Selective Anchoring by Surface Sulfur Species Coupled with Rapid Interface Electron Transfer for Ultrahigh Capacity Extraction of Uranium from Seawater.

Improving the adsorption selectivity, enhancing the extraction capacity, and ensuring the structural stability of the adsorbent are the key to realize the high efficiency recovery of uranium. In this work, we utilized the strong Lewis acid-base interaction between S2- and U(VI)O22+ coupling rapid electron transfer at the MnS/U(VI)O22+ solid-liquid interface to achieve excellent selectivity, high adsorption capacity, and rapid extraction of uranium. The as-synthesized MnS adsorbent exhibited an ultrahigh uranium extraction capacity (2457.05 mg g-1) and a rapid rate constant (K = 9.11 × 10-4 g h-1 mg-1) in seawater with 100.7 ppm of UO2(NO3)2 electrolyte. The kinetic simulation reveals that this adsorption process is a chemical adsorption process and conforms to a pseudo-second-order kinetic model, indicating electron transfer at the MnS/U(VI)O22+ solid-liquid interface. The relevant (quasi) in situ spectroscopic characterization and theoretical calculation results further revealed that the outstanding uranium extraction property of MnS could be attributed to the highly selective UO22+ adsorption of MnS with lower adsorption energy as a result of the strong interaction between S2- and UO22+ and the rapid mass transfer and interface electron transfer from S2- and low-valent Mn(II) to U(VI)O22+.

[Establishment of a quantitative method for GC analysis of polyoxyethylene (35) castor oil in microemulsion extracts].

With the continuous exploration of microemulsions as solvents for traditional Chinese medicine extraction, polyoxyethy-lene(35) castor oil(CrEL), a commonly used surfactant, is being utilized by researchers. However, the problem of detecting residues of this surfactant in microemulsion extracts has greatly hampered the further development of microemulsion solvents. Based on the chemical structures of the components in CrEL and the content determination method of castor oil in the 2020 edition of the Chinese Pharmacopoeia(Vol. Ⅳ), this study employed gas chromatography(GC) and single-factor experiments to optimize the preparation method of methyl ricinoleate from CrEL. The conversion coefficient between the two was validated, and the optimal sample preparation method was used to process microemulsion extracts of Zexie Decoction from three batches. The content of methyl ricinoleate generated was determined, and the content of CrEL in the microemulsion extracts of Zexie Decoction was calculated using the above conversion coefficient. The results showed that the optimal preparation method for CrEL was determined. Specifically, 10 mL of 1 mol·L~(-1) KOH-methanol solution was heated at 60 ℃ for 15 min in a water bath. Subsequently, 10 mL of boron trifluoride etherate-methanol(1∶3) solution was heated at 60 ℃ for 15 min in a water bath, followed by extraction with n-hexane twice. CrEL could stably produce 20.84% methyl ricinoleate. According to this conversion coefficient, the average mass concentration of CrEL in the three batches of Zexie Decoction microemulsion extracts was 11.94 mg·mL~(-1), which was not significantly different from the CrEL mass concentration of 11.57 mg·mL~(-1) during microemulsion formulation, indicating that the established content determination method of this study was highly accurate, sensitive, and repeatable. It can be used for subsequent research on microemulsion extracts of Zexie Decoction and provide a reference for quality control of other drug formulations containing CrEL.

Strengthening Fe(II)/Fe(III) Dynamic Cycling by Surface Sulfation to Achieve Efficient Electrochemical Uranium Extraction at Ultralow Cell Voltage.

Electrochemically mediated Fe(II)/Fe(III) redox-coupled uranium extraction can efficiently reduce the cell voltage of electrochemical uranium extraction (EUE). How to regulate the surface structure to enhance the uranium acyl ion adsorption capacity and strengthen the Fe(II)/Fe(III) redox cycle process is crucial for EUE. In this work, we developed surface sulfated nanoreduced iron (S-NRI) for EUE and exhibited improved properties for EUE at an ultralow cell voltage (-0.1 V). Compared with a nanoreduced iron (NRI) adsorbent, S-NRI displayed faster electrochemical extraction kinetics properties and higher extraction efficiency and capacity for uranium. In a more complex seawater electrolyte containing uranyl ion concentration ranging from 1 to 20 ppm, the removal efficiency could reach almost ∼100% after EUE for 24 h. At a higher 50 ppm uranium acyl ion concentration in a seawater electrolyte, S-NRI exhibited higher extraction capacity (755.03 mg/g), which is better than 528.53 mg/g of NRI at a cell voltage of -0.1 V. Outstanding EUE property could be attributed to the fact that sulfate species (M-SO42-) on the S-NRI surface not only enhanced selective adsorption of uranyl ions but also strengthened the Fe(II)/Fe(III) redox cycle, which accelerated electron transfer between Fe(II) and U(VI), promoted the regeneration of Fe(II) active sites, and finally enhanced the EUE property.

