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Background Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

Enantiopure vicinal diols are important building blocks used in the synthesis of fine chemicals and pharmaceutical compounds. Diol dehydrogenase (DDH) mediated stereoselective oxidation of racemic vicinal is an efficient way to prepare enantiopure vicinal diols. In this study, four new bacterial DDHs (AnDDH from Anoxybacillus sp. P3H1B, HcDDH from Hazenella coriacea, GzDDH from Geobacillus zalihae and LwDDH from Leptotrichia wadei) were mined from the GenBank database and expressed in E. coli T7. The four DDHs were purified and biochemically characterized for oxidation activity toward (R)-1-phenyl-1,2-ethanediol, with the optimal reaction condition of pH9.0 (AnDDH), 10.0 (HcDDH) and 11.0 (GzDDH and LwDDH) and the temperatures at 40°C (AnDDH), 50°C (HcDDH) and 60°C (GzDDH and LwDDH), respectively. The four enzymes were stable at the pH from 7.0 to 9.0 and below 40°C. Kinetic parameters of four DDHs showed that the HcDDH from Hazenella coriacea had high activity toward a broad range of vicinal diols. A series of racemic vicinal diols were successfully resolved by recombinant E. coli (HcDDH-NOX) resting cells co-expression of an NADH oxidase (NOX), affording (S)-diols and (1S, 2S)-trans-diols in ≥99% ee. The synthetic potential of HcDDH was proved by E. coli (HcDDH-NOX) via kinetic resolution of racemic trans-1,2-indandiol on a 100 ml scale reaction, (S, S)- trans-1,2-indandiol was prepared in 46.7% yield and >99% ee. In addition, asymmetric reduction of four α-hydroxy ketones (10-300 mmol•L-1) by E. coli (HcDDH-GDH) resting cells resulted in >99% ee and 69-98% yields of (R)-vicinal diols. The current research expands the toolbox of DDHs to synthesize chiral vicinal diols and demonstrated that the mined HcDDH is a potential enzyme in the synthesis of a broad range of chiral vicinal diols.

The external bacteria will inevitably invade the wound, attach, and subsequently colonize on the wound surface during surgery and biomedical operations, which slows down the process of wound healing and tissue repair, remaining a significant threat to human health. Therefore, developing a smart antibacterial surface has become the focus of antimicrobial research field, which has important social and economic significance. Herein, we present a simple route towards producing ionic interaction-driven switchable multifunctional antibacterial surfaces that decrease bacteria attachment and inactivate attached microorganisms. Briefly, the graded surface was constructed by surface-initiated atom transfer radical polymerization on silicon substrate consisting of antifouling component poly (3-sulfopropyl methacrylate potassium salt) (PSPMA) brushes, an antibacterial positive-charged components lysozyme (LYZ) and hexadecyl trimethyl ammonium bromide (CTAB) were loaded on negative-charged sulfonate groups via electrostatic interaction. The resultant brushes grafted surfaces exhibited more than ~95.5% bactericidal efficacy, and ~92.8% releasing rate after introducing contra-ions (Na+ & Cl-) against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus. More importantly, the ionic interaction-driven method used in this work is straightforward to produce renewable antibacterial surfaces. To further extend the applications, we construct smart cotton fabric to develop Fabric-PSPMA/LYZ and Fabric-PSPMA/Chitosan brushes which can promote wound healing and tissue repair. This work will assist in the wider utilization of the switchable antibacterial functionalization of biomedical materials.

Adventitious root (AR) formation is an essential step in the vegetative propagation of apple rootstocks. Nitrate serves as an essential signaling molecule for regulating root architecture by inducing the expression of auxin-related genes. However, the underlying mechanisms of nitrate-mediated ARs remain to be explored in apple. In this study, stem cuttings of B9 apple rootstocks were treated with different nitrate treatments: T1 (9.4 mM/L), T2 (28.1 mM/L), and T3 (46.9 mM/L). The root morphological parameters indicated that T2 was the optimum nitrate level for AR formation and development in B9 apple rootstocks. Therefore, to identify the underlying molecular mechanism by which nitrate promotes AR formation, stem cuttings of B9 were grown on T2 and T3. Furthermore, morphological and anatomical observations of stem cuttings also revealed that the nitrate treatment (T2) promoted AR formation. The results indicated that nitrate perceptibly upregulated the relative expression of genes related to nitrate (MdNRT1.1, MdNRT2.1, MdNIA1, and MdANR1) and auxin biosynthesis (MdIAA14 and MdIAA23) in T2 cuttings compared with T3 cuttings. This resulted in enhanced expression of AR development-related genes (MdWOX11, MdARRO1, and MdSHR), collectively resulting in elevated expression of the cell cycle-related genes (MdCYCD1;1, MdCYCD3;1, and MdCYCP4;1). Overall, this study established a foundation for applied research work and shed light on nitrate-mediated AR formation in B9 apple rootstock and other fruit rootstock cuttings.

Endoplasmic reticulum stress (ERS) plays a crucial role in myocardial ischemia-reperfusion injury (MIRI). Cellular FLICE-inhibitory protein (cFLIP) is an essential regulator of apoptosis and plays a major role in regulating ERS. The present study aimed to investigate the effects of long isoform cFLIP (cFLIPL) on endogenous apoptosis and the mechanism of ERS in MIRI. The cFLIPL recombinant adenovirus vector was used to infect H9c2 cells and Sprague–Dawley (SD) rats. After infection for 72 h, ischemia was induced for 30 min, and reperfusion was then performed for 2 h to establish the MIRI model in SD rats. H9c2 cells were hypoxic for 4 h and then reoxygenated for 12 h to simulate ischemia/reperfusion (I/R) injury. Model parameters were evaluated by assessing cardiomyocyte viability, cell death (apoptosis), and ERS-related protein expression. In addition, tunicamycin (TM), an ERS agonist, was also added to the medium for pretreatment. Coimmunoprecipitation (Co-IP) of cFLIPL and p38 MAPK protein was performed. cFLIPL expression was decreased in I/R injury and hypoxia/reoxygenation (H/R) injury, and cFLIPL overexpression reduced myocardial infarction in vivo and increased the viability of H9c2 cells in vitro. I/R and H/R upregulated the protein expression of GRP78, IRE-1, and PERK to induce ERS and apoptosis. Interestingly, overexpression of cFLIPL significantly inhibited ERS and subsequent apoptosis, which was reversed by an agonist of ERS. Moreover, Co-IP showed that cFLIPL attenuated ERS and was associated with inhibiting the activation of p38 protein. The expression of cFLIPL is significantly downregulated in MIRI, and it is accompanied by excessive ERS and apoptosis. Upregulated cFLIPL suppresses ERS to reduce myocardial apoptosis, which is associated with inhibiting the activity of p38 MAPK. Therefore, cFLIPL may be a potential intervention target for MIRI.

