Terminal Chemical Modifications of crRNAs Enable Improvement in the Performance of CRISPR-Cas for Point-of-Care Nucleic Acid Detection.

CRISPR-Cas systems, harnessing their precise nucleic acid recognition via CRISPR RNA (crRNA), offer promise for the accurate testing of nucleic acids in the field. However, the inherent susceptibility of crRNA to degradation poses challenges for accurate detection in low-resource settings. Here, we utilized the chemically modified crRNA for the CRISPR-Cas-based assay (CM-CRISPR). We found that the extension and chemical modification to crRNA significantly enhanced the trans-cleavage activity of LbCas12a. The chemically modified crRNA was resistant to degradation, and CM-CRISPR showed superior detection capability in complex environments. CM-CRISPR could be combined with recombinase polymerase amplification (RPA) and applied in a droplet digital platform, enabling attomolar-level sensitivity. We also developed a portable and automated device for a digital CRISPR assay, which is amenable to point-of-care testing (POCT). The extraction-free procedure was integrated with this assay to streamline the workflow, and clinical samples were successfully detected. This work finds a simple and efficient way to improve the performance of CRISPR-Cas and develops a portable platform for POCT, representing a significant advance toward practical applications of CRISPR-based diagnostics.

Broadband generation of a multi-polarization multi-beam using a receiving-transmitting metasurface.

Generating multiple beams in distinct polarization states is promising in multi-mode wireless communication but still remains challenging in metasurface design. Here, we theoretically and experimentally demonstrate a concept of broadband receiving-transmitting metasurface and its application to the generation of multi-polarization multi-beam. By employing U-slot patch, an efficient receiving-transmitting element with full phase coverage is designed within a wide bandwidth. Based on this architecture, a methodology is proposed to generate dual spin-decoupled beams and then developed into the strategy of generating multiple beams at different linear polarizations. To verify our strategy, two lens antennas, respectively radiating dual-spin dual-beam and quad-polarization quad-beam, are devised. With multi-polarization multi-beam radiated, the two lens antennas are both with whole aperture efficiency above 40% within the bandwidth of 10.6-12.3 GHz (14.8%), firmly validating our strategy and design.

Pleiotropic immunoregulation by growth-blocking peptide in Ostrinia furnacalis.

Insects rely on their innate immune system to eliminate pathogenic microbes. As a system component, cytokines transmit intercellular signals to control immune responses. Growth-blocking peptide (GBP) is a member of the stress-responsive peptide family of cytokines found in several orders of insects, including Drosophila. However, the physiological role of GBP in defence against pathogens is not thoroughly understood. In this study, we explored the functions of GBP in a lepidopteran pest, Ostrinia furnacalis. Injection of recombinant O. furnacalis GBP (OfGBP) precursor (proGBP) and chemically synthesised GBP significantly induced the transcription of antimicrobial peptides (AMPs) and other immunity-related genes including immune deficiency (IMD) and Dorsal. The level of OfGBP mRNA was upregulated after bacterial infection. Knockdown of OfGBP expression led to a decrease in IMD, Relish, MyD88 and Dorsal mRNA levels. OfGBP induced phenoloxidase activity and affected hemocyte behaviours in O. furnacalis larvae. In summary, GBP is a potent cytokine, effectively regulating AMP synthesis, melanization response and cellular immunity to eliminate invading pathogens.

Photoelectrochemical Synthesis of Hydrogen Peroxide from Saline Water via the Two-Electron Water Oxidation Reaction.

Hydrogen peroxide (H2O2) production on the anode is more valuable than oxygen and chlorine evolution for photoelectrochemical saline water splitting. In this work, by the introduction of bicarbonate (HCO3-), H2O2 is produced from saline water (2 M KHCO3 + 0.5 M NaCl aqueous solution) via the two-electron water oxidation reaction by a photoanode of bismuth vanadate (BiVO4). Furthermore, the Faradaic efficiency (FE) and accumulation for H2O2 are improved by coating antimony tetroxide (Sb2O4) on BiVO4. A H2O2 FE of 26% at 1.54 V vs RHE is obtained by Sb2O4/BiVO4 and 49 ppm of H2O2 is accumulated after a 135 min chronoamperometry. Similar to that in KHCO3 pure water solution, infrared spectroscopy and electrochemical analysis confirm that HCO3- plays a surface-mediating role in the formation of H2O2 in KHCO3 saline water solution. The presence of HCO3- in the electrolyte is able to not only increase the photocurrent density but also effectively inhibit the chlorine evolution reaction.

