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With the increasing clinical demand for orthopedic implants, bone tissue engineering based on a variety of bioactive materials has shown promising applications in bone repair. And various physiological cues, such as mechanical, electrical, and magnetic stimulation, can influence cell fate and participate in bone regeneration. Natural bone has a piezoelectric effect due to the non-centrosymmetric nature of collagen, which can aid in cell adhesion, proliferation and differentiation, and bone growth by converting mechanical stimuli into electrical stimuli. Piezoelectric materials have the same piezoelectric effect as human bone, and they are able to deform in response to physiological movement, thus providing electrical stimulation to cells or damaged tissue without the need for an external power source. Among them, Barium titanate (BaTiO3) is widely used in tumor therapy, tissue engineering, health detection and drug delivery because of its good biocompatibility, low cytotoxicity and good piezoelectric properties. This review describes the piezoelectric effect of natural bone and the characteristics of various types of piezoelectric materials, from the synthesis and physicochemical characteristics of BaTiO3 and its application in biomedicine. And it highlights the great potential of BaTiO3 as piezoelectric biomaterials in the field of bone tissue engineering in anticipation of providing new ideas and opportunities for researchers.The translational potential of this article: This review systematically discusses barium titanate, a bioactive material that can mimic the piezoelectric effect of natural bone tissue, which can intervene in the regenerative repair of bone by providing a sustained electrical microenvironment for bone repair scaffolds. This may help to solve the current problem of poor osteogenic properties of bioactive materials by utilizing barium titanate.

Abstract Background Precision in detecting pathogens in sepsis patients is crucial for deploying targeted therapeutic strategies. The objective of the present investigation was to assess the efficacy of targeted nanopore sequencing (TNPseq) as a method for detecting sepsis pathogens. Methods For this investigation, we stratified 90 patients with sepsis into ‘improved’ and ‘unimproved’ groups based on their clinical outcomes. Pathogenic microorganisms were detected in various sample types on the day of sepsis diagnosis, utilizing both conventional culture and TNPseq techniques. A comparative analysis of these methodologies was undertaken to assess their performance and efficacy in identifying pathogens in sepsis infections and discern pathogens with significant differences between the distinct patient groups. Results The TNPseq analysis demonstrated superior performance in detecting pathogens in sepsis patients, achieving a significantly higher positivity rate (94.4%) compared to the culture method (30.0%, p

Abstract Background As aquaculture continues to expand globally, diseases caused by Vibrio species are becoming increasingly prevalent. Vibriosis encompasses a range of infections, which can lead to symptoms such as skin lesions, hemorrhaging, and high mortality rates in fish and shellfish, especially in high-density farming systems, resulting in significant economic losses. Simultaneously, the extensive use of antibiotics has fostered the emergence of antibiotic-resistant bacteria, exacerbated disease outbreaks, and complicated control measures. Phage therapy, which leverages bacteriophages as natural antibacterial agents, offers a promising eco-friendly alternative to the antibiotics used in aquaculture. This study aimed to evaluate the potential of two vibriophages for phage therapy in aquaculture. Results Two virulent vibriophages, vB_VcaP_R24D and vB_VcaP_R25D, were isolated from aquaculture wastewater from seafood markets using Vibrio campbellii LMG 11216T as the host strain. The two vibriophages were identified based on their morphology, infection dynamics, host range, genomic features, lytic activity, and environmental stability. Both phages belong to the podovirus morphotype and exhibit a lytic life cycle characterised by a short latent period (

Abstract Background The XEN45 Gel Stent (XGS) is an innovative, minimally invasive glaucoma surgery device, which is typically inserted via an ab-interno method, avoiding conjunctival dissection. With increasing experience, some surgeons have advocated for a transconjunctival ab-externo approach, with or without conjunctival dissection, for the delivery of XGS. Case presentation A 33-year-old male patient with a history of primary open-angle glaucoma diagnosed three years ago presented to the clinic with the complaint of visual field loss. This case report presents the initial implantation of XGS in both glaucoma eyes, using the transconjunctival ab-externo technique without conjunctival dissection. However, subsequent follow-up revealed that in the left eye, the XGS had been fractured as a result of external force. Meanwhile, in the right eye, the displacement of the XGS was attributed to the surgical needlework. To facilitate re-implantation, the transconjunctival ab-externo approach with conjunctival dissection was employed to enhance the securement of the XGS. Conclusions The case highlights that external force and needling can cause XGS fracture and displacement. To reduce this risk, employing a transconjunctival ab-externo approach with conjunctival dissection and securing the XGS with sutures was found to decrease complications, indicating a more effective surgical strategy for XGS implantation.

Abstract Determining the relationships among the epiphyseal ring, cervical nerve and vertebral pedicle isthmus via three-dimensional reconstruction can facilitate the precise removal of part of the uncinate process via spinal endoscopy, allowing safe cervical nerve decompression. C3/4-C7/T1-related indices were measured in 26 patients with cervical spondylotic radiculopathy. The lowest point of epiphyseal ring posterior margin (LPER) was used as the key point for measuring indices, and the following distances were measured around the LPER: the anteroposterior distance from the LPER to the anterior margin of the cervical nerve at the position of the uncinate process tip (ANU), the vertical distance from the LPER to the inferior margin of the cervical nerve at the position of the uncinate process tip (VNU), the vertical distance from the LPER to the cervical nerve superior margin origin (VNS), the vertical distance from the LPER to the cervical nerve inferior margin origin (VNI), the left-right distance from the LPER to the dura mater lateral border (DLB), and the anteroposterior distance from the LPER to the vertebral pedicle isthmus lateral border (PLB). From C3/4 to C7/T1, no significant differences in ANU were detected (P > 0.05), whereas significant differences in VNU, DLB, VNS, VNI, and PLB were detected (P 0.05). No significant differences were found between VNU and VNI in each segment (P > 0.05). The LPER was marked, which grinds part of the uncinate process and osteophyte anteriorly (or posteriorly) and part of the posterior lateral osteophyte of the upper vertebral body upwards to achieve complete decompression of the pedicle and the ventral nerve of the outlet of the pedicle to the cervical nerve origin.

Abstract The electroelastomer cylindrical actuators, a typical representation of soft actuators, have recently aroused increasing interest owing to their advantages in flexibility, deformability, and spatial utilization rate. Proprioception is crucial for controlling and monitoring the shape and position of these actuators. However, most existing flexible sensors have a modulus mismatch with the actuation unit, hindering the free movement of these actuators. Herein, a low-modulus strain sensor based on laser-induced cellular graphitic flakes (CGF) onto the surface of hollow TPU fibers (HTF) is present. Through the electrostatic self-assembly technology, the flexible sensor features a unique hybrid sensing unit including soft HTF as substrate and rigid CGF as conductive path. As a result, the sensor simultaneously possesses desirable modulus (~0.155 MPa), a gauge factor of 220.3 (25%

Abstract Background Prolonged sitting time is associated with an increased risk of cardiovascular disease (CVD) in the general population. However, it is unclear how these risks differ across occupational groups. This study aimed to investigate the association between sitting time and CVD in manual and non-manual workers among Chinese adults. Methods This population-based cohort study recruited 47,931 participants aged 35 to 70 years from 115 communities across 12 provinces in China between 2005 and 2009. Daily sitting time was measured using the International Physical Activity Questionnaire (IPAQ). The main outcome was a major CVD event (defined as cardiovascular death, myocardial infarction, stroke, or heart failure). Information on each participant’s occupation was collected using standardized questionnaires and categorized into manual and non-manual occupations according to the Italian National Institute of Statistics 2001 (ISTAT-2001) occupational classification standard. Cox frailty models were used to examine the associations. Results Of 43,256 in the final sample (excluding those with CVD at baseline and missing data), 25,252 (58.4%) were women, and the mean (± SD, Standard Deviation) age was 50.6 ± 9.5 years. During a median follow-up of 11.9 (IQR, Interquartile Range: 9.5–12.6) years, 3,408 major CVD events (899 myocardial infarctions, 2,400 strokes, 240 incident heart failure, and 764 cardiovascular deaths) were documented. Compared with the reference group (

