Search

Apple replant disease (ARD) is primarily caused by biotic factors that seriously inhibits the development of apple industry. Therefore, the use of biological control measures to inhibit the main pathogens (such as Fusarium spp.) that cause ARD is of great significance to the sustainable development of the apple industry. Trichoderma virens 6PS-2, which exhibited antagonism toward a variety of pathogens, was screened from the rhizosphere soils of healthy apple trees (Malus robusta) in different replanted orchards in the Yantai and Zibo Cities, Shandong Province, China. Its fermentation extract inhibited the growth of pathogenic Fusarium proliferatum f. sp. Malus domestica MR5, which was proportional to the concentration. These substances also increased the hairy root volume and growth of Arabidopsis thaliana lateral roots. The phenotype of Malus hupehensis seedlings and microbial community structure in rhizosphere soils in greenhouse experiment using High-throughput sequencing were analyzed, and the field experiment with grafted apple trees were used for further verification. Compared with the application of potato dextrose broth (PDB) medium, application of 6PS-2 spore suspension directly to replanted soils could improve the growth of M. hupehensis seedlings as well as the elongation of grafted apple trees. Concomitant decreases in the gene copy number of Fusarium and increases in the culturable bacteria/fungi were also observed in the greenhouse and field experiments. The abundance of Trichoderma, Bacillus, and Streptomyces increased significantly, but that of Fusarium, Pseudarthrobacter, and Humicola decreased. The content of esters, phenols, furans, and amino acids in root exudates of M. hupehensis seedlings increased, which significantly inhibited the multiplication of Fusarium, but was positively correlated with Bacillus and Trichoderma. In summary, T. virens 6PS-2 not only directly inhibits the activity of pathogenic Fusarium but also secrets secondary metabolites with antifungal and growth-promoting potential. In addition, 6PS-2 spore suspension can also promote the growth of plants to a certain extent, and change the soil microbial community structure of rhizosphere soils. It is believed that T. virens 6PS-2 has the potential for the alleviation of apple replant disease (ARD) in China.

Rolling contact fatigue and wear failure are the most common forms of failure in heavy rail steel. However, the complicated relationship between fatigue and wear of heavy rail steel remains largely unexplored, with the failure mechanism yet to be fully understood. To investigate the damage and surface microstructure evolution in pearlite rails under rolling contact fatigue and wear interactive loads, a study was conducted on U76CrRE pearlite heavy rail steel, both rolled and heat-treated. The research utilized various methods, including rolling friction and wear testing, laser confocal microscopy, scanning electron microscopy, and electron backscatter diffraction, to measure and observe the wear rate, surface damage, deformation layers, and crack initiation and propagation in heavy rail steel with and without precast cracks. The study quantitatively analyzed the microstructural evolution and failure behaviors of pearlite rail under wear and fatigue interaction loads. The results show that the deformation layer in rolled heavy rail steel is larger than that in heat-treated specimens, especially when there are no precast cracks or the depth of such cracks is less than the wear layer. However, the wear rate and deformation layer in rolled rails were found to exceed those in heat-treated rails. The ferrite in pearlite near the deformation layer is refined and mixed with similarly refined cementite particles. Initially, ferrite grains exhibit mainly small-angle grain boundaries, but as the distance from the surface layer increases, the proportion of large-angle grain boundaries grows, leading to cracks characterized by larger angles, greater depths, and shorter lengths. Conversely, cracks in heat-treated rails are characterized by smaller angles, shallower depths, and longer lengths, with a more pronounced trend of crack propagation compared to rolled rails. When prefabricated crack depth exceeds the wear deformation layer, these cracks expedite wear mechanisms, encouraging the rapid generation and propagation of fatigue cracks and hastening fatigue failure. The cracks tend to demonstrate larger angles, deeper depths, and longer lengths, indicating that both rolling and heat-treated pearlite heavy rails are mainly subject to fatigue failure, with crack propagation being more evident in rolled rails than in heat-treated ones. Furthermore, when rails are matched with wheel steel of higher hardness, the crack angle, depth and length of rails become more pronounced than those with lower hardness. Moreover, the duration of the rail wear mechanism is prolonged.

Abstract Background Inflammatory bowel disease (IBD) is occasionally associated with ophthalmic diseases, including iridocyclitis (IC). The co-occurrence of IBD and IC has been increasingly observed, possibly due to shared genetic structures. Methods A three-part analysis was executed utilizing genome-wide association study (GWAS) data on IBD and IC. First, the overall genetic correlation between the two traits was observed using linkage disequilibrium score regression (LDSC). Subsequent to this, a local genetic correlation analysis was conducted utilizing the heritability estimation from summary statistics (HESS) methodology. Finally, the conditional/conjunctional false discovery rate (cond/conjFDR) statistical framework was utilized to ascertain the degree of genetic overlap between the two traits. Results Positive overall correlations were observed among IBD, ulcerative colitis (UC), and IC, encompassing both acute/subacute and chronic IC presentations. While a significant correlation was identified between Crohn’s disease (CD) and IC, it was not evident for acute/subacute or chronic IC (P > 0.05). Notably, IBD (encompassing CD and UC) demonstrated local genetic correlations with IC and acute/subacute IC, with pronounced enrichment notably on chromosomes 1 and 6, though such correlations were not observed with chronic IC. The conjFDR analysis confirmed the genetic overlap between the two diseases. The shared genes overlapping between IBD (encompassing CD and UC) and IC were IL23R, GPR35, and ERAP1. For acute/subacute IC and chronic IC, there were six overlapping genes (GPR35, RPL23AP12, IL23R, SNAPC4, ERAP1, and INAVA) and one overlapping gene (INAVA), respectively. Conclusion This study confirms the existence of a shared genetic structure between IBD and IC, providing a biological basis for their comorbidity. Additionally, this finding has significant implications for preventing and treating these two diseases.

ABSTRACT: This study established a method for rapid classification of milk products by combining MALDI-TOF MS analysis with machine learning techniques. The analysis of 2 different types of milk products was used as an example. To select key variables as potential markers, integrated machine learning strategies based on 6 feature selection techniques combined with support vector machine (SVM) classifier were implemented to screen the informative features and classify the milk samples. The models were evaluated and compared by accuracy, Akaike information criterion (AIC), and Bayesian information criterion (BIC). The results showed the least absolute shrinkage and selection operator (LASSO) combined with SVM performs best, with prediction accuracy of 100% ± 0%, AIC of −360 ± 22, and BIC of −345 ± 22. Six features were selected by LASSO and identified based on the available protein molecular mass data. These results indicate that MALDI-TOF MS coupled with machine learning technique could be used to search for potential key targets for authentication and quality control of food products.

