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Abstract In this study, the corrosion electrochemistry and corrosion behavior of two steels were studied under the simulated alumina production conditions. The corrosion rate of 16Mn steel is greater than that of Q235 steel. The effect of S2− concentration on corrosion rate was significantly higher than that of S2O3 2−. The synergistic corrosion rates of Q235 and 16Mn steels increase at first and then decrease with the sulfur content, and the peak value appears when the concentration of S2− and S2O3 2− is 4 g/L and 3 g/L respectively. There are two main types of corrosion products: one is surface octahedral grain, which is composed of Fe2O3, Fe3O4 and Al2O3.The other is the interlayer corrosion between the surface layer and the matrix, which is composed of FeS, FeS2 and NaFeO2.The formation mechanism of the corrosion and corrosion mechanism were obtained by analyzing the phenomenon of ion competitive adsorption. Further validation and analysis of ion competition adsorption phenomenon were conducted using first-principles calculations based on density functional theory (DFT). The formation of corrosion products on the steel surface was investigated at an ion level, and the adsorption energies of OH− and S2− at the top site of Fe(110) surface were calculated. It was found that S2− is more likely to be adsorbed on the Fe(110) surface compared to OH−. The corrosion mechanism of steel is discussed preliminarily.

BackgroundCardiomyocyte senescence plays a crucial role as a pathological mechanism in heart failure (HF). However, the exact triggering factors and underlying causes of HF onset and progression are still not fully understood.ObjectivesBy integrating multi-omics data, this study aimed to determine the genetic associations between cardiomyocyte and HF using cell senescence-related genes (SRGs).MethodsThe study utilized the CellAge database and the SenMayo dataset, combined with high-resolution single-cell RNA sequencing (scRNA-seq) data, to identify SRG and examine differences in cardiac cell expression. To explore the causal relationship with HF using Mendelian Randomization (MR). Genetic variations influencing gene expression, DNA methylation, and protein expression (cis-eQTL, cis-mQTL, and cis-pQTL) were analyzed using the two-sample MR (TSMR) and summary-data-based MR (SMR). Additionally, Bayesian colocalization analysis, germline genetic variation, and bulk RNA data were employed to strengthen the reliability of the results. The application potential of therapeutic targets is ultimately assessed by evaluating their druggability.ResultsThe expression of 39 SRGs in cardiomyocytes was identified. In the discovery set revealed that CDKN1A (OR = 1.09, 95% confidence interval (CI) 1.02–1.15, FDR = 0.048) could be causally related to HF, and the results are also replicated in the validation set (OR = 1.20, 95% confidence interval (CI) 1.10–1.30, FDR

In recent years, ferroptosis has gradually attracted increasing attention because of its important role in tumors. Ferroptosis resistance is an important cause of tumor metastasis, recurrence and drug resistance. Exploring the initiating factors and specific mechanisms of ferroptosis has become a key strategy to block tumor progression and improve drug sensitivity. As the external space in direct contact with tumor cells, the tumor microenvironment has a great impact on the biological function of tumor cells. The relationships between abnormal environmental characteristics (hypoxia, lactic acid accumulation, etc.) in the microenvironment and ferroptosis of tumor cells has not been fully characterized. This review focuses on the characteristics of the tumor microenvironment and summarizes the mechanisms of ferroptosis under different environmental factors, aiming to provide new insights for subsequent targeted therapy. Moreover, considering the presence of anticancer drugs in the microenvironment, we further summarize the mechanisms of ferroptosis to provide new strategies for the sensitization of tumor cells to drugs.

Owing to the rapid progress of science and technology, microelectronic devices characterized by high integration and exceptional performance have assumed crucial roles in various industrial fields such as aeronautics, astronautics, energy, medicine, and automobiles. As these devices constantly evolve, the issue of effective thermal management becomes increasingly of utmost importance, specifically in the case of high heat flux. Traditional cooling methods, such as air and liquid cooling, show notable disadvantages. They not only consume significant power but also present lower heat dissipation efficiency. These limitations considerably threaten the stability and reliability of microelectronic devices. Recently, numerous approaches to enhancing heat transfer have been proposed, encompassing both passive strategies, such as nanofluids, surface roughness, and heating element structures, and active techniques involving acoustic, electric, and magnetic fields. Among these approaches, the use of nanofluids stands out due to their inherent advantages, including cost-effectiveness, flexibility, and versatile applications. Aiming to address the low thermal conductivity of basic working fluids such as water, ethylene glycol, and mineral oil, researchers have developed a series of particulate forms including but not limited to silica dioxide (SiO2), aluminum oxide (Al2O3), titanium dioxide (TiO2), carbon nanotubes, copper (Cu), silver (Ag), silicon carbide (SiC), nanodiamond, zinc oxide (ZnO), magnesium oxide (MgO), and cupric oxide (CuO). These materials have led to nanofluids, which can be classified into mono nanofluids and hybrid nanofluids based on the particle composition. Hybrid nanofluids include at least two nanoparticle types. The unique advantages stemming from their mechanical and chemical stability, diverse structural configurations, and varied preparation techniques have significantly fascinated researchers. Currently, hybrid nanofluids present outstanding intensification performance across both single-phase and two-phase heat transfer processes. Some of them have superior performance to their mononanofluids due to the collaborative interplay of diverse nanoparticles. These characteristics enable hybrid nanofluids as promising candidates for diverse technological areas such as national defense, air-conditioner systems, semiconductors, mechanical manufacturing and materials. Combining hybrid nanofluids with heat transfer methodologies has also garnered considerable attention and is gradually evolving into a crucial direction for heat transfer improvement. In this study, we present a comprehensive overview of the research progress on enhancing the heat transfer process with hybrid nanofluids. First, the preparation techniques for hybrid nanofluids encompass both one-step and two-step methodologies, with a focus on emerging innovative approaches. Furthermore, the physical and chemical characteristics (including but not limited to stability, viscosity, and thermal performance) are reviewed. A detailed discussion of the principle of thermal enhancement is presented. Moreover, this review summarizes the applications of hybrid nanofluids in effectively managing heat within microelectronic devices, solar energy, and heat exchangers. Finally, we outline some challenges in this field and further directions for the advancements of hybrid nanofluids.

