Search

Abstract Background Psychological and trauma-related factors are associated with many diseases and mortality. However, a comprehensive assessment of the association between psycho-trauma exposures and aging acceleration is currently lacking. Methods Using data from 332,359 UK Biobank participants, we calculated biological aging acceleration, indexed by the presence of leukocyte telomere length (LTL) deviation (i.e., the difference between genetically determined and observed LTL > 0). The acceleration of facial aging (i.e., looking older than the chronological age) was assessed using a self-report question. Then, we estimated the associations of each psycho-trauma factor with biological and facial aging acceleration, using logistic regression models adjusted for multiple important covariates. Furthermore, restricted to 99,180 participants with complete psychological and trauma-related data, we identified clusters of individuals with distinct psycho-trauma patterns using the latent class analysis method and assessed their associations with aging acceleration using similar models. Results We observed most of the studied psycho-trauma factors were associated with biological and facial aging acceleration. Compared to the “Absence of trauma and psychopathology” cluster, the “adverse childhood experiences (ACEs) with psychopathology” cluster showed strong associations with those aging measurements (odds ratio [OR] = 1.13 [1.05 − 1.23] for biological and 1.52 [1.18 − 1.95] for facial aging acceleration), while no such association was observed for the “ACEs without psychopathology” cluster (1.04 [0.99 − 1.09] and 1.02 [0.84 − 1.24]. Conclusions Our study demonstrated significant associations of psycho-trauma factors with both biological and facial aging acceleration. The differential aging consequences observed among ACEs exposed individuals with and without psychopathology prompt interventions aimed to improve individuals’ psychological resilience to prevent aging acceleration.

Abstract Pancreatic cancer (PC) is one of the most common malignant tumors of the digestive tract and has a very high mortality rate worldwide. Different PC patients may respond differently to therapy and develop therapeutic resistance due to the complexity and variety of the tumor microenvironment. The Eph/ephrin signaling pathway is extensively involved in tumor-related biological functions. However, the key function of the Eph/ephrin signaling pathway in PC has not been fully elucidated. We first explored a pan-cancer overview of Eph/ephrin signaling pathway genes (EPGs). Then we grouped the PC patients into 3 subgroups based on EPG expression levels. Significantly different prognoses and tumor immune microenvironments between different subtypes further validate Eph/ephrin's important role in the pathophysiology of PC. Additionally, we estimated the IC50 values for several commonly used molecularly targeted drugs used to treat PC in the three clusters, which could help patients receive a more personalized treatment plan. Following a progressive screening of optimal genes, we established a prognostic signature and validated it in internal and external test sets. The receiver operating characteristic (ROC) curves of our model exhibited great predictive performance. Meanwhile, we further validated the results through qRT-PCR and immunohistochemistry. Overall, this research provides fresh clues on the prognosis and therapy of PC as well as the theoretical groundwork for future Eph/ephrin signaling pathway research.

Abstract Predicting soil heavy metal (HM) content is crucial for monitoring soil quality and ensuring ecological health. However, existing methods often neglect the spatial dependency of data. To address this gap, our study introduces a novel graph neural network (GNN) model, Multi-Scale Attention-based Graph Neural Network for Heavy Metal Prediction (MSA-GNN-HMP). The model integrates multi-scale graph convolutional network (MS-GCN) and attention-based GNN (AGNN) to capture spatial relationships. Using surface soil samples from the Pearl River Basin, we evaluate the MSA-GNN-HMP model against four other models. The experimental results show that the MSA-GNN-HMP model has the best predictive performance for Cd and Pb, with a coefficient of determination (R2) of 0.841 for Cd and 0.886 for Pb, and the lowest mean absolute error (MAE) of 0.403 mg kg−1 for Cd and 0.670 mg kg−1 for Pb, as well as the lowest root mean square error (RMSE) of 0.563 mg kg−1for Cd and 0.898 mg kg−1 for Pb. In feature importance analysis, latitude and longitude emerged as key factors influencing the heavy metal content. The spatial distribution prediction trend of heavy metal elements by different prediction methods is basically consistent, with the high-value areas of Cd and Pb respectively distributed in the northwest and northeast of the basin center. However, the MSA-GNN-HMP model demonstrates superior detail representation in spatial prediction. MSA-GNN-HMP model has excellent spatial information representation capabilities and can more accurately predict heavy metal content and spatial distribution, providing a new theoretical basis for monitoring, assessing, and managing soil pollution.

Postmenopausal osteoporosis (PMOP) is a prevalent condition among elderly women. After menopause, women exhibit decreased iron excretion, which is prone to osteoporosis. To design a specific titanium implant for PMOP, we first analyze miRNAs and DNA characteristics of postmenopausal patients with and without osteoporosis. The results indicate that iron overload disrupts iron homeostasis in the pathogenesis of PMOP. Further experiments confirm that iron overload can cause lipid peroxidation and ferroptosis of MSCs, thus breaking bone homeostasis. Based on the findings above, we have designed a novel Ti implant coated with nanospheres of caffeic acid (CA) and deferoxamine (DFO). CA can bind on the Ti surface through the two adjacent phenolic hydroxyls and polymerize into polycaffeic acid (PCA) dimer, as well as the PCA nanospheres with the repetitive 1,4-benzodioxan units. DFO was grafted with PCA through borate ester bonds. The experimental results showed that modified Ti can inhibit the ferroptosis of MSCs in the pathological environment of PMOP and promote osseointegration in two main ways. Firstly, DFO was released under high oxidative stress, chelating with excess iron and decreasing the labile iron pool in MSCs. Meanwhile, CA and DFO activated the KEAP1/NRF2/HMOX1 pathway in MSCs and reduced the level of intracellular lipid peroxidation. So, the ferroptosis of MSCs is inhibited by promoting the SLC7A11/GSH/GPX4 pathway. Furthermore, the remained CA coating on the Ti surface could reduce the extracellular oxidative stress and glutathione level. This study offers a novel inspiration for the specific design of Ti implants in the treatment of PMOP.

With the wastewater treatment project of a taurine production enterprise in Hubei as a case study, this paper analyzed the production process and wastewater quality characteristics of the enterprise, the targeted treatment process of “hydrolysis acidification+pre anoxic+aerobic biochemistry+post anoxic+secondary sedimentation” was adopted. When the average influent COD, ammonia nitrogen, and total nitrogen were 956.8, 50.6, 99.1 mg/L, respectively, the average effluent COD, ammonia nitrogen, and TN were 73.6, 1.6, 12.2 mg/L, respectively, with the average removal rates could reach 92.3%, 96.9%, and 87.7%, respectively. The effluent water quality was stable and meet the limits of water pollutants for newly built enterprises in the Chemical Synthesis Pharmaceutical Industry Water Pollutant Discharge Standard(GB 21904-2008). By adopting tapered aeration and fan frequency conversion control, energy consumption was significantly reduced, and the operating cost was 1.60 CNY/m3.

