CXCL10 could be a prognostic and immunological biomarker in bladder cancer.

INTRODUCTION: As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. METHOD: In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. RESULTS: We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. CONCLUSION: Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA.

Integrated and DC-powered superconducting microcomb.

Frequency combs, specialized laser sources emitting multiple equidistant frequency lines, have revolutionized science and technology with unprecedented precision and versatility. Recently, integrated frequency combs are emerging as scalable solutions for on-chip photonics. Here, we demonstrate a fully integrated superconducting microcomb that is easy to manufacture, simple to operate, and consumes ultra-low power. Our turnkey apparatus comprises a basic nonlinear superconducting device, a Josephson junction, directly coupled to a superconducting microstrip resonator. We showcase coherent comb generation through self-started mode-locking. Therefore, comb emission is initiated solely by activating a DC bias source, with power consumption as low as tens of picowatts. The resulting comb spectrum resides in the microwave domain and spans multiple octaves. The linewidths of all comb lines can be narrowed down to 1 Hz through a unique coherent injection-locking technique. Our work represents a critical step towards fully integrated microwave photonics and offers the potential for integrated quantum processors.

Structural transitions enable interleukin-18 maturation and signaling.

Several interleukin-1 (IL-1) family members, including IL-1ß and IL-18, require processing by inflammasome-associated caspases to unleash their activities. Here, we unveil, by cryoelectron microscopy (cryo-EM), two major conformations of the complex between caspase-1 and pro-IL-18. One conformation is similar to the complex of caspase-4 and pro-IL-18, with interactions at both the active site and an exosite (closed conformation), and the other only contains interactions at the active site (open conformation). Thus, pro-IL-18 recruitment and processing by caspase-1 is less dependent on the exosite than the active site, unlike caspase-4. Structure determination by nuclear magnetic resonance uncovers a compact fold of apo pro-IL-18, which is similar to caspase-1-bound pro-IL-18 but distinct from cleaved IL-18. Binding sites for IL-18 receptor and IL-18 binding protein are only formed upon conformational changes after pro-IL-18 cleavage. These studies show how pro-IL-18 is selected as a caspase-1 substrate, and why cleavage is necessary for its inflammatory activity.

Pollution offsets the rapid evolution of increased heat tolerance in a natural population.

Despite the increasing evidence for rapid thermal evolution in natural populations, evolutionary rescue under global warming may be constrained by the presence of other stressors. Highly relevant in our polluted planet, is the largely ignored evolutionary trade-off between heat tolerance and tolerance to pollutants. By using two subpopulations (separated 40 years in time) from a resurrected natural population of the water flea Daphnia magna that experienced a threefold increase in heat wave frequency during this period, we tested whether rapid evolution of heat tolerance resulted in reduced tolerance to the widespread metal zinc and whether this would affect heat tolerance upon exposure to the pollutant. Our results revealed rapid evolution of increased heat tolerance in the recent subpopulation. Notably, the sensitivity to the metal tended to be stronger (reduction in net energy budget) or was only present (reductions in heat tolerance and in sugar content) in the recent subpopulation. As a result, the rapidly evolved higher heat tolerance of the recent subpopulation was fully offset when exposed to zinc. Our results highlight that the many reports of evolutionary rescue to global change stressors may give a too optimistic view as our warming planet is polluted by metals and other pollutants.

Ferroptosis in renal fibrosis: a mini-review.

Ferroptosis is a novel form of programmed cell death that is iron-dependent and distinct from autophagy, apoptosis, and necroptosis. It is primarily characterised by a decrease in glutathione peroxidase 4 (GPX4) activity, or by the accumulation of lipid peroxidation and reactive oxygen species (ROS). Renal fibrosis is a common pathological change in the progression of various primary and secondary renal diseases to end-stage renal disease and poses a serious threat to human health with high morbidity and mortality. Multiple pathways contribute to the development of renal fibrosis, with ferroptosis playing a crucial role in renal fibrosis pathogenesis due to its involvement in the production of ROS. Ferroptosis is related to several signalling pathways, including System Xc-/GPX4, abnormal iron metabolism and lipid peroxidation. A number of studies have indicated that ferroptosis is closely involved in the process of renal fibrosis caused by various kidney diseases such as glomerulonephritis, renal ischaemia-reperfusion injury, diabetic nephropathy and renal calculus. Identifying the underlying molecular mechanisms that determine cell death would open up new insights to address a therapeutic strategy to renal fibrosis. The review aimed to browse and summarise the known mechanisms of ferroptosis that may be associated with biological reactions of renal fibrosis.

