Visible-Light-Driven Decarboxylative Coupling of 2H-Indazoles with α-Keto Acids without Photocatalysts and Oxidants.

An efficient synthesis of functionalized 3-acyl-2H-indazoles via visible-light-induced self-catalyzed energy transfer was developed. This method utilized a self-catalyzed energy transfer process between 2H-indazoles and α-keto acids, offering advantages like absence of photosensitizers, metal catalysts, and strong oxidants, broad substrate compatibility, and operational simplicity under mild conditions.

Water co-catalysis in aerobic olefin epoxidation mediated by ruthenium oxo complexes.

We report the development of a versatile Ru-porphyrin catalyst system which performs the aerobic epoxidation of aromatic and aliphatic (internal) alkenes under mild conditions, with product yields of up to 95% and turnover numbers (TON) up to 300. Water is shown to play a crucial role in the reaction, significantly increasing catalyst efficiency and substrate scope. Detailed mechanistic investigations employing both computational studies and a range of experimental techniques revealed that water activates the RuVI di-oxo complex for alkene epoxidation via hydrogen bonding, stabilises the RuIV mono-oxo intermediate, and is involved in the regeneration of the RuVI di-oxo complex leading to oxygen atom exchange. Distinct kinetics are obtained in the presence of water, and side reactions involved in catalyst deactivation have been identified.

Batch Fabrication of Microelectrode Arrays with Glassy Carbon Microelectrodes and Interconnections for Neurochemical Sensing: Promises and Challenges.

Flexible multielectrode arrays with glassy carbon (GC) electrodes and metal interconnection (hybrid MEAs) have shown promising performance in multi-channel neurochemical sensing. A primary challenge faced by hybrid MEAs fabrication is the adhesion of the metal traces with the GC electrodes, as prolonged electrical and mechanical stimulation can lead to adhesion failure. Previous devices with GC electrodes and interconnects made of a homogeneous material (all GC) demonstrated exceptional electrochemical stability but required miniaturization for enhanced tissue integration and chronic electrochemical sensing. In this study, we used two different methods for the fabrication of all GC-MEAs on thin flexible substrates with miniaturized features. The first method, like that previously reported, involves a double pattern-transfer photolithographic process, including transfer-bonding on temporary polymeric support. The second method requires a double-etching process, which uses a 2 µm-thick low stress silicon nitride coating of the Si wafer as the bottom insulator layer for the MEAs, bypassing the pattern-transfer and demonstrating a novel technique with potential advantages. We confirmed the feasibility of the two fabrication processes by verifying the practical conductivity of 3 µm-wide 2 µm-thick GC traces, the GC microelectrode functionality, and their sensing capability for the detection of serotonin using fast scan cyclic voltammetry. Through the exchange and discussion of insights regarding the strengths and limitations of these microfabrication methods, our goal is to propel the advancement of GC-based MEAs for the next generation of neural interface devices.

Rhodobacteraceae methanethiol oxidases catalyze methanethiol degradation to produce sulfane sulfur other than hydrogen sulfide.

Methanethiol (MT) is a sulfur-containing compound produced during dimethylsulfoniopropionate (DMSP) degradation by marine bacteria. The C-S bond of MT can be cleaved by methanethiol oxidases (MTOs) to release a sulfur atom. However, the cleaving process remains unclear, and the species of sulfur product is uncertain. It has long been assumed that MTOs produce hydrogen sulfide (H2S) from MT. Herein, we studied the MTOs in the Rhodobacteraceae family-whose members are important DMSP degraders ubiquitous in marine environments. We identified 57 MTOs from 1,904 Rhodobacteraceae genomes. These MTOs were grouped into two major clusters. Cluster 1 members share three conserved cysteine residues, while cluster 2 members contain one conserved cysteine residue. We examined the products of three representative MTOs both in vitro and in vivo. All of them produced sulfane sulfur other than H2S from MT. Their conserved cysteines are substrate-binding sites in which the MTO-S-S-CH3 complex is formed. This finding clarified the sulfur product of MTOs and enlightened the MTO-catalyzing process. Moreover, this study connected DMSP degradation with sulfane sulfur metabolism, filling a critical gap in the DMSP degradation pathway and representing new knowledge in the marine sulfur cycle field. IMPORTANCE: This study overthrows a long-time assumption that methanethiol oxidases (MTOs) cleave the C-S bond of methanethiol to produce both H2S and H2O2-the former is a strong reductant and the latter is a strong oxidant. From a chemistry viewpoint, this reaction is difficult to happen. Investigations on three representative MTOs indicated that sulfane sulfur (S0) was the direct product, and no H2O2 was produced. Finally, the products of MTOs were corrected to be S0 and H2O. This finding connected dimethylsulfoniopropionate (DMSP) degradation with sulfane sulfur metabolism, filling a critical gap in the DMSP degradation pathway and representing new knowledge in the marine sulfur cycle field.

