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Diabetes mellitus (DM) is a chronic metabolic disorder that can affect the balance of bone metabolism and bone microenvironment, leading to impaired fracture healing. There are several underlying mechanisms which contributing to the impaired diabetic bone microenvironment such as hyperglycemia, the production of advanced glycation end products (AGEs), inflammation, and oxidative stress, etc. Recent studies have achieved great progress in developing novel smart biomaterials in improving the diabetic bone microenvironment to promote diabetic fracture healing. In this paper, we reviewed the mechanisms on DM-induced impaired fracture healing. Meanwhile, we also summarized the smart biomaterials used to improve the local microenvironment of diabetic fractures healing, which provides a novel perspective for the future treatment of fractures in diabetic patients.

Abstract Background In recent decades, early rehabilitation after Achilles tendon rupture (ATR) repair has been proposed. The aim of this prospective cohort study was to compare different immobilisation durations in order to determine the optimal duration after open surgery for ATR repair. Methods This study included 1088 patients (mean age, 34.9 ± 5.9 years) who underwent open surgery for acute ATR repair. The patients were categorised into four groups (A, B, C, and D) according to postoperative immobilisation durations of 0, 2, 4, and 6 weeks, respectively. All patients received the same suture technique and a similar rehabilitation protocol after brace removal,; they were clinically examined at 2, 4, 6, 8, 10, 12, 14, and 16 weeks postoperatively, with a final follow-up at a mean of 19.0 months. The primary outcome was the recovery time for the one-leg heel-rise height (OHRH). Secondary outcomes included the time required to return to light exercise (LE) and the recovery times for the range of motion (ROM). Data regarding the surgical duration, complications, the visual analogue scale (VAS) score for pain, the Achilles tendon Total Rupture Score (ATRS), and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale score were also collected. Results The recovery times for OHRH, LE, and ROM were significantly shorter in groups A and B than in groups C and D (P

Abstract Background Clinical repair of critical-sized bone defects (CBDs) in the tibial diaphysis presents numerous challenges, including inadequate soft tissue coverage, limited blood supply, high load-bearing demands, and potential deformities. This study aimed to investigate the clinical feasibility and efficacy of employing 3D-printed prostheses for repairing CBDs exceeding 10 cm in the tibial diaphysis. Methods This retrospective study included 14 patients (11 males and 3 females) with an average age of 46.0 years. The etiologies of CBDs comprised chronic osteomyelitis (10 cases) and aseptic non-union (4 cases), with an average defect length of 16.9 cm. All patients underwent a two-stage surgical approach: (1) debridement, osteotomy, and cement spacer implantation; and (2) insertion of 3D-printed prostheses. The interval between the two stages ranged from 8 to 12 weeks, during which the 3D-printed prostheses and induced membranes were meticulously prepared. Subsequent to surgery, patients engaged in weight-bearing and functional exercises under specialized supervision. Follow-up assessments, including gross observation, imaging examinations, and administration of the Lower Extremity Functional Scale (LEFS), were conducted at 3, 6, and 12 months postoperatively, followed by annual evaluations thereafter. Results The mean postoperative follow-up duration was 28.4 months, with an average waiting period between prosthesis implantation and weight-bearing of 10.4 days. At the latest follow-up, all patients demonstrated autonomous ambulation without assistance, and their LEFS scores exhibited a significant improvement compared to preoperative values (30.7 vs. 53.1, P

Abstract Background Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. Methods First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-β1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. Results The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-β1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-β1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. Conclusions MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-β1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.

Based on the conventional high-altitude and ground observation datasets and the 1-hour rainfall datasets from 93 national auto? matic weather stations in Jiangxi from April to September of 1998 to 2019, a total of 204 selected local hourly heavy rainfall events (hereinaf? ter LHR) in Jiangxi were analyzed and classified. With the analysis of synoptic meteorology, radiosonde, and physical properties, the concep? tual models of each category of these LHR events were established. The results are as follows. LHR in Jiangxi can be classified into 5 catego? ries, including Pre-Trough pattern (PRT), Post-Trough pattern (POT), Tropical System pattern (TS), Edge of Subtropical High pattern (ESH), and Control of Subtropical High (CSH) pattern. PRT is the most common type, which accounts for 48% of the total events. These events usual? ly occur in front of the high-altitude trough, near the mid-low-level shear lines, and are usually associated with cold fronts, stationary fronts, or low-pressure troughs on the surface. The second most frequent one is TS, which accounts for 19.1% of the total events. TS can also be divid? ed into the tropical cyclone type and the east wind wave type. The structure and movement of the tropical systems can significantly affect the area of LHR. ESH is divided into western ESH, southern ESH, and northern ESH. For this type, LHR events usually occur near the edge of the subtropical high 588 dagpm line, the low layer shear line, or the convergence line. CSH accounts for 5.5% of the total events. LHR happens when the subtropical high controls the entire Jiangxi Province. Particularly, when a center temperature at 500 hPa over the northern or eastern Jiangnan regions below -4℃ appears under the background of a cold trough, LHR events frequently occur on the ground convergence line, in the high-temperature area, or windward slope of mountains. POT is the least common type, which accounts for 4.4% of the events. It occurs under the northwesterly flow behind a trough, in the exit zone of the low-level jets, in the convergence zone, or on the surface convergence line.

Abstract Background The accelerated growth of older individuals worldwide has increased the number of patients presenting with fragility hip fractures. Having a hip fracture can cause excess mortality, and patients with hip fracture have a higher risk of death than those without hip fracture. Most studies have treated hip fracture as a single, homogeneous condition, but hip fracture includes two major anatomic types: intertrochanteric fracture and femoral neck fracture. Few studies have specifically evaluated 1-year mortality risk in older individuals with femoral intertrochanteric fracture. The aim of this study was to evaluate 1-year mortality and factors associated with mortality in older individuals with femoral intertrochanteric fracture. Methods A retrospective review was conducted of 563 patients ≥ 65 years old who underwent surgery for femoral intertrochanteric fractures at our institution between January 2010 and August 2018. Patient demographics, comorbidities, and treatment were collected by retrospective chart review. Age, sex, Body Mass Index (BMI), American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI), Arbeitsgemeinschaft Für Osteosynthesefragen (AO) fracture classification, haemoglobin value at admission, time to surgery, operation time, and intraoperative blood loss were risk factors to be tested. Multivariable logistic regression was used to evaluate associations between variables and death. Results Among the 563 patients, 49 died within 1 year after surgery, and the 1-year mortality rate was 8.7%. Multivariate analysis identified age > 80 years (OR = 4.038, P = 0.011), haemoglobin 14 d (OR = 3.907, P = 0.030) as independent risk factors for 1-year mortality. Comorbidities such as myocardial infarction and chronic pulmonary disease were associated with 1-year mortality after adjusting for age > 80 years and time to surgery > 14 days. Conclusions Patients over 80 years old with haemoglobin

Abstract The purpose of clustering is to partition data similar with each other into a same group and partition data dissimilar with each other into different groups. However, in most existing fuzzy clustering approaches, the membership degrees of an individual belonging to different clusters are relied on the different distances between the individual and different cluster centroids, the similarity between the individual and data in different clusters are ignored, besides, the outliers cannot be distinguished effectively. For improving the clustering performance and addressing the problems in most existing fuzzy clustering approaches, based on the concept that data close to each other should be grouped together and be assigned to a same cluster, in this paper, we present a novel efficient fuzzy clustering approach, in which the adaptive local neighborhood information of each data referring to different clusters is taken into consideration; an entirely new idea that the membership degree values of an individual referring to different clusters should not only depend on the distances between the individual and different cluster centers, but also rely on the distances between the individual and several nearest neighbor data in different clusters is put forward; a new scheme to search for the outliers is presented, a method for identifying the different importance of different features is introduced. Experiments on synthetic and publicly real-world datasets were conducted, the clustering results show that the approach put forward can yield consistently satisfying clustering performance and has significant advantages.