Winter dormancy (WD) is a crucial strategy for plants coping with potentially deadly environments. In recent decades, this process has been extensively studied in economically important perennial eudicots due to changing climate. However, in evergreen monocots with no chilling requirements, dormancy processes are so far a mystery. In this study, we compared the WD process in closely related evergreen (Iris japonica) and deciduous (I. tectorum) iris species across crucial developmental time points. Both iris species exhibit a ‘temporary’ WD process with distinct durations, and could easily resume growth under warm conditions. To decipher transcriptional changes, full-length sequencing for evergreen iris and short read RNA sequencing for deciduous iris were applied to generate respective reference transcriptomes. Combining results from a multipronged approach, SHORT VEGETATIVE PHASE and FRUITFULL (FUL) from MADS-box was associated with a dormancy- and a growth-related module, respectively. They were co-expressed with genes involved in phytohormone signaling, carbohydrate metabolism, and environmental adaptation. Also, gene expression patterns and physiological changes in the above pathways highlighted potential abscisic acid and jasmonic acid antagonism in coordinating growth and stress responses, whereas differences in carbohydrate metabolism and reactive oxygen species scavenging might lead to species-specific WD durations. Moreover, a detailed analysis of MIKCCMADS-box in irises revealed common features described in eudicots as well as possible new roles for monocots during temporary WD, such as FLOWERING LOCUS C and FUL. In essence, our results not only provide a portrait of temporary WD in perennial monocots but also offer new insights into the regulatory mechanism underlying WD in plants.

Xingan Qiu,* Yifan Wu,* Dong Zhang, Hao Zhang, Aixi Yu, Zonghuan Li Department of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of China*These authors contributed equally to this workCorrespondence: Aixi Yu; Zonghuan LiDepartment of Orthopedics Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People’s Republic of ChinaTel +86-27-67813120; +86-134 76041532Email yuaixi@whu.edu.cn; lizonghuan@whu.edu.cnBackground: Negative-pressure wound therapy (NPWT) is an effective way to promote wound healing. However, its mechanisms have not been investigated thoroughly. Growing evidence suggests that oxidative stress and Raftlin levels play important roles in wound healing. However, whether NPWT promotes wound healing through this mechanism remains unclear.Purpose: Our study focuses on the different levels of oxidative stress and antioxidant response between wounds treated by NPWT and routine dressing change. The objective of this study was to measure the differences in Raftlin levels between the two groups, which is a new biomarker related to wound healing.Methods: We divided 48 male Sprague-Dawley rats with identical full-thickness skin defects into two groups. At specific times (0, 3, 5, 7, 9, 11, and 13 days after surgery), wound tissue samples were obtained for immunohistochemistry and biochemical analysis. The expression of Raftlin and levels of oxidative stress, including malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels were measured by biochemical analysis. Wound-healing times were also compared.Results: In the NPWT group, MDA levels were significantly decreased on days 3, 5, and 7. Furthermore, the expressions of SOD and CAT were significantly reduced on days 3 and 5. Our data also revealed that Raftlin was significantly upregulated across the whole period of wound healing. Moreover, wound healing in the NPWT group was significantly more rapid (16 days on average) than in the control group (24 days on average). On day 13 post surgery, the wound-healing percentage in the NPWT group was 91%, while that in the control group was 48%.Conclusion: NPWT may promote wound healing by upregulating Raftlin and inhibiting oxidative stress levels.Keywords: SOD, CAT, MDA, Raftlin, negative-pressure wound therapy

Zhengzhou is one of the most haze-polluted cities in Central China with high organic carbon emission, which accounts for 15%-20% of particulate matter (PM2.5) in winter and causes significantly adverse health effects. Volatile organic compounds (VOCs) are the precursors of secondary PM2.5 and O3 formation. An investigation of characteristics, sources and health risks assessment of VOCs was carried out at the urban area of Zhengzhou from 1st to 31st December, 2019. The mean concentrations of total detected VOCs were 48.8 ± 23.0 ppbv. Alkanes (22.0 ± 10.4 ppbv), halocarbons (8.1 ± 3.9 ppbv) and aromatics (6.5 ± 3.9 ppbv) were the predominant VOC species, followed by alkenes (5.1 ± 3.3 ppbv), oxygenated VOCs (3.6 ± 1.8 ppbv), alkyne (3.5 ± 1.9, ppbv) and sulfide (0.5 ± 0.9 ppbv). The Positive Matrix Factorization model was used to identify and apportion VOCs sources. Five major sources of VOCs were identified as vehicular exhaust, industrial processes, combustion, fuel evaporation, and solvent use. The carcinogenic and non-carcinogenic risk values of species were calculated. The carcinogenic and non-carcinogenic risks of almost all air toxics increased during haze days. The total non-carcinogenic risks exceeded the acceptable ranges. Most VOC species posed no non-carcinogenic risk during three haze events. The carcinogenic risks of chloroform, 1,2-dichloroethane, 1,2-dibromoethane, benzyl chloride, hexachloro-1,3-butadiene, benzene and naphthalene were above the acceptable level (1.0 × 10−6) but below the tolerable risk level (1.0 × 10−4). Industrial emission was the major contributor to non-carcinogenic, and solvent use was the major contributor to carcinogenic risks.

Dimeric sesquiterpenoids possessing densely substituted 7-norbornenone/7-norbornenol motifs pose a considerable challenge for chemical synthesis. From a strategic perspective, one could envision intermolecular Diels−Alder cycloaddition as a straightforward method for assembling alkyl-substituted 7-norbornenones. However, this approach is hindered by lability of the required dienes, namely alkyl-substituted cyclopentadienones. Here we report a one-pot protocol for construction of alkyl-substituted 7-norbornenones from electron-deficient olefins and a cyclopentenone derivative. DDQ was found to be an effective oxidant for generating a cyclopentadienone intermediate in situ from the enone. A series of sterically congested 7-norbornenone-containing polycyclic compounds were prepared by using this protocol.

Abnormal accumulation of α-synuclein contributes to the formation of Lewy bodies in the substantia nigra, which is considered the typical pathological hallmark of Parkinson’s disease. Recent research indicates that angiotensin-(1–7) plays a crucial role in several neurodegenerative disorders, including Parkinson’s disease, but the underlying mechanisms remain elusive. In this study, we used intraperitoneal administration of rotenone to male Sprague-Dawley rats for 4 weeks to establish a Parkinson’s disease model. We investigated whether angiotensin-(1–7) is neuroprotective in this model by continuous administration of angiotensin-(1–7) into the right substantia nigra for 4 weeks. We found that angiotensin-(1–7) infusion relieved characteristic parkinsonian behaviors and reduced α-synuclein aggregation in the substantia nigra. Primary dopaminergic neurons were extracted from newborn Sprague-Dawley rat substantia nigras and treated with rotenone, angiotensin-(1–7), and/or the Mas receptor blocker A-779 for 24 hours. After binding to the Mas receptor, angiotensin-(1–7) attenuated apoptosis and α-synuclein aggregation in rotenone-treated cells. Primary dopaminergic neurons were also treated with angiotensin-(1–7) and/or the autophagy inhibitor 3-methyladenine for 24 hours. Angiotensin-(1–7) increased α-synuclein removal and increased the autophagy of rotenone-treated cells. We conclude that angiotensin-(1–7) reduces α-synuclein aggregation by alleviating autophagy dysfunction in Parkinson’s disease. Therefore, the angiotensin-(1–7)/Mas receptor axis plays an important role in the pathogenesis of Parkinson’s disease and angiotensin-(1–7) has potential therapeutic value for Parkinson’s disease. All experiments were approved by the Biological Research Ethics Committee of Nanjing First Hospital (approval No. DWSY-2000932) in January 2020.

