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In recent years, there has been a mounting occurrence of lung cancer, which stands as one of the most prevalent malignancies globally. This rise in incidence poses a significant hazard to human health, making lung cancer a matter of grave concern. It has been shown that tRNA-derived small non-coding RNA (tsRNA) is involved in the development of tumors, especially lung cancer, through mechanisms such as regulating mRNA stability, influencing protein translation, and acting as epigenetic regulators. Recent studies have shown that tsRNA is abnormally expressed in the plasma and tissues of lung cancer patients, and its expression level is closely related to the malignancy degree and postoperative recurrence of lung cancer. Therefore, for lung cancer patients, tsRNA represents a promising non-invasive biomarker, exhibiting significant potential for facilitating early diagnosis and prognostic evaluation, and for achieving precision treatment of lung cancer by regulating its expression. This article focuses on the biogenesis of tsRNA and its ability to promote lung cancer cell proliferation and invasion. In addition, the specific clinical significance of tsRNA in lung cancer was discussed. Finally, we discuss the need for further improvement of small RNA sequencing technology, and the future research directions and strategies of tsRNA in lung cancer and tumor diseases were summarized.

Modulation of the immune system has gained significant attention in regenerative medicine. Although most tissues possess intrinsic self-repair capabilities, large-sized defects and complex pathological conditions may still lead to tissue microenvironment imbalance and repair failure. Researchers have applied macrophage-mediated immunotherapeutic strategies to various injured tissue repairs by modulating inflammatory responses, intercellular communication, and multitissue synergies to restore immune microenvironmental homeostasis and promote tissue regeneration. Ongoing advancements in materials science have highlighted the precise immunomodulatory role of biomaterials, with passive targeting strategies based on the material's physicochemical properties and active targeting strategies based on specific molecular modifications becoming increasingly important in research. This review focuses on the mechanisms of action of actively and passively targeted biomaterials to modulate macrophages, which improve the tissue regenerative microenvironment through four basic strategies: (i) modulation of the inflammatory response to remove damaged cells, cellular debris, and pathogens; (ii) remodeling of the extracellular matrix; (iii) reconstruction of vascular tissues; and (iv) macrophage-stem cell crosstalk. This review covers the major mechanisms of macrophage action in the regeneration of injured tissues, while exploring the multiple methods by which advanced biomaterials target macrophages and highlighting their applications in the regeneration of a wide range of tissue injuries. We further discuss the future directions and current limitations in the development of biomaterials for macrophage modulation, aiming to advance biomaterials targeting macrophages, realize the full potential of immunotherapy, and achieve precision medicine.

The fibroblast growth factor receptor (FGFR) is a crucial receptor tyrosine kinase involved in essential biological processes, including growth, development, and tissue repair. However, FGFR gene mutations, including amplification, fusion, and mutation, can disrupt epigenetics, transcriptional regulation, and tumor microenvironment interactions, leading to cancer development. Targeting these kinase mutations with small molecule drugs or antibodies has shown clinical benefits. For example, erdafitinib is approved for treating locally advanced or metastatic urothelial cancer patients with FGFR2/FGFR3 mutations, and pemigatinib is approved for treating cholangiocarcinoma with FGFR2 fusion/rearrangement. Effective screening of FGFR variant patients is crucial for the clinical application of FGFR inhibitors. Various detection methods, such as polymerase chain reaction, next-generation sequencing, fluorescence in situ hybridization, and immunohistochemistry, are available, and their selection should be based on diagnostic and treatment decision-making needs. Our developed expert consensus aims to standardize the diagnosis and treatment process for FGFR gene mutations and facilitate the practical application of FGFR inhibitors in clinical practice.

Cervical tracheal adenoid cystic carcinoma (TACC) invading the thyroid gland is very rare and easily misdiagnosed as thyroid tumor, this paper reports a TACC invading thyroid in a 33-year-old woman who had been diagnosed as a thyroid follicular tumor in right lobe of thyroid by sonography and ultrasound guided fine needle aspiration in other hospital. She accepted surgical treatment in our hospital and was diagnosed as TACC by pathology, locally involving the thyroid. This paper presents the patient's clinical data, imaging findings, pathological diagnosis, treatment process and reviews the literature of TACC mimicking a thyroid tumor.

Green solvents such as water and ionic liquids (ILs) are pillars of the great mansion of green chemistry and green processing. Initially proposed as a new family of ILs, deep eutectic solvents (DESs) have received fast development in the past two decades. In this contribution, DESs are reviewed critically and the concept is extended to low-melting mixture solvents (LoMMSs), which cover all kinds of materials including ionic compounds, molecular compounds, and metals. Six classes of LoMMSs are proposed as the new classification system and examples are given. Finally, several thermodynamic issues concerning LoMMSs are discussed. Two new concepts, robustness of LoMMSs and high-entropy LoMMSs, are proposed.

Saccharomyces cerevisiae, a widely utilized model organism, has seen continuous updates to its genome-scale metabolic model (GEM) to enhance the prediction performance for metabolic engineering and systems biology. This study presents an auxotrophy-based curation of the yeast GEM, enabling facile upgrades to yeast GEMs in future endeavors. We illustrated that the curation bolstered the predictive capability of the yeast GEM particularly in predicting auxotrophs without compromising accuracy in other simulations, and thus could be an effective manner for GEM refinement. Last, we leveraged the curated yeast GEM to systematically predict auxotrophs, thereby furnishing a valuable reference for the design of nutrient-dependent cell factories and synthetic yeast consortia.

The application of ductile rock bolts has been a crucial method for solving the problems of large deformations, energy absorption and stability control issues in deep rock masses. To study the anchoring mechanism of the key expansive structure, this paper proposes a novel type of bolt — the Ductile-Expansion bolt, and conducts research on anchoring mechanics, energy absorption characteristics, and failure modes of the bolt. In addition, this paper defines the concept of load-volume ratio of metal rock bolts and proves the Ductile-Expansion bolt is capable of better improving the unit volume bearing capacity of the bolt material. Furthermore, laboratory and field tests verify the Ductile-Expansion bolt had better anchoring effect than the traditional rebar bolt, with the expansion structure favorably enhancing the ductility and energy absorption performance of the bolt. Finally, this paper microscopically analyzes the crack propagation and distribution morphology of the bolts by establishing a 3D coupled numerical model based on FDM-DEM. Numerical results illustrate the interface at the variable diameter of the Ductile-Expansion bolt serves as the transition zone between high and low stress levels. The expansion structure can impose radial compression on the medium around the bolt, which can improve the bolt anchorage performance.