Water, energy and food (WEF) are important strategic resources for economic development in arid agriculture-based regions. Analyzing development indicators in the management of limited resources to achieve sustainability on a time scale is one of the basic goals of this research. Therefore, a system dynamics model was developed to analyze the WEF system resource flow relationship to achieve sustainable resource development. First, the subsystems of WEF resources were created and their dynamic relationship was formed in the form of a logical loop in a 10-year time frame. The evolution of 7 years (from 2015 to 2022) was taken into consideration to predict the 3-year period (from 2023 to 2025). The results showed that the reduction of water resources exploitation rate in China in interaction with agricultural productivity has automatically improved energy consumption and the nexus index. In China, a dynamic balance between WEF with a focus on water is recommended for planning. HIGHLIGHTS A dynamic relationship is evaluated for the water, agriculture and economy nexus.; The role of water and energy productivity in food security and industrial development has been analyzed.;

Abstract The ependymal epithelium forms the cerebrospinal fluid barrier, separating the brain and spinal cord from the cerebrospinal fluid. However, in specific regions of the central nervous system, there are neurons that directly interface with the cerebrospinal fluid, including neuronal bodies, dendrites, or axons, This constitutes what is referred to as the "cerebrospinal fluid contacting neurons system (CSF-CNS)". The research team led by Professor Zhang has successfully utilized cholera toxin subunit B coupled horseradish peroxidase complex (CB-HRP) to selectively label the specialized neuron system that interfaces with cerebrospinal fluid, pioneeringly designating it as the "cerebrospinal fluid-contacting nucleus", commonly referred to as the "CSF-contacting nucleus". For the first time, the discovery of the CSF-contacting nucleus provides compelling morphological evidence for the existence of a distinct neural structure within the brain parenchyma that establishes a connection with the cerebrospinal fluid, thereby suggesting its potential significance in facilitating material and information exchange between the brain parenchyma and cerebrospinal fluid. After conducting a comprehensive series of studies on the morphological structure, material expression, gene analysis and functional aspects of the CSF-contacting nucleus in rodents and non-human primates, it has been revealed that there are fibrous connections between the CSF-contacting nucleus and the cerebral cortex and subcortical nuclei being involved in the regulatory mechanisms of pain, cognition, learning and memory, emotion, addiction, stress and anxiety responses, visceral activity, olfaction, vision processing and perception, auditory processing, perception, motor control and coordination, homeostasis regulation including maintenance of body energy and fluid balance, as well as the control of sleep–wake cycles and synchronization of biological rhythms. Current experiments have confirmed that the CSF-contacting nucleus is related to pain, morphine dependence and withdrawal, learning and memory, as well as stress. This present article offers a comprehensive review of the neurobiological characteristics and recent advancements in pain regulation of the CSF-contacting nucleus. The aim is to provide novel insights into the investigation of pain regulation within bidirectional regulatory pathway between the brain and cerebrospinal fluid, with a specific focus on elucidating the role of the CSF-contacting nucleus as a bridge structure. Additionally, the objective of this research is to propose innovative strategies for pain management and associated disorders in the future.

Abstract The impact of the Madden‐Julian oscillation (MJO) on the intraseasonal PNA (ISPNA) was investigated and was found to be modulated by the El Niño‐Southern Oscillation (ENSO), which reasonably explains the skewness of the ISPNA during El Niño and La Niña winters. It was shown that the intensity and periodicity of the ISPNA was much stronger and slightly longer in La Niña winters than in the El Niño winters. The phase‐locked association between the ISPNA and MJO indicate that this skewness was controlled by the MJO. The northward Rossby wave activities derived from the tropics associated with the MJO to the subtropical Pacific sector of the ISPNA clarified that the stronger intensity of the MJO convection in the western Pacific during the La Niña winters, as well as the slower eastward propagation of the MJO, led to the asymmetric intensity and period of the ISPNA in the two ENSO phases.

Abstract The impact of the boreal summer intraseasonal oscillation (BSISO) on rainfall anomalies in the Yangtze–Huaihe River Basin (YHRB) was found to be modulated by the stratospheric quasi‐biennial oscillation (QBO), which is reasonable for the close associations between the QBO and summer extreme precipitation in the YHRB. It was found that the extreme precipitation preferentially occurred in the YHRB during the easterly phase of the QBO (EQBO) compared to the westerly phase of the QBO (WQBO). This was primarily because the BSISO was more prone to cause rainfall extremes in the YHRB during the EQBO summers than during the WQBO summers. The EQBO can induce the background stratospheric easterly wind to arch downward into the troposphere, which enhanced the BSISO‐associated moisture transport and moisture convergence and thus resulted in stronger rainfall extremes in the YHRB.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFβ1 in the metastatic bone tissue, and raised the expression of TGFβRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFβRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFβ1, TGFβRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFβ1-TGFβRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Ciliated microeukaryotes (ciliates) are distinguished by their cilia, which are rich in tubulin. We developed a method for tubulin staining in ciliate cells that involves using live-cell tubulin-staining dyes instead of antibodies thereby streamlining the staining process, which is effective across diverse ciliate lineages. Moreover, our method allows integration with immunofluorescence staining using antibodies when needed. The potential applications of this technique extend to cell biology and ciliate morphological and ecological studies.

BackgroundChronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR).MethodsThe research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q-test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software.ResultsThe IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex (P > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: β = 0.015, 95% CI: 0.005–0.025, P = 3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: β = 0.02, 95% CI: 0.010–0.033, P = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO.ConclusionGenetic evidence indicates a positive correlation between CHF and pars opercularis TH.