Cross-domain unmanned cluster is a disruptive new combat mode in the future, and its combat effectiveness is greatly affected by communication networking capabilities. In recent years, satellite Internet, with its technological advantages of wide coverage, low latency, high bandwidth, and low cost, has developed rapidly in the world, and it is the key to further developing the cross-domain unmanned cluster combat mode. In view of the development trend and practical needs of the future unmanned undersea system, the development and technical advantages of satellite Internet, as well as the concept of cross-domain unmanned cluster combat were introduced. The advantages of cross-domain unmanned cluster combat supported by satellite Internet were deeply analyzed. The air-sea cross-domain unmanned cluster combat network was proposed by combining satellite Internet technology and unmanned clusters in airspace, sea surface, and undersea combat domains. In addition, a comprehensive analysis of the technical architecture was given, providing a reference for future research on cross-domain unmanned cluster combat.

In this paper, we consider parameter estimation, kink points testing and statistical inference for a longitudinal multi-kink expectile regression model with nonignorable dropout. In order to accommodate both within-subject correlations and nonignorable dropout, the bias-corrected generalized estimating equations are constructed by combining the inverse probability weighting and quadratic inference function approaches. The estimators for the kink locations and regression coefficients are obtained by using the generalized method of moments. A selection procedure based on a modified BIC is applied to estimate the number of kink points. We theoretically demonstrate the number selection consistency of kink points and the asymptotic normality of all estimators. A weighted cumulative sum type statistic is proposed to test the existence of kink effects at a given expectile, and its limiting distributions are derived under both the null and the local alternative hypotheses. Simulation studies show that the proposed estimators and test have desirable finite sample performance in both homoscedastic and heteroscedastic errors. An application to the Nation Growth, Lung and Health Study dataset is also presented.

Integrating microchannel flow boiling heat transfer with nanofluids is an effective method for cooling electronic devices. However, traditional methods have significant limitations in achieving facile synthesis of nanofluids with desirable properties. In this study, we propose a straightforward synthesis strategy using microfluidic reactors, which enables continuous and high-throughout synthesis of Al2O3 nanofluids with high purity and long-term stability. These nanofluids were found to enhance boiling heat transfer performance by delaying bubbles coalescence, increasing surface nucleation sites, improving the nucleation rate, and enhancing wettability by observation of the bubble behavior. Specifically, the critical heat flux (CHF) and corresponding heat transfer coefficient (HTC) are increased by a maximum of 32 % and 26 %, respectively, with negligible change in pressure drop. Moreover, the heat transfer performance deteriorates with increasing concentration of alumina nanofluids. These findings not only provide guidance of microchannel flow boiling with nanofluids, but also present valuable insights for the application of nanofluids in two-phase cooling systems for electronic devices.

Abstract Minimally invasive testing is essential for early cancer detection, impacting patient survival rates significantly. Our study aimed to establish a pioneering cell-free immune-related miRNAs (cf-IRmiRNAs) signature for early cancer detection. We analyzed circulating miRNA profiles from 15,832 participants, including individuals with 13 types of cancer and control. The data was randomly divided into training, validation, and test sets (7:2:1), with an additional external test set of 684 participants. In the discovery phase, we identified 100 differentially expressed cf-IRmiRNAs between the malignant and non-malignant, retaining 39 using the least absolute shrinkage and selection operator (LASSO) method. Five machine learning algorithms were adopted to construct cf-IRmiRNAs signature, and the diagnostic classifies based on XGBoost algorithm showed the excellent performance for cancer detection in the validation set (AUC: 0.984, CI: 0.980–0.989), determined through 5-fold cross-validation and grid search. Further evaluation in the test and external test sets confirmed the reliability and efficacy of the classifier (AUC: 0.980 to 1.000). The classifier successfully detected early-stage cancers, particularly lung, prostate, and gastric cancers. It also distinguished between benign and malignant tumors. This study represents the largest and most comprehensive pan-cancer analysis on cf-IRmiRNAs, offering a promising non-invasive diagnostic biomarker for early cancer detection and potential impact on clinical practice.

Abstract Background More efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status. Methods Twenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status. Results After stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI. Conclusions In addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status.

