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Abstract Background Uncorrected refractive error (URE) is one of the main causes of visual impairments. URE may reduce interaction and learning in the classroom, leading to social isolation, irreversible amblyopia, lack of external knowledge, and restrictions on education and employment opportunities. Our aim was to investigate the prevalence and related factors of URE in adolescents using epidemiological surveys and questionnaire surveys related to lifestyle habits. Methods A cross-sectional school-based study was conducted in Nantong, China, including adolescents 12–19 years of age from 16 schools. URE was defined as presenting visual acuity worse than 6/12 and improving to ≥ 1 lines after correction in either eye. Univariate and multivariate logistic regression analyses were used to investigate specific correlations between URE and related lifestyle parameters. Non-cycloplegic autorefraction was assessed for each adolescent. Results A total of 2,910 adolescents were analyzed, of which 50.3% (n = 1,465) were male, and 49.7% (n = 1,445) were female. The mean age was 15.23 ± 1.77 years. The overall prevalence of URE was 23.7%. The total prevalence of REC and eREC was 85.1% and 71.7%, respectively, and both of them showed an increasing trend with age (Ptrend = 0.018 and Ptrend = 0.019, respectively). A higher prevalence of URE was related to myopia, anisometropia, and increased daily use of electronic products. Timely visual examination by medical institutions, more extracurricular homework, and older age were protective factors for URE. Among the 689 adolescents with URE, 362 (52.5%) did not receive any refractive correction, and 327 (47.5%) used corrected glasses. Conclusion URE was highly prevalent among adolescents in China. Myopia was the most important risk factor for URE. The impact of anisometropia and increased daily use of electronic devices on URE was significant. Timely visual examinations by medical institutions served as an effective protective factor against URE. Further research on adjusting intervention strategies is therefore needed to eliminate preventable visual impairments.

Abstract Purpose To explore the application value of a multimodal deep learning radiomics (MDLR) model in predicting the risk status of postoperative progression in solid stage I non-small cell lung cancer (NSCLC). Materials and Methods A total of 459 patients with histologically confirmed solid stage I NSCLC who underwent surgical resection in our institution from January 2014 to September 2019 were reviewed retrospectively. At another medical center, 104 patients were reviewed as an external validation cohort according to the same criteria. A univariate analysis was conducted on the clinicopathological characteristics and subjective CT findings of the progression and non-progression groups. The clinicopathological characteristics and subjective CT findings that exhibited significant differences were used as input variables for the extreme learning machine (ELM) classifier to construct the clinical model. We used the transfer learning strategy to train the ResNet18 model, used the model to extract deep learning features from all CT images, and then used the ELM classifier to classify the deep learning features to obtain the deep learning signature (DLS). A MDLR model incorporating clinicopathological characteristics, subjective CT findings and DLS was constructed. The diagnostic efficiencies of the clinical model, DLS model and MDLR model were evaluated by the area under the curve (AUC). Results Univariate analysis indicated that size (p = 0.004), neuron-specific enolase (NSE) (p = 0.03), carbohydrate antigen 19 − 9 (CA199) (p = 0.003), and pathological stage (p = 0.027) were significantly associated with the progression of solid stage I NSCLC after surgery. Therefore, these clinical characteristics were incorporated into the clinical model to predict the risk of progression in postoperative solid-stage NSCLC patients. A total of 294 deep learning features with nonzero coefficients were selected. The DLS in the progressive group was (0.721 ± 0.371), which was higher than that in the nonprogressive group (0.113 ± 0.350) (p

Abstract Boron-doped biochar (B-BC) was synthesized by pyrolysis using solid waste of sorghum straw as raw material. The specific surface area of B-BC increased significantly by 2.38 times compared to that of pure BC. This enhancement allowed B-BC (0.3 g L−1) to achieve complete adsorption of 10 mg L−1 tartrazine (TTZ) within 40 min. Moreover, acidic conditions were more favorable for TTZ adsorption, achieving complete removal of TTZ in only 15 min at a pH of 3.0. Interestingly, the adsorption rate of TTZ by B-BC in the presence of 0.05 M Cl− was approximately 2.12 times higher than that in the absence of Cl−. When other background electrolytes were present, excluding PO4 3−, complete adsorption of TTZ could also be achieved within 60 min. Thermodynamic analysis and DFT calculations described the parameters of B-BC for TTZ adsorption, including $$\Delta {\text{G}}^{\Theta }$$ Δ G Θ (

A novel coated urea (MVCU) was prepared, and its application effect was verified by field trials of oilseed rape in three main cultivation areas. Meanwhile, the nutrient release and coating layer changes of MVCU in static water at 25 °C and different soils were systematically evaluated. MVCU showed a long nutrient release time under static water (77 days) and soil incubation (140 days) conditions due to the slow degradation of the coating layer in MVCU, and its nitrogen release coincided well with oilseed rape nitrogen demand. The above results were further confirmed by FT-IR spectra and SEM analysis. Compared with conventional urea (U), the field trials of MVCU in the three main cultivation areas showed high nitrogen utilization efficiency and yield advantages in oilseed rape. The field trials results indicated that the MVCU significantly enhanced the aboveground dry matter (28.7%), the seed nitrogen concentration (9.5%) and aboveground nitrogen accumulation (42.5%) of oilseed rape at the mature stage as compared to that of the U. The oilseed rape yield enhanced by 932.8 kg/hm2, the average growth rate was 65.1%, and nitrogen utilization efficiency increased by 21.2%. In short, MVCU has the advantages of excellent slow-release performance and strong applicability, and its yield-increasing effect on oilseed rape could reach or even be better than that of traditional fertilization.

Abstract Recognizing micro-expressions (MEs) as subtle and transient forms of human emotional expressions is critical for accurately judging human feelings. However, recognizing MEs is challenging due to their transient and low-intensity characteristics. This study develops a lightweight shallow dual-group symmetric attention network (SDGSA) to address the limitations of existing methods in capturing the subtle features of MEs. This network takes the optical flow features as inputs, extracting ME features through a shallow network and performing finer feature segmentation in the channel dimension through a dual-group strategy. The goal is to focus on different types of facial information without disrupting facial symmetry. Moreover, this study implements a spatial symmetry attention module, focusing on extracting facial symmetry features to emphasize further the symmetric information of the left and right sides of the face. Additionally, we introduce the channel blending technique to optimize the information fusion between different channel features. Extensive experiments on SMIC, CASME II, SAMM, and 3DB-combined mainstream ME datasets demonstrate that the proposed SDGSA method outperforms the metrics of current state-of-the-art methods. As shown by ablation experimental results, the proposed dual-group symmetric attention module outperforms classical attention modules, such as the convolutional block attention module, squeeze-and-excitation, efficient channel attention, spatial group-wise enhancement, and multi-head self-attention. Importantly, SDGSA maintained excellent performance while having only 0.278 million parameters. The code and model are publicly available at https://github.com/YZY980123/SDGSA .