Temperature-responsive resistance transition behaviors of the melamine sponges wrapped with different graphene oxide derivatives (i.e. nanoribbon, wide-ribbon and sheet) were investigated. Melamine sponge composites coated by three types of GO derivatives were prepared by a simple dip-coating approach. All these composites show good mechanical flexibility and reliability (almost unchanged compressive stress at 70 % strain after 100 cycles), high hydrophobicity (water contact angle >120°), excellent flame resistance (self-extinguishing) and structural stability even after burning, which was used to construct the resistance-based fire alarm/warning sensor. Notably, the different resistance response behaviors of such sensors are strongly dependent on the GO size and network formed on the MF skeleton surface. Typically, at a fixed high temperature of ∼350 ℃, the three fire alarm sensors show different response time (to trigger the alarm light) of 6.3, 8.4 and 11.1 s for nanoribbon, wide-ribbon and sheet at the same concentration, respectively. The structural observation and chemical analysis demonstrated that the discrepancy of temperature-responsive resistance transition behaviors of various GO derivatives was strongly determined by their different thermal reduction degrees during the high-temperature or flame treating process. This work offers a design and development for construction of smart fire alarm device for potential fire prevention and safety applications.

Lateral roots (LRs) are critical for plant stress tolerance and productivity. Understanding how hormones and genes interact in a fluctuating environment to coordinate LR development is a major challenge. Abscisic acid (ABA) is the primary stress-responsive hormone and mediates LR development in various plant species. However, the effect of exogenous ABA on LR development has not been elucidated in apple. In this study, ‘Qingzhen 1’ was treated with exogenous 5 µM ABA for 20 days to investigate the regulation mechanism of ABA on LR development. Morphological observations advocated that ABA inhibited both LR and shoot development in ‘Qingzhen 1’ apple plants, where the root number was 16.94%, the root length was 30.32%, the plant height was 10.88%, and the stem thickness was 8.08% lower than those in the control plants. Meanwhile, the endogenous ABA concentration was significantly increased, but the indole-3-acetic acid, zeatin riboside, and jasmonic acid concentrations were significantly decreased with ABA treatment. Furthermore, the expression levels of ABA-related genes (MdCYP707A2, MdABI1, MdAREB2, and MdABF3) were significantly upregulated, while the expression levels of auxin-related genes (MdYUCCA3, MdYUCCA8, MdPIN1, MdPIN2, MdPIN3, and MdARF19), root development-related genes (MdWOX5 and MdWOX11), and cell cycle-related genes (MdCYCD1;1 and MdCYCD3;1) were significantly downregulated at the early stage of ABA treatment, which act together on the inhibition of LR development. Taken together, the changes in hormone levels and gene expression resulted in inhibited LR development of apple plants in response to ABA. This study revealed the mechanism that exogenous ABA application inhibits the LR development of ‘Qinzhen 1’ apple rootstock by affecting the auxin signaling and the expression of growth-related genes.

A comprehensive undergraduate experiment about extraction, separation, and identification of essential oils (EOs) from a natural plant is described. Acori tatarinowii Rhizoma (ATR) was used as the raw plant material. Two devices (Soxhlet and Clevenger) with different extraction principles were employed for EO extraction from ATR, separately. The chemical compounds of the extracted EOs were separated and identified by gas chromatography–mass spectrometry (GC–MS). The differences in the chemical components obtained by the two extraction devices were compared. The experiment can give students a deep insight into the difference between the extraction methods. Additionally, the experiment can enable students to learn how to use GC–MS to identify the chemical structures of the extracted complex samples. The grouped students who performed this experiment gained a deep understanding of extraction and detection techniques, as well as the benefits of teamwork.

The effective components of Coptis chinensis were extracted by ultrasound-assisted technology, and the contents of palmatine and berberine were used as indexes by using Coptis chinensis as raw material and eutectic solvent as extractant. In addition, the effects of hydrogen bond donor type, molar ratio of hydrogen bond donor to acceptor, material-liquid ratio, water content of eutectic solvent system, sonication time, power, and ultrasonic temperature on the extraction rate of palmatine and berberine were studied. The optimum extraction technology of palmatine and berberine from Coptis chinensis was determined by single-factor experiment and response surface optimization test. As a result, it showed that the eutectic solvent system was constructed with choline chloride as hydrogen bond acceptor and phenol as hydrogen bond donor, with a molar ratio of 1 : 3. In addition, water content of the eutectic solvent system was 30%, ratio of material to liquid was 30 g/mL, ultrasonic time was 30 min, ultrasonic power was 200 W, and ultrasonic temperature was 60°C. At this time, the contents of palmatine and berberine in Coptis chinensis were 16.7145 mg/g and 57.4013 mg/g, respectively, which were predicted to be the same as the value, and the extraction effect was better than that of traditional extraction solvent method.

Aspirin eugenol ester (AEE) is a new pharmaceutical compound esterified by aspirin and eugenol, which has anti-inflammatory, antioxidant, and other pharmacological activities. The aim of this study was to investigate the protective effect of AEE on paraquat- (PQ-) induced cell damage of SH-SY5Y human neuroblastoma cells and its potential molecular mechanism. There was no significant change in cell viability when AEE was used alone. PQ treatment reduced cell viability in a concentration-dependent manner. However, AEE reduced the PQ-induced loss of cell viability. Flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and 4 ′ 6-diamidino-2-phenylindole (DAPI) staining were used to evaluate cell apoptosis. Compared with the PQ group, AEE pretreatment could significantly inhibit PQ-induced cell damage. AEE pretreatment could reduce the cell damage of SH-SY5Y cells induced by PQ via reducing superoxide anion, intracellular reactive oxygen species (ROS), and mitochondrial ROS (mtROS) and increasing the levels of mitochondrial membrane potential ( Δ Ψ m ). At the same time, AEE could increase the activity of glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) and decrease the activity of malondialdehyde (MDA). The results showed that compared with the control group, the expression of p-PI3K, p-Akt, and Bcl-2 was significantly decreased, while the expression of caspase-3 and Bax was significantly increased in the PQ group. In the AEE group, AEE pretreatment could upregulate the expression of p-PI3K, p-Akt, and Bcl-2 and downregulate the expression of caspase-3 and Bax in SH-SY5Y cells. PI3K inhibitor LY294002 and the silencing of PI3K by shRNA could weaken the protective effect of AEE on PQ-induced SH-SY5Y cells. Therefore, AEE has a protective effect on PQ-induced SH-SY5Y cells by regulating the PI3K/Akt signal pathway to inhibit oxidative stress.

The mesoporous Ni/KIT-6 catalysts with different composition were prepared by altering reduction temperatures. In addition, their physicochemical properties were characterized by X-ray diffraction, in-situ X-ray photoelectron spectroscopy, and Brunauer–Emmett–Teller techniques. The results shown that the specific surface area, composition and metallic Ni crystallinity of the Ni/KIT-6 catalyst were significantly affected by reduction temperatures. The catalytic performances of the prepared Ni/KIT-6 catalysts were evaluated via the CO2 reforming of CH4 into syngas and followed the order: RT0 0 content of the most representative RT450 catalyst among of them were 646.7 m2 g−1, 0.92 cm3 g−1, 6.5 nm, and 30.9%, respectively. The CH4 and CO2 conversions of RT450 catalyst reached to 69.0 and 39.4% under a reaction temperature of 600 °C, respectively. The CO selectivity was greater than 49% and the RT450 catalyst had good stability.

