA and SA were significantly larger in active GO than in inactive GO group (3.44±0.91 mm2 vs 3.14±0.88 mm2, p=0.046; 1.16 (1.03–1.50) mm2 vs 1.10 (0.96–1.27) mm2, p=0.002, respectively). CAS was positively correlated with TCA (r=0.171, p=0.036) and SA (r=0.172, p=0.035), and negatively associated with CVI (r=−0.174, p=0.032). In multiple regression models, age, diopter and intraocular pressure (IOP) exhibited significant correlations with the SA (β=−0.006, p=0.010; β=0.076, p

BackgroundWWOX-related epileptic encephalopathy is an autosomal recessive disorder caused by mutations in the WW-containing oxidoreductase gene, characterized by the onset of refractory seizures in infants. Early-onset epilepsy, electroencephalography abnormalities, and developmental delay or degeneration are the main clinical manifestations. Early death can occur in severe cases. In the present study, a novel variant in WWOX was detected in a patient with epilepsy and his healthy parents.Case presentationA 5-month-old boy presented with epilepsy. The main manifestations were intractable seizures, mental and motor retardation and hearing impairment. Subsequent genetic testing revealed the presence of an epilepsy-associated novel mutation: c.991C>A (amino acid change: p.Ser304Tyr) in the WWOX gene. Variants were inherited from parents with healthy phenotypes. Finally, a patient died at 6 months of age.ConclusionThe discovery of novel variants has enriched the existing database of WWOX gene variants and may expand the range of clinical options for treating WWOX-related disorders.

The widespread presence of micro(nano)plastics (MNPs) has generated public concern. Studies have indicated that MNPs can accumulate in mammalian bones; however, research on the skeletal toxicity and underlying molecular mechanisms of MNPs in aquatic organisms remains limited. We subjected zebrafish embryos to three varying levels (1, 10, 100 μg/mL) of polystyrene nanoplastics (PSNPs) exposure over a period of 7 days in our research. The results revealed that PSNPs significantly reduced the body length and hatching rate of zebrafish, leading to skeletal deformities. mRNA level analysis showed significant upregulation of sp7, sparc, and smad1 genes transcription by PSNPs. Moreover, PSNPs markedly downregulated the mRNA levels associated with runx2a, bmp2a, and bmp4. Further investigations demonstrated that PSNPs dramatically increased ROS levels in zebrafish larvae, with significant downregulation of transcription levels of sod1 and cat genes, resulting in a sharp increase in transcription levels of apoptosis-related regulatory genes bcl-2 and bax. Furthermore, PSNPs led to a marked rise in Caspase 3 activity in zebrafish larvae, suggesting the initiation of apoptosis. PSNPs also notably inhibited alkaline phosphatase (AKP) activity. Compared to a 4-day exposure, a 7-day exposure to PSNPs intensified abnormalities across multiple indicators. In summary, our research indicates that PSNPs cause significant oxidative stress in zebrafish larvae, resulting in apoptosis. Moreover, PSNPs disrupt the transcription of genes related to skeletal development through the bone morphogenetic protein (BMP) pathway, further disrupting skeletal development processes and ultimately resulting in skeletal deformities in zebrafish larvae. This study provides new insights into the skeletal toxicity of MNPs.

Biologically-derived hydroxyapatite is a widely used biomaterial in various clinical applications including bone augmentation. However, the osteogenic application of biological hydroxyapatite is limited by inflammatory responses, and the underlying mechanism remains unknown. The current study aimed to elucidate the molecular mechanisms underlying the inflammatory response to biological hydroxyapatite. Porcine-derived hydroxyapatite (PHA) with two sintering temperatures (800 and 1600 °C), PHA800 and PHA1600, respectively, were prepared. A PHA/macrophage co-culture model was established. Transcriptome, polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) analyses were used to determine the inflammatory effects and the main pathways activated by PHA800 and PHA1600. Intracellular calcium level, PHA-induced calcium enrichment, and related biological effects were used to determine the molecular mechanism at the PHA-cell interface. PHA800 significantly upregulated a TLR4 mediated inflammatory pathway in a calcium influx-dependent manner, and the calcium enrichment activity on the surface of PHA800 promoted calcium influx. In contrast, the calcium enrichment activity on the surfaces of the PHA1600 and PHA800 pretreated groups was attenuated, resulting in decreased calcium influx and mild inflammatory effects. Our results provide a fundamental basis for the development of novel bone substitutes that elicit low levels of inflammation response.

