Gate-tunable Intrinsic Anomalous Hall Effect in Epitaxial MnBi2Te4 Films.

The anomalous Hall effect (AHE) is an important transport signature revealing topological properties of magnetic materials and their spin textures. Recently, MnBi2Te4 has been demonstrated to be an intrinsic magnetic topological insulator. However, the origin of its intriguing AHE behaviors remains elusive. Here, we demonstrate the Berry curvature-dominated intrinsic AHE in wafer-scale MnBi2Te4 films. By applying back-gate voltages, we observe an ambipolar conduction and n-p transition in ∼7-layer MnBi2Te4, where a quadratic relation between the AHE resistance and longitudinal resistance suggests its intrinsic AHE nature. In particular, for ∼3-layer MnBi2Te4, the AHE sign can be tuned from pristine negative to positive. First-principles calculations unveil that such an AHE reversal originated from the competing Berry curvature between oppositely polarized spin-minority-dominated surface states and spin-majority-dominated inner bands. Our results shed light on the underlying physical mechanism of the intrinsic AHE and provide new perspectives for the unconventional sign-tunable AHE.

Spokewise Total Syntheses of Four Erythrina Alkaloids and Telescoped Syntheses of Six Additional Alkaloids.

Based on rich sulfur-involving chemical transformations, a novel spokewise synthetic strategy, a subclass of the collective strategies, has been developed to concisely synthesize four erythrina alkaloids through a single-step transformation from a common synthetic precursor. Moreover, six additional erythrina alkaloids have also been synthesized by subsequent 1-2 steps chemical transformations. The current synthetic approaches provide a valuable platform for collective total syntheses of erythrina alkaloids and pseudo-natural erythrina alkaloids.

Population Pharmacokinetic Modeling of Pyrazinamide Among Chinese Patients With Drug-Sensitive or Multidrug-Resistant Tuberculosis.

BACKGROUND: Pyrazinamide is used to treat drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB). This study aimed to characterize the factors associated with the pharmacokinetic parameters of pyrazinamide and evaluate the disposition of the current regimen, which could provide suggestions for adequate dosing strategies for therapeutic targets. METHODS: A population pharmacokinetic model of pyrazinamide was developed based on the data from 499 plasma concentrations from 222 Chinese patients diagnosed with DS or MDR TB. Pyrazinamide exposure was best described using a one-compartment model. RESULTS: No significant differences were observed in the pharmacokinetic parameters between DS and MDR TB. The final covariate model showed that total body weight was the only significant covariate for apparent clearance, which increased by 0.45 L/h with a 10 kg increase in body weight. A simulation showed that for typical subjects weighing 40-80 kg, a fixed dosage of 1500 mg daily had an area under the concentration-time curve from 0 to 24 hours (AUC0-24) of 389.9-716.0 mg·h/L and peak serum concentrations of the drug (Cmax) of 32.2-44.8 mg/L. CONCLUSIONS: Fixed pyrazinamide doses of 1500, 1750, and 2000 mg are recommended for patients weighing 40-70, 70-80, and 80-90 kg, respectively, to achieve the exposure targets of AUC0-24 > 363 mg·h/L or Cmax > 35 mg/L to attain efficacy.

Preparation of cellulose acetate based flexible separator and its application in zinc-air batteries.

Flexible solid-state zinc-air batteries as a wearable energy storage device with great potential, and their separators, which control ion permeability, inhibit zinc dendrite generation, and regulate catalytic active sites, have been developed as gel electrolyte separators with high retention of electrolyte uptake. However, the gel electrolyte separator still has problems such as poor affinity with the electrolyte and poor ionic conductivity, which limits its further application. In order to further improve the electrolyte absorption, ionic conductivity and mechanical strength of cellulose acetate(CA)/polyvinyl alcohol (PVA) nanofibers, TiO2was added to CA/PVA to increase the porosity, and glutaraldehyde (GA) was used to modify the CA/PVA/TiO2separator by acetal reaction with CA and PVA to make the molecules closely linked. The results shows that the optimal mass fractions of TiO2and GA were 2% and 5%, respectively. At this time, the porosity and absorption rate of the separator increased from 48% to 68.2% and 142.4% to 285.3%, respectively. The discharge capacity reached 179 mA cm-3, and the cycle stability rate was 89% after 7 stable constant current charge/discharge cycles.

