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Abstract Testosterone deficiency can cause abnormal lipid metabolism in men, leading to hyperlipidemia. We identified the testosterone-degrading bacterium Pseudomonas nitroreducens in the fecal samples of male patients with hyperlipidemia. Gastric administration of P. nitroreducens in mice led to testosterone deficiency and elevated blood lipid levels. Whole-genome sequencing of P. nitroreducens revealed the presence of 3/17β-hydroxysteroid dehydrogenase (3/17β-HSD), a gene responsible for testosterone degradation, which is also associated with hyperlipidemia. Microbiota analysis of fecal samples collected from 158 patients with hyperlipidemia and 151 controls revealed that the relative abundance of P. nitroreducens and 3/17β-HSD in the fecal samples of patients with hyperlipidemia was significantly higher than that in controls. These results suggest that P. nitroreducens and 3/17β-HSD may be related to the onset of testosterone deficiency-induced hyperlipidemia. Therefore, treatments targeted at eradicating testosterone-degrading bacteria are a potential future option for patients with testosterone-induced hyperlipidemia and should thus be studied further.

Abstract Retinal degenerative diseases are a leading cause of vision loss and blindness globally, impacting millions. These diseases result from progressive damage to retinal pigment epithelial (RPE) cells for which no curative or palliative treatments exist. Cell therapy, particularly RPE transplantation, has emerged as a promising strategy for vision restoration. This review provides a comprehensive overview of the recent advancements in clinical trials related to RPE transplantation. We discuss scaffold-free and scaffold-based approaches, including RPE cell suspensions and pre-organized RPE monolayers on biomaterial scaffolds. Key considerations, such as the form and preparation of RPE implants, delivery devices, strategies, and biodegradability of scaffolds, are examined. The article also explores the challenges and opportunities in RPE scaffold development, emphasising the crucial need for functional integration, immunomodulation, and long-term biocompatibility to ensure therapeutic efficacy. We also highlight ongoing efforts to optimise RPE transplantation methods and their potential to address retinal degenerative diseases.

Abstract Background Blastocyst morphology has been demonstrated to be associated with ploidy status. Existing artificial intelligence models use manual grading or 2D images as the input for euploidy prediction, which suffer from subjectivity from observers and information loss due to incomplete features from 2D images. Here we aim to predict euploidy in human blastocysts using quantitative morphological parameters obtained by 3D morphology measurement. Methods Multi-view images of 226 blastocysts on Day 6 were captured by manually rotating blastocysts during the preparation stage of trophectoderm biopsy. Quantitative morphological parameters were obtained by 3D morphology measurement. Six machine learning models were trained using 3D morphological parameters as the input and PGT-A results as the ground truth outcome. Model performance, including sensitivity, specificity, precision, accuracy and AUC, was evaluated on an additional test dataset. Model interpretation was conducted on the best-performing model. Results All the 3D morphological parameters were significantly different between euploid and non-euploid blastocysts. Multivariate analysis revealed that three of the five parameters including trophectoderm cell number, trophectoderm cell size variance and inner cell mass area maintained statistical significance (P

Abstract Ultrasound technology has been recognized as the mainstream approach for the identification of gas-liquid two-phase flow patterns, which holds great value in engineering domain. However, commercial rigid probes are bulky, limiting their adaptability to curved surfaces. Here, we propose a strategy for autonomous identification of flow patterns based on flexible ultrasound array and machine learning. The array features high-performance 1–3 piezoelectric composite material, stretchable serpentine wires, soft Eco-flex layers and a polydimethylsiloxane (PDMS) adhesive layer. The resulting ultrasound array exhibits excellent electromechanical characteristics and offers a large stretchability for an intimate interfacial contact to curved surface without the need of ultrasound coupling agents. We demonstrated that the flexible ultrasound array combined with machine learning can accurately identify gas-liquid two-phase flow patterns, in a circular pipeline. This work presents an effective tool for recognizing gas-liquid two-phase flow patterns, offering engineering opportunities in petroleum extraction and natural gas transportation.

Abstract Urolithiasis, a common and recurrent condition, imposes a significant global health burden. This study investigates the causal relationship between various types of fluid intake and urolithiasis using univariable and multivariable Mendelian randomization (MR) approaches. Genetic data for urolithiasis were obtained from the FinnGen Consortium (n = 400,681), while genetic measures for nine fluid types were sourced from meta-analyses of genome-wide association studies (GWAS). The analysis revealed that genetically predicted coffee intake (OR: 0.571, 95% confidence interval (CI): 0.341–0.958, p = 0.034) and ground coffee intake (OR: 0.219, 95% CI: 0.005–0.923, p = 0.038) were protective factors for upper urinary calculi. Additionally, a standard deviation (SD) increase in tea intake was associated with a 53% reduction in risk (OR: 0.473, 95% CI: 0.320–0.700, p

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Black soldier fly larvae (BSFL) treatment offers a promising avenue for manure valorization. However, there is a lack of larval density studies and ton-scale exploration in swine manure bioconversion. This study delves into the efficiency of larval fatty acid (FA) bioconversion, examining the impact of larval density on a kilogram scale and extending the analysis to a ton scale. Across a range of 50 to 600 larvae/kg, the larval FA content decreased from 15.3% to 7.85%. The peak larval FA yield, at 3.04% (based on manure dry matter), occurred at a density of 200 larvae/kg. Both low (50 larvae/kg) and high (600 larvae/kg) densities adversely affected BSFL bioconversion performance. Dominant larval FAs included C12:0 (39.7%), C16:1 (24.2%), C18:1 (17.5%), and C16:0 (8.3%). The scaling-up process maintained a consistent larval FA content and composition but resulted in decreased larvae FA yield due to increased larval mortality. Ultimately, each ton of swine manure yielded 12.4 kg of fresh larvae or 0.71 kg of larval FA components, corresponding to a 1.14% larval FA yield. This study underscores the feasibility of upscaling swine manure treatment using BSFL for FA bioconversion and emphasizes the necessity for large-scale studies to enhance larval survivorship and bioconversion efficiency.

Abstract Nipah virus (NiV) is a zoonotic emergent paramyxovirus that can cause severe encephalitis and respiratory infections in humans, with a high fatality rate ranging from 40% to 75%. Currently, there are no approved human vaccines or antiviral drugs against NiV. Here, we designed a ferritin-based self-assembling nanoparticle displaying the NiV G head domain on the surface (NiV G-ferritin) and assessed immune responses elicited by the soluble NiV G head domain (NiV sG) or NiV G-ferritin. Immunization with NiV G-ferritin or NiV sG conferred complete protection against lethal NiV challenge without detection of viral RNA in Syrian golden hamsters. Compared to NiV sG, NiV G-ferritin induced significantly faster, broader, and higher serum neutralizing responses against three pathogenic henipaviruses (NiV-Malaysia, NiV-Bangladesh, and Hendra virus). Moreover, NiV G-ferritin induced a durable neutralizing immunity in mice as antisera potently inhibited NiV infection even after six months of the third immunization. Additionally, we isolated a panel of 27 NiV G-binding monoclonal antibodies (mAbs) from NiV G-ferritin immunized mice and found that these mAbs targeted four distinct antigenic sites on NiV G head domain with two sites that have not been defined previously. Notably, 25 isolated mAbs have potent neutralizing activity with 50% inhibitory concentrations less than 10 ng/mL against NiV pseudovirus. Collectively, these findings provide new insights into the immunogenicity of NiV G protein and reveal that NiV G-ferritin is a safe and highly effective vaccine candidate against Nipah virus infection.

Abstract Background Serum neurofilament light chain (sNfL) has been identified as a biomarker for neurologic diseases. However, sNfL remains unknown to be responsible for depression. Aims The aim of this research was to explore the relationship between sNfL levels and depression in US adults. Methods In this cross-sectional survey of the general population, we investigated representative data involving 10,175 participants from the 2013–2014 cycle of the National Health and Nutrition Examination Survey (NHANES). Depression was diagnosed using the Patient Health Questionnaire-9 (PHQ-9). The effect of related factors on depression was analyzed by conducting a univariate analysis. Stratified analysis was utilized to detect the stability and sensitivity of the relationship. After adjusting for race, education, marital status, smoking status, body mass index (BMI), sleep duration, income, and a history of hypertension, sedentary behavior and stroke, multivariable linear regression was performed to demonstrate the correlation between sNfL and depression. Results A total of 1301 individuals between the ages of 20 and 75 were involved in this investigation, of which 108 (8.3%) were diagnosed with depression. A significant positive correlation between sNfL and depression among adults in the US was observed by conducting univariable analyses. After adjusting for confounding factors, the multivariate analyses indicated that elevated sNfL levels might play a pivotal role in the development of depression (odds ratio (OR) = 3.0; 95% confidence interval (CI): (1.5, 6.1), P = 0.002). Conclusion These results indicated that sNfL is closely linked to depression in a nationally representative individual. However, further studies are needed to confirm the biological mechanism as well as the clinical implications of sNfL and depression.

Abstract With the gradual shift of coal mining to the western coal mining region of China, floor heave in weakly cemented mudstone roadways has become an issue affecting the safety and efficiency of coal mine production. Additionally, different mining rates can lead to fluctuating support stresses on the roof and floor of weakly cemented mudstone roadways. Therefore, obtaining a comprehensive understanding of the mechanical properties of weakly cemented mudstone at different loading rates is conducive to improving the issue of floor heave in such roadways and provides a theoretical basis for further study. In this context, a series of uniaxial mechanical tests with concurrent acoustic emission monitoring were conducted on specimens of weakly cemented mudstone under various loading rates (0.005, 0.01, 0.05, and 0.1 mm/s). The stress‒strain and acoustic emission response curves were obtained to effectively characterize the strength, deformation, damage, macroscale instability, and crack propagation characteristics of the mudstone under the influence of loading rate effects. The research results support the following findings: (1) With increasing loading rate, the peak strength and elastic modulus of weakly cemented mudstone significantly increase, while the peak axial strain and peak radial deformation significantly decrease. (2) With increasing loading rate, the stress required to trigger the expansion of weakly cemented mudstone gradually increases, and a significant power-law relationship arises between the strain of the mudstone at the start of expansion and the loading rate. (3) With increasing loading rate, the acoustic emission ringing count of weakly cemented mudstone increases: The failure of weakly cemented mudstone changes from small-range progressive failure to sudden failure, and the failure mode transitions from shear failure to tensile‒shear composite failure. (4) The studied mudstone damage variables increase with increasing loading rate, following an approximate exponential function. The conclusions obtained in this work can provide a theoretical basis for the evolution mechanism and control of floor heave in deep roadway mining.

Abstract The primary objective of multi-objective evolutionary algorithms (MOEAs) is to find a set of evenly distributed nondominated solutions that approximate the Pareto front (PF) of a multi-objective optimization problem (MOP) or a many-objective optimization problem (MaOP). This implies that the approximated solution set obtained by MOEAs should be as close to PF as possible while remaining diverse, adhering to criteria of convergence and diversity. However, existing MOEAs exhibit an imbalance between achieving convergence and maintaining diversity in the objective space. As far as the diversity criterion is concerned, it is still a challenge to achieve an evenly distributed approximation set with different sizes for a problem with a complicated PF shape. Furthermore, Pareto dominance has its own weaknesses as the selection criterion in evolutionary multiobjective optimization. Algorithms based on Pareto criterion (PC) can suffer from problems such as slow convergence to the optimal front and inferior performance on problems with many objectives. To effectively address these challenges, we propose a multi-objective bean optimization algorithm (MOBOA). Given that the selection of parent species, representing global optimal solutions, directly influences the convergence and diversity of the algorithm, MOBOA incorporates a preference order equilibrium parent species selection strategy (POEPSS). By extending the Pareto criterion with the preference order optimization criterion, the algorithm effectively enhances parent species selection pressure across multiple objectives. To balance convergence and diversity, MOBOA proposes a multi-population global search strategy explicitly maintaining an external archive during the search process. Leveraging the inherent multi-population advantages of bean optimization algorithm (BOA), the algorithm facilitates information sharing among the main population, auxiliary populations, and historical archive solution sets. Additionally, a diversity enhancement strategy is employed in the environmental selection stage, introducing the environmental selection strategy of the SPEA2 algorithm to generate a set of evenly distributed nondominated solutions. Experimental results on a series of widely used MOPs and MaOPs demonstrate that the proposed algorithm exhibits higher effectiveness and competitiveness compared to state-of-the-art algorithms.

Abstract Background Hepatocellular carcinoma (HCC) is a common malignant tumor, and glutamine is vital for tumor cells. The role of glutamine transporter SLC1A5 in tumor progression and transarterial chemoembolization (TACE) efficacy is under study. This research seeks to determine the impact of SLC1A5 expression on the prognosis and TACE efficacy of HCC and elucidate its mechanisms. Methods SLC1A5 expression in HCC, correlation with patient outcomes, and response to TACE were studied in an open access liver cancer dataset and confirmed in our cohort. Additionally, the correlation between SLC1A5 expression and hypoxia, angiogenesis and immune infiltration was analyzed and verified by immunohistochemistry, immunofluorescence and transcriptome sequencing. Liver cancer cell lines with SLC1A5 expression knockdown or overexpression were constructed, and cell proliferation, colony formation, apoptosis, migration and drug sensitivity as well as in vivo xenograft tumor were measured. A gene set enrichment analysis was conducted to determine the signaling pathway influenced by SLC1A5, and a western blot analysis was performed to detect protein expression alterations. Results SLC1A5 expression was higher in HCC tissue and associated with poor survival and TACE resistance. Hypoxia could stimulate the upregulation of glutamine transport, angiogenesis and SLC1A5 expression. The SLC1A5 expression was positively correlated with hypoxia and angiogenesis-related genes, immune checkpoint pathways, macrophage, Tregs, and other immunosuppressive cells infiltration. Knockdown of SLC1A5 decreased proliferation, colony formation, and migration, but increased apoptosis and increased sensitivity to chemotherapy drugs. Downregulation of SLC1A5 resulted in a decrease in Vimentin and N-cadherin expression, yet an increase in E-cadherin expression. Upregulation of SLC1A5 increased Vimentin and N-cadherin expression, while decreasing E-cadherin. Overexpression of β-catenin in SLC1A5-knockdown HCC cell lines could augment Vimentin and N-cadherin expression, suppress E-cadherin expression, and increase the migration and drug resistance. Conclusions Elevated SLC1A5 was linked to TACE resistance and survival shortening in HCC patients. SLC1A5 was positively correlated with hypoxia, angiogenesis, and immunosuppression. SLC1A5 may mediate HCC cell migration and drug resistance via Epithelial-mesenchymal transition (EMT) pathway.

BackgroundLifelines Diet Score (LLDS) was developed based on the 2015 Dutch Dietary Guidelines and current international scientific evidence. As a dietary quality assessment tool, the LLDS aims to evaluate the association between the Lifeline diet and the risk of chronic diseases. However, the evidence linking LLDS to lung cancer risk is currently limited.ObjectiveOur objective was to explore whether adherence to the LLDS is associated with reduced incidence and mortality of lung cancer, including its major histological subtypes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).MethodsData for this research were sourced from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Trial. The LLDS for each participant was calculated based on responses to the dietary history questionnaire (DHQ), and subsequently analyzed after being categorized into quintiles. The Cox proportional hazards regression model was utilized to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) for both the incidence and mortality of lung cancer, SCLC and NSCLC. Additionally, stratified analyses were conducted to ascertain possible effect modifiers, and several sensitivity analyses were performed to evaluate the robustness of the findings.ResultsDuring the mean follow-up periods of 8.8 years for incidence and 15.1 years for mortality, we identified 1,642 new cases and 1,172 related deaths from lung cancer. Participants in the highest quartiles of LLDS compared to those in the lowest exhibited a reduced incidence (HRQ4:Q1 = 0.80, 95% CI = 0.68–0.94, P for trend = 0.003) and mortality (HRQ4:Q1 = 0.81, 95%CI = 0.67–0.98, P for trend = 0.009) of lung cancer. Furthermore, this negative association remained for SCLC incidence (HRQ4:Q1 = 0.55, 95% CI = 0.35–0.87, P for trend = 0.002) and mortality (HRQ4:Q1 = 0.42, 95% CI = 0.25–0.70, P for trend 0.05). The sensitivity analyses substantiated the robustness of the results.ConclusionIn conclusion, our research indicates that among 98,459 U.S. adults aged 55 and older, adherence to the LLDS is linked to a diminished incidence and mortality of lung cancer.

Summary: Background: The spread of emerging SARS-CoV-2 immune escape sublineages, especially JN.1 and KP.2, has resulted in new waves of COVID-19 globally. The evolving memory B cell responses elicited by the parental Omicron variants to subvariants with substantial antigenic drift remain incompletely investigated. Methods: Using the single B cell antibody cloning technology, we isolated single memory B cells, delineated the B cell receptor repertoire and conducted the pseudovirus-based assay for recovered neutralizing antibodies (NAb) screening. We analyzed the cryo-EM structures of top broadly NAbs (bnAbs) and evaluated their in vivo efficacy (golden Syrian hamster model). Findings: By investigating the evolution of human B cell immunity, we discovered a new panel of bnAbs arising from vaccinees after Omicron BA.2/BA.5 breakthrough infections. Two lead bnAbs neutralized major Omicron subvariants including JN.1 and KP.2 with IC50 values less than 10 ng/mL, representing ultrapotent receptor binding domain (RBD)-specific class I bnAbs. They belonged to the IGHV3-53/3-66 clonotypes instead of evolving from the pre-existing vaccine-induced IGHV1-58/IGKV3-20 bnAb ZCB11. Despite sequence diversity, they targeted previously unrecognized, highly conserved conformational epitopes in the receptor binding motif (RBM) for ultrapotent ACE2 blockade. The lead bnAb ZCP3B4 not only protected the lungs of hamsters intranasally challenged with BA.5.2, BQ.1.1 and XBB.1.5 but also prevented their contact transmission. Interpretation: Our findings demonstrated that class I bnAbs have evolved an ultrapotent mode of action protecting against highly transmissible and broad Omicron escape variants, and their epitopes are potential targets for novel bnAbs and vaccine development. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Background: Long-snake moxibustion can improve hypothalamic-pituitary-adrenal (HPA) axis function in patients with kidney-yang deficiency (KYDS). 11β-HSD1 controls the HPA axis by boosting CORT production via reductase activity. However, the interaction and mechanism of long snake moxibustion and 11β-HSD1 remain unknown. This study examined the impact of lengthy snake moxibustion on the hypothalamus-pituitary-adrenal axis in KYDS rats. The potential significance of 11β-HSD1 in this process was explored. Methods: Rats were randomly divided into two groups: the blank group and the experimental group. The KYDS model was established with an intramuscular injection of hydrocortisone. Rats were randomly assigned to four groups: model, sham intervention, long snake moxibustion, and long snake moxibustion plus 11β-HSD1 inhibitor. Physical indicators included body weight, toe temperature, rectal temperature, and spontaneous movement. The serum levels of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and CORT were measured. Immunohistochemical examination reveals 11β-HSD1 protein expression in the liver. Western blotting (WB) detected the levels of 11β-HSD1, H6PDH and NADPH/NADP + protein in the liver. Results: The experimental rats' body weight, toe temperature, rectal temperature, time and frequency of spontaneous activity all dropped, as did their serum ACTH, CORT, and CRH levels. The protein expressions of 11β-HSD1, H6PDH, and NADPH/NADP+ in the liver decreased significantly. Long-snake moxibustion improved HPA axis function in rats, boosting expression of 11β-HSD1, H6PDH, and NADPH/NADP+. Adding an 11β-HSD1 inhibitor to Long-snake moxibustion decreased its effect on the HPA axis. Conclusion: Long-snake moxibustion improves KYDS symptoms in rats by increasing 11β-HSD1 expression and reductase activity, which regulates the HPA axis.

High voltage circuit breakers are important equipment in power systems, and the valve motion of the chambers plays a role in the arc extinguishing performance of high-voltage circuit breakers. Therefore, in this paper, a 145 kV auto-expansion SF6 circuit breaker is taken as the research object, and a two-dimensional axisymmetric magnetohydrodynamic arc model considering valve motion process is established. The influence of different short circuit breaking conditions on the valve motion was studied. The results show that the backflow phenomenon of ablated steam is the main reason for the closure of the non-return valve, which plays an important role in opening the pressure relief valve. The closing time of the non-return valve is about 0.4 ms faster at a short circuit current of 40 kA than at a short circuit current of 36 kA.

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43 mg/L of the cured group and the 12.07 ± 2.68 mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138 mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537 mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138 mg/L) on day 5 after dosing.

Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignancies. While PD-1 immune checkpoint inhibitors have demonstrated promising therapeutic efficacy in HCC, not all patients exhibit a favorable response to these treatments. Glutamine is a crucial immune cell regulatory factor, and tumor cells exhibit glutamine dependence. In this study, HCC patients were divided into two subtypes (C1 and C2) based on glutamine metabolism-related genes via consensus clustering. The C1 pattern, in contrast to C2, was associated with a lower survival probability among HCC patients. Additionally, the C1 pattern exhibited higher proportions of patients with advanced tumor stages. The activity of C1 in glutamine metabolism and transport is significantly enhanced, while its oxidative phosphorylation activity is reduced. And, C1 was mainly involved in the progression-related pathway of HCC. Furthermore, C1 exhibited high levels of immunosuppressive cells, cytokine-receptor interactions and immune checkpoint genes, suggesting C1 as an immunosuppressive subtype. After stepwise selection based on integrated four machine learning methods, SLC1A5 was finally identified as the pivotal gene that distinguishes the subtypes. The expression of SLC1A5 was significantly positively correlated with immunosuppressive status. SLC1A5 showed the most significant correlation with macrophage infiltration, and this correlation was confirmed through the RNA-seq data of CLCA project and our cohort. Low-SLC1A5-expression samples had better immunogenicity and responsiveness to immunotherapy. As expected, SubMap and survival analysis indicated that individuals with low SLC1A5 expression were more responsive to anti-PD1 therapy. Collectively, this study categorized HCC patients based on glutamine metabolism-related genes and proposed two subclasses with different clinical traits, biological behavior, and immune status. Machine learning was utilized to identify the hub gene SLC1A5 for HCC classification, which also could predict immunotherapy response.

Unveiling of the mechanism involved in the occurrence and development of trauma-induced heterotopic ossification (tHO) is highly demanding due to current ineffective clinical treatment for it. Previous studies proposed that hydrogen sulfide (H2S) was vital for fate determination of stem cells, suggesting a potential role in the regulation of tHO development. In the current study, We found that expression of metabolic enzyme within sulfur conversion pathway was enhanced after tendon injury, leading to H2S accumulation within the tHO region. Increased production of endogenous H2S was shown to promote aberrant osteogenic activity of tendon-derived stem cells (TDSCs), which accelerated tHO formation. The inhibition of metabolic enzyme of H2S production or directly absorption of H2S could abolished osteogenic induction of TDSCs and the formation of tHO. Mechanistically, through RNA sequencing combined with rescue experiments, we demonstrated that activation of Ca2+/ERK pathway was the downstream molecular event of H2S-induced osteogenic commitment of TDSCs and tHO. For treatment strategy exploration, zine oxide nanoparticles (ZnO) as an effective H2S elimination material was validated to ideally halt the tHO formation in this study. Furthermore, in terms of chirality of nanoparticles, D-ZnO or L-ZnO nanoparticles showed superiority over R–ZnO nanoparticles in both clearing of H2S and inhibition of tHO. Our study not only revealed the mechanism of tHO through the endogenous gas signaling event from a new perspective, but also presented a applicable platform for elimination of the inordinate gas production, thus aiding the development of clinical treatment for tHO.

Abstract To evaluate the predictive and prognostic value of fibroblast growth factor 21 (FGF21) levels in retinal artery occlusion (RAO) patients. In this case–control study, serum FGF21 levels were detected by using the ELISA method. Multivariable logistic regression analyses were performed to evaluate the significance of FGF21 in assessing the risk of developing RAO and its impact on vision and concurrent ischemic stroke. Compared with control group, serum FGF21 levels were significantly higher (median [IQR] = 230.90[167.40,332.20] pg/ml) in RAO patients. Multivariate logistic regression analysis showed that elevated serum FGF21 levels were associated with a higher risk of RAO occurrence (P = 0.025, OR [95%CI] = 9.672 [2.573, 36.359]) after adjustment for multiple confounding factors. Higher serum FGF21 levels were negatively associated with visual acuity improvement (P = 0.029, OR [95%CI] = 0.466[0.235, 0.925]) and positively correlated with concurrent ischemic stroke (P = 0.04, OR [95% CI] = 1.944[1.029, 3.672]) in RAO patients. Elevated serum FGF21 levels could promote the development of RAO and indicate worse visual prognosis and increase the risk of concurrent ischemic stroke, which might help clinicians early diagnose and treat RAO patients.

Abstract Prorocentrum shikokuense (formerly P. donghaiense) is a pivotal dinoflagellate species associating with the HABs in the East China Sea. The complexity of its large nuclear genome hindered us from understanding its genomic characteristics. Full-length transcriptome sequencing offers a practical solution to decipher the physiological mechanisms of a species without the reference genome. In this study, we employed single-molecule real-time (SMRT) sequencing technology to sequence the full-length transcriptome of Prorocentrum shikokuense. We successfully generated 41.73 Gb of clean SMRT sequencing reads and isolated 105,249 non-redundant full-length non-chimeric reads. Our trial has led to the identification of 11,917 long non-coding RNA transcripts, 514 alternative splicing events, 437 putative transcription factor genes from 17 TF gene families, and 34,723 simple sequence repeats. Additionally, a total of 78,265 open reading frames were identified, of them 15,501 were the protein coding sequences. This dataset is valuable for annotating P. shikokuense genome, and will contribute significantly to the in-depth studies on the molecular mechanisms underlining the dinoflagellate bloom formation.

Abstract Accurately predicting traffic flow is crucial for intelligent transportation systems (ITS). In recent years, many deep learning‐based prediction models have been widely applied in traffic flow prediction, and various spatio‐temporal networks have been proposed. However, most of the existing models follow a general technical route to extract the spatio‐temporal features, which lack the capacity of extracting the important historical information with the high spatial and temporal correlations dynamically and deeply. How to develop a well‐performance traffic flow prediction model for a complex transportation network is still facing some challenges. In this paper, a hybrid dynamic spatio‐temporal network (HD‐Net) for traffic flow prediction is proposed. In HD‐Net, the authors first extract the dynamic spatio‐temporal features using dynamic graph convolution and bidirectional gate recurrent uni (BiGRU). Subsequently, the authors extract the important features with high spatial and temporal correlations from the obtained dynamic spatio‐temporal features using an auto‐correlation mechanism from a local perspective, and self‐attention mechanism from a global perspective, respectively. Extensive experiments have been conducted on two real‐world traffic datasets. The experimental results demonstrate that the proposed HD‐Net outperforms the baselines in the field of capturing the dynamic and important spatio‐temporal features with high correlations.

Abstract Background This study intends to explore the role and molecular mechanism of hsa_circ_0005519 in acute kidney injury (AKI). Methods We conducted reverse transcription-qPCR for human serum to determine levels of hsa_circ_0005519 in AKI patients and healthy controls. Hsa_circ_0005519 was inhibited for expression in HK-2 cells using specific siRNAs. A number of techniques, MTT and ELISA assays, were used to analyze the potential role of hsa_circ_0005519 in cell viability, oxidative stress, and inflammation of LPS-induced HK-2 cells. results The serum of patients with AKI exhibited a significant increase in hsa_circ_0005519 expression, compared with healthy controls. Hsa_circ_0005519 was knockdown by siRNA, and its knockdown led to cell viability increase in LPS-induced HK-2 cells. Inhibition of hsa_circ_0005519 can reverse the TNF-α, IL-6 and IL-1β increase in LPS-induced HK-2 cells. Inhibiting hsa_circ_0005519 led to downregulation of MPO and MDA levels. MiR-98-5p was a downstream miRNA for hsa_circ_0005519. MiR-98-5p can offset the effects of hsa_circ_0005519 on LPS-induced HK-2 cells. IFG1R was a target gene for miR-98-5p. Conclusions These findings indicate that the highly expressed hsa_circ_0005519 plays a promoting role in AKI.

Introduction: Acute kidney injury (AKI) was a disease with a high mortality mainly caused by renal ischemia/reperfusion injury (I/R). Although the current non-targeted administration of vascular endothelial growth factor (VEGF) for AKI had been revealed to facilitate the recovery of renal I/R, how to targeted deliver VEGF and to retain it efficiently in the ischemic kidney was critical for its clinical application. Methods: In present study, bi-functional KIT-PR1P peptides were constructed which bond VEGF through PR1P domain, and targeted ischemic kidney through KIT domain to interact with biomarker of AKI-kidney injury molecule-1 (Kim-1). Then the targeted and therapeutic effects of KIT-PR1P/VEGF in AKI was explored in vitro and in vivo. Results: The results showed KIT-PR1P exhibited better angiogenic capacity and targeting ability to hypoxia HK-2 cells with up-regulated Kim-1 in vitro. When KIT-PR1P/VEGF was used for the treatment of renal I/R through intravenous administration in vivo, KIT-PR1P could guide VEGF and retain its effective concentration in ischemic kidney. In addition, KIT-PR1P/VEGF promoted angiogenesis, alleviated renal tubular injury and fibrosis, and finally promoted functional recovery of renal I/R. Conclusion: These results indicated that the bi-functional KIT-PR1P peptides combined with VEGF would be a promising strategy for the treatment of AKI by targeting to Kim-1.

Blue-green eggs exhibit unique shell color; however, compared to commercial layers, blue-green eggshell chickens have lower egg production and lack uniform shell colors. Aiming to confirm the molecular mechanisms that affect shell color and egg production, this study collected the uteruses of 12 blue-green eggshell chickens (BG group) and six Hy-Line layers (Brown group), which had significantly different shell color indexes (SCI) and egg numbers at 300 days of age (EN300). Transcriptome sequencing and comparative analyses were subsequently performed. BG hens were divided into two groups for comparative analysis (BGblue vs. BGgreen and BGlow vs. BGhigh, respectively), based on the differences in SCI and EN300, respectively. The result of weighted gene co-expression network (WGCNA) analysis showed that the sequenced and mapped 16,785 genes were clustered into 18 modules, among which six modules with a total of 4270 genes were highly correlated with SCI and EN300 traits. Five hundred and eleven differentially expressed genes (DEGs) belonged to the six key modules. Through KEGG mapping, GO enrichment, and Cytoscape network analysis, nine Hub genes were tightly associated with SCI and EN300. The up-regulated genes were CCR2, CCR8, CD40LG, IL18RAP, INHBA, and P2RY13, while the down-regulated genes were ABCA13, ADCY2, and GRM1. Co-analyses with the results of comparisons between the BG subgroups revealed that the expression of solute carrier (SLC) proteins and ABC transporters were highly related to eggshell color, while cytokine-cytokine receptor interactions and neuroactive ligand-receptor interactions were key pathways affecting egg production. The expression of extracellular cytokines and membrane receptors were significantly up-regulated in low-yield chickens. The candidate DEGs and pathways found in the study will assist in clarifying the molecular mechanisms affecting shell color and egg production, and improve the breeding of blue-green eggshell chickens.

The C4F7N/CO2 mixed gas is most expected to replace SF6 in high-voltage power equipment, and the generation of free metal particles in gas-insulated equipment is unavoidable and highly susceptible to inducing insulation failures. In this paper, the effects of flaky, spherical, and mixed shape aluminum particle defects on the breakdown characteristics of C4F7N/CO2 mixed gas are investigated and compared to those of SF6 under the same conditions. The experimental results show that the effect of particle defects on the insulating properties of C4F7N/CO2 gas mixtures is visualized by the fact that particle defects reduce the breakdown voltage of C4F7N/CO2 gas mixtures, increase their stochasticity, and reduce the enhancement of the insulating properties of C4F7N/CO2 gas mixtures by increasing the air pressure. The greater the number of particles, the greater is the degree of influence. Comparison of the SF6 and C4F7N/CO2 gas mixtures reveals that, in the case of flake defects, increasing the air pressure improves the insulation performance of the SF6 gas better than that of the C4F7N/CO2 gas mixture. Under the condition of the same number of particles, the larger the proportion of spherical particles in the hybrid particles, the smaller is the influence of metal particles on the C4F7N/CO2 mixed gas and on SF6 gas.

In this study, comparative investigation on the effect of dry heating treatment (DHT) and annealing (ANN) on multi-structure, physicochemical properties and in vitro digestibility of black highland barley (BHB) starch was done. Results revealed that both DHT and ANN did not affect the “A”-type crystalline pattern and FT-IR spectroscopy of BHB starch, but changed the morphology, raised water absorption capacity and lowered viscosities. Compared to native starch, DHT- and ANN-modified samples had totally opposite alteration trends in amylose content, color characteristics, oil absorption capacity, gelatinization parameters and pasting temperature. These changes were positively related to treatment temperature and time for DHT-modified starches, while which were dependant on treatment duration for ANN-modified starches. Total in vitro hydrolysis rate and rapidly digestive starch content in starch markedly raised after DHT, whereas slowly digestive starch and RS levels decreased. Nevertheless, ANN significantly improved the hydrolyzation stability with treatment time prolonging, especially increased RS content and lowered RDS level. Therefore, this study identified both DHT and ANN were effective methods to alter the properties of BHB starch, and more importantly, they had distinguishing influence by different mechanisms, which would remind user to select appropriate means for physical starch modification based on different application purposes.

Spiro-OMeTAD is a primary hole transport material (HTM) employed in most state-of-the-art regular perovskite solar cells (PSCs). The essential reliance on hygroscopic ionic dopants to enhance the conductivity and mobility of Spiro-OMeTAD has dramatically compromised the stability of PSCs. Here, we demonstrated excellent photovoltaic performance of PSCs by developing two dopant-free polymers, namely L1 and L2, using thieno[3,2-b]thiophene as a building block. It is found that the n-hexyl-modified thiophene side chains endow the polymer L2 with favorable crystallinity, unique self-assembly behavior, and a preferable face-on stacking orientation. After the addition of a small amount (10 %) of PM6 to create a polymer alloy named LPA, the above properties were further improved, and the resulting film exhibited a distinct fibrous morphology, resulting in increased hole mobility and effective defect passivation. Consequently, PSCs employing LPA as a dopant-free HTM afforded a high efficiency of 23.81 %. Importantly, LPA-based PSCs exhibit significantly enhanced operational stability with a T80 lifetime of 1572 h at 55 °C. This work provides a crucial guideline for the design of dopant-free polymers, thereby advancing the practical application of PSCs.

Abstract The urgent demand for addressing dye contaminants in water necessitates the development of microrobots that exhibit remote navigation, rapid removal, and molecular identification capabilities. The progress of microrobot development is currently hindered by the scarcity of multifunctional materials. In this study, a plasmonic MXene hydrogel (PM‐Gel) is synthesized by combining bimetallic nanocubes and Ti3C2Tx MXene through the rapid gelation of degradable alginate. The hydrogel can efficiently adsorb over 60% of dye contaminants within 2 min, ultimately achieving a removal rate of >90%. Meanwhile, the hydrogel exhibits excellent sensitivity in surface enhanced Raman scattering (SERS) detection, with a limit of detection (LOD) as low as 3.76 am. The properties of the plasmonic hydrogel can be further adjusted for various applications. As a proof‐of‐concept experiment, thermosensitive polymers and superparamagnetic particles are successfully integrated into this hydrogel to construct a versatile, light‐responsive microrobot for dye contaminants. With magnetic and optical actuation, the robot can remotely sample, identify, and remove pollutants in maze‐like channels. Moreover, light‐driven hydrophilic‐hydrophobic switch of the microrobots through photothermal effect can further enhance the adsorption capacity and reduced the dye residue by up to 58%. These findings indicate of a broad application potential in complex real‐world environments.

In nature, methylmercury (MeHg) is primarily generated through microbial metabolism, and the ability of bacteria to methylate Hg(II) depends on both bacterial properties and environmental factors. It is widely known that, as a metabolic analog, molybdate can inhibit the sulfate reduction process and affect the growth and methylation of sulfate-reducing bacteria (SRB). However, after it enters the cell, molybdate can be involved in various intracellular metabolic pathways as a molybdenum cofactor; whether fluctuations in its concentration affect the growth and methylation of aerobic mercury methylating strains remains unknown. To address this gap, aerobic γ-Proteobacteria strains Raoultella terrigena TGRB3 (B3) and Pseudomonas putida TGRB4 (B4), as well as an obligate anaerobic δ-Proteobacteria strain of the SRB Desulfomicrobium escambiense CGMCC 1.3481 (DE), were used as experimental strains. The growth and methylation ability of each strain were analyzed under conditions of 500 ng·L−1 Hg(II), 0 and 21% of oxygen, and 0, 0.25, 0.50, and 1 mM of MoO42−. In addition, in order to explore the metabolic specificity of aerobic strains, transcriptomic data of the facultative mercury-methylated strain B3 were further analyzed in an aerobic mercuric environment. The results indicated that: (a) molybdate significantly inhibited the growth of DE, while B3 and B4 exhibited normal growth. (b) Under anaerobic conditions, in DE, the MeHg content decreased significantly with increasing molybdate concentration, while in B3, MeHg production was unaffected. Furthermore, under aerobic conditions, the MeHg productions of B3 and B4 were not influenced by the molybdate concentration. (c) The transcriptomic analysis showed several genes that were annotated as members of the molybdenum oxidoreductase family of B3 and that exhibited significant differential expression. These findings suggest that the differential expression of molybdenum-binding proteins might be related to their involvement in energy metabolism pathways that utilize nitrate and dimethyl sulfoxide as electron acceptors. Aerobic bacteria, such as B3 and B4, might possess distinct Hg(II) biotransformation pathways from anaerobic SRB, rendering their growth and biomethylation abilities unaffected by molybdate.

BackgroundIgA nephropathy (IgAN) is a significant contributor to chronic kidney disease (CKD). Renal arteriolar damage is associated with IgAN prognosis. However, simple tools for predicting arteriolar damage of IgAN remain limited. We aim to develop and validate a nomogram model for predicting renal arteriolar damage in IgAN patients.MethodsWe retrospectively analyzed 547 cases of biopsy-proven IgAN patients. Least absolute shrinkage and selection operator (LASSO) regression and logistic regression were applied to screen for factors associated with renal arteriolar damage in patients with IgAN. A nomogram was developed to evaluate the renal arteriolar damage in patients with IgAN. The performance of the proposed nomogram was evaluated based on a calibration plot, ROC curve (AUC) and Harrell’s concordance index (C-index).ResultsIn this study, patients in the arteriolar damage group had higher levels of age, mean arterial pressure (MAP), serum creatinine, serum urea nitrogen, serum uric acid, triglycerides, proteinuria, tubular atrophy/interstitial fibrosis (T1–2) and decreased eGFR than those without arteriolar damage. Predictors contained in the prediction nomogram included age, MAP, eGFR and serum uric acid. Then, a nomogram model for predicting renal arteriolar damage was established combining the above indicators. Our model achieved well-fitted calibration curves and the C-indices of this model were 0.722 (95%CI 0.670–0.774) and 0.784 (95%CI 0.716–0.852) in the development and validation groups, respectively.ConclusionWith excellent predictive abilities, the nomogram may be a simple and reliable tool to predict the risk of renal arteriolar damage in patients with IgAN.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

The consensus of the automotive industry and traffic management authorities is that autonomous vehicles must follow the same traffic laws as human drivers. Using formal or digital methods, natural language traffic rules can be translated into machine language and used by autonomous vehicles. In this paper, a translation flow is designed. Beyond the translation, a deeper examination is required, because the semantics of natural languages are rich and complex, and frequently contain hidden assumptions. The issue of how to ensure that digital rules are accurate and consistent with the original intent of the traffic rules they represent is both significant and unresolved. In response, we propose a method of formal verification that combines equivalence verification with model checking. Reasonable and reassuring digital traffic rules can be obtained by utilizing the proposed traffic rule digitization flow and verification method. In addition, we offer a number of simulation applications that employ digital traffic rules to assess vehicle violations. The experimental findings indicate that our digital rules utilizing metric temporal logic (MTL) can be easily incorporated into simulation platforms and autonomous driving systems (ADS).

Abstract The objective of this study was to analyze the antimicrobial resistance (AMR) characteristics produced by antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and gene cassettes in Escherichia coli isolated from the feces of captive black bears. Antimicrobial susceptibility testing was performed by using the disk diffusion method, and both MGEs and integron gene cassettes were detected by polymerase chain reaction. Our results showed that 43.7% (62/142) of the isolates were multidrug resistant strains and 97.9% (139/142) of the isolates were resistant to at least one antibiotic. The highest AMR phenotype was observed for tetracycline (79.6%, 113/142), followed by ampicillin (50.0%, 71/142), trimethoprim-sulfamethoxazole (43.7%, 62/142) and cefotaxime (35.9%, 51/142). However, all isolates were susceptible to tobramycin. tetA had the highest occurrence in 6 ARGs in 142 E. coli isolates (76.8%, 109/142). Ten mobile genetic elements were observed and IS26 was dominant (88.0%, 125/142). ISECP1 was positively associated with five β-lactam antibiotics. ISCR3/14, IS1133 and intI3 were not detected. Seventy-five E. coli isolates (65 intI1-positive isolates, 2 intI2-positive isolates and 8 intI1 + intI2-positive isolates) carried integrons. Five gene cassettes (dfrA1, aadA2, dfrA17-aadA5, aadA2-dfrA12 and dfrA1-aadA1) were identified in the intI1-positive isolates and 2 gene cassettes (dfrA1-catB2-sat2-aadA1 and dfrA1-catB2-sat1-aadA1) were observed in the intI2-positive isolates. Monitoring of ARGs, MGEs and gene cassettes is important to understand the prevalence of AMR, which may help to introduce measures to prevent and control of AMR in E. coli for captive black bears.

Abstract This paper addressed the challenges associated with the complexity, numerous parameters, computational resource demands, and slow processing speed of transformer fault identification models based on deep learning technologies. Sparse convolutional neural network (CNN) approach is proposed for identifying faults related to dissolved gases in oil. Leveraging an improved Gramian angular field, one‐dimensional fault samples are converted into two‐dimensional feature images and data augmentation is implemented to meet the input requirements of deep learning models. Building upon visual geometry group (VGG)19 and residual networks (ResNet)50 networks for fault diagnosis, sparsity techniques are introduced through pruning, the fusion of convolution layers and batch normalization layers, and parameter quantization. Numerical experiments and performance evaluations on dissolved gas in transformer oil fault data demonstrate that the proposed method effectively reduced model complexity, minimized parameter count, conserved computational resources, and improved processing speed while maintaining a considerable level of fault identification accuracy. This made it applicable to edge computing platforms characterized by small form factors and low power consumption in the power industry.

Long-term failures in flexible converter valve equipment pose significant risks, potentially compromising operational efficiency or leading to complete malfunction. Accurately identifying equipment faults is essential to improve overall reliability and minimize downtime. This study introduces an innovative fault diagnosis method utilizing an attention mechanism. The method integrates a lightweight model incorporating one-dimension depthwise convolutional layers for spatial feature extraction and bidirectional long short-term memory for capturing temporal dynamics. A pioneering time-channel joint attention module enhances the extraction of fault-related data from time series and channel maps. Experimental results underscore the method’s efficacy in fault diagnosis under varying Gaussian noise conditions. Notably, the approach demonstrates remarkable consistency in accuracy across various experimental setups, underscoring its robust performance and potential applicability in real-world scenarios where reliability is critical. In addition, the proposed method has a moderate number of parameters and training time, indicating that the model can be embedded in front-end equipment.

Abstract Under the new power system, a high proportion of new energy is widely connected to the power grid, and it is necessary to increase investment in centralized and distributed energy storage, flexible resource regulation, and transmission and distribution grids, resulting in an increase in power system costs. The current electricity capacity price does not reflect the economic value of the added system adequately, and flexible capacity is needed to ensure the safety of the power grid under the new power system. In the context of the transformation of the new power system and investment function, it is increasingly difficult to recover the costs according to the traditional electricity price. It is necessary to establish a coordinated development mechanism for the electricity capacity price and the electricity price that recovers the fixed costs according to the investment function to ensure a reasonable return on investment in flexible resources and to provide effective investment signals. Therefore, this work first studied and proposed a mechanism for the formation of capacity and electricity prices based on the proportion of allowed income and fixed costs at different voltage levels and calculates the level of electricity capacity (demand) prices and electricity consumption prices. Then, using the BARY curve, genetic algorithm, and clustering of user load rates, a collaborative mechanism between the electricity capacity price and the electricity price was designed. With the goal of optimizing the electricity capacity price and considering constraints such as the flexibility and reliability of the new power system, the ratio of the capacity cost allocated to the electricity capacity price by voltage level users to the capacity cost allocated to the electricity price was calculated, and the optimal combination of electricity capacity price and electricity price for different load‐rate intervals was determined. Finally, the effectiveness of the model was verified through numerical simulations. On the basis of the investment characteristics of the new power system, suggestions for a capacity pricing mechanism under the new power system were proposed from the perspectives of transfer capacity function, transfer electricity function, grid reliability, and environmental and social benefits.