Abstract Developing a regional damage function to quickly estimate direct economic losses (DELs) caused by heavy rain and floods is crucial for providing scientific supports in effective disaster response and risk reduction. This study investigated the factors that influence regional rainfall-induced damage and developed a calibrated regional rainfall damage function (RDF) using data from the 2016 extreme rainfall event in Hebei Province, China. The analysis revealed that total precipitation, asset value exposure, per capita GDP, and historical geological disaster density at both the township and county levels significantly affect regional rainfall-induced damage. The coefficients of the calibrated RDF indicate that doubling the values of these factors leads to varying increases or decreases in rainfall-induced damage. Furthermore, the study demonstrated a spatial scale dependency in the coefficients of the RDF, with increased elasticity values for asset value exposure and per capita GDP at the county level compared to the township level. The findings emphasize the challenges of applying RDFs across multiple scales and highlight the importance of considering socioeconomic factors in assessing rainfall-induced damage. Despite the limitations and uncertainties of the RDF developed, this study contributes to our understanding of the relationship between physical and socioeconomic factors and rainfall-induced damage. Future research should prioritize enhancing exposure estimation and calibrating RDFs for various types of rainfall-induced disasters to improve model accuracy and performance. The study also acknowledges the variation in RDF performance across different physical environments, especially concerning geological disasters and slope stability.

Summary: Increasing cohort studies have examined the link between mitochondrial DNA copy number (mtDNA-CN) and cardiovascular disease (CVD), with inconsistent findings. We searched PubMed, EMBASE, and Web of Science up to July 11, 2023 and used a random-effects model to calculate summary hazard ratios (HRs) and 95% confidence intervals (CIs). This systematic review and meta-analysis included 8 articles encompassing 29 studies with 646,398 participants. Individuals with the lowest mtDNA-CN had a summary HR of 1.27 (95% CI 1.02–1.59) for CVD, 1.18 (95% CI 0.92–1.50) for coronary heart disease (CHD), 1.10 (95% CI 0.89–1.37) for stroke, and 1.30 (95% CI 1.07–1.56) for heart failure (HF). Decreased mtDNA-CN is linked to an increased risk of CVD and HF but not CHD and stroke. These findings suggest mtDNA-CN from leukocytes may be a potential early biomarker for CVD. However, more prospective studies with long follow-up are needed.

Summary: Blood microbiome signatures in patients with type 1 diabetes (T1D) remain unclear. We profile blood microbiome using 16S rRNA gene sequencing in 77 controls and 64 children with new-onset T1D, and compared it with the gut and oral microbiomes. The blood microbiome of patients with T1D is characterized by increased diversity and perturbed microbial features, with a significant increase in potentially pathogenic bacteria compared with controls. Thirty-six representative genera of blood microbiome were identified by random forest analysis, providing strong discriminatory power for T1D with an AUC of 0.82. PICRUSt analysis suggested that bacteria capable of inducing inflammation were more likely to enter the bloodstream in T1D. The overlap of the gut and oral microbiome with the blood microbiome implied potential translocation of bacteria from the gut and oral cavity to the bloodstream. Our study raised the necessity of further mechanistic investigations into the roles of blood microbiome in T1D.

Abstract Acquired drug resistance poses a challenge for single-target FGFR inhibitors, leading to the development of dual- or multi-target FGFR inhibitors. Sulfatinib is a multi-target kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1/CSF-1R. To elucidate the molecular mechanisms behind its binding and kinase selectivity, we determined the crystal structures of sulfatinib with FGFR1/CSF-1R. The results reveal common structural features and distinct conformational adaptability of sulfatinib in response to FGFR1/CSF-1R binding. Further biochemical and structural analyses disclose sensitivity of sulfatinib to FGFR/CSF-1R gatekeeper mutations. The insensitivity of sulfatinib to FGFR gatekeeper mutations highlights the indispensable interactions with the hydrophobic pocket for FGFR selectivity, whereas the rotatory flexibility may enable sulfatinib to overcome CSF-1RT663I. This study not only sheds light on the structural basis governing sulfatinib’s FGFR/CSF-1R inhibition, but also provides valuable insights into the rational design of dual- or multi-target FGFR inhibitors with selectivity for CSF-1R and sensitivity to gatekeeper mutations.

With the deepening of the integration of power system and communication network.The failure of the power communication network often leads to a cascading failure of the power system. Evaluating the potential risks in the power communication network is crucial to ensure the stable operation of the power system. This paper proposes a comprehensive risk assessment method for qualitative and quantitative measures. Firstly, an index system for risk assessment, considering both static structure and dynamic operation, is established. The optimal weight of each index is determined using the combination game weighting method. Additionally, a risk assessment model for the power communication network is established by coupling gray cloud theory and matter-element extension model. The fuzzy theory’s triangular modulus operator is utilized to fuse three types of fault probabilities, quantify the risk value of the power communication network, and assign it a grade. Finally, experimental results demonstrate that this method improves discrimination degree by 1.2%, 92%, and 85% respectively compared to other traditional algorithms.

Not available.

Juvenile myelomonocytic leukemia (JMML) is a disorder characterized by the simultaneous presence of myeloproliferative and myelodysplastic features, primarily affecting infants and young children. Due to the heterogeneous genetic background among patients, the current clinical and laboratory prognostic features are insufficient for accurately predicting outcomes. Thus, there is a pressing need to identify novel prognostic indicators. Red cell distribution width (RDW) is a critical parameter reflecting the variability in erythrocyte size. Recent studies have emphasized that elevated RDW serves as a valuable predictive marker for unfavorable outcomes across various diseases. However, the prognostic role of RDW in JMML remains unclear. Patients with JMML from our single-center cohort between January 2008 and December 2019 were included. Overall, 77 patients were eligible. Multivariate Cox proportional hazard models showed that patients with red cell distribution width coefficient of variation (RDW-CV) >17.35% at diagnosis were susceptible to much worse overall survival rate (hazard ratio [HR] = 5.22, confidence interval [CI] = 1.50–18.21, P = .010). Besides, the combination of RDW elevation and protein phosphatase non-receptor type 11 (PTPN11) mutation was likely to predict a subgroup with the worst outcomes in our cohort. RDW is an independent prognostic variable in JMML subjects. RDW may be regarded as an inexpensive biomarker to predict the clinical outcome in patients with JMML.