Enhanced Efflux Activity Facilitates Drug Tolerance in Dormant Bacterial Cells.

Natural variations in gene expression provide a mechanism for multiple phenotypes to arise in an isogenic bacterial population. In particular, a sub-group termed persisters show high tolerance to antibiotics. Previously, their formation has been attributed to cell dormancy. Here we demonstrate that bacterial persisters, under ß-lactam antibiotic treatment, show less cytoplasmic drug accumulation as a result of enhanced efflux activity. Consistently, a number of multi-drug efflux genes, particularly the central component TolC, show higher expression in persisters. Time-lapse imaging and mutagenesis studies further establish a positive correlation between tolC expression and bacterial persistence. The key role of efflux systems, among multiple biological pathways involved in persister formation, indicates that persisters implement a positive defense against antibiotics prior to a passive defense via dormancy. Finally, efflux inhibitors and antibiotics together effectively attenuate persister formation, suggesting a combination strategy to target drug tolerance.

Combined PET/CT and Autoantibody Detection in Lung Nodules Diagnosis.

Objective: To assess the usefulness of combining positron emission tomography/computed tomography (PET/CT) with lung cancer autoantibody detection in identifying and managing lung nodules. Methods: The researchers identified 160 patients with pulmonary nodules admitted to their hospital between January 2018 and January 2021. These patients were designated as the experimental group. Additionally, 60 healthy individuals without pulmonary nodules were admitted to the hospital during the same period. The individuals constituted the control group. All study participants underwent digital PET/CT detection and had their lung cancer autoantibody levels determined through enzyme-linked immunosorbent assay. Further testing, such as puncture or surgical pathology, was performed for patients with lung nodules. The aim was to evaluate the significance of combining PET/CT with autoantibody detection in diagnosing and treating lung nodules. Results: The study found that testing multiple autoantibodies together increased sensitivity and accuracy compared to testing individual autoantibodies. Combining PET/CT screening with autoantibody detection improved the diagnostic rate for identifying lung nodules, including benign and suspected malignant ones. Several autoantibodies were significantly higher in the experimental group compared to the control group. Testing for multiple autoantibodies showed higher sensitivity and accuracy than testing for one. Pathological examination confirmed 129 benign nodules and 31 malignant nodules. The median SUVmax values were measured at 0.7 for benign nodules and 4.8 for malignant nodules. The diagnostic efficacy of PET/CT combined with autoantibodies was determined through comparison with pathology testing and was as follows: PET/CT combined with autoantibody detection > PET/CT > autoantibody detection. Conclusion: Combining PET/CT with the detection of autoantibodies enhances the positive diagnostic rate and accuracy of lung nodules in the case of lung cancer. The SUVmax also shows excellent potential as a supplement in diagnosing both benign and malignant lung nodules, providing valuable guidance in determining the pathological types.

Perfect Is Perfect: Nickel Prussian Blue Analogue as A High-Efficiency Electrocatalyst for Hydrogen Peroxide Production.

Prussian blue analogues (PBA) are a large family of functional materials with diverse applications such as in electrochemical fields. However, their use in the emerging two-electron oxygen reduction reaction for clean production of hydrogen peroxide (H2O2) is lagging. Herein, a general solvent exchange induced reconstruction strategy is demonstrated, through which an abnormal NiNi-PBA superstructure is synthesized as a high-performance electrocatalyst for H2O2 generation. The resultant NiNi-PBA superstructure has a stoichiometric composition with saturated lattice water, and a leaf-like morphology composed of interconnected small-size nanosheets with identical orientation and predominate {210} side surface exposure. Our studies show that the Ni-N centers on {210} facets are the active sites, and the saturated lattice H2O favors a six-coordinated environment that results in high selectivity. The "perfect" structure including stoichiometric composition and ideal facet exposure leads to a high selectivity of ~100% and H2O2 yield of 5.7 mol g-1 h-1, superior to the reported MOF-based electrocatalysts and most other electrocatalysts.

