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Abstract Background Growth hormone-secreting pituitary neuroendocrine tumors can be pathologically classified into densely granulated (DGGH) and sparsely granulated types (SGGH). SGGH is more aggressive and associated with a poorer prognosis. While epigenetic regulation is vital in tumorigenesis and progression, the role of N6-methyladenosine (m6A) in aggressive behavior has yet to be elucidated. Methods We performed m6A-sequencing on tumor samples from 8 DGGH and 8 SGGH patients, complemented by a suite of assays including ELISA, immuno-histochemistry, -blotting and -fluorescence, qPCR, MeRIP, RIP, and RNA stability experiments, aiming to delineate the influence of m6A on tumor behavior. We further assessed the therapeutic potential of targeted drugs using cell cultures, organoid models, and animal studies. Results We discovered a significant reduction of m6A levels in SGGH compared to DGGH, with an elevated expression of fat mass and obesity-associated protein (FTO), an m6A demethylase, in SGGH subtype. Series of in vivo and in vitro experiments demonstrated that FTO inhibition in tumor cells robustly diminishes hypoxia resistance, attenuates growth hormone secretion, and augments responsiveness to octreotide. Mechanically, FTO-mediated m6A demethylation destabilizes desmoplakin (DSP) mRNA, mediated by the m6A reader FMR1, leading to prohibited desmosome integrity and enhanced tumor hypoxia tolerance. Targeting the FTO-DSP-SSTR2 axis curtailed growth hormone secretion, therefor sensitizing tumors to octreotide therapy. Conclusion Our study reveals the critical role of FTO in the aggressive growth hormone-secreting pituitary neuroendocrine tumors subtype and suggests FTO may represent a new therapeutic target for refractory/persistent SGGH.

Abstract Skull-base chordoma is a rare, aggressive bone cancer with a high recurrence rate. Despite advances in genomic studies, its molecular characteristics and effective therapies remain unknown. Here, we conduct integrative genomics, transcriptomics, proteomics, and phosphoproteomics analyses of 187 skull-base chordoma tumors. In our study, chromosome instability is identified as a prognostic predictor and potential therapeutic target. Multi-omics data reveals downstream effects of chromosome instability, with RPRD1B as a putative target for radiotherapy-resistant patients. Chromosome 1q gain, associated with chromosome instability and upregulated mitochondrial functions, lead to poorer clinical outcomes. Immune subtyping identify an immune cold subtype linked to chromosome 9p/10q loss and immune evasion. Proteomics-based classification reveals subtypes (P-II and P-III) with high chromosome instability and immune cold features, with P-II tumors showing increased invasiveness. These findings, confirmed in 17 paired samples, provide insights into the biology and treatment of skull-base chordoma.

The species of Amemboa Esaki, 1925 from China are reviewed. Amemboa hainanica sp. nov., is described from Hainan Island, and Amemboa burmensis J. Polhemus & Andersen, 1984 is newly recorded from China. Additionally, diagnoses and new distribution records are provided for six species previously reported from China: A. brevifasciata Miyamoto, 1967, A. cristata J. Polhemus & Andersen, 1984, A. esakii J. Polhemus & Andersen, 1984, A. fumi Esaki, 1925, A. riparia J. Polhemus & Andersen, 1984, and A. speciosa J. Polhemus & Andersen, 1984. Photographs and line drawings of the habitus, the diagnostic characteristics of males, in-situ habitus, and their habitats are presented. A key and a distribution map are also provided for species of Amemboa occurring in China.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusion : s: In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

FOLFOX, composed of 5-FU, oxaliplatin and leucovorin, is a first line chemotherapy regimen for colorectal cancer (CRC) treatment. In this study, we show that 5-FU and oxaliplatin induce DNA damage and activate cGAS/STING signaling leading to enhanced expression of interferon (IFN) β, IFN-stimulated genes and inflammatory cytokines in mouse and human colon cancer cells as well as increased intratumoral CD8+ T cells in mice. Crucially, 5-FU and oxaliplatin increase PD-L1 expression at the mRNA and protein levels, which has been shown to inhibit CD8+ T cell function. Depletion of cGAS, STING, IRF3, or IFNα/β receptor 1 (IFNAR1) abolishes this increase, indicating that 5-FU/oxaliplatin mediated upregulation of PD-L1 expression is dependent on tumor cell intrinsic cGAS/STING signaling. These results imply opposing roles for FOLFOX during cancer treatment. On one hand, 5-FU and oxaliplatin activate the innate immune response to facilitate anti-tumor immunity, and conversely upregulate PD-L1 expression to evade immune surveillance. Analysis of TCGA colon cancer dataset shows a positive correlation between expression of PD-L1 and components of the cGAS/STING pathway, supporting a role for cGAS/STING signaling in upregulating PD-L1 expression in colon cancer patients. Tumor studies in syngeneic immune competent mice demonstrate that the combination of 5-FU/oxaliplatin and anti-PD-1 significantly reduced tumor growth of colon cancer cells compared to 5-FU/oxaliplatin treatment alone. Taken together, our studies have identified a unique pathway leading to chemoresistance and provide a rationale to combine FOLFOX with anti-PD-1/PD-L1 as an effective CRC treatment.

Continuous operating reference station (CORS) networks, underpinned by GNSS technology, support various technological services including comprehensive surveying, navigation, and remote sensing. The stability of these CORS networks is crucial for maintaining the high accuracy and reliability of data services. In this paper, we focus on analyzing the GPS deformation array of Vancouver Island, Canada, and present a thorough stability analysis scheme for CORS networks that is adaptable to other areas with frequent tectonic activity. For this study, we first conducted a data quality assessment based on three primary indices — namely, multipath effect on L1 and L2 frequency, signal-to-noise ratio in both frequency and cycle slip ratio — using the Transfer Edit Quality Check (TEQC) software. Then, we achieved high-precision data processing using the GAMIT/GLOBK software, in order to quantify the changes at each station over the specific periods. Seasonality analysis was also incorporated into the pipeline. Considering the potential variances affecting the deformation array over time, the coordinates were transformed under a unified reference frame, enabling the study of changes with station coordinates from different epochs under the same systematic conditions. Additionally, the impact of plate tectonic was examined through correlation analysis. The results showed that, while the observation data from the QUAD station in the island deformation array are of poor quality, relative stability was maintained within the deformation array. The PTRF and CLRS stations exhibited vertical instability in the fall season, while the QUAD station showed a weaker instability trend. The remaining stations maintained good stability with closer stations demonstrating stronger consistency in their displacement. In terms of plate tectonic, the deformation array stations exhibit a similar southwestward displacement trend as the North American Plate in the horizontal direction, but no significant trend in the vertical direction.