Abstract Osteogenesis imperfecta (OI) is a disorder of low bone mass and increased fracture risk due to a range of genetic variants that prominently include mutations in genes encoding type I collagen. While it is well known that OI reflects defects in the activity of bone-forming osteoblasts, it is currently unclear whether OI also reflects defects in the many other cell types comprising bone, including defects in skeletal vascular endothelium or the skeletal stem cell populations that give rise to osteoblasts and whether correcting these broader defects could have therapeutic utility. Here, we find that numbers of skeletal stem cells (SSCs) and skeletal arterial endothelial cells (AECs) are augmented in Col1a2 oim/oim mice, a well-studied animal model of moderate to severe OI, suggesting that disruption of a vascular SSC niche is a feature of OI pathogenesis. Moreover, crossing Col1a2 oim/oim mice to mice lacking a negative regulator of skeletal angiogenesis and bone formation, Schnurri 3 (SHN3), not only corrected the SSC and AEC phenotypes but moreover robustly corrected the bone mass and spontaneous fracture phenotypes. As this finding suggested a strong therapeutic utility of SHN3 inhibition for the treatment of OI, a bone-targeting AAV was used to mediate Shn3 knockdown, rescuing the Col1a2 oim/oim phenotype and providing therapeutic proof-of-concept for targeting SHN3 for the treatment of OI. Overall, this work both provides proof-of-concept for inhibition of the SHN3 pathway and more broadly addressing defects in the stem/osteoprogenitor niche as is a strategy to treat OI.

Abstract Background The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. Results To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. Conclusions Our study underscores the importance of Blautia A species in the gut microbiota’s rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Abstract Background Soil salinity is one of the major abiotic stresses that threatens crop growth. Cotton has some degree of salt tolerance, known as the “pioneer crop” of saline-alkali land. Cultivation of cotton is of great significance to the utilization of saline-alkali land and the development of cotton industry. Gossypium hirsutum and G. barbadense, as two major cotton species, are widely cultivated worldwide. However, until recently, the regulatory mechanisms and specific differences of their responses to salt stress have rarely been reported. Results In this study, we comprehensively compared the differences in the responses of G. hirsutum acc. TM-1 and G. barbadense cv. Hai7124 to salt stress. The results showed that Hai7124 exhibited better growth than did TM-1 under salt stress, with greater PRO content and antioxidant capability, whereas TM-1 only presented greater K+ content. Transcriptome analysis revealed significant molecular differences between the two cotton species in response to salt stress. The key pathways of TM-1 induced by salt are mainly related to growth and development, such as porphyrin metabolism, DNA replication, ribosome and photosynthesis. Conversely, the key pathways of Hai7124, such as plant hormone signal transduction, MAPK signaling pathway-plant, and phenylpropanoid biosynthesis, are mainly related to plant defense. Further comparative analyses of differentially expressed genes (DEGs) revealed that antioxidant metabolism, abscisic acid (ABA) and jasmonic acid (JA) signalling pathways were more strongly activated in Hai7124, whereas TM-1 was more active in K+ transporter-related genes and ethylene (ETH) signalling pathway. These differences underscore the various molecular strategies adopted by the two cotton species to navigate through salt stress, and Hai7124 responded more strongly to salt stress, which explains the potential reasons for the greater salt tolerance of Hai7124. Finally, we identified 217 potential salt tolerance-related genes, 167 of which overlapped with the confidence intervals of significant SNPs identified in previous genome-wide association studies (GWASs), indicating the high reliability of these genes. Conclusions These findings provide new insights into the differences in the regulatory mechanisms of salt tolerance between G. hirsutum and G. barbadense, and identify key candidate genes for salt tolerance molecular breeding in cotton.

Abstract Membranes tailored for selective ion transport represent a promising avenue toward enhancing sustainability across various fields including water treatment, resource recovery, and energy conversion and storage. While nanochannels formed by polymers of intrinsic microporosity (PIM) offer a compelling solution with their uniform and durable nanometer-sized pores, their effectiveness is hindered by limited interactions between ions and nanochannel. Herein, we introduce the randomly twisted V-shaped structure of Tröger’s Base unit and quaternary ammonium groups to construct ionized sub-nanochannel with a window size of 5.89–6.54 Å between anion hydration and Stokes diameter, which enhanced the dehydrated monovalent ion transport. Combining the size sieving and electrostatic interaction effects, sub-nanochannel membranes achieved exceptional ion selectivity of 106 for Cl-/CO3 2- and 82 for Cl-/SO4 2-, significantly surpassing the state-of-the-art membranes. This work provides an efficient template for creating functionalized sub-nanometer channels in PIM membranes, and paves the way for the development of precise ion separation applications.

Abstract Alzheimer’s disease (AD) is a progressive neurological disorder that primarily impacts cognitive function. Currently there are no disease-modifying treatments to stop or slow its progression. Recent studies have found that several peripheral and systemic abnormalities are associated with AD, and our understanding of how these alterations contribute to AD is becoming more apparent. In this review, we focuse on amyloid‑beta (Aβ), a major hallmark of AD, summarizing recent findings on the source of brain-derived Aβ and discussing where and how the brain-derived Aβ is cleared in vivo. Based on these findings, we propose future strategies for AD prevention and treatment, from a novel perspective on Aβ metabolism.

Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and lethal tumor with poor prognosis. Its survival period ranges from four months to one year, and the 5-year survival rate is only about 10%. MPM is highly resistant to chemotherapy, and conventional treatments such as cisplatin combined with pemetrexed or raltitrexed only have a certain effect in about 20% of patients. In recent years, with the continuous in-depth understanding of the genetic variation characteristics of MPM, some progress has been made in the molecular mechanism underlying the chemotherapy resistance of MPM. This article will summarize the research progress of the molecular mechanism underlying the chemotherapy resistance of MPM, including BAP1 gene mutation, microRNA, MTA1-mediated DNA damage repair pathway, GITR-GITRL pathway, TGFa pathway, tumor stem cell, EGFR, and PTEN. The aim of this work is to provide a reference for exploring new therapeutic targets and combined treatment options for MPM.

Abstract Background To explore the feasibility and effectiveness of a segmented sodium citrate solution anticoagulation strategy in patients receiving CRRT. Methods A prospective, randomized controlled study was conducted. Results According to the inclusion and exclusion criteria, 80 patients were included and randomly divided into two groups. Moreover, coagulation indices, liver function indices, renal function indices, and SOFA and APACHE II scores did not significantly differ between the two groups (P > 0.05). The coagulation grade of the venous ports in the experimental group was lower than that in the control group and the two groups of filters, but the difference was not statistically significant (P = 0.337). Both sodium citrate solution infusion methods maintained a low blood calcium concentration (0.25–0.45 mmol/L) in the peripheral circulation pathway, and no patient developed hypocalcaemia (

Abstract Protein therapeutics are essential in treating various diseases, but their inherent biological instability and short circulatory half-lives in vivo pose challenges. Herein, a quantitative one-pot iterative living polymerization technique is reported towards precision control over the molecular structure and monomer sequence of protein-polymer conjugates, aiming to maximize physicochemical properties and biological functions of proteins. Using this quantitative one-pot iterative living polymerization technique, we successfully develop a series of sequence-controlled protein-multiblock polymer conjugates, enhancing their biostability, pharmacokinetics, cellular uptake, and in vivo biodistribution. All-atom molecular dynamics simulations are performed to disclose the definite sequence-function relationship of the bioconjugates, further demonstrating their sequence-encoded cellular uptake behavior and in vivo biodistribution in mice. Overall, this work provides a robust approach for creating precision protein-polymer conjugates with defined sequences and advanced functions as a promising candidate in disease treatment.