Cylindrin from Imperata cylindrica inhibits M2 macrophage formation and attenuates renal fibrosis by downregulating the LXR-α/PI3K/AKT pathway.

Imperata cylindrica, a medicinal plant used in Traditional Chinese Medicine, has been used to treat chronic kidney disease. Extracts of I. cylindrica display anti-inflammatory, immunomodulatory, and anti-fibrotic properties. However, the active components of the extracts and their protective mechanisms have not been fully elucidated. In this study, we explored the ability of cylindrin, the main active compound extracted from I. cylindrica, to protect against renal fibrosis and to investigate the potential mechanisms involved. At high doses, cylindrin exerted protective effects against folic acid-induced kidney fibrosis in mice. Bioinformatic analysis predicted the LXR-α/PI3K/AKT pathway as a target of regulation by cylindrin. This was supported by our in vitro and in vivo results showing that cylindrin significantly downregulated the expression of LXR-α and phosphorylated PI3K/AKT in M2 macrophages and mouse renal tissues. Furthermore, high-dose cylindrin inhibited M2 polarization of IL-4-stimulated macrophages in vitro. Our results suggest that cylindrin alleviates renal fibrosis by attenuating M2 macrophage polarization through inhibition of the PI3K/AKT pathway via downregulation of LXR-α.

Network pharmacology- and molecular simulation-based exploration of therapeutic targets and mechanisms of heparin for the treatment of sepsis/COVID-19.

Critically infected patients with COVID-19 (coronavirus disease 2019) are prone to develop sepsis-related coagulopathy as a result of a robust immune response. The mechanism underlying the relationship between sepsis and COVID-19 is largely unknown. LMWH (low molecular weight heparin) exhibits both anti-inflammatory and anti-coagulating properties that result in a better prognosis of severely ill patients with COVID-19 co-associated with sepsis-induced coagulopathy or with a higher D-dimer value. Heparin-associated molecular targets and their mechanism of action in sepsis/COVID-19 are not well understood. In this work, we characterize the pharmacological targets, biological functions and therapeutic actions of heparin in sepsis/COVID-19 from the perspective of network pharmacology. A total of 38 potential targets for heparin action against sepsis/COVID-19 and 8 core pharmacological targets were identified, including IL6, KNG1, CXCL8, ALB, VEGFA, F2, IL10 and TNF. Moreover, enrichment analysis showed that heparin could help in treating sepsis/COVID-19 through immunomodulation, inhibition of the inflammatory response, regulation of angiogenesis and antiviral activity. The pharmacological effects of heparin against these targets were further confirmed by molecular docking and simulation analysis, suggesting that heparin exerts effective binding capacity by targeting the essential residues in sepsis/COVID-19. Prospective clinical practice evaluations may consider the use of these key prognostic indicators for the treatment of sepsis/COVID-19.Communicated by Ramaswamy H. Sarma.

Identification of circular RNA biomarkers for Pien Tze Huang treatment of CCl4­induced liver fibrosis using RNA­sequencing.

Pien Tze Huang (PZH), a common hepatoprotective Traditional Chinese Medicine that has been found to be an effective treatment for carbon tetrachloride­induced hepatic damage, including liver fibrosis. Circular RNAs (circRNAs) serve a crucial role in regulating gene expression levels via circRNA/micro (mi)RNA/mRNA networks in several human diseases and biological processes. However, whether circRNAs are involved in the underlying mechanism of the therapeutic effects of PZH on liver fibrosis remains unclear. Therefore, the aim of the present study was to investigate these effects using circRNA expression profiles from PZH­treated fibrotic livers in model mice. A case­control study on >59,476 circRNAs from CCl4­induced (control group, n=6) and PZH­treated (case group, n=6) mice was performed using circRNA sequencing in liver tissues. PZH treatment resulted in the differential expression of 91 circRNAs, including 58 upregulated and 33 downregulated circRNAs. Furthermore, the construction of competing endogenous networks also indicated that differentially expressed circRNAs acted as miRNA sponges. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of miRNA targets demonstrated that PZH­affected circRNAs were mainly involved in biological processes such as 'positive regulation of fibroblast proliferation', 'cellular response to interleukin­1' and 'regulation of DNA­templated transcription in response to stress' and in a number of important pathways, such as 'TNF signaling pathway', 'PI3K­Akt signaling pathway', 'IL­17 signaling pathway' and 'MAPK signaling pathway'. To further validate the bioinformatics data, reverse transcription­-quantitative PCR was performed on seven miRNA targets in a human hepatic stellate LX­2 cell model. The results suggested that seven of the miRNAs exhibited regulatory patterns that were consistent with those of the transcriptome sequencing results. Kaplan­Meier survival analysis demonstrated that the expression levels of dihydrodiol dehydrogenase and solute carrier family 7, member 11 gene were significantly associated with patient survival, 269 patients with liver hepatocellular carcinoma from The Cancer Genome Atlas database. To the best of our knowledge, this was the first study to provide evidence that PZH affects circRNA expression levels, which may serve important roles in PZH­treated fibrotic liver through the regulation of functional gene expression. In conclusion, the present study provided new insights into the mechanism underlying the pathogenesis of liver fibrosis and identified potential novel, efficient, therapeutic targets against liver injury.

