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Ovarian cancer (OC) is a lethal disease occurring in women worldwide. Due to the lack of obvious clinical symptoms and sensitivity biomarkers, OC patients are often diagnosed in advanced stages and suffer a poor prognosis. Circulating tumor cells (CTCs), released from tumor sites into the peripheral blood, have been recognized as promising biomarkers in cancer prognosis, treatment monitoring, and metastasis diagnosis. However, the number of CTCs in peripheral blood is low, and it is a technical challenge to isolate, enrich, and identify CTCs from the blood samples of patients. This work develops a simple, effective, and inexpensive strategy to capture and identify CTCs from OC blood samples using the folic acid (FA) and antifouling-hydrogel-modified fluorescent-magnetic nanoparticles. The hydrogel showed a good antifouling property against peripheral blood mononuclear cells (PBMCs). The FA was coupled to the hydrogel surface as the targeting molecule for the CTC isolation, held a good capture efficiency for SK-OV-3 cells (95.58%), and successfully isolated 2–12 CTCs from 10 OC patients’ blood samples. The FA-modified fluorescent-magnetic nanoparticles were successfully used for the capture and direct identification of CTCs from the blood samples of OC patients.

In order to obtain the rotor position information and speed information of permanent magnet synchronous motor with magnetic resistance rotary transformer，the system of spin decoding is designed.The design is based on decoding chip AD2S1205.Firstly, the working principle of the magnetic resistance rotary transformer is analyzed.Then the hardware circuit of the rotary decoding system is designed, and the rotor position information and motor speed information are calculated by C code.Finally, single chip microcomputer and motor drive plate are used to drive motor rotation.The rotor position information and motor speed information are sent to dSPACE in real time through the CAN bus.The experimental results show that the system can effectively solve the motor rotor position information and the motor speed information.

The article presents a study that demonstrates how the nitrogen nutrition influences the community succession and selection of Pseudo-nitzschia species, alexandrium catenella, and dinophysis acuminate found in the west coast of South Africa. It notes the use of Seabird Electronics Seacat CTD with Weststar Fluorometer in establishing the vertical profiles of temperature and fluorescence of the sample species and of statistical analysis in comparing the data of the samples from 2006 and 2007. It presents the standard nutrient uptake incubations, cell concentrations of the species, and the temperature control plots. It also reveals the extreme variable structure of the phytoplankton community due to the upwelling and other oceanographic condition.

Ba2Co9O14 is a charge-ordered Co2+/3+ cobaltite that consists of building blocks of Cdl2-type Co2+/3+O6/3 layers, face-shared Co3+3O12 octahedral trimers, and corner-sharing Co2+04 tetrahedra. The Co-L2,3 x-ray absorption spectroscopy spectrum at room temperature indicates a high and a low spin state for Co2+ and Co3+ ions, respectively. Measurements of high-temperature resistivity and thermoelectric power revealed an insulator-to-insulator phase transition at Tt = 570 K, above which the inverse magnetic susceptibility X-1(T) deviates from the Curie-Weiss law. By using a combination of soft x-ray absorption spectroscopy at the O-K edge and high-resolution synchrotron x-ray powder diffraction measurements on crossing Tt, we have successfully determined the origin of this phase transition as a low-to-higher spin-state transition of Co3+ ions within the face-shared Co3O12 octahedral trimers in Ba2Co9O14. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), which is distinguished by the accumulation of fat in the liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a renowned traditional Chinese medicine (TCM) blend extensively utilized in China to address liver disease, has demonstrated its efficacy in reducing lipid buildup and effectively combating inflammation. Hence, the primary objective of this research is to examine the impacts and possible mechanisms of CSP on NASH through assessments of liver histopathology, lipidomic analysis, and gene expression. To induce a mouse model of NASH, we employed a diet which deficient in methionine and choline, known as methionine-choline deficient (MCD) diet. Initially, we examined the impact of administering CSP to NASH mice by assessing the levels of serum and liver indicators. We found that CSP was able to reduce lipid buildup and inflammation in mice. In addition, a total of 1009 genes exhibited enrichment in both the autophagy and ferroptosis pathways. The liver protein levels of Adenosine monophosphate-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR)-mediated autophagy and ferroptosis markers, such as p-AMPK α /AMPK α , p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 (Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), were restored by CSP. Furthermore, our findings indicated that the suppression of autophagy had a repressive impact on the occurrence of ferroptosis in the mouse model, indicating that autophagy activation likely plays a role in mediating ferroptosis in NASH., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Zheng Liang et al.)