Abstract Alzheimer’s disease (AD) is an age-related neurodegenerative disorder that poses a significant burden on socio-economic and healthcare systems worldwide. However, the currently available therapy of AD is limited, and new strategies are needed to enhance the clearance of β-amyloid (Aβ) protein and improve cognitive function. Photobiomodulation (PBM) is a non-invasive and effective therapeutic method that has shown promise in treating various brain diseases. Here, we demonstrate that 1267-nm PBM significantly alleviates cognitive decline in the 5xFAD mouse model of AD and is safe as it does not induce a significant increase in cortical temperature. Moreover, with the combination of 3D tissue optical clearing imaging and automatic brain region segmentation, we show that PBM-mediated reductions of Aβ plaques in different subregions of prefrontal cortex and the hippocampus are different. The PBM-induced lymphatic clearance of Aβ from the brain is associated with improvement of memory and cognitive functions in 5xFAD mice. Our results suggest that the modulation of meningeal lymphatic vessels (MLVs) should play an important role in promoting Aβ clearance. Collectively, this pilot study demonstrates that PBM can safely accelerate lymphatic clearance of Aβ from the brain of 5xFAD mice, promoting improvement of neurocognitive status of AD animals suggesting that PBM can be an effective and bedside therapy for AD. Graphical Abstract

Abstract Interrogation of subcellular biological dynamics occurring in a living cell often requires noninvasive imaging of the fragile cell with high spatiotemporal resolution across all three dimensions. It thereby poses big challenges to modern fluorescence microscopy implementations because the limited photon budget in a live-cell imaging task makes the achievable performance of conventional microscopy approaches compromise between their spatial resolution, volumetric imaging speed, and phototoxicity. Here, we incorporate a two-stage view-channel-depth (VCD) deep-learning reconstruction strategy with a Fourier light-field microscope based on diffractive optical element to realize fast 3D super-resolution reconstructions of intracellular dynamics from single diffraction-limited 2D light-filed measurements. This VCD-enabled Fourier light-filed imaging approach (F-VCD), achieves video-rate (50 volumes per second) 3D imaging of intracellular dynamics at a high spatiotemporal resolution of ~180 nm × 180 nm × 400 nm and strong noise-resistant capability, with which light field images with a signal-to-noise ratio (SNR) down to -1.62 dB could be well reconstructed. With this approach, we successfully demonstrate the 4D imaging of intracellular organelle dynamics, e.g., mitochondria fission and fusion, with ~5000 times of observation.

Abstract The dysfunction of microglia in the development of diabetes is associated with various diabetic complications, while traditional insulin therapy is insufficient to rapidly restore the function of microglia. Therefore, the search for new alternative methods of treating diabetes-related dysfunction of microglia is urgently needed. Here, we evaluate the effects of transcranial photobiomodulation (tPBM) on microglial function in diabetic mice and investigate its mechanism. We find tPBM treatment effectively improves insulin therapy on microglial morphology and reactivity. We also show that tPBM stimulates brain drainage system through activation of meningeal lymphatics, which contributes to the removal of inflammatory factor, and increase of microglial purinergic receptor P2RY12. Besides, the energy expenditure and locomotor activity of diabetic mice are also improved by tPBM. Our results demonstrate that tPBM can be an efficient, non-invasive method for the treatment of microglial dysfunction caused by diabetes, and also has the potential to prevent diabetic physiological disorders.

BackgroundThe triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, is significantly associated with chronic kidney disease (CKD). However, there is limited research on the longitudinal trajectory of TyG index over time and its relationship with CKD.ObjectiveTo analyse the characteristics of the longitudinal trajectory of the TyG index over time and its association with the development of CKD in a health check-up population.MethodsParticipants who underwent at least three annual health check-ups at the Health Management Center of Sichuan Provincial People’s Hospital from 2015 to 2022 were included in this retrospective cohort study. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The latent class mixed model (LCMM) was used to identify the TyG index trajectory of the study population. A Cox proportional hazard model was used to estimate the CKD incidence risk in different quartile groups and the association of changes in the TyG index trajectory with the development of CKD.ResultsA total of 4,921 participants were included in this study, and they were divided into four groups according to the quartiles of the baseline TyG index: Q1 (5.43-6.66), Q2 (6.67-7.04), Q3 (7.05-7.43), and Q4 (7.43-9.97). There was no difference in the risk of CKD occurrence among the TyG groups. Three different TyG index trajectories were identified in this study: a high-level group, middle-level stable group and low-level stable group, respectively. The incidence rate of CKD in the high-level TyG index trajectory group was 2.399 times greater than that in the low-level stable trajectory group (HR=2.399, 95% CI 1.167-4.935).ConclusionIndividuals with long-term exposure to high TyG index levels had a significantly greater risk of CKD. Routine monitoring of the TyG index and its longitudinal trend will aid in the risk stratification of CKD in the general population and will be helpful for CKD prevention and targeted management.

Abstract Bacterial σI factors of the σ70-family are widespread in Bacilli and Clostridia and are involved in the heat shock response, iron metabolism, virulence, and carbohydrate sensing. A multiplicity of σI paralogues in some cellulolytic bacteria have been shown to be responsible for the regulation of the cellulosome, a multienzyme complex that mediates efficient cellulose degradation. Here, we report two structures at 3.0 Å and 3.3 Å of two transcription open complexes formed by two σI factors, SigI1 and SigI6, respectively, from the thermophilic, cellulolytic bacterium, Clostridium thermocellum. These structures reveal a unique, hitherto-unknown recognition mode of bacterial transcriptional promoters, both with respect to domain organization and binding to promoter DNA. The key characteristics that determine the specificities of the σI paralogues were further revealed by comparison of the two structures. Consequently, the σI factors represent a distinct set of the σ70-family σ factors, thus highlighting the diversity of bacterial transcription.