Abstract Background Growth-regulating factors (GRFs) play a crucial role in plant growth and development, particularly in cell division and expansion. Citrus fruit cracking, a prevalent issue, adversely impacts both yield and fruit quality. Gibberellins (GAs) are known to ameliorate citrus fruit cracking by inducing thicker peel formation, which is attributed to cell division and expansion. However, the mechanistic link between gibberellins and citrus peel thickening, and whether this process is mediated by GRF genes regulation, has not been definitively established. Results In this study, 8 CsGRFs (Citrus sinensis), 11 CcGRFs (Citrus clementina), and 8 CgGRFs (Citrus grandis) were identified from the citrus genome which divided into six clusters, with the genes of the same cluster sharing similar gene structures. Cis-elements analysis revealed that the promoter regions of GRF genes contained numerous hormone-responsive elements. Tissue expression profiles showed that CsGRF genes had higher expression levels in young tissues, including early fruit tissues, one-year-leaf, ovules, and root tips. RNA-seq and qPCR analyses revealed that the expression levels of CsGRF3, 4, 7, and 8 were significantly regulated in response to GA3 treatment. Notably, CsGRF8 was the most significantly induced by GA3 and highly expressed in the early stages of peel development. These findings indicate gibberellins may exert regulatory effects on peel development through the induction of CsGRF genes. Conclusion This study systematically analyzed the characteristics of the citrus GRF gene family, as well as the changes in citrus peel thickness and the expression patterns of CsGRF genes under gibberellin treatment. These findings provide valuable insights for advancing research on the role of CsGRF genes in regulating citrus peel development, which could help reduce the occurrence of fruit cracking. Clinical trial number Not applicable.

Abstract Annexins (Anns) are a family of evolutionarily conserved, calcium-dependent, phospholipid-binding proteins that play critical roles in plant growth, development, and stress responses. Utilizing the pan-genome of 26 high-quality maize genomes, we identified 12 Ann genes, comprising 9 core genes (present in all 26 lines) and 3 near-core genes (present in 24–25 lines). This highlights the limitations of studying ZmAnn genes based on a single reference genome. Evaluating the Ka/Ks values of Ann genes in 26 varieties revealed that ZmAnn10 was under positive selection in certain varieties, while the remaining genes had Ka/Ks values less than 1, indicating purifying selection. Phylogenetic analysis divided ZmAnn proteins into six groups, with group VI containing only ZmAnn12. Structural variation in certain varieties altered the conserved domains, generating many atypical genes. Transcriptome analysis showed that different Ann members have distinct expression patterns in various tissues and under different abiotic and biotic stress treatments. Weighted gene co-expression network analysis of transcriptome data from various maize tissues under cold stress identified four Ann genes (ZmAnn2, ZmAnn6, ZmAnn7, ZmAnn9) involved in co-expression modules. Overall, this study utilized high-quality maize pangenomes to perform a bioinformatic analysis of ZmAnn genes, providing a foundation for further research on ZmAnn genes.

Abstract Background Patients with colorectal cancer (CRC) harboring BRAF mutation have a poor prognosis. The median survival time for patients with advanced BRAFV600E-mutant CRC is only approximately one year. Owing to the insensitivity to standard chemotherapy, there are still no effective and highly specific treatment strategies available in clinical practice for CRC patients with BRAF mutation. Therefore, targeting the BRAFV600E mutation site, researching and exploring novel targeted therapies are essential to improve the survival rate of patients with this CRC subtype. Aim This study aims to develop a precise therapeutic system for BRAFV600E CRC, based on the carrier properties of extracellular vesicles (EVs) and gene therapy targeting BRAFV600E. Method We first obtained engineered cells capable of stably producing EVs loaded with BRAFV600E nucleic acid drugs (siBRAFV600E). Next, BRAFV600E-mutant and wild-type CRC cell lines, as well as corresponding subcutaneous and metastasis models, were used to evaluate the therapeutic efficacy of EVs-siBRAFV600E and explored the mechanism. Notably, patient-derived xenograft (PDX) models, which share the same molecular characteristics, pathological features, and heterogeneity as patients do, were utilized to further explore the therapeutic efficacy and mechanisms. Result EVs-siBRAFV600E specifically inhibited BRAFV600E CRC but didn’t affect BRAF wild-type CRC in vitro and vivo. EVs-siBRAFV600E exerts its therapeutic effect by regulating the MEK1/2-ERK1/2 pathway, and it has demonstrated excellent therapeutic efficacy in PDX models. Conclusion The therapeutic EVs we constructed are effective and specific for the BRAFV600E-mutant CRC. This study provides a novel strategy for the treatment of CRC patients with BRAFV600E mutation.

Abstract Androgen exposure (AE) poses a profound health threat to women, yet its transgenerational impacts on male descendants remain unclear. Here, employing a large-scale mother-child cohort, we show that maternal hyperandrogenism predisposes sons to β-cell dysfunction. Male offspring mice with prenatal AE exhibited hyperglycemia and glucose intolerance across three generations, which were further exacerbated by aging and a high-fat diet. Mechanistically, compromised insulin secretion underlies this transgenerational susceptibility to diabetes. Integrated analyses of methylome and transcriptome revealed differential DNA methylation of β-cell functional genes in AE-F1 sperm, which was transmitted to AE-F2 islets and further retained in AE-F2 sperm, leading to reduced expression of genes related to insulin secretion, including Pdx1, Irs1, Ptprn2, and Cacna1c. The methylation signatures in AE-F1 sperm were corroborated in diabetic humans and the blood of sons with maternal hyperandrogenism. Moreover, caloric restriction and metformin treatments normalized hyperglycemia in AE-F1 males and blocked their inheritance to offspring by restoring the aberrant sperm DNA methylations. Our findings highlight the transgenerational inheritance of impaired glucose homeostasis in male offspring from maternal AE via DNA methylation changes, providing methylation biomarkers and therapeutic strategies to safeguard future generations’ metabolic health.

Abstract Background Clinical practice guidelines (CPGs) are intended to offer appropriate recommendations for clinical practice based on the available evidence while acknowledging existing gaps and uncertainties. The quality of CPGs for gastric precancerous lesions (GPL), distribution of evidence quality, and strength of recommendations are unknown. Objective Systematically evaluate the quality of CPGs for GPL and identify areas for improvement in the development process. Methods PubMed, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, and six online CPG repositories were systematically searched for CPGs related to GPL. Three researchers independently assessed the methodological quality of the included CPGs by using the AGREE II tool. The reporting and recommendation quality of the CPGs were evaluated using the RIGHT and AGREE-REX tools through consensus. Evidence-based CPGs were analyzed using the Grading of Recommendation Assessment, Development, and Evaluation system to determine the distribution of quality of evidence and strength of recommendations. Results A total of 4046 records were identified; nine CPGs met the eligibility criteria for this study. The mean overall score for the methodological quality of the CPGs was 46.22%. Among the six domains, the mean score for clarity of presentation was the highest (71.67%), while the mean score for applicability was the lowest (24.56%). Among the nine CPGs, only one was considered high quality. Regarding reporting quality, domains 1, 3, and 4 had mean reporting rates equal to or higher than 60%. The mean overall score for the recommendation quality was 19.11%. In total, 235 recommendations were identified through the screening process, of which 64.4% were classified as strong. However, only 17.5% of the strong recommendations were supported by high-quality evidence. Conclusion The overall quality of CPGs for GPL was poor, with uneven quality across domains. In addition, the consistency between the strength of recommendations and the quality of evidence was poor.