Purpose: The presence of lymphovascular invasion (LVI) influences the management and outcomes of patients with clinical stage IA lung adenocarcinoma. The objective was the development of a deep learning (DL) signature for the prediction of LVI and stratification of prognosis. Methods: A total of 2077 patients from three centers were retrospectively enrolled and divided into a training set (n = 1515), an internal validation set (n = 381), and an external set (n = 181). A -three-dimensional residual neural network was used to extract the DL signature and three models, namely, the clinical, DL, and combined models, were developed. Diagnostic efficiency was assessed by ROC curves and AUC values. Kaplan-Meier curves and Cox proportional hazards regression analyses were conducted to evaluate links between various factors and disease-free survival. Results: The DL model could effectively predict LVI, shown by AUC values of 0.72 (95 %CI: 0.68–0.76) and 0.63 (0.54–0.73) in the internal and external validation sets, respectively. The incorporation of DL signature and clinical-radiological factors increased the AUC to 0.74 (0.71–0.78) and 0.77 (0.70–0.84) in comparison with the DL and clinical models (AUC of 0.71 [0.68–0.75], 0.71 [0.61–0.81]) in the internal and external validation sets, respectively. Pathologic LVI, LVI predicted by both DL and combined models were associated with unfavorable prognosis (all p < 0.05). Conclusion: The effectiveness of the DL signature in the diagnosis of LVI and prognosis prediction in patients with clinical stage IA lung adenocarcinoma was demonstrated. These findings suggest the potential of the model in clinical decision-making.

This paper explores the significance of digital governance for sustainable rural development in China, emphasizing the collaborative efforts of village administrative organizations, new agricultural business entities, and peasant households. Utilizing an evolutionary game approach, we examine the decision-making behaviors and stability points of these three entities within the context of rural digital governance. Our analysis is grounded in a mechanism of interest linkage among the stakeholders, with numerical simulations used to assess the impact of key variables and parameters on their evolutionary outcomes. The paper reveals that village administrative organizations are highly sensitive to changes in performance gains, special subsidies, penalty losses, and benefit distribution coefficients. Enhancing these variables can significantly motivate these organizations to engage in digital governance. In contrast, new agricultural business entities and peasant households demonstrate a stronger and more consistent willingness to collaborate, minimally affected by variable changes, which suggests a solid economic and social foundation for rural digital governance in China. Our paper underscores the need for positive incentives and a robust fault-tolerance mechanism to foster collaboration among village administrative organizations. It also highlights the importance of integrating new agricultural business entities into the digital governance framework to promote sustainable rural development. These insights provide valuable theoretical and practical implications for policymakers aiming to enhance the efficacy and inclusivity of digital governance in rural China.

To improve the signal-to-noise ratio (SNR) of vibration signals in a phase-sensitive optical time-domain reflectometer (Φ-OTDR) system, a principal component analysis variable step-size normalized least mean square (PCA-VSS-NLMS) denoising method was proposed in this study. First, the mathematical principle of the PCA-VSS-NLMS algorithm was constructed. This algorithm can adjust the input signal to achieve the best filter effect. Second, the effectiveness of the algorithm was verified via simulation, and the simulation results show that compared with the wavelet denoising (WD), Wiener filtering, variational mode decomposition (VMD), and variable step-size normalized least mean square (VSS-NLMS) algorithms, the PCA-VSS-NLMS algorithm can improve the SNR to 30.68 dB when the initial SNR is −1.23 dB. Finally, the PCA-VSS-NLMS algorithm was embedded into the built Φ-OTDR system, an 11.22 km fiber was measured, and PZT was added at 10.19–10.24 km to impose multiple sets of fixed-frequency disturbances. The experimental results show that the SNR of the vibration signal is 8.77 dB at 100 Hz and 0.07 s, and the SNR is improved to 26.17 dB after PCA-VSS-NLMS filtering; thus, the SNR is improved by 17.40 dB. This method can improve the SNR of the system’s position information without the need to change the existing hardware conditions, and it provides a new scheme for the detection and recognition of long-distance vibration signals.

Abstract Mitochondrial apoptosis is strictly controlled by BCL-2 family proteins through a subtle network of protein interactions. The tumor suppressor protein p53 triggers transcription-independent apoptosis through direct interactions with BCL-2 family proteins, but the molecular mechanism is not well understood. In this study, we present three crystal structures of p53-DBD in complex with the anti-apoptotic protein BCL-2 at resolutions of 2.3–2.7 Å. The structures show that two loops of p53-DBD penetrate directly into the BH3-binding pocket of BCL-2. Structure-based mutations at the interface impair the p53/BCL-2 interaction. Specifically, the binding sites for p53 and the pro-apoptotic protein Bax in the BCL-2 pocket are mostly identical. In addition, formation of the p53/BCL-2 complex is negatively correlated with the formation of BCL-2 complexes with pro-apoptotic BCL-2 family members. Defects in the p53/BCL-2 interaction attenuate p53-mediated cell apoptosis. Overall, our study provides a structural basis for the interaction between p53 and BCL-2, and suggests a molecular mechanism by which p53 regulates transcription-independent apoptosis by antagonizing the interaction of BCL-2 with pro-apoptotic BCL-2 family members.