Abstract DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure. Restoration of DDX17 expression in cardiomyocytes protects cardiac function under pathological conditions. Further studies showed that DDX17 can bind to the transcriptional repressor B-cell lymphoma 6 (BCL6) and inhibit the expression of dynamin-related protein 1 (DRP1). When DDX17 expression is reduced, transcriptional repression of BCL6 is attenuated, leading to increased DRP1 expression and mitochondrial fission, which in turn leads to impaired mitochondrial homeostasis and heart failure. We also investigated the correlation of DDX17 expression with cardiac function and DRP1 expression in myocardial biopsy samples from patients with heart failure. These findings suggest that DDX17 protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1 pathway in heart failure.

Abstract To address the issue of tracking drift and failures in thermal infrared (TIR) tracking tasks caused by target occlusion, this study proposes an anti‐occlusion TIR target tracker named AODiMP‐TIR. This approach involves an anti‐occlusion strategy that relies on target occlusion status determination and trajectory prediction. This enables the prediction of the target's current position when it is identified as occluded, ensuring swift recapture upon reappearance. A criterion is introduced for occlusion status determination based on the classification response map of SuperDiMP. Additionally, a trajectory mapping module designed to decouple target motion from camera motion is presented, enhancing the precision of trajectory prediction. Comparative experiments with other state‐of‐the‐art trackers are conducted on the large‐scale high‐diversity thermal infrared object tracking benchmark (LSOTB‐TIR), LSOTB‐TIR100, and thermal infrared pedestrian tracking benchmark (PTB‐TIR) datasets. The results indicate that the AODiMP‐TIR performs well across all three datasets, particularly exhibiting outstanding performance in occlusion sequences. Furthermore, ablation study experiments confirm the effectiveness of the anti‐occlusion strategy, occlusion determination criterion and trajectory mapping module.

Abstract Background This empirical study aims to investigate the association between mathematics self-efficacy and mathematics achievement gaps among students in Grades 4, 8, and 12, utilizing data from the 2019 National Assessment of Educational Progress (NAEP). The study also considers student-level (e.g., mathematics self-efficacy, gender, race/ethnicity) and school-level (e.g., school location, proportion of underrepresented students) demographics to provide a comprehensive analysis of the factors contributing to mathematics achievement gaps. Methods A two-level cross-sectional multilevel modeling approach was employed to analyze the variance in mathematics achievement, partitioning it into within- and between-school components. This approach allowed for an examination of association between mathematics self-efficacy and achievement gaps while considering various student and school characteristics. The rationale behind this methodology lies in its ability to capture the hierarchical nature of educational data and provide a nuanced understanding of the factors associated with mathematics achievement. Results The analysis of the NAEP data revealed substantial variability in mathematics achievement across schools in the United States at all grade levels. Furthermore, mathematics self-efficacy emerged as a robust predictor of students' mathematics achievement, exhibiting significant effect sizes for Grades 4, 8, and 12. Remarkably, when students' mathematics self-efficacy was held constant, the mathematics achievement gaps among different student subgroups by gender, race/ethnicity, ELL, IEP, NSLP status narrowed, highlighting the importance of self-efficacy in addressing these disparities. The study also identified the presence of significant school contextual effects, further emphasizing the role of the educational environment in shaping mathematics achievement. Conclusions This study underscores the critical role of mathematics self-efficacy in influencing mathematics achievement gaps among students. By acknowledging the association between self-efficacy beliefs and mathematics achievement, policymakers and educators can develop targeted interventions to enhance students' confidence and motivation in mathematics, ultimately promoting equitable educational outcomes. The findings also emphasize the significance of school-level factors, calling for comprehensive approaches that consider both individual and contextual factors in narrowing achievement gaps. The implications of adopting a self-efficacy perspective to address mathematics achievement gaps extend to educational policy, curriculum development, and instructional practices, ultimately fostering more inclusive and effective mathematics education for all students.

PurposeRadiation encephalopathy (REP) is one of the most common complications of radiotherapy for malignant tumors of the head and neck. Symptoms usually appear months to years following radiotherapy, with headache, insomnia, and memory loss as the main clinical features. We report a patient who was admitted to the hospital with anxiety and depressive disorder and was eventually diagnosed with REP.Patients and methodsA 48-year-old patient who had undergone over 2 years of radiotherapy for nasopharyngeal carcinoma was admitted to the Department of Psychosomatic Medicine of our hospital because of recurrent fear, low mood, and waking up from dreams. Magnetic resonance imaging (MRI) revealed a mass in the left temporal lobe with a large peripheral edema. After multidisciplinary consultation, the possibility of tumor recurrence could not be excluded.ResultsResection of the lesioned brain tissue to obtain pathological tissue showed glial cell proliferation and small focal areas of degeneration and necrosis, which indicated that the lesions were inflammatory. Postoperative MRI showed no abnormal signal, and the patient’s condition improved.ConclusionNasopharyngeal carcinoma patients with a history of radiotherapy and symptoms of increased intracranial pressure and neurological damage should be examined for REP. Furthermore, patients may experience anxiety and depressive disorders as a result of temporal lobe damage caused by REP.

Bone is a dynamically active tissue whose health status is closely related to its construction and remodeling, and imbalances in bone homeostasis lead to a wide range of bone diseases. The sulfated glycoprotein C-type lectin structural domain family 11 member A (Clec11a) is a key factor in bone mass regulation that significantly promotes the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts and stimulates chondrocyte proliferation, thereby promoting longitudinal bone growth. More importantly, Clec11a has high therapeutic potential for treating various bone diseases and can enhance the therapeutic effects of the parathyroid hormone against osteoporosis. Clec11a is also involved in the stress/adaptive response of bone to exercise via mechanical stimulation of the cation channel Pieoz1. Clec11a plays an important role in promoting bone health and preventing bone disease and may represent a new target and novel drug for bone disease treatment. Therefore, this review aims to explore the role and possible mechanisms of Clec11a in the skeletal system, evaluate its value as a potential therapeutic target against bone diseases, and provide new ideas and strategies for basic research on Clec11a and preventing and treating bone disease.

Abstract Tibetan Buddhism has an inseparable connection with the spatial characteristics, development process, and human-natural environment of the Tibetan Plateau. This paper takes monasteries as carriers of Tibetan Buddhist culture in U-Tsang region which is one of the traditional geographical units of Tibet. Using geospatial analysis methods, this study explores the spatial quantification characteristics of Tibetan Buddhist monasteries and qualitatively and quantitatively analyzes the factors that influence the spatial distribution of monasteries. The results indicate that: (1) Political activities of human society influence the pattern of political power. Under the unique context of Tibetan theocracy system, the scope of political authority has a significant influence and affects the religious spatial pattern in the U-Tsang region throughout history. The distribution of monasteries in the U-Tsang region shows significant spatial differences at three sub-regional scales. (2) The religious spatial pattern in the U-Tsang is the result of the diverse interaction of human-natural factors. The results indirectly endorse that religious space is an inevitable product of the interaction between humans and the environment. (3) The religious spatial distribution patterns in the three major Tibetan regions have distinct characteristics, closely related to the superior conditions of their respective historical and geographical environments.