Nanoscale Investigation of Bubble Nucleation and Boiling on Random Rough Surfaces.

Surface roughness is one of the significant factors affecting liquid-vapor phase change heat transfer. This paper explores the effect of surface roughness on bubble nucleation and boiling heat transfer, as well as the microscopic mechanism, by constructing random rough surfaces using molecular dynamics (MD) simulation. Bubbles randomly nucleate on a flat surface and tend to nucleate in pits on rough surfaces. The pits on the random rough surface gather more argon atoms than the protrusions, forming low potential energy regions on the surface, thus providing stable nucleation sites for bubbles. As the surface roughness increases, bubble generation, merging, and growth are advanced. In addition, rough surfaces offer a larger effective heat transfer area for the heat transfer process, increase the strength of solid-liquid coupling, and obtain smaller solid-liquid interaction energy. The critical heat flux (CHF) value positively correlates with surface roughness. As the roughness increases, the surface superheat at the onset of CHF decreases accordingly. This paper provides new insights into the mechanism of heat transfer enhancement on rough surfaces and surface design in thermal management.

Aberrant brain structure in patients with schizophrenia and violence: A meta-analysis.

Previous studies have indicated that schizophrenia is associated with an increased risk of violence, which may constitute a public health concern, leading to poor treatment outcomes and stigmatization of patients. Investigating brain structural features of violence in schizophrenia could help us understand its specific pathogenesis and find effective biomarkers. Our study aimed at identifying reliable brain structural changes associated with violence in patients with schizophrenia by conducting a meta-analysis and meta-regression of magnetic resonance imaging studies. Specific brain changes in patients with schizophrenia and violence (VSZ) were studied, compared with patients with schizophrenia and violence (VSZ), patients with non-violent schizophrenia (NVSZ), and individuals with a history of violence only and health controls. Primary outcomes revealed that there was no significant difference of gray matter volume between patients with VSZ and patient with NVSZ. Compared with controls, patients with VSZ exhibited decreased gray matter volume in the insula, the superior temporal gyrus (STG), the left inferior frontal gyrus, the left parahippocampus, and the right putamen. Compared with individuals with a history of violence only, patients with VSZ exhibited decreased volume in the right insula and the right STG. Meta-regression analysis revealed a negative correlation between the duration of schizophrenia and the volume of the right insula in patients with VSZ. These findings may suggest a shared neurobiological basis for both violence and psychiatric symptoms. The impaired frontotemporal-limbic network may serve as a neurobiological basis for higher prevalence of violent behaviour in patients with schizophrenia. However, it is important to note that these changes are not unique to patients with VSZ. Further investigation is needed to explore the neural mechanism that drive the interaction between violent behaviour and specific aggression-related dimensions of schizophrenia.

3D printing for customized carbon electrodes.

Traditional carbon electrodes are made of glassy carbon or carbon fibers and have limited shapes. 3D printing offers many advantages for manufacturing carbon electrodes, such as complete customization of the shape and the ability to fabricate devices and electrodes simultaneously. Additive manufacturing is the most common 3D printing method, where carbon materials are added to the material to make it conductive, and treatments applied to enhance electrochemical activity. A newer form of 3D printing is 2-photon lithography, where electrodes are printed in photoresist via laser lithography and then annealed to carbon by pyrolysis. Applications of 3D printed carbon electrodes include nanoelectrode measurements of neurotransmitters, arrays of biosensors, and integrated electrodes in microfluidic devices.

Investigating the debrominations of a subset of brominated flame retardants by biogenic reactive sulfur species.

Brominated flame retardants (BFRs) are persistent organic pollutants. Many bacteria are able to debrominate BFRs, but the underlying mechanism is unclear. Herein, we discovered that reactive sulfur species (RSS), which have strong reductive activity and are commonly present in bacteria, might be one of the reasons leading to such ability. Experiments performed with RSS (H2S and HSSH) and BFRs indicated that RSS can debrominate BFRs via two different mechanisms simultaneously: the substitutive debromination that generates thiol-BFRs and the reductive debromination that generates hydrogenated BFRs. Debromination reactions rapidly happened under neutral pH and ambient temperature, and the debromination degree was around 30% - 55% in one hour. Two Pseudomonas strains, Pseudomonas sp. C27 and Pseudomonas putida B6-2 both produced extracellular RSS and showed debromination activity. C27 debrominated HBCD, TBECH, and TBP by 5.4%, 17.7%, and 15.9% in two days. Whereas, B6-2 debrominated the three BFRs by 0.4%, 0.6%, and 0.3% in two days. The two bacteria produced different amounts and species of RSS, which were likely responsible for the contrasted degrees of the debromination. Our finding unveiled a novel, non-enzymatic debromination mechanism that many bacteria may possess. RSS producing bacteria have potentials to contribute to bioremediation of BFRs-polluted environments.

Stable in-vivo electrochemical sensing of tonic serotonin levels using PEDOT/CNT-coated glassy carbon flexible microelectrode arrays.

Chronic sampling of tonic serotonin (5-hydroxytryptamine, 5-HT) concentrations in the brain is critical for tracking neurological disease development and the time course of pharmacological treatments. Despite their value, in vivo chronic multi-site measurements of tonic 5-HT have not been reported. To fill this technological gap, we batch-fabricated implantable glassy carbon (GC) microelectrode arrays (MEAs) onto a flexible SU-8 substrate to provide an electrochemically stable and biocompatible device/tissue interface. To achieve detection of tonic 5-HT concentrations, we applied a poly(3,4-ethylenedioxythiophene)/carbon nanotube (PEDOT/CNT) electrode coating and optimized a square wave voltammetry (SWV) waveform for selective 5-HT measurement. In vitro, the PEDOT/CNT-coated GC microelectrodes achieved high sensitivity to 5-HT, good fouling resistance, and excellent selectivity against the most common neurochemical interferents. In vivo, our PEDOT/CNT-coated GC MEAs successfully detected basal 5-HT concentrations at different locations within the CA2 region of the hippocampus of both anesthetized and awake mice. Furthermore, the PEDOT/CNT-coated MEAs were able to detect tonic 5-HT in the mouse hippocampus for one week after implantation. Histology reveals that the flexible GC MEA implants caused less tissue damage and reduced inflammatory response in the hippocampus compared to commercially available stiff silicon probes. To the best of our knowledge, this PEDOT/CNT-coated GC MEA is the first implantable, flexible sensor capable of chronic in vivo multi-site sensing of tonic 5-HT.

The Pleiotropic Regulator AdpA Regulates the Removal of Excessive Sulfane Sulfur in Streptomyces coelicolor.

Reactive sulfane sulfur (RSS), including persulfide, polysulfide, and elemental sulfur (S8), has important physiological functions, such as resisting antibiotics in Pseudomonas aeruginosa and Escherichia coli and regulating secondary metabolites production in Streptomyces spp. However, at excessive levels it is toxic. Streptomyces cells may use known enzymes to remove extra sulfane sulfur, and an unknown regulator is involved in the regulation of these enzymes. AdpA is a multi-functional transcriptional regulator universally present in Streptomyces spp. Herein, we report that AdpA was essential for Streptomyces coelicolor survival when facing external RSS stress. AdpA deletion also resulted in intracellular RSS accumulation. Thioredoxins and thioredoxin reductases were responsible for anti-RSS stress via reducing RSS to gaseous hydrogen sulfide (H2S). AdpA directly activated the expression of these enzymes at the presence of excess RSS. Since AdpA and thioredoxin systems are widely present in Streptomyces, this finding unveiled a new mechanism of anti-RSS stress by these bacteria.

Implantable flexible multielectrode arrays for multi-site sensing of serotonin tonic levels.

Real-time multi-channel measurements of tonic serotonin (5-hydroxytryptamine, 5-HT) concentrations across different brain regions are of utmost importance to the understanding of 5-HT’s role in anxiety, depression, and impulse control disorders, which will improve the diagnosis and treatment of these neuropsychiatric illnesses. Chronic sampling of 5-HT is critical in tracking disease development as well as the time course of pharmacological treatments. Despite their value, in vivo chronic multi-site measurements of 5-HT have not been reported. To fill this technological gap, we batch fabricated implantable glassy carbon (GC) microelectrode arrays (MEAs) on a flexible SU-8 substrate to provide an electrochemically stable and biocompatible device/tissue interface. Then, to achieve multi-site detection of tonic 5-HT concentrations, we incorporated the poly(3,4-ethylenedioxythiophene)/functionalized carbon nanotube (PEDOT/CNT) coating on the GC microelectrodes in combination with a new square wave voltammetry (SWV) approach, optimized for selective 5-HT measurement. In vitro , the PEDOT/CNT coated GC microelectrodes achieved high sensitivity towards 5-HT, good fouling resistance in the presence of 5-HT, and excellent selectivity towards the most common neurochemical interferents. In vivo , our PEDOT/CNT-coated GC MEAs were able to successfully detect basal 5-HT concentrations at different locations of the CA2 hippocampal region of mice in both anesthetized and awake head-fixed conditions. Furthermore, the implanted PEDOT/CNT-coated MEA achieved stable detection of tonic 5-HT concentrations for one week. Finally, histology data in the hippocampus shows reduced tissue damage and inflammatory responses compared to stiff silicon probes. To the best of our knowledge, this PEDOT/CNT-coated GC MEA is the first implantable flexible multisite sensor capable of chronic in vivo multi-site sensing of tonic 5-HT. This implantable MEA can be custom-designed according to specific brain region of interests and research questions, with the potential to combine electrophysiology recording and multiple analyte sensing to maximize our understanding of neurochemistry. Highlights: PEDOT/CNT-coated GC microelectrodes enabled sensitive and selective tonic detection of serotonin (5-HT) using a new square wave voltammetry (SWV) approach PEDOT/CNT-coated GC MEAs achieved multi-site in vivo 5-HT tonic detection for one week. Flexible MEAs lead to reduced tissue damage and inflammation compared to stiff silicon probes.

Visible-light-mediated aerobic Ritter-type C-H amination of diarylmethanes using DDQ/tert-butyl nitrite.

A metal-free photocatalytic Ritter-type C-H amination of unactivated sp3 carbons using molecular oxygen as a terminal oxidant has been developed. By employing a co-catalytic system of 3-dichloro-4,5-dicyano-1,4-benzoquinone (DDQ) and tert-butyl nitrite (TBN), this novel strategy provides a low cost, sustainable and scalable way to synthesise a broad range of secondary amides in moderate to excellent yields under mild conditions.

Why is reusable bag consumption easier to say than do?

White pollution has become a global problem. China issued a strict plastic ban but fell into an awkward position. Despite the increasing environmental awareness, the positive attitude of consumers toward using reusable bags instead of plastic bags is difficult to reflect on from their behavior. This article bridges this gap by utilizing a consumer behavior framework based on the behavioral reasoning theory (BRT) and the attitude-behavior-context (ABC) model. This framework is tested using structural equation modeling with 481 Chinese consumers. This article confirms that the value has a significant impact on consumer attitudes. Meanwhile, the article reveals the positive influence of "reasons for" in predicting attitudes and the negative influence of "reasons against" in predicting intentions. Reusable bag consumption behavior is a result of multiple pathways working together, which causes the gap between attitudes and behaviors. This article also confirms the moderating role of the Chinese face and the enforcement of the plastic ban in influencing behavior. These findings offer interesting insights for enterprises and governments to solve the problem of plastic consumption.

Erratum: A novel probe for measuring tissue bioelectrical impedance to enhance pedicle screw placement in spinal surgery.

[This corrects the article on p. 2205 in vol. 10, PMID: 30093957.].

Prenatal persistent left superior vena cava in low population: Not a benign vascular anomaly.

OBJECTIVE: The aim of this study is to identify prenatally diagnosed cases of persistent left superior vena cava (PLSVC) in our clinic, to evaluate the associated structural and chromosomal results, and to review their outcome. MATERIALS AND METHODS: During a four-year period, patients with fetal PLSVC were detected by echocardiography. We reviewed medical records of these affected pregnancies, including maternal demographics, sonographic findings, chromosomal microarray results and pregnancy outcomes. RESULTS: There were a total of 140 cases of fetal PLSVC. Eighty-nine fetuses (63.6%) had associated structural anomalies, while the remaining 51 fetuses (36.3%) had PLSVC as an isolated finding. In the non-isolated cases, cardiac anomalies were present in 72 fetuses (80.9%), and extracardiac abnormalities in 45 fetuses (50.6%). Among the 89 cases with non-isolated PLSVC, 12 cases had chromosomal abnormalities including 5 cases of aneuploidies. Among the 51 cases with isolated PLSVC, one pregnancy of chromosomal microduplication was detected. CONCLUSION: Isolated PLSVC is a benign vascular anomaly in low risk population. However, the information about background risk of identifying an abnormal clinically significant CMA result should be conveyed to all pregnant women when they consults this vascular variation.

Sulfane Sulfur Posttranslationally Modifies the Global Regulator AdpA to Influence Actinorhodin Production and Morphological Differentiation of Streptomyces coelicolor.

The transcription factor AdpA is a key regulator controlling both secondary metabolism and morphological differentiation in Streptomyces. Due to its critical functions, its expression undergoes multilevel regulations at transcriptional, posttranscriptional, and translational levels, yet no posttranslational regulation has been reported. Sulfane sulfur, such as hydro polysulfide (HSnH, n ≥ 2) and organic polysulfide (RSnH, n ≥ 2), is common inside microorganisms, but its physiological functions are largely unclear. Here, we discovered that sulfane sulfur posttranslationally modifies AdpA in Streptomyces coelicolor via specifically reacting with Cys62 of AdpA to form a persulfide (Cys62-SSH). This modification decreases the affinity of AdpA to its self-promoter PadpA, allowing increased expression of adpA, further promoting the expression of its target genes actII-4 and wblA. ActII-4 activates actinorhodin biosynthesis, and WblA regulates morphological development. Bioinformatics analyses indicated that AdpA-Cys62 is highly conserved in Streptomyces, suggesting the prevalence of such modification in this genus. Thus, our study unveils a new type of regulation on the AdpA activity and sheds a light on how sulfane sulfur stimulates the production of antibiotics in Streptomyces. IMPORTANCEStreptomyces species produce a myriad of natural products with (potential) clinical applications. While the database of biosynthetic gene clusters is quickly expanding, their regulation mechanisms are rarely known. Sulfane sulfur species are commonly present in microorganisms with unclear functions. Here, we discovered that sulfane sulfur increases actinorhodin (ACT) production in S. coelicolor. The underlying mechanism is that sulfane sulfur specifically reacts with AdpA, a global transcription factor controlling both ACT gene cluster and morphological differentiation-related genes, to form sulfhydrated AdpA. This modification changes the dynamics of AdpA-controlled gene networks and leads to high expression of ACT biosynthetic genes. Given the wide prevalence of AdpA and sulfane sulfur in Streptomyces, this mechanism may represent a common regulating pattern of all AdpA-controlled biosynthetic pathways. Thus, this finding provides a new strategy for mining and activating valuable biosynthetic gene clusters.

Effects of vacancy defects on the interfacial thermal resistance of partially overlapped bilayer graphene.

Graphene has been extensively applied in composite materials due to its high thermal conductivity. Multi-layered graphene has great potential in the construction of a continuous filler network but is restricted by the high interfacial thermal resistance between adjacent graphene layers. This paper investigates the effects of the overlapping area and interlayer sp3 bonding of partially overlapped bilayer graphene on the interfacial thermal resistance using molecular dynamic simulations. The results show the linear relationship between the interfacial thermal resistance and the overlapping area. Then, identical vacancy defects of the same plane coordinates were added to each of the two graphene sheets, and it was found that the presence of an armchair edge restricted the formation of interface sp3 bonding to some extent, while the zigzag edge did not. However, their similar bond length and the phonon density of state of bonded atoms in the models with different edges indicated their similar effects on the heat transfer. Therefore, the thermal resistance of all single sp3 bonds in different models could be approximated to 14.3 × 10-9 m2 KW-1. A formula is proposed to describe the inverse relationship between the number of sp3 bonds and the interfacial thermal resistance. Finally, the vacancy defect on the upper graphene sheet was moved to stagger the two vacancies. The length of sp3 bonds was changed slightly due to the staggered arrangement, and the interfacial thermal resistance was found to be positively correlated with the bond length. This allows valuable interfacial heat-transfer properties of the partially overlapped bilayer graphene to contribute to the thermal management of the 3D filler network.

