Sleep-disordered breathing and nocturnal hypoxemia in chronic thromboembolic pulmonary disease.

BACKGROUND AND AIMS: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown. METHODS: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO2 (Mean SpO2) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH. RESULTS: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05). CONCLUSION: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH.

[Evaluation of chemical constituents of Draconis Sanguis and its protective effect on renal tubular injury in diabetic kidney disease].

The chemical constituents of Draconis Sanguis were preliminarily studied by macroporous resin, silica gel, dextran gel, and high-performance liquid chromatography. One retro-dihydrochalcone, four flavonoids, and one stilbene were isolated. Their chemical structures were identified as 4-hydroxy-2,6-dimethoxy-3-methyldihydrochalcone(1), 4'-hydroxy-5,7-dimethoxy-8-methylflavan(2), 7-hydroxy-4',5-dimethoxyflavan(3),(2S)-7-hydroxy-5-methoxy-6-methylflavan(4),(2S)-7-hydroxy-5-methoxyflavan(5), and pterostilbene(6) by modern spectroscopy, physicochemical properties, and literature comparison. Compound 1 was a new compound. Compounds 2 and 6 were first found in the Arecaceae family. Compound 5 had the potential to prevent and treat diabetic kidney disease.

Rapid Defect Engineering in FeCoNi/FeAl2O4 Hybrid for Enhanced Oxygen Evolution Catalysis: A Pathway to High-Performance Electrocatalysts.

Rational modulation of surface reconstruction in the oxygen evolution reaction (OER) utilizing defect engineering to form efficient catalytic activity centers is a topical interest in the field of catalysis. The introduction of point defects has been demonstrated to be an effective strategy to regulate the electronic configuration of electrocatalysts, but the influence of more complex planar defects (e.g., twins and stacking faults), on their intrinsic activity is still not fully understood. This study harnesses ultrasonic cavitation for rapid and controlled introduction of different types of defects in FeCoNi/FeAl2O4 hybrid coatings, optimizing OER catalytic activity. Theoretical calculations and experiments demonstrate that the different defects optimize the coordination environment and facilitate the activation of surface reconstruction into true catalytic activity centers at lower potentials. Moreover, it demonstrates exceptional durability, maintaining stable oxygen production at a high current density of 300 mA cm-2 for over 120 hours. This work not only presents a novel pathway for designing advanced electrocatalysts but also deepens our understanding of defect-engineered catalytic mechanisms, showcasing the potential for rapid and efficient enhancement of electrocatalytic performance.

Supramolecularly modulated carbon-centered radicals: toward selective oxidation from benzyl alcohol to aldehyde.

The reactivity of ketyl radicals and benzoyl radicals, two key intermediates of photo-induced oxidation of benzyl alcohol, can be stabilized by the host-guest interaction of the radicals with cucurbit[7]uril. As a result, the selectivity of photo-induced oxidation from benzyl alcohol to aldehyde is significantly improved by diminishing side reactions and inhibiting the generation of carboxylic acid products. This work presents a new route to modulate the reactivity of radical intermediates, enriching the chemistry of supramolecular intermediates and the toolbox of supramolecular catalysis.

Targeted Gene Deletion or Antagonism of the Prostaglandin E2 EP3 Receptor Protects Against Cardiac Injury Postmyocardial Infarction.

BACKGROUND: Prostaglandin E2 acts through 4 G-protein-coupled receptors (EP1-EP4). We previously reported that activation of the EP3 receptor reduces cardiac contractility, and its expression increases after a myocardial infarction (MI), mediating the reduction in cardiac function. In contrast, cardiac overexpression of the EP4 receptor in MI substantially improves cardiac function. Moreover, we recently reported that mice overexpressing EP3 have heart failure under basal conditions and worsened cardiac function after MI. Thus, the deleterious effects of the prostaglandin E2 EP receptors in the heart are mediated via its EP3 receptor. We, therefore, hypothesized that cardiomyocyte-specific knockout (CM-EP3 KO) or antagonism of the EP3 receptor protects the heart after MI. METHODS: To test our hypothesis, we made the novel CM-EP3 KO mouse and subjected CM-EP3 KO or controls to sham or MI surgery for 2 weeks. In separate experiments, C57BL/6 mice were subjected to 2 weeks of MI and treated with either the EP3 antagonist L798 106 or vehicle starting 3 days post-MI. RESULTS: CM-EP3 KO significantly prevented a decline in cardiac function after MI compared with WT animals and prevented an increase in hypertrophy and fibrosis. Excitingly, mice treated with L798 106 3 days after MI had significantly better cardiac function compared with vehicle-treated mice. CONCLUSIONS: Altogether, these data suggest that EP3 may play a direct role in regulating cardiac function, and pharmaceutical targeting of the EP3 receptor may be a therapeutic option in the treatment of heart failure.