A novel fire-preventing composite gel, mainly made from steel slag (SS) and silica fume (SF), was created for a coal mine’s spontaneous combustion. The gelation mechanism of the steel slag-based composite gel (SSG) was investigated using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (SEM). The findings suggest that SSG is generated through the processes of hydration and geopolymerization involving SS and SF. And in the alkaline milieu of a 1.5 M water glass solution, SSG manifests enhanced strength and water retention capacities. Moreover, the fire prevention and extinguishing performance of the SSG was analyzed and verified using low-temperature oxidation, thermogravimetry, and low temperature nitrogen adsorption experiment (LTNA). The SSG has proven highly effective in suppressing spontaneous coal combustion by inhibiting CO production, raising the coal oxidation temperature, and reducing the contact area between oxygen and the coal body.

BackgroundGanoderma lucidum (G. lucidum) is a famous medicinal mushroom that has been reported to prevent and treat a variety of diseases. Different extractions from G. lucidum have been used to manage age-related diseases, including cancer. Nevertheless, the senolytic activity of G. lucidum against senescent cancer cells has not been investigated. Although cellular senescence causes tumor growth inhibition, senescent cells promote the growth of the neighboring tumor cells through paracrine effects. Therefore, the elimination of senescent cells is a new strategy for cancer treatment.MethodsIn this study, senescence was triggered in HCC cells by the chemotherapeutic agent Adriamycin (ADR), and subsequently, cells were treated with TC to assess its senolytic activity.ResultsWe found for the first time that the triterpenoid complex (TC) from G. lucidum had senolytic effect, which could selectively eliminate adriamycin (ADR)-induced senescent cells (SCs) of hepatocellular carcinoma (HCC) cells via caspase-dependent and mitochondrial pathways-mediated apoptosis and reduce the levels of senescence markers, thereby inhibiting the progression of cancers caused by SCs. TC could block autophagy at the late stage in SCs, resulting in a significant activation of TC-induced apoptosis. Furthermore, TC inhibited the senescence-associated secretory phenotype (SASP) in SCs through the inhibition of NF-κB, TFEB, P38, ERK, and mTOR signaling pathways and reducing the number of SCs. Sequential administration of ADR and TC in vivo significantly reduced tumor growth and reversed the toxicity of ADR.ConclusionA triterpenoid complex isolated from G. lucidum may serve as a novel senolytic agent against SCs, and its combination with chemotherapeutic agents may enhance their antitumor efficacy.

Carnivores play key roles in maintaining ecosystem structure and function as well as ecological processes. Understanding how sympatric species coexist in natural ecosystems is a central research topic in community ecology and biodiversity conservation. In this study, we explored intra- and interspecific niche partitioning along spatial, temporal, and dietary niche partitioning between apex carnivores (wolf Canis lupus, snow leopard Panthera uncia, Eurasian lynx Lynx lynx) and mesocarnivores (Pallas’s cat Otocolobus manul, red fox Vulpes vulpes, Tibetan fox Vulpes ferrilata) in Qilian Mountain National Park, China, using camera trapping data and DNA metabarcoding sequencing data. Our study showed that apex carnivore species had more overlap temporally (coefficients of interspecific overlap ranging from 0.661 to 0.900) or trophically (Pianka’s index ranging from 0.458 to 0.892), mesocarnivore species had high dietary overlap with each other (Pianka’s index ranging from 0.945 to 0.997), and apex carnivore and mesocarnivore species had high temporal overlap (coefficients of interspecific overlap ranging from 0.497 to 0.855). Large dietary overlap was observed between wolf and snow leopard (Pianka’s index = 0.892) and Pallas’s cat and Tibetan fox (Pianka’s index = 0.997), suggesting the potential for increased resource competition for these species pairs. We concluded that spatial niche partitioning is likely to key driver in facilitating the coexistence of apex carnivore species, while spatial and temporal niche partitioning likely facilitate the coexistence of mesocarnivore species, and spatial and dietary niche partitioning facilitate the coexistence between apex and mesocarnivore species. Our findings consider partitioning across temporal, spatial, and dietary dimensions while examining diverse coexistence patterns of carnivore species in Qilian Mountain National Park, China. These findings will contribute substantially to current understanding of carnivore guilds and effective conservation management in fragile alpine ecosystems.

