A chemical investigation on

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P

Organic carbonates (OCs) are a class of compounds featured by a carbonyl flanked by two alkoxy/aryloxy groups. They exist in either linear or cyclic forms, of which the majority encountered in nature adopt a pentacyclic structure. However, the enzymatic basis for pentacyclic carbonate ring formation remains elusive. Here, we reported that a four-protein metabolon (AlmUII-UV) assembled by a small peptide protein (AlmUV) appends a reactive

In order to study the influence of tympanic membrane lesion and ossicular erosion caused by otitis media on the hearing compensation performance of round-window stimulation, a human ear finite element model including cochlear asymmetric structure was established by computed tomography (CT) technique and reverse engineering technique. The reliability of the model was verified by comparing with the published experimental data. Based on this model, the tympanic membrane lesion and ossicular erosion caused by otitis media were simulated by changing the corresponding tissue structure. Besides, these simulated diseases' effects on the round-window stimulation were studied by comparing the corresponding basilar-membrane's displacement at the frequency-dependent characteristic position. The results show that the thickening and the hardening of the tympanic membrane mainly deteriorated the hearing compensation performance of round-window stimulation in the low frequency; tympanic membrane perforation and the minor erosion of ossicle with ossicular chain connected slightly effected the hearing compensation performance of round-window stimulation. Whereas, different from the influence of the aforementioned lesions, the ossicular erosion involving the ossicular chain detachment increased its influence on performance of round-window stimulation at the low frequency. Therefore, the effect of otitis media on the hearing compensation performance of round-window stimulation should be considered comprehensively when designing its actuator, especially the low-frequency deterioration caused by the thickening and the hardening of the tympanic membrane; the actuator's low-frequency output should be enhanced accordingly to ensure its postoperative hearing compensation performance.
Acoustic Stimulation ; Ear Ossicles ; pathology ; Finite Element Analysis ; Hearing ; Humans ; Otitis Media ; physiopathology ; Reproducibility of Results ; Round Window, Ear ; physiology ; Tomography, X-Ray Computed ; Tympanic Membrane Perforation

Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.

Accelerated forgetting has been identified as a feature of Alzheimer's disease (AD), but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal models. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTPase, has been shown to regulate active forgetting in Drosophila and mice. Here, we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal models. Moreover, amyloid-beta 42 could induce Rac1 activation in cultured cells. The elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice, but also significantly contributed to severe memory loss in aged APP/PS1 mice. A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly model. Moreover, inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal models. Finally, two novel compounds, identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models, were found to be capable of inhibiting Rac1 activity. Thus, multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss.

Four interesting sequoiatones stereoisomers (-) were isolated from a wetland soil-derived fungusby chiral HPLC. On the basis of comprehensive NMR and mass analyses, their planar structures were elucidated as the same as that of sequoiatone B. Among them,and(orand) were a pair of enantiomers, andand(orand) were a pair of stereoisomers with epimerization at C-12, which indicated that sequoiatione-type metabolites exist as enantiomers rather than as optically pure compounds in some strains. With the quantum chemical ECD calculations, the absolute configurations of C-8 in-were determined, which is the first report to establish the absolute configuration of C-8 in sequoiatones. However, the absolute configurations of C-12 in sequoiatones are still unsolved.

Objective To explore the formation process of vacuum pressure differential of micro power negative pressure technology to facilitate its clinical application.MethodsThe formation of negative pressure differential and changes of negative pressure values in enclosure space were studied which was formed by liquid aspiration after the compressive polyvinyl alcohol foam material was enclosed.Micro power negative pressure technology was applied to the treatment of the right ear necrosis patient after focal cleaning,and the efficacy was observed.Results Medical adhesive film was raised gradually during the expansion of polyvinyl alcohol foam due to liquid aspiration,and then the enclosure space extended increasingly to form local vacuum negative pressure.The range of maximal negative pressure was between-110 and-200 Pa,and the mean maximal negative pressure value was-132.7 Pa.Micro power negative pressure technology behaved well in healing the wound.Conclusion Micro power negative pressure technology gains advantages in reliability and easy operation over other technologies and products,and may be a new choice for healing of refractory wounds.