Concentration-resistance relationship and PK/PD evaluation of danofloxacin against emergence of resistant Pasteurella multocida in an in vitro dynamic model.

AIMS: This study aimed to assess the pharmacokinetic/pharmacodynamic (PK/PD) targets of danofloxacin to minimize the risk of selecting resistant Pasteurella multocida mutants and to identify the mechanisms underlying their resistance in an in vitro dynamic model, attaining the optimum dosing regimen of danofloxacin to improve its clinical efficacy based on the mutant selection window (MSW) hypothesis. METHODS AND RESULTS: Danofloxacin at seven dosing regimens and 5 days of treatment were simulated to quantify the bactericidal kinetics and enrichment of resistant mutants upon continuous antibiotic exposure. The magnitudes of PK/PD targets associated with different efficacies were determined in the model. The 24 h area under the concentration-time curve (AUC) to minimum inhibitory concentration (MIC) ratios (AUC24h/MIC) of danofloxacin associated with bacteriostatic, bactericidal and eradication effects against P. multocida were 34, 52, and 64 h. This translates to average danofloxacin concentrations (Cav) over 24 h being 1.42, 2.17, and 2.67 times the MIC, respectively. An AUC/MIC-dependent antibacterial efficacy and AUC/mutant prevention concentration (MPC)-dependent enrichment of P. multocida mutants in which maximum losses in danofloxacin susceptibility occurred at a simulated AUC24h/MIC ratio of 72 h (i.e. Cav of three times the MIC). The overexpression of efflux pumps (acrAB-tolC) and their regulatory genes (marA, soxS, and ramA) was associated with reduced susceptibility in danofloxacin-exposed P. multocida. The AUC24h/MPC ratio of 19 h (i.e. Cav of 0.8 times the MPC) was determined to be the minimum mutant prevention target value for the selection of resistant P. multocida mutants. CONCLUSIONS: The emergence of P. multocida resistance to danofloxacin exhibited a concentration-dependent pattern and was consistent with the MSW hypothesis. The current clinical dosing regimen of danofloxacin (2.5 mg kg-1) may have a risk of treatment failure due to inducible fluoroquinolone resistance.

Three-Dimensional Digital Reconstruction of the Cerebellar Cortex: Lobule Thickness, Surface Area Measurements, and Layer Architecture.

The cerebellum is ontogenetically one of the first structures to develop in the central nervous system; nevertheless, it has been only recently reconsidered for its significant neurobiological, functional, and clinical relevance in humans. Thus, it has been a relatively under-studied compared to the cerebrum. Currently, non-invasive imaging modalities can barely reach the necessary resolution to unfold its entire, convoluted surface, while only histological analyses can reveal local information at the micrometer scale. Herein, we used the BigBrain dataset to generate area and point-wise thickness measurements for all layers of the cerebellar cortex and for each lobule in particular. We found that the overall surface area of the cerebellar granular layer (including Purkinje cells) was 1,732 cm2 and the molecular layer was 1,945 cm2. The average thickness of the granular layer is 0.88 mm (± 0.83) and that of the molecular layer is 0.32 mm (± 0.08). The cerebellum (both granular and molecular layers) is thicker at the depth of the sulci and thinner at the crowns of the gyri. Globally, the granular layer is thicker in the lateral-posterior-inferior region than the medial-superior regions. The characterization of individual layers in the cerebellum achieved herein represents a stepping-stone for investigations interrelating structural and functional connectivity with cerebellar architectonics using neuroimaging, which is a matter of considerable relevance in basic and clinical neuroscience. Furthermore, these data provide templates for the construction of cerebellar topographic maps and the precise localization of structural and functional alterations in diseases affecting the cerebellum.

Analysis of Medication Rules of Traditional Chinese Medicine for Malaria Treatment Based on Data Mining.

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.

Long-Life, High-Rate Rechargeable Lithium Batteries Based on Soluble Bis(2-pyrimidyl) Disulfide Cathode.