Abstract This study aimed to compare the anthropometric and physical characteristics of elite 15-, 16-, and 17-year-old male soccer players by playing position. We recruited 238 players under 17 years of age from Chinese professional soccer clubs. The measurements included body height and mass, body girth and length, and body composition. The countermovement jump (CMJ), T-test, and Yo-Yo intermittent recovery test level 1 (YYIR1) were used to assess physical ability. The results revealed that the U16 and U17 players had significantly greater body mass (p

Abstract Background The quadriceps during activities mainly affect patellar movement in the sagittal plane. This study was to analyze the pattern of sagittal patellar tilt in patellofemoral pain (PFP) patients by four-dimensional computed tomography (4DCT). Methods Thirty-four knees of PFP patients and 34 control knees were scanned with 4DCT. Patella-patellar tendon angle (P-PTA), patella-lateral tibial plateau angle (P-LTPA), patella-screen horizontal line angle (P-SHLA), articular facet of the patella-lateral tibial plateau angle (PA-LTPA), articular facet of the patella-screen horizontal line angle (PA-SHLA), and upper margin of the patella-quadriceps tendon angle (PU-QTA) were used to evaluate the sagittal patellar tilt. Two-factor repeated-measures ANOVA was used to compare all parameters between the two groups. Results At 30°−40° of flexion, P-PTA was significantly lower in PFP group than in control group (p = 0.004). At 0°–10°, PU-QTA was significantly higher in PFP group than in control group (p = 0.027). During flexion and extension, P-SHLA and PA-SHLA were significantly higher in PFP group than in control group, but there were no significant differences in P-LTPA and PA-LTPA. From − 10° to 30°, P-PTA decreased as the knee flexion angle increased. PU-QTA, P-LTPA, and PA-LTPA also decreased as the knee flexion angle increased, but P-SHLA and PA-SHLA increased. Conclusions In PFP group, sagittal patellar tilt was abnormal, and patella showed anterior tilt relative to the screen horizontal line during active knee flexion and extension. The pattern of patellar sagittal motion during dynamic process was consistent between PFP and control groups. The characteristics of patellofemoral sagittal alignment should not be ignored when analyzing patellofemoral stability.

Abstract Background Cancer poses significant economic and societal burdens on countries in the coming decades. During chemotherapy, patients frequently encounter adverse reactions. Recent research has revealed that Chinese medicine plays a crucial role in mitigating the side effects of chemotherapy. Therefore, in this article, we propose that the cancer treatment process can be likened to an unequal game. To refine treatment strategies, we suggest employing the Steinberg model to incorporate Chinese medicine into the chemotherapy regimen for tumor treatment. Results We found that when malignant tumors exhibit vigorous proliferation, doctors should administer Chinese medicine in conjunction with chemotherapy drugs, continuously optimizing the therapeutic effect of the Chinese medicine. Upon reaching a specific threshold in the treatment effect of the Chinese medicine, doctors may appropriately augment the dosage of chemotherapy drugs, building upon the initial regimen. Conversely, in cases where the proliferation ability of malignant tumors is weak, the dosage of chemotherapy and the adjuvant therapy with Chinese medicine should be kept in a relatively balanced state. Once the effect of the Chinese medicine attains a particular threshold, the dosage of chemotherapy can be concurrently increased to achieve a superior therapeutic result. Conclusions From a game theory perspective, doctors can devise strategies to minimize drug toxicity and improve tumor treatment outcomes by coordinating the use of chemotherapy drugs with appropriate adjustments to Chinese medicine therapy methods.

Abstract We typically think of the demand volume for a business in a city as a function of basic characteristics, such as the type of business, the quality of the product or service offered and its pricing. In addition, factors related to the urban environment, such as population density and accessibility are also crucial and have been considered in the literature. However, these considerations have typically been at the macro level. In this work we are interested in exploring the complementarity between specific (pairs) of venues. Simply put, venue B is complementary to venue A, if customers are more probable to visit venue B after being at venue A. This can increase the traffic for a business beyond the demand expected from the aforementioned factors, and it has been largely ignored in the literature. In this study we take a simulation-based approach to estimate this complementarity. We perform our simulations and analysis on two different spatial levels, namely, the venue level, as well as, the urban area level (e.g., zip code, neighborhood, etc.). The estimated complementarity provides insights for business owners and urban planners that can allow them to satisfy more demand, which consequently can increase the revenue for the businesses, but also can create more convenient urban navigation for city dwellers.

Abstract Effective classification and identification algorithms of small fishing vessels are the key to strengthen ship management. This paper proposes a classification and recognition method for small fishing boats based on GASF sequence diagram coding, addressing the complex and challenging recognition environment. The method focuses on four typical small fishing vessels, utilizing Gramian Summation Angular Field (GASF) time series images and the Efficiency MPViT (EMPViT) model. Unlike traditional approaches, this study initially employs a high-precision laser sensor to gather one-dimensional contour data of fishing boats. Subsequently, the polynomial fitting method is used to delineate the shape of the fishing boat contour, which is then encoded into a two-dimensional time series image using the GASF encoding method. The enhanced EMPViT model is then applied to classify and identify small fishing vessels, with the results verified through ablation experiments. These experiments demonstrate that the EMPViT model surpasses traditional neural network models such as CNN and ViT in both accuracy and performance, achieving a peak accuracy of 99.98%.

Abstract Background The relationship between cancer development and alterations in IgG N-glycosylation has been well-established. However, comprehensive profiling of the N-glycome and N-glycoproteome in gastric cancer (GC) remains limited. Furthermore, the prognostic potential of IgG N-glycan patterns in identifying precursors to GC has yet to be fully elucidated. Methods The IgG N-glycome in GC was characterized using a custom high-throughput orthogonal mass spectrometry approach. Multivariate analysis was employed to identify and assess glycomic alterations. A comprehensive bioinformatics analysis was also conducted to investigate the differential expression of N-glycosylation-related genes and their potential roles in GC pathogenesis. Additionally, interleukin-11 (IL-11) levels were quantified using a standardized enzyme-linked immunosorbent assay (ELISA). Results Galactosylation and sialylation of IgG decreased mainly in the IgG1 and IgG2 subclasses in GC, with subclass-specific changes in IgG3 and IgG4 galactosylation. These glycan modifications were represented by unique glycopeptides (IgG1_H5N5, IgG2_H4N3F1, IgG2_H4N4, IgG2_H4N4F1S1, IgG3/4_H4N4F1, IgG3/4_H4N4F1S1), which outperformed CA72-4 for GC diagnosis. Analysis of key glycogenes revealed differential expression patterns, implicating a functional role for IgG N-glycosylation in GC. Notably, the abundance of specific IgG glycosylation exhibited a significant correlation with serum level of IL-11. Conclusions Alterations in subclass-specific IgG N-glycosylation represent promising biomarkers for the detection and monitoring of GC progression, potentially influenced by cytokine-driven inflammation. Understanding these changes could improve our knowledge of molecular mechanisms, aiding in diagnostic improvements and therapeutic development.

Abstract The phenomenon of hydrogen spillover usually involved in the hydrogenation reactions over supported metal catalysts has been seldom reported over molecular catalysts. Herein, we report the important role of hydrogen spillover in homogeneous hydrogenation with the asymmetric hydrogenation of quinolines as a model reaction. It is observed that the conversion of quinaldine over TsDPEN-Rh-Cp*-Cl catalyst is sharply increased by 2.1 folds in the presence of Ni/TiO2 and the ee value remained at the same level. The mechanism study shows that Ni/TiO2 is mainly used as H2 dissociation site, TsDPEN-Rh-Cp*-Cl is the active site to control the enantioselectivity of the product, and hydrogen spillover acts as a bridge between the two catalysts in the homogeneous and heterogeneous hybrid system. The hydrogen spillover makes it possible for heterogeneous catalysts and homogeneous organometallic complexes to cooperate, breaking the boundary between homogeneous and heterogeneous catalysis.