PurposeTo investigate the predictive value of leukocyte subsets and C-reactive protein (CRP) in coronary artery disease (CAD).MethodsWe conducted a Mendelian randomization analysis (MR) on leukocyte subsets, C-reactive protein (CRP) and CAD, incorporating data from 68,624 patients who underwent coronary angiography from 2010 to 2022. After initial screening, clinical data from 46,664 patients were analyzed. Techniques employed included propensity score matching (PSM), logistic regression, lasso regression, and random forest algorithms (RF). Risk factors were assessed, and the sensitivity and specificity of the models were evaluated using receiver operating characteristic (ROC) curves. Additionally, survival analysis was conducted based on a 36-month follow-up period.ResultsThe inverse variance weight (IVW) analysis showed that basophil count (OR 0.92, 95% CI: 0.84–1.00, P = 0.048), CRP levels (OR 0.87, 95% CI: 0.73–1.00, P = 0.040), and lymphocyte count (OR 1.10, 95% CI: 1.04–1.16, P = 0.001) are significant risk factors for CAD. Using LASSO regression, logistic regression, and RF analysis, both CRP and lymphocyte counts were consistently identified as risk factors for CAD, prior to and following PSM. The ROC curve analysis indicated that the combination of lymphocyte and CRP levels after PSM achieves a higher diagnostic value (0.85). Survival analysis revealed that high lymphocyte counts and low CRP levels are associated with a decreased risk of Major Adverse Cardiovascular Events (MACE) (P

Tumor-associated macrophages (TAMs), fundamental constituents of the tumor microenvironment (TME), significantly influence cancer development, primarily by promoting epithelial-mesenchymal transition (EMT). EMT endows cancer cells with increased motility, invasiveness, and resistance to therapies, marking a pivotal juncture in cancer progression. The review begins with a detailed exposition on the origins of TAMs and their functional heterogeneity, providing a foundational understanding of TAM characteristics. Next, it delves into the specific molecular mechanisms through which TAMs induce EMT, including cytokines, chemokines and stromal cross-talking. Following this, the review explores TAM-induced EMT features in select cancer types with notable EMT characteristics, highlighting recent insights and the impact of TAMs on cancer progression. Finally, the review concludes with a discussion of potential therapeutic targets and strategies aimed at mitigating TAM infiltration and disrupting the EMT signaling network, thereby underscoring the potential of emerging treatments to combat TAM-mediated EMT in cancer. This comprehensive analysis reaffirms the necessity for continued exploration into TAMs’ regulatory roles within cancer biology to refine therapeutic approaches and improve patient outcomes.

Integrating large-scale renewable energy sources in modern power systems has altered fault characteristics, resulting in the performance degradation of conventional current differential protection. This paper proposes a novel high-sensitivity time-domain current differential protection scheme. The proposed scheme utilizes the Bergeron model to eliminate the impact of the distributed capacitive current. Furthermore, the Bergeron model error is analyzed theoretically during normal operation, and an algorithm is designed to identify and adjust the α- and β-mode line parameters. Additionally, novel internal fault criteria are presented to mitigate the negative impact of the 0-mode line parameter error. Compared to traditional frequency-domain approaches, the proposed method can more accurately and rapidly distinguish internal and external faults, while reducing the dependency on precise line parameters. Eventually, a VSC-HVDC sending-end grid model consisting of 100% renewable power generations is established using PSCAD/EMTDC software. Simulation results confirm that the proposed protection scheme exhibits exceptional performance in terms of operating speed, sensitivity, and tolerance to fault resistance and noise.

Abstract Background To explore the relationship between occupational stress, burnout and depressive symptoms among railroad workers in Fuzhou, and to analyze the interaction of burnout and occupational stress on depressive symptoms. Methods In this study, 861 railway employees of Fuzhou railway bureau were randomly selected from January to April, 2022. Occupational stress inventory revised edition (OSI-R), China job burnout inventory (CMBI) and Symptom Checklist-90 (SCL-90) were used to investigate the occupational stress, job burnout and depressive symptoms of railway workers. Interactions associated with depressive symptoms were assessed by linear hierarchical regression analysis and SPSS macros (PROCESS). Results Occupational stress, job burnout and depressive symptoms accounted for 50.58%, 93.47%, and 11.19% of the study population, respectively. There were intergroup differences between age, marriage status, and length of service (P