Abstract BackgroundCardiovascular-kidney-metabolic (CKM) health is affected by social determinants of health, especially education. CKM syndrome has not been evaluated in Chinese population, and the association of education with CKM syndrome in different sexes and its intertwined relation with lifestyles have not been explored. ObjectiveWe aimed to explore the association between educational attainment and the prevalence of CKM syndrome stages in middle-aged and older Chinese men and women as well as the potential role of health behavior based on Life’s Essential 8 construct. MethodsThis study used data from the nationwide, community-based REACTION (Risk Evaluation of Cancers in Chinese diabetic individuals: a longitudinal study). A total of 132,085 participants with complete information to determine CKM syndrome stage and education level were included. Educational attainment was assessed by the self-reported highest educational level achieved by the participants and recategorized as low (elementary school or no formal education) or high (middle school, high school, technical school/college, or above). CKM syndrome was ascertained and classified into 5 stages according to the American Heart Association presidential advisory released in 2023. ResultsAmong 132,085 participants (mean age 56.95, SD 9.19 years; n=86,675, 65.62% women) included, most had moderate-risk CKM syndrome (stages 1 and 2), and a lower proportion were at higher risk of CKM (stages 3 and 4). Along the CKM continuum, low education was associated with 34% increased odds of moderate-risk CKM syndrome for women (odds ratio 1.36, 95% CI 1.23-1.49) with a significant sex disparity, but was positively correlated with high-risk CKM for both sexes. The association between low education and high-risk CKM was more evident in women with poor health behavior but not in men, which was also interactive with and partly mediated by behavior. ConclusionsLow education was associated with adverse CKM health for both sexes but was especially detrimental to women. Such sex-specific educational disparity was closely correlated with health behavior but could not be completely attenuated by behavior modification. These findings highlight the disadvantage faced by women in CKM health ascribed to low education, underscoring the need for public health support to address this inequality.

As one of the most geologically active regions on Earth, accurate delineation of active land blocks and analysis of crustal deformation characteristics in the southeastern margin of the Tibetan Plateau are crucial for understanding regional tectonic movements and assessing seismic hazards. Current studies in this region are limited and predominantly rely on single clustering methods. In this study, we proposed a general pipeline for active block delineation, which aggregated three clustering methods (K-means clustering, hierarchical clustering (HC), and density peak clustering (DPC)) to cluster the GNSS horizontal velocity field sites in the southeast margin of the Tibetan Plateau, and assessed the outcomes using the Davies–Bouldin Index (DBI) and Silhouette Coefficient to determine the optimal result. Subsequently, we calculated strain field parameters using GNSS horizontal velocity field data and analyzed seismic hazard combining historical earthquake data. By considering the stress and activity of fault zones, we refined the boundaries of active blocks and verified the reasonableness of the division. Finally, we divided the southeastern margin of the Tibetan Plateau into six land blocks: Bayan Kola, Qiangtang, South China, Southwest Yunnan, North Chuandian Subblock and South Chuandian Subblock. Analysis of strain field parameters revealed that the region is predominantly dilatational, transitioning from compressive to extensional states from west to east. The active zones of plate motion are mainly concentrated around specific fault zones around the Sichuan–Yunnan rhombic massif. Furthermore, we validated the generalization of the proposed pipeline in the other region, namely the Kazakhstan-Tienshan region. The clustering results were also consistent with the geologically determined block delineation model.

Abstract Background 3D visualization technology applies computers and other devices to create a realistic virtual world for individuals with various sensory experiences such as 3D vision, touch, and smell to gain a more effective understanding of the relationships between real spatial structures and organizations. The purpose of this study was to comprehensively evaluate the effectiveness of 3D visualization technology in human anatomy teaching/training and explore the potential factors that affect the training effects to better guide the teaching of classroom/laboratory anatomy. Methods We conducted a meta-analysis of randomized controlled studies on teaching human anatomy using 3D visualization technology. We extensively searched three authoritative databases, PubMed, Web of Science, and Embase; the main outcomes were the participants’ test scores and satisfaction, while the secondary outcomes were time consumption and enjoyment. Heterogeneity by I² was statistically determined because I²> 50%; therefore, a random-effects model was employed, using data processing software such as RevMan, Stata, and VOSviewer to process data, apply standardized mean difference and 95% confidence interval, and subgroup analysis to evaluate test results, and then conduct research through sensitivity analysis and meta-regression analysis. Results Thirty-nine randomized controlled trials (2,959 participants) were screened and included in this study. The system analysis of the main results showed that compared with other methods, including data from all regions 3D visualization technology moderately improved test scores as well as satisfaction and enjoyment; however, the time that students took to complete the test was not significantly reduced. Meta-regression analysis also showed that regional factorsaffected test scores, whereas other factors had no significant impact. When the literature from China was excluded, the satisfaction and happiness of the 3D virtual-reality group were statistically significant compared to those of the traditional group; however, the test results and time consumption were not statistically significant. Conclusion 3D visualization technology is an effective way to improve learners’ satisfaction with and enjoyment of human anatomical learning, but it cannot reduce the time required for testers to complete the test. 3D visualization technology may struggle to improve the testers’ scores. The literature test results from China are more prone to positive results and affected by regional bias.

The species of Ptilomera Amyot & Serville, 1843 from China are reviewed. Two new species, Ptilomera acutidentata sp. n. and Ptilomera valida sp. n., are described from Yunnan, China. Diagnoses and new distribution records are provided for four previously recorded species, i.e., Ptilomera burmana D. Polhemus, 2001, Ptilomera hemmingseni Andersen, 1967, Ptilomera hylactor Breddin, 1903, and Ptilomera tigrina Uhler, 1860. Photographs and line drawings of the habitus, diagnostic characteristics of both sexes, habitat and in-situ photographs are presented. A distribution map of Ptilomera in China is also provided.

Abstract Aim Patients with diabetes mellitus have poor prognosis after myocardial ischemic injury. However, the mechanism is unclear and there are no related therapies. We aimed to identify regulators of diabetic myocardial ischemic injury. Methods and results Mass spectrometry-based, non-targeted metabolomic approach was used to profile coronary sinus blood from diabetic and non-diabetic Bama-mini pigs at 0.5-h post coronary artery ligation. Six metabolites had a |log2 (Fold Change)|> 1.3. Among them, the most changed is arachidonic acid (AA), levels of which were 32 times lower in diabetic pigs than in non-diabetic pigs. The AA-derived products, PGI2 and 6-keto-PGF1α, were also significantly reduced. AA treatment of cultured cardiomyocytes protected against cell death by 30% at 48 h of high glucose and oxygen deprivation, which coincided with increased mitophagic activity (as indicated by increased LC3II/LC3I, decreased p62 and increased parkin & PINK1), improved mitochondrial renewal (upregulation of Drp1 and FIS1), reduced ROS generation and increased ATP production. These cardioprotective effects were abolished by PINK1(a crucial mitophagy protein) knockdown or the autophagy inhibitor 3-Methyladenine. The protective effect of AA was also inhibited by indomethacin and Cay10441, a prostacyclin receptor antagonist. Furthermore, diabetic Sprague Dawley rats were subjected to coronary ligation for 40 min and AA treatment (10 mg/day per animal gavaged) decreased myocardial infarct size, cell apoptosis index, inflammatory cytokines and improved heart function. Scanning electron microscopy showed more intact mitochondria in the border zone of infarcted myocardium in AA treated rats. Lastly, diabetic patients after myocardial infarction had lower plasma levels of AA and 6-keto-PGF1α and reduced cardiac ejection fraction, compared with non-diabetic patients after myocardial infarction. Plasma AA level was inversely correlated with fasting blood glucose. Conclusions AA protects against diabetic ischemic myocardial damage by promoting mitochondrial autophagy and renewal, which is related to AA derived PGI2 signaling. AA may represent a new strategy to treat diabetic myocardial ischemic injury.