Abstract Drought stress can significantly affect plant growth, development, and yield. Fewer comparative studies have been conducted between different species of pines, particularly involving Pinus yunnanensis var. pygmaea (P. pygmaea). In this study, the physiological indices, photosynthetic pigment and related antioxidant enzyme changes in needles from P. pygmaea, P. elliottii and P. massoniana under drought at 0, 7, 14, 21, 28 and 35 d, as well as 7 days after rehydration, were measured. The PacBio single-molecule real-time (SMRT) and Illumina RNA sequencing were used to uncover the gene expression differences in P. pygmaea under drought and rehydration conditions. The results showed that the total antioxidant capacity (TAOC) of P. pygmaea was significantly higher than P. massoniana and P. elliottii. TAOC showed a continuous increase trend across all species. Soluble sugar (SS), starch content and non-structural carbohydrate (NSC) of all three pines displayed a "W" pattern, declining initially, increasing, and then decreasing again. P. pygmaea exhibits stronger drought tolerance and greater recovery ability under prolonged drought conditions. Through the PacBio SMRT-seq, a total of 50,979 high-quality transcripts were generated, and 6,521 SSR and 5,561 long non-coding RNAs (LncRNAs) were identified. A total of 2310, 1849, 5271, 5947, 7710, and 6854 differentially expressed genes (DEGs) were identified compared to the control (Pp0D) in six pair-wise comparisons of treatment versus control. bHLH, NAC, ERF, MYB_related, C3H transcription factors (TFs) play an important role in drought tolerance of P. pygmaea. KEGG enrichment analysis and Gene set enrichment analysis (GSEA) analysis showed that P. pygmaea may respond to drought by enhancing metabolic processes such as ABA signaling pathway, alpha-linolenic acid. Weighted gene co-expression network analysis (WGCNA) revealed GST, CAT, LEC14B, SEC23 were associated with antioxidant enzyme activity and TAOC. This study provides a basis for further research on drought tolerance differences among coniferous species.

The shear behavior of backfill-rock composites is crucial for mine safety and the management of surface subsidence. For exposing the shear failure mechanism of backfill-rock composites, we conducted shear tests on backfill-rock composites under three constant normal loads, compared with the unfilled rock. To investigate the macro- and meso-failure characteristics of the samples in the shear tests, the cracking behavior of samples was recorded by a high-speed camera and acoustic emission monitoring. In parallel with the experimental test, the numerical models of backfill-rock composites and unfilled rock were established using the discrete element method to analyze the continuous-discontinuous shearing process. Based on the damage mechanics and statistics, a novel shear constitutive model was proposed to describe mechanical behavior. The results show that backfill-rock composites had a special bimodal phenomenon of shearing load-deformation curve, i.e. the first shearing peak corresponded to rock break and the second shearing peak induced by the broken of aeolian sand-cement/fly ash paste backfill. Moreover, the shearing characteristic curves of the backfill-rock composites could be roughly divided into four stages, i.e. the shear failure of the specimens experienced: stage I: stress concentration; stage II: crack propagation; stage III: crack coalescence; stage IV: shearing friction. The numerical simulation shows that the existence of aeolian sand-cement/fly ash paste backfill inevitably altered the coalescence type and failure mode of the specimens and had a strengthening effect on the shear strength of backfill-rock composites. Based on damage mechanics and statistics, a shear constitutive model was proposed to describe the shear fracture characteristics of specimens, especially the bimodal phenomenon. Finally, the micro- and meso-mechanisms of shear failure were discussed by combining the micro-test and numerical results. The research can advance the better understanding of the shear behavior of backfill-rock composites and contribute to the safety of mining engineering.

Abstract Background Macular hole (MH) development following scleral buckling (SB) surgery for rhegmatogenous retinal detachment (RRD) repair is rare. This study presents both full-thickness MH (FTMH) and lamellar MH (LMH) cases following SB for the treatment of RRD. Methods Clinical records of patients undergoing SB surgery for treatment of RRD at the Xi’an People’s Hospital (Xi’an Fourth Hospital) from January 2016 to December 2021 were reviewed, and cases with postoperative MH were selected. Clinical features and follow-up data were summarised, and possible causes were analysed. Results Among 483 identified cases (483 eyes), four eyes (three male patients, one female patient) had postoperative MH, with prevalence, mean age, and mean axial length of 0.83%, 43.5 ± 10.66 years, and 29.13 ± 3.80 mm, respectively. All patients did not undergo subretinal fluid (SRF) drainage. The mean time for detecting MH was 26 ± 15.5 days postoperatively. Macula-off RRD with high myopia and FTMH combined with retinal re-detachment were diagnosed in three patients. One patient had macula-on RRD with outer LMH. The average follow-up duration was 7.25 ± 1.5 months. The FTMH closed successfully after reoperation, while the outer LMH closed without intervention. Visual acuity insignificantly improved or slightly decreased in all patients. Conclusions Patients with high myopia combined with macula-off RRD might be more susceptible to FTMH, causing MH related retinal detachment. Additionally, LMH following SB was noted in patients with macula-on RRD. Therefore, we should raise awareness of MH following SB for RRD repair.

Background: We sought to establish a prospective hospital-based cohort, featuring detailed multidimensional data of trauma patients with active follow-ups, which can be a reliable data source for all studies focusing on the effects or underlying mechanistic pathways of environmental and biological factors on multiple interested trauma-related outcomes, particularly the incidence and trajectory of trauma-related psychopathology, in a Chinese population. Methods: The China Severe Trauma Cohort (CSTC) enrolled all traumatized individuals aged 12 to 80 years admitted to the Trauma Center of West China Hospital between March 1st, 2020 and July 8th, 2022. The bio-sample and detailed questionnaire data were collected at recruitment, and phone/internet follow-ups were scheduled at 1, 3, 6, and 12 months after the baseline. Long-term health outcomes are planned to be obtained from administrative databases through data linkage. Results: A total of 2,500 trauma patients were enrolled (response rate = 87.1%) with an average age of 46.01 years, and most of the participants were males (62.6%). The proportions of participants with blood and fecal sample collected at baseline were 93.8% and 66.3%, respectively. As of August 31st, 2022, the follow-up rate was 90.0%, 77.0%, 76.5%, and 89.0% for 1-, 3-, 6-, and 12-month follow-ups, respectively. Fall/wrench (47.6%) and traffic accident (26.2%) were the top causes of current trauma. The most common psychopathology at recruitment was sleep disturbance (39.4%), followed by depression (22.6%), anxiety (18.2%), and acute stress reaction (7.8%), all of which showed recovering trajectories during the follow-up period, particularly the first 3 months after baseline. Conclusion: CSTC provides a platform with multidimensional data to study both short-term and long-term trauma-related health consequences, prompting early identification and intervention for individuals with high risk of health decline after trauma exposures.

In order to improve the efficiency of energy utilization, the integrated energy system (IES) has emerged. The IES typically acts as a whole system during operations, the subsystems are separated, and the interests of each system are independent. In this paper, considering the relationship between the various energy systems, non-cooperative game theory is used to establish the optimal dispatch model. The proposed model mainly relies on the relationship between the cooperation and competition among various subsystems to obtain the maximum benefit they can accept. Furthermore, the basic definition is combined with the particle swarm optimization algorithm to solve the problem. The results show that the optimization strategy proposed in this paper can operate safely and reliably, and effectively distribute the benefits of each energy system.