Prevention and treatment of HPV-related cancer through a mRNA vaccine expressing APC-targeting antigen.

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7+ tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8+ T-cell immune response was induced, contributing to preventing and curing of E6 and E7+ tumour. Antigen-specific CD8+ T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence.

Study on the influence of pore water pressure on shear mechanical properties and fracture surface morphology of sandstone.

To further investigate the weakening effect of pore water pressure on intact rock mechanics properties and characteristics of fracture surface after failure, direct shear tests of sandstone were conducted under different pore pressure. A 3D scanner was employed to digitize the morphology of the post-shear fracture surface. The variogram function was applied to quantify the anisotropic characteristics of post-shear fracture surface. The relationship between deformation during shear failure of intact rock and quantitative parameters of fracture surface after shear failure was initially established. It can be found that amplitudes of the sinusoidal surface determine the maximum value of variogram, and period affect lag distance that reach the maximum value of variogram. Test results revealed that the increase of pore pressure has obvious weakening effect on shear strength and deformation of rock. Moreover, the increase of pore pressure makes the shear fracture surface flatter. It can be obtained that both Sillmax and Rangemax are positively related to shear strain, but negatively related to normal strain.

A Polymeric Nanoparticle to Co-Deliver Mitochondria-Targeting Peptides and Pt(IV) Prodrug: Toward High Loading Efficiency and Combination Efficacy.

Developing combination chemotherapy systems with high drug loading efficiency at predetermined drug ratios to achieve a synergistic effect is important for cancer therapy. Herein, a polymeric dual-drug nanoparticle composed of a Pt(IV) prodrug derived from oxaliplatin and a mitochondria-targeting cytotoxic peptide is constructed through emulsion interfacial polymerization, which processes high drug loading efficiency and high biocompatibility. The depolymerization of polymeric dual-drug nanoparticle and the activation of Pt prodrug can be effectively triggered by the acidic tumor environment extracellularly and the high levels of glutathione intracellularly in cancer cells, respectively. The utilization of mitochondria-targeting peptide can inhibit ATP-dependent processes including drug efflux and DNA damage repair. This leads to increased accumulation of Pt-drugs within cancer cells. Eventually, the polymeric dual-drug nanoparticle demonstrates appreciable antitumor effects on both cell line derived and patient derived xenograft lung cancer model. It is highly anticipated that the polymeric dual-or multi-drug systems can be applied for combination chemotherapy to achieve enhanced anticancer activity and reduced side effects.

Scalable production of recombinant three-finger proteins: from inclusion bodies to high quality molecular probes.

BACKGROUND: The three-finger proteins are a collection of disulfide bond rich proteins of great biomedical interests. Scalable recombinant expression and purification of bioactive three-finger proteins is quite difficult. RESULTS: We introduce a working pipeline for expression, purification and validation of disulfide-bond rich three-finger proteins using E. coli as the expression host. With this pipeline, we have successfully obtained highly purified and bioactive recombinant α-Βungarotoxin, k-Bungarotoxin, Hannalgesin, Mambalgin-1, α-Cobratoxin, MTα, Slurp1, Pate B etc. Milligrams to hundreds of milligrams of recombinant three finger proteins were obtained within weeks in the lab. The recombinant proteins showed specificity in binding assay and six of them were crystallized and structurally validated using X-ray diffraction protein crystallography. CONCLUSIONS: Our pipeline allows refolding and purifying recombinant three finger proteins under optimized conditions and can be scaled up for massive production of three finger proteins. As many three finger proteins have attractive therapeutic or research interests and due to the extremely high quality of the recombinant three finger proteins we obtained, our method provides a competitive alternative to either their native counterparts or chemically synthetic ones and should facilitate related research and applications.

Beyond genome: Advanced omics progress of Panax ginseng.

Ginseng is a perennial herb of the genus Panax in the family Araliaceae as one of the most important traditional medicine. Genomic studies of ginseng assist in the systematic discovery of genes related to bioactive ginsenosides biosynthesis and resistance to stress, which are of great significance in the conservation of genetic resources and variety improvement. The transcriptome reflects the difference and consistency of gene expression, and transcriptomics studies of ginseng assist in screening ginseng differentially expressed genes to further explore the powerful gene source of ginseng. Protein is the ultimate bearer of ginseng life activities, and proteomic studies of ginseng assist in exploring the biosynthesis and regulation of secondary metabolites like ginsenosides and the molecular mechanism of ginseng adversity adaptation at the overall level. In this review, we summarize the current status of ginseng research in genomics, transcriptomics and proteomics, respectively. We also discuss and look forward to the development of ginseng genome allele mapping, ginseng spatiotemporal, single-cell transcriptome, as well as ginseng post-translational modification proteome. We hope that this review will contribute to the in-depth study of ginseng and provide a reference for future analysis of ginseng from a systems biology perspective.