Organosulfides are promising candidates as cathode materials for the development of electric vehicles and energy storage systems due to their low-cost and high capacity properties. However, they generally suffer from slow kinetics because of the large rearrangement of S-S bonds and structural degradation upon cycling in batteries. In this paper, we reveal that soluble bis(2-pyrimidyl) disulfide (Pym2 S2 ) can be a high-rate cathode material for rechargeable lithium batteries. Benefiting from the superdelocalization of pyrimidyl group, the extra electrons prefer to be localized on the π* (pyrimidyl group) than σ* (S-S bond) molecular orbitals initially, generating the anion-like intermedia of [Pym2 S2 ]2- and thus decreasing the dissociation energy of the S-S bond. It makes the intrinsic energy barrier of dissociative electron transfer depleted, therefore the lithium half cell exhibits 2000 cycles at 5 C. This study provides a distinct pathway for the design of high-rate, long-cycle-life organic cathode materials.

Resource Allocation and Computation Offloading for Wireless Powered Mobile Edge Computing.

In this paper, we investigate a resource allocation and computation offloading problem in a heterogeneous mobile edge computing (MEC) system. In the considered system, a wireless power transfer (WPT) base station (BS) with an MEC sever is able to deliver wireless energy to the mobile devices (MDs), and the MDs can utilize the harvested energy for local computing or task offloading to the WPT BS or a Macro BS (MBS) with a stronger computing server. In particular, we consider that the WPT BS can utilize full- or half-duplex wireless energy transmission mode to empower the MDs. The aim of this work focuses on optimizing the offloading decision, full/half-duplex energy harvesting mode and energy harvesting (EH) time allocation with the objective of minimizing the energy consumption of the MDs. As the formulate problem has a non-convex mixed integer programming structure, we use the quadratically constrained quadratic program (QCQP) and semi-definite relaxation (SDR) methods to solve it. The simulation results demonstrate the effectiveness of the proposed scheme.

Quad-channel independent wavefront encoding with dual-band multitasking metasurface.

Achieving multiple electromagnetic (EM) functionalities on a shared aperture in dual frequency bands is crucial for many applications; however, existing dual-band metasurfaces are affected by limited channels or narrow bandwidths. Herein, we propose a reflective coding metasurface that empowers four independent EM functionalities in quad-polarization channels in two wide frequency bands. By integrating quasi-I-shaped and cross-shaped metastructures, the meta-atom can feature independent phase modulation for two orthogonally linear and two decoupled circular polarizations at low and high frequencies, respectively. To validate the proposed metasurface, a multifunctional metadevice is designed that integrates beam deflection, diffuse scattering, and vortex beam generation. Both experimental and simulation results indicate distinct wavefront tailoring in each channel. The proposed multi-functional metasurface with low cross-talk and independent phase modulation depending on frequencies and polarizations may unlock the metasurfaces' potentials for complete wavefront control in EM function integration, multiple channel communication, polarization optics, etc.

Modified Nasoseptal Rescue Flap Technique for Pituitary Adenoma Resection via Endoscopic Endonasal Approach.

ABSTRACT: Nasoseptal rescue flap (NSRF), which preserves the pedicle of the flap and is harvested as a nasoseptal flap (NSF) when intraoperative leakage of cerebrospinal fluid (CSF) occurs, is an alternative strategy for skull base reconstruction in patients with pituitary adenoma resection via an endoscopic endonasal approach. However, in practice, the original NSRF technique cannot meet the needs during operation. Therefore, the authors aimed to describe a modified NSRF technique for the resection of pituitary adenoma via endoscopic endonasal approach and to examine its utility and outcomes. The authors retrospectively analyzed the medical records of 87 consecutive patients with pituitary adenoma who underwent endoscopic endonasal surgery performed using NSRF technique from September 2019 to August 2020. Data on intraoperative CSF leakage, NSF conversion rate, and reconstruction-related complications were analyzed. The average age of patients was 50.1 years (men, 50.5%). Twenty-five cases of intraoperative CSF leakage were observed: 23 cases of low-flow CSF leakage and two cases of high-flow CSF leakage. NSRF was converted to NSF in 11 cases. Two patients experienced postoperative CSF leakage after reconstruction without NSF and required unplanned reoperation to rebuild the skull base with NSF. In conclusion, this modified NSRF utilized a minimally invasive way to provide sufficient surgical corridor without the need for pedicle retraction, and it can be effectively converted to an NSF for skull base reconstruction in patients with pituitary adenoma.

Endoscopic Endonasal Approach for Clipping Anterior Communicating Artery Aneurysms From Cadaver Studies and Three-Dimensional Printed Models to a Clinical Case.

