The pericyclases are a growing superfamily of enzymes that catalyze pericyclic reactions. We report pericyclase IccD catalyzing an inverse-electron demand Diels-Alder (IEDDA) reaction with rate acceleration 3 × 105-fold in the biosynthesis fungal natural product ilicicolin H. demonstrate is highly periselective toward IEDDA cycloaddition over competing normal electron (NEDDA) from ambimodal transition state. A predicted flavoenzyme IccE was identified to epimerize 8- epi-ilicicolin H H, step...

<ns4:p>Bacterial aromatic polyketides, exemplified by anthracyclines, angucyclines, tetracyclines, and pentangular polyphenols, are a large family of natural products with diverse structures biological activities usually biosynthesized type II polyketide synthases (PKSs). Since the starting point biosynthesis combinatorial in 1984–1985, there has been continuous effort to investigate biosynthetic logic polyketides owing urgent need developing promising therapeutic candidates from these...

Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (TCs) and nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The of 1 is tetracyclic, cage-like, oxygenated sesquiterpene connected dimethylcadaverine via C–N bond acylated with 5,5-dimethyl-l-pipecolate. roles all are established...

Acetohydroxyacid synthase (AHAS) is the first enzyme in branched-chain amino acid biosynthetic pathway and a validated target for herbicide fungicide development. Here we report harzianic (HA,

Subscription RequiredScientific InvestigationsStellate ganglion block alleviates postoperative sleep disturbance in patients undergoing radical surgery for gastrointestinal malignancies Shiting Yan, MM, Ying Wang, Leyang Yu, Wei Xia, Feng Xue, Yanlong Bo Yuan, Ning Li, Hu Hailiang Liang, Jianming Ma, Zhuan Zhang, MD MM Department of Anesthesiology, the Affiliated Hospital Yangzhou University, Yangzhou, China Graduate School, Dalian Medical Dalian, , General Surgery, Published Online:May 2,...

Significance Enzymatic modifications of anthracycline antibiotics are urgently needed in the fields biosynthesis, biocatalysis, and even medical chemistry. However, neither hydroxyl regioisomerization nor dehydroxylation core was described previously. Here, we discover an unprecedented process biosynthesis a rare carbon-4 deoxyanthracycline, which includes three tailoring steps performed by four-enzyme cascade: two-component hydroxylases mediated cryptic hydroxylation, two NmrA-like...

Fungal highly reducing polyketide synthases (HRPKSs) biosynthesize polyketides using a single set of domains iteratively. Product release is critical step in HRPKS function to ensure timely termination and enzyme turnover. Nearly all the HRPKSs characterized date employ separate thioesterase (TE) or acyltransferase for product release. In this study, we two fungal that have fused C-terminal TE domains, new domain architecture HRPKSs. We showed both HRPKS-TEs synthesize aminoacylated an...

The clinical utility of gemcitabine, an antimetabolite antineoplastic agent applied in various chemotherapy treatments, is limited due to the required intravenous injection. Although chemical structure modifications gemcitabine result enhanced oral bioavailability, these compromise complex synthetic routes and cause unexpected side effects. In this study, gemcitabine-loaded glycocholic acid-modified micelles (Gem-PPG) were prepared for chemotherapy.

Phenylfuropyridone natural products from fungi exhibit a range of antibacterial and cytotoxicity activities, can potentiate azole antifungal compounds. We elucidated the biosynthetic pathway compounds in citridone family through heterologous reconstitution pfp pathway. demonstrate that multiple members this be accessed reactive ortho-quinone methide (o-QM) intermediate electrocyclization, cycloisomerization, or conjugate addition. Formation quaternary carbon center B is catalyzed by an...

Recombinant protein vaccines, with highly pure ingredients and good safety, are gradually replacing some attenuated inactivated vaccines in clinical practice. However, since their low immunogenicity of the recombinant proteins, adjuvants often needed to enhance immune response after vaccination. Aluminum adjuvant has been widely used for decades, it can induce strong humoral immunity, but deficiency cellular immunity limits its application vaccines. Therefore, is urgently develop novel...

Abstract Background Dexmedetomidine has controversial influence on cardiac electrophysiology. The aim of this study was to explore the effects dexmedetomidine perioperative electrophysiology in patients undergoing general anesthesia. Methods Eighty-one were randomly divided into four groups: groups D 1 , 2 3 receiving 1, 0.5 μg/kg over 10 min and 0.5, μg/kg/h continuous infusion respectively, control group (group C) normal saline. Twelve-lead electrocardiograms recorded at time before...