MOF-on-MOF Heterostructured Electrocatalysts for Efficient Nitrate Reduction to Ammonia.

Electrocatalytic nitrate reduction reaction (NO3-RR) is an important route for sustainable NH3 synthesis and environmental remediation. Metal-organic frameworks (MOFs) are one family of promising NO3-RR electrocatalysts, however, there is plenty of room to improve in their performance, calling for new design principles. Herein, a MOF-on-MOF heterostructured electrocatalyst with interfacial dual active sites and build-in electric field is fabricated for efficient NO3-RR to NH3 production. By growing Co-HHTP (HHTP=2,3,6,7,10,11-hexahydroxytriphenylene) nanorods on Ni-BDC (BDC=1,4-benzenedicarboxylate) nanosheets, experimental and theoretical investigations demonstrate the formation of Ni-O-Co bonds at the interface of MOF-on-MOF heterostructure, leading to dual active sites tailed for NO3-RR. The Ni sites facilitate the adsorption and activation of NO3-, while the Co sites boost the H2O decomposition to supply active hydrogen (Hads) for N-containing intermediates hydrogenation on adjacent Ni sites, cooperatively reducing the energy barriers of NO3-RR process. Together with the accelerated electron transfer enabled by built-in electric field, remarkable NO3-RR performance is achieved with an NH3 yield rate of 11.46 mg h-1 cm-2 and a Faradaic efficiency of 98.4%, outperforming most reported MOF-based electrocatalysts. This work provides new insights into the design of high-performance NO3-RR electrocatalysts.

Exhaled Anesthetic Xenon Regeneration by Gas Separation Using a Metal-Organic Framework with Sorbent-Sorbate Induced-Fit.

Noble gas xenon (Xe) is an excellent anesthetic gas, but its rarity, high cost and constrained production prohibits wide use in medicine. Here, we have developed a closed-circuit anesthetic Xe recovery and reusage process with highly effective CO2-specific adsorbent CUPMOF-5 that is promising to solve the anesthetic Xe supply problem. CUPMOF-5 possesses spacious cage cavities interconnected in four directions by confinement throat apertures of ~3.4 Å, which makes it an ideal molecular sieving of CO2 from Xe, O2, N2 with the benchmark selectivity and high uptake capacity of CO2. In situ single-crystal X-ray diffraction (SCXRD) and computational simulation solidly revealed the vital sieving role of the confined throat and the sorbent-sorbate induced-fit strengthening binding interaction to CO2. CUPMOF-5 can remove 5 % CO2 even from actual moist exhaled anesthetic gases, and achieves the highest Xe recovery rate (99.8 %) so far, as verified by breakthrough experiments. This endows CUPMOF-5 great potential for the on-line CO2 removal and Xe recovery from anesthetic closed-circuits.

High Shear Thin Film Synthesis of Partially Oxidized Gallium and Indium Composite 2D Sheets.

Reducing resistance in silicon-based devices is important as they get miniaturized further. 2D materials offer an opportunity to increase conductivity whilst reducing size. A scalable, environmentally benign method is developed for preparing partially oxidized gallium/indium sheets down to 10 nm thick from a eutectic melt of the two metals. Exfoliation of the planar/corrugated oxide skin of the melt is achieved using the vortex fluidic device with a variation in composition across the sheets determined using Auger spectroscopy. From an application perspective, the oxidized gallium indium sheets reduce the contact resistance between metals such as platinum and silicon (Si) as a semiconductor. Current-voltage measurements between a platinum atomic force microscopy tip and a Si-H substrate show that the current switches from being a rectifier to a highly conducting ohmic contact. These characteristics offer new opportunities for controlling Si surface properties at the nanoscale and enable the integration of new materials with Si platforms.

Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens.

Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus to form a HlaH35A-PA0833 fusion protein (HPF). Immunization with HPF resulted in increased PA0833-specific antibody titers, higher protective efficacy, and decreased bacterial burden and pro-inflammatory cytokine secretion compared with PA0833 immunization alone. Using fluorescently labeled antigens to track antigen uptake and delivery, we found that HlaH35A fusion significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that the increased antigen uptake after immunization with HPF was mainly due to monocyte- and macrophage-dependent macropinocytosis, which was probably the result of HPF binding to ADAM10, the Hla host receptor. Furthermore, a transcriptome analysis showed that several immune signaling pathways were activated by HPF, shedding light on the mechanism whereby HlaH35A fusion improves immunogenicity. Finally, the improvement in immunogenicity by HlaH35A fusion was also confirmed with two other antigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, indicating that HlaH35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens.

Brain regions susceptible to alpha-synuclein spreading.

The spreading of misfolded alpha-synuclein (α-syn) protein has been observed in animal models of Parkinson's disease (PD) and other α-synucleinopathies that mimic human PD pathologies. In animal models, the spreading of α-syn has been associated with motor dysfunction and neuronal death. However, variability in both susceptible brain regions and cellular populations limits our understanding of the consequences of α-syn spreading and the development of associated therapies. Here, we have reviewed the physiological and pathological functions of α-syn and summarized the susceptible brain regions and cell types identified from human postmortem studies and exogenous α-syn injection-based animal models. We have reviewed the methods for inducing α-syn aggregation, the specific hosts, the inoculation sites, the routes of propagation, and other experimental settings that may affect the spreading pattern of α-syn, as reported in current studies. Understanding the spread of α-syn to produce a consistent PD animal model is vital for future drug discovery.

Electroactive poly(thionine) as imprinted polymer and reference probe simultaneously for ratiometric ion imprinted electrochemical Pb2+sensor.

In this work, an electrochemical sensor based on ion-imprinted polymer/Au nanoparticles/porous biochar (IIP/AuNPs/PBC) composite was proposed for the highly selective and sensitive detection of Pb2+. In this work, poly (thionine) (pTHI) served simultaneously as imprinted polymer and reference probe. It could not only realize the specific detection of Pb2+, but also provide an internal reference signal to eliminate the influence of human and environmental factors on the detection signal and further improve the stability of the sensor. In addition, the AuNPs/PBC composite with large specific surface area, excellent electron transport and electrocatalytic performance could effectively enhance the detection signal as a carrier material. At the same time, the AuNPs on the PBC surface would promote the formation of uniform and stable IIP through Au-S bonds. The synergistic effect between IIP, AuNPs/PBC and ratiometric signal mode gave the Pb2+sensor excellent performance, including a wide linear range (0.1-1000µg l-1), low detection limit (0.03µg l-1, S/N = 3), excellent selectivity and stability. All these results indicate that the proposed sensor could provide a meaningful reference for highly selective detection of heavy metal ions (HMIs).

Electrochemical activation of oxygen vacancy-rich TiO2@MXene as high-performance electrochemical sensing platform for detecting imidacloprid in fruits and vegetables.

Heterostructured TiO2@MXene rich in oxygen vacancies defects (VO-TiO2@MXene) has been developed to construct an electrochemical sensing platform for imidacloprid (IMI) determination. For the material design, TiO2 nanoparticles were firstly in situ grown on MXene and used as a scaffolding to prevent the stack of MXene nanosheets. The obtained TiO2@MXene heterostructure displays excellent layered structure and large specific surface area. After that, electrochemical activation is utilized to treat TiO2@MXene, which greatly increases the concentration of surface oxygen vacancies (VOs), thereby remarkably enhancing the conductivity and adsorption capacity of the composite. Accordingly, the prepared VO-TiO2@MXene displays excellent electrocatalytic activity toward the reduction of IMI. Under optimum conditions, cyclic voltammetry and linear sweep voltammetry techniques were utilized to investigate the electrochemical behavior of IMI at the VO-TiO2@MXene/GCE. The proposed sensor based on VO-TiO2@MXene presents an obvious reduction peak at -1.05 V(vs. Hg|Hg2Cl2) with two linear ranges from 0.07 - 10.0 µM and 10.0 - 70.0 µM with a detection limit of 23.3 nM (S/N= 3). Furthermore, the sensor provides a reliable result for detecting IMI in fruit and vegetable samples with a recovery of 97.9-103% and RSD≤ 4.3%. A sensitive electrochemical sensing platform was reported for imidacloprid (IMI) determination based on heterostructured TiO2@MXene rich in oxygen vacancy defects.

