"Hepatic hilum area priority, liver posterior first": An optimized strategy in laparoscopic resection for type III-IV hilar cholangiocarcinoma.

BACKGROUND: In recent years, pure laparoscopic radical surgery for Bismuth-Corlette type III and IV hilar cholangiocarcinoma (HCCA) has been preliminarily explored and applied, but the surgical strategy and safety are still worthy of further improvement and attention. AIM: To summarize and share the application experience of the emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" in pure laparoscopic radical resection for patients with HCCA of Bismuth-Corlette types III and IV. METHODS: The clinical data and surgical videos of 6 patients with HCCA of Bismuth-Corlette types III and IV who underwent pure laparoscopic radical resection in our department from December 2021 to December 2023 were retrospectively analyzed. RESULTS: Among the 6 patients, 4 were males and 2 were females. The average age was 62.2 ± 11.0 years, and the median body mass index was 20.7 (19.2-24.1) kg/m2. The preoperative median total bilirubin was 57.7 (16.0-155.7) µmol/L. One patient had Bismuth-Corlette type IIIa, 4 patients had Bismuth-Corlette type IIIb, and 1 patient had Bismuth-Corlette type IV. All patients successfully underwent pure laparoscopic radical resection following the strategy of "hepatic hilum area dissection priority, liver posterior separation first". The operation time was 358.3 ± 85.0 minutes, and the intraoperative blood loss volume was 195.0 ± 108.4 mL. None of the patients received blood transfusions during the perioperative period. The median length of stay was 8.3 (7.0-10.0) days. Mild bile leakage occurred in 2 patients, and all patients were discharged without serious surgery-related complications. CONCLUSION: The emerging strategy of "hepatic hilum area dissection priority, liver posterior separation first" is safe and feasible in pure laparoscopic radical surgery for patients with HCCA of Bismuth-Corlette types III and IV. This strategy is helpful for promoting the modularization and process of pure laparoscopic radical surgery for complicated HCCA, shortens the learning curve, and is worthy of further clinical application.

Hybrid Integrated Wearable Patch for Brain EEG-fNIRS Monitoring.

Synchronous monitoring electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) have received significant attention in brain science research for their provision of more information on neuro-loop interactions. There is a need for an integrated hybrid EEG-fNIRS patch to synchronously monitor surface EEG and deep brain fNIRS signals. Here, we developed a hybrid EEG-fNIRS patch capable of acquiring high-quality, co-located EEG and fNIRS signals. This patch is wearable and provides easy cognition and emotion detection, while reducing the spatial interference and signal crosstalk by integration, which leads to high spatial-temporal correspondence and signal quality. The modular design of the EEG-fNIRS acquisition unit and optimized mechanical design enables the patch to obtain EEG and fNIRS signals at the same location and eliminates spatial interference. The EEG pre-amplifier on the electrode side effectively improves the acquisition of weak EEG signals and significantly reduces input noise to 0.9 µVrms, amplitude distortion to less than 2%, and frequency distortion to less than 1%. Detrending, motion correction algorithms, and band-pass filtering were used to remove physiological noise, baseline drift, and motion artifacts from the fNIRS signal. A high fNIRS source switching frequency configuration above 100 Hz improves crosstalk suppression between fNIRS and EEG signals. The Stroop task was carried out to verify its performance; the patch can acquire event-related potentials and hemodynamic information associated with cognition in the prefrontal area.

Surface Acoustic Wave Sensors for Wireless Temperature Measurements above 1200 Degree Celsius.

High-temperature wireless sensing is crucial for monitoring combustion chambers and turbine stators in aeroengines, where surface temperatures can reach up to 1200 °C. Surface Acoustic Wave (SAW) temperature sensors are an excellent choice for these measurements. However, at extreme temperatures, they face issues such as agglomeration and recrystallization of electrodes, leading to loss of conductivity and reduced quality factor, hindering effective wireless signal transmission. This study develops an LGS SAW sensor with a Pt-10%Rh/Zr/Pt-10%Rh/Zr/Pt-10%Rh/Zr multilayer composite electrode structure to address these challenges. We demonstrate that the sensor can achieve wireless temperature measurements from room temperature to 1200 °C with an accuracy of 1.59%. The composite electrodes excite a quasi-shear wave on the LGS substrate, maintaining a Q-factor of 3526 at room temperature, providing an initial assurance for the strength of the wireless interrogation echo signal. The sensor operates stably for 2.18 h at 1200 °C before adhesion loss between the composite electrode and the substrate causes a sudden increase in resonant frequency. This study highlights the durability of the proposed electrode materials and structure at extreme temperatures and suggests future research to improve adhesion and extend the sensor's lifespan, thereby enhancing the reliability and effectiveness of high-temperature wireless sensing in aerospace applications.

