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Abstract Background Glutathione plays critical roles in detoxifying xenobiotics, cell signaling, cell death and the antioxidant defence in an emerging body of evidence, the most abundant intracellular low molecular weight thiol in tissues. However, all glutathione metabolism pertinent genes (GMPGs) expression and their diagnostic/prognostic/micropeptide potential analyses have not been investigated to perform in pan-cancers. Methods We gained GMPGs from the MsigDB 7.2, 12,123 samples were used to reveal the differentially expressed genes (DEGs) and the survival analysis in 32 types of cancers from TCGA, GTEx, and GEO datasets for the first time. All statistical analyses were performed by R for bioinformatics, such as DEGs, prognostic, diagnostic analysis, ceRNA, micropeptide prediction and immune infiltration. In addition, we utilized siRNA technology to target knockdown the expression of the G6PD gene in Huh7 hepatocellular carcinoma cells. Results G6PD was significantly expressed and poor prognosis in liver hepatocellular carcinoma (LIHC) and predicted RBM26-AS1 encoded micropeptide might target G6PD in LIHC. In vitro experiments show that G6PD knockout in Huh7 cells reduces their proliferation, migration, and invasion capabilities. Conclusions We confirmed that G6PD played a crucial role in the occurrence and progression of LIHC. G6PD is positively associated with Th2 cells in LIHC, regulating immune responses in the immune system. We considered that micropeptide RBM26-AS1 might be a new player involved in LIHC by interacting with G6PD, might perform a key function in liver cancer.

Titanium alloys are typically processed using various heat treatment or thermomechanical processing to precipitate different nanoscale phases within the matrix through distinct formation mechanisms. During the processing, the association among the processing parameters, formation mechanisms, and types of nanophases is closely related, and the effects of different nanophases on the mechanical properties of titanium alloys vary significantly. Consequently, investigating the processing methods, formation mechanisms, and their relationship with mechanical properties concerning the precipitation of different nanophases in titanium alloys is of paramount importance. Currently, there are relatively few relevant reviews. This article discusses the main formation mechanisms of four nanophases including α phase, α′ phase, α″ phase, and ω phase in the processing of dual-phase titanium alloys, metastable β titanium alloys, and β titanium alloys. It summarizes how the size and number of these nanophases affect the mechanical properties, along with the distinct strengthening mechanisms and their effects on titanium alloys associated with these four nanophases. Furthermore, this review discusses that when nanoscale α′ phase forms in the titanium alloy matrix, the strength of alloys can reach 1200–1600 MPa, while maintaining a good elongation range (9–22%). These findings provide insights for designing high-strength-ductility titanium alloys and are potentially applicable to other titanium alloys.

Higher alcohols are key factors affecting sensory quality and post-drinking comfort of alcoholic beverages. A strategy combining solid-phase extraction and gas chromatography-mass spectrometry (SPE-GC-MS) was established to analyze the metabolism pattern of higher alcohols in rat plasma after gavage of 4 common alcoholic beverages including huangjiu, baijiu, wine and brandy.7 mL of dichloromethane was determined as the optimal extraction condition, and 8 higher alcohols were precisely quantified with detection limits of 1.82−11.65 μg/L, recoveries of 89.07%−110.89% and fine repeatability. The fastest absorption and elimination rates of plasma total higher alcohols were observed in baijiu and huangjiu group, respectively, and the highest peak concentration was found in brandy group. Additionally, the metabolic rate of plasma isoamyl alcohol in huangjiu group was faster than that in wine group at the same intragastric administration dosage. This study may provide potential insight for evaluation of alcoholic beverage quality.

Objective Infrasound is an effective approach for debris flow warning. Traditional threshold-based warning methods focus solely on individual infrasound characteristics, which can lead to false alarms or missed detections. Thus, incorporating multiple time-frequency characteristics is essential to improve warning accuracy. Methods Infrasound data from Caodianshui Village, Beijing, were analyzed to differentiate the infrasound characteristics of debris flows from environmental background. A random forest algorithm was employed to establish an infrasound warning model for debris flows. Results The effective pressure of debris flow infrasound ranges from 0.4 to 1.0 Pa, while environmental infrasound typical remains below 0.1 Pa, though noise can raise it above 0.4 Pa.Noise infrasound energy is primarily concentrated below 6 Hz, whereas debris flow infrasound exhibits significantly higher energy in the 6-15 Hz. Therefore, comprehensive time-frequency characteristics, especially the energy in the range of 6-15 Hz, should be considered when identifying debris flow infrasound. Using effective infrasound pressure, infrasound pressure within 6-15 Hz, zero crossing rate, dominant frequency, and its amplitude as characteristic variables, a debris flow warning model was constructed based on a random forest algorithm. The model achieved an AUC of 0.99, with a 90% recognition accuracy for test data, a 15% improvement over threshold methods. Conclusion The random forest-based infrasound warning model substantially improves warning accuracy for debris flows and is applicable to typical basins in the Beijing mountainous areas. This approach offers a valuable reference for infrasound-based debris flow warning research in other areas.

Abstract The incidence of growth hormone deficiency (GHD) after subarachnoid hemorrhage (SAH) is significantly higher than that of other neuroendocrine disorders, but the mechanism is still elusive. We used mass spectrometry to identify differentially expressed proteins in cerebrospinal fluid samples from a well-characterized cohort of patients. A total of 683 proteins were identified, including 39 upregulated proteins in the GHD group. ADAM9 was most highly associated with GHD. In vivo, ADAM9 colocalized with M1 microglia markers, GH and cognitive ability of mice decreased significantly, and microglia secreted ADAM9 significantly. ADAM9 regulates pyroptosis of GHRH neurons by the Mad2L2-JNK-caspase-1 pathway. Sorafenib inhibits ADAM9 secretion by microglia and improves GH levels and the cognitive ability of mice. This study found that the crosstalk between GHRH neurons and neuroglial cells in the hypothalamic arcuate nucleus, i.e., microglia, is an essential factor in the formation of GHD in SAH. We propose that neutralization of ADAM9 production by microglia might be a potential therapy for GHD after SAH. Graphical abstract

The effects of bran types and solid-state fermentation conditions on the enzyme activity of bran-koji inoculated with Penicillium oxalicum M1816 were investigated, and the bran-koji with the highest enzyme activity was applied to Huangjiu production to evaluate its effects on the phenolic content, physicochemical indexes, and sense of Huangjiu. The results showed that when the diameter of bran was 20-mesh, the enzyme activity of bran-koji was corn bran>wheat bran>oat bran>rye bran. The highest enzyme activity in corn bran-koji was achieved under the following conditions: Glacial acetic acid was used to adjust the pH of the solid medium to 6.5, the initial moisture content of the bran-koji was 85% (V/W), the incubation temperature was 30 ℃, and the incubation time was 120 h. Compared with factory Huangjiu, the total amount of phenolic acids in the Huangjiu produced by adding corn bran-koji was 116.48 mg/L, which increased to 1.1-folds in comparison with that of the Huangjiu produced by adding no-corn bran-koji (55.53 mg/L). The volatile phenolic compounds of 4-ethylphenol, 4-ethylguaiacol, 4-vinylguaiacol, guaiacol, and vanillin were increased significantly (P

Abstract Defect tolerance is a critical enabling factor for efficient lead-halide perovskite materials, but the current understanding is primarily on band-edge (cold) carriers, with significant debate over whether hot carriers can also exhibit defect tolerance. Here, this important gap in the field is addressed by investigating how intentionally-introduced traps affect hot carrier relaxation in CsPbX3 nanocrystals (X = Br, I, or mixture). Using femtosecond interband and intraband spectroscopy, along with energy-dependent photoluminescence measurements and kinetic modelling, it is found that hot carriers are not universally defect tolerant in CsPbX3, but are strongly correlated to the defect tolerance of cold carriers, requiring shallow traps to be present (as in CsPbI3). It is found that hot carriers are directly captured by traps, instead of going through an intermediate cold carrier, and deeper traps cause faster hot carrier cooling, reducing the effects of the hot phonon bottleneck and Auger reheating. This work provides important insights into how defects influence hot carriers, which will be important for designing materials for hot carrier solar cells, multiexciton generation, and optical gain media.