A Novel Ultrafiltrate Extract of Propolis Exerts Anti-inflammatory Activity through Metabolic Rewiring.

Thousands of years ago, humans started to use propolis because of its medicinal properties, and modern science has successfully identified several bioactive molecules within this resinous bee product. However, a natural propolis extract which has been removed the adhesive glue and preserved propolis bioactive compounds is urgently needed to maximise the therapeutic opportunities. In this study, a novel ultrafiltrate fraction from Brazilian green propolis, termed P30K, was demonstrated with anti-inflammatory properties, both in vitro and in vivo. Total flavonoids and total phenolic acids content in P30K were 244.6 mg/g and 275.8 mg/g respectively, while the IC50 value of inhibition of cyclooxygenase-2 (COX-2) was 8.30 µg/mL. The anti-inflammatory activity of P30K was furtherly corroborated in experimental models of lipopolysaccharides (LPS)-induced acute liver and lung injury. Mechanistically, integrated GC-MS and LC-MS based serum metabolomics analysis revealed that P30K modulated citrate cycle (TCA), pyruvate, glyoxylate and dicarboxylate metabolism pathways to inhibit secretion of pro-inflammatory cytokines. Results of network pharmacology and molecular docking suggested that P30K targeted catechol-O-methyltransferases (COMT), 11ß-hydroxysteroid dehydrogenases (HSD11B1), and monoamine oxidases (MAOA and MAOB) to promote cellular metabolomic rewiring. Collectively, our work reveals P30K as an efficient therapeutic agent against inflammatory conditions and its efficacy is related to metabolic rewiring.

Theta burst stimulation: what role does it play in stroke rehabilitation? A systematic review of the existing evidence.

Various post-stroke dysfunctions often result in poor long-term outcomes for stroke survivors, but the effect of conventional treatments is limited. In recent years, lots of studies have confirmed the effect of repetitive transcranial magnetic stimulation (rTMS) in stroke rehabilitation. As a new pattern of rTMS, theta burst stimulation (TBS) was proved recently to yield more pronounced and long-lasting after-effects than the conventional pattern at a shorter stimulation duration. To explore the role of TBS in stroke rehabilitation, this review summarizes the existing evidence from all the randomized controlled trials (RCTs) so far on the efficacy of TBS applied to different post-stroke dysfunctions, including cognitive impairment, visuospatial neglect, aphasia, dysphagia, spasticity, and motor dysfunction. Overall, TBS promotes the progress of stroke rehabilitation and may serve as a preferable alternative to traditional rTMS. However, it's hard to recommend a specific paradigm of TBS due to the limited number of current studies and their heterogeneity. Further high-quality clinical RCTs are needed to determine the optimal technical settings and intervention time in stroke survivors.

Precise coordination of high-loading Fe single atoms with sulfur boosts selective generation of nonradicals.

Nonradicals are effective in selectively degrading electron-rich organic contaminants, which unfortunately suffer from unsatisfactory yield and uncontrollable composition due to the competitive generation of radicals. Herein, we precisely construct a local microenvironment of the carbon nitride-supported high-loading (~9 wt.%) Fe single-atom catalyst (Fe SAC) with sulfur via a facile supermolecular self-assembly strategy. Short-distance S coordination boosts the peroxymonosulfate (PMS) activation and selectively generates high-valent iron-oxo species (FeIV=O) along with singlet oxygen (1O2), significantly increasing the 1O2 yield, PMS utilization, and p-chlorophenol reactivity by 6.0, 3.0, and 8.4 times, respectively. The composition of nonradicals is controllable by simply changing the S content. In contrast, long-distance S coordination generates both radicals and nonradicals, and could not promote reactivity. Experimental and theoretical analyses suggest that the short-distance S upshifts the d-band center of the Fe atom, i.e., being close to the Fermi level, which changes the binding mode between the Fe atom and O site of PMS to selectively generate 1O2 and FeIV=O with a high yield. The short-distance S-coordinated Fe SAC exhibits excellent application potential in various water matrices. These findings can guide the rational design of robust SACs toward a selective and controllable generation of nonradicals with high yield and PMS utilization.

