Elucidation of a distinct photoreduction pathway in class II photolyase.

Class II photolyases (PLs) are a distant subclade in the photolyase/cryptochrome superfamily, displaying a unique Trp-Tyr tetrad for photoreduction and exhibiting a lower quantum yield (QY) of DNA repair (49%) than class I photolyases (82%) [M. Zhang, L. Wang, S.

Catalytic Promiscuity of Fatty Acid Photodecarboxylase Enables Stereoselective Synthesis of Chiral α-Tetralones.

In the field of biocatalysis, discovering novel reactivity from known enzymes has been a longstanding challenge. Fatty acid photo-decarboxylase from Chlorella variabilis (CvFAP) has drawn considerable attention as a promising photoenzyme with potential green chemistry applications; however, its non-natural reactivity has rarely been exploited to date. Herein we report a non-natural reductive dehalogenation (deacetoxylation) reactivity of CvFAP inspired by its natural oxidative decarboxylation process, enabling the stereoselective synthesis of a series of chiral α-substituted tetralones with high yields (up to 99 %) and e.

Intracerebroventricular infusion of secretoneurin inhibits neuronal NLRP3-Apoptosis pathway and preserves learning and memory after cerebral ischemia.

Transient global cerebral ischemia (GCI) results in delayed neuronal death, primarily apoptosis, in the hippocampal CA1 subregion, which leads to severe cognitive deficits. While therapeutic hypothermia is an approved treatment for patients following cardiac arrest, it is associated with various adverse effects. Secretoneurin (SN) is an evolutionarily conserved neuropeptide generated in the brain, adrenal medulla and other endocrine tissues.

Elementary Reactions in the Functional Triads of the Blue-Light Photoreceptor BLUF Domain.

The blue light using the flavin (BLUF) domain is one of the smallest photoreceptors in nature, which consists of a unique bidirectional electron-coupled proton relay process in its photoactivation reaction cycle. This perspective summarizes our recent efforts in dissecting the photocycle into three elementary processes, including proton-coupled electron transfer (PCET), proton rocking, and proton relay. Using ultrafast spectroscopy, we have determined the temporal sequence, rates, kinetic isotope effects (KIEs), and concertedness of these elementary steps.

MiR-2113 overexpression attenuates sepsis-induced acute pulmonary dysfunction, inflammation and fibrosis by inhibition of HMGB1.

Purpose: Sepsis-induced acute lung injury is related to high mortality. MiR-2113 possesses important functions in human diseases. This research aimed to clarify the role and mechanism of miR-2113 in sepsis-induced acute lung injury.

Origin of the multi-phasic quenching dynamics in the BLUF domains across the species.

Blue light using flavin (BLUF) photoreceptors respond to light via one of nature's smallest photo-switching domains. Upon photo-activation, the flavin cofactor in the BLUF domain exhibits multi-phasic dynamics, quenched by a proton-coupled electron transfer reaction involving the conserved Tyr and Gln. The dynamic behavior varies drastically across different species, the origin of which remains controversial.

Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis.

Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated the great potential of non-natural photoenzymes, all of the transformations are initiated by single-electron reduction of the substrate, with only one notable exception. Herein, we report an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins using a novel mutant of gluconobacter ene-reductase (GluER-W100F-W342F).

[Research advances on neurally adjusted ventilatory assist].

Mechanical ventilation has, since its introduction into clinical practice, undergone a major evolution from controlled ventilation to diverse modes of assisted ventilation. Conventional mechanical ventilators depend on flow sensors and pneumatic pressure and controllers to complete the respiratory cycle. Neurally adjusted ventilatory assist (NAVA) is a new form of assisted ventilation in recent years, which monitors the electrical activity of the diaphragm (EAdi) to provide an appropriately level of pressure support.

The association between serum anion gap and acute kidney injury after coronary artery bypass grafting in patients with acute coronary syndrome.

Background: The purpose of this study was to explore the association between serum anion gap (SAG) and acute kidney injury (AKI) after coronary artery bypass grafting (CABG) in patients with acute coronary syndrome (ACS) in the Intensive Care Unit (ICU).

Methods: We retrospectively analyzed the clinical data of 2,428 ACS patients who underwent CABG in the Medical Information Mart for Intensive Care IV (Mimic-IV) database. The endpoint of this study was AKI after CABG.

An ultrafast phototrigger of the Trp5CN-Trp motif in a β-hairpin peptide.

Phototriggers are useful molecular tools to initiate reactions in enzymes by light for the purpose of photoenzymatic design and mechanistic investigations. Here, we incorporated the non-natural amino acid 5-cyanotryptophan (W5CN) in a polypeptide scaffold and resolved the photochemical reaction of the W5CN-W motif using femtosecond transient UV/Vis and mid-IR spectroscopy. We identified a marker band of ∼2037 cm-1 from the CN stretch of the electron transfer intermediate W5CN·- in the transient IR measurement and found UV/Vis spectroscopic evidence for the W·+ radical at 580 nm.

Dissecting the Ultrafast Stepwise Bidirectional Proton Relay in a Blue-Light Photoreceptor.