Abstract An important concern for tea consumers is whether appropriate storage can effectively improve the ability of oolong tea to alleviate type 2 diabetes mellitus (T2DM). In this study, the antidiabetic effects of three aged oolong tea (2001, 2011, and 2020) extracts (aged TEs) in db/db T2DM mice were investigated and compared for the first time. The results showed that aged oolong tea extracts (aged TEs) alleviated the abnormal fasting blood glucose levels, lipid profiles, insulin resistance, and reduced ectopic fat deposition in liver. Moreover, aged TEs alleviated T2DM‐related tissue damage and activated insulin receptor (INSR)/insulin receptor substrate (IRS)/phosphatidylinositol‐3 kinase (PI3K)/phosphatidylinositol‐3 kinase (AKT)/glycogen synthase kinase 3 beta (GSK‐3β)/glycogen synthase (GYS)‐mediated hepatic glycogen synthesis signaling pathway. In addition, aged TEs altered gut microbiota composition and gut metabolite profiles associated with T2DM. Together, all three aged TEs (400 mg/kg/day in mice, a human equivalent dose of 7 g/60 kg/day), especially 2011, can effectively alleviate T2DM, and proper storage can effectively improve the ability of oolong tea to alleviate T2DM.

Abstract Background Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. Methods We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan–Meier method. The chi-square and Fisher’s exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan–Meier method. Prognostic variables were assessed through univariate Cox analyses. Results The median patient age was 28 years (range, 16–82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. Conclusions The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.

Abstract Liver cancer, a chronic non-communicable disease, represents a serious public health problem. Long-term trends in the burden of liver cancer disease are heterogeneous across regions. Incidence and mortality of liver cancer, based on the Global Burden of Disease, were collected from the Chinese Centre for Disease Control and Prevention. Age–period–cohort model was utilized to reveal the secular trends and estimate the age, period and cohort effects on primary liver cancer due to specific etiologies. Both the age-standardized incidence and mortality rate of liver cancer in Hubei province were on the rise, although there were discrepancies between gender groups. From age–period–cohort analysis, both incidence and mortality of liver cancer due to Hepatitis B virus were the highest in all age groups. The incidence of all liver cancer groups increased with time period in males, while this upward trend was observed in females only in liver cancer due to alcohol use group. Cohort effects indicated the disease burden of liver cancer decreased with birth cohorts. Local drifts showed that the incidence of liver cancer due to specific etiologies was increasing in the age group of males between 40 and 75 years old. The impact of an aging population will continue in Hubei Province. the disease burden of liver cancer will continue to increase, and personalized prevention policies must be adopted to address these changes.

It is essential to achieve the high-accuracy recognition of low probability of intercept (LPI) radar signals in modern electronic warfare. However, under low signal-to-noise ratio (SNR), the recognition accuracy of the LPI radar signals is relatively low. In this paper, a novel radar signal recognition method based on Convolutional Stacked Recurrent Deep Neural Network (CSRDNN) is proposed. Firstly, we design a Convolutional Neural Network (CNN) to expand the feature space of input time domain signals, the features extracted by CNN were then used as inputs of the Stacked Recurrent Neural Networks (SRNN) module. In the SRNN module, we sequentially stack GRU, LSTM, and BGRU, enabling the model to better handle the short-term and long-term dependence of signal features and effectively solve asynchronous problems in unidirectional RNN networks. Subsequently, a Fully Connected Deep Neural Network (FCDNN) was employed to accomplish the recognition task. In addition, we design a training algorithm composed of the Nesterov-Adaptive Moment Estimation (Nadam) algorithm and the CosineAnnealing Learning Rate (LR) adjustment strategy to improve the training efficiency of the model. The experimental results demonstrate that the proposed model has higher recognition accuracy at low SNR compared to other models, with an overall recognition accuracy of 92.96% at −4 dB.

Abstract This study aimed to identify new pyroptosis-associated tumor antigens for use in mRNA vaccines and the screening of sensitive LUAD populations suitable for vaccination. The association between tumor immune infiltrating cell abundance and potential tumor antigens was investigated and visualized using the analysis modules of gene expression, clinical outcomes, and somatic copy number variation. In addition, the pyroptosis-related genes (PRGs) were clustered, the relative pyroptosis subtypes (PSs) and gene modules were identified, and the prognostic value of the PSs was examined. The expression of key PRGs in two lung adenocarcinoma cell lines was verified by RT-qPCR. Four tumor pyroptosis-associated antigens, CARD8, NAIP, NLRP1, and NLRP3, were screened as potential candidates for LUAD mRNA vaccine development. In the construction of consensus clusters for PRGs, two PSs, PS1 and PS2, were classified, in which patients with PS1 LUAD had a better prognosis. In contrast, patients with PS2 LUAD may have better responsiveness to mRNA vaccine treatment. The key PRGs can be regarded as biomarkers to predict the LUAD prognosis and identify patients suitable for mRNA vaccines. The RT-qPCR results showed that the expression levels of CSMD3, LRP1B, MUC16 and TTN were significantly increased in the two lung adenocarcinoma cell lines, while the expression levels of CARD8, TP53 and ZFHX4 were significantly reduced. The antigens CARD8, NAIP, NLRP1, and NLRP3, which are associated with tumor pyroptosis, could be candidate molecules for LUAD mRNA vaccine development. Patients with PS2 LUAD may be suitable candidates for mRNA vaccine treatment.

Radar signal recognition plays a crucial role in modern electronic reconnaissance systems. With the increasing complexity of electromagnetic environments, radar signals are susceptible to noise interference under low signal-to-noise ratio (SNR) conditions, posing a challenge to accurate radar signal recognition. To address this issue, we propose a multilayer decomposition denoising empowered convolutional neural network (CNN) for radar signal recognition. Specifically, the original radar signals are first processed by multilayer decomposition denoising, which consists of variational mode decomposition (VMD), local mean decomposition (LMD), and wavelet thresholding (WT) in sequence, termed as VMD-LMD-WT. Then we use the Choi-Williams distribution (CWD) to convert the denoised signals into time-frequency images (TFIs). Finally, an improved CNN with dilated convolution is employed for radar signal recognition. Experiments demonstrate that the multilayer decomposition denoising method effectively improves the SNR of the original signal, which is beneficial for the subsequent recognition task. The recognition accuracy is improved by about 11% compared to that directly using the original signal. Furthermore, compared to the current network models, the proposed CNN network can efficiently extract the signal features and improve the detection accuracy of low probability of intercept (LPI) radar signals. The recognition accuracy reaches 75.3% for 12 signals when the SNR is low to −14dB.

For the Doppler parameters coupling and spectral aliasing in the hybrid sliding spotlight mode of the spaceborne–airborne bistatic SAR (SA-BiSAR), a frequency-domain imaging algorithm based on echo preprocessing is proposed in this article. The article utilizes the idea of spectral analysis (SPECAN) technology to remove the spectrum aliasing by echo preprocessing, without subaperture partition and subaperture stitching operations, which reduces the computational burden. On this basis, the Legendre orthogonal polynomial expansion method is used to achieve a high-accuracy approximation of the SA-BiSAR slant range function. Combined with the method of series reversion, the accurate two-dimensional (2-D) spectrum of the point target is derived so that the high-quality decoupling of the 2-D spectrum is achieved. Finally, the compensation functions are designed to complete the focusing imaging in the frequency domain. The simulation results of point targets and distributed targets show that the imaging algorithm proposed in this article has good focusing performance and can improve the imaging quality of scene edge points.