Abstract Background The magnitude of the risk of death and cardiac arrest associated with emergency surgery and anesthesia is not well understood. Our aim was to assess whether the risk of perioperative and anesthesia-related death and cardiac arrest has decreased over the years, and whether the rates of decrease are consistent between developed and developing countries. Methods A systematic review was performed using electronic databases to identify studies in which patients underwent emergency surgery with rates of perioperative mortality, 30-day postoperative mortality, or perioperative cardiac arrest. Meta-regression and proportional meta-analysis with 95% confidence intervals (CIs) were performed to evaluate global data on the above three indicators over time and according to country Human Development Index (HDI), and to compare these results according to country HDI status (low vs. high HDI) and time period (pre-2000s vs. post-2000s). Results 35 studies met the inclusion criteria, representing more than 3.09 million anesthetic administrations to patients undergoing anesthesia for emergency surgery. Meta-regression showed a significant association between the risk of perioperative mortality and time (slope: -0.0421, 95%CI: from − 0.0685 to -0.0157; P = 0.0018). Perioperative mortality decreased over time from 227 per 10,000 (95% CI 134–380) before the 2000s to 46 (16–132) in the 2000–2020 s (p

Abstract Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Abstract Background The public health measures associated with the COVID-19 pandemic may have indirectly impacted other health outcomes, such as falls among older adults. The purpose of this study was to examine trends in fall-related hospitalizations and emergency department visits among older adults before and during the COVID-19 pandemic in Ontario, Canada. Methods We obtained fall-related hospitalizations (N = 301,945) and emergency department visit (N = 1,150,829) data from the Canadian Institute for Health Information databases from 2015 to 2022 for adults ages 65 and older in Ontario. Fall-related injuries were obtained using International Classification of Diseases, 10th edition, Canada codes. An interrupted time series analysis was used to model the change in weekly fall-related hospitalizations and emergency department visits before (January 6, 2015-March 16, 2020) and during (March 17, 2020-December 26, 2022) the pandemic. Results After adjusting for seasonality and population changes, an 8% decrease in fall-related hospitalizations [Relative Rate (RR) = 0.92, 95% Confidence Interval (CI): 0.85, 1.00] and a 23% decrease in fall-related emergency department visits (RR = 0.77, 95%CI: 0.59, 1.00) were observed immediately following the onset of the pandemic, followed by increasing trends during the pandemic for both outcomes. Conclusions Following an abrupt decrease in hospitalizations and emergency department visits immediately following the onset of the pandemic, fall-related hospitalizations and emergency department visits have been increasing steadily and are approaching pre-pandemic levels. Further research exploring the factors contributing to these trends may inform future policies for public health emergencies that balance limiting the spread of disease among this population while supporting the physical, psychological, and social needs of this vulnerable group.

Abstract Background Adipose-derived stem cells (ASCs) represent the most advantageous choice for soft tissue regeneration. Studies proved the recruitment of ASCs post tissue injury was mediated by chemokine CXCL12, but the mechanism by which CXCL12 is generated after tissue injury remains unclear. Migrasomes are newly discovered membrane-bound organelles that could deliver CXCL12 spatially and temporally in vivo. In this study, we sought to investigate whether migrasomes participate ASC-mediated tissue regeneration. Methods Discrepant and asymmetrical soft tissue regeneration mice model were established, in which HE staining, immunofluorescent staining, western blot and qPCR were conducted to confirm the role of CXCL12 and migrasomes in ASC-mediated tissue regeneration. Characterization of ASC-derived migrasomes were carried out by confocal microscopy, scanning electron microscopy, transmission electron microscopy as well as western blot analysis. The function and mechanism of migrasomes were further testified by assisting tissue regeneration with isolated migrasomes in vivo and by in vitro transwell combined with co-culture system. Results Here, we show for the first time that migrasomes participate in soft tissue regeneration. ASCs generate migrasomes enriched with CXCL12 to mediate tissue regeneration. Migrasomes from ASCs could promote stem cells migration by activating CXCR4/RhoA signaling in vivo and in vitro. Chemoattracted ASCs facilitate regeneration, as demonstrated by the upregulation of an adipogenesis-associated protein. This positive feed-back-loop creates a favorable microenvironment for soft tissue regeneration. Thus, migrasomes represent a new therapeutic target for ASC-mediated tissue regeneration. Conclusions Our findings reveal a previously unknown function of ASCs in mediating tissue regeneration by generating migrasomes. The ASC-derived migrasomes can restore tissue regeneration by recruiting stem cells, which highlighting the potential application of ASC-derived migrasomes in regenerative medicine.