Background/Aims: Necrotizing pancreatitis (NP) presents a more severe clinical trajectory and increased mortality compared to edematous pancreatitis. Prompt identification of NP is vital for patient prognosis. A risk prediction model for NP among Chinese patients has been developed and validated to aid in early detection. Methods: A retrospective analysis was performed on 218 patients with acute pancreatitis (AP) to examine the association of various clinical variables with NP. The least absolute shrinkage and selection operator (LASSO) regression was utilized to refine variables and select predictors. Subsequently, a multivariate logistic regression was employed to construct a predictive nomogram. The model's accuracy was validated using bootstrap resampling (n=500) and its calibration assessed via a calibration curve. The model's clinical utility was evaluated through decision curve analysis. Results: Of the 28 potential predictors analyzed in 218 AP patients, the incidence of NP was 25.2%. LASSO regression identified 14 variables, with procalcitonin, triglyceride, white blood cell count at 48 hours post-admission, calcium at 48 hours post-admission, and hematocrit at 48 hours post-admission emerging as independent risk factors for NP. The resulting nomogram accurately predicted NP risk with an area under the curve of 0.822, sensitivity of 82.8%, and specificity of 76.4%. The bootstrap-validated area under the curve remained at 0.822 (95% confidence interval, 0.737 to 0.892). This model exhibited excellent calibration and demonstrated greater predictive efficacy and clinical utility for NP than APACHE II, Ranson, and BISAP. Conclusions: We have developed a prediction nomogram of NP that is of great value in guiding clinical decision.

Financing and investing in sustainable infrastructure play a pivotal role in achieving the United Nations Sustainable Development Goals, particularly considering their multifaceted benefits to the environment, society, and economy. This systematic literature review applies the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to explore the financing and investment aspects of sustainable infrastructure. With support of a comprehensive collection of 4,308 publications dated from 2009 to 2023, we analyse various types of sustainable infrastructure and their investment and financing strategies by employing bibliometric analysis on 74 most closely related journal articles in a network approach setting. Results show the growing significance of green finance as a central research theme and a prevailing trend within this domain. Drawing upon these findings, we propose a conceptual framework for the integration of green finance into sustainable infrastructure development, offering insights to policy makers and guide future research agendas aimed at advancing green finance in infrastructure sectors.

The ICESat-2 satellite equipped with a new photon-counting laser altimeter has received much attention as a source of accurate elevation observations. However, in this research field, there is a lack of an open-source high-accuracy elevation control point dataset with the specific quality requirements at a global scale. To this end, using ICESat-2 altimeter data as the main data source, we constructed and organized a dataset as a useful supplement for this research field. The dataset was generated by a methodology based on detection environment evaluation, photon spatial analysis, and the redundant observation statistics. The dataset includes more than 600 million elevation control points and covers the global land areas, except for Greenland and Antarctica. The dataset has been validated by multiple digital elevation models (DEMs) from around the world (sourced from airborne LiDAR data). The results show that the dataset has high-accuracy elevation control points. The overall root-mean-square error (RMSE) of the original elevations of ICESat-2 is about 1.384–4.820 m, but the overall RMSE of the elevation control points in the new dataset is about 0.279–0.642 m. Moreover, the results obtained in this study show that the dataset is suitable for application within high vegetation cover areas.

ABSTRACT Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies.IMPORTANCESepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestines that can significantly impact quality of life and lead to various complications. Currently, 5-aminosalicylic acid derivatives, corticosteroids, immunosuppressants, and biologics are the major treatment strategies for UC, but their limitations have raised concerns. Atractylenolides (ATs), sesquiterpene metabolites found in Atractylodes macrocephala Koidz., have shown promising effects in treating UC by exerting immune barrier modulation, alleviating oxidative stress, gut microbiota regulation, improving mitochondrial dysfunction and repairing the intestinal barrier. Furthermore, ATs have been shown to possess remarkable anti-fibrosis, anti-thrombus, anti-angiogenesis and anti-cancer. These findings suggest that ATs hold important potential in treating UC and its complications. Therefore, this review systematically summarizes the efficacy and potential mechanisms of ATs in treating UC and its complications, providing the latest insights for further research and clinical applications.

Semantic segmentation using cross-modal data is a hot topic in the field of Earth observation. Compared with single-modal strategies, cross-modal networks fuse multiaspect information and yield higher segmentation accuracy, which is widely used in urban planning, environmental monitoring and so on. In this study, an end-to-end adaptive cross-modal fusion network (ACFNet) is proposed for semantic segmentation task using high resolution and light detection and ranging images, because of the difference of sensor resolution, different modal data have different abilities of ground object expression. Therefore, multimodal data fusion should consider the features with different spatial scales, while most existing methods simply use the same spatial scale features for fusion. In this work, we first design an adaptive scale fusion module that can automatically choose the features with optimal spatial scales, making full use of the representation properties of ground object details. Second, the important feature guidance module is designed, which can evaluate the influence weights of deep semantic features and shallow spatial detailed features, achieving adaptive deep and shallow feature fusion, and reducing the semantic-spatial information dilution caused by layer-by-layer up and down sampling. Finally, we introduce a divide Fourier context learning (DFCL) module to transform the feature maps from spatial domain to frequency domain. Compared to the limited perception of current spatial convolution kernels, the DFCL module can easily model the contextual dependencies of cross-modal features, which will improve the segmentaion accuracy for complex ground objects of cities, especially for occlusion. To demonstrate the generalisation performance of our module, we conduct extensive experiments and ablation studies on three datasets: Potsdam, Vaihingen, and IEEE GRSS DFC 2018. Results show that the proposed ACFNet is effective in semantic segmentation.

Mismatch removal is a crucial step in multiview matching of lunar orbiter images. This process involves complex challenges like terrain-induced distortion and nonunique geometric structures due to repetitive textures. Traditional methods, whether global constraints or local constraints, fall short in adequately addressing these issues in orbiter imagery. Therefore, this article proposes an effective method for mismatch removal of orbiter images based on global constraint and local geometry preservation combined with the imaging model. In this method, a clean neighborhood of each matching point based on the characteristic of centralized distribution of the back-projection residuals globally is constructed. In the local region, we define a local minimum geometric polygon consisting of the center feature point and its three neighbors, and combine the similarity of the back-projection difference vectors with the affine invariance of the polygon to distinguish the correct matches and mismatches by measuring the degree of local geometry preservation. A series of experiments encompassing parameter sensitivity analysis, comparison studies and ablation experiments were conducted on the lunar reconnaissance orbiter image datasets to demonstrate the effectiveness and reliability of the proposed method. The results indicate that our method exhibits a notable insensitivity to parameter variations, and outperforms other advanced methods in both qualitative and quantitative evaluations. Moreover, a large-scale orbiter images multiview matching tie points extraction framework is extended based on the proposed mismatch removal method, which can achieve better results than commonly used photogrammetric software in terms of the number and accuracy of tie points.

Deep learning (DL) plays an increasingly important role in Earth observation by multisource remote sensing. However, the current DL-based methods do not make a fully use of the complementary information among multisource remote sensing data, such as hyperspectral image and light detection and ranging data, and lack the consideration of multiscale, directional, and fine-grained features. To address these issues, a multiscale and multidirection feature extraction network is proposed in this article. Specifically, the multiscale spatial feature (MSSpaF) module is designed to extract the MSSpaFs, and then, these features are fused by feature concatenation operation. In addition, the multidirection spatial feature module is designed to further extract multidirection and frequency information, employing cross-layer connection and multiscale feature fusion strategy to improve the fineness of the proposed network. Moreover, the spectral feature module is employed to provide detailed spectral information for enhancing the expression ability of multiscale features. Experimental results on three different datasets demonstrate the superior classification performance of the proposed framework.

