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Antarctic krill (Euphausia superba) is a vital species in the Antarctic ecosystem, boasting substantial reserves and high nutritional value. It has emerged as a significant commercial fishery resource in the Southern Ocean. However, because of its exceptionally high autolytic enzyme activity, it is susceptible to autolysis and blackening during processing, storage, and transportation, resulting in a decline in the sensory quality and nutritional value of raw materials. Shrimp melanosis is caused by a series of enzymatic reactions mediated by phenoloxidase (PO) within the body. PO facilitates the oxidation of phenolic substances, leading to the formation of highly unstable quinone compounds, which further react to produce melanin. The accumulation of melanin significantly affects the appearance of Antarctic krill, thereby reducing its commercial value. On account of their cost-effectiveness and potent anti-blackening effects, sulfites are commonly used as shrimp anti-black agents. Sodium metabisulfite is one of the compounds whose use is allowed for shrimp preservation under GB 2760-2014 regulations. It not only inhibits PO activity, but also reduces quinone compounds to prevent blackening. However, excessive sulfite use can lead to discomfort and health issues such as gastrointestinal problems, liver disturbances, dyspnea, vomiting, diarrhea, and headaches. Therefore, GB 2760-2014 regulations stipulate that the residual SO2 content should not exceed 0.1 g/kg. Currently, the use of sodium metabisulfite in production is widespread but lacks standardized requirements, with limited guidance available on how to regulate its usage. Therefore, to assess the impact of sodium metabisulfite on blackening control in Antarctic krill and refine the treatment process, experiments were conducted to measure the changes in SO2 residue and PO activity in Antarctic krill subjected to various concentrations of sodium metabisulfite solutions and soaking times. Furthermore, observations and analyses were conducted to monitor the blackening of Antarctic krill during cold storage and frozen storage. The results demonstrated a positive correlation between the SO2 residue in Antarctic krill and the concentration of sodium metabisulfite solution. A concentration of 1 g/L sodium metabisulfite solution resulted in a SO2 residue of 0.065 g/kg in Antarctic krill, which is below the national standard limit of 0.1 g/kg. However, treatment with a 2 g/L solution led to a SO2 residue of 0.166 g/kg in shrimp, exceeding the national standard limit. Treatment with a 3 g/L solution resulted in a SO2 residue of 0.254 g/kg in shrimp, which significantly surpassed the national standard limit. Consequently, we recommended using 1 g/L or 2 g/L sodium metabisulfite solutions to prevent blackening in Antarctic krill while maintaining the SO2 residue below 0.1 g/kg. Under these conditions, the treatment time for a 1 g/L sodium pyrosulfite solution could be extended to 300 s, with a relative PO activity of 21.2%. For a 2.0 g/L sodium pyrosulfite solution, a treatment time of 30 s was suitable, yielding a relative PO activity of 34.5%. During storage, the control group exhibited noticeable blackening after storage at 4 ℃ for 24 h and frozen storage for 6 months, predominantly in the head, chest, abdomen, and tail sections, and slight variations were observed in the blackening process among individuals. Compared with the control group, the sodium metabisulfite treatment group displayed significantly lower blackening scores during storage (P < 0.05). Specifically, the 1 g/L sodium metabisulfite solution with 300 s treatment group and the 2 g/L sodium metabisulfite solution with 30 s treatment group showed obvious blackening at 48 h and 72 h of cold storage, respectively, and after 12 months of frozen storage, indicating that higher concentrations of sodium metabisulfite solution during treatment led to a better control effect on the blackening of Antarctic krill during storage. Notably, PO activity is just one of the factors influencing the melanosis process. Although the 1 g/L sodium metabisulfite solution with treatment for 300 s could better inhibit PO activity, the anti-blackening effect of this group was not as pronounced as that of the 2 g/L sodium metabisulfite solution with treatment for 30 s during storage. In summary, soaking in 1 g/L sodium metabisulfite solution for 300 s and 2 g/L sodium metabisulfite solution for 30 s resulted in relative PO enzyme activities of 21.2% and 34.5%, respectively. Simultaneously, the SO2 residues in shrimp were measured at 0.094 g/kg and 0.096 g/kg, respectively, meeting the GB 2760-2014 limit of SO2 residue not exceeding 0.1 g/kg. Compared with the control group, sodium metabisulfite treatment effectively delayed the blackening process of Antarctic krill during cold storage and frozen storage, with the 2 g/L sodium metabisulfite solution soaking for 30 s exhibiting superior anti-blackening effects. This suggests that a high concentration of sodium metabisulfite solution and a short treatment period had a better blackening inhibition effect. These findings offer a theoretical foundation and technical guidance for maintaining the quality of Antarctic krill during storage and transportation.

Abstract Acute pancreatitis (AP) can result in acute kidney injury (AKI), which is linked to poor outcomes. We aimed to assess the relationship between the hematocrit-to-albumin ratio (HAR) and AKI in this population. This retrospective cohort study included consecutive patients diagnosed with AP and admitted to hospital. Data were systematically extracted from electronic medical records, covering baseline demographic and clinical characteristics. Total 1514 AP patients were enrolled, with 17% (257/1514) developing AKI. Multivariable-adjusted regression analysis, curve fitting, threshold effects analyses, and subgroup analyses were conducted to evaluate the relationship between HAR and AKI incidence in AP patients. Compared to the reference tertile of HAR, the adjusted OR values for the lower and higher tertiles of HAR were 1.25 (95% CI, 0.82–1.91, P = 0.297) and 1.50 (95% CI, 1.03–2.20, P = 0.037), respectively, after adjusting for covariates. The curve fitting results showed a J-shaped relationship between HAR and AKI (non-linear, p = 0.001), with an inflection point of 8.969. Furthermore, validation using the Medical Information Mart for Intensive Care (MIMIC-IV) database AP population revealed a similar relationship with an inflection point at 10.257. Our findings suggest a J-shaped relationship between HAR and AKI in AP patients, indicating higher risk of AKI when HAR exceeds 8.969.

Abstract Bovine parainfluenza virus type 3 (BPIV3) is a viral respiratory pathogen that infects cattle and causes significant economic losses. We generated a recombinant adenovirus called rHAd5-F + HN by expressing the fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein of BPIV3 using the human adenovirus serotype 5 (rHAd5). We evaluated its effects on humoral and cellular immune responses in mice (n = 45) and calves (n = 9). Serum antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA), hemagglutination inhibition (HI), and neutralising antibodies (NAb). After boosting immunity with rHAd5-F + HN, mice produced significantly higher levels of antibodies against the BPIV3 genotype A and genotype C strains. The production of antibodies exceeded those produced by adenoviruses rHAd5-F and rHAd5-HN, which express the F and HN glycoprotein, respectively. The percentages of splenic CD3+/CD8+T lymphocytes and IL-4+ cytokines in rHAd5-F + HN mice were considerably higher than those in the control group. Mice immunised with rHAd5-F + HN exhibited much lower viral loads in the lungs and tracheas compared to the control group. Additionally, the lungs of mice vaccinated with rHAd5-F + HN showed no notable histopathological changes. On the other hand, rHAd5-F + HN produced a humoral immune response in calves. Following the booster intramuscular injection with the rHAd5-F + HN, the serum antibody levels against BPIV3 genotype C strain were 1:20 452, 1:1024, and 1:426 in calves, as detected by ELISA, HI, and NAb, respectively. The HI and NAb levels against the BPIV3 genotype A strain were 1:213 and 1:85 in calves, respectively. These results indicate that rHAd5-F + HN effectively induced immunity against BPIV3 infection.