Olfactory receptors, classified as G-protein coupled receptors (GPCRs), have been a subject of scientific inquiry since the early 1950s. Historically, investigations into the sensory mechanisms of olfactory receptors were often confined to behavioral characteristics in model organisms or the expression of related proteins and genes. However, with the development of cryo-electron microscopy techniques, it has gradually become possible to decipher the specific structures of olfactory receptors in insects and humans. This has provided new insights into the binding mechanisms between odor molecules and olfactory receptors. Furthermore, due to the rapid advancements in related fields such as computer simulations, the prediction and exploration of odor molecule binding to olfactory receptors have been progressively achieved through molecular dynamics simulations. Through this comprehensive review, we aim to provide a thorough analysis of research related to the binding mechanisms between odor molecules and olfactory receptors from the perspectives of structural biology and molecular dynamics simulations. Finally, we will provide an outlook on the future of research in the field of olfactory receptor sensory mechanisms.

PurposeTo explore the effects of recombinant human growth hormone (r-hGH) on inflammatory mediators, immune cells and prognosis in severe neurosurgical patients.MethodsFrom August 2020 to June 2021, a total of 236 patients who admitted to the neurosurgical intensive care unit (NSICU) were retrospectively analyzed. The patients were divided into GH group (97 cases) and nGH group (139 cases) according to whether they received r-hGH treatment. Parameters including CD4+ T cell counts, inflammatory mediators and prognosis were recorded and assessed.ResultsThe results showed that the cure time of pneumonia and intracranial infection in GH group patients was significantly shorter than in the nGH group (24.25 ± 4.89 days and 21.33 ± 1.53 days versus 29.13 ± 7.43 days and 25.17 ± 2.32 days, respectively). However, there was no significant difference in GOS scores between two groups (31.96% ≤ 3 and 68.04% > 3 vs 39.57% ≤ 3 and 60.43% > 3) (P = 0.232). Furthermore, the number of CD4+ T cells and CD8+ T cells in the GH group showed a significant upward trend. Last but not least, significant differences were also observed in IL-6 and IL-10 levels between two groups at days 1, 3, and 7.ConclusionThe application of r-hGH in severe neurosurgical patients was effective in increasing the number of CD4+ T cells, down-regulating inflammatory mediators, shortening the cure time of pneumonia, intracranial infections and urinary tract infections, and improving patients' prognosis.

BackgroundBronchopulmonary Dysplasia (BPD) is a chronic lung disease affecting preterm infants, with limited prevention and treatment options. Inhaled Nitric Oxide (iNO) is sometimes used to treat Persistent Pulmonary Hypertension of the Newborn (PPHN) and Hypoxemic Respiratory Failure (HRF), and its impact on BPD development remains debated.ObjectiveTo assess whether iNO-related factors are potential contributors to the development of BPD Grade Ⅱ-Ⅲ in very premature infants (VPI) diagnosed with PPHN or HRF at birth using Propensity Score Matching (PSM).MethodsWe conducted a retrospective cohort study of infants born at 22–32 weeks gestation with PPHN or HRF, treated with iNO for over 3 h. PSM matched groups by gestational age, birth weight, and gender, etc. Multivariate logistic regression evaluated the association between iNO treatment and BPD outcomes to identify influencing factors, while Restricted Cubic Spline (RCS) and mediation analysis examined iNO dose effects and potential mediators like mechanical ventilation time and oxygenation index (OI).ResultsA higher initial iNO dose was significantly associated with a reduced risk of BPD Grade Ⅱ-Ⅲ (adjusted OR = 0.68, 95% CI: 0.52–0.89, p < 0.01). Additionally, administration of iNO within the first 7 days of life was identified as an important influencing factor No significant mediation effects were observed for factors such as mechanical ventilation time and OI.ConclusionA higher initial iNO dose within the first 7 days was associated with a reduced risk of BPD Grade Ⅱ-Ⅲ in VPI with PPHN or HRF.

This study aimed to isolate and characterize Seselopsis Tianschanica Schischk Polysaccharide (STSP), a natural functional ingredient, and to develop a compound fermented beverage of nutritional and health combining STSP with highland barley. Firstly, the STSP was isolated and characterized with ultrasound-assisted enzymatic method and chromatography, and analyzed the structural features of polysaccharide STSP-1. Then, a compounded fermented beverage integrating Tibet STSP and highland barley was created, with technology and flavor substances studied. Five kinds of organic acids, 18 kinds of amino acids, and 57 kinds of volatile flavor compounds were determined by GC–MS and HPLC, and quantified significantly enhancing the overall flavor profile of the compound drink-fermented. Moreover, it exhibited higher hydroxyl radical scavenging capacity (IC50 value was 42.68 μL) compared to conventional highland barley drink. This research is expected to provide a theoretical foundation for the utilization of STSP in the functional food industry and other industries.

Abstract Missing labels in multi-label datasets are a common problem, especially for minority classes, which are more likely to occur. This limitation hinders the performance of classifiers in identifying and extracting information from minority classes. Oversampling is an effective method for addressing imbalanced multi-label problems by generating synthetic instances to create a class-balanced dataset. However, the existing oversampling algorithms mainly focus on the location of the generated data, and there is a lack of design on how to complete the labels of the synthetic data. To address this issue, we propose MLAWSMOTE, a synthetic data generation algorithm based on matrix factorization weights. We introduce a weak supervised learning method in the oversampling method, optimize the weights of features and labels by using label correlation, and iteratively learn the ideal label weights. The mapping relationship between features and labels is learned from the dataset and the label correlation matrix. The oversampling ratio is defined based on the discrepancy between observed labels and the ideal label of synthetic instances. It mitigates the impact of missing minority labels on the model’s predictions. The labeling of synthetic instances is performed based on label prediction, and the potential labeling distribution is complemented. Experimental results on multiple multi-label datasets under different label missing ratios demonstrate the effectiveness of the proposed method in terms of ACC, Hamming loss, MacroF1 and MicroF1. In the validation of the four classifiers, MacroF1 decreased by 24.78%, 17.81%, 3.8% and 19.56%, respectively, with the increase of label loss rate. After applying MLAWSMOTE only decreased by 15.79%, 13.63%, 3.78% and 15.21%.