Background: Machine learning has shown to be an effective method for early prediction and intervention of Gestational diabetes mellitus (GDM), which greatly decreases GDM incidence, reduces maternal and infant complications and improves the prognosis. However, there is still much room for improvement in data quality, feature dimension, and accuracy. The contributions and mechanism explanations of clinical data at different pregnancy stages to the prediction accuracy are still lacking. More importantly, current models still face notable obstacles in practical applications due to the complex and diverse input features and difficulties in redeployment. As a result, a simple, practical but accurate enough model is urgently needed. Design and methods: In this study, 2309 samples from two public hospitals in Shenzhen, China were collected for analysis. Different algorithms were systematically compared to build a robust and stepwise prediction system (level A to C) based on advanced machine learning, and models under different levels were interpreted. Results: XGBoost reported the best performance with ACC of 0.922, 0.859 and 0.850, AUC of 0.974, 0.924 and 0.913 for the selected level A to C models in the test set, respectively. Tree-based feature importance and SHAP method successfully identified the commonly recognized risk factors, while indicated new inconsistent impact trends for GDM in different stages of pregnancy. Conclusion: A stepwise prediction system was successfully established. A practical tool that enables a quick prediction of GDM was released at https://github.com/ifyoungnet/MedGDM.This study is expected to provide a more detailed profiling of GDM risk and lay the foundation for the application of the model in practice.

Allogeneic hematopoietic stem cell transplantation (aHSCT) is utilized as a potential curative treatment for various hematologic malignancies. However, graft-versus-host disease (GVHD) post-aHSCT is a severe complication that significantly impacts patients' quality of life and overall survival, becoming a major cause of non-relapse mortality. In recent years, the association between epigenetics and GVHD has garnered increasing attention. Epigenetics focuses on studying mechanisms that affect gene expression without altering DNA sequences, primarily including DNA methylation, histone modifications, non-coding RNAs (ncRNAs) regulation, and RNA modifications. This review summarizes the role of epigenetic regulation in the pathogenesis of GVHD, with a focus on DNA methylation, histone modifications, ncRNA, RNA modifications and their involvement and applications in the occurrence and development of GVHD. It also highlights advancements in relevant diagnostic markers and drugs, aiming to provide new insights for the clinical diagnosis and treatment of GVHD.

Abstract Pathogenic bacteria are the main cause of bacterial infectious diseases, which have posed a grave threat to public health. Single‐atom nanozymes have emerged as promising candidates for antibacterial applications, but their activities need to be further improved. Considering diatomic nanozymes exhibit superior metal loading capacities and enhanced catalytic performance, a new interlayer coupling diatomic nanozyme (IC‐DAN) is constructed by modulating the coordination environment in an atomic‐level engineering. It is well demonstrated that IC‐DAN exhibited superior peroxidase‐mimetic activity in the presence of H2O2 to yield abundant ∙OH and possessed high photothermal conversion ability, which synergistically achieves efficient antibacterial therapy. Therefore, IC‐DAN shows great potential used as antibacterial agent in clinic and this study open a new route to developing high‐performance artificial enzymes.

Objective Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN).Methods This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression.Results Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280).Conclusion Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus.

IntroductionChimerism is closely correlated with disease relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, chimerism rate is dynamic changes, and the sensitivity of different chimerism requires further research.MethodsTo investigate the predictive value of distinct chimerism for relapse, we measured bone marrow (BM), peripheral blood (PB), and T-cell (isolated from BM) chimerism in 178 patients after allo-HSCT.ResultsReceiver operating characteristic (ROC) curve showed that T-cell chimerism was more suitable to predict relapse after allo-HSCT compared with PB and BM chimerism. The cutoff value of T-cell chimerism for predicting relapse was 99.45%. Leukemia and myelodysplastic syndrome (MDS) relapse patients’ T-cell chimerism was a gradual decline from 2 months to 9 months after allo-HSCT. Higher risk of relapse and death within 1 year after allo-HSCT. The T-cell chimerism rates in remission and relapse patients were 99.43% and 94.28% at 3 months after allo-HSCT (P = 0.009), 99.31% and 95.27% at 6 months after allo-HSCT (P = 0.013), and 99.26% and 91.32% at 9 months after allo-HSCT (P = 0.024), respectively. There was a significant difference (P = 0.036) for T-cell chimerism between early relapse (relapse within 9 months after allo-HSCT) and late relapse (relapse after 9 months after allo-HSCT) at 2 months after allo-HSCT. Every 1% increase in T-cell chimerism, the hazard ratio for disease relapse was 0.967 (95% CI: 0.948–0.987, P

The evaluation of geological suitability for urban underground space (UUS) development is an indispensable prerequisite for its optimal utilization. As the actual carrier of underground facilities, the evaluation of rock mass quality plays a crucial role in assessing geological suitability. However, it is notable that the evaluation of rock mass quality has regrettably remained somewhat marginalized within the broader framework of the geological suitability assessment in recent years. The selection of pertinent indicators for the evaluation of rock mass quality inherently presents an appreciable degree of subjectivity. Predominantly subjective evaluation methods continue to dominate the field, while the application of objective algorithms, such as unsupervised clustering, remains in its nascent stage. Furthermore, there is a lack of comprehensive investigations into distinct combinations of attributes. This limitation confines the broader applicability of the evaluation outcomes in the context of urban underground space. Within this study, we meticulously amassed rock core test data from over 40 boreholes of engineering geological significance within the urban planning ambit of Guang'An City. Utilizing the K-means unsupervised clustering algorithm and the Principal Component Analysis (PCA) algorithm. We successfully conducted an unsupervised clustering procedure with nine distinct physical and mechanical attributes. This yielded an aggregation into five discernible clusters. Building upon the derived clustering outcomes, a stratification of rock mass quality was effectuated into three distinct tiers: Level 1 (characterized by pure sandstone), Level 2 (primarily dominated by sandstone), and Level 3 (denoting fair conditions predominantly influenced by mudstone). This structured stratification facilitates a relatively objective and comprehensive evaluation of rock mass quality within the context of the red-bed hilly terrain. In the course of this analytical trajectory, we conducted a dissection of the clustering efficacy. For strongly correlated attributes, we propose a preliminary dimensionality reduction procedure prior to the clustering endeavor. Moreover, we recommend intervals of 10 m for the stratified evaluation in red bed hilly urban terrains.