Abstract Background Medical school learning environment (MSLE) has a holistic impact on students’ psychosomatic health, academic achievements, and personal development. Students in different grades perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student’s grade in the perception of MSLE. Methods Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student’s grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch’s ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student’s grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed. Results A significant difference between two JHLES categories among students in different grades was observed (p

Abstract Background Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect. Objective To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota. Method In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing. Results Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group. Conclusion These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota. Trial registration The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043).

Abstract. Background:. Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. Methods:. In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. Results:. In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962–1.000 in the training cohort and 0.969–0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. Conclusion:. ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. Trial Registration:. Chictr.org.cn: ChiCTR2200059599.

Abstract Background Currently, no normal ultrasound data of the fetuses during the 20–40 gestation have been obtained for references of fetal growth and development. If such ultrasound data existed for prenatal diagnosis of possible diseases and abnormalities, neonates would be able to get timely treatment immediately after birth. This study was thus performed to obtain ultrasound parameters of normal fetuses during the 20–40 week gestation and the distribution of ultrasound parameters with the gestational age for references of detecting potential fetal diseases and abnormalities. Methods Normal fetuses without any abnormalities were enrolled, and the ultrasound parameters of the general biology, arteries, and aorta were measured and analyzed. Results 417 normal fetuses were enrolled. A significant (P

Abstract With the development of science and technology and economy, UAV is used more and more widely. However, the existing UAV trajectory planning methods have the limitations of high cost and low intelligence. In view of this, grey Wolf algorithm is being used to achieve collaborative trajectory optimization of UAV groups. However, it is found that the Grey Wolf optimization algorithm (GWO) has the problem of weak cooperation. In this study, based on the traditional GWO pheromone factor is introduced to improve it.. Aiming at the problem of unstable performance of swarm intelligence optimization algorithm under dynamic threat, deep reinforcement learning is used to optimize the model. An unmanned aerial vehicle swarm trajectory planning model was constructed based on the improved grey wolf algorithm. Through experimental analysis, the optimal fitness value of the improved grey wolf algorithm was lower than 0.43 of the grey wolf algorithm. Compared with other algorithms, the fitness value of this algorithm is significantly reduced and the stability is higher. In complex scenarios, the improved grey wolf algorithm had a trajectory length of 70.51 km and a planning time of 5.92 s, which was clearly superior to other algorithms. The path length planned by the research and design model was 58.476 km, which was significantly smaller than the other three models. The planning time was 5.33 s and the number of path extension points was 46. The indicator values of the Unmanned Aerial Vehicle swarm trajectory planning model designed by this research were all smaller than the other three models. By analyzing the results, the model can achieve low-cost trajectory optimization, providing more reasonable technical support for unmanned aerial vehicle mission execution.

Abstract Background BMI variability has been associated with increased cardiovascular disease risk in individuals with type 2 diabetes, however comparison between clinical studies and real-world observational evidence has been lacking. Furthermore, it is not known whether BMI variability has an effect independent of HbA1c variability. Methods We investigated the association between BMI variability and 3P-MACE risk in the Harmony Outcomes trial (n = 9198), and further analysed placebo arms of REWIND (n = 4440) and EMPA-REG OUTCOME (n = 2333) trials, followed by real-world data from the Tayside Bioresource (n = 6980) using Cox regression modelling. BMI variability was determined using average successive variability (ASV), with first major adverse cardiovascular event of non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death (3P-MACE) as the primary outcome. Results After adjusting for cardiovascular risk factors, a + 1 SD increase in BMI variability was associated with increased 3P-MACE risk in Harmony Outcomes (HR 1.12, 95% CI 1.08–1.17, P

Abstract Background This study aimed to explore the efficacy of hookwire for computed tomography (CT)-guided pulmonary nodule (PN) localization before video-assisted thoracoscopic surgery (VATS) resection and determine the risk factors for localization-related complications. Methods We enrolled 193 patients who underwent preoperative CT-guided PN hookwire localization. The patients were categorized into groups A (103 patients had no complications) and B (90 patients had complications) according to CT and VATS. Uni- and multivariate logistic regression analyses were used to identify risk factors for localization-related complications. A numerical rating scale was used to evaluate hookwire localization-induced pain. Results We successfully performed localization in 173 (89.6%) patients. Pneumothorax was the main complication in 82 patients (42.5%). Patient gender, age, body mass index, tumor diameter, consolidation tumor ratio, pathologic diagnosis, position adjustment during location, lesion location, waiting time for surgery, and pleural adhesions were not significantly different between the two groups. The number of nodules, number of punctures, scapular rest position, and depth of insertion within the lung parenchyma were significant factors for successful localization. Multivariate regression analysis further validated the number of nodules, scapular rest position, and depth of insertion within the lung parenchyma as risk factors for hookwire-localization-related complications. Hookwire localization-induced pain is mainly mild or moderate pre- and postoperatively, and some patients still experience pain 7 days postoperatively. Conclusions Hookwire preoperative PN localization has a high success rate, but some complications remain. Thus, clinicians should be vigilant and look forward to further improvement.

Abstract Background This study aims to explore the bidirectional causal relationship between immune cell phenotypes and chronic periodontitis using a Mendelian randomization framework. Materials and methods Through a two-sample Mendelian randomization analysis, this research examined genetic data related to 731 immune cell traits and chronic periodontitis. Instrumental variables were chosen based on their genetic links to either immune traits or periodontitis. Various statistical techniques, including MR-Egger regression, weighted median, and inverse-variance weighted (IVW) analysis, were employed to determine the causal connections. Results Predominantly using the IVW method, 26 distinct immune phenotypes were identified as potentially influencing periodontitis (P

Abstract Objective Medical staff, especially nurses, suffered great anxiety and stress from the COVID-19 pandemic, which negatively affected their sleep quality. In this study, we aimed to analyze the sleep quality of nursing staff after terminating the Zero-COVID-19 policy in China. Methods 506 participants were involved in our study. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep status of the participants. Binary regression was performed to evaluate the impact factors related to sleep difficulty. Results The majority of participants (96.44%) suffered from sleep disturbances. There were significant differences in age, education level and front-line activity between participants with good sleep quality and sleep difficulty. Younger age (16–25 years old) was independently associated with less sleep difficulty, while front-line activity was independently associated with severe sleep difficulty. Conclusion Sleep disorder was very common among nurses after ending the Zero-COVID-19 policy in China. More front-line nurses suffered severe sleep difficulty in particular, which should be worthy of attention.

