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The research on the hot corrosion resistance of nickel-based superalloys is critical to determining and enhancing their service life. Therefore, this study investigates the cyclic hot corrosion behavior of GH4738 alloy coated with a mixed salt (75 wt% Na2SO4+25 wt% NaCl) at 750 °C and 800 °C. X-ray diffractometer (XRD), scanning electron microscope (SEM), energy dispersive spectrometer (EDS), and transmission electron microscope (TEM) are used to analyze the phase compositions and film structures of the corrosion products, as well as to explore the corrosion mechanism. The results show that a thicker oxide layer is formed at higher temperatures, indicating poorer hot corrosion resistance at elevated temperatures. The corrosion products form at both temperatures to show a distinct layered structure, the outer layer is mainly composed of Cr2O3 and a small amount of TiO2, while the inner layer consists of Al2O3, CrS, and TiS. In addition, it is found that the corrosion mechanism of O, S, and Cl elements in the corrosion process is synergistic and accompanied by alkaline melting.

Abstract Background In recent years, significant morbidity and mortality in patients with severe inflammatory bowel disease (IBD) and cytomegalovirus (CMV) have drawn considerable attention to the status of CMV infection in the intestinal mucosa of IBD patients and its role in disease progression. However, there is currently no high-throughput sequencing data for ulcerative colitis patients with CMV infection (CMV + UC), and the immune microenvironment in CMV + UC patients have yet to be explored. Method The xCell algorithm was used for evaluate the immune microenvironment of CMV + UC patients. Then, WGCNA analysis was explored to obtain the co-expression modules between abnormal immune cells and gene level or protein level. Next, three machine learning approach include Random Forest, SVM-rfe, and Lasso were used to filter candidate biomarkers. Finally, Best Subset Selection algorithms was performed to construct the diagnostic model. Results In this study, we performed transcriptomic and proteomic sequencing on CMV + UC patients to establish a comprehensive immune microenvironment profile and found 11 specific abnormal immune cells in CMV + UC group. After using multi-omics integration algorithms, we identified seven co-expression gene modules and five co-expression protein modules. Subsequently, we utilized various machine learning algorithms to identify key biomarkers with diagnostic efficacy and constructed an early diagnostic model. We identified a total of eight biomarkers (PPP1R12B, CIRBP, CSNK2A2, DNAJB11, PIK3R4, RRBP1, STX5, TMEM214) that play crucial roles in the immune microenvironment of CMV + UC and exhibit superior diagnostic performance for CMV + UC. Conclusion This 8 biomarkers model offers a new paradigm for the diagnosis and treatment of IBD patients post-CMV infection. Further research into this model will be significant for understanding the changes in the host immune microenvironment following CMV infection.

Abstract Different chemical solutions can significantly change the contact angle (CA) of soil, but few studies have studied the change rule and action mechanism of the CA from the mineral composition of soil essence. In unsaturated soil mechanics, the CA is an important parameter to calculate the wet suction between soil particles in unsaturated soil. When the chemical composition of the soil pore liquid changes, the CA will also change, which will affect the wet suction and other parameters, thus changing the macroscopic mechanical properties of the soil. In this study, the CA of air-solution-mineral phases with different solution components (pH, type and concentration of salt solution) of different minerals (quartz, orthoclase and plagioclase) were measured. The results show that the CAs of quartz, orthoclase and plagioclase all rise first and then drop with the rise of pH. The peak CAs are pH = 5, pH = 4 and pH = 3, respectively. Quartz, orthoclase and plagioclase all have valley values in different concentrations of NaCl and KCl solutions. In CaCl2 solution, only quartz has valley value, while orthoclase and plagioclase increase monotonously. Quartz in soil plays a main role in the influence of soil CA, followed by orthoclase and plagioclase. The CA of different minerals in different chemical solutions is mainly controlled by electric double layer interaction and functional groups interaction. In different salt solution environment, in addition to the above two effects, the mineral CA is also affected by the surface tension.

Abstract The sole use of single modality data often fails to capture the complex heterogeneity among patients, including the variability in resistance to anti-HER2 therapy and outcomes of combined treatment regimens, for the treatment of HER2-positive gastric cancer (GC). This modality deficit has not been fully considered in many studies. Furthermore, the application of artificial intelligence in predicting the treatment response, particularly in complex diseases such as GC, is still in its infancy. Therefore, this study aimed to use a comprehensive analytic approach to accurately predict treatment responses to anti-HER2 therapy or anti-HER2 combined immunotherapy in patients with HER2-positive GC. We collected multi-modal data, comprising radiology, pathology, and clinical information from a cohort of 429 patients: 310 treated with anti-HER2 therapy and 119 treated with a combination of anti-HER2 and anti-PD-1/PD-L1 inhibitors immunotherapy. We introduced a deep learning model, called the Multi-Modal model (MuMo), that integrates these data to make precise treatment response predictions. MuMo achieved an area under the curve score of 0.821 for anti-HER2 therapy and 0.914 for combined immunotherapy. Moreover, patients classified as low-risk by MuMo exhibited significantly prolonged progression-free survival and overall survival (log-rank test, P

Abstract In the KEYNOTE-811 study, anti-HER2 and immunotherapy treatments resulted in longer survival in HER2-positive gastric cancer patients with CPS ≥ 1, whereas CPS

Abstract Background While body mass index (BMI) defines obesity as a well-established risk factor for cardiovascular disease, the paradoxical theory of BMI suggests that obesity may indeed have a favorable impact on the prognosis of cardiovascular disease. Therefore, this study aims to assess the correlation between body shape index (ABSI), which is a novel measure of obesity, and coronary heart disease (CHD) among obese individuals in the United States. Methods The data from the National Health and Nutrition Examination Survey (NHANES) were evaluated by us for 5046 patients. We assessed the exposure variable ABSI, which includes waist circumference (WC), height, and BMI. The outcome variable was CHD. Results The cross-sectional study included a total of 5046 obese adults aged over 20 years, with an average age (standard deviation: SD) of 49.86 (16.24) years and a male proportion of 44.57%.The odds ratio (OR) values for CHD in Model 1, Model 2, 3 were found to be 2.45 (95%CI: 2.12, 2.83), 1.53 (95%CI:1.30, 1.81) and 1.31 (95%CI:1.09, 1.56) per SD increase in ABSI, respectively. In the fully adjusted model, we designated participants in the T1 group as the reference group. Our findings indicate a significant increase in the prevalence of CHD (OR:1.82, 95%CI: 1.07–3.10) only within the T3 group. Although there is an increased prevalence of CHD (OR:1.32, 95%CI: 0.77–2.29) in the T2 group, no statistically significant difference was observed. Conclusions The increase in ABSI is strongly associated with the rise in CHD prevalence among obese individuals in the United States.

Abstract Background There is ongoing debate around rate versus rhythm control strategies for managing atrial fibrillation (AF), however, much of the data comes from Western cohorts. Kerala‐AF represents the largest prospective AF cohort study from the Indian subcontinent. Objectives To compare 12‐month outcomes between rate and rhythm control strategies. Methods Patients aged ≥18 years with non‐transient AF were recruited from 53 hospitals across Kerala. Patients were stratified by rate or rhythm control. The primary outcome was a composite of all‐cause mortality, arterial thromboembolism, acute coronary syndrome or hospitalization due to heart failure or arrhythmia at 12 months. Secondary outcomes included bleeding events and individual components of the primary. Predictors of the composite outcome were analysed by logistic regression. Results A total of 2901 patients (mean age 64.6 years, 51% female) were included (2464 rate control, 437 rhythm control). Rates of the primary composite outcome did not differ between groups (29.7% vs 30.0%; p = .955), nor did any component of the primary. Bleeding outcomes were also similar (1.6% vs 1.9%; p = .848). Independent predictors of the primary composite outcome were older age (aOR 1.01; p = .013), BMI

Abstract Eleocharis dulcis (Burm. f.) Trin. ex Hensch., commonly known as Chinese water chestnut, is a traditional aquatic vegetable in China, and now is widely cultivated throughout the world because of its high nutritional value and unique tastes. Here, we report the assembly of a 493.24 Mb telomere-to-telomere (T2T) genome of E. dulcis accomplished by integrating ONT ultra-long reads, PacBio long reads and Hi-C data. The reference genome was anchored onto 111 gap-free chromosomes, containing 48.31% repeat elements and 33,493 predicted protein-coding genes. Whole genome duplication (WGD) and inter-genomic synteny analyses indicated that chromosome breakage and genome duplication in E. dulcis possibly occurred multiple times during genome evolution after its divergence from a common ancestor with Rhynchospora breviuscula at ca. 35.6 Mya. A comparative time-course transcriptome analysis of corm development revealed different patterns of gene expression between cultivated and wild accessions with the highest number of differentially expressed genes (DEGs, 15,870) at the middle swelling stage and some of the DEGs were significantly enriched for starch metabolic process.