A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo, facilitating PTX prodrugs accumulation in the tumor region via albumin receptor-mediated active targeting. The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells. Moreover, disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo. This simple and facile strategy integrates the biomimetic characteristic of albumin, tumor redox-responsive on-demand drug release, and provides new opportunities for the development of the high-efficiency antitumor nanomedicines., Graphical abstract The paclitaxel–maleimide prodrugs nanoparticles integrate the biomimetic characteristic of albumin, tumor redox-responsive on-demand drug release and pave the way for designing targeted delivery nano-platform for tumor therapy.Image 1

Background: Knee Osteoarthritis (KOA) is a chronic degenerative joint disease commonly occurring in middle-aged and elderly people. The main clinical manifestations are joint pain, limited activity, and decreased muscle strength resulting in decreased motor control ability. Exercise therapy is an effective method to enhance muscle strength of lower limbs, while China's traditional skill Tai Chi is a combination of activity and inertia, internal and external exercise therapy. In recent years, scholars at home and abroad have found that regular Tai Chi can effectively improve patients' lower limb function and balance ability. The purpose of this study is to explore the effects of Tai Chi on lower limb function and balance ability in patients with knee osteoarthritis. Methods: This is a prospective randomized controlled clinical trial. 146 cases of knee osteoarthritis patients will be randomly divided into experimental group and control group according to 1:1 ratio, 73 cases in each group, the control group: sodium hyaluronate; experimental group: Tai Chi added on the basis of the control group. Both groups will receive standard treatment for 5 weeks and will be followed up for 3 months. Observation indicators include: the western Ontario and McMaster universities osteoarthritis index (WOMAC); hospital for special surgery knee score (HSS); balance stability index, liver and kidney function, adverse reaction rate, etc. SPSS 23.0 software will be used for data analysis. Discussion: This study will evaluate the effects of Tai Chi on lower limb function and balance ability of patients with knee osteoarthritis. The results of this trial will provide a clinical basis for the selection of exercise therapy for patients with knee osteoarthritis.

In the process of vegetative propagation of apple rootstocks, the development of adventitious roots (ARs) has crucial importance. Nitrate is an essential nutrient necessary for plant growth; however, the inhibitory effect of high nitrate on ARs formation has not been explored. The physiological and molecular mechanisms underlying ARs inhibition were examined in this study. Stem cuttings of B9 apple rootstock were cultured on two nitrate treatments (T1 = 18.7 mM L-1 and T2 = 37.5 mM L-1 ), where T2 was identified as ARs inhibiting treatment. Morphological and anatomical observations advocating that high availability of nitrate inhibited AR formation by delaying the ARs initiation and emergence stages, where the root number was 287%, and the length was 604.6% lower than the T1 cuttings. Moreover, the contents of endogenous hormones were also elevated in response to T2 at most of the time points, which may cause a hormonal imbalance within the plant body and drive toward ARs inhibition. Furthermore, 3686 genes were differentially expressed by high-throughput sequencing. Out of these, 1797 genes were upregulated, and 1889 genes were downregulated. Approximately 238 genes related to nitrate, hormones, root development, and cell-cycle induction pathways were selected according to their potential to be involved in ARs regulation. This is the first study providing information regarding the inhibitory effect of high nitrate on ARs formation in apple rootstock.

A dilactosyl-dicyanovinyl-functionalized tetraphenylethene (TPELC) was designed, synthesized and used for ratiometric sensing of cyanide. TPELC was comprised of three moieties (tetraphenylethylene, dicyanovinyl group and lactose unit) in one molecule, making TPELC water-soluble and aggregation-induced emission (AIE)-active and selectively reactive to cyanide. Compared with other reported fluorescent probes containing dicyanovinyl group, TPELC is the first AIE luminogen to be assembled as fluorescent organic nanoparticles (FONs) for sensing of cyanide in water without the use of surfactant or the help of organic solvents based on the nucleophilic addition reaction. The detection mechanism was verified by liquid chromatograph mass spectrometry experiments and by protonation of cyanide to reduce the nucleophilicity of cyanide. In addition, TPELC was used for detection of the cyanide content of food samples and test strips were developed to simplify the detection procedure.

Hydrophobic micro-porous membrane such as polyvinylidene fluoride (PVDF) with excellent thermal-/chemical-stability and low surface energy has received extensive attention in industrial water treatment and sustainable energy conversion. However, undesirable contaminants caused by inevitable proteins or microorganisms adhesion may lead to a rapid loss of separation efficiency, which significantly deteriorate their porous structures and eventually limit their practical performance. Herein, we present a scalable approach for fabricating comb-like copolymer modified PVDF membranes (PVDF-PN@AgNPs) that prevent bacteria from proliferating on the surface and temperature-controlled release of adhered contaminants. Comb-like structured copolymers were imparted to a polydopamine (PDA)-treated PVDF membrane by Michael addition reaction, which enabled a covalent binding of comb-like structured copolymers to the membrane. Such unique structural design of grafted copolymer, containing hydrophilic side chain and temperature-responsive chain backbone, stably prevents bacteria adhesion and provides reversible surface wettability. Therefore, the resultant membranes were evaluated to prevent bacterial adhesion, high touch-killing efficiency and temperature-controlled contaminants release (~99% of protein and ~75% of bacteria). Moreover, with the collapse and stretch of grafted copolymer chain backbone, the synthetic membrane further reversibly adjusted inner micro-porous structure and surface wettability, which eventually helped to achieve variable water fluid transport efficiency. This study not only provides a feasible structural design for stably coping with the challenging of antifouling and subsequent contamination adhesion of PVDF membrane, but also potentially answers the significant gap between lab research advances and practical application, particularly in the industrial membrane field.

G-quadruplex DNA (G4DNA) structure, which widely exists in the chromosomal telomeric regions and oncogenic promoter regions, plays a pivotal role in extending telomeric DNA with the help of telomerase in human cells. Bloom (BLM) helicase, a crucial member of the family of genome surveillance proteins, plays an essential role in DNA metabolic and repair pathways, including DNA replication, repair, transcription, recombination during chromosome segregation, and assuring telomere stability. The unwinding of G4DNA requires the participation of DNA helicase, which is crucial for maintaining chromosomal stability in cancer cells. Using fluorescence polarization and the electrophoretic mobility shift assay (EMSA), this study aimed to investigate the DNA-binding and unwinding properties of BLM helicase, cloned and purified from prostate cancer cells, toward G4DNA. The results revealed that BLM helicase derived from prostate cancer cells could bind and unwind G4DNA. The molecular affinity of bond between G4DNA and the helicase was dependent on the single-stranded DNA (ssDNA) terminals in G4DNA; the helicase was effectively bound to the G4DNA when the helicase monomer sufficiently covered approximately 10 nucleotides at the 3′ or 5′ ssDNA tail of G4DNA. For the unwinding of G4DNA, there was an apparent requirement of a 3′ ssDNA tail and ATP; a G4DNA with only a 3′ ssDNA tail was identified to be the most suitable substrate to be unwound by BLM helicase and required 3′ ssDNA tails of at least 10 nt in length for efficient unwinding. Besides, BLM helicase was loosely bound and partly unwound the blunt-ended G4DNA. Although further mechanistic studies are warranted, the experimental results presented in this study are beneficial to further our understanding of the functional implication of BLM helicase in prostate cancer cells.