Objective To observe the effect of parecoxib united with local anaesthesia analgesia system on analgesia after radical resection of liver cancer. Methods Ninety patients undergoing elective radical resection of liver cancer were randomly assigned to three groups, with 30 patients in each group. The patients in parecoxib group (P group) received parecoxib 40 mg through vein before the end of operation for 30 min, and were injected parecoxib 40 mg at 12 h, 24 h and 46 h after operation. The patients in local anethsia analgesia system group (L group) received embedding hypodermic pervasion canal in incision subcutaneously, then connected the pump with 0.25% ropivacaine 250 ml, with infusion speed of 4 ml/h.The patients in united group(U group)receiced the same methods with those in P group and L group. When the patients'visual analogue scale (VAS) scores were higher than 5 scores, they were given muscle injection of pethidine 50 mg. The VAS scores and Ramsay sedation scores at the time of tracheal extubation (T0), postoperative 2 h(T1), 6 h(T2), 12 h(T3), 24 h(T4) and 48 h(T5), the adverse reaction rate, dosage of pethidine, and analgesia satisfaction were compared. Results The resting and movement of VAS scores and Ramsay sedation scores at each time in P group and L group had no significant difference (P>0.05). The resting and movement of VAS scores and Ramsay sedation scores at each time in U group were significantly better than those in P group and L group (P<0.05). The rate of nausea and vomiting in three groups had no significant difference among three groups (P > 0.05). The rate of drowsiness in U group was significantly lower than that in P group and L group:6.67%(2/30) vs. 26.67%(8/30) and 23.33%(7/30), P < 0.05. The analgesia satisfaction in U group was significantly higher than that in P group and L group:93.33%(28/30) vs. 56.67%(17/30) and 53.33%(16/30), P<0.05. Conclusions The analgesia effect of the parecoxib united with local anaesthesia analgesia system for radical resection of liver cancer is perfect.

Objective To evaluate the quality of intraoperative wake?up test in the patients undergoing scoliosis correction surgery under etomidate?based anesthesia. Methods Thirty patients of both sexes, aged 13-32 yr, weighing 40-65 kg, of ASA physical statusⅠorⅡ, undergoing elective scoliosis correction surgery, were randomly assigned into etomidate group ( group E, n=15 ) or propofol group (group P, n=15) using a random number table. Anesthesia was induced with etomid 0.3 mg∕kg (group E) or propofol 2mg∕kg ( group P ) injected intravenously, midazolam, fentanyl and rocuronium. The patients were mechanically ventilated after naso?tracheal intubation. Etomidate 0.6-1. 2 mg · kg-1 · h-1 and propofol 8- 10 mg·kg-1 ·h-1 were infused intravenously during surgery in E and P groups, respectively. Both remifentanil and cisatracurium were used for maintenance of anesthesia in the two groups. Cisatracurium infusion was stopped before wake?up test. The infusion rate of propofol was adjusted to 4 mg·kg-1 ·h-1 at 15 min before wake?up test. After the scoliotic angle was corrected, infusion of etomidate and propofol was stopped, and the infusion rate of remifentanil was adjusted to 0.025μg·kg-1 ·min-1 in both groups. The wake?up time was recorded, and the quality of wake?up was assessed. Mean arterial pressure (MAP) and heart rate were recorded before anesthesia ( T0 ) , immediately before the patients were awakened ( T1 ) , when the patients responded to commands from doctors ( T2 ) , and after anesthesia was deepened ( T3 ) . At T0 , the end of surgery ( T4 ) , and 24 h after surgery ( T5 ) , blood samples were collected from the internal jugular vein for determination of plasma cortisol concentrations. Results The patients were awakened successfully in the two groups, and there were no significant differences in the wake?up time, quality of wake?up, and MAP, HR and plasma cortisol concentrations at each time point between the two groups. MAP and HR were significantly higher at T2 than at T0 in the two groups. MAP and HR were within the normal range during wake?up test, and no patients developed severer cardiovascular events in the two groups. Conclusion Etomidate?based anesthesia provides better quality of intraoperative wake?up test in the patients undergoing scoliosis correction surgery, which is similar to that of propofol?based anesthesia.