Abstract Objective Since January 8, 2023, China has managed COVID-19 as a Class-B infectious disease, marking the epidemic's transition to a low-level stage. This study analyzes the relationship between the public's perceived a community with shared future for doctor-patient (PCSF), health self-consciousness, benefit finding, and anxiety in this stage. Additionally, it compares changes in these variables across different stages of COVID-19. Methods Using a repeated cross-sectional design, three surveys were conducted respectively in three different stages of COVID-19 in China. Specifically, the first survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, and Shangrao from November 13 to 20, 2021 in the outbreak stage of COVID-19, yielding 1,252 valid responses out of 1,534 collected questionnaires. The second survey was conducted in Dalian, Zhengzhou, Heihe, Shangrao, and Lanzhou from December 1 to 19, 2021 in the stable stage of COVID-19, with 872 valid responses obtained from 1,075 collected questionnaires. The third survey was conducted in Beijing, Dalian, Zhengzhou, Heihe, Shangrao, Lanzhou, and Chengdu from January 29 to February 4, 2023 in the low epidemic level stage of COVID-19, achieving 2,113 valid responses from the 2,461 questionnaires collected. Results Unlike in the outbreak stage but similar to the stable stage, the public's anxiety, health self-consciousness and benefit finding decreased while PCSF was improved in the low epidemic level stage. Consistent with both the outbreak and stable stage, PCSF, health self-consciousness, benefit finding, and anxiety showed positive correlations in the low epidemic level stage, with health self-consciousness partially mediating the positive impact of PCSF on benefit finding. Unlike in the stable stage but similar to the outbreak stage, anxiety did not moderate the relationship between PCSF and health self-consciousness in the low epidemic level stage. Conclusions The public's health self-consciousness, benefit finding, and anxiety decreased, while PCSF increased in the low epidemic level stage. Furthermore, PCSF had a greater impact on benefit finding, and anxiety's impact on health self-consciousness was significantly reduced. Across different stages of COVID-19, PCSF directly increased benefit finding and also enhanced benefit finding by improving health self-consciousness. Thus, comprehensive intervention measures are beneficial in the low epidemic level stage.

Objective As a key structure for carrying the vehicle, the abnormal vibration of bogies has a direct impact on the service performance of rail transit trains. Therefore, it is necessary to conduct in-depth research on the fatigue of vehicle bogies. Method In response to the abnormal bogie vibration on a certain urban rail transit train, a main line passenger tracking test is conducted to analyze the dynamic stress in the key areas for the testing vehicle. Combined with the elastic mode of bogie frame, the frame vibration and main frequency of wheel-rail excitation under different track types are compared and studied. Result & Conclusion The equivalent stress (σaeq) of 17 measuring points on train bogie frame exceeds the limit of 70 MPa before wheel reprofiling, while only one measuring point exceeds the limit after wheel reprofiling. Therefore, wheel off roundness has a significant impact on the dynamic stress of the frame. The main frequency of the frame dynamic stress signal both before and after wheel reprofiling is 59 Hz in the low-frequency range, and the main frequency energy still exists after wheel reprofiling, indicating that its correlation with train running speed and wheel off roundness is relatively small. The main frequency of dynamic stress signal is above 700 Hz in the high-frequency range. Since the high-frequency σaeq is mainly within 25 MPa, its contribution to the damage of bogie frame is very small. This type of bogie frame has an elastic mode with a frequency of about 59 Hz, where motor and side beam nod in the opposite direction. The frequency of this elastic mode is consistent with the main frequency of the dynamic stress signal of vehicle dynamic stress measurement points on three track types: long sleeper integrated track bed+ZX-2 fastener, short sleeper integrated track bed+ZX-2 fastener, and floating plate track bed (high-end steel)+ZX-2 fastener. However, this main frequency does not exist on other track types, indicating that the elastic mode of the frame is excited on some track types, causing excessive fatigue damage values. The vertical vibration main frequencies of the vehicle axle box on this line are 60.5 Hz and 37.0 Hz respectively, of which 60.5 Hz is mainly generated by the coupling effect between the vehicle and the track, and 37.0 Hz has a certain correlation with the vibration damping fasteners. Therefore, the combination of track bed and fastener types has a significant impact on the wheel rail vibration.

Abstract Accurate detection of algae in microscopic image plays a crucial role in water quality monitoring. However, the existing object detection methods still face challenges in accurately detecting different categories of algae in microscopic image. In order to improve the accuracy, an improved YOLOv5s model is proposed for microalgae detection, by combining a Receptive Field Enhancement (RFE) module, the Wise‐IoU v3 dynamic non‐monotonic focal loss function, and a Dynamic head (Dyhead), which is termed receptive field enhancement wise‐IoU dyhead (RWD)‐you only look once (YOLO). Firstly, to detect microalgae of various scales, the Bottleneck in the C3 module of YOLOv5s is replaced with a more reasonable RFE module. Secondly, Wise‐IoU v3 is applied to enhance detection accuracy by assigning varying weights between high‐quality and low‐quality images. Finally, Dyhead is introduced to enhance the representation capacity of the detection head by integrating three attention mechanisms: scale awareness, spatial awareness, and task awareness. The proposed RWD‐YOLO model significantly enhances the accuracy of algae detection in microscopic image. Specifically, the experimental results on the microalgae dataset show that the RWD‐YOLO achieves an mAP@0.5 of 93.2% and an mAP@0.5:0.95 of 65.1%. Compared to the original YOLOv5s, mAP@0.5 and mAP@0.5:0.95 are improved by 3.7% and 5.7%, respectively.

Abstract Background To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development. Methods We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP. Results LINC00665 employs its Alu elements to interact with the 3’-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context. Conclusions lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs.

Abstract Background The prevalence of pre-frailty is notably high among maintenance hemodialysis (MHD) patients. Pre-frailty, an early and reversible condition between non-frailty and frailty, can lead to adverse outcomes such as increased unplanned hospital admissions and a higher risk of other chronic diseases. Early identification and intervention of pre-frailty in MHD patients are crucial. This study aimed to establish a simple and effective model for screening and identifying MHD patients at high risk of pre-frailty by using 50 kHz-Whole Body Phase Angle (PhA) measured by bioelectrical impedance analysis (BIA), hand grip strength (HGS), the Five-Times-Sit-to-Stand Test (FTSST), and laboratory parameters, with a specific focus on gender differences. Methods This prospective cross-sectional study was conducted from September to December 2023 at the Wenjiang Hemodialysis Center in the Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China. A total of 244 MHD patients, including 130 males and 114 females, were enrolled, comprising 128 non-frail and 116 pre-frail individuals. Data were collected prospectively, including demographic information, physical measurements, and laboratory test results. All participants provided informed consent before enrollment. The FRAIL scale (FS) was used to assess pre-frailty in MHD patients. Grip strength was measured using an electronic grip strength tester, physical function was assessed using the Five-Times-Sit-to-Stand Test, and whole-body phase angle was measured using the InBody S10 device. Results A total of 244 MHD patients with a mean age of 53.75 ± 0.90 years were enrolled, including 130 males with a mean age of 54.12 ± 1.26 years and 114 females with a mean age of 53.32 ± 1.29 years. ROC curve analysis showed that in male patients, the AUC of PhA for predicting pre-frailty was 0.919, with a sensitivity of 94.5% and specificity of 91.3%, and a cutoff value of 6.05°; in female patients, the AUC of PhA was 0.870, with a sensitivity of 70.5% and specificity of 90.6%, and a cutoff value of 5.25°. The AUC of FTSST for screening pre-frailty in male patients was 0.827, with a sensitivity of 62.3% and specificity of 96.2%, and a cutoff value of 12.95 s; in female patients, the AUC of FTSST was 0.784, with a sensitivity of 67.3% and specificity of 84.0%, and a cutoff value of 12.95 s. Additionally, in male patients, the combination of PhA and FTSST resulted in an AUC of 0.930, with a sensitivity of 96.4% and specificity of 81.3%; in female patients, the AUC was 0.911, with a sensitivity of 78.7% and specificity of 92.5%. Conclusion PhA measured by BIA, in combination with the Five-Times-Sit-to-Stand Test, serves as an effective screening tool and predictor of pre-frailty in MHD patients. The combination of PhA and FTSST shows enhanced diagnostic value in female patients, while PhA alone is sufficient for predicting pre-frailty in male patients. Trial registration Chinese Clinical Trial Registry (ChiCTR2100051111), registered on 2021–09-13.