The authors have previously demonstrated that one phage-displayed keratinocyte growth factor (KGF) model peptide that can bind to epidermal cells and facilitate cellular proliferation. In this study, the authors investigated the role of phage-displayed KGF model peptide on wound healing in diabetic rats. Full-thickness excisional dorsal wounds were created in the diabetic rats, after which the rats were randomly divided into five groups: negative control group [normal saline (NS)], two KGF control groups which were respectively treated with low-dose KGF (5 ng/mL, K-LD) and high-dose KGF (50 ng/mL, K-HD), and two KGF model-peptide-treated groups which were respectively treated with low-dose model peptide (5 ng/mL, M-LD) and high-dose model peptide (50 ng/mL, M-HD). On day 14 post-injury, wound closure was followed by digital planimetry and wound tissues were harvested for histologic assay and real-time polymerase chain reaction. Wounds treated with model peptide closed markedly faster than negative control wounds and were comparable to KGF treated wounds. Histology and immunohistology results demonstrated significantly higher levels of re-epithelization, granulation tissue formation and vascularization in the model peptide groups. Furthermore, real-time polymerase chain reaction expression of KGFR, collagen I and transforming growth factor-β1 in model peptide groups, were also generally higher than that in negative control group. Phage-displayed KGF peptide promotes wound healing through accelerating re-epithelialization, enhancing dermal regeneration, and inducing angiogenesis. Model peptide possesses the potential to be a promising therapeutic option for the treatment of diabetic ulcers.

The promising combustion and emission properties of polyoxymethylene dimethyl ethers (PODEn) are of significant interest. However, the synthesis of PODEn products with desired chain lengths is still a problem facing synthetic PODEn. Herein, a series of unique IL@SBA-16-Cx solid catalysts are prepared by encapsulation of ionic liquids (ILs) within the nanocage of SBA-16 through a silylation method. The structure of the encapsulated catalyst was characterized by UV–vis spectra, Fourier transform infrared (FT-IR), N2 adsorption–desorption isotherms, Powder X-ray diffraction (XRD), Transmission electron microscopy (TEM) and Elemental analysis. The encapsulated catalysts show similar catalytic activity to the homogeneous counterparts and display higher selectivity to the targeted PODE3–5 products than their homogeneous counterparts in the synthesis of PODEn from methanol (MeOH) and trioxymethylene (TOM). The encapsulated catalysts exhibit a superior PODE3–5 selectivity and could be the promising catalysts for PODEn synthetic reaction.

Objective. We aimed to investigate the risk factors associated with hemorrhage and clarify the relation of homocysteine (Hcy) with brain arteriovenous malformations (bAVMs). Method. We retrospectively reviewed bAVM patients from Beijing Tiantan Hospital between January 2019 and December 2019. Clinical and laboratory variables were analyzed in enrolled patients with bAVMs. Potential predictors associated with hemorrhage were evaluated by logistic regression analysis. Results. A total of 143 bAVM patients were identified in the study, including 69 unruptured and 74 ruptured cases. Patients with hemorrhage were less likely to have hyperhomocysteinemia ( P = 0.023 ). Logistic regression analysis showed that increased maximum diameter of bAVM lesions (odds ratio (OR) 0.634, 95% confidence intervals (CI) 0.479-0.839; P = 0.001 ) and serum Hcy level (OR 0.956, 95% CI 0.920-0.993; P = 0.021 ) were associated with lower risk of hemorrhage in bAVMs. Conclusion. The present study provided evidence regarding the association between serum Hcy and hemorrhage in patients with bAVMs. Higher Hcy level was correlated with a lower risk of rupture. Detection of factors for subsequent hemorrhage is necessary to develop therapeutic strategies for bAVMs preferably.

Development of smart switchable surfaces to solve the inevitable bacteria attachment and colonization has attracted much attention; however, it proves very challenging to achieve on-demand regeneration for noncontaminated surfaces. We herein report a smart, host-guest interaction-mediated photo/temperature dual-controlled antibacterial surface, topologically combining stimuli-responsive polymers with nanobactericide. From the point of view of long-chain polymer design, the peculiar hydration layer generated by hydrophilic poly(2-hydroxyethyl methacrylate) (polyHEMA) segments severs the route of initial bacterial attachment and subsequent proliferation, while the synergistic effect on chain conformation transformation poly(N-isopropylacrylamide) (polyNIPAM) and guest complex dissociation azobenzene/cyclodextrin (Azo/CD) complex greatly promotes the on-demand bacterial release in response to the switch of temperature and UV light. Therefore, the resulting surface exhibits triple successive antimicrobial functions simultaneously: (i) resists ∼84.9% of initial bacterial attachment, (ii) kills ∼93.2% of inevitable bacteria attack, and (iii) releases over 94.9% of killed bacteria even after three cycles. The detailed results not only present a potential and promising strategy to develop renewable antibacterial surfaces with successive antimicrobial functions but also contribute a new antimicrobial platform to biomedical or surgical applications.

The acetylcholinesterase (AChE) inhibitors remain key therapeutic drugs for the treatment of Alzheimer's disease (AD). However, the low-safety window limits their maximum therapeutic benefits. Here, a novel kinetics-driven drug design strategy was employed to discover new-generation AChE inhibitors that possess a longer drug-target residence time and exhibit a larger safety window. After detailed investigations, compound 12 was identified as a highly potent, highly selective, orally bioavailable, and brain preferentially distributed AChE inhibitor. Moreover, it significantly ameliorated cognitive impairments in different mouse models with a lower effective dose than donepezil. The X-ray structure of the cocrystal complex provided a precise binding mode between 12 and AChE. Besides, the data from the phase I trials demonstrated that 12 had good safety, tolerance, and pharmacokinetic profiles at all preset doses in healthy volunteers, providing a solid basis for its further investigation in phase II trials for the treatment of AD.

In this paper, the components of Zanthoxylum bungeanum Maxim. essential oil (ZBMEO) were analyzed. The efficacy of different concentrations of ZBMEO on the change in physical and chemical indicators of the rabbit meat patty was evaluated. Furthermore, kinetics models were employed to calculate the lipid oxidation induction period and microbial growth lag time. GC–MS analysis revealed that the major chemical components in ZBMEO included linalool, limonene, and sabinene. Results of the storage experiment indicated that ZBMEO had a good inhibition effect on lipid and protein oxidation, microbial growth, and formation of TVB-N, as well as slowed down the rate of change in color and pH during the 12 days storage time of rabbit meat. The models showed that adding ZBMEO could delay the lipid oxidation induction period, and extend the microbial growth lag time. Overall data showed that ZBMEO is a promising natural additive to maintain the quality of rabbit meat patty.

Low capacity and rate performance are important factors restricting the development of Li4Ti5O12 (LTO). The addition of an appropriate amount of polyethylene glycol (PEG) is an effective method to increase the capacity and rate performance of LTO anode material. In this study, LTO anode material was synthesised by the sol–gel method using PEG as a template agent. X-ray diffraction (XRD) results show that the addition of PEG can improve the crystallinity of the material and retain the spinel lattice type of LTO. Scanning electron microscopy (SEM) results show that the addition of an appropriate amount of PEG can promote the formation of a more uniform and much finer morphology. The results of high-resolution transmission electron microscopy (HRTEM) show that the material with PEG had good crystallinity. The charge and discharge data verify that the electrochemical performance of the material could be improved by adding PEG. P2-LTO exhibits a smaller particle size, largest capacity, best cycling performance and best rate performance. The capacity of P2-LTO at 0.2C can reach 224.3 mAgh−1, which is much higher than the theoretical specific capacity of LTO (175 mAgh−1). The discharge capacity of P2-LTO in the first cycle at 10C is 178.9 mAgh−1. The results of cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) show that the electrode polarisation and electrochemical impedance of P2-LTO were lower than that of pure LTO. Better capacity and rate performance can be obtained by adding PEG as a template agent to a LTO system. It is a simple and effective method to produce high-performance LTO anode materials.