Summary: Energy metabolism in the context of erythropoiesis and related diseases remains largely unexplored. Here, we developed a primary cell model by differentiating hematopoietic stem progenitor cells toward the erythroid lineage and suppressing the mitochondrial oxidative phosphorylation (OXPHOS) pathway. OXPHOS suppression led to differentiation failure of erythroid progenitors and defects in ribosome biogenesis. Ran GTPase-activating protein 1 (RanGAP1) was identified as a target of mitochondrial OXPHOS for ribosomal defects during erythropoiesis. Overexpression of RanGAP1 largely alleviated erythroid defects resulting from OXPHOS suppression. Coenzyme Q10, an activator of OXPHOS, largely rescued erythroid defects and increased RanGAP1 expression. Patients with Diamond-Blackfan anemia (DBA) exhibited OXPHOS suppression and a concomitant suppression of ribosome biogenesis. RNA-seq analysis implied that the substantial mutation (approximately 10%) in OXPHOS genes accounts for OXPHOS suppression in these patients. Conclusively, OXPHOS disruption and the associated disruptive mitochondrial energy metabolism are linked to the pathogenesis of DBA.

Summary: Pathologic visceral pleural invasion (VPI) in patients with early-stage lung cancer can result in the upstaging of T1 to T2, in addition to having implications for surgical resection and prognostic outcomes. This study was designed with the goal of establishing and validating a CT-based deep learning (DL) model capable of predicting VPI status and stratifying patients based on their prognostic outcomes. In total, 2077 patients from three centers with pathologically confirmed clinical stage IA lung adenocarcinoma were enrolled. DL signatures were extracted with a 3D residual neural network. DL model was able to effectively predict VPI status. VPI predicted by the DL models, as well as pathologic VPI, was associated with shorter disease-free survival. The established deep learning signature provides a tool capable of aiding the accurate prediction of VPI in patients with clinical stage IA lung adenocarcinoma, thus enabling prognostic stratification.

Abstract Background Lignin played an important role in the establishment of coated fertilizers coating material as a substitute for petrochemical raw materials. However, so far, the lignin-based coated fertilizers was limited in only the poor slow-release performance. To achieve good slow-release performance of lignin-based coated fertilizers, hydrophilic of lignin need to be resolved to establish an green and better controllable lignin-based coated fertilizers. Results In the study, a novel green double layer coating with lignin-based polyurethane (LPU) as the inner coating and epoxy resin (EP) as the outer coating was effectively constructed for coated urea. Fourier transform infrared spectra confirmed that lignin and polycaprolactone diol successfully reacted with Hexamethylene diisocyanate. The loss weight and water contact angle (WCA, 75.6–63.6°) of the LPUs decreased with the increased lignin content. The average particle hardness of the lignin-based double-layer coated urea (LDCU) first increased from 58.1 N (lignin of 30%) to 67.0 N (lignin of 60%), but then decreased to 62.3 N (lignin of 70%). The release longevity of the coated urea was closely related to the preparation parameters of the coating material. The optimal cumulative nutrient release rate (79.4%) of LDCU was obtained (lignin of 50%, –CNO/–OH molar ratios of 1.15, EP of 35%, and coating ratio of 5%). The aggregates of hydrone on the LDCU caused the dissolution and swelling of nutrients, and then the diffusion of nutrients through the concentration gradient. Conclusions A though the nutrient release of the LDCUs was affected by many factors, the successful development of the LDCUs will help improve the rapid development of the coated fertilizer industry.

Satellite-based remote sensing enables the quantification of tropospheric NO2 concentrations, offering insights into their environmental and health impacts. However, remote sensing measurements are often impeded by extensive cloud cover and precipitation. The scarcity of valid NO2 observations in such meteorological conditions increases data gaps and thus hinders accurate characterization and variability of concentration across geographical regions. This study utilizes the Empirical Orthogonal Function interpolation in conjunction with the Extreme Gradient Boosting (XGBoost) algorithm and dense urban atmospheric observed station data to reconstruct continuous daily tropospheric NO2 column concentration data in cloudy and rainy areas and thereby improve the accuracy of NO2 concentration mapping in meteorologically obscured regions. Using Chengdu City as a case study, multiple datasets from satellite observations (TROPOspheric Monitoring Instrument, TROPOMI), near-surface NO2 measurements, meteorology, and ancillary data are leveraged to train models. The results showed that the integration of reconstructed satellite observations with provincial and municipal control surface measurements enables the XGBoost model to achieve heightened predictive accuracy (R2 = 0.87) and precision (RMSE = 5.36 μg/m3). Spatially, this approach effectively mitigates the problem of missing values in estimation results due to absent satellite data while simultaneously ensuring increased consistency with ground monitoring station data, yielding images with more continuous and refined details. These results underscore the potential for reconstructing satellite remote sensing information and combining it with dense ground observations to greatly improve NO2 mapping in cloudy and rainy areas.

Gardenia is both a food and medicine plant. It is widely used for cardiovascular protection, and its main bioactive ingredient is crocetin. This study aims to observe the therapeutic effects of crocetin on chronic heart failure in rats induced by various etiologies. It further compares the efficacy differences between preventative and treatment administration, varying dosages, and treatment durations, to provide improved guidance for medication in heart failure rats and determine which categories of chronic heart failure rats might benefit most from crocetin. Chronic heart failure models induced by abdominal aorta constriction, renal hypertension, and coronary artery ligation were constructed. By examining cardiac function, blood biochemistry, and histopathology, the study assessed the preventive and therapeutic effects of crocetin on load-induced and myocardial ischemia-induced heart failure. The results showed that in all three models, both treatment and preventative administration of crocetin significantly improved chronic heart failure in rats, especially in preventative administration. The results indicate crocetin may be beneficial for improving symptoms and functional capacity in rats with heart failure. Furthermore, long-term administration was more effective than short-term administration across all three rat models, with therapeutic onset observed over 6 weeks.

Carbon dots (CDs), a novel type of nanomaterial, play crucial roles in the agriculture field. However, it remains unclear their impacts on the flavor quality of vegetables. The present study synthesized a novel chitooligosaccharide-peanut oligopeptide-carbon dots (COS-POP-CDs) material through the chitooligosaccharide (COS) and peanut oligopeptide (POP) high temperature Maillard reactions and studied its effect on the flavor quality of Chinese cabbage (Choy sum). Results indicated that COS-POP-CDs emit blue visible light that readily absorbed by chloroplasts, while also demonstrating some degree of antibacterial and antioxidant activities. After transplanting of Choy sum, foliar spraying 0.12 mg/mL COS-POP-CDs twice can increase the content of soluble proteins, Vitamin C, and enhance the strawberry and spicy flavors of Choy Sum. After harvest of Choy Sum, foliar spraying 0.12 mg/mL COS-POP-CDs once can slow down the spoilage. These results suggest that COS-POP-CDs have significant potential to improve crop quality.