Abstract The aim of this study was to develop a real-time risk prediction model for extrauterine growth retardation (EUGR). A total of 2514 very preterm infants were allocated into a training set and an external validation set. The most appropriate independent variables were screened using univariate analysis and Lasso regression with tenfold cross-validation, while the prediction model was designed using binary multivariate logistic regression. A visualization of the risk variables was created using a nomogram, while the calibration plot and receiver operating characteristic (ROC) curves were used to calibrate the prediction model. Clinical efficacy was assessed using the decision curve analysis (DCA) curves. Eight optimal predictors that namely birth weight, small for gestation age (SGA), hypertensive disease complicating pregnancy (HDCP), gestational diabetes mellitus (GDM), multiple births, cumulative duration of fasting, growth velocity and postnatal corticosteroids were introduced into the logistic regression equation to construct the EUGR prediction model. The area under the ROC curve of the training set and the external verification set was 83.1% and 84.6%, respectively. The calibration curve indicate that the model fits well. The DCA curve shows that the risk threshold for clinical application is 0–95% in both set. Introducing Birth weight, SGA, HDCP, GDM, Multiple births, Cumulative duration of fasting, Growth velocity and Postnatal corticosteroids into the nomogram increased its usefulness for predicting EUGR risk in very preterm infants.

Abstract Imbalanced class distributions are common in real-world scenarios, including datasets with multiple labels. One widely acknowledged approach to addressing imbalanced distributions is through oversampling, a technique that both balances the class distribution and improves the effectiveness of classification models. However, when generating synthetic data for multi-label datasets, complexities arise due to the presence of multiple-label sets, which require careful placement and labeling. We propose MLCSMOTE-FRST, an algorithm for synthetic data generation based on label-specific clustering and fuzzy rough set theory. Generation ratios and dependency samples are provided by clusters specific to each label, with a focus on the overall label distribution and the distribution within each cluster. The labels are supported by intra-cluster positive samples, determined using fuzzy rough set theory, which helps to capture the consensus label set. Experimental results on multi-label datasets using four classifiers demonstrate the effectiveness of the proposed method in terms of macro-F1 and micro-F1 scores.

Bletilla striata, a medicinal orchidaceous plant, is recognized for its significant pharmacological value. However, the lack of comparative metabolomic data across different extraction methods for analyzing its bioactive components has significantly undervalued the application potential of B. striata in the traditional Chinese medicine market. Using six ultrasound-assisted extraction methods and UPLC-MS/MS, this study identified 1,945 metabolites in B. striata extracts. The dominant categories were lipids (51.35%), flavonoids (18.00%), and phenolic acids (12.51%). KEGG analysis revealed alterations in flavonoids and isoflavonoids biosynthesis pathways. Thirteen bitter metabolites, including cinnamic acid, were identified in B. striata tubers, underscoring their potential pharmacological applications, such as anti-inflammatory, antioxidant and antibacterial activities. Optimizing different extraction methods can better preserve the bioactive components of B. striata extracts, thereby enhancing its potential applications in the food and pharmaceutical industries.

In this work, an inclined θ′ morphology with terraced Cu/Mn-rich multilayers is observed in Al–Cu based alloys. The GPA (geometric phase analysis) results indicate that the inclined (∼3.1°) θ′ precipitates could induce significant lattice distortion at the interface. The chemical analysis results demonstrate that Mn atoms could get into the coherent (001)θ′//(001)Al interface with large misfit strains, which may contribute to maintaining the coherent relationship of the (001)θ'//(001)Al interface. Additionally, the interfacial energy between coherent Cu/Mn-rich (001)θ'//(001)Al interface and semi-coherent (010)θ′//(010)Al interface is more closer than that of the normal (001)θ'//(001)Al interface, suggesting a weakness of the anisotropic interfacial energy of θ′ with Cu/Mn-rich layers. The phase field simulation results suggest the formation of inclined θ′ precipitates when elastic strain energy dominates the θ′ morphology. Therefore, the inclined morphology of θ′ precipitates with terraced Cu/Mn-rich multilayers is a plausible outcome in Al–Cu alloys.

Abstract Anomaly detection poses a significant challenge in the industry and knowledge distillation constructed using a frozen teacher network and a trainable student network is the prevailing approach for detecting suspicious regions. Forward and reverse distillation are the main ways to achieve anomaly detection. To design an effective model and aggregate detection results, we propose a dual-student knowledge distillation (DSKD) based on forward and reverse distillation. Taking advantage of the priority of reverse distillation to obtain high-level representation, we combine a skip connection and an attention module to build a reverse distillation student network that simultaneously focuses on high-level representation and low-level features. DSKD uses a forward distillation network as an auxiliary to allow the student network to preferentially obtain the query image. For different anomaly score maps obtained by the dual-student network, we use synthetic noise enhancement in combination with image segmentation loss to adaptively learn the weight scores of individual maps. Empirical experiments conducted on the MVTec dataset show that the proposed DSKD method achieves good performance on texture images as well as competitive results on object images compared with other state-of-the-art methods. Meanwhile, ablation experiments and a visualization analysis validate the contributions of each of the model’s components.

A quantitative method of main components (total sugar, reducing sugar, total acid, ammonia nitrogen, anthocyanins, procyanidins, total phenols, flavonoids and polysaccharides) in Lycium ruthenicum Murr was developed using Fourier transform near infrared spectroscopy (FT-NIR) combined with chemometric analysis. Firstly, 11 pretreatment methods were compared for the original spectra, and the optimal pretreatment method of each component was selected. Then, the model results established by partial least squares (PLS), interval partial least squares (iPLS) and synergistic interval partial least squares (siPLS) algorithms were compared, and finally siPLS was adopted for modeling. The results showed that the correlation coefficient of calibration (Rc) and prediction (RP) of total acids, ammonia nitrogen, anthocyanins, procyanidins, total phenols and flavonoids were all greater than 0.9818, and the relative analysis error (RPD) was more than 2.5, indicating an excellent model performance. The modeling effect of total sugar, reducing sugar, and polysaccharide was also good. The established calibration models could be used for actual detection. The predicted values of the verification samples did not significantly differ from the measured values, with a prediction error of only ±0.1%. Therefore, the prediction model had high reliability. The prediction model established in this study can enable nondestructive, rapid and accurate main components in dried and fresh fruits of Lycium ruthenicum Murr.

Abstract Background Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease, primarily affects preterm newborns and occurs after 7 days of life (late-onset NEC, LO-NEC). Unfortunately, over the past several decades, not much progress has been made in its treatment or prevention. This study aimed to analyze the risk factors for LO-NEC, and the impact of LO-NEC on short-term outcomes in very preterm infants (VPIs) with a focus on nutrition and different onset times. Method Clinical data of VPIs were retrospectively collected from 28 hospitals in seven different regions of China from September 2019 to December 2020. A total of 2509 enrolled VPIs were divided into 2 groups: the LO-NEC group and non-LO-NEC group. The LO-NEC group was divided into 2 subgroups based on the onset time: LO-NEC occurring between 8 ~ 14d group and LO-NEC occurring after 14d group. Clinical characteristics, nutritional status, and the short-term clinical outcomes were analyzed and compared among these groups. Results Compared with the non-LO-NEC group, the LO-NEC group had a higher proportion of anemia, blood transfusion, and invasive mechanical ventilation (IMV) treatments before NEC; the LO-NEC group infants had a longer fasting time, required longer duration to achieve the target total caloric intake (110 kcal/kg) and regain birthweight, and showed slower weight growth velocity; the cumulative dose of the medium-chain and long-chain triglyceride (MCT/LCT) emulsion intake in the first week after birth was higher and breastfeeding rate was lower. Additionally, similar results including a higher proportion of IMV, lower breastfeeding rate, more MCT/LCT emulsion intake, slower growth velocity were also found in the LO-NEC group occurring between 8 ~ 14d when compared to the LO-NEC group occurring after 14 d (all (P

Xiangzao brine is a special flavored food produced by the natural fermentation of Huangjiu lees. To clarify fermentation time on its quality, this study integrated flavoromics analysis, macro-genomics, and polypeptide omics to analyze the volatile flavor components, microbial species, and flavor peptide distributions of four groups of samples (XZ-1Y, XZ-2Y, XZ-3Y, and XZ-4Y) fermented for 1–4 years. The results showed that the samples fermented for 1 year had the highest contents of umami amino acids and umami peptides, and the samples fermented for 4 years had the highest contents of organic acids and fruity components. In addition, 42 volatile flavor components and 532 peptides were identified, including 393 umami taste peptides and only 37 bitter taste peptides. Correlation analysis showed that ethyl lactate and furfural were positively correlated with the abundance of Nocardioides and Stenotrophomonas, respectively. The abundance of Pseudomonas was positively correlated with four previously unreported umami peptides (FATPR, RELER, FNLERP, and RSSFLGQ) screened by molecular docking. This study provides a reference for the flavor metabolism regulation of Xiangzao brine.

Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) have become a major global health burden, but the detailed pathogeneses of neurodegenerative diseases are still unknown, and current treatments are mainly aimed at controlling symptoms; there are no curative treatments for neurodegenerative diseases or treatments for the progressive cognitive, behavioral, and functional impairments that they cause. Studies have shown that some plant extracts with pungent flavor components have a certain neuroprotective effect in neurodegenerative diseases, and their mechanisms mainly involve inhibiting neuronal apoptosis, promoting neuronal regeneration, reducing mitochondrial degeneration, and reducing the production of oxides such as reactive oxygen species in cells, which are of great significance for exploring the treatment of neurodegenerative diseases. In this review, we searched the PubMed database for relevant literature collected in the past 15 years. Finally, we summarized the protective effects of pungent flavor components such as capsaicin, piperine, curcumin, cannabinoids, allicin, and nicotine on the nervous system, focusing on the molecular mechanisms and signaling pathways that they activate. In addition, we also compiled and summarized the laboratory experiments, preclinical experiments, and effects of various pungent flavor components in neurodegenerative diseases. The goal is to further explore their potential as effective drugs for the treatment of neurodegenerative diseases and provide new ideas for further research on the specific protective mechanisms of these substances for the treatment of neurodegenerative diseases and the targets of drug action in the future.

To accurately diagnose and evaluate the degree of myocardial injury and predict myocardial infarction disease, the rapid and sensitive detection of cardiac troponin I (cTnI) is required. Therefore, a label-less electrochemical aptasensor was prepared for cTnI determination. Ionic liquid 1-hydroxyethy l-3- methyl imidazole four fluorine boric acid salt (IL)-reduced graphene oxide − four ethylene oxidation reduction five amine (rGO-TEPA)/silica (SiO2)- gold platinum (AuPt) (IL-rGO-TEPA/SiO2-AuPt) nanocomposites were synthetized as the substrate nanocomposite and were characterized using a series of characterization methods. The performance of the prepared aptasensor was characterized through electrochemical methods. Result displayed that better substrate materials were synthesized, and the prepared electrochemical aptasensor showed excellent electrochemical performance. Under optimal conditions, the electrochemical aptasensor had a salient analytical performance. The electrochemical signals linearly decreased with the logarithm of the cTnI concentration between the 0.5 pg·mL−1 and 1 × 106 pg·mL−1 concentration range (R2 value = 0.9955) and the aptasensor had a wide detection range (0.5 ∼ 1 × 106 pg·mL−1) and a low detection limit of 0.4 pg·mL−1. At the same time, the aptasensor had good selectivity, repeatability and stability. Relative standard deviation (RSD) values ranged from 3.45 % ∼ 4.97 % and the recovery rate was 97.5 % ∼ 103 % in human serum samples, the RSD values of the spiked recovery and ELISA method were less than 5 %. This study provides a new theoretical basis and method for the clinical detection of cTnI.

Abstract Background Hospital Examination Reservation System (HERS) was designed for reducing appointment examination waiting time and enhancing patients’ medical satisfaction in China, but implementing HERS would encounter many difficulties. This study would investigate the factors that influence patients’ utilization of HERS through UTAUT2, and provide valuable insights for hospital managements to drive the effective implementation of HERS. It is helpful for improving patients’ medical satisfaction. Methods We conducted a survey through the Sojump platform, targeting patients were who have already used HERS. We collected questionnaire information related to factors behavior intention, performance expectancy, and effort expectancy. Subsequently, we employed a structural equation model to analyze the factors influencing patients’ utilization of HERS. Results A total of 394 valid questionnaires were collected. Habit was the main direct positive factor influencing the behavioral intention of HERS (β = 0.593; 95%CI: 0.072, 1.944; P = 0.002), followed by patient innovation (β = 0.269; 95%CI: 0.002, 0.443; P

Abstract Background Symptomatic lumbar disc herniation (LDH) and lumbar isthmic spondylolisthesis (LIS) present significant challenges for military pilots, which may result in grounding if not effectively managed. Surgical treatment for LDH and LIS may offer a pathway to return to flight duty (RTFD), but recent data on this crucial topic is lacking. This study seeks to address this gap by investigating the RTFD outcomes among Chinese military pilots who have undergone lumbar spine surgery for symptomatic LDH and LIS. Methods A retrospective review was conducted on active-duty military pilots who underwent isolated decompressive or fusion procedures at an authorized military medical center from March 1, 2007, to March 1, 2023. The analysis utilized descriptive statistics to examine demographic, occupational, surgical, and outcome data, with a particular focus on preoperative flight status, recommended clearance by spine surgeons, and actual RTFD outcomes and time. Results Among the identified cases of active-duty military pilots with LDH or LIS treated by lumbar surgery (n = 24), 70.8% (17 of 24) consistently maintained RTFD status without encountering surgical complications or medical issues during the follow-up period. Of the seven pilots who did not RTFD, one retired within a year of surgery, two had anterior cruciate ligament injuries, three had residual radicular symptoms, and one had chronic low back pain. Excluding pilots who retired and did not RTFD for reasons unrelated to their lumbar conditions, the RTFD rate stood at 81.0% (17 of 21). The median time for recommended clearance by spine surgeons was 143.0 days (inter-quartile range, 116.5–196.0), while the median duration for actual RTFD attainment was 221.0 days (inter-quartile range, 182.0–300.0). The median follow-up post-lumbar surgery was 1.7 years (inter-quartile range, 0.4–2.9). Conclusion Most military pilots diagnosed with symptomatic LDH and LIS can continue their careers and regain active-duty flight status following lumbar spine surgery, as reflected by the high RTFD rate. Lumbar spine surgery can successfully alleviate the physical constraints associated with spinal conditions, facilitating the return of military pilots to their demanding profession.