Abstract Objective Through this study we aimed to present the latest and most comprehensive pooled analysis, providing an updated evaluation of the efficacy and safety of sequential therapy for primary osteoporosis, using bone formation promoters followed by bone resorption inhibitors. Methods PubMed, the Cochrane Library, Web of Science, and Embase databases were retrieved to identify pertinent studies. Randomized controlled trials (RCTs) on the sequential therapy of primary osteoporosis with bone formation promoters followed by bone resorption inhibitors were included. Data from clinical studies that met the eligibility criteria were extracted, and quality assessment and meta-analysis were performed using RevMan v5.4 and Stata v15.0. Sensitivity and subgroup analyses were performed to find the source of heterogeneity and discover more findings. Results A total of 10 eligible articles involving 14,510 patients (7171 in the intervention group versus 7339 in the comparator group) were included for the evidence synthesis. The baseline characteristics of the two groups were similar. Pooled analysis showed that the intervention group (bone formation promoters followed by bone resorption inhibitors) increased BMD at the spine (SMD:1.64; 95% CI: 0.97, 2.31; P

Abstract Highly myopic cataract (HMC) is a leading cause of blindness among the working-age individuals, with its pathogenesis poorly understood. This study aimed to elucidate the role of ferroptosis in HMC development as well as the underlying mechanisms. In HMC lens epithelia, levels of Fe2+ and lipid peroxidation were found elevated, with increased vulnerability towards ferroptosis as revealed by transmission electron microscopy. Mechanistically, RNA sequencing of HMC lens epithelial samples identified up-regulated expression of discoidin domain receptor tyrosine kinase 2 (DDR2) as a key factor, which could enhance ferroptosis sensitivity via the Src-Hippo pathway. Specifically, DDR2 interacted with Src kinase, leading to the nuclear translocation of homologous transcriptional regulators (yes-associated protein 1 [YAP1] and WW domain containing transcription regulator 1 [WWTR1]) of the Hippo pathway, which altered the expression level of ferroptosis-related genes. Notably, highly myopic eyes of mice exhibited higher sensitivity to RSL3, a ferroptosis inducer, manifested as more severe nuclear lens opacities both in vitro and in vivo compared with the contralateral control eyes, which could be alleviated by inhibitors of either ferroptosis or DDR2. Altogether, these findings highlighted the role of DDR2 in mediating ferroptosis in HMC formation, providing a novel insight for therapeutic interventions.

Abstract Background Although the second booster dose of COVID-19 vaccines is available, vaccine hesitancy among the public may have peaked due to the surge in infections caused by the Omicron variant. To improve coverage of the second booster dose, it is crucial to investigate the prevalence of vaccine hesitancy among the general population during this period and explore the reasons for this phenomenon. Methods A cross-sectional survey was conducted between January 5 to February 9, 2023. Variables including sociodemographics, mental health, COVID-19 infection status, COVID-19 vaccination status, and vaccine hesitancy were collected. Univariate and multivariate logistic regression analysis were performed to identify factors associated with the hesitancy of the second booster dose of COVID-19 vaccine among the general population. Results Among the 10,623 participants, the uptake rate of the second booster dose was 4.3%. Among those who did not receive the second booster dose, 43.6% expressed vaccine hesitancy. The highest hesitancy rate was observed among participants who had not completed primary immunization (71.4%), followed by those with chronic diseases (48.6%) and those aged 60 and above (33.2%). The COVID-19 vaccine hesitancy was higher among females, participants with high incomes, those with a history of COVID-19 infection, those with depressive symptoms and post-traumatic stress disorder, and those with adverse events after COVID-19 vaccination. Conversely, lower hesitancy was observed among students, participants aged 60 and above, those from southern China, and those with higher level of perceived social support. Conclusions COVID-19 vaccine hesitancy remains prevalent among the general population in China after the surge period of the pandemic. Crucial steps, such as raising public awareness of the benefits and potential side effects of regular COVID-19 vaccination, ensuring timely monitoring and disclosure of pandemic information, and implementing targeted measures to improve social support and mental health, should be taken. These efforts will be instrumental in reducing vaccine hesitancy, advancing vaccination campaigns, and effectively preparing for the potential future outbreaks.

Abstract Objective This study aimed to examine the factors that affect treatment delay in early childhood caries (ECC), guided by a modern medical model. This study attempted to analyze the pathways influenced by these factors and provide a theoretical foundation for designing targeted intervention programs. Methods Data were collected from young children who visited the department of stomatology at a tertiary hospital from January to December 2023. Data were collected via a general information survey questionnaire, the Scale of Oral Health Outcomes for 5-year-old Children (SOHO-5), the Children’s Fear Survey Schedule-Dental Subscale-Chinese (CFSS-DS-C), the Parental Caregiver Perceptions Questionnaire-8 (P-CPQ-8), the Family Impact Scale (FIS-8), and the Perceived Barriers to Health Care-Seeking Decision-Chinese (PBHSD-C). The data in this study were analyzed using a variety of statistical tests, including the Kruskal-Wallis and Mann-Whitney tests, correlation analysis, multiple stepwise regression analysis, and structural equation modeling (SEM). Results The treatment delay score of early childhood caries was 36.77 ± 10.11, indicating that the state of early childhood caries was currently at a moderate level of delay. The SOHO-5 score was 6.41 ± 1.78, the CFSS-DS-C score was 23.60 ± 6.91, the P-CPQ-8 score was 18.43 ± 4.33, and the FIS-8 score was 18.66 ± 4.28. Multi-factor analysis revealed key factors affecting treatment delay, including permanent residence, medical insurance type, oral health habits, reasons for visit, first symptoms, the time of first discovery of oral problems, brushing teeth before bedtime every day, a genetic history of dental caries and the staging of dental caries. A positive correlation existed between oral health, children’s dental fear and treatment delay, whereas social support was negatively correlated with treatment delay. The SEM, which is based on the modern medical model, revealed that children’s dental fear plays a mediating role in the relationships among social support, oral health, and treatment delay. Conclusion The present study developed a novel model to study the ECC treatment delay, elucidated the causal links between the identified variables, and proposed potential intervention strategies to enhance oral health awareness, knowledge, and skills among young children and their parents. These strategies can help improve children’s dental visiting behavior and reduce treatment delay.

Abstract Aims This study explores the clinical application of lung ultrasound scoring(LUS) combined with echocardiography in assessing right heart function in patients undergoing maintenance hemodialysis(MHD) and those with elevated pulmonary artery systolic pressure(PASP), as well as the correlation between LUS and right ventricular(RV) function. Methods Eighty five patients who underwent MHD combined with elevated PASP, at the First Central Hospital of Baoding City were selected. Divided into three groups based on PASP, and perform echocardiography and lung ultrasound examinations. Compare the right heart function parameters and LUS among the three groups. Using Pearson correlation analysis to examine the relationship between LUS and right heart function parameters. Perform multivariate logistic regression analysis to identify predictive factors for RV systolic dysfunction. A receiver operating characteristic (ROC) curve and calculate the area under the curve(AUC) to compare the diagnostic efficacy of various parameters. Results Patients undergoing MHD exhibited varying degrees of reduced left ventricular (LV) and RV systolic function. Correlation analysis revealed that Tricuspid annular plane systolic excursion (TAPSE), Fractional area change (FAC), and Tricuspid annular peak systolic velocity(S') were negatively correlated with LUS(r = -0.81, -0.86, -0.69), while Right ventricular free wall longitudinal strain(RVFWLS) was positively correlated with LUS (r = 0.85, P

Abstract The global marine gravity anomalies are primarily recovered from geoid gradients in the along-track directions obtained through satellite altimetry. However, the accuracy of the gravity model is significantly constrained by the sparse geoid gradients in the cross-track directions. To overcome the scarcity of cross-track geoid gradients, we employ a mean sea surface model to calculate geoid gradients in multiple directions, thereby recovering marine gravity anomalies. A global marine gravity anomaly model with 1-arcmin grid was determined from an optimized mean sea surface model. The accuracy of this gravity anomaly model was assessed by shipborne gravity and released marine gravity anomaly models. By the combination of geoid gradients in multiple directions, the meridian components and the prime vertical components of deflections of the vertical achieved consistent accuracy. The accuracy of the gravity anomaly model is 4.31 mGal, derived from shipborne gravity anomalies. Furthermore, the accuracy of this model has been validated across various regions, encompassing different latitudes, bathymetry, and distances from the coastline. The new gravity anomaly model slightly outperforms the released model.