The negative pressure wave (NPW) signal caused by leakage of water supply pipeline contains a lot of noise due to the influence of water flow state and circuit noise, which will adversely affect the accuracy of leakage detection and leak location. To solve this problem, a novel pipeline pressure signal denoising method based on variational mode decomposition (VMD) is proposed in the paper. Firstly, the key parameters which affect the performance of VMD method: IMFs K and penalty factor $\alpha $ are optimized by genetic algorithm (GA) without prior knowledge. At the same time, different parameters are combined to form different reconstructed signals based on the correlation coefficient (CC). Secondly, the optimal combination of parameters is adaptively determined by using a fitness evaluation function based on the information entropy (IE). Thirdly, based on the optimal parameter combination, reconstruct the signal to achieve noise reduction. Finally, the denoised signal will be used for leak detection and leak location calculation. In order to verify the effectiveness of the proposed method, simulation analysis and laboratory experiments are carried out. Simulation analysis results show that the noise suppression effect of our method is better than that of wavelet, empirical mode decomposition (EMD) and VMD. The highest SNR obtained by our method is 16.187. The laboratory experiment results showed that the NPW signal denoised by proposed method had less error and more stable results in location, with an average relative error of 2.97%.

BackgroundSubclinical hypothyroidism (SCH) is a common endocrine subclinical disorder, the main adverse consequences of which are the development of clinical hypothyroidism and the promotion of ischemic heart disease. Metabolic syndrome (MetS) is a collection of metabolic problems. The goal of this meta-analysis was to evaluate the relationship between MetS and SCH.MethodsSuitable publications were identified using PubMed, Embase, and the Cochrane Library. The meta-analysis included only studies in English that reported odds ratio (OR) data for MetS and SCH. Two researchers combined data using a random-effects model. OR and 95% confidence intervals (CIs) were used to present the results.ResultsMetS was associated with an elevated risk of developing SCH (OR 2.56, 95% CI 1.44–4.55). However, the individual components of MetS were not associated with the risk of SCH. Subgroup analysis revealed that different definitions of MetS had varying effects on SCH. Sensitivity analysis confirmed that our results were robust.ConclusionsThis meta-analysis indicates that patients with MetS have an increased risk of SCH, while there is no significant association between the five individual components of MetS and the risk of SCH.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023454415.

BackgroundLocoregionally advanced nasopharyngeal carcinoma (NPC) is an epithelial malignancy that primarily occurs in East and Southeast Asia, and it is associated with relatively poor overall survival (OS). Currently, there is no reliably effective standard treatment for NPC that progresses after first-line therapy with platinum-based chemotherapy.Case reportA 55-year-old woman diagnosed with stage IVa NPC received two cycles of platinum-based chemotherapy but encountered an increase in the size of cervical lymph nodes and suffered from adverse events. The patient was then switched to toripalimab plus cetuximab combined with radical radiotherapy and had a complete clinical response within 2 months following the completion of radiotherapy without severe treatment-related adverse events.ConclusionThis case report showed that toripalimab plus cetuximab combined with radiotherapy for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma may result in a fast and durable response with a manageable safety profile.

Phthalates, widely utilized in industrial products, are classified as endocrine-disrupting chemicals (EDCs). Although certain phthalate and their metabolites have been implicated in cancer development, the reported findings have exhibited inconsistencies. Therefore, we conducted the comprehensive literature search to assess the association between phthalate and their metabolites and cancer risk by identifying original studies measuring phthalates or their metabolites and reporting their correlation with cancer until July 4, 2023. The Odds Ratios (ORs) and corresponding 95% confidence intervals (CIs) were extracted and analyzed to estimate the risk. Pooled data from eleven studies, including 3101 cancer patients and 6858 controls, were analyzed using a fixed- or random-effects model based on heterogeneity tests. When comparing extreme categories of different phthalates and their metabolites, we observed a significant association between urinary phthalates and phthalate metabolites (MEHHP, MECPP, DBP and MBzP) and cancer risk. The findings of our meta-analysis reinforce the existing evidence that urinary phthalates and phthalate metabolites is strongly associated with cancer development. Further investigations are warranted to elucidate the underlying mechanisms of this association. These results may offer novel insights into cancer development.

Abstract Purpose Patellofemoral arthroplasty (PFA) was shown to be a potentially effective surgical technique for isolated patellofemoral osteoarthritis but varying reports on PFA-related implant failure and complications have rendered the procedure controversial. This study aimed to identify impactful publications, research interests/efforts, and collaborative networks in the field of PFA research. Methods The study used the Web of Science Core Collection (WOSCC) database, Medline, Springer, BIOSIS Citation Index, and PubMed to retrieve relevant publications on PFA research published between 1950–2022. Statistical tests in R software were used for analysis while VOSviewer, Bibliometrix, and CiteSpace were employed for data visualization. Results Two hundred forty-one articles were analyzed with the number of published papers increasing over time. Knee was the most frequent journal and Clinical Orthopaedics and Related Research was the most cited journal. Clinical outcomes, such as prosthesis survival, revision, and complications, were researched most frequently as demonstrated by keyword analysis. The United States was the top contributor to cooperative networks, followed by the United Kingdom while Technical University Munich formed close ties among authors. Conclusion Publications on PFA research have witnessed a notable surge. They primarily came from a limited number of centers and were characterized by low-level evidence. The majority of studies primarily focused on the clinical outcomes of PFA, while revision of PFA and patient satisfaction have emerged as new research areas.

In order to investigate the mechanism of extracellular polysaccharide (EPS) synthesis in Lactobacillus plantarum, a strain of Lactobacillus plantarum YZH81 with high EPS production was selected for the study of extracellular polysaccharide synthesis gene cluster (cps). After whole-genome sequencing, alignment and analysis, it was determined that the genome of YZH81 contained two cps gene clusters, one of which (cps1) had yet to be identified in terms of structure and function, while the other (cps2) was highly homologous to other reported Lactobacillus plantarum strains. The conclusions in this study, the cps1 gene cluster resulted 52.28% reduction in EPS production, accelerated self-aggregation, reduced adhesion and 32.42% reduction in the ability to generated 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH·) in the YZH81∆cps1 strain compared to the wild-type YZH81 strain. The results suggested that the cps1 gene cluster of strain YZH81 was associated with EPS synthesis and established favorable conditions for further studies on the mechanism of EPS biosynthesis in this strain.

High-entropy MXenes, as a new emerging class of materials, possess diverse compositions, unexpected physicochemical characteristics, and great potentials for electromagnetic (EM) wave absorption. Herein, two single-to-few-layer high-entropy MXenes, (Mo0.25Cr0.25Ti0.25V0.25)3C2Tx and (Mo0.2Cr0.2Nb0.2Ti0.2V0.2)4C3Tx, were synthesized for the first time. During the exfoliation and delamination processes, the structural, morphological, and compositional evolutions were analyzed, verifying the successful formation of single-to-few-layer two-dimensional MXene nanosheets. Investigations indicate that with the filling content of only 35 wt%, MXene powder filled composites exhibit high-efficiency EM wave absorption performances. The f-(Mo0.25Cr0.25Ti0.25V0.25)3C2Tx possesses the minimum reflection loss (RLmin) of −45.0 dB with the matching thickness of 1.52 mm and the maximum effective absorption bandwidth (EAB) of 5.6 GHz at 1.65 mm thickness. Also, f-(Mo0.2Cr0.2Nb0.2Ti0.2V0.2)4C3Tx can attain an RLmin of −52.8 dB with the thickness of 1.58 mm and an optimum EAB value of 3.6 GHz at 1.50 mm. The satisfactory EM wave absorption efficiency and bandwidth, thin matching thickness, and low filling content prove the lightweight advantage and great application potential of high-entropy MXenes in EM wave absorption. In this work, the high-entropy strategy is applied to tune the EM wave absorption performances for MXenes. Furthermore, high-entropy engineering is expected to provide control and tunability of many other properties, such as electrochemical, catalytic, and mechanical behaviors.