Nonalcoholic steatohepatitis (NASH) is a form of chronic liver disease that is characterized by liver inflammation and steatosis, with possible progression to fibrosis. Currently, no drugs have been approved for the treatment of NASH. In this study, we isolated a polysaccharide from Atractylodes lancea rhizome (AP) and established a methionine- and choline-deficient (MCD) diet -induced NASH mouse model to investigate the preventive effect and potential mechanism of AP on NASH. The results showed that AP effectively reduced liver lipid accumulation and inflammation and reduced autophagy and ferroptosis in hepatocytes, thereby preventing the development of NASH. These findings suggest that AP may be a promising natural candidate for the treatment of NASH.

Leonurine is a natural product unique to the Lamiaceae plant Leonurus japonicus Houtt. , and it has attracted attention due to its anti-oxidative stress, anti-apoptosis, anti-fibrosis, and metabolic regulation properties. Also, it plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms, but its mechanism of action remains to be elucidated. Therefore, this study aims to preliminarily explore the mechanisms of action of leonurine in NAFLD. Mice were randomly divided into four groups: the normal control (NC) group, the Model (M) group, the leonurine treatment (LH) group, and the fenofibrate treatment (FB) group. The NAFLD model was induced by a high-fat high-sugar diet (HFHSD) for 12 weeks, and liver pathological changes and biochemical indices were observed after 12 weeks. Transcriptomic analysis results indicated that leonurine intervention reversed the high-fat high-sugar diet-induced changes in lipid metabolism-related genes such as stearoyl-CoA desaturase 1 ( Scd1 ), Spermine Synthase ( Sms ), AP-1 Transcription Factor Subunit ( Fos ), Oxysterol Binding Protein Like 5 ( Osbpl5 ), and FK506 binding protein 5 ( Fkbp5 ) in liver tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results suggest that leonurine may exert its lipid-lowering effects through the AMP-activated protein kinase (AMPK) signaling pathway. Liver lipidomic analysis showed that leonurine could alter the abundance of lipid molecules related to fatty acyl (FAs) and glycerophospholipids (GPs) such as TxB3, carnitine C12-OH, carnitine C18:1-OH, and LPC (20:3/0:0). Molecular biology experiments and molecular docking techniques verified that leonurine might improve hepatic lipid metabolism through the alpha-1A adrenergic receptor (ADRA1a)/AMPK/SCD1 axis. In summary, the present study explored the mechanism by which leonurine ameliorated NAFLD by inhibiting hepatic lipid synthesis via the ADRA1a/AMPK/SCD1 axis.

Abstract: Background: Pediatric sepsis is a common and complex syndrome characterized by a dysregulated immune response to infection. Aberrations in the renin-angiotensin system (RAS) are factors in several infections of adults. However, the precise impact of RAS dysregulation in pediatric sepsis remains unclear. Methods: Serum samples were collected from a derivation cohort (58 patients with sepsis, 14 critically ill control subjects, and 37 healthy controls) and validation cohort (50 patients with sepsis, 37 critically ill control subjects, and 46 healthy controls). Serum RAS levels on day of pediatric intensive care unit admission were determined and compared with survival status and organ dysfunction. Results: In the derivation cohort, the serum renin concentration was significantly higher in patients with sepsis (3,678 ± 4,746) than that in healthy controls (635.6 ± 199.8) ( P < 0.0001). Meanwhile, the serum angiotensin (1-7) was significantly lower in patients with sepsis (89.7 ± 59.7) compared to that in healthy controls (131.4 ± 66.4) ( P < 0.01). These trends were confirmed in a validation cohort. Nonsurvivors had higher levels of renin (8,207 ± 7,903) compared to survivors (2,433 ± 3,193) ( P = 0.0001) and lower levels of angiotensin (1-7) (60.9 ± 51.1) compared to survivors (104.0 ± 85.1) ( P < 0.05). A combination of renin, angiotensin (1-7) and procalcitonin achieved a model for diagnosis with an area under the receiver operating curve of 0.87 (95% CI: 0.81-0.92). Conclusion: Circulating renin and angiotensin (1-7) have predictive value in pediatric sepsis., Competing Interests: The authors report no conflicts of interest. The authors have no other conflicts of interest to declare., (Copyright © 2024 by the Shock Society.)