Abstract Background Cisplatin (DDP) chemotherapy is commonly used in therapy for non-small cell lung cancer (NSCLC), but increased drug resistance has become a huge obstacle. Baicalin (BA) contributed to the sensitivity of NSCLC to DDP. Here, we aimed to further probe the pathophysiological mechanisms of BA in NSCLC. Methods A549 and A549/DDP cells and xenograft mice were treated with BA and DDP. Xenograft mice were treated additionally with the NRF2 inducer (Bardoxolone methyl, BM) and KEAP1 knockdown. The levels of ferritinophagy-related proteins and biomarkers were determined. The autophagosomes were observed. M1 macrophage polarization and the contents of related indicators were analyzed. The involvement of KEAP1/NRF2/HO-1 was determined. Results BA inhibited cell development, and the effect of BA and DDP on cell development was additive. The abundance of ferritinophagy-related proteins and the number of autophagosomes were induced by BA. BA also promoted the transition of GSH to GSSH. BA favored M1 macrophage polarization and affected the expression of related proteins. When BA and DDP combined, these molecular phenomena were further exacerbated. BA induced accumulation of KEAP1 and reduction of NRF2 and HO-1. However, BM and KEAP1 knockdown disrupted the synergistic effects of BA and DDP on inhibiting NSCLC growth. BM and KEAP1 knockdown reversed DDP and BA-promoted protein expression activity and M1 macrophage polarization. Conclusion Our findings suggest that BA is involved in ferritinophagy and macrophage immunity through the KEAP1-NRF2/HO-1 axis, thereby improving the DDP sensitivity in NSCLC, which could provide new candidates for treatment strategies.

Abstract Vertical transistors, in which the source and drain are aligned vertically and the current flow is normal to the wafer surface, have attracted considerable attention recently. However, the realization of high-density vertical transistors is challenging, and could be largely attributed to the incompatibility between vertical structures and conventional lateral fabrication processes. Here we report a T-shape lamination approach for realizing high-density vertical sidewall transistors, where lateral transistors could be pre-fabricated on planar substrates first and then laminated onto vertical substrates using T-shape stamps, hence overcoming the incompatibility between planar processes and vertical structures. Based on this technique, we vertically stacked 60 MoS2 transistors within a small vertical footprint, corresponding to a device density over 108 cm−2. Furthermore, we demonstrate two approaches for scalable fabrication of vertical sidewall transistor arrays, including simultaneous lamination onto multiple vertical substrates, as well as on the same vertical substrate using multi-cycle layer-by-layer laminations.

Objective Compared to conventional bogies, the new type of turntable bogie exhibits smaller slewing resistance coefficients and better curve negotiation performance. Therefore, it is necessary to analyze the vehicle dynamics performance. Method Using SIMPACK dynamics software, vehicle dynamics models with turntable bogies and conventional bogies are established. A comparative analysis is conducted on the slewing resistance coefficients, curve negotiation performance, and vehicle dynamics performance of the two types of bogies. The impact of bearing friction coefficient on the dynamics performance of vehicle with turntable bogies is studied. Result & Conclusion For the two bogie types, under conditions where the curve radius is 110 m and the speed limit is set to 30 km/h, the derailment coefficient, wear rate, and axial lateral force of TBV (turntable bogie vehicle) are significantly better than those of CBV (conventional bogie vehicle) under both new and worn wheels working conditions. The wheel load reduction rate of TBV is slightly better than that of CBV. As the vehicle passing straight tracks at different speeds, the vehicle stability of both bogie types increases as the vehicle operating speed increases. Under new wheel working condition, the lateral stability of TBV is significantly better than that of CBV, and the vertical stability is slightly better. Under worn wheel working condition, the lateral and vertical stability of TBV are significantly better than those of CBV. When the rotation of TBV is restricted, the stability, lateral stability, and curve negotiation safety of the vehicle deteriorate with the increasing bearing friction coefficient, but all values remain within the range specified by relevant standards.

Abstract Background The myeloblastosis (MYB) transcription factor (TF) family is one of the largest and most important TF families in plants, playing an important role in a life cycle and abiotic stress. Results In this study, 268 Avena sativa MYB (AsMYB) TFs from Avena sativa were identified and named according to their order of location on the chromosomes, respectively. Phylogenetic analysis of the AsMYB and Arabidopsis MYB proteins were performed to determine their homology, the AsMYB1R proteins were classified into 5 subgroups, and the AsMYB2R proteins were classified into 34 subgroups. The conserved domains and gene structure were highly conserved among the subgroups. Eight differentially expressed AsMYB genes were screened in the transcriptome of transcriptional data and validated through RT-qPCR. Three genes in AsMYB2R subgroup, which are related to the shortened growth period, stomatal closure, and nutrient and water transport by PEG-induced drought stress, were investigated in more details. The AsMYB1R subgroup genes LHY and REV 1, together with GST, regulate ROS homeostasis to ensure ROS signal transduction and scavenge excess ROS to avoid oxidative damage. Conclusion The results of this study confirmed that the AsMYB TFs family is involved in the homeostatic regulation of ROS under drought stress. This lays the foundation for further investigating the involvement of the AsMYB TFs family in regulating A. sativa drought response mechanisms.

Many studies now indicate that brain disorders are associated with functional connectivity between brain regions, but the impact of interactions among functional connections on diseases remains to be explored. Moreover, existing models for analyzing the temporal and spatial attributes of fMRI data exhibit limitations in their efficacy. Currently, there is an absence of a comprehensive model capable of simultaneously capturing disease-related interactions within functional connectivity, fully leveraging the temporal and spatial characteristics of fMRI, and achieving superior diagnostic accuracy. To address these gaps, we propose a model to classify brain disorders that employs a novel algorithm and multimodal graph convolutional networks to process the temporal and spatial features of fMRI data separately, along with the demographic information. In the proposed model, a deep feature selection algorithm is employed to discover disease-related biomarkers and evaluate their impact on brain disorders. Remarkably, this approach has led to a classification accuracy of 80.66%, which surpasses the performance of graph neural networks by approximately 10%. Notably, our investigations have uncovered novel biomarkers linked to autism, with our findings corroborated by relevant literature. These achievements underscore the model's potential in revealing critical insights pertinent to autism, thereby facilitating groundbreaking experimental research in the field.

For many years, multi-scale models of chromatin domains, such as A/B compartments, sub-compartments, topologically associated domains (TADs), sub-TADs, and loops have been popular. However, existing methods can only identify structures at a single scale and cannot partition multi-scale structures. In this paper, we proposed a method (TORNADOES) for chromatin domain partitioning based on hypergraph clustering. First, we use a density clustering algorithm to identify TADs at different scales based on Hi-C data with different resolutions. Then, by combining ChIP-seq data features and TAD results at different scales, we generate a hypergraph based on these TADs. Finally, we partition the chromatin domain structure at different scales, including A/B, A1, A2, B1, B2, and B3 based on the Laplacian matrix feature of the hypergraph. Similarity comparison experiments and ChIP-seq signal enrichment analysis are performed on the A/B region and sub-TAD levels, respectively, demonstrating that our method can identify chromatin domains with distinct features and provide a deeper understanding of the organizational patterns and functional differences in TADs at the genomic hierarchical structure. Comparative analysis of multiple cell line data shows that TORNADOES can better classify different numbers and types of compartments by changing the factors ChIP-seq data and clustering number used to characterize TAD compared to other methods. Source code for the TORNADOES method can be found at https://github.com/ghaiyan/TORNADOES.