Abstract The presence of cancer stem cells (CSCs) contributes significantly to treatment resistance in various cancers, including head and neck squamous cell carcinoma (HNSCC). Despite this, the relationship between cancer stemness and immunity remains poorly understood. In this study, we aimed to identify potential immunotherapeutic targets and sensitive drugs for CSCs in HNSCC. Using data from public databases, we analyzed expression patterns and prognostic values in HNSCC. The stemness index was calculated using the single-sample gene set enrichment analysis (ssgsea) algorithm, and weighted gene co-expression network analysis (WGCNA) was employed to screen for key stemness-related modules. Consensus clustering was then used to group samples for further analysis, and prognosis-related key genes were identified through regression analysis. Our results showed that tumor samples from HNSCC exhibited higher stemness indices compared to normal samples. WGCNA identified a module highly correlated with stemness, comprising 187 genes, which were significantly enriched in protein digestion and absorption pathways. Furthermore, we identified sensitive drugs targeting prognostic genes associated with tumor stemness. Notably, two genes, HLF and CCL11, were found to be highly associated with both stemness and immunity. In conclusion, our study identifies a stemness-related gene signature and promising drug candidates for CSCs of HNSCC. Additionally, HLF and CCL11, which are associated with both stemness and immunity, represent potential targets for immunotherapy in HNSCC.

Abstract Segmental bone defects, arising from factors such as trauma, tumor resection, and congenital malformations, present significant clinical challenges that often necessitate complex reconstruction strategies. Hydrogels loaded with multiple osteogenesis-promoting components have emerged as promising tools for bone defect repair. While the osteogenic potential of the Piezo1 agonist Yoda1 has been demonstrated previously, its hydrophobic nature poses challenges for effective loading onto hydrogel matrices.In this study, we address this challenge by employing Yoda1-pretreated bone marrow-derived mesenchymal stem cell (BMSCs) exosomes (Exo-Yoda1) alongside exosomes derived from BMSCs (Exo-MSC). Comparatively, Exo-Yoda1-treated BMSCs exhibited enhanced osteogenic capabilities compared to both control groups and Exo-MSC-treated counterparts. Notably, Exo-Yoda1-treated cells demonstrated similar functionality to Yoda1 itself. Transcriptome analysis revealed activation of osteogenesis-associated signaling pathways, indicating the potential transduction of Yoda1-mediated signals such as ErK, a finding validated in this study. Furthermore, we successfully integrated Exo-Yoda1 into gelatin methacryloyl (GelMA)/methacrylated sodium alginate (SAMA)/β-tricalcium phosphate (β-TCP) hydrogels. These Exo-Yoda1-loaded hydrogels demonstrated augmented osteogenesis in subcutaneous ectopic osteogenesis nude mice models and in rat skull bone defect model. In conclusion, our study introduces Exo-Yoda1-loaded GELMA/SAMA/β-TCP hydrogels as a promising approach to promoting osteogenesis. This innovative strategy holds significant promise for future widespread clinical applications in the realm of bone defect reconstruction. Graphical Abstract

Abstract Passively harmonic mode-locking has been experimentally demonstrated in an erbium-doped fiber laser with large normal dispersion using single-multi-single mode structure as artificial saturable absorber. By increasing the pump power under the same polarization setting, the mode-locking operation can switch from fundamental mode-locked to 5th order harmonic mode-locked. Highest repetition rate of 4.26 MHz (5th order harmonic) is observed, with pulse width and pulse energy ascertained at 290 fs and 3.0 nJ, respectively. Excellent signal-to-noise ratio (SNR) of above 50 dB is observed for all harmonic orders. The findings validated that SMS structure can be used to generate stable and switchable high order of harmonic mode-locked. The low-cost SMS fiber for harmonic mode-locked generation technique could lay the groundwork for future sustainable industrial growth.

Abstract Long-term treatment of myocardial infarction is challenging despite medical advances. Tissue engineering shows promise for MI repair, but implantation complexity and uncertain outcomes pose obstacles. microRNAs regulate genes involved in apoptosis, angiogenesis, and myocardial contraction, making them valuable for long-term repair. In this study, we find downregulated miR-199a-5p expression in MI. Intramyocardial injection of miR-199a-5p into the infarcted region of male rats revealed its dual protective effects on the heart. Specifically, miR-199a-5p targets AGTR1, diminishing early oxidative damage post-myocardial infarction, and MARK4, which influences long-term myocardial contractility and enhances cardiac function. To deliver miR-199a-5p efficiently and specifically to ischemic myocardial tissue, we use CSTSMLKAC peptide to construct P-MSN/miR199a-5p nanoparticles. Intravenous administration of these nanoparticles reduces myocardial injury and protects cardiac function. Our findings demonstrate the effectiveness of P-MSN/miR199a-5p nanoparticles in repairing MI through enhanced contraction and anti-apoptosis. miR199a-5p holds significant therapeutic potential for long-term repair of myocardial infarction.

Abstract Objectives Esophagectomy after chemoradiotherapy is associated with an increased risk of surgical complications. The significance of preoperative neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio after chemoradiotherapy in predicting pulmonary complications following radical esophagectomy in esophageal squamous cell carcinoma patients receiving preoperative chemoradiotherapy remains unknown. We aimed to investigate the utility of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in predicting the pulmonary complications of esophagectomy after preoperative chemoradiotherapy. Methods We retrospectively reviewed 111 consecutive patients with stage III esophageal squamous cell carcinoma who received preoperative chemoradiotherapy followed by esophagectomy between January 2009 and December 2017. Laboratory data were collected before the operation and surgical outcomes and complications were recorded. We calculated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio and correlated them with the clinical parameters, postoperative complications, overall survival, and disease-free survival. Results Postoperative complications were observed in 75 (68%) patients, including 32 (29%) with pulmonary complications. The preoperative neutrophil-to-lymphocyte ratio of ≥ 3 (P = 0.008), clinical T4 classification (P = 0.007), and advanced stage IIIC (P = 0.012) were significantly associated with pulmonary complications. Pulmonary complication rates were 15% and 38% in patients with preoperative neutrophil-to-lymphocyte ratio of

Abstract H7N9 subtype avian influenza viruses (AIVs) cause 1567 human infections and have high mortality, posing a significant threat to public health. Previously, we reported that two avian-derived H7N9 isolates (A/chicken/Eastern China/JTC4/2013 and A/chicken/Eastern China/JTC11/2013) exhibit different pathogenicities in mice. To understand the genetic basis for the differences in virulence, we constructed a series of mutant viruses based on reverse genetics. We found that the PB2-E627K mutation alone was not sufficient to increase the virulence of H7N9 in mice, despite its ability to enhance polymerase activity in mammalian cells. However, combinations with PB1-V719M and/or PA-N444D mutations significantly enhanced H7N9 virulence. Additionally, these combined mutations augmented polymerase activity, thereby intensifying virus replication, inflammatory cytokine expression, and lung injury, ultimately increasing pathogenicity in mice. Overall, this study revealed that virulence in H7N9 is a polygenic trait and identified novel virulence-related residues (PB2-627K combined with PB1-719M and/or PA-444D) in viral ribonucleoprotein (vRNP) complexes. These findings provide new insights into the molecular mechanisms underlying AIV pathogenesis in mammals, with implications for pandemic preparedness and intervention strategies.