Abstract Background Autologous fat grafting (AFG) often needs multiple sessions due to low volume retention. Young adipose tissue demonstrates a more pronounced therapeutic effect; thus, the cryopreservation of adipose tissue of young origin is particularly crucial. This study investigated the protective effect of a new cryopreservation solution combining trehalose, glycerol, and metformin on adipose tissue. Methods This study initially examined the effect of various concentrations of metformin (0, 1, 2, 4, and 8 mM) on oxidative damage in adipose tissue to identify the optimal concentration. Subsequently, 1.5 mL of fresh human adipose tissue was subjected to freezing using trehalose + glycerol (TG group), trehalose + glycerol + metformin (TGM group), and the common cryoprotectant dimethyl sulfoxide (DMSO) + fetal bovine serum (FBS) (DF group). Samples were cryopreserved in liquid nitrogen for 2 weeks. After thawing, 1 mL of adipose tissue from each group was transplanted subcutaneously into the backs of nude mice. The cryoprotective effects on adipose tissue viability were evaluated during transplantation one month after transplantation. Results The 2 mM concentration of metformin exhibited the lowest reactive oxygen species (ROS) level (29.20 ± 1.73) compared to other concentrations (P

Abstract The development of an efficient and durable photoelectrode is critical for achieving large-scale applications in photoelectrochemical water splitting. Here, we report a unique photoelectrode composed of reconfigured gallium nitride nanowire-on-silicon wafer loaded with Au nanoparticles as cocatalyst that achieved an impressive applied bias photon-to-current efficiency of 10.36% under AM 1.5G one sun illumination while exhibiting stable PEC hydrogen evolution over 800 h at a high current density. Specifically, by tailoring the GaN nanowires via a simple alkaline-etching step to expose the inner (10 $$\bar{1}\bar{1}$$ 1 ¯ 1 ¯ ) facets, we achieve a highly coupled semiconductor nanowire-cocatalyst heterointerface with strong electron interaction. The strongly coupled reconfigured GaN nanowire/Au heterointerface not only optimizes the electronic structure of Au nanoparticles to form abundant highly active interfacial regions, eventually realizing superior hydrogen evolution activity but also enables GaN nanowires to provide a stronger anchoring effect for Au nanoparticles, preventing the detachment of Au nanoparticles during the intense hydrogen evolution process. The proposed photoelectrode offers a feasible structure for overcoming the efficiency-reliability bottleneck of PEC devices for producing clean hydrogen fuel.

Abstract Regulator of cell death-1 (RCD-1) governs the heteroallelic expression of RCD-1-1 and RCD-1-2, a pair of fungal gasdermin (GSDM)-like proteins, which prevent cytoplasmic mixing during allorecognition and safeguard against mycoparasitism, genome exploitation, and deleterious cytoplasmic elements (e.g., senescence plasmids) by effecting a form of cytolytic cell death. However, the underlying mechanisms by which RCD-1 acts on the cell membrane remain elusive. Here, we demonstrate that RCD-1 binds acidic lipid membranes, forms pores, and induces membrane bending. Using atomic force microscopy (AFM) and AlphaFold, we show that RCD-1-1 and RCD-1-2 form heterodimers that further self-assemble into ~14.5 nm-wide transmembrane pores (~10 heterodimers). Moreover, through AFM force spectroscopy and micropipette aspiration, we reveal that RCD-1 proteins bend membranes with low bending moduli. This combined action of pore formation and membrane deformation may constitute a conserved mechanism within the broader GSDM family.

Abstract Background To improve the success rate of mini-implants, some surgical guides have been developed through digital technologies to achieve three-dimensional (3D) guided mini-implants insertion. However, there is no a surgical guide which can be applied for the insertion of infrazygomatic mini-implant. In this study, we introduced a two-trajectories surgical guide and investigated the success rate of infrazygomatic mini-implants under the guidance of the template. Methods An individualized surgical guide was fabricated based on the cone-beam computed tomography images, digital intraoral scanning images and the predesigned insertion plans. In the surgical guide group, 62 mini-implants were inserted between the maxillary first and second molars under the guidance of surgical guides (n = 62). In the historical control group, 54 mini-implants were placed by the direct manual method at the same site (n = 54). Then the mini-implant success rate in these two groups was compared. Results After implantation, 2 out of the 62 mini-implants fell off and a success rate of 96.8% was indicated in the surgical guide group. In the historical control group, 11 of 54 mini-implants fell off and the success rate was 79.6%. There was statistically significant difference between the success rate of two groups (P = 0.003). Conclusions The two-trajectories surgical guide is advantageous for the insertion of infrazygomatic mini-implant. Both the success rate and stability of infrazygomatic mini-implant were improved significantly with the use of the guide. But further studies with enlarged sample are needed to evaluate the accuracy and stability of the mini-implant placement.

Abstract Background There is still no consensus regarding the correlation between TLS and the prognosis of lung cancer patients. This meta-analysis aimed to investigate the association between TLS and prognosis in patients with lung cancer. In addition, the prognostic value of TLS for the efficacy of immunotherapy was also studied. Methods We systematically searched the PubMed, Embase, Cochrane Library, and Web of Science databases from database inception to November 1, 2023. The hazard ratio (HR) and corresponding 95% confidence interval (CI) for overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS), progression-free survival (PFS) and disease-specific survival (DSS) were extracted and merged with STATA 14.0. The study protocol was registered with PROSPERO (CRD42024502483). Results A total of 17 studies comprising 4291 patients were included in this meta-analysis. The pooled results revealed that high TLS/TLS + patients had better OS (HR = 0.66, 95% CI: 0.50–0.88), DFS (HR = 0.46, 95% CI: 0.33–0.64), DSS (HR = 0.48, 95% CI: 0.39–0.60) and RFS (HR = 0.43, 95% CI: 0.33–0.57). High TLS/TLS + patients tended to have longer PFS than low TLS/TLS + patients (HR = 0.68, 95% CI: 0.35–1.35). Interestingly, in the Asia subgroup, the association between TLS and survival was especially significant, whereas there was no significant difference in Europe. In addition, in patients who received neoadjuvant chemoimmunotherapy, high TLS/TLS + was associated with prolonged DFS (HR = 0.21, 95%CI: 0.05–0.93). Conclusion High TLS/TLS + was associated with improved survival and an improved response to neoadjuvant chemoimmunotherapy in lung cancer patients, suggesting that TLS may be a prognostic biomarker and may also be a promising predictive marker for the response to neoadjuvant chemoimmunotherapy. However, additional original studies are needed to further confirm these findings.

Abstract Lampreys are early jawless vertebrates that are the key to understanding the evolution of vertebrates. However, the lack of cytomic studies on multiple lamprey organs has hindered progress in this field. Therefore, the present study constructed a comprehensive cell atlas comprising 604,460 cells/nuclei and 70 cell types from 14 lamprey tissue samples. Comparison of cellular evolution across species revealed that most lamprey cell types are homologous to those in jawed vertebrates. We discovered acinar- and islet-like cell populations despite the lack of parenchymal organs in lampreys, providing evidence of pancreatic function in vertebrates. Furthermore, we investigated the heterogeneity of lamprey immune cell populations. Natterin was highly expressed in granulocytes, and NATTERIN was localized to the lipid droplets. Moreover, we developed a transgenic mouse model expressing Natterin to elucidate the role of NATTERIN in lipid metabolism, whereas the browning of white adipose tissue was induced. These findings elucidate vertebrate cellular evolution and advance our understanding of adipose tissue plasticity and metabolic regulation in lampreys.