Thrombotic complications of atrial fibrillation continue to pose a significant challenge in clinical practice today. Left appendage occlusion (LAAO) has emerged as promising alternative oral anticoagulation for high-risk patients with fibrillation. However, despite the potential benefits, there is still possibility life-threatening such device dislocation. In this case study, we present patient who experienced severe hemodynamic disturbances due embolization LAAO into left ventricular...

To determine the median effective dose (ED50) of prophylactic intravenous lidocaine for prevention propofol medium-chain triglyceride/long-chain triglyceride (MCT/LCT) emulsion injection pain.Prospective trial, Dixon up-and-down sequential method.Operating room a single hospital.Thirty patients aged 18-65 years with American Society Anesthesiologists (ASA) status I or II who were scheduled elective surgery under general anesthesia (GA) included.The initial before MCT/LCT was set at 0.5 mg/kg...

To investigate the optimal dose of pretreated-dexmedetomidine in fentanyl-induced cough (FIC) suppression.

A four-enzyme catalyzed hydroxy regioisomerization of anthracycline was integrated into the biosynthetic pathway aclacinomycin (ALM-A), to generate a series iso-ALMs via directed combinatorial biosynthesis combined with precursor-directed mutasynthesis. Most newly acquired exhibit obviously (1–5-fold) improved antitumor activity. Therefore, we not only developed potential as clinical drugs but also demonstrated utility this tailoring tool for modification antibiotics in drug discovery and...

Purpose To evaluate the optimal dose of dexmedetomidine for perioperative blood glucose regulation in non-diabetic patients with gastrointestinal malignant tumor.Methods One hundred were randomly divided into four groups: control group (group C), 1 μg/kg + 0.25 mcg/kg/h D1); 0.5 D2); and D3). Blood concentrations measured before infusion (T1), h after surgery beginning (T2), at end (T3), PACU (T4). Duration surgery, extubation time, anesthetics doses, adverse reactions, postoperative...

Abstract Phenylfuropyridone natural products from fungi exhibit a range of antibacterial and cytotoxicity activities, can potentiate azole antifungal compounds. We elucidated the biosynthetic pathway compounds in citridone family through heterologous reconstitution pfp pathway. demonstrate that multiple members this be accessed reactive ortho ‐quinone methide ( o ‐QM) intermediate electrocyclization, cycloisomerization, or conjugate addition. Formation quaternary carbon center B is catalyzed...

The aim of this paper was to explore pupillary monitoring for determining remifentanil consumption during general anesthesia and evaluating postoperative recovery quality.Eighty patients undergoing elective laparoscopic uterine surgery were randomly divided into group (Group P) control C). In Group P, dosage determined according pupil dilation reflex; in C, it adjusted hemodynamic changes. Intraoperative endotracheal tube extraction time recorded. Numerical Rating Scale (NRS) Score, changes,...

Purpose. A prospective controlled study was designed to observe the pharmacodynamics of rocuronium in cholestatic patients with or without hepatocellular injury. Methods. Sixty undergoing abdominal surgery were allocated into three groups: group I had 20 injury; II injury, and III (control group) hepatic disease. Anesthetized propofol fentanyl, all received 0.6 mg/kg for initial dose followed by intermittent repeated administration 0.15 mg/kg. The twitch high adductor pollicis muscle...

Abstract A biodegradable local drug release system consisting of poly(sebacic anhydride) and polylactic acid was developed for the purpose osteomyelitis therapy. Five kinds with different molecular weights were synthesized, levofloxacin chosen as a model antibacterial in vitro within 38 days. As weight increased, melting point (Tm) matrices increased surface morphology became smoother. Consequently, initial burst effect reduced rate significantly decreased. In addition, kinetics pills...

This study aimed to test the effects of hypophysin on hemodynamics and coronary artery caliber patients with hypotension decreased systemic vascular resistance (SVR) following cardiopulmonary bypass (CPB).Twenty-four mean arterial pressure (MAP) < 60 mmHg, aorta 70 SVR 800 dynes.sec.cm-5, cardiac index (CI) > 2.5 l.min-1.m-2, central venous 8 mmHg refractory dopamine, norepinephrine, fluid resuscitation were treated at an initial dose 0.6 IU a continuous infusion rate 1 - 4 IU/h till end...