Oxidative stress, the renin-angiotensin system (RAS), and inflammation are some of the mechanisms involved in the pathogenesis of hypertension. The aim of this study is to examine the protective effect of the chronic administration of astaxanthin, which is extracted from the shell of crabs and shrimps, into hypothalamic paraventricular nucleus (PVN) in spontaneously hypertensive rats. Animals were randomly assigned to 2 groups and treated with bilateral PVN infusion of astaxanthin or vehicle (artificial cerebrospinal fluid) through osmotic minipumps (Alzet Osmotic Pumps, Model 2004, 0.25 μL/h) for 4 weeks. Spontaneously hypertensive rats had higher mean arterial pressure and plasma level of norepinephrine and proinflammatory cytokine; higher PVN levels of reactive oxygen species, NOX2, NOX4, IL-1β, IL-6, ACE, and AT1-R; and lower PVN levels of IL-10 and Cu/Zn SOD, Mn SOD, ACE2, and Mas receptors than Wistar-Kyoto rats. Our data showed that chronic administration of astaxanthin into PVN attenuated the overexpression of reactive oxygen species, NOX2, NOX4, inflammatory cytokines, and components of RAS within the PVN and suppressed hypertension. The present results revealed that astaxanthin played a role in the brain. Our findings demonstrated that astaxanthin had protective effect on hypertension by improving the balance between inflammatory cytokines and components of RAS.

Only a few known epoxide hydrolases (EHs) displayed activity towards o-nitrostyrene oxide (4a), presumably owing to the large steric hindrance caused by o-nitro substituent. Therefore, excavating EHs with high activity and enantio- and/or regio-selectivity towards racemic (rac-) 4a is essential but challenging. Here, AuEH2 from Aspergillus usamii was expressed in E. coli BL21(DE3). E. coli/Aueh2, an E. coli transformant expressing AuEH2, possessed EH activities of 16.2–184 U/g wet cell towards rac-styrene oxide (1a) and its derivatives (2a–13a), and the largest enantiomeric ratio of 96 towards rac-4a. The regioselectivity coefficients, βR and βS, of AuEH2 were determined to be 99.2% and 98.9%, suggesting that it regiopreferentially attacks the Cβ in the oxirane rings of (R)- and (S)-4a. Then, the nearly perfect kinetic resolution of 20 mM rac-4a in pure water was carried out using 20 mg/mL wet cells of E. coli/Aueh2 at 25 °C for 50 min, retaining (S)-4a with over 99% ees and 48.9% yields, while producing (R)-o-nitrophenyl-1,2-ethanediol (4b) with 95.3% eep and 49.8% yieldp. To elucidate the molecular mechanism of AuEH2 with high enantiopreference for (R)-4a, its crystal structure was solved by X-ray diffraction and the molecular docking of AuEH2 with (R)- or (S)-4a was simulated.

Growing evidence has suggested that hyperhomocysteinemia (HHcy) is a risk factor for cerebral infarction. However, the effect of HHcy on postoperative cerebral ischemia is still unclear. We aim to investigate the relationship between HHcy and postoperative ischemia of adult patients with moyamoya disease (MMD). A total of 138 adult patients with MMD were prospectively recruited from July 1 to December 31, 2019. After excluding 14 patients accepting conservative therapy, all 124 patients who underwent surgical treatment were enrolled. Patients were grouped according to postoperative ischemia and HHcy presentation, respectively. Clinical data and laboratory examinations were compared by statistical analyses. Potential risk factors were evaluated by univariate and multivariate logistic regression analysis. Comparing to the normal, patients with postoperative ischemia were higher in serum homocysteine (Hcy) level (P = 0.039) and HHcy ratio (P = 0.035). Furthermore, HHcy was more common in males (P = 0.007) than females. Logistic analysis results showed that HHcy (OR 5.234, 95% CI 1.127-24.315; P = 0.035) was an independent risk factor. HHcy was significantly associated with postoperative ischemia in MMD patients. Our study found that HHcy was correlated to the risk of postoperative ischemia. HHcy can be used as an indicator and a potential therapeutic target for postoperative ischemia in adult patients with MMD. URL: http://www.chictr.org . Unique identifier: ChiCTR2000031412.

Blunt snout bream (Megalobrama amblycephala) were randomly assigned into three diets: normal-carbohydrate diet (NCD, 30% carbohydrate, w/w), high-carbohydrate diet (HCD, 43% carbohydrate), and HCB (HCD supplemented with 50 mg/kg berberine (BBR)). After 10 weeks' feeding trial, the results showed that higher levels of plasma glucose, triglyceride, and total cholesterol were observed in HCD-fed fish than in NCD-fed fish, while HCB feeding significantly ameliorated this effect. Moreover, HCB feeding remarkably reversed HCD-induced hepatic glycogen and lipid contents. In insulin signaling, BBR inclusion restored HCD-induced suppression of insulin receptor substrate mRNA expression and elevation of forkhead transcription factor 1 mRNA expression. In glucose metabolism, upregulated glucose transporter 2 and glycogen synthase mRNA expressions in the HCD group were observed compared to the NCD group. However, BBR adding reduced the mRNA expressions of glycogen synthase, phosphoenolpyruvate carboxykinase, and glucose-6-phosphatase and increased the transcriptional levels of glucose transporter 2 and pyruvate kinase. In lipid metabolism, BBR supplementation could reverse downregulated hepatic carnitine palmitoyl transferase I mRNA expression and upregulated hepatic acetyl-CoA carboxylase and fatty acid synthetase mRNA expressions in the HCD group. Taken together, it demonstrates that BBR could improve glucose metabolism of this species via enhancing liver's glycolysis and insulin signaling, while inhibiting liver's glycogen synthesis and gluconeogenesis. It also indicates that BBR could reduce the metabolic burden of the liver by inhibiting fat synthesis and promoting lipid decomposition, and then enhance fat uptake in peripheral tissues.

Cleavage of siloxane bonds (Si-O) in organosiloxanes (OSs) is one of the most fundamentally and practically important challenges in the modern chemistry of silicones. However, no benign approaches have been found to cleave these bonds under mild conditions. In this paper, siloxane bond cleavage in polydimethylsiloxane (PDMS) was studied using a mixture of the “green” reagent dimethyl carbonate (DMC) and an environmentally benign reagent, tris(pentafluorophenyl)borane (B(C6F5)3). The obtained results indicate that the Si-O bonds are cleaved by reaction with DMC to form lower-weight polymer fragments with alkoxy end groups, while the addition of B(C6F5)3 to the depolymerizing mixture significantly increases the degree of PDMS depolymerization at room temperature or with increasing temperature. Quantum chemical calculations show that the DMC molecules form stable complexes with B(C6F5)3 by preferable formation of C=O····B bonds, which increases the solvation effects and kinetic energy upon collision with PDMS. This result provides an appropriate electronic structure and orientation for the complexes for more effective interaction with Si-O-Si via a concert mechanism. This proposed benign approach can be used for the production of new OS polymers, silicone recycling and functionalization of metal or metalloid oxides. We report a novel approach of siloxane bond splitting in organosiloxane using mixture of tris(pentafluorophenyl)borane and dimethyl carbonate. In the first part of this note, depolymerization of polydimethylsiloxane by dimethyl carbonate and with the addition of tris(pentafluorophenyl)borane is studied. Reactions are studied at different concentrations of above-mentioned reagents and temperature while the second part of this note represents theoretical calculation results which explain the mechanism of the depolymerization reaction.