Abstract Intraventricular hemorrhage is one of the most fatal forms of brain injury that is a common complication of premature infants. However, the therapy of this type of hemorrhage is limited, and new strategies are needed to reduce hematoma expansion. Here we show that the meningeal lymphatics is a pathway to remove red blood cells from the brain’s ventricular system of male human, adult and newborn rodents and is a target for non-invasive transcranial near infrared photobiomodulation. Our results uncover the clinical significance of phototherapy of intraventricular hemorrhage in 4-day old male rat pups that have the brain similar to a preterm human brain. The course of phototherapy in newborn rats provides fast recovery after intraventricular hemorrhage due to photo-improvements of lymphatic drainage and clearing functions. These findings shed light on the mechanisms of phototherapy of intraventricular hemorrhage that can be a clinically relevant technology for treatment of neonatal intracerebral bleedings.

Infant intestinal microbiome is closely linked with health and risk of disease. Bifidobacterium are important components of the infant gut and are known to confer various health effects on the host. However, few studies have described the precise composition and dynamics of early infant gut bifidobacterial communities. Thus, this was a pilot study aiming to describe the developmental trajectories and temporal dynamics of bifidobacterial communities in infants before 6 months of age. A total of 28 fecal samples from 4 infants (GF, ZZ, QM, TN, respectively) were collected and analyzed after 5, 15, 30, 60, 90, 120, 150, and 180 days of birth by a bifidobacteria-target method (based on single-molecule real-time sequencing of partial bifidobacterial rpsK genes) in conjunction with droplet digital polymerase chain reaction (ddPCR). The infant fecal microbiota comprised a total of 11 bifidobacterial species, including 4 major species, i.e., B. dentium (37.35 %), B. catenulatum (32.04 %), B. breve (22.24 %), and B. animalis (8.02 %). The infant microbiota showed highly individualized developmental trajectories. The leading species for GF was B. catenulatum, with a relatively stable developmental trajectory. In ZZ, B. breve was enriched, and the developmental trajectory was rather fluctuating. The most abundant species for QM and TN was B. dentium. The developmental trajectory of B. dentium in QM showed a trend of gradual decrease, whereas an opposite trend was seen in samples of TN. The results of ddPCR confirmed large variations in quantities of bifidobacteria between infants and suggested discordances in temporal dynamics of bifidobacterial communities during the first half year of infancy. In conclusion, our results suggested that the early infant gut bifidobacterial microbiota was highly complex and temporal dynamics, with individualized developmental trajectories, which should be considered in future research of infant gut microbiota.

IntroductionBeta-amyloid accumulation in the brain appears to be a key initiating event in Alzheimer’s disease (AD), and factors associated with increased deposition of beta-amyloid are of great interest. Enhanced deposition of amyloid-β peptides is due to an imbalance between their production and elimination. Previous studies show that diminished levels of CSF amyloid beta 42 (Aβ42) is a biomarker in AD; however, the role of serum Aβ42 in AD is contradictory. BMI and obesity have been reported to be related to increased serum Aβ42 levels. Therefore, we aimed to investigate the relation between metabolic syndrome (MetS), its clinical measures (abdominal obesity, high glucose, high triglyceride, low high-density lipoprotein cholesterol level, and hypertension), and serum Aβ42 levels.MethodsA total of 1261 subjects, aged 18–89 years in Chengdu, China, were enrolled from January 2020 to January 2021 to explore the correlation of serum Aβ42 levels with body mass index (BMI), blood lipids, and blood pressure. Furthermore, as the risk of MetS is closely related to age, 1,212 participants (N = 49 with age ≥ 80 years old were excluded) were analyzed for the correlation of serum Aβ42 level and MetS clinical measures.ResultsThe results showed that log-transformed serum Aβ42 level was positively correlated with BMI (R = 0.29; p < 0.001), log-transformed triglyceride (R = 0.14; p < 0.001), and diastolic blood pressure (DBP) (R = 0.12; p < 0.001) and negatively correlated with high-density lipoprotein (HDL-c) (R = −0.18; p < 0.001). After adjusting for age, sex, and other covariates, elevated serum Aβ42 level was correlated with higher values of BMI (βmodel1 = 2.694, βmodel2 = 2.703) and DBP (βmodel1 = 0.541, βmodel2 = 0.546) but a lower level of HDL-c (βmodel2 = −1.741). Furthermore, serum Aβ42 level was positively correlated with MetS and its clinical measures, including BMI and DBP, and negatively correlated with HDL-c level in the Han Chinese population. However, the level of serum Aβ42 did not show a significant correlation with high glucose or high triglyceride.DiscussionThese observations indicate that MetS and its components are associated with higher levels of serum Aβ42 and hence limit the potential of serum Aβ42 as a suitable diagnostic biomarker for AD. As such, we recommend serum Aβ42 serve as a direct risk biomarker for MetS rather than for AD.

Cancer stem cells are the key link between malignant tumor progression and drug resistance. This cell population has special properties that are different from those of conventional tumor cells, and the role of cancer stem cell-related exosomes in progression of tumor malignancy is becoming increasingly clear. Cancer stem cell-derived exosomes carry a variety of functional molecules involved in regulation of the microenvironment, especially with regard to immune cells, but how these exosomes exert their functions and the specific mechanisms need to be further clarified. Here, we summarize the role of cancer stem cell exosomes in regulating immune cells in detail, aiming to provide new insights for subsequent targeted drug development and clinical strategy formulation.