Abstract Background Extended reality (XR), including virtual reality, augmented reality (AR), and mixed reality, has been used to help achieve accurate acetabular cup placement in total hip arthroplasty (THA). This study aimed to compare the differences between XR-assisted and conventional THA. Methods In this systematic review and meta-analysis, electronic databases including PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov were searched for studies from inception to September 10, 2023. The outcomes were accuracy of inclination and anteversion, duration of surgery, and intraoperative blood loss. Meta-analysis was performed using Review Manager 5.4 software. Results A total of five studies with 396 patients were included in our study. The pooled results indicated AR-assisted THA had better accuracy of inclination and anteversion than conventional THA (SMD = − 0.51, 95% CI [− 0.96 to − 0.07], P = 0.02; SMD = − 0.96, 95% CI [− 1.19 to − 0.72], P

Abstract Background Effective orthodontic treatment planning hinges on accurately defining incisor position objectives (IPO) in cephalograms. The purpose of this study was to estimate the inter-examiner and intra-examiner reliability of different orthodontists in devising IPOs on cephalograms. Methods Ten orthodontists, who were divided into to the senior group (N = 5) and the junior group (N = 5) based on their clinical experience, formulated IPOs for 60 pre-treatment cephalograms twice with an interval of 2 weeks, utilizing SmartOrtho software. The type and magnitude of movement were read directly in the software. A paired t-test assessed the absolute differences between the first and second IPO devising within each group and between the senior and junior groups in each time’s IPO devising. The intra-examiner and inter-examiner reliabilities were calculated. Results There were significant differences in all types of upper incisor movement and lower incisor protrusion/retraction movement between the first and second IPO devising of the senior group. The junior group exhibited significant differences in the twice the upper incisor extrusion/intrusion movement and upper incisor torque movement devising. Additionally, significant differences in all types of incisor movement between the senior and junior groups in each time’s IPO devising. Intra-examiner reliabilities were excellent for both two groups and moderate for the junior group in most types of incisor movement, respectively. The inter-examiner reliability between the two groups ranged from moderate to good across different types of incisor movement. Conclusions Among orthodontists, both senior and junior practitioners displayed the best inter-examiner reliability in lower incisor extrusion/intrusion movement. In terms of intra-examiner reliability, senior orthodontists had better intra-examiner reliability in upper incisor position objectives devising than the junior orthodontists. Furthermore, senior orthodontists tended to adopt a more recessive, intrusive, and lingually torqued incisor position approach compared to junior orthodontists.

Abstract To clarify the risk of tuberculosis (TB) infection in patients with Takayasu arteritis (TAK). In this study, we conducted a comprehensive search across multiple databases, including PubMed, Web of Science, Embase, Cochrane, and Medline, from the inception of the Literature Library to May 16, 2023. Using a specific set of keywords, including “Takayasu Arteritis”, “Tuberculosis”, and “Mycobacterium tuberculosis”, the main objective of this search was to identify all relevant observational studies, including case-control studies, cohort studies, and cross-sectional studies, that report the prevalence of TB in individuals diagnosed with TAK. Two independent evaluators rigorously screened the studies, extracted data, and assessed the study quality using the Joanna Briggs Institute (JBI) critical appraisal tools. Statistical analyses were conducted using R software version 4.3.0, which allowed for the synthesis of prevalence and subgroup analyses. Subgroup analyses were stratified based on quality scores, World Health Organization regional categorizations, and TB categories. Assessment of publication bias was performed using a funnel plot. The study included a total of 30 studies with 5548 participants. The findings showed that individuals with TAK exhibited an average prevalence of TB infection at 31.27% (95% CI 20.48–43.11%). Significantly, the prevalence of TB infection demonstrated notable regional disparities, ranging from 16.93% (95% CI 7.71–28.76%) in the Western Pacific Region to 63.58% (95% CI 35.70–87.66%) in the African Region. Moreover, the study revealed that patients with TAK displayed a high prevalence of latent TB infection (LTBI) at 50.01% (95% CI 31.25–68.77%) and active TB at 14.40% (95% CI 9.03–20.68%). The high heterogeneity observed in the data highlights significant variability in TB infection rates among the populations studied, with the African Region exhibiting the highest rates. The study concludes that there is a high prevalence of TB infection in the TAK population, with regional variations. Consideration should be given to implementing rigorous TB screening measures and preventive interventions specifically tailored for the TAK population.

Abstract Background The nitro group constitutes a significant functional moiety within numerous valuable substances, such as nitroimidazoles, a class of antimicrobial drugs exhibiting broad spectrum activity. Conventional chemical methods for synthesizing nitro compounds suffer from harsh conditions, multiple steps, and environmental issues. Biocatalysis has emerged as a promising alternative to overcome these drawbacks, with certain enzymes capable of catalyzing nitro group formation gradually being discovered in nature. Nevertheless, the practical application is hindered by the restricted diversity and low catalytic activity exhibited by the reported nitrifying enzymes. Results A novel N-oxygenase SaRohS harboring higher catalytic capability of transformation 2-aminoimidazole to azomycin was characterized from Saccharothrix sp. Phylogenetic tree analysis revealed that SaRohS belongs to the heme-oxygenase-like diiron oxygenase (HDOs) family. SaRohS exhibited optimal activity at pH 5.5 and 25 ℃, respectively. The enzyme maintained relatively stable activity within the pH range of 4.5 to 6.5 and the temperature range of 20 ℃ to 35 ℃. Following sequence alignment and structural analysis, several promising amino acid residues were meticulously chosen for catalytic performance evaluation. Site-directed mutations showed that threonine 75 was essential for the catalytic activity. The dual mutant enzyme G95A/K115T exhibited the highest catalytic efficiency, which was approximately 5.8-fold higher than that of the wild-type and 22.3-fold higher than that of the reported N-oxygenase KaRohS from Kitasatospora azatica. The underlying catalytic mechanism was investigated through molecular docking and molecular dynamics. Finally, whole-cell biocatalysis was performed and 2-aminoimidazole could be effectively converted into azomycin with a reaction conversion rate of 42% within 14 h. Conclusions An efficient N-oxygenase that catalyzes 2-aminoimidazole to azomycin was screened form Saccharothrix sp., its phylogenetics and enzymatic properties were analyzed. Through site-directed mutation, enhancements in catalytic competence were achieved, and the molecular basis underlying the enhanced enzymatic activity of the mutants was revealed via molecular docking and dynamic simulation. Furthermore, the application potential of this enzyme was assessed through whole cell biocatalysis, demonstrating it as a promising alternative method for azomycin production. Graphical Abstract

Refractory high-entropy alloy (RHEA) has superior mechanical properties but low room-temperature ductility. However, eutectic heterostructure alloy has strength-ductility trade-off. In this study, the AlFeCrMoNbx (x = 1, 1.2, 1.4, 1.6, 1.8, and 2.0) RHEA coatings were successfully prepared on the surface of an M2 high-speed steel (HSS) by laser cladding. The increase of Nb content promoted the formation of eutectic microstructure, the coating changed from hypoeutectic structure to hypereutectic structure. When x = 1.8, the coating exhibited a near-eutectic structure consisting of BCC and Laves phases with high hardness and wear resistance. After annealed at 750 °C for 8 h, the phases and microstructure of Nb1.8 REHEA coating did not change, contributing to a high microhardness and wear resistance. With annealing temperature rising, the microhardness and wear resistance decreased. After annealing at 1050 °C, the hardness of the coating still remained 549 HV0.2, indicating a good high-temperature softening resistance of REHEA coating.