Matching planetary remote sensing images (PRSI) is essential for deep space exploration. Through matching optical images collected by different probes, the terrain of planets can be accurately mapped; however, PRSI lacks surface texture information and exhibits noticeable nonlinear radiation differences, e.g., illumination differences. It is not easy to achieve satisfactory results through traditional matching methods. In order to cope with the above problems, a new PRSI matching method has been proposed. It can extract low–high frequency features by building double-frequency scale space. In addition, we also use the nonmaximum suppression strategy for rejecting overlapped feature points, which reduces the time consumption and improves the matching accuracy. The experimental results show that the proposed method can effectively match PRSI and be superior to comparable methods.

Abstract Non-alcoholic fatty liver disease (NAFLD) has been shown to influence breast cancer progression, but the underlying mechanisms remain unclear. In this study, we investigated the impact of NAFLD on breast cancer tumor growth and cell viability through the potential mediator, hepatic fibroblast growth factor 21 (FGF21). Both peritumoral and systemic administration of FGF21 promoted breast cancer tumor growth, while FGF21 knockout attenuated the tumor-promoting effects of the high-fat diet. Mechanistically, exogenous FGF21 treatment enhanced the anti-apoptotic ability of breast cancer cells through STAT3 and Akt/FoXO1 signaling pathways, and mitigated doxorubicin-induced cell death. Furthermore, we observed overexpression of FGF21 in tumor tissues from breast cancer patients, which was associated with poor prognosis. These findings suggest a novel role for FGF21 as an upregulated mediator in the context of NAFLD, promoting breast cancer development and highlighting its potential as a therapeutic target for cancer treatment.

With the increasing interest in the south polar region of the Moon, there is an urgent need for high-resolution mapping products to support future exploration. Bundle block adjustment (BBA) is able to improve the spatial positioning accuracy of images used to generate high-precision mapping products. However, the impacts of weak-convergence geometry and poor illumination conditions in lunar south pole on BBA still need to be solved. This article proposes a large-scale robust BBA method for narrow angle camera (NAC) images in south pole. The NAC images are taken from the Lunar Reconnaissance Orbiter, which are scanner-type images requiring special treatment beyond the classical BBA of framing camera images. To handle the weak-convergence geometry issue of stereo NAC imagery, a topographic constraint using reference digital elevation model is integrated into BBA with an appropriate weighting scheme to estimate local topographic relief. In addition, a two-stage outlier elimination strategy for BBA with absolute-relative thresholding and iteratively reweighting methods is presented to reject outliers caused by the poor illumination conditions in lunar south pole. Thousands of images are used for experimental tests and lunar orbiter laser altimeter digital elevation models (DEMs) with different resolutions are used as reference data. The satisfactory experimental results demonstrate the effectiveness and reliability of our BBA method. The proposed large-scale BBA method reduces the relative positioning errors in block network to within 1 m, and decreases the inconsistency between NAC images caused by the orientation errors to less than 0.5 pixel, which offers a reliable solution for large-scale controlled mapping.

Aim: To observe the effects of Ningmitai capsule on semen parameters of infertile patients with chronic prostatitis (CP) and explore the mechanisms. Methods: A total of 43 patients diagnosed with CP were included in the study and administered Ningmitai capsules (4 capsules per dose) for a duration of 6 weeks. Subsequently, assessments were conducted on parameters including sperm concentration, forward progressive motility, total motility, oxidative and anti-oxidative indicators, as well as the concentration of interleukin-8 (IL-8) in seminal plasma before and after the treatment period. Results: Compared to pre-treatment, forward progressive motility and total motility of the semen increased significantly (37.15% ± 18.77% vs. 45.44% ± 19.08%, P < 0.05 and 42.56% ± 21.22% vs. 51.64% ± 19.48%, P < 0.05). And the expression of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) increased significantly after treatment as well (11.36 μmol/L ± 3.28 μmol/L vs. 12.79 μmol/L ± 2.87 μmol/L, P < 0.05 and 9.34 U/mL ± 3.22 U/mL vs. 11.21 U/mL ± 4.87 U/mL, P < 0.05). In addition, the expression of malondialdehyde (MDA) and IL-8 decreased significantly after treatment (41.06 μmol/L ± 24.39 μmol/L vs. 32.17 μmol/L ± 15.04 μmol/L, P < 0.05 and 79.69 ng/L ± 26.24 ng/L vs. 61.35 ng/L ± 23.41 ng/L, P < 0.05). No significant difference in sperm concentration and sperm DNA fragmentation index was observed after the treatment (P > 0.05). Conclusions: Ningmitai capsule can enhance the antioxidant capacity and down-regulate the expression of cytokines in the semen, thereby improving the semen parameters of infertile patients with CP.

ABSTRACTAccurate carbon (C) stock estimation is crucial for C sequestration research, environmental protection, and policy formulation related to C management. Although research on C stock in forests, oceans, soil, and desert has received increasing attention, relatively few studies have focused on urban C stock. Moreover, the current mainstream methods for C stock assessment, including field surveys and satellite mapping, are characterised by notable limitations, including being labour-intensive and having limited real-time data acquisition capabilities. Therefore, this paper aims to assess urban C stock and proposes a novel two-stage estimation model based on deep learning and unmanned aerial vehicle (UAV) remote sensing. The first stage is that tree areas recognition via YOLOv5 and achieved 0.792 precision, 0.814 recall, and 0.805 mAP scores, respectively. In the second stage, a grid generation strategy and a Convolutional Neural Network (CNN) regression model were developed to estimate C stock based on recognised tree areas (R2 = 0.711, RMSE = 26.08 kg). Three regions with a minimum of 300 trees in each area were selected as validation sets. The experimental results, in terms of R2 and RMSE in kg, were (0.717, 0.711, 0.686) and (27.263, 27.857, 28.945), respectively.

Abstract Background The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by “Life’s Essential 8” has not been characterized. We aim to examine the associations of early adulthood weight change and midlife “Life’s Essential 8” CVH status with cardiometabolic outcomes in a Chinese cohort. Methods The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in “Life’s Essential 8” was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. Results 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04–1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25–1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01–2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90–2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. Conclusions Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.

Abstract Studies describing the clinical presentation and prognosis of patients with silent PIT1 (pituitary specific transcription factor)‐lineage pituitary neuroendocrine tumors (PitNETs) are rare. We identified patients with positive PIT1 tumor staining but without evidence of hormone hypersecretion at a tertiary center. Clusters were obtained according to cell morphology and immunostaining from each patient's digitally segmented whole slide image. We compared the clinical presentations, radiological features, and prognoses of the different clusters. We identified 146 patients (68 male, 42.9 ± 14.1 years old) with silent PIT1‐lineage PitNETs. Morphology clustering suggested that tumors with large nuclei and apparent eccentricity were associated with a higher proportion of aggressiveness and a higher hazard of recurrence [hazard ratio (HR): 2.64, (95% CI, 1.06–6.55), p = 0.037]. Immunohistochemical clustering suggested that tumors with thyroid stimulating hormone (TSH) staining or all negative PIT1‐lineage hormones were associated with a higher proportion of aggressiveness and a higher risk of recurrence [HR: 12.4, (95% CI, 1.60–93.5), p = 0.015]. We obtained three‐tier risk profiles by combining morphological and immunohistochemical clustering. Patients with the high‐risk profile presented the highest recurrence rate compared with those in the medium‐risk and low‐risk profiles [HR: 3.54, (95% CI, 1.40–8.93), p = 0.002]. In conclusion, digital image analysis based on cell morphology and immunohistochemical staining allows objective stratification of patients with silent PIT1‐lineage tumors. Typical morphological characteristics of high‐risk tumors are large tumor nuclei and high eccentricity, and typical immunostaining characteristics are TSH staining or negative staining for all PIT1‐lineage hormones.

