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Ceftriaxone-resistant Neisseria gonorrhoeae FC428-like strains have disseminated across the Asia-Pacific region, with a continuous rise in prevalence during 2015–2022. To mitigate the effect of these strains, we advocate for enhanced molecular diagnostics, expanded surveillance networks, and a regionally coordinated effort to combat the global spread of FC428-like strains.

IntroductionThis study aims to determine the etiological, sociodemographic, and clinical characteristics of STIs, and the level of resistance in M. genitalium in Shenzhen, a representative first-tier city of southern China.MethodsA multicenter cross-sectional study was conducted and 7886 sexually active participants attending STI-related departments were involved from 22 hospitals. Nine STI-related organisms including N. gonorrhoeae, C. trachomatis, T. vaginalis, M. genitalium, HSV-1, HSV-2, M. hominis, U. parvum, and U. urealyticum were screened.ResultsBeing single or divorced was associated with increased detection of N. gonorrhoeae, C. trachomatis, M. genitalium, HSV-1, HSV-2 and M. hominis. Lower education level was associated with increased detection of C. trachomatis, HSV-2 and M. hominis. No insurance coverage was an independent risk factor for T. vaginalis, M. hominis and U. parvum positivity. Three resistance-determining regions related to macrolide and fluoroquinolone were sequenced in 154 M. genitalium positive samples, among which 90.3% harbored mutations related to macrolide or fluroquinolone resistance and 67.5% were multidrug-resistant M. genitalium. A2072G in 23S rRNA and Ser83Ile in parC were the most common mutations. M. hominis was associated with manifestations of bacterial vaginosis in female and epididymitis in male.ConclusionsSingle or divorced individuals, those with lower education level and individuals without insurance are higher-risk key populations for STIs. The prevalence of antimicrobial-resistant M. genitalium in Shenzhen is high. Detection of M. hominis increased significantly with lower education level and no health insurance coverage, and it is associated with bacterial vaginosis or epididymitis, indicating that M. hominis deserves further attention.

In‐sensor computing architecture has a great advantage especially in massive data sampling, transfer, and processing compared with the separated intelligent sensor systems. However, most of the in‐sensor computing device is proposed based on the traditional neural network model, where the synapse performs linear multiplication of input and weight. This approach fails to make the most use of the nonlinearity of in‐sensor computing devices. Therefore, in this article, first a modified feedforward neural network model with the nonlinear in‐sensor computing synapse (NSCS) located at the input layer is presented, and the backpropagation (BP) algorithm is modified to train the network. Then, the nonlinear characteristics of the NSCS composed of the spin‐transfer‐torque magnetic tunnel junction (STT–MTJ) devices and simple complementary metal‐oxide‐semiconductor (CMOS) circuit are analyzed. Based on the nonlinear response of STT–MTJ NSCS, the small‐scale network with NSCS synapse is experimented on the Modified National Institute of Standards and Technology dataset and compared with the traditional network of the same network size. In the simulation result, it is shown that better performance can be achieved with the STT–MTJ NSCS, including a 2–15 times improvement in convergence speed and a 2.5%–5.1% increase in accuracy.

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.

Abstract 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.

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.

ABSTRACT 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.

ABSTRACT 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.

Summary 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 highly sensitive superconductor/tunnel magnetoresistance (TMR) composite magnetic sensor was designed and fabricated to satisfy the demands of detecting weak magnetic fields down to the pT range at low frequencies. First, analysis of the 1/f noise provided an optimized design scheme for the TMR unit to reduce the noise level. Then, the key structural parameters of the superconducting flux transformation amplifier (SFTA) were optimized with focus on the bonding quality between SFTA and TMR units using the finite element method to enhance the magnetic field magnification factor. An SFTA–TMR composite method with secondary alignment and multi-step bonding was proposed to fabricate the composite magnetic sensor and ensure the designed bonding gap and alignment accuracy. Experiments showed that the magnetic field sensitivity reached 5 pT/Hz0.5 (@ 13 Hz), which is beyond the highest level of superconductor/TMR composite magnetic sensors reported to date and is a further step toward the application of weak magnetic field detection.