Abstract Cryo-electron tomography (cryo-ET) is widely used to explore the 3D density of biomacromolecules. However, the heavy noise and missing wedge effect prevent directly visualizing and analyzing the 3D reconstructions. Here, we introduced REST, a deep learning strategy-based method to establish the relationship between low-quality and high-quality density and transfer the knowledge to restore signals in cryo-ET. Test results on the simulated and real cryo-ET datasets show that REST performs well in denoising and compensating the missing wedge information. The application in dynamic nucleosomes, presenting either in the form of individual particles or in the context of cryo-FIB nuclei section, indicates that REST has the capability to reveal different conformations of target macromolecules without subtomogram averaging. Moreover, REST noticeably improves the reliability of particle picking. These advantages enable REST to be a powerful tool for the straightforward interpretation of target macromolecules by visual inspection of the density and of a broad range of other applications in cryo-ET, such as segmentation, particle picking, and subtomogram averaging.

Abstract Background Dermatomyositis (DM) is an acquired autoimmune disease that can cause damage to various organs, including the heart muscle. However, the mechanisms underlying myocardial injury in DM are not yet fully understood. Methods In this study, we utilized publicly available datasets from the Gene Expression Omnibus (GEO) database to identify hub-genes that are enriched in the immune system process in DM and myocarditis. Weighted gene co-expression network analysis (WGCNA), differentially expressed genes (DEGs) analysis, protein–protein interaction (PPI), and gene ontology (GO) analysis were employed to identify these hub-genes. We then used the CIBERSORT method to analyze immune cell infiltration in skeletal muscle specimens of DM and myocardium specimens of myocarditis respectively. Correlation analysis was performed to investigate the relationship between key genes and infiltrating immune cells. Finally, we predicted regulatory miRNAs of hub-genes through miRNet and validated their expression in online datasets and clinical samples. Results Using integrated bioinformatics analysis, we identified 10 and 5 hub-genes that were enriched in the immune system process in the database of DM and myocarditis respectively. The subsequent intersections between hub-genes were IFIT3, OAS3, ISG15, and RSAD2. We found M2 macrophages increased in DM and myocarditis compared to the healthy control, associating with the expression of IFIT3, OAS3, ISG15, and RSAD2 in DM and myocarditis positively. Gene function enrichment analysis (GSEA) showed that IFIT3, OAS3, ISG15, and RSAD2 were mainly enriched in type I interferon (IFN) signaling pathway, cellular response to type I interferon, and response to type I interferon. Finally, we verified that the expression of miR-146a-5p was significantly higher in the DM with myocardial injury than those without myocardial injury (p = 0.0009). Conclusion Our findings suggest that IFIT3, OAS3, ISG15, and RSAD2 may play crucial roles in the underlying mechanism of myocardial injury in DM. Serum miR-146a-5p could be a potential biomarker for myocardial injury in DM.

In this article, a broadband frequency measurement system based on optical spectrum manipulation and stimulated Brillouin scattering (SBS) is proposed and experimentally demonstrated, which can implement wide-range and high-resolution frequency measurement, and generate corresponding broadband interference signals in some frequency bands, that is, it has versatility. Since the frequency range of the pump light to excite SBS is expanded based on the optical spectrum manipulation and high resolution is ensured by the narrow scattering spectrum of SBS, high-resolution spectrum measurement covering a wide frequency band is finally implemented. In addition, the double sideband pump light can be used as the source of electronic interference signal. In the experiments, the frequency measurement range of the proposed system is tested to be 0.03–44 GHz, and the resolution is up to 3 MHz. Furthermore, the frequency measurement and electronic interference sharing the same work band can be carried out in the ranges of 6.3367–7.8367 GHz and 20.36–22.16 GHz.

(1) Background: It has yet to be determined whether preoperative flexible bronchoscopy (FB) should be routinely performed in patients with peripheral lung cancer. The aim of this study was to construct a model to predict the probability of positive FB findings, which would help assess the necessity of preoperative FB. (2) Methods: A total of 380 consecutive patients with peripheral lung cancer who underwent preoperative FB were recruited for this study. A prediction model was developed through univariate and multivariate logistic regression, with predictors including gender, age, body mass index (BMI), smoking, history of chronic lung diseases, respiratory symptoms, lesion size, lesion type, lesion location in the bronchi, and lesion location in the lobe. The predictive performance of the model was evaluated by validation using 1000 iterations of bootstrap resampling. Model discrimination was assessed using the area under the receiver operating characteristics curve (AUC), and calibration was assessed using the Brier score and calibration plots. (3) Results: The model suggested that male patients with respiratory symptoms, decreased BMI, solid lesions, and lesions located in lower-order bronchi were more likely to have positive FB findings. The AUC and Brier score of the model for internal validation were 0.784 and 0.162, respectively. The calibration curve for the probability of positive FB findings showed convincing concordance between the predicted and actual results. (4) Conclusions: Our prediction model estimated the pretest probability of positive FB findings in patients with peripheral lung cancers. Males and patients with lower BMI, the presence of respiratory symptoms, larger lesions, solid lesions, and lesions located in lower-order bronchi were associated with increased positive FB findings. The use of our model can be of assistance when making clinical decisions about preoperative FB.

