Normal-Direction Graded Hemispheres for Ionic Flexible Sensors with a Record-High Linearity in a Wide Working Range.

Flexible pressure sensors developed rapidly with increased sensitivity, a fast response time, high stability, and excellent deformability. These progresses have expanded the application of wearable electronics under high-pressure backgrounds while also bringing new challenges. In particular, the nonlinearity and narrow working range lead to a gradually insensitive response, principally because the microstructure deforms inconsistently on the device interfaces in the whole working range. Herein, we report an ionic flexible sensor with a record-high linearity (R2 = 0.99994) in a wide working range (up to 600 kPa). The linearity response comes from the normal-direction graded hemisphere (GH) microstructure. It is prepared from poly(dimethylsiloxane) (PDMS)/carbon nanotubes (CNTs)/Au into flexible and deformable electrodes, and its geometry is precisely designed from the linear elastic theory and optimized through finite element simulation. The sensor can achieve a high sensitivity of S = 165.5 kPa-1, a response-relaxation time of <30 ms, and superb consistency, allowing the device to detect vibration signals. Our sensor has been assembled with circuits and capsulation in order to monitor the function state of players in underwater sports in the frequency domain. This work deepens the theory of linearized design of microstructures and provides a strategy to make flexible pressure sensors that have combined the performances of ultrahigh linearity, high sensitivity, and a wide working range.

Genomic epidemiology of Neisseria gonorrhoeae in Shenzhen, China, during 2019-2020: increased spread of ceftriaxone-resistant isolates brings insights for strengthening public health responses.

The antimicrobial resistance (AMR) in gonorrhea poses global threat of increasing public health concern. In response to this concern, molecular surveillance has been widely utilized to detail the changes in the evolution and distribution of Neisseria gonorrhoeae during AMR transmission. In this study, we performed a comprehensive molecular surveillance of 664 N. gonorrhoeae isolates collected in Shenzhen, one of the cities with the largest mobile population in China, 2019-2020. In 2020, ceftriaxone showed an unprecedented high resistance rate of 24.87%, and 67.83% of the ceftriaxone-resistant (Cro-R) isolates harbored a nonmosaic penA allele. The Cro-R isolates with nonmosaic penA alleles showed a tremendous increasing trend from 0.00% in 2014 to 20.45% in 2020, which proves the need for monitoring nonmosaic penA-related resistance. Importantly, genotyping indicated that multilocus sequence typing ST11231 (35.71%) had a notable rate of ceftriaxone resistance, which might become the focus of future surveillance. Whole-genome sequencing analysis showed that the internationally spreading FC428 clones have circulated in Shenzhen region with typical ceftriaxone resistance (MIC ≥ 0.5 mg/L) maintained. Our surveillance combined with genomic analysis provides current information to update gonorrhea management guidelines and emphasizes that continuous AMR surveillance for N. gonorrhoeae is essential. IMPORTANCE We conducted a comprehensive molecular epidemiology analysis for antimicrobial-resistant Neisseria gonorrhoeae in Shenzhen during 2019-2020, which provided important data for personalized treatment and adjustment of monitoring strategy. Briefly, the proportion of ceftriaxone-resistant (Cro-R) isolates reached a stunning prevalence rate of 24.87% in 2020. A typical increment of Cro-R isolates with nonmosaic penA alleles proves the necessity of monitoring nonmosaic AMR mechanism and involving it into developing molecular detection methods. Whole-genome sequencing analysis showed that the international spreading FC428 clone has been circulating in Shenzhen with typical ceftriaxone resistance (MIC ≥ 0.5 mg/L) maintained. In summary, we conducted a comprehensive epidemiology study, providing significant data for therapy management. Our results not only improve the understanding of the distribution and transmission of AMR in N. gonorrhoeae but also provide effective AMR data for improving surveillance strategies in China.

Enhanced external counterpulsation treatment regulates blood flow and wall shear stress metrics in femoral artery: An in vivo study in healthy subjects.