Objective: A meta-analysis is conducted to evaluate the effectiveness and safety of bevacizumab in hereditary hemorrhagic telangiectasia (HHT) epistaxis.Method: Two researchers search PubMed, EMBASE and Web of Science databases from their inception until September 3th, 2023. The literature is read and screened, and valid data extracted, collated and analyzed. Its quality is then assessed using the Cochrane risk assessment scale. This study uses Endnote 9.3 software for literature management and RevMan 5.3.1 software for evaluation.Results: A total of 7 documents met the requirements, including a total of 359 patients, and the literature quality evaluation was grade B. The Meta-analysis results showed that:Bevacizumab reduces the Epistaxis Severity Score (ESS) in patients with HHT epistaxis compared with the control [WMD = −0.22,95%CI (−0.38, −0.05), p = 0.01]. However, there is no significant effect on duration of epistaxis [WMD = −15.59, 95%CI (−70.41,39.23), p = 0.58] and number of epistaxes [WMD = −1.27,95%CI (−10.23,7.70), p = 0.78] in patients with HHT epistaxis. In terms of adverse effects, there is no significant difference between the bevacizumab group and control group [OR = 1.36, 95% CI (0.54, 3.44), p = 0.52].Conclusion: Bevacizumab is superior to the control group in the treatment of HHT epistaxis, and adverse reactions are not further increased in the bevacizumab group than in the control group, suggesting that bevacizumab has clinical value in the treatment of HHT epistaxis.

Lysine methyltransferase 2A-rearranged acute myeloid leukemia (KMT2A-r AML) is a special entity in the 2022 World Health Organization classification of myeloid neoplasms, characterized by high relapse rate and adverse outcomes. Current risk stratification was established on the treatment response and translocation partner of KMT2A. To study the transcriptomic feature and refine the current stratification of pediatric KMT2A-r AML, we analyzed clinical and RNA sequencing data of 351 patients. By implementing least absolute shrinkage and selection operator algorithm, we identified 7 genes (KIAA1522, SKAP2, EGFL7, GAB2, HEBP1, FAM174B, and STARD8) of which the expression levels were strongly associated with outcomes. We then developed a transcriptome-based score, dividing patients into 2 groups with distinct gene expression patterns and prognosis, which was further validated in an independent cohort and outperformed the LSC17 score. We also found cell cycle, oxidative phosphorylation, and metabolism pathways were upregulated in patients with inferior outcomes. By integrating clinical characteristics, we proposed a simple-to-use prognostic scoring system with excellent discriminability, which allowed us to distinguish allogeneic hematopoietic stem cell transplantation candidates more precisely. In conclusion, pediatric KMT2A-r AML is heterogenous on transcriptomic level and the newly proposed scoring system combining clinical characteristics and transcriptomic features can be instructive in clinical routines.

c-Met has been an attractive target of prognostic and therapeutic studies in various cancers. TPX-0022 is a macrocyclic inhibitor of c-Met, c-Src and CSF1R kinases and is currently in phase I/II clinical trials in patients with advanced solid tumors harboring MET gene alterations. In this study, we determined the co-crystal structures of the c-Met/TPX-0022 and c-Src/TPX-0022 complexes to help elucidate the binding mechanism. TPX-0022 binds to the ATP pocket of c-Met and c-Src in a local minimum energy conformation and is stabilized by hydrophobic and hydrogen bond interactions. In addition, TPX-0022 exhibited potent activity against the resistance-relevant c-Met L1195F mutant and moderate activity against the c-Met G1163R, F1200I and Y1230H mutants but weak activity against the c-Met D1228N and Y1230C mutants. Overall, our study reveals the structural mechanism underlying the potency and selectivity of TPX-0022 and the ability to overcome acquire resistance mutations and provides insight into the development of selective c-Met macrocyclic inhibitors.

Objective: Cystic lung cancer is a rare type of lung cancer with special morphological manifestations on imaging that have not been completely recognized. This study aimed to improve the understanding and diagnosis of this lung cancer by analyzing its computed tomography (CT) features and clinicopathological findings. Methods: The clinical data, pathological types, and CT features of patients with cystic lung cancer who were diagnosed at our hospital between January 2015 and June 2021 were analyzed retrospectively. Results: We identified 44 cases (86.27%) of adenocarcinomas; these included 7 (13.73%) and 35 (68.63%) cases of microinvasive adenocarcinomas and invasive adenocarcinomas, respectively. Regarding the histological type, 11 (21.57%), 8 (15.69%), and 15 (29.41%) cases were of the adjoint, papillary, and acinar types, respectively. Two cases (3.92%) contained micropapillary components that accounted for more than 20% . Furthermore, one case (1.96%) was not classified, and in another case (1.96%), pathological examination after chemotherapy suggested an adenocarcinoma. Lymph node biopsy in one case (1.96%) suggested a metastatic lung adenocarcinoma. Squamous cell carcinoma was observed in five cases (9.80%); these included three (5.89%) and two (3.92%) cases of keratinizing and non-keratinizing squamous cell carcinomas, respectively. A large cell carcinoma and a high-grade mucoepidermoid carcinoma were observed in one case each (1.96%). A peripheral distribution was observed in 40 cases (80.30%). The mean diameter was 4.7± 2.7 cm. A cystic cavity with ground glass, cystic cavity with solid components, and cystic cavity with mixed components were observed in 20 (39.22%), 22 (43.14%), and 9 (17.65%) cases, respectively. According to the Mario classification, 24 (47.06%), 8 (15.69%), 9 (17.65%), and 10 (19.61%) cases were of types I, II, III, and IV, respectively. The cyst wall was uneven in 42 cases (82.35%); furthermore, a lobular lesion edge and the burr sign were observed in 28 (54.90%) and 14 (27.45%) cases, respectively. Moreover, 33 cases (64.71%) showed a separation within the lesions, while 36 cases (70.59%) had a smooth inner lesion wall. Regarding the relationship with the pleura, pleural traction and closed pleura were observed in 24 (47.06%) and 11 (21.57%) cases, respectively. The peripheral blood vessels passed through the lesion in eight cases (15.69%) and adhered closely to the edge of the lesion in 16 cases (31.37%). The surrounding bronchi passed through the lesion in eight cases (15.69%) and moved toward the edge of the lesion in 21 cases (41.18%). Conclusion: Cystic lung cancer has certain features on CT that can allow its suggestive diagnosis.