Prevention of postpancreatectomy hemorrhage after laparoscopic pancreaticoduodenectomy by wrapping ligamentum teres hepatis surrounding hepatic portal artery.

Postpancreatectomy hemorrhage (PPH) is an important risk factor for postoperative complications after laparoscopic pancreaticoduodenectomy (LPD). Recent studies have reported that the use of ligamentum teres hepatis (LTH) in LPD may reduce the risk of PPH. Therefore, this study aims to investigate whether wrapping the hepatic hilar artery with the LTH can reduce PPH after LPD. We reviewed the data of 131 patients who underwent LPD in our team from April 2018 to December 2023. The patients were divided into Groups A (60 patients) and B (71 patients) according to whether the hepatic portal artery was wrapped or not. The perioperative data of the two groups were compared to evaluate the effect of LTH wrapping the hepatic hilar artery on LPD. The platelet count of Group A was (225.25 ± 87.61) × 10^9/L, and that of Group B was (289.38 ± 127.35) × 10^9/L, with a statistically significant difference (p < 0.001). The operation time of group A [300.00 (270.00, 364.00)] minutes was shorter than that of group B [330.00 (300.00, 360.00)] minutes, p = 0.037. In addition, A set of postoperative hospital stay [12.00 (10.00, 15.00)] days shorter than group B [15.00 (12.00, 19.50)] days, p < 0.001. No PPH occurred in Group A, while 8 patients in Group B had PPH (7 cases of gastroduodenal artery hemorrhage and 1 case of proper hepatic artery hemorrhage), p = 0.019. The new technique of wrapping the hepatic hilar artery through the LTH can effectively reduce the occurrence of PPH after LPD.

TaMYB-CC5 gene specifically expressed in root improve tolerance of phosphorus deficiency and drought stress in wheat.

Phosphate deficiency and drought are significant environmental constraints that impact both the productivity and quality of wheat. The interaction between phosphorus and water facilitates their mutual absorption processes in plants. Under conditions of both phosphorus deficiency and drought stress, we observed a significant upregulation in the expression of wheat MYB-CC transcription factors through the transcriptome analysis. 52 TaMYB-CC genes in wheat were identified and analyzed their evolutionary relationships, structures, and expression patterns. The TaMYB-CC5 gene exhibited specific expression in roots and demonstrated significant upregulation under phosphorus deficiency and drought stress compared to other TaMYB-CC genes. The overexpression of TaMYB-CC5A in Arabidopsis resulted in a significant increase of root length under stress conditions, thereby enhancing tolerance to phosphate starvation and drought stress. The wheat lines with silenced TaMYB-CC5 genes exhibited reduced root length under stress conditions and increased sensitivity to phosphate deficiency and drought stress. In addition, silencing the TaMYB-CC5 genes resulted in altered phosphorus content in leaves but did not lead to a reduction in phosphorus content in roots. Enrichment analysis the co-expression genes of TaMYB-CC5 transcription factors, we found the zinc-induced facilitator-like (ZIFL) genes were prominent associated with TaMYB-CC5 gene. The TaZIFL1, TaZIFL2, and TaZIFL5 genes were verified specifically expressed in roots and regulated by TaMYB-CC5 transcript factor. Our study reveals the pivotal role of the TaMYB-CC5 gene in regulating TaZIFL genes, which is crucial for maintaining normal root growth under phosphorus deficiency and drought stress, thereby enhanced resistance to these abiotic stresses in wheat.

Theoretical Study on the P-C Bond Dissociation Enthalpy in 9,10-Dihydro-9-oxa-10-phosphaphenanthrene-10-oxide Flame Retardants.

