Bacteriophage protein Gp46 is a cross-species inhibitor of nucleoid-associated HU proteins.

The architectural protein histone-like protein from Escherichia coli strain U93 (HU) is the most abundant bacterial DNA binding protein and highly conserved among bacteria and Apicomplexan parasites. It not only binds to double-stranded DNA (dsDNA) to maintain DNA stability but also, interacts with RNAs to regulate transcription and translation. Importantly, HU is essential to cell viability for many bacteria; hence, it is an important antibiotic target. Here, we report that Gp46 from bacteriophage SPO1 of Bacillus subtilis is an HU inhibitor whose expression prevents nucleoid segregation and causes filamentous morphology and growth defects in bacteria. We determined the solution structure of Gp46 and revealed a striking negatively charged surface. An NMR-derived structural model for the Gp46-HU complex shows that Gp46 occupies the DNA binding motif of the HU and therefore, occludes DNA binding, revealing a distinct strategy for HU inhibition. We identified the key residues responsible for the interaction that are conserved among HUs of bacteria and Apicomplexans, including clinically significant Mycobacterium tuberculosis, Acinetobacter baumannii, and Plasmodium falciparum, and confirm that Gp46 can also interact with these HUs. Our findings provide detailed insight into a mode of HU inhibition that provides a useful foundation for the development of antibacteria and antimalaria drugs.

Decoding molecular features of bovine oocyte fate during antral follicle growth via single-cell multi-omics analysis†.

Antral follicle size is a useful predictive marker of the competency of enclosed oocytes for yielding an embryo following in vitro maturation and fertilization. However, the molecular mechanisms underpinning oocyte developmental potential during bovine antral follicle growth are still unclear. Here, we used a modified single-cell multi-omics approach to analyze the transcriptome, DNA methylome, and chromatin accessibility in parallel for oocytes and cumulus cells collected from bovine antral follicles of different sizes. Transcriptome profiling identified three types of oocytes (small, medium, and large) that underwent different developmental trajectories, with large oocytes exhibiting the largest average follicle size and characteristics resembling metaphase-II oocytes. Differential expression analysis and real-time polymerase chain reaction assay showed that most replication-dependent histone genes were highly expressed in large oocytes. The joint analysis of multi-omics data revealed that the transcription of 20 differentially expressed genes in large oocytes was associated with both DNA methylation and chromatin accessibility. In addition, oocyte-cumulus interaction analysis showed that inflammation, DNA damage, and p53 signaling pathways were active in small oocytes, which had the smallest average follicle sizes. We further confirmed that p53 pathway inhibition in the in vitro maturation experiments using oocytes obtained from small antral follicles could improve the quality of oocytes and increased the blastocyte rate after in vitro fertilization and culture. Our work provides new insights into the intricate orchestration of bovine oocyte fate determination during antral folliculogenesis, which is instrumental for optimizing in vitro maturation techniques to optimize oocyte quality.

Transistor-based immunosensor using AuNPs-Ab2-HRP enzyme nanoprobe for the detection of antigen biomarker in human blood.

Alpha-fetoprotein (AFP) is inextricably linked to various diseases, including liver cancer. Thus, detecting the content of AFP in biology has great significance in diagnosis, treatment, and intervention. Motivated by the urgent need for affordable and convenient electronic sensors in the analysis and detection of aqueous biological samples, we combined the solution-gated graphene transistor (SGGT) with the catalytic reaction of enzyme nanoprobes (HRP-AuNPs-Ab2) to accurately sense AFP. The SGGT immunosensor demonstrated high specificity and stability, excellent selectivity, and excessive linearity over a range of 4 ng/mL to 500 ng/mL, with the lower detection limit down to 1.03 ng/mL. Finally, clinical samples were successfully detected by the SGGT immunosensor, and the results were consistent with chemiluminescence methods that are popular in hospitals for detecting AFP. Notably, the SGGT immunosensor is also recyclable, so it has excellent potential for use in high-throughput detection.

Alumina inorganic molecularly imprinted polymer modified multi-walled carbon nanotubes for uric acid detection in sweat.