Septic shock is a life-threatening disease worldwide often associated with thrombocytopenia. Platelets play a crucial role in bridging the gap between immunity, coagulation, and endothelial cell activation, potentially influencing the course of the disease. However, there are few studies specifically evaluating the impact of thrombocytopenia on the prognosis of pediatric patients. Therefore, the study investigates effects of early thrombocytopenia in the prognosis of children with septic shock. Pediatric patients with septic shock from 2015 to 2022 were included monocentrically. Thrombocytopenia was defined as a platelet count of <100 × 10 9 /L during the first 24 hours of septic shock onset. The primary outcome was the 28-day mortality. Propensity score matching was used to pair patients with different platelet counts on admission but comparable disease severity. A total of 419 pediatric patients were included in the analysis. Patients with thrombocytopenia had higher 28-day mortality (55.5% vs. 38.7%, p  = .005) compared to patients with no thrombocytopenia. Thrombocytopenia was associated with reduced 28-PICU free days (median value, 0 vs. 13 days, p  = .003) and 28-ventilator-free (median value, 0 vs. 19 days, p  = .001) days. Among thrombocytopenia patients, those with platelet count ≤50 × 10 9 /L had a higher 28-day mortality rate (63.6% vs. 45%, p  = .02). Multiple logistic regression showed that elevated lactate (adjusted odds ratio (OR) = 1.11; 95% confidence interval (CI): 1.04-1.17; P <0.001) and white blood cell (WBC) count (OR = 0.97; 95% CI: 0.95-0.99; p  = .003) were independent risk factors for the development of thrombocytopenia. Thrombocytopenia group had increased bleeding events, blood product transfusions, and development of organ failure. In Kaplan-Meier survival estimates, survival probabilities at 28 days were greater in patients without thrombocytopenia ( p value from the log-rank test, p  = .004). There were no significant differences in the type of pathogenic microorganisms and the site of infection between patients with and without thrombocytopenia. In conclusion, thrombocytopenia within 24 hours of shock onset is associated with an increased risk of 28-day mortality in pediatric patients with septic shock.

Nonalcoholic steatohepatitis (NASH) is a critical stage in the progression of nonalcoholic fatty liver disease (NAFLD). Tanshinone IIA (TIIA) is a tanshinone extracted from Salvia miltiorrhiza; due to its powerful anti-inflammatory and antioxidant biological activities, it is commonly used for treating cardiovascular and hepatic diseases. A NASH model was established by feeding mice a methionine and choline-deficient (MCD) diet. Liver surface microblood flow scanning, biochemical examination, histopathological examination, cytokine analysis through ELISA, lipidomic analysis, transcriptomic analysis, and Western blot analysis were used to evaluate the therapeutic effect and mechanism of TIIA on NASH. The results showed that TIIA effectively reduced lipid accumulation, fibrosis, and inflammation and alleviated endoplasmic reticulum (ER) stress. Lipidomic analysis revealed that TIIA normalized liver phospholipid metabolism in NASH mice. A KEGG analysis of the transcriptome revealed that TIIA exerted its effect by regulating the PPAR signalling pathway, protein processing in the ER, and the NOD-like receptor signalling pathway. These results suggest that TIIA alleviates NASH by activating the PPARα/FGF21 axis to negatively regulate the ER stress-induced unfolded protein response (UPR).

Objective: To investigate the effect of Kaixinsan (KXS, a traditional Chinese medicine formula) for alleviating adriamycin-induced depression-like behaviors in mice bearing breast cancer xenografts and explore the pharmacological mechanism., Methods: Forty female BALB/c mice were randomized equally into control group, model group, and low- and high-dose KXS treatment groups, and in the latter 3 groups, mouse models bearing orthotopic breast cancer 4T1 cell xenografts were established and treated with adriamycin along with saline or KXS via gavage. Depression-like behaviors of the mice were assessed using open field test and elevated plus-maze test, and the changes in serum levels of depression-related factors were examined. RNA-seq analysis and transmission electron microscopy were used and ferroptosis-related factors were detected to explore the mechanisms of adriamycin-induced depression and the therapeutic mechanism of KXS. The results were verified in SH-SY5Y cells using ferroptosis inhibitor Fer-1 as the positive control., Results: KXS significantly alleviated depression-like behaviors and depression-related serological changes induced by adriamycin in the mouse models. RNA-seq results suggested that KXS alleviated chemotherapy-induced depression by regulating oxidative stress, lipid metabolism and iron ion binding in the prefrontal cortex. Pathological analysis and detection of ferroptosis-related factors showed that KXS significantly reduced ferroptosis in the prefrontal cortex of adriamycin-treated mice. In SH-SY5Y cells, both KXS-medicated serum and the ferroptosis inhibitor were capable of attenuating adriamycin-induced cell ferroptosis., Conclusion: KXS alleviates adriamycininduced depression-like behaviors in mice by reducing ferroptosis in the prefrontal cortex of breast cancer-bearing mice.

The computer-generated hologram provides an approach to modulate the coherent wavefront and has been widely applied in holographic displays. In the actual application, holograms need to be transmitted through the network, which results in the illegal acquisition and malicious manipulation of holographic images. Therefore, it is necessary to develop a practical method to protect the content and copyright of holographic images. In this paper, we develop a high-security holographic display method based on complex amplitude modulation. In our proposed method, the complex hologram of a holographic image is decomposed into two phase-only holograms, one of which is designed as the ciphertext, and the other is regarded as the key. As a result, the holographic image can be reconstructed only when the ciphertext and the key are paired, which boosts the security of the holographic image. Meanwhile, the copyright of the holographic image is protected via a watermark that is embedded in the ciphertext in the form of a hologram. Due to the simultaneous use of encryption and watermark technology, our proposed method could transmit holographic images at a high security level, and has great potential to be applied in holographic displays in the future.