Proton relays through H-bond networks are essential in realizing the functionality of protein machines such as in photosynthesis and photoreceptors. It has been challenging to dissect the rates and energetics of individual proton-transfer steps during the proton relay. Here, we have designed a proton rocking blue light using a flavin (BLUF) domain with the flavin mononucleotide (FMN)-glutamic acid (E)-tryptophan (W) triad and have resolved the four individual proton-transfer steps kinetically using ultrafast spectroscopy.

The nature of proton-coupled electron transfer in a blue light using flavin domain.

Proton-coupled electron transfer (PCET) is key to the activation of the blue light using flavin (BLUF) domain photoreceptors. Here, to elucidate the photocycle of the central FMN-Gln-Tyr motif in the BLUF domain of OaPAC, we eliminated the intrinsic interfering W90 in the mutant design. We integrated the stretched exponential function into the target analysis to account for the dynamic heterogeneity arising from the active-site solvation relaxation and the flexible H-bonding network as shown in the molecular dynamics simulation results, facilitating a simplified expression of the kinetics model.

Targeting A and p-Tau Clearance in Methamphetamine-Induced Alzheimer's Disease-Like Pathology: Roles of Syntaxin 17 in Autophagic Degradation in Primary Hippocampal Neurons.

Methamphetamine (Meth), a central nervous system (CNS) stimulant with strong neurotoxicity, causes progressive cognitive impairment with characterized neurodegenerative changes. However, the mechanism underlying Meth-induced pathological changes remains poorly understood. In the current study, Meth elicited a striking accumulation of the pathological proteins hyperphosphorylated tau (p-tau) and amyloid beta (A) in primary hippocampal neurons, while the activation of autophagy dramatically ameliorated the high levels of these pathological proteins.

Direct Observation of Ultrafast Proton Rocking in the BLUF Domain.

We present direct observation of ultrafast proton rocking in the central motif of a BLUF domain protein scaffold. The mutant design has taken consideration of modulating the proton-coupled electron transfer (PCET) driving forces by replacing Tyr in the original motif with Trp, in order to remove the interference of a competing electron transfer pathway. Using femtosecond pump-probe spectroscopy and detailed kinetics analysis, we resolved an electron-transfer-coupled Grotthuss-type forward and reverse proton rocking along the FMN-Gln-Trp proton relay chain.

Exosomes derived from hypoxic bone marrow mesenchymal stem cells rescue OGD-induced injury in neural cells by suppressing NLRP3 inflammasome-mediated pyroptosis.

Exosomes have been shown to have therapeutic potential for cerebral ischemic diseases. In this study, we investigated the neuroprotective effects of normoxic and hypoxic bone marrow mesenchymal stromal cells-derived exosomes (N-BM-MSCs-Exo and H-BM-MSCs-Exo, respectively) on oxygen-glucose deprivation (OGD) injury in mouse neuroblastoma N2a cells and rat primary cortical neurons. The proportions of dead cells in N2a and primary cortical neurons after OGD injury were significantly increased, and N-BM-MSCs-Exo (40 μg/ml) could reduce the ratios, noteworthily, the protective effects of H-BM-MSCs-Exo (40 μg/ml) were more potent.

CircRNA circ_0006892 regulates miR-24/PHLPP2 axis to mitigate cigarette smoke extract-induced bronchial epithelial cell injury.

Chronic obstructive pulmonary disease (COPD) is a chronic airway disorder mainly resulted from cigarette smoke exposure. The dysregulated circular RNAs (circRNAs) are relevant to the pathogenesis of COPD. This study aims to explore the function and mechanism of circRNA hsa_circ_0006892 (circ_0006892) in cigarette smoke extract (CSE)-induced bronchial epithelial injury.

Effects of extracellular vesicles from mesenchymal stem cells on oxygen-glucose deprivation/reperfusion-induced neuronal injury.

Background: Small extracellular vesicles (sEVs) from bone marrow mesenchymal stem cells (BMSCs) have shown therapeutic potential for cerebral ischemic diseases. However, the mechanisms by which BMSC-derived sEVs (BMSC-sEVs) protect neurons against cerebral ischemia/reperfusion (I/R) injury remain unclear. In this study, we explored the neuroprotective effects of BMSC-sEVs in the primary culture of rat cortical neurons exposed to oxygen-glucose deprivation and reperfusion (OGD/R) injury.

[Analysis of the positive rate of anal swab nucleic acid test and clinical characteristics in patients with different severity of coronavirus disease 2019].

Objective: To compared the positive rate of anal swab nucleic acid test and clinical characteristics of critical and general coronavirus disease 2019 (COVID-19) patients.

Methods: Clinical data of 18 patients with COVID-19 admitted to the First People's Hospital of Lianyungang City from February to March 2020 were retrospectively analyzed. The patients were divided into general group (n = 11) and critical ill group (n = 7) according to the severity of the disease.

NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497-5p and upregulating MCM2.

Background: Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer.

Diode laser photoacoustic spectroscopy of CO, HS and O in a differential Helmholtz resonator for trace gas analysis in the biosciences and petrochemistry.

Photoacoustic spectroscopy in a differential Helmholtz resonator has been employed with near-IR and red diode lasers for the detection of CO, HS and O in 1 bar of air/N and natural gas, in static and flow cell measurements. With the red distributed feedback (DFB) diode laser, O can be detected at 764.3 nm with a noise equivalent detection limit of 0.