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-basedapproach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries.

Identification of high-level ceftriaxone-resistant Neisseria gonorrhoeae isolates with diverse penA alleles in Zhejiang, China.

OBJECTIVES: The prevalence of ceftriaxone-resistant Neisseria gonorrhoeae poses a significant threat to the effectiveness of gonorrhoea treatment. The aim of the present study was to analyse the characteristics of ceftriaxone-resistant N. gonorrhoeae, with a specific focus on high-level ceftriaxone-resistant strains. METHODS: A total of 207 strains of N. gonorrhoeae were collected from hospitals in Zhejiang, China, between 2019 and 2020. From this collection, we selected 8 strains of ceftriaxone-resistant N. gonorrhoeae for whole-genome sequencing, genotyping, and molecular profile analysis. For clonal strains (FC428-like), we conducted a phylogenetic analysis to understand their origin and evolutionary path. RESULTS: Among the selected strains, 5 demonstrated high-level ceftriaxone resistance (MIC 1-2 mg/L). The genotyping results showed that these isolates had a higher diversity of penA alleles than expected. Four isolates had mosaic penA-60.001 allele and the remaining four had different non-mosaic penA alleles. Phylogenetic analysis suggested that the emergence of FC428-like clones containing penA-60.001 may result from further dissemination of different FC428 subclones from different regions of China. The identification of high-level ceftriaxone resistance in non-mosaic penA gonococci, specifically in the ZJ20-3 isolate (penA-21.001) with an MIC of 2 mg/L, is a groundbreaking discovery. CONCLUSIONS: We present a comprehensive analysis of ceftriaxone-resistant N. gonorrhoeae isolates in Zhejiang, highlighting a significant diversity of penA alleles. The identification of strains exhibiting resistance to ceftriaxone at high levels in our study underscores the potential threat to existing protocols for gonorrhoea treatment. Consequently, we strongly emphasize the urgent need to enhance surveillance initiatives focused on ceftriaxone-resistant N. gonorrhoeae.

Identification of ceftriaxone-resistant Neisseria gonorrhoeae FC428 clone and isolates harboring a novel mosaic penA gene in Chengdu in 2019-2020.

BACKGROUND: Antimicrobial resistance in gonorrhea has become a growing global public health burden. Neisseria gonorrhoeae isolates with resistance to ceftriaxone, the last remaining first-line option, represent an emerging threat of untreatable gonorrhea. METHODS: A total of ten ceftriaxone-resistant N. gonorrhoeae FC428 isolates and two isolates harboring a novel mosaic penA-232.001 allele from 160 gonococcal isolates in Chengdu in 2019-2020 was described in the present study. Multilocus sequence typing (MLST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) were performed to characterize the isolates. Whole genome sequencing and maximum-likelihood method were performed to infer how the genetic phylogenetic tree of these isolates looks like. Recombination analysis was performed using the RDP4 software. This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100048771, registration date: 20210716). RESULTS: The genetic phylogeny showed that the ten FC428 isolates sporadically clustered into different phylogenetic clades, suggesting different introductions and local transmission of FC428. Two isolates showed close genetic relatedness to ceftriaxone-resistant clone A8806, which was only reported from Australia in 2013. Homologous recombination events were detected in penA between Neisseria gonorrhoeae and commensal Neisseria species (N. perflava and N. polysaccharea), providing evidence of commensal Neisseria species might serve as reservoirs of ceftriaxone resistance-mediating penA sequences in clinical gonococcal strains. CONCLUSIONS: Our results demonstrate further dissemination of FC428 in China and resurgence risks of sporadic ceftriaxone-resistant A8806 to become the next clone to spread.

Rapid Detection of Predominant SARS-CoV-2 Variants Using Multiplex High-Resolution Melting Analysis.