Abstract As a systematic investigation of the correlations between physical examination indicators (PEIs) is lacking, most PEIs are currently independently used for disease warning. This results in the general physical examination having limited diagnostic values. Here, we systematically analyzed the correlations in 221 PEIs between healthy and 34 unhealthy statuses in 803,614 individuals in China. Specifically, the study population included 711,928 healthy participants, 51,341 patients with hypertension, 12,878 patients with diabetes, and 34,997 patients with other unhealthy statuses. We found rich relevance between PEIs in the healthy physical status (7662 significant correlations, 31.5%). However, in the disease conditions, the PEI correlations changed. We focused on the difference in PEIs between healthy and 35 unhealthy physical statuses and found 1239 significant PEI differences, suggesting that they could be candidate disease markers. Finally, we established machine learning algorithms to predict health status using 15–16% of the PEIs through feature extraction, reaching a 66–99% accurate prediction, depending on the physical status. This new reference of the PEI correlation provides rich information for chronic disease diagnosis. The developed machine learning algorithms can fundamentally affect the practice of general physical examinations.

A comprehensive assessment of motor function and skeletal muscle development in neonatal mice provides insight into the structural status of the neuromuscular system during motor development.

Background and aimThe association between Helicobacter pylori (H. pylori) infection and metabolic syndrome (MetS) has been studied previously; however, the results remain controversial, which could be partly due to the different criteria used for defining MetS. We adopted five MetS criteria to provide better understanding of the association between H. pylori infection and MetS.MethodsPhysical examination data of 100,708 subjects were obtained from January 2014 to December 2018. MetS was defined based on five criteria including: International Diabetes Federation (IDF), The Third Report of the National Cholesterol Education Program Expert Panel, Adult Treatment Panel III (ATP III), Joint Statement of International Multi-Societies (JIS), Chinese Diabetes Society (CDS), and the Guidelines for the Prevention and Treatment of Type 2 Diabetes in China (2017 edition)(CDS DM). Multivariate logistic regression analysis was performed to elucidate the association between H. pylori infection and MetS and its components.ResultsThe prevalence of MetS defined assessed using IDF, ATP III, JIS, CDS and CDS DM criteria was 15.8%, 19.9%, 23.7%, 8.7% and 15.4%, respectively. In males, the prevalence of MetS assessed using the five criteria in H. pylori-positive group was higher than that in negative-group; however, in females, same results were obtained using the three international criteria. In males, the prevalence of all MetS components was found to be higher in the H. pylori-positive group than those in the negative group; however, in females, only the prevalence of dyslipidemia and waist circumferences exhibited significant differences. Multivariate logistic regression analysis revealed that H. pylori infection in males was positively correlated with MetS. Additionally, H. pylori infection was found to be positively correlated with the waist circumference in the general population, and with hypertension and hyperglycemia in males.ConclusionsH. pylori infection was found to be positively associated with MetS in males in China.

The upconversion color tuning of Lanthanide ions usually requires complex core–shell structures and excitation configurations. This work presents simple Er3+ doped Yttria phosphors capable of color change through the manipulation of 1530 nm excitation intensity. Compared to the reported results of Er3+ color change from green to red with the increase in excitation intensity, the formed color-tunable phosphors show an inverse change of red to green. The color tuning mechanisms are attributed to the competition between the upward absorption and the downward decay at the Er3+ intermediate state. Finally, the potential applications of the formed color-tunable phosphors are demonstrated. This work provides a simple solution for high-performance upconversion color tuning and thus shows wide application prospects.

BackgroundPatients usually suffer acute pain after cardiac surgery. Numerous regional anesthetic techniques have been used for those patients under general anesthesia. The most effective regional anesthetic technique was still unclear.MethodsFive databases were searched, including PubMed, MEDLINE, Embase, ClinicalTrials.gov, and Cochrane Library. The efficiency outcomes were pain scores, cumulative morphine consumption, and the need for rescue analgesia in this Bayesian analysis. Postoperative nausea, vomiting and pruritus were safety outcomes. Functional outcomes included the time to tracheal extubation, ICU stay, hospital stay, and mortality.ResultsThis meta-analysis included 65 randomized controlled trials involving 5,013 patients. Eight regional anesthetic techniques were involved, including thoracic epidural analgesia (TEA), erector spinae plane block, and transversus thoracic muscle plane block. Compared to controls (who have not received regional anesthetic techniques), TEA reduced the pain scores at 6, 12, 24 and 48 h both at rest and cough, decreased the rate of need for rescue analgesia (OR = 0.10, 95% CI: 0.016–0.55), shortened the time to tracheal extubation (MD = −181.55, 95% CI: −243.05 to −121.33) and the duration of hospital stay (MD = −0.73, 95% CI: −1.22 to −0.24). Erector spinae plane block reduced the pain score 6 h at rest and the risk of pruritus, shortened the duration of ICU stay compared to controls. Transversus thoracic muscle plane block reduced the pain scores 6 and 12 h at rest compared to controls. The cumulative morphine consumption of each technique was similar at 24, 48 h. Other outcomes were also similar among these regional anesthetic techniques.ConclusionsTEA seems the most effective regional postoperative anesthesia for patients after cardiac surgery by reducing the pain scores and decreasing the rate of need for rescue analgesia.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, ID: CRD42021276645

Abstract This paper addresses constrained robust control for dynamic positioning of the Liquefied Natural Gas (LNG) Carrier in side‐by‐side offloading operations subject to input time delay. During the LNG offloading operation, the relative motions of the multibody system are connected by the LNG offloading arm. To ensure the operation safety, robust control with asymmetric Barrier Lyapunov Function is proposed considering predefined output constraints under the unknown dynamics and external disturbances. In offshore engineering, due to the mechanical effects, the thrusters of the LNG carrier in the presence of time‐delay should be investigated to guide the design practice. The predictor‐based method is employed to deal with the time delay induced by the control inputs. It is proven that the proposed scheme can guarantee semi‐global uniform ultimate boundedness. The performance and feasibility of the proposed control are further verified by simulation studies.