Abstract Wheat leaf rust, caused by Puccinia triticina (Pt), remains a constant threat to wheat production worldwide. Deployment of race-specific leaf rust (Lr) resistance genes in wheat provides effective protection against leaf rust, but often leads to selective pressures that drive the rapid emergence of new virulent Pt isolates in nature. However, the molecular mechanisms underlying the evasion of Lr-delivered resistance by leaf rust remain largely unknown. Here, we identify an avirulence gene AvrLr21 in Pt that triggers Lr21-dependent immune responses. BSMV (Barley stripe mosaic virus)-mediated host-induced gene silencing assay shows that silencing AvrLr21 compromises Lr21-mediated immunity. AvrLr21 interacts directly with Lr21 protein to induce a hypersensitive response in tobacco leaves. The evolved Lr21-breaking Pt isolates can suppress Lr21-mediated immunity. Our data provide a basis for studying the molecular determinants in Pt-wheat incompatible interaction and monitoring natural Pt populations to prioritize the deployment of Lr resistance genes in the field.

Abstract Background Although clinical guidelines exist for diagnosing abnormal uterine bleeding, there is a significant lack of agreement on the best management strategies for women presenting with symptom, particularly in diagnosing endometrial cancer. This study aimed to develop a preoperative risk model that utilizes demographic factors and transvaginal ultrasonography of the endometrium to assess and predict the risk of malignancy in females with endometrial cancer. Methods In this retrospective study, a logistic regression model was developed to predict endometrial carcinoma using data from 356 postmenopausal women with endometrial lesions and an endometrial thickness (ET) of 5 mm or more. These patients had undergone transvaginal ultrasonography prior to surgery, with findings including 247 benign and 109 malignant cases. The model’s predictive performance was evaluated using receiver operating characteristic (ROC) curve analysis and compared with post-surgical pathological diagnoses. Results Our model incorporates several predictors for endometrial carcinoma, including age, history of hypertension, history of diabetes, body mass index (BMI), duration of vaginal bleeding, endometrial thickness, completeness of the endometrial line, and endometrial vascularization. It demonstrated a strong prediction with an area under the curve (AUC) of 0.905 (95% CI, 0.865–0.945). At the optimal risk threshold of 0.33, the model achieved a sensitivity of 82.18% and a specificity of 92.80%. Conclusions The established model, which integrates ultrasound evaluations with demographic data, provides a specific and sensitive method for assessing and predicting endometrial carcinoma.

Abstract Background To date, the relationship between the Transesophageal Echocardiography (TEE) monitoring indicator tricuspid annular plane systolic excursion (TAPSE) and the incidence of postoperative acute kidney injury (AKI) in Coronary Artery Bypass Grafting(CABG) patients remains unknown. The main objective of this study was to explore the relationship between the TAPSE and the incidence of AKI in CABG patients. Methods This was a multicenter prospective cohort study was conducted between September 2021 and July 2022. Among 266 patients aged at least 18 years who underwent elective CABG, 140 were included. Results We measured TAPSE via M-mode TEE via the mid-esophageal (ME) right ventricle(RV) inflow-outflow view (60°). All echocardiographic measurements were performed three separate times at each time point: T0 (before the start of CABG), T2 (approximately 5 ∼ 10 min after neutralization of protamine) and T3 (before leaving the operating room), and then averaged. Serum creatinine was measured 1 day before and within 7 days after CABG. There was no statistically significant association between the TEE-monitoring indicator TAPSE and the incidence of postoperative AKI in patients who underwent CABG. Conclusions The TAPSE was not significantly correlated with postoperative AKI incidence and could not predict the early occurrence of postoperative AKI in CABG patients. TEE needs more evaluation for clinical efficacy of predicting the early occurrence of postoperative AKI in isolated CABG.

Abstract The Omicron subvariants of SARS-CoV-2, especially for BA.2.86 and JN.1, have rapidly spread across multiple countries, posing a significant threat in the ongoing COVID-19 pandemic. Distinguished by 34 additional mutations on the Spike (S) protein compared to its BA.2 predecessor, the implications of BA.2.86 and its evolved descendant, JN.1 with additional L455S mutation in receptor-binding domains (RBDs), are of paramount concern. In this work, we systematically examine the neutralization susceptibilities of SARS-CoV-2 Omicron subvariants and reveal the enhanced antibody evasion of BA.2.86 and JN.1. We also determine the cryo-EM structures of the trimeric S proteins from BA.2.86 and JN.1 in complex with the host receptor ACE2, respectively. The mutations within the RBDs of BA.2.86 and JN.1 induce a remodeling of the interaction network between the RBD and ACE2. The L455S mutation of JN.1 further induces a notable shift of the RBD–ACE2 interface, suggesting the notably reduced binding affinity of JN.1 than BA.2.86. An analysis of the broadly neutralizing antibodies possessing core neutralizing epitopes reveals the antibody evasion mechanism underlying the evolution of Omicron BA.2.86 subvariant. In general, we construct a landscape of evolution in virus-receptor of the circulating Omicron subvariants.

Acute lung injury (ALI) or its more severe form, acute respiratory distress syndrome, is a life-threatening disease closely associated with an imbalance of M1/M2 macrophage polarization. However, current therapeutic strategies for ALI are controversial due to their side effects, restricted administration routes, or poor targeted delivery. The development of herbal medicine has uncovered numerous anti-inflammatory compounds potentially beneficial for ALI therapy. One such compound is the bergapten, a coumarin, which has been isolated from Ficus simplicissima Lour. However, it's been used as an anti-cancer drug and it's effects on ALI remain unexplored. The poor solubility and biodistribution of bergapten heavily limit its application. In this timely report, we developed a bioactive and lung-targeting lipid-nanomedicine by integrating bergapten and DPPC liposome, named as Ber-lipo. A comprehensive series of in vitro experiments confirmed the anti-inflammatory effects of Ber-lipo and its protective roles in maintaining the homeostasis of macrophage polarization and epithelial–endothelial integrity. In a lipopolysaccharide (LPS)-induced ALI mouse model, Ber-lipo can target inflamed lungs and significantly improve lung edema, tissue injury, and pulmonary function, relieve body weight loss, pulmonary permeability, and proinflammatory status, and especially maintain a balance of M1/M2 macrophage polarization. Furthermore, RNA sequencing analysis showed Ber-lipo's potential in effectively treating inflammatory lung diseases such as pneumonia, inhibiting proinflammatory signals, and altering the transcriptome of M1/M2 macrophages-associated genes in lung tissues. Molecular docking and Western blot analyses validated that Ber-lipo suppressed the activation of the TLR4/MyD88/NF-κB signaling axis responsible for ALI progression. In conclusion, this study demonstrates for the first time that new inhalable nanomedicine (Ber-lipo) can target inflamed lungs and ameliorates ALI by reprogramming macrophage polarization to an anti-inflammatory state via inactivating the TLR4/MyD88/NF-κB pathway, hence providing a promising strategy for enhanced ALI therapy in the clinic.

Abstract Objective To study the effects of selective serotonin reuptake inhibitors (SSRIs) on cognitive functions, mental improvements, and adverse effects in patients with Alzheimer’s disease (AD). Methods Registered in INPLASY (INPLASY202450004), five drugs (citalopram, s-citalopram, quetiapine, olanzapine, and sertraline) were selected as representatives. A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to May 15, 2024. Search terms were combined using Boolean operators, specifically ‘AND’ between different categories (e.g., ‘Alzheimer’s Disease’ AND ‘SSRIs’) and ‘OR’ within the same category (e.g., ‘citalopram OR s-citalopram OR quetiapine OR olanzapine OR sertraline’), to ensure a thorough retrieval of relevant studies. The selection followed rigorous inclusion and exclusion criteria for meta-analysis. Results Fourteen articles from 1118 were selected for meta-analysis. The indicators, including Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), Brief Psychiatric Rating Scale (BPRS), and Cornell Scale for Depression in Dementia (CSDD), were used to assess the effects of the drugs on AD treatment. According to the results of NPI, CSDD, BPRS, MMSE, and security assessments, the five antidepressants have significant advantages in AD treatment compared with placebo, while the MMSE of the patient treated with the antidepressants did not show notable changes compared with patients treated only with placebo. Statistical analyses were conducted using Review Manager 5.3, employing random-effects models to account for study heterogeneity and sensitivity analyses to test the robustness of our findings. Conclusion This study suggests that SSRI-related antidepressants have great potential values in AD treatment, and further research on the application of SSRI-related antidepressants in AD treatment is necessary.

Abstract The Pleurotomarioidea, commonly referred to as slit shells, constitute one of the most ancient and enduring lineages within the phylum Mollusca, with its fossil record tracing back to the Upper Cambrian epoch. Its rareness and evolutionary antiquity surpass even that of the nautilus. In this study, we conducted the first transcriptome sequencing and analyses of Entemnotrochus rumphii (Schepman, 1879), a representative species of Pleurotomarioidea. Full-length transcriptome sequencing of E. rumphii was performed using the PacBio Sequel II platform with SMRT technology. A total of 64.38 gigabytes of data and 964,550 polymerase reads were generated, resulting in 28,068,998 subreads after data filtering. After de-duplication, correction, and clustering, we identified 19,273 genes. Additionally, next-generation sequencing was performed on 11 tissues of E. rumphii. This investigation provides a detailed portrayal and analytical scrutiny of its transcriptomic landscape.

Abstract The second-order periodic system with p-Laplacian and unbounded time-dependent perturbation terms is investigated. Using the principle integral method, it is shown that under certain assumptions on the unbounded and periodic terms, all solutions to the equation possess boundedness.

Abstract Background Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. Methods Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5–84 years), year (1990–2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. Results In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from −0.54% (−0.61%, −0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. Conclusions Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.

Background The control rate for patients with hypertension remains suboptimal, with hypertensive patients experiencing a lower quality of life compared to healthy individuals. Enhancing life quality and lowering blood pressure in patients with hypertension through behavioral interventions is currently a critical area of research. Theoretical-based behavioral interventions are shown to be more effective and sustainable in modifying the behaviors of hypertensive patients. The Behavior Change Wheel (BCW) and Behavior Change Techniques (BCTs) are widely utilized in the management of chronic diseases globally to maximize the exploration of modifiable factors. Nevertheless, in the domestic context, studies on the impact of BCW and BCTs-driven behavioral interventions on the ambulatory blood pressure and quality of life of hypertensive patients are relatively limited, indicating a need for more comprehensive research. Objective This study aims to develop and evaluate the intervention based on BCW and BCTs, focusing on its impact on behavior, ambulatory blood pressure, and quality of life in hypertensive patients. Methods From December 2021 to August 2022, a hundred hypertensive patients who met the inclusion criteria were selected as study participants. They were allocated into an intervention group and a control group using a simple randomization method, with each group comprising fifty participants. Patients in the control group received conventional outpatient medication and health education lifestyle guidance. In contrast, patients in the intervention group was treated with standard medication supplemented by the BCW and BCTs-based intervention guidance.Before and after the intervention, assessments were conducted using the Hypertension Knowledge-Level Scale, the Chinese Version of the 8-item Morisky Medication Adherence Scale, the International Physical Activity Questionnaire-Short, the Patient Health Questionnaire-9, the General Anxiety Disorder-7, ambulatory blood pressure monitoring, and the 12-Item Short-Form Health Survey. The study examined changes in behavioral indicators, results of ambulatory blood pressure monitoring, and quality of life pre- and post-intervention. Results The results indicated that after the intervention, the intervention group exhibited significantly higher levels of hypertension knowledge, medication adherence, quality of life scores, proportions of high medication adherence and engagement in moderate physical activity compared to the control group (P

Background In recent years, numerous studies have indicated that hyperuricemia (HUA) is a contributing factor to certain diseases. However, whether HUA is a contributing factor to chronic pulmonary heart disease (CPHD) still requires further investigation. Objective To explore the association between HUA and CPHD, aiming to provide a theoretical basis for the management of serum uric acid (SUA) levels in patients with CPHD. Methods A total of1 171 patients with chronic obstructive pulmonary disease (COPD) admitted to the First Affiliated Hospital of Xinjiang Medical University from 2019 to 2023 were included in the study. They were divided into a CPHD group (470 cases) and a COPD group (701 cases) based on whether they had CPHD. General information, laboratory test results, and echocardiographic findings of the patients were collected. LASSO regression was used to select variables, and propensity score matching (PSM) was employed to eliminate the influence of confounding factors. Multivariate Logistic regression analysis was conducted to explore the influencing factors of CPHD in COPD patients. Results The CPHD group had lower proportions of females, Han ethnicity, smokers, drinkers, idiopathic pulmonary fibrosis, chronic bronchitis, bronchial asthma, lymphocyte percentage, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, cardiac output, left ventricular ejection fraction compared to the COPD group. Higher proportions of heart function class 3-4, HUA, pulmonary embolism, congenital heart disease, red blood cell count, neutrophil percentage, SUA, blood urea nitrogen, D-dimer, N-terminal pro-B-type natriuretic peptide, right atrial diameter, right ventricular diameter, left atrial diameter, right ventricular outflow tract diameter, and pulmonary artery diameter were observed in the CPHD group, with statistically significant differences (P381.29 μmol/L) had a 1.421-fold inScrsed risk of having CPHD. Conclusion HUA is a contributing factor to the occurrence and development of CPHD. Actively controlling SUA levels may help prevent the occurrence and development of CPHD.

Abstract The deltoid muscle and rotator cuff tissue are structural components that maintain the dynamic stability of the shoulder joint. However, atrophy of the deltoid muscle may affect the stability of the shoulder joint, which in turn alters the mechanical distribution of rotator cuff tissue. Currently, the effect of muscle volume changes in the deltoid muscle on reducing the load on the rotator cuff tissue is still unknown. Therefore, this paper intends to analyze the mechanical changes of rotator cuff tissue by deltoid muscle atrophy through finite elements. Based on previously published finite element shoulder models, the deltoid muscle was modeled by constructing deltoid muscle models with different degrees of atrophy as, 100% deltoid muscle (Group 1), 80% deltoid muscle (Group 2), and 50% deltoid muscle (Group 3), respectively. The three models were given the same external load to simulate glenohumeral joint abduction, and the stress changes in the rotator cuff tissue were analyzed and recorded. In all three models, the stress in the rotator cuff tissue showed different degrees of increase with the increase of abduction angle, especially in the supraspinatus muscle. At 90° of glenohumeral abduction, supraspinatus stress increased by 58% and 118% in Group 2 and Group 3, respectively, compared with Group 1; In the subscapularis, the stress in Group 3 increased by 59% and 25% compared with Group 1 and Group 2, respectively. In addition, the stress of the infraspinatus muscle and teres minor muscle in Group 2 and Group 3 were higher than that in Group 1 during the abduction angle from 30° to 90°. Deltoid atrophy alters the abduction movement pattern of the glenohumeral joint. During glenohumeral abduction activity, deltoid atrophy significantly increases the stress on the rotator cuff tissue, whereas normal deltoid volume helps maintain the mechanical balance of the rotator cuff tissue.

Abstract Background Lamb-Shaffer syndrome (LAMSHF, OMIM: 616803) is a rare neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, which is attributed to haploinsufficiency by heterozygous variants of SOX5 gene (SRY-Box Transcription Factor 5, HGNC: 11201) on chromosome 12p12. A total of 113 cases have been reported in the world, however, only 3 cases have been reported.in China. Here, we aimed to report novel variants of SOX5 gene and provide examples for clinical diagnosis by reporting the clinical phenotype of a series of Chinese patients with LAMSHF. Methods This study retrospectively collected the information of families of LAMSHF patients in China. Whole Exome Sequencing (WES) were performed to confirm the diagnosis of 4 children with unexplained developmental delay or epilepsy. A minigene splicing assay was used to verify whether the splice variant affected splicing. Meanwhile, a literature review was conducted to analyze the clinical and genetic characteristics of patients with LAMSHF. Results Three of the LAMSHF patients had a de novo heterozygous mutation in the SOX5 gene respectively, c.290delC (p.Pro97fs*30), chr12:23686019_24048958del, c.1772-1C > A, and the remaining one had a mutation inherited from his father, c.1411C > T (p.Arg471*). The main clinical manifestations of these children were presented with global developmental delays, and one of them also had seizures. And the results of the minigene experiment indicated that the splice variant, c.1772-1C > A, transcribed a novel mRNA product which leaded to the formation of a truncated protein. Conclusions Through a comprehensive review and analysis of existing literature and this study showed intellectual disability, speech delay and facial dysmorphisms were common clinical manifestation, while the seizures and EEG abnormalities were rare (21/95, 22.16%). Notably, we represent the largest sample size of LAMSHF in Asia that encompasses previously unreported SOX5 gene mutation, and a minigene testing have been conducted to validate the pathogenicity of the c.1772-1C > A splice variant. The research further expands the phenotype and genotype of LAMSHF while offers novel insights for potential pathogenicity of genes locus.

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia (OIH), but the underlying mechanisms remain elusive. The presence of astrocyte-neuron lactate shuttle (ANLS) makes astrocytes necessary for some neural function and communication. The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH. After 7 days consecutive morphine injection, a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4 (PDK4), phosphorylated pyruvate dehydrogenase (p-PDH) and accumulation of L-lactate was elevated in the spinal dorsal horn. Intrathecally administration of inhibitors of PDK, lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns. The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro. In this study, we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS. In this process, PDK-p-PDH-lactate axis serves a pivotal role, which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

Abstract Background Human health is a complex, dynamic concept encompassing a spectrum of states influenced by genetic, environmental, physiological, and psychological factors. Traditional Chinese Medicine categorizes health into nine body constitutional types, each reflecting unique balances or imbalances in vital energies, influencing physical, mental, and emotional states. Advances in machine learning models offer promising avenues for diagnosing conditions like Alzheimer's, dementia, and respiratory diseases by analyzing speech patterns, enabling complementary non-invasive disease diagnosis. The study aims to use speech audio to identify subhealth populations characterized by unbalanced constitution types. Methods Participants, aged 18–45, were selected from the Acoustic Study of Health. Audio recordings were collected using ATR2500X-USB microphones and Praat software. Exclusion criteria included recent illness, dental issues, and specific medical histories. The audio data were preprocessed to Mel-frequency cepstral coefficients (MFCCs) for model training. Three deep learning models—1-Dimensional Convolution Network (Conv1D), 2-Dimensional Convolution Network (Conv2D), and Long Short-Term Memory (LSTM)—were implemented using Python to classify health status. Saliency maps were generated to provide model explainability. Results The study used 1,378 recordings from balanced (healthy) and 1,413 from unbalanced (subhealth) types. The Conv1D model achieved a training accuracy of 91.91% and validation accuracy of 84.19%. The Conv2D model had 96.19% training accuracy and 84.93% validation accuracy. The LSTM model showed 92.79% training accuracy and 87.13% validation accuracy, with early signs of overfitting. AUC scores were 0.92 and 0.94 (Conv1D), 0.99 (Conv2D), and 0.97 (LSTM). All models demonstrated robust performance, with Conv2D excelling in discrimination accuracy. Conclusions The deep learning classification of human speech audio for health status using body constitution types showed promising results with Conv1D, Conv2D, and LSTM models. Analysis of ROC curves, training accuracy, and validation accuracy showed all models robustly distinguished between balanced and unbalanced constitution types. Conv2D excelled with good accuracy, while Conv1D and LSTM also performed well, affirming their reliability. The study integrates constitution theory and deep learning technologies to classify subhealth populations using noninvasive approach, thereby promoting personalized medicine and early intervention strategies.

Abstract Lead-free halide double perovskite Cs2AgInCl6 has been extensively studied in recent years due to the lead toxicity and poor stability of common lead halide perovskites. In this study, sodium (Na+) and bismuth (Bi3+) doped into Cs2AgInCl6 double perovskite, then Cs2Ag1− xNaxIn1 − yBiyCl6 films with broadband warm-yellow emissions were achieved by the blade coating method. Herein, Na and Bi content were changed as variables at a series of parameter optimization experiments, respectively. In the Cs2Ag1− xNaxIn1 − yBiyCl6 systems, Na+ broke the parity-forbidden transition of Cs2AgInCl6, and Bi3+ suppressed non-radiative recombination. The partial replacement of Ag+ with Na+ ions and doping with Bi3+ cations were crucial for increasing the intensity of the PL emission. The experimental results showed that the photoluminescence quantum yield of the Cs2Ag0.4Na0.6In0.8Bi0.2Cl6 film was 66.38%, which was the highest data among all samples. It demonstrated remarkable stability under heat and ultraviolet conditions. After five thermal cycles, the PL intensity of the Cs2Ag0.4Na0.6In0.8Bi0.2Cl6 film is only reduced to approximately 5.7% of the initial value. After 720 h continuous ultraviolet irradiation, there occurred 31.9% emission decay of the film.

Abstract Light-weight, high-strength, aluminum (Al) alloys have widespread industrial applications. However, most commercially available high-strength Al alloys, like AA 7075, are not suitable for additive manufacturing due to their high susceptibility to solidification cracking. In this work, a custom Al alloy Al92Ti2Fe2Co2Ni2 is fabricated by selective laser melting. Heterogeneous nanoscale medium-entropy intermetallic lamella form in the as-printed Al alloy. Macroscale compression tests reveal a combination of high strength, over 700 MPa, and prominent plastic deformability. Micropillar compression tests display significant back stress in all regions, and certain regions have flow stresses exceeding 900 MPa. Post-deformation analyses reveal that, in addition to abundant dislocation activities in Al matrix, complex dislocation structures and stacking faults form in monoclinic Al9Co2 type brittle intermetallics. This study shows that proper introduction of heterogeneous microstructures and nanoscale medium entropy intermetallics offer an alternative solution to the design of ultrastrong, deformable Al alloys via additive manufacturing.

Abstract Supercapacitor is highly demanded in emerging portable electronics, however, which faces frequent charging and inevitable rapid self-discharging of huge inconvenient. Here, we present a flexible moisture-powered supercapacitor (mp-SC) that capable of spontaneously moisture-enabled self-charging and persistently voltage stabilizing. Based on the synergy effect of moisture-induced ions diffusion of inner polyelectrolyte-based moist-electric generator and charges storage ability of inner graphene electrochemical capacitor, this mp-SC demonstrates the self-charged high areal capacitance of 138.3 mF cm−2 and ~96.6% voltage maintenance for 120 h. In addition, a large-scale flexible device of 72 mp-SC units connected in series achieves a self-charged 60 V voltage in air, efficiently powering various commercial electronics in practical applications. This work will provide insight into the design self-powered and ultra-long term stable supercapacitors and other energy storage devices.

ABSTRACT Global climate change and agricultural practices have increased atmospheric nitrogen (N) deposition, significantly affecting the nitrogen cycling process in grasslands. The impact of different N forms on key soil enzyme activities involved in N nitrification, particularly in the saline‐alkali grasslands of the Hexi Corridor, using natural grassland as a control (CK) and adding three N treatments: inorganic N (IN), organic N (ON) and a mixed N treatment (MN, with a 4:6 ratio of organic to inorganic N). Our study assessed the effects of these N forms on soil properties and enzyme activities crucial for N cycling. The findings indicate that different N forms significantly enhance soil mineral N content, with ON treatment leading to the highest increases in nitrate and ammonium content 92.44% and 35.6%, respectively, compared to CK. Both IN and ON treatments significantly boosted soil nitrate reductase and urease activities (p

Programmed cell death receptor 1 (PD-1), when bound to the ligand programmed death-ligand 1 (PD-L1), can suppress cellular immunity and play a critical role in the initiation and development of cancer. Immune drugs targeting these two sites have been developed for different cancers, including malignant melanoma. The accompanying diagnostic method has been approved by the FDA to guide patient medication. However, the method of immunohistochemical staining, which varies widely due to the antibody and staining cut-off values, has certain limitations in application and does not benefit all patients. Increasing researches begin to focus on new biomarkers to improve objective response rates and survival in cancer patients. In this article, we enumerated three major groups, including tumour microenvironment, peripheral circulation, and gene mutation, which covered the current main research directions. In the future, we hope those biomarkers may be used to guide the treatment of patients with malignant melanoma.

Magnetic and ferroelectric oxide thin films have long been studied for their applications in electronics, optics, and sensors. The properties of these oxide thin films are highly dependent on the film growth quality and conditions. To maximize the film quality, epitaxial oxide thin films are frequently grown on single‐crystal oxide substrates such as strontium titanate (SrTiO3) and lanthanum aluminate (LaAlO3) to satisfy lattice matching and minimize defect formation. However, these single‐crystal oxide substrates cannot readily be used in practical applications due to their high cost, limited availability, and small wafer sizes. One leading solution to this challenge is film transfer. In this demonstration, a material from a new class of multiferroic oxides is selected, namely bismuth‐based layered oxides, for the transfer. A water‐soluble sacrificial layer of Sr3Al2O6 is inserted between the oxide substrate and the film, enabling the release of the film from the original substrate onto a polymer support layer. The films are transferred onto new substrates of silicon and lithium niobate (LiNbO3) and the polymer layer is removed. These substrates allow for the future design of electronic and optical devices as well as sensors using this new group of multiferroic layered oxide films.

Abstract Background Colorectal cancer (CRC) is a malignancy that arises within the gastrointestinal tract. Despite ongoing research, the etiology and pathogenesis of CRC remain elusive; particularly, the distribution and characteristics of tumor‐associated macrophages is currently an active area of investigation in understanding the pathological progression and prevention of CRC. Methods This study utilized CRC patient surgical samples, mouse models of colitis‐associated cancer, colonic organoid, and co‐culture cell line to examine the changes in CD11b/CD86 at different pathological region and detect the Wnt signaling pathway activity. Results Our findings revealed a sensitive and increased expression of CD11b from the early to the advanced CRC tissues and correlated with poor prognosis, while CD86 expression was reduced in advanced CRC tissues. CD133 expression was also elevated in advanced CRC tissues and mainly co‐localized with CD11b, suggesting a positive regulatory effect of CD11b and CD133 expression that may contribute to CRC progression. In AOM/DSS mouse models, activation of the Wnt signaling pathway was associated with increased CD133 and CD11b expression. In vitro, THP‐1 cell was induced to high expression of CD11b, and the above conditional cultural medium enhanced HCT116 cell colony number and CD133 protein expression. Furthermore, colonic crypts from AOM/DSS mouse models were isolated to culture, and the colonic organoids exhibited dilation and significant increases expression of CD133 and β‐Catenin/N‐P‐B‐Catenin. Conclusions CD11b might be an important factor to participate the progress of CRC. And the high CD11b of CRC microenviroment might potentially promote CD133 expression and associate with Wnt signal activation.

In today’s digital and internet era, threat intelligence analysis is of paramount importance to ensure network and information security. Named Entity Recognition (NER) is a fundamental task in natural language processing, aimed at identifying and extracting specific types of named entities from text, such as person names, locations, organization names, dates, times, currencies, and more. The quality of entities determines the effectiveness of upper-layer applications such as knowledge graphs. Recently, there has been a scarcity of training data in the threat intelligence field, and single models suffer from poor generalization ability. To address this, we propose a multi-view learning model, named the Few-shot Threat Intelligence Named Entity Recognition Model (FTM). We enhance the fusion method based on FTM, and further propose the FTM-GRU (Gate Recurrent Unit) model. The FTM model is based on the Tri-training algorithm to collaboratively train three few-shot NER models, leveraging the complementary nature of different model views to enable them to capture more threat intelligence domain knowledge at the coding level.FTM-GRU improves the fusion of multiple views. FTM-GRU uses the improved GRU model structure to control the memory and forgetting of view information, and introduces a relevance calculation unit to avoid redundancy of view information while highlighting important semantic features. We label and construct a few-shot Threat Intelligence Dataset (TID), and experiments on TID as well as the publicly available National Vulnerability Database (NVD) validate the effectiveness of our model for NER in the threat intelligence domain. Experimental results demonstrate that our proposed model achieves better recognition results in the task.

To understand the explosion characteristics of methane-lignite coal dust mixtures and the spatiotemporal evolution of the early flame flow field, explosion pressure, OH* emission spectra, and early flame schlieren images were captured in a 60L constant volume combustion bomb. Schlieren image velocimetry was used to obtain the instantaneous velocity distribution of the methane-coal dust flame front. The results indicate that adding coal dust causes a nonlinear increase in explosion pressure, particularly at low methane concentrations. At a 5 % methane concentration, adding coal dust can increase the maximum explosion pressure by up to 39 % (190 kPa). The trend of the OH* emission spectra corresponds with the maximum explosion pressure. A slight increase in coal dust significantly enhances the OH* emission spectra, especially at lower concentrations, potentially increasing it by nearly five times. However, at higher coal dust concentrations, the OH* emission spectra are significantly reduced. Additionally, within the considered concentration range (≤58.14 g/m³), larger turbulent integral length scales in initial conditions consistently result in the fastest flame acceleration. These findings provide experimental evidence for further exploration of the explosion mechanisms of methane-coal dust mixtures and the development of chemical reaction kinetic models.

ABSTRACT: In the late growth stage of commercial Pekin ducks, a significant increase in feed intake and a decline in body weight gain have been observed, leading to impaired feed conversion efficiency. To address this issue, we investigated alterations in production performance, blood biochemical indices, ileum tissue architecture, and microbial community structure in Pekin ducks. The primary objective was to provide robust data supporting the improvement of meat duck production efficiency during the late growth stage (28–42-days-old). Forty 28-day-old Pekin ducks were randomly assigned to 8 replicates, with five ducks per replicate. The rearing period lasted 14 days, with feed and water provided ad libitum. Our findings indicated a significant increase in Pekin duck body and heart weights with advancing age (P < 0.05). Moreover, serum antioxidant enzyme and high-density lipoprotein concentrations significantly increased, whereas triglyceride levels decreased (P < 0.05). Notably, the height of the ileal villi was significantly reduced (P < 0.05). The microbial community structure of the ileum exhibited significant changes as ducks aged, accompanied by a substantial increase in microbial flora diversity, particularly with the formation of more tightly connected microbial network modules. Time-dependent enrichment was observed in microbial gene functions related to energy metabolism pathways. At the genus level, Sphingomonas and Subdoligranulum have emerged as crucial players in microbial differential functional pathways and network formation. These bacteria likely serve as the key driving factors in the dynamic microbial changes that occur in Pekin ducks over time. Overall, our findings suggest a potential decline in the absorption function of the small intestine and fat deposition performance of Pekin ducks during later growth stages, which may be attributed to the maturation and proliferation of the gut microbial community.

Laser powder bed fusion is capable of fabricating aluminum (Al) alloy parts with great geometrical flexibility and rapid prototyping for various industries. However, high strength Al alloys generally suffer from solidification cracks due to the steep thermal gradient associated with the laser fusion process. Here, we report several strategies to mitigate the hot crack susceptibility of a high strength Al92Ti2Fe2Co2Ni2 alloy. Routine processing parameter optimization based on varying laser power and scanning speed has to trade off porosity for producing crack-free parts, making it not suitable for load-bearing structural applications. Furthermore, secondary printing parameters, including laser strip length, laser defocus, scanning strategies, etc., improved printability but were insufficient to eliminate all the cracks. Crack morphology and residual stress measurements indicate that the cracks are generated in the solid state driven by large tensile residual stress, instead of solidification cracking or liquation cracking. Thus, an attempt was made to alleviate the residual stress in a controlled manner. By properly introducing a compliant, sacrificial, scaffold support structure to regulate crack propagation, near fully dense, crack-free parts could be successfully printed. The results were further verified by micro computed tomography, showing that cracking could be arrested in the support before propagating through the parts. This method can be readily applied to other alloy systems without modifying the chemistry.

Abstract Multicomponent oxides are intriguing materials in heterogeneous catalysis, and the interface between various components often plays an essential role in oxidations. However, the underlying principles of how the hetero-interface affects the catalytic process remain largely unexplored. Here we report a unique structure design of MnCoO x catalysts by chemical reduction, specifically for ethane oxidation. Part of the Mn ions incorporates with Co oxides to form spinel Mn x Co3-x O4, while the rests stay as MnO2 domains to create the MnO2-Mn x Co3-x O4 interface. MnCoO x with Mn/Co ratio of 0.5 exhibits an excellent activity and stability up to 1000 h under humid conditions. The synergistic effects between MnO2 and Mn x Co3-x O4 are elucidated, in which the C2H6 tends to be adsorbed on the interfacial Co sites and subsequently break the C-H bonds on the reactive lattice O of MnO2 layer. Findings from this study provide valuable insights for the rational design of efficient catalysts for alkane combustion.

Abstract Background With the development and utilization of three-dimensional (3D) intraoral scanning (IOS) technology, the morphological characteristics of teeth were quantitatively assessed. In this research, we aimed to explore the prevalence of dental caries in relation to each measurable morphological indicator of the tooth body via 3D intraoral scanning techniques. Methods A hospital-based single-centre study was conducted at our hospital from Dec. 2021 to Apr. 2023. A total of 53 patients were involved in the study, providing complete morphological data for 79 teeth. Each patient completed an oral hygiene routine questionnaire and underwent examination by an experienced dentist to evaluate caries conditions before undergoing 3D intraoral scanning to obtain a digital dental model. Geomagic Studio 2014 was used to extract oral morphological data from the models. The acquired data were entered, cleaned and edited using Excel 2016 and subsequently exported to SPSS version 25.0 for analysis. Chi-square analysis and logistic regression analyses were employed to test the associations. Results Among the participants, 33 (61.1%) were female, with a mean age of 26.52 ± 10.83 years. Significant associations were found between dental caries and the vertical distance between the distal tip and the gum (OR 14.02; 95% CI 1.80-109.07; P = 0.012), the distal lateral horizontal distance of occlusion (OR 0.40; 95% CI 0.18–0.90; P = 0.026), and the mesial horizontal distance of occlusion (OR 2.20; 95% CI 1.12–4.31; P = 0.021). The Hosmer–Lemeshow test indicated a P value of 0.33. Conclusions The vertical distance between the distal tip and the gum, the distal lateral horizontal distance of the occlusion and the mesial horizontal distance of the occlusion were the influencing factors for dental caries (identified as independent risk factors). We hypothesize that these factors may be associated with the physiological curvature of teeth and the role of chewing grooves in plaque formation over time. However, further studies involving larger population samples and more detailed age stratification are still needed.

We aimed to explore the performance of bone marrow mesenchymal stem cells (BMSCs) in modulating signal transducer and activator of transcription 3 (STAT3)/β-catenin to facilitate alveolar bone remodeling in periodontitis rats in the process of orthodontic tooth movement. Flow cytometry was employed to identify BMSCs isolated, and then their osteogenic capacity was examined by alizarin red staining assay. BMSCs group (n=10), periodontitis + orthodontic tooth movement (PO+OTM) group (n=10), BMSCs+Static group (n=10) and negative control (NC) group (n=10) were set up for random allocation of 40 rats. The PO+OTM group had significantly decreased bone mineral density (BMD), trabecular number (Tb.N), bone volume/total volume (BV/ TV), trabecular thickness (Tb.Th), phosphorylated STAT3 (p-STAT3) ratio in alveolar bone tissues, but increased receptor activator of nuclear factor-κB ligand protein expression, trabecular space (Tb.Sp), cement-enamel junction to alveolar bone crest, and osteoclast count in comparison to those of the NC group (P

Abstract Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress and natural killer cell lysis, thereby promoting their colonization and metastasis to distant organs. Platelets can affect the tumor microenvironment via interactions between platelet-related factors and tumor cells. Metastasis is a key event in cancer-related death and is associated with platelet-related factors in lung, breast, and colorectal cancers. Although the factors that promote platelet expression vary slightly in terms of their type and mode of action, they all contribute to the overall process. Recognizing the correlation and mechanisms between these factors is crucial for studying the colonization of distant target organs and developing targeted therapies for these three types of tumors. This paper reviews studies on major platelet-related factors closely associated with metastasis in lung, breast, and colorectal cancers.

Abstract The α-tubulin subtype, Tubulin α-1b chain (TUBA1B), has been shown to influence immune cell infiltration, cancer growth, and survival across various malignancies. However, a comprehensive study has not yet been undertaken examining the immunological and predictive effects of TUBA1B in a pan-carcinoma context. Using data from TCGA, GEO, and other databases, we analyzed TUBA1B expression across various carcinoma types using transcriptional profiling, prognostic implications, genetic and epigenetic alterations, methylation patterns, and immunological significance. To validate our findings, we conducted Western blot analysis to assess TUBA1B protein levels in matched breast cancer tissue samples and performed CCK-8 proliferation assay, flow cytometry, transwell invasion, and migration assays to comprehensively examine the functional impact of TUBA1B on breast cancer cells. Our pan-cancer analysis found TUBA1B upregulation across most tumor types, with varying expression patterns in distinct immune and molecular subtypes. High TUBA1B expression was an independent risk factor and associated with poor prognoses in several cancers, including BRCA, KICH, LGG, LUAD, and MESO. TUBA1B also demonstrates moderate to high diagnostic accuracy in most tumor types. Increased m6A methylation levels were observed in the TUBA1B gene, while its promoter region displayed low methylation levels. TUBA1B's expression impacted some cancers by elevating tumor mutation burden, microsatellite instability, neoantigen formation, immune cell infiltration, and the modulation of immune checkpoints. Functional enrichment analysis highlights TUBA1B’s involvement in important cellular processes such as the cell cycle, p53 signaling, cell senescence, programmed cell death, and the regulation of immune-related pathways. Moreover, our study reveals higher TUBA1B protein expression in breast cancer tissues compared to adjacent tissues. In vitro experiments confirm that TUBA1B deletion reduces breast cancer cell proliferation, invasion, and migration while increasing apoptosis. In conclusion, our study suggests that TUBA1B could potentially serve as a diagnostic marker for predicting cancer immunological profiles and survival outcomes and shed light on the expression and role of TUBA1B in breast cancer, providing a solid foundation for considering it as a promising therapeutic target for breast cancer patient treatment.

Objective To explore the application of machine learning in scientific and rational blood preparation and predictive analysis for surgical blood usage before liver transplantation surgery. Methods Clinical basic information including gender, age, clinical diagnosis and surgical methods of 356 liver transplantation patients were collected. The duration (Time) and preoperative laboratory test results of hemoglobin (Hb), hematocrit (Hct), platelet count (Plt), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), total bilirubin (TBIL), albumin (ALB), creatinine (Crea) and total protein (TP), as well as the amount of intraoperative blood transfusion were collected. A machine learning model capable of predicting the risk of massive blood transfusion during liver transplantation surgery was established by Python, and was evaluated to select the optimal predictive model. Results Among the 7 machine learning models constructed, the logistic regression model performed the best (AUROC: 0.90, F1 score: 0.82), with an accuracy of 79.44% and precision of 79.69%, followed by the random forest classifier (AUROC: 0.87, F1 score: 0.83), with an accuracy of 79.44% and precision of 77.94%. Conclusion Establishing a machine learning prediction model by Python is of significant clinical importance for scientific blood preparation, predicting the risk of massive blood transfusion and ensuring the safety of blood use in liver transplantation surgery.

Abstract Objectives To develop a multiparameter magnetic resonance imaging (MRI)-based radiomics approach that can accurately predict the tumor cell proliferation status of serous ovarian carcinoma (SOC). Materials and methods A total of 134 patients with SOC who met the inclusion and exclusion criteria were retrospectively screened from institution A, spanning from January 2016 to March 2022. Additionally, an external validation set comprising 42 SOC patients from institution B was also included. The region of interest was determined by drawing each ovarian mass boundaries manually slice-by-slice on T2-weighted imaging fat-suppressed fast spin-echo (T2FSE) and T1 with contrast enhancement (T1CE) images using ITK-SNAP software. The handcrafted radiomic features were extracted, and then were selected using variance threshold algorithm, SelectKBest algorithm, and least absolute shrinkage and selection operator. The optimal radiomic scores and the clinical/radiological independent predictors were integrated as a combined model. Results Compared with the area under the curve (AUC) values of each radiomic signature of T2FSE and T1CE, respectively, the AUC value of the radiomic signature (T1CE-T2FSE) was the highest in the training set (0.999 vs. 0.965 and 0.860). The homogeneous solid component of the ovarian mass was considered the only independent predictor of tumor cell proliferation status among the clinical/radiological variables. The AUC of the radiomic–radiological model was 0.999. Conclusions The radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can accurately predict tumor cell proliferation status of SOC which has high repeatability and may enable more targeted and effective treatment strategies. Critical relevance statement The proposed radiomic–radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can predict tumor cell proliferation status of SOC which has high repeatability and may guide individualized treatment programs. Key points • The radiomic–radiological nomogram may guide individualized treatment programs of SOC. • This radiomic–radiological nomogram showed a favorable prediction ability. • Homogeneous slightly higher signal intensity on T2FSE is vital for Ki-67. Graphical Abstract

Abstract Background Parkinson’s disease (PD) is characterized by death of dopaminergic neurons leading to dopamine deficiency, excessive α-synuclein facilitating Lewy body formation, etc. Latroeggtoxin-VI (LETX-VI), a proteinaceous neurotoxin discovered from the eggs of spider L. tredecimguttatus, was previously found to promote the synthesis and release of PC12 cells, showing a great potential as a drug candidate for PD. However, the relevant mechanisms have not been understood completely. The present study explored the mechanism underlying the effects of LETX-VI on dopamine and α-synuclein of PC12 cells and the implications for PD. Results After PC12 cells were treated with LETX-VI, the level of dopamine was significantly increased in a dose-dependent way within a certain range of concentrations. Further mechanism analysis showed that LETX-VI upregulated the expression of tyrosine hydroxylase (TH) and L-dopa decarboxylase to enhance the biosynthesis of dopamine, and downregulated that of monoamine oxidase B to reduce the degradation of dopamine. At the same time, LETX-VI promoted the transport and release of dopamine through modulating the abundance and/or posttranslational modification of vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT). While the level of dopamine was increased by LETX-VI treatment, α-synuclein content was reduced by the spider toxin. α-Synuclein overexpression significantly decreased the dopamine level and LETX-VI efficiently alleviated the inhibitory action of excessive α-synuclein on dopamine. In the MPTP-induced mouse model of PD, application of LETX-VI ameliorated parkinsonian behaviors of the mice, and reduced the magnitude of MPTP-induced α-synuclein upregulation and TH downregulation. In addition, LETX-VI displayed neuroprotective effects by inhibiting MPTP-induced decrease in the numbers of TH-positive and Nissl-stained neurons in mouse brain tissues. Conclusions All the results demonstrate that LETX-VI promotes the synthesis and release of dopamine in PC12 cells via multiple mechanisms including preventing abnormal α-synuclein accumulation, showing implications in the prevention and treatment of PD.

