A Novel Cocrystal of Daidzein with Piperazine to Optimize the Solubility, Permeability and Bioavailability of Daidzein.

It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, cholesterol lowering, neuroprotective, cardioprotective and so on. To our disappointment, poor solubility, low permeability and inferior bioavailability seriously limit its clinical application and market development. To optimize the solubility, permeability and bioavailability of daidzein, the cocrystal of daidzein and piperazine was prepared through a scientific and reasonable design, which was thoroughly characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Combining single-crystal X-ray diffraction analysis with theoretical calculation, detailed structural information on the cocrystal was clarified and validated. In addition, a series of evaluations on the pharmacogenetic properties of the cocrystal were investigated. The results indicated that the cocrystal of daidzein and piperazine possessed the favorable stability, increased solubility, improved permeability and optimized bioavailability of daidzein. Compared with the parent drug, the formation of cocrystal, respectively, resulted in 3.9-, 3.1-, 4.9- and 60.8-fold enhancement in the solubility in four different media, 4.8-fold elevation in the permeability and 3.2-fold in the bioavailability of daidzein. Targeting the pharmaceutical defects of daidzein, the surprising elevation in the solubility, permeability and bioavailability of daidzein was realized by a clever cocrystal strategy, which not only devoted assistance to the market development and clinical application of daidzein but also paved a new path to address the drug-forming defects of insoluble drugs.

Current advances on the therapeutic potential of scutellarin: an updated review.

Scutellarin is widely distributed in Scutellaria baicalensis, family Labiatae, and Calendula officinalis, family Asteraceae, and belongs to flavonoids. Scutellarin has a wide range of pharmacological activities, it is widely used in the treatment of cerebral infarction, angina pectoris, cerebral thrombosis, coronary heart disease, and other diseases. It is a natural product with great research and development prospects. In recent years, with in-depth research, researchers have found that wild scutellarin also has good therapeutic effects in anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, treatment of metabolic diseases, and protection of kidney. The cancer treatment involves glioma, breast cancer, lung cancer, renal cancer, colon cancer, and so on. In this paper, the sources, pharmacological effects, in vivo and in vitro models of scutellarin were summarized in recent years, and the current research status and future direction of scutellarin were analyzed.

Optimized solubility and bioavailability of genistein based on cocrystal engineering.

With various potential health-promoting bioactivities, genistein has great prospects in treatment of a series of complex diseases and metabolic syndromes such as cancer, diabetes, cardiovascular diseases, menopausal symptoms and so on. However, poor solubility and unsatisfactory bioavailability seriously limits its clinical application and market development. To optimize the solubility and bioavailability of genistein, the cocrystal of genistein and piperazine was prepared by grinding assisted with solvent based on the concept of cocrystal engineering. Using a series of analytical techniques including single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis, the cocrystal was characterized and confirmed. Then, structure analysis on the basis of theoretical calculation and a series of evaluation on the stability, dissolution and bioavailability were carried out. The results indicated that the cocrystal of genistein and piperazine improved the solubility and bioavailability of genistein. Compared with the previous studies on the cocrystal of genistein, this is a systematic and comprehensive investigation from the aspects of preparation, characterization, structural analysis, stability, solubility and bioavailability evaluation. As a simple, efficient and green approach, cocrystal engineering can pave a new path to optimize the pharmaceutical properties of natural products for successful drug formulation and delivery.

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease.

BACKGROUND: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking. METHODS: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD. RESULTS: The absolute number of DNT cells in the healthy Chinese population was 109 (70-157)/µL, accounting for 5.82 (3.98-8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23-0.93; P = 0.031). CONCLUSIONS: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

Application potential of zero-valent aluminum in nitrophenols wastewater decontamination: Enhanced reactivity, electron selectivity and anti-passivation capability.