The 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) flame retardants (DOPO-FRs) have attracted more and more attention in the flame-retardant industry due to their high efficiency, environmental protection, and good molecular design. During the flame-retardant process, the breakage of P-C bonds is very important to the flame-retardant effect. Through the comparison of different density functional theories (DFTs) on P-C BDEs, it was found that MN12-L has the highest calculation accuracy, and the root-mean-square error is the smallest with 1.85 kcal/mol. Therefore, MN12-L was selected to investigate P-C BDEs of different DOPO-FRs including thiophen-amine, benzo[d]thiazol-amine, triazol-amine, and aniline DOPO-FRs. By comparing the theoretical calculation of BDE with the experimental parameters of high limiting oxygen index (LOI) and vertical combustion test (UL-94 test), it was found that the P-C BDEs have a certain correlation with the flame-retardant effect. Finally, based on P-C BDEs, substituent effects, and effective flame-retardant fragments, a series of new DOPO-FRs were designed. The results showed that when only one DOPO fragment was contained, the effective fragments of flame retardants were ranked as furan > thiophene > triazole > imidazole. When bis-DOPO fragment was contained, the flame-retardant effect of diamino-triazole fragments was better than that of benzyldimethylamine fragments. In addition, when the substituents on the effective fragment have two EDGs, the flame-retardant effect is superimposed, which makes the flame-retardant performance more excellent.

Prosthesis optimization and mechanical analysis of artificial lumbar disc replacement.

BACKGROUND: Artificial lumbar disc replacement is an effective method for the treatment of lumbosacral degenerative diseases. An appropriate artificial intervertebral disc device is of great significance for the maintenance of spinal stability and activity. METHODS: Two finite element models of ProDisc-L prosthesis replacement and improved prosthesis replacement were constructed by using the finite element model of complete lumbar L1-L5 segment established by CT image data. The mechanical properties of the surgical models before and after improvement were analyzed and evaluated. RESULTS: The ProDisc-L group and the improved group showed similar lumbar's ROM and maintained a similar ROM with the normal lumbar spine. There was no significant change in the intervertebral disc's pressure between the adjacent segments of the two prosthesis groups compared with the normal group, but the stress value of the improved prosthesis group was slightly lower than that of the ProDisc-L group. In addition, the improved prosthesis replacement has more reasonable stress distribution. CONCLUSIONS: Compared with the ProDisc-L prosthesis, the improved prosthesis can reduce the pressure in the intervertebral disc of the adjacent segment, the contact stress of the facet joint and the artificial prosthesis, which provides reference for the subsequent design of the prosthesis structure.

Prognostic significance of migrasomes in neuroblastoma through machine learning and multi-omics.

This study explores migrasomes' role in neuroblastoma, a common malignant tumor in children, and their potential impact on tumor formation. We analyzed neuroblastoma RNA-seq datasets from public databases, including GSE62564, GSE181559, target, and fwr144. Through data normalization and unsupervised classification using migrasome-specific molecular markers, Differentially Expressed Genes were identified, followed by functional enrichment analysis. Our novel migrasome-associated machine learning model, MigScore, was developed using ten algorithms and 101 combinations, validated on two single-cell datasets. This enabled immune infiltration assessment and drug compatibility prediction, highlighting the utility of MS275, a histone deacetylase inhibitor. Results showed a significant inverse relationship between MigScore and favorable clinical outcomes, elucidating the link between migrasome pathways and tumor immunogenicity. These findings suggest that migrasomes are crucial in neuroblastoma prognosis, leading to the possibility of personalized treatment strategies and improved outcomes.

Isophorone-based crystallization-induced-emission sensors detect proteome aggregation in live cells and tissues with breast cancer.