TA15 titanium alloy is widely used in aerospace industry in terms of its high specific strength, good thermal stability, and excellent corrosion resistance. To further improve its mechanical properties, thermal deformation combined with heat treatment is always used, during which the microstructure evolution and mechanical response are absolutely complex leading to the difficulty in control of final mechanical properties. Therefore, in-depth research on the relationship between microstructure and mechanical response of TA15 titanium alloy during these processes is of great significance. At present, less relevant review has been reported. In this article, the effects of process parameters such as heating temperature, strain rate, deformation amount, deformation mode, deformation path, cooling method and soaking time on the microstructure and mechanical properties of TA15 alloy, namely tensile performance and damage tolerance properties have been discussed. In addition, some strengthening models suitable for TA15 titanium alloy have been analyzed. In conclusion, different microstructure morphologies formed in various processing processes will display diverse mechanical performances in which the direct relationship between the yield strength and microstructure morphology can be established through distinct calculation models but with some limitations. So, in future works, microstructure and mechanical properties should be optimized further through adjusting processing parameters. Moreover, strengthening models remains to be modified by adopting more accurate statistical methods and considering more factors. Finally, establishing the relationship between damage tolerance properties such as fracture toughness, creep performance and LCF property and microstructure features should be considered more for TA15 alloy.

ABSTRACTThe effects of microbial contamination on the rancidity of Huangjiu (Chinese rice wine) during pottery jar storage were studied. With the increase in the rancidity of Huangjiu, the alcohol content decreased, while the conductivity increased significantly. The sour taste and umami taste of Huangjiu increased, leading to flavor deterioration. Meanwhile, the increase in biogenic amine content makes Huangjiu unfit for drinking. The changes in components showed that the degree of rancidity was related to the metabolism of organic acids and amino acids caused by contaminated microorganisms. According to the analysis of microbial community structure, more microorganisms were found in the severe rancid Huangjiu. This indicated that with the aggravation of the degree of rancidity, the community structure of the contaminated microorganisms becomes complex, and potentially pathogenic microorganisms such as Arcobacter species were detected. Therefore, the change of components of Huangjiu will also affect the community structure of contaminated microorganisms.

Huangjiu is known for its unique aroma, primarily attributed to its high concentration of β-phenylethanol (ranging from 40 to 130 mg/L). Phenylalanine aminotransferase Aro9p and phenylpyruvate decarboxylase Aro10p are key enzymes in the β-phenylethanol synthetic pathway of Saccharomyces cerevisiae HJ. This study examined the enzymatic properties of these two enzymes derived from S. cerevisiae HJ and S288C. After substrate docking, Aro9pHJ (−24.05 kJ/mol) and Aro10pHJ (−14.33 kJ/mol) exhibited lower binding free energies compared to Aro9pS288C (−21.93 kJ/mol) and Aro10pS288C (−12.84 kJ/mol). ARO9 and ARO10 genes were heterologously expressed in E. coli BL21. Aro9p, which was purified via affinity chromatography, showed inhibition by l-phenylalanine (L-PHE), but the reaction rate Vmax(Aro9pHJ: 23.89 μmol·(min∙g)−1) > Aro9pS288C: 21.3 μmol·(min∙g)−1) and inhibition constant Ki values (Aro9pHJ: 0.28 mol L−1>Aro9pS288C 0.26 mol L−1) indicated that Aro9p from S. cerevisiae HJ was more tolerant to substrate stress during Huangjiu fermentation. In the presence of the same substrate phenylpyruvate (PPY), Aro10pHJ exhibited a stronger affinity than Aro10pS288C. Furthermore, Aro9pHJ and Aro10pHJ were slightly more tolerant to the final metabolites β-phenylethanol and ethanol, respectively, compared to those from S288C. The study suggests that the mutations in Aro9pHJ and Aro10pHJ may contribute to the increased β-phenylethanol concentration in Huangjiu. This is the first study investigating enzyme tolerance mechanisms in terms of substrate and product, providing a theoretical basis for the regulation of the β-phenylethanol metabolic pathway.

Pullulan is a high-value biopolymer synthesized by Aureobasidium pullulans through the fermentation of starch and sugars. It finds extensive applications in food, packaging, biomedicine, and other sectors. However, the high production costs significantly limit the development and application of pullulan. Consequently, there is an urgent need to identify high-quality fermentation substrates. In recent years, the rapid growth of Huangjiu industry has led to the generation of waste Huangjiu lees, which not only contribute to environmental pollution but also represent a significant waste of resources. As a result, the resource utilization of Huangjiu lees has garnered considerable attention. In this study, Huangjiu lees were employed as raw materials for fermentation to produce pullulan. Following fermentation of Huangjiu lees powder with the primary strain Aureobasidium pullulans LL1, the yield of pullulan was notably reduced. Through adaptive evolution, an evolved strain, Aureobasidium pullulans AP9, was isolated, demonstrating enhanced efficiency in producing pullulan from Huangjiu lees. The impact of Huangjiu lees on pullulan biosynthesis was elucidated via transcriptome analysis. Fermentation conditions were optimized using a single-factor approach, and a multi-strain staged fermentation strategy involving Aspergillus niger and Aureobasidium pullulans was employed to further enhance pullulan yield. Under optimal conditions, the pullulan yield reached 22.06 g/L, with a molecular weight of 1.04 × 106 Da. This study underscores the significant potential of utilizing Huangjiu lees for pullulan production and offers valuable insights for the resource utilization of this byproduct.

The unique flavour contribution of higher alcohols in alcoholic beverages has received growing attention; however, there is a dearth of information on their in vivo metabolic kinetics. In this study, the composition and content of higher alcohols in different alcoholic beverages from Chinese Baijiu and Lujiu were studied via in vivo analysis using Bama pigs to elucidate the mechanisms for intoxication of alcohol in vitro and in drinkers. Direct injection combined with gas chromatography–mass spectrometry (GC-MS) were used to accurately quantify a total of 14 higher alcohols in five alcoholic beverages. Based on the external standard method, a total content of 289.37–938.33 mg/L was detected, mainly 1-butanol, 3-methyl-1-butanol, 1-hexanol, 2-methyl-1-propanol and 2-butanol. Then, headspace solid-phase microextraction (HS-SPME) and solid-phase extraction (SPE) combined with GC-MS analysis strategy, respectively, were adopted to continuously monitor the changes in the concentrations of ethanol and 11 higher alcohols in the blood within 24 h after gavage of different alcoholic beverages, and the key pharmacokinetic parameters were analysed. The peak concentration (Cmax) and area under curve (AUC) of blood higher alcohols were significantly lower than those of ethanol (p < 0.05), accompanied by a later peak time (Tmax) and a larger apparent clearance rate (CL_F), and there were certain differences between the same higher alcohols in different alcoholic beverages and between different higher alcohols in the same alcoholic beverage. This work provides valuable insights into the metabolism of alcoholic beverages.

Carbon dots (CDs) have garnered extensive interest in basic physical chemistry as well as in biomedical applications due to their low cost, good biocompatibility, and great aqueous solubility. However, the synthesis of multi-functional carbon dots has always been a challenge for researchers. Here, we synthesized novel CDs with a high quantum yield of 28.2% through the straightforward hydrothermal method using Diaminomaleonitrile and Boc-D-2, 3-diaminopropionic acid. The size, chemical functional group, and photophysical properties of the CDs were characterized by TEM, FTIR, XPS, UV, and fluorescence. It was demonstrated in this study that the prepared CDs have a high quantum yield, excellent photostability, and low cytotoxicity. Regarding the highly water-soluble property of CDs, they were proven to possess selective and sensitive behavior against Cu2+ ions (linear range = 0–9 μM and limit of detection = 1.34 μM). Moreover, the CDs were utilized in fluorescent ink in anti-counterfeiting measures. Because of their low cytotoxicity and good biocompatibility, the CDs were also successfully utilized in cell imaging. Therefore, the as-prepared CDs have great potential in fluorescence sensing, anti-counterfeiting, and bioimaging.