In the Ordos mining area of North China, the Jurassic coal seam is commonly overlain by extremely thick cretaceous sandstone strata. Based on the seismic displacement field and relative moment tensor inversion method, this paper investigates the mine earthquake mechanism and roof fracture characteristics of coal seams under extremely thick strata. In this study, by using seismic source groups as units and microseismic stations as objects, the source mechanism of mine earthquakes is inverted by constructing an inversion matrix, which greatly improves the inversion efficiency and accuracy. The focal mechanism of large-energy mine earthquakes located in solid coal section and goaf section under extremely thick strata is calculated. The characteristics of roof fracture evolution and the influence of vibration wave radiation are quantitatively analyzed. The results show that the extremely thick strata of Cretaceous goaf start to break when the panel below retreats along goaf. During this period, the surface subsidence increases rapidly, and the significant mine earthquakes with energy above 100 kJ begin to occur, and the mine earthquake distribution is more concentrative than that in the solid coal stage. Most of the large-energy mine earthquakes are located behind the goaf, which is closely related to the breakage and slide of the thick roof. Roof tension rupture accounts for more than 85% of the mine earthquakes. During mining along goaf, the seismic sources tend to expand upward, and more shear slip ruptures are presented compared with that in the solid coal mining stage. The strike of the fracture surface has a similar direction or an angle of “X” with the advancing direction. However, compared with that in the solid coal stage, the angle of “X” during mining along goaf increases from 30° to 45°. For the source rupture surface, the dip angle of between 0°−30° accounts for about 50% of the total. The failure type of roof is dominated by horizontal separation tension and roof rotation compression. The generated P waves mostly propagate to the goaf below, which causes a minor influence on the mining face. Only a small part of the P waves propagate to the surrounding working face, which may pose a great impact on the working face. The prevention and control strategy on the extremely-thick-strata type mine earthquakes can be conducted by weakening the integrity of thick strata and making thick strata break in tiers, aiming to reduce the rockburst risks to the working face induced by the breakage of the whole thick strata.

Abstract Platelet-rich plasma (PRP) has gained significant attention in the field of regenerative medicine due to its potential therapeutic applications. However, few studies have reported the components, especially anti-ageing-related components, of PRP derived from umbilical cord blood (UCB). It is essential to understand the influence of age on the composition and efficacy of PRP to optimize its clinical use. The present study compared the concentrations of bioactive components in PRP from healthy female adults and UCB-derived PRP. PRP was obtained from blood samples from females in four age groups (12 per group): neonates (UCB donors) and adults aged 18–25, 26–45, and 46–65 years, respectively. The concentrations of epidermal growth factor, basic fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1, platelet-derived growth factor-AA (PDGF-AA), PDGF-AB/BB, vascular endothelial growth factor A, RANTES, TIMP-1, TIMP-2, GDF11, and clusterin and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPx) in the PRP samples were determined and compared among groups. Pairwise comparisons between the groups showed statistically significant differences in the concentrations of some bioactive components of PRP, such as FGF-2, PDGF-AB/BB, and clusterin, and GPx activity. UCB-derived PRP contains various active ingredients such as VEGF-A, CAT activity, and TIMP-2. Contrary to expectations, UCB-derived PRP did not show higher concentrations of the anti-ageing protein GDF11. Because UCB is a rich source of bioactive components with low immunogenicity, its use in PRP preparation is an important research direction for future studies.

Mineral elements and non-structural carbohydrates (NSCs) are important nutrients and energy sources for flower development in plants. However, no studies were reported on the dynamic changes of nutrient stoichiometry and NSC contents in Houpoea officinalis (H. officinalis) flower. In this study, the changes in carbon (C), nitrogen (N), phosphorus (P), and NSC contents as well as C:N:P stoichiometry in the pistil, stamen, and petal of H. officinalis flowers at four developmental stages were comparatively analyzed. The results showed that C, N, P, and NSC contents, as well as C:N:P stoichiometric ratios in the three parts of the flower exhibited large variations at four development stages. Development stages and organs had significant effects on the measured parameters in the three organs of H. officinalis flowers, but their interactions had no significant effects. During the flower development, C, N, and P contents in different floral parts ranged from 418.7 to 496.3 mg/g, 26.6 to 45.3 mg/g, and 0.396 to 0.656 mg/g. P content decreased continuously with development, C:N in stamen were significantly higher than those in other flower parts at the same developmental stage. Glucose, starch, fructose, and sucrose contents showed significant differences in three parts of H. officinalis flowers at four development stages. These differences may reflect differences in elemental storage capacity and biomass allocation patterns of H. officinalis flowers. In general, our data will help to improve our understanding of the relationship between NSCs and C:N:P stoichiometry in response to development stages and organs in H. officinalis flowers.

Lonicera similis Hemsl. (L. similis) is a promising industrial crop with flowers rich in phenolic compounds. In this study, an ultrasound-assisted extraction (UAE) was designed to extract phenolic compounds from L. similis flowers (LSFs). A contrastive analysis on the phenolic compounds’ yield and characterization and the antioxidant activity of the extracts at three harvest stages (PGS I, PGS II, and PGS III) are reported. The results indicate that the optimal conditions are a sonication intensity of 205.9 W, ethanol concentration of 46.4%, SLR of 1 g: 31.7 mL, and sonication time of 20.1 min. Under these optimized conditions, the TPC values at PGS I, PGS II, and PGS III were 117.22 ± 0.55, 112.73 ± 1.68, and 107.33 ± 1.39 mg GAE/g, respectively, whereas the extract of PGS I had the highest TFC (68.48 ± 2.01 mg RE/g). The HPLC analysis showed that chlorogenic acid, rutin, quercetin, isoquercitrin, and ferulic acid are the main components in the phenolic compounds from LSFs, and their contents are closely corrected with the harvest periods. LSF extracts exhibited a better antioxidant activity, and the activity at PGS I was significantly higher than those at PGS II and PGS III. The correlation analysis showed that kaempferol and ferulic acid, among the eight phenolic compounds, have a significant positive correlation with the antioxidant activity, while the remaining compounds have a negative correlation. Minor differences in extracts at the three harvest stages were found through SEM and FTIR. These findings may provide useful references for the optimal extraction method of phenolic compounds from LSFs at three different harvest periods, which will help to achieve a higher phytochemical yield at the optimal harvest stage (PGS I).