Nitrophenols (NPs) are highly toxic and easy to accumulate to high concentrations (> 500 mg/L) in real wastewater. The nitro group contained in NPs is an electron-absorbing group that is easy to reduce and difficult to oxidize, so there is an urgent need to develop reduction removal technology. Zero-valent aluminum (ZVAl) is an excellent electron donor that can reductively transform various refractory pollutants. However, ZVAl is prone to rapid deactivation due to non-selective reactions with water, ions, etc. To overcome this critical limitation, we prepared a new type of carbon nanotubes (CNTs) modified microscale ZVAl, CNTs@mZVAl, through a facile mechanochemical ball milling method. CNTs@mZVAl had outstanding high reactivity in degrading p-nitrophenol even 1000 mg/L and showed up to 95.50% electron utilization efficiency. Moreover, CNTs@mZVAl was highly resistant to the passivation by dissolved oxygen, ions and natural organic matters coexisting in water matrix, and remained highly reactive after aging in the air for 10 days. Furthermore, CNTs@mZVAl could effectively remove dinitrodiazophenol from real explosive wastewater. The excellent performance of CNTs@mZVAl is due to the combination of selective adsorption of NPs and CNTs-mediated e-transfer. CNTs@mZVAl looks promising for the efficient and selective degradation of NPs, with broader prospects for real wastewater treatment.

Toward rapid reduction of carbon tetrachloride in water by zero-valent aluminum/persulfate system.

The oxidation performance of the zero-valent aluminum (ZVAl)/persulfate (PS) combined system had been studied by researchers in the past, which relied on the activation of PS by ZVAl to generate potent oxidizing radicals (•OH and SO4•-) to degrade pollutants. However, ZVAl is a strong reductant and its reduction effect cannot be ignored. The reductive performance of the ZVAl/PS combined system is still unknown. Therefore, carbon tetrachloride (CT), an antioxidant organic pollutant, was selected as the target pollutant to test the reductive performance of the ZVAl/PS system in this study. We found a significant synergistic effect between ZVAl and PS, and the ZVAl/PS combined system could rapidly degrade CT in a wide pH range of 3-11 after an induction period. By SEM-EDS, TEM, XPS, and XRD analysis, it was found that PS could promote the corrosion of the oxide film on the ZVAl surface. The quenching experiment proved that PS could accept the electrons released from ZVAl to produce superoxide radical anion (O2•-), which led to the degradation of CT rather than the oxidative process by •OH and SO4•-. The hydrogen evolution experiment indicated that electronic reduction might play a secondary role in CT degradation. In conclusion, our study further explored the reductive performance of the ZVAl/PS combined system and expanded the pathway of CT degradation without any organic solvent addition, which provides a new strategy for the efficient degradation of refractory halogenated organic pollutants.

Cocrystals of Praziquantel with Phenolic Acids: Discovery, Characterization, and Evaluation.

Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using the SAG method have the structural characteristics of carboxylic acid dimer, and two cocrystals prepared using the SSE method formed cocrystal solvates with the structural characteristics of carboxylic acid monomer. For phenolic acids containing only one phenolic hydroxyl group (ferulic acid), when preparing cocrystals with PRA by using SAG and SSE, the same product was obtained. In addition, the weak molecular interactions that were observed in the cocrystal are explained at the molecular level by using theoretical calculation methods. Finally, the in vitro solubility of cocrystals without crystal solvents and in vivo bioavailability of PRA-FA were evaluated to further understand the influence on the physicochemical properties of API for the introduction of CCF.

Mechanochemical destruction and mineralization of solid-phase hexabromocyclododecane assisted by microscale zero-valent aluminum.