Numerous efforts to fabricate antimicrobial surfaces by simple yet universal protocols with high efficiency have attracted considerable interest but proved to be particularly challenging. Herein, we designed and fabricated a series of antimicrobial polymeric coatings with different functions from single to multiple mechanisms by selectively utilizing diethylene glycol diglycidyl ether (PEGDGE), polylysine, and poly[glycidylmethacrylate-co-3-(dimethyl(4-vinylbenzyl)ammonium)propyl sulfonate] (poly(GMA-co-DVBAPS)) via straightforward mussel-inspired codeposition techniques. Bactericidal polylysine endowed the modified surfaces with a high ability (∼90%) to kill attached bacteria, while PEGDGE components with unique surface hydration prevented bacterial adhesion, avoiding the initial biofilm formation. Moreover, excellent salt-responsive poly(GMA-co-DVBAPS) enabled reactant polymeric coatings to change chain conformations from shrinkable to stretchable state and subsequently release >90% attached bacteria when treated with NaCl solution, even after repeated cycles. Therefore, the obtained polymeric coatings, polydopamine/poly(GMA-co-DVBAPS) (PDA/PDV), polydopamine/polylysine/poly(GMA-co-DVBAPS) (PDA/l-PDV), and polydopamine/polylysine/poly(GMA-co-DVBAPS)/diethylene glycol diglycidyl ether (PDA/l-PDV-PEGDGE), controllably realized functions from single and dual to multiple antimicrobial mechanisms, as evidenced by long-term antifouling activity to bacteria, high bactericidal efficiency, and salt-responsive bacterial regeneration performance with several bacterial killing-release cycles. This study not only contributes to mussel-inspired chemistry for polymeric coatings with controllable functions but also provides a series of reliable and highly efficient antimicrobial surfaces for potential biomedical applications.

Titania (titanium(IV) oxide) is a highly active, stable, cheap and abundant photocatalyst, and is thus commonly applied in various environmental applications. However, two main shortcomings of titania, i.e., charge carrier recombination and inactivity under visible-light (vis) irradiation, should be overcome for widespread commercialization. Accordingly, titania has been doped, surface modified and coupled with various ions/compounds, including narrower bandgap semiconductors, such as oxides of copper and silver. Unfortunately, these oxides are not as stable as titania, and thus loss of activity under long-term irradiation (photo-corrosion) has been observed. Therefore, this study has focused on the preparation of stable coupled photocatalysts, i.e., CuxO@TiO2 core–shell nanostructures, by the microemulsion method from commercial Cu2O as a core and TiO2 (ST01-fine anatase) as a shell. The photocatalysts have been characterized by DRS, SEM, TEM, XRD, XPS and reversed double-beam photo-acoustic spectroscopy (RDB-PAS) methods, and activity tests under UV (anaerobic dehydrogenation of methanol and oxidative decomposition of acetic acid) and vis (phenol oxidation) irradiation. The higher activities of coupled photocatalysts than their counterparts have been found in all studied systems under UV/vis irradiation. Moreover, long-term experiments (10 h) have shown high stability of CuxO@TiO2. However, the change of oxidation state of copper has also been observed, i.e., to negative and positive values, confirming the charge transfer according to the Z-scheme under UV irradiation and type-II heterojunction under vis irradiation, respectively. The property-governed activity and the mechanism have been discussed in detail.

Herein, we developed a novel strategy for the shape-controlled synthesis of iron oxide nanostructures with superior r2 values through the introduction of fluoride ions as a morphology controlling agent and dopant. The selective adsorption of fluoride ions onto the specified crystal planes of iron oxide nanocrystals leads to the formation of octapod nanoparticles (ONPs) and cubic nanocrystal clusters (CNCs). Both ONPs and CNCs present high r2 values (526.5 and 462.2 mM-1 s-1, respectively) due to the synergistic effect of a larger effective radius, clustering and fluorine doping. The in vivo MRI results show significant enhancement in T2-weighted images of the liver after the intravenous injection of ONPs and CNCs, suggesting their great potential as efficient T2-weighted MRI contrast agents. This new approach of achieving anisotropic fluorine-doped iron oxide nanostructures with high r2 relaxivity provides an alternative strategy for the development of highly sensitive T2 contrast agents for MRI.

Titanium dioxide (TiO2) is widely used in various major industries owing to its different crystal forms and functions. Therefore, fabricating suitable crystalline TiO2 through reasonable processes is necessary. In this study, Fe-doped TiO2 precursors were prepared via hydrolysis. Further, in situ high-temperature X-ray diffraction and transmission electron microscopy were used to transform the synthesized precursor in its crystal form. The Rietveld full-spectrum fitting method could accurately yield two different crystal forms at instant temperatures. Additionally, the rate relation between the crystal form transformation and reaction conditions was obtained. Results showed that the addition of Fe increased the temperature of phase transition of TiO2 anatase to rutile and accelerated the anatase → rutile transformation process. Further, crystal phase transition kinetic analysis showed that the phase transition kinetic model of Fe-doped TiO2 matched the Johnson-Mehl-Avrami-Kohnogorov (JMAK) model and that its phase transition was affected by crystal defects. Finally, Fe3+ in Fe-doped TiO2 was reduced to Fe2+ to generate oxygen vacancies, thus promoting the rate of transformation from titanium ore to rutile.

COVID-19 has recently caused a global health crisis and an effective interventional therapy is urgently needed. Remdesivir is one effective inhibitor for SARS-CoV-2 viral RNA replication. It supersedes other NTP analogues because it not only terminates the polymerization activity of RNA-dependent RNA polymerase (RdRp), but also inhibits the proofreading activity of intrinsic exoribonuclease (ExoN). Even though the static structure of Remdesivir binding to RdRp has been solved and biochemical experiments have suggested it to be a "delayed chain terminator", the underlying molecular mechanisms is not fully understood. Here, we performed all-atom molecular dynamics (MD) simulations with an accumulated simulation time of 24 microseconds to elucidate the inhibitory mechanism of Remdesivir on nucleotide addition and proofreading. We found that when Remdesivir locates at an upstream site in RdRp, the 1'-cyano group experiences electrostatic interactions with a salt bridge (Asp865-Lys593), which subsequently halts translocation. Our findings can supplement the current understanding of the delayed chain termination exerted by Remdesivir and provide an alternative molecular explanation about Remdesivir's inhibitory mechanism. Such inhibition also reduces the likelihood of Remdesivir to be cleaved by ExoN acting on 3'-terminal nucleotides. Furthermore, our study also suggests that Remdesivir's 1'-cyano group can disrupt the cleavage site of ExoN via steric interactions, leading to a further reduction in the cleavage efficiency. Our work provides plausible and novel mechanisms at the molecular level of how Remdesivir inhibits viral RNA replication, and our findings may guide rational design for new treatments of COVID-19 targeting viral replication.