Abstract Background Influenza B virus induced myocarditis is a rare complication with potentially wide variations in severity and clinical presentation, and the pathogenesis is unclear. Case presentation We describe a rare case of a 7-year-old boy who developed fulminant myocarditis (FM) due to influenza B virus infection. Treatment measures included mechanical ventilation, vasoactive agents, Extracorporeal membrane oxygenation (ECMO), Continuous Renal Replacement Therapy (CRRT), anti-inflammatory, antiviral, anti-infection, and enteral nutrition support. After 10 days of treatment, the patient succumbed to multiorgan failure. Conclusions After a systematic review of the literature, we found that this disease predominantly affects females, with pediatric cases exceedingly rare. Fulminant myocarditis (FM) progresses rapidly, poses significant treatment challenges sporadic, and carries a poor prognosis. Interestingly, literature reports suggest that anti-thymocyte globulin therapy may have a positive impact in treating FM, potentially offering new insights into its pathogenesis and clinical management.

Abstract Background Given increases in China’s aging population, the growing demand for public health services and the shortage of human resources among nurses have become more prominent. Under such a background, “Internet + Nursing Services” have received more attention. Thus, exploring the barriers to and facilitators of nurses’ willingness to participate in “Internet + Nursing Services” and utilizing internet technology to increase the supply of nursing services has become a key issue. Objective This study aimed to develop a scale for assessing the barriers to and facilitators of nurses’ willingness to participate in “Internet + Nursing Services” and to test the validity and reliability of the scale. Methods A preliminary scale was developed based on a literature review, theoretical research, semistructured qualitative interviews, and two rounds of Delphi expert inquiry. A convenient sampling method was used for the questionnaire survey. A 5-point Likert scale was used to evaluate the importance of the items. The survey data of 659 clinical nurses obtained from February to March 2023 were used for item analysis, exploratory factor analysis (EFA), and reliability and validity tests of the scale. The survey data of 538 clinical nurses obtained in April 2023 were used for confirmatory factor analysis (CFA) of the final scale. Results The final scale consists of 25 items and 4 dimensions (performance expectations, perceived risk, need for professional knowledge training, and nonprofessional knowledge training). The scale showed good structural validity and content validity: the Cronbach’s α coefficient of the scale was 0.955, the split-half reliability was 0.778, the test-retest reliability was 0.944, the kaiser-meyer-olkin(KMO) value was 0.960, and the cumulative variance contribution rate of the 4 common factors was 83.147%. The scale content validity index(S-CVI) was 0.914. The confirmatory factor analysis model had favorable fit indices: χ2/df = 4.234, RMSEA = 0.078, NFI = 0.940, IFI = 0.953, TLI = 0.947, and CFI = 0.953. Conclusion The scale for assessing the barriers to and facilitators of nurses’ willingness to participate in “Internet + Nursing Services” has good reliability and validity, and provides a reference for evaluating nurses’ willingness to participate in “Internet + Nursing Services”.

Abstract Background The Diplolepideae are the larger group within the Arthrodontae mosses, characterized by peristomes formed from residual cell walls. It is now understood that these peristomes exhibit diverse hygroscopic movements, playing a crucial role in spore release. However, the exact mechanism behind this movement remains unclear, lacking direct evidence. This study investigated the microscopic and submicroscopic structures of the peristomes in three Diplolepideae species: Hypopterygium fauriei (Besch.), Pylaisia levieri (Müll. Hal.) Arikawa and Regmatodon declinatus (Hook.) Brid. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to reveal the differences in their hygroscopic movement mechanisms. Results The three species exhibited distinct responses upon wetting: H. fauriei’s exostome closed inwards, P. levieri’ opened outwards, and R. declinatus’ elongated significantly. These differences are attributed to the varying microfibril deposition in the exostome layers. Uniform deposition in the inner layer and minimal deposition in the outer layer enabled exostome opening upon wetting and closing when dry. Our findings suggest that the diastole and contraction of fine microfibrils in the exostome plates and ridges are the key drivers of hygroscopic movement. Conclusions This study provides further evidence at both the structural and submicroscopic levels, contributing to the unraveling of the hygroscopic movement mechanism in Diplolepideae peristomes. This enhanced understanding sheds light on the relationship between peristome structure and function.

Infections caused by Acinetobacter baumannii (A. baumannii) have emerged as a global public health concern because of high pathogenicity of this bacterium. Monoclonal antibodies (mAbs) have a lower likelihood of promoting drug resistance and offer targeted treatment, thereby reducing potential adverse effects; however, the therapeutic potential of mAbs targeting A. baumannii has not been fully characterized. In this study, mAbs against the outer membrane proteins (OMPs) of A. baumannii were isolated in a high-throughput manner. The ability of Omp38-specific mAbs to bind to A. baumannii strains from diverse sources was confirmed via enzyme-linked immunosorbent assay (ELISA). Intravenous administration of the Omp38-specific mAbs significantly improved the survival rate and reduced the bacterial load in a mouse model of lethal A. baumannii infection. Flow cytometry and ELISA confirmed that immune cell infiltration and cytokine production, respectively, decreased in a mouse model of sublethal A. baumannii infection. In addition, analysis of the Omp38-mAb C3 binding conformation revealed the potential mechanism of broad-spectrum binding activity of this mAb against A. baumannii. Taken together, these findings indicate that mAbs against Omp38 facilitate bacterial clearance from host, minimize inflammatory mediator release and reduce host damage, highlighting the potential of Omp38-specific mAbs in the clinical treatment of A. baumannii infection.

Global climate change presents substantial threats to marine ecosystems, with particularly profound impacts on widely distributed migratory species. The basking shark (Cetorhinus maximus), the second-largest fish species, faces significant conservation challenges due to overfishing, habitat degradation, and climate change, necessitating urgent research to address knowledge gaps in its spatial distribution and interactions with changing marine environments. This study employs various environmental variables and distribution data to construct a global species distribution model for basking sharks, predicting their distribution patterns under current and future climate scenarios. The results indicate that chlorophyll, sea surface temperature, silicate and mixed layer depth are the primary factors determining habitat suitability for basking sharks. Under high-emission scenarios (Shared Socioeconomic Pathway, SSP5–8.5), our model predicts a shift toward the higher latitudes of the northern hemisphere in basking shark habitats, including temperate and sub-Arctic waters. Ecological corridor analysis identifies critical migratory pathways and pinch points, emphasizing the importance of incorporating the effects of climate change and human activities in the formulation of conservation strategies. The finding underscores the importance of integrated conservation strategies, highlighting how positive human interventions can aid in accurately identifying critical ecological corridors to ensure the long-term survival of the basking shark. Adaptive, science-based conservation measures are crucial to mitigating the effects of climate change and human activities, supporting the resilience of marine ecosystems.

Carbon nanotubes (CNTs) reinforced cement based grouting material is an important part of green manufacturing industry. Our previous research showed that this material can effectively enhance the impact resistance of rock matrix. In this study, We conducted a comprehensive study and quantitative analysis of the changes in pore structure of this material under impact conditions. Dynamic impact testing and computed tomography (CT) revealed that CNTs significantly increased the cement content in the sample by 79.11 %. The CNTs group exhibited higher internal pore density and uniformity, effectively suppressing the formation of dynamic cracks in the sample. Compared to Non-carbon nanotubes (Non-CNTs) cement-based materials, the peak dynamic stress of the CNTs group increased by 4.76–21.54 %, while the porosity decreased by 57.26 %.This study further refined the enhancement behaviors of carbon nanotubes reinforced cement based, and making outstanding contributions to engineering practice.