Hexabromocyclododecane (HBCD) has been listed in Annex A of the Stockholm Convention as a persistent and bio-accumulative chemical. While HBCD is often present in the solid form for its low solubility, cost-effective technologies have been lacking for the degradation of solid-phase HBCD. In this work, mechanochemical (MC) destruction of high-energy ball milling was employed for direct destruction of solid-phase HBCD, where a strong reducer, microscale zero-valent aluminum (mZVAl), was used as the co-milling agent. The new mZVAl-assisted MC process achieved complete debromination and mineralization of HBCD within 3 h milling. The optimal operating parameters were determined, including the milling atmosphere, the milling speed, the mZVAl-to-HBCD molar ratio, and the ball-to-mZVAl mass ratio. Fourier transform infrared spectrometry and Raman analyses revealed that the organic structures of HBCD were destroyed and organic bromine was completely converted into inorganic bromide, accompanied by the generation of amorphous and graphite carbon. Analysis of the milled samples by GC-MS demonstrated the absence of obvious organic matter after MC treatment, also indicating the complete degradation and conversion of HBCD to inorganic compounds. Further X-ray photoelectron spectroscopic analysis indicates that the fresh surface of mZVAl was generated upon the MC treatment, and Al(0) served as a strong reducing agent (e-donor) for reductive debromination and destruction of the carbon skeleton. The mZVAl-assisted MC milling appears promising as a non-combustion approach for effective destruction and carbonization/mineralization of solid-phase HBCD or potentially other persistent organic pollutants.

CircEXOC6B Suppresses the Proliferation and Motility and Sensitizes Ovarian Cancer Cells to Paclitaxel Through miR-376c-3p/FOXO3 Axis.

Background: Circular RNAs (circRNAs) are regarded as important regulators in the tumorigenesis of multiple cancers. However, the characterization of circRNA exocyst complex component 6B (circEXOC6B) in ovarian cancer is barely known. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the enrichment of circEXOC6B, microRNA-376c-3p (miR-376c-3p), and forkhead box O3 (FOXO3). Cell proliferation was examined by Cell Counting Kit-8 (CCK8) assay and colony formation assay. Cell metastasis was measured by transwell assays. Western blot assay was conducted to examine the expression of proliferation and metastasis-related proteins and FOXO3. The chemoresistance of ovarian cancer cells was analyzed by CCK8 assay. Flow cytometry was used to detect cell apoptosis. The activities of caspase3 and caspase9 were analyzed through using colorimetric assay kits. The direct interaction between miR-376c-3p and circEXOC6B or FOXO3 was predicted by StarBase software and confirmed by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Murine xenograft assay was conducted to verify the role of circEXOC6B on the paclitaxel (PTX) resistance of ovarian cancer cells in vivo. Results: The level of circEXOC6B was notably decreased in ovarian cancer tissues. Low level of circEXOC6B was associated with malignant pathological characteristics in ovarian cancer patients. CircEXOC6B suppressed the proliferation and motility and decreased the chemoresistance of ovarian cancer cells to PTX. CircEXOC6B functioned through directly targeting and downregulating miR-376c-3p. FOXO3 was a direct target of miR-376c-3p, and the abundance of FOXO3 was regulated by circEXOC6B/miR-376c-3p axis. CircEXOC6B accelerated the PTX sensitivity of ovarian cancer cells through acting as a decoy of miR-376c-3p to upregulate FOXO3 in vivo. Conclusion: CircEXOC6B suppressed the progression and PTX resistance of ovarian cancer cells through sequestering miR-376c-3p, thus enhancing FOXO3 level.

Vitellogenin from planthopper oral secretion acts as a novel effector to impair plant defenses.

Vitellogenin (Vg) is a well-known nutritious protein involved in reproduction in nearly all oviparous animals, including insects. Recently, Vg has been detected in saliva proteomes of several piercing-sucking herbivorous arthropods, including the small brown planthopper (Laodelphax striatellus, SBPH). Its function, however, remains unexplored. We investigated the molecular mechanism underlying SBPH orally secreted Vg-mediated manipulation of plant-insect interaction by RNA interference, phytohormone and H2 O2 profiling, protein-protein interaction studies and herbivore bioassays. A C-terminal polypeptide of Vg (VgC) in SBPH, when secreted into rice plants, acted as a novel effector to attenuate host rice defenses, which in turn improved insect feeding performance. Silencing Vg reduced insect feeding and survival on rice. Vg-silenced SBPH nymphs consistently elicited higher H2 O2 production, a well-established defense mechanism in rice, whereas expression of VgC in planta significantly hindered hydrogen peroxide (H2 O2 ) accumulation and promoted insect performance. VgC interacted directly with the rice transcription factor OsWRKY71, a protein which is involved in induction of H2 O2 accumulation and plant resistance to SBPH. These findings indicate a novel effector function of Vg: when secreted into host rice plants, this protein effectively weakened H2 O2 -mediated plant defense through its association with a plant immunity regulator.