A superconductor/magnetoresistance (SC/MR) mixed sensor often has very high-precision detection capability, but it is only sensitive to the out-of-plane magnetic field that is perpendicular to the superconducting flux-to-field transformation amplifier (SFTA). This inherent characteristic makes it impossible for a primary SC/MR mixed sensor to measure the in-plane magnetic field, which limits its application in many fields. This paper presents a new architecture of SC/MR mixed sensors with two magnetic flux guides (MFGs) to realize in-plane magnetic field measurement, which is attributed to the combined effects of MFGs and SFTA. The finite element method simulations are used to study the magnetic flux converting effect of MFGs and magnetic field amplification effect of SFTA, which theoretically proves the feasibility of in-plane magnetic field measurement and reveals the influences of the sizes and spacing of MFGs on magnetic field magnification. Experimental results show that the SC/MR mixed sensor with MFGs can simultaneously sense the in-plane and out-of-plane magnetic fields, and the performance of the mixed sensor with MFGs is comparable to the primary one. The magnification and resolution of the mixed sensors with MFGs to the in-plane magnetic fields are, respectively, improved by 2.91 times and 2.23 times compared to those without MFGs to the out-of-plane magnetic fields. The work described in this paper is of great significance for the development of three-component weak magnetic field detection.

ABSTRACT 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.

Summary Chlamydia trachomatis is the most common sexually transmitted pathogen globally, causing serious health problems and representing a burden on public health. A new variant of C. trachomatis (nvCT) that carries mutations (C1514T, C1515T and G1523A) in the 23S rRNA gene has eluded detection in Aptima Combo 2 assays. This has led to false negatives in diagnostics tests and poses a challenge for C. trachomatis diagnostics on a global level. In this study, we developed a simple and cost‐effective assay to identify C. trachomatis, with a potential application to screen for nvCT. We developed a screening assay based on high‐resolution melting (HRM), targeting the 23S rRNA gene and cryptic plasmid. To evaluate the performance of the assay, 404 archived C. trachomatis DNA specimens and 570 extracted clinical specimens were analysed. Our HRM assay not only identified C. trachomatis in clinical specimens, but also correctly differentiated nvCT carrying C1514T, C1515T and G1523A mutations from the wild‐type. We observed no cross‐reactions with other clinically related agents, and the limit of detection was 11.26 (95% CI; 7.61–31.82) copies per reaction. Implementation of this screening assay could reduce detection times and costs for C. trachomatis diagnoses, and facilitate increased research on the presence and monitoring of nvCT.

Enhanced external counterpulsation is a Food and Drug Administration–approved, non-invasive, assisted circulation therapy for ischemic cardiovascular and cerebrovascular diseases. Previous studies have confirmed that EECP stimulation induces largely different cerebral hemodynamic responses in patients with ischemic stroke and healthy controls. However, the underlying mechanisms remain uncertain. We hypothesize that different blood redistributions at the carotid bifurcation may play a key role. Ten subjects were enrolled in this study, namely, five patients with neurological disorders and five young healthy volunteers as controls. Magnetic resonance angiography (MRA) was performed on the carotid artery. All the subjects received a single session of EECP treatment, with external cuff pressures ranging from 20 to 40 kPa. Vascular ultrasound measurements were taken in the common carotid artery (CCA), external carotid artery (ECA) and internal carotid artery (ICA). Three-dimensional patient-specific numerical models were developed to calculate the WSS-derived hemodynamic factors. The results indicated that EECP increased CCA and ECA blood flow in both groups. The ICA blood flow in the patient group exhibited a mean increase of 6.67% during EECP treatment compared with the pre-EECP condition; a mean decrease of 9.2% was observed in the healthy control group. EECP increased the averaged wall shear stress (AWSS) throughout the carotid bifurcation in the patient group; the ICA AWSS of the healthy group decreased during EECP. In both groups, the oscillatory shear index (OSI) in the ICA increased proportionally with external cuff pressure. In addition, the relative resident time (RRT) was constant or slightly decreased in the CCA and ECA in both groups but increased in the ICA. We suggest that the benefits of EECP to patients with neurological disorders may partly result from blood flow promotion in the ICA and increase in WSS at the carotid bifurcation. In the healthy subjects, the ICA blood flow remained constant during EECP, although the CCA blood flow increased significantly. A relatively low external cuff pressure (20 kPa) is recommended as the optimal treatment pressure for better hemodynamic effects. This study may play an important role in the translation of physiological benefits of EECP treatment in populations with or without neurological disorders.