Melanin is a high value bioproduct generated through the fermentation of Aureobasidium pullulans, playing a crucial role in various fields, including food, medicine, environmental protection, and materials science. However, its high production costs and low synthetic yields significantly limit its applications. Therefore, it is essential to identify high-yield strains, reduce production costs, and optimize fermentation strategies. In this study, a high melanin-yielding Aureobasidium pullulans 53LC7 was screened and identified, and the fermentation process was optimized based on melanin yield, color value, and pullulan yield. The results indicated that the melanin yield peaked at an initial pH of 6.0, temperature of 27 °C, fermentation time of 6.5 d, and inoculation quantity of 2.5%, achieving a melanin yield of 16.33 g/L. Subsequently, huangjiu lees, a byproduct of huangjiu production, was incorporated into the fermentation medium, resulting in a melanin yield of 5.91 g/L. This suggests that the Aureobasidium pullulans was not effectively utilizing huangjiu lees. To address this, we employed an adaptive evolution strategy, which increased the melanin yield to 8.72 g/L. The enhanced production was correlated with the expression of key genes, including FKS, PKS, and Cmr1. Finally, cellulase was utilized to convert the crude fibers in huangjiu lees, which were difficult to utilize, into usable substrates, while pullulanase was employed to minimize byproduct formation in the fermentation system, resulting in a melanin yield of 19.07 g/L. This study not only provides promising strains for further research but also offers valuable insights for resource production technologies.

Abstract Different microorganisms can produce different proteases, which can adapt to different industrial requirements such as pH, temperature, and pressure. Salt-tolerant proteases (STPs) from microorganisms exhibit higher salt tolerance, wider adaptability, and more efficient catalytic ability under extreme conditions compared to conventional proteases. These unique enzymes hold great promise for applications in various industries including food, medicine, environmental protection, agriculture, detergents, dyes, and others. Scientific studies on microbial-derived STPs have been widely reported, but there has been little systematic review of microbial-derived STPs and their application in high-salt conventional soybean fermentable foods. This review presents the STP-producing microbial species and their selection methods, and summarizes and analyzes the salt tolerance mechanisms of the microorganisms. It also outlines various techniques for the isolation and purification of STPs from microorganisms and discusses the salt tolerance mechanisms of STPs. Furthermore, this review demonstrates the contribution of modern biotechnology in the screening of novel microbial-derived STPs and their improvement in salt tolerance. It highlights the potential applications and commercial value of salt-tolerant microorganisms and STPs in high-salt traditional soy fermented foods. The review ends with concluding remarks on the challenges and future directions for microbial-derived STPs. This review provides valuable insights into the separation, purification, performance enhancement, and application of microbial-derived STPs in traditional fermented foods. Graphical Abstract

Abstract Identification of the core functional microorganisms in food fermentations is necessary to understand the ecological and functional processes for making those foods. Wheat qu, which provides liquefaction and saccharifying power, and affects the flavor quality, is a key ingredient in ancient alcoholic huangjiu fermentation, while core microbiota of them still remains indistinct. In this study, metagenomics, metabolomics, microbial isolation and co-fermentation were used to investigate huangjiu. Although Aspergillus is usually regarded as core microorganism in wheat qu to initiate huangjiu fermentations, our metagenomic analysis showed that bacteria Saccharopolyspora are predominant in wheat qu and responsible for breakdown of starch and cellulose. Metabolic network and correlation analysis showed that Saccharopolyspora rectivirgula, Saccharopolyspora erythraea, and Saccharopolyspora hirsuta made the greatest contributions to huangjiu’s metabolites, consisting of alcohols (phenylethanol, isoamylol and isobutanol), esters, amino acids (Pro, Arg, Glu and Ala) and organic acids (lactate, tartrate, acetate and citrate). S. hirsuta J2 isolated from wheat qu had the highest amylase, glucoamylase and protease activities. Co-fermentations of S. hirsuta J2 with S. cerevisiae HJ resulted in a higher fermentation rate and alcohol content, and huangjiu flavors were more similar to that of traditional huangjiu compared to co-fermentations of Aspergillus or Lactiplantibacillus with S. cerevisiae HJ. Genome of S. hirsuta J2 contained genes encoding biogenic amine degradation enzymes. By S. hirsuta J2 inoculation, biogenic amine content was reduced by 45%, 43% and 62% in huangjiu, sausage and soy sauce, respectively. These findings show the utility of Saccharopolyspora as a key functional organism in fermented food products.

Summary: Alzheimer’s disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aβ is a typical AD hall marker, but Aβ-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aβ-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aβ-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration.

BackgroundHyperglycemia in pregnancy (HGP) has generally been considered a risk factor associated with adverse outcomes in offspring, but its impact on the short-term outcomes of very preterm infants remains unclear.MethodsA secondary analysis was performed based on clinical data collected prospectively from 28 hospitals in seven regions of China from September 2019 to December 2020. According to maternal HGP, all infants were divided into the HGP group or the non-HGP group. A propensity score matching analysis was used to adjust for confounding factors, including gestational age, twin or multiple births, sex, antenatal steroid administration, delivery mode and hypertensive disorders of pregnancy. The main complications and the short-term growth status during hospitalization were evaluated in the HGP and non-HGP groups.ResultsA total of 2,514 infants were eligible for analysis. After matching, there were 437 infants in the HGP group and 874 infants in the non-HGP group. There was no significant difference between the two groups in main complications including respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus, culture positive sepsis, intraventricular hemorrhage, periventricular leukomalacia, anemia, feeding intolerance, metabolic bone disease of prematurity, or parenteral nutrition-associated cholestasis. The incidences of extrauterine growth retardation and increased growth retardation for weight and head circumference in the non-HGP group were all higher than those in the HGP group after matching (P

Abstract Background To analyze the real-world growth pattern of very premature infants (VPI) with small for gestational age (SGA) after birth by using the ΔZ value of weight at discharge. Methods The clinical data were collected from 28 hospitals in China from September 2019 to December 2020. They were divided into the EUGR(Extrauterine Growth Restriction) and the non-EUGR group according to the criterion of ΔZ value of weight at discharge

Typical Internet of Things (IoT) systems are event-driven platforms, in which smart sensing devices sense or subscribe to events (device state changes), and react according to the preconfigured trigger-action logic, as known as, automation rules. "Events" are essential elements to perform automatic control in an IoT system. However, events are not always trustworthy. Sensing fake event notifications injected by attackers (called event spoofing attack) can trigger sensitive actions through automation rules without involving authorized users. Existing solutions verify events via "event fingerprints" extracted by surrounding sensors. However, if a system has homogeneous sensors that have strong correlations among them, traditional threshold-based methods may cause information redundancy and noise amplification, consequently, decreasing the checking accuracy. Aiming at this, in this paper, we propose "EScope" , an effective event validation approach to check the authenticity of system events based on device state correlation. EScope selects informative and representative sensors using an Neural-Network-based (NN-based) sensor selection component and extracts a verification sensor set for event validation. We evaluate our approach using an existing dataset provided by Peeves. The experiment results demonstrate that EScope achieves an average 67% sensor amount reduction on 22 events compared with the existing work, and increases the event spoofing detection accuracy.