OBJECTIVES: Anterior communicating artery (ACoA) aneurysm is one of the most common intracranial aneurysms, and it is also the aneurysm with the highest rupture rate. With the improvement of endoscopic techniques, it is possible to use an endoscopic endonasal approach (EEA) to clip ACoA aneurysms. For further analysis of the EEA for clipping ACoA aneurysms, we used cadaver heads and three-dimensional (3D)-printed models to finish the anatomical study, and we finally selected 1 clinical case to complete the clipping through the EEA. MATERIALS AND METHODS: We first collected 3 cadaver heads to simulate the EEA. Then, the imaging data of 29 real cases of ACoA aneurysm were collected, and the model of an aneurysm was prepared by 3D printing technology; then, the EEA was used to simulate the clipping of the aneurysm model. Finally, a clinical case with 2 ACoA aneurysms was selected to adopt the EEA for clipping. RESULTS: Both the cadaver head and 3D-printed aneurysm model could simulate aneurysm clipping with the EEA. The clinical case of the selected ACoA aneurysm can successfully complete the clipping through the EEA. CONCLUSIONS: 3D-printed models are a good method to study the anatomical characteristics of a surgical approach. For specially selected ACoA aneurysms, the EEA is relatively simple method that can be used to clip the aneurysm successfully. The EEA for clipping ACoA aneurysms is a useful complement to the current traditional craniotomy approaches and endovascular embolization.

Helicity-dependent metasurfaces employing receiver-transmitter meta-atoms for full-space wavefront manipulation.

Manipulating orthogonal circularly polarized (CP) waves independently in both reflection and transmission modes in a single metasurface is pivotal. However, independently controlling CP waves with different polarizations is difficult especially for both reflection and transmission modes. Here, we designed a receiver-transmitter metasurface with helicity-dependent reflection and transmission properties. Our design breaks the fixed phases of the geometry metasurface-carrying Pancharatnam-Berry operators by combining the receive and transmit antennas. To verify the effectiveness of the modulation, we designed three linear deflectors with: (a) reflection phase gradient, (b) transmission phase gradient, and (c) both of gradients to achieve anomalous reflection, anomalous refraction, and simultaneous anomalous reflection and refraction, respectively. As proof of the concept, a bifunctional meta-device with functions of anomalous reflection and focusing transmission for different incident CP waves was simulated and measured. Our findings offer an easy strategy for achieving arbitrary bifunctional CP devices.

Binary geometric phase metasurface for ultra-wideband microwave diffuse scatterings with optical transparency.

Diffuse scatterings of electromagnetic (EM) waves by thin-thickness metasurfaces have promising prospects in many fields due to their abilities of significantly reducing the backward scatterings of targets. One of the major challenges is to further improve the working bandwidth. Here, we propose a binary geometric phase metasurface with high optical transparency to realize ultra-wideband backward scattering reduction through diffuse scatterings. A multi-layered reflective meta-structure is used as the basic building block while its out-of-phase counterpart is achieved through a geometric rotating operation. The proposed metasurface shows a polarization-insensitive wave-diffusion property with about 10 dB scattering reduction in an ultra-wide frequency band from 3.5 GHz to 16.6 GHz, reaching a fractional bandwidth of 130%. As the experimental demonstration, prototype is fabricated and measured that is in agreement with simulated results. The proposed metasurface provides an efficient way to tailor the exotic scattering features with simultaneously high optical transmittance, which can offer crucial benefits in many practical uses, for example, window stealth applications.

Multi-functional coding metasurface for dual-band independent electromagnetic wave control.

Multi-functional metasurfaces have exhibited powerful abilities of manipulating electromagnetic (EM) wave in predetermined manners, largely improving their information capacities. However, most works are implemented with EM functions controlled by one of the intrinsic properties of EM wave, such as polarization, frequency, etc. Herein, we propose a coding scheme to design a broadband and high-efficient multi-functional metasurface independently controlled by both frequency and polarization. To achieve this goal, we design anisotropic coding particles to realize independent phase functions and polarization-selectivity in the microwave region. Meta-atoms are finally optimized to exhibit 2-bit phase responses insensitive to incident polarization in the X-band while showing a 1-bit phase shift sensitive to incident polarization in the Ku-band. As a proof of concept, a metasurface is configured as an isotropic lens in the X-band, whereas the metasurface is designed as an anisotropic beam deflector in the Ku-band with or without polarization-conversion functionality dependent on the input polarization. The measured results, which agree well with the simulated ones, show excellent performances in the designed dual bands. Such a multi-functional coding metasurface may provide a flexible and robust approach to manipulate EM wave of multiple frequencies, as well as to integrate diverse functionalities into a single flat device.