Objective: To determine the extent to which Lycium barbarum polysaccharide (LBP) improves 60Co γ-ray radiation-induced brain injury (RIBI) by regulating the gut microbiota. Methods: The RIBI model of mice was established with the appropriate dose of 60Co γ-ray to identify the changes in the body weight, behaviors, gut microbiota, and inflammatory reactions of mice. Mice were randomly divided into healthy, RIBI model, and LBP groups. The related inflammatory cytokines were determined using an enzyme linked immunosorbent assay kit. Then, 16S rRNA sequencings of feces were carried out to evaluate the differences in intestinal flora. Results: Compared with the spontaneous activity and exploratory spirit of the healthy group, those traits in the RIBI model mice in the open field significantly decreased, the freezing time in the elevated plus maze (EPM) significantly increased, and the number of times the mice discriminated the novel object was significantly lower. Hematoxylin-eosin slides showed that the main histopathological changes of RIBI occurred in the hippocampus. In addition, the diversity and relative abundances ratio of the gut bacterial phylum, order, family, and genus in the model group varied widely. Changes in Bacteroidetes, Firmicutes, and Proteobacteria were the most obvious after head radiation exposure. In comparison, LBP could accelerate the recovery of weight loss in RIBI mice. The frequency that mice entered the center of the open field, facing the open arm in the EPM, and the number of times they discriminated the novel object were significantly increased with LBP administration. LBP could also reduce the levels of inflammatory factor caused by RIBI. LBP increased the diversity and abundance of gut microbiota in RIBI model mice. In addition, LBP increased the relative abundance of Bacteroidetes but decreased the levels of Firmicutes and Proteobacteria for irradiated mice. Conclusion: LBP can improve depression and tension by regulating the composition of gut microbiota, including lowering the relative abundance of Clostridia and Burkholderiales and raising that of Lactobacillales. Thus, LBP provides a new strategy for improving the protective effects of RIBI.

Abstract Background IL-6 induces the upregulation of indoleamine 2,3-dioxygenase (IDO1) at the maternal-foetal interface, but the regulation mechanisms of IDO1 by IL-6 at this interface have not been fully understood. Methods Western blotting, qRT–PCR and/or immunohistochemistry were employed to measure the expression of IDO1, IL-6, SHP-1/2, SOCS3 and STAT3/p (STAT3 and pSTAT3) in tissues of chorionic villi and decidua (TCVD) in vivo and in cultured TCVD that were treated with IL-6 in the presence or absence of an IL-6 inhibitor. Results Mutually positive relationships among the protein levels of IL-6, IDO1, SHP-1/2 and STAT3/p was observed, and the expression of IDO1, SHP-1/2 and STAT3/p was increased in a dose-dependent manner in TCVD in vivo and in cultured TCVD treated with IL-6 at increasing concentrations (0–100 ng/ml). The level of IL-6 was negatively related to SOCS3 level in TCVD. The expression of SOCS3 was increased in a dose-dependent manner, and SOCS3 level was positively correlated with SHP-1, SHP-2 and STAT3/p level in cultured TCVD treated with 0–2 ng/ml IL-6; however, opposite results were observed after treatment with 2–100 ng/ml IL-6. The IL-6-induced upregulation of IDO1, SHP-1, SHP-2 and STAT3/p expression could be reversed, while the IL-6-induced upregulation of SOCS3 expression was exacerbated by Corylifol A. Conclusions In normal pregnancy, IL-6 upregulates the expression of IDO1 by promoting SHP-1/2 expression via STAT3/p and simultaneously negatively regulates the expression of SOCS3. High expression of IL-6 causes the upregulation of IDO1 expression and the downregulation of SOCS-3 expression, which may be beneficial for maintaining immunological tolerance.

The aryl hydrocarbon receptor (AHR) plays important roles in regulating xenobiotic metabolism, cellular differentiation, and immunity. Here, the authors present multiple crystal structures of the Drosophila AHR PAS-B domain, providing insights into the mechanism of AHR ligand binding

Here, by performing multi-omics microbiome analyses in a cohort of children with new-onset T1D, the authors characterize altered microbial functional and metabolic traits involved in T1D, which they validate in animal experiments, together providing potential avenues for microbiome-based interventions.

Herba Gynostemma (Jiaogulan) is an herbaceous plant of the genus Gynostemma in the family Cucurbitaceae. Gynostemma longipes has lipid-lowering activity, thus, it is used as a medicinal material. However, its medicinal using parts have been recorded as whole plants or aerial parts in different provincial quality standards; therefore, it is necessary to conduct a comprehensive compositional analysis of the different parts of G. longipes (rhizomes, stems, and leaves) used in traditional medicine. In this study, offline two-dimensional liquid chromatography-ion mobility-quadrupole time-of-flight mass spectrometry (2D-LC/IM-QTOF-MS) was used to analyze the different parts of G. longipes obtained from Shaanxi province, China. By combining the retention times, mass fragments, collision cross-section values, reference standards, and information concerning literature compounds, 396 components were identified from the three parts of the plant, including 94 groups of isomers, and 217 components were identified or tentatively identified as new compounds. In the rhizomes, leaves, and stems, 240, 220, and 168 compounds, respectively, were identified. Differential analysis of the compounds in the rhizomes and aerial parts was also carried out, and 36 differential components were identified, of which 32 had higher contents in the rhizomes. Therefore, these findings indicate that the number of chemical components and the content of major differential components are higher in the rhizomes than the leaves and stems of G. longipes from the Maobaling Planting Base in Pingli county, Shaanxi province. Thus, the rhizomes of G. longipes are also an important part for medicinal use. These results will contribute to the establishment of quality control methods for G. longipes.

The primary objective of this investigation was to study the effect of altitude on fish swimming ability. Different species were tested to ensure that the differences observed are not associated with a single species. Fish critical swimming speed and burst speed were determined using stepped-velocity tests in a Brett-type swimming respirometer. Based on the effects of water temperature and dissolved oxygen, it is clear that the swimming ability of fish decreases as altitude increases. Further, because the effects of high altitude on fish physiology go beyond the effects of lower temperature and dissolved oxygen, we recommend that fish swimming ability be tested at an altitude similar to the target fishway site to ensure the validity of fish data used for fishway design.