Saccharopolyspora is a key microorganism in the fermentation of traditional fermented foods, capable of producing saccharifying and liquefying enzymes at elevated temperatures. However, the specific mechanisms and regulatory pathways governing Saccharopolyspora’s response to ambient temperatures are not yet fully understood. In this study, the morphological differences in Saccharopolyspora rosea screened from traditional handmade wheat Qu at different temperatures were initially explored. At 37 °C, the mycelium exhibited abundant growth and radiated in a network-like pattern. As the temperature increased, the mycelium aggregated into clusters. At 50 °C, it formed highly aggregated ellipsoidal structures, with the mycelium distributed on the spherical surface. Subsequently, we assessed the biomass, saccharifying enzyme activity and liquefying enzyme activity of Saccharopolyspora rosea cultured at 37 °C, 42 °C and 50 °C. Furthermore, transcriptome analysis demonstrated that Saccharopolyspora rosea employs mechanisms related to the carbon metabolism, the TCA cycle, glycine, serine and threonine metabolisms, and microbial metabolism in diverse environments to coordinate its responses to changes in environmental temperature, as verified by the expression of typical genes. This study enhances our understanding of the differences in high-temperature enzyme production by Saccharopolyspora, and offers valuable guidance for the traditional fermented food industry to drive innovation.

Polysaccharides derived from diverse sources exhibit distinct rheological and gel properties, exerting a profound impact on their applicability in the food industry. In this study, we collected five Gracilaria chouae samples from distinct geographical regions, namely Rizhao (RZ), Lianyungang (LYG), Ningde (ND), Beihai (BH), and a wild source from Beihai (BHW). We conducted analyses on the chemical composition, viscosity, and rheological properties, as well as gel properties, to investigate the influence of chemical composition on variations in gel properties. The results revealed that the total sugar, sulfate content, and monosaccharide composition of G. chouae polysaccharides exhibit similarity; however, their anhydrogalactose content varies within a range of 15.31% to 18.98%. The molecular weight distribution of G. chouae polysaccharides ranged from 1.85 to 2.09 × 103 kDa. The apparent viscosity of the LYG and BHW polysaccharides was relatively high, whereas that of RZ and ND was comparatively low. The gel strength displayed a similar trend. BHW and LYG exhibited solid-like behavior, while ND, RZ, and BH demonstrated liquid-like characteristics at low frequencies. The redundancy analysis (RDA) analysis revealed a positive correlation between the texture profile analysis (TPA) characteristics and anhydrogalactose. The study could provide recommendations for the diverse applications of G. chouae polysaccharides derived from different geographical regions.

Carrageenans were widely utilized as thickening and gelling agents in the food and cosmetic industries, and their oligosaccharides have been proven to possess enhanced physicochemical and biological properties. In this study, Shewanella sp. LE8 was utilized for the depolymerization of κ-, ι-, and λ-carrageenan under conditions of fermentation. During a 24-h fermentation at 28 °C, the apparent viscosity of κ-, ι-, and λ-carrageenan decreased by 53.12%, 84.10%, and 59.33%, respectively, accompanied by a decrease in storage modulus, and loss modulus. After a 72-h fermentation, the analysis of methylene blue and molecular weight distribution revealed that ι-carrageenan was extensively depolymerized into smaller polysaccharides by Shewanella sp. LE8, while exhibiting partial degradation on κ- and λ-carrageenan. However, the impact of Shewanella sp. LE8 on total sugars was found to be limited; nevertheless, a significant increase in reduced sugar content was observed. The ESIMS analysis results revealed that the purified components obtained through ι-carrageenan fermentation for 72 h were identified as tetrasaccharides, while the two purified components derived from λ-carrageenan fermentation consisted of a hexasaccharide and a tetrasaccharide, respectively. Overall, the present study first reported the depolymerization of ι-and λ-carrageenan by Shewanella and suggested that the Shewanella could be used to depolymerize multiple carrageenans, as well as complex polysaccharides derived from red algae, to further obtain their oligosaccharides.

The fusion of global contextual information with local cropped block details is crucial for segmenting ultra-high resolution images. In this study, A novel fusion mechanism termed global–local deep fusion (GL-Deep Fusion) is introduced, based on an enhanced transformer architecture that efficiently integrates global contextual information and local details. Specifically, we propose the global–local synthesis networks (GLSNet), a dual-branch network where one branch processes the entire original image, while the other branch handles cropped local patches as input. The feature fusion of different branches in GLSNet is achieved through GL-Deep Fusion, significantly enhancing the accuracy of ultra-high resolution image segmentation. Identifying tiny overlapping items is a task where the model excels, demonstrating its particular effectiveness. To optimize GPU memory utilization, a dual-branch architecture was meticulously designed. This architecture proficiently leverages the features it extracts and seamlessly integrates them into the enhanced transformer framework of GL-Deep Fusion. Benchmarks on the DeepGlobe and Vaihingen datasets demonstrate the efficiency and accuracy of the proposed model. It significantly reduces GPU memory usage by 24.1% on the DeepGlobe dataset, enhancing segmentation accuracy by 0.8% over the baseline model. On the Vaihingen dataset, our model delivers a Mean F1 score of 90.2% and achieves a mIoU of 90.9%, highlighting its exceptional memory efficiency and segmentation precision.

Abstract Telomeres, at the ends of chromosomes, protect chromosomes from fusion and preserve genomic stability. However, the molecular mechanisms underlying telomere attrition-induced genome instability remain to be understood. We systematically analyzed the expression of retrotransposons and performed genomic sequencing of different cell and tissue types with telomeres of varying lengths due to telomerase deficiency. We found that critically short telomeres altered retrotransposon activity to promote genomic instability in mouse embryonic stem cells, as evidenced by elevated numbers of single nucleotide variants, indels and copy number variations (CNVs). Transpositions of retrotransposons such as LINE1 resulting from the short telomeres can also be found in these genomes with elevated number of mutations and CNVs. Retrotransposon activation is linked to increased chromatin accessibility, and reduced heterochromatin abundance correlates with short telomeres. Re-elongation of telomeres upon recovery of telomerase partly represses retrotransposons and heterochromatin accumulation. Together, our findings suggest a potential mechanism by which telomeres maintain genomic stability by suppressing chromatin accessibility and retrotransposon activity.

Abstract Background It is proposed that the development of parenteral nutrition-associated cholestasis (PNAC) was significantly associated with preterm birth, low birth weight, infection, etc.; however, the etiology and pathogenesis of PNAC are not fully understood. Most of the studies examining PNAC-associated risk factors were single-center studies with relatively small sample sizes. Objective To analyze the risk factors associated with PNAC in preterm infants in China. Methods This is a retrospective multicenter observational study. Clinical data on the effect of multiple oil-fat emulsions (soybean oil-medium chain triglycerides-olive oil-fish oil, SMOF) in preterm infants were collected from a prospective multicenter randomized controlled study. A secondary analysis was performed in which preterm infants were divided into the PNAC group and the non-PNAC group based on the PNAC status. Results A total of 465 cases very preterm infants or very low birth weight infants were included in the study in which 81 cases were assigned to the PNAC group and 384 cases were assigned to the non-PNAC group. The PNAC group had a lower mean gestational age, lower mean birth weight, longer duration of invasive and non-invasive mechanical ventilation, a longer duration oxygen support, and longer hospital stay (P

The identification and analysis of the deposit slope stability is the focus of geological disaster prevention and control. Taking dense-fine grained slopes and loose gravel slopes as examples, a series of flume tests under rainfall infiltration were carried out. The effects of density, material composition, slope angle and vegetation coverage on slope stability and rainfall threshold were systematically analyzed. The results show that under rainfall infiltration, the dense-fine grained slope with uniform material composition and high density was more stable, resulting in a higher rainfall threshold and a lower catastrophability. The slope with non-uniformmaterial composition and loose gravel was more likely to fail than the slope with dense fine particles. The influence of the stone content on the stability of the slope is greater than that of the slope gradient. The critical rainfall of landslides increases first and then decreases with an increasing vegetation coverage; that is, when rainfall infiltration causes the slope soil to be supersaturated, the higher vegetation coverage will trigger the whole deformation of slope and vegetation due to the strong development of vegetation roots, which increases the catastrophability of the slope.The research results can provide a theoretical basis for the instability mechanism and stability evaluation of deposit slopes.