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1β, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines., Conclusion: After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes., Trial Registration: This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022., What Is Known: • Inflammation is an important secondary physiological response to TBI., What Is New: • The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Non-alcoholic fatty liver disease (NAFLD) has emerged as a burgeoning health problem worldwide, but no specific drug has been approved for its treatment. Shenling Baizhu powder (SL) is extensively used to treat NAFLD in Chinese clinical practice. However, the therapeutic components and pharmacological mechanisms of SL against NAFLD have not been thoroughly investigated., Purpose: This study aimed to investigate the pharmacological impact and molecular mechanism of SL on NAFLD., Methods: First, we established an animal model of NAFLD by high-fat diet (HFD) feeding, and evaluated the therapeutic efficacy of SL on NAFLD by physiological, biochemical, pathological, and body composition analysis. Next, the effect of SL on autophagic flow in NAFLD rats was evaluated by ultrastructure, immunofluorescence staining, and western blotting. Moreover, an integrated strategy of targeted energy metabolomics and network pharmacology was performed to characterize autophagy-related genes and explore the synergistic effects of SL active compounds. UPLC-MS/MS, molecular docking combined with in vivo and in vitro experiments were conducted to verify the key compounds and genes. Finally, a network was established among SL-herb-compound-genes-energy metabolites-NAFLD, which explains the complicated regulating mechanism of SL on NAFLD., Results: We discovered that SL decreased hepatic lipid accumulation, hepatic steatosis, and insulin resistance, and improved systemic metabolic disorders and pathological abnormalities. Subsequently, an integrated strategy of targeted energy metabolomics and network pharmacology identified quercetin, ellagic acid, kaempferol, formononetin, stigmasterol, isorhamnetin and luteolin as key compounds; catalase (CAT), AKT serine/threonine kinase 1 (AKT), nitric oxide synthase 3 (eNOS), NAD(P)H quinone dehydrogenase 1 (NQO1), heme oxygenase 1 (HO-1) and hypoxia-inducible factor 1 subunit alpha (HIF-1α) were identified as key genes; while nicotinamide adenine dinucleotide phosphate (NADP) and succinate emerged as key energy metabolites. Mechanistically, we revealed that SL may exert its anti-NAFLD effect by inducing autophagy activation and forming a comprehensive regulatory network involving key compounds, key genes, and key energy metabolites, ultimately alleviating oxidative stress, endoplasmic reticulum stress, and mitochondrial dysfunction., Conclusion: Our study demonstrated the therapeutic effect of SL in NAFLD models, and establishes a basis for the development of potential products from SL plant materials for the treatment of NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Leakage and tampering problems in collection and transmission of biomedical data have attracted much attention as these concerns instigates negative impression regarding privacy, security, and reputation of medical networks. This article presents a novel security model that establishes a threat-vector database based on the dynamic behaviours of smart healthcare systems. Then, an improved and privacy-preserved SRU network is designed that aims to alleviate fading gradient issue and enhance the learning process by reducing computational cost. Then, an intelligent federated learning algorithm is deployed to enable multiple healthcare networks to form a collaborative security model in a personalized manner without the loss of privacy. The proposed security method is both parallelizable and computationally effective since the dynamic behaviour aggregation strategy empowers the model to work collaboratively and reduce communication overhead by dynamically adjusting the number of participating clients. Additionally, the visualization of the decision process based on the explainability of features enhances the understanding of security experts by enabling them to comprehend the underlying data evidence and causal reasoning. Compared to existing methods, the proposed security method is capable of thoroughly analyzing and detecting severe security threats with high accuracy, reduce overhead and lower computation cost along with enhanced privacy of biomedical data.