Background: Vascular smooth muscle cell (VSMC) intimal migration, proliferation, and phenotypic transformation from a contractile to a synthetic state are hallmarks of the progression of atherosclerotic plaques. This study aims to explore the effects of exosomes derived from M2 macrophages (ExoM2) on the pathological changes of VSMCs in atherosclerosis (AS). Methods: Cell Counting Kit-8 (CCK8) and wound healing assays were used to examine the impact of ExoM2 on platelet-derived growth factor-BB (PDGF-BB)-induced VSMC proliferation and migration, respectively. Western blotting was employed to analyze changes in the expression levels of contractile markers (e.g., alpha-smooth muscle actin [α-SMA]) and synthetic ones (e.g., osteopontin [OPN]) in VSMCs with or without ExoM2 treatment. ApoE-⁣/- mice on a high fat diet were utilized to observe the effects of ExoM2 on plaque progression and stability. Serial histopathological analysis was performed to elucidate the cellular mechanisms underlying the atheroprotective effects of ExoM2. Results: Compared with controls, ExoM2 significantly inhibited PDGF-BB-induced VSMC proliferation, migration, and phenotypic transformation in vitro. In ApoE-⁣/- mice, ExoM2 treatment led to a marked reduction in plaque size, necrotic core area, the CD68/α-SMA ratio, and matrix metalloproteinase 9 (MMP9) and OPN levels, while enhancing plaque stability. Conclusions: ExoM2 inhibit AS progression by regulating VSMC proliferation, migration, and phenotypic transformation.

Abstract Background Roxadustat is a novel oral medication used to treat anemia in CKD patients. Several studies have shown that Roxadustat can alleviate anemia in CKD patients by increasing hemoglobin levels and regulating iron metabolism. We aimed to evaluate the effect of Roxadustat on ventricular repolarization in PD patients. This study may provide a new integrated approach to the assessment and treatment of CKD. Methods The present prospective cohort study enrolled 65 CKD patients who were treated with Roxadustat and 31 CKD patients who received conventional therapy between January 2021 and June 2022. All patients were examined for ECG in the absence of clinical symptoms and compared the ECG indicators. Demographic and clinical data of all patients were collected. All data used SPSS 18.0 for statistical analyses. Results The T peak-to-end (Tpe) of PD patients in the Roxadustat group was remarkably slower than that of patients in the conventional group. Additionally, the Tpe/QT ratio in the conventional group was significantly elevated than that in the Roxadustat group. The results of logistic regression analysis showed that Tpe (95%CI 1.191 ~ 2.141, P = 0.002) and Roxadustat treatment (95%CI 1.357 ~ 42.121, P = 0.021) were the risk factors of PD patients with high Tp-e/QT ratio. Conclusion In summary, we found that Roxadustat could improve ventricular repolarization in peritoneal dialysis patients, which indicated a potential cardiovascular protective effect of Roxadustat. This study might provide a new integrated approach to the assessment and treatment of CKD.

Abstract Background The prognosis of patients with colorectal cancer is related to early detection. However, commonly used screening markers lack sensitivity and specificity. In this study, we identified diagnostic methylation sites for colorectal cancer. Methods After screening the colorectal cancer methylation dataset, diagnostic sites were identified via survival analysis, difference analysis, and ridge regression dimensionality reduction. The correlation between the selected methylation sites and the estimation of immune cell infiltration was analyzed. The accuracy of the diagnosis was verified using different datasets and the 10-fold crossover method. Results According to Gene Ontology, the main enrichment pathways of genes with hypermethylation sites are axon development, axonogenesis, and pattern specification processes. However, the Kyoto Encyclopedia of Genes and Genomes (KEGG) suggests the following main enrichment pathways: neuroactive ligand–receptor interaction, calcium signaling, and cAMP signaling. In The Cancer Genome Atlas (TCGA) and GSE131013 datasets, the area under the curve of cg07628404 was > 0.95. For the NaiveBayes machine model of cg02604524, cg07628404, and cg27364741, the accuracies of 10-fold cross-validation in the GSE131013 and TCGA datasets were 95% and 99.4%, respectively. The survival prognosis of the hypomethylated group (cg02604524, cg07628404, and cg27364741) was better than that of the hypermethylated group. The mutation risk did not differ between the hypermethylated and hypomethylated groups. The correlation coefficient between the three loci and CD4 central memory T cells, hematological stem cells, and other immune cells was not high (p

Abstract Objective This article aims at exploring the role of hypoxia-related genes and immune cells in spinal tuberculosis and tuberculosis involving other organs. Methods In this study, label-free quantitative proteomics analysis was performed on the intervertebral discs (fibrous cartilaginous tissues) obtained from five spinal tuberculosis (TB) patients. Key proteins associated with hypoxia were identified using molecular complex detection (MCODE), weighted gene co-expression network analysis(WGCNA), least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature Elimination (SVM-REF) methods, and their diagnostic and predictive values were assessed. Immune cell correlation analysis was then performed using the Single Sample Gene Set Enrichment Analysis (ssGSEA) method. In addition, a pharmaco-transcriptomic analysis was also performed to identify targets for treatment. Results The three genes, namely proteasome 20 S subunit beta 9 (PSMB9), signal transducer and activator of transcription 1 (STAT1), and transporter 1 (TAP1), were identified in the present study. The expression of these genes was found to be particularly high in patients with spinal TB and other extrapulmonary TB, as well as in TB and multidrug-resistant TB (p-value

Evodia rutaecarpa, the near-ripe fruit of Euodia rutaecarpa (Juss.) Benth, Euodia rutaecarpa (Juss.) Benth. var. officinalis (Dode) Huang, or Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode) Huang, is a famous herbal medicine with several biological activities and therapeutic values, which has been applied for abdominalgia, abdominal distension, vomiting, and diarrhea as a complementary and alternative therapy in clinic. Indole alkaloids, particularly evodiamine (EVO), rutaecarpine (RUT), and dedhydroevodiamine (DHE), are received rising attention as the major bioactivity compounds in Evodia rutaecarpa. Therefore, this review summarizes the physicochemical properties, pharmacological activities, pharmacokinetics, and therapeutic effects on gastrointestinal diseases of these three indole alkaloids with original literature collected by PubMed, Web of Science Core Collection, and CNKI up to June 2023. Despite sharing the same parent nucleus, EVO, RUT, and DHE have different structural and chemical properties, which result in different advantages of biological effects. In their wide range of pharmacological activities, the anti-migratory activity of RUT is less effective than that of EVO, and the neuroprotection of DHE is significant. Additionally, although DHE has a higher bioavailability, EVO and RUT display better permeabilities within blood-brain barrier. These three indole alkaloids can alleviate gastrointestinal inflammatory in particular, and EVO also has outstanding anti-cancer effect, although clinical trials are still required to further support their therapeutic potential.