Phenolic profiles, bioaccessibility and antioxidant activity of plum (Prunus Salicina Lindl).

Plum (Prunus Salicina Lindl) is a rich source of phenolic compounds. However, the bound phenolics and its bioaccessibility and antioxidant activity remain unclear. Hence, the purpose of this study was to determine: 1) phenolic profiles of plum, including both free and bound phenolic fractions, 2) bioaccessibility of phenolic compounds in plum during simulated gastrointestinal digestions, 3) their antioxidant properties. A total of 17 phenolic compounds were identified by UPLC-Q-Exactive Orbitrap/MS with most epicatechin, neochlorogenic acid and procyanidin B2 in the free phenolics fraction, while catechin and epicatechin was the main compounds in the bound phenolics fraction. After the gastrointestinal digestion phase, the most bioaccessible phenolics were quercetin-pentoside (61.64%), cyanidin-3-O-glucoside (43.26%), and naringenin-7-O-ß-D-glucoside (42.04%). The antioxidant capacity of both undigested plum and its digested fractions showed a positive correlation with the total phenolics, and with specific individual phenolic compounds such as neochlorogenic acid, epicatechin and procyanidin B2 in undigested plum whereas catechin, neochlorogenic acid, and epicatechin in digested one. The results confirm that bound fraction of plum contribution to the total phenolic content must be taken into account in the assessment of the improving human health effects of plum.

Citrate ligand-enhanced microscale zero-valent aluminum corrosion for carbon tetrachloride degradation with high electron utilization efficiency.

Carbon tetrachloride (CT) is highly toxic and recalcitrant in groundwater. In recent years, zero-valent aluminum (ZVAl) is highly reductive but limited by its surface passivation film. One of the effective ways to overcome this bottleneck is to add ligands. In this paper, compared with several other ligands, sodium citrate (SC), a natural organic ligand, was introduced to enhance microscale ZVAl (mZVAl) reactivity for the reductive degradation of CT. The results showed that the SC system could effectively reduce but not completely dechlorinate CT and electron utilization efficiency was as high as 94%. However, without ligands, mZVAl is chemically inert for CT degradation. Through SEM-EDS, BET, XRD, and XPS characterizations and H2 evolution experiments, enhanced mZVAl surface corrosion at the solid-liquid interface of mZVAl/SC system was verified. SC participated in the complexation corrosion reaction with surface inert film to form Al[Cit] complex, which made internal Al0 active sites exposed and then promoted mZVAl corrosion. In the five consecutive reuse experiments of mZVAl, CT can be completely degraded, which indicates that mZVAl, with the help of SC, has excellent sustainable utilization efficiency.

A novel ball-milled aluminum-carbon composite for enhanced adsorption and degradation of hexabromocyclododecane.