Alumina inorganic molecularly imprinted polymer (MIP) modified multi-walled carbon nanotubes (MWCNTs) on a glassy carbon electrode (MWCNTs-Al2O3-MIP/GCE) was firstly designed and fabricated by one-step electro deposition technique for the detection of uric acid (UA) in sweat. The UA templates were embedded within the inorganic MIP by co-deposition with Al2O3. Through the evaluation of morphology and structure by Field Emission Scanning Electron Microscope (SEM), Energy Dispersive X-ray Spectroscopy (EDS), X-ray Photoelectron Spectroscopy (XPS) and Transmission Electron Microscopy (TEM), it was verified that the specific recognition sites can be fabricated in the electrodeposited Al2O3 molecular imprinted layer. Due to the high selectivity of molecular imprinting holes, the MWCNTs-Al2O3-MIP/GCE electrode demonstrated an impressive imprinting factor of approximately 2.338 compared to the non-molecularly imprinted glassy carbon electrode (MWCNTs-Al2O3-NIP/GCE) toward uric acid detection. Moreover, it exhibited a remarkable limit of detection (LOD) of 50 nM for UA with wide detection range from 50 nM to 600 µM. The MWCNTs-Al2O3-MIP/GCE electrode also showed strong interference resistance against common substances found in sweat. These results highlight the excellent interference resistance and selectivity of MWCNTs-Al2O3-MIP/GCE sensor, positioning it as a novel sensing platform for non-invasive uric acid detection in human sweat.

Novel solution-gated transistor sensor-based SnO2 epitaxial thin films grown by pulsed laser deposition for nitrite detection.

A solution-gate controlled thin-film transistor with SnO2 epitaxial thin films (SnO2-SGTFT) is successfully utilized for highly sensitive detection of nitrite. The SnO2 films are deposited as channel materials on a c-plane sapphire (c-Al2O3) substrate through pulsed laser deposition (PLD), with superior crystal quality and out-of-plane atomic ordering. PtAu NPs/rGO nanocomposites are electrodeposited on a gold electrode to function as a transistor gate to further enhance the nitrite catalytic performance of the device. The change in effective gate voltage due to the electrooxidation of nitrite on the gate electrode is the primary sensing mechanism of the device. Based on the inherent amplification effect of transistors, the superior electrical properties of SnO2, and the high electrocatalytic activity of PtAu NPs/rGO, the SnO2-SGTFT sensor has a low detection limit of 0.1 nM and a wide linear detection range of 0.1 nM ~ 50 mM at VGS = 1.0 V. Furthermore, the sensor has excellent characteristics such as rapid response time, selectivity, and stability. The practicability of the device has been confirmed by the quantitative detection of nitrite in natural lake water. SnO2 epitaxial films grown by PLD provide a simple and efficient way to fabricate nitrite SnO2-SGTFT sensors in environmental monitoring and food safety, among others. It also provides a reference for the construction of other high-performance thin-film transistor sensors.

Integration of Perylene Diimide into a Covalent Organic Framework for Photocatalytic Oxidation.

Perylene diimides (PDIs) have garnered considerable attention due to its immense potential in photocatalysis. However, manipulating the molecular packing within their aggregates and enhancing the efficiency of photogenerated carrier recombination remain significant challenges. In this study, we demonstrate the incorporation of a PDI unit into a covalent organic framework (COF), named PDI-PDA, by linking an ortho-substituted PDI with p-phenylenediamine (PDA) to control its intermolecular aggregation. The incorporation enables precise modulation of electron transfer dynamics, leading to a ten-fold increase in the efficiency of photocatalytic oxidation of thioether to sulfoxide with PDI-PDA compared to the PDI molecular counterpart, achieving yields exceeding 90%. Electron property studies and density functional theory calculations show that the PDI-PDA with its well-defined crystal structure, enhances π-π stacking and lowers the electron transition barrier. Moreover, the strong electron-withdrawing ability of the PDI unit promotes the spatial separation of the valency band maximum and conduction band minimum of PDI-PDA suppressing the rapid recombination of photogenerated electron-hole pairs and improving charge separation efficiency to give high photocatalytic efficiency. This study provides a brief yet effective way for the improvement of the photocatalytic efficiency of commonly used PDI-based dyes by integrating them into a framework skeleton.

Vincristine and dexamethasone pulses in addition to maintenance therapy among pediatric acute lymphoblastic leukemia (GD-ALL-2008): An open-label, multicentre, randomized, phase III clinical trial.