This study primarily discusses the influence of internal structure on the performance of sludge concentrators. The focus is to evaluate the influence of internal structural changes on the improvement of sludge settling and clarifying efficiency through numerical simulation, so as to achieve the optimal design of sludge settling equipment parameters. The results show that with the increase of the bottom outlet width of the cone guide blade, the turbulence decreases, and the sludge thickening efficiency is significantly increased by about 27.1%, from 0.01036 at 300 mm to 0.0132 at 500 mm, which significantly improves the sludge settling and thickening efficiency. Also, the addition of the extended deflector significantly increased the bottom sludge settling concentration from 0.0129 to 0.0134 by about 3.87% and reduced the outlet suspended matter by about 13.6%. Obviously, the influence of effluent width and extended diversion length on sludge settling efficiency and water purification cannot be ignored. Therefore, an optimal design that takes into account the outlet width and the length of the extended deflector is critical to achieve optimal sludge concentration and water quality in the sludge concentrator. These findings provide numerical theoretical insights for improving the performance of sludge thickeners and the efficiency of water treatment. HIGHLIGHTS The baffle structure has a significant impact on the sludge settling effect.; Optimization of the baffle structure can accelerate the speed of sludge settling and aggregation.; The bottom width of the guide cone and the extended baffle plate are key factors that affect the purification effect and sludge settling efficiency.;

Objective To investigate the effect of bone window closure on moderate to severe traumatic brain injury (TBI) in mice by controlled cortical impact (CCI). Methods A total of 200 healthy male mice were divided into 2 groups for moderate and severe TBI. Fifty were randomly selected from each group for bone window closed, and the remaining 50 were not closed. The intracranial pressure (ICP) was monitored, the water content of brain tissue and the volume of cerebral edema were measured, the degree of neurological impairment was assessed by modified Neurological Severity Score (mNSS), and the spatial learning ability and memory were evaluated by Morris water maze test. Nissl staining assessed the degree of neuronal damage in the cerebral cortex and CA1 region of the hippocampus. Results For ICP, there were differences in ICP between the bone window closed group and the unclosed group in both the moderate and severe TBI (P = 0.007, 0.000). There were also significant differences in ICP at different observation time points after modeling (P = 0.000, 0.000). The ICP on 1 d of the moderate bone window closed group was higher than that in the moderate bone window unclosed group (P = 0.009), 1 d (P = 0.000) and 3 d (P = 0.038) of the severe bone window closed group was higher than that of the severe bone window unclosed group. On 7 d, the ICP in the moderate bone window closed group (P = 0.000, 0.000) and the severe bone window closed group (P = 0.000, 0.008) was lower than that on 1 and 3 d, and the ICP on 3 d was also lower than that on 1 d (P = 0.000, 0.000). The ICP in the moderate bone window unclosed group on 7 d was lower than that on 1 d (P = 0.031). The water content of brain tissue was lower on 1 d (P = 0.028), 3 d (P = 0.023) and 7 d (P = 0.023) in severe bone window closed group than that of severe bone window unclosed group. The volume of brain edema in the bone window closed group was smaller than that in the bone window unclosed group (P = 0.021, 0.037). In the evaluation of the degree of neurological impairment, there were differences in mNSS scores at different observation time points between the bone window closed group and the bone window unclosed group (P = 0.000, 0.001). On 7 d, the mNSS scores of the moderate bone window closed group (P = 0.002), the moderate bone window unclosed group (P = 0.013) and the severe bone window closed group (P = 0.009) were all lower than those on 1 d. The mNSS scores of the severe bone window closed group (P = 0.006) and the severe bone window unclosed group (P = 0.002) were all lower than those of 3 d. Morris water maze test showed that the platform latency of mice in the severe bone window closed group was longer than that in the severe bone window unclosed group (P = 0.045), and the target quadrant residence time was shorter than that in the severe bone window unclosed group (P = 0.025). Nissl staining showed compared with the moderate bone window unclosed group, the density of Nissl bodies in cerebral cortex neurons was decreased, the staining was lighter, and the density of Nissl bodies in cerebral cortex neurons of CA1 region of hippocampus was decreased, the Nissl staining was lighter and the shape was blurred in the moderate bone window closed group. In severe TBI model mice, compared with the bone window unclosed group, the density of Nissl bodies in cerebral cortex and hippocampal CA1 region of the bone window closed group was decreased, the staining was blurred, and more metachromic particles appeared, hippocampal CA1 region body edema, the Nissl staining blurred. Conclusions In moderate TBI model mice, bone window closure increases ICP in the acute stage, but has no significant effect on the degree of cerebral edema, neurological function and cognitive function. In severe TBI model mice, bone window closure can lead to increased ICP and decreased spatial learning ability and memory, but it can reduce the degree of brain edema and improve neurological function. It is suggested that bone window closure should be selected according to the purpose of the study.

In response to the challenging task of accurately identifying the main hazard-causing layer of overlying strata in the coal mine surface hydraulic fracturing construction, this study focuses on the industrial test of ground hydraulic fracturing at the 401102 working face of the Mengcun Coal Mine. The research is conducted using the methods of theoretical analysis, microseismic monitoring, and on-site investigation to reveal the dynamic disaster mechanism of mine earthquakes and rock bursts induced by the movement of thick and hard overlying strata in the coal mines. The relationship between the movement characteristics of thick and hard overlying strata based on a three-zone structure loading model of overlying strata and induced dynamic disasters is analyzed, and a prediction model for mining seismic energy and an estimation model for equivalent additional stress in mining areas based on the movement state of key layers are established. A coal mine identification technology for the main hazard-causing layer of overlying strata is proposed based on the K-means clustering algorithm and the elbow rule. The construction layer for hydraulic fracturing is determined, and an industrial test is carried out on-site. The effectiveness is verified based on the microseismic monitoring data and theoretical analysis results, leading to the following conclusions. In the Mengcun Coal Mine’s 401102 working face, both the key stratum responsible for rock bursts and mine seismic activities can be traced to the R9 key stratum of the Anding Group, situated 66 meters away from the coal seam. The primary fracturing movement of this critical stratum R9 imparts an equivalent supplementary disturbance stress value of 7.23 MPa, with the seismic energy liberated by this initial rupture motion quantifying to 6.08×105 J, thereby indicating a pronounced susceptibility towards catastrophic occurrences. After fracturing the key layer which induces mining earthquakes and rock bursts, the theoretical value of the mine earthquake energy is reduced by 94%, and the theoretical value of the equivalent disturbance stress of the working face is reduced by 76%. High-energy microseismic events above the working face with an energy of 5×103 J show a noticeable upward trend, with an upward movement of approximately 15 m. The frequency ratio of microseismic events with an energy level of 103 J or higher significantly decreases from 60.39% to 17.89%, and the maximum microseismic event energy decreases from 6.65×105 J to 9.75×103 J. The proportion of microseismic events with an energy level of 102 J and below significantly increases from 39.61% to 82.11%.

Abstract Underground coal seam mining significantly alters the stress and energy distribution within the overlying rock, leading to eventual structural degradation. Therefore, it is imperative to quantitatively identify the temporal and spatial characteristics of stress evolution of overlying rock caused by mining. This paper introduces a novel rock stress model integrating entropy and a spatial–temporal cube. Similar material model tests are used to identify the abrupt entropy changes within the mining rock, and the trend analysis is carried out to describe the spatial–temporal evolution law of stress during mining. Experimental findings indicate elevated stress levels in the unmined rock preceding and following the panel, as well as within specific rock strata above it. Definitively, dynamic stress arches within the surrounding rock of the stope predominantly bear and distribute the load and pressure from the overlying rock, and each stress mutation is accompanied by a sudden stress entropy change. Over time, z-score shows that the noticeable reduction in mining-induced overburden stress becomes increasingly pronounced, especially in the water-conducting fracture zone. The model's bifurcation set serves as the comprehensive criterion for the entropy-induced sudden changes in the rock system, signifying overall failure.