Deciphering Structure-Activity Relationship Towards CO2 Electroreduction over SnO2 by A Standard Research Paradigm.

Authentic surface structures under reaction conditions determine the activity and selectivity of electrocatalysts, therefore, the knowledge of the structure-activity relationship can facilitate the design of efficient catalyst structures for specific reactivity requirements. However, understanding the relationship between a more realistic active surface and its performance is challenging due to the complicated interface microenvironment in electrocatalysis. Herein, we proposed a standard research paradigm to effectively decipher the structure-activity relationship in electrocatalysis, which is exemplified in the CO2 electroreduction over SnO2 . The proposed practice has aided in discovering authentic/resting surface states (Sn layer) of SnO2 accountable for the electrochemical CO2 reduction reaction (CO2 RR) performance under electrocatalytic conditions, which then is corroborated in the subsequent CO2 RR experiments over SnO2 with different morphologies (nanorods, nanoparticles, and nanosheets) in combination with in situ characterizations. This proposed methodology is further extended to the SnO electrocatalysts, providing helpful insights into catalytic structures. It is believed that our proposed standard research paradigm is also applicable to other electrocatalytic systems, in the meantime, decreases the discrepancy between theory and experiments, and accelerates the design of catalyst structures that achieve sustainable performance for energy conversion.

Percutaneous Endoscopic Lumbar Discectomy for Calcified Lumbar Disc Herniation: A Retrospective Cohort Study, Systematic Review and Meta-Analysis.

BACKGROUND: Calcified lumbar disc herniation (CLDH) is a subtype characterized by calcification, leading to increased surgical complexity. Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive technique, but its effectiveness and complications in CLDH patients remain to be fully evaluated. OBJECTIVE: To assess the effectiveness and complications of PELD in treating CLDH patients. STUDY DESIGN: A retrospective cohort study combined with a systematic review and meta-analysis. SETTING: Department of Pain Medicine, an affiliated hospital of a university. METHODS: Data from patients who underwent PELD in our department between March 2020 and May 2021 were collected. Forty CLDH patients were included in the study group, and equally matched cases with uncalcified lumbar disc herniation (UCLDH) served as controls. A systematic search was conducted on October 5, 2022, using EMBASE, PubMed, Cochrane Library, the China Biology Medicine disk, the China National Knowledge Infrastructure, and the Wanfang databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effects model was used to calculate pooled results. RESULTS: Eighty patients were included in the retrospective cohort, and 41 studies were included in the meta-analysis. Both the retrospective cohort and meta-analysis consistently showed a significant decrease in visual analog scale (VAS) and Oswestry Disability Index (ODI) scores in the CLDH group after the operation. In the retrospective cohort, the excellent or good rate according to the MacNab classification was 85%, with no reported complications. The meta-analysis revealed a pooled excellent or good rate of 91.8% and a low complication rate of 2.9%. Combining the findings from our retrospective cohort and meta-analysis, we observed that the CLDH group had longer operation times and slightly higher postoperative ODI scores compared to the UCLDH group. LIMITATIONS: Small sample size and lack of long-term follow-up in the retrospective cohort, as well as limited inclusion of comparative studies in the meta-analysis. CONCLUSION: PELD is an effective and safe treatment option for CLDH patients. In comparison to UCLDH patients, CLDH patients may experience longer operation times and slightly slower functional recovery than those with UCLDH.

Formulation and application of the "hospital-to-home + online-to-offline" treatment scheme in caring for and supporting vulnerable patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is the terminal stage of cardiovascular disease. OBJECTIVE: In this study, the "hospital-to-home + online-to-offline" (H2H + O2O) care scheme was implemented for patients with CHF during vulnerable periods, and its effect was evaluated. METHODS: Patients with CHF in the cardiovascular department of a Class III/Grade A hospital in Jiangxi Province from January to December 2020 were selected using a convenience sampling method and randomly divided into a control and intervention group (n= 100 each). The patients in the control group received routine in-hospital treatment and out-of-hospital follow-up, while in the intervention group, a multi-disciplinary cooperation team with CHF specialist nurses evaluated and stratified the patients before discharge and formulated individualized prescriptions and care plans. Based on the "Health & Happiness" chronic disease follow-up application designed for this study, the specialist nurses provided patients with one-to-one guidance. After three months, the cardiac function, heart failure knowledge, self-care behavior, and re-hospitalization rate of the patients were compared between the two groups. Cardiac function was evaluated by the serum B-type natriuretic peptide (BNP), the left ventricular ejection fraction (LVEF), and a six-minute walking test (6MWT). Heart failure knowledge and self-care behavior was assessed using specific questionaries. RESULTS: The level of cardiac function in the intervention group was significantly higher than that in the control group, and the difference was statistically significant (P< 0.001). The mastery of heart failure knowledge and self-care behavior in the intervention group were significantly higher than those in the control group, and the differences were statistically significant (P< 0.05). The re-hospitalization rate due to CHF in the intervention group was 21.0%, which was lower than that in the control group (35.0%), and the difference was statistically significant (P< 0.05). CONCLUSION: The H2H + O2O care scheme can be used for the transition of vulnerable patients with CHF from the hospital to family care to improve the patients' level of cardiac function, elevate their knowledge level and self-care abilities, and improve their overall health outcomes.