Objectives: To investigate the association between diabetes and cognitive dysfunction in the elderly population, and examine the impact of cognitive dysfunction on level of activities of daily living (ADL) in patients with diabetes. Methods: Data analysis was conducted on 2,951 individuals aged over 65 years from the Chinese Longitudinal Healthy Longevity Survey cohort. Propensity score matching was utilized to mitigate selection bias. Multivariate binary logistic regression was performed to analyse the association between diabetes and cognitive dysfunction in the study subjects. In addition, the relationship between ADL and cognitive function in patients with diabetes was analysed using the Wilcoxon rank-sum test. Results: A significant association (p = 0.017) was found between diabetes and the occurrence of cognitive dysfunction in older adults. Subgroup analyses revealed that diabetes patients with cognitive dysfunction exhibited a worse ADL dependence compared with those without cognitive dysfunction (p

Filtration rate is a crucial characteristic for bivalves that engage in filter feeding, and is subject to regulation in response to various environmental factors. Golden mussel, Limnoperna fortunei, known as intensively invasive species in South America and many Asian regions, has been observed to exhibit a wide range of filtration rate, resulting in challenges in hydraulic modeling and impact assessment. In this study, we performed a series of experiments and developed a mussel pump model to assess the filtration rate of golden mussels with different shell lengths and to investigate the impact of environmental factors that influence the filtration rate, i.e., food type, water temperature, and flow condition. We found that filtration rates increased with shell length, while filtration rates per unit weight decreased with shell length. Additionally, we observed that filtration rates were comparable when the mussels were fed with food that share similar/identical cellular properties, e.g., Saccharomyces cerevisiae and Chlorella pyrenoidosa. The temperature's effect on filtration rates followed a skewed unimodal pattern, with an optimal temperature near 20 ℃. Interestingly, the experiments also showed that the golden mussel can filter at low temperatures (2 ℃), indicating its capacity for overwinter survival in cold regions. Moreover, the golden mussel's filtering was promoted under low-velocity flowing conditions. The relationship between filtration rate and multiple factors was explicable using our pump mussel model, which could be simplified to reveal the effect of each single factor. The model shows superior mechanical explanations and better accuracy performance compare to previous statistical models.

Premna puberula, a medicine food homologous plant, is utilized in the preparation of cold tofu and as traditional Chinese medicine. This study aimed to identify the chemical components of P. puberula root petroleum ether extract (PEE) and clarify its anticancer properties and associated mechanisms. The MTT results of the four extracts (petroleum ether extract, ethyl acetate extract, n-butanol extract, and water extract) from P. puberula root showed that the PEE had good cytotoxic activity against A549 cells (IC50 = 38.01 ± 3.36 μg/mL) and low toxicity to normal cells (IC50 = 76.85 ± 3.18 μg/mL). The GC-FID/MS analysis revealed fifty compounds, which made up 98.6 % of the total PEE. Further antitumor assay demonstrated that PEE induced cell cycle arrest in the S phase by up-regulating p21 and cyclin E2 expression, thereby inhibiting the proliferation of A549 cells. Simultaneously, it induces apoptosis through the mitochondrial-mediated apoptosis pathway, which significantly up-regulated the ratio of Bax/Bcl-2, down-regulated mitochondrial membrane potential (ΔΨm), promoted the release of Cyt c, activated caspase-9 and caspase-3, thereby resulting in PARP cleavage. It prevented the migration and invasion of A549 cells by reducing the expression of MMP-2 and N-cadherin. In conclusion, P. puberula root PEE can be a new source of antitumor agents and has significant anticancer activity in vitro.

Inter-basin water diversion projects have led to accelerated colonization of aquatic organisms, including the freshwater golden mussel (Limnoperna fortunei), exacerbating global biofouling concerns. While the influence of environmental factors on the mussel's invasion and biofouling impact has been studied, quantitative correlations and underlying mechanisms remain unclear, particularly in large-scale inter-basin water diversion projects with diverse hydrodynamic and environmental conditions. Here, we examine the comprehensive impact of environmental variables on the establishment risk of the golden mussel in China's 1432-km-long Middle Route of the South-to-North Water Diversion Project. Logistic regression and multiclass classification models were used to investigate the environmental influence on the occurrence probability and reproductive density of the golden mussel. Total nitrogen, ammonia nitrogen, water temperature, pH, and velocity were identified as crucial environmental variables affecting the biofouling risk in the project. Logistic regression analysis revealed a negative correlation between the occurrence probability of all larval stages and levels of total nitrogen and ammonia nitrogen. The multiclass classification model showed that elevated levels of total nitrogen hindered mussel reproduction, while optimal water temperature enhanced their reproductive capacity. Appropriate velocity and pH levels were crucial in maintaining moderate larval density. This research presents a quantitative analytical framework for assessing establishment risks associated with invasive mussels, and the framework is expected to enhance invasion management and mitigate biofouling issues in water diversion projects worldwide.

Micro-alloying Mg alloys with rare earth elements is an economical and promising way to improve their corrosion resistance. It is of great importance to understand their corrosion behavior for designing corrosion-resistant Mg alloys. In this work, Mg-11Al-0.2Y alloy was prepared for exploring its corrosion behavior in 3.5 wt.% neutral NaCl solution. It exhibits a low corrosion current density of 2.3 µA/cm2 after immersion for 1 d due to the formation of a protective surface film containing Al2O3, MgO and Mg(OH)2. However, nano-scaled pores exhibit at the film/matrix interface, which undermines integrity and protectiveness of the surface film after long-term exposure to chloride solution.

Abstract Background Low back pain (LBP) is one of the leading causes of disability worldwide. Differences in social backgrounds and lifestyles in various regions and countries may contribute to the discrepancies in the disease burden of LBP. Methods Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of LBP disability-adjusted life years (DALYs). Temporal trends in ASR were also analyzed using estimated annual percentage change (EAPC). The Age-period-cohort (APC) model was used to estimate age, period and cohort trends in DALYs of LBP. An autoregressive integrated moving average (ARIMA) model was used to forecast DALYs of LBP trends from 2020 to 2035. Results The DALYs due to LBP increased from 1990 to 2019. The APC model showed that the risk of DALYs for global LBP increased with age and year and that the risk of DALYs was lower in the later-born cohort than in the earlier-born cohort. The main risk factors which GBD estimates were available for DALYs of LBP include smoking, occupational ergonomic factors and high BMI. It is expected that DALYs of LBP will continue to rise until 2035. Conclusion From 1990 to 2019, the global disease burden of LBP remained high. It is necessary to pay attention to the influence of social factors and lifestyle on LBP. Focusing on the impact of social factors as well as lifestyle on the prognosis of LBP and targeting interventions may further reduce the disease burden of LBP.

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

This study presents an innovative pulse-rotating biological contactor (P-RBC) designed to enrich glycogen-accumulating organisms (GAOs), thereby facilitating low-energy chemical oxygen demand (COD) removal. It then investigates the impact of rotational speed and hydraulic retention time (HRT) on GAO enrichment and COD removal efficiency. Optimized conditions at lower speeds and longer HRTs significantly enhance GAO proliferation and Polyhydroxyalkanoate (PHA) synthesis, the key to COD removal. Noteworthy findings include a maximum GAO abundance of 21.34% at a half round per hour (rph) rotating speed, which correlates with a 90.2% COD removal rate and an HRT of 6 h, yielding a 21.23% GAO abundance and 89.8% COD removal. This study also explores various carbon sources for PHA synthesis, with sodium acetate proving the most effective. Compared to other wastewater treatment methods, P-RBC demonstrates minimal energy consumption (0.09 kWh per ton of wastewater), highlighting its potential as a sustainable and effective approach for wastewater treatment.