Social media analytics have played an important role in disaster identification. Recent advances in deep learning (DL) technologies have been applied to design disaster classification models. However, the DL-based models are hindered by insufficient training samples, because data collection and labeling are very expensive and time-consuming. To solve this issue, a privacy-preserving federated transfer learning approach for disaster classification (FedTL) is proposed, which can allow distributed social computing nodes to collaboratively train a comprehensive model. In the FedTL, Paillier homomorphic encryption method is used to protect the social computing nodes’ data privacy. In particular, the transfer learning technology is adopted as a novel application to reduce the computation and communication costs in the federated learning system. The FedTL is verified by a real disaster image dataset collected from social networks. Theoretical analyses and experiment results show that the FedTL is effective, secure, efficient. In addition, the FedTL is highly extensible and can be easily applied in other transfer learning models.

Summary: Efficient labeling of the vasculature is important for understanding the organization of vascular networks. Here, we propose VALID, a vessel-labeling method that enables visualization of vascular networks with tissue clearing and light-sheet microscopy. VALID transforms traditional lipophilic dye solution into hydrogel by introducing gelatin and restrains the dye aggregation, resulting in complete and uniform vessel-labeling patterns with high signal-to-background ratios. VALID also enhances the compatibility of lipophilic dyes with solvent-based tissue-clearing protocols, which was hard to achieve previously. Using VALID, we combined lipophilic dyes with solvent-based tissue-clearing techniques to perform 3D reconstructions of vasculature within mouse brain and spinal cord. We also employed VALID for 3D visualization and quantification of microvascular damage in a middle cerebral artery occlusion mouse model. VALID should provide a simple, cost-effective vessel-labeling protocol that would significantly widen the applications of lipophilic dyes in research on cerebrovascular complications. Motivation: 3D reconstruction of the entire vasculature is fundamental to understanding vascular lesions during the progression of various neurovascular diseases. The combination of vessel-labeling, tissue-clearing, and optical imaging techniques allow 3D mapping of the vasculature of different tissues/organs. Current vessel-specific marker-based labeling methods can provide biological ground truth for blood vessels but are restricted by either insufficient signal-to-background ratios, incomplete labeling for large vessels, or high cost. Perfusion-based methods can serve as useful alternatives with relative high signal-to-background ratios; however, dye leakage has greatly limited their applications. Additionally, the tissue-clearing compatibility of these methods still needs to be improved. Here, we developed VALID, an efficient, easy-handling, and cost-effective protocol that enables complete and uniform labeling of different vasculatures with bright fluorescence.

BackgroundGastric cancer is the most prevalent solid tumor form. Even after standard treatment, recurrence and malignant progression are nearly unavoidable in some cases of stomach cancer. GLIS Family Zinc Finger 3 (GLIS3) has received scant attention in gastric cancer research. Therefore, we sought to examine the prognostic significance of GLIS3 and its association with immune infiltration in gastric cancer.MethodUsing public data from The Cancer Genome Atlas (TCGA), we investigated whether GLIS3 gene expression was linked with prognosis in patients with stomach cancer (STAD). The following analyses were performed: functional enrichment analysis (GSEA), quantitative real-time PCR, immune infiltration analysis, immunological checkpoint analysis, and clinicopathological analysis. We performed functional validation of GLIS3 in vitro by plate cloning and CCK8 assay. Using univariate and multivariate Cox regression analyses, independent prognostic variables were identified. Additionally, a nomogram model was built. The link between OS and subgroup with GLIS3 expression was estimated using Kaplan-Meier survival analysis. Gene set enrichment analysis utilized the TCGA dataset.ResultGLIS3 was significantly upregulated in STAD. An examination of functional enrichment revealed that GLIS3 is related to immunological responses. The majority of immune cells and immunological checkpoints had a positive correlation with GLIS3 expression. According to a Kaplan-Meier analysis, greater GLIS3 expression was related to adverse outcomes in STAD. GLIS3 was an independent predictive factor in STAD patients, as determined by Cox regression (HR = 1.478, 95%CI = 1.478 (1.062-2.055), P=0.02)ConclusionGLIS3 is considered a novel STAD patient predictive biomarker. In addition, our research identifies possible genetic regulatory loci in the therapy of STAD.

Light field microscopy (LFM), featured for high three-dimensional imaging speed and low phototoxicity, has emerged as a technique of choice for instantaneous volumetric imaging. In contrast with other scanning-based three-dimensional (3D) imaging approaches, LFM enables to encode 3D spatial information in a snapshot manner, permitting high-speed 3D imaging that is only limited by the frame rate of the camera. In this review, we first introduce the fundamental theory of LFM and current corresponding advanced approaches. Then, we summarize various applications of LFM in biological imaging.