Abstract Objective Coronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery. Methods This was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias. Results A total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events. Conclusions Postoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.

Background/Aims: Incidence of colorectal cancer is rapidly increasing worldwide. Extracellular superoxide dismutase (EcSOD; SOD3) is an antioxidant enzyme. However, SOD3 roles in colorectal cancer progression remain uncertain. Materials and Methods: Superoxide dismutase 3 expression was evaluated, and we analyzed clinical relevance of SOD3 expression in colorectal cancer. Subsequently, SOD3 roles in colorectal cancer progression were detected by gain of function experiments. Changes in subcutaneous tumor and liver nodule size after SOD3 overexpression were examined in nude mice. The expression of proliferation marker Ki67 was assessed by immunohistochemical staining. Results: Supperoxide dismutase 3 was downregulated in colorectal cancer (P < .01). Downregulation of SOD3 was correlated with unfavorable outcomes (P < .05). Superoxide dismutase 3 upregulation limited the proliferative (P < .05), migrative (P < .01) and invasive actions of colorectal cancer cells (P < .01) by suppressing epithelial–mesenchymal transition. Moreover, SOD3 overexpression reduced Ki67 expression (P < .01) and blocked tumor growth (P < .01) and liver metastasis (P < .001) in mouse tumor model. Conclusion: Superoxide dismutase 3 upregulation attenuates tumor growth and liver metastasis in colorectal cancer, suggesting that SOD3 has potential diagnostic and prognostic values regarding colorectal cancer treatment.

Abstract Introduction Most patients undergoing the Nuss procedure reported moderate to severe pain after surgery. This study aimed to investigate the efficacy and safety of ultrasound-guided serratus anterior plane block (SAPB) combined with transversus thoracic muscle plane (TTMP) block for relieving acute pain in patients undergoing the Nuss procedure. Methods The enrolled patients in our study were allocated to either receive combined nerve blocks with ropivacaine (NB group) or saline (CON group). The primary outcome of this study was postoperative pain at 2, 4, 8, 16, 24, 36, and 48 h during rest and movement (coughing). Secondary outcomes included intraoperative dosage of remifentanil, the time to extubation and the length of stay in the post-anesthesia care unit (PACU), the total acetaminophen and codeine tablet consumption, time to first bowel movement, time to first flatus, opioid-related adverse events, and the length of hospital stay. Results Patients in the NB group had significantly lower Numerical Rating Scale (NRS) pain scores compared with the CON group. The NB group required significantly less postoperative acetaminophen consumption and lower dosages of perioperative sufentanyl and remifentanil compared with the CON group. The length of stay in the PACU and time to extubation were significantly increased in the CON group compared with the NE group. Time to first bowel movement and time to first flatus were earlier in the NB group. But there were no significant differences between the groups in terms of the length of hospital stay and codeine tablet consumption. Conclusion Ultrasound-guided SAPB and TTMP blocks in patients undergoing the Nuss procedure could provide effective analgesia. Trial Registration This study was registered in the Chinese Clinical Trial Registry (ChiCTR2000038506).

Introduction The rapid growth of e-cigarette usage among youth and young people has emerged as a significant public health concern. It is imperative to initiate effective vaping prevention campaigns and undertake relevant research to address this pressing issue. This research seeks to identify effective video advertisements to deter young people from starting to use e-cigarettes. It aims to offer evidencebased insights and recommendations for creating communication materials and designing messages for youth e-cigarette prevention efforts. Methods College students aged 18–24 years (n=40) participated in focus groups within this qualitative study. After viewing four stimulus videos, participants discussed what they perceived as effective and ineffective video characteristics, as well as suggestions for future videos. Results Effective video characteristics included the use of real-life testimonials, displaying specific health hazards, revealing harmful chemical ingredients and the deceptive nature of flavors, and positively perceived effectiveness. Participants generally found that videos with strong visual impact and graphics were more engaging and that approaches using fear and emotion were more effective. Ineffective characteristics included complex and exaggerated information, lack of empathy and irrelevance, insufficiently specific information, extreme and death-themed content, industry messages, as well as preachy tones, animations, metaphors, dull formats, excessive length, and scenes of e-cigarette use. Conclusions Developing anti-e-cigarette campaign materials for youth necessitates target audience-focused qualitative research. This helps in deeply exploring and identifying effective themes and messages, as well as video characteristics and details while avoiding ineffective or even misleading messages and themes from young people’s perspectives outside the United States. Future development of e-cigarette prevention videos for Chinese college students may consider incorporating localized real-life testimonial cases to convey specific harms, including self-efficacy information, and utilizing fear and emotional appeals.

Objective To observe the effects of a 1 470 nm semiconductor laser on vaporization cutting, coagulation, and thermal injury of ex vivo animal tissues, aiming to explore the feasibility of its application in the treatment of benign prostatic hyperplasia. Methods The experimental group and control group were treated with HANS-D1 and ML-DD01FI 1 470 nm semiconductor laser therapy equipment, respectively. Fresh ex vivo pig bladder tissue was exposed to lasers with the optical fiber placed at distances of 0.5 cm and 1 cm from the tissue for 5 s. The effects of layers at powers of 60, 90, 120, 150, and 160 W on tissue injury were observed. Ex vivo dog prostate and pig kidney tissues were used for vaporization ablation and cutting to observe the effects of lasers at the same power levels on tissue vaporization and cutting thermal injury. Additionally, in coagulation mode, the effects of 30, 40, and 50 W semiconductor lasers on tissue coagulation were observed after irradiating ex vivo pig kidney tissue for 5, 10, and 15 seconds.Results When the optical fiber was placed 1 cm away from the tissue, the 1 470 nm semiconductor lasers did not cause accidental damage to adjacent normal bladder tissue. However, at a distance of 0.5 cm, the 120 W, 150 W, or 160 W lasers caused slight damage to the bladder tissue. In addition, with the increase in output power, the vaporization ablation efficiency of 60-160 W lasers on dog prostate tissue gradually increased, showing a good linear correlation between vaporization volume and total energy consumption (P0.05). Moreover, when performing vaporization cutting on ex vivo pig kidney tissue with a cross-sectional area of 1 cm2, the efficiency of vaporization cutting by the 60-160 W 1 470 nm semiconductor lasers increased with the increase in output power (P0.05). Conclusion The 1 470 nm semiconductor laser shows good vaporization ablation, cutting, and coagulation effect on ex vivo tissues, with a good linear correlation between the effect and the output energy.

Foam cells play a pivotal role in the progression of atherosclerosis progression by triggering inflammation within arterial walls. They release inflammatory molecules that attract additional immune cells, leading to further macrophage recruitment and plaque development. In this study, we develop an osteopontin (OPN) antibody-conjugated niobium carbide (Nb2C-aOPN) MXenzyme designed to selectively target and mildly ablate foam cells while reducing inflammation in the plaque microenvironment. This approach utilizes photonic hyperthermia to decrease plaque size by enhancing cholesterol regulation through both passive cholesterol outflow and positive cholesterol efflux. Nb2C-aOPN MXenzyme exhibits multiple enzyme-mimicking properties, including catalase, superoxide dismutase, peroxidase and glutathione peroxidase, and acts as a scavenger for reactive oxygen and nitrogen species. The inhibition of reactive oxygen and nitrogen species synergizes with photothermal ablation to promote positive cholesterol efflux, leading to reduced macrophage recruitment and a shift in macrophage phenotype from M1 to M2. This integrative strategy on cholesterol regulation and anti-inflammation highlights the potential of multifunctional 2D MXenzyme-based nanomedicine in advancing atherosclerotic regression.

Abstract In the context of green transportation, the automotive industry is undergoing a revolution in autonomous, connected, electric, and shared (ACES) vehicles. ACES vehicles have a relatively short history and there is limited relevant market data available. Therefore, quantitative research on the economic impact of ACES trends remains a new area of exploration. The purpose of the paper is to explore the economic impact of ACES trends on the automotive value chain, with a specific focus on the production and aftermarket segments. In the paper, a detailed quantitative analysis of the installation scale and the market size of Chinese automotive production as well as the income changes of Chinese automotive aftermarket in 2030 is conducted. The findings show that the new markets for power batteries, electric powertrains, sensors, in-vehicle software and chips are created, thereby delivering more value to the business. While the ACES trends are expected to decrease the average aftermarket income per vehicle, the growth of the vehicle stock suggests significant potential for the development of the automotive aftermarket in 2030. Our research contributes by offering a business perspective on the impact of ACES trends. The quantitative insights presented are timely and crucial for all the stakeholders along the value chain, enabling them to adapt and thrive in the dynamic automotive landscape and align their strategies with the transformative ACES trends.

Abstract Background The accurate diagnosis and effective management of arrhythmias are crucial, with nurses playing a key role in the early detection and treatment, significantly impacting patient outcomes. Improving education on arrhythmias among nurses, especially in critical care and perioperative settings, can enhance patient safety and the quality of care. Methods A total of 116 trainee nurses were randomly divided into two groups: one utilizing the conceive-design-implement-operate (CDIO) model and the other employing a traditional lecture-based learning (LBL) method, to undergo arrhythmia training. The studyassessed the effects of the two teaching methods and investigated the students’ attitudes toward these educational practices, with all participants completing pre- and post-course tests. Results The CDIO model significantly enhances nursing students’ arrhythmia proficiency, yielding higher test scores and sustained improvement after 24-week compared to the traditional LBL method, alongside markedly better self-learning enthusiasm, understanding, satisfaction with the teaching approach and effectiveness, and interest in learning arrhythmia. The CDIO model in nursing arrhythmia courses boosts theoretical knowledge and application, showing potential in clinical skill enhancement. Conclusions Our study introduces the CDIO model in nursing arrhythmia courses, with improvement in knowledge and skills, and promise for broader application.

Abstract Objective To analyze the vulnerability factors of snakebite patients in China. Methods Multi-stage random sampling was used as the main sampling method and snowball sampling as the auxiliary sampling method. The knowledge, attitude and behavior of snakebite among Chinese residents were investigated. Non-parametric test was used to compare the percentage differences in residents’ knowledge, attitude and behavior of snakebite, and generalized linear regression analysis was used to analyze the influencing factors, and the vulnerability factors of snakebite patients were comprehensively analyzed. Results A total of 6338 subjects were included in this study, of which 68.4% were males, and 58.6% were farmers, workers and service personnel. The median total score of knowledge, attitude, and behavior was 26 (22,36). The patients who were improperly treated after injury were ligation proximal to the affected area (23.43%), squeezing (21.82%), and oral and suction wounds (8.74%). Did not go to hospital due to poverty (1351 cases) and did not receive antivenom (2068 cases). There were 21.32% and 32.63%, respectively. Among 4270 patients injected with antivenom 30.7% were vaccinated within 2 h. Among the patients who went to the hospital for treatment (4987), 75.0% arrived at the hospital within 6 h; Among the 4,761 patients who made emergency calls, 37.4% were treated within 0.5 h. Conclusions Snakebite patients in China have weak knowledge about snakebite, low awareness of medical treatment, lack of correct prevention and emergency treatment measures, dependence on folk remedies, poor housing and so on. In addition, there are low availability of antivenoms and unreasonable distribution of medical resources in some areas of China. Multisectoral and multidisciplinary cooperation should be developed to prevent and control snakebites in order to reduce the burden caused by snakebites.

Abstract SARS-CoV-2 infection is initiated by Spike glycoprotein binding to the human angiotensin-converting enzyme 2 (ACE2) receptor via its receptor binding domain. Blocking this interaction has been proven to be an effective approach to inhibit virus infection. Here we report the discovery of a neutralizing nanobody named VHH60, which was directly produced from an engineering nanobody library based on a commercialized nanobody within a very short period. VHH60 competes with human ACE2 to bind the receptor binding domain of the Spike protein at S351, S470-471and S493-494 as determined by structural analysis, with an affinity of 2.56 nM. It inhibits infections of both ancestral SARS-CoV-2 strain and pseudotyped viruses harboring SARS-CoV-2 wildtype, key mutations or variants at the nanomolar level. Furthermore, VHH60 suppressed SARS-CoV-2 infection and propagation 50-fold better and protected mice from death for twice as long as the control group after SARS-CoV-2 nasal infections in vivo. Therefore, VHH60 is not only a powerful nanobody with a promising profile for disease control but also provides evidence for a highly effective and rapid approach to generating therapeutic nanobodies.

Abstract In eukaryotes, the nucleolus is the critical non-membranous organelle within nuclei that is responsible for ribosomal DNA (rDNA) transcription and ribosome biogenesis. The transcription of rDNA, a rate-limiting step for ribosome biogenesis, is tightly regulated to meet the demand for global protein synthesis in response to cell physiology, especially in neurons, which undergo rapid changes in morphology and protein composition during development and synaptic plasticity. However, it is unknown how the pre-initiation complex for rDNA transcription is efficiently assembled within the nucleolus in neurons. Here, we report that the nucleolar protein, coronin 2B, regulates rDNA transcription and maintains nucleolar function through direct interaction with upstream binding factor (UBF), an activator of RNA polymerase I transcriptional machinery. We show that coronin 2B knockdown impairs the formation of the transcription initiation complex, inhibits rDNA transcription, destroys nucleolar integrity, and ultimately induces nucleolar stress. In turn, coronin 2B-mediated nucleolar stress leads to p53 stabilization and activation, eventually resulting in neuronal apoptosis. Thus, we identified that coronin 2B coordinates with UBF to regulate rDNA transcription and maintain proper nucleolar function in neurons.

Abstract The influences of thermal cycling ageing on structures and insulation performances of polypropylene (PP)/elastomer/boron nitride (BN) nanocomposites are investigated. The Melt blending method was used to prepare the nanocomposites, in which propylene‐based elastomer (PBE) or ethylene‐octene copolymer elastomer (EOC) was contained for comparison. Then, the samples were treated using a thermal cycling process with a temperature range from −30 to 150°C, and the number of thermal cycles was set from 0 to 15. Scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry and X‐ray diffraction measurements were taken to facilitate the comprehension of structural changes. Additionally, measurements were taken to assess the trap distribution and direct current (DC) breakdown strength of the samples. The obtained results revealed that following thermal cycling ageing, the morphology and crystallinity of PP/PBE/BN remained almost unchanged. In contrast, PP/EOC/BN exhibited substantial microstructural damage accompanied by a significant reduction in crystallinity. As the number of thermal cycles increased, the trap level and DC breakdown strength of PP/PBE/BN were maintained at high levels, while those of PP/EOC/BN initially remained stable but then experienced a sharp decline. It is suggested that the addition of BN nanoparticles enhances the thermal cycling ageing resistance of the PP/PBE blend, whereas it weakens this resistance of the PP/EOC blend.

Abstract In response to the current challenges fire detection algorithms encounter, including low detection accuracy and limited recognition rates for small fire targets in complex environments, we present a lightweight fire detection algorithm based on an improved YOLOv5s. The introduction of the CoT (Contextual Transformer) structure into the backbone neural network, along with the creation of the novel CSP1_CoT (Cross stage partial 1_contextual transformer) module, has effectively reduced the model’s parameter count while simultaneously enhancing the feature extraction and fusion capabilities of the backbone network; The network’s Neck architecture has been extended by introducing a dedicated detection layer tailored for small targets and incorporating the SE (Squeeze-and-Excitation) attention mechanism. This augmentation, while minimizing parameter proliferation, has significantly bolstered the interaction of multi-feature information, resulting in an enhanced small target detection capability; The substitution of the original loss function with the Focal-EIoU (Focal-Efficient IoU) loss function has yielded a further improvement in the model’s convergence speed and precision; The experimental results indicate that the modified model achieves an mAP@.5 of 96% and an accuracy of 94.8%, marking improvements of 8.8% and 8.9%, respectively, over the original model. Furthermore, the model’s parameter count has been reduced by 1.1%, resulting in a compact model size of only 14.6MB. Additionally, the detection speed has reached 85 FPS (Frames Per Second), thus satisfying real-time detection requirements. This enhancement in precision and accuracy, while simultaneously meeting real-time and lightweight constraints, effectively caters to the demands of fire detection.

Abstract Background Though tamoxifen achieves success in treating estrogen receptor α (ERα)-positive breast cancer, the followed development of tamoxifen resistance is a common challenge in clinic. Signals downstream of prolactin receptor (PRLR) could synergize with ERα in breast cancer progression. However, the potential effect of targeting PRL-PRLR axis combined with tamoxifen has not been thoroughly investigated. Methods High-throughput RNA-seq data obtained from TCGA, Metabric and GEO datasets were analyzed to explore PRLR expression in breast cancer cell and the association of PRLR expression with tamoxifen treatment. Exogenous or PRL overexpression cell models were employed to investigate the role of activated PRLR pathway in mediating tamoxifen insensitivity. Immunotoxin targeting PRLR (N8-PE24) was constructed with splicing-intein technique, and the efficacy of N8-PE24 against breast cancer was evaluated using in vitro and in vivo methods, including analysis of cells growth or apoptosis, 3D spheroids culture, and animal xenografts. Results PRLR pathway activated by PRL could significantly decrease sensitivity of ERα-positive breast cancer cells to tamoxifen. Tamoxifen treatment upregulated transcription of PRLR and could induce significant accumulation of PRLR protein in breast cancer cells by alkalizing lysosomes. Meanwhile, tamoxifen-resistant MCF7 achieved by long-term tamoxifen pressure exhibited both upregulated transcription and protein level of PRLR. Immunotoxin N8-PE24 enhanced sensitivity of breast cancer cells to tamoxifen both in vitro and in vivo. In xenograft models, N8-PE24 significantly enhanced the efficacy of tamoxifen and paclitaxel when treating PRLR-positive triple-negative breast cancer. Conclusions PRL-PRLR axis potentially associates with tamoxifen insensitivity in ERα-positive breast cancer cells. N8-PE24 could inhibit cell growth of the breast cancers and promote drug sensitivity of PRLR-positive breast cancer cells to tamoxifen and paclitaxel. Our study provides a new perspective for targeting PRLR to treat breast cancer.

Esophageal cancer is a common malignant tumor of digestive tract. Remarkable regional difference is a prominent feature of the clinical epidemiology of esophageal cancer. They are mainly manifested in incidence rate, incidence type, onset age, and gene mutation. These differences may be related to dietary habits, lifestyle, and environmental factors. In recent years, research on the regional differences in esophageal cancer has gradually deepened. This article summarizes the differences in incidence rate, incidence type, gene mutations, epigenetics, risk factors, and prognosis of esophageal cancer in different regions, including Asia (China, India, Japan, and other countries), Europe, America (the United States), Africa, and other regions. Understanding these differences can help doctors and public health experts understand the risk factors and causes of esophageal cancer and further develop highly effective prevention and treatment strategies to reduce the occurrence and mortality rate of this malignancy.

Pen shell (Atrina pectinata) is a Bivalvia species with high commercial value in China. However, large scale production is difficult owing to the lack of seed. Pen shell uses external fertilization with sperm stored in the testis in a nonmotile state. Sperm motility is initiated when they are released from the reproductive tract into the aquatic environment, which enables fertilization. Various chemical signals including pH, ions, and cyclic nucleotides control sperm motility. However, there are interspecific differences in activation conditions between different Bivalvia species. Screening out an effective activating medium is the basis of artificial breeding technology.Swimming parameters, such as total motile sperm (TM), movement velocity, and beat-cross frequency (BCF) are common indicators to evaluate sperm quality. Sperm must have sufficient motility to reach the egg to complete fertilization. In addition, sperm needs a large amount of ATP to maintain its swimming movement. Intracellular ATP content controls the duration of the sperm movement phase in most marine species. Studying the movement characteristics and energy metabolism of sperm during activation will help develop and optimize artificial breeding technology. Studies of A. pectinata mainly focus on their oocytes. However, the activation conditions, moving characteristics, and energy metabolism of sperm during activation remains unknown. Thus, there is an urgent need to screen appropriate media and study the activation mechanisms of A. pectinata sperm.Adult A. pectinata were collected from Wuzhizhou Island, Hainan Province in November 2021. Artificial seawater with different levels of ammonia ions and pH were used to activate sperm. This study examined A. pectinata sperm activation in artificial seawater by varying the ammonia ion concentration and pH. The change in sperm motility, curvilinear velocity (VCL), straight-line velocity (VSL), average path velocity (VAP), and BCF were described. The ATP content, ATPase activities, and superoxide dismutase (SOD) activity were quantitatively recorded during the full activated stage. The motility was slightly improved by increasing the pH of seawater, but could not achieve the fully activated stage. Furthermore, the motility was significantly improved when activated by alkalized seawater containing ammonia ions, and the best results were observed in groups containing 3 mmol/L ammonia ion: The sperm motility index (MI) was in the fully activated stage (MI ≥ 4) until the end of the experiment, with TM ≥ 80%, VCL > 56 μm/s, VSL > 17 μm/s, VAP > 30 μm/s, and BCF > 6 Hz. Sperm ATP content decreased to 30.29% of their initial values [(128.80±66.92) μmol/g prot] during 5 min post activation and was maintained at this level during post-activation. ATPase activities were maintained at a constant level. Na+-K+-ATPase activity was lower [(0.62±0.03) U/mg prot] compared to Ca2+-Mg2+-ATPase activity [(6.08±0.04) U/mg prot]. The SOD activity of sperm steadily decreased to [(1.23±0.73) U/mg prot] during 15 min post activation and remained stable.In conclusion, pH was not the decisive factor in pen shell sperm motility. Instead, ammonium ion promoted sperm activation. There was a significant decrease in sperm ATP concentration (P

Abstract Background Epidermal patterning factor / -like (EPF/EPFL) gene family encodes a class of cysteine-rich secretory peptides, which are widelyfound in terrestrial plants.Multiple studies has indicated that EPF/EPFLs might play significant roles in coordinating plant development and growth, especially as the morphogenesis processes of stoma, awn, stamen, and fruit skin. However, few research on EPF/EPFL gene family was reported in Gossypium. Results We separately identified 20 G. raimondii, 24 G. arboreum, 44 G. hirsutum, and 44 G. barbadense EPF/EPFL genes in the 4 representative cotton species, which were divided into four clades together with 11 Arabidopsis thaliana, 13 Oryza sativa, and 17 Selaginella moellendorffii ones based on their evolutionary relationships. The similar gene structure and common motifs indicated the high conservation among the EPF/EPFL members, while the uneven distribution in chromosomes implied the variability during the long-term evolutionary process. Hundreds of collinearity relationships were identified from the pairwise comparisons of intraspecifc and interspecific genomes, which illustrated gene duplication might contribute to the expansion of cotton EPF/EPFL gene family. A total of 15 kinds of cis-regulatory elements were predicted in the promoter regions, and divided into three major categories relevant to the biological processes of development and growth, plant hormone response, and abiotic stress response. Having performing the expression pattern analyses with the basic of the published RNA-seq data, we found most of GhEPF/EPFL and GbEPF/EPFL genes presented the relatively low expression levels among the 9 tissues or organs, while showed more dramatically different responses to high/low temperature and salt or drought stresses. Combined with transcriptome data of developing ovules and fibers and quantitative Real-time PCR results (qRT-PCR) of 15 highly expressed GhEPF/EPFL genes, it could be deduced that the cotton EPF/EPFL genes were closely related with fiber development. Additionally, the networks of protein–protein interacting among EPF/EPFLs concentrated on the cores of GhEPF1 and GhEPF7, and thosefunctional enrichment analyses indicated that most of EPF/EPFLs participate in the GO (Gene Ontology) terms of stomatal development and plant epidermis development, and the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways of DNA or base excision repair. Conclusion Totally, 132 EPF/EPFL genes were identified for the first time in cotton, whose bioinformatic analyses of cis-regulatory elements and expression patterns combined with qRT-PCR experiments to prove the potential functions in the biological processes of plant growth and responding to abiotic stresses, specifically in the fiber development. These results not only provide comprehensive and valuable information for cotton EPF/EPFL gene family, but also lay solid foundation for screening candidate EPF/EPFL genes in further cotton breeding.

Abstract Sarcopenia (low muscle mass, i.e., quantity) is associated with poor clinical outcomes in patients with acute-on-chronic liver failure (ACLF). In this study, we aimed to illustrate the clinical prognostic value of myosteatosis (muscle fat infiltration) for short-term mortality in patients with ACLF. We retrospectively enrolled consecutive patients with ACLF between January 2019 and January 2022. Computed tomography-based body composition analysis was performed at the third lumbar vertebral level to determine skeletal muscle radiation attenuation. Fine and Gray’s competing risk regression model, with liver transplantation as a competing risk, was used to assess the factors associated with 90-day mortality. A total of 431 patients with ACLF were included. Myosteatosis and sarcopenia were observed in 261 (60.6%) and 87 (20.2%) patients, respectively. Competitive risk regression showed that age (HR 1.021, 95% CI 1.000–1.043, P = 0.042), APASL ACLF Research Consortium (AARC) score (HR 1.498, 95% CI 1.312–1.710, P

Abstract Background Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurosurgical emergency with a high mortality rate. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) are delayed products of early brain injury (EBI), which may constitute the principal determinant of an unfavorable patient prognosis. Consequently, the mitigation of DCI and CVS assumes paramount significance in the pursuit of enhanced patient outcomes. However, except for oral nimodipine, there is no effective therapy available in the current guideline. Hence, the exigency arises to proffer novel treatment paradigms. The diversity of hydrogen therapeutic targets has been largely reported in basic research, unveiling its latent capacity to ameliorate EBI in aSAH patients. Methods Early Hydrogen–Oxygen Gas Mixture Inhalation in Patients with Aneurysmal Subarachnoid Hemorrhage (HOMA), a single-center, prospective, open-labeled, randomized controlled clinical trial, endeavors to evaluate the efficacy and safety of hydrogen–oxygen gas mixture inhalation therapy in aSAH patients. A cohort of 206 patients will be randomized to either hydrogen–oxygen gas mixture inhalation group (8 h per day, 3 L/min, hydrogen concentration of 67%, oxygen concentration of 33%) or oxygen inhalation group (8 h per day, 3 L/min, oxygen concentration of 33%) within 72 h after aSAH and treated for 7 days in the ICU ward. The primary outcomes are the incidence of DCI and CVS during hospitalization. Discussion The HOMA aims to evaluate the effectiveness of hydrogen–oxygen gas mixture inhalation therapy in preventing DCI or CVS and improving outcomes in aSAH patients. Notably, this is the first large-scale trial of hydrogen therapy in aSAH patients. Given that the Chinese population represents a significant portion of the global population and the increasing incidence of stroke due to aging, optimizing patient care is vital. Given the current challenges in aSAH patient outcomes, initiating more prospective clinical trials is essential. Recent research has shown hydrogen’s therapeutic potential, aligning with EBI in aSAH, driving our exploration of hydrogen therapy’s mechanisms in post-aneurysm rupture damage. Ethics and dissemination The protocol for the HOMA study was approved by the Ethics Committee of Beijing Tiantan Hospital, Capital Medical University (KY 2022–020-02). All results of the present study will be published in peer-reviewed journals and presented at relevant conferences. Trial registration ClinicalTrials.gov NCT05282836. Registered on March 16, 2022.