Introduction: Breast cancer (BC) is a malignant disease that occurs worldwide and poses serious health burden. Objectives: To assess the prevalence of BC burden in the Western Pacific region (WPR) from 1990 to 2019, and to predict trends from 2020 to 2044. To analyze the driving factors and put forward the region-oriented improvement. Methods: Based on the Global Burden of Disease Study 2019, BC cases, deaths, disability-adjusted life years (DALYs) cases, age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate in WPR from 1990 to 2019 was obtained and analysed. Age-period-cohort (APC) model was used to analyze age, period, and cohort effects in BC, and Bayesian APC (BAPC) was used to predict trends over the next 25 years. Results: In conclusion, BC incidence and deaths in the WPR have increased rapidly over the past 30 years and are expected to continue to increase between 2020 and 2044. Among behavioral and metabolic factors, high body-mass index was the main risk factor for BC mortality in middle-income countries, whereas alcohol use was the main risk factor in Japan. Age is a key factor in the development of BC, with 40 years being the critical point. Incidence trends coincide with the course of economic development. Conclusions: The BC burden remains an essential public health issue in the WPR and will increase substantially in the future. More efforts should be made in middle-income countries to prompt the health behavior and minimize the burden of BC because these nations accounts for the majority of BC burden in the WPR.

This study aimed to explore the efficacy of a multimodal analgesic regimen during the perioperative period for male patients undergoing knee replacement surgery. A total of 80 male patients scheduled for elective knee replacement surgery in our hospital’s orthopedic department from March 2022 to March 2023 were selected through digital randomization. They were equally divided into a control group (received a conventional analgesic protocol) and an observation group (treated with a multimodal analgesic protocol that included patient-controlled analgesia (PCA), ultrasound-guided nerve block and physical analgesia). Parameters such as postoperative celecoxib capsule dosage, Visual Analog Scale (VAS) scores at 6, 12, 24 and 72 hours after surgery, levels of neurotransmitters and stress markers at the time of surgery, 24 hours post-surgery, and 72 hours post-surgery, sleep quality scores, the timing of first ambulation, and the overall incidence of adverse reactions were compared between the groups. After intervention, the observation group showed a statistically significant reduction in the dosage of celecoxib capsules compared to the control group (p < 0.05). VAS scores in the observation group were significantly lower than those in the control group at all measured time points. Furthermore, levels of substance P (SP), beta-endorphin (β-EP), 5-hydroxytryptamine (5-HT), cortisol (Cor), C-reactive protein (CRP) and white blood cell (WBC) counts in the observation group were significantly lower than those in the control group at 24- and 72-hours post-surgery. The incidence of adverse reactions was also significantly lower in the observation group (p < 0.05). We conclude that implementing a multimodal analgesic protocol in the perioperative period could significantly reduce pain, regulate neurotransmitter and stress levels, and enhance sleep quality in the early postoperative phase of male patients undergoing knee replacement surgery.

Acoustic metamaterials (AMs) composed of periodic artificial structures have extraordinary sound wave manipulation capabilities compared with traditional acoustic materials, and they have attracted widespread research attention. The sound insulation performance of thin-walled structures commonly used in engineering applications with restricted space, for example, vehicles’ body structures, and the latest studies on the sound insulation of thin-walled metamaterial structures, are comprehensively discussed in this paper. First, the definition and math law of sound insulation are introduced, alongside the primary methods of sound insulation testing of specimens. Secondly, the main sound insulation acoustic metamaterial structures are summarized and classified, including membrane-type, plate-type, and smart-material-type sound insulation metamaterials, boundaries, and temperature effects, as well as the sound insulation research on composite structures combined with metamaterial structures. Finally, the research status, challenges, and trends of sound insulation metamaterial structures are summarized. It was found that combining the advantages of metamaterial and various composite panel structures with optimization methods considering lightweight and proper wide frequency band single evaluator has the potential to improve the sound insulation performance of composite metamaterials in the full frequency range. Relative review results provide a comprehensive reference for the sound insulation metamaterial design and application.