Etoposide (VP16) is commonly used in the treatment of small cell lung cancer (SCLC) in clinical practice. However, severe adverse reactions such as bone marrow suppression toxicity limit its clinical application. Although several studies on VP16 liposomes were reported, no significant improvement in bone marrow suppression toxicity has been found, and there was a lack of validation of animal models for in vivo antitumor effects. Therefore, we attempted to develop a PEGylated liposomal formulation that effectively encapsulated VP16 (VP16-LPs) and evaluated its therapeutic effect and toxicity at the cellular level and in animal models. First, we optimized the preparation process of VP16-LPs using an orthogonal experimental design and further prepared them into freeze-dried powder to improve storage stability of the product. Results showed that VP16-LPs freeze-dried powder exhibited good dispersibility and stability after redispersion. In addition, compared to marketed VP16 injection, VP16-LPs exhibited sustained drug release characteristics. At the cellular level, VP16-LPs enhanced the cellular uptake of drugs and exhibited strong cytotoxic activity. In animal models, VP16-LPs could target and aggregate in tumors and exhibit a higher anti-tumor effect than VP16-injection after intravenous injection. Most importantly, hematological analysis results showed that VP16-LPs significantly alleviated the bone marrow suppression toxicity of drug. In summary, our study confirmed that PEGylated liposomes could enhance therapeutic efficacy and reduce toxicity of VP16, which demonstrated that VP16-LPs had enormous clinical application potential., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Bisphenol S (BPS), one of the substitutes for bisphenol A (BPA), is widely used in various commodities. The BPS concentrations in surface water have gradually increased in recent years, making it a predominant bisphenol analogue in the aquatic environment and raising concerns about its health and ecological effects on aquatic organisms. For this study, we conducted a 96 h acute toxicity test and a 15-day developmental exposure test to assess the adverse effects of BPS exposure in Chinese medaka ( Oryzias sinensis ), a new local aquatic animal model. The results indicate that the acute exposure of Chinese medaka embryos to BPS led to relatively low toxicity. However, developmental exposure to BPS was found to cause developmental abnormalities, such as decreased hatching rate and body length, at 15 dpf. A transcriptome analysis showed that exposure to different concentrations of bisphenol S often induced different reactions. In summary, environmental concentrations of BPS can have adverse effects on the hatching and physical development of Chinese medaka, and further attention needs to be paid to the potential toxicity of environmental BPS.

Background: Accumulating clinical evidence suggests that lung microbiome is closely linked to the progression of pulmonary diseases; however, it is still controversial which specimen type is preferred for the evaluation of lung microbiome., Methods and Results: To address this issue, we established a classical acute lung injury (ALI) mice model by intratracheal instillation of lipopolysaccharides (LPS). We found that the bacterial DNA obtained from the bronchoalveolar lavage fluid (BALF), intact lung tissue [Lung(i)], lung tissue after perfused [Lung(p)], and feces of one mouse were enough for 16S rRNA sequencing, except the BALF of mice treated with phosphate buffer saline (PBS), which might be due to the biomass of lung microbiome in the BALF were upregulated in the mice treated with LPS. Although the alpha diversity among the three specimens from lungs had minimal differences, Lung(p) had higher sample-to-sample variation compared with BALF and Lung(i). Consistently, PCoA analysis at phylum level indicated that BALF was similar to Lung(i), but not Lung(p), in the lungs of mice treated with LPS, suggesting that BALF and Lung(i) were suitable for the evaluation of lung microbiome in ALI. Importantly, Actinobacteria and Firmicutes were identified as the mostly changed phyla in the lungs and might be important factors involved in the gut-lung axis in ALI mice. Moreover, Actinobacteria and Proteobacteria might play indicative roles in the severity of lung injury., Conclusion: This study shows both Lung(i) and BALF are suitable for the evaluation of murine lung microbiome in ALI, and several bacterial phyla, such as Actinobacteria, may serve as potential biomarkers for the severity of ALI. Video Abstract., (© 2024. The Author(s).)

Background: Sepsis is a severe condition characterized by acute organ dysfunction resulting from an imbalanced host immune response to infections. Apolipoprotein H (APOH) is a critical plasma protein that plays a crucial role in regulating various biological processes. However, the precise role of APOH in the immunopathology of paediatric sepsis remains unclear., Methods: In this study, we evaluated the concentration of APOH in paediatric patients with sepsis and healthy individuals. In an experimental sepsis model of caecal ligation and puncture (CLP), the impact of APOH on survival, organ injury, and inflammation was measured. Furthermore, the anti-inflammatory effects of APOH were investigated across diverse immune cell types, encompassing peripheral blood mononuclear cells (PBMCs), peritoneal macrophages (PMs), bone marrow-derived macrophages (BMDMs), and RAW 264.7 macrophages., Results: In the pilot cohort, the relative abundance of APOH was found to be decreased in patients with sepsis (2.94 ± 0.61) compared to healthy controls (1.13 ± 0.84) (p < 0.001), non-survivors had lower levels of APOH (0.50 ± 0.37) compared to survivors (1.45 ± 0.83) (p < 0.05). In the validation cohort, the serum concentration of APOH was significantly decreased in patients with sepsis (202.0 ± 22.5 ng/ml) compared to healthy controls (409.5 ± 182.9 ng/ml) (p < 0.0001). The application of recombinant APOH protein as a therapeutic intervention significantly lowered the mortality rate, mitigated organ injury, and suppressed inflammation in mice with severe sepsis. In contrast, neutralizing APOH with an anti-APOH monoclonal antibody increased the mortality rate, exacerbated organ injury, and intensified inflammation in mice with non-severe sepsis. Intriguingly, APOH exhibited minimal effects on the bacterial burden, neutrophil, and macrophage counts in the sepsis mouse model, along with negligible effects on bacterial phagocytosis and killing during Pseudomonas aeruginosa infection in PMs, RAW 264.7 cells, and PBMCs. Mechanistic investigations in PMs and RAW 264.7 cells revealed that APOH inhibited M1 polarization in macrophages by suppressing toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signalling pathway., Conclusion: This proof-of-concept study demonstrated that APOH has a protective role in the host defense response to sepsis, highlighting the potential therapeutic value of APOH in sepsis treatment., (© 2024. The Author(s).)