Functional 2D Iron-Based Nanosheets for Synergistic Immunotherapy, Phototherapy, and Chemotherapy of Tumor.

Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.

[Optimization of extraction process of Congrong Shujing Granules based on AHP-CRITIC analysis].

The index weight coefficients were determined by comparing the analytic hierarchy process(AHP), the criteria importance through inter-criteria correlation(CRITIC), and the AHP-CRITIC mixed weighting method. The comprehensive scores of index components(echinacoside, salvianolic acid B, paeoniflorin, and ointment yield) of each group in the orthogonal test were compared to optimize the extraction process of Congrong Shujing Granules. The results showed that the AHP-CRITIC mixed weighting method scientifically optimized the extraction process. To be specific, the decoction pieces should be added with the 6-fold amount of water and extracted twice, 1 h each time. After three verification tests, the average mass fractions of echinacoside, salvianolic acid B, and paeoniflorin were 0.72, 9.34, and 5.92 mg·g~(-1), respectively, and the average ointment yield was 47.18%. As verified by the AHP-CRITIC mixed weighting method and the orthogonal test, the optimized extraction process of Congrong Shujing Granules was stable and feasible and could be applied to industrial production.

[Preparation of paclitaxel-loaded and folic acid-modified poly (lactic-co-glycolic acid) nano-micelles and in vitro anticancer effect on cervical cancer HeLa cells].

The paclitaxel-loaded and folic acid-modified poly(lactic-co-glycolic acid) nano-micelles(PTX@FA-PLGA-NMs) were prepared by the emulsion solvent evaporation method, and the parameters of paclitaxel-loaded nano-micelles were optimized with the particle size and PDI as evaluation indexes. The morphology of the nano-micelles was observed by transmission electron microscopy(TEM), and the stability, drug loading and encapsulation efficiency were systematically investigated. In vitro experiments were performed to study the cytotoxic effects of nano-micelles, apoptosis, and cellular uptake. Under the optimal parameters, the nano-micelles showed the particle size of(125.3±1.2) nm, the PDI of 0.086±0.026, the zeta potential of(-20.0±3.8) mV, the drug loading of 7.2%±0.75%, and the encapsulation efficiency of 50.7%±1.0%. The nano-micelles were in regular spherical shape as observed by TEM. The blank FA-PLGA-NMs exhibited almost no inhibitory effect on the proliferation and growth of tumor cells, while the drug-loaded nano-micelles and free PTX exhibited significant inhibitory effects. The IC_(50) of PTX@FA-PLGA-NMs and PTX was 0.56 µg·mL~(-1) and 0.66 µg·mL~(-1), respectively. The paclitaxel-loaded nano-micelles were potent in inhibiting cell migration as assessed by the scratch assay. PTX@FA-PLGA-NMs had good pro-apoptotic effect on cervical cancer HeLa cells and significantly promoted the uptake of HeLa cells. The results of in vitro experiments suggested that PTX@FA-PLGA-NMs could target and treat cervical cancer HeLa cells. Therefore, as nanodrug carriers, PTX@FA-PLGA-NMs with anti-cancer activity are a promising nano-system for improving the-rapeutic effects on tumors.

New strategy for identifying potential natural HIV-1 non-nucleoside reverse transcriptase inhibitors against drug-resistance: an in silico study.