The low efficiency of light and nitrogen resources, poor yield and profit, and environmental pollution of maize production are main problems in many areas of China. We hypothesized that optimizing nitrogen fertilizer density management strategies could alleviate the above issues. To address this, a 3-year on-site experiment with three planting densities and four nitrogen rates was conducted in the Sichuan Hilly Region. The results indicated that increasing the planting density could increase the extinction coefficient and solar radiation interception of maize populations as well as enhance the utilization efficiency of light and nitrogen resources and yield. For every 100 kg ha−1 increase in nitrogen fertilizer, RUE increased by 0.16%, NUE decreased by 25.0%, and soil apparent nitrogen loss quantity increased by 67.8 kg ha−1. There was a certain interaction between planting density and nitrogen rate. The appropriate planting density and nitrogen rate combination was 67,500 plants ha−1 with 180 kg N ha−1 under the experimental condition. Excessive close planting in weak-light areas and excessive nitrogen reduction after densification are not advisable. This study indicated that nitrogen–density strategies should be matched with the local natural resources such as sunlight. The results provide a theoretical for high-yield and high-quality maize production in these areas.

Objectives To comprehensively synthesise evidence regarding the validity and reliability of the Anaesthetists’ Non-Technical Skills (ANTS) behavioural marker system and its application as a tool for the training and assessment of non-technical skills to improve patient safety.Design Systematic review.Data sources We employed a citation search strategy. The Scopus and Web of Science databases were searched for articles published from 2002 to May 2022.Eligibility criteria English-language publications that applied the ANTS system in a meaningful way, including its use to guide data collection, analysis and reporting.Data extraction and synthesis Study screening, data extraction and quality assessment were performed by two independent reviewers. We appraised the quality of included studies using the Joanna Briggs Institute Critical Appraisal Checklists. A framework analysis approach was used to summarise and synthesise the included articles.Results 54 studies were identified. The ANTS system was applied across a wide variety of study objectives, settings and units of analysis. The methods used in these studies varied and included quantitative (n=42), mixed (n=8) and qualitative (n=4) approaches. Most studies (n=47) used the ANTS system to guide data collection. The most commonly reported reliability statistic was inter-rater reliability (n=35). Validity evidence was reported in 51 (94%) studies. The qualitative application outcomes of the ANTS system provided a reference for the analysis and generation of new theories across disciplines.Conclusion Our results suggest that the ANTS system has been used in a wide range of studies. It is an effective tool for assessing non-technical skills. Investigating the methods by which the ANTS system can be evaluated and implemented for training within clinical environments is anticipated to significantly enhance ongoing enhancements in staff performance and patient safety.PROSPERO registration number CRD42022297773.

The role of traditional Chinese medicine (TCM) in treating diseases is receiving increasing attention. Chinese herbal medicine is an important part of TCM with various applications and the active ingredients extracted from Chinese herbal medicines have physiological and pathological effects. Tissue engineering combines cell biology and materials science to construct tissues or organs in vitro or in vivo. TCM has been proposed by the World Health Organization as an effective treatment modality. In recent years, the potential use of TCM in tissue engineering has been demonstrated. In this review, the classification and efficacy of TCM active ingredients and delivery systems are discussed based on the TCM theory. We also summarized the current application status and broad prospects of Chinese herbal active ingredients in different specialized biomaterials in the field of tissue engineering. This review provides novel insights into the integration of TCM and modern Western medicine through the application of Chinese medicine in tissue engineering and regenerative medicine.

ObjectivePrecocious puberty (PP) is a prevalent endocrine disorder affecting the physical and mental wellbeing of children. Identifying the triggering factors of PP has become a central issue. This study seeks to investigate the metabolomic and transcriptomic alterations in PP.Material and methodsFirst, 37 school-aged girls diagnosed with PP and 25 age-matched prepubertal control girls were recruited, and the fecal samples were collected for non-targeted metabolomic analysis to screen for differentially expressed metabolites (DEMs). Subsequently, an animal model of PP was constructed by danazol administration to neonatal female rats, and both fecal non-targeted metabolomics and serum next-generation transcriptomic sequencing were performed to screen DEMs and differentially expressed genes (DEGs) in PP. Moreover, the DEM co-existing in clinical and animal models was administrated to PP rats to explore the role of the target metabolite in PP.ResultsA total of 24 DEMs in PP clinical samples and 180 DEMs and 425 DEGs in PP animal samples were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEMs and DEGs were enriched in disease-associated pathways, including fatty acid synthesis, glycerolipid metabolism, pyrimidine metabolism, steroid hormone biosynthesis, progesterone-mediated oocyte maturation, and gonadotropin-releasing hormone (GnRH) signaling pathway, forming a tight DEM–DEG pathway regulatory network. Further DEM validation demonstrated that thymine supplementation delayed the opening of the vagina and development of PP in model rats.ConclusionThis study reveals that the metabolomic and transcriptomic changes, along with enriched pathways, are implicated in PP based on clinical and animal analyses. The findings may provide new strategies and research avenues for PP treatment.

Lipid deposition has emerged as a looming challenge worldwide. Previous studies have confirmed the fat-lowering effect of tea polyphenols (TP) in mice, but the underlying mechanism remains elusive. Furthermore, it remains unclear whether TP has the same effect in larger animals. Herein, we simultaneously investigated the regulatory effects of TP on lipid deposition in rats and Ningxiang pigs. The results showed that TP could effectively reduce fat accumulation in rats on a high-fat diet (HFD). As expected, TP supplementation led to a reduction in backfat thickness, fat rate, and subcutaneous fat cell size in Ningxiang pigs. Additionally, TP attenuated gut microbiota dysbiosis by enhancing microbial diversity and increasing the relative abundance of Bacteroides and Akkermansia in both models. Collectively, our results suggest that TP may reduce fat accumulation in rats and Ningxiang pigs by regulating gut microbiota. Therefore, TP could potentially serve as a functional agent for improving fat deposition in humans and Ningxiang pigs.

The asynchronous advantage actor-critic (A3C) algorithm is widely regarded as one of the most effective and powerful algorithms among various deep reinforcement learning algorithms. However, the distributed and asynchronous nature of the A3C algorithm brings increased algorithm complexity and computational requirements, which not only leads to an increased training cost but also amplifies the difficulty of deploying the algorithm on resource-limited field programmable gate array (FPGA) platforms. In addition, the resource wastage problem caused by the distributed training characteristics of A3C algorithms and the resource allocation problem affected by the imbalance between the computational amount of inference and training need to be carefully considered when designing accelerators. In this paper, we introduce a deployment strategy designed for distributed algorithms aimed at enhancing the resource utilization of hardware devices. Subsequently, a FPGA architecture is constructed specifically for accelerating the inference and training processes of the A3C algorithm. The experimental results show that our proposed deployment strategy reduces resource consumption by 62.5% and decreases the number of agents waiting for training by 32.2%, and the proposed A3C accelerator achieves 1.83× and 2.39× improvements in speedup compared to CPU (Intel i9-13900K) and GPU (NVIDIA RTX 4090) with less power consumption respectively. Furthermore, our design shows superior resource efficiency compared to existing works.