Abstract Background Lung cancer (LC), characterized by high incidence and mortality rates, presents a significant challenge in oncology. Despite advancements in treatments, early detection remains crucial for improving patient outcomes. The accuracy of screening for LC by detecting volatile organic compounds (VOCs) in exhaled breath remains to be determined. Methods Our systematic review, following PRISMA guidelines and analyzing data from 25 studies up to October 1, 2023, evaluates the effectiveness of different techniques in detecting VOCs. We registered the review protocol with PROSPERO and performed a systematic search in PubMed, EMBASE and Web of Science. Reviewers screened the studies’ titles/abstracts and full texts, and used QUADAS-2 tool for quality assessment. Then performed meta-analysis by adopting a bivariate model for sensitivity and specificity. Results This study explores the potential of VOCs in exhaled breath as biomarkers for LC screening, offering a non-invasive alternative to traditional methods. In all studies, exhaled VOCs discriminated LC from controls. The meta-analysis indicates an integrated sensitivity and specificity of 85% and 86%, respectively, with an AUC of 0.93 for VOC detection. We also conducted a systematic analysis of the source of the substance with the highest frequency of occurrence in the tested compounds. Despite the promising results, variability in study quality and methodological challenges highlight the need for further research. Conclusion This review emphasizes the potential of VOC analysis as a cost-effective, non-invasive screening tool for early LC detection, which could significantly improve patient management and survival rates.

In recent years, plasma medicine, as an innovative and rapidly growing field, has garnered increasing attention. Nonetheless, the fundamental mechanisms of the interaction processes of cold atmospheric plasma (CAP) and biomolecules remain under investigation. In this paper, a reactive molecular dynamic (MD) simulation with ReaxFF potential was performed to explore the interactions of reactive oxygen species (ROS) produced in CAP, exemplified by OH radicals, and four distinct oligonucleotides. The breakage of single-stranded oligonucleotides induced by OH is observed in the simulation, which could seriously influence the biological activity of cellular DNA. The base release induced by OH radicals means the loss of base sequence information, and the H-abstraction at nucleobases affects the gene strand complementarity, gene transcription, and replication. In addition, the dose effects of OH radicals on bond formation and breaking of oligonucleotides are also discussed by adjusting the number of ROS in the simulation box. This study can enhance the comprehension of interactions between CAP and DNA, thereby indicating possible improvements in plasma device optimization and operation for medical applications.

Abstract Chinese rose (Rosa chinensis) is an important ornamental plant, with economic, cultural, and symbolic significance. During the application of outdoor greening, adverse environments such as high temperature and drought are often encountered, which affect its application scope and ornamental quality. The starch phosphorylase (Pho) gene family participate in the synthesis and decomposition of starch, not only related to plant energy metabolism, but also plays an important role in plant stress resistance. The role of Pho in combating salinity and high temperature stress in R. chinensis remains unknown. In this work, 4 Phos from R. chinensis were detected with Pfam number of Pho (PF00343.23) and predicted by homolog-based prediction (HBP). The Phos are characterized by sequence lengths of 821 to 997 bp, and the proteins are predicted to subcellularly located in the plastid and cytoplasm. The regulatory regions of the Phos contain abundant stress and phytohormone-responsive cis-acting elements. Based on transcriptome analysis, the Phos were found to respond to abiotic stress factors such as drought, salinity, high temperature, and plant phytohormone of jasmonic acid and salicylic acid. The response of Phos to abiotic stress factors such as salinity and high temperature was confirmed by qRT-PCR analysis. To evaluate the genetic characteristics of Phos, a total of 69 Phos from 17 species were analyzed and then classified into 3 groups in phylogenetic tree. The collinearity analysis of Phos in R. chinensis and other species was conducted for the first time. This work provides a view of evolution for the Pho gene family and indicates that Phos play an important role in abiotic stress response of R. chinensis.

Abstract Background The aim of this case report is to evaluate minimally invasive stabilization using screws and cement for acetabular metastatic tumor and summarize the indications and contraindications for minimally invasive stabilization of acetabular metastatic tumors with screw and cement techniques. Case presentation Under imaging guidance, a patient with acetabular metastatic tumor was treated with hollow screw combined with bone cement fixation. Ischial screw, ascending branch screw, and anterior and posterior screws were inserted to firmly fix the anterior and posterior column of the acetabulum. At the same time, the third screw connected the anterior and posterior columns together, combined with bone cement into the fracture site to further increase local stability and resist bone defects caused by local tumor osteolysis. The patient was a 52-year-old Uygur male. Herein, we summarize his clinical symptoms and operation. Differences in visual analog scale and walking function (Musculoskeletal Tumor Society) before operation and at 2 months, 6 months, and 12 months after operation were compared. Results Postoperative complications and tumor progression were recorded. The patient was followed up for 16 months, and the operative time was 60 minutes. In total, 20 ml of bone cement was injected into the acetabular posterior column and the top of the acetabulum. VIsual analog scale score was 8 before operation, 3 at 2 months, 3 at 6 months, and 2 at 12 months after operation. Musculoskeletal Tumor Society function was 13 before operation, 23 at 2 months, 25 at 6 months, and 26 at 12 months after operation. During follow-up, no cement leakage, fever, hip nerve injury, pulmonary embolism, or imaging findings of further destruction of the acetabulum and surrounding bone were noted. Conclusion This case report shows that the treatment of acetabular metastatic cancer with minimally invasive stabilization using screws and cement under the C arm can effectively relieve pain and enhance the strength of the pelvis, and is innovative and feasible.

Abstract Background Intramuscular fat content is an important index reflecting the quality of mutton, which directly affects the flavor and tenderness of mutton. Livestock and poultry intramuscular fat content is influenced by genetics, nutritional level, and environmental factors. Key regulatory factors play a crucial role in intramuscular fat deposition. However, there is a limited amount of research on the identification and function of key genes involved in intramuscular fat content deposition specifically in sheep. Results Histological differences in the longest dorsal muscle of the small-tailed frigid sheep increased in diameter and decreased in several muscle fibers with increasing monthly age; The intramuscular fat content of the longest dorsal muscle of the small-tailed cold sheep varied with age, with a minimum of 1 month of age, a maximum of 6 months of age, and a minimum of 12 months of age. Transcriptomic sequencing and bioinformatics analysis revealed a large number of differential genes in the longest dorsal muscles of little-tailed billy goats of different months of age, which were enriched in multiple GO entries and KEGG pathways. Among them, the pathway associated with intramuscular fat was the AMPK signaling pathway, and the related genes were PPARGC1A and ADIPOQ; Immunohistochemical studies showed that PPARGC1A and ADIPOQ proteins were expressed in connective tissues, cell membranes, and, to a lesser extent, the cytoplasm of the longest dorsal muscle of the little-tailed frigid sheep; Real-time PCR and Western Blot validation showed that PPARGC1A and ADIPOQ were both expressed in the longest dorsal muscle of the little-tailed frigid sheep at different ages, and there were age differences in the amount of expression. The ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle, and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle; As inferred from the above results, the ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle (r = -0.793, P

Abstract Objective Previous studies have shown a clear link between insulin resistance (IR) and an elevated risk of atrial fibrillation (AF). However, the relationship between the estimated glucose disposal rate (eGDR), which serves as a marker for IR, and the risk of AF recurrence after radiofrequency catheter ablation (RFCA) remains uncertain. Therefore, this study aimed to examine the potential association between the eGDR and the risk of AF recurrence following RFCA. Methods This retrospective study was conducted at Nanchang University Affiliated Second Hospital. The study enrolled 899 patients with AF who underwent RFCA between January 2015 and January 2022. The formula used to calculate the eGDR was as follows: 19.02 − (0.22 * body mass index) − (3.26 * hypertension) − (0.61 * HbA1c). Cox proportional hazard regression models and exposure–effect curves were used to explore the correlation between the baseline eGDR and AF recurrence. The ability of the eGDR to predict AF recurrence was evaluated using the area under the receiver operating characteristic curve (AUROC). Results The study observed a median follow-up period of 11.63 months, during which 296 patients experienced AF recurrence. K‒M analyses revealed that the cumulative incidence AF recurrence rate was significantly greater in the group with the lowest eGDR (log-rank p