BACKGROUND: Protein misfolding and aggregation can lead to various diseases. Recent studies have shed light on the aggregated protein in breast cancer pathology, which suggests that it is crucial to design chemical sensors that visualize protein aggregates in breast cancer, especially in clinical patient-derived samples. However, most reported sensors are constrained in cultured cell lines. RESULTS: In this work, we present the development of two isophorone-based crystallization-induced-emission fluorophores for detecting proteome aggregation in breast cancer cell line and tissues biopsied from diseased patients, designated as A1 and A2. These probes exhibited viscosity sensitivity and recovered their fluorescence strongly at crystalline state. Moreover, A1 and A2 exhibit selective binding capacity and strong fluorescence for various aggregated proteins. Utilizing these probes, we detect protein aggregation in stressed breast cancer cells, xenograft mouse model of human breast cancer and clinical patient-derived samples. Notably, the fluorescence intensity of both probes light up in tumor tissues. SIGNIFICANCE: The synthesized isophorone-based crystallization-induced-emission fluorophores, A1 and A2, enable sensitive detection of protein aggregation in breast cancer cells and tissues. In the future, aggregated proteins are expected to become indicators for early diagnosis and clinical disease monitoring of breast cancer.

Tandem "One-Shot" Measurement of Residual Chemical Shift Anisotropy and Residual Dipolar Coupling using Biphasic Supramolecular Peptide Liquid Crystals.

Both solitary and tandem applications of residual chemical shift anisotropy (RCSA) and residual dipolar coupling (RDC) show great potential for the structural and configurational determination of organic molecules. A critical component of both RDC and RCSA methodologies is the alignment medium, whose availability is limited, especially for RCSA measurement. Moreover, reported RDC and RCSA acquisitions mainly rely on two experiments conducted under two different conditions, which are relatively time-consuming and easily cause experimental errors. Herein, a biphasic supramolecular lyotropic liquid crystalline (LLC) system was developed through the self-assembly of C21H43-CONH-V4K3-CONH2, which could act as an alignment medium for not only RDC but also RCSA extraction in DMSO-d6. Notably, the RCSA extraction was easily achieved via one-shot measurement from a single one-dimensional 13C NMR experiment, with no need for special instruments, devices, and correction. Relying on the biphasic LLC medium, meanwhile, RDC data were simply extracted from a single F1-coupled HSQC experiment, different from the standard protocol that requires two spectral acquisitions corresponding to the isotropic and anisotropic conditions. Collectively, the biphasic LLC medium is applicable for tandem RCSA and RDC measurements in one single sample, advancing the stereochemical elucidation of molecules of interest.

A robust ultra-performance liquid chromatography-tandem mass spectrometry method for simultaneous determination of 10 components in glutathione cycle.

Glutathione (GSH) is an important antioxidant that is generated and degraded via the GSH cycle. Quantification of the main components in the GSH cycle is necessary to evaluate the process of GSH. In this study, a robust ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of 10 components (GSH; γ-glutamylcysteine; cysteinyl-glycine; n-acetylcysteine; homocysteine; cysteine; cystine; methionine; glutamate; pyroglutamic acid) in GSH cycle was developed. The approach was optimized in terms of derivative, chromatographic, and spectrometric conditions as well as sample preparation. The unstable thiol groups of GSH, γ-glutamylcysteine, cysteinyl-glycine, n-acetylcysteine, cysteine, and homocysteine were derivatized by n-ethylmaleimide. The derivatized and underivatized analytes were separated on an amino column with gradient elution. The method was further validated in terms of selectivity (no interference), linearity (R2 > 0.99), precision (% relative standard deviation [RSD%] range from 0.57 to 10.33), accuracy (% relative error [RE%] range from -3.42 to 10.92), stability (RSD% < 5.68, RE% range from -2.54 to 4.40), recovery (RSD% range from 1.87 to 7.87) and matrix effect (RSD% < 5.42). The validated method was applied to compare the components in the GSH cycle between normal and oxidative stress cells, which would be helpful in clarifying the effect of oxidative stress on the GSH cycle.

Oncolytic virotherapy for hepatocellular carcinoma: A potent immunotherapeutic landscape.

Hepatocellular carcinoma (HCC) is a systemic disease with augmented malignant degree, high mortality and poor prognosis. Since the establishment of the immune mechanism of tumor therapy, people have realized that immunotherapy is an effective means for improvement of HCC patient prognosis. Oncolytic virus is a novel immunotherapy drug, which kills tumor cells and exempts normal cells by directly lysing tumor and inducing anti-tumor immune response, and it has been extensively examined as an HCC therapy. This editorial discusses oncolytic viruses for the treatment of HCC, emphasizing viral immunotherapy strategies and clinical applications related to HCC.