Hexabromocyclododecane (HBCD) is one of the priority persistent organic pollutants (POPs), yet a cost-effective technology has been lacking for the removal and degradation of HBCD. Zero-valent aluminum (ZVAl) is an excellent electron donor. However, the inert and hydrophilic surface oxide layer impedes the release of the electrons from the core metallic Al, resulting in poor reactivity towards HBCD. In this research, a new type of modified mZVAl particles (AC@mZVAlbm/NaCl) were prepared through ball milling mZVAl in the presence of activated carbon (AC) and NaCl, and tested for adsorption and reductive degradation of HBCD in water. AC@mZVAlbm/NaCl was characterized with a metallic Al core with newly created reactive surface coated with a thin layer of crushed carbon nanoparticles. AC@mZVAlbm/NaCl was able to rapidly (within 1 h) adsorb HBCD (C0 = 2 mg L-1) and thus effectively enriched HBCD on the carbon surface of AC@mZVAlbm/NaCl. The pre-enriched HBCD was subsequently degraded by the electrons from the core Al, and ∼63.44% of the pre-sorbed HBCD was completely debrominated after 62 h of the contact. A notable time lag (∼12 h) from the onset of the adsorption to the debromination was observed, signifying the importance of the solid-phase mass transfer from the initially adsorbed AC particles to the reactive Al-AC interface. Overall, AC@mZVAlbm/NaCl synergizes the adsorptive properties of AC and the high reactivity of metallic Al, and enables a novel two-step adsorption and reductive degradation process for treating HBCD or likely other POPs.

Iron(II) sulfate crystals assisted mechanochemical modification of microscale zero-valent aluminum (mZVAl) for oxidative degradation of phenol in water.

Microscale zero-valent aluminum (mZVAl) is prone to surface passivation due to formation of the surface Al-(hydr)oxide layer, resulting in short reactive life. To overcome this critical drawback, we developed a mechanochemical ball milling approach to modify and activate commercially available mZVAl assisted by the fragile FeSO4·7H2O crystals. SEM-EDS and XPS analyses indicated that the particle surface of the mechanochemically modified mZVAl (Fe-mZVAlbm) was not only fractured with newly formed fresh reactive surfaces, but also attached with a rough layer of Fe-oxides that were uniformly distributed on mZVAl. While pristine mZVAl failed to degrade any phenol, Fe-mZVAlbm was able to rapidly degrade 88.8% within 90 min (initial phenol = 20 mg/L, pH = 2.50, dosage = 3 g/L) under normal oxic conditions, with a pseudo first-order rate constant of 0.040 min-1 and about 70.0% of phenol mineralized in 8 h. Moreover, Fe-mZVAlbm also showed prolonged reactive life, and no significant reactivity drop was evident after six cycles of consecutive runs for phenol degradation. The much enhanced reactivity and reactive longevity of Fe-mZVAlbm are attributed to the critical roles of the surface Fe-oxides, including 1) protecting the newly exposed reactive Al0 from being oxidized by side reactions, 2) serving as an electron mediator facilitating the electron transfer from the core Al0 reservoir to the exterior surface, and 3) acting as an Fe2+ source and a heterogeneous catalyst to enable the Fenton (-like) reactions. This study provides a novel and practical approach for preparing Fe-oxides modified mZVAl with enhanced and long-lasting reactivity.

Incidence and Risk Factors of Moderate to Severe Postoperative Pain Following the Placement of Primary and Secondary Orbital Implants: A Prospective Observational Study.

PURPOSE: To prospectively explore the incidence and risk factors of moderate to severe pain after primary and secondary orbital implantation following evisceration or enucleation surgery. METHODS: One hundred eighteen patients under general anesthesia for orbital implantation were enrolled in this study. In 91 patients, primary orbital implantation followed evisceration, and in 27 patients, the implantation was secondary after previous evisceration or enucleation surgery. Medical interventions for all participants were followed by standardized surgical, anesthetic, and analgesic protocols. Postoperative pain (POP) intensity was quantified by an 11-point numerical rating scale within 72 hours after the surgery, numerical rating scale ≥4 was considered moderate to severe POP. Multivariate logistic regression was utilized to identify the risk factors related to the development of POP. RESULTS: Thirty-five patients (29.7%) displayed moderate to severe POP, particularly within 6 to 24 hours after surgery, which peaked at 24 hours. Of these patients, 26 patients who were unable to tolerate the pain received additional doses of analgesics during in-hospital stay. Logistic regression model revealed that preoperative anxiety (odds ratios = 4.890; p = 0.002), congenital microphthalmia (odds ratios = 14.602; p = 0.038), and surgical time longer than 60 minutes (odds ratios = 5.586; p = 0.001) were significantly associated with moderate to severe POP after orbital implantation. CONCLUSIONS: Orbital implantation after evisceration or enucleation surgery is likely to cause moderate to severe pain intensity in the early postoperative period. Preoperative anxiety, prolonged surgical time, and congenital microphthalmia were the risk factors.