Compared with traditional two-level inverters, multilevel inverters have many solid-state switches and complex composition methods. Therefore, diagnosing and treating inverter faults is a prerequisite for the reliable and efficient operation of the inverter. Based on the idea of intelligent complementary fusion, this paper combines the genetic algorithm–binary granulation matrix knowledge-reduction method with the extreme learning machine network to propose a fault-diagnosis method for multi-tube open-circuit faults in T-type three-level inverters. First, the fault characteristics of power devices at different locations of T-type three-level inverters are analyzed, and the inverter output power and its harmonic components are extracted as the basis for power device fault diagnosis. Second, the genetic algorithm–binary granularity matrix knowledge-reduction method is used for optimization to obtain the minimum attribute set required to distinguish the state transitions in various fault cases. Finally, the kernel attribute set is utilized to construct extreme learning machine subclassifiers with corresponding granularity. The experimental results show that the classification accuracy after attribute reduction is higher than that of all subclassifiers under different attribute sets, reflecting the advantages of attribute reduction and the complementarity of different intelligent diagnosis methods, which have stronger fault-diagnosis accuracy and generalization ability compared with the existing methods and provides a new way for hybrid intelligent diagnosis.

Objectives: Smear-negative pulmonary TB (PTB) is difficult to diagnose. Current diagnosis and treatment monitoring methods have inherent limitations. Droplet digital PCR (ddPCR) is a new technique with high sensitivity. This study presents a novel ddPCR for rapid and sensitive identification of Mycobacterium tuberculosis (MTB). Methods: MTB DNA was detected in respiratory specimens from suspected PTB cases using ddPCR assay, which was directed at two different locations within IS6110. We, for the first time, evaluated the clinical diagnostic ability of this ddPCR for paucibacillary smear-negative PTB. Results: A total of 605 PTB suspects were recruited, including 263 patients with confirmed PTB (84.03% from smear-negative PTB) and 342 without PTB. The sensitivity and specificity of IS6110 ddPCR were 61.22% (95% confidence interval (CI) 55.00-67.10%) and 95.03% (95% CI 92.20-97.10%) for total PTB and 57.92% (95% CI 51.10-64.50%) and 94.57% (95% CI 91.20-96.90%) for smear-negative PTB. ddPCR assay outperformed Xpert MTB/RIF (53.08% vs 28.46%, P = 0.020) in smear-negative PTB detection. Furthermore, effective anti-TB treatment was linked to significantly lower IS6110 copies detected by ddPCR. Conclusion: Herein, we developed and validated a highly sensitive and robust ddPCR assay for MTB quantification in respiratory specimens, which improves diagnosis and therapeutic effect evaluation of smear-negative PTB.

hPSCs model of Maturity Onset Diabetes of the Young caused by mutations in the transcription factor HNF1A (HNF1A-MODY), regulates the expression of genes required for the formation of dense-core insulin granules and calcium-dependent insulin secretion, demonstrating a basis to treat HNF1A-MODY patients with sulfonylureas.

Pemigatinib is an FDA-approved drug for the treatment of cholangiocarcinoma, but while it is known to target fibroblast growth factor receptors, its mechanism of action is still not fully understood. Here, biochemical and structural analyses reveal that pemigatinib is a potent and selective FGFR1–3 inhibitor, and has excellent potency against the Val-to-Ile gatekeeper mutation.

ObjectiveThis study seeks to systematically evaluate and test the effects of yoga exercise intervention programs on sleep quality in breast cancer patients in order to suggest more optimized exercise programs.MethodComputer searches of the PubMed, Embase, Cochrane Library, Web of Science and CINAHL databases are conducted from the date of their inception to June 8th, 2022 to collect randomized controlled trials on the effects of yoga exercise intervention on sleep quality in breast cancer patients. Two investigators independently carry out the inclusion and exclusion criteria literature screening, data extraction and methodological quality assessment of the included literature by applying the Cochrane risk of bias tool. Subgroup analysis is performed using RevMan 5.4.1 software, and the six moderating variables of intervention format, intervention type, weekly intervention frequency, total intervention duration, single intervention duration and intervention evaluation at different time points are set for the 782 subjects of the 12 included publications.ResultsTwelve randomized controlled trials with a total sample size of 782 subjects are included, including 393 subjects in the experimental group and 389 subjects in the control group. The meta-analysis shows that yoga exercise intervention is effective in improving sleep quality in breast cancer patients [SMD = -0.40, 95% CI: (-0.71, -0.09), P = 0.01]; yoga exercise intervention focusing on positive meditation [SMD = -0.55, 95% CI: (-1.08, -0.03), P = 0.04] is effective in improving sleep; yoga exercise intervention two or three times a week is effective in improving sleep quality [SMD = -0.69, 95% CI: (-1.19, -0.19), P = 0.007]; yoga exercise intervention for 6–8 weeks significantly improves sleep quality [SMD = -0.86, 95% CI: (-1.65, -0.08), P =0.03]; and evaluation immediately after the end of intervention improves sleep outcomes [SMD = -0.17, 95% CI: (-0.33, 0.00), P = 0.05], while differences in sleep quality improvement are not statistically significant for the remaining subgroup outcomes (P > 0.05).ConclusionThe available evidence suggests that yoga exercise intervention has good effects on improving sleep quality in breast cancer patients. Positive meditation intervention type, intervention frequency of two or three times per week, total intervention duration of 6–8 weeks and evaluation immediately after the end of intervention are shown to be effective in improving sleep quality.

IntroductionMassive pulmonary embolism (PE) is a life-threatening complication of major surgery with a mortality rate of up to 50%. Extracorporeal membrane oxygenation (ECMO) is primarily used for respiratory and circulatory support. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to stabilize patients with acute massive PE. Acute brain injury, vascular disease, and immunosuppression are contraindications to ECMO, as stated in the 2021 Extracorporeal Life Support Organization guidelines.Case summaryWe report a case of a patient with craniocerebral trauma whose postoperative course was complicated by massive PE and subsequent cardiac arrest that required urgent VA-ECMO, followed by anticoagulation with heparin. The patient showed hemodynamic improvement and was discharged 68 days after hospitalization.DiscussionECMO has gradually been accepted for patients with craniocerebral injuries. The safety and effectiveness of ECMO in patients with craniocerebral injury, along with the optimal duration of ECMO and anticoagulation strategies, require further study.

