The ß-subunit of tryptophan synthase is a latent tyrosine synthase.

Aromatic amino acids and their derivatives are diverse primary and secondary metabolites with critical roles in protein synthesis, cell structure and integrity, defense and signaling. All de novo aromatic amino acid production relies on a set of ancient and highly conserved chemistries. Here we introduce a new enzymatic transformation for L-tyrosine synthesis by demonstrating that the ß-subunit of tryptophan synthase-which natively couples indole and L-serine to form L-tryptophan-can act as a latent 'tyrosine synthase'. A single substitution of a near-universally conserved catalytic residue unlocks activity toward simple phenol analogs and yields exclusive para carbon-carbon bond formation to furnish L-tyrosines. Structural and mechanistic studies show how a new active-site water molecule orients phenols for a nonnative mechanism of alkylation, with additional directed evolution resulting in a net >30,000-fold rate enhancement. This new biocatalyst can be used to efficiently prepare valuable L-tyrosine analogs at gram scales and provides the missing chemistry for a conceptually different pathway to L-tyrosine.

Production of hybrid AgNPs - TEMPO-mediated oxidation cellulose composite from jackfruit peduncle agro-waste and its thermal management application in electronic devices.

The urgent need for eco-friendly and cost-effective cellulose paper substrates in thermal management for biomedical electronic devices has driven the exploration of agro-waste materials. In this study, jackfruit peduncle waste was utilized as a precursor to produce a hybrid of AgNPs-tempo-mediated oxidation cellulose strands (AgNPs-TOCS) through acid hydrolysis, TEMPO oxidation, and an in-situ generation process. The resulting hybrid AgNPs-TOCS composite exhibited a cylindrical cellulose structure with a diameter of 27.3 µm, on which spherical AgNPs with a diameter of 16.3 nm were embedded. This hybrid AgNPs-TOCS displayed an impressive inhibition zone diameter against E. coli bacteria (15.2 nm) and exhibited excellent thermal stability up to 269 °C. Furthermore, the AgNPs-TOCS composite paper substrate was fabricated using non-solvent techniques, and its mechanical, thermal, and electrical properties were investigated. This composite paper substrate exhibits good tensile strength (65 ± 2 MPa), in-plane thermal conductivity (5.8 ± 0.2 W/(m·K)), and electrical resistivity (0.0575 KΩ·m). These findings strongly suggest that this type of composite paper substrate holds promise for applications in thermal management within the field of biomedical electronics.

Central nervous system manifestations of dengue infection: data from a tertiary care Centre in South India.

BACKGROUND: Dengue fever is the second most common mosquito-borne disease affecting human beings and neurological manifestations (NMs) of this arboviral infection are increasingly being reported. METHODS: In this retrospective study, conducted in a tertiary care centre in south India, we sought to describe the spectrum of NMs of dengue fever. The records of all patients admitted in the Department of Internal Medicine over 8 years, with a diagnosis of dengue-based on clinical symptoms and the detection of dengue IgM antibodies or detection of NS1 antigen or nucleic acid by reverse transcriptase-polymerase chain reaction (RT-PCR); with Glasgow coma score (GCS) ≤14, neck stiffness, focal neurological signs, seizures, or visual disturbances-were explored. RESULTS: Of 1121 patients admitted with dengue fever, 341 (30%) had severe dengue and 23 (2%) had NMs. Encephalopathy was seen in 9 patients (39%), encephalitis in 6 (27%), cerebellitis in 4 (17%), acute disseminated encephalomyelitis (ADEM) in 2 (9%), ischaemic stroke in 1 (4%) patient, and neuro-ophthalmological manifestations in 1 (4%) patient. The median duration of hospital stay was 7 days. Nine (39% of) patients required intensive care unit (ICU) admission and 5 (22%) had fatal outcomes. There was no association between thrombocytopenia, metabolic acidosis, transaminitis, hyponatremia, the type of dengue infection, and the various NMs described. CONCLUSIONS: The NMs of dengue infection are varied, and a high index of suspicion is needed to identify them in patients who present with lethargy or altered sensorium on the background of an acute febrile illness suggestive of dengue.

Molecular-orbital-based machine learning for open-shell and multi-reference systems with kernel addition Gaussian process regression.

We introduce a novel machine learning strategy, kernel addition Gaussian process regression (KA-GPR), in molecular-orbital-based machine learning (MOB-ML) to learn the total correlation energies of general electronic structure theories for closed- and open-shell systems by introducing a machine learning strategy. The learning efficiency of MOB-ML(KA-GPR) is the same as the original MOB-ML method for the smallest criegee molecule, which is a closed-shell molecule with multi-reference characters. In addition, the prediction accuracies of different small free radicals could reach the chemical accuracy of 1 kcal/mol by training on one example structure. Accurate potential energy surfaces for the H10 chain (closed-shell) and water OH bond dissociation (open-shell) could also be generated by MOB-ML(KA-GPR). To explore the breadth of chemical systems that KA-GPR can describe, we further apply MOB-ML to accurately predict the large benchmark datasets for closed- (QM9, QM7b-T, and GDB-13-T) and open-shell (QMSpin) molecules.

Internet of Things-assisted intelligent monitoring model to analyze the physical health condition.

BACKGROUND: Physical health monitoring may take several forms, from individual quality changes to complex health checks carried out by health staff. Present health issues are detected with monitoring, and potential health problems are expected. Wearable sensors provide users with ease in everyday tracking, although many issues must be addressed in such sensor systems. The devices take a long time to obtain the requisite detection and diagnostic expertise and produce false alarms. OBJECTIVE: In this paper, the Internet of Things-assisted Health Condition Monitoring system (IoT-HCMS) has been proposed to track and analyze the patient physical health condition. METHOD: The proposed IoT-HCMS utilizes the intelligent monitoring model to follow the patient physical health day by day activities and instantaneously generate the health records. The system will indeed support patients in tracking psychological signs to minimize risks to their well-being. RESULTS: The experimental results show that the IoT-HCMS improves accuracy in patient health monitoring and has less response time.

Extracorporeal Membrane Oxygenation in Drug Overdose: A Clinical Case Series.

Overdose of cardiovascular medications such as beta blockers and calcium channel blockers cause impaired cardiac contractility, vasoplegia, and/or rhythm disturbances. In addition to conventional management of limiting absorption, increasing elimination and hemodynamic support intravenous (IV) calcium infusion, hyperinsulinemia-euglycemia therapy, glucagon infusion, and IV lipid emulsion have been tried. Extracorporeal circulatory assist device support has been reported as a rescue therapy in overdose refractory to maximal medical therapy. We report three patients with cardiovascular medication overdose presenting with profound cardiovascular instability refractory to medical therapy. Venoarterial extracorporeal membrane oxygenation support (VA ECMO) was initiated to provide hemodynamic support. Despite the occurrence of device-associated complications, the outcome was good and all patients survived. VA ECMO may be considered in patients with severe refractory shock due to cardiotoxic medication overdose.

Acute right heart syndrome: Rescue treatment with inhaled nitric oxide.

Acute right heart syndrome is a common occurrence in intensive care units and is associated with a poor prognosis. There is lack of understanding of the involved pathophysiology, standard diagnostic protocols and treatment guidelines. Management goals include ensuring adequate right ventricle (RV) filling, maximizing RV contraction and reducing RV afterload. We describe a 39-year-old female with acute decompensated right heart failure secondary to multiple causes. She was managed with inhaled nitric oxide. Her condition improved, which was evident by a decrease in her pulmonary artery systolic pressure on serial echocardiography, decreased requirement of vasopressors and successful weaning from the ventilator.