A Novel Co-Crystal of Bexarotene and Ligustrazine Improves Pharmacokinetics and Tissue Distribution of Bexarotene in SD Rats.

Bexarotene (BEX), a specific retinoic acid X receptor (RXR) agonist granted by Food and Drug Administration (FDA) approval for the clinical treatment of T cell lymphoma, has now been found to exert pharmacological effects in the nervous system, with low bioavailability and poor cerebral distribution limiting its application in treatment on neurological disorders. Pharmaceutical co-crystal was a helpful method to improve the bioavailability and tissue distribution of active pharmaceutical ingredients (APIs). Here, 2bexarotene-ligustrazine (2BEX-LIG), a novel co-crystal system of BEX and ligustrazine (LIG) of which with BEX is an API, was constructed with satisfactory stability and enhanced solubility. The pharmacokinetics characteristics of BEX were detected, and the results showed that the absolute bioavailability and the cerebral concentration of BEX in rats administrated with 2BEX-LIG were enhanced from 22.89% to 42.86% and increased by 3.4-fold, respectively, compared with those in rats administrated an equivalent of BEX. Hence, our present study indicated that the novel co-crystal of 2BEX-LIG contributed to improving BEX oral bioavailability and cerebral distribution, thereby providing significant advantages for clinical application of brain tumors and other neurological diseases.

Using Clinical-Based Discharge Criteria to Discharge Patients After Ophthalmic Ambulatory Surgery Under General Anesthesia: An Observational Study.

PURPOSE: To verify the feasibility of the clinical-based discharge (CBD) criteria and identify the reasons of long postanesthesia care unit length of stay (PACU-LOS) for ophthalmic ambulatory surgical patients under general anesthesia. DESIGN: A prospectively observational study conducted at a tertiary eye center in China. METHODS: Medical records were collected from patients admitted for strabismus ambulatory surgery under general anesthesia from September 2018 to March 2019. The patients were discharged home once met the CBD criteria based on a combination of the modified Aldrete's scoring system and Chung's Post-Anesthetic Discharge Scoring System. Postoperative complications were recorded in the PACU and within 24 hours after discharge. Multivariate logistic regression was applied to identify the factors relating to late discharges. FINDINGS: All patients (N = 400) were safely and successfully same-day discharged home as none of the patients informed severe emergency events or unanticipated readmission. Nine displayed discharge delays mainly because of mild postoperative nausea and vomiting (PONV) although met the discharge criteria. About 85.5% of patients were discharged within a PACU-LOS of 150 minutes, 379 (94.8%) were within 180 minutes, and the cutoff time in PACU-LOS was 150 minutes. Multivariable analysis indicated that sevoflurane anesthesia and the presence of PONV were related to late discharges (PACU-LOS of greater than 150 minutes, all P < .05). CONCLUSIONS: The CBD criteria can efficiently and safely guide the ophthalmic ambulatory surgical patients to discharge home on the same-surgery day, whereas sevoflurane anesthesia and the presence of PONV are associated with a relatively long PACU-LOS.

Control over Polymorph Formation of Polydatin in Binary Solvent System and Structural Characterization.