Vascular morphogenesis requires a delicate gradient of Notch signaling controlled, in part, by the distribution of ligands (Dll4 and Jagged1). How Jagged1 (JAG1) expression is compartmentalized in the vascular plexus remains unclear. Here, we show that Jag1 mRNA is a direct target of zinc-finger protein 36 (ZFP36), an RNA-binding protein involved in mRNA decay that we find robustly induced by vascular endothelial growth factor (VEGF). Endothelial cells lacking ZFP36 display high levels of JAG1 and increase angiogenic sprouting in vitro. Furthermore, mice lacking Zfp36 in endothelial cells display mispatterned and increased levels of JAG1 in the developing retinal vascular plexus. Abnormal levels of JAG1 at the sprouting front alters NOTCH1 signaling, increasing the number of tip cells, a phenotype that is rescued by imposing haploinsufficiency of Jag1. Our findings reveal an important feedforward loop whereby VEGF stimulates ZFP36, consequently suppressing Jag1 to enable adequate levels of Notch signaling during sprouting angiogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Chaihu Shugan powder (CSP) plays an important role in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD) through a variety of biological mechanisms. However, whether the mechanism involves microRNA (miRNA) regulation remains unknown., Aim of the Study: To investigate the effects of CSP on the miRNA expression profile of rats with NAFLD induced by high-fat diet (HFD), and to explore the mechanism of CSP in the treatment of NAFLD., Methods: NAFLD rat models were established by an 8-week HFD. The therapeutic effects of CSP on NAFLD were evaluated by physiological, biochemical and pathological analysis and hepatic surface microcirculation perfusion test. MicroRNA sequencing was used to study the effect of CSP on the miRNA expression profile of NAFLD rats, and the target genes of differentially expressed (DE) miRNAs were predicted for further function enrichment analysis. Next, targets of CSP and NAFLD were collected by a network pharmacological approach, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were performed for the common target genes of CSP, NAFLD and DE miRNAs, and the expression levels of key genes and proteins were verified by quantitative Real-time PCR and Western blot. Finally, a network among formula-herb-compound-miRNA-target-biological processes-disease was established to explained the complex regulation mechanism of CSP on NAFLD., Results: The results showed that CSP significantly improved liver lipid accumulation, serum lipid and transaminase levels and liver surface microcirculation disturbance in HFD-induced NAFLD rats. The intervention of CSP reversed the high expression of 15 miRNAs in liver tissues induced by HFD, including miR-34a-5p, miR-146a-5p, miR-20b-5p and miR-142-3p. The results of pathway and functional enrichment analysis showed that, CSP might play an anti-NAFLD role via regulating DE miRNAs related to fatty acid metabolic process. Combined with the network pharmacological analysis, it was found that the DE miRNAs might affected the fatty acid biosynthesis pathway in the treatment of NAFLD by CSP. Molecular biology experiments have conformed the decreased the gene and protein levels of acetyl-CoA carboxylase alpha (ACACA), fatty acid synthase (FASN) and other fatty acid biosynthesis related enzymes on NAFLD rats after intervention of CSP., Conclusions: CSP can significantly reduce hepatic lipid accumulation of NAFLD rat model induced by HFD, and its mechanism may be through the action of 15 miRNAs such as miR-34a-5p, miR-146a-5p, miR-20b-5p and miR-142-3p. Reduce the gene and protein expression levels of ACACA, FASN and other fatty acid biosynthesis related enzymes, thus reducing fatty acid biosynthesis. Based on an epigenetic perspective, this study explains the key anti-NAFLD mechanism of CSP via combination of microRNA sequencing and network pharmacological analysis, providing a new reference for the modernization of traditional Chinese medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To evaluate the effects of Yifei Sanjie Pills (YFSJ) on weight, strength, pathology, glycogen and lipid contents and metabolism of skeletal muscles in tumor-bearing mice and explore the therapeutic mechanism of YFSJ for cancer-related skeletal muscle atrophy., Methods: Sixteen female ICR mice bearing intraperitoneal Lewis lung adenocarcinoma xenografts were randomized into model group and YFSJ treatment group (daily dose of 4 g/kg for 21 days, n =8), with another 8 normal mice as the normal control group. The changes in body weight and gastrocnemius muscle weight of the mice were recorded. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the drug components in YFSJ entering the blood. Enzyme-linked immunosorbent assay was used to detect serum blood glucose and insulin concentrations and inflammatory cytokine levels in the serum and gastrocnemius. RNA-seq was performed to analyze the signaling pathways involved in the pathologies of the gastrocnemius muscle, and lipid contents in the muscle were observed using Oil red O staining. Adenosine triphosphatase staining was used to assess the metabolic intensity of the gastrocnemius muscle, and inflammatory cell infiltration and P-AKT level were evaluated using immunohistochemical staining; the contents of creatine kinase, lactate dehydrogenase and myoglobin in the gastrocnemius muscle were also detected., Results: Treatment with YFSJ significantly increased skeletal muscle strength and gastrocnemius muscle weight ( P < 0.001) and reduced the levels of gastrocnemius muscle injury markers in the tumor-bearing mice ( P < 0.01). RNA-seq and LC-MS showed that YFSJ alleviated gastrocnemius muscle injury in the tumor-bearing mice possibly by improving inflammatory infiltration, insulin resistance and lipid metabolism ( P < 0.05). YFSJ lowered inflammatory cytokine levels in both the serum and gastrocnemius muscle ( P < 0.05), reduced pro-inflammatory cell infiltration, increased P-AKT level, and improved glycogen and lipid contents and metabolic levels in the gastrocnemius muscle., Conclusion: YFSJ alleviates cancer-related skeletal muscle atrophy possibly by reducing inflammatory insulin resistance.