Abstract Background In the elderly, osteoporotic vertebral compression fractures (OVCFs) of the thoracolumbar vertebra are common, and percutaneous vertebroplasty (PVP) is a common surgical method after fracture. Machine learning (ML) was used in this study to assist clinicians in preventing bone cement leakage during PVP surgery. Methods The clinical data of 374 patients with thoracolumbar OVCFs who underwent single-level PVP at The First People's Hospital of Chenzhou were chosen. It included 150 patients with bone cement leakage and 224 patients without it. We screened the feature variables using four ML methods and used the intersection to generate the prediction model. In addition, predictive models were used in the validation cohort. Results The ML method was used to select five factors to create a Nomogram diagnostic model. The nomogram model's AUC was 0.646667, and its C value was 0.647. The calibration curves revealed a consistent relationship between nomogram predictions and actual probabilities. In 91 randomized samples, the AUC of this nomogram model was 0.7555116. Conclusion In this study, we invented a prediction model for bone cement leakage in single-segment PVP surgery, which can help doctors in performing better surgery with reduced risk.

Velia (Cesavelia) bui sp. nov. from Hubei Province, China is described, and Velia (Cesavelia) tonkina Polhemus & Polhemus, 2003 is newly recorded from China. In addition, new distribution data for three species of Velia (Cesavelia), V. longiconnexiva Tran, Zettel & Buzzetti, 2009, V. sinensis Andersen, 1981 and V. tonkina Polhemus & Polhemus, 2003 are provided. Photographs of the habitus in dorsal and lateral views, metafemora of males, genitalic structures and habitats, along with a distribution map of this subgenus, are provided.

Abstract Background The nature of student learning in problem-based learning (PBL) largely depends on the quality of the case scenarios presented to them. The effect of case scenarios with higher challenge degree, especially common disease with atypical symptoms (CDAS)- and rare disease (RD)-based case scenarios, on undergraduate medical students remains unclear. This study compared the impact of all scenarios pertaining to common disease with typical symptoms (CDTS) case scenarios, CDTS interspersed with CDAS case scenarios, and CDTS interspersed with RD case scenarios on perceptions of undergraduate students studying organ/system integration curriculum via PBL. Methods After finishing four CDTS case scenarios, 294 third-year medical students were randomly allocated into three groups: CDTS, CDAS and RD, studying via CDTS, CDAS and RD case scenarios, respectively. A questionnaire with 15 items was conducted to evaluate the students’ perceptions. The students’ responses were scored using a 4-point rating scale. The data were analysed using the Kruskal–Wallis test. Results Among the three PBL conditions, the ones with a higher degree of challenge were rated higher by the students, which included the quality of the case scenarios and the overall performances of the students. The CDAS and RD cases were more effective in developing students’ self-directed learning skills, stimulating them to acquire more knowledge required for future work. The satisfaction percentage of RD case scenario sessions was higher. Conclusions Of all the three kinds of case scenarios, both CDTS interspersed with CDAS and RD case scenarios had more positive effects on the self-evaluated performance of students. Increasing the challenge and variety of case scenarios by the inclusion of CDAS and RD especially RD might be an effective stimulus in improving students’ performance in PBL sessions.

The species of Rhyacobates Esaki, 1923 are reviewed. Three new species, R. bui sp. nov. from Guangxi, China and Lạng Sơn, Vietnam, R. elongatus sp. nov. from Hà Tĩnh, Vietnam and R. turgidus sp. nov. from Sichuan and Chongqing, China are described. Supplemental descriptions, diagnoses and new distribution records are provided for the fourteen previously known species, i.e., R. abdominalis Andersen & Chen, 1995, R. anderseni Tran & Yang, 2006, R. angustus Tran & Nguyen, 2016, R. chinensis Hungerford & Matsuda, 1959, R. constrictus Tran & Nguyen, 2016, R. edentatus Andersen & Chen, 1995, R. gongvo Tran & Yang, 2006, R. lundbladi (Hungerford, 1957), R. malaisei Andersen & Chen, 1995, R. recurvus Andersen & Chen, 1995, R. scorpio Andersen & Chen, 1995, R. svenhedini (Lundblad, 1934), R. takahashii Esaki, 1923, and R. zetteli Tran & Nguyen, 2016. Photographs and line drawings of the habitus, diagnostic characteristics of both sexes, the habitat and in-situ photographs are presented. A revised key to the species of Rhyacobates is also provided.

The malignant lung cancer has a high morbidity rate and very poor 5-year survival rate. About 80% - 90% of protein degradation in human cells is occurred through the ubiquitination enzyme pathway. Ubiquitin ligase (E3) with high specificity plays a crucial role in the ubiquitination process of the target protein, which usually occurs at a lysine residue in a substrate protein. Different ubiquitination forms have different effects on the target proteins. Multiple short chains of ubiquitination residues modify substrate proteins, which are favorable signals for protein degradation. The dynamic balance adapted to physiological needs between ubiquitination and deubiquitination of intracellular proteins is beneficial to the health of the organism. Ubiquitination of proteins has an impact on many biological pathways, and imbalances in these pathways lead to diseases including lung cancer. Ubiquitination of tumor suppressor protein factors or deubiquitination of tumor carcinogen protein factors often lead to the progression of lung cancer. Ubiquitin proteasome system (UPS) is a treasure house for research and development of new cancer drugs for lung cancer, especially targeting proteasome and E3s. The ubiquitination and degradation of oncogene proteins with precise targeting may provide a bright prospect for drug development in lung cancer; Especially proteolytic targeted chimerism (PROTAC)-induced protein degradation technology will offer a new strategy in the discovery and development of new drugs for lung cancer.

Abstract Thin ferroelectric layers are capable of generating large dielectric and electromechanical responses at relatively low voltages, thus can be utilized in various applications including energy storage, energy harvesting, sensors, and actuators. Among ferroelectrics, relaxor ferroelectrics (1 − x)Pb(Mg1/3Nb2/3)O3 − xPbTiO3 are particularly interesting due to their superior dielectric and piezoelectric properties. However, dielectric and piezoelectric responses of the ferroelectric thin films are significantly suppressed relative to their bulk counterparts. The physical mechanism of the properties degradation still remains elusive, which greatly hinders their technological applications. Herein, this work systematically investigates the dielectric nonlinearity and the relationship between composition and intrinsic/extrinsic contributions of high‐quality (1 − x)Pb(Mg1/3Nb2/3)O3 − xPbTiO3 epitaxial thin films (x = 0, 0.1, 0.32) fabricated by pulsed laser deposition. Through the Rayleigh analysis, it is found that the suppression of domain wall motion by substrate clamping is the main cause of thin film performance degradation and is further confirmed by continuous application of background dc bias to extract the dielectric response's intrinsic and extrinsic contributions. This work will pave the way for practical applications of (1 − x)Pb(Mg1/3Nb2/3)O3 − xPbTiO3 thin films in energy storage and electromechanical devices.