A Novel Strategy for Detecting Permittivity and Loss Tangent of Low-Loss Materials Based on Cylindrical Resonant Cavity.

Accurate measurement of the permittivity and loss tangent of low-loss materials is essential due to their special applications in the field of ultra large scale integrated circuits and microwave devices. In this study, we developed a novel strategy that can accurately detect the permittivity and loss tangent of low-loss materials based on a cylindrical resonant cavity supporting the TE111 mode in X band (8-12 GHz). Based on an electromagnetic field simulation calculation of the cylindrical resonator, permittivity is precisely retrieved by exploring and analyzing the perturbation of the coupling hole and sample size on the cutoff wavenumber. A more precise approach to measuring the loss tangent of samples with various thicknesses has been proposed. The test results of the standard samples verify that this method can accurately measure the dielectric properties of samples that have smaller sizes than the high Q cylindrical cavity method.

Nitrogen Doped Porous Biochar/ß-CD-MOFs Heterostructures: Bi-Functional Material for Highly Sensitive Electrochemical Detection and Removal of Acetaminophen.

Acetaminophen (AC) is one of the most common over-the-counter drugs, and its pollutant in groundwater has attracted more attention due to its serious risk to human health. Currently, the research on AC is mainly focused on its detection, but few are concerned about its removal. In this work, for the first time, nitrogen-doped Soulangeana sepals derived biochar/ß-cyclodextrin-Metal-organic frameworks (N-SC/ß-CD-MOFs) composite was proposed for the simultaneous efficient removal and detection of AC. N-SC/ß-CD-MOFs combined the properties of host-guest recognition of ß-CD-MOFs and porous structure, high porosity, and large surface area of N-SC. Their synergies endowed N-SC/ß-CD-MOFs with a high adsorption capacity toward AC, which was up to 66.43 mg/g. The adsorption type of AC on the surface of N-SC/ß-CD-MOFs conformed to the Langmuir adsorption model, and the study of the adsorption mechanism showed that AC adsorption on N-SC was mainly achieved through hydrogen bonding. In addition, the high conductivity, large specific surface area and abundant active sites of N-SC/ß-CD-MOFs were of great significance to the high-performance detection of AC. Accordingly, the sensor prepared with N-SC/ß-CD-MOFs presented a wide linear range (1.0-30.0 µM) and a low limit of detection of 0.3 nM (S/N = 3). These excellent performances demonstrate that N-SC/ß-CD-MOFs could act as an efficient dual-functional material for the detection and removal of AC.

An Electrochemical Sensor Based on a Porous Biochar/Cuprous Oxide (BC/Cu2O) Composite for the Determination of Hg(II).

Mercuric ion (Hg2+) in aqueous media is extremely toxic to the environment and organisms. Therefore, the ultra-trace electrochemical determination of Hg2+ in the environment is of critical importance. In this work, a new electrochemical Hg2+ sensing platform based on porous activated carbon (BC/Cu2O) modified with cuprous oxide was developed using a simple impregnation pyrolysis method. Differential pulse anodic stripping voltammetry (DPASV) was used to investigate the sensing capability of the BC/Cu2O electrode towards Hg2+. Due to the excellent conductivity and large specific surface area of BC, and the excellent catalytic activity of Cu2O nanoparticles, the prepared BC/Cu2O electrode exhibited excellent electrochemical activity. The high sensitivity of the proposed system resulted in a low detection limit of 0.3 ng·L-1 and a wide linear response in the ranges from 1.0 ng·L-1 to 1.0 mg·L-1. In addition, this sensor was found to have good accuracy, acceptable precision, and reproducibility. All of these results show that the BC/Cu2O composite is a promising material for Hg2+ electrochemical detection.

Knowledge and belief of fecal occult blood screening: A systematic review.