Background: Exposed, infected and necrotic tendons often occur in the middle and late stages of diabetic foot ulcers (DFUs). The exposed tendon is both a potential source and route of infection, which prolongs the treatment period and affects recovery, leading to amputation and even death. Therefore, management of the exposed tendon in patients with DFU is the key to treatment. This study aimed to evaluate the clinical efficacy of Shengji ointment combined with bromelain in the treatment of DFU with tendon exposure and to provide clinical treatment options and evidence-based medicine. Methods: This study was a multicenter, nonblinded, randomized, positive controlled clinical trial involving 180 patients with DFU with tendon exposure at four tertiary-grade A-class hospitals. The included patients were randomly assigned 1:1 to an observation group (n = 90) that received Shengji ointment combined with bromelain and a control group (n = 90) that received hydrocolloid dressing, with dressing changes once daily for 4 weeks. Patients in both groups continued with conventional treatments, such as blood glucose and blood pressure medication, lipid regulation, and antiplatelets. The primary outcome measure was wound coverage with granulation tissue. The secondary outcome measures included the wound healing rate, time to granulation, Maryland foot score, time to debridement of necrotic tendon tissue, and granulation tissue score. We performed measurements before enrollment and after the end of treatment for comparison. Results: There was no significant difference in the baseline data between the two groups before treatment (P > 0.05). After treatment, the primary outcome indicators of the two groups were compared, and the wound granulation tissue coverage rate of the treatment group was greater than that of the control group (P = 0.003). For the secondary outcome outcomes, the wound healing rate, time to granulation, Maryland foot function score, time to debridement of necrotic tendon tissue, and granulation tissue score in the treatment group were significantly better than those in the control group (P

Depression is one of the most common affective disorders in people’s life. Women are susceptibility to depression during puberty, peripartum and menopause transition, when they are suffering from sex hormone fluctuation. A lot of studies have demonstrated the neuroprotective effect of estrogen on depression in women, however, the effect of FSH on depression is unclear. In this study, we investigated the role of FSH on depression in mice. Our study demonstrated that FSH induced depression-like behaviors in mice in a dose-dependent manner. This induction was associated with elevated levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α in both serum and hippocampal tissues. Additionally, FSH treatment resulted in impaired synaptic plasticity and a reduction in the expression of key synaptic proteins. It is noteworthy that the depression-like behaviors, inflammatory cytokines expression and synaptic plasticity impairment induced by FSH could be alleviated by knocking down the expression of FSH receptor (FSHR) in the hippocampus of the mice. Therefore, our findings reveal that FSH may play an important role in the pathogenesis of depression and targeting FSH may be a potential therapeutic strategy for depression during hormone fluctuation in women.

The artificial reproduction of endangered marine species populations is becoming increasingly crucial. Determining the potential for reintegration into their natural ecological niche remains a persistent obstacle in conservation biology. Spotted seals (Phoca largha) are a flagship species in the Chinese marine ecosystem. Efforts have been made to artificially breed them to prevent local extinction. Our study monitored 18 captive-born (nine) and rehabilitated (nine) individuals released into the Bohai Sea between 2010 and 2020. We examined the ecological niche-seeking behavior of captive-born seals (CS) using rehabilitated wild seals (RS) as benchmarks. It encompassed three oceanic gradients, habitat patterns, and potential threats. The findings demonstrated that CS did not return to the appropriate latitudes, horizontals, and sea surface salinity gradients in the ocean. Despite a larger potential habitat area for CS, it exhibited high temporal variability (with an average monthly fluctuation of 53 %) and demonstrated limited spatial overlap with the RS habitat (27 % overlap in July), and four indices, including the Splitting and Global Moran's Indices indicated a higher level of habitat fragmentation. Additionally, the number of shipping hotspots and collision risk within the CS habitats were twice those of the RS. These findings suggest that the released CS did not fully integrate into its native ecological niche. Our objective is to offer a pragmatic approach and framework for monitoring and assessing marine species released into the ocean.

Abstract Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua How.) fruit development starts post pollination. With the continuous expansion of the fruit, the soluble solid content of the fruit decreases. Because there are no reports on the early development of Chieh-qua fruit, this study compared fruit transcriptomes at 0-, 3-, and 7 day post pollination (dpp). 104,747 unigenes were assembled from clean reads and compared using six public databases for similarity searching. Compared with those of 0 dpp (C), there were differences in the expression of 12,982 and 6541 genes in the fruit tissue at 3 dpp and 7 dpp, respectively. Compared with 3 dpp (B), there were 14,314 differentially expressed genes in the fruit at 7 dpp (A). Based on the analysis of transcription factors, 213 nucleotides in the MYB superfamily were identified; among them, 94 unigenes of the MYB superfamily were differentially expressed at the three stages. In the pairwise comparison of differential expression, eight unigenes (Gene_id: TRINITY_DN32880_c1_g2, TRINITY_DN35142_c2_g2, TRINITY_DN32454_c11_g6, TRINITY_DN34105_c2_g7, TRINITY_DN32758_c3_g3, TRINITY_DN33604_c4_g10, TRINITY_DN34466_c3_g1, TRINITY_DN35924_c3_g2) were homologous to those of MYB59, MYB-GT3b, MYB18, MYB4, MYB108, MYB306, MYB340, and MYB-bHLH13. These unigenes differed significantly among the three stages. Furthermore, MYB59 and MYB18 exhibited higher expression at 7 dpp. MYB4, MYB-GT3b, MYB108, and MYB306 showed the highest expression levels in fruits at 3 dpp. In addition, MYB340 and MYB-bHLH13 showed higher expression levels during the unpollinated stage. MYB59, MYB-GT3b, MYB18, MYB4, MYB108, MYB306, MYB340, and MYB-bHLH13 may play crucial roles in Chieh-qua fruit development, defense, and blossoming. This study provides a basis for further investigation of MYB superfamily genes involved in early fruit expansion in chieh-qua.

Abstract Climate change is exerting unprecedented impacts on marine habitats, and many sessile invertebrate species, such as the endangered giant clam Tridacna maxima, are particularly sensitive to climate driven changes in their environment. Understanding its spatial distribution and conservation requirements is of crucial significance in formulating effective protection strategies. However, the species has been extensively harvested and depleted in many regions, leading to its listing as endangered species by the International Union for Conservation of Nature (IUCN). While marine protected areas (MPAs) are considered effective conservation tools, it remains uncertain whether existing MPAs adequately protect these vulnerable giant clams. To enhance the management and conservation of this species, we employed a Species Distribution Models (SDMs) approach, integrating occurrence records of T. maxima with environmental variables, to predict its potential distribution based on habitat suitability and capture spatiotemporal changes. Based on geographical and genetic variations, the T. maxima in the Indo‐Pacific core region is primarily divided into two populations: the East Indian Ocean‐South China Sea population (EIOS) and the West Pacific‐Indonesia population (WPI). We first quantified realized niche to reveal significant differences in ecological niche space among different populations. Subsequently, SDMs were constructed at both species and population levels, demonstrating that population‐level SDMs provide more reliable predictions of population distributions due to differential responses to climatic predictor variables. Finally, we conducted an assessment to identify conservation gaps for T. maxima beyond the existing MPAs and proposed recommendations for future establishment of MPAs within the current framework. Based on these findings, appropriate conservation policies have been proposed to effectively protect the habitat of different geographical populations of T. maxima. Additionally, spatiotemporal predictions of habitat suitability provide crucial information for developing adaptive management strategies for T. maxima in response to climate change, including designing new protected areas and adjusting the location and extent of existing protected areas based on their geographical distribution.

Abstract Social defeat stress is associated with endoplasmic reticulum (ER) stress, inflammation and apoptosis. ER stress is thought to contribute to many lifestyle diseases such as liver injury, cardiovascular dysfunction and depression. We investigated the expression of the ER stress markers RNA-dependent protein kinase-like ER kinase (PERK), eukaryotic translation initiation factor 2α (eIF2α) and C/EBP homologous protein (CHOP), as well as inflammatory and apoptotic factors, to assess how social defeat stress induces liver injury. Furthermore, we evaluated the effects of the ER stress inhibitor phenylbutyric acid (PBA) and ER stress inducer thapsigargin (TG) on liver injury. Adult mice were divided into the control, social defeat, social defeat + PBA, TG, PBA and TG + PBA groups. The social defeat and social defeat + PBA groups were simultaneously exposed to social defeat stress for 10 days. The social defeat + PBA, TG, PBA and TG + PBA groups were treated with PBA or TG via intraperitoneal injections. PBA was injected 1 h before the TG injection into the TG + PBA group. Liver samples from six groups of mice were analyzed by histological analysis and western blotting. Social defeat stress promoted ER stress, increased the expression of inflammatory factors and induced apoptosis in the liver of socially defeated mice, which was reversed by PBA. Moreover, ER stress induces TG-induced liver injury by initiating ER stress. Social defeat stress initiates ER stress, promotes the expression of inflammatory and apoptotic factors, and induces liver injury. PBA suppresses liver injury caused by social defeat stress and TG treatment.

In this study, we analyzed the fracture mechanism of the 6252-armor steel target exposed to the impact of a kinetic energy projectile made of 93W alloy. By examining the impact pressure, crater morphology, and fracture mechanism at various impact velocities, we established the relationship among these factors. As the impact velocity increased, the ratio of penetration depth to crater diameter initially increased, then stabilized, and ultimately approached 0.7 when impact pressures exceeded 49.78 GPa. For impact pressures below 70.71 GPa, macroscopic cracks were predominantly observed on the side of the crater, with no macroscopic cracks found at the bottom. However, if the pressure exceeded 70.71 GPa, the majority of macroscopic cracks occurred at the bottom of the crater. We also found a decrease in spacing between cracks or shear bands and the recrystallized grain size at the interface when the impact velocity increased. Notably, the fracture patterns demonstrated a mixture of brittle and ductile failure modes simultaneously.

In the high-frequency (HF) region, specifically within the 150 kHz to 30 MHz range for conducting electromagnetic interference (EMI) modeling, NiZn inductors exhibit enhanced efficiency due to their low core losses and stable permeability. Consequently, the accurate modeling of NiZn ferrite toroidal inductors is essential, given their widespread applications in the HF domain, with the aim of addressing existing knowledge gaps. Previous inductor models often relied on the perfect electric conductor (PEC) assumption, which simplifies the analysis but does not fully represent the electromagnetic behavior of the cores to which the PEC assumption cannot be applied. This study investigates the actual electromagnetic behavior of NiZn cores, treating them as dielectrics, which diverges from the traditional PEC-based models. Furthermore, this research fully considers the actual geometry of the inductors, proposing a comprehensive and precise analytical model for NiZn ferrite toroidal inductors. The impact of various winding methods on core capacitance is also explored. The paper provides a detailed explanation of the physical significance underlying the proposed model. A comparative analysis of both modeling methods is presented, and the efficacy of the suggested approach is validated through simulations and experimental results in several distinct scenarios.

Airborne radar forward-looking imaging holds significant promise for applications such as autonomous navigation, battlefield reconnaissance, and terrain mapping. However, traditional methods are hindered by complex system design, azimuth ambiguity, and low resolution. This paper introduces a distributed array collaborative, forward-looking imaging approach, where multiple aircraft with linear arrays fly in parallel to achieve coherent imaging. We analyze signal model characteristics and highlight the limitations of conventional algorithms. To address these issues, we propose a high-resolution imaging algorithm that combines an enhanced missing-data iterative adaptive approach with aperture interpolation technique (MIAA-AIT) for effective signal recovery in distributed arrays. Additionally, a novel reference range cell migration correction (reference RCMC) is employed for precise range–azimuth decoupling. The forward-looking algorithm effectively transforms distributed arrays into a virtual long-aperture array, enabling high-resolution, high signal-to-noise ratio imaging with a single snapshot. Simulations and real data tests demonstrate that our method not only improves resolution but also offers flexible array configurations and robust performance in practical applications.

Background Previous criteria had limited value in early diagnosis of periprosthetic joint infection (PJI). Here, we constructed a novel machine learning (ML)-derived, “in-time” diagnostic system for PJI and proved its validity. Methods We filtered “in-time” diagnostic indicators reported in the literature based on our continuous retrospective cohort of PJI and aseptic prosthetic loosening patients. With the indicators, we developed a two-level ML model with six base learners including Elastic Net, Linear Support Vector Machine, Kernel Support Vector Machine, Extra Trees, Light Gradient Boosting Machine and Multilayer Perceptron), and one meta-learner, Ensemble Learning of Weighted Voting. The prediction performance of this model was compared with those of previous diagnostic criteria (International Consensus Meeting in 2018 (ICM 2018), etc.). Another prospective cohort was used for internal validation. Based on our ML model, a user-friendly web tool was developed for swift PJI diagnosis in clinical practice. Results A total of 254 patients (199 for development and 55 for validation cohort) were included in this study with 38.2% of them diagnosed as PJI. We included 21 widely accessible features including imaging indicators (X-ray and CT) in the model. The sensitivity and accuracy of our ML model were significantly higher than ICM 2018 in development cohort (90.6% vs. 76.1%, P = 0.032; 94.5% vs. 86.7%, P = 0.020), which was supported by internal validation cohort (84.2% vs. 78.6%; 94.6% vs. 81.8%). Conclusions Our novel ML-derived PJI “in-time” diagnostic system demonstrated significantly improved diagnostic potency for surgical decision-making compared with the commonly used criteria. Moreover, our web-based tool greatly assisted surgeons in distinguishing PJI patients comprehensively. Level of evidence Diagnostic Level III.

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development. Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function. Increasing amounts of evidence highlight several key points: (1) Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease, and potentially, similar alterations occur in humans. (2) Genetic mutations of Netrin-1 receptors increase an individuals’ susceptibility to neurodegenerative disorders. (3) Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function. (4) Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers. These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases. Through a comprehensive review of Netrin-1 signaling pathways, our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

Heterogeneous structure is practical to improve the strain hardening abilities of materials due to the effect of hetero-deformation induced hardening, especially of composites. In this study, a series of TiB/TC4 composites with a pseudo core–shell structure of bimodal grain distribution were fabricated via a two-step ball-milling and spark plasma sintering. The synthesized TiB/TC4 composites have a structure of coarse lamella α-Ti grains of average 23.6 μm in diameter surrounded by fine α-Ti lamella grains of average 4.2 μm, with TiB distributed on the primary TC4 surface areas. TiB/TC4 composites with 0.4 wt% TiB2 exhibited the best comprehensive mechanical properties with an ultimate tensile strength of 1161.95 MPa (a 35.1% increase compared with that of pure TC4) and an elongation of 7.57%. In conclusion, the pseudo core–shell structure improved the strength by improving the strain-hardening abilities, achieved by the coordinated deformation between coarse grains and fine grains.

Abstract Alzheimer’s disease (AD) is the most common dementia. It is known that women with one ApoE4 allele display greater risk and earlier onset of AD compared with men. In mice, we previously showed that follicle–stimulating hormone (FSH), a gonadotropin that rises in post–menopausal females, activates its receptor FSHR in the hippocampus, to drive AD–like pathology and cognitive impairment. Here we show in mice that ApoE4 and FSH jointly trigger AD-like pathogenesis by activating C/EBPβ/δ-secretase signaling. ApoE4 and FSH additively activate C/EBPβ/δ-secretase pathway that mediates APP and Tau proteolytic fragmentation, stimulating Aβ and neurofibrillary tangles. Ovariectomy-provoked AD-like pathologies and cognitive defects in female ApoE4-TR mice are ameliorated by anti-FSH antibody treatment. FSH administration facilitates AD-like pathologies in both young male and female ApoE4-TR mice. Furthermore, FSH stimulates AD-like pathologies and cognitive defects in ApoE4-TR mice, but not ApoE3-TR mice. Our findings suggest that in mice, augmented FSH in females with ApoE4 but not ApoE3 genotype increases vulnerability to AD-like process by activating C/EBPβ/δ-secretase signalling.

Abstract Background Diabetic foot ulcers often affect tendon tissue. Consequently, the infection may spread proximally along the tendon, leading to amputation or even the death of patients. Exposed, degenerated, and necrotic tendons are key factors affecting the healing of diabetic foot ulcers. The effective treatment of the tendon involvement may positively affect the prognosis. In clinical practice, treatment with Shengji ointment and bromelain induces islands of granulation tissue on the denatured tendon surface, which gradually grows and merges. Ideally, the exposed tendon is covered entirely by granulation tissue. This trial aims to assess the effect of a combined treatment regime of Shengji ointment, which has been shown to regenerate muscle tissue and pineapple protease in preventing the loss of function and amputation caused by tendon necrosis. This trial will provide high-quality evidence for the effectiveness of this combination in healing diabetic ulcers with tendon necrosis. Methods The sample size will be 180 patients who will be randomly assigned 1:1 to a treatment group (90 patients) using Shengji ointment combined with bromelain and a control group (90 patients) using hydrocolloid dressing. Both groups will continue their conventional treatments, such as blood glucose and blood pressure medication, lipid regulation, antiplatelets, and others. The primary outcome will be the wound coverage with granulation tissue. Secondary outcomes will be the wound healing rate, amputation extent (where needed), time to granulation, and the Maryland Foot Score. Other efficacy outcomes will be the time to debridement of necrotic tendon tissue and granulation tissue score. Discussion This study will treat patients with diabetic foot ulcers with exposed, degenerated, and necrotic tendons with Shengji ointment and bromelain. The trial aims to promote regeneration and healing, to preserve the limb and its function, and to develop a comprehensive and effective protocol that can be applied to promote the healing of exposed tendons in diabetic foot wounds. Trial registration ChiCTR2000039327 ; date of registration: 2020-10-23.

The metallurgical tasks at different stages of converter blowing are different. The process operation and physical properties of molten baths are also different. It is very important to determine the flow characteristics of molten baths at different blowing stages for optimizing process operation. In this paper, a three-dimensional, full-scale model of a 120 t top–bottom combined blowing converter is established. Based on the parameters of oxygen lance position, bath temperature, bottom blowing intensity, and bath physical properties at different blowing stages, the changes in bath flow field, turbulent kinetic energy, impact depth, impact area, and wall shear force with blowing process are studied. The results show that at the initial stage of blowing, the lance position is high, the impact depth of the molten bath is 0.23 m, the impact area is 5.06 m2, the dead zone area of the longitudinal section is 0.40 m2, and the high-speed zone area is 2.73 m2. As the blowing time increases, the lance position decreases, the impact depth of the molten bath increases, the impact area decreases, and the internal velocity of the molten bath increases. In the later stage of tuyere blowing, the lance level decreases to its lowest, the impact depth increases to 0.42 m, the impact area decreases to 2.83 m2, the dead zone area of longitudinal section decreases to 0.18 m2, and the high-speed area increases to 3.34 m2. The area with the highest wall shear stress is situated within the gas–slag–metal three-phase region, where the lining experiences the most significant erosion. The fluctuation in the slag–metal interface is small, and the wall shear force is 2.80 Pa at the initial stage of blowing. From the early to late stages of blowing, the lance position decreases, the fluctuation range of the slag–metal interface increases, and the erosion of the furnace lining increases. In the later stage of blowing, the maximum wall shear force is 3.81 Pa.

Mosses are an integral component in the tufa sedimentary landscape. In this study, we investigated the use of the porous moss-tufa structure as a filtration system for removing potentially toxic elements (PTEs) from water samples. Three species of mosses that commonly grow on tufa were selected, and the PTEs filtered by the moss-tufa system were identified by inductively coupled plasma mass spectrometry. The bioconcentration factor (BCF) of mosses was calculated to compare the enrichment effects of different mosses on PTEs. Likewise, the level of PTEs flowing through the moss-tufa system was measured, and the water quality removal rate (C) was calculated accordingly. The results revealed that the moss-tufa system was mainly composed of Fissidens grandifrons Brid., Hydrogonium dixonianum P. C. Chen, and Cratoneuron filicinum (Hedw.) Spruce var. filicinum. Among these, Fissidens grandifrons Brid. reported the highest retention capacity for PTEs. Collectively, the moss-tufa filtration system displayed a strong retention capacity and removal rate of Mn, Pb, and Ni from the water sample. The removal of PTEs by the moss-tufa system was mainly based on the enrichment of mosses and the adsorption-retention ability of tufa. In conclusion, the moss-tufa micro-filtration system displayed the effective removal of PTEs from water samples and could be applied to control the levels of toxic elements in karst water bodies.

BackgroundBreast cancer patients face significant psychological challenges, including difficulties in accepting the diagnosis, treatment, and long-term impact of the disease. Acceptance and Commitment Therapy (ACT) has shown promise in enhancing acceptance and psychological flexibility in various populations. This study aims to investigate the effectiveness of ACT in promoting disease acceptance among breast cancer patients through a randomized controlled trial.MethodsThis study will recruit 90 breast cancer patients and randomly allocate them to an ACT intervention or control group. The ACT intervention, focusing on acceptance, mindfulness, value clarification, and committed action, will be delivered over 4 weeks. Meanwhile, the control group will receive standard care with non-therapeutic intervention. The study's primary outcome is disease acceptance, while secondary outcomes include depression, anxiety, social support, quality of life (QoL), and psychological inflexibility. Data will be collected at three points: baseline, post-intervention, and three-month follow-up. Statistical analysis will compare outcomes between groups to evaluate the effectiveness and mechanism of this intervention using covariance and mediation analysis.DiscussionThis study evaluates the effectiveness of ACT in promoting disease acceptance among breast cancer patients. It hypothesizes that the ACT group will show higher disease acceptance and improvements in social support, QoL, and psychological flexibility compared to the control group. The findings will contribute to research on psychological interventions and demonstrate ACT's effectiveness in enhancing disease acceptance.Trial registrationThe research project is registered in the ClinicalTrials (NCT05327153).

Cerebrotendinous xanthomatosis (CTX), an autosomal recessive disorder characterized by high levels of cholestanol in the blood and accumulation of cholestanol in multiple tissues, especially the brain, often presents in parkinsonism. However, it remains unknown whether cholestanol plays a role in the pathogenesis of sporadic Parkinson’s disease (PD). Here, we show that the levels of serum cholestanol in patients with sporadic PD are higher than those in control participants. Cholestanol activates the protease asparagine endopeptidase (AEP) and induces the fragmentation of α-synuclein (α-syn) and facilitates its aggregation. Furthermore, cholestanol promotes the spreading of α-syn pathology in a mouse model induced by intrastriatal injection of α-syn fibrils. KO of AEP or administration of an AEP inhibitor ameliorates α-syn pathology, degeneration of the nigrostriatal dopaminergic pathway, and PD-like motor symptoms. These results not only indicate that cholestanol contributes to the aggregation and spreading of α-syn by activating AEP but also reveal an opportunity for treating PD with AEP inhibitors.

Summary: The molecular mechanisms that trigger Tau aggregation in Alzheimer’s disease (AD) remain elusive. Fungi, especially Saccharomyces cerevisiae (S. cerevisiae), can be found in brain samples from patients with AD. Here, we show that the yeast protein Ure2p from S. cerevisiae interacts with Tau and facilitates its aggregation. The Ure2p-seeded Tau fibrils are more potent in seeding Tau and causing neurotoxicity in vitro. When injected into the hippocampus of Tau P301S transgenic mice, the Ure2p-seeded Tau fibrils show enhanced seeding activity compared with pure Tau fibrils. Strikingly, intracranial injection of Ure2p fibrils promotes the aggregation of Tau and cognitive impairment in Tau P301S mice. Furthermore, intranasal infection of S. cerevisiae in the nasal cavity of Tau P301S mice accelerates the aggregation of Tau. Together, these observations indicate that the yeast protein Ure2p initiates Tau pathology. Our results provide a conceptual advance that non-mammalian prions may cross-seed mammalian prion-like proteins.