Abstract Objective This study developed and validated a nomogram utilizing clinical and multi-slice spiral computed tomography (MSCT) features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma. Additionally, we assessed the predictive accuracy of Ki-67 expression levels, as determined by our model, in estimating the prognosis of stage IA lung adenocarcinoma. Materials and methods We retrospectively analyzed data from 395 patients with pathologically confirmed stage IA lung adenocarcinoma. A total of 322 patients were divided into training and internal validation groups at a 6:4 ratio, whereas the remaining 73 patients composed the external validation group. According to the pathological results, the patients were classified into high and low Ki-67 labeling index (LI) groups. Clinical and CT features were subjected to statistical analysis. The training group was used to construct a predictive model through logistic regression and to formulate a nomogram. The nomogram’s predictive ability and goodness-of-fit were assessed. Internal and external validations were performed, and clinical utility was evaluated. Finally, the recurrence-free survival (RFS) rates were compared. Results In the training group, sex, age, tumor density type, tumor-lung interface, lobulation, spiculation, pleural indentation, and maximum nodule diameter differed significantly between patients with high and low Ki-67 LI. Multivariate logistic regression analysis revealed that sex, tumor density, and maximum nodule diameter were significantly associated with high Ki-67 expression in stage IA lung adenocarcinoma. The calibration curves closely resembled the standard curves, indicating the excellent discrimination and accuracy of the model. Decision curve analysis revealed favorable clinical utility. Patients with a nomogram-predicted high Ki-67 LI exhibited worse RFS. Conclusion The nomogram utilizing clinical and CT features for the preoperative prediction of Ki-67 expression in stage IA lung adenocarcinoma demonstrated excellent performance, clinical utility, and prognostic significance, suggesting that this nomogram is a noninvasive personalized approach for the preoperative prediction of Ki-67 expression.

Abstract Background Prior studies have suggested a potential relationship between osteoporosis and sarcopenia, both of which can present symptoms of compromised mobility. Additionally, fractures among the elderly are often considered a common outcome of both conditions. There is a strong correlation between fractures in the elderly population, decreased muscle mass, weakened muscle strength, heightened risk of falls, and diminished bone density. This study aimed to pinpoint crucial diagnostic candidate genes for osteoporosis patients with concomitant sarcopenia. Methods Two osteoporosis datasets and one sarcopenia dataset were obtained from the Gene Expression Omnibus (GEO). Differential expression genes (DEGs) and module genes were identified using Limma and Weighted Gene Co-expression Network Analysis (WGCNA), followed by functional enrichment analysis, construction of protein–protein interaction (PPI) networks, and application of a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to determine candidate hub genes for diagnosing osteoporosis combined with sarcopenia. Receiver operating characteristic (ROC) curves and column line plots were generated. Results The merged osteoporosis dataset comprised 2067 DEGs, with 424 module genes filtered in sarcopenia. The intersection of DEGs between osteoporosis and sarcopenia module genes consisted of 60 genes, primarily enriched in viral infection. Through construction of the PPI network, 30 node genes were filtered, and after machine learning, 7 candidate hub genes were selected for column line plot construction and diagnostic value assessment. Both the column line plots and all 7 candidate hub genes exhibited high diagnostic value (area under the curve ranging from 1.00 to 0.93). Conclusion We identified 7 candidate hub genes (PDP1, ALS2CL, VLDLR, PLEKHA6, PPP1CB, MOSPD2, METTL9) and constructed column line plots for osteoporosis combined with sarcopenia. This study provides reference for potential peripheral blood diagnostic candidate genes for sarcopenia in osteoporosis patients.

Objective To retrospectively analyze the blood use of transfusion-dependent thalassemia (TDT) patients in 9 designated transfusion medical institutions from 2018 to 2023 in Nanning, and to evaluate the effect of " three designated " blood transfusion mode (hereby means TDT patients undergoing blood transfusion in designated transfusion medical institutions regularly) and " collection-based-supply" blood management mode on blood security of TDT patients. Methods The " three designated" blood transfusion mode was implemented to ensure that TDT patients registered in the local household registration (referred to as the " register" ) obtain the rights and interests of outpatient transfusion and blood security of designated medical institutions. The " collection-based-supply" blood management mode was implemented to assess the blood needs of "register" TDT patients and meet their needs to the maximum extent according to the blood inventory (collection). Results From 2018 to 2023, the total blood supply of "register" TDT patients was 10.37% of the total red blood supply of all medical institutions (138 509.5 U /1 335 788.0 U), with the highest proportion of type O blood as 46.34% (64 181.0 U/138 509.5 U) and the lowest proportion of type AB blood as 3.85% (5 331.0 U/138 509.5 U). In 2018, 9 transfusion medical institutions were designated for TDT patients.There were a total of 766 TDT patients in the register, with the per capita annual blood transfusion volume increased from 20.28 U (15 531.0 U/766 patients) in 2018 to 36.01 U (27 586.0 U/766 patients) in 2023, maintaining a positive growth every year(30.26%, 4.94%, 11.71%, 8.61%, 4.94% and 7.10%). Conclusion The " three designated" blood transfusion mode and the " collection-based-supply " blood management mode can effectively guarantee the blood supply of TDT patients.

Objective To analyze the correlation between frailty and living conditions in the elderly. Methods A convenience sampling method was used to select 4 869 elderly people who underwent physical examination and hospitalization in 20 medical institutions in hospitals,communities and nursing homes from August 2021 to February 2022.According to the Fried frailty diagnostic criteria,the research subjects were divided into a non-frailty group(2 904 cases),pre-frailty group(1 284 cases) and frailty group(681 cases).Multivariate logistic regression was used to analyze the correlation between living conditions and frailty. Results The total prevalence of frailty was 14.0%(95% CI:13.0-15.0),and the prevalence of men and women was compared(11.9% and 16.3%),and the difference was statistically significant(P

Abstract Although long-read sequencing enables the generation of complete genomes for unculturable microbes, its high cost limits the widespread adoption of long-read sequencing in large-scale metagenomic studies. An alternative method is to assemble short-reads with long-range connectivity, which can be a cost-effective way to generate high-quality microbial genomes. Here, we develop Pangaea, a bioinformatic approach designed to enhance metagenome assembly using short-reads with long-range connectivity. Pangaea leverages connectivity derived from physical barcodes of linked-reads or virtual barcodes by aligning short-reads to long-reads. Pangaea utilizes a deep learning-based read binning algorithm to assemble co-barcoded reads exhibiting similar sequence contexts and abundances, thereby improving the assembly of high- and medium-abundance microbial genomes. Pangaea also leverages a multi-thresholding algorithm strategy to refine assembly for low-abundance microbes. We benchmark Pangaea on linked-reads and a combination of short- and long-reads from simulation data, mock communities and human gut metagenomes. Pangaea achieves significantly higher contig continuity as well as more near-complete metagenome-assembled genomes (NCMAGs) than the existing assemblers. Pangaea also generates three complete and circular NCMAGs on the human gut microbiomes.

Objective In response to stability alarm faults occurring in CR200J EMU trailer and control cars in certain sections, it is necessary to analyze the factors affecting the dynamics performance to analyze the causes and address the issues. Method Tracked measurements are conducted on the wheel wear status of a set of CR200J EMU trailer and control cars. The actual rail profiles along the operating routes of vehicles are measured to identify the development patterns of wheel wear. Through SIMPACK software simulation, and combined with real wheel-rail matching conditions, the impact of wheel wear on vehicle dynamics performance is analyzed. Result & Conclusion The wheel wear of CR200J EMU trailer and control cars mainly concentrates at the rolling circle. As wheel wear increases, changes occur in the wheel-rail contact relationship, leading to a linear increase in wheel equivalent conicity, and noticeable changes in lateral stability indicators of the vehicles. Some sections of the measured track profiles exhibit abrupt changes, causing lateral harmonic motion in the bogies. Finally, based on the patterns and characteristics of wheel wear, improvement suggestions are proposed.