The objective of this study was to evaluate the value of molecular methods in the management of community-acquired pneumonia (CAP) in children. Previously developed mass spectrometry (MS)-based methods combined with quantitative real-time PCR (combined-MS methods) were used to describe the aetiology and evaluate antibiotic therapy in the enrolled children. Sputum collected from 302 children hospitalized with CAP were analyzed using the combined-MS methods, which can detect 19 viruses and 12 bacteria related to CAP. Based on the results, appropriate antibiotics were determined using national guidelines and compared with the initial empirical therapies. Respiratory pathogens were identified in 84.4% of the patients (255/302). Co-infection was the predominant infection pattern (51.7%, 156/302) and was primarily a bacterial-viral mixed infection (36.8%, 111/302). Compared with that using culture-based methods, the identification rate for bacteria using the combined-MS methods (61.8%, 126/204) increased by 28.5% (p

ABSTRACTThe growing multidrug-resistant Neisseria gonorrhoeae is a serious global threat to gonococcal therapy. During 2017–2018, we identified a rare multidrug-resistant (ceftriaxone and azithromycin) strain (GC250) and four strains (GC185, GC195, GC196 and GC249) with both resistance to ceftriaxone and decreased susceptibility to azithromycin. All strains belonged to NG-STAR ST1143, including the mosaic penA-60.001, which is closely related to ceftriaxone resistance. The characterization of antimicrobial resistance (AMR) determinants and phylogenetic analysis showed these five strains were closely related to internationally spreading ceftriaxone-resistant N. gonorrhoeae FC428, but with higher azithromycin MIC. Findings here demonstrated that this clone not only initiated clonal expansion in China, but acquired azithromycin resistance.

Owing to the attractive advantages of the simple preparation process, convenient frequency adjustment, and stable mechanical structure, magnetic flux modulation with electric controlled permeability exhibits a better performance in the reduction of 1/f noise for magnetoresistive (MR) sensors than other schemes of magnetic flux modulation. However, the magnetic flux electric modulation (MFEM) has not been experimentally verified. In this work, a prototype of the MFEM structure was established by preparing an FeGaB film on a Pb(Mg1/3Nb2/3)0.7O3–PbTi0.3O3 substrate, and the modulation structure was integrated into an MR sensor. A test system was built to evaluate the modulation efficiency of the MFEM structure, and the results showed that the modulation efficiency reached 9.8% with an applied electric field of 2 kV/cm at a frequency of 10 010 Hz. Meanwhile, experiments were carried out to study the effects of driving electric fields’ amplitude and frequency on modulation efficiency, and it was revealed that the modulation efficiency could be further improved by increasing the amplitude of driving voltage and reducing the thickness of the ferroelectric layer.

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.

Magnetic tunnel junction (MTJ) as a key spintronics device can be used for the high-sensitivity magnetic field sensor and high-density non-volatile magnetic random access memory (MRAM). To obtain a high tunneling magnetoresistance (TMR), precise control of the etching process for MTJs is an essential step. In order to investigate the effect of the etching angle on the performance of MTJ devices, a series of MTJ pillars are fabricated by etching with the incidence angle of 10°, 20° and 30°. The prepared samples are characterized by the optical microscopy and SEM, and the R-H curves are also measured and then statistically analyzed. The results reveal that the performance of the MTJ is strongly affected by the IBE process, displaying the uniformity of the pillars edge and MTJ performance will improve as well with the increase of the etching angle. Then, a simplified model based on the re-deposition effect of the etching process is established to explain the experimental phenomena. Furthermore, a newly defined material parameter is introduced in this model and obtained with fitting the experimental results. This proves a valuable way to evaluate the quality of the MTJ stack film without the interference of the device fabrication process.

The low frequency magnetic field detection ability of magnetoresistive (MR)sensor is seriously affected by 1/f noise. At present, the method to suppress the influence of low frequency noise is mainly to modulate the measured magnetic field by mechanical resonance. In this paper, a novel modulation concept employing a magnetoelectric coupling effect is proposed. A design method of modulation structure based on an equivalent magnetic circuit model (EMCM) and a single domain model of in-plane moment was established. An EMCM was established to examine the relationship between the permeability of flux modulation film (FMF) and modulation efficiency, which was further verified through a finite element simulation model (FESM). Then, the permeability modulated by the voltage of a ferroelectric/ferromagnetic (FE/FM) multiferroic heterostructure was theoretically studied. Combining these studies, the modulation structure and the material were further optimized, and a FeSiBPC/PMN-PT sample was prepared. Experimental results show that the actual magnetic susceptibility modulation ability of FeSiBPC/PMN-PT reached 150 times, and is in good agreement with the theoretical prediction. A theoretical modulation efficiency higher than 73% driven by a voltage of 10 V in FeSiBPC/PMN-PT can be obtained. These studies show a new concept for magnetoelectric coupling application, and establish a new method for magnetic field modulation with a multiferroic heterostructure.

Reference values on atrial and ventricular strain from cardiovascular magnetic resonance (CMR) are essential in identifying patients with impaired atrial and ventricular function. However, reference values have not been established for Chinese subjects. One hundred and fifty healthy volunteers (75 Males/75 Females; 18–82 years) were recruited. All underwent CMR scans with images acceptable for further strain analysis. Subjects were stratified by age: Group 1, 18–44 years; Group 2, 45–59 years; Group 3, ≥60 years. Feature tracking of CMR cine imaging was used to obtain left atrial global longitudinal (LA Ell) and circumferential strains (LA Ecc) and respective systolic strain rates, left ventricular longitudinal (LV Ell), circumferential (LV Ecc) and radial strains (LV Err) and their respective strain rates, and right ventricular longitudinal strain (RV Ell) and strain rate. LA Ell and LA Ecc were 32.8 ± 9.2% and 40.3 ± 13.4%, respectively, and RV Ell was −29.3 ± 6.0%. LV Ell, LV Ecc and LV Err were −22.4 ± 2.9%, −24.3 ± 3.1%, and 79.0 ± 19.4%, respectively. LV Ell and LV Ecc were higher in females than males (P < 0.05). LA Ell, LA Ecc, and LV Ecc decreased, while LV Err increased with age (P < 0.05). LV Ell and RV Ell were not shown to be associated with age. Normal ranges for atrial and ventricular strain and strain rates are provided using CMR feature tracking in Chinese subjects.

To improve the sensitivity of the magnetic tunnel junction(MTJ)sensor, a novel architecture for a double-gap magnetic flux concentrator (MFC) was studied theoretically and experimentally in this paper. The three-dimensional finite element model of magnetic flux was established to optimize the magnetic field amplification factor, with different gaps. The simulation results indicate that the sensitivity of an MTJ sensor with a double-gap MFC can be significantly better than that of a sensor with a traditional single-gap MFC, due to the fact that the magnetic magnification sharply increases with the decrease in effective gap width. Besides this, the half-bridge MTJ sensors with the double-gap MFC were fabricated using photolithography, ion milling, evaporation, and electroplating processes. Experimental results show that the sensitivity of the MTJ sensor increased by ten times compared to the sensor without the double-gap MFC, which underlines the theoretical predictions. Furthermore, there is no significant increase in the sensor noise. The work in this paper contributes to the development of high-performance MTJ sensors.

Pneumonia and meningitis continue to present an enormous public health burden and pose a major threat to young children. Among the causative organisms of pneumonia and meningitis, bacteria are the most common causes of serious disease and deaths. It is challenging to accurately and rapidly identify these agents. To solve this problem, we developed and validated a 12-plex PCR coupled with matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) method (bacterial pathogen-mass spectrometry, BP-MS) that can be used to simultaneously screen for 11 key bacterial pathogens related to pneumonia and meningitis. Forty-six nasopharyngeal swabs and 12 isolates were used to determine the specificity of the method. The results showed that, using the BP-MS method, we could accurately identify the expected bacteria without cross-reactivity with other pathogens. For the 11 target bacterial pathogens, the analytical sensitivity of the BP-MS method was as low as 10 copies/reaction. To further evaluate the clinical effectiveness of this method, 204 nasopharyngeal swabs from hospitalized children with suspected pneumonia were tested using this method. In total, 81.9% (167/204) of the samples were positive for at least one of the 11 target pathogens. Among the 167 bacteria-positive samples, the rate of multiple infections was 55.7% (93/167), and the most frequent combination was Streptococcus pneumoniae with Haemophilus influenzae, representing 46.2% (43/93) two-pathogen mixed infections. We used real-time PCR and nested PCR to confirm positive results, with identical results obtained for 81.4% (136/167) of the samples. The BP-MS method is a sensitive and specific molecular detection technique in a multiplex format and with high sample throughput. Therefore, it will be a powerful tool for pathogen screening and antibiotic selection at an early stage of disease.

There are four human coronaviruses (HCoVs), distributed worldwide, that are associated with a range of respiratory symptoms. The discovery of severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV shows that HCoVs pose a significant threat to human health. Our work aims to develop a sensitive method (mCoV-MS) which can not only identify known HCoVs accurately, but also have the ability to provide clues for the emerging HCoVs. The method was performed using a MassARRAY matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system. We developed a 17-plex analysis to detect six HCoVs in Panel A and another 17-plex analysis to detect Alphacoronavirus and Betacoronavirus in Panel B. All tested primers and probes for the mCoV-MS method were effective, with no cross-reactivity observed with other common respiratory viruses. To confirm the usefulness of the mCoV-MS method we screened 384 pharyngeal and/or anal swab samples collected from bats/rodents, and 131 nasal and throat swabs from human patients. The results showed good concordance with the results of metagenomic analysis or PCR-sequencing. The validation test showed mCoV-MS method can detect potentially pathogenic CoVs in Alphacoronavirus and Betacoronavirus and provide convincingly phylogenetic evidences about unknown CoVs. The mCoV-MS method is a sensitive assay that is relatively simple to carry out. We propose that this method be used to complement next generation sequencing technology for large-scale screening studies.

Characterization of expression profile of organisms in response to antimicrobials provides important information on the potential mechanism of action of the drugs. The special expression signature can be used to predict whether other drugs act on the same target. Here, the common response of Shigella flexneri to two inhibitors of RNA polymerase was examined using gene expression profiling. Consistent with similar effects of the two drugs, the gene expression profiles indicated that responses of the bacteria to these drugs were roughly the same, with 225 genes affected commonly. Of them, 88 were induced and 137 were repressed. Real-time PCR was performed for selected genes to verify the microarray results. Analysis of the expression data revealed that more than 30% of the plasmid-encoded genes on the array were up-regulated by the antibiotics including virF regulon, other virulence-related genes, and genes responsible for plasmid replication, maintenance, and transfer. In addition, some chromosome-encoded genes involved in virulence and genes acquired from horizontal transfer were also significantly up-regulated. However, the expression of genes encoding the beta-subunit of RNA polymerase was increased moderately. The repressed genes include those that code for products associated with the ribosome, citrate cycle, glycolysis, thiamine biosynthesis, purine metabolism, fructose metabolism, mannose metabolism, and cold shock proteins. This study demonstrates that the two antibiotics induce rapid cessation of RNA synthesis resulting in inhibition of translation components. It also indicates that the production of virulence factors involved in intercellular dissemination, tissue invasion and inflammatory destruction may be enhanced through derepressing horizontal transfer genes by the drugs.

BackgroundThe completion of numerous genome sequences introduced an era of whole-genome study. However, many genes are missed during genome annotation, including small RNAs (sRNAs) and small open reading frames (sORFs). In order to improve genome annotation, we aimed to identify novel sRNAs and sORFs in Shigella, the principal etiologic agents of bacillary dysentery.Methodology/principal findingsWe identified 64 sRNAs in Shigella, which were experimentally validated in other bacteria based on sequence conservation. We employed computer-based and tiling array-based methods to search for sRNAs, followed by RT-PCR and northern blots, to identify nine sRNAs in Shigella flexneri strain 301 (Sf301) and 256 regions containing possible sRNA genes. We found 29 candidate sORFs using bioinformatic prediction, array hybridization and RT-PCR verification. We experimentally validated 557 (57.9%) DOOR operon predictions in the chromosomes of Sf301 and 46 (76.7%) in virulence plasmid.We found 40 additional co-expressed gene pairs that were not predicted by DOOR.Conclusions/significanceWe provide an updated and comprehensive annotation of the Shigella genome. Our study increased the expected numbers of sORFs and sRNAs, which will impact on future functional genomics and proteomics studies. Our method can be used for large scale reannotation of sRNAs and sORFs in any microbe with a known genome sequence.