The efficacy and safety on the addition of vincristine (VCR) and dexamethasone (DEX) pulses to maintenance therapy among childhood acute lymphoblastic leukemia (ALL) remain uncertain. Herein, we perform an open-label, multicentre, randomized, phase III clinical trial that was conducted at nine major medical centers in Guangdong Province, China. Patients were randomly assigned either the conventional maintenance therapy (control group, n = 384) or the VCR/DEX pulse (treatment group, n = 375). When limited to the SR cohort, 10-year EFS was 82.6% (95% CI: 75.9-89.9) in the control group and 80.7% (95% CI: 74-88.1) in the treatment group (pnon-inferiority  = .0002). Similarly, patients with IR also demonstrated non-inferiority of the treatment group to the control group in terms of 10-year EFS (73.6% [95% CI: 67.6-80] vs. 77.6% [95% CI: 71.8-83.9]; pnon-inferiority  = .005). Among the HR cohort, compared with the control group, patients in the treatment group experienced a significant benefit in terms of 10-year EFS (61.1% [95% CI: 47.7-78.2] vs. 72.6% [95% CI: 55.6-94.7], p = .026) and a trend toward higher 10-year OS (73.8% [95% CI: 61.6-88.4] vs. 87.9% [95% CI: 579.2-97.5], p = .068). In the HR cohort, the total rate of drug-induced liver injury and Grade 3 chemotherapy-induced anemia were both lower for patients in the treatment group than in the control group (55.6% vs. 100%, p = .033; 37.5% vs. 60%, p = .036). Conversely, the total prevalence of chemotherapy-induced thrombocytopenia was higher for patients in the treatment group than in the control group (88.9% vs. 40%, p = .027). Pediatric acute lymphoblastic leukemia with high risk is suitable to VCR/DEX pulse during maintenance phase for the excellent outcome, while the standard-to-intermediate-risk patients could eliminate the pulses.

Anatomical Analysis of the Cervical Sympathetic Ganglion and Spinal Ganglion and its Physiological Significance in the Pathogenesis of Cervical Vertigo.

Objective: Investigating the anatomical connections between cervical sympathetic ganglia and spinal ganglia in rabbits and assessing the role of Neuropeptide Y in the pathogenesis of cervical vertigo. Method: Part 1: 32 adult healthy male New Zealand white rabbits (whose skin is very sensitive, so rabbits are generally used for stimulation experiments) were randomly divided into the upper cervical sympathetic ganglia (SCSG) stimulation group and the lower cervical sympathetic ganglia (ICSG) stimulation group, with 16 rabbits in each group. The two groups were divided into an experimental group and a control group, with 8 rabbits in each group. The cervical ganglia of each group of white rabbits were injected with 4% FluoroGold solution and observed under a section microscope. Part 2: Sixty New Zealand white rabbits were randomly divided into a blank control (n = 12), SCSG stimulation group (n = 12), SCSG sham surgery control (n = 12), ICSG stimulation group (n = 12), and ICSG sham surgery control group (n = 12). The SCSG group and ICSG group were subjected to electrical stimulation (i.e. 30.0Hz, 10.0V, 5-minute pulse width of 0.5 ms square wave pulse), and specimens were made. The expression of NPY was detected using immunohistochemical methods. Result: Neuropeptide Y was weakly expressed in all cervical ganglia (C1-C8). Compared with the sham surgery group, the superior cervical sympathetic ganglion stimulation group showed an increase in Neuropeptide Y positive cells in C2, C3, C4, and C5, with C2 and C3 showing the most significant increase. The number of C6, C7, and C8 Neuropeptide Y positive cells in the 3 C、3D and 4B, lower cervical sympathetic ganglion stimulated groups was higher than in the sham sham-operated group, and C6 and C7 significantly increased. Neuropeptide Y is like immunoreactive neurons in the cervical spinal ganglia, and the immunoreactive products are small brown particles distributed in the cytoplasm after electrical stimulation of the cervical sympathetic ganglia. The Neuropeptide Y content in the corresponding segment of the cervical spinal ganglia is significantly increased compared to the control group (P < .05). Conclusion: In New Zealand white rabbits, nerve fibers are interconnected between the cervical sympathetic ganglion and the cervical spinal ganglion, and this neural fiber connection has a certain segmental nature, providing experimental basis for the existence of the cervical spinal cord external nerve reflex arc and elucidating the pathogenesis of cervical vertigo in terms of neural anatomy. By using neuroelectrophysiological methods, it has been confirmed that electrical stimulation in the cervical spinal ganglia can reach the corresponding cervical sympathetic ganglia on the same side through a certain conduction pathway, providing experimental basis in neuroelectrophysiology for the existence of the cervical extraspinal nerve reflex arc and elucidating the pathogenesis of cervical vertigo. NPY may be involved in the pathogenesis of cervical vertigo, providing a theoretical basis for the clinical diagnosis of cervical vertigo.