Polydatin is a natural product used for anti-oxidant, anti-inflammatory and anti-tumor purposes, and often added in medicine, nutraceutical, cosmetics, and dietary supplement. Polymorphism is a key feature of solid-state pharmaceutical products. Polymorphic modifications may exhibit different physical and chemical properties. Here we report two different polymorphs, and the amorphous form of Polydatin. Polymorphs were prepared in binary solvent system. The crystal structures of the two forms were revealed for the first time. The structure and 3D packing were determined with single crystal X-ray diffraction analysis. The batch consistency and stability were identified with Powder X-ray diffraction analysis. Various functional groups present in the polymorphs were analyzed with fourier transform infrared spectroscopic method. The thermal properties were investigated with DSC and TGA. HPLC-MS was used for the pharmacokinetic study. Results show that form B has the faster absorption, and can be maintained in animal bodies for a longer time than form A.

miR-34c Targets MET to Improve the Anti-Tumor Effect of Cisplatin on Ovarian Cancer.

BACKGROUND: Cisplatin is a commonly used drug for the treatment of various types of malignant cancers, including ovarian cancer. However, resistance to cisplatin is still a considerable obstacle to achieve a satisfactory therapeutic effect. The purpose of this study is to develop a strategy to sensitize ovarian cancer cells to cisplatin-induced cytotoxicity. METHODS: miR-34c levels in ovarian cancer tissues and cell lines were tested by qRT-PCR analysis. In vitro assays, the effect of miR-34c on cisplatin was evaluated by using MTT. Expression of MET and phosphorylation of PI3K and AKT were tested by Western blot assays. Conjugation with Bad and Bcl-xl was evaluated through immunoprecipitation. Flow cytometry analysis was performed to measure the apoptotic rate of ovarian cancer cells. RESULTS: Downregulation of miR-34c was observed in ovarian cancer tissues and cell lines. However, miR-34c overexpression was found to sensitize ovarian cancer cells to cisplatin treatment in vitro and in vivo. Mechanically, we found that miR-34c targeted the MET gene, thereby inhibiting the phosphorylation of PI3K and AKT to activate Bad. As a result, miR-34c reduced resistance of ovarian cancer cells to cisplatin-induced apoptosis. CONCLUSION: miR-34c/MET axis promotes cisplatin-induced cytotoxicity against ovarian cancer by targeting the MET/PI3K/AKT/Bad pathway.

Enhanced reactivity of zero-valent aluminum with ball milling for phenol oxidative degradation.

Micron-sized zero-valent aluminum (ZVAl), a heterogeneous Fenton-like catalyst in organic wastewater treatment, whose catalytic activity is limited by the dense and stable oxide layer coating on its surface. In this paper, a simple method of ball milling was exploited to pretreat inert aluminum particles with the addition of low-cost and non-toxic sodium chloride (NaCl) grains. Then the pretreated ZVAl (marked as ZVAlbm) was employed to activate molecular oxygen catalytically for phenol oxidative degradation. No induction period was observed in ZVAlbm/Air system. Meanwhile, the reaction rate and mineralization efficiency of phenol degradation had improved in contrast with the original ZVAl. The characterization results of SEM-EDS, BET, XRD and XPS revealed that the native oxide layer of ZVAlbm was destroyed and became rougher, where its surface was embedded in NaCl grains. Thus the dissolution of NaCl in aqueous solution was imagined to expose the fresh surface of ZVAlbm, facilitating the electron transfer at the interface of ZVAlbm/H2O. Moreover, the specific surface area of ZVAlbm increased for ball milling improved its surface roughness, resulting in the enhanced reactivity of ZVAlbm. The interfacial reaction mechanism was revealed that more dissolved oxygen (DO) was activated by the exposed surface of ZVAlbm to form large amounts of hydrogen peroxide (H2O2). Then in-situ production of H2O2 was catalyzed by the active-surface of ZVAlbm via a Fenton-like process to generate massive OH, which was detected as the predominant active species for phenol degradation. Finally, the reusability experiment indicated that ball milling could rejuvenate the main catalytic activity of used ZVAlbm easily. In summary, ball milling provides a green and easily-operated method to promote the reactivity of inert ZVAl for its application in organic wastewater treatment.