Abstract China witnessed an Omicron COVID-19 outbreak at the end of 2022. During this period, medical crowding and enormous pressure on the healthcare systems occurred, which might result in the occurrence of occupational burnout among healthcare workers (HCWs). This study aims to investigate the prevalence of occupational burnout and associated mental conditions, such as depressive symptoms, anxiety, PTSD symptoms, perceived social support, resilience, and mindfulness among HCWs of the Chinese mainland during the Omicron COVID-19 outbreak, and to explore the potential risk and protective factors influencing occupational burnout of HCWs. A multicenter cross-sectional study was conducted among HCWs working in the Chinese mainland from January 5 to February 9, 2023. A total of 6552 participants were recruited by convenience sampling. Data were collected on demographic characteristics, occupational burnout, depressive symptoms, anxiety, PTSD, perceived social support, resilience, and mindfulness by online questionnaires. Descriptive analyses were performed to describe the participants’ demographic characteristics. Univariate-Multivariate analyses were used to determine the influencing factors of occupational burnout. The results showed that the prevalence of occupational burnout and associated mental disorders, such as depressive symptoms, anxiety, and PTSD in HCWs were 44.56%, and 70.75%, 47.87%, and 37.49%, respectively. Older age, female gender, higher income, more doses of COVID-19 vaccine, a higher level of mindfulness, resilience, and perceived social support were protective factors of occupational burnout. Working as nurses, in a department currently taking charge of the treatment of COVID-19 patients, perceived high risk of contracting COVID-19 due to work, perceived high work intensity, and a higher level of anxiety and depressive symptoms were risk factors of occupational burnout. Tailored interventions on perceived social support, resilience, and mindfulness should be implemented to alleviate occupational burnout and associated mental disorders among HCWs.

TiAl alloy, renowned for its high temperature resistance while maintaining lightweight properties, serves as a crucial structural material for hot-end components. However, the widespread application of additive manufacturing (AM) for TiAl alloys is constrained by their limited ductility. To enable the engineering-scale production of TiAl alloys with enhanced strength and ductility, this study introduces advancements in the heat source, material composition, and deposition processes. The characteristics of the cold-cathode electron beam heat source were used to manufacture low-cost in-situ alloyed TiAl alloys through wire-fed electron beam additive manufacturing. Mo, Zr, and Si elements were introduced into the TiAl alloy, and precise thermal control allowed the separated twin wires to simultaneously form a stable co-molten pool, and the specimens with good appearance and no internal microcracks and pores were obtained. Furthermore, a detailed comparison between Ti48Al alloy and Ti48Al1Mo0.45Zr0.3Si alloy was carried out, focusing on aspects such as grain morphology, chemical composition homogeneity, phase constitution, and mechanical properties. The influence of dual-wire synergistic control on process stability, microstructure evolution, and strengthening mechanisms was discussed. The results show that the cold-cathode electron beam heat source under low vacuum and the co-molten pool mode reduce aluminum evaporation and promote element mixing through layer-by-layer temperature control and remelting. Compared to the lamellar microstructure of Ti48Al alloy, the Ti48Al1Mo0.45Zr0.3Si alloy exhibits a dual-γ phase microstructure, consisting of fine lamellar colonies and equiaxed γ grains. This modification led to a 90% and 150% increase in elongation at room temperature and 650 °C, respectively. These findings offer important insights into enhancing the performance of TiAl alloys through cost-effective alloying strategies.

Abstract Background Biochar is widely recognized for its capacity to capture and store carbon in soil attributed to its stable structure. However, in most field studies examining the effects of biochar application on soil respiration, the impact of rainfall events on the experimental outcomes has not been taken into account. To address the existing gap in this research field, we conducted a one-year study on soil respiration in an urban camphor forest and collected the data of soil respiration, soil temperature, soil moisture, and the rainfall events closest to the soil respiration monitoring time. We specifically examined how different stages of rainfall events influenced soil respiration in relation to biochar application. Results This study found that the annual average soil respiration rate increased with the doses of biochar application, and the soil respiration rate under the biochar application at the dose of 45 t/ha showed a significant rise. The stages of rainfall events, rainfall amount, and the interaction effect of the two, and biochar doses significantly affected soil respiration. The parameters in the regression model for soil respiration, soil temperature and moisture varied with the different stages of rainfall events and the doses of biochar application. The biochar application eliminated the significant effect of soil moisture on soil respiration during one day after rainfall events. The significant correlation between soil moisture and the temperature sensitivity of soil respiration (Q 10) was eliminated by biochar application, both during one day after rainfall events and more than eight days after rainfall events. Conclusions Our findings indicated that the rice straw biochar application has a short-term positive effect on soil respiration in urban camphor forests. The rainfall events affect the field soil respiration monitored in the biochar applications, possibly by affecting the soil respiration response to soil temperature and moisture under different doses of biochar application. The impact of rainfall events on soil respiration in biochar application experiments should be considered in future forest monitoring management and practice.

Abstract Immune checkpoint inhibitors (ICIs) plus chemotherapy have become the standard of care for first-line treatment of advanced non-small cell lung cancer (NSCLC) with EGFR/ALK negative. However, there is no clear second-line treatment option after first-line treatment failure. To investigate the efficacy and safety of ICIs alone or in combination rechallenge treatment after first-line ICIs plus chemotherapy progression in advanced NSCLC. We retrospectively analyzed the cases of patients who received ICIs alone or in combination rechallenge treatment after first-line ICIs plus chemotherapy progression in advanced NSCLC at Hunan Cancer Hospital between January 2020 and May 2024. We evaluated the effects of continued immunotherapy on patients’ objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse events after first-line treatment progression, and analyzed the relationship between outcomes and clinical characteristics. A total of 154 patients were included, with 146 patients developing resistance, 8 patients showing no progression. The ORR was 16.44%, the DCR was 68.49%, and the median PFS was 4.6 months. Patients treated with the new immune drug therapy had longer PFS than those treated with the original immunotherapy (5.0 months vs. 3.7 months, p = 0.0438). The PFS in patients receiving ICIs plus targeted therapy was significantly longer than that in patients who receiving ICIs alone, chemo-ICIs plus targeted therapy and ICIs plus chemotherapy (chemo-ICIs) (5.7 months vs. 3.6 months vs3.2 months vs. 2.9 months, p = 0.0086). Multivariate analysis showed that treatment regimen was a risk factor for immune rechallenge PFS, but there was no statistical correlation between gender, age, smoking history, pathological type, intermittent treatment or first-line drug resistance and immune rechallenge PFS. Our findings suggest that selecting ICIs plus targeted therapy may improve PFS in patients with advanced NSCLC after first-line chemo-ICIs progression. while replacement with new BSAb/PD-1 may be more beneficial to patients. However, there is a lack of large sample randomized controlled studies and evidence-based medical evidence, and more clinical studies are needed to further confirm.

Abstract The placenta is the critical interface between mother and fetus, and consequently, placental dysfunction underlies many pregnancy complications. Placental formation requires an adequate expansion of trophoblast stem and progenitor cells followed by finely tuned lineage specification events. Here, using single-cell RNA sequencing of mouse trophoblast stem cells during the earliest phases of differentiation, we identify gatekeepers of the stem cell state, notably Nicol1, and uncover unsuspected trajectories of cell lineage diversification as well as regulators of lineage entry points. We show that junctional zone precursors and precursors of one of the two syncytial layers of the mouse placental labyrinth, the Syncytiotrophoblast-I lineage, initially share similar trajectories. Importantly, our functional analysis of one such lineage precursor marker, CXADR, demonstrates that this cell surface protein regulates the differentiation dynamics between the two syncytial layers of the mouse labyrinth, ensuring the correct establishment of the placental exchange surface. Deciphering the mechanisms underlying trophoblast lineage specification will inform our understanding of human pregnancy in health and disease.

Abstract Upwelling in the Equatorial Pacific nurtures an expansive, westward-stretching chlorophyll-rich tongue (CRT), supporting 18% of the annual global new production. Surrounding the CRT are the oligotrophic subtropical gyres to the north and south, which are suggested to be expanding under global warming. Yet, how this productive CRT has changed, expanding or contracting, remains unknown. By applying the empirical mode decomposition (EMD) method to 20-year monthly measurements of chlorophyll-a concentration from MODIS-Aqua satellite (2002-2022), we demonstrate that the CRT exhibited a significant westward extension, at an average expanding rate of 1.87 ( ± 0.82) × 105 km2/yr. The westward extension of the CRT is attributed to strengthened equatorial upwelling and a strengthened South Equatorial Current from 2002 to 2022, driven by intensified easterly trade winds as the Pacific Decadal Oscillation predominantly remains in its negative phase during this period. Interestingly, EMD analysis on central locations of the Pacific gyres suggested simultaneous extension of the gyres and the CRT during 2002-2022, with the gyres extending poleward. Our findings imply a broader cover of productive water along the equator, while its impact on tropical climate, ecosystems, and carbon cycle deserves further investigation.