Abstract Background Infants with rule-out infections are responsible for the majority of empirical antibiotics treatment (EAT) in neonatal intensive care units (NICUs), particularly very preterm infants (VPIs). Antibiotic overuse has been linked to adverse outcomes. There is a paucity of data on the association between EAT and clinical outcomes (containing the nutritional outcomes) of VPIs without infection-related morbidities. Methods Clinical data of VPIs admitted in 28 hospitals in 20 provinces of China from September 2019 to December 2020 were collected. EAT of VPIs was calculated as the number of days with initial usage in the first week after birth, and then categorized into 3 groups (antibiotic exposure: none, 1-4 days, and > 4 days). Clinical characteristics, nutritional status , and the short-term clinical outcomes among 3 groups were compared and analyzed. Results In total, 1834 VPIs without infection-related morbidities in the first postnatal week were enrolled, including 152 cases (8.3%) without antibiotics, 374 cases (20.4%) with EAT ≤4 days and 1308 cases (71.3%) with EAT > 4 days. After adjusting for the confounding variables, longer duration of EAT was associated with decreased weight growth velocity and increased duration of reach of full enteral feeding in EAT > 4 days group (aβ: -4.83, 95% CI: − 6.12 ~ − 3.53; aβ: 2.77, 95% CI: 0.25 ~ 5.87, respectively) than those receiving no antibiotics. In addition, the risk of feeding intolerance (FI) in EAT > 4 days group was 4 times higher than that in non-antibiotic group (aOR: 4.14, 95%CI: 1.49 ~ 13.56) and 1.8 times higher than that in EAT ≤4 days group (aOR: 1.82, 95%CI: 1.08 ~ 3.17). EAT > 4 days was also a risk factor for greater than or equal to stage 2 necrotizing enterocolitis (NEC) than those who did not receive antibiotics (aOR: 7.68, 95%CI: 1.14 ~ 54.75) and those who received EAT ≤4 days antibiotics (aOR: 5.42, 95%CI: 1.94 ~ 14.80). Conclusions The EAT rate among uninfected VPIs was high in Chinese NICUs. Prolonged antibiotic exposure was associated with decreased weight growth velocity, longer duration of reach of full enteral feeding, increased risk of feeding intolerance and NEC ≥ stage 2. Future stewardship interventions to reduce EAT use should be designed and implemented.

Pure aluminium (Al) powder is widely used in aerospace fields as fuel while its corrosion mechanisms and anti-corrosion strategies are not thoroughly studied. Herein, corrosion mechanisms of Al nanoparticles are revealed by density functional theory (DFT) and experiments. Moreover, by utilizing the behaviour of ions moving in the electric field, an interfacial electric field is designed to endow spherical aluminium powder (sAl) with high anti-corrosion for chloride ions (Cl−). Because TiO2 presents lower electrostatic potential than Al2O3 which is on the surface of sAl, the prepared core@shell structural material (sAl@TiO2) holds an interfacial electric field and its direction is from TiO2 to Al2O3. The electric field repels the Cl− adsorption on the surface of sAl@TiO2, bringing about superior Cl− anti-corrosion.

Introduction: The body’s ability to metabolize nicotine and the disposition of nicotine in the brain are important determinants of its exposure. Limited knowledge about the near real-time changes of neurochemicals during the brain nicotine metabolic process hinders the recognition of its multiple neuropharmacological effects.Methods: An online microdialysis coupled with UHPLC-HRMS/MS method for the in vivo multi-analysis of nicotine metabolites and several neurotransmitters in rat brain was developed. Whether the systemic modulation of metabolic enzyme CYP2B would modulate nicotine pharmacokinetics and local neurochemical effects was further investigated.Results: The dynamic profiles of over 10 nicotine metabolites and neurotransmitters were simultaneously obtained after a single injection of nicotine (2 mg·kg−1, i.p.) using the new method. Proadifen pretreatment (50 mg·kg−1·d−1, i.p., 4 days) caused significant inhibition of brain CYP2B1 activity. When exposed to nicotine, the brain Cmax of nicotine was 1.26 times higher and the levels of nicotine metabolites, nornicotine, and nicotine-N-oxide, were decreased by 85.3% and 34.4% in proadifen-pretreated rats. The higher level of brain nicotine induced a greater release of dopamine, serotonin, glutamate, and γ-amino-butyric acid in the nucleus accumbens. The concentrations of nicotine and dopamine were positively correlated, and the average levels of γ-amino-butyric acid and serotonin were 2.7 and 1.2 times higher, respectively, under the inhibition of nicotine metabolism.Discussion: These results demonstrated that inhibiting nicotine metabolism in rats can enhance the residence of brain nicotine and its local neurotransmitter effects. The metabolic activity of nicotine under different physiological conditions could regulate nicotine’s bioavailability and its resulting pharmacology.

Distiller’s grains resourcing is a crucial problem for the sustainable development of the Chinese Baijiu industry. In order to improve the protein utilization of distiller’s grains. In this study, distiller’s grains pretreated by wet crushing combined with amylase/cellulase were further hydrolyzed with neutral protease combined with papain at 50 °C for 3 h. The hydrolysates were decolorized by 1% coconut shell activated carbon for 15 min, and separated and purified by macroporous resin and Sephadex gel to yield peptide fractions (F1, F2, F3 and F4). The F3 fraction with the highest radical scavenging activity was analyzed by nano-LC-MS/MS and peptidomics to identify peptides. Three peptides (especially newly discovered AAHVLAAAFL) displayed strong alcohol solubility and antioxidant activity and were stably bound to key regulatory pathway receptors (Keap1-Nrf2) and myeloperoxidase (MPO), further elucidating molecular mechanism of anti-oxidation. These findings provided knowledge for potential functional peptide candidates and facilitates the high-value commercial development of distiller’s grains.

Based on a multi-source error model, this paper discusses the principle of error element identification and uses the mirror bias method to compensate the geometric errors of a process system. Firstly, a nine-line measurement method to determine the geometric error of the linear feed axes of machine tools is introduced, and the geometric error identification model based on the “nine-line method” is established. Then, using a ballbar mounted in the axial, tangential, and radial directions of the machine, the geometric error elements of the rotation axis are identified by three simple measurements in each direction. Subsequently, for the more common flat vise clamping workpiece in actual production, the workpiece position error is identified by using the traditional process of dimensional chain, and the workpiece attitude error is identified by fitting the angle between the positioning plane and the horizontal plane by the least squares method. Finally, based on the tool position points and tool axis vectors obtained from the multi-source error model, the error compensation value is solved using inverse machine tool kinematics to offset the machining error by mirroring the error value of the same size, and based on the “S-shaped specimen” to compensate the processing experiments, after compensation, the processing error is reduced by 30~45%, verifying the effectiveness of the compensation method.