Search

ABSTRACT Fusarium pseudograminearum, a soil-borne fungus, is the cause of the devastating wheat disease known as wheat crown rot (WCR). The persistence of this pathogen in the soil and crop residues contributes to the increased occurrence and severity of WCR. Therefore, developing effective strategies to prevent and manage WCR is of great importance. In this study, we isolated a bacterial strain, designated as SR9, from the stem of wheat, that exhibited potent antagonistic effects against F. pseudograminearum, as well as the biocontrol efficacy of SR9 on WCR was quantified at 83.99% ± 0.11%. We identified SR9 as Pseudomonas khavaziana and demonstrated its potential as a plant probiotic. SR9 displayed broad-spectrum antagonism against other fungal pathogens, including Neurospora dictyophora, Botrytis californica, and Botryosphaeria dothidea. Whole-genome sequencing analysis revealed that SR9 harbored genes encoding various cell wall-degrading enzymes, cellulases, and lipases, along with antifungal metabolites, which are responsible for its antagonistic activity. Gene knockout and quantitative PCR analyses reveal that phenazine is the essential factor for antagonism. SR9 possessed genes related to auxin synthesis, flagellar biosynthesis, biofilm adhesion, and the chemotaxis system, which play pivotal roles in plant colonization and growth promotion; we also evaluated the effects of SR9 on plant growth in wheat and Arabidopsis. Our findings strongly suggest that SR9 holds great promise as a biocontrol agent for WCR in sustainable agriculture.IMPORTANCEThe escalating prevalence of wheat crown rot, primarily attributed to Fusarium pseudograminearum, necessitates the development of cost-effective and eco-friendly biocontrol strategies. While plant endophytes are recognized for their biocontrol potential, reports on effective strains targeting wheat crown rot are sparse. This study introduces the Pseudomonas khavaziana SR9 strain as an efficacious antagonist to the wheat crown rot pathogen Fusarium pseudograminearum. Demonstrating a significant reduction in wheat crown rot incidence and notable plant growth promotion, SR9 emerges as a key contributor to plant health and agricultural sustainability. Our study outlines a biological approach to tackle wheat crown rot, establishing a groundwork for innovative sustainable agricultural practices.

Liver fibrosis is a group of diseases that seriously affect the health of the world’s population. Despite significant progress in understanding the mechanisms of liver fibrogenesis, the technologies and drugs used to treat liver fibrosis have limited efficacy. As a revolutionary genetic tool, gene editing technology brings new hope for treating liver fibrosis. Combining nano-delivery systems with gene editing tools to achieve precise delivery and efficient expression of gene editing tools that can be used to treat liver fibrosis has become a rapidly developing field. This review provides a comprehensive overview of the principles and methods of gene editing technology and commonly used gene editing targets for liver fibrosis. We also discuss recent advances in common gene editing delivery vehicles and nano-delivery formulations in liver fibrosis research. Although gene editing technology has potential advantages in liver fibrosis, it still faces some challenges regarding delivery efficiency, specificity, and safety. Future studies need to address these issues further to explore the potential and application of liver fibrosis technologies in treating liver fibrosis.

Abstract As a naturally occurring cytolytic peptide, melittin (MLT) not only exhibits a potent direct tumor cell-killing effect but also possesses various immunomodulatory functions. MLT shows minimal chances for developing resistance and has been recognized as a promising broad-spectrum antitumor drug because of this unique dual mechanism of action. However, MLT still displays obvious toxic side effects during treatment, such as nonspecific cytolytic activity, hemolytic toxicity, coagulation disorders, and allergic reactions, seriously hampering its broad clinical applications. With thorough research on antitumor mechanisms and the rapid development of nanotechnology, significant effort has been devoted to shielding against toxicity and achieving tumor-directed drug delivery to improve the therapeutic efficacy of MLT. Herein, we mainly summarize the potential antitumor mechanisms of MLT and recent progress in the targeted delivery strategies for tumor therapy, such as passive targeting, active targeting and stimulus-responsive targeting. Additionally, we also highlight the prospects and challenges of realizing the full potential of MLT in the field of tumor therapy. By exploring the antitumor molecular mechanisms and delivery strategies of MLT, this comprehensive review may inspire new ideas for tumor multimechanism synergistic therapy.

Abstract Background Rare as membranous ventricular septal aneurysms (MVSA) is, the possibility that occurs after ventricular septum defect (VSD) repair surgery is even more uncommon. Presentation A girl developed a MVSA 3 years after the VSD repair surgery at the age of 1 and increasing growth was noted during the follow-up. Aneurysm plication was carried done when she was 11 years old because it was observed to have a close relationship to the right coronary and obstructed the right ventricular outflow tract. Postoperative echocardiography follow-up revealed no abnormalities. Conclusion Though the prognosis of most patients with VSD repaired surgery was good, there remains varieties type of complications despite surgical advances. Accurate and rapid diagnosis of acute and delayed complications is essential to improve prognosis. In this case, the aneurysm was diagnosed by multiple imaging modalities and the girl underwent successful surgery again which provides direction for awareness and knowledge of delayed complications of VSD repair.

ObjectiveTo investigate the clinical characteristics and outcomes of three patients with symptomatic Spinal epidural lipomatosis (SEL) treated using Unilateral Biportal Endoscopic (UBE) surgery.MethodsThis report retrospectively analyzed the clinical data of three patients with SEL admitted to our hospital. The analysis covers onset characteristics, clinical manifestations, and the most recent radiologic grading system of neural compression (Manjila classification). Furthermore, it details the decompression accomplished through the application of a minimally invasive UBE surgical technique, specifically targeting the removal of proliferated fat responsible for nerve and spinal cord compression.ResultsThis technique was performed successfully in 3 patients with SEL. Radiating pain was reduced, and the functional disability and radiologic compression were improved in all three patients. Postoperative spinal instability and surgical complications related to the procedure were not observed.ConclusionsFor SEL, timely diagnosis and appropriate intervention can prevent the progression of neurological disability. UBE is a minimally invasive muscle-preserving technique that achieves neural decompression directly by the removal of excessive intraspinal adipose tissue buildup.

This study investigated carbon-based electrode materials for the application of wearable biosensors measuring uric acid concentration [...]

MarvelD3, a recently identified tight junction membrane protein, could be associated with hepatocellular carcinoma (HCC). We aimed to investigate the role of marvelD3 in Epithelial–Mesenchymal Transition (EMT) and migration of HCC and explore the underlying molecular mechanisms. First, we assessed marvlD3 expression in HCC and normal liver tissues and found loss of marvelD3 expression was significantly correlated with the occurrence and TNM stage of HCC. Second, we detected that marvelD3 was downregulated in HCC cells with transforming growth factor β1 and snail/slug-induced EMT. Finally, we analyzed expression of marvelD3 protein was significantly associated with EMT and the NF-κB signaling pathway. Our study demonstrated that MarvelD3 inhibited EMT and migration of HCC cells along with inhibiting NF-κB signaling pathway. Abbreviations: HCC, Hepatocellular carcinoma; TJ, Tight junction; MARVEL, MAL and related proteins for vesicle trafficking and membrane link; EMT, Epithelial–mesenchymal transition; NF-κB, Nuclear factor kappa B; TAMPs, Tight junction-associated marvel proteins; TGF-β1, Transforming growth factor-β1; MMP9, matrix metallopeptidase 9; RT-PCR, Real-time PCR; IHC, Immunohistochemistry; IF, Immunofluorescence.

Abstract Background Dubin-Johnson syndrome (DJS) is a rare autosomal recessive disorder characterized by predominantly conjugated hyperbilirubinemia that is caused by pathogenic mutations in the adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2) gene, which encodes multidrug resistance-associated protein 2 (MRP2). However, little is known about the causative mutation of DJS in China. Recently, we have reported ABCC2 p.G693R mutation in two unrelated cases. In the present study, we investigated the pathogenicity of the ABCC2 p.G693R mutation in DJS in China. Methods Clinical and genetic analysis was conducted for the two patients with the ABCC2 p.G693R mutation. Whole exome sequencing for mutations in other known hyperbilirubinemia-related genes was conducted for the cases with ABCC2 p.G693R. Expression and cellular localization of the mutant MRP2 p.G693R were analyzed by Western blotting and immunofluorescence assay, respectively. Organic anion transport activity was evaluated by the analysis of glutathione-conjugated-monochlorobimane. Results The two DJS patients with ABCC2 p.G693R mutation, which was conserved among different species, showed typical hyperbilirubinemia phenotype. No pathogenic mutation was identified in the other known hyperbilirubinemia related genes. Functional studies in three cell lines showed that the expression, localization and the organic anion transport activity were significantly compromised by MRP2 p.G693R mutation compared with wild-type MRP2. Conclusions The recurrent ABCC2 p.G693R mutation is associated with loss of function of the MRP2 protein and may result in hyperbilirubinemia in DJS in China.

Background: Colorectal cancer (CRC) comprises a large proportion of malignant tumors, and early detection of CRC is critical for effective treatment and optimal prognosis. We aimed to discover and validate serum autoantibodies for early detection of CRC.Methods: Combined with CRC-associated autoantibodies discovered by serological proteome and multiplex analyses, 26 predefined autoantibodies were evaluated in 315 samples (130 CRCs, 75 advanced adenomas, and 110 healthy controls) by protein microarray analysis. Autoantibodies with potential detection value were verified by enzyme-linked immunosorbent assays (ELISAs). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the accuracy of the biomarkers.Results: Four serum autoantibodies (ALDH1B1, UQCRC1, CTAG1, and CENPF) showed statistically different levels between patients with advanced neoplasm (CRC or advanced adenoma) and controls in microarray analysis, which were validated by ELISAs. Among the four biomarkers, the ALDH1B1 autoantibody showed the highest detection value with area under the curve (AUC) values of 0.70 and 0.74 to detect CRC and advanced adenoma with sensitivities of 75.68 and 62.31% and specificities of 63.06 and 73.87%, respectively. By combining the four biomarkers, the performance was improved with an AUC of 0.79 to detect CRC and advanced adenomas.Conclusion: The ALDH1B1 autoantibody has a good potential for early detection of CRC and advanced adenoma, and measuring serum autoantibodies against tumor-associated antigens may improve detection of early CRC.

Rotor syndrome, a rare autosomal-recessive genetic disorder characterized by conjugated hyperbilirubinemia, is caused by biallelic pathogenic variants in both SLCO1B1 and SLCO1B3 genes. Long interspersed nuclear elements (LINEs) make up about 17% of the human genome and insertion of LINE-1 in genes can result in genetic diseases. In the current study, we examined SLCO1B1 and SLCO1B3 genes in two Chinese patients diagnosed with Rotor syndrome based on laboratory tests. In one patient, a novel exon 4 inversion variant was identified. This variant may have been induced by LINE-1 retrotransposon insertion into SLCO1B3 intron 3, and was identified using genome walking. Splicing assay results indicated that the exon inversion, resulting in SLCO1B3 exon 4 (122 bp) exclusion in the mature mRNA, might generate a premature termination codon. Here, we describe an exon inversion contributing to the molecular etiology of Rotor syndrome. Our results may inform future diagnoses and guide drug prescriptions and genetic counseling.

In this paper, the X210CrW12 steel was subjected to gas nitriding to obtain a complex phase compound layer with limited porosity. The nitrided layer was characterized by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and X-ray diffraction (XRD). The fretting wear behavior and the evolution of fretting wear damage of the compound layer were studied, and the worn surfaces were characterized by SEM/EDS and 3D optical profilometry. The results indicated that the compound layer showed superior fretting wear resistance and sufficient load-carrying capacity in the low loading case of 35 N, but the fracture of coarse nitrides (transformed primary carbides) was obviously detrimental to wear resistance. For the high loading case of 70 N, the low toughness of the compound layer led to the occurrence of brittle cracks, and the decrease in the thickness of the compound layer due to wear resulted in the cracking and spalling of the compound layer.

Abstract We explore the decay of bound neutrons in the JUNO liquid scintillator detector into invisible particles (e.g., $$n\rightarrow 3 \nu $$ n → 3 ν or $$nn \rightarrow 2 \nu $$ n n → 2 ν ), which do not produce an observable signal. The invisible decay includes two decay modes: $$ n \rightarrow { inv} $$ n → inv and $$ nn \rightarrow { inv} $$ n n → inv . The invisible decays of s-shell neutrons in $$^{12}\textrm{C}$$ 12 C will leave a highly excited residual nucleus. Subsequently, some de-excitation modes of the excited residual nuclei can produce a time- and space-correlated triple coincidence signal in the JUNO detector. Based on a full Monte Carlo simulation informed with the latest available data, we estimate all backgrounds, including inverse beta decay events of the reactor antineutrino $${\bar{\nu }}_e$$ ν ¯ e , natural radioactivity, cosmogenic isotopes and neutral current interactions of atmospheric neutrinos. Pulse shape discrimination and multivariate analysis techniques are employed to further suppress backgrounds. With two years of exposure, JUNO is expected to give an order of magnitude improvement compared to the current best limits. After 10 years of data taking, the JUNO expected sensitivities at a 90% confidence level are $$\tau /B( n \rightarrow { inv} ) > 5.0 \times 10^{31} \, \textrm{years}$$ τ / B ( n → inv ) > 5.0 × 10 31 years and $$\tau /B( nn \rightarrow { inv} ) > 1.4 \times 10^{32} \, \textrm{years}$$ τ / B ( n n → inv ) > 1.4 × 10 32 years .

With the development of deep learning and computer vision, face detection has achieved rapid progress owing. Face detection has several application domains, including identity authentication, security protection, media, and entertainment. Although multi-task cascaded convolutional neural networks (MTCNN) have high accuracy and robustness, the model has the disadvantages of large parameters and computational overhead in the real scene due to the complexity of the real scene and the constraints of hardware facilities. Therefore, the development of an improved network model is crucial. This paper improves the MTCNN model by reducing the number of parameters and the computational overhead and using better model parameters to locate the key points of the face. This model improves the accuracy and robustness of the face age estimation. The WiderFace and CelebA datasets are used for training. The final face detection accuracy reaches 98.7% while simultaneously reducing the number of model parameters to 70% under the same conditions. This model meets the application needs of modern society for face detection and demonstrates the efficiency and accuracy of the improved network model. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to evaluate the impact of prolonged fasting on the physiological and biochemical alterations and metabolic shifts in healthy adults and to provide experimental data and theoretical support for the hypometabolic state induced by prolonged fasting. Thirteen volunteers were selected through public recruitment to undergo a 21-day complete fasting experiment. The experimental period lasted 34 days, including a 3-day baseline, 21-day completing fasting, 5-day calorie restriction and 5-day full recovery diet. Physiological indicators such as body weight, blood pressure, blood glucose, blood ketones, and blood uric acid were evaluated along with resting metabolic rate, routine blood tests, liver function, and heart function indexes employing traditional approaches. During the 21-day complete fasting period, there was a significant decrease in body weight (average − 14.96 ± 1.55%), a reduction in blood glucose (average − 21.63 ± 0.058%), an increase in blood ketones (from baseline 0.1 ± 0.04 mmol/L to 6.61 ± 1.25 mmol/L) and blood uric acid (from baseline 385.38 ± 57.78 µmol/L to 866.31 ± 172.01 µmol/L), a continuous decline in resting energy expenditure (average − 20.3 ± 11.13%), and the respiratory quotient tending towards fat metabolism. Most of the items in the complete blood count and liver indicators remained stable and within the normal range. Heart function showed functional adaptive changes without structural damage. Prolonged fasting can reduce the body’s resting energy expenditure and adapt to body weight loss through physiological regulatory mechanisms without adverse effects on basic physiological functions or the structure of important organs. Under medical supervision, healthy adults can safely engage in prolonged fasting for up to 21 days with metabolic adaption and no damage to pivotal organ, which could provide potential technical support for human health and survival strategies in extreme conditions such as food shortages during long-duration manned spaceflight.

Abstract We explore the mechanism that can explain the production of lepton asymmetry and two types of sterile neutrino dark matter. The first type involves heavy sterile dark matter produced directly by the decay of Q-balls which are formed by first-order phase transition in the early universe; the second consists of keV sterile neutrino dark matter, produced resonantly with the aid of lepton asymmetry from Q-ball decay. Besides, gravitational waves from cosmic strings generated during the phase transition process could be detected at future interferometers.

The vaginal microbiota is proposed to be associated with reproductive health. Exposure to metals during pregnancy is a risk factor for premature rupture of membranes (PROM). PROM can lead to serious maternal complications, thus, identifying the cause and therapeutic targets for it is crucial. However, the role of vaginal microbiota in the association between metals exposure and the risk of PROM are not clear. Based on a prospective birth cohort study including 668 pregnant women, maternal blood levels of 15 metals in the first trimester (n=668) and microbiota of vaginal secretions in the third trimester (n=244) were assessed. The metals that significantly associated with the risk of PROM were screened out via four statistical models, the top three were barium (Ba), chromium (Cr) and thallium (Tl) according to their weight indices. The results from the BKMR model showed a positive association of the mixture (Ba, Cr and Tl) with the risk of PROM. PROM and non-PROM were characterised by different beta diversities, moreover, the relative abundances of Bifidobacterium, Corynebacterium and Collinsella were statistically and negatively related to the risk of PROM [the adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were 0.06 (0.00, 0.82), 0.32 (0.14, 0.74) and 0.50 (0.30, 0.84), respectively]. On the other hand, women with different levels of Ba exposure were also characterised by different beta diversities (p value = 0.047); and blood Ba levels were also negatively associated with the relative abundances of Collinsella; additionally, Cr levels were positively associated with alpha diversity indices [Shannon index: β (95 % CI) = 0.25 (0.01, 0.50); Simpson index: β (95 % CI) = 0.08 (0.00, 0.17), respectively]. The results from mediation analysis showed the proportion of the relationship between Ba exposure and PROM risk mediated by the relative abundance of Collinsella was 26.4 %. Further verification analysis exploring the potential cause of the above phenomenon indicated that the neutrophil count, one of blood inflammation indicators for PROM, was higher in women with the absence of Collinsella (p value = 0.039), moreover, the cumulative hazard of PROM for women with the presence of Collinsella was also significantly lower than that of those without Collinsella (p value = 0.007). Collectively, the changes in the diversity and composition of the bacterial community, especially the reduction in Collinsella abundance caused by metal exposure, may be related to the occurrence of PROM, which provides a new microbiota-based perspective for intervention in metal exposure-related PROM. Confirming these relationships and determining the possible processes at play will require more investigation.

Abstract As a new type of dynamical dark matter mechanism, we discuss the stability of the gauged Q-ball dark matter and its production mechanism through a cosmological first-order phase transition. This work delves into the study of gauged Q-ball dark matter generated during the cosmic phase transition. We demonstrate detailed discussions on the stability of gauged Q-balls to rigorously constrain their charge and mass ranges. Additionally, employing analytic approximations and the mapping method, we provide qualitative insights into gauged Q-balls. We establish an upper limit on the gauge coupling constant and give the relic density of stable gauged Q-ball dark matter formed during a first-order phase transition. Furthermore, we discuss potential observational signatures or constraints of gauged Q-ball dark matter, including astronomical observations and gravitational wave signals.

Hibernation, an adaptive mechanism to extreme environmental conditions, is prevalent among mammals. Its main characteristics include reduced body temperature and metabolic rate. However, the mechanisms by which hibernating animals re-enter deep sleep during the euthermic phase to sustain hibernation remain poorly understood. We selected the Tamias sibiricus as a model organism and conducted transcriptomic sequencing of its hypothalamus at multiple time points throughout hibernation. Through the strategies of gene set filtering and intersection analysis, we effectively filtered out redundant data, identifying a subset of genes whose expression was downregulated during the euthermic phase potentially inducing re-enter deep sleep, thereby maintaining the periodic cycles of torpor and arousal. These cycles are crucial for sustaining the overall hibernation process. Notably, genes associated with sodium and potassium ion channels were significantly enriched. Specifically, potassium ion-related genes such as Kcnc1, Kcna2, Kcng4, and Kcna6, along with sodium ion-related genes such as Scn1a and Hcn2, were markedly downregulated. qRT-PCR validation of four of these genes (Kcnc1, Kcna6, Scn1a, and Hcn2) confirmed significant downregulation during the euthermic phase compared to the deep sleep phase, further supporting our transcriptomic findings. This study provides novel insights into the hypothalamic transcriptome dynamics at various hibernation stages. Although the functional roles of these genes require further investigation, our findings lay the groundwork for future studies to elucidate the molecular mechanisms underlying hibernation.

Abstract Background Multifaceted SARS-CoV-2 interventions have modified exposure to air pollution and dynamics of respiratory diseases. Identifying the most vulnerable individuals requires effort to build a complete picture of the dynamic health effects of air pollution exposure, accounting for disparities across population subgroups. Methods We use generalized additive model to assess the likely changes in the hospitalisation and mortality rate as a result of exposure to PM2.5 and O3 over the course of COVID-19 pandemic. We further disaggregate the population into detailed age categories and illustrate a shifting age profile of high-risk population groups. Additionally, we apply multivariable logistic regression to integrate demographic, socioeconomic and climatic characteristics with the pollution-related excess risk. Results Overall, a total of 1,051,893 hospital admissions and 34,954 mortality for respiratory disease are recorded. The findings demonstrate a transition in the association between air pollutants and hospitalisation rates over time. For every 10 µg/m3 increase of PM2.5, the rate of hospital admission increased by 0.2% (95% CI: 0.1–0.7%) and 1.4% (1.0–1.7%) in the pre-pandemic and dynamic zero-COVID stage, respectively. Conversely, O3-related hospitalization rate would be increased by 0.7% (0.5–0.9%) in the pre-pandemic stage but lowered to 1.7% (1.5–1.9%) in the dynamic zero-COVID stage. Further assessment indicates a shift of high-risk people from children and young adolescents to the old, primarily the elevated hospitalization rates among the old people in Lianyungang (RR: 1.53, 95%CI: 1.46, 1.60) and Nantong (RR: 1.65, 95%CI: 1.57, 1.72) relative to those for children and young adolescents. Over the course of our study period, people with underlying diseases would have 26.5% (22.8–30.3%) and 12.7% (10.8–14.6%) higher odds of having longer hospitalisation and over 6 times higher odds of deaths after hospitalisation. Conclusions Our estimates provide the first comprehensive evidence on the dynamic pollution-health associations throughout the pandemic. The results suggest that age and underlying diseases collectively determines the disparities of pollution-related health effect across population subgroups, underscoring the urgency to identifying the most vulnerable individuals to air pollution.