Core-shell architectured NH2-UiO-66@ZIF-8/multi-walled carbon nanotubes nanocomposite-based sensitive electrochemical sensor towards simultaneous determination of Pb2+ and Cu2.

Amino functionalized zirconium-based metal-organic framework (NH2-UiO-66) and zinc-based zeolitic imidazolate framework (ZIF-8) were integrated to develop a core-shell architectured hybrid material (NH2-UiO-66@ZIF-8, NU66@Z8). The morphology and structure evolutions of core-shell NU6@Z8 were investigated by FE-SEM, XRD, FTIR, and XPS. The NU66@Z8 combined with carboxylated multi-walled carbon nanotubes (CMWCNT) was deposited on a glassy carbon electrode (GCE) for fabricating an electrochemical platform towards detecting Pb2+ and Cu2+. The NU66@Z8/CMWCNT/GCE revealed significantly improved electrochemical performance for determination of Pb2+ and Cu2+ compared with the individual components, which can be attributed to the strong adsorption capacity, unique core-shell structure, and large electrochemical active surface area of NU66@Z8/CMWCNT. Under the optimal conditions, the developed sensor exhibited excellent sensing capability with a low limit of detection (Pb2+,1 nM; Cu2+, 10 nM) and a wide determination range (Pb2+,0.003-70 µM; Cu2+, 0.03-50 µM). The sensor showed high selectivity towards common interfering ions and good repeatability. The real sample recoveries of proposed sensor were in the range 95.0-103% for Pb2+ (RSD ≤ 5.3%) and 94.2-106% for Cu2+ (RSD ≤ 5.9%), suggesting that the NU66@Z8/CMWCNT is suitable for examining trace heavy metals in natural environment.

Ag nanocubes monolayer-modified PDMS as flexible SERS substrates for pesticides sensing.

A new approach is presented to fabricate flexible surface-enhanced Raman scattering (SERS) substrate of Ag nanocubes monolayer-modified polydimethylsiloxane (Ag NCs/PDMS) through a powerful three-phase interface self-assemble method. The morphologies and crystal structures were characterized by scanning electron microscopy and X-ray diffraction. The self-assembled Ag NCs/PDMS substrate exhibited high SERS activity and good signal homogeneity, which was successfully used for quantitative detection of thiram; the detection limit reached 10 ng/mL, and the linear range is 10-1000 ng/mL. Furthermore, the flexible SERS substrates were successfully employed to detect thiram residues on factual apple samples, and trace amount (1 ng/cm2) of thiram residues was detected on apple peels. The excellent SERS detection ability of self-assembled Ag NCs/PDMS substrate indicated that it will play an important role in pesticide detection in the future.

Confined Thermolysis for Oriented N-Doped Carbon Supported Pd toward Stable Catalytic and Energy Storage Applications.

Carbon-based nanomaterials have been widely utilized in catalysis and energy-related fields due to their fascinating properties. However, the controllable synthesis of porous carbon with refined morphology is still a formidable challenge due to inevitable aggregation/fusion of resulted carbon particles during the high-temperature synthetic process. Herein, a hierarchically oriented carbon-structured (fiber-like) composite is fabricated by simultaneously taking advantage of a confined pyrolysis strategy and disparate bond environments within metal-organic frameworks (MOFs). In the resultant composite, the oriented carbon provides a fast mass (molecule/ion/electron) transfer efficiency; the doping-N atoms can anchor or act as active sites; the mesoporous SiO2 (mSiO2 ) shell not only effectively prevents the derived carbon or active metal nanoparticles (NPs) from aggregation or leaching, but also acts as a "polysulfide reservoir" in the Li-S batteries to suppress the "shuttle" effect. Benefiting from these advantages, the synthesized composite Pd@NDHPC@mSiO2 (NDHPC means N-doped hierarchically porous carbon) exhibits extremely high catalytic activity and stability toward the one-pot Knoevenagel condensation-hydrogenation reaction. Furthermore, the oriented NDHPC@mSiO2 manifests a boosted capacity and cycling stability in Li-S batteries compared to the counterpart that directly pyrolyzes without silica protection. This report provides an effective strategy of fabricating hierarchically oriented carbon composites for catalysis and energy storage applications.