Abstract Nanotwinned metals have been intensely investigated due to their unique microstructures and superior properties. This work aims to investigate the nanovoid formation mechanism in sputter-deposited nanotwinned Cu. Three different types of epitaxial or polycrystalline Cu films are fabricated by magnetron sputtering deposition technique. In the epitaxial Cu (111) films deposited on Si (110) substrates, high fractions of nanovoids and nanotwins are formed. The void size and density can be tailored by varying deposition parameters, including argon pressure, deposition rate, and film thickness. Interestingly, nanovoids become absent in the polycrystalline Cu film deposited on Si (111) substrate, but they can be regained in the epitaxial nanotwinned Cu (111) when deposited on Si (111) substrate with an Ag seed layer. The nanovoid formation seems to be closely associated with twin nucleation and film texture. Based on the comparative studies between void-free polycrystalline Cu films and epitaxial nanotwinned Cu films with nanovoids, the underlying mechanisms for the formation of nanovoids are discussed within the framework of island coalescence model. Graphical abstract

Abstract The rapid development of the Internet technology along with the emergence of intelligent applications has put forward higher requirements for task offloading. In Cloud-Edge-End (CEE) environments, offloading computing tasks of terminal devices to edge and cloud servers can effectively reduce system delay and alleviate network congestion. Designing a reliable task offloading strategy in CEE environments to meet users’ requirements is a challenging issue. To design an effective offloading strategy, a Service Reliability Analysis and Elite-Artificial Bee Colony Offloading model (SRA-E-ABCO) is presented for cloud-edge-end environments. Specifically, a Service Reliability Analysis (SRA) method is proposed to assist in predicting the offloading necessity of terminal tasks and analyzing the attributes of terminal devices and edge nodes. An Elite Artificial Bee Colony Offloading (E-ABCO) method is also proposed, which optimizes the offloading strategy by combining elite populations with improved fitness formulas, position update formulas, and population initialization methods. Simulation results on real datasets validate the efficient performance of the proposed scheme that not only reduces task offloading delay but also optimize system overhead in comparison to baseline schemes.

Abstract Energy supply policy quality is an important factor that would impact national energy security. While existing research conducted policy evaluation from the lens of performance assessment, less study has been devoted to evaluating energy supply policy from the perspective of policy making. This study takes the energy supply policy documents issued by China's central government during the ‘13th Five‐Year Plan’ period (2016–2020) as the research sample, and pioneers the use of the extended policy modelling consistency (PMC) index model combined with the text mining methodology to construct a policy evaluation index system with the characteristics of the energy supply policy which conducts a more in‐depth quantitative evaluation of the energy supply policy documents. The results show that the average PMC index value of China's energy supply policies is 7.26, and the overall quality is high. The concerns of existing policies are mainly focused on reform and development planning, safety production management and project engineering construction, but there is still room for improvement in policy predictability, coordination of policy areas, clarity of policy basis and goals and comprehensiveness of policy tool combinations. Based on this, China should improve the comprehensiveness of its energy supply policy tool combinations in terms of policy design norm; strengthen policy predictability and coordination of policy areas in terms of policy implementation guarantee; and clarify the basis and goals of policies in terms of policy orientation enhancement, to provide a reference basis for the formulation and improvement of future energy supply policies and to realise the sustainable development of energy supply.

Abstract The randomized, multicenter, double-blind, placebo-controlled, phase III PEONY trial (NCT02586025) demonstrated significantly improved total pathologic complete response (primary endpoint) with dual HER2 blockade in HER2-positive early/locally advanced breast cancer, as previously reported. Here, we present the final, long-term efficacy (secondary endpoints: event-free survival, disease-free survival, overall survival) and safety analysis (62.9 months’ median follow-up). Patients (female; n = 329; randomized 2:1) received neoadjuvant pertuzumab/placebo with trastuzumab and docetaxel, followed by adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, then pertuzumab/placebo with trastuzumab until disease recurrence or unacceptable toxicity, for up to 1 year. Five-year event-free survival estimates are 84.8% with pertuzumab and 73.7% with placebo (hazard ratio 0.53; 95% confidence interval 0.32–0.89); 5-year disease-free survival rates are 86.0% and 75.0%, respectively (hazard ratio 0.52; 95% confidence interval 0.30–0.88). Safety data are consistent with the known pertuzumab safety profile and generally comparable between arms, except for diarrhea. Limitations include the lack of ado-trastuzumab emtansine as an option for patients with residual disease and the descriptive nature of the secondary, long-term efficacy endpoints. PEONY confirms the positive benefit:risk ratio of neoadjuvant/adjuvant pertuzumab, trastuzumab, and docetaxel treatment in this patient population.

ABSTRACTIn many cases, the Digital Surface Models (DSMs) and Digital Elevation Models (DEMs) are obtained with Light Detection and Ranging (LiDAR) or stereo matching. As an active method, LiDAR is very accurate but expensive, thus often limiting its use in small-scale acquisition. Stereo matching is suitable for large-scale acquisition of terrain information as the increase of satellite stereo sensors. However, underperformance of stereo matching easily occurs in textureless areas. Accordingly, this study proposed a Shading Aware DSM GEneration Method (SADGE) with high resolution multi-view satellite images. Considering the complementarity of stereo matching and Shape from Shading (SfS), SADGE combines the advantage of stereo matching and SfS technique. First, an improved Semi-Global Matching (SGM) technique is used to generate an initial surface expressed by a DSM; then, it is refined by optimizing the objective function which modeled the imaging process with the illumination, surface albedo, and normal object surface. Different from the existing shading-based DEM refinement or generation method, no information about the illumination or the viewing angle is needed while concave/convex ambiguity can be avoided as multi-view images are utilized. Experiments with ZiYuan-3 and GaoFen-7 images show that the proposed method can generate higher accuracy DSM (12.5–56.3% improvement) with sound overall shape and temporarily detailed surface compared with a software solution (SURE) for multi-view stereo.

Dendrobium officinale is a well-recognized functional food material. Considering its therapeutic effect and price vary among different geographical origins, this paper proposed an origin identification method based on Raman spectroscopy and NNRW (neural network with random weights)-stacking ensemble model. In a case study of dendrobium officinale samples from three different geographical origins, we compare both single estimators, i.e., KNN (k-nearest neighbors), MLP (multi-layer perceptron), DTC (decision tree classifier), and NNRW, and their stacking ensemble counterparts. The results showed that the NNRW-stacking ensemble has the best test accuracy (96.3%) and an impressive fitting speed (the fastest among all ensembles). In conclusion, the NNRW-stacking ensemble model combined with Raman spectroscopy can be a promising method for herb geographical original identification. The proposed model has demonstrated the speed advantage of NNRW (no need for gradient-based iterations) and the generalization power of stacking ensembles (reduce single-estimator bias).