The 16-week sonographic findings in fetuses with increased nuchal translucency and a normal array.

OBJECTIVE: The aim of this prospective study is to evaluate the performance of the intermediate 16-week ultrasound in fetuses with increased nuchal translucency (NT) and a normal chromosomal microarray analysis (CMA). METHODS: During a one-year period, a detailed ultrasound was performed at 16 week' gestation for patients with an increased NT (≥3.5 mm) and normal CMA. Pregnancy work-up included a traditional 22-week ultrasound scan, an echocardiography, and the option of a 10-gene Rasopathy panel after a normal 16-week scan. Abnormal findings and pregnancy outcomes were collected and analyzed. RESULTS: In 52 fetuses with an isolated increased NT and normal CMA, 14 (26.5%) were noted to have structural defects on the 16-week ultrasound. Intrauterine fetal death occurred in one (1.9%) case identified by the 16-week scan. Of the remaining 37 cases, six opted for a RASopathy panel. In this group, one case of Noonan syndrome was detected. One case of unilateral duplex kidney had not been found until the 22-week scan. One case of fetal growth restriction was identified in the third trimester. The remaining 34 cases proceeded with normal ultrasound to term. CONCLUSION: The 16-week ultrasound scan performed on fetuses with increased NT and normal CMA could detect the majority of structural abnormalities that are expected to be identified traditionally at 20-24 weeks.

Carbon nanospike coated nanoelectrodes for measurements of neurotransmitters.

Carbon nanoelectrodes enable the detection of neurotransmitters at the level of single cells, vesicles, synapses and small brain structures. Previously, the etching of carbon fibers and 3D printing based on direct laser writing have been used to fabricate carbon nanoelectrodes, but these methods lack the ability of mass manufacturing. In this paper, we mass fabricate carbon nanoelectrodes by growing carbon nanospikes (CNSs) on metal wires. CNSs have a short, dense and defect-rich surface that produces remarkable electrochemical properties, and they can be mass fabricated on almost any substrate without using catalysts. Tungsten wires and niobium wires were electrochemically etched in batch to form sub micrometer sized tips, and a layer of CNSs was grown on the metal wires using plasma-enhanced chemical vapor deposition (PE-CVD). The thickness of the CNS layer was controlled by the deposition time, and a thin layer of CNSs can effectively cover the entire metal surface while maintaining the tip size within the sub micrometer scale. The etched tungsten wires produced tapered conical nanotips, while the etched niobium wires were long and thin. Both showed excellent sensitivity for the detection of outer sphere ruthenium hexamine and the inner sphere test compound ferricyanide. The CNS nanosensors were used for the measurement of dopamine, serotonin, ascorbic acid and DOPAC with fast-scan cyclic voltammetry. The CNS nanoelectrodes had a large surface area and numerous defect sites, which improved the sensitivity, electron transfer kinetics and adsorption. Finally, the CNS nanoelectrodes were compared with other nanoelectrode fabrication methods, including flame etching, 3D printing, and nanopipettes, which are slower to make and more difficult for mass fabrication. Thus, CNS nanoelectrodes are a promising strategy for the mass fabrication of nanoelectrode sensors for neurotransmitters.

A New Hemoglobin Variant: Hb Jiujiang [α18(A16)Gly→Cys, HBA2: c.55G>T].

We have identified a new α chain hemoglobin (Hb) variant in a Chinese subject. Sequencing of the α-globin gene revealed a mutation in exon 1 at nucleotide 55, which results in the replacement of a glycine by cysteine at codon 18 [α18(A16)Gly→Cys, HBA2: c.55G>T] that we have named Hb Jiujiang for the region of origin of the proband.