[Introduction] The paper aims to research the technology feasibility of steam conversion system for industrial steam supply by pressurized water reactor (PWR) nuclear power. [Method] we took a 1 000 MW (PWR) nuclear power plant as an example, supplying industrial steam 300 t/h, 1.8 MPa and 250 ℃. This paper demonstrated the technical feasibility of a steam conversion system which could meet the industrial steam needs by using steam in the secondary loop of PWR nuclear power plant to heat industrial water, based on the first law and the second law of thermodynamics. This paper designed the process flow of the system, calculated the thermodynamic parameters of the key heat exchangers in the system. [Result] The reasonable value of the heat source drainage temperature was analyzed. Our data suggest heat source drainage temperature is 65 ℃ for the industrial steam supply of PWR nuclear power plants. The temperature of heat source would be lower than the industrial water if the drainage temperature was lower than 60 ℃ ，which would violate the second law of thermodynamics. [Conclusion] The research results can provide technical reference for industrial steam supply of PWR nuclear power plant.

While the role of platelets in cardiovascular diseases among the general population has been widely reported, evidence is inconsistent regarding the association between platelet indices with hypertension in pregnant women. In this study, we explored the associations between platelet parameters before 20 gestational weeks, an understudied period, with hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PEEC) and gestational hypertension (GH). Based on the Born in Guangzhou Cohort Study, 12053 singleton pregnant women with platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) measured at 14–19 gestational weeks were included. Conventional multivariable adjustment and propensity score analysis were used to control for confounders. The restricted cubic spline showed that the risk of PEEC increased linearly for PC, and non-linearly for PCT. For GH, the risk increased linearly for PC, MPV, and PCT, and non-linearly for PDW. When these indices were categorized into quintiles, women with higher PC and PCT were associated with increased risk of both PEEC and GH. Women with MPV exceeding the second quintile (≥ 8.8 fL) had a greater risk for GH, but not for PEEC. When HDP was classified into two groups (early- vs late-onset) based on the occurrence time, significant associations persisted for early-onset PEEC, early-onset GH, and late-onset GH. In conclusion, increased PC and PCT before 20 weeks of gestation were both associated with higher risk of PEEC and GH, while elevated MPV was only linked to GH.

Abstract Background Angle kappa plays a vital role in the implantation of multifocal intraocular lens (MIOL). Large angle kappa is related to a higher risk of postoperative photic phenomena. This study aims to compare preoperative angle kappa in the eyes of cataract patients obtained from the Pentacam Scheimpflug system (Pentacam), optical low-coherence reflectometry (Lenstar), and ray-tracing aberrometry (iTrace). Methods One hundred thirteen eyes of 113 patients with cataracts were included. Each eye was examined 3 times using all devices to obtain angle kappa and pupil diameter. When considering dependent eyes for one individual, angle kappa in both right eyes and left eyes should be analysed separately. The repeatability and reproducibility were evaluated using the within-subject standard deviation (Sw), repeatability (2.77 Sw), and intraclass correlation coefficient (ICC). The difference, correlation, and agreement between devices were evaluated by paired t-tests, Pearson tests, and Bland-Altman analysis, respectively. Results Intraoperator repeatability and interoperator and intersession reproducibility of angle kappa showed an Sw of less than 0.05 mm, a 2.77 Sw of 0.14 mm or less, and an ICC of more than 0.96. Angle kappa was not significantly different between Pentacam and Lenstar (P > 0.05), while angle kappa was significantly different between Pentacam and iTrace and between Lenstar and iTrace (P < 0.05). There was a strong correlation between Pentacam and Lenstar for angle kappa (r =0.907 to 0.918) and a weak or moderate correlation between Pentacam and iTrace and between Lenstar and iTrace (r =0.292 to 0.618). There were narrow 95% limits of agreement (LoA) between Pentacam and Lenstar for angle kappa and wide 95% LoA between Pentacam and iTrace and between Lenstar and iTrace. No significant differences in pupil diameter were found between Pentacam and Lenstar in either eye (P > 0.05). Positive angle kappa (nasal light reflex) was found in most cataract patients (79.25% to 84.91%) through 3 different devices in both eyes. Conclusions The 3 devices provided high intraoperator repeatability and interoperator and intersession reproducibility for angle kappa measurements. The measurement of preoperative angle kappa in the eyes of patients with cataracts by Pentacam and Lenstar has good agreement.

Porous NiTi shape memory alloys (SMAs) possess compatible mechanical properties with human bones and can effectively reduce the risk of stress shielding and stress concentration; therefore, they have been termed promising candidates for orthopedic implants. However, microstructure characteristics of porous NiTi SMAs during plastic deformation have rarely been investigated. The present study aims to specifically investigate microstructure characteristics and the corresponding underlying mechanisms of fabricated porous NiTi SMAs via a conventional sintering (CS) process with NaCl space holder during compressive deformation at room temperature. To realize the aforementioned target, X-ray diffraction (XRD), scanning electron microscope (SEM), electron backscattered diffraction (EBSD), transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM) are applied in the present study. The results show that the fabricated porous NiTi SMA is 51.8% for porosity, 181.65 μm for the average pore size, and 0.78 μm for the average grain size. Many Ni4Ti3 and NiTi2 phases are formed in the mixed matrix with dominant B2 (NiTi) and some B19′ (NiTi). Severe inhomogeneous deformation happens within compressed specimens, leading to the occurrence of tangled dislocation and shear bands. Microcracks occur within fabricated porous NiTi SMAs at a deformation degree of 9.2%; then, they extend quickly to form macrocracks, which finally results in the failure of regions between pores. The observed nanocrystallization and amorphization around microcrack tips within the 12.5%-deformed sample can be attributed to the relatively small grain size and the grain segmentation effect via statistically stored dislocation (SSD) and geometrically necessary dislocation (GND).

Fibroblast growth factor receptor 4 (FGFR4) is a promising target for the treatment of hepatocellular carcinoma, but current FGFR4 covalent inhibitors target only one of the two cysteine residues (Cys477 or Cys552) that provide FGFR4-specificity. Here, a dual-warhead covalent FGFR4 inhibitor that can covalently target both cysteine residues of FGFR4 is reported, and strong selectivity for FGFR4 is observed.