ObjectiveThe efficacy of the first-line monodrug chemotherapy has been generally established for low-risk GTN. Most patients can achieve a complete response after the first-line monodrug chemotherapy. However, which monodrug chemotherapy regimen is better for individual patients with GTN is not yet certain. This study aimed to assess the efficacy of first-line monodrug chemotherapy in low-risk gestational trophoblastic neoplasia (GTN).MethodDatabases, including PubMed, Embase, Web of Science, and Cochrane Library, were searched from inception to November 1, 2022, for case–control studies on first-line monodrug chemotherapy in GTN. Network meta-analysis was performed to compare the efficacy outcome of six monodrug chemotherapy regimens in GTN, with a complete response rate as the endpoint.ResultTwenty-four studies were considered eligible, including 9 randomized controlled trials (RCTs) and 15 non-RCTs. A total of 3344 patients with low-risk GTN were involved. Six monodrug chemotherapy regimens were included and analyzed. In descending order of efficacy, these six regimens were VP-16 (5 days), ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30–50 mg/m2) in all study, and five regimens were ACT-D (5 days), MTX (5 days), ACT-D (1.25 mg/m2), MTX (8 days), and MTX (30–50 mg/m2) in RCT.ConclusionAmong the six first-line monodrug chemotherapy regimens for low-risk GTN in all study, VP-16 (5 days) was the best in terms of efficacy. And five regimens in RCT, ACT-D was the best. However, the finding needs to be validated through more high-quality clinical studies.

Abstract Background Non‐small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR)‐mutated who progressed on EGFR tyrosine‐kinase inhibitor (EGFR‐TKI) therapy have limited therapeutic options. There is still no consensus on the role of immune checkpoint inhibitors (ICIs) in NSCLC with EGFR mutations. Methods We did a network meta‐analysis (NMA) with a systematic literature search on PubMed, Embase, Web of Science, and The Cochrane Library. We included all phase II and III randomized controlled trials (RCTs), non‐randomized controlled trials (Non‐RCTs), and retrospective studies. Progression‐free survival (PFS) and overall survival (OS) were assessed through hazard ratios (HR). Objective response rate (ORR) and adverse events (AEs) were assessed through odds ratio (OR) and relative risk (RR), respectively. R software was used to compare the outcomes of different treatments by Bayesian NMA. Findings We identified 1835 published results and 17 studies were included ultimately. A total of 2085 patients were included and accepted the following six treatments: ICIs plus chemotherapy (ICIs+Chemo), chemotherapy (Chemo), ICIs monotherapy (ICIs), ICIs plus chemotherapy and antiangiogenic therapy (ICIs+Chemo+Antiangio), antiangiogenic therapy plus chemotherapy (Antiangio+Chemo), ICIs plus antiangiogenic therapy (ICIs+Antiangio). ICIs+Chemo+Antiangio was associated with longer PFS and OS, as well as higher ORR (surface under the cumulative ranking curve [SUCRA], 96%, 90%, 91%). ICIs conferred the safety profile in terms of any‐grade AEs, grade greater than or equal to 3 AEs and any grade leading to treatment discontinuation occurred AEs (SUCRA, 99%, 68%, 94%). Interpretation ICIs+Chemo+Antiangio brings the greatest survival benefit in NSCLC patients with EGFR mutations who progressed on EGFR‐TKI therapy, even for whom with baseline brain metastases. Compared with chemotherapy, ICIs has a low incidence of AEs and a benefit in OS.

Surfactants were proposed to be added into magnesium sulfate solution to improve the leaching process of weathered crust elution-deposited rare earth ores (WREOs). Effects of surfactants and their concentration on the seepage of leaching solutions and the leaching efficiency of rare earth (RE) and aluminum (Al) were investigated, and the leaching kinetics, the mass transfer process, the adhesion work and the adhesion work reduction factor were analyzed to reveal its strengthening leaching mechanism. The results show that cetyltrimethylammonium bromide (CTAB) has a better strengthening effect on the leaching process than dodecyl trimethyl ammonium bromide (DTAB), sodium dodecyl sulfate (SDS), sodium oleate and oleic acid. In the presence of 0.04% CTAB in 0.2 mol/L solution, the permeability coefficient of WREOs increases from 0.945×10−5 to 1.640×10−5 cm·s−1, and the leaching efficiency of RE increases from 80% to 90%, confirming the promotion of surfactants on the leaching process of WREOs. Kinetic analysis shows that the leaching process conforms to the inner diffusion control model, and the leaching kinetics equations of RE and Al related to CTAB content are obtained. Mass transfer discussion shows a smaller height equivalent to theoretical plate (HETP) of RE and Al at CTAB content of 0.04%, suggesting the higher mass transfer efficiency here. According to the interfacial properties of leaching solutions, the calculated adhesion work and the adhesion work reduction factor further demonstrate the strengthening leaching effect of CTAB on the leaching process of WREOs.

In this study, we conducted the morphological observation, biological and genomic characterization, evolutionary analysis, comparative genomics description, and proteome identification of a recently isolated mycobacteriophage, WIVsmall. Morphologically, WIVsmall is classified as a member of the Siphoviridae family, characterized by a flexible tail, measuring approximately 212 nm in length. The double-stranded phage genome DNA of WIVsmall spans 53,359 base pairs, and exhibits a G + C content of 61.01%. The genome of WIVsmall comprises 103 protein-coding genes, while no tRNA genes were detected. The genome annotation unveiled the presence of functional gene clusters responsible for mycobacteriophage assembly and maturation, replication, cell lysis, and functional protein synthesis. Based on the analysis of the phylogenetic tree, the genome of WIVsmall was classified as belonging to subgroup F1. A comparative genomics analysis indicated that the WIVsmall genome exhibited the highest similarity to the phage SG4, with a percentage of 64%. The single-step growth curve analysis of WIVsmall revealed a latent period of 120 min, and an outbreak period of 200 min.

Abstract Aim To investigate the prevalence of SUI and explore the factors that could influence the severity of SUI in adult females. Design A cross‐sectional study. Methods A total of 1178 subjects were assessed using a risk‐factor questionnaires and International Consultation on Incontinence Questionnaire Short Form (ICIQ‐SF) and then divided into no SUI group, mild SUI group and moderate‐to‐severe SUI group according to the ICIQ‐SF score. Univariate analysis between adjacent groups and ordered logistic regression models in three groups were then performed to analysis the possible associated factor with the progressive of SUI. Results The prevalence of SUI among adult women was 22.2% of them; 16.2% and 6% had mild SUI and moderate‐to‐severe SUI, respectively. Moreover, logistic analysis revealed that age, BMI, smoking, position preference for urination, urinary tract infections, urinary leaks during pregnancy, gynaecological inflammation and poor sleep quality were independent risk for the severity of SUI. Conclusion SUI symptoms were mostly mild among Chinese females, specific risk factors such as unhealthy living habits and urination behaviours increased the risk of SUI and the aggravation of symptoms. Therefore, targeted interventions should be formulated for women to delay disease progression.