Ultimate Corrosion to Pt-Cu Electrocatalysts for Enhancing Methanol Oxidation Activity and Stability in Acidic Media.

Alloying platinum (Pt) with transition metals (M), as an established class of electrocatalysts, reduces the use of Pt and improves the electrocatalytic performance. However, the stability of transition metals in nanostructured platinum alloys is a fundamental and practical problem in electrocatalysis, due to leaching of transition metals under acidic operating condition. Here, a corrosion method has been developed for a Pt-Cu electrocatalyst with high activity (6.6 times that of commercial Pt/C) and excellent stability for the methanol oxidation reaction (MOR) under acidic operating conditions. The mechanism of formation has been studied, and possible mesostructured re-formation and atomic re-organization have been proposed. This work offers an effective strategy for the facile synthesis of a highly acid-stable PtM alloying and opens a door to high-performance design for electrocatalysts.

Reduced intensity of early intensification does not increase the risk of relapse in children with standard risk acute lymphoblastic leukemia - a multi-centric clinical study of GD-2008-ALL protocol.

BACKGROUND: The prognosis of childhood acute lymphoblastic leukemia (ALL) is optimistic with a 5-year event-free survival (EFS) rate of 70-85%. However, the major causes of mortality are chemotherapy toxicity, infection and relapse. The Guangdong (GD)-2008-ALL collaborative protocol was carried out to study the effect of reduced intensity on treatment related mortality (TRM) based on Berlin-Frankfurt-Münster (BFM) 2002 backbone treatment. The study was designed to elucidate whether the reduced intensity is effective and safe for children with ALL. METHODS: The clinical data were obtained from February 28, 2008 to June 30, 2016. A total of 1765 childhood ALL cases from 9 medical centers were collected and data were retrospectively analyzed. Patients were stratified into 3 groups according to bone marrow morphology, prednisone response, age, genotype, and karyotype information: standard risk (SR), intermediate risk (IR) and high risk (HR). For SR group, daunorubicin was decreased in induction IA while duration was reduced in Induction Ib (2 weeks in place of 4 weeks). Doses for CAM were same in all risk groups - SR patients received one CAM, others got two CAMs. RESULTS: The 5-year and 8-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) were 83.5±0.9% and 83.1±1.0%, 71.9±1.1% and 70.9±1.2%, and 19.5±1.0% and 20.5±1.1%, respectively. The 2-year treatment-related mortality (TRM) was 5.2±0.5%. The 5-year and 8-year OS were 90.7±1.4% and 89.6±1.6% in the SR group, while the 5-year and 8-year EFS were 81.5±1.8% and 80.0±2.0%. In the SR group, 74 (15.2%) patients measured minimal residual disease (MRD) on Day 15 and Day 33 of induction therapy. Among them, 7 patients (9.46%) were MRD positive (≥ 0.01%) on Day 33. The incidence of relapse in the MRD Day 33 positive group (n=7) was 28.6%, while in the MRD Day 33 negative group (n=67) was 7.5% (p=0.129). CONCLUSIONS: The results of GD-2008-ALL protocol are outstanding for reducing TRM in childhood ALL in China with excellent long term EFS. This protocol provided the evidence for further reducing intensity of induction therapy in the SR group according to the risk stratification. MRD levels on Day 15 and Day 33 are appropriate indexes for stratification.

Spatial Heterojunction in Nanostructured TiO2 and Its Cascade Effect for Efficient Photocatalysis.

A highly efficient photoenergy conversion is strongly dependent on the cumulative cascade efficiency of the photogenerated carriers. Spatial heterojunctions are critical to directed charge transfer and, thus, attractive but still a challenge. Here, a spatially ternary titanium-defected TiO2@carbon quantum dots@reduced graphene oxide (denoted as VTi@CQDs@rGO) in one system is shown to demonstrate a cascade effect of charges and significant performances regarding the photocurrent, the apparent quantum yield, and photocatalysis such as H2 production from water splitting and CO2 reduction. A key aspect in the construction is the technologically irrational junction of Ti-vacancies and nanocarbons for the spatially inside-out heterojunction. The new "spatial heterojunctions" concept, characteristics, mechanism, and extension are proposed at an atomic-/nanoscale to clarify the generation of rational heterojunctions as well as the cascade electron transfer.