Alzheimer’s disease (AD) is the primary cause of dementia and is anticipated to impose a substantial economic burden in the future. Over a significant period, the widely accepted amyloid cascade hypothesis has guided research efforts, and the recent FDA approval of an anti- amyloid-beta (Aβ) protofibrils antibody, believed to decelerate AD progression, has further solidified its significance. However, the excessive emphasis placed on the amyloid cascade hypothesis has overshadowed the physiological nature of Aβ and tau proteins within axons. Axons, specialized neuronal structures, sustain damage during the early stages of AD, exerting a pivotal influence on disease progression. In this review, we present a comprehensive summary of the relationship between axonal damage and AD pathology, amalgamating the physiological roles of Aβ and tau proteins, along with the impact of AD risk genes such as APOE and TREM2. Furthermore, we underscore the exceptional significance of axonal damage in the context of AD.

Atherosclerosis is an important cause of cerebrovascular and cardiovascular disease (CVD). Lipid infiltration, inflammation, and altered vascular stress are the critical mechanisms that cause atherosclerotic plaque formation. The hallmarks of the progression of atherosclerosis include plaque ulceration, rupture, neovascularization, and intraplaque hemorrhage, all of which are closely associated with the occurrence of CVD. Assessing the severity of atherosclerosis and plaque vulnerability is crucial for the prevention and treatment of CVD. Integrating imaging techniques for evaluating the characteristics of atherosclerotic plaques with computer simulations yields insights into plaque inflammation levels, spatial morphology, and intravascular stress distribution, resulting in a more realistic and accurate estimation of plaque state. Here, we review the characteristics and advancing techniques used to analyze intracranial and extracranial atherosclerotic plaques to provide a comprehensive understanding of atheroma.

Context Ellagic acid (EA) is a phenolic constituent in certain fruits and has largely been recognized for its role as an antioxidant compound.Objective To evaluate the effect of EA on beryllium sulphate-induced splenic toxicity in rats.Materials and methods Male Sprague-Dawley rats were divided into four groups. The first group was used as control. Group 2 was exposed to BeSO4 (12 mg/kg, b.w.). Groups 3 and 4 were treated with EA (100 and 300 mg/kg, b.w.) daily for 6 weeks after exposing to BeSO4 (12 mg/kg, b.w.). Various biochemical and molecular biomarkers were assessed in blood and spleen.Results BeSO4-intoxicated rats showed significant higher WBC (6.74 ± 0.20 × 109/L vs. 11.02 ± 1.31 × 109/L, p

The H13 steel was formed by selective laser melting process, and the as-deposited samples were cryogenically treated at -196 °C and tempered at a low temperature of 200 °C, respectively. The microstructure and properties of the samples under cryogenic treatment and low temperature tempering were analyzed. The results show that the grain structure of the as-deposited H13 steel parts is very fine and accompanied by 19.1% retained austenite at the grain boundaries, which is due to the very fast laser melting and cooling rate. The purpose of cryogenic treatment and low temperature tempering is to retain the desired misconstruction characteristics and to eliminate retained austenite and stresses accumulated during rapid solidification and cryogenic treatment thermal history. After the post-treatment, it was found that many fine carbides were precipitated in the gaps of the martensitic laths, and the retained austenite content was reduced to 5%. Through the tensile test, it was found that the tensile strength of the cryogenically treated and low temperature tempering samples reached 1917.3 MPa, and the elongation after fracture reached 19.3%, which was 4% higher than the deposited tensile strength, and the elongation after fracture increased 64%. It can be seen that the cryogenic treated and low temperature tempered samples obtained excellent mechanical properties.

Abstract Background Group 2 innate lymphoid cells (ILC2s) are the most dominant ILCs in heart tissue, and sex-related differences exist in mouse lung ILC2 phenotypes and functions; however, it is still unclear whether there are sex differences in heart ILC2s. Results Compared with age-matched wild-type (WT) male mice, 8-week-old but not 3-week-old WT female mice harbored an obviously greater percentage and number of heart ILC2s in homeostasis. However, the percentage of killer-cell lectin-like receptor G1 (Klrg1)− ILC2s was higher, but the Klrg1+ ILC2s were lower in female mice than in male mice in both heart tissues of 3- and 8-week-old mice. Eight-week-old Rag2 −/− mice also showed sex differences similar to those of age-matched WT mice. Regarding surface marker expression, compared to age-matched male mice, WT female mice showed higher expression of CD90.2 and Ki67 and lower expression of Klrg1 and Sca-1 in heart total ILC2s. There was no sex difference in IL-4 and IL-5 secretion by male and female mouse heart ILC2s. Increased IL-33 mRNA levels within the heart tissues were also found in female mice compared with male mice. By reanalyzing published single-cell RNA sequencing data, we found 2 differentially expressed genes between female and male mouse heart ILC2s. Gene set variation analysis revealed that the glycine, serine and threonine metabolism pathway was upregulated in female heart ILC2s. Subcluster analysis revealed that one cluster of heart ILC2s with relatively lower expression of Semaphorin 4a and thioredoxin interacting protein but higher expression of hypoxia-inducible lipid droplet-associated. Conclusions These results revealed greater numbers of ILC2s, higher expression of CD90.2, reduced Klrg1 and Sca-1 expression in the hearts of female mice than in male mice and no sex difference in IL-4 and IL-5 production in male and female mouse heart ILC2s. These sex differences in heart ILC2s might be due to the heterogeneity of IL-33 within the heart tissue.

Abstract Astaxanthin is a type of carotenoid widely used as powerful antioxidant and colourant in aquaculture and the poultry industry. Production of astaxanthin by yeast Xanthophyllomyces dendrorhous has attracted increasing attention due to high cell density and low requirements of water and land compared to photoautotrophic algae. Currently, the regulatory mechanisms of astaxanthin synthesis in X. dendrorhous remain obscure. In this study, we obtained a yellow X. dendrorhous mutant by Atmospheric and Room Temperature Plasma (ARTP) mutagenesis and sequenced its genome. We then identified a putative GATA transcription factor, white collar 2 (XdWC2), from the comparative genome data and verified that disruption of the XdWC2 gene resulted in a similar carotenoid profile to that of the ARTP mutant. Furthermore, transcriptomic analysis and yeast one‐hybrid (Y1H) assay showed that XdWC2 regulated the expression of phytoene desaturase gene CrtI and astaxanthin synthase gene CrtS. The yeast two‐hybrid (Y2H) assay demonstrated that XdWC2 interacted with white collar 1 (XdWC1) forming a heterodimer WC complex (WCC) to regulate the expression of CrtI and CrtS. Increase of the transcriptional levels of XdWC2 or CrtS in the wild‐type strain did not largely modify the carotenoid profile, indicating translational and/or post‐translational regulations involved in the biosynthesis of astaxanthin. Overexpression of CrtI in both the wild‐type strain and the XdWC2‐disrupted strain apparently improved the production of monocyclic carotenoid 3‐hydroxy‐3′, 4′‐didehydro‐β, ψ‐carotene‐4‐one (HDCO) rather than β‐carotene and astaxanthin. The regulation of carotenoid biosynthesis by XdWC2 presented here provides the foundation for further understanding the global regulation of astaxanthin biosynthesis and guides the construction of astaxanthin over‐producing strains.

Abstract Glomerella leaf spot (GLS) is a devastating fungal disease that damages the leaves and fruits and reduces tree vigor of apple (Malus domestica). The pathogen infection mechanism, however, remains elusive. Histone-modifying enzymes, which regulate eukaryotic chromatin conformation and gene expression, are key epigenetic factors controlling fungal development, virulence, and secondary metabolism. To dissect the epigenetic regulation of GLS pathogenesis, we characterized a histone deacetylase gene Cfhos2 in Colletotrichum fructicola, the causing agent of GLS. Cfhos2 deletion mutants were mildly reduced in vegetative growth rate, but almost lost pathogenicity on apple leaves. Cfhos2 deletion mutants induced strong plant defense responses manifested by epidermal cell browning, granulation, and distortion of pathogen invasive hyphae. The mutants also showed defect in appressorial development on cellophane, but not on parafilm or on apple leaf surface, suggesting that the defect in appressorial development is surface-dependent. RNA-seq based transcriptome analysis highlighted that Cfhos2 regulates secondary metabolism-related virulence genes during infection. Moreover, the expression of an apple defense-related F-box protein was strongly induced by infection with Cfhos2 deletion mutants. Taken together, we demonstrate that Cfhos2 is a key epigenetic factor regulating appressorium development, virulence gene expression, and GLS pathogenesis in C. fructicola. The results provide important information for understanding the virulence mechanisms of C. fructicola.