Heterozygous Apex1 deficiency exacerbates lipopolysaccharide-induced systemic inflammation in a murine model.

The biological role of apurinic/apyrimidinic endonuclease 1/redox factor-1 (Apex1) in modulating systemic inflammation remains unclear. This study aimed to assess the impact of Apex1 deficiency on systemic inflammation triggered by lipopolysaccharide (LPS) in a murine model. The methods involved transcriptomic analysis and assessments of inflammatory responses in age-matched 8-week-old Apex1+/- and wild-type Apex1+/+ mice, generated using the CRISPR/Cas9 system. Apex1+/- mice displayed no overt changes in body weight, however, Apex1 protein expressions in tissues were significantly reduced compared to wild-type mice. Furthermore, in Apex1+/- mice transcriptomic analysis showed that genes associated with antioxidant pathways were downregulated, and levels of superoxide production, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and malondialdehyde (MDA) were increased. Moreover, hematological analysis showed increased neutrophil levels and a twofold increase in the count of splenic lymphocyte antigen 6 family member G+ (Ly6G+) neutrophils in the Apex1+/- mice compared to those in Apex1+/+ mice. Furthermore, following LPS treatment, the levels of cytokines and chemokines, including interleukin-1ß, interleukin-10, tumor necrosis factor-α, and monocyte chemoattractant protein 1, increased in the Apex1+/- mice. The Kaplan-Meier curve showed a significant reduction in the survival rates of Apex1+/- mice treated with LPS compared to those of Apex1+/+ mice. The hepatic and lung injury scores and Ly6G+ neutrophil infiltration levels also increased in Apex1+/- mice after LPS treatment. These results showed that Apex1 deficiency exacerbated the LPS-induced tissue damage in the lung and liver. These findings illustrate that in vivo Apex1 deficiency exacerbates LPS-induced systemic inflammation, tissue damage, and mortality in a murine model, highlighting the crucial role of Apex1 in mitigating inflammatory responses and maintaining a holistic physiological equilibrium.

Oncolytic adenovirus encoding LHPP exerts potent antitumor effect in lung cancer.

LHPP has been shown to be a new tumor suppressor, and has a tendency to be under-expressed in a variety of cancers. Oncolytic virotheray is a promising therapeutics for lung cancer in recent decade years. Here we successfully constructed a new recombinant oncolytic adenovirus GD55-LHPP and investigated the effect of GD55-LHPP on the growth of lung cancer cells in vitro and in vivo. The results showed that LHPP had lower expression in either lung cancer cells or clinical lung cancer tissues compared with normal cells or tissues, and GD55-LHPP effectively mediated LHPP expression in lung cancer cells. GD55-LHPP could effectively inhibit the proliferation of lung cancer cell lines and rarely affected normal cell growth. Mechanically, the oncolytic adenovirus GD55-LHPP was able to induce stronger apoptosis of lung cancer cells compared with GD55 through the activation of caspase signal pathway. Notably, GD55-LHPP also activated autophagy-related signal pathway. Further, GD55-LHPP efficiently inhibited tumor growth in lung cancer xenograft in mice and prolonged animal survival rate compared with the control GD55 or PBS. In conclusion, the novel construct GD55-LHPP provides a valuable strategy for lung cancer-targeted therapy and develop the role of tumor suppress gene LHPP in lung cancer gene therapy.

Recent advances in breast cancer metastasis with special emphasis on metastasis to the brain.

Understanding the underlying mechanisms of breast cancer metastasis is of vital importance for developing treatment approaches. This review emphasizes contemporary breakthrough studies with special focus on breast cancer brain metastasis. Acquired mutational changes in metastatic lesions are often distinct from the primary tumor, suggesting altered mutagenesis pathways. The concept of micrometastases and heterogeneity within the tumors unravels novel therapeutic targets at genomic and molecular levels through epigenetic and proteomic profiling. Several pre-clinical studies have identified mechanisms involving the immune system, where tumor associated macrophages are key players. Expression of cell proteins like Syndecan1, fatty acid-binding protein 7 and tropomyosin kinase receptor B have been implicated in aiding the transmigration of breast cancer cells to the brain. Changes in the proteomic landscape of the blood-brain-barrier show altered permeability characteristics, supporting entry of cancer cells. Findings from laboratory studies pave the path for the emergence of new biomarkers, especially blood-based miRNA and circulating tumor cell markers for prognostic staging. The constantly evolving therapeutics call for clinical trials backing supportive evidence of efficacies of both novel and existing approaches. The challenge lying ahead is discovering innovative techniques to replace use of human samples and optimize small-scale patient recruitment in trials.