Objective Wheel wear directly affects the vibration environment of metro vehicles. Severe abnormal wear can lead to structural fatigue exceeding the limit, reducing the safety of train operation. Therefore, it is necessary to study the wear and reprofiling strategy of metro vehicle wheels to improve the maintenance level. Method Taking a certain type of metro vehicle in China as the research object, the wear law of metro vehicle wheels is analyzed. Based on the wear model of metro vehicle wheels and the prediction of wheel remaining service life, the variation characteristics of wheel key parameters in different operating stages are analyzed. Based on the comprehensive results of simulation models and field-measured data, an optimization plan for the operation and maintenance strategy is proposed. Result & Conclusion The results indicate that in the early stage of operation, the proportion of wheel loss from reprofiling is relatively high, and with the improvement of wheel-rail matching, wheel-rail wear replaces reprofiling loss as the main wear mode. Properly reducing the wheel-rail friction coefficient and the operating speed is beneficial for reducing the wheel-rail wear power. The use of small-scale reprofiling methods and flexible feed amount effectively reduces wheel radial wear and prolongs their service life. The research results can provide corresponding measures for reducing wheel-rail wear on metro lines and optimizing wheel reprofiling technology.

Abstract Oligonucleotide synthesis is vital for molecular experiments. Bioinformatics has been employed to create various algorithmic tools for the in vitro synthesis of nucleotides. The main approach to synthesizing long-chain DNA molecules involves linking short-chain oligonucleotides through ligase chain reaction (LCR) and polymerase chain reaction (PCR). Short-chain DNA molecules have low mutation rates, while LCR requires complementary interfaces at both ends of the two nucleic acid molecules or may alter the conformation of the nucleotide chain, leading to termination of amplification. Therefore, molecular melting temperature, length, and specificity must be considered during experimental design. POSoligo is a specialized offline tool for nucleotide fragment synthesis. It optimizes the oligonucleotide length and specificity based on input single-stranded DNA, producing multiple contiguous long strands (COS) and short patch strands (POS) with complementary ends. This process ensures free 5′- and 3′-ends during oligonucleotide synthesis, preventing secondary structure formation and ensuring specific binding between COS and POS without relying on stabilizing the complementary strands based on Tm values. POSoligo was used to synthesize the linear RBD sequence of SARS-CoV-2 using only one DNA strand, several POSs for LCR ligation, and two pairs of primers for PCR amplification in a time- and cost-effective manner.

Geotechnical engineering data are usually small-sample and high-dimensional, which brings a lot of challenges in predictive modeling. This paper uses a typical high-dimensional and small-sample swell pressure (Ps) dataset to explore the possibility of using multi-algorithm hybrid ensemble and dimensionality reduction methods to mitigate the uncertainty of soil parameter prediction. Based on six machine learning (ML) algorithms, the base learner pool is constructed, and four ensemble methods, Stacking (SG), Blending (BG), Voting regression (VR), and Feature weight linear stacking (FWL), are used for the multi-algorithm ensemble. Furthermore, the importance of permutation is used for feature dimensionality reduction to mitigate the impact of weakly correlated variables on predictive modeling. The results show that the proposed methods are superior to traditional prediction models and base ML models, where FWL is more suitable for modeling with small-sample datasets, and dimensionality reduction can simplify the data structure and reduce the adverse impact of the small-sample effect, which points the way to feature selection for predictive modeling. Based on the ensemble methods, the feature importance of the five primary factors affecting Ps is the maximum dry density (31.145%), clay fraction (15.876%), swell percent (15.289%), plasticity index (14%), and optimum moisture content (13.69%), the influence of input parameters on Ps is also investigated, in line with the findings of the existing literature.

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative disorders. The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72 (C9orf72) is the most genetic cause of both ALS and FTD. According to the previous studies, GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation, which produces dipeptide repeat (DPR) proteins. Although there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD, whether these DPRs can affect autophagy remains unclear. In the present study, we find that poly-GR and poly-PR, two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies, strongly inhibit starvation-induced autophagy. Moreover, our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation, therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in cells. Importantly, our study not only highlights the role of C9orf72 DPR in autophagy dysfunction, but also provides novel insight that pharmacological intervention of autophagy using SW063058, a small molecule compound that can disrupt the interaction between BECN1 and BCL2, may reduce C9orf72 DPR-induced neurotoxicity.

Abstract Background While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype. Results The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy − Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the − 600 to − 1200 segment, in which the four SNPs were located. Conclusions The morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.

Abstract The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared metabolic pathways and the importance of these pathways in cancer development. Based on the gut microbiota-related metabolic pathways, human gene expression profile and patient prognosis, we established a novel BC subtyping system and identified a subtype called “challenging BC”. Tumours with this subtype have more genetic mutations and a more complex immune environment than those of other subtypes. A score index was proposed for in-depth analysis and showed a significant negative correlation with patient prognosis. Notably, activation of the TPK1-FOXP3-mediated Hedgehog signalling pathway and TPK1-ITGAE-mediated mTOR signalling pathway was linked to poor prognosis in “challenging BC” patients with high scores, as validated in a patient-derived xenograft (PDX) model. Furthermore, our subtyping system and score index are effective predictors of the response to current neoadjuvant therapy regimens, with the score index significantly negatively correlated with both treatment efficacy and the number of immune cells. Therefore, our findings provide valuable insights into predicting molecular characteristics and treatment responses in “challenging BC” patients.

Abstract Featuring low power loss and high reliability, voltage source converter medium voltage direct current (VSC-MVDC) systems have been widely employed for grid-tied renewable energy applications. To maintain high operational safety, circuit breakers are needed to isolate faulted powerlines by comprehensively considering response speed and installation cost. Research efforts have been put to realizing DC fault isolation by coordinating resistive type superconducting fault current limiter (R-SFCL) and integrated-gate-commutated-thyristor (IGCT) based hybrid DC circuit breaker. In this paper, a controllable current commutation based superconducting DC circuit breaker (CCCB-SDCCB) is proposed. By integrating R-SFCL with IGCT based hybrid DC circuit breakers, the current interrupting capacity can be greatly enlarged with the advantage of low cost and fast speed, and hence the overall cost for suppress large fault currents can be greatly reduced for MVDC systems. In addition, a new current injection circuit branch using H-bridge structure is designed to recycle the residual capacitor voltage from the previous fault stage to trigger the IGCTs without the capacitor pre-charging process. Simulation results show that the fault current can be successfully suppressed from 24.2 to 2.1 kA and fully interrupted within 4.11 ms by the proposed CCCB-SDCCB.

Abstract Ovarian Hyperstimulation Syndrome (OHSS) is a systemic condition marked by the enlargement of the ovaries and heightened vascular permeability. And hypothyroidism (HT) emerges as a potential risk factor for OHSS occurrence. This review presented a comprehensive summary of pertinent case reports involving patients diagnosed with both HT and OHSS. Detailed exploration was conducted into their clinical presentations, diagnostic methodologies, and treatment modalities. Additionally, the review delved into potential interaction mechanisms between HT and OHSS, encompassing various aspects including hormone levels. Moreover, management strategies for mitigating the risk of OHSS in HT patients were thoroughly reviewed and the importance of monitoring thyroid function in those experiencing OHSS was emphasized. This review indicated that the association between HT and OHSS, underscoring its multifaceted complexity. It could accentuate the ongoing necessity for rigorous research and clinical refinement to deepen our comprehension of this association and to bolster diagnostic and therapeutic methodologies for optimal patient care. In conclusion, this review offered valuable insights for future research directions and clinical practices for patients afflicted with OHSS and HT.

As advanced silicon manufacturing processes slow down in scaling, three-dimensional stacking of chips has become a future trend in microelectronic industry. High-density bonding technology is one of the core technologies used to achieve the stacking. In this work, we explored a new bonding technology that is possible to manufacture future high-density interconnects. We fabricated a series of sandwich structure solder joints with different thicknesses using SnBiIn-based nanoparticles under a low bonding temperature of 100 °C. The intermetallic compound (IMC) at the interface is proven to be η′-Cu6(Sn, In)5 nanocrystals with random grain orientations through X-ray diffraction (XRD), high-resolution transmission electron microscope (HRTEM), and atomic probe tomography (APT). The hardness and elastic modulus of η′-Cu6(Sn, In)5 were measured to be 4.093 GPa and 79.586 GPa by micropillar compression tests, respectively, decreasing by 35% and 29.1% compared to Cu6Sn5. Therefore, doping In atoms reduces the brittleness of IMCs, providing a new approach for mitigating the mechanical failures of full IMC bump. First-principles calculation also verified the change in mechanical properties. Furthermore, a full-Cux(Sn, In)y IMCs solder joint and an array of 3 μm solder joints were fabricated experimentally using the bonding technology. This technology successfully demonstrates a pioneer interconnection bonding methodology for future ultra-high-density chip stacking using low melting point solder nanoparticles.