Summary: Pancreatic amyloid deposits composed of a fibrillar form of the human islet amyloid polypeptide (hIAPP) are the pathological hallmark of type 2 diabetes (T2D). Although various cryo-EM structures of polymorphic hIAPP fibrils were reported, the underlying polymorphic mechanism of hIAPP remains elusive. Meanwhile, the structure of hIAPP fibrils with all residues visible in the fibril core is not available. Here, we report the full-length structures of two different polymorphs of hIAPP fibrils, namely slim form (SF, dimer) and thick form (TF, tetramer), formed in a salt-free environment, which share a similar ζ-shaped protofilament but differ in inter-protofilament interfaces. In the absence of salt, electrostatic interactions were found to play a dominant role in stabilizing the fibril structure, suggesting an antagonistic effect between electrostatic and hydrophobic interactions in different salt concentrations environments. Our results shed light on understanding the mechanism of amyloid fibril polymorphism.

Aims: This study explored the advantages and limitations of novel series of three-dimensional (3D) echocardiographic techniques and summarized their application methods for congenital heart diseases (CHDs).Method and result: Two-dimensional (2D), traditional 3D echocardiography, and TrueVue plus light and/or Glass novel 3D technologies were performed on 62 patients with CHD, and a clinical survey was designed to judge whether the novel 3D images were more helpful for understanding the cardiac condition and guide treatment than traditional 3D images. TrueVue increased the visual resolution and simulated the true texture of cardiac tissue, significantly improving the display ability of abnormal anatomical structures in CHDs. TrueVue Glass displayed the blood channel and the internal structure of cardiac cavity more intuitively, indicating a new observation aspect not shown by conventional echocardiography. The clinical survey results showed that the new 3D imaging methods effectively increased the diagnostic confidence of echocardiographers, enabled surgeons to better understand the details of lesions, promoted efficient communication, and improved the confidence of both doctors and patients in treatment.Conclusion: The combined application of TrueVue, TrueVue Light, and TrueVue Glass more closely simulated real anatomical features, showed more comprehensive and subtle blood flow in the lumen, not only increased the visual effect but also provided more useful diagnostic information, improved the accuracy of evaluation and treatment of CHD when compared to traditional imaging techniques, indicating that this combined application has significant clinical value.

Diabetes mellitus (DM) has become the world’s third major disease after tumors and cardiovascular disease. With the exploitation of marine biological resources, the efficacy of using polysaccharides isolated from marine organisms in blood glucose regulation has received widespread attention. Some marine polysaccharides can reduce blood glucose by inhibiting digestive enzyme activity, eliminating insulin resistance, and regulating gut microbiota. These polysaccharides are mainly fucose-containing sulphated polysaccharides from algae and sea cucumbers. It follows that the hypoglycemic activity of marine fucosyl-polysaccharides is closely related to their structure, such as their sulfate group, monosaccharide composition, molecular weight and glycosidic bond type. However, the structure of marine fucosyl-polysaccharides and the mechanism of their hypoglycemic activity are not yet clear. Therefore, this review comprehensively covers the effects of marine fucosyl-polysaccharides sources, mechanisms and the structure–activity relationship on hypoglycemic activity. Moreover, the potential regulatory effects of fucosyl-polysaccharides on vascular complications caused by hyperglycemia are also summarized in this review. This review provides rationales for the activity study of marine fucosyl-polysaccharides and new insights into the high-value utilization of marine biological resources.

The emergence of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) revolutionized the treatment of advanced-stage non-small cell lung cancer (NSCLC). Detected in more than 50% of late-stage lung adenocarcinoma in Asian patients, the EGFR mutation was regarded as a golden mutation for Asians. However, resistance to TKIs seems inevitable and severely hinders patients from getting further benefits from treatment. Even though resistance caused by EGFR T790M could be effectively managed by third-generation EGFR-TKIs currently, resistance to third-generation EGFR-TKIs is still a troublesome issue faced by both clinicians and patients. Various efforts have been made to maximize the benefits of patients from EGFR-TKIs therapy. Thus, new requirements and challenges have been posed to clinicians of this era. In this review, we summarized the clinical evidence on the efficacy of third-generation EGFR-TKIs in patients with EGFR-mutated NSCLC. Then, we discussed advancements in sequential treatment aiming to delay the onset of resistance. Moreover, the resistance mechanisms and features were depicted to help us better understand our enemies. Lastly, we put forward future strategies, including recent approaches involving the utilization of antibody drug conjugates against resistance and research directions about shaping the evolution of NSCLC as a core idea in the management of NSCLC.

This paper studies motor structures and optimization methods for space robots, proposing an optimized stepped rotor bearingless switched reluctance motor (BLSRM) to solve the poor self-starting ability and significant torque fluctuation issues in traditional BLSRMs. Firstly, the advantages and disadvantages of the 12/14 hybrid stator pole type BLSRM were analyzed, and a stepped rotor BLSRM structure was designed. Secondly, the particle swarm optimization (PSO) algorithm was improved and combined with finite element analysis for motor structure parameter optimization. Subsequently, a performance analysis of the original and new motors was conducted using finite element analysis software, and the results showed that the stepped rotor BLSRM had an improved self-starting ability and significantly reduced torque fluctuation, verifying the effectiveness of the proposed motor structure and optimization method.