ObjectiveThe relationship between different autoimmune diseases and bone mineral density (BMD) and fractures has been reported in epidemiological studies. This study aimed to explore the causal relationship between autoimmune diseases and BMD, falls, and fractures using Mendelian randomization (MR).MethodsThe instrumental variables were selected from the aggregated statistical data of these diseases from the largest genome-wide association study in Europe. Specifically, 12 common autoimmune diseases were selected as exposure. Outcome variables included BMD, falls, and fractures. Multiple analysis methods were utilized to comprehensively evaluate the causal relationship between autoimmune diseases and BMD, falls, and fractures. Additionally, sensitivity analyses, including Cochran’s Q test, MR-Egger intercept test, and one analysis, were conducted to verify the result’s reliability.ResultsStrong evidence was provided in the results of the negatively association of ulcerative colitis (UC) with forearm BMD. UC also had a negatively association with the total body BMD, while inflammatory bowel disease (IBD) depicted a negatively association with the total body BMD at the age of 45–60 years. Horizontal pleiotropy or heterogeneity was not detected through sensitivity analysis, indicating that the causal estimation was reliable.ConclusionThis study shows a negative causal relationship between UC and forearm and total body BMD, and between IBD and total body BMD at the age of 45–60 years. These results should be considered in future research and when public health measures and osteoporosis prevention strategies are formulated.

Introduction To explore the epidemiological characteristics of ankylosing spondylitis (AS) in Guangxi Province of China through a large sample survey of more than 50 million aboriginal aboriginal population. Material and methods A systematic search was conducted using the International Classification of Diseases 10 (ICD-10) codes M45.x00(AS), M45.x03+(AS with iridocyclitis), and M40.101(AS with kyphosis) to search the database in the National Health Statistics Network Direct Reporting System (NHSNDRS). 14004 patients were eventually included in the study. The parameters analyzed included the number of patients, gender, marriage, blood type, occupation, age at diagnosis, and location of household registration data each year, and statistical analysis was performed. Results AS incidence rates increased from 1.30 (95% CI: 1.20–1.40) per 100,000 person-years in 2014 to 5.71 (95% CI: 5.50–5.92) in 2020 in Guangxi Province, and decreased slightly in 2021. Males have a higher incidence than females; the ratio was 5.61 : 1. The mean age of diagnosis in male patients was 45.4 (95% CI: 45.1–45.7) years, in females 47.6 (95% CI: 46.8–48.4) years. The most frequent blood type was O, and the most frequent occupation was farmer. The AS incidence rate was disparate in different cities. Liuzhou city had the highest eight-year average AS incidence rates from 2014 to 2021, and Chongzuo city had the lowest (p 0.05). Conclusions The AS person-years incidence rate was increasing in Guangxi province of China from 2014 to 2020, which had obvious gender and regional differences, showing the characteristics of local area aggregation.

Abstract Since the beginning of the Holocene era, human activities have seriously impacted animal habitats and vegetative environments. Species that are dependent on natural habitats or with narrow niches might be more severely affected by habitat changes. Malcus inconspicuus is distributed in subtropical China and highly dependent on the mountain environment. Our study investigated the role of the mountainous landscape in the historical evolution of M. inconspicuus and the impact of Holocene human activities on it. A phylogeographical approach was implemented with integrative datasets including double‐digest restriction site‐associated DNA (ddRAD), mitochondrial data, and distribution data. Three obvious clades and an east–west phylogeographical pattern were found in subtropical China. Mountainous landscape has “multifaceted” effects on the evolutionary history of M. inconspicuus, it has contributed to population differentiation, provided glacial refuges, and provided population expansion corridors during the postglacial period. The effective population size (Ne) of M. inconspicuus showed a sharp decline during the Holocene era, which revealed a significantly negative correlation with the development of cropland in a hilly area at the same time and space. It supported that the species which are highly dependent on natural habitats might undergo greater impact when the habitat was damaged by agricultural activities and we should pay more attention to them, especially in the land development of their distribution areas.

Recently, convolutional neural network based methods have been studied for ship detection in optical remote sensing images. However, it is challenging to apply them to microwave synthetic aperture radar (SAR) images. First, most of the regions in the inshore scene include scattered spots and noises, which dramatically interfere with ship detection. Besides, SAR ship images contain ship targets of different sizes, especially small ships with dense distribution. Unfortunately, small ships have fewer distinguishing features making it difficult to be detected. In this article, we propose a novel SAR ship detection network called feature enhanced pyramid and shallow feature reconstruction network (FEPS-Net) to solve the above problems. We design a feature enhancement pyramid, which includes a spatial enhancement module to enhance spatial position information and suppress background noise, and the feature alignment module to solve the problem of feature misalignment during feature fusion. Additionally, to solve the problem of small ship detection in SAR ship images, we design a shallow feature reconstruction module to extract semantic information from small ships. The effectiveness of the proposed network for SAR ship detection is demonstrated by experiments on two publicly available datasets: SAR ship detection dataset and high-resolution SAR images dataset. The experimental results show that the proposed FEPS-Net has advantages in SAR ship detection over the current state-of-the-art methods.

Abstract Background Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them. Methods Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self‐report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator. Results Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12–1.27), while college‐educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73–0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (β[SE] 0.0387 [0.0037]) and negative in women (β[SE] −0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women. Conclusions In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women.

Abstract Background Fast track surgery has shown its effectiveness to accelerate recovery and gained acceptance in many operations. However, data for paramedics using fast track surgery are limited in China. The aims of our study are to evaluate the knowledge, attitude and application status of fast track surgery in paramedics and to provide suggestions for the better application of fast track surgery. Methods Two Hundred Ninety-one operating room paramedics were investigated by simple random sampling from October 20 to December 20, 2019 time. A self-reported questionnaire was used to collect data with five dimensions: demographic data, cognitive level, knowledge, attitude and application of fast track surgery. Data were analyzed using qualitative and quantitative methods. Results 19.93% of participants never heard fast track surgery and only 3.32% of participants were very familiar with it. Gender (0.702, 95% CI 0.109–1.294), technical title (0.342, 95% CI 0.126–0.558) and awareness of the concept of fast track surgery (0.471, 95% CI 0.165–0.776) had a correlation with the knowledge level of paramedics towards fast track surgery. In terms of attitude towards fast track surgery, gender (− 1.944, 95% CI -3.830- -0.058), age (0.303, 95% CI 0.021–0.585) and knowledge score of fast track surgery (0.426, 95% CI 0.014–0.838) are related. Half of the paramedics believe the most difficult problem in the application of fast track surgery was the lack of multi-team communication and cooperation. Conclusion The knowledge of fast track surgery among paramedics in Wuhan is poor, and some paramedics have a negative attitude towards it. As the attitude is positively correlated with the knowledge, it is necessary to improve the knowledge level of fast track surgery among paramedics in Wuhan.