AgCu bimetallic· nanoparticles (NPs) represent a novel class of inorganic, broad-spectrum antimicrobial agents that offer enhanced antimicrobial effectiveness and reduced cytotoxicity compared to conventional Ag NP antibacterial materials. This study examines the antimicrobial performance and structural characteristics of AgCu nanoparticles (NPs) synthesized via two distinct chemical reduction processes using PVP-PVA as stabilizers. Despite identical chemical elements and sphere-like shapes in both synthesis methods, the resulting AgCu nanoparticles exhibited significant differences in size and antimicrobial properties. Notably, AgCu NPs with smaller average particle sizes demonstrated weaker antimicrobial activity, as assessed by the minimum inhibitory concentration (MIC) measurement, contrary to conventional expectations. However, larger average particle-sized AgCu NPs showed superior antimicrobial effectiveness. High-resolution transmission electron microscopy analysis revealed that nearly all larger particle-sized nanoparticles were AgCu nanoalloys. In contrast, the smaller particle-sized samples consisted of both AgCu alloys and monometallic Ag and Cu NPs. The fraction of Ag ions (relative to the total silver amount) in the larger AgCu NPs was found to be around 9%, compared to only 5% in that of the smaller AgCu NPs. This indicates that the AgCu alloy content significantly contributes to enhanced antibacterial efficacy, as a higher AgCu content results in the increased release of Ag ions. These findings suggest that the enhanced antimicrobial efficacy of AgCu NPs is primarily attributed to their chemical composition and phase structures, rather than the size of the nanoparticles.

A large amount of ammonium salt leaching agent will remain in the leaching site of weathered crust elution-deposited rare earth ore (WREOs). The release of residual ammonium (RA) will seriously affect the water system ecology of the mining area, and it is urgent to control it. In this paper, column eluting was used to simulate the eluting process of RA in rare earth (RE) ore tailings, and the effects of calcium chloride concentration, eluting temperature, liquid-solid ratio, eluent pH and eluent flow rate on the eluting process of RA in rare earth ore tailings were discussed. It was found that calcium chloride could effectively elute the RA from ore tailings. Eluting agent pH almost had no effect on the eluting process of RA in the pH range of 4–6, and a greater impact on it at pH 8. The flow rate could effectively enhance the elution efficiency. The optimum conditions were calcium ion concentration of 0.1 mol/L, liquid-solid ratio of 2:1, pH 4–6, flow rate of 0.6 mL/min and elution at room temperature. At this time, the elution efficiency of RA was 91.85%. The eluting process of RA in ore tailings was controlled by the inner particle diffusing according to the kinetic analysis. The reaction order was 0.368, and the activation energy of the reaction is 12.450 kJ/mol. This will provide a theoretical basis and technical support for the efficient eluting process of residual ammonium in the leaching site of WREOs.

Abstract Background Silica-induced pulmonary fibrosis (silicosis) is a diffuse interstitial fibrotic disease characterized by the massive deposition of extracellular matrix in lung tissue. Fibroblast to myofibroblast differentiation is crucial for the disease progression. Inhibiting myofibroblast differentiation may be an effective way for pulmonary fibrosis treatment. Methods The experiments were conducted in TGF-β treated human lung fibroblasts to induce myofibroblast differentiation in vitro and silica treated mice to induce pulmonary fibrosis in vivo. Results By quantitative mass spectrometry, we revealed that proteins involved in mitochondrial folate metabolism were specifically upregulated during myofibroblast differentiation following TGF-β stimulation. The expression level of proteins in mitochondrial folate pathway, MTHFD2 and SLC25A32, negatively regulated myofibroblast differentiation. Moreover, plasma folate concentration was significantly reduced in patients and mice with silicosis. Folate supplementation elevated the expression of MTHFD2 and SLC25A32, alleviated oxidative stress and effectively suppressed myofibroblast differentiation and silica-induced pulmonary fibrosis in mice. Conclusion Our study suggests that mitochondrial folate pathway regulates myofibroblast differentiation and could serve as a potential target for ameliorating silica-induced pulmonary fibrosis.

Objective Currently, there are no reports on the specific classification of cervical spine trauma (CST) in ankylosing spondylitis (AS) based on the trauma mechanism. In this study, we aimed to describe a novel classification of CST in AS with more details, and put forward the corresponding surgical outcomes related to different types, hoping to provide a practical reference for clinical decision‐making and academic communication. Methods From January 2008 to December 2021, AS patients who experienced CST were retrospectively reviewed and included. Clinical data including gender, age, reason of trauma, time interval between AS diagnosis and trauma were collected. The American Spinal Injury Association (ASIA) grade system was used to describe patients' neurological status. Based on the combination of surgical experience and follow‐up observation, the lower cervical spine trauma in AS patients was divided into three main types, namely single level fracture‐dislocation (type 1), spinal cord injury without fracture‐dislocation (type 2), and Andersson lesion (type 3). Furthermore, we performed detailed subtypes according to whether cervical spine was completely fused and the location of injury. Meanwhile, according to different approaches, surgical methods mainly included Anterior Cervical Discectomy and Fusion (ACDF), Anterior Cervical Corpectomy and Fusion (ACCF), Posterior Expansive Open‐door Cervical Laminoplasty (PEOLP), Posterior Cervical Laminectomy Decompression and Fusion (PCLDF), and their combination. Postoperative general and surgery‐related complications were also recorded. Results A total of 102 patients were enrolled, including 91 males and 11 females, with an average age of 51.9 years. Their average interval time between AS diagnosis and injury was 27.8 years. Patients with high‐energy and low‐energy trauma were 54 and 48 respectively. There were 79 patients suffering spinal cord nerve impairment after trauma. With regard to the distribution of different types, the number of patients in type 1, type 2, and type 3 were 86, 14, and two, respectively. For different types, PCLDF was the most commonly used surgical method, accounting for 55.9%, while ACCF was only applied for one time. In type 1, the frequencies of ACDF, ACCF, PCLDF, and ACDF+PCLDF were 10.5%, 1.2%, 55.8%, and 32.5%. In type 2, the frequencies of ACDF, PCLDF, ACDF+PCLDF, and PEOLP were 7.1%, 50.0%, 7.1%, 35.8%. Postoperatively, 21 patients achieved neurological function improvement. The incidences of general and surgery‐related complications were 19.6% and 5.9%, respectively. All patients achieved bone fusion and durable decompression at the last follow‐up. Conclusions Our novel classification could enrich the scope of CST in AS patients and provide valuable references to the corresponding clinical management. Besides, there are strict indications of different surgical methods, factors like patient's physical condition, trauma type, surgical purpose, and expected efficacy were all required to consider before making a clinical decision.