In this paper, we propose a convolutional symmetric compressed look-up-table (CSC-LUT) method to accelerate computer-generated hologram (CGH) computation based on the Fresnel diffraction theory and LUT. The proposed method can achieve one-time high-quality fast generation of color holograms by utilizing dynamic convolution operation, which is divided three processes. Firstly, the pre-calculated data of maximum horizontal modulation factor is compressed in 1D array by coordinate symmetry. Then, the test object is resampled to satisfy convolutional translation invariance. Finally, the dynamic convolution operation is used to simplify CGH computation process rather than the point-by-point computation. Numerical simulation and optical experimental results show that our proposed method can achieve faster computation speed, higher reconstruction quality and wider application compared to conventional SC-LUT method. The further optimization method for parallel acceleration on the GPU framework can achieve real-time (>24fps) color holographic display corresponding to three perspectives of a 3D scene.

Caffeine is a metabolite derived from purine nucleotides, typically accounting for 2-5% of the dry weight of tea and 1-2% of the dry weight of coffee. In the tea and coffee plants, the main synthesis pathway of caffeine is a four-step sequence consisting of three methylation reactions and one nucleosidase reaction using xanthine as a precursor. In bacteria, caffeine degradation occurs mainly through the pathways of N-demethylation and C-8 oxidation. However, a study fully and systematically summarizing the metabolism and application of caffeine in microorganisms has not been established elsewhere. In the present study, we provide a review of the biosynthesis, microbial degradation, gene expression, and application of caffeine microbial degradation. The present review aims to further elaborate the mechanism of caffeine metabolism by microorganisms and explore the development prospects in this field.

The spatial frequency of the reconstructed image of planar computer-generated hologram(CGH) is limited by the sampling interval and the lack of thickness. To break through this limitation of planar CGH, we propose a new computer-generated volume hologram(CGVH) for full-color dynamic holographic three-dimensional(3D) display, and an iteration-free layered CGVH generation method. The proposed CGVH is equivalent to a volume hologram sampled discretely in three directions. The generation method employs the layered angular spectral diffraction to calculate the light field in the layered CGVH, and then encodes it into a CGVH. Numerical simulation results show that the CGVH can accurately reconstruct full-color 3D objects, where better imaging quality, more concentrated diffraction energy, denser reconstructed spatial frequency information, and larger viewing angle are achieved. The proposed CGVH is expected to be applied to realize dynamic modulation, wavelength multiplexing, and angle multiplexing in various optical fields in the future.