Coronavirus disease 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a considerable threat to global public health. This study developed and evaluated a rapid, low-cost, expandable, and sequencing-free high-resolution melting (HRM) assay for the direct detection of SARS-CoV-2 variants. A panel of 64 common bacterial and viral pathogens that can cause respiratory tract infections was employed to evaluate our method's specificity. Serial dilutions of viral isolates determined the sensitivity of the method. Finally, the assay's clinical performance was assessed using 324 clinical samples with potential SARS-CoV-2 infection. Multiplex HRM analysis accurately identified SARS-CoV-2 (as confirmed with parallel reverse transcription-quantitative PCR [qRT-PCR] tests), differentiating between mutations at each marker site within approximately 2 h. For each target, the limit of detection (LOD) was lower than 10 copies/reaction (the LOD of N, G142D, R158G, Y505H, V213G, G446S, S413R, F486V, and S704L was 7.38, 9.72, 9.96, 9.96, 9.50, 7.80, 9.33, 8.25, and 8.25 copies/reaction, respectively). No cross-reactivity occurred with organisms of the specificity testing panel. In terms of variant detection, our results had a 97.9% (47/48) rate of agreement with standard Sanger sequencing. The multiplex HRM assay therefore offers a rapid and simple procedure for detecting SARS-CoV-2 variants. IMPORTANCE In the face of the current severe situation of increasing SARS-CoV-2 variants, we developed an upgraded multiplex HRM method for the predominant SARS-CoV-2 variants based on our original research. This method not only could identify the variants but also could be utilized in subsequent detection of novel variants since the assay has great performance in terms of flexibility. In summary, the upgraded multiplex HRM assay is a rapid, reliable, and economical detection method, which could better screen prevalent virus strains, monitor the epidemic situation, and help to develop measures for the prevention and control of SARS-CoV-2.

A multiplex method for detection of SARS-CoV-2 variants based on MALDI-TOF mass spectrometry.

The recent outbreak of the coronavirus disease 2019 (COVID-19) pandemic and the continuous evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have highlighted the significance of new detection methods for global monitoring and prevention. Although quantitative reverse transcription PCR (RT-qPCR), the current gold standard for diagnosis, performs excellently in genetic testing, its multiplexing capability is limited because of the signal crosstalk of various fluorophores. Herein, we present a highly efficient platform which combines 17-plex assays with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), enabling the targeting of 14 different mutation sites of the spike gene. Diagnosis using a set of 324 nasopharyngeal swabs or sputum clinical samples with SARS-CoV-2 MS method was identical to that with the RT-qPCR. The detection consistency of mutation sites was 97.9% (47/48) compared to Sanger sequencing without cross-reaction with other respiratory-related pathogens. Therefore, the MS method is highly potent to track and assess SARS-CoV-2 changes in a timely manner, thereby aiding the continuous response to viral variation and prevention of further transmission.

An Ultrahighly Pressure Sensitive Electronic Fish Skin for Underwater Wave Sensing.

Underwater flexible sensors have a future for wide application, which is promising for attaching them to underwater creatures to monitor vital signals and biomechanical analysis of their motion and perceive tiny environmental disturbances. However, the pressure waves induced by biological swimming are extremely weak and susceptible to undercurrents, making them difficult to sense. Here, we report an ultrahighly sensitive biomimetic electronic fish skin designed by embedding an artificial pseudocapacitive-based hair cell into a simulated canal neuromast encapsulation structure, in which the artificial hair cell, as the key sensitive unit, is assembled from hybrid film electrodes and polyurethane-acidic electrolyte foam. Such a film is prepared by inter-cross-linking MXene and holey reduced graphene oxide with the assistance of l-cysteine, effectively increasing the interfacial capacitance and alleviating the oxidation issues of MXene. Meanwhile, the acidic foam with high porosity shows great compressibility to adapt to a high-pressure underwater environment. Consequently, the device exhibits ultrahighly sensitivity (maximum sensitivity ∼173688 kPa-1) over a wide range of depths (0-100 m) and remains stable after 10000 repeated tests. As an example case, the device is integrated as a motion monitoring system to identify the minor disturbances triggered by instantaneous postural changes of fish. The electronic fish skin is expected to demonstrate enormous potentials in flow field monitoring, ocean current detecting, and even seismic waves warning.

Multicentre Clinical Evaluation of a Molecular Diagnostic Assay to Identify Neisseria gonorrhoeae Infection and Detect Antimicrobial Resistance.

OBJECTIVES: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae (N. gonorrhoeae) is an urgent threat to public health, with the emergence of highly resistant strains such as the FC428 clone. This study aimed to evaluate the high-resolution melting assay of N. gonorrhoeae AMR (HRM-NG-AMR) for diagnosing N. gonorrhoeae infection and detecting extended-spectrum cephalosporins and azithromycin resistance. METHODS: A multicentre collection of 1488 samples, including 770 isolates and 718 urogenital swabs, was used to evaluate the performance of the HRM-NG-AMR assay. The presence of N. gonorrhoeae was confirmed by culture. Minimum inhibitory concentrations of antibiotics against the tested isolates were determined using the agar dilution method. RESULTS: Regarding N. gonorrhoeae identification, HRM-NG-AMR had a sensitivity of 95.15% (95% CI 91.65-97.28) and a specificity of 96.44% (95% CI 94.17-97.89) using culture as standard. Regarding AMR detection, the specificity ranged from 96.29% (95% CI 94.57-97.50) for cefixime to 99.52% (95% CI 98.68-99.85) for azithromycin. Additionally, the sensitivity ranged from 31.34% (95% CI 20.87-43.97) for azithromycin to 79.10% (95% CI 63.52-89.42) for ceftriaxone. It was determined that 664 of 672 (98.81%) and 615 of 672 (91.52%) N. gonorrhoeae isolates were susceptible to ceftriaxone and cefixime, respectively, by detecting non-mosaic penA. Lastly, 40 genotypic FC428-related strains with the penA-60.001 allele were accurately identified. CONCLUSIONS: The HRM-NG-AMR assay showed promising diagnostic performance for detecting N. gonorrhoeae infection and predicting AMR. This study aimed to evaluate the application of this assay in the clinical setting to enhance AMR surveillance and treatment intervention.

Wide-Range Linear Iontronic Pressure Sensor with Two-Scale Random Microstructured Film for Underwater Detection.

A broad linear range of ionic flexible sensors (IFSs) with high sensitivity is vital to guarantee accurate pressure acquisition and simplify back-end circuits. However, the issue that sensitivity gradually decreases as the applied pressure increases hinders the linearity over the whole working range and limits its wide-ranging application. Herein, we design a two-scale random microstructure ionic gel film with rich porosity and a rough surface. It increases the buffer space during compression, enabling the stress deformation to be more uniform, which makes sure that the sensitivity maintains steady as the pressure loading. In addition, we develop electrodes with multilayer graphene produced by a roll-to-roll process, utilizing its large interlayer spacing and ion-accessible surface area. It benefits the migration and diffusion of ions inside the electrolyte, which increases the unit area capacitance and sensitivity, respectively. The IFS shows ultra-high linearity and a linear range (correlation coefficient ∼ 0.9931) over 0-1 MPa, an excellent sensitivity (∼12.8 kPa-1), a fast response and relaxation time (∼20 and ∼30 ms, respectively), a low detection limit (∼2.5 Pa), and outstanding mechanical stability. This work offers an available path to achieve wide-range linear response, which has potential applications for attaching to soft robots, followed with sensing slight disturbances induced by ships or submersibles.

Advances in antimicrobial resistance testing.

Antimicrobial resistance (AMR), especially bacterial AMR, poses a global threat to public health and has become a huge obstacle to the effective control of related infectious diseases. Following the golden age of antimicrobials discovery between the 1940s and 1960s, antimicrobial abuse resulted in the rapid emergence of AMR. Nowadays, the problem of AMR has become increasingly serious, and some bacteria have reached the brink of no suitable antimicrobials available. Rapid detection of AMR and level quantification are the prerequisites to control the spread of AMR. Although time-consuming, traditional phenotype-based methods are still the primary methods used in clinical laboratories and are regarded as the gold standard for AMR identification. To offset the limitation of the long turnaround time of phenotype-based methods, molecular detection methods such as polymerase chain reaction (PCR), isothermal amplification, high-throughput sequencing, gene microarray, and mass spectrometry have begun to be widely used and served as important complements to phenotype-based methods. This chapter will describe the advances in the above technologies applied in AMR testing.

Rapid Detection of Antimicrobial Resistance in Mycoplasma genitalium by High-Resolution Melting Analysis with Unlabeled Probes.

With looming resistance to fluoroquinolones in Mycoplasma genitalium, public health control strategies require effective antimicrobial resistance (AMR) diagnostic methods for clinical and phenotypic AMR surveillance. We developed a novel AMR detection method, MGparC-AsyHRM, based on the combination of asymmetric high-resolution melting (HRM) technology and unlabeled probes, which simultaneously performs M. genitalium identification and genotypes eight mutations in the parC gene that are responsible for most cases of fluoroquinolone resistance. These enhancements expand the traditional HRM from the conventional detection of single-position mutations to a method capable of detecting short fragments with closely located AMR positions with a high diversity of mutations. Based on the results of clinical sample testing, this method produces an accordance of 98.7% with the Sanger sequencing method. Furthermore, the specificity for detecting S83I, S83N, S83R, and D87Y variants, the most frequently detected mutations in fluoroquinolone resistance, was 100%. This method maintained a stable and accurate performance for genomic copies at rates of ≥20 copies per reaction, demonstrating high sensitivity. Additionally, no specific cross-reactions were observed when testing eight common sexually transmitted infection (STI)-related agents. Notably, this work highlights the significant potential of our method in the field of AMR testing, with the results suggesting that our method can be applied in a range of scenarios and to additional pathogens. In summary, our method enables high throughput, provides excellent specificity and sensitivity, and is cost-effective, suggesting that this method can be used to rapidly monitor the molecular AMR status and complement current AMR surveillance. IMPORTANCE Mycoplasma genitalium was recently added to the antimicrobial-resistant (AMR) threats "watch list" of the U.S. Centers for Disease Control and Prevention because this pathogen has become extremely difficult to treat as a result of increased resistance. M. genitalium is also difficult to culture, and therefore, molecule detection is the only method available for AMR testing. In this work, we developed a novel AMR detection method, MGparC-AsyHRM, based on the combination of asymmetrical HRM technology and unlabeled probes, and it simultaneously performs M. genitalium identification and genotypes eight mutations in the parC gene that are responsible for most cases of fluoroquinolone resistance. The MGparC-AsyHRM method is a high-throughput, low-cost, simple, and culture-free procedure that can enhance public health and management of M. genitalium infections and AMR control, providing a strong complement to phenotypic AMR surveillance to address the spread of fluoroquinolone resistance.

Detection and classification of SARS-CoV-2 using high-resolution melting analysis.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently posed a significant threat to global public health. The objective of this study was to develop and evaluate a rapid, expandable and sequencing-free high-resolution melting (HRM) approach for the direct detection and classification of SARS-CoV-2. Thirty-one common pathogens that can cause respiratory tract infections were used to evaluate the specificity of the method. Synthetic RNA with serial dilutions was utilized to determine the sensitivity of the method. Finally, the clinical performance of the method was assessed using 290 clinical samples. The one-step multiplex HRM could accurately identify SARS-CoV-2 and differentiate mutations in each marker site within approximately 2 h. For each target, the limit of detection was lower than 10 copies/reaction, and no cross-reactivity was observed among organisms within the specificity testing panel. The method showed good uniformity for SARS-CoV-2 detection with a consistency of 100%. Regarding the clade classification performance, the results showed good concordance compared with sequencing, with the rate of agreement being 95.1% (78/82). The one-step multiplex HRM method is a rapid method for SARS-CoV-2 detection and classification.

A Multiplex Molecular Assay for Detection of Six penA Codons To Predict Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae.

The emerging cephalosporin-resistant Neisseria gonorrhoeae poses an urgent threat to the continued efficacy of the last-line monotherapy for gonorrhea. Consequently, high-throughput, accurate, and reasonable molecular assays are urgently needed for strengthening antimicrobial-resistance surveillance in N. gonorrhoeae. In this study, we designed a high-throughput multiplex method that incorporates high-resolution melting technology and is based on a 6-codon assay (among the most parsimonious assays) developed following comprehensive and systematic reviews. The results showed that our method can precisely distinguish specific single-nucleotide polymorphisms in resistance-associated genes with a specificity and sensitivity of 100% and a detection limit as low as 10 copies per reaction. This method can be directly applied to clinical samples without cumbersome culture and successfully predicted all cephalosporin-resistant isolates (sensitivity: 100%). The method presented here represents a technique for rapid testing of antimicrobial resistance and will serve as a valuable tool for tailor-made antimicrobial therapy and for monitoring the transmission of cephalosporin-resistant strains.

Controlled Epitaxial Growth and Atomically Sharp Interface of Graphene/Ferromagnetic Heterostructure via Ambient Pressure Chemical Vapor Deposition.

The strong spin filtering effect can be produced by C-Ni atomic orbital hybridization in lattice-matched graphene/Ni (111) heterostructures, which provides an ideal platform to improve the tunnel magnetoresistance (TMR) of magnetic tunnel junctions (MTJs). However, large-area, high-quality graphene/ferromagnetic epitaxial interfaces are mainly limited by the single-crystal size of the Ni (111) substrate and well-oriented graphene domains. In this work, based on the preparation of a 2-inch single-crystal Ni (111) film on an Al2O3 (0001) wafer, we successfully achieve the production of a full-coverage, high-quality graphene monolayer on a Ni (111) substrate with an atomically sharp interface via ambient pressure chemical vapor deposition (APCVD). The high crystallinity and strong coupling of the well-oriented epitaxial graphene/Ni (111) interface are systematically investigated and carefully demonstrated. Through the analysis of the growth model, it is shown that the oriented growth induced by the Ni (111) crystal, the optimized graphene nucleation and the subsurface carbon density jointly contribute to the resulting high-quality graphene/Ni (111) heterostructure. Our work provides a convenient approach for the controllable fabrication of a large-area homogeneous graphene/ferromagnetic interface, which would benefit interface engineering of graphene-based MTJs and future chip-level 2D spintronic applications.

Nano-magnetic tunnel junctions controlled by electric field for straintronics.

The magnetic tunneling junction (MTJ) controlled by electric field as an alternate approach for energy efficiency is the highlight for nonvolatile RAM, while there is still a lack of research on resistance manipulation with the electric field in nanoscale MTJs. In this study, we integrated nanoscale MTJs on the (011) orientated Pb(Mg1/3Nb2/3)0.7Ti0.3O3 (PMN-PT) ferroelectric substrates and systematically investigated the magnetoresistance as a function of the magnetic field and electric field. A single domain state of the nanoscale MTJ was demonstrated by the experimental result and theoretical simulation. Afterward, the obvious electric field control of R-H curves was obtained and explained by the competition between magnetoelastic energy and shape anisotropy. More importantly, simulation results also predicted that the switching pathway of magnetic moments under the magnetic field is strongly dependent on the applied electric field, displaying the electric field control of chiral switching in the nano-MTJ. Our work is a milestone in the realization of the emerging dubbed straintronics field.