Abstract Background and Aim Programmed death 1 (PD‐1) and programmed death ligand 1 (PD‐L1) inhibitors have transformed the treatment landscape of advanced hepatocellular carcinoma (HCC), but consistent responses are not observed in all patients, and prognostic biomarkers to guide treatment decisions are lacking. We aimed to evaluate the predictive value of PD‐L1 expression in advanced HCC patients treated with PD‐1/PD‐L1 inhibitors. Methods A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted. Studies comparing the objective response rate (ORR) and/or disease control rate (DCR) based on the tumor PD‐L1 status of HCC were included. Results Eleven studies with 1,330 HCC patients treated with PD‐1/PD‐L1 inhibitors were included. Pooled odds ratio (OR) analysis demonstrated a significantly improved ORR in PD‐L1‐positive patients compared with PD‐L1‐negative patients (OR, 1.86, 95% CI, 1.35–2.55). Similar results were observed in the anti‐PD‐1 treatment (p

Abstract Experimental Advanced Superconducting Tokamak (EAST) was built to demonstrate high-power, long-pulse operations under fusion-relevant conditions, with major radius R = 1.9 m, minor radius a = 0.5 m, and design pulse length up to 1000s. It has an ITER-like D-shaped cross-section with two symmetric divertors at the top and bottom, accommodating both single null and double null divertor configurations. EAST construction was started in 2000, and its first plasma was successfully obtained in 2006. In the past 15 years, plasma-facing components, plasma heating, diagnostics, and other systems have been upgraded step by step to meet its mission on exploring of the scientific and technological bases for fusion reactors and studying the physics and engineering technology issues with long pulse steady-state operation. An advanced steady-state plasma operation scenario has been developed, and plasma parameters were greatly improved. Meanwhile, front physics on the magnetic confinement plasmas have been systemically investigated and lots of fruitful results were realized, covering transport and confinement, MHD stabilities, pedestal physics, divertor and scrap-off layer (SOL) physics, and energetic particle physics. This brief review of EAST on engineering upgrading, stand-steady operation scenario development, and plasma physics investigation would be useful for the reference on construction and operation of a superconducting tokamak, such as ITER and future fusion reactor.

Plant respiratory burst oxidase homologs (RBOHs) are key enzymes regulating superoxide production, which is important for plant development and responses to biotic and abiotic stresses. This study aimed to characterize the RBOH gene family in pea (Pisum sativum L.). Seven PsRBOH genes were identified in the pea genome and were phylogenetically clustered into five groups. Collinearity analyses of the RBOHs identified four pairs of orthologs between pea and soybean. The gene structure analysis showed that the number of exons ranged from 6 to 16. Amino acid sequence alignment, conserved domain, and conserved motif analyses showed that all seven PsRBOHs had typical features of plant RBOHs. The expression patterns of PsRBOH genes in different tissues provided suggested their roles in plant growth and organ development. In addition, the expression levels of PsRBOH genes under different abiotic stresses were analyzed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results demonstrated that PsRBOH genes exhibited unique stress-response characteristics, which allowed for functional diversity in response to different abiotic stresses. Furthermore, four PsRBOHs had a high probability of localization in the plasma membrane, and PsRBOH6 was localized to the plasma membrane and endoplasmic reticulum. The results of this study provide valuable information for further functional analysis of pea RBOH genes and their role in plant adaptation to climate-driven environmental constraints.

ABSTRACTObservational studies have shown that the gut microbiome is associated with frailty. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between the genetically predicted gut microbiome and frailty using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from a genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We used LDSC and MR analyses to estimate the genetic correlation and causality between the genetically predicted gut microbiome and frailty. Our findings indicate a suggestive genetic correlation between Christensenellaceae R-7 and frailty. Moreover, we found evidence for suggestive causal effects of twelve genus-level gut microbes on frailty using at least two MR methods. There was no evidence of horizontal pleiotropy or heterogeneity in the MR analysis. This study provides suggestive evidence for a potential genetic correlation and causal association between several genetically predicted gut microbes and frailty. More population-based observational studies and animal experiments are required to clarify this association and the underlying mechanisms.

Idiopathic pulmonary arterial hypertension (IPAH) is a serious and fatal disease. Recently, m6A has been reported to play an important role in the lungs of IPAH patients and experimental pulmonary hypertension models. However, the meaning of m6A mRNAs in the peripheral blood of IPAH patients remains largely unexplored. We aimed to construct a transcriptome-wide map of m6A mRNAs in the peripheral blood of IPAH patients. M6A RNA Methylation Quantification Kit was utilized to measure the total m6A levels in the peripheral blood of IPAH patients. A combination of MeRIP-seq, RNA-seq and bioinformatics analysis was utilized to select m6A-modified hub genes of IPAH. MeRIP-qPCR and RT-qPCR were used to measure the m6A levels and mRNA levels of TP53, RPS27A, SMAD3 and FoxO3 in IPAH patients. Western blot was performed to assess the protein levels of m6A related regulators and m6A related genes in experimental PH animal models, hypoxia-treated and PDGF-BB induced PASMCs. We found that the total m6A levels were increased in peripheral blood of IPAH patients and verified that m6A levels of RPS27A and SMAD3 were significantly elevated and m6A levels of TP53 and FoxO3 were significantly reduced. The mRNA or protein levels of RPS27A, SMAD3, TP53 and FoxO3 were changed in human blood samples, experimental PH animal models and PDGF-BB induced PASMCs. Moreover, METTL3 and YTHDF1 were increased in the hypoxia induced pulmonary hypertension rat model, hypoxia-treated and PDGF-BB induced PASMCs. These finding suggested that m6A may play an important role in IPAH.

AbstractWith the increase of mining depth and mining intensity of the large inclined extra-thick coal seam (LIETCS), the number of rock bursts increases significantly. In this paper, based on a rock burst during upper roadway driving of the LIETCS, the distribution characteristics and fracture mechanism of microseismic (MS) events are analyzed using data statistics and seismic moment tensor inversion. By means of mechanical analysis and numerical simulation, this paper studies the static load distribution characteristics and dynamic load action effect of the LIETCS under upper slice mining condition. Based on the theory of dynamic and static combined load, the mechanism of rock bursts is proposed. The results show that the coal and rock mass of the LIETCS are mainly destroyed by shearing. The “shear-clamping” stress produced by the joint action of the roof and floor is the static load source. In upper slice mining, the shear stress and energy of the coal pillar behind the slice and the coal body below the coal pillar always remain high. Under the superposition of floor dynamic load, the regional stress environment changes, which induces rock bursts. This study provides a theoretical basis for rock burst prevention under similar conditions.