Relationship between iron homeostasis and prognosis in patients with heart failure: a retrospective study based on the MIMIC-IV database.

INTRODUCTION: The role of iron homeostasis has become increasingly recognized as a key factor in determining a prognosis of patients with heart failure (HF). Disruptions in iron balance, encompassing deficiency and overload, can affect patient prognosis, and therefore, significantly impact treatment and management strategies. OBJECTIVES: The study investigated possible associations between iron homeostasis-related indicators and long­term mortality as well as first­admission mortality in individuals with HF. PATIENTS AND METHODS: Data on 3483 HF patients from the MIMIC­IV database were retrospectively analyzed. The relationship between iron homeostasis-related indicators (ferritin, serum iron, transferrin, and total iron binding capacity [TIBC]) and the first-admission and long-term mortality of HF patients was discerned utilizing the Cox proportional hazards model and the Kaplan-Meier survival analysis. Additionally, the predictive capability of these indicators for patient prognosis was assessed using the receiver operating characteristic curve. RESULTS: Fourth quartile levels of ferritin and serum iron were obviously associated with poor long­term outcomes in HF patients. Conversely, fourth quartile levels of transferrin and TIBC served as protective factors and were associated with a lower mortality. Additionally, iron homeostasis indicators exhibited a certain predictive value for both long­term mortality and first­admission mortality in HF patients. CONCLUSIONS: This study underscores a significant association between iron homeostasis indicators and the prognosis of HF patients, providing valuable insights into risk stratification and clinical decision­making for this population. Future studies should focus on dynamic fluctuations in iron homeostasis and explore interventions to improve the prognosis of HF patients.

Shotgun metagenomic analysis of microbiota dynamics during long-term backslopping fermentation of traditional fermented milk in a controlled laboratory environment.

Traditional fermented milks are produced through an inoculation process that involves the deliberate introduction of microorganisms that have been adapted and perpetuated across successive generations. However, the changes in the microbiota of traditional fermented milk during long-term inoculation fermentation in a laboratory environment remain unclear. In this study, we collected 5 samples of traditional fermented milk samples from 5 different counties in Tibet (3 kurut products) and Xinjiang (2 tarag products) of China, which served as starter cultures for a 9-mo continuous inoculation fermentation experiment. We analyzed the inter- and intra-population variations in the microbial communities of the collected samples, representing their macrodiversity and microdiversity, using shotgun metagenomic sequencing. Across all samples, we obtained a total of 186 high-quality metagenomic-assembled genomes, including 7 genera and 13 species with a relative abundance of more than 1%. The majority of these genomes were annotated as Lactobacillus helveticus (60.46%), Enterococcus durans (9.52%), and Limosilactobacillus fermentum (6.23%). We observed significant differences in species composition and abundance among the 5 initial inoculants. During the long-term inoculation fermentation, we found an overall increasing trend in species diversity, composition, and abundances of carbohydrate metabolism module-encoding genes in the fermented milk bacterial metagenome, while the fermented milk virome exhibited a relatively narrow range of variation. Lactobacillus helveticus, a dominant species in traditional fermented milk, displayed high stability during the long-term inoculation fermentation. Our study provides valuable insights for the industrial production of traditional fermented milk.

The Extraction Using Deep Eutectic Solvents and Evaluation of Tea Saponin.

Tea saponins have high surface-active and biological activities and are widely used in chemicals, food, pharmaceuticals, and pesticides. Tea saponins are usually extracted using ethanol or water, but both methods have their disadvantages, including a negative impact on the environment, high energy consumption, and low purity. In this study, we explored an effective process for extracting tea saponins from tea meal using deep eutectic solvents combined with ultrasonic extraction and enzymatic techniques. The experimental results showed that a high extraction efficiency of 20.93 ± 0.48% could be achieved in 20 min using an ultrasonic power of 40% and a binary DES consisting of betaine and ethylene glycol (with a molar ratio of 1:3) at a material-liquid ratio of 1:35 and that the purity of the tea saponins after purification by a large-pore adsorption resin reached 95.94%, which was higher than that of commercially available standard tea saponin samples. In addition, the extracted tea saponins were evaluated for their antioxidant and bacteriostatic activities using chemical and biological methods; the results showed that the tea saponins extracted using these methods possessed antioxidant properties and displayed significant antibacterial activity. Therefore, the present study developed a method for using deep eutectic solvents as an environmentally friendly technological solution for obtaining high-purity tea saponins from tea meal oil. This is expected to replace the current organic solvent and water extraction process and has great potential for industrial development and a number of possible applications.

Mechanistic exploration of the shenlian formula in the suppression of atherosclerosis progression via network pharmacology and in vivo experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: The Shenlian formula (SL) is a Chinese medicine formula used to curb the development of atherosclerosis (AS) and cardiovascular disease in clinical practice. However, owing to the complexity of compounds and their related multiple targets in traditional Chinese medicine (TCM), it remains difficult and urgent to elucidate the underlying mechanisms at a holistic level. AIM: To investigate the intrinsic mechanisms by which SL suppresses AS progression and to gain new insight into its clinical use. METHODS: We proposed a network pharmacology-based workflow to evaluate the mechanism by which SL affects AS via data analysis, target prediction, PPI network construction, GO and KEGG analyses, and a "drug-core ingredient-potential target-key pathway" network. Then, non-targeted lipidomic analysis was performed to explore the differential lipid metabolites in AS rats, revealing the possible mechanism by which SL affects atherosclerotic progression. Moreover, an AS rabbit model was constructed and gavaged for SL intervention. Serum lipid profiles and inflammatory cytokine indices were tested as an indication of the mitigating effect of SL on AS. RESULTS: A total of 89 bioactive compounds and 298 targets related to SL and AS, which play essential roles in this process, were identified, and a component-target-disease network was constructed. GO and KEGG analyses revealed that SL regulated metabolic pathway, lipids and atherosclerosis, the PI3K-Akt pathway, the MAPK pathway and so on. In vivo experimental validation revealed that a total of 43 different lipid metabolites regulated by SL were identified by non-targeted lipidomics, and glycerophospholipid metabolism was found to be an important mechanism for SL to interfere with AS. SL reduced the plaque area and decreased the levels of inflammatory cytokines (TNF-α and IL-4) and blood lipids (TC, TG, LDL-C, and ApoB) in HFD-induced AS models. In addition, HDL and ApoA1 levels are increased. PLA2 and Lipin1 are highly expressed in AS model, indicating their role in destabilizing glycerophosphatidylcholine metabolism and contributing to the onset and progression of ankylosing spondylitis. Moreover, SL intervention significantly reduced the level of pro-inflammatory cytokines; significantly down-regulated NF-kB/p65 expression, exhibiting anti-inflammatory activity. CONCLUSION: The Shenlian formula (SL) plays a pivotal role in the suppression of AS progression by targeting multiple pathways and mechanisms. This study provides novel insights into the essential genes and pathways associated with the prognosis and pathogenesis of AS.

A body-brain circuit that regulates body inflammatory responses.

The body-brain axis is emerging as a principal conductor of organismal physiology. It senses and controls organ function1,2, metabolism3 and nutritional state4-6. Here we show that a peripheral immune insult strongly activates the body-brain axis to regulate immune responses. We demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body-brain circuit produced unregulated and out-of-control inflammatory responses. By contrast, activating, rather than silencing, this circuit affords neural control of immune responses. We used single-cell RNA sequencing, combined with functional imaging, to identify the circuit components of this neuroimmune axis, and showed that its selective manipulation can effectively suppress the pro-inflammatory response while enhancing an anti-inflammatory state. The brain-evoked transformation of the course of an immune response offers new possibilities in the modulation of a wide range of immune disorders, from autoimmune diseases to cytokine storm and shock.