Atherosclerosis (AS) is a chronic inflammatory reaction that primarily affects large and medium-sized arteries. It is a major cause of cardiovascular disease and peripheral arterial occlusive disease. The pathogenesis of AS involves specific structural and functional alterations in various populations of vascular cells at different stages of the disease. The immune response is involved throughout the entire developmental stage of AS, and targeting immune cells presents a promising avenue for its treatment. Over the past 2 decades, studies have shown that gut microbiota (GM) and its metabolites, such as trimethylamine-N-oxide, have a significant impact on the progression of AS. Interestingly, it has also been reported that there are complex mechanisms of action between GM and their metabolites, immune responses, and natural products that can have an impact on AS. GM and its metabolites regulate the functional expression of immune cells and have potential impacts on AS. Natural products have a wide range of health properties, and researchers are increasingly focusing on their role in AS. Now, there is compelling evidence that natural products provide an alternative approach to improving immune function in the AS microenvironment by modulating the GM. Natural product metabolites such as resveratrol, berberine, curcumin, and quercetin may improve the intestinal microenvironment by modulating the relative abundance of GM, which in turn influences the accumulation of GM metabolites. Natural products can delay the progression of AS by regulating the metabolism of GM, inhibiting the migration of monocytes and macrophages, promoting the polarization of the M2 phenotype of macrophages, down-regulating the level of inflammatory factors, regulating the balance of Treg/Th17, and inhibiting the formation of foam cells. Based on the above, we describe recent advances in the use of natural products that target GM and immune cells crosstalk to treat AS, which may bring some insights to guide the treatment of AS.

Adipokines are biologically active factors secreted by adipose tissue that act on local and distant tissues through autocrine, paracrine, and endocrine mechanisms. However, adipokines are believed to be involved in an increased risk of atherosclerosis. Classical adipokines include leptin, adiponectin, and ceramide, while newly identified adipokines include visceral adipose tissue-derived serpin, omentin, and asprosin. New evidence suggests that adipokines can play an essential role in atherosclerosis progression and regression. Here, we summarize the complex roles of various adipokines in atherosclerosis lesions. Representative protective adipokines include adiponectin and neuregulin 4; deteriorating adipokines include leptin, resistin, thrombospondin-1, and C1q/tumor necrosis factor-related protein 5; and adipokines with dual protective and deteriorating effects include C1q/tumor necrosis factor-related protein 1 and C1q/tumor necrosis factor-related protein 3; and adipose tissue-derived bioactive materials include sphingosine-1-phosphate, ceramide, and adipose tissue-derived exosomes. However, the role of a newly discovered adipokine, asprosin, in atherosclerosis remains unclear. This article reviews progress in the research on the effects of adipokines in atherosclerosis and how they may be regulated to halt its progression.

Toxic arsenic (As) and cadmium (Cd) pollution threatens organisms and humans in coastal ecosystems, but their biomagnification in marine systems remains under debate. This study investigated the levels and trophodynamic features of As and Cd, and potential human health risks of marine fauna within continuous trophic levels (TLs) from the Yellow River Estuary, China, and adjacent sea (YRE), as indicated by nitrogen stable isotope analyses. Individual faunal samples were grouped into continuous TL ranges and analyzed separately in fish and invertebrates. As and Cd concentrations varied significantly between fish and invertebrates within different TL ranges. Trophic magnification factors (TMFs) also revealed different bioaccumulation features of As and Cd with increasing TL via trophic transfer in the food chain. Although As and Cd were biodiluted in marine organisms overall from the YRE, they were biomagnified in invertebrates through trophic transfer, with TMFs of 1.91 and 1.70, respectively. As and Cd biomagnification in invertebrates was hidden by overall evaluation of toxic element bioaccumulation in marine fauna. Crustacea accounted for 55% of the invertebrate taxa in the study, which could have an important role in the biomagnification of these two elements in invertebrates as a whole. Given that marine organisms occupying higher trophic positions at higher risk of As and Cd biomagnification might be underestimated in the analyses of mean values at the species level, the target hazard quotient through fish and invertebrate consumption was calculated separately based on individuals distributed within continuous TL ranges corresponding to element concentrations, and the health risks to adults and children were evaluated. Results indicated that, in the study area, the non-carcinogenic health risk associated with As and Cd from consuming invertebrates was higher than that from fish, especially for children. In addition, estimation of As carcinogenic risk (>10–4 in both invertebrates and fish) also indicated that ingestion of seafood from the YRE with suggested meal size would cause cancer risk with long-term consumption, especially of invertebrates. Therefore, it is necessary to monitor toxic metal concentrations in aquatic organisms to devise regulations around seafood consumption by humans.

Neurodegenerative diseases are prevalent and currently incurable conditions that progressively impair cognitive, behavioral, and psychiatric functions of the central or peripheral nervous system. Fibrinogen, a macromolecular glycoprotein, plays a crucial role in the inflammatory response and tissue repair in the human body and interacts with various nervous system cells due to its unique molecular structure. Accumulating evidence suggests that fibrinogen deposits in the brains of patients with neurodegenerative diseases. By regulating pathophysiological mechanisms and signaling pathways, fibrinogen can exacerbate the neuro-pathological features of neurodegenerative diseases, while depletion of fibrinogen contributes to the amelioration of cognitive function impairment in patients. This review comprehensively summarizes the molecular mechanisms and biological functions of fibrinogen in central nervous system cells and neurodegenerative diseases, including Alzheimer’s disease, Multiple Sclerosis, Parkinson’s disease, Vascular dementia, Huntington’s disease, and Amyotrophic Lateral Sclerosis. Additionally, we discuss the potential of fibrinogen-related treatments in the management of neurodegenerative disorders.

Shift work may adversely affect individuals’ health, thus, the current study aimed to investigate the association between shift work and health outcomes in the general population. A total of 41,061 participants were included in this online cross-sectional survey, among which 9612 (23.4%) individuals engaged in shift work and 31,449 (76.6%) individuals engaged in non-shift work. Multiple logistic regression analyses were conducted to explore the association between shift work and health outcomes (psychiatric disorders, mental health symptoms, and physical disorders). In addition, associations between the duration (≤1 year, 1–3 years, 3–5 years, 5–10 years, ≥10 years) and frequency of shift work (p < 0.001), mental health symptoms (OR = 1.76, 95% CI = 1.68–1.85, p < 0.001), and physical disorders (OR = 1.48, 95% CI = 1.39–1.57, p < 0.001). In addition, inverted U-shaped associations were observed between the duration of shift work and health outcomes. These results indicated that shift work was closely related to potential links with poor health outcomes. The findings highlighted the importance of paying attention to the health conditions of shift workers and the necessity of implementing comprehensive protective measures for shift workers to reduce the impact of shift work.

BDNS and TrkB are involved in bone fracture healing by inhibiting AEP. Here the authors show that a TrkB agonist prodrug can inhibit AEP and promote bone formation in osteoporotic mice.