A chromosome-level genome assembly of anesthetic drug-producing Anisodus acutangulus provides insights into its evolution and the biosynthesis of tropane alkaloids.

Tropane alkaloids (TAs), which are anticholinergic agents, are an essential class of natural compounds, and there is a growing demand for TAs with anesthetic, analgesic, and spasmolytic effects. Anisodus acutangulus (Solanaceae) is a TA-producing plant that was used as an anesthetic in ancient China. In this study, we assembled a high-quality, chromosome-scale genome of A. acutangulus with a contig N50 of 7.4 Mb. A recent whole-genome duplication occurred in A. acutangulus after its divergence from other Solanaceae species, which resulted in the duplication of ADC1 and UGT genes involved in TA biosynthesis. The catalytic activities of H6H enzymes were determined for three Solanaceae plants. On the basis of evolution and co-expressed genes, AaWRKY11 was selected for further analyses, which revealed that its encoded transcription factor promotes TA biosynthesis by activating AaH6H1 expression. These findings provide useful insights into genome evolution related to TA biosynthesis and have potential implications for genetic manipulation of TA-producing plants.

Controllable chemical redox reactions to couple microbial degradation for organic contaminated sites remediation: A review.

Global environmental concern over organic contaminated sites has been progressively conspicuous during the process of urbanization and industrial restructuring. While traditional physical or chemical remediation technologies may significantly destroy the soil structure and function, coupling moderate chemical degradation with microbial remediation becomes a potential way for the green, economic, and efficient remediation of contaminated sites. Hence, this work systematically elucidates why and how to couple chemical technology with microbial remediation, mainly focused on the controllable redox reactions of organic contaminants. The rational design of materials structure, selective generation of reactive oxygen species, and estimation of degradation pathway are described for chemical oxidation. Meanwhile, current progress on efficient and selective reductions of organic contaminants (i.e., dechlorination, defluorination, -NO2 reduction) is introduced. Combined with the microbial remediation of contaminated sites, several consideration factors of how to couple chemical and microbial remediation are proposed based on both fundamental and practical points of view. This review will advance the understanding and development of chemical-microbial coupled remediation for organic contaminated sites.

Particle-Scale Understanding of Arsenic Interactions with Sulfidized Nanoscale Zerovalent Iron and Their Impacts on Dehalogenation Reactivity.

Co-occurrence of organic contaminants and arsenic oxoanions occurs often at polluted groundwater sites, but the effect of arsenite on the reactivity of sulfidized nanoscale zerovalent iron (SNZVI) used to remediate groundwater has not been evaluated. Here, we study the interaction of arsenite [As(III)] with SNZVI at the individual-particle scale to better understand the impacts on the SNZVI properties and reactivity. Surface and intraparticle accumulation of As was observed on hydrophilic FeS-Fe0 and hydrophobic FeS2-Fe0 particles, respectively. X-ray absorption spectroscopy indicated the presence of realgar-like As-S and elemental As0 species at low and high As/Fe concentration ratios, respectively. Single-particle inductively coupled plasma time-of-flight mass spectrometry analysis identified As-containing particles both with and without Fe. The probability of finding As-containing particles without Fe increased with the S-induced hydrophobicity of SNZVI. The interactions of SNZVI materials with coexisting arsenite inhibited their reactivity with water (∼5.8-230.7-fold), trichloroethylene (∼3.6-67.5-fold), and florfenicol (∼1.1-5.9-fold). However, the overall selectivity toward trichloroethylene and florfenicol relative to water was improved (up to 9.0-fold) because the surface-associated As increased the SNZVI hydrophobicity. These results indicate that reactions of SNZVI with arsenite can remove As from groundwater and improve the properties of SNZVI for dehalogenation selectivity.

[Effect and mechanism of Zexie Decoction in promoting white adipose tissue browning/brown adipose tissue activation based on GLP-1R/cAMP/PKA/CREB pathway].

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1ß, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.