Hypoxia is a pathological hallmark of solid tumors. Detection of hypoxia is therefore of great interest for tumor diagnosis and treatment. As a well-established biomarker of hypoxia, nitroreductase (NTR) has been widely exploited in the development of hypoxia-responsive fluorescent probes on the basis of its enzymatic activity to reduce nitroaryl groups. However, studies on the relationship between the nitroaryl structure and the probe performance for optimal probe design are still rare. Here we report a comparative investigation of nitroaryl groups and identification of the optimal nitroaryl structure for developing new fluorescent probes with extremely high efficiency in the detection of NTR and the imaging of hypoxic tumor cells. Specifically, we synthesized a series of resorufin-based fluorescent probes containing different nitroaryl groups, compared their fluorescence responses to NTR, and identified 2-nitro-N-methyl-imidazolyl as the optimal nitroaryl group that is much more efficient than the most widely used 4-nitrophenyl for NTR detection. The structure-performance relationship was then studied by theoretical molecular docking, revealing the unique features of 2-nitro-N-methyl-imidazolyl in binding and reaction with NTR. We further incorporated the 2-nitro-N-methyl-imidazolyl group into a near-infrared (NIR) hemicyanine fluorophore and developed a NIR fluorescent probe NFP-7 for the detection of NTR and hypoxic tumor cells. NFP-7 exhibits a strong fluorescence increase toward NTR in vitro with an ultrafast (within 40 seconds to fluorescence maximum) and ultrasensitive (0.2 ng mL-1 detection limit) response. NFP-7 has also been demonstrated for imaging the degree of hypoxia in live tumor cells and, more importantly, in a murine tumor model. Our study provides important insights into hypoxia probe development and new tools for hypoxia imaging.

Background Thromboembolic stroke is a rare but devastating consequence of atrial fibrillation (AF) ablation. Transesopheageal echocardiography (TEE) is recommended to rule out left atrial appendage thrombus (LAA); however, its utilization is variable. Objective To assess whether TEE is mandatory in patients undergoing AF ablation on uninterrupted DOACs. Methods Data from our prospective, multicenter registry of AF patients undergoing radiofrequency catheter ablation on uninterrupted DOACs was analyzed. All included patients were on anticoagulation for at least four-weeks before ablation. All AF ablation procedures were performed under ICE guidance. Prior to transseptal puncture, heparin bolus was administered, followed by continuous infusion, with target activated clotting time over 300 seconds. Results A total of 6186 patients [3180 (51.4%): apixaban, 2528 (40.9%): rivaroxaban, 404 (6.5%): dabigatran, and 74 (1.2%): edoxaban] were analyzed. The mean age of the study population was 69.4 ± 10.3 years, of which 4194 (67.8%) patients were male and 5120 (82.8%) patients had persistent and long-standing persistent AF. The mean CHA2DS2-VASc score was 2.86 ± 1.58; the mean CHADS2 score was 1.65 ± 1.14. ICE ruled out LAA and LA thrombus in all patients and revealed ‘smoke’ in 1672 (27.03%) patients. Transient ischemic attack was noted in one patient with long-standing persistent AF, in the setting of a missed dose of rivaroxaban prior to ablation. Conclusion Our study showed that performance of AF ablation in patients on uninterrupted DOACs without TEE is safe and feasible in high stroke-risk patients. Elimination of routine pre-ablation TEE would have significant economic and clinical implications.

Methyl orange (MO) is a main organic water pollutants that has been attracted a lot of attention; it can be degraded under photoirradiation in the presence of H2O2. Herein, we developed two Cu(I)-b...

In this work, In2O3 thin films were grown on (111) yttria-stabilized zirconia (YSZ) by metal-organic chemical vapor deposition (MOCVD) at different temperature. It is found that samples grown at low temperature showed lower residual stress but higher mosaicity while high growth temperatures could also cause deterioration in crystal quality due to increasing lattice mismatch. To obtain high quality In2O3 film with low residual strain, a 30-nm thick layer grown at 530 °C was introduced as buffer layer, considering both stress relaxation and crystalline mosaicity. By using two-step growth method, a 400 nm-thick, high quality, near-strain-free In2O3 thin film with the full width at half maximum (FWHM) values of (222) diffraction peaks being as narrow as 648 arcsec was successfully obtained.

Background Melatonin (MT) is important for plant growth and development; however, it is not known whether MT is involved in apple adventitious root (AR) development. In this study, we treated Malus prunifolia (MP) at four different stages of AR development, and analyzed the level of the endogenous hormones MT, auxin (IAA), zeatin-riboside (ZR), abscisic acid (ABA), and gibberellins (GA1 + 3) in all four treatment groups and the untreated control group. The expression of MT, IAA biosynthesis, transport and signal transduction, the cell cycle, and root development related genes were quantified by RT-qPCR. The function of MdWOX11 was analyzed in transgenic apple plants. Results The promotion of AR development by MT was dependent on the stage of AR induction between 0 and 2 d in apple rootstocks. MT-treatment increased the level of IAA and crosstalk existed between MT and IAA during AR formation. The expression of MdWOX11 was induced by MT treatment and positively regulated AR formation in apple. Furthermore, transgenic lines that overexpressed MdWOX11 lines produced more ARs than ‘GL3’. Phenotypic analysis indicated that MdWOX11 overexpression lines were more sensitive to exogenous MT treatment than ‘GL3’, suggesting that MdWOX11 regulates AR formation in response to MT in apple rootstock. Conclusions MT promotes AR formation mainly during the AR induction stage by inducing IAA levels and upregulating MdWOX11.

Purpose Nitrous oxide (N2O) abuse has become an increasingly severe problem in China. The aim of the study was to summarize the features of N2O-induced neurology and enhance the awareness of this disease among physicians. Patients and methods We retrospectively reviewed the clinical, imaging, electrophysiological characteristics and the prognosis of patients with N2O neurotoxicity in our hospital from January 2016 to August 2019. Results Twenty-one patients (average age: 22.6±4.6 years) were collected. Eighty-six percent (18/21) patients presented with acute or subacute neurological disorders as their initial symptoms. The remaining fourteen percent (3/21) had psychiatric symptoms as the earliest symptoms. With progression, movement dysfunction appeared in ninety percent (19/21) of the patients with fifty-three percent (10/19) presented with weakness limited to both lower extremities. Sixty-two percent (13/21) of the patients presented with subjective sensory deficit. Seventy-one percent (15/21) had vibration sense impairment and positive Romberg's sign. Sixty-seven percent of the patients had hyporeflexia or areflexia. Fourteen percent (3/21) showed positive Babinski's sign. Seventy-eight percent (14/18) showed significantly increased homocysteine (HCY) level and only seventeen percent (3/18) showed decreased serum vitamin B12 level. T2 hyperintensity involving the posterior columns and lateral columns with inverted V sign in cervical spinal MRI had been observed in forty-seven percent (8/17) of the patients. Axonal peripheral neuropathy occurred in eighty-five percent (17/20) of the patients. The level of serum vitamin B12 and HCY, as well as imaging findings, were rapidly recovered after supplementation of Vitamin B12. Conclusion The N2O-induced neuropsychiatric disturbances mainly occurred in the young groups and should be recognized by clinicians. The prognosis of N2O intoxication is relatively good.