Aims: The objectives of this study were to identify clinical predictors of the Traditional Chinese medicine (TCM) clinical index for diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, develop a clinical prediction model, and construct a nomogram. Methods: We collected the TCM clinical index from 3590 T2DM recruited at the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine from January 2019 to October 2020. The participants were randomly assigned to either the training group (n = 3297) or the validation group (n = 1426). TCM symptoms and tongue characteristics were used to assess the risk of developing DPN in T2DM patients. Through 5-fold cross-validation in the training group, the least absolute shrinkage and selection operator (LASSO) regression analysis method was used to optimize variable selection. In addition, using multifactor logistic regression analysis, a predictive model and nomogram were developed. Results: A total of eight independent predictors were found to be associated with the DPN in multivariate logistic regression analyses: advanced age of grading (odds ratio/OR 1.575), smoke (OR 2.815), insomnia (OR 0.557), sweating (OR 0.535), loose teeth (OR 1.713), dry skin (OR 1.831), purple tongue (OR 2.278). And dark red tongue (OR 0.139). The model was constructed using these eight predictor's medium discriminative capabilities. The area under the curve (AUC) of the training set is 0.727, and the AUC of the validation set is 0.744 on the ROC curve. The calibration plot revealed that the model's goodness-of-fit is satisfactory. Conclusions: We established a TCM prediction model for DPN in patients with T2DM based on the TCM clinical index.

BackgroundFunctional near-infrared spectroscopy (fNIRS) identifies neurophysiological differences between psychiatric disorders by assessing cortical hemodynamic function. Few trials have studied differences in brain functional activity between first-episode medication-naïve depression patients (FMD) and recurrent major depression (RMD). We aimed to determine the differences between FMD and RMD in oxygenated hemoglobin concentration ([oxy-Hb]), and to investigate the correlation between frontotemporal cortex activation and clinical symptoms.MethodsWe recruited 40 patients with FMD, 53 with RMD, and 38 healthy controls (HCs) from May 2021 to April 2022. Symptom severity was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and the Hamilton Anxiety Rating Scale (HAM-A). A 52-channel fNIRS measured changes in [oxy-Hb] during VFT performance.ResultsBoth patient groups performed poorly during the VFT task compared with HC (FDR p < 0.05), but there was no significant difference between the two patient groups. Analysis of variance showed that mean [oxy-Hb] activation was lower in both the frontal and temporal lobes in the MDD group compared with HCs (FDR p < 0.05). Additionally, patients with RMD had a significantly lower hemodynamic response in the right dorsolateral prefrontal cortex (DLPFC) and dorsal frontal pole cortex (DFPC) than patients with FMD (FDR p < 0.05). No significant correlation was found between changes in mean [oxy-Hb] and either medical history or clinical symptoms (FDR p < 0.05).ConclusionThe presence of different neurofunctional activity in some of the same brain regions in FMD and RMD patients implied a link between the level of complexity activation in frontal regions and the stage of MDD. Cognitive impairment may already be present at the beginning of an MDD episode.Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR2100043432.

Abstract Lysophosphatidic acid (LPA) is a common glycerol phospholipid and an important extracellular signaling molecule. LPA binds to its receptors and mediates a variety of biological effects, including the pathophysiological process underlying ischemic brain damage and traumatic brain injury. However, the molecular mechanisms mediating the pathological role of LPA are not clear. Here, we found that LPA activates cyclin-dependent kinase 5 (CDK5). CDK5 phosphorylates tau, which leads to neuronal cell death. Inhibition of LPA production or blocking its receptors reduced the abnormal activation of CDK5 and phosphorylation of tau, thus reversing the death of neurons. Our data indicate that the LPA-CDK5-Tau pathway plays an important role in the pathophysiological process after ischemic stroke. Inhibiting the LPA pathway may be a potential therapeutic target for treating ischemic brain injury.

Abstract Background Docosahexaenoic acid (DHA) supplementation is beneficial for several chronic diseases; however, its effect on immune regulation is still debated. Given the prevalence of cytomegalovirus (CMV) infection and because natural killer (NK) cells are a component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility to murine (M) CMV infection and the NK cell effector response to MCMV infection. Results Male C57BL/6 mice fed a control or DHA-enriched diet for 3 weeks were infected with MCMV and sacrificed at the indicated time points postinfection. Compared with control mice, DHA-fed mice had higher liver and spleen viral loads at day 7 postinfection, but final MCMV clearance was not affected. The total numbers of NK cells and their terminal mature cell subset (KLRG1+ and Ly49H+ NK cells) were reduced compared with those in control mice at day 7 postinfection but not day 21. DHA feeding resulted in higher IFN-γ and granzyme B expression in splenic NK cells at day 7 postinfection. A mechanistic analysis showed that the splenic NK cells of DHA-fed mice had enhanced glucose uptake, increased CD71 and CD98 expression, and higher mitochondrial mass than control mice. In addition, DHA-fed mice showed reductions in the total numbers and activation levels of CD4+ and CD8+ T cells. Conclusions These results suggest that DHA supplementation represses the early response to CMV infection but preserves NK cell effector functions by improving mitochondrial activity, which may play critical roles in subsequent MCMV clearance.

Cleaning is one of the most important steps in the harvesting process, and the prolonged and high-load operation of the vibrating sieve can decrease its reliability. To uncover the structural flaws of the cleaning sieve in the crawler combine harvester and establish a foundation for quality inspection, this paper proposes a method for durability testing and analysis using vibration and strain signals. Via the modal analysis of the cleaning sieve, the most susceptible areas for fault signals are identified. Subsequently, a specialized test rig exclusively designed for the examination of the durability of the cleaning sieve is constructed. After following 96 h of uninterrupted operation, the vibration plate of the cleaning sieve sustains damage, resulting in atypical noise. A signal analysis reveals that the primary vibration signal of the cleaning sieve primarily consists of a fundamental frequency of 5 Hz, corresponding to the driving speed, as well as a frequency doubling signal of 50 Hz. After the occurrence of damage, the peak amplitude of the received vibration signal increases by over 86.3%. Furthermore, the strain gauge sensor situated on the support plate of the rear sieve detects anomalous signals with frequencies exceeding 300 Hz, which are accompanied by a considerable rise in the power spectral density. This research has significant importance for enhancing the service life of the cleaning sieve and optimizing the overall machine efficiency.

Abstract Background Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Summary: The molecular mechanisms mediating the aggregation and transmission of tau in AD remain unclear. Here, we show that the actin-binding protein cofilin is cleaved by a cysteine protease asparagine endopeptidase (AEP) at N138 in the brains of patients with AD. The AEP-generated cofilin 1-138 fragment interacts with tau and promotes its aggregation. The mixed fibrils consisting of cofilin 1-138 and tau are more pathogenic to cells than pure tau fibrils. Furthermore, overexpression of cofilin 1-138 in the brain facilitates the propagation of pathological tau aggregates and promotes AD-like cognitive impairments in tau P301S mice. However, mice infected with adeno-associated viruses (AAVs) encoding an AEP-uncleavable cofilin mutant show attenuated tau pathology and cognitive impairments compared with mice injected with AAVs encoding wild-type cofilin. Together, these observations support the role of the cofilin 1-138 fragment in the aggregation and transmission of tau pathology during the onset and progression of AD.

Abstract Background Understanding the genetic structure and local adaptive evolutionary mechanisms of marine organisms is crucial for the management of biological resources. As the ecologically and commercially important small-sized shallow-sea fish, Collichthys lucidus plays a vital role in the structure and functioning of marine ecosystem processes. C. lucidus has been shown to have an obvious population structure. Therefore, it is an ideal candidate for investigating population differentiation and local adaptation under heterogeneous environmental pressure. Results A total of 184,708 high-quality single nucleotide polymorphisms (SNPs) were identified and applied to elucidate the fine-scale genetic structure and local thermal adaptation of 8 C. lucidus populations. Population structure analysis based on all SNPs indicated that the northern group and southern group of C. lucidus have a strong differentiation. Moreover, 314 SNPs were found to be significantly associated with temperature variation, and annotations of genes containing temperature-related SNPs suggested that genes were involved in material (protein, lipid, and carbohydrate) metabolism and immune responses. Conclusion The high genetic differentiation of 8 C. lucidus populations may have been caused by long-term geographic isolation during the glacial period. Moreover, we suspected that variation in these genes associated with material (protein, lipid, and carbohydrate) metabolism and immune responses was critical for adaptation to spatially heterogeneous temperatures in natural C. lucidus populations. In conclusion, this study could help us determine how C. lucidus populations will respond to future ocean temperature rising.