INTRODUCTION: Colorectal cancer (CRC) is associated with a high incidence and mortality rate. Fecal occult blood test (FOBT) is effective in the prevention of CRC. OBJECTIVE: This study aimed to assess knowledge and beliefs regarding FOBT-based screening. METHODS: This study used PubMed, Cochrane Library, MEDLINE Complete, and Web of Science to search for articles. Original full-text studies in English language focusing on knowledge and beliefs of FOBT screening were included. RESULTS: A total of 32 articles were included. This study indicated that the population in most studies had inadequate knowledge and lacked beliefs toward FOBT-based screening. Most of the extracted studies showed that less than half of the participants had heard of FOBT-based screening. Six studies showed that less than 50% of participants had knowledge of FOBT age. Three studies found that less than 40% of participants were aware of the screening interval. Some participants perceived the benefits of FOBT-based screening, while others perceived many barriers to the test. CONCLUSION: Participants' knowledge and belief in FOBT-based screening were insufficient. This review highlights the importance of educational programs to increase knowledge and beliefs regarding FOBT-based screening. It is important to include FOBT-based screening in the health care system to promote the secondary prevention of CRC.

Population Pharmacokinetic Modeling of Bedaquiline among Multidrug-Resistant Pulmonary Tuberculosis Patients from China.

Bedaquiline has been widely used as a part of combination dosage regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) patients with limited options. Although the effectiveness and safety of bedaquiline have been demonstrated in clinical trials, limited studies have investigated the significant pharmacokinetics and the impact of genotype on bedaquiline disposition. Here, we developed a population pharmacokinetic model of bedaquiline to describe the concentration-time data from Chinese adult patients diagnosed with MDR-TB. A total of 246 observations were collected from 99 subjects receiving the standard recommended dosage. Bedaquiline disposition was well described by a one-compartment model with first-order absorption. Covariate modeling identified that gamma-glutamyl transferase (GGT) and the single-nucleotide polymorphism (SNP) rs319952 in the AGBL4 gene were significantly associated with the apparent clearance of bedaquiline. The clearance (CL/F) was found to be 1.4 L/h lower for subjects with allele GG in SNP rs319952 than for subjects with alleles AG and AA and to decrease by 30% with a doubling in GGT. The model-based simulations were designed to assess the impact of GGT/SNP rs319952 on bedaquiline exposure and showed that patients with genotype GG in SNP rs319952 and GGT ranging from 10 to 50 U/L achieved the targeted maximum serum concentration at steady state (Cmax,ss). However, when GGT was increased to 100 U/L, Cmax,ss was 1.68-fold higher than the highest concentration pursued. The model developed provides the consideration of genetic polymorphism and hepatic function for bedaquiline dosage in MDR-TB adult patients.

Understanding Micro and Atomic Structures of Secondary Phases in Cu-Doped SnTe.

Highly efficient thermoelectric materials require, including point defects within the host matrix, secondary phases generating positive effects on lowering lattice thermal conductivity (κL ). Amongst effective dopants for a functional thermoelectric material, SnTe, Cu doping realizes the ultra-low κL approaching the SnTe amorphous limit. Such effective κL reduction is first attributed to strong phonon scattering by substitutional Cu atoms at Sn sites and interstitial defects in the host SnTe. However, other crystallographic defects in secondary phases have been unfocused. Here, this work reports micro- to atomic-scale characterization on secondary phases of Cu-doped SnTe using advanced microscopes. It is found that Cu-rich secondary phases begin precipitation ≈1.7 at% Cu (x = 0.034 where Sn1- x Cux Te). The Cu-rich secondary phases encapsulate two distinct solids: Cu2 SnTe3 ( F 4 ¯ 3 m $F\bar{4}3m$ ) has semi-coherent interfaces with SnTe ( F m 3 ¯ m $Fm\bar{3}{\rm{m}}$ ) such that they minimize lattice mismatch to favor the thermoelectric transport; the other resembles a stoichiometric Cu2 Te model, yet is so meta-stable that it demonstrates not only various defects such as dislocation cores and ordered/disordered Cu vacancies, but also dynamic grain-boundary migration with heating and a subsequent phase transition ≈350 °C. The atomic-scale analysis on the Cu-rich secondary phases offers viable strategies for reducing κL through Cu addition to SnTe.