Spatial Structure Regulation: A Rod-Shaped Viologen Enables Long Lifetime in Aqueous Redox Flow Batteries.

A stable rod-like sulfonated viologen (R-Vi) derivative is developed through a spatial-structure-adjustment strategy for neutral aqueous organic redox flow batteries (AORFBs). The obtained R-Vi features four individual methyl groups on the 2,2',6,6'-positions of the 4,4'-bipyridine core ring. The tethered methyls confine the movement of the alkyl chain as well as the sulfonic anion, thus driving the spatial structure from sigmoid to rod shape. The R-Vi with weak charge attraction and large molecular dimension displays an ultralow membrane permeability that is only 14.7 % of that of typical sigmoid viologen. Moreover, the electron-donating effect of methyls endows R-Vi with the lowest redox potential of -0.55 V vs. SHE among one-electron-storage viologen-based AORFBs. The AORFB with the R-Vi anolyte and a K4 Fe(CN)6 catholyte exhibits an energy efficiency up to 87 % and extremely low capacity-fade rate of 0.007 % per cycle in 3200 continuous cycles.

Serologic Detection of SARS-CoV-2 Infections in Hemodialysis Centers: A Multicenter Retrospective Study in Wuhan, China.

RATIONALE & OBJECTIVE: Patients receiving maintenance hemodialysis (MHD) are highly vulnerable to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current study was designed to evaluate the prevalence of SARS-CoV-2 infection based on both nucleic acid testing (NAT) and antibody testing in Chinese patients receiving MHD. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: From December 1, 2019, to March 31, 2020, a total of 1,027 MHD patients in 5 large hemodialysis centers in Wuhan, China, were enrolled. Patients were screened for SARS-CoV-2 infection by symptoms and initial computed tomography (CT) of the chest. If patients developed symptoms after the initial screening was negative, repeat CT was performed. Patients suspected of being infected with SARS-CoV-2 were tested with 2 consecutive throat swabs for viral RNA. In mid-March 2020, antibody testing for SARS-CoV-2 was obtained for all MHD patients. EXPOSURE: NAT and antibody testing results for SARS-CoV-2. OUTCOMES: Morbidity, clinical features, and laboratory and radiologic findings. ANALYTICAL APPROACH: Differences between groups were examined using t test or Mann-Whitney U test, comparing those not infected with those infected and comparing those with infection detected using NAT with those with infection detected by positive serology test results. RESULTS: Among 1,027 patients receiving MHD, 99 were identified as having SARS-CoV-2 infection, for a prevalence of 9.6%. Among the 99 cases, 52 (53%) were initially diagnosed with SARS-CoV-2 infection by positive NAT; 47 (47%) were identified later by positive immunoglobulin G (IgG) or IgM antibodies against SARS-CoV-2. There was a spectrum of antibody profiles in these 47 patients: IgM antibodies in 5 (11%), IgG antibodies in 35 (74%), and both IgM and IgG antibodies in 7 (15%). Of the 99 cases, 51% were asymptomatic during the epidemic; 61% had ground-glass or patchy opacities on CT of the chest compared with 11.6% among uninfected patients (P<0.001). Patients with hypertensive kidney disease were more often found to have SARS-CoV-2 infection and were more likely to be symptomatic than patients with another primary cause of kidney failure. LIMITATIONS: Possible false-positive and false-negative results for both NAT and antibody testing; possible lack of generalizability to other dialysis populations. CONCLUSIONS: Half the SARS-CoV-2 infections in patients receiving MHD were subclinical and were not identified by universal CT of the chest and selective NAT. Serologic testing may help evaluate the overall prevalence and understand the diversity of clinical courses among patients receiving MHD who are infected with SARS-CoV-2.

A novel solution-gated graphene transistor biosensor for ultrasensitive detection of trinucleotide repeats.