Non-nucleosides reverse transcriptase inhibitors (NNRTIs), specifically targeting the HIV-1 reverse transcriptase (RT), play a unique role in anti-AIDS agents due to their high antiviral potency, structural diversity, and low toxicity in antiretroviral combination therapies used to treat HIV. However, due to the emergence of new drug-resistant strains, the development of novel NNRTIs with adequate potency, improved resistance profiles and less toxicity is highly required. In this work, a novel virtual screening strategy combined with structure-based drug design was proposed to discover the potential inhibitors against drug-resistant HIV strains. Seven structure-variant RTs, ranging from the wild type to a hypothetical multi-mutant were regarded as target proteins to perform structure-based virtual screening. Totally 23 small molecules with good binding affinity were identified from the Traditional Chinese Medicine database (TCM) as potential NNRTIs candidates. Among these hits, (+)-Hinokinin has confirmed anti-HIV activity, and some hits are structurally identical with anti-HIV compounds. Almost all these hits are consistent with external experimental results. Molecular simulations analysis revealed that top 2 hits (Pallidisetin A and Pallidisetin B) bind stably and in high affinity to HIV-RT, which are ready to be experimental confirmed. These results suggested that the strategy we proposed is feasible, trustworthy and effective. Our finding might be helpful in the identification of novel NNRTIs against drug-resistant, and also provide a new clue for the discovery of HIV drugs in natural products.Communicated by Ramaswamy H. Sarma.

Atractylenolide III Attenuates Muscle Wasting in Chronic Kidney Disease via the Oxidative Stress-Mediated PI3K/AKT/mTOR Pathway.

Oxidative stress contributes to muscle wasting in advanced chronic kidney disease (CKD) patients. Atractylenolide III (ATL-III), the major active constituent of Atractylodes rhizome, has been previously reported to function as an antioxidant. This study is aimed at investigating whether ATL-III has protective effects against CKD-induced muscle wasting by alleviating oxidative stress. The results showed that the levels of serum creatinine (SCr), blood urea nitrogen (BUN), and urinary protein significantly decreased in the ATL-III treatment group compared with the 5/6 nephrectomy (5/6 Nx) model group but were higher than those in the sham operation group. Skeletal muscle weight was increased, while inflammation was alleviated in the ATL-III administration group compared with the 5/6 Nx model group. ATL-III-treated rats also showed reduced dilation of the mitochondria, increased CAT, GSH-Px, and SOD activity, and decreased levels of MDA both in skeletal muscles and serum compared with 5/6 Nx model rats, suggesting that ATL-III alleviated mitochondrial damage and increased the activity of antioxidant enzymes, thus reducing the production of ROS. Furthermore, accumulated autophagosomes (APs) and autolysosomes (ALs) were reduced in the gastrocnemius (Gastroc) muscles of ATL-III-treated rats under transmission electron microscopy (TEM) together with the downregulation of LC3-II and upregulation of p62 according to Western blotting. This evidence indicated that ATL-III improved skeletal muscle atrophy and alleviated oxidative stress and autophagy in CKD rats. Furthermore, ATL-III could also increase the protein levels of p-PI3K, p-AKT, and p-mTOR in skeletal muscles in CKD rats. To further reveal the relevant mechanism, the oxidative stress-mediated PI3K/AKT/mTOR pathway was assessed, which showed that a reduced expression of p-PI3K, p-AKT, and p-mTOR in C2C12 myoblast atrophy induced by TNF-α could be upregulated by ATL-III; however, after the overexpression of Nox2 to increase ROS production, the attenuated effect was reversed. Our findings indicated that ATL-III is a potentially protective drug against muscle wasting via activation of the oxidative stress-mediated PI3K/AKT/mTOR pathway.

Dabigatran as an alternative for atrial thrombosis resistant to rivaroxaban: A case report.

RATIONALE: Anti-thrombosis therapy for atrial fibrillation (AF) management and stroke prevention is an important aspect of disease management. Novel oral anticoagulants (NOACs) are recommended by guidelines for AF management. However, if one can switch one NOAC to another when the former showed a poor effect has not been fully determined. PATIENT CONCERNS: A 52-year-old man was admitted to our center for heart failure and AF with a thrombus in the left atrium. DIAGNOSES: Cardiomyopathy was diagnosed by cardiac magnetic resonance (CMR) and echocardiography. INTERVENTIONS: He was prescribed rivaroxaban (20 mg daily) as treatment, and dabigatran (150 mg twice daily) was used when the thrombus was found to be non-response to rivaroxaban. OUTCOMES: The rivaroxaban did not diminish the atrial thrombus, and dabigatran was given instead which finally eliminated the thrombus. LESSONS: Individualized responsiveness to NOACs should be considered and paid more attention to during clinical practice.

Flavored Guilu Erxian decoction inhibits the injury of human bone marrow mesenchymal stem cells induced by cisplatin.

To examine the exact role of flavored Guilu Erxian decoction, a Traditional Chinese Medicine (TCM) in the treatment of cisplatin-induced side-effects in bone marrow mesenchymal stem cells (BM-MSCs). BM-MSCs were isolated from bone marrow collected from SD rats and identified by flow cytometry. Cells were cultivated in MEM alpha medium containing 5% (TCM-L), 10% (TCM-M) and 20% (TCM-H) dosages of flavored Guilu Erxian decoction with or without cisplatin. Cell viability was determined through CCK-8 and thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Flow cytometry was used to determine cell cycle and apoptosis. The expression of p21 and cleaved-caspase-3 were examined using Western blot assay. The PI3K-AKT-mTOR pathway associated proteins, including p-PI3K, p-AKT and p-mTOR, were also examined by Western blot assay. CCK-8 and EdU staining assay demonstrated that cisplatin could inhibit cell proliferation in BM-MSCs in a dose and time dependent manner. Further, cisplatin could induce apoptosis through increasing G0/G1 cell cycle arrest, p21 and cleaved-caspase-3 expression. However, these phenomena would be significantly alleviated when adding the serum containing flavored Guilu Erxian decoction. Furthermore, the PI3K-AKT-mTOR pathway activation could be inhibited by cisplatin in BM-MSCs, while flavored Guilu Erxian decoction treatment successfully abrogated this effect. Combination of flavored Guilu Erxian decoction and cisplatin could reduce the damage to BM-MSCs. This indicates that the flavored Guilu Erxian decoction can enhance the possibility of BM-MSCs repairing and rehabilitating the normal function of injured tissues induced by cisplatin, which could provide a new direction for therapeutic applications.

Daily 10 mg rivaroxaban as a therapy for ventricular thrombus related to left ventricular non-compaction cardiomyopathy: A case report.

RATIONALE: Left ventricular non-compaction cardiomyopathy (LVNC) is a rare heart disorder related to thrombosis. Anticoagulant therapy is suggested for the treatment of this disease. The success of the novel oral anticoagulant rivaroxaban as a treatment option for this disorder is unclear. PATIENT CONCERNS: A 43-year-old man who felt dizzy at rest was found to have an intraventricular thrombus. DIAGNOSES: The thrombus was confirmed by echocardiography. And LVNC was diagnosed by cardiac magnetic resonance (CMR) and echocardiography. INTERVENTIONS: He was prescribed a low dose (10 mg daily) of rivaroxaban as treatment. OUTCOMES: After 3 months, the thrombus diminished, and the manifestation disappeared. LESSONS: Low dose of rivaroxaban may serve as a viable option for anticoagulation therapy in LVNC patients, with large clinical trials needed to determine the best course of treatment.

Predicting interatrial septum rotation: is the position of the heart or the direction of the coronary sinus reliable?: Implications for interventional electrophysiologists from CT studies.

BACKGROUND: Determining the location of the interatrial septum (IAS) is crucial for cardiac electrophysiology procedures. Empirical methods of predicting IAS orientation depend on anatomical landmarks, including determining it from the direction of the coronary sinus (CS) and the position of the heart (e.g., vertical or transverse). However, the reliability of these methods for predicting IAS rotation warrants further study. The purpose of this study was to assess the clinical utility of the relationship between IAS orientation, CS direction, and heart position. METHODS: Data from 115 patients undergoing coronary computed tomography (CT) angiography with no evidence of cardiac structural disease were collected and analyzed. Angulations describing IAS orientation, CS direction, and heart position were measured. The relationships between IAS orientation and each of the other two parameters were subsequently analyzed. RESULTS: The mean angulations for IAS orientation, CS direction, and heart position were 36.8 ± 7.3° (range 19.1-53.6), 37.7 ± 6.6° (range 21.3-50.1), and 37.1 ± 8.3° (range 19.2-61.0), respectively. We found a significant correlation between IAS orientation and CS direction (r = 0.928; P < 0.01), and the linear regression equation was drawn: IAS orientation = 2.01 + 1.03 × CS direction (r(2) = 0.86). No correlation was observed between IAS orientation and heart position (P = 0.86). CONCLUSION: In patients without structural heart disease, CS direction may be a reliable predictor of IAS orientation, and may serve as a helpful reference for clinicians during invasive electrophysiological procedures. Further study is warranted to clarify the relationship between IAS orientation and heart position.