Highly Branched Metal Alloy Networks with Superior Activities for the Methanol Oxidation Reaction.

Three-dimensional (3D) interconnected metal alloy nanostructures possess superior catalytic performance owing to their advantageous characteristics, including improved catalytic activity, corrosion resistance, and stability. Hierarchically structured Ni-Cu alloys composed of 3D network-like microscopic branches with nanoscopic dendritic feelers on each branch were crafted by a facile and efficient hydrogen evolution-assisted electrodeposition approach. They were subsequently exploited for methanol electrooxidation in alkaline media. Among three hierarchically structured Ni-Cu alloys with different Ni/Cu ratios (Ni0.25 Cu0.75 , Ni0.50 Cu0.50 , and Ni0.75 Cu0.25 ), the Ni0.75 Cu0.25 electrode exhibited the fastest electrochemical response and highest electrocatalytic activity toward methanol oxidation. The markedly enhanced performance of Ni0.75 Cu0.25 eletrocatalyst can be attributed to its alloyed structure with the proper Ni/Cu ratio and a large number of active sites on the surface of hierarchical structures.

Safety and Efficacy Outcomes Following Spinal Endoscopic Procedures for Thoracic Ligamentous Ossification: A Systematic Review and Meta-Analysis.

STUDY DESIGN: A systematic review and meta-analysis. OBJECTIVE: This study systematically reviewed and evaluated the safety and efficacy of spinal endoscopic techniques as a treatment for thoracic ligamentum flavum ossification (TOLF). SUMMARY OF BACKGROUND DATA: The use of spinal endoscopic techniques for the treatment of TOLF has increased in recent years. The present study is the first comprehensive systematic review and meta-analysis focused on the use of spinal endoscopic techniques for TOLF. MATERIALS AND METHODS: The Cochrane Central, PubMed, Web of Science, and Embase databases were systematically searched for studies focused on patients undergoing spinal endoscopic techniques to treat symptomatic TOLF. RESULTS: This meta-analysis included 23 studies. We included 323 patients (177 males, 146 females) with a mean age of 58.40±10.06 years, with 304 total recorded lesion locations of which 245 were located in the lower thoracic spine. Complications affected 35/323 patients, and the mean operative duration for 305 patients was 108.15±47.34 minutes. For 187 patients, the mean operative bleeding was 25.13±12.54 mL, while for 87 patients the mean duration of hospitalization was 4.59±1.93 days. At last follow-up, functional assessment was performed for 260 patients, of whom 200 were in excellent condition, visual analog scale (VAS) scores were assessed for 160 patients, with a mean improvement of 4.40 (3.95, 4.86) Japanese Orthopedic Association (JOA) scores were recorded for 115 patients, with a mean improvement of 3.49 (2.79,4.18), and modified Japanese Orthopedic Association (mJOA) scores were recorded for 208 patients, with a mean improvement of 3.62 (2.89,4.35). CONCLUSIONS: These results support several advantages of spinal endoscopic techniques for the treatment of symptomatic TOLF. These include low complication rates, rapid postoperative recovery, and good functional recovery when used for single-segment, non-nodular ossification and no combined dural ossification.

Recurrent Cushing's Disease Caused by a TPIT-Lineage Densely Granulated Corticotroph Pituitary Neuroendocrine Tumor: A Case Report.

INTRODUCTION: Recurrent Cushing's disease (recurrent CD) is an uncommon and intricate clinical form of Cushing's syndrome. However, the connection between the pathological types of ACTH-secreting PitNETs and the clinical signs of recurrent CD remains uncertain. CASE DESCRIPTION: A 64-year-old woman, previously diagnosed with renal carcinoma, was admitted to our hospital due to recent weight gain. Previous endocrine tests indicated fluctuating hypercortisolemia and a recurrent pituitary tumor over the past six years. She underwent two transsphenoidal hypophysectomies, and histopathological analysis of the tumor revealed it as a densely granulated corticotroph tumor (DGCT), a subtype of TPIT-lineage PitNET, accompanied by tumor apoplexy. CONCLUSION: This case highlights the connection between recurrent CD and the pathological subtypes of TPIT-lineage DGCT-PitNETs.