Ionic Liquid Modified Fe-Porphyrinic Metal-Organic Frameworks as Efficient and Selective Photocatalysts for CO2 Reduction.

Porphyrin-based metal-organic frameworks (MOFs) are ideal platforms for heterogeneous photocatalysts toward CO2 reduction. To further explore photocatalytic MOF systems, it is also necessary to consider their ability to fine-tune the microenvironments of the active sites, which affects their overall catalytic operation. Herein, a kind of ionic liquid (IL, here is 3-butyric acid-1-methyl imidazolium bromide, BAMeImBr) was anchored to iron-porphyrinic Zr-MOFs with different amounts to obtain ILx@MOF-526 (MOF-526 = Zr6O4(OH)4(FeTCBPP)3, FeTCBPP = iron 5,10,15,20-tetra[4-(4'-carboxyphenyl)phenyl]-porphyrin, x = 100, 200, and 400). ILx@MOF-526 series was designed to investigate the effects of the microenvironmental and electronic structural modification on the efficiency and selectivity of the photochemical reduction of CO2 after introducing IL fragments. Compared to parent MOF-526, the production and selectivity of CO were greatly improved in the absence of any photosensitizer under visible light by the ILx@MOF-526 series. Among them, the CO yield of IL200@MOF-526 was up to 14.0 mmol g-1 within 72 h with a remarkable CO selectivity of 97%, which is superior to that of MOF-526 without BAMeIm+ modification and other amounts of BAMeIm+ loaded. Furthermore, density functional theory calculations were performed to study the mechanism of the CO2 reduction.

Performance enhancement, bacterial communities optimization and emerging pollutants elimination by microalgal-bacterial consortium for treating aquaculture pond sediments.

Aquaculture pond sediments have a notable influence on the ecosystem balance and farmed animal health. In this study, microalgal-bacterial immobilization (MBI) was designed to improve aquaculture pond sediments via synergistic interactions. The physicochemical characteristics, bacterial communities, and the removal efficiencies of emerging pollutants were systematically investigated. The consortium containing diatom Navicula seminulum and Alcaligenes faecalis was cultivated and established in the free and immobilized forms for evaluating the treatment performance. The results indicated that the immobilized group exhibited superior performance in controlling nutrient pollutants, shaping and optimizing the bacterial community compositions with the enrichment of functional bacteria. Additionally, it showed a stronger positive correlation between the bacterial community shifts and nutrient pollutants removal compared to free cells. Furthermore, the immobilized system maintained the higher removal performance of emerging pollutants (heavy metals, antibiotics, and pathogenic Vibrios) than free group. These findings confirmed that the employment of immobilized N. seminulum and A. faecalis produced more synergistic benefits and exerted more improvements than free cells in ameliorating aquaculture pond sediments, suggesting the potential for engineering application of functional microalgal-bacterial consortium in aquaculture.

Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.

Characterisation and critical processes identification for production of herbal preparations using 1H-NMR and chemometrics: A case study of Trichosanthis Pericarpium injection.

INTRODUCTION: Herbal preparations are extensively utilised for the treatment of diseases in Asian countries. However, the variations in origin, climate, and production processes can lead to inconsistencies in the quality of herbal preparations. Existing quality control methods only target a few components in the finished product but ignore the control in the pharmaceutical process. Therefore, this study intends to develop a comprehensive component analysis method for intermediates in the pharmaceutical process to reveal the change patterns of substances and deepen the process understanding. OBJECTIVE: This study aims to develop a rapid and comprehensive process characterisation and critical process identification method for herbal preparations. METHODS: Six batches of Trichosanthis Pericarpium injection (TPI) intermediates were collected from the production process. Proton nuclear magnetic resonance (1H-NMR) spectra were acquired for qualitative and quantitative analysis of the se intermediates. Subsequently, chemometrics were used to identify critical processes and potential chemical markers. RESULTS: A total of 39 components in intermediates were identified, and the transfer of 25 components during the production process was investigated. Column chromatography was determined as the critical process. Nine components were identified as chemical markers. CONCLUSION: The application of 1H-NMR facilitated a comprehensive reflection of the chemical composition information of process intermediates, enabling investigations into the transfer of multi-component substances and accurate identification of critical processes and chemical markers.

Spirobifluorene Trimers : High Triplet Pure Hydrocarbon Hosts for Highly Efficient Blue Phosphorescent Organic Light-Emitting Diodes.

Pure aromatic hydrocarbon materials (PHC) represent a new generation of host materials for phosphorescent OLEDs (PhOLEDs), free of heteroatoms. They reduce the molecular complexity, can be easily synthesized and are an important direction towards robust devices. As heteroatoms can be involved in bonds dissociations in operating OLEDs through exciton induced degradation process, developing novel PHCs appear particularly relevant for the future of this technology. In the present work, we report a series of extended PHCs constructed on the assembly of three spirobifluorene fragments. The resulting positional isomers present a high triplet energy level, a wide HOMO/LUMO difference and improved thermal and morphological properties compared to previously reported PHCs. These characteristics are beneficial for the next generation of host materials for PhOLEDs and provide relevant design guidelines. Used as host in blue-emitting PhOLEDs, which are still the weakest link of the field, a very high EQE of 24 % and low threshold voltage of 3.56 V were obtained with a low-efficiency roll-off. This high performance strengthens the position of PHC strategy as an efficient alternative for OLED technology and opens the way to a more simple electronic.

Plasma levels of Sirtuin 7 are decreased in patients with essential hypertension.

BACKGROUND: Sirtuin 7 (SIRT7), as a nicotinamide adenine dinucleotide-dependent protein/histone deacetylase, has been implicated in the pathogenesis of cardiovascular diseases. However, whether SIRT7 is related to hypertension remains largely unclear. Thus, this study aims to explore the effects and correlation between SIRT7 and hypertension. METHODS: A total of 72 patients with essential hypertension and 82 controls with non-hypertension were recruited at Beijing Tongren Hospital Affiliated with Capital Medical University from July 2022 to June 2023. Plasma SIRT7 expression was measured using enzyme-linked immunosorbent assay analysis. Clinical baseline characteristics, laboratory measurements, echocardiographic data, and medical therapy were collected. RESULTS: Plasma levels of SIRT7 were lower in hypertensive patients compared with non-hypertensive patients [0.97 (0.58-1.30) vs. 1.24 (0.99-1.46) ng/mL, P < 0.001, respectively]. Furthermore, compared with the low SIRT7 group, there were lower levels of systolic blood pressure, hyperlipidemia, and the ultrasonic electrocardiogram parameters left ventricular end-diastolic diameter and left atrial in diastole in the high SIRT7 group (P < 0.05, respectively). More importantly, multivariate logistic regression analyses indicated that plasma SIRT7 was a predictor of hypertension [OR: 0.06, 95 % CI (0.02-0.19), P < 0.001]. Receiver operating characteristics curve analysis revealed that the optimal cutoff value for plasma SIRT7 levels in detecting hypertension was determined as 0.85 ng/mL with a sensitivity of 73.6 % and a specificity of 89.0 %. The area under the curve for SIRT7 was 0.821 (95 % CI, 0.751-0.878; P < 0.001). CONCLUSION: Plasma levels of SIRT7 are decreased in patients with essential hypertension, implying its potential as a biomarker for diagnosing essential hypertension..

Toroidic phase transitions in a direct-kagome artificial spin ice.

Ferrotoroidicity-the fourth form of primary ferroic order-breaks both space and time-inversion symmetry. So far, direct observation of ferrotoroidicity in natural materials remains elusive, which impedes the exploration of ferrotoroidic phase transitions. Here we overcome the limitations of natural materials using an artificial nanomagnet system that can be characterized at the constituent level and at different effective temperatures. We design a nanomagnet array as to realize a direct-kagome spin ice. This artificial spin ice exhibits robust toroidal moments and a quasi-degenerate ground state with two distinct low-temperature toroidal phases: ferrotoroidicity and paratoroidicity. Using magnetic force microscopy and Monte Carlo simulation, we demonstrate a phase transition between ferrotoroidicity and paratoroidicity, along with a cross-over to a non-toroidal paramagnetic phase. Our quasi-degenerate artificial spin ice in a direct-kagome structure provides a model system for the investigation of magnetic states and phase transitions that are inaccessible in natural materials.

ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D.

Gasdermin D (GSDMD) is the common effector for cytokine secretion and pyroptosis downstream of inflammasome activation and was previously shown to form large transmembrane pores after cleavage by inflammatory caspases to generate the GSDMD N-terminal domain (GSDMD-NT)1-10. Here we report that GSDMD Cys191 is S-palmitoylated and that palmitoylation is required for pore formation. S-palmitoylation, which does not affect GSDMD cleavage, is augmented by mitochondria-generated reactive oxygen species (ROS). Cleavage-deficient GSDMD (D275A) is also palmitoylated after inflammasome stimulation or treatment with ROS activators and causes pyroptosis, although less efficiently than palmitoylated GSDMD-NT. Palmitoylated, but not unpalmitoylated, full-length GSDMD induces liposome leakage and forms a pore similar in structure to GSDMD-NT pores shown by cryogenic electron microscopy. ZDHHC5 and ZDHHC9 are the major palmitoyltransferases that mediate GSDMD palmitoylation, and their expression is upregulated by inflammasome activation and ROS. The other human gasdermins are also palmitoylated at their N termini. These data challenge the concept that cleavage is the only trigger for GSDMD activation. They suggest that reversible palmitoylation is a checkpoint for pore formation by both GSDMD-NT and intact GSDMD that functions as a general switch for the activation of this pore-forming family.

Associations of Dietary Cholesterol Consumption With Incident Diabetes and Cardiovascular Disease: The Role of Genetic Variability in Cholesterol Absorption and Disease Predisposition.

OBJECTIVE: Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear. RESEARCH DESIGN AND METHODS: DC consumption was assessed by repeated 24-h dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n = 96,826) and CVD (n = 94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models. RESULTS: Each additional 300 mg/day of DC consumption was associated with incident diabetes (hazard ratio [HR], 1.17 [95% CI, 1.07-1.27]) and CVD (HR, 1.09 [95% CI, 1.03-1.17]), but further adjusting for BMI nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90-1.09]; HR for CVD, 1.04 [95% CI, 0.98-1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction ≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction = 0.04), but the stratum-level association estimates were not statistically significant. CONCLUSIONS: DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation.

Sustainable treatment of aquaculture water employing fungi-microalgae consortium: Nutrients removal enhancement, bacterial communities optimization, emerging contaminants elimination, and mechanism analysis.

Fungi-microalgae consortium (FMC) has emerged as a promising system for advanced wastewater treatment due to its high biomass yield and environmental sustainability. This study aimed to investigate the nutrients removal, bacterial community shift, emerging contaminants elimination, and treatment mechanism of a FMC composed of Cordyceps militaris and Navicula seminulum for aquaculture pond water treatment. The fungi and microalgae were cultured and employed either alone or in combination to evaluate the treatment performance. The results demonstrated that the FMC could improve water quality more significantly by reducing nutrient pollutants and optimizing the bacterial community structures. Furthermore, it exhibited stronger positive correlation between the enrichment of functional bacteria for water quality improvement and pollutants removal performance than the single-species treatments. Moreover, the FMC outperformed other groups in eliminating emerging contaminants such as heavy metals, antibiotics, and pathogenic Vibrios. Superiorly, the FMC also showed excellent symbiotic interactions and cooperative mechanisms for pollutants removal. The results collectively corroborated the feasibility and sustainability of using C. militaris and N. seminulum for treating aquaculture water, and the FMC would produce more mutualistic benefits and synergistic effects than single-species treatments.

The effects of Atractylodes macrocephala extract BZEP self-microemulsion based on gut-liver axis HDL/LPS signaling pathway to ameliorate metabolic dysfunction-associated fatty liver disease in rats.

OBJECTIVES: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway. METHODS: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. RESULTS: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. CONCLUSION: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.

Alteration of the intestinal microbiota and serum metabolites in a mouse model of Pon1 gene ablation.

Mutations in the Paraoxonase 1 (Pon1) gene underlie aging, cardiovascular disease, and impairments of the nervous and gastrointestinal systems and are linked to the intestinal microbiome. The potential role of Pon1 in modulating the intestinal microbiota and serum metabolites is poorly understood. The present study demonstrated that mice with genomic excision of Pon1 by a multiplexed guide RNA CRISPR/Cas9 approach exhibited disrupted gut microbiota, such as significantly depressed alpha-diversity and distinctly separated beta diversity, accompanied by varied profiles of circulating metabolites. Furthermore, genomic knock in of Pon1 exerted a distinct effect on the intestinal microbiome and serum metabolome, including dramatically enriched Aerococcus, linoleic acid and depleted Bacillus, indolelactic acid. Specifically, a strong correlation was established between bacterial alterations and metabolites in Pon1 knockout mice. In addition, we identified metabolites related to gut bacteria in response to Pon1 knock in. Thus, the deletion of Pon1 affects the gut microbiome and functionally modifies serum metabolism, which can lead to dysbiosis, metabolic dysfunction, and infection risk. Together, these findings put forth a role for Pon1 in microbial alterations that contribute to metabolism variations. The function of Pon1 in diseases might at least partially depend on the microbiome.