Abstract Background Human primordial germ cells (hPGCs) initiate from the early post-implantation embryo at week 2–3 and undergo epigenetic reprogramming during development. However, the regulatory mechanism of DNA methylation during hPGC specification is still largely unknown due to the difficulties in analyzing early human embryos. Using an in vitro model of hPGC induction, we found a novel function of TET proteins and NANOG in the hPGC specification which was different from that discovered in mice. Methods Using the CRISPR–Cas9 system, we generated a set of TET1, TET2 and TET3 knockout H1 human embryonic stem cell (hESC) lines bearing a BLIMP1-2A-mKate2 reporter. We determined the global mRNA transcription and DNA methylation profiles of pluripotent cells and induced hPGC-like cells (hPGCLCs) by RNA-seq and whole-genome bisulfite sequencing (WGBS) to reveal the involved signaling pathways after TET proteins knockout. ChIP-qPCR was performed to verify the binding of TET and NANOG proteins in the SOX17 promoter. Real-time quantitative PCR, western blot and immunofluorescence were performed to measure gene expression at mRNA and protein levels. The efficiency of hPGC induction was evaluated by FACS. Results In humans, TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) impaired the NODAL signaling pathway and impeded hPGC specification in vitro, while the hyperactivated NODAL signaling pathway led to gastrulation failure when Tet proteins were inactivated in mouse. Specifically, TET proteins stimulated SOX17 through the NODAL signaling pathway and directly regulates NANOG expression at the onset of hPGCLCs induction. Notably, NANOG could bind to SOX17 promoter to regulate its expression in hPGCLCs specification. Furthermore, in TKO hESCs, DNMT3B-mediated hypermethylation of the NODAL signaling-related genes and NANOG/SOX17 promoters repressed their activation and inhibited hPGCLC induction. Knockout of DNMT3B in TKO hESCs partially restored NODAL signaling and NANOG/SOX17 expression, and rescued hPGCLC induction. Conclusion Our results show that TETs-mediated oxidation of 5-methylcytosine modulates the NODAL signaling pathway and its downstream genes, NANOG and SOX17, by promoting demethylation in opposition to DNMT3B-mediated methylation, suggesting that the epigenetic balance of DNA methylation and demethylation in key genes plays a fundamental role in early hPGC specification.

Enterobacter aerogenes, the gram-negative bacteria belonging to the family Enterobacteriaceae, lacks the ability to synthesize chemicals. However, in this study, a strain of Enterobacter aerogenes NJ1023 screened from the soil containing petrochemicals was found to be capable of producing extracellular polysaccharides (EPSs). After purification of the polysaccharide, the chemical composition and physicochemical properties of the polysaccharide were analyzed by UV–Vis spectra, FTIR spectroscopy and GC-MS, etc. The results showed that: The molecular weight of the polysaccharide produced by this strain was only 2.7×103 Da, which was lower than that reported in other polysaccharides from the same genus. The polysaccharide produced by E. aerogenes NJ1023 mainly comprised xylose, glucose, galactose, and N-acetylglucosamine with a molar ratio of 0.27: 4.52: 1.74: 0.2, which differed from those reported from the same genus. The results demonstrated that lower incubation temperatures and shaking speeds were more favorable for EPSs synthesis, while higher incubation temperatures and shaking speeds favored cell growth. Additionally, the EPSs produced by E. aerogenes NJ1023 significantly protected the Escherichia coli cells against cadaverine stress. Overall, the discovery of EPSs produced by E. aerogenes increased the diversity of bacterial polysaccharides and broadened the potential applications of this species.

ABSTRACT Aims/Introduction There are mixed opinions on the influence of diabetes on the prognosis of patients receiving percutaneous coronary intervention (PCI). Therefore, in this study, the quantitative flow ratio (QFR), an emerging technology of functional evaluation, was used to explore the impact of diabetes on coronary physiology in patients who underwent PCI. Materials and Methods Patients who underwent successful PCI and a 1‐year angiographic follow up were retrospectively screened and analyzed by the QFR. Based on the presence or absence of diabetes, 677 enrolled patients (794 vessels) were classified into a diabetes group (211 patients, 261 vessels) and a non‐diabetes group (466 patients, 533 vessels). The results of QFR analysis and clinical outcomes were compared between the two groups. Results The two groups reached a similar level of post‐PCI QFR (0.95 ± 0.09 vs 0.96 ± 0.06, P = 0.292). However, at the 1‐year follow up, the QFR was lower (0.93 ± 0.11 vs 0.96 ± 0.07, P

Stress can trigger cardiovascular disease. Both imbalance of autonomic nervous activity and increase of neurohormonal output are core aspects of stress responses and can lead to cardiovascular disease. PC6 as a very important acupoint is used to prevent and treat cardiovascular disease and to improve stress-related activities. We examined the influence of electroacupuncture (EA) at PC6 on stress-induced imbalance of autonomic nervous activity and increase of neurohormonal output. EA at PC6 relieved increased cardiac sympathetic nervous activity and decreased cardiac vagal nervous activity induced by immobilization stress. Also, EA at PC6 reduced immobilization stress-induced increases of plasma norepinephrine (NE) and adrenaline (E) released from sympatho-adrenal-medullary axis. Finally, EA at PC6 reduced immobilization stress-induced increases of corticotropin-releasing hormone (CRH) in paraventricular hypothalamic nucleus and plasma cortisol (CORT) released from hypothalamic-pituitary-adrenal axis. However, EA at tail had no significant effect on the stress-induced autonomic and neuroendocrine responses. The results demonstrate the role of EA at PC6 regulating the autonomic and neuroendocrine responses induced by stress and provide insight into the prevention and treatment of EA at PC6 for stress-induced cardiovascular disease by targeting autonomic and neuroendocrine systems.

Airborne laser scanning (ALS) has experienced significant development and boosted widespread applications over the recent years. With increasing data quality and acquisition convenience, multi-temporal ALS point clouds have been used for change detection (CD) in earth observation. Data registration or geometric difference calculations can effectively obtain geometric changes using point clouds acquired from various epochs. However, the lack of semantic labeling means that traditional CD methods are unable to distinguish the changes in semantic information or remove the interference in some categories. Therefore, we propose a semantic supported change detection (SSCD) method. First, a point cloud semantic segmentation network is developed under the classic PointNet++ frame to provide semantic labeling for change detection, including an attention-based local feature embedding module that uses the spatially sensitive features of 3D points and an integrated multi-scale framework with local spatial attention convolution. Secondly, the point cloud is voxelized based on an Octree, where the label of each voxel is determined by the result of semantic segmentation. Finally, the change detection result is obtained by comparing the changes in voxel coordinates and semantic information of the two point clouds. We tested the proposed method using experiments conducted on the AHN datasets. In the two selected experimental areas, the accuracy of change detection rate reached 0.9099 and 0.9029, respectively. The F1 rate reached 0.4571 and 0.3455. Evaluations using the object-based method show that changes were correctly identified in both of the tested areas.

Three-dimensional printing models (3DPs) have been widely used in medical anatomy training. However, the 3DPs evaluation results differ depending on such factors as the training objects, experimental design, organ parts, and test content. Thus, this systematic evaluation was carried out to better understand the role of 3DPs in different populations and different experimental designs. Controlled (CON) studies of 3DPs were retrieved from PubMed and Web of Science databases, where the participants were medical students or residents. The teaching content is the anatomical knowledge of human organs. One evaluation indicator is the mastery of anatomical knowledge after training, and the other is the satisfaction of participants with 3DPs. On the whole, the performance of the 3DPs group was higher than that of the CON group; however, there was no statistical difference in the resident subgroup, and there was no statistical difference for 3DPs vs. 3D visual imaging (3DI). In terms of satisfaction rate, the summary data showed that the difference between the 3DPs group (83.6%) vs. the CON group (69.6%) (binary variable) was not statistically significant, with p > 0.05. 3DPs has a positive effect on anatomy teaching, although there are no statistical differences in the performance tests of individual subgroups; participants generally had good evaluations and satisfaction with 3DPs. 3DPs still faces challenges in production cost, raw material source, authenticity, durability, etc. The future of 3D-printing-model-assisted anatomy teaching is worthy of expectation.