Bisphenol F (BPF) has been used in the syntheses of polymers, which are widely used in coatings, varnishes, adhesives, and other plastics. During the past decades, BPF contamination in the aquatic environment has dramatically increased due to its release from manmade products. Concerns have driven much attention to whether it may adversely impact aquatic lives or human beings. The present study performed an acute toxic exposure experiment and a 15 d developmental exposure of BPF at environmental concentrations (20, 200, and 2000 ng/L) using Chinese medaka ( Oryzias sinensis ). In the acute toxic exposure, the LC 50 of BPF to Chinese medaka is 87.90 mg/L at 96 h. Developmental exposure induced a significant increase in the frequency of larvae with abnormalities in the 2000 ng/L BPF group compared to the control group. Transcriptomic analysis of the whole larvae revealed 565 up-regulated and 493 down-regulated genes in the 2000 ng/L BPF exposure group. Analysis of gene ontology and KEGG pathways enrichments indicated endocrine disorders to be associated with BPF-induced developmental toxicity. The present results suggest that BPF is developmentally toxic at 2000 ng/L concentration in Chinese medaka and causes endocrine-related aberrations in the transcriptional network of genes.

Object detection has been widely applied in various fields with the rapid development of deep learning in recent years. However, detecting small objects is still a challenging task because of the limited information in features and the complex background. To further enhance the detection accuracy of small objects, this paper proposes an efficient single-shot detector with weight-based feature fusion (WFFA-SSD). First, a weight-based feature fusion block is designed to adaptively fuse information from several multi-scale feature maps. The feature fusion block can exploit contextual information for feature maps with large resolutions. Then, a context attention block is applied to reinforce the local region in the feature maps. Moreover, a pyramids aggregation block is applied to combine the two feature pyramids to classify and locate target objects. The experimental results demonstrate that the proposed WFFA-SSD achieves higher mean Average Precision (mAP) under the premise of ensuring real-time performance. WFFA-SSD increases the mAP of the car by 4.12% on the test set of the CARPK., (© 2023. The Author(s).)

Surface roughness is a key indicator of the quality of mechanical products, which can precisely portray the fatigue strength, wear resistance, surface hardness and other properties of the products. The convergence of current machine-learning-based surface roughness prediction methods to local minima may lead to poor model generalization or results that violate existing physical laws. Therefore, this paper combined physical knowledge with deep learning to propose a physics-informed deep learning method (PIDL) for milling surface roughness predictions under the constraints of physical laws. This method introduced physical knowledge in the input phase and training phase of deep learning. Data augmentation was performed on the limited experimental data by constructing surface roughness mechanism models with tolerable accuracy prior to training. In the training, a physically guided loss function was constructed to guide the training process of the model with physical knowledge. Considering the excellent feature extraction capability of convolutional neural networks (CNNs) and gated recurrent units (GRUs) in the spatial and temporal scales, a CNN-GRU model was adopted as the main model for milling surface roughness predictions. Meanwhile, a bi-directional gated recurrent unit and a multi-headed self-attentive mechanism were introduced to enhance data correlation. In this paper, surface roughness prediction experiments were conducted on the open-source datasets S45C and GAMHE 5.0. In comparison with the results of state-of-the-art methods, the proposed model has the highest prediction accuracy on both datasets, and the mean absolute percentage error on the test set was reduced by 3.029% on average compared to the best comparison method. Physical-model-guided machine learning prediction methods may be a future pathway for machine learning evolution.

Overactivation of cardiac fibroblasts (CFs) is one of the main causes of myocardial fibrosis (MF), and inhibition of CF activation is a crucial strategy for MF therapy. A previous study by our group demonstrated that leonurine (LE) effectively inhibits collagen synthesis and myofibroblast generation originated from CFs, and eventually mitigates the progression of MF (where miR-29a-3p is likely to be a vital mediator). However, the underlying mechanisms involved in this process remain unknown. Thus, the present study aimed to investigate the precise role of miR-29a-3p in LE-treated CFs, and to elucidate the pharmacological effects of LE on MF. Neonatal rat CFs were isolated and stimulated by angiotensin II (Ang II) to mimic the pathological process of MF in vitro. The results show that LE distinctly inhibits collagen synthesis, as well as the proliferation, differentiation and migration of CFs, all of which could be induced by Ang II. In addition, LE promotes apoptosis in CFs under Ang II stimulation. During this process, the down-regulated expressions of miR-29a-3p and p53 are partly restored by LE. Either knockdown of miR-29a-3p or inhibition of p53 by PFT-α (a p53 inhibitor) blocks the antifibrotic effect of LE. Notably, PFT-α suppresses miR-29a-3p levels in CFs under both normal and Ang II-treated conditions. Furthermore, ChIP analysis confirmed that p53 is bound to the promoter region of miR-29a-3p, and directly regulates its expression. Overall, our study demonstrates that LE upregulates p53 and miR-29a-3p expression, and subsequently inhibits CF overactivation, suggesting that the p53/miR-29a-3p axis may play a crucial role in mediating the antifibrotic effect of LE against MF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)