ABSTRACTIn China, the number of newly reported HIV infections in older people is increasing rapidly. However, clear information on the impact of older people on HIV transmission is limited. This study aims to reveal the local HIV transmission patterns, especially how older people affect virus transmission. Subtype analysis based on available pol sequences obtained from HIV patients revealed that CRF01_AE and CRF08_BC were predominant in patients aged

Probiotics are receiving significant attention due to their considerable health advantages. However, research involving the effect of probiotic biofilm and planktonic cells on the health of the host is limited. This study ascertained that the biofilm cells of Lactiplantibacillus paraplantarum LR-1 displayed stronger immunomodulation activity than their planktonic counterparts. Furthermore, the LR-1 biofilm cells more distinctly influenced the relative abundance of the intestinal marker bacteria than the planktonic cells. In comparison to the planktonic cells and the control group, the biofilm cells exhibited a stronger potential positive effect on the metabolism of the mice. Correlation analysis revealed the interaction between the metabolites, genera, and immune factors, which could explain the mechanism behind the beneficial effect of LR-1 biofilm or planktonic cells on host health. The results of this study enhance the understanding of the beneficial impact of probiotic biofilm cells while providing references for further investigation.

Abstract Pinus elliottii used as rootstock instead of homologous rootstock, have been proved to accelerate early growth of the scion (Pinus massoniana), for cultivation of large diameter wood. However, the basal diameter of scions in heterologous grafts was significantly smaller than self-graft 10 years later, according to field investigation, which was opposed to cultivation objectives. Although advantage of heterologous grafts has been reported, less is known about the long term effect of heterologous rootstock on scions of P. massoniana. The aim of present study was to investigate the mechanism of the above difference. Toward this aim, the growth traits and physiological characteristics of scions in the two graft groups were studied, and the underlying mechanism was preliminarily explored through transcriptome sequencing technology. Results showed that scions of heterologous grafts had less TSCA compared to self-grafts, while no significant difference of plant height, number of branches and canopy volume between two graft groups. Besides, scion leaves of heterologous grafts displayed higher antioxidant enzyme activity and lower chlorophyll content. And interactions between rootstocks and scions had also changed the mineral element composition of scion leaves. Compared with homologous grafts, scion leaves of heterologous grafts accumulated more K+, Mg2+ and Zn2+, but less Ca2+,which have been proved to be conducive to the growth of stem diameter of P. massoniana. Moreover, a comparative transcriptome analysis of two graft groups showed that DEGs between them were mainly caused by the specificity of rootstock. GO and KEGG analysis found that heterologous rootstock had different gene expression preferences, and the gene expression level between rootstocks and scions were significantly different, such as auxin auxin-related genes and stress responsive genes. That may imply that auxin pathway played an important role not only in grafting healing process, but also in maintaining the growth between scion and stock. Summary of all above results, we concluded that the long term effect of heterologous rootstock on scions may be unsatisfactory with the later rapidly growth of scion, probably due to delayed graft incompatibility between scion and stock of heterologous grafts. This study may remind us that the long-term growth of the scion deserves attention as well as the healing process, which could also provide a basis for delayed graft incompatibility.

Abstract Introduction Due to the high recurrence, the HCC prognosis remains poor. Yet, the biomarkers for predicting the recurrence of high‐risk patients are currently lacking. We aimed to develop a signature to predict the recurrence of HCC based on NKG2D ligands. Methods The multivariate Cox proportional hazards regression was used to select recurrence‐related variables of NKG2D ligands in HCC patients from The Cancer Genome Atlas (TCGA). HCC patients from the OEP000321 dataset and Guilin cohort were used to validate the predictive signature. The mRNA expression of NKG2D ligands was measured by QRT‐PCR. Immunohistochemistry analysis of HCC tissue microarray samples was used to identify the expression of NKG2D ligands. Results In this study, NKG2D ligands expression in the mRNA and protein level was both abnormally expressed in HCC and associated with recurrence‐free survival (RFS). Then, the recurrence‐related variables of NKG2D ligands in HCC were selected by the multivariate Cox proportional hazards regression. Among the eight NKG2D ligands, MICA (HR = 1.347; 95% CI = 1.012–1.793; p = 0.041), ULBP3 (HR = 0.453; 95% CI = 0.231–0.889; p = 0.021) and ULBP5 (HR = 3.617; 95% CI = 1.819–7.194; p

Abstract To provide high‐quality imaging by decreasing the sparse view imaging artefact from the computed tomography (CT) images, this study addresses a new artefact suppression technique for sparse data for both single material and multi‐material objects that have diverse materials. It begins with a pre‐reconstructed image and a network of target patches that have been trained beforehand and then uses the forward projection (FP) approach to resolve the structural mutation brought on by sparse‐view projection. As an edge‐preserving operator to commit to the forward operator for sinogram correction, the bilateral filter was used. Both simulated and actual data have been gathered and evaluated in experiments. The suggested forward operator and normalized compensation (FONC) method produce results that have far smaller artefact and errors than those of more traditional techniques. For simulation # blade, the Normalized Mean Square Distance (NMSD) of the proposed method was reduced by 8.94%, Structural Similarity Index (SSIM) and the Universal Quality Index (UQI) were increased by 78.17% and 80.49%, respectively, which also demonstrate better uniformity of the results to practical data # pan, where the root mean squared error was reduced by 13.93%. SSIM and UQI were increased by 25.66% and 37.02%, respectively. The results conclusively show that the planned strategies are successful in eliminating artefact for irregular objects.

Abstract Background and objective Liver fibrosis has been considered a predictor of cardiovascular disease. This study aimed to evaluate whether the degree of liver fibrosis is related to post-stroke depression (PSD) at 3 months follow-up. Methods We prospectively and continuously enrolled patients with first-ever ischemic stroke from June 2020 to January 2022. Liver fibrosis was measured after admission by calculating the Fibrosis-4 index (FIB-4) and stratified into two categories ( 7 were further evaluated using the Chinese version of the structured clinical interview of DSM-IV, for diagnosing PSD at 3 months. Results A total of 326 patients (mean age 66.6 years, 51.5% male) were recruited for the study. As determined by the FIB-4 score, 80 (24.5%) patients had advanced liver fibrosis. During the follow-up, PSD was observed in 91 patients, which accounted for 27.9% (95% confidence interval [CI] 25.5%–30.5%) of the cohort. The prevalence of advanced liver fibrosis was higher in PSD patients than those without PSD (40.0% versus 24.0%; P = 0.006). After adjustment for covariates in the multivariate logistic analysis, advanced fibrosis was significantly associated with PSD (odds ratio [OR], 1.88; 95% CI, 1.03–3.42; P = 0.040). Similar results were found when the FIB-4 was analyzed as a continuous variable. Conclusions This study found that advanced liver fibrosis was associated with an increased risk of 3-month PSD. FIB-4 score may be valuable for screening depressive symptoms in ischemic stroke patients.

Abstract Background The vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC). Methods Immunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases. Results Among 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively. Conclusion Claudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

AIM: To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma. METHODS: Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining. RESULTS: During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1β (IL-1β) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1β expression. Ozurdex suppressed the expression of IL-1β, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits. CONCLUSION: The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1β, and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1β inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis–apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.