A new way to detect GAA trinucleotide repeats (TNRs) based on a solution-gated graphene transistor (SGGT) with high performance was developed. Friedreich's ataxia (FRDA) is a neurodegenerative disease where the first intron of the frataxin (FXN) gene exhibits an extended GAA repeat region. Herein, a SGGT biosensor was constructed based on G-quadruplex DNAzymes and graphene channels. The DNAzymes quantify the captured target DNA by producing a strong catalytic current signal depending on the peroxidase-like activity. The higher the target DNA quantity captured on the gate electrode is, the higher is the concentration of DNAzymes on the surface of the gate electrode, which generates a high catalytic current. Due to the excellent self-amplifying performance of the transistor, the current signal of the SGGT is several hundreds of times larger than in conventional electrochemistry under identical detection conditions. Moreover, a large current signal can be obtained in the case of a low concentration of H2O2 when compared to the case of an enzyme-catalyzed transistor. The SGGT biosensor also exhibits an ultra-low detection limit (32.25 fM), a wide linear range (100 fM-100 nM), and excellent selectivity. The results show that the SGGT biosensor has great potential in the early diagnosis of neurodegenerative diseases.

Non-invasive detection of glucose via a solution-gated graphene transistor.

Owing to its high sensitivity, a solution-gated graphene transistor has rapidly emerged as a cutting edge technology in electrochemical sensing. In this work, composites of gold nanoparticles and reduced graphene oxide were synthesized on a glassy carbon electrode by using the electrodeposition method. A modified glassy carbon electrode was used as the gate electrode and assembled into the solution-gated graphene transistor device along with the graphene channel for a non-invasive glucose detection. The sensing mechanism was based on the change in current in the channel of the device caused by the addition of glucose, of which electro-oxidation on the surface of the gold nanoparticles and reduced graphene oxide led to a change in equivalent gate voltage, and consequently, affected the channel carrier concentration. The self-amplification effect of transistors was utilized in our sensors, which resulted in a detection limit that was 10 times lower than those of conventional electrochemical sensors. Compared to traditional enzymatic transistor sensors, the novel solution-gated graphene transistor nonenzymatic sensors based on gold nanoparticles and reduced graphene oxide demonstrated significant sensing advantages, such as a simple structure, wide linear range from 10 µM to 400 µM and 400 µM to 31 mM, and low detection limit down to 4 µM. The chemicals coexisting in human sweat e.g. sodium chloride, urea, and lactic acid imposed no distinct interference for the glucose detection. Therefore, we achieved a non-invasive detection of glucose in the artificial sweat samples with satisfactory sensing results. This work demonstrates an effective route for non-invasive glucose testing in practical clinical diagnosis by using nonenzymatic, solution-gated graphene transistor devices.

Spatially Ordered Arrangement of Multifunctional Sites at Molecule Level in a Single Catalyst for Tandem Synthesis of Cyclic Carbonates.

With fossil energy resources increasingly drying up and gradually causing serious environmental impacts, pursuing a tandem and green synthetic route for a complex and high-value-added compound by using low-cost raw materials has attracted considerable attention. In this regard, the selective and efficient conversion of light olefins with CO2 into high-value-added organic cyclic carbonates (OCCs) is of great significance owing to their high atom economy and absence of the isolation of intermediates. To fulfill this expectation, a multifunctional catalytic system with controllable spatial arrangement of varied catalytic sites and stable texture, in particular, within a single catalyst, is generally needed. Here, by using a stepwise electrostatic interaction strategy, imidazolium-based ILs and Au nanoparticles (NPs) were stepwise immobilized into a sulfonic group grafted MOF to construct a multifunctional single catalyst with a highly ordered arrangement of catalytic sites. The Au NPs and imidazolium cation are separately responsible for the selective epoxidation and cycloaddition reaction. The mesoporous cage within the MOF enriches the substrate molecules and provides a confined catalytic room for the tandem catalysis. More importantly, the highly ordered arrangement of the varied active sites and strong electrostatic attraction interaction result in the intimate contact and effective mass transfer between the catalytic sites, which allow for the highly efficient (>74% yield) and stable (repeatedly usage for at least 8 times) catalytic transformation. The stepwise electrostatic interaction strategy herein provides an absolutely new approach in fabricating the controllable multifunctional catalysts, especially for tandem catalysis.

Monoterpene indole alkaloids with acetylcholinesterase inhibitory activity from the leaves of Rauvolfia vomitoria.

Seventeen monoterpene indole alkaloids, including seven new alkaloids (1-7) and ten known analogues (8-17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C22 yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2-3) and affinisine oxindole (5-6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2-3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1-17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 µM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC50 value of 16.39 ± 1.41 µM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were weak inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD.