Chelation-directed interface engineering of in-place self-cleaning membranes.

Water-energy sustainability will depend upon the rapid development of advanced pressure-driven separation membranes. Although energy-efficient, water-treatment membranes are constrained by ubiquitous fouling, which may be alleviated by engineering self-cleaning membrane interfaces. In this study, a metal-polyphenol network was designed to direct the armorization of catalytic nanofilms (ca. 18 nm) on inert polymeric membranes. The chelation-directed mineralized coating exhibits high polarity, superhydrophilicity, and ultralow adhesion to crude oil, enabling cyclable crude oil-in-water emulsion separation. The in-place flux recovery rate exceeded 99.9%, alleviating the need for traditional ex situ cleaning. The chelation-directed nanoarmored membrane exhibited 48-fold and 6.8-fold figures of merit for in-place self-cleaning regeneration compared to the control membrane and simple hydraulic cleaning, respectively. Precursor interaction mechanisms were identified by density functional theory calculations. Chelation-directed armorization offers promise for sustainable applications in catalysis, biomedicine, environmental remediation, and beyond.

Protein-activated atomic layer deposition for robust crude-oil-repellent hierarchical nano-armored membranes.

Atomic layer deposition (ALD) offers unique capabilities to fabricate atomically engineered porous materials with precise pore tuning and multi-functionalization for diverse applications like advanced membrane separations towards sustainable energy-water systems. However, current ALD technique is inhibited on most non-polar polymeric membranes due to lack of accessible nucleation sites. Here, we report a facile method to efficiently promote ALD coating on hydrophobic surface of polymeric membranes via novel protein activation/sensitization. As a proof of concept, TiO2 ALD-coated membranes activated by bovine serum albumin exhibit remarkable superhydrophilicity, ultralow underwater crude oil adhesion, and robust tolerance to rigorous environments including acid, alkali, saline, and ethanol. Most importantly, excellent cyclable crude oil-in-water emulsion separation performance can be achieved. The mechanism for activation/sensitization is rooted in reactivity for a particular set of amino acids. Furthermore, the universality of protein-sensitized ALD is demonstrated using common egg white, promising numerous potential usages in biomedical engineering, environmental remediation, low-carbon manufacturing, catalysis, and beyond.

Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury.

BACKGROUND: Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear. METHODS: In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro. RESULTS: We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells. CONCLUSIONS: ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.

Dexamethasone induces an imbalanced fetal-placental-maternal bile acid circulation: involvement of placental transporters.

BACKGROUND: The use of prenatal dexamethasone remains controversial. Our recent studies found that prenatal dexamethasone exposure can induce maternal intrahepatic cholestasis and have a lasting adverse influence on bile acid (BA) metabolism in the offspring. The purpose of this study was to investigate the effects of dexamethasone on fetal-placental-maternal BA circulation during the intrauterine period, as well as its placental mechanism. METHODS: Clinical data and human placentas were collected and analyzed. Pregnant Wistar rats were injected subcutaneously with dexamethasone (0.2 mg/kg per day) from gestational day 9 to 20. The metabolomic spectra of BAs in maternal and fetal rat serum were determined by LC-MS. Human and rat placentas were collected for histological and gene expression analysis. BeWo human placental cell line was treated with dexamethasone (20-500 nM). RESULTS: Human male neonates born after prenatal dexamethasone treatment showed an increased serum BA level while no significant change was observed in females. Moreover, the expression of organic anion transporter polypeptide-related protein 2B1 (OATP2B1) and breast cancer resistance protein (BCRP) in the male neonates' placenta was decreased, while multidrug resistance-associated protein 4 (MRP4) was upregulated. In experimental rats, dexamethasone increased male but decreased female fetal serum total bile acid (TBA) level. LC-MS revealed that primary BAs were the major component that increased in both male and female fetal serum, and all kinds of BAs were significantly increased in maternal serum. The expression of Oatp2b1 and Bcrp were reduced, while Mrp4 expression was increased in the dexamethasone-treated rat placentas. Moreover, dexamethasone increased glucocorticoid receptor (GR) expression and decreased farnesoid X receptor (FXR) expression in the rat placenta. In BeWo cells, dexamethasone induced GR translocation into the nucleus; decreased FXR, OATP2B1, and BCRP expression; and increased MRP4 expression. Furthermore, GR was verified to mediate the downregulation of OATP2B1, while FXR mediated dexamethasone-altered expression of BCRP and MRP4. CONCLUSIONS: By affecting placental BA transporters, dexamethasone induces an imbalanced fetal-placental-maternal BA circulation, as showed by the increase of primary BA levels in the fetal serum. This study provides an important experimental and theoretical basis for elucidating the mechanism of dexamethasone-induced alteration of maternal and fetal BA metabolism and for exploring early prevention and treatment strategies.

SIRT6 as a key event linking P53 and NRF2 counteracts APAP-induced hepatotoxicity through inhibiting oxidative stress and promoting hepatocyte proliferation.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively. Sirt6 knockdown in AML12 cells aggravated APAP-induced hepatocyte death and oxidative stress, inhibited cell viability and proliferation, and downregulated CCNA1, CCND1 and CKD4 protein levels. Sirt6 knockdown significantly prevented APAP-induced NRF2 activation, reduced the transcriptional activities of GSTµ and NQO1 and the mRNA levels of Nrf2, Ho-1, Gstα and Gstµ. Furthermore, SIRT6 showed potential protein interaction with NRF2 as evidenced by co-immunoprecipitation (Co-IP) assay. Additionally, the protective effect of P53 against APAP-induced hepatocytes injury was Sirt6-dependent. The Sirt6 mRNA was significantly down-regulated in P53 -/- mice. P53 activated the transcriptional activity of SIRT6 and exerted interaction with SIRT6. Our results demonstrate that SIRT6 protects against APAP hepatotoxicity through alleviating oxidative stress and promoting hepatocyte proliferation, and provide new insights in the function of SIRT6 as a crucial docking molecule linking P53 and NRF2.

p53 attenuates acetaminophen-induced hepatotoxicity by regulating drug-metabolizing enzymes and transporter expression.

Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. Inhibition of APAP metabolic activation and promotion in APAP disposition are important to protect against APAP-induced liver injury. Tumor suppressor p53 is traditionally recognized as a surveillance molecule to preserve genome integrity. Recent studies have emerged on discovering its functions in metabolic regulation. Our previous study reported that p53 promoted bile acid disposition and alleviated cholestastic syndrome. Here, we examined the effect of doxorubicin (Dox)-mediated p53 activation on APAP-induced hepatotoxicity in mice and revealed a novel role of p53 in regulating APAP metabolism and disposition. Histopathological and biochemical assessments demonstrated that administration of Dox (10 mg/kg/d) before APAP treatment (400 mg/kg) significantly alleviated APAP-induced hepatotoxicity. Dox treatment prevented APAP-induced GSH depletion and lipid peroxidation. p53-null mice were more susceptible to APAP-induced liver injury. Further, we found that the expression of drug-metabolizing enzymes and transporters CYPs, SULTs and MRPs was regulated by p53. Dox treatment also promoted Nrf2 activation and increased the expression of Nrf2 target genes including GSTα/µ and NQO1, which contribute to APAP detoxification. Overall, this study is the first to demonstrate the protective role of p53 in regulating APAP metabolism and disposition, which provides a potential new therapeutic target for APAP-induced liver injury.

Intrathecal dexmedetomidine as adjuvant to ropivacaine in hysteroscopic surgery: a prospective, randomized control study.

BACKGROUND: To compare the effects and side effects of intrathecal ropivacaine supplemented with dexmedetomidine and fentanyl in hysteroscopic surgery under spinal anesthesia. METHODS: Female patients (n = 108) undergoing operative hysteroscopic procedures under spinal anesthesia were randomly allocated to the following groups for subarachnoid drug delivery: R (n = 36) received 7.5 mg ropivacaine; RD (n = 36) received 7.5 mg ropivacaine plus 5 µg dexmedetomidine; RF (n = 36) received 7.5 mg ropivacaine plus 15 µg fentanyl. The onset and regression time of sensory and motor blockade, together with the postoperative analgesia and side effects were recorded. RESULTS: There was no significant difference as to sensory and motor onset time between groups. RD had significantly longer sensory and motor blockade time than RF and R. The mean time of sensory regression to the S1 segment was 191.25 ± 40.24 minutes in RD, 149.86 ± 37.46 minutes in RF, and 139.44 ± 38.97 minutes in R (RD vs. R and RD vs. RF, p < 0.001). The regression time of motor blockade to Bromage score 0 was 146.31 ± 40.72 minutes in RD, 80.28 ± 41.18 minutes in RF, and 84.94 ± 26.11 minutes in R (RD vs. R and RD vs. RF, p < 0.001). RD produced similar analgesia effect with RF, (2 hour visual analog scale (VAS) was 0.00 ± 0.00 and 0.31 ± 0.79, respectively) better than the R group (1.35 ± 1.65, p < 0.005). No pruritus occurred in the RD group, while the rate was 36.1% in the RF group. However, the RD group produced milder postsurgical hypotension (RD vs. R and RD vs. RF, p < 0.05). CONCLUSION: Intrathecal dexmedetomidine (5 µg) produced prolonged motor and sensory blockade and less pruritus compared with fentanyl (15 µg) in hysteroscopic surgery.