Abstract Background Empathy of medical students is crucial, yet it tends to decline as students enter later academic years. Empathy appeared to be affected by the learning environment (LE), which could be a potential contributor. We conducted a cross-sectional study to investigate the association between LE and empathy. Method The study comprised overall 10,901 medical students from 12 Chinese medical schools. Jefferson Scale of Empathy (JSE) was utilized to assess empathy, while a 5-point question and the Johns Hopkins Learning Environment Scale were employed to evaluate LE. JSE scores were compared across LE levels using Pearson Chi-square, Welch’s ANOVA, and univariable linear regression. After adjusting for covariates, multivariable linear and logistic regression were used to assess the independent connection between LE and empathy. Confounders were controlled by stratified subgroup analysis. Results LE was significantly associated with medical students’ empathy, as shown by the Pearson Chi-square test (p

To clarify the quality characteristics and flavor characteristics of hemp pepper chicken products, 14 different kinds of commercially available hemp pepper chicken (represented by the letters A~N) were used as the research objects, and their color, texture, shear force, electronic nose, volatile flavor substances and electronic tongue were determined. Meanwhile, the correlation between the sensory evaluation indexes and the instrumental analysis indexes was further explored in conjunction with the sensory evaluation. The results showed that the hardness of 14 kinds of hemp pepper chicken breast ranged from 1742.81 to 4587.54 g, and the shear force ranged from 14.41 to 35.07 N. The hardness of the chicken thighs ranged from 797.09 to 3389.61 g, and the shear force ranged from 7.70 to 26.34 N. The electronic nose evaluation's findings indicated that the nitrogen oxides, inorganic sulfides, organic sulfides, and short-chain alkanes were the main volatile odor constituents of the 14 kinds of hemp pepper chicken. The results of gas chromatography-ion mobility spectrometry (GC-IMS) showed that overall coordination of the aroma of the chicken itself and spices contributed to the formation of the flavor of hemp pepper chicken. Seventy-seven volatile compounds were identified in 14 kinds of hemp pepper chicken. Combined with orthogonal partial least squares discriminant analysis (OPLS-DA), it was found that 26 substances such as butanal, linalool, alpha-pinene, ethyl acrylate, alpha-terpineol, 2-heptanone, 1-octen-3-ol were the characteristic flavor substances of hemp pepper chicken products. The freshness and saltiness were the main factors influencing the taste of hemp pepper chicken. The correlation analysis results revealed that the overall liking index in the sensory evaluation showed a highly significant positive correlation with butanal, linalool, alpha-pinene, ethyl acrylate, alpha-terpineol, 2-heptanone, 1-octen-3-ol, W5S, W1W, W2W, W1S, saltiness, L* and b* response values (P

Abstract Flavonoids are a major class of polyphenolic compounds that occur naturally in plants and are widely distributed in various dietary products. Flavonoids exhibit prominent physicochemical properties and biological activities, thereby garnering considerable attention. Notably, the physicochemical properties and functionalities of flavonoids are structurally dependent. Variations in chemical structure lead to differences in physicochemical characteristics among different flavonoid types. Structural alterations can modify these characteristics, influencing biological activities and mechanisms of action. However, these structural variations and their biological implication have not been comprehensively elucidated. In this review, we outline the structural characteristics of flavonoids, discuss biosynthesis, in vivo digestion, and absorption, and particularly emphasize the diverse biological activities and action mechanisms associated with different flavonoid structures. By summarizing the current scientific findings, we aim to elucidate the structure–activity relationships of flavonoids and provide a theoretical basis for the development of new flavonoid applications, which will help to target the design of functional molecules and moieties in the food and pharmaceutical industries for use in drug design and development. Practical Application: Understanding the structural characteristics and biological activities of flavonoids can guide the development of functional food products and dietary supplements with targeted health benefits. By leveraging the knowledge of flavonoid structure–activity relationships, food, and pharmaceutical industries can innovate formulations to enhance bioavailability and efficacy, potentially leading to the creation of tailored products for specific health conditions or dietary needs. This research lays the groundwork for the design of novel flavonoid‐based interventions aimed at promoting human health and well‐being.

Abstract Three-spotted seahorse (Hippocampi trimaculata) is a unique fish with important economic and medicinal values, and its total chromosome number is potentially quite different from other seahorse species. Herein, we constructed a chromosome-level genome assembly for this special seahorse by integration of MGI short-read, PacBio HiFi long-read and Hi-C sequencing techniques. A 416.57-Mb haplotypic genome assembly was obtained. Subsequently, 99.38% of its scaffold sequences were anchored onto 18 chromosomes, with identification of 29.1% repeat sequences in the assembled genome. Additional karyotype analysis validated the diploid chromosomes of 2n = 36, which are remarkably different from other seahorses’ 2n = 42 or 44. The genome completeness (BUSCO score: 96.5%, CEGMA score: 97.87%) confirmed that this chromosome-scale assembly is indeed of high quality. Moreover, a total of 18,712 protein-coding genes were annotated, of which 96.36% could be predicted with functions. Based on construction of a phylogenetic tree, we estimated that Hippocampus and Syngnathoides diverged approximately 50.1 million years ago (Mya). Taken together, our genome data presented in this study provide a valuable genetic resource for numerical chromosome changes and in-depth evolutionary and functional investigations, as well as conservation and molecular breeding of this endangered teleost.

Micro-milling has been employed in various fields due to its efficiency, flexibility, material, and structural versatility in the machining of small and high-quality parts. However, when micro-milling highly plastic aluminum alloys, it is difficult to produce a smooth surface due to the easy sticking of tools. To solve this problem, a multi-energy field coupling method of adding nano-lubricant to the micro-milling area by minimum quantity lubrication (MQL) and modifying the aluminum alloy by cold plasma (CP) was introduced. In this paper, the experiments of CP and h-BN nano-lubricant minimum quantity lubrication (NMQL) multi-field coupling assisted (CPNMQL) micro-milling of aluminum alloy 6061-T65 were carried out to analyze 3D surface roughness (Sa), tool texture, milling forces (Fx and Fy), and surface morphology. The results revealed that the CP could increase the surface microhardness and improve material removal rate; Cottonseed oil with h-BN nanoparticles exhibited superior lubricating properties; The milling forces Fx and Fy were significantly reduced; Sa (0.029 µm) under CPNMQL condition decreased by 60 %, 72.1 %, 27.5 %, and 53.2 % comparing to dry (0.104 µm), NMQL (0.04 µm), and CP (0.062 µm) conditions. In addition, the smallest and most uniform tool mark texture height and depth of 0.038 µm was obtained under CPNMQL condition, a 76.3 % reduction over dry condition.