Evaluating aviation emissions and examining the dispersion properties of contaminants are crucial for understanding atmospheric pollution. To assess the pollutant emissions and dispersion of aircraft during the landing and takeoff (LTO) cycle, and address air pollution surrounding the airport resulting from flight operations, this study evaluated emissions throughout the LTO phase based on Quick Access Recorder (QAR) data in conjunction with the first-order approximation method. An improved Gaussian diffusion model for mobile point sources was employed to examine the diffusion characteristics of contaminants. Additionally, CFD calculation outcomes for various exhaust velocities and wind speeds were utilized to validate the trustworthiness of the improved Gaussian model. The discussion also encompasses the influence of diffusion time, wind direction, wind speed, temperature gradient, and particle deposition on the concentration distribution of contaminants. The findings indicated that the Gaussian diffusion model aligned with the results of the CFD calculations. The diffusion distribution of contaminants around airports varies over time and is significantly influenced by atmospheric environmental factors, including wind direction, wind speed, and atmospheric stability. Specifically, a change in wind direction from 0° to 45° caused a shift of approximately 1000 m in the contaminant’s center. An increase in wind speed from 3 m/s to 5 m/s led to a decrease in concentration by about 15%. Furthermore, a transition in atmospheric stability from category ‘a’ (very unstable) to ‘f’ (very stable) resulted in a two-order-of-magnitude increase in contaminant concentrations.

In the context of constructing new power systems, the intermittency and volatility of high-penetration renewable generation pose new challenges to the stability and secure operation of power systems. Enhancing the ramping capability of power systems has become a crucial measure for addressing these challenges. Therefore, this paper proposes a bi-level peak regulation optimization model for power systems considering ramping capability and demand response, aiming to mitigate the challenges that the uncertainty and volatility of renewable energy generation impose on power system operations. Firstly, the upper-level model focuses on minimizing the ramping demand caused by the uncertainty, taking into account concerned constraints such as the constraint of price-guided demand response, the constraint of satisfaction with electricity usage patterns, and the constraint of cost satisfaction. By solving the upper-level model, the ramping demand of the power system can be reduced. Secondly, the lower-level model aims to minimize the overall cost of the power system, considering constraints such as power balance constraints, power flow constraints, ramping capability constraints of thermal power units, stepwise ramp rate calculation constraints, and constraints of carbon capture units. Based on the ramping demand obtained by solving the upper-level model, the outputs of the generation units are optimized to reduce operation cost of power systems. Finally, the proposed peak regulation optimization model is verified through simulation based on the IEEE 39-bus system. The results indicate that the proposed model, which incorporates ramping capability and demand response, effectively reduces the comprehensive operational cost of the power system.

In this study, a kilowatt-level high-efficiency narrow-linewidth all-fiber Tm3+-doped continuous-wave laser operating at 1.95 μm is demonstrated. Benefitting from an advanced boost design of a two-stage main amplifier, it not only effectively manages heat dissipation resulting from the high pump-induced quantum defect but also realizes the controlled extraction of optical gain and improves the optical conversion efficiency. Finally, this laser system has realized an output power of 1018 W, a linewidth of 3.8 GHz, and a slope efficiency of 60.0% simultaneously. Moreover, a high optical signal-to-noise ratio of over 45 dB and excellent beam quality of M2 factors 1.19 are obtained. To the best of our knowledge, this represents the narrowest linewidth and highest slope efficiency achieved in a kilowatt-level Tm³⁺-doped fiber laser. Such a high-performance laser is ideally suited for mid-infrared generation and remote sensing applications.

Objectives Prostate cancer (PRAD) is a highly malignant disease with poor prognosis, and its development is regulated by a complex network of genes and signaling pathways. LncRNAs and miRNAs have significant regulatory roles in PRAD through the ceRNA network. Cuproptosis is a unique form of programmed cell death that is involved in various signaling pathways and biological processes related to tumor development. Nuclear factor of activated T cells 5 (NFAT5), a transcription factor that activates T cells, has been implicated in cuproptosis. However, the regulatory mechanism by which NFAT5 is involved in the ceRNA network in PRAD remains unclear. Methods Through bioinformatics analysis, we found the ceRNA axis that regulates cuproptosis. By performing ROS assay and copper ion concentration assay, we demonstrated that inhibiting NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. By using luciferase assay, we discovered that AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. Results In this study, we found that lncRNA AP000842.3, as a ceRNA of miR-206, was involved in the regulation of levels of the transcription factor NFAT5 associated with cuproptosis in PRAD. First, knocking down NFAT5 can increase the sensitivity of PRAD to cuproptosis inducers. Meanwhile, changes in the expression of AP000842.3 and miR-206 could affect the proliferation of PRAD by regulating NFAT5. Mechanistically, AP000842.3 acts as the ceRNA of miR-206 to regulate the expression of NFAT5. In addition, the effects of lncRNA AP000842.3 on malignant progression of PRAD and NFAT5 were partially dependent on miR-206. Conclusion Taken together, our study reveals a key ceRNA regulatory network in PRAD and can be regarded as a new potential target for PRAD diagnosis and treatment.

Ammonia oxidation is the rate-limiting step in nitrification and the key step in the nitrogen (N) cycle. Most soil nutrients and biological indicators are extremely sensitive to irrigation systems, from the perspective of improving soil fertility and soil ecological environment, the evaluation of different irrigation systems and suitability of selection, promote crop production and soil quality, study the influence of the soil microenvironment contribute to accurate evaluation of irrigation farmland soil health. Based on the amoA gene, the abundance and community diversity of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) and their responses to soil physicochemical factors and enzyme activities were studied in semi-arid areas of Northeast China. The study consisted of three irrigation systems: flood irrigation (FP), shallow buried drip irrigation (DI), and mulched drip irrigation (MF). The results showed that DI and MF significantly increased the contents of alkaline hydrolyzed nitrogen (AN), nitrate nitrogen (NO3–-N), soil moisture, and the activities of ammonia monooxygenase (AMO) and hydroxylamine oxidase (HAO). Compared with FP, DI significantly increased the abundance of soil AOA and AOB, while MF significantly increased the abundance of soil AOB. Irrigation systems significantly affected the community composition of ammonia-oxidizing microorganisms (AOM). Also, AN and soil moisture had the greatest influence on the community composition of AOA and AOB, respectively. The AOB community had better stability and stress resistance. Moreover, the symbiotic network of AOB in the three irrigation systems was more complex than that of AOA. Compared with FP, the AOA community under treatment DI had higher complexity and stability, maintaining the versatility and sustainability of the ecosystem, while the AOB community under treatment MF had higher transfer efficiency in terms of matter and energy. In conclusion, DI and MF were more conducive to the propagation of soil AOM in the semi-arid area of Northeast China, which can provide a scientific basis for rational irrigation and N regulation from the perspective of microbiology.

Cumulative light exposure, including electronic device radiation, may induce retinal pigment epithelium (RPE)-related retinal diseases, potentially mitigated by lutein. However, there is limited 3D RPE monolayer model to study the effect of phytochemicals on their activity and action mechanisms in vitro. Here, we present a method using a monolayer RPE tissue model on a 3D-printed polycaprolactone scaffold. Six-hour of phone screen light increased reactive oxygen species (ROS) in RPE cells, leading to oxidative stress, cytotoxicity, and inhibited metabolism. Pre-treating RPE cells (24 h) with 0.5 µM lutein reduced ROS levels and maintained viability under the same light exposure. Additionally, lutein demonstrated protective effects on crucial RPE functions, including phagocytosis and the retinal-blood barrier. This study underscores the importance of optimal lutein content in shielding RPE from phone screen light damage, and our model holds promise for evaluating the efficacy of antioxidants against light radiation.

Bone defects and non-union are prevalent in clinical orthopedy, and the outcomes of current treatments are often suboptimal. Bone tissue engineering offers a promising approach to treating these conditions effectively. Bone morphogenetic protein 9 (BMP9) can commit mesenchymal stem cells to osteogenic lineage, and a knowledge of the underlying mechanisms may help advance the field of bone tissue engineering. Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4), a member of G protein-coupled receptors, is essential for modulating bone development. This study is aimed at investigating the impact of LGR4 on BMP9-induced osteogenesis in mesenchymal stem cells as well as the underlying mechanisms. Bone marrow stromal cells from BMP9-knockout mice exhibited diminished LGR4 expression, and exogenous LGR4 clearly restored the impaired osteogenic potency of the bone marrow stromal cells. Furthermore, LGR4 expression was increased by BMP9 in C3H10T1/2 cells. LGR4 augmented the benefits of BMP9-induced osteogenic markers and bone formation, whereas LGR4 inhibition restricted these effects. Meanwhile, the BMP9-induced lipogenic markers were increased by LGR4 inhibition. The protein levels of Raptor and p-Stat3 were elevated by BMP9. Raptor knockdown or p-Stat3 suppression attenuated the osteoblastic markers and LGR4 expression brought on by BMP9. LGR4 significantly reversed the blocking effect of Raptor knockdown or p-Stat3 suppression on the BMP9-induced osteoblastic markers. Raptor interacts with p-Stat3, and p-Stat3 activates the LGR4 promoter activity. In conclusion, LGR4 boosts BMP9 osteoblastic potency in mesenchymal stem cells, and BMP9 may up-regulate LGR4 via the mTORC1/Stat3 signal activation.

Introduction: Precise fault diagnosis is crucial for enhancing the reliability and lifespan of the flexible converter valve equipment. To address this issue, depthwise separable convolution, bidirectional gate recurrent unit, and multi-head attention module (DSC-BiGRU-MAM) based fault diagnosis approach is proposed.Methods: By DSC and BiGRU operation, the model can capture the correlation between local features and temporal information when processing sequence data, thereby enhancing the representation ability and predictive performance of the model for complex sequential data. In addition, by incorporating a multi-head attention module, the proposed method dynamically learns important information from different time intervals and channels. The proposed MAM continuously stimulates fault features in both time and channel dimensions during training, while suppressing fault independent expressions. As a result, it has made an important contribution to improving the performance of the fault diagnosis model.Results and Discussion: Experimental results demonstrate that the proposed method achieves higher accuracy compared to existing methods, with an average accuracy of 95.45%, average precision of 88.67%, and average recall of 89.03%. Additionally, the proposed method has a moderate number of model parameters (17,626) and training time (935 s). Results indicate that the proposed method accurately diagnoses faults in flexible converter valve equipment, especially in real-world situations with noise overlapping signals.

Au–Sn alloy is an important high-temperature solder, but it has some disadvantages such as high cost and brittleness. Multicomponent alloying is often performed to improve performance and reduce their cost. However, due to the absence of an atomic structure model, there has been a lack of effective theory to guide their composition design. Since Au–Sn solders are typically eutectic-based, understanding the Au–Sn eutectic at the atomic level is of great significance for clarifying the composition origin of Au–Sn solders and the subsequent multi-component composition design. In the present work, the short-range order of Au–Sn eutectics is characterized using a dual-cluster model. In the dual-cluster formulism, the two eutectics Au69.6Sn30.3 and Sn94.6Au5.4 at. % are interpreted in terms of the hypoeutectic [SnAu12]Sn2Au3 + [Au–Au2Sn6]Au3 = Au70.0Sn30.0 and [Au–Sn8]Au1 + 2{[Sn–Sn10]Sn5} = Sn95.2Au4.8 alloys, respectively. The compositions of Au–Sn solders are then analyzed based on the interpreted dual-cluster formulas, which indicate that the number of atoms of the alloying elements that replace the atoms in the dual-cluster formulas is always an integer. The present method provides a quantitative approach toward developing a practical composition interpretation and design tool for Au–Sn-based solders.

Abstract Nipah virus (NiV) is a highly lethal zoonotic paramyxovirus that poses a severe threat to humans due to its high morbidity and the lack of viable countermeasures. Vaccines are the most crucial defense against NiV infections. Here, a recombinant chimpanzee adenovirus-based vaccine (AdC68-G) and a DNA vaccine (DNA-G) were developed by expressing the codon-optimized full-length glycoprotein (G) of NiV. Strong and sustained neutralizing antibody production, accompanied by an effective T-cell response, was induced in BALB/c mice by intranasal or intramuscular administration of one or two doses of AdC68-G, as well as by priming with DNA-G and boosting with intramuscularly administered AdC68-G. Importantly, the neutralizing antibody titers were maintained for up to 68 weeks in the mice that received intramuscularly administered AdC68-G and the prime DNA-G/boost AdC68-G regimen, without a significant decline. Additionally, Syrian golden hamsters immunized with AdC68-G and DNA-G via homologous or heterologous prime/boost immunization were completely protected against a lethal NiV virus challenge, without any apparent weight loss, clinical signs, or pathological tissue damage. There was a significant reduction in but not a complete absence of the viral load and number of infectious particles in the lungs and spleen tissue following NiV challenge. These findings suggest that the AdC68-G and DNA-G vaccines against NiV infection are promising candidates for further development.

Abstract In this paper, we investigate some characteristics of phantom Reissner-Nordström-de Sitter (RN-dS) black holes. The peculiar features of phantom field render this kind of black holes quite different from their counterparts. We can only find at most two horizons in this spacetime, i.e. event horizon and cosmological horizon. For the black hole charge parameter, we find that it is not bounded from below. We calculate quasinormal modes (QNMs) frequencies of massless neutral scalar field perturbation in this black hole spacetime, and some properties related to the large charge parameter are disclosed.

Abstract Cyanophages, together with their host cyanobacteria, play important roles in marine biogeochemical cycles and control of marine food webs. The recently identified MPP-C (Marine Picocyanobacteria Podovirus clade C) cyanophages, belonging to the T7-like podoviruses, contain the smallest genomes among cyanopodoviruses and exhibit distinct infection kinetics. However, understanding of the MPP-C cyanophage infection process is hindered by the lack of high-resolution structural information. Here, we report the cryo-EM structure of the cyanophage P-SCSP1u, a representative member of the MPP-C phages, in its native form at near-atomic resolution, which reveals the assembly mechanism of the capsid and molecular interaction of the portal-tail complex. Structural comparison of the capsid proteins of P-SCSP1u and other podoviruses with known structures provides insights into the evolution of T7-like viruses. Furthermore, our study provides the near-atomic resolution structure of portal-tail complex for T7-like viruses. On the basis of previously reported structures of phage T7, we identify an additional valve and gate to explain the DNA gating mechanism for the T7-like viruses.