The anti-hyperlipidemia effect of Atractylodes macrocephala Rhizome increased HDL via reverse cholesterol transfer.

Aim: Atractylodes macrocephala Rhizome (AM) has been used to treat hyperlipidemia for centuries, but its functional components and mechanisms are not clear. This research aimed to investigate the active components in AM and the mechanisms that underlie its anti-hyperlipidemia effect. Methods: SD rats were fed a high-sucrose high-fat diet in conjunction with alcohol (HSHFDAC) along with different AM extracts (AMW, AMO, AME, and AMP) for 4 weeks. AM's active components were analyzed using multiple databases, and their mechanisms were explored through network pharmacology. The relationship between AM's effect of enhancing serum HDL-c and regulating the expression of reverse cholesterol transport (RCT)-related proteins (Apo-A1, LCAT, and SR-BI) was further validated in the HSHFDAC-induced hyperlipidemic rats. The kidney and liver functions of the rats were measured to evaluate the safety of AM. Results: AMO, mainly comprised of volatile and liposoluble components, contributed the most significant anti-hyperlipidemia effect among the four extracts obtained from AM, significantly improving the blood lipid profile. Network pharmacology analysis also suggested that volatile and liposoluble components, comprise AM's main active components and they might act on signaling pathways associated with elevated HDL-c. Validation experiments found that AMO substantially and dose-dependently increased HDL-c levels, upregulated the expression of Apo-A1, SR-BI, and LCAT, improved the pathological changes in the kidney and liver, and significantly reduced the serum creatinine levels in rats with hyperlipidemia. Conclusion: The main anti-hyperlipidemia active components of AM are its volatile and liposoluble components, which may enhance serum HDL-c by increasing the expression of the RCT-related proteins Apo-A1, LCAT, and SR-BI.

Antifouling binary liquid-infused membranes for biological sample pretreatment.

Hydrophobic membranes infused with mixed solvents including a low polar solvent and a specific solvent can efficiently separate analytes from blood upon applying a voltage. In contrast, membranes infused with a specific solvent alone show significantly reduced separation efficiencies for blood samples. Infusion of a low polar solvent is of importance for achieving antifouling ability of membranes for biological sample pretreatment.

Bioinformatics and LC-QTOF-MS based discovery of pharmacodynamic and Q-markers of Pitongshu against functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Pitongshu (PTS) is a clinically effective empirical formula for the treatment of FD. The efficacy and safety of PTS have been demonstrated in randomized, controlled, double-blind trials, but there is a lack of understanding of the systematic evaluation of the efficacy of PTS and its material basis. OBJECTIVE: To investigate the efficacy of PTS in Functional dyspepsia (FD) mice and possible Q-markers. METHOD: In this study, we used "irregular feeding + chronic unpredictable chronic stimulation" to establish a mice model of FD with hepatogastric disharmony. The efficacy of PTS was assessed from hair condition, behavioral, pain, gastrointestinal function, and serum 5-HT, GAS, MTL levels in mice by instillation of different doses of PTS. In addition, the composition of drugs in blood was analyzed by LC-QTOF-MS and potential Q-markers were selected by combining network pharmacology, molecular docking and actual content. RESULT: Our study showed that different doses of PTS increased pain threshold and writhing latency, decreased the number of writhings, increased gastric emptying rate and small intestinal propulsion rate, decreased total acidity of gastric contents and gastric acid secretion, and increased serum levels of 5-HT, GAS, and MTL in mice to different degrees. Enrichment analysis showed that PTS may be anti-FD through multiple pathways such as Serotonergic synapse, thyroid hormone signaling pathway, cholinergic synapse, and dopaminergic synapse. In addition, potential active ingredient substances were explored by LC-QTOF-MS combined with bioinformatics. Combined with the actual contentselected six constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol, possible as Q-markers. CONCLUSION: PTS may exert its anti-FD effects through multi-component, multi-target and multi-pathway". Constituents, hesperidin, neohesperidin, naringin, paeoniflorin, magnolol and honokiol may be the Q-markers of its anti-FD effects.