Abstract Peri-prosthesis osteolysis (PPO) represents the most severe complication of total joint arthroplasty (TJA) surgery and imposes the primary cause of prosthesis failure and subsequent revision surgery. Antiresorptive therapies are usually prescribed to treat PPO, especially for elderly people. Nevertheless, the efficacy of anti-osteoporotic medications remains constrained. Recent therapeutic strategies to promote periprosthetic osseointegration by restoring osteoblast function are considered more effective approaches. However, the precise mechanism underlying the inhibition of osteogenesis triggered by wear particles remains enigmatic. Herein, we demonstrate that wear particles inhibit osteoblast function by inducing ferroptosis to sabotage extracellular mineralization and arouse periprosthetic osteolysis. The suppression of ferroptosis could significantly rescue osteogenesis thus alleviating PPO. Furthermore, Glutathione Peroxidase 4 (GPX4) has been identified as a key target in regulating osteoblastic ferroptosis. By utilizing virtual screening techniques, we have successfully conducted a comprehensive screening of a natural compound known as Urolithin A (UA), which exhibits remarkable inhibition of osteoblastic ferroptosis while simultaneously promoting the process of osteogenesis through its precise targeting mechanism on GPX4. Meanwhile, UA improves the osteolytic conditions significantly in vivo even when the adjunction of titanium (Ti) nanoparticles. This strategy has great potential in treating peri-prosthesis osteolysis and potentially broadens the scope of clinical therapy. Graphical Abstract

Light is one of the most important environmental factors for plant growth and development. In relay cropping systems, crop layouts influence light distribution, affecting light use efficiency (LUE). However, the response of light interception, light conversion, and LUE for relay maize and relay soybean to different crop layouts remains unclear. We aimed to quantify the effect of crop layout on intraspecific and interspecific competition, light interception, light conversion, LUE, and land productivity between relay maize and relay soybean. We conducted a field experiment for four consecutive years from 2017 to 2020 in Sichuan province, China, comparing different crop layouts (bandwidth 2.0 m, row ratio 2:2; bandwidth 2.4 m, row ratio 2:3; bandwidth 2.8 m, row ratio 2:4), with sole maize and sole soybean as controls. The results showed that relay maize in the 2.0 m bandwidth layout had the largest leaf area index and plant biomass, the lowest intraspecific competitive intensity and the highest aggressiveness. Compared to a bandwidth of 2.0 m, a bandwidth of 2.8 m significantly decreased relay maize leaf area index by 11% and plant biomass by 24%, while a 2.4 m bandwidth caused roughly half these reductions. The 2.0 m bandwidth layout also significantly improved crop light interception and LUE compared to sole maize. The light interception, light interception rate, light conversion rate and LUE in relay maize all decreased significantly with increasing bandwidth, but they increased in relay soybean. The increased light transmittance to the lower and middle canopy with increasing bandwidth did not compensate for the loss of relay maize yield caused by increased intraspecific competition. However, it enhanced the yield of relay soybeans. Increasing the bandwidth by 80 cm increased the relay maize intraspecific competition by 580%, and reduced maize yield by 33%, light interception by 12%, and LUE by 18%. In contrast, the relay soybean intraspecific competition was reduced by 64%, and the soybean yield was increased by 26%, light interception by 32% and LUE by 46%. Relay cropping systems with a 2.0 m bandwidth optimize the trade-off between light transmittance and intraspecific competition of relay crops. These systems achieve the highest LUE, group yield and economic benefits, making them a recommended crop layout for the southwest regions of China. Our study offers valuable insights for developing strip relay cropping systems that maximize light utilization and contributes to the theoretical understanding of efficient sunlight use in relay cropping practices.

The prevalence of cardiovascular diseases (CVDs) has increased markedly as the world population has aged. Long non-coding RNAs (lncRNAs) have been reported as novel regulators in diverse pathophysiological conditions. Here, we performed RNA sequencing (RNA-seq) and observed that the lncRNA Zeb1os1 (zinc finger E-box binding homeobox 1, opposite strand 1), which is known as ZEB1-AS1 (zinc finger E-box binding homeobox 1 antisense 1) in humans, was upregulated in the aged mice hearts, senescent cardiomyocytes, and human blood from elderly individuals. The human blood ZEB1-AS1 level was positively relevant to human age but negatively relevant to peak E to peak A (E/A). Silencing Zeb1os1 ameliorated diastolic dysfunction and cardiac senescence in aged mice. On the other hand, Zeb1os1 overexpression triggered cardiac dysfunction resembling that observed in aged mice. Mechanistically, we provide compelling evidence that Zeb1os1 interacts with the transient receptor potential mucolipin 1 (TRPML1) for ubiquitination (UB)-mediated degradation. This process inhibits lysosomal Ca2+ efflux, impairing lysosome function. In addition, the functional domain of Zeb1os1, which contains the key nucleotides responsible for the pro-senescence property of full-length Zeb1os1 in cardiomyocytes. Together, these data suggest that Zeb1os1 is a potential target for ameliorating lysosomal dysfunction and aging-related cardiac impairment.

Abstract Purpose The objective of the current research was to assess the clinicopathological characteristics and long-term prognosis of triple-negative breast cancer (TNBC) patients with human epidermal growth factor receptor 2 (HER2)-low status following breast surgery. Methods A total of 202 TNBC patients treated at Qingdao Central Hospital from January 2010 to December 2019 were included, comprising 71 HER2-low and 131 HER2-zero patients. Propensity score matching (PSM) was applied to minimize differences between the cohorts. Results HER2-low TNBC patients had lower histological grade, lower Ki-67 expression levels, and a higher prevalence of hypertension compared to HER2-zero TNBC patients. Before and after PSM, the HER2-low group consistently exhibited a lower recurrence rate and longer RFS compared to HER2-zero TNBC patients. HER2-low status was validated as an independent low-risk factor for RFS both pre-PSM (HR 0.354, 95% CI 0.178–0.706, p = 0.003) and post-PSM (HR 0.405, 95% CI 0.185–0.886, p = 0.024). No statistically significant differences in mortality rate and OS were observed, both before and after PSM. Conclusions HER2-low and HER2-zero TNBC patients show significant clinicopathological differences. Compared to HER2-zero, HER2-low status is linked to better long-term prognosis and serves as an independent low-risk factor for RFS in TNBC patients.

Abstract Advancements in satellite altimetry have significantly enhanced high-resolution mean sea surface (MSS) models, enabling the computation of high-resolution vertical gravity anomaly gradient (VGAG) models. This study focused on the methodology for computing VGAG models using MSS models, introducing innovative improvements to established techniques. Using the SDUST2020 MSS model within the Arabian Sea research area, the DTU22 and CNES-CLS22 mean dynamic topography (MDT) models, and the XGM2019e_2159 Earth gravity field model for the remove–restore process, the short-wavelength geoid was derived. To harness the extensive marine gravity field information within the MSS model, the study considered the complex marine environment and calculated the second-order derivatives of the geoid in multiple directions. These derivatives were then used to determine their north–south and east–west components through the least squares method, resulting in the computation of the short-wavelength VGAG. By restoring the long-wavelength VGAG, a VGAG model for the study area was established. Finally, the results were analyzed using the SIO V32.1 VGAG model (named curv). Experimental results demonstrated that this approach effectively extracted marine gravity field information from the MSS model using multidirectional data, mitigating the amplification of geoid uncertainties caused by second-order derivatives. Graphical Abstract

This study revealed that the presence of Cr and Ni in stainless steel is one of the leading causes for the weakening of the Mg / Fe interface when using a traditional Mg-Zn-Al (i.e., AZ61) filler wire. By using a novel Mg-Gd-Y-Zr filler wire without Al, the interfacial structure between Mg / Fe was optimized, and the joint integrity was significantly improved. Using advanced multiscale characterization tools, the coherent matching mechanism of rare earth elements in regulating Mg / Fe interfacial compounds was clarified. The results showed that Gd and Y exhibited lower diffusion activation energy and faster diffusion rates in Fe compared to Al resulting in IMCs with more stiffness and mechanical integrity than Al-Mg compounds that are generated at the Mg / Fe interface when using the AZ61 filler wire. High-resolution TEM results revealed that the lattice distortion caused by the diffusion of metal elements changes the original semi-coherent matching interfaces of (0 0 0 1)HCP−Mg and (0 1 2)BCC−Mg24(Y, Gd)5, as well as lattice planes of (0 1 2)BCC−Mg24(Y, Gd)5 and (57¯ 2 3)HCP-Fe17(Y, Gd)2 into a coherent matching interface, which is known to improve mechanical strength. Although lattice planes of (57¯ 2 3)HCP-Fe17(Y, Gd)2 and (1 1 1)BCC-Fe were found to be incoherent interfaces, it was found that Gd, Y, and Zr with larger atomic radii compared to Al diffused into the bulk Fe to form a wide range of (Fe, Gd, Y, Zr, Cr, Ni, Mn) interstitial solid solutions, which helped strengthen the integrity of the joint. The results showed that the load bearing capacity of the AZ31B / Mg-RE / 316 L joint was about 290 N/mm, which is 2.5 times that of the AZ31B / AZ61 / 316 L joints, which was measured at 115 N/mm.