Biochar-assisted anaerobic digestion (AD) remains constrained due to the inefficient decomposition of complex organics, even with the direct interspecies electron transfer (DIET) pathway. The coupling of electrochemistry with the anaerobic biological treatment could shorten lengthy retention time in co-digestion by improving electron transfer rates and inducing functional microbial acclimation. Thus, this work investigated the potential of improving the performance of AD by coupling low-magnitude electric fields with biochar derived from the anaerobically digested biogas residue. Different voltages (0.3, 0.6, and 0.9 V) were applied at various stages to assess the impact on biochar-assisted AD. The results indicate that an external voltage of 0.3 V, coupled with 5 g/L of biochar, elevates CH4 yield by 45.5% compared to biogas residue biochar alone, and the coupled approach increased biogas production by up to 143% within 10 days. This finding may be partly explained by the enhanced utilization of substrates and the increased amounts of specific methanogens such as Methanobacterium and Methanosarcina. The abundance of the former increased from 4.0 to 11.3%, which enhances the DIET between microorganisms. Furthermore, the coupling method shows better potential for enhancing AD compared to preparing iron-based biochar, and these results present potential avenues for its broader applications. HIGHLIGHTS Biochar coupled with electric fields was used to enhance AD.; Coupling of biogas residue biochar and electric fields accelerated the initiation of AD.; The coupled approach improved biogas production by 143% within 10 days.; The abundance of DIET-mediated Methanobacterium was improved to 11.27%.;

Abstract Background Sacituzumab govitecan (SG) has recently been approved in China for the post-line treatment of metastatic triple-negative breast cancer (mTNBC). SG substantially improves progression-free survival and overall survival compared with single-agent chemotherapy for pretreated mTNBC. However, in view of the high price of SG, it is necessary to consider its value in terms of costs and outcomes. This study aimed to estimate the cost-effectiveness of SG versus single-agent treatment of physician’s choice (TPC) in the post-line setting for patients with mTNBC from a Chinese healthcare system perspective. Methods The cohort characteristics were sourced from the ASCENT randomized clinical trial, which enrolled 468 heavily pretreated patients with mTNBC between November 2017 and September 2019. A partitioned survival model was constructed to assess the long-term costs and effectiveness of SG versus TPC in the post-line treatment of mTNBC. Quality-adjusted life-months (QALMs) and total costs in 2022 US dollars were used to derive incremental cost effectiveness ratio (ICER). QALMs and costs were discounted at 5% annually. The willingness-to-pay (WTP) threshold was defined as $3188 per QALM, three times China’s average monthly per capita gross domestic product in 2022. One-way sensitivity analysis, probabilistic sensitivity analysis, and scenario analyses were performed to estimate the robustness of the results. Results Treatment with SG yielded an incremental 5.17 QALMs at a cost of $44,792 per QALM, much above the WTP threshold of $3188/QALM in China. One-way sensitivity analysis showed that SG price was a crucial factor in the ICER. Probabilistic sensitivity analysis revealed that the cost-effective acceptability of SG was 0% in the current setting. Scenario analyses indicated that the result was robust in all subgroups in ASCENT or under different time horizons. Furthermore, SG must reduce the price to enter the Chinese mainland market. When the monthly cost of SG reduce to $2298, SG has about 50% probability to be a preferred choice than TPC. Conclusions SG was estimated to be not cost-effective compared with TPC for post-line treatment for mTNBC in China by the current price in HK under a WTP threshold of $3188 per QALM. A drastic price reduction is necessary to improve its cost-effectiveness.

Abstract The oxidative potential (OP) of particulate matter (PM) is a major driver of PM-associated health effects. In India, the emission sources defining PM-OP, and their local/regional nature, are yet to be established. Here, to address this gap we determine the geographical origin, sources of PM, and its OP at five Indo-Gangetic Plain sites inside and outside Delhi. Our findings reveal that although uniformly high PM concentrations are recorded across the entire region, local emission sources and formation processes dominate PM pollution. Specifically, ammonium chloride, and organic aerosols (OA) from traffic exhaust, residential heating, and oxidation of unsaturated vapors from fossil fuels are the dominant PM sources inside Delhi. Ammonium sulfate and nitrate, and secondary OA from biomass burning vapors, are produced outside Delhi. Nevertheless, PM-OP is overwhelmingly driven by OA from incomplete combustion of biomass and fossil fuels, including traffic. These findings suggest that addressing local inefficient combustion processes can effectively mitigate PM health exposure in northern India.

Abstract Drug addiction represents a multifaceted and recurrent brain disorder that possesses the capability to create persistent and ineradicable pathological memory. Deep brain stimulation (DBS) has shown a therapeutic potential for neuropsychological disorders, while the precise stimulation targets and therapeutic parameters for addiction remain deficient. Among the crucial brain regions implicated in drug addiction, the dorsal raphe nucleus (DRN) has been found to exert an essential role in the manifestation of addiction memory. Thus, we investigated the effects of DRN DBS in the treatment of addiction and whether it might produce side effects by a series of behavioral assessments, including methamphetamine priming-induced reinstatement of drug seeking behaviors, food-induced conditioned place preference (CPP), open field test and elevated plus-maze test, and examined brain activity and connectivity after DBS of DRN. We found that high-frequency DBS of the DRN significantly lowered the CPP scores and the number of active-nosepokes in the methamphetamine-primed CPP test and the self-administration model. Moreover, both high-frequency and sham DBS group rats were able to establish significant food-induced place preference, and no significant difference was observed in the open field test and in the elevated plus-maze test between the two groups. Immunofluorescence staining and functional magnetic resonance imaging revealed that high-frequency DBS of the DRN could alter the activity and functional connectivity of brain regions related to addiction. These results indicate that high-frequency DBS of the DRN effectively inhibits methamphetamine priming-induced relapse and seeking behaviors in rats and provides a new target for the treatment of drug addiction.

Abstract The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Abstract Temporary neurological dysfunction (TND), a common complication following surgical repair of Type A Aortic Dissection (TAAD), is closely associated with increased mortality and long-term cognitive impairment. Currently, effective treatment options for TND remain elusive. Therefore, we sought to investigate the potential of postoperative relative band power (RBP) in predicting the occurrence of postoperative TND, with the aim of identifying high-risk patients prior to the onset of TND. We conducted a prospective observational study between February and December 2022, involving 165 patients who underwent surgical repair for TAAD at our institution. Bedside Quantitative electroencephalography (QEEG) was utilized to monitor the post-operative brain electrical activity of each participant, recording changes in RBP (RBP Delta, RBP Theta, RBP Beta and RBP Alpha), and analyzing their correlation with TND. Univariate and multivariate analyses were employed to identify independent risk factors for TND. Subsequently, line graphs were generated to estimate the incidence of TND. The primary outcome of interest was the development of TND, while secondary outcomes included intensive care unit (ICU) admission and length of hospital stay. A total of 165 patients were included in the study, among whom 68 (41.2%) experienced TND. To further investigate the independent risk factors for postoperative TND, we conducted both univariate and multivariate logistic regression analyses on all variables. In the univariate regression analysis, we identified age (Odds Ratio [OR], 1.025; 95% CI, 1.002–1.049), age ≥ 60 years (OR, 2.588; 95% CI, 1.250–5.475), hemopericardium (OR, 2.767; 95% CI, 1.150–7.009), cardiopulmonary bypass (CPB) (OR, 1.007; 95% CI, 1.001–1.014), RBP Delta (OR, 1.047; 95% CI, 1.020–1.077), RBP Alpha (OR, 0.853; 95% CI, 0.794–0.907), and Beta (OR, 0.755; 95% CI, 0.649–0.855) as independent risk factors for postoperative TND. Further multivariate regression analyses, we discovered that CPB time ≥ 180 min (OR, 1.021; 95% CI, 1.011–1.032), RBP Delta (OR, 1.168; 95% CI, 1.105–1.245), and RBP Theta (OR, 1.227; 95% CI, 1.135–1.342) emerged as independent risk factors. TND patients had significantly longer ICU stays (p